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The Economic Impact of


Primary Open Angle Glaucoma -
A Dynamic Economic Model
Centre for Eye Research Australia
Centre for Eye Research Australia
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This report was prepared jointly by the Centre
for Eye Research Australia and Access Economics
Pty Limited.
We acknowledge particularly the expert input
and prior research of
Professor Hugh Taylor AC
Centre for Eye Research Australia and
University of Melbourne
Professor Jonathan Crowston
Centre for Eye Research Australia and
University of Melbourne
Associate Professor Jill Keeffe OAM
Centre for Eye Research Australia and
University of Melbourne
Ms Lynne Pezzullo
Access Economics Pty Ltd
Ms Penny Taylor
Access Economics Pty Ltd
Mr Peter Moore
Access Economics Pty Ltd

Acknowledgments and Disclaimer
While every effort has been made to ensure the accuracy of this document, the uncertain nature of economic data,
forecasting and analysis means that Access Economics Pty Limited is unable to make any warranties in relation to the
information contained herein. Access Economics Pty Limited, its employees and agents disclaim liability for any loss or
damage which may arise as a consequence of any person relying on the information contained in this document.
Publication of this work has been made possible by an unrestricted grant from Allergan who had no part in the direction
or fndings contained in this report.
Centre for Eye Research Australia, University of Melbourne, Australia, February 2008.
Centre for Eye Research Australia
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Weih L, Van Newkirk M, McCarty C, Taylor H (1998) Patterns of glaucoma medication use in
urban and rural Victoria Australian and New Zealand Journal of Ophthalmology, 26[Suppl]:
S12 S15.
Weinand F, Althen F (2006) Long term clinical results of SLT in the treatment of POAG Eur J
Ophthalmology, 16: 100-4.
Weinreb RN, Khaw PT (2004) Primary open-angle glaucoma The Lancet, 363: 1711-20.
Weinreb RN, Friedman DS, Fechtner RD, Cioff GA, Coleman AL, Girkin CA, Liebmann JM, Singh K,
Wilson MR, Wilson R, Kannel WB (2004) Perspective: Risk Assessment in the Management of
Patients with Ocular Hypertension American Journal of Ophthalmology, 138[3]: 458-67.
Wensor M, McCarty C, Stanislavsky Y, Livingston P, Taylor H (1998) The prevalence of glaucoma
in the Melbourne Visual Impairment Project Ophthalmology, 105: 733-9.
Wilson MR, Coleman AL, Fei Yu, Sasaki IF, Kim MH (2002) Depression in patients with glaucoma
as measured by self-reported surveys Ophthalmology, 105[5]: 1018-22.
Wolfs RC, Klauver CC, Ramrattan RS, van Duijin CM, Hofman A, de Jong PT (1998) Genetic risk
of primary open-angle glaucoma. Population based familial aggregation study Arch Ophthal,
116: 1640-45.
Zahari M, Mukesh B, Rait J, Taylor H, McCarty C (2006) Progression of visual feld loss in open
angle glaucoma in the Melbourne Visual Impairment Project Clinical and Experimental
Ophthalmology, 34: 206.
Zeiter JH, Shin DH (1994) Diabetes in primary open-angle glaucoma patients with inferior
visual feld defects Graefes Archive for Clinical & Experimental Ophthalmology, 232[4]:
205-10.
Zghal I, Jeddi A, Hadj Alouane WB, Malouche N, Ayed S, Gaigi S (2000) Primary open-angle
glaucoma and diabetes [French] Tunisie Medicale, 78[8-9]: 518-21.
Zwerling C, Sprince NL, Davis CS, Whitten PS, Wallace RR, Herringa SG (1998) Occupational
injuries among older workers with disabilities: a prospective cohort study of the Health and
Retirement Survey, 1992 to 1994 American Journal of Public Health, 88: 1691-16.
11. References
The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model 105
1 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
Main heading to go here
EXECUTIVE SUMMARY 7
1. Background 10
2. Primary Open Angle Glaucoma 11
3. Risk Factors 13
3.1 Intraocular pressure 13
3.2 Age 15
3.3 Cup-to-disc ratio 16
3.4 Central corneal thickness 16
3.5 Family history and genetics 17
3.6 Ethnicity 17
3.7 Diabetes mellitus 18
3.8 Other potential risk factors 19
4. Epidemiology 20
4.1 Denition of disease stage 20
4.2 Remission 20
4.3 Mortality 20
4.4 Population 21
4.5 Progression 21
4.6 Prevalence and incidence 29
4.7 Disease stages dened 33
5. Treatment 34
5.1 Medication 34
5.2 Laser treatment 39
5.3 Conventional surgery (trabeculectomy) 41
5.4 Prevalence estimates for each treatment group 43
5.5 Treatment efcacy 44
5.6 Side effects 50
6. Disease Costs 55
6.1 Discount rates 55
6.2 The cost to quality of life and wellbeing 56
6.3 Health system costs 60
6.4 Indirect costs 68
6.5 Deadweight losses 69
7. Summary of Model Parameters 70
8. The Model 73
9. Intervention Scenarios 76
9.1 The base case 76
9.2 Improved diagnosis rate 80
9.3 Change in the treatment protocol (Primary laser) 83
9.4 Research and development 87
9.5 Combinations 89
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10. Appendix 1: Meta-Analysis - Falls and Hip Fractures 92
10.1 Fixed-effects versus random-effects 92
10.2 Heterogeneity 92
10.3 Forest plots 93
10.4 Publication bias 96
10.5 Additional supportive literature 97
11. References 98
Figures
Figure 1.1: Peripheral visual eld loss in POAG 10
Figure 2.1: The glaucoma continuum 11
Figure 2.2: Healthy optic nerve 12
Figure 2.3 Glaucomorous optic nerve 12
Figure 3.1: Goldmen tonometery 14
Figure 3.2: Demographic distribution of glaucoma, Australians over 40 15
Figure 3.3: Cup-To-Disk ratio 16
Figure 3.4: Corneal thickness 17
Figure 3.5: Pseudoexfoliation pupil margin 19
Figure 4.1: Schematic of the level of impairment for denite glaucoma 29
Figure 4.2: Original prevalence rates 30
Figure 4.3: Smoothed prevalence rates (moving average across three age groups) 31
Figure 5.1: Glaucoma medication dispensed by year and type of script
(% of total scripts) 35
Figure 5.2: MBS Trabeculoplasty Procedures, 1994-2005 40
Figure 5.3: Trabeculectomy 41
Figure 5.4: MBS Total of Trabeculectomy Procedures, 1994-2005 42
Figure 8.1: Main Menu 73
Figure 8.2: Options Sheet 74
Figure 8.3: Model Design 75
Figure 9.1: Prevalence OHT and POAG, base case 77
Figure 9.2: Value burden of disease due to POAG ($m), base case 78
Figure 9.3: Impact of increased diagnosis rates on DALYs(a) 82
Figure 9.4: Impacts of increased diagnosis rates on treatment costs 82
Figure 9.5: Cost Effectiveness Plane - Increase Diagnosis Rate(a) 83
Figure 9.6: Cost-savings resulting from a protocol change(a) 85
Figure 9.7: Burden of Disease 85
Figure 9.8: Decline in DALYs from new efcacious treatment 88
Contents
2
The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
Main heading to go here
3
Figure 9.9: Treatment costs with new treatment costing $1000 per person per year 88
Figure 9.10: Reduction in DALYs, combined interventions 90
Figure 9.11: Treatment costs, combined interventions 91
Figure 9.12: Total costs, combined scenarios 91
Figure 9.13: Cost effectiveness plane, Combined Scenarios(a) 91
Figure 10.1: Annotated Forest Plot (Random Effects Model) for Visual 94
Impairment and Falls
Figure 10.2: Annotated Forest Plot (Random Effects Model) Glaucome/VFL and Falls 95
Figure 10.3: Annotated Forest Plot (Random Effects Model) for Visual Impairment
and Hip Fractures 95
Tables
Table 1.1: Disease stage 7
Table 3.1: Signicant risk factors for OHT progression to glaucoma,
identied by the OHTS 14
Table 3.2: Hazard ratios for development of POAG from OHT 14
Table 3.3: Risk factors for glaucoma progression, identied by the early
manifest glaucoma trial 15
Table 3.4: Association Between Diabetes Mellitus and Glaucoma 19
Table 4.1: Relative risk of mortality by stage of Visual Impairment 21
Table 4.2: Natural progression rates (cumulative probability) 15 year period 25
Table 4.3: Estimates of disease progression in untreated patients 27
Table 4.4: Denitions of level of impairment for denite glaucoma 29
Table 4.5: OHT and Glaucoma prevalence rates 30
Table 4.6: Incidence and prevalence of ocular hypertension (% of age group) 32
Table 4.7: Proportion of people with glaucoma by age and severity (%),
smoothed (moving average across three age groups) 32
Table 4.8: Disease Stage 33
Table 5.1: IOP lowering medications 35
Table 5.2: Proportion of each drug class by state, 2005 36
Table 5.3: Number of medications taken in combination 37
Table 5.4: Trabeculectomy - MBS services processed by jurisdiction by year 42
Table 5.5: Incidence and treatment failure rate for each stage of treatment
from dismod II 44
Table 5.6: Progression rates (cumulative probability) in treated patients (15 year period) 46
Table 5.7: Studies of the efcacy of laser treatment 47
Table 5.8: Success rates for trabeculectomy 49
Table 5.9: Medication side effects 50
Table 5.10: Risk of COPD (% of Population), 2001 51
Table 5.11: Health System Cost of COPD ($ per Person), 2005 52
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Table 5.12: Trabeculectomy Side-Effects 53
Table 5.13: Prevalence of Cataract (% of Population) 54
Table 5.14: Health System Cost of Cataract ($ per Person), 2005 54
Table 6.1: AIHW Disability Weightings 59
Table 6.2: Health Costs by Who Bears the Cost, 2004-05 60
Table 6.3: Cost of Medication per Person per Annum 61
Table 6.4: Total Cost of Trabeculoplasty Per Treatment 61
Table 6.5: Total Cost of Trabeculectomy Per Treatment 62
Table 6.6: Probability of Residing in an Aged Care facility, 2004-05 63
Table 6.7: Increased Risk of Falls FromVisual impairment 64
Table 6.8: Meta-Analysis, Falls (Random Effects Model) 64
Table 6.9: Relative Risk of an accidental fall by Severity 65
Table 6.10: Risk of Accidental Fall (% of Population), 2001 65
Table 6.11: Health System Cost of an Accidental Fall ($ per Person), 2005 66
Table 6.12: Depression and Vision Loss 67
Table 6.13: Risk of Depression (% of Population), 2001 67
Table 6.14: Health System Cost of Depression ($ per Person), 2005 68
Table 6.15: Indirect Costs ($ per annum), 2005 69
Table 7.1 Prevalence of OHT and POAG 70
Table 7.2 Severity of visual impairment initial proportional split 71
Table 7.3: Modelled treatment assumptions 71
Table 7.4: Modelled treatment costs $2005 (including side-effects and adverse events) 72
Table 7.5: Other modelled variables 72
Table 9.1: Prevalence of OHT and POAG, base case (number of people) 77
Table 9.2: Costs of POAG, 2005 and 2025, base case 78
Table 9.3 Base case (standard treatment) net present value of DALYs and costs 78
Table 9.4 Comparison of prevalence of OHT and POAG with original and
smoothed data 79
Table 9.5 Net present value of DALYs and costs, sensitivity analysis on OHT
Prevalence and incidence for those aged 80+ years 79
Table 9.6: Model Results Increased Diagnosis Rate, Net present value 2005 to 2025 81
Table 9.7: Model Results Protocol Change Trabeculoplasty as primary treatment 84
Table 9.8: Sensitivity Analysis - A conservative approach to surgery failure rates 86
Table 9.9: Model Results Research and Development - showing the impact of
new treatment to reduce progression by 50% and 75% 89
Table 9.10: Model Results - Combined Scenarios 90
Table 10.1: Fixed Effects and Random Effects, Meta-Analysis Results 92
Table 10.2: Heterogeneity within the Combined Studies 93
Table 10.3: Measures of Publication Bias 96
Table 10.4: Non-quantitative supporting literature 97
Contents
5 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
Main heading to go here
ABS Australian Bureau of Statistics
AGIS Advanced Glaucoma Intervention Study
AIHW Australian Institute of Health and Welfare
ALT Argon Laser Trabeculoplasty
AMD Age related macular degeneration
AWE Average Weekly Earning
BMES Blue Mountains Eye Study
CERA Centre for Eye Research Australia
CI Condence interval
EDS Early Disease Stage
CIGTS Collaborative Initial Glaucoma Treatment Study
CNTGS Collaborative Normal Tension Glaucoma Study
COPD Chronic Obstructive Pulmonary Disease
DALYs Disability adjusted life years
DRG Diagnosis Related Group
EGPS European Glaucoma Prevention Study
EMGT Early Manifest Glaucoma Trial
GLT, GLTFU Glaucoma Laser Trial, Glaucoma Laser Trial Follow Up
HAP Hodapp-Anderson-Parrish grading system for disease stage
IOP Intraocular pressure
mmHg Millimetres of mercury, Measure of intraocular pressure.
MBS Medicare Benets Schedule
MMC Mitomycin C - an anti brotic drug which inhibits scarring.
MVIP Melbourne Visual Impairment Project
OHT Ocular hypertension
OHTS Ocular Hypertension Treatment Study
OR Odds ratio
POAG Primary Open Angle Glaucoma
PR Prevalence Ratio
Pseudoexfoliation Pseudoexfoliation syndrome is a systemic condition characterised by
glaucoma/ the production and progressive accumulation of pseudoexfoliative
pseudoexfoliation material in many ocular tissues. Glaucoma occurs more commonly in
syndrome eyes with this syndrome than in those without it. Exfoliative glaucoma
has a more rapid clinical course and worse prognosis than primary
open-angle glaucoma.
RR Relative risk
SD Standard deviation
SLT Selective Laser Trabeculoplasty
VA Visual acuity
VF Visual eld - the ability to detect objects to either side, or above or
below, the direction of vision. It is measured in terms of degrees from
the point of xation, for example, <10 degree eld means that the
person can only see in a visual eld of less than 10 degrees radius from
the point of xation (CERA 2004).
VFL Visual eld loss
Glossary and Acronyms
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7 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
Main heading to go here
Access Economics was commissioned by the Centre for Eye Research Australia (CERA) to
construct a dynamic model of primary open angle glaucoma (POAG) in Australia, to inform
policy development in relation to this serious source of visual impairment and blindness.
The model is based on data from a wide variety of sources, and an intensive literature review
informed the estimation of parameters, such as risk factors for POAG, natural progression of the
disease, treatment efcacy, quality of life, and comorbid conditions (falls and depression).
Intraocular pressure (IOP) was identied as the only modiable risk factor for the
development and progression of POAG. Current medical and surgical treatments are centred
on reducing IOP and maintaining it at lower levels.
Age, cup-to-disc ratio and central corneal thickness are non-modiable risk factors
for glaucoma.
Studies of links between POAG and diabetes mellitus have shown mixed results, so diabetes
was not incorporated in the modelling. As future studies are completed this association will
become better understood.
Studies of family history suggest it is an apparent non-modiable risk factor, but support for
an association is not strong possibly because of ascertainment bias.
The incidence, prevalence and mortality associated with POAG and the incidence and prevalence
of ocular hypertension (OHT) were based on data from the Melbourne Visual Impairment
Project (MVIP) and the Blue Mountains Eye Study (BMES) and use of the DISMOD II model,
and based on severity of visual impairment (with severity splits based on MVIP and BMES
data). Disease stages are dened in Table 1.1. Demographic groups within the population are
projected on the basis of Access Economics Dynamic model population by gender and year of
age projections to 2025.
TABLE 1.1: DISEASE STAGE
Disease stage Description Visual Visual eld
acuity loss (VFL)
No POAG No visual impairment
(OHT or normal
tension)
Early Disease Stage Denite or Probable Better And No VFL
(EDS) Glaucoma. No visual than 6/12
impairment but changes to
optic nerve and/or retinal
nerve bre layer
Mild Denite Glaucoma with mild <6/12 Or Any loss of
visual impairment visual eld (VF)
Moderate Denite Glaucoma with <6/18 Or <20
o
eld
moderate visual impairment
Severe Denite Glaucoma with severe <6/60 Or <10
o
eld
or profound visual impairment
Executive Summary
Australian health care
cost of glaucoma
in 2005 was $342
million.
The total annual cost
of glaucoma in 2005
was $1.9 billion.
The total cost is
expected to increase
to $4.3 billion by
2025.
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In studies of glaucoma, disease progression is not always measured in terms of vision loss.
Clinical studies often use a combination of changes in VF, IOP and optic disc as indicators of
progression. Further, denitions of vision loss vary across researchers, and different researchers
have developed different grading systems to measure progression. The application of progression
rates from the literature therefore proved too problematic. Initially, the approach was to apply
the progression rates from the Weinreb et al, (2004) synthesis in the modelling. Unfortunately,
it was not possible to match the Weinreb et al, (2004) rates with the available incidence and
prevalence data from the MVIP and BMES to obtain sensible projections. To overcome these
problems natural progression rates were derived from prevalence data from the MVIP and BMES
to achieve sensible projections and mindful of the approach used to synthesise progression
rates in Weinreb et al, (2004). This led to annual progression rates that are for the most part
substantially higher than expected so more research and population data particularly by
stage of visual impairment for POAG are clearly required.
The progression rates for people with treated glaucoma are half of those for untreated
glaucoma, in line with the literature on treatment efcacy (key clinical trials such as the Early
Manifest Glaucoma Trial EMGT and the Ocular Hypertension Treatment Study (OHTS)) and the
methodology fromWeinreb et al, (2004). (For treatment efcacy, Weinreb et al, (2004) used
the results from the OHTS and the EMGT as the only trials which compared treatment with no
treatment.)
Treatment failure rates are around 4% of patients per annum failing medication (consistent
with Australian data on rates of trabeculoplasty), 50% of patients per annum failing laser
therapy (consistent with the literature on the efcacy of laser treatment) and 50% of patients
per annum failing surgery (a conservative estimate which is higher than the literature but
sensitivity analysis provided in the report shows it makes little difference to the results).
Remission was modelled as nil, with relative risks for mortality depending on vision loss
(1.67 for mild POAG, 2.34 for moderate POAG and 3.01 for severe POAG decreasing in line
with older age).
The costs of POAG include:
health system costs derived from data from the Australian Institute for Health and
Welfare, Medicare fees and the Department of Health and Ageing National Hospital
Costs Data Collection. Health cost data are also included in the model in relation to the
costs of falls and depression that are associated with vision loss from POAG.
Indirect costs including productivity losses (lower than average employment rates of
people with visual impairment). Productivity losses are low since POAG generally affects
older people. Carer costs and the costs of aids and equipment and deadweight losses based
on CERAs research and previous Access Economics calculations are also included.
Loss of wellbeing (measured as the burden of disease Disability Adjusted Life
Years (DALYs).
The model itself is constructed on a user-friendly Excel platform to enable ease of policy
simulations. Three scenarios were analysed in relation to the base case. The results reported
here are calculated for smoothed prevalence rates and reect the net present value of costs and
benets over the period 2005 to 2025.
A dynamic model of
POAG was developed
to inform policy
development on an
ongoing basis.
Executive Summary
The savings from a
new treatment will
depend on the annual
treatment cost.
Initial laser
trabeculoplasty
gives signicant
cost savings.
Increasing the rate
of diagnosis to 80%
would cost $80,189
per DALY.
Centre for Eye Research Australia
9 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
The rst scenario reects an improvement in diagnostic methods. More than 50% of
individuals with glaucoma in the developed world are unaware they have the disease
(Quigley, 1996). In a population based study (the MVIP), Wensor et al, (1998) found that
50% of those with denite POAG had not been diagnosed previously, and Wong et al, (2004)
examined MVIP data and found that 59% of denite cases of OAG were undiagnosed in
people who had visited an eye care provider in the previous year. Even at zero additional
costs (ie. no additional costs of educating clinicians) and improved diagnosis rates of 70%,
80% and 90%, the modelling suggests that these scenarios are cost effective but relatively
expensive, at between $153,000 to $167,000 per DALY avoided. Improved diagnosis rates
are associated with a rise in health system costs as more people are treated. However, the
burden of disease (DALYs) falls.
The second scenario is a change in the treatment protocol, with laser replacing medication
as rst line therapy. The Glaucoma Laser Trial (GLT) showed that Argon Laser Therapy was
as efcacious as timolol (prostaglandins and Selective Laser Therapy were not in use at
that time). However, Argon Laser Trabeculoplasty (ALT) was not commonly adopted as a
primary treatment because of concern about side effects and the reduced efcacy of repeat
ALT treatments. More recent evidence for the effectiveness of laser treatments as a primary
therapy include the EMGT, Nagar et al, (2005), and McIlraith et al, (2006). The modelling
shows that changing the treatment protocol (based on the assumption that current laser
treatments are as efcacious as medication) is cost saving, reecting the assumption that
primary laser would be provided alone whereas as a second line treatment (as per current
approaches), laser and medication are provided together. Even tripling the cost of laser
trabeculoplasty or increasing it ve fold (from $724 to $3,622) to account for the possibility
of side effects (and assuming these dont affect quality of life), a change in the treatment
protocol remains cost saving.
The nal scenario modelled a new potential therapy to delay progression (for example
availability of a neuroprotectant drug that protects by means other than IOP lowering ).
The model allows for a new therapy that reduces the progression of glaucoma by a further
50% or 75% over and above the reduction in progression from current treatments to
be analysed. Cost effectiveness depends on the cost per person per annum of the new
treatment. At treatment costs of $1,000 per person per annum, new treatments are
cost saving. New treatments remain cost effective and relatively cheap at $5,000 per
diagnosed patient per annum ($44,700/DALY avoided if progression is delayed by 50% over
the base case and $23,400/DALY avoided if progression is delayed by 75% over the base
case). At $10,000 per diagnosed patient per annum, new treatments are still cost effective
but become relatively expensive ($114,400/DALY avoided and $71,914/DALY avoided
respectively).
The POAG dynamic model enables rapid comparison of the cost-effectiveness of
various interventions for the disease and is a valuable tool for ongoing policy formulation
and best practice treatment to address visual impairment and blindness from POAG.
1
Memantine is used for Alzheimers disease and in phase III trials for glaucoma at the time of writing.
Executive Summary
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Access Economics Pty Limited was commissioned by the Centre for Eye Research
Australia (CERA) to:
1. Construct a dynamic model of primary open angle glaucoma (POAG) in Australia,
that encompassed prevalence, incidence, risk factors, health and indirect nancial costs,
treatment options and measures of wellbeing; and
2. Document the model and report on the impacts over the period 2005-2025 of:
< better detection of POAG;
< a change in treatment protocol; and
< a potential new therapy to delay disease progression.
A similar model was previously developed to examine the impact of a number of new
treatments modes on age-related macular degeneration: a quit smoking program; new research
that delays progression; and a new therapy that enhances treatment efcacy (CERA 2006).
The model has the capacity to be adapted to incorporate other sources of visual impairment
in the future, such as diabetic retinopathy, cataract, and refractive error.
This project follows on from earlier reports
2
:
Clear Insight: The Economic Impact and Cost of Vision Loss in Australia (CERA 2004);
Investing in Sight: Strategic Interventions to Prevent Vision Loss in Australia
(CERA 2005); and
Centrally Focused: The Impact of Age-related Macular Degeneration,
A Dynamic Economic Model (CERA 2006).
Due to the technical nature of the modelling, this report assumes familiarity with the
terminology used in these previous reports.
This report is structured as follows:
Description of POAG;
Epidemiology of the disease (including remission, mortality, progression of the disease when
untreated and incidence and prevalence);
Treatment of the disease (including a description of the conventional treatment steps, their
side effects and efcacy);
The costs of the disease (including its impact on quality of life, the health system costs,
productivity costs and other indirect costs);
Description of the Model, its structure and user interface; and
Discussion of the scenarios that the model can be used to analyse.
1. Background
Glaucoma causes
characteristic loss of
peripheral vision and
optic nerve changes.
2
Available online at www.cera.org.au.
Figure 1.1: Peripheral visual
eld loss in POAG.
Main heading to go here
11 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
2. Primary Open Angle Glaucoma
Moderate
glaucoma is
characterised
by loss of
peripheral vision
and sparing of
central vision.
Glaucoma is a progressive, neurodegenerative disease that causes accelerated loss of optic
nerve neurons. Initial changes to the optic nerve and retina are asymptomatic and often
undetectable with current diagnostics (Weinreb et al, 2004). Glaucoma can be described as a
continuum (Figure 2.1) where undetectable disease progresses to asymptomatic disease with
optic nerve and visual eld (VF) change, and nally to symptomatic visual impairment and
blindness.
FIGURE 2.1: THE GLAUCOMA CONTINUUM
Source: reproduced fromWeinreb et al, (2004).
Box 1: Vision loss from POAG
Central vision is the detailed vision people use to read and recognize faces, while
peripheral vision is the side vision that is used for navigating obstacles in the environment
(like doorways and coffee tables) and for detecting oncoming vehicles from a side street.
The diagnosis of glaucoma is often made late in the disease course, because early stages of
glaucoma are usually asymptomatic. Moderate glaucoma is characterised by loss of
peripheral vision and sparing of central vision. Patients often fail to notice peripheral vision
loss until it has progressed towards the centre of vision.
Source: Reproduced from Kwon et al (2007), A patients guide to glaucoma,
http://www.medrounds.org/glaucoma-guide/2006/02/table-of-contents-patients-guide-
to.html, accessed 4 May 2007
In advanced
glaucoma central
vision may be lost.
1 in 10 Australians
over 80 will
develop glaucoma.
12
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There are several different types of glaucoma: primary open angle, angle closure, congenital
and secondary glaucoma. Primary open angle glaucoma (POAG) is the most common worldwide
and the topic of this report (Box 2). POAG is characterised by
3
:
open anterior-chamber angles;
loss of neuroretinal rim and nerve bre layer defects;
VF abnormality;
adult onset; and
absence of other known mechanisms.
While many POAG patients present with elevated intraocular pressure (IOP), a signicant
number of patients with POAG do not have detectable IOP elevation. Elevated IOP is a risk
factor for glaucoma and not necessarily an integral part of the disease.
Box 2: Primary Open Angle Glaucoma
Glaucoma is a degenerative disease of the optic nerve that can lead to vision loss and
blindness. The optic nerve comprises over a million nerve bres (axons) that connect the
retina with the brain. In the front of the eye is a space called the anterior chamber -
clear uid (aqueous humour) ows in to this space and leaves the chamber at the angle
where the cornea and iris meet. When the aqueous humour reaches the angle, it ows
through a meshwork and leaves the eye. Increased IOP occurs when there is increased
resistance to outow.
Elevated intraocular
pressure is a risk
factor for glaucoma
although not
necessarily an
integral part of the
disease.
2. Primary Open Angle Glaucoma
3
American Academy of Ophthalmology (2005).
Figure 2.2: Healthy optic nerve Figure 2.3: Glaucomorous optic nerve
Centre for Eye Research Australia
13 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
Not all cases of glaucoma have an endpoint of unilateral or bilateral blindness. There is
considerable variation in the risk of progression across patients (Weinreb et al, 2004). This
section discusses the current theory on the risk factors associated with glaucoma. More
research is needed to fully establish the role and impact of these.
3.1: INTRAOCULAR PRESSURE
IOP is a measurement of the uid pressure within the eye. IOP is determined by aqueous
humour ow into and out of the anterior chamber (the space between the lens and cornea.
This uid is produced in the ciliary body and ows through the pupil and the trabecular
meshwork or through non-trabecular pathways, commonly called uveoscleral pathways.
The balance between the production and outow of aqueous humour controls the IOP.
The normal range for IOP is between 10 and 21 millimetres of mercury (mm Hg) with an
average of 16 mm Hg, but average IOP varies across populations. High IOP for populations is
usually dened as being greater than two standard deviations (SDs) from the population mean.
IOPs that are within the normal population range may still be too high for individual patients.
Increased IOP is a risk factor for the development and progression of POAG. However, the
level of IOP that causes nerve damage varies between individuals. A certain proportion of those
with elevated IOP (ocular hypertension or OHT) will develop glaucoma. However, a signicant
proportion of those with POAG do not appear to have increased IOP.
A univariate and multivariate analysis completed by the Ocular Hypertension Treatment Study
(OHTS) showed that for the OHTS population, every 1mm Hg increase in mean IOP level was
associated with a 10% increased risk of progression from OHT to glaucoma (Table 3.1) (Gordon,
Beiser and Brandt et al, 2002). The OHTS Group and the European Glaucoma Prevention
Study Group et al, (2007) conrmed that IOP is a risk factor for the development of POAG in
untreated individuals with OHT (Table 3.2).
3. Risk Factors
Intraocular pressure
is a measurement
of the uid pressure
within the eye.
Intraocular pressure
is a risk factor for
glaucoma.
A signicant
proportion of
glaucoma patients
have IOPs in the
normal range.
14
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Inaliteraturereviewofprogressionrates,Friedmanetal,(2004)alsofoundthatIOPwasarisk
factorforprogressionofglaucoma(Table3.3).Inparticular,theEMGTfoundthattheriskof
deteriorationoftheopticnerveinapopulationofpatientswithPOAGdecreasedby10%for
each1mmHgreductioninIOP(forexample,Leskeetal,2003).JayandMurdoch(1993)also
foundprogressionwasfasterwithhigherIOP.
IOPiscurrentlytheonlytreatableriskfactorthathasbeenidentifedtodelayprogression
ofglaucoma.CurrentmedicalandsurgicaltreatmentsarecentredonreducingIOPand
maintainingitatlowerlevels.
TABLE 3.1: SIGNIfICANT RISK fACTORS fOR OhT PROGRESSION TO GLAUCOMA,
IDENTIfIED BY ThE OhTS
hazard Ratio (95%
Confdence Interval - CI)
Putative Predictive factor Univariate Multivariate
Age(perdecade) 1.43(1.19-1.71) 1.22(1.01-1.49)
Blackrace 1.59(1.09-2.32) 0.98(0.65-1.46)*
Sex(male) 1.87(1.31-2.67) 1.42(0.98-2.05)*
Heartdisease 2.11(1.23-3.62) 1.71(0.95-3.09)*
IOP(permmHg) 1.11(1.04-1.18) 1.10(1.04-1.17)
Cornealthickness(per40mmthinner)(seesection3.4) 1.88(1.55-2.29) 1.71(1.40-2.09)
PatternSD(per0.2dBgreater)(seeBox3) 1.36(1.16-1.60) 1.27(1.06-1.52)
Horizontalcup-to-discratio(per0.1larger)(seesection3.3) 1.25(1.14-1.38) 1.27(1.14-1.40)
Verticalcup-to-discratio(per0.1larger)(seesection3.3) 1.32(1.19-1.46) 1.32(1.19-1.47)
*Notsignifcantatp<=0.05.mm=micrometer.dB=decibels.
Source:reproducedfromGordon,BeiserandBrandtetal,(2002).
TABLE 3.2: hAZARD RATIOS fOR DEVELOPMENT Of POAG fROM OhT
Source:OcularHypertensionTreatmentStudyGroupandtheEuropeanGlaucomaPreventionStudyGroupetal,(2007).
3. Risk factors
IOP is currently
the only treatable
risk factor that has
been identifed to
delay progression of
glaucoma.
Figure3.1:Goldmentonometery
In the following example, we estimate the 5-year risk of de-
veloping POAG for a 55-year-old male whose baseline IOPs for
right and left eyes are 22 and 26 mmHg; vertical C/D ratios, 0.4
and 0.4; CCT measurements, 532 and 548 m; and PSDs, 2.2 and
2.2 dB. Means of the values for the right and left eyes are averaged
for each eye-specic predictor and the points are summed (Table
6) to estimate the 5-year risk of developing POAG. The sum of
points for this theoretical patient is 11, which yields an estimated
5-year risk of developing POAG of 20% (Table 6). The estimated
risk for this same patient from the Cox proportional hazards model
is 16.9%.
Discussion
Using data from the OHTS observation group, we devel-
oped a multivariate model that identied baseline older
age, higher IOP, larger vertical C/D ratio, thinner central
corneal measurement, and greater PSD as predictive fac-
tors for the development of POAG in ocular hypertensive
individuals. When the generalizability of the OHTS
model was tested by applying it to data from the placebo
group of the EGPS, the same predictive factors were
identied. The hazard ratios for the predictive factors
were very similar in the separate models, the pooled
model, as well as recently published models by Medeiros
et al
22
and the EGPS Group.
23
Thus, the OHTS predictive
model, including CCT, has been replicated in a European
sample and a separate U.S. sample. The pooled OHTS
EGPS sample has a large number of participants and
large number of POAG end points, which yield greater
stability of the hazard ratios and narrower CIs for
predictions.
Table 5. Univariate and Multivariate Hazard Ratios (HRs) and 95% Condence Intervals (CIs) for the Development of POAG
in the Pooled OHTS and EGPS Control Groups
Baseline Variables
Model
Univariate Final Multivariate
n
No. of
Events HR
95% Lower
CI
95% Upper
CI P Value n
No. of
Events HR
95% Lower
CI
95% Upper
CI P Value
Age (decade) 1312 165 1.41 1.20 1.65 0.0001 1123 154 1.26 1.06 1.50 0.0072
Male gender 1312 165 1.23 0.91 1.67 0.1772
Mean IOP per mmHg* 1312 165 1.10 1.03 1.17 0.0052 1123 154 1.09 1.03 1.17 0.0067
Mean CCT per 40 m thinner 1128 156 2.16 1.81 2.59 0.0001 1123 154 2.04 1.70 2.45 0.0001
Mean vertical C/D ratio per
0.1 larger
1311 165 1.21 1.12 1.32 0.0001 1123 154 1.19 1.09 1.31 0.0001
Mean PSD per 0.2 dB greater 1308 163 1.12 1.04 1.21 0.0019 1123 154 1.13 1.04 1.24 0.0065
History of heart disease 1312 165 1.62 1.00 2.61 0.0488
Mean deviation defect per 0.1
dB greater
1308 163 0.93 0.81 1.06 0.2799
History of high blood pressure 1312 165 1.14 0.83 1.56 0.4300
History of migraine 1312 165 0.90 0.51 1.58 0.7073
Current use systemic
-blockers
1309 165 0.99 0.49 2.01 0.9736
Current use systemic
calcium-channel blockers
1309 165 1.00 0.61 1.66 0.9876
Myopia 1 D spherical
equivalent
1312 165 0.89 0.64 1.25 0.5108
CCT central corneal thickness; CID cup-to-disc; D diopters; dB decibels; IOP intraocular pressure; PSD pattern standard deviation.
*Eye-specic variables are the mean of right and left eyes for each participant.
Table 6. A Point System for Estimating an Ocular Hypertensive Patients 5-Year Risk of Developing Primary
Open-Angle Glaucoma (POAG)
Baseline Predictor
Points for Baseline Predictor
0 1 2 3 4
Age (yrs) 45 45 to 55 55 to 65 65 to 75 75
Mean IOP (mmHg)* 22 22 to 24 24 to 26 26 to 28 28
Mean CCT (m)* 600 576600 551575 526550 525
Mean vertical cup-to-disc ratio by contour* 0.3 0.3 to 0.4 0.4 to 0.5 0.5 to 0.6 0.6
Mean PSD (dB)* 1.8 1.8 to 2.0 2.0 to 2.4 2.4 to 2.8 2.8
Sum of points 06 78 910 1112 12
Estimated 5-yr risk of POAG 4.0% 10% 15% 20% 33%
CCT central corneal thickness; dB decibels; IOP intraocular pressure; PSD pattern standard deviation.
*Eye-specic variables are the mean of right and left eyes.
OHTS Group and EGPS Group Validated Prediction Model for POAG
7
ARTICLE IN PRESS
Centre for Eye Research Australia
15 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
TABLE 3.3: RISK fACTORS fOR GLAUCOMA PROGRESSION, IDENTIfIED BY ThE EARLY
MANIfEST GLAUCOMA TRIAL
hazard Ratio (95% CI)
Baseline factors Univariate Multivariate
Age(68,<68years*) 1.42(1.01-1.98)

1.47(1.04-2.09)

IOP(21,<21mmHg*) 1.67(1.19-2.35)

1.70(1.18-2.43)

PatternSD(-4,>-4*) 1.46(1.04-2.05)

1.58(1.10-2.28)

Pseudoexfoliation(yes,no*) 3.15(1.93-5.15)

2.22(1.31-3.74)

Botheyeseligible(yes,no*) 1.92(1.34-2.75)

1.96(1.36-2.82)

Post Baseline factors


||
InitialchangeinIOPat3months(permmHg) 0.90(0.86-0.94)

IOPatfrstfollow-upvisit(permmHg ) 1.11(1.06-1.17)

MeanIOPatallfollow-upvisits(permmHg ) 1.13(1.07-1.19)

Percentofvisitswithdischaemorrhage(per% )(a) 1.02(1.01-1.03)

*Referencecategoryformultivariateanalysis;P0.05;P<0.005;P<0.001;
||
AdjustedforbaselineIOP,
pseudoexfoliation,numberofeligibleeye,meandeviationandage.
(a)Haemorrhagesorbleedingaroundtheopticnervecanindicateongoingdamagetotheopticnerveandinadequate
controlofglaucoma.
Source:reproducedfromLeskeetal,(2003)
3.2: AGL
Theprevalenceofglaucomaincreasesmarkedlywithage(Figure3.2).Intheirliterature
reviewofprogressionrates,Friedmanetal,(2004)foundthattherewasstrongevidenceofa
linkbetweenolderageandtheriskofprogressionfromOHTtoglaucoma(Table3.1)andfor
progressionofglaucoma(Table3.3).TheOHTSGroupandtheEuropeanGlaucomaprevention
StudyGroupetal,(2007)confrmedthatage(bydecade)isasignifcantriskfactorfor
progressionfromOHTtoglaucoma(Table3.2).
fIGURE 3.2: DEMOGRAPhIC DISTRIBUTION Of GLAUCOMA, AUSTRALIANS OVER 40

Source:Taylor(2001)
The prevalence of
glaucoma increases
markedly with age.
Undiagnosed
Diagnosed
P
e
r
c
e
n
t
10%
8%
6%
4%
2%
0%
Age
40-49 50-59 60-69 70-79 80-89 90+
3. Risk factors
The cost of eye
care will continue
to increase as the
population ages.
16
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3.3: CU-1O-DISC kA1IO
Theopticdiscistheregionoftheeyewherethenervefbresconvergetoformtheopticnerve
andexitthebackoftheeyeintotheorbit.Theopticcupisthecentreportionoftheopticdisc
andissmallerbycomparison.The loss of optic nerve cells causes the cup to become larger
relativetotheopticdisc,increasingthecup-to-discratio.
4
Thecuptodiscratiocompares
thediameterofthecuptotheentirediameteroftheopticdisc.Thecup-to-discratioisoften
measuredbothintheverticalandhorizontalpositiontoestimatetheamountofcuppingand
amountofopticnervedamage.Thecuptodiscratioalsoincreasesinnon-glaucomatousnerves
withincreasingdiscdiameter(Crowstonetal,2004).
Largecup-to-discratioshavebeenidentifedasabaselineriskfactorfordiseaseprogressionwith
valuesof>0.4and0.5associatedwithanincreasedriskofprogression.Theunivariateanalysis
completedintheOHTSshowsthattheriskofglaucomaissignifcantlyincreasedwithincreases
incup-to-discratios(Table3.1)asdidtheOHTSGroupandtheEuropeanGlaucomaprevention
StudyGroupetal,(2007)(Table3.2).However,largercup-to-discratiosinocularhypertensive
patientsmaybeanindicationofearlystructuraldamageandthereforeserveasadiseasemarker
ratherthanariskfactor.
fIGURE 3.3: CUP-TO-DISK RATIO
Cup-to-diskratioreferstotheratioofthecupdiameter
totheverticaldiscdiameter.
Source:http://hubnet.buffalo.edu/ophthalmology/site/Home/
Physical_Exam/Cup-to-Disc_ratio_normal_.jpgaccessed
September2006
3.4: CLN1kAL COkNLAL 1HICkNLSS
Athincentralcorneahasbeenshowntohaveastrongassociationwiththeprogressionfrom
ocularhypertensiontoPOAG(Table3.1andTable3.2).Thisrelationshiphasbeenexplainedby
thepossibilitythatlowcornealthicknessmaybeassociatedwithstructuraldifferencesinthe
opticnervearchitecturethatpredisposetothedevelopmentofglaucoma.Anotherexplanation
isthatmeasurementofIOPisaffectedbythethicknessofthecornea.Inthickercorneas,the
trueIOPislowerthanthemeasuredIOP.Ontheotherhand,inthinnercorneas,thetrueIOPis
higherthanthemeasuredIOP.IntheOHTS,thinnercorneaswereassociatedwithahigherrisk
ofdiseaseprogression(Gordonetal,2002).
A thin central cornea
has been shown to
have an independent
association with the
progression from
ocular hypertension
to POAG
4
Axonsfromtheopticnerveformtheopticrim.Centralexcavation(thecup)isfreefromopticnerveaxons.Theneuroretinal
rimthinsfocallyordiffuselyduetoaxonlossinglaucoma.Thisleadstoenlargementofthecupinrelationtotheopticnerve
(increasingthecuptodiscratio).
3. Risk factors
Centre for Eye Research Australia
17 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
fIGURE 3.4: CORNEAL ThICKNESS
Source:UniversityofIllinoisEyeand
EarInfrmaryPositions,TheEyeDigest,
http://www.agingeye.net/mainnews/
glaucomapachymetry.php
3.5: IAMILY HIS1OkY AND GLNL1ICS
first-degree relatives of individuals with primary open-angle glaucoma have up to an eight-
fold increase in the risk of developing the diseasecomparedtothegeneralpopulation(Wolfs
etal,1998;Tielschetal,1994).Weihetal,(2001)foundthat,inmultivariatelogisticregression
modelsandadjustedforage,thestrongestriskfactorforglaucomawasafamilyhistoryof
glaucoma(OddsRatio-OR3.5,95%CI:1.9to6.7).Friedmanetal,(2004)ontheotherhand
concludedthatstrongsupportforanassociationbetweenfamilyhistoryandprogressionfrom
OHTtoPOAGislacking,refectingthatmanystudiesofthelinkbetweenfamilyhistoryand
POAGmaybeaffectedbyascertainmentbiasduetopoorrecallorlackofknowledgeoffamily
history.Forexample,McNaughtetal,(2000)foundthat27%ofpreviouslydiagnosedPOAG
patientswereunawareoftheirpositivefamilyhistory,suggestingthatahigherpercentageof
adultPOAGmaybeinheritedthanhithertoreported.
POAGhasanapparentcomplexormultifactorialaetiology(WeinrebandKhaw,2004).The
chromosomallocationsofseveralgenesthatcanindependentlycausethediseasehavebeen
mapped.More than 43 different glaucoma gene mutationshavebeenreportedinopen-angle
glaucomapatients,andseverallargestudieshavesuggestedthatasagroupthesemutations
areassociated with 3-4% of patients withtheconditioninpopulationsworldwide(Fingertet
al,2002).TheglaucomageneatGLC1Alocus(myocilin)hasbeenshowntobeassociatedwith
bothjuvenileandadult-onsetprimaryopen-angleglaucoma(Sheffeldetal,1993;Stoneetal,
1997;Alwardetal,1998;Fingertetal,1999;Polanskyetal,2000;Clarketal,2001).Thelow
attributableriskportionofgeneticfactorsindicatesthatnon-geneticfactorsplayaninfuential
roleinthedevelopmentandprogressionofglaucoma.
3.6: L1HNICI1Y
Ethnicityhasbeenproposedasariskfactorinmanystudies.Inparticular,Americanbased
studieshavenotedahigherprevalenceandrateofprogressioninAfrican-Americanpopulations.
ResultsfromtheOHTSsuggestthattheAfrican-Americanraceitselfdoesnotincreasethe
riskofglaucomaprogressionbutrefectsahigherprevalenceofotherriskfactorswithinthat
population.AfricanAmericanstendtohavethinnercorneas,higherIOPandlargercuptodisc
ratiosonaveragethanCaucasians(Friedmanetal,2004).
3. Risk factors
POAG has a complex,
multifactorial
aetiology.
first degree relatives
of OAG patients have
an 8-fold increased
risk of developing
glaucoma.
Corneal thickness
18
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3.7: DIA8L1LS MLLLI1US
TheOHTSshowedthatdiabetesmellitusmayprotectagainstprogressionfromOHTtoPOAG
-(hazardratio0.37inmultivariateanalysis,p<0.05)-however,thepeoplewithdiabetes
enrolledinthestudywerecarefullyselected(thosewithdiabeticretinopathywereexcluded)
andmayrepresentanunusuallyhealthydiabeticpopulation(OHTSGroup;EuropeanGlaucoma
PreventionStudyGroupetal,2006).
Twoglaucomamanagementtrialsshowedalinkbetweenthelikelihoodofglaucomaprogression
andthepresenceofdiabetesmellitus(theAdvancedGlaucomaInterventionStudy(AGIS,2002)
andtheCollaborativeInitialGlaucomaTreatmentStudy-CIGTS(Lichteretal,2001)),while
manyothershaveeitherexcludedindividualswithdiabetesornotexaminedanyrelationships
(Friedmanetal,2004).
Populationbasedstudiesaswellasretrospectiveandprospectivecohortstudiesalsoprovide
mixedresults(seeTable3.4)-includingpopulationbasedstudiesinAustralia.WhileMitchell
etal(1997)foundanincreasedprevalenceofglaucomaforthosewithdiabetes(OR=2.12)and
OHT(OR=1.86),astudybyWeihetal,(2001)foundthatwithadjustmentforage,therewas
nosignifcantdifferenceintheprevalenceofglaucomaamongthosewithdiabetesandthose
without(resultsfordiabetesnotpresentedinthearticle).
VariationsinthedefnitionofPOAGmayexplainsomeofthedifferentfndings(deVoogdetal,
2006).Forexample,deVoogdetal,(2006)notethatarevisionintheirdefnitionofPOAGled
toarevisionintheresultsfromtheRotterdamEyeStudy-fromaninitiallysignifcantrelative
risk(RR)oftheprevalenceofPOAGinparticipantswithdiabetesmellitusof3.11(95%CI1.12
to8.66)toanon-signifcantRRof1.40(95%CI0.96to2.03)(DeVoogdetal,2006:1830).De
Voogdetal,(2006)alsonotedthattheresultsfromthemetaanalysisbyBonovasetal(2004)
(seeTable3.4)werebasedonpreviousworkfromtheRotterdamEyeStudywhichhasbeen
revisedbasedonanewdefnitionofPOAG
5
.
The association
between POAG and
Diabetes is not clear.
3. Risk factors
5
TheresultschangedfromaninitiallysignifcantRRoftheprevalenceofPOAGinparticipantswithdiabetesmellitusof
3.11(95%CI1.12to8.66)toanon-signifcantRRof1.40(95%CI0.96to2.03).(DeVoogdetal,2006:1830).
Over 40 gene
mutations have been
reported in POAG.
Centre for Eye Research Australia
19 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
TABLE 3.4: ASSOCIATION BETWEEN DIABETES MELLITUS AND GLAUCOMA
Source Details Assoc.
Bonovasetal,2004
*
Statisticallysignifcantassociationassumingarandomeffects 3
model(OR=1.50,95%CI1.16to1.93)orfxedeffectsmodel
(OR=1.27,95%CI1.10to1.45)
deVoogdetal,2006

RRofincidentopen-angleglaucomawithdiabeteswas0.82 x
(95%CI0.33to2.05)
Dielemansetal,1996

Associationbetweennewlydiagnoseddiabetesmellitusandhighlevelsof 3
bloodglucosewithhigh-tensionglaucoma,OR=3.11(95%CI,1.12to8.66)
Kleinetal,1994

Open-angleglaucomaincreasedwithage-relateddiabetes ?^
(4.2%versus2.0%,inpeoplewithdiabetesversuspeoplewithout)
Weihetal,2001 Withadjustmentforage,morepeoplewithselfreporteddiabetes x
hadpossible,probablyordefniteglaucoma(12/230,5.2%)than
thosewithoutdiabetes(175/4392,2.5%)butthedifferencewas
notstatisticallysignifcant(chisqtest,1df=0.86,p=0.36)
Mitchelletal,1997

PrevalenceofglaucomaandOHTincreasedinpeoplewithdiabetes 3
OR=2.12,95%CI1.18to3.79)(OHT:OR=1.86,95%CI1.09to3.20)
Tielschetal,1995
#
DiabeteswasnotassociatedwithPOAG(OR=1.03,95%CI0.85to1.25)
Pasqualeetal,2006 Type2diabeteswasassociatedtoPOAGinwomenwitha 3
RR=1.82(95%CI,1.23to2.70)
Zghaletal,2000 volutionofopen-angleglaucomaindiabetesdidnot x
signifcantlydifferenttopeoplewithoutdiabetes
Buddeetal,1998 Patientswithorwithoutdiabetesdidnotsignifcantly x
differinthemorphologyoftheopticdisc
Zeiteretal,1994 Peoplewithprimaryopen-angleglaucomaandpredominantly 3
inferiorVFdefectsinoneorbotheyesaremorelikelytohavediabetes
*-Meta-analysis;-RotterdamStudy;-BeaverDamEyeStudy;-BMES;#-BaltimoreEyeSurvey
^Theseresultswereobtainedfromthestudyabstract.Itwasunclearwhetheragewascontrolledinthiscomparison,
thereforetheresultcannotbedeterminedtobeeithersupportiveonnon-supportiveofanassociation.
Withsuchmixedresults,theassociationbetweendiabetesmellitusandglaucomahasnotbeen
modelledhere.Asfuturestudiesarecompletedthisassociationwillbecomebetterunderstood
andcanthusbeincludedinmodellingsomeindirectinterventionscenariossuchasimproved
diagnosisofdiabetesandbetterglycemiccontrol.
3.8: O1HLk O1LN1IAL kISk IAC1OkS
Anumberofotherpotentialriskfactorshavebeenhighlightedincluding:
migraine:theOHTSshowedapositiveassociationalthoughnotstatisticallysignifcant;
myopia(nearsightedness);
hyperopia(farsightedness);
pseudoexfoliation:foundtobeamajorriskfactorforprogressionintheEMGTwhich
includedasmallnumberofpatientswiththiscondition;
outfowfacility:confictingresultsfromprogressionstudies;
malegender;
opticdischaemorrhage;
sleepapnoea;and
peripheralvasospasm
6
.
Ingeneral,thelimitednumberofstudiesinwhichtheseadditionalsuspectedriskfactorswere
evaluateddoesnotsupportfrmconclusionsconcerningtheirrelativeimportance.
3. Risk factors
6
Aperipheralvasospasmisacontractionofabloodvesselreducingitsinternaldiameterandbloodfow
intheouterpartofthevisualfeld.
Figure3.5:Pseudoexfoliation
pupilmargin.
20
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The effect of the
disease and its
treatment on a
patients health
and quality of life
is a key outcome
for measuring the
economic impact
of disease.
In this section, the characteristics of the disease are discussed - remission, mortality, progression
and nally, prevalence and incidence. Estimates of prevalence and incidence were modelled
based on Melbourne Visual Impairment Project (MVIP) and BMES data and knowledge of
remission, and mortality drawn from the literature. Progression rates were modelled based on
the literature, previous modelling work and taking into account the available data on prevalence
and incidence by age and visual impairment.
The key outcome for measuring the economic impact of disease is the effect of the disease and
its treatment on a patients health and quality of life. For eye disease, the key outcome is vision
loss. Deterioration in vision is a fundamental determinant of the costs of glaucoma (particularly
indirect costs such as participation in the workforce, need for care and vision aids, as well as
quality of life). In the case of glaucoma, however, non-vision, physiological changes (changes in
IOP or optic disc for example) may also determine treatment, and therefore health system costs.
While the costs of the disease are measured and incurred by individuals, diagnosis and quality
of life depend on the interrelationship between vision in each eye. In some patients, glaucoma
may affect only one eye. If it affects both eyes, disease severity and progression in each eye can
differ, so there is often a better eye and a worse eye. Further, eyes that were originally better
may become the worse eye over time. While a diagnosis of glaucoma is based on the worst
eye, quality of life - on the other hand - is determined by the best eye (Brown, 1999, Kobelt
et al, 2006:369).
4.1: DEFINITION OF DISEASE STAGE
There are ve disease stages in the model which are discussed and dened throughout the text
below. For ease of reference, a summary of the disease stages is provided in Table 4.8.
4.2: REMISSION
Currently there is no natural remission in open angle glaucoma (to either no disease or
an earlier stage of the disease), nor any current treatments that improve VF or acuity.
Consequently the remission rate for every stage of the disease is nil.
4.3: MORTALITY
General population mortality rate forecasts are from the Access Economics Demographic Model
(AE-DEM) of the Australian population (see Section 4.4 for more information).
The rate of mortality from glaucoma is assumed to be determined by the persons level of visual
impairment people do not die from glaucoma itself but from associated complications such
as higher rates of accidental falls, isolation and depression (which are implicit in the calculation
of the RR of mortality). McCarty et al, (2001) estimated that visual impairment (best corrected
visual acuity of <6/12) was associated with a signicantly increased risk of mortality (OR
adjusted for age, sex, country of birth, smoking, hypertension and arthritis of 2.34), which
converted to a RR is 2.15.
The RRs of mortality from vision loss by disease stage used in the model are loosely based on
McCarty et al (2001)
7
and fall with age as per Table 4.1.
4. Epidemiology
7
2.34 plus 0.67 (the difference between 1 and 1.67 or between 1.67 and 2.34).
21 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
Main heading to go here
The impact of disease
on vision determines
the impact on health
and quality of life.
TABLE 4.1: RELATIVE RISK OF MORTALITY BY STAGE OF VISUAL IMPAIRMENT
Age OHT/EDS Mild Moderate Severe
40-44 1.00 1.67 2.33 3.00
45-49 1.00 1.67 2.33 3.00
50-54 1.00 1.67 2.33 2.99
55-59 1.00 1.66 2.32 2.98
60-64 1.00 1.66 2.31 2.95
65-69 1.00 1.65 2.29 2.91
70-74 1.00 1.64 2.26 2.85
75-79 1.00 1.62 2.20 2.75
80-84 1.00 1.59 2.11 2.59
85-89 1.00 1.53 1.98 2.37
90+ 1.00 1.45 1.79 2.06
Source: Loosely based on McCarty et al, (2001).
The aetiological fraction for mortality due to glaucoma (as opposed to the number of
people who died) is 1.27% based on the same techniques used in CERA (2004: 37) but using
updated data.
4.4: POPULATION
Forecasts of the Australian population are fromAE-DEM which uses a combination of fertility,
mortality and migration rates to project the future Australian population. Base fertility and
mortality proles for each age and gender (for mortality) are sourced from Productivity
Commission (2005), and adjust over time to match the projection for the total value. Migration
rates are projected in line with the assumptions in the Australian Bureau of Statistics (ABS)
publications: Australian Demographic Statistics (catalogue number 3101.0) and Overseas
Arrivals and Departures (catalogue number 3401.0), with adjustments for changes to Australias
migration program and to reect the latest actual migration (international and interstate) results.
4.5: PROGRESSION
For this dynamic study, a key parameter is the rate at which POAG causes vision to deteriorate
(the rate of disease progression). The impact of disease on vision determines the impact on
health and quality of life. Unfortunately, in studies of glaucoma, disease progression is not
always measured in terms of vision loss. Clinical studies often use a combination of changes in
VF, IOP and optic disc as indicators of progression. As IOP is the focus of treatment, treatment
efcacy is generally measured according to its impact on IOP. Further, denitions of vision loss
vary across researchers.
4. Epidemiology
22
Tunne l Vi s i on
Centre for Eye Research Australia
Measuring and grading glaucomatous vision loss
MeasuringtheprogressionofVFLinglaucomaiscomplex(seeBox3foranexplanationofthe
methodoftestingVF).
Glaucomatouschangeneedstobeisolatedfromotherfactorssuchaschangesinlens
opacityduetocataract,orphysiologicalchangeduetoageing.
Therecanbesubstantialmeasurementvariability(causedforexamplebylossoffxation),
andthereisalearningeffect,bothofwhichneedtobeaccommodatedwhenexamining
patients.
Glaucomatousvisiondeteriorationisveryslow.Evenwhenachangeinfeldisdetectedvia
perimetry,thepatientmaynotnoticeanyvisionloss.Clinicalstudieshavefoundthatonlya
subsetofpatientswithOHTdevelopglaucoma,andofthese,asmallproportionlose
functionalvisionduringthecourseoftheirlifetime.
Further,differentresearchershavedevelopeddifferentgradingsystemstomeasureprogression.
Forexample,theAGIS,EMGTandCIGTSalluseddifferentgradingsystemstomeasure
progression.OthergradingsystemsincludethosedevelopedbyAnderson,Blumenthal,and
Hodapp-Anderson-Parrish(HAP).
Differentgradingsystemsshowdifferentratesofprogressioninthesamepopulation(Zahariet
al,2006,Wilsonetal,2002).Thereisnogoldstandard,soitisdiffculttocompareprogression
ratesderivedfromstudiesusingdifferentmethodologies(Katzetal,1999).Comparisonsof
progressionratessuggestthatratesproducedusingtheAGISmethodmightrepresentalower
boundinjudgingprogression,andtheCIGTSandEMGTmethodsproducerelativelysimilar
results(Katzetal,1999,Wilsonetal,2002,Zaharietal,2006).
Weinrebetal,(2004)developedamethodologyforovercomingthisproblem(section4.5.1.).
8ox 3: Measuring change in VI
VFistestedbyexaminingapatientsabilitytodetectlightatvariousintensitiesatvarious
testlocationsintheVF.Thedimmerthelightdetected,thebetterthevisionatthatpoint
inthefeld.Theresultsoftestsaregenerallyexpressedinadecibelscalederivedfrom
thereciprocalofthelogintensityofthelightprojected.Thusdetectionofdimmerlight
(representingbettervision)isindicatedbyhighernumbers.Thesenumberscanbeusedto
createagradingsystemforVFL.ParametersfromVFtestsusedtomeasurefeldlossare:
a) Meandeviationordefect-themeasurementofhowthemeanofthepatientsresponses
variesfromthemeanoftheresponsesofaseriesofnormalpatientsofsimilarageunder
similartestingconditions.Meandeviationisaffectedbymediaopacity,refractiveerror
andglaucoma.
b) PatternSD,alsoknownascorrectedlossvariance,representsnon-uniformlossoffeld
thusprovidinganindicationoffocaldefectsasoccuringlaucoma.
4. Epidemiology
Patients enrolled in
clinical trials do not
necessarily represent
the community norm.
Where possible
population-based
data has been used.
23 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
4. Epidemiology

The importance of study population characteristics in selecting progression
rates for modelling
Ideally,inselectingprogressionratesformodelling,dataneedtobedrawnfromstudiesthat
arebasedonpopulationswithsimilarcharacteristicstothatbeingmodelled.Asnotedin
section3,anumberoffactorscanaffectprogressionratesincludingage,IOP,centralcorneal
thicknessandcuptodiscratio,orAfricanAmericanorigin(forexample).Inaddition,patients
withpseudoexfoliationsyndromeandpigmentaryglaucomaareoftenincludedtogetherwith
POAGpatientsinstudiesoftreatmenteffcacyanddiseaseprogression.Whiletheidealwould
involverecalculationoftheresultswheretheinclusionofthesepatientshasamaterialimpact
ontheprogressionestimates,thereportedresultsoftenprecludere-calculationexcludingthese
participants.
Further,theparametersselectedforthemodellingneedtorefectthelikelyoutcomesof
administeringtherapyinthecommunity,ratherthansimplyreplicatingthetrials.Progression
ratesbasedonestimatesfromclinicaltrialsdonotnecessarilyrefecttheexperienceinthe
community.Those enrolled in clinical trials often do nothavediseaseriskproflesorhealth
serviceutilisationhabitsthatrepresent the average or community norm.Asanexample,
Hensonetal,(2006)suggestedthatglaucomaprogressionratesfoundinretrospectivestudies
tendtobehigherthanratesderivedfromprospectivestudiesbecausepatientswillingtoenrol
inprospectivestudiesmaybemoreconcernedabouttheirconditionandarelikelytobemore
attentive,demandingandcompliantwiththeirtherapythanaverage.
Constant or variable linear progression
Somestudieshavefoundthatprogressionratesspeedupasdamageworsens(forexample,
Martusetal,2005),whileothershavefoundtheopposite(eg.Raskeretal2000).Thereisalso
someevidencethatprogressionisepisodicratherthanconstant,forexample,Kwonetal,(2001)
foundthataround25%patientsshowednon-lineardiseaseprogression.
4.5.1: NATURAL (UNTREATED) PROGRESSION
Dataondiseaseprogressioninuntreatedpatientsisavailablefromtheplaceboorobservation
armsofclinicaltrials(withtheprovisoabovethattheexperienceofparticipantsinclinicaltrials
maynotmatchthatofthecommunityatlarge).Inaddition,JayandMurdoch(1993)estimated
untreatedprogressionandWilsonetal,(2002)examineduntreatedprogressioninblackpatients.
ThesestudiesaresummarisedinTable4.3.Despiteexaminingprogressionratesintreated
patients,Hattenhaueretal,(1998)isincludedinthetableforthereasonsoutlinedbelow.
ThedatainthetablesuggestthefollowingnaturalpopulationprogressionratesforOhT to
POAG(notingthatthedistinctionbetweenOHTandglaucomaisbasedonclinicianobservation
ofclinicalsignsaswellasinmostcasesdetectionofVFL):
DatafromtheOHTSsuggestprogressionratesforwhitepatientsof2%peryear.
Forallparticipants,theratewasjustunder2%peryear.
DatafromtheEGPSsuggestannualprogressionratesforOHTtoPOAGofaround3.4%.
24
Tunne l Vi s i on
Centre for Eye Research Australia
4. Epidemiology
DatafromTable4.3suggestthefollowingprogression rates for POAG(notingthatprogression
isdefnedindifferentwaysasperthediscussionabove):
FortheEMGT,themostrecentdata(Leskeetal,2007)suggestannualprogressionrates
ofbetween9and10%,whereasLeskeetal,(2003)foundannualprogressionratesof
justover10%.
FromWilsonetal(2002),progressiontoatleastunilateralblindnessinblackpatientswas
1.6%peryearaccordingtotheAGIScriteria,and3.5%accordingtotheCIGTScriteria.
DatafromtheCNTGSsuggestanannualprogressionrateof6.6%.
Weinrebetal,(2004)synthesisedtheseresultsbymodellingtheriskofblindnessinpatients
withOHTusingtheOHTS,Hattenhaueratal,(1998),andWilsonetal,(2002).Theselected
endpointwasunilateralblindnessasanindicatoroftheseverityofVFdeteriorationthatcanbe
comparedacrossdifferentstudies.Weinrebetal,(2004)assumedthatprogressionratesfrom
OHTtoblindnesscanbeestimatedbyaddingthetimereportedforprogressionofOHTto
glaucomafromonestudywiththetimereportedforprogressionfromglaucomatoblindness
inanotherstudy(Weinrebetal,2004:462).Inaddition,progressionwasassumedtobelinear
(Weinrebetal,2004:462).ProgressionratesfromHattenhaueretal,(1998)werealsoused
despiteostensiblybeingbasedontreatedpatients.Weinrebetal,(2004)arguedthatthe
treatmentregimensintheHattenhauerpopulationbasedonpatientsnewlydiagnosedwith
POAGbetween1965and1980maynotrefectcurrentorevenrecenttherapyandthus
thesepatientscouldbeconsideredonlypartiallytreatedoruntreated.TheHattenhaueretal
(1998)progressionratesmightalsobeerroneouslyhighbecauseoflackofdataonothercauses
ofvisionloss,thusWeinrebetal,(2004:465)usedtheseasanupperbound.Theestimatesof
theprobabilityofapatientwithOHTdevelopingglaucomaandfnallybecomingblindinone
eyeover15yearscalculatedbyWeinrebetal,(2004)were:
1.5%OHTSandWilsonetal,(2002)AGIS;
2.6%OHTSandHattenhaueretal,(1998);
3.3%OHTSandWilsonetal,(2002)CIGTS;and
10.5%Hattenhaueretal,(1998).
ResultsfromtheEGPS(2005)werenotavailablefortheWeinrebanalysis.Ifthese
aresubstitutedfortheOHTS,thecalculatedprobabilitiesare:2.7%,4.5%,5.9%
and10.5%respectively.
ItisworthnotingthattherelativevalueofHattenhaueretal,(1998)isthatthedatawere
drawnfromadatabaseofmedicalrecordsforallsourcesofmedicalcareusedbythelocal
populationofOlmstedCounty(USA).Asapopulationbasedstudy,theresultsareprobably
morerefectiveofexperienceinthecommunity.Bycomparison,longitudinalstudiesofmedical
recordsfromspecifcmedicalcentresmaybebiasedbecauseofthetypesofpatientspresenting
totheclinic,orbecauseofthetreatmentapproachattheclinic(forexample,treatmentmaybe
moreaggressive).
Centre for Eye Research Australia
25 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
TwoexamplesofratesmarkedlylowerthanthoseofHattenhaueretal,(1998)arebelow:
Chen(2003)examinedrecordsfor186patients,(82%white),diagnosedwithPOAGin1975
orlaterandwhopresentedtoatertiaryreferralclinic(UniversityofWashingtonMedical
Centre).Heestimatedthattheprobabilityofprogressionfromglaucomatounilateral
blindnessat15yearswas14.6%(95%CI7.6-21.6)andtobilateralblindnesswas6.4%
(95%CI0-14.4).
Similarly,Kwonetal,(2001)studied40eyesof40patientsfollowedataUniversityclinic
since1972withPOAGandfoundthataround13%ofeyeswerelegallyblindafter15years,
noting,however,thattheselectionofpatientsmayhavebeenbiasedtowardsthosewith
worseglaucoma.
Table4.2providesasummaryofthefndingsofthestudiesofnaturalprogression.Notably,
progressionfromOHTtounilateralblindnessislowerthanfromPOAGtounilateralblindness
sincesomeofthosewithdetectedOHTdonotprogresstoglaucoma.
TABLE 4.2: NATURAL PROGRESSION RATES (CUMULATIVE PROBABILITY) 15 YEAR PERIOD
Start point Unilateral blindness Bilateral Blindness
OHT 1.5%to10.5%(Weinrebetal,2004) 3%(Hattenhaueretal,1998)
Glaucoma 40.5%(Hattenhaueretal,1998) 16.5%(Hattenhaueretal,1998)
Initially, the approach was to apply the progression rates from the Weinreb et al, (2004)
synthesis in the modelling. Unfortunately,itwasnotpossibletomatchtheWeinrebetal,
(2004)rateswiththeavailableincidenceandprevalencedatafromtheMVIPandBMESto
obtainsensibleprojections(seeSection4.6).Inaddition,forthemodelitwasnecessaryto
measureprogressofmildormoderatevisionloss,buttheWeinrebetal,(2004)rateswereonly
forblindnessasdefnedintheUSA.TheestimatesoftheproportionofpeoplewithPOAGin
eachvisualimpairmentseveritygroup(earlystage,mild,moderateandsevere)fromMVIP/BMES
datawerebasedonsmallsamplesizes.Further,MVIPandBMESdataarebasedonamixed
populationwithbothtreatedanduntreateddisease.
final progression rates were therefore derived using the available MVIP and BMES incidence
and prevalence data and the splits of disease severity(themethodologyisoutlinedinmore
detailinSection4.6below).Smoothedprevalencerateswereused,andthediagnosisratewas
setat50%(consistentwithresearchfndings).Thisledtoannualprogressionratesthatarefor
themostpartsubstantiallyhigherthanexpected(andhigherthanWeinrebetal,(2004))but
internallyconsistentwiththeotherparametersfromtheliteratureandpopulationstudiesused
inthemodel.Clearlymoreresearchandpopulationstudiesinvestigatingincidence,prevalence
andprogressionofbasedonstandardclassifcationsofvisualimpairmentareclearlyrequired.
4. Epidemiology

26
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Centre for Eye Research Australia
Insummaryandforthepurposesofmodelling,the annual natural progression rates are:
OHTtoEDS:31.2%oftheOHTpopulationperannum(markedlyhigherthan
studiessuggest)
8
;
NormotensivetoEDS:approximateaverageof0.22%oftheAustralianpopulation
perannum;
EDStoMild:1.5%ofthosewithPOAGperannum(intherangeofwhatstudiessuggest);
MildtoModerate:85.0%(markedlyhigherthanstudiessuggest);and
Moderatetosevere:30.0%(markedlyhigherthanstudiessuggest).
4. Epidemiology
8
Whilethisnumberappearshigh,itisimportanttonotethattheprevalenceofOHTwasonlyrecordedforindividuals
thatwere40yearsandoverandasdiscussedearlierinSection2theaetiologyofPOAGresemblesthatofacontinuum.
Itisthereforeverylikelythat,byonlyincludingpeopleagedover40yearsofage,thetotalprevalenceofOHTisbeing
underestimated.
Centre for Eye Research Australia
27 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
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7
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28
Tunne l Vi s i on
Centre for Eye Research Australia
T
A
B
L
E

4
.
3
:


E
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Centre for Eye Research Australia


29 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
4. Epidemiology
4.6: kLVALLNCL AND INCIDLNCL
Asforeshadowedpreviously,theincidenceandprevalenceestimatesusedinthemodelare
derivedfrombothMVIP
9
andBMESdata.
Dataforpersonswereused,ratherthanbygendertoensurethelargestsamplesizepossible.
Noconsistentgenderdifferencesarereportedinglaucomaincidence,prevalenceofseverity
studies.
TheEDSgroupisbasedonMVIPdataforpeoplewithprobableordefniteglaucoma.
Thisstagelackedvisionlossbydefnitionandsothediagnosishadbeenmadeonoptic
discchangesorapreviousdiagnosisofglaucoma.TheotherstagesofPOAGarebasedon
combinedMVIPandBMESdataforpeoplewithdefniteglaucoma.
Thedataweredisaggregatedintodegreeofvisualimpairment,withVImeasuredusinga
combinationofVAandVFloss(seedefnitionsandschematicinTable44andFigure
4.1).TheVAcategoriesarecreatedfromthebest-presentedVAdata,andVFL(constriction)
categoriesarecreatedfromPatternDeviationdata.
Forthisanalysis,severeandprofoundwerecombined.
IncidenceandprevalenceofOHTisbasedonMVIPdataforthosewithIOP21mmHgusing
tonopenmeasurements.
Theprogressionratesbetweenthestagesofglaucomahavebeenpreviouslydescribedin
Section4.5.1.
TABLE 4.4: DEfINITIONS Of LEVEL Of IMPAIRMENT fOR DEfINITE GLAUCOMA
VA VfL
EDS/None Betterthan6/12 AND NoVFL
MildImpairment <6/12 OR AnylossofVF
ModerateImpairment <6/18 OR <20
o
feldloss
SevereorprofoundImpairment <6/60 OR <10
o
feldloss
fIGURE 4.1: SChEMATIC Of ThE LEVEL Of IMPAIRMENT fOR DEfINITE GLAUCOMA
for both OhT and POAG an increase in prevalence is observable with age, althoughthistails
offforOHT,asprogressiontoglaucomabecomesmorelikelyandtherebytreatmentstoreduce
IOP(Table4.5).Asmallnumberofindividualswererecordedintheoldestagegroupforpeople
withOHT,whichresultedinaprevalencerateestimateofzero.Itispossiblethatoncepeople
reachacertainagewithoutcontractingOHTorglaucoma,theyareunlikelyevertodevelopit,
however,thismayalsoresultfromthesmallsamplesize(Table4.5).
Loss of visual
acuity and visual
feld affect quality
of life.
Visual Acuity No Loss
Some VF
Loss
VF <20 - !10
degrees
VF <10 - !5
degrees
VF <5
degrees
VA <3/60 or worse
VA <6/60 - !3/60 Severe
VA <6/18 - !6/60 Moderate
VA <6/12 - !6/18 Mild
VA <6/6 - !6/12 None
VA !6/6
Visual Field Loss
9
SeeforexampleMukeshetal,(2002),Wensoretal(1998)andWeihetal,(2001).
30
Tunne l Vi s i on
Centre for Eye Research Australia
TABLE 4.5: OhT AND GLAUCOMA PREVALENCE RATES
OhT prevalence - Glaucoma prevalence -
Original (%) (%)
Age Males females Original Smoothed
0-39 0.00 0.00 0.00 0.00
40-44 0.13 0.13 0.00 0.07
45-49 0.13 0.13 0.22 0.14
50-54 0.31 0.31 0.21 0.60
55-59 0.31 0.31 1.45 0.94
60-64 0.37 0.37 1.50 2.29
65-69 0.37 0.37 4.22 3.46
70-74 0.49 0.49 5.30 5.51
75-79 0.49 0.49 6.85 5.78
80-84 0.00 0.00 6.19 6.74
85-89 0.00 0.00 9.09 9.66
90+ 0.00 0.00 18.18 20.66
Source:specialrequestfromCERAbasedonMVIPandBMES
DISMODIIwasusedtocalculateincidenceandprevalencebyageforOHTandPOAG.
Anumberofstepsweretaken.
First,glaucoma prevalence data from the MVIP and BMES database were smoothed by taking
a moving average across three age groups to remove prevalence fuctuations between age-
cohorts.Whilethedynamicmodelallowstheusertoswitchbetweentheoriginalprevalence
ratesandthesmoothedprevalencerates,thesmootheddataispreferredformodellingpurposes,
asthetrendsfollowamorelogicalpathway.
Thedifferencesbetweentheoriginalprevalenceratesandthesmoothedratesareshownin
Figure4.2andFigure4.3.
fIGURE 4.2: ORIGINAL PREVALENCE RATES
4. Epidemiology
Economic impact of primary open angle glaucoma Commercial-in-Confidence
26
FIGURE 4-2: ORIGINAL PREVALENCE RATES
0-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85-89 90-94 95+
0%
2%
4%
6%
8%
10%
12%
14%
16%
18%
20%
EDS
Mild
Moderate
Severe
FIGURE 4-3: SMOOTHED PREVALENCE RATES (MOVING AVERAGE ACROSS THREE AGE GROUPS)
0-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85-89 90-94 95+
0%
5%
10%
15%
20%
25%
30%
35%
40%
EDS
Mild
Moderate
Severe
Second, raw OHT prevalence estimates (based on a special data request from the MVIP
database) were then run through DISMOD II (assuming no remission) and the resulting total
prevalence numbers formed the denominator for the progression rate in step three.
A progression rate from OHT to glaucoma was calculated by dividing half the number of
incident cases of glaucoma by total prevalence of OHT. This was justified by findings from the
Early Manifest Glaucoma Trial where 52% of glaucoma cases identified through population
screening had an IOP <21mmHg (Grodum et al, 2002). This resulted in a progression rate of
Centre for Eye Research Australia
31 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
4. Epidemiology
fIGURE 4.3: SMOOThED PREVALENCE RATES
(MOVING AVERAGE ACROSS ThREE AGE GROUPS)
Second,rawOHTprevalenceestimates(basedonaspecialdatarequestfromtheMVIP
database)werethenrunthroughDISMODII(assumingnoremission)andtheresultingtotal
prevalencenumbersformedthedenominatorfortheprogressionrateinstepthree.
AprogressionratefromOHTtoglaucomawascalculatedbydividinghalfthenumberof
incidentcasesofglaucomabytotalprevalenceofOHT.Thiswasjustifedbyfndingsfromthe
EarlyManifestGlaucomaTrialwhere52%ofglaucomacasesidentifedthroughpopulation
screeninghadanIOP<21mmHg(Grodumetal,2002).Thisresultedinaprogressionrateof
approximately31.2%perannum.Asnotedearlier,thisnumberappearshighandmoreresearch
anddataareneeded.ItisalsoimportanttonotethattheprevalenceofOHTwasonlyrecorded
forindividualsthatwere40yearsandoverandasdiscussedearlierinSection2theaetiology
ofPOAGresemblesthatofacontinuum.Itisthereforepossiblethat,byonlyincludingpeople
agedover40yearsofage,thetotalprevalenceofOHTmaybeunderestimated.
TheincidenceofearlystagePOAGfromnormotensiveAustralianswasthenestimatedusing
DISMODII,withanapproximateannualincidencerateof0.22%oftheAustralianpopulation.
IncidenceandprevalenceratesforOHTwerethenrecalculatedusingtheratesofprogression
fromOHTtoearlystagePOAG,aswellasanORofmortalityof1.Theresultingoutputis
showninTable4.6.WhileOHTamongstthoseinolderagegroupswaszerointheoriginaldata
(Table4.4),thisislikelyafunctionofthesmallsamplesizeandsoprevalenceratesofthoseaged
80orolderhavebeenassumedthesameasthoseaged75-79years.The results of sensitivity
analysis of maintaining the incidence and prevalence of OhT for those aged 80 or over at
zero are presented in Chapter 9, Section 9.1.2.
Basedontheprevalenceofglaucomausingthesmoothedrates,theproportionofpeoplewithin
eachdiseasestagebyageisshowninTable4.7.
Economic impact of primary open angle glaucoma Commercial-in-Confidence
26
FIGURE 4-2: ORIGINAL PREVALENCE RATES
0-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85-89 90-94 95+
0%
2%
4%
6%
8%
10%
12%
14%
16%
18%
20%
EDS
Mild
Moderate
Severe
FIGURE 4-3: SMOOTHED PREVALENCE RATES (MOVING AVERAGE ACROSS THREE AGE GROUPS)
0-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85-89 90-94 95+
0%
5%
10%
15%
20%
25%
30%
35%
40%
EDS
Mild
Moderate
Severe
Second, raw OHT prevalence estimates (based on a special data request from the MVIP
database) were then run through DISMOD II (assuming no remission) and the resulting total
prevalence numbers formed the denominator for the progression rate in step three.
A progression rate from OHT to glaucoma was calculated by dividing half the number of
incident cases of glaucoma by total prevalence of OHT. This was justified by findings from the
Early Manifest Glaucoma Trial where 52% of glaucoma cases identified through population
screening had an IOP <21mmHg (Grodum et al, 2002). This resulted in a progression rate of
32
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Centre for Eye Research Australia
4. Epidemiology

TABLE 4.6: INCIDENCE AND PREVALENCE Of OCULAR hYPERTENSION (% Of AGE GROUP)
Prevalence - Original Incidence - DISMOD II Prevalence - DISMOD II
Age Males females Males females Males females
0-39 0.00 0.00 0.00 0.00 0.00 0.00
40-44 0.13 0.13 0.02 0.02 0.08 0.08
45-49 0.13 0.13 0.03 0.03 0.15 0.15
50-54 0.31 0.31 0.05 0.05 0.23 0.23
55-59 0.31 0.31 0.08 0.08 0.30 0.30
60-64 0.37 0.37 0.11 0.11 0.35 0.35
65-69 0.37 0.37 0.13 0.13 0.39 0.39
70-74 0.49 0.49 0.14 0.14 0.44 0.44
75-79 0.49 0.49 0.15 0.15 0.49 0.49
80-84 0.49 0.49 0.15 0.15 0.49 0.49
85-89 0.49 0.49 0.15 0.15 0.49 0.49
90+ 0.49 0.49 0.15 0.15 0.49 0.49
Source:AccessEconomicsandMVIP
TABLE 4.7: PROPORTION Of PEOPLE WITh GLAUCOMA BY AGE AND SEVERITY (%),
SMOOThED (MOVING AVERAGE ACROSS ThREE AGE GROUPS)
EDS Mild Moderate Severe
0-39 0.0 0.0 0.0 0.0
40-44 100.0 0.0 0.0 0.0
45-49 100.0 0.0 0.0 0.0
50-54 100.0 0.0 0.0 0.0
55-59 100.0 0.0 0.0 0.0
60-64 95.1 0.2 1.7 2.9
65-69 94.3 0.4 2.8 2.6
70-74 92.5 0.5 3.7 3.3
75-79 88.6 1.2 8.4 1.8
80-84 84.4 1.7 11.5 2.5
85-89 78.0 2.2 15.1 4.8
90+ 70.6 1.1 7.7 20.6
Centre for Eye Research Australia
33 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
4
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34
Tunne l Vi s i on
Centre for Eye Research Australia
Current treatment regimens centre on the only known treatable risk factor for glaucoma
- intraocular pressure (IOP). Management is directed at establishing and maintaining targets
for reducing IOP. No level of IOP is safe for every patient. In general, the initial target aims to
achieve a 20-50% reduction from the initial pressure at which damage occurred.
Patients with a lower than average risk of glaucoma (<5%) could be observed and monitored
without treatment. For those patients who are at moderate risk of glaucoma (5% to 15%),
a well-informed patient can decide with his or her physician whether to treat or not.
In patients with a higher than average risk (>15%), treatment for all should be considered
(Weinreb et al, 2004).
Clinicians attempt to achieve IOP reductions and control glaucoma by stepping patients through
the following course of treatment:
1) Medication;
2) laser therapy (ALT or Selective Laser Trabeculoplasty (SLT) and medication combined;
and nally
3) surgery.
The treatment pattern in most cases is the same regardless of the stage at which the disease
is diagnosed - that is, patients presenting with both early stage disease and severe disease
commence treatment with medication. Occasionally, laser (if compliance is likely to be poor)
or surgery (if medical therapy is likely to fail or not be tolerated) are used as rst line therapy.
The side effects of treatment are discussed later in Section 5.6.
5.1: MEDICATION
Medication is the rst stage of treatment, usually in a topical form (eye drops), but an oral form
also exists. A range of medications are available for the reduction of IOP, summarised in Table
5.1. Prostaglandin analogues and beta ()-adrenergic antagonists are the most frequently used,
with topical prostaglandins now the drug of choice in Australia - Lumigan (bimatoprost), Xalatan
(latanoprost), Travatan (travoprost). The proportions of medication types used have shifted over
time, particularly since the introduction of prostaglandin analogues in 1997 (Figure 5.1). Based
on MVIP data, Weih et al (1998) found that the most common glaucoma medications used were
()-adrenergic antagonists (63%), followed by sympathomimetics (18%) and cholinergic agents
(16%). The authors also noted the shift to ()-adrenergic antagonists and away from the use of
pilocarpine over the previous 20 years.
Medications reduce the amount of aqueous humour being produced and/or increase the outow
of aqueous humour from the eye. This can be via the conventional outow pathway through
the trabecular meshwork or by the non-conventional outow pathway (uveo-scleral outow
pathway). Some medications do both.
A topical medication can enter the blood supply through the naso-lacrimal drainage system
leading to systemic side-effects (ie. side effects in the rest of the body as well as the eye).
Systemic side-effects can be reduced substantially with the use of punctal occlusion and gentle
eye lid closure for more than two minutes. Side effects are discussed in Section 5.6.
5. Treatment
Current treatment
regimens centre
on the only known
treatable risk factor
for glaucoma -
intraocular pressure
(IOP).
35 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
Main heading to go here
TABLE 5.1: IOP LOWERING MEDICATIONS
Medication Features
Prostaglandin analogues (prostamides) Improve the ow of aqueous humour out of the eye through
the non-conventional (uveo-scleral) outow pathway.
First-line treatment. Once daily application. Effective IOP
reduction (bimatoprost, latanoprost, travoprost)
adrenergic blockers Reduces the production of aqueous humour (betaxolol,
carteolol, levobunolol, metipranolol, timolol).
Alpha () 2 adrenergic agonists Reduce secretion of aqueous humour, and increase aqueous
outow. Less effective in reducing IOP than prostaglandin
analogues (apraclonidine, brimonidine).
Carbonic anhydrase inhibitors Reduce aqueous secretion, used two to four times a day
(dorzolamide and brinzolamide - topical - acetazolamide
and methazolamide - oral).
Topical forms are not as effective as oral forms.
Cholinergic agonists Increase aqueous outow through the conventional outow
pathway, used up to four times daily (pilocarpine, carbachol).
Source: Weinreb and Khaw (2004:1716).
FIGURE 5.1: GLAUCOMA MEDICATION DISPENSED BY YEAR AND TYPE OF SCRIPT
(% OF TOTAL SCRIPTS)
Source: Australian Statistics on Medicine 1997, 1998, 1999-2000, 2001-2002, 2003.
If a medication fails to reduce IOP, it is generally replaced with an alternative agent or combined
with other agents until effective IOP control is established. Some recent studies
10
from the
literature show the number of medications taken in combination (Table 5.3).
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
1997 1998 1999 2000 2001 2002 2003
%
t
o
t
a
l
s
c
r
i
p
t
s
Other Anti Glaucoma
Preparations
Carbonic Anhyrase
Inhibitors
Cholinergic Agonists
2 Adrenergic Agonists
Beta Blocking Agents
Prostaglandin
Analogues
5. Treatment
10
Recent studies are preferred because medication efcacy has been improving over time.
36
Tunne l Vi s i on
Centre for Eye Research Australia
Ingeneral,mostpatientsaretakingtwoormoremedicationsbythetimetheyareconsidered
inneedoflasertreatmentorsurgery.Formodelling,thetotalcostsofmedicationsusedwere
dividedbythenumberofpeopleaffected(thisisexplainedinsection6.3.2).Theproportionof
eachmedicationtypedispensedwastakenintoaccountinthecalculationfortotalmedication
costs,withsimilarproportionsofmedicationsreportedbystateandterritory.
TABLE 5.2: PROPORTION Of EACh DRUG CLASS BY STATE, 2005
Prostaglandin b-blocker Carbonic a2 Cholinergic
Anhydrase Adrenergic Agonist
Inhibitor Agent
NSW 51.2 26.2 12.4 7.2 3.0
VIC 53.6 24.2 12.5 7.5 2.3
QLD 55.4 26.4 10.4 4.6 3.3
SA 54.2 28.9 8.5 5.8 2.6
WA 52.9 29.0 10.2 5.9 2.0
TAS 54.2 29.5 9.5 5.2 1.8
ACT 56.2 22.6 14.3 4.4 2.4
NT 61.8 19.6 11.3 5.5 1.7
Source:PBSItemdatabase.

5. Treatment
Centre for Eye Research Australia
37 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
5. Treatment
TABLE 5.3: NUMBER Of MEDICATIONS TAKEN IN COMBINATION
Source Number medications in combination
OHTS(Kassetal,2002) SeeBox4foradescriptionoftheOHTS.At60months,inthe
medicationgroup,39.7%ofparticipantswerereceivingtwoor
moremedicationsand9.3%werereceivingthreeormore.
WeinandandAlthen(2006) Nonrandomisedprospectivenon-comparativeclinicalstudyof
52eyesof52patientsoftheeffectofSLTasanadjunctivetreat
mentoneyeswithadvancedglaucomatousdamage.Patients
wereincludediftheyhaduncontrolledIOP(20mmHg)onmaxi
mumtolerablemedicaltherapy,orhadfailedpreviousALT.
Patientshadalonghistoryofglaucomatreatmentandweresent
forfurthertreatmenttothehospitalandsomaybeconsidered
tohaveglaucomathatismorediffculttocontrol.Theaverage
numberofhypotensivemedicationstakenincombinationprior
totreatmentwas2.5.
Damjietal,(2006)(a) InCanada,176eyesof152patientswereincludedina
randomisedclinicaltrialcomparingALTandSLTintermsoftheir
abilitytolowerIOPinpatientswithOAG.Patientsweregiven
laseriftheyhaduncontrolledIOP(16mmHg),wereon
maximummedicaltherapyorhadfailedprevious180/360ALT
(>6monthspreviously),wereover18andhadtwosightedeyes.
PatientswereexcludediftheyhadadvancedVFdefectwithin
10degreesoffxation,orhadpreviousglaucomasurgery.
Themeannumberofmedicationspretreatmentwas2.4for
ALTpatientsand2.6forSLTpatients.
Fontanaetal,(2006)(a) 292eyesand225patientswereincludedinaretrospective
cohortstudyofphakicpatientswithOAGwhounderwentinitial
trabeculectomywithadjunctiveMitomycinC(MMC)between
August1997andDecember2003.Eyesthathadundergone
previoussurgeryforcataractorglaucomawereexcluded.
97%ofeyeswerereceivingmedicaltreatmentbeforesurgery
withameanof2.7medications(SD1.0).
Ehrnroothetal,(2002)(a) InFinland,aretrospectiveevaluationofpatientsundergoing
trabeculectomywithoutantimetaboliteswasconducted.
IndicationsfortrabeculectomywereuncontrolledIOPdespite
maximaltoleratedmedicationanddiseaseprogression.Priorto
surgery,POAGpatientshadbeenonglaucomamedicationfora
mean(SD)of7.8(5.6)years.Around2%ofpatientswereon
zeromedication,12-15%ononemedication,55-64%ontwo
medications,20-29%onthreemedications.Around55%were
onoralmedications.
(a)Theremaybeselectionbiasinthesestudiesandthereforeahigherrateofprescribing.
5.1.1: COMPLIANCE AND PERSISTENCE WITh MEDICATIONS
Thedefnitionsofadherence,complianceandpersistenceinthissectionaredrawnfromthe
journalarticlesthemselves.Defnitionsandmethodsofmeasurementdifferacrossstudies.
Adequate treatment of glaucoma and preservation of vision requires adherence to therapy
(Schwartz,2005;Chen,2003),althoughtheexactrelationshipbetweencomplianceand

38
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Centre for Eye Research Australia
progressionofdiseasehasnotbeenquantifed(Olthoffetal,2005).Studiesindicate relatively
poor adherence to therapy in one-third or more of patients,dependingonthemedications
used(AAO,2005:13).
Nordstrometal,(2005)calculatedthedurationofcontinuoustreatmentwiththeinitially
prescribedmedication(defnedinthearticleaspersistence)andtheprevalenceofuseofthe
initialmedicationatvarioustimepoints(defnedinthearticleasadherence)fromhealth
insuranceclaimsdata.Claimsfrom3,623peoplewithnewlydiagnosedglaucomaand
from1,677glaucomasuspectswereexamined.Fourdrugclasseswereincluded:
beta-blockers,alpha-agonists,carbonicanhydraseinhibitors,andprostaglandinanalogs.
Nearlyhalfofthosewhohadflledaglaucomaprescriptiondiscontinuedalltopical
hypotensivetherapywithinsixmonths,and37%hadreflledtheirinitialmedicationat3
yearsafterthefrstdispensing.Prostaglandinswereassociatedwithbetterpersistenceand
betteradherencethanotherdrugs.Patientswithdiagnosedglaucomaweremorelikelyto
adheretotreatmentthanglaucomasuspects.
Schwartz(2005)conductedaliteraturereviewofresearchpublishedbetween1980and
October2004oncomplianceandpersistencewithtreatmentbypatientswithPOAGor
OHT.Compliancewasdefnedastheextenttowhichpatientsbehaviourscorresponded
withprovidersrecommendations.Schwartz(2005)foundthatnon-complianceratesof
25%werecommonlyreported.Usingelectronicmonitoring(themostaccuratemethodof
estimatingpatientcompliance),non-complianceratesrangedfrom14%to24%.Persistence
over12months(thetotaltimeontherapy)wasaround25%(rangingfrom20%to64%).
Olthoffetal,(2005)conductedaliteraturereviewofarticlespublishedfrom1970to
February2004oncompliancewithglaucomamedications.(POAGaswellasothertypes
ofglaucomawereincluded.)Compliancewasdefnedasthedegreeofcorrespondence
betweentheprescribedtreatmentregimeandthepatientsactualdosinghistory.The
proportionofpatientswhodeviatedfromtheirprescribedmedicationregimenrangedfrom
5%to80%(thefgureof5%camefromastudyonPOAGpatients).30%ofpatientsfor
whomtimololwasprescribeddeviatedfromtheirtreatmentregimen.
Tsai(2006)undertookaliteraturereviewofarticlespublishedonMedlineduringthe18
monthstoOctober2005andfoundthatnon-adherence(extentofdisagreementbetween
theprescribedmedicalregimenandactualpatientpractice)tomedicinalregimensin
patientswithglaucomavariedfrom24%to59%.
Reardonetal,(2004)examinedpatientpersistenceusingrecordsfromamanagedcare
databaseintheUS.PatientshadinitiatedmonotherapybetweenJuly1996andJune2002
withbetaxolol,bimatoprost,brimonidine,dorzolamide,latanoprost,timolol,ortravoprost.
Thenumberofpatientsincludedintheanalysiswas28,741.Discontinuationwasdefned
asnofurtherindexdrug(monotherapydrug)refll90days(ifdispensedonebottle)or180
days(ifdispensedtwobottles)afterthelastprescriptionfll.Persistencewasdefnedasthe
numberofdaysfromdispensedatetodiscontinuationdateorchangeofmedicationdate
(whicheverisearlier).Latanoprostwasthereferencegroupagainstwhichdiscontinuation
dateswerecompared.At12months,33%ofpatientswerepersistingwithlatanoprost
(hadnotdiscontinued);and19%ofthosetreatedwithotherocularhypotensiveshad
notdiscontinued.Thedifferencebetweenlatanoprostandotheragentswassignifcant
(p<0.001).Inthepopulation(28,741patientsonmonotherapy),thethreemostfrequently
prescribeddrugsweretimolol(43%),latanoprost(33%)andbrimonidine(18%).Relatively
fewpatientswereprescribedeithertravoprostorbimatoprost(1%ofpatientsforeach).
5. Treatment
Ongoing adherence
with daily glaucoma
drops is a major
problem.
Centre for Eye Research Australia
39 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
5. Treatment
Meta-analysisisnotusefulinsynthesisingtheresultsofthesestudiesbecauseofthedifferences
indefnitionsandmethodsofmeasurement.However,compliance rates of 75% seem a
reasonable assumption, with persistence rates of 33% for latanoprost and 19% for other
medications at 12 months(basedonReardonetal,2004).Themedicationcostestimates
usedinthemodellingarecalculatedbasedonthecostsofdispensedmedicationsforPOAGin
Australia,andsoimplicitlyincludepersistence.
5.2: LASLk 1kLA1MLN1
ThosewhoseIOPisnotcontrolledonmedicationareconsideredforlasertherapy.Twotypesof
lasertherapyareavailable,forthereductionofIOP,butvaryinusagedependingonthestatein
whichglaucomahasprogressed.
Lasertrabeculoplastyisthemainformoftreatment.
LaserdiodecyclophotocoagulationisrarelyusedinPOAGandnotthereforeincludedin
modelling.
LASER TRABECULOPLASTY
Lasertrabeculoplastyaimsto improve outfow through the trabecular meshwork. Itisusually
performedundertopicalanesthesia.Therearetwotypesoftrabeculoplasty.Argon Laser
Trabeculoplasty (ALT)wasdevelopedseveraldecadesago.Itwasfollowedmorerecently
bythedevelopmentofSelective Laser Trabeculoplasty (SLT). Whilethereissomeevidence
thattherearefewersideeffectswithSLT(LatinaanddeLeon2005),thisremainsunprovenin
arandomisedclinicaltrialsetting.Forthepurposesofthisstudy,theeffcacyofALTandSLT
areconsideredthesame.StudieshaveshownequivalencyofSLTtoALTinpatientsinwhom
maximalmedicaltherapyhasbeenunsuccessful(McIlraithetal,2006,Juzychetal,2004and
Damjietal,2006).
Thelaseriseitherappliedtoallofthetrabecularmeshworkatonce(360degrees)ortojusthalf
(180degrees).Thereisnoconsensusaboutwhichapproachispreferable,butwhere180degree
laserisundertakenfrstandglaucomaremainsuncontrolled,afurther180degreetreatmentwill
beconductedonthepreviouslyuntreatedsegmentofthetrabecularmeshwork.
Thepressureloweringeffectoflaserdiminishesovertime(Feldmanetal,1991).Repeatlaser
(anyALTofthetrabecularmeshworkafteracomplete360degreeALT(Feldmanetal,1991))
iscontroversial.RepeatALThasamarkedlyreducedeffectcomparedwithinitiallaser
11
andis
associatedwithanincreaseintheriskofanadverseriseinIOP.
DatafromtheMedicareBeneftsSchedule(MBS)forlasertrabeculoplastyarepresentedin
Figure5.2.ThedataareforMBSitemnumber42782(defnedaseachtreatmenttooneeyetoa
maximumoffourtreatmentstothateyeinatwoyearsperiod)
12
.TheMBSfeeforitemnumber
42782fromthe1November2006ScheduleisA$398.65.
11
Forexample,Feldmanetal,(1991)concludedthatrepeatALTwasnotgenerallyeffectiveforthelongtermcontrolof
OAG.Intheirstudy,repeatALTwassuccessfulin21%ofeyesatoneyear,and5%ofeyesat48months.Richteretal,
(1987)foundthatIOPcontrolwassuccessfulin33%ofeyesoneyearafterrepeatALTandinonly14%ofeyesafter1.75
years.Bothstudiesdefnedsuccessasa3mmHgorgreaterdecreaseinIOPtolessthan22mmHgandnofurthersurgical
intervention.
12
MBSitemnumber42783(Lasertrabeculoplastyeachtreatmentto1eyewhereitcanbedemonstratedthata5thor
subsequenttreatmenttothateye(includinganytreatmentstowhichitem42782applies)isindicatedina2yearperiod)
isextremelyrarelyusedoneprocedurerecordedagainstthisitemnumberin2002,threeproceduresrecordedin2003
andnegativeoneprocedurein2005.Otherwisezeroproceduresfortherestoftheperiodbetween1994and2006.
Laser trabeculoplasty
aims to improve
outfow through the
trabecular meshwork.
40
Tunne l Vi s i on
Centre for Eye Research Australia
TheMedicaredatainFigure5.2includeonlyprocedurescoveredbyMedicareie.theyexclude
proceduresundertakenonpublicpatients(bothadmittedandnon-admitted)inpublichospitals
(fundedbythehospital)andproceduresoncompensablepatients(forexample,fundedby
workerscompensationorganisations).
13
However,ingeneral,trabeculoplastiesareundertaken
atadoctorspracticeandadmittedpatienthospitalproceduresrepresentanexception.Hence,
forthemodelling,theMedicaredataareassumedtoadequatelyrepresentthenumberof
trabeculoplastyproceduresundertakeninAustralia.
ThenumberofMBSproceduresfellfrom16,809in1996,to6,201in2003,beforeincreasing
againto11,113in2006.Thisprobablyrefectstosomeextentgreateruseofprostaglandin
analogueswhichreplacedordelayedtrabeculoplastyprocedures.Itmayalsorefectthe
increaseduseofSLToverALT.
Itisestimatedthathalfthepeoplethatreceiveatrabeculoplastyprocedurehavetwo180
degreetreatmentswhiletheremaininghalfreceiveone(personalcommunication,Professor
JonathanCrowston15thMay2007).Thecostsoftrabeculoplastyhavebeenadjustedupwards
by1.5inthemodelaccordingly(seeSection6.3.2).
fIGURE 5.2: MBS TRABECULOPLASTY PROCEDURES, 1994-2005
Source:MedicareAustraliastatistics,MBSitemnumber42782(Lasertrabeculoplasty-eachtreatmentto1eye,
toamaximumof4treatmentstothateyeina2yearperiod).
13
TheAustralianHealthCareAgreementsspecifythataneligiblepatientpresentingatapublichospitaloutpatient
departmentwillbetreatedfreeofchargeasapublicpatientunless:(a)thereisathirdpartypaymentarrangementwith
thehospitalorQueenslandtopayforsuchservices;or(b)thepatienthasbeenreferredtoanamedmedicalspecialist
whoisexercisingarightofprivatepracticeandthepatientchoosestobetreatedasaprivatepatient.AustralianHealth
CareAgreementbetweentheCommonwealthofAustraliaandtheStateofQueensland,2003-08,http://www.health.qld.
gov.au/publications/aust_hlth_care_agreement/Queensland.pdfaccessed7May2007.
5. Treatment
0
2,000
4,000
6,000
8,000
10,000
12,000
14,000
16,000
18,000
1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
Year
N
u
m
b
e
r

o
f

p
r
o
c
e
d
u
r
e
s
Centre for Eye Research Australia
41 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
LASER DIODE CYCLOPhOTOCOAGULATION
Cyclodiodelaserlightisdirectedtopassthroughthesurfaceoftheeyeandbehindtheiristo
affecttheciliarybodyinorderto reduce the production of aqueous humourandtherefore
decreasetheIOPwithintheeye.Thistechniqueisusedforrefractorycasesthatdontrespond
toconventionaltreatment.Notmanyoftheseproceduresareundertakeneachyear.Forthe
fnancialyears2004-05and2005-06,MedicareAustraliadatasuggestthat,respectively,137
and145cyclodestructiveproceduresforintractableglaucomawereperformed(itemnumbers
42770and42771).TheseproceduresarerarelyusedforPOAGandsonotincludedinthemodel.
5.3: CONVLN1IONAL SUkGLkY {1kA8LCULLC1OMY)
If medical and laser therapies fail, surgery is performed. Trabeculectomyisperformedunder
localorgeneralanaesthesiaandcreatesanalternativepathwayfortheoutfowofaqueous
humour.Atinyportionofthetrabecularmeshworkorsurroundingtissueisremoved,anda
smallfapinsertedtoproduceapassagewayfromtheanteriorchamberoftheeyetoapocket
betweentheconjunctivaandsclera.Asmallblister(flteringbleb)isformedundertheupperlid,
calledatrabeculectomybleb.
fIGURE 5.3: TRABECULECTOMY
14

Insomecases,scartissuedevelopsandpreventsthe
operationfromworking.Incasesthoughttobeat
increasedriskofscarformation,thesurgeonmaygive
thepatientantifbrotics-drugstoinhibitscaringsuchas
5-fuoracil or MMC to reduce scarring andimprovethe
outcomesofsurgery.
Aswithtrabeculoplasty,itisdiffculttoestimatethe
totalnumberofproceduresundertakenforPOAG
eachyear.Medicaredatadonotincludeprocedures
undertakenonpublicpatientsinpublichospitals
(admittedornon-admitted).Hospitaldataincludebothpublicandprivateadmittedpatients
arethereforethemorereliableinthecaseoftrabeculectomy.
ThetotalnumberoftrabeculectomyproceduresforpeoplewithPOAGduringtheperiodof
200405hasbeensourcedfromtheAustralianInstituteofHealthandWelfare(AIHW)asa
specialdatarequest.
ThetotalnumberofproceduresforICD-10-codesH401andH409(whichrelatetopatients
withPOAGandUnspecifedGlaucoma)havebeenincludedinthemodelling.Fortheperiod
200405,1,683trabeculectomyprocedureswereperformed.Ofthese,583procedureswere
performedinapublichospitalwhile1,060wereperformedinaprivatehospital.
14
InternationalGlaucomaAssociationwebsite,accessed10thMay2007
http://www.glaucoma-association.com/nqcontent.cfm?a_id=382&=fromcfc&tt=article&lang=en&site_id=176
5. Treatment
42
Tunne l Vi s i on
Centre for Eye Research Australia
Somepatientshavemorethanonetrabeculectomy.Itisnotpossibletodeterminetheextent
ofrepeatsurgeryfromtheAIHWdata.TheMBSdatasuggestthataround1,435trabeculectomy
procedureswereundertakenin2004-05,with212repeatoperationsinthesameyear(Table
5.4)andwhile1302flteringoperationswereundertakenin2005-06,therewerealso230
repeatoperations.Repeattrabeculectomieswerealsohighercost(Table5.4).Thecostsof
trabeculectomyinthemodelhavebeenadjustedupwardsaccordinglybasedonthesefguresby
summingthetwoyearstofndthatrepeatsmadeup16%offlteringoperationsandcost25%
morewhichsuggeststhecostoftrabeculectomiesneedstobeadjustedupwardsbyaround20%
(seeSection6.3.2).
TABLE 5.4: TRABECULECTOMY MBS SERVICES PROCESSED BY JURISDICTION BY YEAR
(Anaes.)Meanstheserviceattractsananaesthetic.(Assist.)Medicarebeneftsarepayableunderitem51300for
assistancerenderedatanyoperationidentifedbythewordAssist.forwhichthefeedoesnotexceedthefeethreshold
specifedintheitemdescriptor,orataseriesorcombinationofoperationsidentifedbythewordAssist.forwhichthe
aggregateSchedulefeethresholdspecifedintheitemdescriptorhasnotbeenexceeded.
Source:MedicareAustraliastatistics,FeesbasedonMBS1November2006.
AtimeserieswasnotavailablefromtheAIHW,butMedicaredatasuggestthatthenumber
ofinitialMBStrabeculectomyprocedures(item42746)hasfallenfrom3,996in1996to
1,246in2006(Figure5.4).Thisprobablyresultsfromthefowoneffectoftheintroduction
ofprostaglandinanalogueeyedrops(discussedearlier),whichhaveimprovedIOPcontroland
delayedtheneedfordownstreamtreatments.
fIGURE 5.4: MBS TOTAL Of TRABECULECTOMY PROCEDURES, 1994-2005
Source:MedicareAustraliastatistics,MBSitemnos.42746(Filteringoperationforglaucoma)and42749
(Filteringoperationforglaucoma,wherepreviousflteringoperationhasbeenperformed).
Decreasing rates of
surgery refect better
medical treatment.
Economic impact of primary open angle glaucoma Commercial-in-Confidence
38
trabeculectomy procedures were undertaken in 2004-05, with 212 repeat operations in the
same year (Table 5-4) and while 1302 filtering operations were undertaken in 2005-06, there
were also 230 repeat operations. Repeat trabeculectomies were also higher cost (Table 5-4).
The costs of trabeculectomy in the model have been adjusted upwards accordingly based on
these figures by summing the two years to find that repeats made up 16% of filtering
operations and cost 25% more which suggests the cost of trabeculectomies needs to be
adjusted upwards by around 20% (see Section 6.3.2).
TABLE 5-4: TRABECULECTOMY MBS SERVICES PROCESSED BY JURISDICTION BY YEAR
Item No. Description Fee ($) Year NSW VIC QLD SA WA Tas ACT NT Total
2004-05 559 337 234 110 118 57 20 0 1,435
2005-06 513 311 232 81 117 36 9 3 1,302
2004-05 77 62 36 17 10 4 5 1 212
2005-06 77 62 49 17 17 6 1 1 230
42749
Filtering operation for glaucoma, where
previous filtering operation has been
performed (Anaes.) (Assist.)
1056.55
42746
Filtering operation for glaucoma (Anaes.)
(Assist.)
843.85
(Anaes.) Means the service attracts an anaesthetic. (Assist.) Medicare benefits are payable under item 51300 for
assistance rendered at any operation identified by the word "Assist." for which the fee does not exceed the fee
threshold specified in the item descriptor, or at a series or combination of operations identified by the word "Assist."
for which the aggregate Schedule fee threshold specified in the item descriptor has not been exceeded.
Source: Medicare Australia statistics, Fees based on MBS 1 November 2006.
A time series was not available from the AIHW, but Medicare data suggest that the number of
initial MBS trabeculectomy procedures (item 42746) has fallen from 3,996 in 1996 to 1,246 in
2006 (Figure 5-4). This probably results from the flow on effect of the introduction of
prostaglandin analogue eye drops (discussed earlier), which have improved IOP control and
delayed the need for downstream treatments.
FIGURE 5-4: MBS TOTAL OF TRABECULECTOMY PROCEDURES, 1994-2005
0
500
1,000
1,500
2,000
2,500
3,000
3,500
4,000
4,500
1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
Year
N
u
m
b
e
r
o
f
p
r
o
c
e
d
u
r
e
s
42746 42749
Source: Medicare Australia statistics, MBS item nos. 42746 (Filtering operation for glaucoma) and 42749 (Filtering
operation for glaucoma, where previous filtering operation has been performed).
Economic impact of primary open angle glaucoma Commercial-in-Confidence
38
trabeculectomy procedures were undertaken in 2004-05, with 212 repeat operations in the
same year (Table 5-4) and while 1302 filtering operations were undertaken in 2005-06, there
were also 230 repeat operations. Repeat trabeculectomies were also higher cost (Table 5-4).
The costs of trabeculectomy in the model have been adjusted upwards accordingly based on
these figures by summing the two years to find that repeats made up 16% of filtering
operations and cost 25% more which suggests the cost of trabeculectomies needs to be
adjusted upwards by around 20% (see Section 6.3.2).
TABLE 5-4: TRABECULECTOMY MBS SERVICES PROCESSED BY JURISDICTION BY YEAR
Item No. Description Fee ($) Year NSW VIC QLD SA WA Tas ACT NT Total
2004-05 559 337 234 110 118 57 20 0 1,435
2005-06 513 311 232 81 117 36 9 3 1,302
2004-05 77 62 36 17 10 4 5 1 212
2005-06 77 62 49 17 17 6 1 1 230
42749
Filtering operation for glaucoma, where
previous filtering operation has been
performed (Anaes.) (Assist.)
1056.55
42746
Filtering operation for glaucoma (Anaes.)
(Assist.)
843.85
(Anaes.) Means the service attracts an anaesthetic. (Assist.) Medicare benefits are payable under item 51300 for
assistance rendered at any operation identified by the word "Assist." for which the fee does not exceed the fee
threshold specified in the item descriptor, or at a series or combination of operations identified by the word "Assist."
for which the aggregate Schedule fee threshold specified in the item descriptor has not been exceeded.
Source: Medicare Australia statistics, Fees based on MBS 1 November 2006.
A time series was not available from the AIHW, but Medicare data suggest that the number of
initial MBS trabeculectomy procedures (item 42746) has fallen from 3,996 in 1996 to 1,246 in
2006 (Figure 5-4). This probably results from the flow on effect of the introduction of
prostaglandin analogue eye drops (discussed earlier), which have improved IOP control and
delayed the need for downstream treatments.
FIGURE 5-4: MBS TOTAL OF TRABECULECTOMY PROCEDURES, 1994-2005
0
500
1,000
1,500
2,000
2,500
3,000
3,500
4,000
4,500
1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
Year
N
u
m
b
e
r
o
f
p
r
o
c
e
d
u
r
e
s
42746 42749
Source: Medicare Australia statistics, MBS item nos. 42746 (Filtering operation for glaucoma) and 42749 (Filtering
operation for glaucoma, where previous filtering operation has been performed).
5. Treatment
Centre for Eye Research Australia
43 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
5. Treatment
DRAINAGE IMPLANTS
Inpatientsforwhomtrabeculectomyislikelytofailbecauseofinfammationorscarring,
adrainagedeviceisimplanted(calledaglaucomadrainagedevice)tocreateadrainagepathway.
Variousdevicesexist(eg.Moltenovalves).DrainageimplantsarerarelyusedinPOAG,butare
morecommonlyusedinsecondaryglaucoma.
DatafromtheAIHWhospitalmorbiditydatabasefor2004-05suggestthat136aqueous
shuntinsertion
15
procedureswererecordedforglaucoma.
Forthefnancialyears2004-05and2005-06,MedicareAustraliadatasuggestthat,
respectively,57and70Moltenovalveinsertionswereperformed(itemnumber42752).
TheseproceduresarerelativelyexpensivetheMBSfeeforthe1November2006was
$1,182.75.
Sincetheyarerelativelyrareinprimaryopenangleglaucomapatients,theseproceduresarenot
includedinthemodel.
5.4: kLVALLNCL LS1IMA1LS IOk LACH 1kLA1MLN1 GkOU
Asnotedearlier,oncediagnosedwithPOAG,patientsgenerallyfollowastandardtreatment
protocol.Theprotocolisindependentoftheseverityofthediseasestageatdiagnosis.Patients
usuallycommencewithmedicationswhethertheyhaveseverediseaseorearlystagedisease.
Initially,DismodIIwasusedtomodeltheprogressionfromonetreatmentphasetothenext,
byusingthetotalnumberofpeoplenewlydiagnosedwithPOAGin2005astheincidencerate
forthemedicationtreatmentphase,thetotalnumberoftrabeculoplastyproceduresasthe
indicatoroftreatmentfailureforthemedicationgroup,andthetotalnumberoftrabeculectomy
proceduresasanindicatoroftreatmentfailureforthetrabeculoplastygroup(theoverallRR
ofmortalityof1.18theweightedaverageRRofmortalityfromallprevalentseveritygroups
wasappliedinthemodellingforeachtreatmentphase).
Inthecaseoftrabeculoplasty,thetotalnumberofMBSproceduresneededtobescaleddown
torefectfrst-timeprocedures.Asnotedearlier,itisestimatedthathalfofthepeopleinthe
trabeculoplastytreatmentphasereceivetwo180degreetreatmentswhiletheotherhalfreceive
one.Thetotalnumberoftrabeculoplastyprocedureswasscaleddownby1.5accordingly.
DismodIIwasalsoinitiallyusedtomodeltheremainingtreatmentphases(Table5.5)toensure
thatthefowthrougheachphasewasinternallyvalidandrefectedthenumberofprocedures
occurringinpractice.
However,thesemodelledrateswerenotconsistentwiththeliteratureonfailureratesfor
lasertherapyandsurgery.Inparticular,anumberofstudiesoutlinedinTable5.7andTable5.8
suggestedfailureratesforlaserandsurgerywereoftheorderof50%(withfailuredefnedas
thepatientrequiringfurthertreatment).failure rates applied in the model are therefore:
50% per year for laser trabeculoplasty (consistent with Weinand and Althen 2006); and
50 % for trabeculectomy. While this is a very conservative estimate higher than
the literature sensitivity analysis shows that it makes little difference to the results.
Sensitivity analysis is presented in Section 9.3.3
15
ICD10AMcode42752.
44
Tunne l Vi s i on
Centre for Eye Research Australia
TABLE 5.5: INCIDENCE AND TREATMENT fAILURE RATE fOR EACh STAGE Of TREATMENT
fROM DISMOD II.
Age Group Incidence of Medication Medication Trabeculoplasty Trabeculectomy
(% of population in each failure rates (% of failure rates failure rates
age group) those on medication
40-44 0.02 4.3% 3.2% 2.0%
45-49 0.05 4.3% 3.2% 2.0%
50-54 0.07 4.3% 3.2% 2.0%
55-59 0.10 4.3% 3.2% 2.0%
60-64 0.12 4.3% 3.2% 2.0%
65-69 0.14 4.3% 3.2% 2.0%
70-74 0.17 4.3% 3.2% 2.0%
75-79 0.22 4.3% 3.2% 2.0%
80-84 0.26 4.3% 3.2% 2.0%
85-89 0.32 4.3% 3.2% 2.0%
90+ 0.35 4.3% 3.2% 2.0%
5.5: 1kLA1MLN1 LIIICACY
ForthereasonsoutlinedearlierinSection4.5,manyofthestudiesoftreatmenteffcacy
(ie.theimpactoftreatmentcomparedwithalternativesincludingnotreatment)arediffcultto
applytoacosteffectivenessstudybecauseprogressionisnotdefnedconsistentlyandbecause
ofthenatureoftheendpointsselected.Themajorclinicaltrialsoftreatmenteffcacyare
outlinedinBox4.
8ox 4: Ma|or c|inica| tria|s of g|aucoma treatment efficacy
TheOcular hypertension Treatment Study (OhTS) intheUSAexaminedpatientswho,
atentrytothetrial,hadOHT,butnoevidenceofglaucomatousdamage.Enrolmentended
in1996.1,636participantswererandomisedeithertoobservation,ortoreceivetreatment
withcommerciallyavailabletopicalhypotensivemedicationsusedsinglyorincombination.
TheaimoftreatmentwastoachieveatargetIOPof24mmHgorlessandaminimum
20%reductioninIOP.ProgressionwasdefnedaseitherthedevelopmentofaVFdefector
deteriorationintheopticdisc.
TheEuropean Glaucoma Prevention Study (EGPS) enrolled1,081patientsbetween1997
and1999inBelgium,Germany,ItalyandPortugal.ParticipantshadOHT,butnormalVF
andopticdisc.Patientswererandomisedtotreatmentwithdorzolamide(topicalcarbonic
anhydraseinhibitor)oraplacebo.Participantsandinvestigatorswerebothmasked.Theaim
wastoreduceIOP,buttheprotocoldidnotspecifyatargetIOPreduction.Endpointswere
changesinVFand/ortheopticdisc.
AtentryintheCollaborative Normal Tension Glaucoma Study (CNTGS),145patients
fromspecialtycentresintheUSAhadnormalIOP,butopticdiscabnormalitiesandVF
defects.Participantswererandomlyassignedtotreatmentornotreatment.Progression
wasbasedonachangeintheVForachangeintheopticnerveappearance.Inthetreatment
group,theaimwastoreduceeyepressureby30%in6monthsusingeyedrops,laserand/
orflteringsurgery.
5. Treatment
Centre for Eye Research Australia
45 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
5. Treatment
TheEarly Manifest Glaucoma Trial (EMGT)wasconductedinSweden,andincluded255
participantsscreenedbetween1992and1997.Atentry,patientswerenewlydiagnosed
withVFdefects,butwerepreviouslyuntreated.PatientswithadvancedVFdefectswere
excludedfromentry.Participantswererandomisedtoeither360olasertreatment(ALT)
plusbetaxololhydrochloride(topicalbetablocker)ornoinitialtreatment.Theaimwasto
evaluatetheeffectofimmediatetreatmentcomparedwithnoinitialtreatmentorlater
treatment.ProgressionwasbasedonnewVFdefectoropticdiscdeteriorationorboth.
TheCollaborative Initial Glaucoma Treatment Study (CIGTS)wasconductedinthe
USA.Enrolmenttookplacebetween1993and1997.607patientswithnewlydiagnosed
glaucoma,withlimitedornopriortreatment,IOPof20mmHgorgreaterandevidence
ofopticnervedamageand/orVFLinoneorbotheyeswereenrolled.Participantswere
randomisedtoinitialtrabeculectomy(withorwithout5-fuorouacil)ortopicalmedication
(topicalbeta-blocker,followedbyanalternatesingletopicaltherapeuticagent,dual
topicaltherapy,tripletopicaltherapy,analternatecombinationoftripletopicaltherapy
andoptionaladditionaltopicalandororalmedications).Furthertreatment,ifconsidered
necessary,followedstandardtreatmentpatterns(variouscombinationsofALT,medications
andtrabeculectomy).ProgressionwasbasedonchangesinVF.
TheGlaucoma Laser Trial (GLT)andtheGlaucoma Laser Trial follow Up (GLTfU) Study
wereconductedintheUSA.TheGLT(271participants)endedin1989,butaproportionof
GLTpatients(203participants)werethenobservedaspartoftheGLTFUfrom1990to1993.
ParticipantsintheGLTwerenewlydiagnosedwithPOAGandhadanIOPofatleast22mm
Hgineacheyeplusoneof:aVFdefect,orcertainOHTandcuptodiscratiocharacteristics.
OneeyeofeachpatientwasrandomisedtoALTandtheothereyetotimolol.Endpoints
wereVFandIOP.
TheAdvanced Glaucoma Intervention Study (AGIS)conductedintheUSAfocusedon
thosewhosediseasewasnolongercontrolledbymedication.Between1988and1992,
591patientswereenrolled.Atentry,patientshadconsistentlyelevatedIOP,opticdiscrim
deteriorationandaVFdefectscorebasedontheAGISgradingsystemofbetween1and
16
16
.Patientsweregivenadifferentsequenceofinterventionsineacheyeinoneeye,
thesequencewasALT,trabeculectomy,trabeculectomy;intheothereye,thesequencewas
trabeculectomy,ALT,trabeculectomy.ThegoalwastoreduceIOPtolessthan18mmHg.
TheprimaryoutcomevariableintheAGISwastheaveragepercentofeyeswithadecrease
ofvision(eitherVForVA).
Otherstudiesfocussinginparticularontheeffcacyoflasertreatmentandtrabeculectomy
administeredtopatientsfollowingfailureofmaximumtolerablemedicationtocontrol
thediseasegenerallyfocusontheimpactoftreatmentonIOPandtheneedforadditional
intervention.VeryfewmeasuretheeffectoftreatmentonVF.Thestudieshavedifferent
endpointsanddefneprogressiondifferently.Somearenotbasedonintenttotreat.Some
examplesofstudiesoftheeffcacyoftrabeculoplastyareoutlinedinTable5.7andexamples
ofstudiesoftheeffcacyoftrabeculectomyareoutlinedinTable5.8.
16
AGISVFdefectscoresrangefrom0(nodefect)to20(advancedglaucoma).Iftheeyehasinsuffcientvisionfora
patienttocountfngersat30cm,theVFdefectscoreisrecordedas20.
46
Tunne l Vi s i on
Centre for Eye Research Australia
Inordertosynthesisetheimpactoftreatmentonprogression,Weinrebetal,(2004)usedthe
resultsfromtheOHTSandtheEMGTastheonlytrialswhichcomparedtreatmentwithno
treatment.Asnotedearlier,theEGPS(2005)resultswerenotavailableatthetimeWeinreb
etal,(2004)wasreleased.Inanycase,theEGPS(summarisedinBox4)facedcertaindesign
problemsandsoisnotusedherefortheimpactoftreatmentontheriskofdevelopingPOAG
17
.
Weinrebetal,(2004:464)combinedtheimpactoftreatmentonconversionratesfromOHTto
glaucomafromtheOHTSwithresultsfromtheEMGTontheimpactoftreatmentontheriskof
progressionofdisease.
TheOHTS(summarisedinBox4)foundthatafter60months,thosewhowerenot
receivingtreatmentweremorethantwiceaslikelytodevelopPOAGthanthoseontopical
medicationswhohadtheirIOPreducedby20%,ie.thecumulativeprobabilityofdeveloping
POAGwas4.4%inthemedicationgroupand9.5%intheobservationgroup(hazardratioof
0.4,witha95%CIof0.27to0.59).Thedifferenceinprogressionrateswas46%(4.4/9.5).
TheEMGT(summarisedinBox4)showedthatearlyinitialtreatmentwith360
o
ALTplus
betablockereyedropsdelayedprogressioncomparedwithnotreatment.Themediantime
toprogressionwas48monthsinthecontrolgroupand66monthsinthetreatmentgroup
(althoughtimetoprogressionvariedgreatly).At48months,49%ofcontrolshadprogressed
comparedwith30%inthetreatmentgroup(Heijletal,2002).Leskeetal,(2003)foundthat
after6years,53%ofpatientsprogressed.Inmultivariateregressionanalysis,progressionrisk
washalvedbytreatment(HR=0.5,witha95%CIof0.35to0.71).
Thus,Weinrebetal,(2004)estimatedthattreatment reduced the risk of progression from
OhT to blindness by 77%(ie.progressionratesintreatedpatientsare46%x50%=23%that
ofprogressionratesinuntreatedpatients).Progressionfromglaucomatoblindnessintreated
patientsisassumedtobe50%ofthatinuntreatedpatients.Ratesofprogressionintreated
patientsbasedonWeinrebetal,(2004)arepresentedinTable5.6.
TABLE 5.6: PROGRESSION RATES (CUMULATIVE PROBABILITY)
IN TREATED PATIENTS (15 YEAR PERIOD)
Start point Unilateral blindness Bilateral Blindness
OHT 0.3%to2.4%(Weinrebetal,2004) 0.7%(Hattenhaueretal,1998)
Glaucoma 20.25%(Hattenhaueretal,1998) 8.25%(Hattenhaueretal,1998)
17
IntheEGPS,therewasnostatisticallysignifcantdifferencebetweenmedicaltherapyandplaceboinreducingthe
incidenceofPOAG,althoughtheactivelytreatedarmhadameanIOPreductionrangingbetweenapproximately15%to
22%throughoutthe5yearsofthetrial.TheresultsaremostlyexplainedbyaclinicallysignifcantplaceboeffectonIOP
ofapproximately9%to19%,whichincreasedduringthestudy.
5. Treatment
Centre for Eye Research Australia
47 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
T
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o
n
.

K
a
p
l
a
n

M
e
i
e
r

s
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r
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l

a
n
a
l
y
s
i
s

r
e
v
e
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d

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n
e

y
e
a
r

s
u
c
c
e
s
s

r
a
t
e

o
f

6
0
%
,

t
w
o

y
e
a
r

s
u
c
c
e
s
s

r
a
t
e

o
f

5
3
%
,

t
h
r
e
e

y
e
a
r

s
u
c
c
e
s
s

r
a
t
e

o
f

4
4
%

a
n
d

f
o
u
r

y
e
a
r

s
u
c
c
e
s
s

r
a
t
e

o
f

4
4
%
.
T
h
e

p
r
o
p
o
r
t
i
o
n

o
f

e
y
e
s

t
h
a
t

a
c
h
i
e
v
e
d

a
t

l
e
a
s
t

2
0
%

l
o
w
e
r
i
n
g

o
f

I
O
P

o
u
t

t
o

o
n
e

y
e
a
r

w
a
s

s
i
m
i
l
a
r

b
e
t
w
e
e
n

t
h
e

t
w
o

g
r
o
u
p
s

(
5
9
.
7
%

S
L
T

(
n
=
4
3
)

a
n
d

6
0
.
3
%

A
L
T
(
n
=
4
8
)
)
.

A
t

o
n
e

y
e
a
r

a
f
t
e
r

t
r
e
a
t
m
e
n
t

8
2
%

o
f

e
y
e
s

i
n

t
h
e

S
L
T

g
r
o
u
p

w
e
r
e

m
a
i
n
t
a
i
n
e
d

o
n

t
h
e

s
a
m
e

n
u
m
b
e
r

o
f

m
e
d
i
c
a
t
i
o
n
s

a
n
d

1
8
%

h
a
d

a
d
d
e
d

o
n
e

m
e
d
i
c
a
t
i
o
n
.

I
n

t
h
e

A
L
T

g
r
o
u
p

6
9
%

o
f

e
y
e
s

r
e
m
a
i
n
e
d

o
n

t
h
e

s
a
m
e

n
u
m
b
e
r

o
f

m
e
d
i
c
a
t
i
o
n
s

a
n
d

2
9
%

r
e
q
u
i
r
e
d

o
n
e

a
d
d
i
t
i
o
n
a
l

m
e
d
i
c
a
t
i
o
n
.

I
n

t
h
e

A
L
T

g
r
o
u
p
,

p
e
r
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p
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e
r
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l

a
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t
e
r
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o
r

s
y
n
e
c
h
i
a
e

f
o
r
m
e
d

i
n

1
.
2
%

(
1
/
8
7
)
,

A
L
T

t
r
e
a
t
m
e
n
t

o
c
c
u
r
r
e
d

w
i
t
h
i
n

o
n
e

y
e
a
r

i
n

5
.
7
%

(
5
/
8
7
)

S
L
T

t
r
e
a
t
m
e
n
t

o
c
c
u
r
r
e
d

w
i
t
h
i
n

o
n
e

y
e
a
r

i
n

4
.
6
%

(
4
/
8
7
)

a
n
d

t
r
a
b
e
c
u
l
e
c
t
o
m
y

o
c
c
u
r
r
e
d

w
i
t
h
i
n

o
n
e

y
e
a
r

i
n

8
%

(
7
)

p
a
t
i
e
n
t
s
.

I
n

t
h
e

S
L
T

g
r
o
u
p

t
h
e

e
q
u
i
v
a
l
e
n
t

p
r
o
p
o
r
t
i
o
n
s

w
e
r
e
:

1
.
1
%
(
1
/
8
9
)
,

3
.
4
%
(
3
/
8
9
)

6
.
7
%
(
6
/
8
9
)

a
n
d

9
%
(
8
/
8
9
)
.

A
L
T

a
n
d

S
L
T

s
i
m
i
l
a
r
l
y

e
f
f
e
c
t
i
v
e

i
n

d
e
c
r
e
a
s
i
n
g

I
O
P

a
t

e
a
c
h

f
o
l
l
o
w
-
u
p

t
i
m
e

c
o
m
p
a
r
e
d

w
i
t
h

t
h
e

p
r
e
-
t
r
e
a
t
m
e
n
t

I
O
P
.

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L
T

s
u
c
c
e
s
s

r
a
t
e
s

a
t

o
n
e
,

t
h
r
e
e

a
n
d

f
v
e

y
e
a
r
s

w
e
r
e
:

6
8
%
,

4
6
%

a
n
d

3
2
%

b
y

c
r
i
t
e
r
i
o
n

(
1
)

a
n
d

5
8
%
,

3
8
%

a
n
d

3
1
%

b
y

c
r
i
t
e
r
i
o
n

(
2
)
.

E
q
u
i
v
a
l
e
n
t

A
L
T

s
u
c
c
e
s
s

r
a
t
e
s

w
e
r
e

5
4
%
,

3
0
%

a
n
d

3
1
%

b
y

c
r
i
t
e
r
i
o
n

(
1
)

a
n
d

4
6
%
,

2
3
%

a
n
d

1
3
%

b
y

c
r
i
t
e
r
i
o
n

(
2
)
.
48
Tunne l Vi s i on
Centre for Eye Research Australia
T
A
B
L
E

5
.
7
:


S
T
U
D
I
E
S

O
f

T
h
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f
f
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f

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o
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.
.

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p
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h

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e
f
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t
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p
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O
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h
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t

a
l
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(
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9
9
3
)
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t
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r

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q
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9
m
m
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g

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m
m
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g

b
e
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t
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l
T
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b
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f
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t
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t
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n

y
e
a
r
s

w
a
s

3
2
%

f
o
r

a
l
l

9
3

e
y
e
s
.

C
u
m
u
l
a
t
i
v
e

p
r
o
b
a
b
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l
i
t
y

o
f

s
u
c
c
e
s
s

w
a
s

7
7
%

a
f
t
e
r

o
n
e

y
e
a
r
,

4
0
%

a
f
t
e
r

f
v
e

y
e
a
r
s

a
n
d

3
2
%

a
f
t
e
r

t
e
n

y
e
a
r
s
.

T
h
e

h
i
g
h
e
s
t

p
r
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b
a
b
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l
i
t
y

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f

f
a
i
l
u
r
e

w
a
s

i
n

t
h
e

f
r
s
t

y
e
a
r

w
i
t
h

c
u
m
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l
a
t
i
v
e

f
a
i
l
u
r
e

r
a
t
e

o
f

2
3
%
.

I
n

s
u
b
s
e
q
u
e
n
t

y
e
a
r
s

t
h
e

p
r
o
b
a
b
i
l
i
t
y

o
f

f
a
i
l
u
r
e

w
a
s

a
p
p
r
o
x

5
%

t
o

9
%

p
e
r

y
e
a
r
.

L
i
f
e

t
a
b
l
e

a
n
a
l
y
s
i
s

o
f

t
h
e

6
0

e
y
e
s

w
i
t
h

P
O
A
G

d
i
s
c
l
o
s
e
d

s
i
m
i
l
a
r

p
r
o
b
a
b
i
l
i
t
y

o
f

r
e
m
a
i
n
i
n
g

s
u
c
c
e
s
s
f
u
l

u
p

t
o

t
e
n

y
e
a
r
s

o
f

3
1
%
.

A
g
e

o
r

p
r
e
v
i
o
u
s

I
O
P

d
i
d

n
o
t

s
i
g
n
i
f
c
a
n
t
l
y

a
f
f
e
c
t

s
u
c
c
e
s
s

r
a
t
e
s
.

P
r
o
b
a
b
i
l
i
t
y

s
u
c
c
e
s
s

g
i
v
e
n

s
u
r
v
i
v
a
l

f
o
r

o
n
e

y
e
a
r

w
a
s

6
4
%

a
f
t
e
r

f
v
e

y
e
a
r
s

a
n
d

4
2
%

a
f
t
e
r

t
e
n

y
e
a
r
s
.

I
f

p
a
t
i
e
n
t

w
a
s

s
u
c
c
e
s
s
f
u
l

a
t

f
v
e

y
e
a
r
s
,

p
r
o
b
a
b
i
l
i
t
y

o
f

r
e
m
a
i
n
i
n
g

s
u
c
c
e
s
s
f
u
l

a
t

t
e
n

y
e
a
r
s

w
a
s

6
5
%
.
S
p
a
e
t
h

a
n
d

B
a
e
z

(
1
9
9
2
)
R
e
t
r
o
s
p
e
c
t
i
v
e

r
e
c
o
r
d

r
e
v
i
e
w

o
f

1
0
9

e
y
e
s

o
f

7
8

p
a
t
i
e
n
t
s
.

A
L
T

w
a
s

e
m
p
l
o
y
e
d

a
s

s
u
b
s
t
i
t
u
t
e

f
o
r

t
r
a
b
e
c
u
l
e
c
t
o
m
y
.

E
i
t
h
e
r

1
8
0

d
e
g
r
e
e

o
r

3
6
0

d
e
g
r
e
e

t
r
e
a
t
m
e
n
t
s

w
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r
e

a
p
p
l
i
e
d
.
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L
T

w
a
s

c
o
n
s
i
d
e
r
e
d

s
u
c
c
e
s
s

w
h
e
n

n
o

f
l
t
r
a
t
i
o
n

s
u
r
g
e
r
y

w
a
s

r
e
q
u
i
r
e
d

o
r

f
a
i
l
u
r
e

w
h
e
n

s
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r
g
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r
y

w
a
s

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e
q
u
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r
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d
.
S
u
b
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e
q
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e
n
t

s
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r
g
e
r
y

b
e
c
a
m
e

n
e
c
e
s
s
a
r
y

i
n

3
2
%

o
f

a
l
l

e
y
e
s

w
i
t
h

o
n
e

y
e
a
r

o
f

A
L
T
.

B
y

f
v
e

y
e
a
r
s
,

6
5
%

o
f

a
l
l

e
y
e
s

h
a
d

f
a
i
l
e
d

(
i
e
.

3
5
%

e
y
e
s

s
t
i
l
l

c
o
n
s
i
d
e
r
e
d

s
u
c
c
e
s
s
f
u
l
)
.

F
o
r

e
y
e
s

w
i
t
h

P
O
A
G
,

1
9
.
3
%

o
f

e
y
e
s

f
a
i
l
e
d

(
8
0
%

s
u
c
c
e
s
s
)

a
f
t
e
r

o
n
e

y
e
a
r
,

a
n
d

5
6
.
7
%

h
a
d

f
a
i
l
e
d

b
y

y
e
a
r

f
v
e

(
i
e
.

s
u
c
c
e
s
s

r
a
t
e

a
t

f
v
e

y
e
a
r
s

o
f

4
3
.
3
%
)
.
Centre for Eye Research Australia
49 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
T
A
B
L
E

5
.
8
:


S
U
C
C
E
S
S

R
A
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f
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R

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R
A
B
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C
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C
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e

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p
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D
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f

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s
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d
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t

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l
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r
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.

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a
i
n

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y
:

F
a
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l
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r
e

o
f

m
e
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c
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t
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t
o

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o
n
t
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l

I
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P

i
n

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7
.
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a
s
e
s
;

V
F

d
e
t
e
r
i
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r
a
t
i
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n

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n

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6
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f

c
a
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r
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e

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n
d

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o
n
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c
o
m
p
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a
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e

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r
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l
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s

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s
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r
g
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r
y
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1
4
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a
t
i
e
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t
s

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9
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h
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t
e
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l
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c
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u
t
c
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t

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r

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a
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s

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h
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P

(
a
s

m
e
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s
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d

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h
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n

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t
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n
g

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h
e

p
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e
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f

s
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c
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n

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P

l
e
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s

t
h
a
n

2
1
m
m
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g

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n
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t

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u
a
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r
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n
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d

s
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s

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c
h
i
e
v
e
d

i
n

6
6
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6
%

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f

c
a
s
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s

(
8
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3

c
a
s
e
s
)
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u
a
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n
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n

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c
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d

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n

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f

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s
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7
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)
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n

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e
r
m
s

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n

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O
P

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m
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g
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h
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n
q
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l
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s
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e

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s

8
4
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d

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a
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c
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s
s

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t
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n

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P

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6
m
m
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g

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s

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d

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n

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4
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f

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s
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t

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l
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2
0
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R
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t
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d
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R
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s
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t
s

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p
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r
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f
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r

4
9

p
a
t
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t
s

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n
d
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r
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t

c
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Q
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s
c
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P

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m
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r

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t

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f

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P

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s

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d

b
y

K
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p
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M
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s

8
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%

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t

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e
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r

p
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s
t
-
o
p
e
r
a
t
i
o
n
,

6
4
%

a
t

t
h
r
e
e

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r
s

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t

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p
e
r
a
t
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o
n
.

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a
p
l
a
n

M
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r

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l
y
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s

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h
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b
a
b
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t
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f

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l
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n
d
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e
s
s
1
8

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a
s

2
2
%

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t

f
v
e

y
e
a
r
s

a
n
d

4
6
%

a
t

t
e
n

y
e
a
r
s

p
o
s
t
-
o
p
e
r
a
t
i
v
e

a
n
d

5
4
%

p
r
o
b
a
b
i
l
i
t
y

o
f

s
u
r
g
e
r
y

a
t

1
5

y
e
a
r
s

a
f
t
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r

f
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t
r
a
t
i
o
n
.

F
o
n
t
a
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a

e
t

a
l
,

2
0
0
6
R
e
t
r
o
s
p
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t
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v
e

c
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h
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r
t

s
t
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d
y

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f

p
h
a
k
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c

p
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t
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t
s

w
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t
h

O
A
G

w
h
o

u
n
d
e
r
w
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t

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n
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t
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a
l

t
r
a
b
e
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c
t
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m
y

w
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t
h

a
d
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u
n
c
t
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v
e

M
M
C
.

I
O
P

d
e
e
m
e
d

b
y

t
h
e

t
r
e
a
t
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g

p
h
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b
e

a
s
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d

w
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h

h
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h

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k

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f

g
l
a
u
c
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m
a

p
r
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r
e
s
s
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n

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n
d

g
l
a
u
c
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m
a
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s

w
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f

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h
e

V
F

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r

o
p
t
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c

d
i
s
c
.

2
9
2

e
y
e
s

2
2
5

p
a
t
i
e
n
t
s

(
7
3
%

C
a
u
c
a
s
i
a
n
)
C
r
i
t
e
r
i
a

f
o
r

s
u
c
c
e
s
s
:

(
A
)

f
n
a
l

I
O
P

1
8
m
m
H
g

a
n
d

o
n
e

o
f

t
h
e

f
o
l
l
o
w
i
n
g
:

2
0
%

r
e
d
u
c
t
i
o
n

o
f

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O
P

o
r

r
e
d
u
c
t
i
o
n

o
f

m
e
d
i
c
a
t
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o
n
s

w
i
t
h

f
n
a
l

I
O
P

r
e
q
u
i
r
e
d

t
o

b
e

l
e
s
s

t
h
a
n

o
r

e
q
u
a
l

t
o

b
a
s
e
l
i
n
e

I
O
P

i
f

b
a
s
e
l
i
n
e

I
O
P

1
8
.

(
B
)

F
i
n
a
l

I
O
P

1
5

a
n
d

o
n
e

o
f

t
h
e

f
o
l
l
o
w
i
n
g
:

2
5
%

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e
d
u
c
t
i
o
n

o
f

I
O
P

o
r

r
e
d
u
c
t
i
o
n

o
f

m
e
d
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c
a
t
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n
s

w
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t
h

f
n
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l

I
O
P

r
e
q
u
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r
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d

t
o

b
e

l
e
s
s

t
h
a
n

o
r

e
q
u
a
l

b
a
s
e
l
i
n
e

I
O
P

i
f

b
a
s
e
l
i
n
e

I
O
P

1
5
.

(
C
)

F
i
n
a
l

I
O
P

1
2

a
n
d

o
n
e

o
f

t
h
e

f
o
l
l
o
w
i
n
g
:

3
0
%

r
e
d
u
c
t
i
o
n

i
n

I
O
P

o
r

r
e
d
u
c
t
i
o
n

o
f

m
e
d
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c
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t
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n
s

w
i
t
h

f
n
a
l

I
O
P

r
e
q
u
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r
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d

t
o

b
e

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s

t
h
a
n

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r

e
q
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a
l

t
o

b
a
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e
l
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e

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i
f

b
a
s
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l
i
n
e

I
O
P

1
2
.

K
a
p
l
a
n

M
e
i
e
r

s
u
c
c
e
s
s

r
a
t
e
s

a
t

f
r
s
t

a
n
d

t
h
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r
d

y
e
a
r
s

a
f
t
e
r

f
o
l
l
o
w
-
u
p
:

8
5
%
(

2
%
)

a
n
d

6
2
%
(

4
%
)
,

8
4
%
(

2
%
)

a
n
d

5
6
%
(

4
%
)
.

7
9
%
(

2
%
)

a
n
d

4
5
%

4
%
)
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B
r
a
r
t

e
t

a
l
,

2
0
0
4
R
a
n
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m
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d

c
l
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n
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c
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l

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r
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t
r
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c
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y

w
i
t
h

v
i
s
c
o
c
a
n
a
l
o
s
t
o
m
y
.

(
R
e
s
u
l
t
s

f
o
r

t
r
a
b
e
c
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l
e
c
t
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m
y

o
n
l
y

r
e
p
o
r
t
e
d

h
e
r
e
)
.

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n
t
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m
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a
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u
s
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d

a
s

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p
r
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f
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r

p
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s

a
t

h
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h

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f

d
r
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f
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n
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r

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O
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G

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n

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a
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m
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y

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d

m
e
d
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c
a
t
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o
n
.

5
0

e
y
e
s

(
1
6

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y
e
s

C
a
u
c
a
s
i
a
n
,

2
9

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y
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s

b
l
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4
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S
u
c
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f
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n

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P

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f

2
1
m
m
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g

w
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t

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t

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2

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o
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s
,

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h
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n

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f

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c
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s
f
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l

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y
e
s

w
a
s

9
1
%

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t
h

t
r
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b
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c
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l
e
c
t
o
m
y
.

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t

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h
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t

f
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p

v
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t

(
m
e
a
n

2
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50
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5.6: SIDL LIILC1S
5.6.1: MEDICATIONS
Topicalanti-glaucomamedications can result in an array of side effects,rangingfrom
minorimpactssuchaseye-lashelongationanddarkeningoftheiristomajorimpactssuchas
cardiovascularevents(Table5.9).
TABLE 5.9: MEDICATION SIDE EffECTS
Medication Side effect
Prostaglandinanalogues(prostamides) Browndiscolouringoftheiris,lengtheninganddarkeningof
eyelashes,ocularirritationandredness,macularoedemaor
iritisinsusceptiblepatients.
badrenergicblockers Ocularirritationanddryeyes.Contraindicatedinpatients
withbradycardia,heartblock,heartfailure,asthmaor
obstructiveairwaydisease.Canhavesubstantial
cardiovascularandrespiratoryside-effects,especially
intheelderly.
Alpha(a)2adrenergicagonists Redeyeandocularirritation,centralnervoussystem
effectsandrespiratoryarrestinyoungchildren,allergic
conjunctivitis,sedation,cautionadvisedinpatientswith
cerebralorcoronaryinsuffciency,Raynaudsdisease,
posturalhypotension(dizzyspells),hepatic(liverfailure)
orrenalimpairment.
Carbonicanhydraseinhibitors Topicalformshavefewsideeffects,howeveroralforms
maycausetransientmyopia,nausea,diarrhoea,lossof
appetiteandtaste,parasthesiae,lassitude,renalstones
andhaematologicalproblems.
Cholinergicagonists Substantialocularside-effectsincludingblurringofvision
duetothesmallpupilandinducedmyopia,ciliaryspasm
leadingtoheadachesespeciallyinyoungerpatients.
Cataractsandiris-lensadhesionsinthelong-term.
Prostaglandinandb-blockersarethemostfrequentlyusedantiglaucomamedicationsinAustralia.
Thesideeffectprofleforprostaglandinmedicationsisrelativelyminor.Topical
prostaglandinsarerapidlybrokendowninthebloodstreamasaresult,systemicsideeffects
arerare.Ocularsideeffectscanincludeconjunctivalhyperemia,increasedirispigmentation
andpigmentationoftheperiocularskinaswellaslengtheningoftheeyelashes.Because
theyarerare,nosideeffectsforprostaglandinsareincludedinthemodelling.
Moresignifcantsideeffectsarepossibleforpatientstakingb-blockers.Twotypesoftopical
b-blockersarecommerciallyavailable,nonselective(timolol,levobunolol,metipranololand
carteolol)andcardioselective(betaxolol),(BrooksandGillies,1992).TheIOPloweringability
ofthenonselectiveb-blockersisgreaterthanthecardioselectivebblockers,providinga
greatertreatmenteffcacy,althoughthesideeffectproflemaybemoresignifcantinthe
nonselectivebblockermedicationgroup.Thesesideeffectsinclude:stinging,achingor
rednessintheeyesafterusingdrops;dryeyesandforeignbodysensation(thefeelingofa
foreignbodyintheeye);bradycardia(slowheartbeat);spasmsofthetubesleadingto
5. Treatment
Prostaglandin
analogues are the
most frequently
used anti glaucoma
medications in
Australia.
Centre for Eye Research Australia
51 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
thelungs(bronchospasmorasthma);heartfailureduetothebuildupoffuid;depression;
confusion;fatigue,dizzinessandinabilitytotolerateexercise;and/orreducedlibido.
Bronchospasmcanexacerbateasthmaandchronicobstructivepulmonarydisease(COPD)
whilebradycardiacanexacerbatecongestiveheartfailure
19
.Prolongeduseoftopical
b-blockershasalsobeenlinkedtodepression,moodalterations,memoryloss,hallucinations,
decreasedlibidoaswellasimpotence.
Themostsignifcantsideeffect(whichhasbeenincludedinthedynamicmodelling)
associatedwithbblockersisCOPD.Apopulationbasedcohortstudyconductedinthe
UK,examiningwhethertopicalbblockersareassociatedwithexcessrespiratorydiseasein
elderlypatientsnotconsideredtobeatexcessrisk(Kirwanetal,2002)showedahigherrisk
ofrespiratorydiseasethanwouldnormallybeexpected.Ahazardratiousedinthemodel
of2.29(95%CI1.71to3.07)wasproducedforpeopletreatedwithbblockerstoreceivea
frst-timemedicaltreatmentforreversibleairwaysobstruction,althoughthisriskceasesto
besignifcantafterthefrstyearoftreatmentwithtopicalbblockers.TheriskofCOPDfora
personnotbeingtreatedwithtopicalbblockersisassumedtobeequaltotheprevalenceof
COPDinthegeneralpopulation.
TABLE 5.10: RISK Of COPD (% Of POPULATION), 2001
Age Males females Persons
0-4 0.00 0.00 0.00
5-14 0.00 0.00 0.00
15-24 0.05 0.01 0.03
25-34 0.44 0.22 0.33
35-44 1.15 0.57 0.86
45-54 2.61 1.06 1.84
55-64 5.71 2.08 3.92
65-74 10.42 3.61 6.91
75-84 14.22 5.26 9.01
85+ 16.01 6.37 9.35
AllAges 2.51 1.09 1.80

Source:AIHWspecialrequest.
ThecostofCOPDperpersonisbasedonAIHWdata,indexedto2005dollars(Table5.11).
19
www.agingeye.net/glaucoma/glaucomadrugtreatment.php
5. Treatment

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TABLE 5.11: hEALTh SYSTEM COST Of COPD ($ PER PERSON), 2005
Age Males females Persons
0-4 0 0 0
5-14 255,006 476,620 304,254
15-24 2,893 13,717 5,167
25-34 88 527 233
35-44 291 978 522
45-54 373 962 543
55-64 858 1,843 1,117
65-74 1,427 2,717 1,775
75-84 1,904 2,524 2,115
85+ 2,010 2,224 2,111
AllAges 1,191 2,085 1,465
Source:AIHWspecialrequest.
5.6.2: LASER TREATMENT
Anumberofstudiesnotethatthesideeffectsoflaserincludeformationofperipheralanterior
synechiae(LatinaanddeLeon,2005;GLTandGLTFU),uveitis(Nagaretal,2005)andtransient
IOPspikes(LatinaanddeLeon,2005).Theseareexcludedfromthemodellingasforthe
mostparttheydonotaffectqualityoflife.Othermoreserioussideeffects,suchasretinal
detachment,arealsoexcludedfromthemodellingbecausetheyoccuratsuchalowrate.
5.6.3: SURGERY
Thecomplicationsoftrabeculectomyincludecataractandanincreasedriskofeyeinfection.
Cataractisthemostsevereandcostlyofthese(becauseofthenumberinvolved)andthushas
beenincludedinthemodelling.
Trabeculectomyisaninvasiveprocedurethathasaknownassociationwiththedevelopment
ofcataractsfollowingsurgery.Lichteretal,2001(CIGTS)foundthatinitialsurgicaltreatment
resultedinthedevelopmentofmorecataractsrequiringremovalthaninitialmedicaltreatment.
Kaplan-Meierestimatesshowedthatbythreeyearsaftertreatmentinitiation,theprobabilityof
cataractextractionwas11.6%(standarderror,1.9%)inthesurgicalgroupversus2.7%(standard
error,1.0%)inthemedicalgroup.Thedifferencewassignifcant(p=0.0001).Cataracts
occurredinapproximately20%to35%ofpatientsfollowingfrsttimetrabeculectomyover20
monthsto10years(Table5.12).Theoccurrenceofcataractfollowingtrabeculectomypresents
asasignifcantsideeffectthatresultsdirectlyfromglaucomatreatment,withanassociated
morbidityfromVAlossaswellascostsfromsubsequentcataractsurgery.
Other more serious
side effects, such as
retinal detachment,
are also excluded
from the modelling
because they occur at
such a low rate.
5. Treatment
Centre for Eye Research Australia
53 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model

5. Treatment
TABLE 5.12: TRABECULECTOMY SIDE-EffECTS
Source Incidence of Cataract following Trabeculectomy Timeframe
Edmundsetal, Cataractsdevelopedin20.2%ofeyesfollowingsurgery. *Cross-sectional
1999 survey
Parcetal,2001 Probabilityofcataractsurgeryatfveyears(aftersurgery) 5,10and
was15%andattenyearswas37%.Nostatistical 20years
differencebetweenpatientsandtherestofthecohort
at20years.
Fontanaetal, Cataractextractionoccurredin35%ofeyesfollowing 36months
2006 trabeculectomy.
AGIS TheRRofcataractfollowingfrsttrabeculectomywas 10years
1.78.WhencomplicationsoccurredinsurgerytheRR=
2.04andwhentheydidnotoccurRR=1.47.
Ehrnroothetal, Cataractsurgerywascompletedin35%ofeyes 3.5years
2002 followingtrabeculectomyduringthefollowupperiod
(mean3.5years).
Ehrnroothetal, Cataractsurgerywascompletedin34.8%ofeyes. 3.5years
2005
OBrartetal, Cataractformationwassimilarbetweenthe 20months
2004 trabeculectomyandviscocanalostomygroups.
*Edmundsetal,1999isacrosssectionalsurveyoftrabeculectomypatientsintheNationalHealthServiceintheUK.
Notimeframewasprovidedinthissurveybetweentrabeculectomyandcataractoccurrence
ThemajorityofstudiesshowninTable5.12measuretheincidencerateofcataractdevelopment
orsurgeryfollowingafrsttimetrabeculectomy.Thesemeasuresdonottakeintoaccountthe
rateofcataractdevelopmentorsurgeryinpeopleofanidenticaldemography.Ifanincident
rateofbetween20%and35%fromthesestudieswereusedtheincreasedmorbidityandhealth
systemcostwouldbeoverestimated.
TheAGISstudyontheotherhandmeasuredtheRRofcataractfollowingtrabeculectomy.
People that undergo a frst time trabeculectomy procedure have a 78% increased chance
of developing a cataract (RR=1.78)accordingtoAGIS.Thisincreasedriskisappliedinthe
modeltopeoplethathaveundergoneatrabeculectomyprocedure,withtheriskofcataractfora
personthathasnotundergonethisprocedureassumedtobeequaltotheprevalenceofcataract
inthegeneralpopulation.
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5. Treatment
TABLE 5.13: PREVALENCE Of CATARACT (% Of POPULATION)
Age Persons
40-44 0.0000
45-49 0.0000
50-54 0.0000
55-59 0.0844
60-64 0.0107
65-69 0.1620
70-74 0.7254
75-79 2.3713
80-84 5.4910
85-89 8.7109
90+ 15.1689
Source:MVIP&BMESspecialdatarequest.
ThecostofcataractsperpersonisbasedonAIHWdata,indexedto2005dollars.
TABLE 5.14: hEALTh SYSTEM COST Of CATARACT ($ PER PERSON), 2005
Age Males females Persons
0-4 0 0 0
5-14 0 0 0
15-24 0 0 0
25-34 0 0 0
35-44 70 71 73
45-54 107 113 110
55-64 118 112 115
65-74 171 178 176
75-84 206 219 215
85+ 210 132 152
AllAges 178 177 178
Source:AIHWspecialrequest.
5.6.4: SUMMARY Of SIDE EffECTS INCLUDED IN ThE MODELLING
Insummary,twosideeffectshavebeenincludedinthemodellingforglaucoma.Theseare:
cataract,RRof1.78followingtrabeculectomy;and,
COPD,RRof2.29followinguseofab-blockertopicaleyemedication.
Healthsystemcostsforthesesideeffectshavebeenincludedintotheperpersontreatment
costsofmedicationandtrabeculectomy.Themodelallocatesthesecostsbyincreasingthebase
costoftreatmenttoincorporatethetotalexpectedhealthsystemcostsofthesesideeffects.
Centre for Eye Research Australia
55 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
Main heading to go here 5. Treatment
The calculation of disease costs over time is discussed in this section, including:
the impact of glaucoma on a patients quality of life (wellbeing);
the health system costs of glaucoma; and
the indirect costs of glaucoma (including the impact on employment, the need for informal
and paid formal care, the impact on the paid employment of informal carers, aids and
equipment, and the economic costs of welfare payments).
However, rst, discount rates are discussed, as the model is dynamic and calculates the
economic impact of glaucoma in net present value terms over time (2005 to 2025).
6.1: DISCOUNT RATES
Choosing an appropriate discount rate for present valuations in cost analysis is a subject
of some debate, and can vary depending on which future income or cost stream is being
considered. There is a substantial body of literature, which often provides conicting advice, on
the appropriate mechanism by which costs should be discounted over time, properly taking into
account risks, ination, positive time preference and expected productivity gains.
The absolute minimum option that one can adopt in discounting future income and costs is
to set future values in current day dollar terms on the basis of a risk free assessment about the
future (that is, assume the future ows are similar to the certain ows attaching to a long term
Government bond).
Wages should be assumed to grow in dollar terms according to best estimates for ination and
productivity growth. In selecting discount rates for this project, we have thus settled upon the
following as the preferred approach.
Positive time preference: We use the long term nominal bond rate of 5.8% pa (from recent
history) as the parameter for this aspect of the discount rate. (If there were no positive time
preference, people would be indifferent between having something now or a long way off in
the future, so this applies to all ows of goods and services.)
General Ination: The Reserve Bank has a clear mandate to pursue a monetary policy that
delivers 2 to 3% ination over the course of the economic cycle. This is a realistic longer run
goal and we therefore endorse the assumption of 2.5% pa for this variable. (It is important
to allow for ination in order to derive a real (rather than nominal) rate.)
Productivity growth: The Commonwealth Governments Intergenerational report assumed
productivity growth of 1.7% in the decade to 2010 and 1.75% thereafter. We suggest
1.75% for the purposes of this analysis.
Health Ination: Health cost ination from 2005 onwards is assumed to be 3.2%, based on
estimates of increases in health expenditure from the AIHW estimates that health ination
in the eight years to 2004-05 has been around 3.2% per annum (AIHW 2006). This rate is
partially general price ination and partially productivity growth. To be on the conservative
side, productivity growth in the health sector is assumed to be equal to general
productivity growth.
6. Disease Costs
Glaucoma has
signicant social and
economic costs.
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Therearethendifferent discount rates that should be applied:
Todiscountincomestreamsoffutureearnings,thediscountrateis:
5.8-2.5-1.75=1.55%
Todiscounthealthcosts,thediscountrateis:
5.8-(3.2-1.75)-1.75=2.6%
Todiscountotherfuturestreams(healthylife)thediscountrateis:
5.82.5=3.3%
Whiletheremaybesensibledebateaboutwhetherhealthservices(orothercostswithahigh
labourcomponentintheircosts)shouldalsodeductproductivitygrowthfromtheirdiscount
rate,wearguethatthesecostsgrowinrealtermsovertimesignifcantlyasaresultofother
factorssuchasnewtechnologiesandimprovedquality,andwecouldreasonablyexpectthisto
continueinthefuture.
6.2: 1HL COS1 1O QUALI1Y OI LIIL AND wLLL8LING
6.2.1: DISEASE WEIGhTS
Asnotedabove,the impact of treatment on a patients health and quality of life is of
primary importanceinmodellingtheeconomicimpactofdisease.Inthisstudy,eachstage
intheprocessofvisionlossneedstobematchedwithautilityweight(apatientsmeasureof
hisorherqualityoflife)refectingthelossofqualityoflifeexperiencedatthatpointinthe
progressionofthedisease.ThisisverydiffcultforPOAGbecause:
changesinIOPdonoteasilytranslateintoahealthbeneftforpatients(Kobeltetal,2006,
Hymanetal,2005,Jampeletal,2002andMillsetal,2001);and
thereisnoagreeddiseasestagingsystembasedonvisionloss(seeSection4.5).
Thevariousvisiongradingsystemscannotbeeasilytranslatedintoaquantifableimpact
onqualityoflife.
Thereisagrowingliteraturethatattemptstomeasuretheimpactofglaucomaonqualityof
life,althoughthelackofaconsistentdiseasestagingsystemremainsaproblemindrawing
conclusionsfromthesestudies.Theliteraturesuggeststhatduringtheearlystagesofdisease,
glaucomahaslittleimpact,withquality of life deteriorating over time, particularly in the
later stages of the disease. Someexamplesareasfollows.
20

1) Kobeltetal,(2006)undertookacrosssectionalpilotstudytotestwhetherutilitiesfor
differentlevelsofVFdefectcouldbeassessedusingageneralquestionnairesuchasthe
EQ5D.UtilityweightsdevelopedusingtimetradeoffunderlietheEQ5D.InSweden,199
patientswithOHTorPOAGweregroupedaccordingtosixstagesofvisionlossbasedonVF
defectsintheworsteye.ThediseasestageswereadaptedfromtheHAPscalefromno
defect(OHT)toendstagediseasewhereVFmeasurementwasdiffcultornolongerpossible.
Theauthorsfoundthatutilitywasstronglycorrelatedwithoverallvision,andpatients
withsevereglaucomatousdamagehavesignifcantlylowerutility.However,whileutility
decreasedwithincreasingglaucomatousdamage,thedifferencebetweenthestageswasnot
statisticallysignifcantwhencontrollingforco-morbidity.When17outlierswereremoved,
utilityscoresforpatientswithsevereglaucomatousdamageweresignifcantlyworse.
Patientsinstage5hadameanutilityof0.71(autilitylossof0.29),comparedto
6. Disease Costs
20
Foranexplanationofthelinearratingscale,standardgamble,timetrade-off,persontrade-offandEQ-5D,
seeMathersetal,(1999:10).
Centre for Eye Research Australia
57 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
0.88instage1andameanof0.84(autilitylossof0.16)instages2.4.Thesamplesizewas
smallandthenumberofpatientswithmoderatetoseverebilateralvisionlosswaslimited,
however,theresultswereconsistentwithotherstudies(Kobeltetal,2006).
2) Jampeletal,(2002)examinedhow191glaucomapatientsand46glaucomasuspects
ratingoftheirvisioncorrelatedwithEstermanbinocularVFtestingandothervisualfunction
tests.Theyfoundthatutilityvaluesthatpatientsassigntotheirvisiondonotcorrelatewell
withEstermanresultsandsuggestedthiswasbecause,there may not be a close relationship
between visual function and patient perception of that function, especially when the vision loss
is mild ... Perhaps early visual feld loss really does not affect patient assessment of their vision
and in fact is more of an all or none phenomenon with patients only noticing marked visual feld
loss. (Ontheotherhand,appropriatetestsmaynothavebeendeveloped.)Alinearrating
scaleandtimetradeoffwereusedtogaugethepreferencesofpatientswithglaucomafor
visualstates.Basedonthelinearratingscale,glaucomapatientsratedtheirvisionas0.72
andsuspectsratedtheirvisionas0.71(ona0to1scale).Blindglaucomapatients(witha
VAnobetterthancountingfngersinthebettereyeandwhohadbeenblindfor10years)
ratedtheirvisualstateas0.54.Glaucomapatientsandsuspectsassignedavalueof0.38and
0.34respectivelytototalblindness.Timetradeoffresultswerelessinformativeasfewwere
willingtogiveuptimeforimprovedvision.
3) AUKstudy(Brownetal,2001)usedatimetradeoffandastandardgambletomeasure
utilityassociatedwithblindnessfrom65patientswithvariousvisiondiseasesincluding
glaucoma,cataract,agerelatedmaculardegeneration(AMD)anddiabeticretinopathy.
Autilityvalueof1.0indicatesastateofperfecthealthwhereasautilityvalueof0indicates
death.Participantsweregroupedaccordingtovariousmeasuresofblindnessasfollows:
b) totallyblind:15patientswithnolightperceptioninatleastoneeyeandwhowereasked
toassumeascenarioofnolightperceptioninthesecondeyeaswell;
c) somelightperception:17patientswithlightperceptiontocountingfngersinthebetter
seeingeye;
d) justoverthelineforlegalblindness:33patientswith20/200-20/400visioninthebetter
seeingeye.
Thetimetradeoffresultssuggestedutilityvaluesforeachgroupof(a)0.26QALYs(95%CI0.19
to0.33);(b)0.47QALYs(95%CI0.33to0.61);and(c)0.65QALYs(95%CI0.58to0.72).
Thus patients with no light perception in one eye who were presented with the same
scenario in the second eye as well were willing to trade almost 3 out of every 4 years of
remaining life in return for perfect vision in each eye. Thosewithlightperceptiontocounting
fngerswouldtradeapprox1of2remainingyearsandthosewith20/200-20/400wouldtrade
approx1of3remainingyears.
Thestandardgambleutilityresultsweresubstantiallyhigher:(a)0.32(95%CI0.2to0.44);(b)
0.60(95%CI0.46to0.74);and(c)0.80(95%CI0.73to0.87).However,theauthorssuggested
thestandardgambleresultsoverestimateriskaversionbecauseparticipantshavediffculty
understandingthisapproach.
Notably,inblindpatients,utilityimprovedovertimesuggestingadaptationtoblindness(there
weresignifcantdifferencesbetweenthoseblindforlessthanoneyearandthoseblindformore
thanoneyear)andtheworsethevisioninthebettereye,thelowertheutility.Brownetal,
(2001)concludedthat:
6. Disease Costs
Vision loss has a very
signifcant impact
on the quality of life
that is highly valued.
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There is a wide range of utility values associated with legal blindness the preservation of even
small amounts of vision in patients with legal blindness is critically important to their wellbeing
and functioning in life. (Brown et al, 2001:327)
AIHw wLIGH1S
The choice of disease weights is very important.Iftheutility(QALY)weightsassociated
withvisionlossaretooloworthedisabilityweights(DisabilityAdjustedLifeYears-DALYs)are
toohigh,theresultswilloverestimatethecosteffectivenessofinterventions(andviceversa).
Previousmodelsinthisseries(seetheBackgroundSection1ofthisreport)appliedthe
disabilityweightsusedbytheAIHWintheirlossofwellbeingstudy(Mathersetal,1999,Table
6.1).Theseweightsaredrawnfroma Dutch study that used a person trade off methodto
estimateweightsfor53diseases,includingtheestimationofweightsfor175diseasestages,
sequelaeandseveritylevels(citedinMathersetal,1999:11).TheDutchweightsarebasedon
diseasestagesdefnedasfollows(Mathersetal,1999:159):
Milddisease:Somediffcultywithnewspaper,nodiffcultyrecognisingfacesat4m;
Moderatedisease:Greatdiffcultynewspaper,somediffcultyrecognisingfacesat4m;and
Severedisease:Unabletoreadnewspaperorrecognisefacesat4m.
WhileitisdiffculttorelatethesedefnitionstostagesofVFLinthestudiesoutlinedabove,
andspecifcallytoadiseasesuchasglaucomawhichinitiallyaffectsmid-peripheralVF,the
AIHWweightsarenotinconsistentwiththepreviousliteraturereviewnotingthattheAIHW
weightsrefectdisabilityweights(DALYs)ratherthanutilityweights(QALYs).
ManypatientswithOHTortheclinicalsignsofglaucomadonotexperiencevisionlossfor
severalyears.Thusthereisnolossofutilityduringearlystagediseaseandthedisability
weightis0.0.
TheAIHW(Dutch)weightformoderatediseaseliesbelowthelowestweightforsevere
diseasefoundintheliteraturereview(0.17comparedwith0.26).However,ifglaucoma
reallyonlyaffectsqualityoflifeinthelatterstagesofdisease,thenthedisabilityweightsfor
mildandmoderatediseasemightbetoohigh.
LegalblindnessinAustraliaisdefnedasVAof<6/60inthebettereyewithcorrection
(spectacles)oraVFoflessthan10degreesorboth(CERA2004:11).Totalblindnessrefersto
peoplewhoareunabletoseelight.TheseareencompassedintheAIHWweightforsevere
diseasewhichis0.43(comparedwiththerangeofestimatesof0.26tomorethan0.6inthe
studiesoutlinedabove).
The AIhW disease weights will be used here. Theyaredrawnfromastudyofanumberof
diseasesandcomparisonwithotherdiseasesandinterventionsisimportantforbudget/resource
allocationdecisions.Inaddition,itisalsopreferabletouseweightsfromthesamestudysothat
thesamemethodologyhasbeenusedandthesetofweightsisinternallyconsistent.TheAIHW
weightsarealsoconsistentwiththepreviousmodelsdevelopedbyCERAandsoallowforeasy
comparisonsacrossthese.
BasicAIHWweightsareonlyforthediseaseanddonottakeintoaccountco-morbidities.
Glaucomaisassociatedwithbothaccidentalfallsanddepression.Accidentalfallsand
depressionarediscussedbelowinSections6.3.4and6.3.5.Thediseaseweightsarenotadditive
addingtheweightsforapersonwithsevereglaucomaandseveredepressionresultsina
weightgreaterthan1whichisnotintuitivelypossible.
Many patients with
OhT or the clinical
signs of glaucoma do
not experience vision
loss for several years.
6. Disease Costs
Centre for Eye Research Australia
59 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
Consequently,thefollowingformulaeareused:
whereWisthedisabilityweight,
VI
denotestheseverityofvisualimpairment(EDS,Mild,
ModerateorSevere),
DEP
denotesdepressionand
FALL
denotesafall.TheAIHWweighting
foraccidentalfallsis0.141andfordepressionis0.223basedon20%ofglaucomasuffers
experiencingmilddepressionwithaweightingof0.140and5%ofglaucomasuffers
experiencingmoderatetosevererdepressionwithaweightingof0.555(seeSection6.3.5for
theevidencebasisforcomorbiddepression)(seeMathersetal,1999,forthederivationofthe
respectivedisabilityweights).
TABLE 6.1: AIhW DISABILITY WEIGhTINGS
EDS Mild Moderate Severe
Glaucomaonly 0.000 0.020 0.170 0.430
Glaucomaandaccidentalfalls 0.141 0.158 0.287 0.510
Glaucomaanddepression 0.223 0.239 0.335 0.557
Glaucoma,accidentalfallsanddepression 0.333 0.346 0.446 0.620
CLkA wLIGH1S
CERAweightsarealsoavailableforusewithinthemodel.Thesearenotcorrelatedwithseverity
ofdiseasebasedonafndingfromresearchduringthedevelopmentoftheVisQoL,thetool
toderivevision-relatedutilities.Therewasnosignifcantdifferencebetweenmild,moderate
andseverevisionloss.TheCERAQALYweightforvisualimpairmentof0.83(utilitylossor
DALYof0.17)appliestoalllevelsofvisualimpairmentandisconsistentwithresultsfromthe
VIPsuggestingthat,withcancer,blindnessisthemostfearedhealthcondition.Noadditional
adjustmentforfallsanddepressionaremadeifCERAweightsareused.Itshouldbenotedthat
usingthesamedisabilityweightforalllevelsofseverityofglaucomareducesthebeneftsof
slowingprogressionofglaucoma.
6.2.2: PLACING A DOLLAR VALUE ON ThE LOSS Of WELLBEING
LossofwellbeingisestimatedusingDALYsandapplyingthelowerboundVSLof$3.7millionto
yieldthe estimated value of a life year of $162,561 (CERA, 2004).

DEP VI VI DEP VI
W W W W ! " + = ) 1 (
,
FALL VI VI FALL VI
W W W W ! " + = ) 1 (
,
FALL DEP VI DEP VI FALL DEP VI
W W W W ! " + = ) 1 (
, , , ,
6. Disease Costs
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6.3: HLAL1H SYS1LM COS1S
Thehealthsystemcostsofglaucomaarecategorisedanddiscussedinthissectionasfollows:
thecostofmonitoringanindividualwithglaucoma(notincludingtreatmentcosts);
thecostsoftreatmentforPOAG;
theincreasedlikelihoodofbeingadmittedtoanagedcarefacilityandtheassociatedcosts;
thecostsassociatedwithanincreasedlikelihoodoffallsandhipfractures;and
thecostsassociatedwithanincreasedlikelihoodofdepression.
DataonthehealthsystemcostsofPOAGarefromaspecialrequestfromtheAIHW.
Themostrecentdataforexpenditurebydiseaseareforthefnancialyear2000-01andhave
beenfactoredupforhealthinfation.Basedonestimatesofincreasesinhealthexpenditure
fromtheAIHW,healthinfationinthelasteightyearsto2004-05hasbeenaround3.2%per
annum(AIHW2006).
TheAIHWincludeonly87.5%(AIHW2005)oftotalrecurrenthealthexpenditureintheir
estimatesofexpenditurebydiseaseandinjury,referredtoasallocatedhealthexpenditure.
Theunallocatedremainderincludescapitalexpenditures,expenditureoncommunity
health(excludingmentalhealth),publichealthprograms(exceptcancerscreening),health
administrationandhealthaidsandappliancesthecodingfortheseareasofexpendituredoes
notallowallocationbydiseasecategory.Toensurecomprehensiveness,theseaspectsofhealth
systemcostshavebeenincorporatedbymultiplyingtheAIHWallocatedexpenditureestimates
by1.143(=1/0.875).Factoringuptheallocatedexpenditureinthiswaymeansthatcareneeds
tobetakentoavoiddoublecounting.Forexample,manyaidsandappliancecostsareprovided
bycommunityprograms(ratherthangovernmentprograms),andarenotincorporatedinthe
AIHWexpenditure.
Theproportionofhealthcostsbornebythegovernment(68.2%)andtheindividual(19.0%)is
basedonAIHW(2006:30).
TABLE 6.2: hEALTh COSTS BY WhO BEARS ThE COST, 2004-05
federal State/Territory Private health Individuals Other Total
Government Government Insurance
% 45.6% 22.6% 6.5% 19.0% 6.3% 100.0%
Source:AIHW(2006:30).
6.3.1: ThE COST Of MONITORING AN INDIVIDUAL WITh GLAUCOMA
Thecostofmonitoringanindividualwithglaucomain2005notincludingmedical,laser
andsurgicaltreatmentsis$649perpersonperyear.Thiswascalculatedbyadjustingthetotal
healthcostsforglaucoma($148.3min2000-01)inthefollowingways:
adjustforthechangeinthepopulationbetween2000-01and2005;
includeunallocatedhealthexpenditure(factoredupby1.143);
indexspendingto$2005(healthinfationof2.6%pa);and
removeexpenditureontreatment(medication,laserandsurgery)andagedcare;
dividebythenumberofpeoplereceivingtreatmentin2005.
6. Disease Costs
Overall, individuals
still pay 19% of
health costs.
Centre for Eye Research Australia
61 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
6. Disease Costs
6.3.2: COST Of TREATMENT
Medication
ThecostestimateswerederivedusingdatafromtheDepartmentofHealthandAgeingweb
publicationAustralian Statistics on Medicines 2005,andAustralianMedicareBeneftsSchedule
fees.Thetotalcostofanti-glaucomamedicationsfor2005isinTable6.3,andisdividedby
thetotalnumberofpeoplereceivingmedicationin2005(ie.thenumberofpeoplewith
diagnosedPOAGin2005estimatedinthedynamicmodel)toderivethecostofmedication
perpersonperannum.
TABLE 6.3: COST Of MEDICATION PER PERSON PER ANNUM
TotalCostofAnti-glaucomaMedications $99,694,643
TotalNo.ofPeopleonMedication 103,820
CostofMedicationperPerson $960
Source:AustralianStatisticsonMedicines2005andAccessEconomicsEconomicModeloftheImpactofPrimaryOpen
AngleGlaucoma.
Thecostofthesideeffectsofmedicationswereaddedtothecostofmedicationsperperson.
TheORofCOPDfollowingtheuseofatopicalbeta-blockerappliedtotheaverageriskof
COPDinTable510is2.29andthecostofCOPDperpersonisinTable5.11.Thetotalcostof
medicationwithsideeffectsincludedbyageandgenderisinTable7.1.
Trabeculoplasty
Thecostofatrabeculoplastyisappliedinthemodelonceatthepointwhenapatient
transitionsintothelasertreatmentphase.To account for people that have more than one
trabeculoplasty procedure, the cost calculated inTable6.4is infated by 1.5 in the modelling
calculations (see Section 5.2). Thecostofthisprocedureisbasedonthetreatmentfeeinthe
MBSforthetreatmentaswellasthecostoftheanaesthesiaservice(Table6.5).Basedonclinical
adviceforthisreport,thecostofanassistanthasnotbeenincluded.
TABLE 6.4: TOTAL COST Of TRABECULOPLASTY PER TREATMENT
MBS Code Description Cost
42782 LaserTrabeculoplastyeachtreatmentto1eye,toamaximum $398.65
of4treatmentstothateyeina2yearperiod(Anaes.)(Assist.)
20140 Initiationofmanagementofanaesthesiaforproceduresoneyes, $84.25
notbeingaservicetowhichanotheriteminthisgroupapplies
(5basicunits)
Total $482.90
Source:MBSBook,1November2006
Medication costs on
average: $960.80
per person per year.
Trabeculoplasty costs
on average $482.90.
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6. Disease Costs
Trabeculectomy
Aswithtrabeculoplasty,thecostofatrabeculectomyisappliedinthemodelonce,whenthe
personmovesintothesurgerytreatmentphase.To account for people that have a second
trabeculectomy procedure, the total cost of surgery in Table6.6is scaled up by 1.2 to
$4,122.50.
Thecostofthisprocedureisbasedontheaveragediagnosisrelatedgroup(DRG)costfor
trabeculectomy,weightedforpublicandprivatehospitals,fromtheNationalHospitalCostData
Collection.ThecodethatrelatestotrabeculectomyproceduresisDRGC15AGlaucomaand
ComplexCataractProcedures.Thetotalcostsofprivatehospitaltrabeculectomyproceduresare
inTable6.5.
TABLE 6.5: TOTAL COST Of TRABECULECTOMY PER TREATMENT
Total Cost No. of Procedures Weighted Average
PrivateHospital $3,027 656 0.3993
PrivateFreeStandingHospital $3,027 404 0.2459
PublicHospital $4,178 583 0.3548
$3,435.42
Source:PersonalCommunication(MarcFoley,EarandEyeHospital);NationalHospitalCostDataCollectionRound9
PublicHospitalCostsandAIHWspecialdatarequest
6.3.3: AGED CARE
Visual impairment compounds the presence of other disabling conditions,leadingtoan
increasedlikelihoodofutilisinginstitutionalisedagedcare.UsingBMESdata,Wangetal,(2003)
foundaRRofpermanentnursinghomeadmissionafteradjustingfornon-cognitivefactors
thatpredictednursinghomeplacementforpeoplewithbestcorrectedvisualimpairment
(6/12)agedover40years,of1.8(95%CI1.12.9).InthismodelforpeoplewithEDStheRR
ofbeinginanagedcarefacilityisassumedtobeunity,whileforMild,ModerateandSevere
visualimpairmenttheRRofbeinginanagedcarefacilityisbasedonalinearadjustment,with
moderatevisualimpairmentasthemidpoint:
1.4formild;
1.8formoderate;and
2.2forseverevisualimpairment.
TheRRisappliedtothegeneralpopulationofbeinginanagedcarefacility,andtheaveragecost
peryearof$52,800,fromtheAccessEconomicsAgedCareDynamicCohortModel.

Centre for Eye Research Australia


Trabeculectomy
surgery cost on
average $3435.
63 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
6. Disease Costs
TABLE 6.6: PROBABILITY Of RESIDING
IN AN AGED CARE fACILITY, 2004-05
Age % of Population
0-54 0.0002
55-59 0.02
60-64 0.14
65-69 0.29
70-74 0.60
75-79 1.40
80-84 3.40
85-89 8.51
90+ 25.40
Source:AccessEconomicsAgedCareDynamicCohortModel
6.3.4: fALLS AND hIP fRACTURES
Itiswellestablishedthatolderpeopleareatahigherriskoffalls,approximatelyhalfofwhich
resultinaninjury.Manystudieshaveexaminedthefactorsunderlyingtheincreasedpropensity
offallsintheelderlyandseveralhavefoundasignifcantlinkbetweenfallsandvisionloss.
Elderlyindividualsprogressivelyrelyonvisualfeedbacktomaintainbalancewithincreasingage
becauseproprioceptivefeedback,musculoskeletalstrengthandoftenvestibularfunctiondecline
withage(Ramrattanetal,2001).Thedeteriorationofvisualfunctioncoupledwiththelossof
othersensoryfunctionsresultinthehigher risk of falls in elderly visually impaired people.
Theriskofafallhasbeenlinkedtomanydifferentmeasuresofvisualimpairment.Themajority
ofstudiescomparetheriskoffallstoVAoranothermeasureofvisualimpairmentwithvery
fewstudiesexaminingthelinksbetweenglaucomaandfalls.Ofthesmallnumberofstudies
linkingglaucomaandfallssomeusedtheconsumptionofnon-miotictopicaleyemedicationsas
aproxyforVFL,whileonlyonestudyconductedadiagnostictesttodeterminethepresenceof
glaucomaandtheextentofVFL.
Ameta-analysisoftheavailableliteraturethatexaminedtherelationshipbetweenvisual
impairmentandtheriskofanaccidentalfallwasconducted(Table6.10).Additionalsupportive
articleswerefoundduringtheliteraturesearches,butcouldnotbeincludedduetoalackof
quantitativeinformation.ThesearticlesarelistedandsummarisedinAppendix1,Table10.4.
ArandomeffectsmodelhasbeenappliedtothedatainTable6.7andTable6.8,withstudiesthat
usedVFLandglaucomaproxiesormeasuresevaluatedseparately.
Older people with
vision impairment
are at a higher
risk of falls,
approximately
half of which result
in an injury.
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6. Disease Costs

TABLE 6.7: INCREASED RISK Of fALLS fROM VISUAL IMPAIRMENT
Source Impairment RR / OR 95% CI
Arfkenetal,1994 ImpairedVA RR=0.91 0.45to1.83
Colemanetal,2004 Lossof0-5letters OR=2.08 1.39to3.12
Colemanetal,2004 Lossof6-10letters OR=1.85 1.16to2.95
Colemanetal,2004 Lossof11-15letters OR=2.51 1.39to4.52
Colemanetal,2004 Lossof>15letters OR=2.08 1.01to4.30
Do|inis J et a|, 1997 Medica| history of g|aucoma kk = 1.63 1.13 to 2.37
G|ynn kJ et a|, 1991 40% or greater VIL |oss kk = 3.00 0.94 to 9.80
GlynnRJetal,1991 Mioticeyemedication RR=3.20 1.00to10.10
G|ynn kJ et a|, 1991 Non-miotic eye medication kk = 5.40 1.80 to 16.40
Haymes SA et a|, 2007 G|aucoma Ok = 3.71 1.14 to 12.05
IversRQetal,1998 Posteriorsubcapsularcataract PR=2.10 1.00to4.30
IversRQetal,1998 Non-mioticeyemedication PR=2.00 1.10to3.60
IversRQetal,1998 LowVA PR=1.90 1.20to3.00
IversRQetal,1998 Lowcontrastsensitivity PR=1.20 1.10to1.30
Ivers kQ et a|, 1998 G|aucoma k = 1.50 1.00 to 2.30
kamrattan et a|, 2001 Uni|atera| VIL kk = 5.31 2.82 to 9.99
kamrattan et a|, 2001 8i|atera| VIL kk = 6.32 2.46 to 16.24
TinettiMEetal,1988 VisuallyImpaired RR=1.70 1.20to2.30
Vuetal,2005 <6/12bettereye OR=0.98 0.12to7.70
Vuetal,2005 <6/12worseeye OR=2.86 1.16to7.08
ZwerlingCetal,1998 Visuallyimpaired RR=1.60 1.10to2.40
HighlightedstudiesprovideVFand/orglaucomarelatedestimates.
RR=RelativeRisk,OR=OddsRatio,PR=PrevalenceRatio
TABLE 6.8: META-ANALYSIS, fALLS (RANDOM EffECTS MODEL)
RR 95% CI
RiskofAccidentalFallVisualImpairment 2.05 1.54to2.71
RiskofAccidentalFallVFLorGlaucoma 3.18 1.82to5.55
VFL=VisualFieldLoss
TheRRofanaccidentalfallinpeoplewhosevisualimpairmentwascausedbyVFLorglaucoma
washigherthantheoverallvisualimpairmentgroup.Althoughcautionisadvisedwiththis
groupastheVFL/glaucomashowedahigherlevelofestimatedpublicationbiasthanthevisual
impairmentgroup.Itmaybethecasethatthesmallnumberofpublished(andincluded)trials
whereVFLwasincludedmaybepushingtheRRhigherthanitshouldbe.Thiscanonlybe
resolvedwiththecompletionandinclusionofmorestudiesonVFL.
TheRRsofaccidentalfallsaresplitbyvisualimpairmentseveritybyapplyingtheRRinTable
6.10tothosewithmoderatestagedisease,allocatingaRRof1.0totheOHTgroupand
applyingalinearextrapolationtodeterminetheRRsforthemildandseveregroup(Table6.11).
Centre for Eye Research Australia
65 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
6. Disease Costs
TABLE 6.9: RELATIVE RISK Of AN ACCIDENTAL fALL BY SEVERITY
Visual Impairment VfL / Glaucoma
OHT 1.00 1.00
Mild 1.52 2.09
Moderate 2.05 3.18
Severe 2.57 4.27
Source:AnalysisbyAccessEconomics.
TheseresultsareconsistentwithBlackandWood(2005)whoconcludedthattheORoffallsand
fracturesfromreducedvisionlaybetween1.5and2.0.
Theriskofhavinganaccidentalfallforapersonwithoutglaucomaisassumedtobeequalto
theprevalenceofaccidentalfallsinthegeneralpopulation.
TABLE 6.10: RISK Of ACCIDENTAL fALL (% Of POPULATION), 2001
Age Males females Persons
0-4 0.64 0.50 0.57
5-14 0.83 0.551 0.68
15-24 0.74 0.27 0.51
25-34 0.55 0.24 0.40
35-44 0.44 0.28 0.36
45-54 0.42 0.34 0.38
55-64 0.47 0.56 0.51
65-74 0.75 1.16 0.96
75-84 1.78 3.21 2.61
85+ 5.07 7.80 6.95
AllAges 0.68 0.70 0.69
Source:AIHW,specialrequest.
ThecostofanaccidentalfallperpersonisbasedonAIHW2000-01data,
indexedto2005dollars.
The risk of having
an accidental fall for
a person without
glaucoma is assumed
to be equal to
the prevalence of
accidental falls in the
general population.
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TABLE 6.11: hEALTh SYSTEM COST Of AN ACCIDENTAL fALL ($ PER PERSON), 2005
Age Males females Persons
0-4 8,829 8,071 8,505
5-14 7,718 12,166 9,363
15-24 8,307 7,967 8,218
25-34 7,324 8,394 7,655
35-44 7,522 9,905 8,455
45-54 8,861 12,613 10,561
55-64 11,291 11,011 11,140
65-74 13,660 14,224 14,012
75-84 14,659 11,464 12,375
85+ 15,246 12,381 13,025
AllAges 9,737 11,500 10,643
Source:AIHW,specialrequest.
6.3.5: DEPRESSION
StudiesexaminingthelossofVAandlinkstotheonsetofdepressivestatehaveshownahigher
RRofsufferingdepressionincomparisontothegeneralpopulation.Thesedonotnecessarily
relatetoopenangleglaucomastudiesforPOAGarerequired.
Onestudy,however,reportedthatglaucomadoesnotsharethesameRRassociationas
othervisualimpairments.Wilsonetal,(2002)reportedthatthereisnoassociationbetween
depressionandVAlevel,VFseverityortheuseoftopicalbblockersinpeoplewithglaucoma.
Howeverthisstudywasconductedonasmallnumberofpatientsandreliedonselfreported
surveys.
Prevalenceratesofdepressioninelderlyvisuallyimpairedpopulationsareestimatedtorange
between25%45%(Burmedietal,2002).Withinthegeneralelderlypopulation,lessthan20%
havemilddysphoriawithlessthan5%sufferingfromseveredepression.Comparingrisksfrom
thesestudies,theRRofdepressionislikelytobeintheorderof35%/10%=3.5timeshigher.
SummaryresultsfromthesestudieslinkingvisionimpairmentarepresentedinTable6.12.

6. Disease Costs
Depression occurs
three times more
commonly in those
with vision loss.
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67 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
6. Disease Costs
TABLE 6.12: DEPRESSION AND VISION LOSS
Source finding
Brodyetal,2003 33%depressed
Karisson,1998 Lessthan10%depressed
Kleinschmidt,1995 22%mildly;4%moderatelytoseverelydepressed
Rovneretal,1997 39%-70%depressiondependingonmeasurementscaleused
Wahl,1994 43%ofblind,29%ofvisuallyimpaireddepressed
Robbinsetal,1988 Meanscoreof10.3(10+indicatesdepression)
Vuetal,2005 OR6.28forhealthandemotionalproblems;OR4.7fornotfulloflife
Wilsonetal,2002 Nodifferenceindepressivestate
ChenandHe2005 Measuresformildanxietyandmoderatesevereanxietywereallhigherfor
bothacuteangleclosureglaucomaandchronicangleclosureglaucomathan
thenationalnorm.
Forthemodelbasecase,people with glaucoma have an OR of depression which is
approximately 3.5. Theriskofhavingdepressionforapersonwithoutglaucomaisassumedto
beequaltotheprevalenceofdepressioninthegeneralpopulation.Thecostofdepressionper
personisalsobasedonAIHW2000-01data,indexedto2005dollars(Table6.14).
TABLE 6.13: RISK Of DEPRESSION (% Of POPULATION), 2001
Age Males females Persons
0-4 0.00 0.00 0.00
5-14 0.02 0.01 0.01
15-24 0.95 1.02 0.99
25-34 3.29 4.45 3.87
35-44 4.38 5.95 5.17
45-54 4.35 6.32 5.33
55-64 3.82 5.72 4.76
65-74 2.77 3.97 3.39
75-84 1.93 2.37 2.19
85+ 1.34 1.45 1.41
AllAges 2.53 3.52 3.03
Source:AIHW,specialrequest.

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TABLE 6.14: hEALTh SYSTEM COST Of DEPRESSION ($ PER PERSON), 2005
Age Males females Persons
0-4 0 0 0
5-14 18,544 75,852 36,831
15-24 2,793 5,659 4,250
25-34 1,555 2,296 1,983
35-44 1,346 1,831 1,627
45-54 1,634 1,870 1,774
55-64 1,799 2,167 2,017
65-74 2,657 3,610 3,233
75-84 5,872 9,304 8,033
85+ 17,672 12,551 14,052
AllAges 1,915 2,632 2,334
Source:AIHW,specialrequest.
6.4: INDIkLC1 COS1S
Theindirectcostsofglaucomacanincludeareducedlikelihoodofemployment,theneedfor
formalaswellasinformalpersonalcare(andtheassociatedimpactontheemploymentof
informalcarers),aidsandequipment,andtheeconomiccostsofwelfarepayments.Manyofthese
indirect costs are related to the level of visual impairment rather than glaucoma per se,and
arethereforesimilartotheindirectcostsassociatedwithothereyediseasessuchasAMD.
EMPLOYMENT
Glaucomaoverwhelminglyaffectstheelderlysoveryfewpeoplewithseverevisualimpairment
arelikelytobeemployed.Forthepurposesofmodelling,peoplewithEDSareassumedtohave
anORofbeingemployedofunity,whileforMild,ModerateandSeverevisualimpairmentthe
ORofbeingemployedisbasedonalinearadjustmentoftheORcontainedinCERA(2004:66),
withmoderatevisualimpairmentasthemidpoint:
0.75formild;
0.5formoderate;and
0.25forseverevisualimpairment.
TheRRsareappliedtothegeneralemploymentratesbyagefromABS(2005)andtheAverage
WeeklyEarnings(AWE)ratesfromABS(2004),indexedto2005dollars.
OThER INDIRECT COSTS
Otherindirectcostsperperson(suchastheimpact on employment of informal carers, formal
care costs, aids and modifcations, and other indirect costs)wereextractedfromtheMVIP
databaseforthosepeoplewithVAloss(indirectcostsforpeoplewithoutvisualimpairmentare
assumedtobenil).DuetohighSDsinthedata,themeanindirectcostsacrossalllevelsofvisual
impairmentwereused,insteadofindirectcostsbymild,moderateandseverevisualimpairment.
6. Disease Costs
Glaucoma
overwhelmingly
affects the elderly
- fewer people
with severe visual
impairment are likely
to be employed.
Centre for Eye Research Australia
69 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
6. Disease Costs
Informalcareandsupportissplitbetweencostsandlostproductivityofthecarerbasedon
theratiocontainedinCERA(2004:75).TheproportionofMedicines,productsandequipment
thatareaidsandmodifcationsisbasedonthesplitusedinCERA(2004:70-72).Carer
productivitycostswereindexedto2005accordingtoAWEovertime,whiletheremaining
indirectcostswereindexedtohealthinfation.
TABLE 6.15: INDIRECT COSTS ($ PER ANNUM), 2005
Cost
FormalCare 439
LostProductivityofCarer 1,544
AidsandModifcations 337
OtherExpenses 630
Sources:MVIP,CERA(2004).
6.5: DLADwLIGH1 LOSSLS
Thefollowingparameterswereusedtoestimatelost taxes and additional welfare payments
fromglaucoma,whichinturnunderlietheestimationofdeadweightlossestotheeconomy.
Averagepersonalincometaxrateof21.20%andaverageindirecttaxrateof15.51%,based
onAccessEconomicsMacroeconomicmodel(AEM).
Thelevelofdisabilitysupportperannumof$10,340.20($397.70x26fromwww.
centrelink.gov.auin2005),isindexedtotheAWEandisreceivedbyallindividualswithVA
worsethan6/60whoareaged15to65(afterthisageitislikelytheywouldreceivethe
agedpensionregardlessoftheirVA)
21
.
Therateofdeadweightlossis0.275per$1oftaxrevenueraised,basedonProductivity
Commission(2003),plus0.0125per$1oftaxrevenueraisedforAustralianTaxationOffce
(ATO)administration,andisappliedtohealthsystemcostsincurredbythegovernment,lost
taxesandwelfarepayments.

21
Ifapersononthedisabilitypensionisemployed,then(dependingonthelevelofincomeandhoursofemployment)
theamountreceivedmaybeadjustedslightlydownwards.However,givenglaucomamainlyaffectsolderpeople,and
thosethatreceivethepensionarepermanentlyblind,thenumberofpeopleemployedwouldbelowandanyslight
adjustmentsdownwardswouldmakenegligibleimpactontheresults(especiallysinceweonlyincludethedeadweight
lossofthegovernmentexpenditureratherthantheexpenditureitself).
Indirect costs of
vision loss are often
overlooked.
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This section summarises the parameters used in the model.
Modelled prevalence rates are in Table 7.1.
Initial severity of visual impairment splits are in Table 7.2.
Modelled treatment assumptions are in Table 7.3.
The costs of treatment including the expected health system costs of side-effects and
adverse events are in Table 7.4. There is also a cost of monitoring those who are diagnosed
with POAG at $649 per patient per year.
The Sections explaining the other parameters used within the model are listed in Table 7.5.
TABLE 7.1: PREVALENCE OF OHT AND POAG
OHT POAG
Age Males Females Males Females
0-4 0% 0% 0.0% 0.0%
5-9 0% 0% 0.0% 0.0%
10-14 0% 0% 0.0% 0.0%
15-19 0% 0% 0.0% 0.0%
20-24 0% 0% 0.0% 0.0%
25-29 0% 0% 0.0% 0.0%
30-34 0.00% 0.00% 0.00% 0.0%
35-39 0.02% 0.02% 0.00% 0.00%
40-44 0.08% 0.08% 0.07% 0.07%
45-49 0.15% 0.15% 0.14% 0.14%
50-54 0.23% 0.23% 0.60% 0.60%
55-59 0.30% 0.30% 0.94% 0.94%
60-64 0.35% 0.35% 2.29% 2.29%
65-69 0.39% 0.39% 3.46% 3.46%
70-74 0.44% 0.44% 5.51% 5.51%
75-79 0.49% 0.49% 5.78% 5.78%
80-84 0.49% 0.49% 6.74% 6.74%
85-89 0.49% 0.49% 9.66% 9.66%
90+ 0.49% 0.49% 20.66% 20.66%
Source: BMES and MVIP data
7. Summary of Model Parameters
71 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
Main heading to go here 7. Summary of Model Parameters
TABLE 7.2: SEVERITY OF VISUAL IMPAIRMENT INITIAL PROPORTIONAL SPLIT
Age EDS Mild Moderate Severe
0-4 0% 0% 0% 0%
5-9 0% 0% 0% 0%
10-14 0% 0% 0% 0%
15-19 0% 0% 0% 0%
20-24 0% 0% 0% 0%
25-29 0% 0% 0% 0%
30-34 0% 0% 0% 0%
35-39 0% 0% 0% 0%
40-44 100.0% 0.0% 0.0% 0.0%
45-49 100.0% 0.0% 0.0% 0.0%
50-54 100.0% 0.0% 0.0% 0.0%
55-59 100.0% 0.0% 0.0% 0.0%
60-64 95.1% 0.2% 1.7% 2.9%
65-69 94.3% 0.4% 2.8% 2.6%
70-74 92.5% 0.5% 3.7% 3.3%
75-79 88.6% 1.2% 8.4% 1.8%
80-84 84.4% 1.7% 11.5% 2.5%
85-89 78.0% 2.2% 15.1% 4.8%
90+ 70.6% 1.1% 7.7% 20.6%
Source: BMES and MVIP data
TABLE 7.3: MODELLED TREATMENT ASSUMPTIONS
Treatment efcacy Compliance Treatment Incidence
(reduction in and failure rates
progression of
visual impairment)
Medication 50% Inherent in the data See Table 5.5
and calculation (total
costs of medications for
POAG in 2005 divided by
prevalence of diagnosed POAG)
Trabeculoplasty 50% 100% 50% of patients
fail each year
Trabeculectomy 50%
#
100% 50% of patients
fail each year
#
Based on equivalence between medication and trabeculectomy demonstrated in CIGTS.

72
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7. Summary of Model Parameters
TABLE 7.4: MODELLED TREATMENT COSTS $ 2005
(INCLUDING SIDE-EFFECTS AND ADVERSE EVENTS)
Medication (a) Trabeculoplasty (b) Trabeculectomy (c)
Male Female Male Female
40-44 964.58 967.45 724.35 4122.50 4122.50
45-49 972.82 973.42 724.35 4122.50 4122.50
50-54 972.82 973.42 724.35 4122.50 4122.50
55-59 1023.46 1009.71 724.35 4122.58 4122.58
60-64 1023.46 1009.71 724.35 4122.51 4122.51
65-69 1152.08 1086.79 724.35 4122.72 4122.73
70-74 1152.08 1086.79 724.35 4123.47 4123.51
75-79 1309.53 1131.53 724.35 4126.31 4126.55
80-84 1309.53 1131.53 724.35 4131.33 4131.88
85-89 1375.39 1143.02 724.35 4136.77 4131.47
90+ 1375.39 1143.02 724.35 4147.35 4138.12
Calculation of these estimates is explained in Section 6.3.2. a) Cost of anti-glaucoma medications plus the costs of
the risk of COPD. b) Cost of trabeculoplasty adjusted upwards by 1.5 to account for people who have a second laser
treatment. c) Trabeculectomy adjusted upwards by 1.2 to account for people who have a second trabeculectomy and
also adjusted upwards in the older age groups to account for the increasing risk of cataract surgery as a side effect.
TABLE 7.5: OTHER MODELLED VARIABLES
Item Reference
Disability weights Table 6.1, page 59
Health System Costs Page 60
Aged Care Table 6.6, page 63
Accidental Falls Table 6.9, Table 6.10 and Table 6.11, pages 65 to 66
Depression Table 6.13 and Table 6.14, pages 67 to 68
Employment Page 66
Other Indirect Costs Table 6.15, page 69
Deadweight losses Page 69
Other indirect costs include formal care, lost productivity of carers, aids and modications and other expenses.
73 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
8. The Model
The model was built in Microsoft Ofce Excel 2003 which ensures portability. The model can
be navigated by clicking on the relevant button on the Main Menu (see Figure 8.1) or by clicking
on the sheet tabs at the bottom of the window. In order to access and view the sheets with the
parameters and the models workings, click the Show/Hide Parameter Sheets button.
Prevalence rates are assumed to be the number of people with the disease at the start of the
year. During the year people are treated, progress, or die, with the impacts of these pathways on
prevalence rates occurring at the start of the following year (see Figure 8.3 for a diagram of the
models logical structure).
To select scenarios, click on the User Options sheet button (see Figure 8.2). To view output, click
the Cost-effectiveness Analysis, PopChart, CostChart or CE-PlaneChart buttons.
FIGURE 8.1: MAIN MENU
Cost effectiveness analysis can be conducted comparing various scenarios with the base case.
To set the base case, tick the No new intervention (Standard treatment) box on the
Options sheet.
Three treatment phases are modelled, consistent with the current treatment regimen:
medication, laser (trabeculoplasty) and surgery (trabeculectomy). The order in which these
treatments is applied can be switched in the Select intervention and Select intervention
detail windows on the options sheet.
74
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8. The Model
fIGURE 8.2: OPTIONS ShEET
Cost effectiveness
analysis can be
conducted by running
various scenarios of
current treatment
and comparing with
the base case.
Economic impact of primary open angle glaucoma Commercial-in-Confidence
72
FIGURE 8-2: OPTIONS SHEET
Centre for Eye Research Australia
75 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
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76
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Centre for Eye Research Australia
The model has been adapted so that users can test the economic impact of changes to current
treatment patterns. The scenarios are as follows:
the base case (No new intervention (standard treatment));
an increase in the rate at which POAG is diagnosed (to 70%, 80% or 90%);
a change in the treatment protocol (using laser trabeculoplasty as the primary treatment
instead of medication, with medication becoming the second treatment phase and surgery
the third phase);
research to delay progression (by 50% or 75%); and
combination scenarios an increase in the rate at which POAG is diagnosed from 50% to
80% together with:
- A change in the treatment protocol; or
- The introduction of a new treatment to delay progression by a further 50%.
9.1: THE BASE CASE
The base case scenario can be set to either the current situation (no new intervention/standard
treatment) or an other intervention which can be chosen using the Select intervention and
Select intervention detail from the Options sheet.
9.1.1: TO RUN A BASE CASE
To select the current situation (No new intervention (Standard treatment)) as the base case
for comparison:
tick the No new intervention (Standard treatment) box on the Options sheet (note: it will
take a little while to reset all the parameters to reect the current situation).
Select frequency every year.
click the Set as Base Case button.
In brief, the base case parameters are: a POAG diagnosis rate of 50%, treatment regimen of
medication rst, followed by laser and then nally by surgery, and an impact of treatment
(treatment efcacy) of a 50% reduction in the progression of visual impairment. The previous
chapters explain the base case in more detail.
If you wish to chose another scenario as the base case (for example, increased diagnosis rates),
you must rst un-tick the No new intervention (Standard treatment) box. Then choose an
intervention from the Select Intervention box and the Select Intervention Detail box.
Then click the Set as Base Case button.
9.1.2: RESULTS
If current standard treatments continue for the next 20 years, and no new intervention scenarios
are applied:
the prevalence of OHT in Australia will increase from 26,000 people in 2005, to 41,000
people in 2025;
the prevalence of POAG in Australia will increase over the same period from 208,000
people to 379,000; and
9. Intervention Scenarios
77 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
Main heading to go here
the prevalence of visual impairment from POAG in Australia is expected to grow from
24,000 people in 2005 to 52,000 people in 2025 (Table 9.1).
The prevalence estimates here vary somewhat from those in Clear Insight, (CERA 2004) that
used age and gender specic prevalence rates from the MVIP and BMES, with visual impairment
based on loss of VA. This analysis also uses data from the combined MVIP/BMES data set,
but for persons rather than by gender, and measuring visual impairment measured using a
combination of VA and VF.
Figure 9.1 shows a steady increase in the prevalence of POAG from 2005 and 2025, driven by an
ageing population.
TABLE 9.1: PREVALENCE OF OHT AND POAG, BASE CASE (NUMBER OF PEOPLE)
2005 2025
OHT 25,986 40,004
POAG
Early stage 183,530 326,659
Mild stage 1,872 3,667
Moderate stage 12,914 26,047
Severe stage 9,312 22,613
POAG (all stages) 207,628 378,985
Visual Impairment from POAG 24,098 52,327
Prevalence (Total OHT & POAG) 233,614 419,989
Source: Access Economics/CERA dynamic model
FIGURE 9.1: PREVALENCE OHT AND POAG, BASE CASE
The health system costs of glaucoma in 2005 were $355 million and the total annual cost of
glaucoma in 2005 was $1.9 billion. In real dollar terms, these costs are expected to increase to
$784 million and $4.3 billion respectively by 2025 (Table 9.2). The net present value of DALYs
and other costs of POAG are depicted in Table 9.3.
The total cost of
glaucoma will
increase in 2005 to
$1.92 billion, and
$4.3 billion in 2025.
9. Intervention Scenarios
Prevalence (diagnosed and undiagnosed)
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TABLE 9.2: COSTS OF POAG, 2005 AND 2025, BASE CASE
2005 2025
DALYs 6,940 15,592
YLD 6,678 15,184
YLL 262 408
Burden of Disease Costs ($) 1,043,713,812 2,325,613,694
Health System Costs ($) 355,121,086 783,978,738
Comorbid Health Costs ($) 166,419,635 423,192,582
Treatment Costs ($) 188,701,450 360,786,156
Productivity Costs ($) 60,406,596 130,614,278
Other Indirect Costs ($) 109,422,685 240,987,552
Total Costs ($) 1,923,785,265 4,265,173,000
TABLE 9.3: BASE CASE (STANDARD TREATMENT) NET PRESENT VALUE OF DALYS AND COSTS
Net present value 2005 to 2025
DALYs 155,150
Burden of Disease Costs ($ million) 23,896
Health System Costs ($ million) 8,759
Comorbid Health Costs ($million) 4,505
Treatment Costs ($million) 4,254
Productivity Costs ($ million) 1,665
Other Indirect Costs ($million) 2,695
Total Costs ($million) 37,015
The value of the burden of disease due to POAG over time is depicted in Figure 9.2.
FIGURE 9.2: VALUE OF BURDEN OF DISEASE DUE TO POAG ($M), BASE CASE
Sensitivity analysis zero prevalence and incidence of OHT among those aged 80 and over
9. Intervention Scenarios
Over half the costs
of glaucoma relate to
loss of well being.
0
500
1,000
1,500
2,000
2,500
2005 2010 2015 2020 2025
M
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l
l
i
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n
s
Burden of Disease Costs
Centre for Eye Research Australia
79 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
9. Intervention Scenarios
9.1.3: SENSITIVITY ANALYSIS ZERO PREVALENCE AND INCIDENCE Of OhT AMONG
ThOSE AGED 80 AND OVER
Asnotedearlier,prevalencedataweresmoothedinpartbecauseofthesmallsamplesizesinthe
originaldataset.UnsmoothedoriginaldatashowedzeroprevalenceratesforOHTamongthose
aged80yearsorover.Theimpactofusingsmoothedratherthanoriginaldataispresentedin
Table9.4andTable9.5.ThetotalcostsofPOAGareslightlylower(Table9.5).
TABLE 9.4: COMPARISON Of PREVALENCE Of OhT AND POAG WITh ORIGINAL AND
SMOOThED DATA
Original OhT prevalence Smoothed OhT
data (Zero OhT prevalence prevalence data
and incidence for those
aged 80 years or over)
2005 2025 2005 2025
reva|ence OH1 and OAG 227,827 406,840 233,614 419,989
PrevOHT 23,684 36,340 25,986 41,004
PrevearlystagePOAG 180,149 318,477 183,530 326,659
PrevMildPOAG 1,826 3,550 1,872 3,667
PrevModeratePOAG 12,871 25,918 12,914 26,047
PrevSeverePOAG 9,297 22,555 9,312 22,613
TABLE 9.5: NET PRESENT VALUE Of DALYS AND COSTS, SENSITIVITY ANALYSIS ON OhT
PREVALENCE AND INCIDENCE fOR ThOSE AGED 80+ YEARS
Net present value Net present value
2005 to 2025 2005 to 2025
Zero OhT prevalence and Smoothed data
incidence for those aged
80 years or over
DALYs 154,656 155,150
BurdenofDiseaseCosts($million) 23,836 23,896
HealthSystemCosts($million) 8,636 8,759
ComorbidHealthCosts($million) 4,474 4,505
TreatmentCosts($million) 4,162 4,254
ProductivityCosts($million) 1,660 1,665
OtherIndirectCosts($million) 2,666 2,695
TotalCosts($million) 36,798 37,015

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9.2: IMkOVLD DIAGNOSIS kA1L
Morethan50%ofthoseindevelopedcountrieswithglaucomaareunawaretheyhavethe
disease(Quigley,1996).Inapopulationbasedstudy(theMVIP),Wensoretal,(1998)found
that50%ofthosewithdefnitePOAGhadnotbeendiagnosedpreviously,andWongetal,
(2004)examinedthepresenceofundiagnosedOAGinpeoplewhohadvisitedaneyecare
providerinthepreviousyearusingVisualImpairmentProjectdatafromMelbourneandrural
communitiesinVictoria.Theyfoundthat81%ofpossiblecases,72%ofprobablecasesand
59%ofdefnitecasesofOAGwerepreviouslyundiagnosed.Ofthe115participantswith
probableordefniteOAG,72(63%)werepreviouslyundiagnosed.Oftheseundiagnosed
probableanddefnitecases,35(49%)hadvisitedaneyecareproviderwithintheprevious12
monthperiod.The35undiagnosedpatientswerecomparedwith43diagnosedpatientswho
hadvisitedanoptometristorophthalmologistorbothintheprevious12months.Thetype
ofeyeprofessionalseen,andthepresenceofVFdefectsweretheonlystatisticallysignifcant
variablesbetweenthediagnosedandundiagnosedglaucomagroups.
DiagnosisratesforPOAGcouldbeimprovedby:
1) atthecurrentdiagnosisthreshold,enhancingthequalityofcarebyensuring
ophthalmologistsincludetheappropriateVFtestswhenexaminingpatientseyes;
2) carefulexaminationoftheopticdiscinallpatientsregardlessofIOP;and
3) improvingthefocusonfamilyhistorysincepeoplewithafamilyhistoryofglaucoma
haveahigherchanceofdevelopingPOAG.
Underthebasecasescenario,50%ofpeoplewithPOAGarediagnosedandtreated.Underthis
scenario,theimpactofincreasingtheproportionofpeoplediagnosedwithPOAGto(i)70%,
(ii)80%and(iii)90%canbeassessed.Nocostshavebeenaddedtothemodeltoallowfor
educationofclinicians.
Underthisscenariotheonlyparameterthatisvariedistherateatwhichpeoplearediagnosed.
Thecostsandbeneftsthatresultfromthisanalysisrefectmorepeoplereceivingtreatmentto
slowprogressionofPOAG.
9.2.1: TO RUN ThIS INTERVENTION ThROUGh ThE MODEL
TicktheNonewIntervention(Standardtreatment)boxandclickontheSetasBaseCase
buttontoensurethecurrentsituationisthecomparator.
Un-ticktheNonewIntervention(Standardtreatment)boxandmakesurethatthe
FrequencyEveryYearboxisticked.
OntheOptionssheet,chooseImprovedDiagnosisRateintheSelectInterventionbox
andDiagnosisRate70%,orDiagnosisRate80%,orDiagnosisRate90%intheSelect
InterventionDetailbox.
ThenclicktheSetasScenario1button,torunthenewscenario.
AsecondscenariocanbeevaluatedbyreselectingfromtheSelectInterventionandSelect
InterventionDetailwindows.ThenclicktheSetasScenario2button,torunthenew
scenario.
ClickCompareScenarios(CEA).
9. Intervention Scenarios
At present,
50% of people
with POAG are
undiagnosed.
Centre for Eye Research Australia
81 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
9. Intervention Scenarios
9.2.2: RESULTS
Inthebasecase,50%ofpeoplewithPOAGarediagnosed.Theresultsofincreasingtherateof
diagnosisarepresentedinTable96.Theestimatesinthetablerefectthenetpresentvalueof
costsandbeneftsovertheentireperiod(2005to2025).Incomparisonwiththebasecase,the
increaseddiagnosisratereducesthetotalnumberofDALYs(Table96)asmorepeoplereceive
benefcialtreatment,however,thismeansthattreatmentcostsrise.Productivitycostsand
comorbidhealthcostsarelessthanforthebasecasebecauseagreaterproportionofpeople
receivetreatmentwhichslowdiseaseprogressionallowingthemtospendmoretimein
employment,andtoavoidcomorbidconditionssuchasdepression,fallsandfracturesassociated
withthelaterstagesofglaucoma.
TABLE 9.6: MODEL RESULTS INCREASED DIAGNOSIS RATE, NET PRESENT VALUE 2005 TO 2025
Net Present Values, Base Case
2005 to 2025 (Standard Diagnosis rate Diagnosis rate Diagnosis rate
treatment) 70% 80% 90%
DALYs 155,150 146,141 142,248 138,702
BurdenofDiseaseCosts($m) 23,896 22,249 21,529 20,866
HealthSystemCosts($m) 8,759 10,091 10,747 11,400
ComorbidHealthCosts($m) 4,505 4,403 4,354 4,307
TreatmentCosts($m) 4,254 5,687 6,393 7,093
ProductivityCosts($m) 1,665 1,514 1,443 1,373
OtherIndirectCosts($m) 2,695 2,894 2,993 3,092
TotalCosts($m) 37,015 36,748 36,711 36,731
CL ratio: keturn on $1 spent{a) $1.19 $1.14 $1.10
$/DALY avoided{b) $153,144 $159,908 $166,948
(a)CEratioisthechangeintotaldiseasecostsdividedbythechangeintreatmentcosts.(b)$/DALYavoidedisthe
changeinhealthsystem,productivityandotherindirectcostsdividedbythedifferenceinDALYs.
Figure9.3showstheoutcomeofadiagnosisrateof70%and90%.Inthebasecase,DALYsrise
to15,600in2025(Table9.2).Withimproveddiagnosis,theburdenofdiseaseislowerin2025
thaninthebasecase14,300DALYs(70%diagnosed)and13,200DALYs(90%)diagnosedin
2025(Figure9.3).However,withhigherdiagnosisrates,treatmentcostsarealsohigherthanin
thebasecase(Figure9.4).
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9. Intervention Scenarios
fIGURE 9.3: IMPACT Of INCREASED DIAGNOSIS RATES ON DALYS(A)
fIGURE 9.4: IMPACTS Of INCREASED DIAGNOSIS RATES ON TREATMENT COSTS
TherelativecosteffectivenessofeachscenarioisdepictedinFigure9.5.Thebasecaseis
representedattheorigin.EffectivenessismeasuredasthetotalnumberofDALYsavoidedand
costsaretotalcosts(excludingthevalueoftheburdenofdisease).
Atzeroadditionalcosts(ie.noadditionalcostsofeducatingcliniciansinordertoimprove
diagnosisrates),improveddiagnosisratesfrom50%to70%,80%and90%,are cost
effective at between $153,000 and $167,000 per DALY avoided.
Ifeducatingclinicianswerecostly,thesescenarioswouldbecomelesscosteffective.

Economic impact of primary open angle glaucoma Commercial-in-Confidence
80
diagnosed in 2025 (Figure 9-3). However, with higher diagnosis rates, treatment costs are
also higher than in the base case (Figure 9-4).
FIGURE 9-3: IMPACT OF INCREASED DIAGNOSIS RATES ON DALYS(A)
DALYs
0
2,000
4,000
6,000
8,000
10,000
12,000
14,000
16,000
18,000
2005 2010 2015 2020 2025
Base Case (Standard treatment)
Diagnosis rate 70%
Diagnosis rate 90%
FIGURE 9-4: IMPACTS OF INCREASED DIAGNOSIS RATES ON TREATMENT COSTS
Treatment Costs
0
100,000,000
200,000,000
300,000,000
400,000,000
500,000,000
600,000,000
700,000,000
2005 2010 2015 2020 2025
Base Case (Standard treatment)
Diagnosis rate 70%
Diagnosis rate 90%
The relative cost effectiveness of each scenario is depicted in Figure 9-5. The base case is
represented at the origin. Effectiveness is measured as the total number of DALYs avoided
and costs are total costs (excluding the value of the burden of disease).
At zero additional costs (ie. no additional costs of educating clinicians in order to improve
diagnosis rates), improved diagnosis rates from 50% to 70%, 80% and 90%, are cost
effective at between $153,000 and $167,000 per DALY avoided.
If educating clinicians were costly, these scenarios would become less cost effective.
Economic impact of primary open angle glaucoma Commercial-in-Confidence
80
diagnosed in 2025 (Figure 9-3). However, with higher diagnosis rates, treatment costs are
also higher than in the base case (Figure 9-4).
FIGURE 9-3: IMPACT OF INCREASED DIAGNOSIS RATES ON DALYS(A)
DALYs
0
2,000
4,000
6,000
8,000
10,000
12,000
14,000
16,000
18,000
2005 2010 2015 2020 2025
Base Case (Standard treatment)
Diagnosis rate 70%
Diagnosis rate 90%
FIGURE 9-4: IMPACTS OF INCREASED DIAGNOSIS RATES ON TREATMENT COSTS
Treatment Costs
0
100,000,000
200,000,000
300,000,000
400,000,000
500,000,000
600,000,000
700,000,000
2005 2010 2015 2020 2025
Base Case (Standard treatment)
Diagnosis rate 70%
Diagnosis rate 90%
The relative cost effectiveness of each scenario is depicted in Figure 9-5. The base case is
represented at the origin. Effectiveness is measured as the total number of DALYs avoided
and costs are total costs (excluding the value of the burden of disease).
At zero additional costs (ie. no additional costs of educating clinicians in order to improve
diagnosis rates), improved diagnosis rates from 50% to 70%, 80% and 90%, are cost
effective at between $153,000 and $167,000 per DALY avoided.
If educating clinicians were costly, these scenarios would become less cost effective.
Increasing the
diagnosis rate to
80% would cost
$160,000/DALY.
Centre for Eye Research Australia
83 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
9. Intervention Scenarios
fIGURE 9.5: COST EffECTIVENESS PLANE INCREASE DIAGNOSIS RATE(A)
(a)EffectivenessmeasuredasDALYsavoided.Costsrefecthealthsystem,productivityandotherindirectcosts.
(CosteffectivenessismeasuredasthecostperDALYavoided.Thevalueoftheburdenofdiseaseisexcludedfrom
thecostestimateinthenumeratorsincethisisrepresentedbyDALYsavoidedinthedenominator).
9.3: CHANGL IN 1HL 1kLA1MLN1 kO1OCOL {kIMAkY LASLk)
Asnotedabove,inbrief,thebasecaseparametersare:aPOAGdiagnosisrateof50%,
treatmentregimenofmedicationfrst,followedbylaserandthenfnallybysurgery,failure
ratesformedicationof4.3%ofpatientsperannum,50%forlasertrabeculoplastyand50%
fortrabeculectomy,andanoverallimpactoftreatmentonvision(treatmenteffcacy)ofa
50%reductionintheprogressionofvisualimpairment.UnderthisscenarioChangeinthe
treatmentprotocollaserreplacestopicalmedicationasfrstlinetherapyfrom2005onwards
sothatpatientsbegintreatmentwithalasertrabeculoplasty,thenfollowwithmedicationand
fnallytrabeculectomy.
Treatmentcost-savingsarepossiblefromthisscenario,asmedicationisnolongerrequired
incombinationwithlasertreatment.Underthebasecase,ontheotherhand,wherelaseris
secondlinetherapy,itiscombinedwithmedication.
TheGLT(whichcomparedtwo180degreeALTtreatmentswithtimolol)showedthatALTwasat
leastaseffcaciousasmedicationasaninitialtreatmentforglaucoma(GlaucomaLaserTrialResearch
Group,1995).However,ALTwasnotcommonlyadoptedasaprimarytreatmentbecauseofconcern
aboutsideeffectsandthereducedeffcacyofrepeatALTtreatments.Inaddition,atthetimeofthe
GLT,prostaglandinswerenotinuseastopicalmedicationsforglaucoma(asMcIlraithetal,(2006)
noted).Evidencefortheeffectivenessoflasertreatmentsasaprimarytherapyinclude:
TheEMGT,arandomisedclinicaltrialcomparingALTandmedicationwithnotreatment,
foundthat,whenadjustedforcensoringandothercovariates,progressionriskwashalvedby
treatment.After6years,theHRwas0.5(95%CI0.35to0.71).
Nagaretal,2005,whoconductedarandomisedprospectivestudycomparing360degree
selectivelasertherapy(SLT)with0.005%latanoprostatnight,foundnodifferencesinmean
VFdefectsbetweengroupsafter12months.
McIlraithetal,2006,inanon-randomisedpilotstudyof100eyesnewlydiagnosedPOAG
andOHTin61patients,andcomparing180degreeSLTwithlatanoprost,foundthatthetwo
treatmentswereequallyeffcaciousinreducingIOPinover12months.
Commercial-in-Confidence Economic impact of primary open angle glaucoma
81
FIGURE 9-5: COST EFFECTIVENESS PLANE INCREASE DIAGNOSIS RATE(A)
Diagnosis rate 70%
Diagnosis rate 90%
0
500,000,000
1,000,000,000
1,500,000,000
2,000,000,000
2,500,000,000
3,000,000,000
0 2,000 4,000 6,000 8,000 10,000 12,000 14,000 16,000 18,000
Effectiveness
C
o
s
t
s
(a) Effectiveness measured as DALYs avoided. Costs reflect health system, productivity and other indirect costs.
(Cost effectiveness is measured as the cost per DALY avoided. The value of the burden of disease is excluded
from the cost estimate in the numerator since this is represented by DALYs avoided in the denominator).
9.3 CHANGE IN THE TREATMENT PROTOCOL (PRIMARY
LASER)
As noted above, in brief, the base case parameters are: a POAG diagnosis rate of 50%,
treatment regimen of medication first, followed by laser and then finally by surgery, failure
rates for medication of 4.3% of patients per annum, 50% for laser trabeculoplasty and 50% for
trabeculectomy, and an overall impact of treatment on vision (treatment efficacy) of a 50%
reduction in the progression of visual impairment. Under this scenario Change in the
treatment protocol laser replaces topical medication as first line therapy from 2005
onwards so that patients begin treatment with a laser trabeculoplasty, then follow with
medication and finally trabeculectomy.
Treatment cost-savings are possible from this scenario, as medication is no longer required in
combination with laser treatment. Under the base case, on the other hand, where laser is
second line therapy, it is combined with medication.
The GLT (which compared two 180 degree ALT treatments with timolol) showed that ALT was
at least as efficacious as medication as an initial treatment for glaucoma (Glaucoma Laser
Trial Research Group, 1995). However, ALT was not commonly adopted as a primary
treatment because of concern about side effects and the reduced efficacy of repeat ALT
treatments. In addition, at the time of the GLT, prostaglandins were not in use as topical
medications for glaucoma (as McIlraith et al, (2006) noted). Evidence for the effectiveness of
laser treatments as a primary therapy include:
The EMGT, a randomised clinical trial comparing ALT and medication with no treatment,
found that, when adjusted for censoring and other covariates, progression risk was
halved by treatment. After 6 years, the HR was 0.5 (95% CI 0.35 to 0.71).
Nagar et al, 2005, who conducted a randomised prospective study comparing 360
degree selective laser therapy (SLT) with 0.005% latanoprost at night, found no
differences in mean VF defects between groups after 12 months.
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9. Intervention Scenarios
Sanflippo(1999)citedresearchsuggestingALTwasmoreeffcaciousthatpilocarpine.Two
yearsuccessrateswhenassessingIOPwere63%and44%fortheALTandpilocarpinegroups
respectively.ItwasfoundthatALTgaveasignifcantlybetterpreservationoftheVFthan
pilocarpine.ThroughregressionanalysisthetimelefttoblindnessfortheALTgroupwas31years
andforthepilocarpine-treatedgroup,12years(assumingalineardecay)(SanflippoP,1999).
9.3.1: TO RUN ThIS INTERVENTION ThROUGh ThE MODEL
Toensureyoustartwithablankpage,ontheOptionssheet,clickthescenarioresetbuttons.
TicktheNonewintervention(Standardtreatment)box
Selectfrequencyeveryyear
clickontheSetasBaseCasebutton(sothatstandardtreatmentisthecomparator).
Un-ticktheNonewintervention(Standardtreatment)box.
MakesurethattheFrequencyEveryYearboxisticked.
OntheOptionssheets,chooseChangeTreatmentProtocolintheSelectInterventionbox
andPrimarylasertrabeculoplastyintheSelectInterventionDetailbox.Thenclickthe
SetasScenario1button,torunthenewscenario.
ClickCompareScenarios(CEA).
9.3.2: RESULTS
TheresultsarepresentedinTable9.7.Thechangeintreatmentprotocoliscost-saving
(consistentwiththehypothesisabove).Thereislittleimpactontheresultsifthecostoflaseris
tripledorincreasesfvefoldtoaccountforthecostofsideeffects(assumingthesecanbefxed
relativelyquicklysothereisnoimpactonthepatientsqualityoflife)(Table9.7).
Figure9.6showsthatthecost-savingsassociatedwiththenewprotocolincreaseovertimeas
morepeoplearediagnosedandtreatedforPOAGbecauseofpopulationageing.Theburdenof
diseaseisdepictedinFigure9.7.
TABLE 9.7: MODEL RESULTS PROTOCOL ChANGE TRABECULOPLASTY AS PRIMARY TREATMENT
Net Present Standard Primary Standard Primary Standard Primary
Values Laser treatment treatment Laser treatment Laser
($724) ($2,173) ($3,622)
DALYs 155,150 155,974 155,150 155,974 155,150 155,974
BurdenofDisease 23,896 24,095 23,877 24,070 23,858 24,046
Costs($m)
HealthSystem 8,759 8,392 8,865 8,548 8,971 8,703
Costs($m)
ComorbidHealth 4,505 4,519 4,505 4,519 4,505 4,519
Costs($m)
TreatmentCosts($m) 4,254 3,873 4,360 4,029 4,465 4,184
ProductivityCosts($m) 1,665 1,671 1,665 1,671 1,665 1,671
OtherIndirectCosts($m) 2,695 2,628 2,715 2,658 2,736 2,689
TotalCosts($m) 37,015 36,787 37,122 36,948 37,230 37,109
CL ratio: keturn on $0.40 $0.47 $0.57
$1 spent{a) Cost- Cost- Cost-
$/DALY avoided Saving Saving Saving

(a)Defnedasthedifferenceinindirectcostsbetweenprimarylaserandthebasecaseforeveryadditionaldollarspentontreatment.

Centre for Eye Research Australia
85 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
9. Intervention Scenarios
fIGURE 9.6: COST-SAVINGS RESULTING fROM A PROTOCOL ChANGE(A)
(a)Lasercosting$724pertreatment.
fIGURE 9.7: BURDEN Of DISEASE
Economic impact of primary open angle glaucoma Commercial-in-Confidence
84
FIGURE 9-7 BURDEN OF DISEASE
DALYs
0
2,000
4,000
6,000
8,000
10,000
12,000
14,000
16,000
18,000
2005 2010 2015 2020 2025
Base Case (Standard treatment)
Primary laser trabeculoplasty
Scenario 2
9.3.3 SENSITIVITY ANALYSIS THE IMPACT OF THE CONSERVATIVE
APPROACH TO SURGERY FAILURE RATES
Taking a conservative approach to the surgery failure rate doesnt substantively affect the
results because treatment efficacy is measured according to whether a patient is treated or not
rather than the particular treatment the patient receives. In other words, all treated patients
(no matter what order they receive treatments) experience a reduction in progression of visual
impairment by 50% compared with people who have undiagnosed POAG. Taking a
conservative approach to the surgery failure rate means that more patients progress more
quickly to medications bringing forward the costs of medications for those patients and
leading to higher health system cost estimates (Table 9-8) . Repeat surgery may also be
performed. Based on MBS data surgery is performed at a rate of 1.2 and costs have been
factored accordingly.
Commercial-in-Confidence Economic impact of primary open angle glaucoma
83
TABLE 9-7: MODEL RESULTS PROTOCOL CHANGE TRABECULOPLASTY AS PRIMARY
TREATMENT
Net Present
Values
Standard
treatment
Primary
Laser
($724)
Standard
treatment
Primary
Laser
($2,173)
Standard
treatment
Primary
Laser
($3,622)
DALYs 155,150 155,974 155,150 155,974 155,150 155,974
Burden of
Disease
Costs ($m) 23,896 24,095 23,877 24,070 23,858 24,046
Health
System
Costs ($m) 8,759 8,392 8,865 8,548 8,971 8,703
Comorbid
Health Costs
($m) 4,505 4,519 4,505 4,519 4,505 4,519
Treatment
Costs ($m) 4,254 3,873 4,360 4,029 4,465 4,184
Productivity
Costs ($m) 1,665 1,671 1,665 1,671 1,665 1,671
Other Indirect
Costs ($m) 2,695 2,628 2,715 2,658 2,736 2,689
Total Costs
($m) 37,015 36,787 37,122 36,948 37,230 37,109
CE ratio:
Return on $1
spent(a) $0.40 $0.47 $0.57
$/DALY
avoided
Cost-
Saving
Cost-
Saving
Cost-
Saving
(a) Defined as the difference in indirect costs between primary laser and the base case for every additional dollar
spent on treatment.
FIGURE 9-6: COST-SAVINGS RESULTING FROM A PROTOCOL CHANGE(A)
Treatment Costs
0
50,000,000
100,000,000
150,000,000
200,000,000
250,000,000
300,000,000
350,000,000
400,000,000
2005 2010 2015 2020 2025
Base Case (Standard treatment)
Primary laser trabeculoplasty
Scenario 2
(a) Laser costing $724 per treatment.
Laser trabeculoplasty
actually saves money
when used as the
initial treatment.
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9. Intervention Scenarios

9.3.3: SENSITIVITY ANALYSIS ThE IMPACT Of ThE CONSERVATIVE APPROACh
TO SURGERY fAILURE RATES
Takingaconservativeapproachtothesurgeryfailureratedoesntsubstantivelyaffectthe
resultsbecausetreatmenteffcacyismeasuredaccordingtowhetherapatientistreatedornot
ratherthantheparticulartreatmentthepatientreceives.Inotherwords,alltreatedpatients
(nomatterwhatordertheyreceivetreatments)experienceareductioninprogressionofvisual
impairmentby50%comparedwithpeoplewhohaveundiagnosedPOAG.Takingaconservative
approachtothesurgeryfailureratemeansthatmorepatientsprogressmorequicklyto
medicationsbringingforwardthecostsofmedicationsforthosepatientsandleadingto
higherhealthsystemcostestimates(Table9.8).Repeatsurgerymayalsobeperformed.Based
onMBSdatasurgeryisperformedatarateof1.2andcostshavebeenfactoredaccordingly.
TABLE 9.8: SENSITIVITY ANALYSIS A CONSERVATIVE APPROACh TO SURGERY
fAILURE RATES
Net Present Standard Primary Laser Standard Primary Laser
Values treatment ($724) treatment ($724)
Laser failure rate 50%, Laser failure rate 50%,
surgery failure rate 50% surgery failure rate 10%
DALYs 155,150 155,974 155,150 155,974
BurdenofDiseaseCosts($m) 23,896 24,095 23,950 24,144
HealthSystemCosts($m) 8,759 8,392 8,468 8,128
ComorbidHealthCosts($m) 4,505 4,519 4,505 4,519
TreatmentCosts($m) 4,254 3,873 3,963 3,609
ProductivityCosts($m) 1,665 1,671 1,665 1,671
OtherIndirectCosts($m) 2,695 2,628 2,638 2,576
TotalCosts($m) 37,015 36,787 36,721 36,520
CL ratio: keturn on $1 spent{a) $0.40 $0.43
$/DALY avoided Cost-Saving Cost-Saving
(a)Defnedasthedifferenceinindirectcostsbetweenprimarylaserandthebasecaseforeveryadditionaldollarspent
ontreatment.
Centre for Eye Research Australia
87 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
9. Intervention Scenarios
9.4: kLSLAkCH AND DLVLLOMLN1
Thisscenariolooksatthepossiblereturnsfromnewtreatmentsthatmightbedevelopedto
furtherslowtheprogressionofPOAG.Onepossibleexamplecurrentlyunderinvestigation
mightbeneuroprotectionwiththedrugMemantine(anNMDA
22
-receptorantagonistcurrently
usedforAlzheimersdisease).MemantineiscurrentlyinphaseIIItrialsforglaucomaandatthe
timeofwritingtreatmenteffcacyresultswerenotavailable.
Themodelallowsfortwopossiblenewtreatmenteffcacyoptionsthenewtherapyreduces
theprogressionofglaucomabyafurther50%or75%overandabovethereductionin
progressionfromcurrenttreatments.Itisassumedthatthehypotheticaltreatmentisgiven
toeachpersonbeingtreatedforPOAG,regardlessoftheirtreatmentstage.The new therapy
is taken continuously over the patients remaining life. Thetreatmentisaddedtocurrent
treatmentsratherthansubstitutingforthem.Inthismodel,theannualcostperpersonforthis
treatmenthasbeensetat$1,000regardlessofeffcacy.
9.4.1: TO RUN ThIS INTERVENTION ThROUGh ThE MODEL
Toensureyoustartwithablankpage,ontheOptionssheet,clicktheresetbuttons.
OntheOptionssheets,chooseResearchandDevelopmentintheSelectInterventionbox
andR&DReducesProgression(50%),orR&DReducesProgression(75%).
TicktheNonewIntervention(StandardTreatment)boxandclickontheSetasBaseCase
buttontosetthecurrentsituationasthebasecomparator.
Un-ticktheNonewIntervention(StandardTreatment)boxandmakesurethatthe
FrequencyEveryYearboxisticked.ThenclicktheSetasScenario1button,torunthe
newscenario.
ClickCompareScenarios(CEA).
9.4.2: RESULTS
Theresultsofintroducingtwonewtherapiesthatreduceprogressionby50%andby75%over
thebasecasearepresentedinTable9.8.Comparedwiththebasecase,thenetpresentvalue
ofDALYs,productivitycostsandcomorbidcostsarelower.Theresultsrefectthebenefts
ofdelayingprogression,allowingpeopletoremaininwork,andexperiencefewercomorbid
conditionsthatareassociatedwiththelaterstagesofglaucoma.ThedeclineinDALYsovertime
associatedwithdelayingprogressionby50%and75%overthebasecaseisdepictedinFigure9.8.
22
N-methyl-D-aspartate
The impact of new
treatments to reduce
progression was
examined.
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9. Intervention Scenarios
Treatments with
annual costs over
$5000 are expensive
but cost effective.
fIGURE 9.8: DECLINE IN DALYS fROM NEW EffICACIOUS TREATMENT
Healthsystemcostsontheotherhandarehigherwiththenewtreatmentbecausethe
treatmentisaddedtocurrentlyavailabletherapies(Figure9.9).
fIGURE 9.9: TREATMENT COSTS WITh NEW TREATMENTS COSTING $1000 PER PERSON PER YEAR
Overall,costeffectivenessdependsonthecostperpersonperannumofthenewtreatment
(Table9.8).Attreatmentcostsof$1,000perpersonperannum,newtreatmentsarecostsaving.
However,ifthenewtreatmentsthatdelayprogressionby50%overthebasecasecostmore
than$5,000perpersonperannum,theywouldbecomerelativelyexpensive(costeffectiveness
ratiosofbeyond$60,000perDALYavoided).
Economic impact of primary open angle glaucoma Commercial-in-Confidence
86
Tick the No new Intervention (Standard Treatment) box and click on the Set as Base
Case button to set the current situation as the base comparator.
Un-tick the No new Intervention (Standard Treatment) box and make sure that the
Frequency Every Year box is ticked. Then click the Set as Scenario 1 button, to run
the new scenario.
Click Compare Scenarios (CEA).
9.4.2 RESULTS
The results of introducing two new therapies that reduce progression by 50% and by 75% over
the base case are presented in Table 9-9. Compared with the base case, the net present
value of DALYs, productivity costs and comorbid costs are lower. The results reflect the
benefits of delaying progression, allowing people to remain in work, and experience fewer
comorbid conditions that are associated with the later stages of glaucoma. The decline in
DALYs over time associated with delaying progression by 50% and 75% over the base case is
depicted in Figure 9-8.
FIGURE 9-8: DECLINE IN DALYS FROM NEW EFFICACIOUS TREATMENT
DALYs
0
2,000
4,000
6,000
8,000
10,000
12,000
14,000
16,000
18,000
2005 2010 2015 2020 2025
Base Case (Standard treatment)
R&D reduces progression 50%
R&D reduces progression 75%
Health system costs on the other hand are higher with the new treatment because the
treatment is added to currently available therapies (Figure 9-9).
Commercial-in-Confidence Economic impact of primary open angle glaucoma
87
FIGURE 9-9 TREATMENT COSTS WITH NEW TREATMENTS COSTING $1000 PER PERSON PER YEAR
Treatment Costs
0
50,000,000
100,000,000
150,000,000
200,000,000
250,000,000
300,000,000
350,000,000
400,000,000
450,000,000
2005 2010 2015 2020 2025
Base Case (Standard treatment)
R&D reduces progression 50%
R&D reduces progression 75%
Overall, cost effectiveness depends on the cost per person per annum of the new treatment
(Table 9-9). At treatment costs of $1,000 per person per annum, new treatments are cost
saving. However, if the new treatments that delay progression by 50% over the base case
cost more than $5,000 per person per annum, they would become relatively expensive (cost
effectiveness ratios of beyond $60,000 per DALY avoided).
Centre for Eye Research Australia
89 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
9. Intervention Scenarios
TABLE 9.9: MODEL RESULTS RESEARCh AND DEVELOPMENT ShOWING ThE IMPACT Of
NEW TREATMENT TO REDUCE PROGRESSION BY 50% AND 75%
Cost of new $1,000 per person $5,000 per person $10,000 per person
treatment per annum per annum per annum
Net resent 8ase 50% 75% 50% 75% 50% 75%
Va|ues Case
DALYs 155,150 134,793 125,718 134,793 25,718 134,793 125,718
Burdenof
DiseaseCosts
($m) 23,896 20,660 19,240 20,510 19,091 20,324 18,905
HealthSystem 8,759 8,843 8,773 9,793 9,729 10,980 10,924
Costs($m)
Comorbid 4,505 4,319 4,227 4,319 4,227 4,319 4,227
Health
Costs($m)
Treatment 4,254 4,524 4,545 5,474 5,501 6,661 6,697
Costs($m)
Productivity 1,665 1,428 1,317 1,428 1,317 1,428 1,317
Costs($m)
OtherIndirect 2,695 2,623 2,575 2,808 2,762 3,040 2,995
Costs($m)
TotalCosts($m) 37,015 33,553 31,905 34,539 32,899 35,772 34,141
CL ratio: keturn $13.82 $18.55 $3.03 $4.30 $1.52 $2.18
on $1 spent
$/DALY avoided Cost- Cost- $44,670 $23,380 $114,386 $71,914
Saving Saving
9.5: COM8INA1IONS
Thissectionexaminestheimpactofcombiningtheinterventionswemodel.Twoscenariosare
availablehere.Bothinvolveanincreaseinthediagnosisrateforglaucomafrom50%to80%,
togetherwitheither:
theadditionofanewtherapythatdelaysprogressionbyafurther50%;or
achangeinthetreatmentprotocolsothatlaserbecomesthefrstlinetherapyinsteadof
medication.
9.5.1: TO RUN ThIS INTERVENTION ThROUGh ThE MODEL
Toensureyoustartwithablankpage,ontheOptionssheet,clicktheresetbuttons.
OntheOptionssheets,choose5.CombinedscenariosintheInterventionFocusboxand
5.1Scenario1.2and4.1,or5.1Scenario1.2and3.1intheInterventionDetailbox.
TicktheNoIntervention(CurrentSituation)boxandclickontheSetasBaseCasebutton
tosetthecurrentsituationasthebasecomparator.
Un-ticktheNoIntervention(CurrentSituation)boxandmakesurethattheFrequency
EveryYearboxisticked.ThenclicktheSetasScenario1button,torunthenewscenario.
AsecondscenariocanbeevaluatedbyreselectingfromtheInterventionsFocusboxaswellas
theInterventionsDetailbox.ThenclicktheSetasScenario2button,torunthenewscenarios.
ClickCompareScenarios(CEA).
The combined effects
of better diagnosis
and laser frst, or
better diagnosis and a
new treatment were
examined.
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9. Intervention Scenarios

Economic impact of primary open angle glaucoma Commercial-in-Confidence
90
FIGURE 9-10: REDUCTION IN DALYS, COMBINED INTERVENTIONS
DALYs
0
2,000
4,000
6,000
8,000
10,000
12,000
14,000
16,000
18,000
2005 2010 2015 2020 2025
Base Case (Standard treatment)
Diagnosis rate 80% and R&D
reduces progression 50%
Diagnosis rate 80% and primary
laser trabeculoplasty
Treatment costs increase over time (driven by an ageing population and an increase in the
proportion of people with POAG who are diagnosed from 50% in the base case to 80% in each
of the combined scenarios) (Figure 9-11). The pattern of total costs over time are shown in
Figure 9-12.
FIGURE 9-11: TREATMENT COSTS, COMBINED INTERVENTIONS
Treatment Costs
0
100,000,000
200,000,000
300,000,000
400,000,000
500,000,000
600,000,000
700,000,000
2005 2010 2015 2020 2025
Base Case (Standard treatment)
Diagnosis rate 80% and R&D
reduces progression 50%
Diagnosis rate 80% and primary
laser trabeculoplasty
9.5.2: RESULTS
TheresultsofthecombinedscenariosarerefectedinTable9.10.Bothscenariosreducethe
totalDALYscomparedwiththebasecase(Table9.10).
TABLE 9.10: MODEL RESULTS COMBINED SCENARIOS
Net Present Base Case Diagnosis rate Diagnosis rate
Values standard 80% and 80% and
treatment R&D reduces primary laser
progression 50% trabeculoplasty
DALYs 155,150 121,220 149,999
BurdenofDiseaseCosts($m) 23,896 18,184 21,752
HealthSystemCosts($m) 8,759 10,921 10,156
ComorbidHealthCosts($m) 4,505 4,132 4,367
TreatmentCosts($m) 4,254 6,789 5,789
ProductivityCosts($m) 1,665 1,133 1,448
OtherIndirectCosts($m) 2,695 2,918 2,882
TotalCosts($m) 37,015 33,157 36,237
CL ratio: keturn on $1 spent $2.52 $1.51
$/DALY avoided $54,607 $112,411
TheimprovementstototalDALYsincreaseoverthedurationofthemodel(Figure9.10)withthe
increasedbeneftfromthefrstScenariobecomingmoreprominentovertime.
fIGURE 9.10: REDUCTION IN DALYS, COMBINED INTERVENTIONS
Treatmentcostsincreaseovertime(drivenbyanageingpopulationandanincreaseinthe
proportionofpeoplewithPOAGwhoarediagnosedfrom50%inthebasecaseto80%ineach
ofthecombinedscenarios)(Figure9.11).Thepatternoftotalcostsovertimeareshownin
Figure9.12.
Treatment costs
increase over time
because of an ageing
population and
an increase in the
proportion of people
with POAG who are
diagnosed from 50%
in the base case to
80% in each of the
combined scenarios.
Centre for Eye Research Australia
91 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
9. Intervention Scenarios
Thecosteffectiveness(relativetothebasecase)ofthetwoscenariosisshowninFigure9.13.
Thebasecaseisrepresentedattheorigin.
fIGURE 9.13: COST EffECTIVENESS PLANE, COMBINED SCENARIOS(A)
(a)EffectivenessmeasuredasDALYsavoided.Costsrefecthealthsystem,productivityandotherindirectcosts.(Cost
effectivenessismeasuredasthecostperDALYavoided.Thevalueoftheburdenofdiseaseisexcludedfromthecost
estimateinthenumeratorsincethisisrepresentedbyDALYsavoidedinthedenominator).
Combining better
diagnosis rates with
a hypothetical new
therapy to further
reduce progression is
more cost effective
than combining
better diagnosis
rates with primary
trabeculoplasty.
fIGURE 9.11: TREATMENT COSTS, COMBINED INTERVENTIONS
fIGURE 9.12: TOTAL COSTS, COMBINED SCENARIOS
Economic impact of primary open angle glaucoma Commercial-in-Confidence
90
FIGURE 9-10: REDUCTION IN DALYS, COMBINED INTERVENTIONS
DALYs
0
2,000
4,000
6,000
8,000
10,000
12,000
14,000
16,000
18,000
2005 2010 2015 2020 2025
Base Case (Standard treatment)
Diagnosis rate 80% and R&D
reduces progression 50%
Diagnosis rate 80% and primary
laser trabeculoplasty
Treatment costs increase over time (driven by an ageing population and an increase in the
proportion of people with POAG who are diagnosed from 50% in the base case to 80% in each
of the combined scenarios) (Figure 9-11). The pattern of total costs over time are shown in
Figure 9-12.
FIGURE 9-11: TREATMENT COSTS, COMBINED INTERVENTIONS
Treatment Costs
0
100,000,000
200,000,000
300,000,000
400,000,000
500,000,000
600,000,000
700,000,000
2005 2010 2015 2020 2025
Base Case (Standard treatment)
Diagnosis rate 80% and R&D
reduces progression 50%
Diagnosis rate 80% and primary
laser trabeculoplasty
Commercial-in-Confidence Economic impact of primary open angle glaucoma
91
FIGURE 9-12: TOTAL COSTS, COMBINED SCENARIOS
Total Costs
0
500,000,000
1,000,000,000
1,500,000,000
2,000,000,000
2,500,000,000
3,000,000,000
3,500,000,000
4,000,000,000
4,500,000,000
2005 2010 2015 2020 2025
Base Case (Standard treatment)
Diagnosis rate 80% and R&D
reduces progression 50%
Diagnosis rate 80% and primary
laser trabeculoplasty
The cost effectiveness (relative to the base case) of the two scenarios is shown in Figure 9-13.
The base case is represented at the origin.
FIGURE 9-13: COST EFFECTIVENESS PLANE, COMBINED SCENARIOS(A)
Diagnosis rate 80% and R&D
reduces progression 50%
Diagnosis rate 80% and
primary laser trabeculoplasty
0
500,000,000
1,000,000,000
1,500,000,000
2,000,000,000
2,500,000,000
0 5,000 10,000 15,000 20,000 25,000 30,000 35,000 40,000
Effectiveness
C
o
s
t
s
(a) Effectiveness measured as DALYs avoided. Costs reflect health system, productivity and other indirect costs.
(Cost effectiveness is measured as the cost per DALY avoided. The value of the burden of disease is excluded
from the cost estimate in the numerator since this is represented by DALYs avoided in the denominator).
Commercial-in-Confidence Economic impact of primary open angle glaucoma
91
FIGURE 9-12: TOTAL COSTS, COMBINED SCENARIOS
Total Costs
0
500,000,000
1,000,000,000
1,500,000,000
2,000,000,000
2,500,000,000
3,000,000,000
3,500,000,000
4,000,000,000
4,500,000,000
2005 2010 2015 2020 2025
Base Case (Standard treatment)
Diagnosis rate 80% and R&D
reduces progression 50%
Diagnosis rate 80% and primary
laser trabeculoplasty
The cost effectiveness (relative to the base case) of the two scenarios is shown in Figure 9-13.
The base case is represented at the origin.
FIGURE 9-13: COST EFFECTIVENESS PLANE, COMBINED SCENARIOS(A)
Diagnosis rate 80% and R&D
reduces progression 50%
Diagnosis rate 80% and
primary laser trabeculoplasty
0
500,000,000
1,000,000,000
1,500,000,000
2,000,000,000
2,500,000,000
0 5,000 10,000 15,000 20,000 25,000 30,000 35,000 40,000
Effectiveness
C
o
s
t
s
(a) Effectiveness measured as DALYs avoided. Costs reflect health system, productivity and other indirect costs.
(Cost effectiveness is measured as the cost per DALY avoided. The value of the burden of disease is excluded
from the cost estimate in the numerator since this is represented by DALYs avoided in the denominator).
92
Tunne l Vi s i on
Centre for Eye Research Australia
10. Appendix 1: Meta-Analysis -
Falls and Hip Fractures
Section 6.3.4 presents the results of a meta analysis of literature that examined the increased
likelihood of an accidental fall and hip fracture with a visual impairment as well as specic VFL
or glaucoma impairment. The list of articles used in the meta-analysis is presented in Table 10.4,
Table 6.7 and Table 6.8. From those lists, studies that reported the risks of an accidental fall or
hip fracture as an OR were excluded, due to their technical incompatibility with RR (as well as a
lack of data to accurately convert the ORs into RRs).
Meta-analysis refers to the statistical analysis of analyses, where the results of multiple trials are
combined to estimate an overall effect size. A number of studies have been published examining
the impact that visual impairment has on the risk of an accidental fall and/or hip fracture. The
results of these studies have been combined to estimate an overall RR of an accidental fall for
people that have a visual impairment.
10.1: FIXED-EFFECTS VERSUS RANDOM-EFFECTS
An inverse variance methodology has been used to weight the study trials for both the xed
effects and random effects models
23
. The results of which are presented in Table 10.1.
TABLE 10.1: FIXED EFFECTS AND RANDOM EFFECTS, META-ANALYSIS RESULTS
Accidental Falls Hip Fractures
Visual Impairment VFL / Glaucoma
No. of Studies 13 6 9
Weighting Method, Inverse variance Inverse variance Inverse variance
FE RE Inverse variance +

Inverse variance +

Inverse variance +

Fixed Effects 1.33 (1.24 1.43) 2.52 (1.92 3.30) 1.43 (1.25 1.64)
(95% CI)
Random Effects 2.05 (1.54 2.71) 3.18 (1.82 5.55) 1.46 (1.24 1.73)
(95% CI)
The studies that specically examined VFL/Glaucoma are a subset of the visual impairment
group of studies. Overall the RR of an accidental fall was higher for people with glaucoma
(or VFL) than people with any type of visual impairment and the RR of an accidental fall is
higher than the RR of a hip fracture.
For all three groups, the RR of an accidental fall is greater in the random effects model than the
xed effects model. This indicates that heterogeneity exists between the combined studies.
The presence of heterogeneity is not unexpected as the studies incorporated into the meta-
analysis include different denitions, measures and severity criteria for visual impairment.
10.2: HETEROGENEITY
Heterogeneity between studies can be problematic when using a xed effects model (which
assumes that the studies used to determine the treatment effect have the same criteria). In this
instance the studies use a variety of different visual impairment, severity and other criteria and
it is not unexpected that (as seen in Table 10.1) heterogeneity exists. Table 10.2 displays a series
of statistical tests that estimate the presence of heterogeneity within the meta-analysis.
23
An inverse variance plus tau weighting method has been used for the random effects model.
93 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
Main heading to go here 10. Appendix 1: Meta-Analysis -
Falls and Hip Fractures
TABLE 10.2: HETEROGENEITY WITHIN THE COMBINED STUDIES
Accidental Falls Hip Fractures
Visual Impairment VFL / Glaucoma
Fixed Effects
Q-statistic 55.11 17.44 9.66
p-value (two-tailed) <0.0001 0.0037 0.2894
H-statistic (95% CI) 2.14 (1.65 2.78) 1.87 (1.23 2.85) 1.10 (1.00 1.57)
I
2
-statistic (95% CI) 78.22% 71.33% 17.22%
(63.23% - 87.10%) (33.42% - 87.66%) (0.00% - 59.21%)
Random Effects

2
-statistic 0.1630 0.3191 0.0110
Q statistic: is the main analysis of heterogeneity and tests whether the assumption that all
of the effect sizes are estimating the same population is reasonable. The test statistic has a
chi-square distribution with k-1 degrees of freedom. If the test is rejected, the distribution
of effect sizes is assumed to be heterogeneous.
H-statistic: describes the relative excess in Q over its degrees of freedom. When
considering a regression of a standardised treatment effect on the standard error, the slope
of an unweighted least squares regression line corresponds with the xed effect pooled
value. The H statistic is the residual SD from this regression. A low H statistic means high
consistency among study results.
I
2
-statistic: describes the percentage of total variation across studies that cannot be
attributed to chance or sampling error and varies between 0% and 100%. In the case of
consistent study results, the I2 is 0 or very low. P-values and CIs can be used to describe the
compatibility of the data-based statistic with a null-hypothesis.

2
-statistic: is an estimate of the between study variance. The -value is used in the
random effects model as an addition to the inverse variance study weight.
The statistical tests for heterogeneity presented in Table 10.2 indicate that heterogeneity
is present in the results of the accidental falls studies, however heterogeneity for studies
examining the relationship between visual impairment and falls is small.
The random effects methodology of meta-analysis has been used to control for this inter study
heterogeneity, for each interest group. The results are presented in the following section.
10.3: FOREST PLOTS
Figure 10.1, Figure 10.2 and Figure 10.3 display the forest plots of each study group using a
random effects meta-analysis methodology. The effect size of each trial is represented by the
red square with a black line indicating the 95% CI. The size of the red square for each trial
indicates the relative weight applied to each study result (using an inverse variance plus tau)
weighting methodology. This gives studies with lower standard errors higher weights, as results
with more accurate estimations are assumed to provide better estimations of the true effect
size. The overall effect size is displayed at the bottom of the gure as a grey diamond with a
horizontal line providing the 95% CI.
94
Tunne l Vi s i on
Centre for Eye Research Australia
10. Appendix 1: Meta-Analysis -
falls and hip fractures
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95 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
10. Appendix 1: Meta-Analysis -
falls and hip fractures
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96
Tunne l Vi s i on
Centre for Eye Research Australia
10. Appendix 1: Meta-Analysis -
falls and hip fractures
10.4: U8LICA1ION 8IAS
Publicationbiaspresentsasauniqueproblemformeta-analyses.Whiletheinclusionand
exclusionofstudiescanimpartsomecontroloverpublicationbias,thepotentialforitsexistence
isstillpresentwithstudiesshowinganeffectmorelikelytobepublishedthanstudiesthatshow
noeffectatall.Tosomeextentpublicationbiaswillalwaysbepresentwithinameta-analysis,
theproblemisthentoestimatehowlargeandwhateffecttheproblemhasontheresult.
TABLE 10.3: MEASURES Of PUBLICATION BIAS
Accidental falls hip fracture
Visual Impairment VfL / Glaucoma
Model RandomEffects RandomEffects RandomEffects
WeightingMethod IV+

IV+

IV+

OriginalOutcome 2.05(1.542.71) 3.18(1.825.55) 1.46(1.241.73)


(95%CI)
Lffect Assessment
RegressionModel Egger Egger Egger
Intercepts(95%CI) 2.22(1.173.27) 3.44(-1.117.99) 0.22(-1.652.09)
p-value(two-tailed) 0.0007 0.1036 0.7884
Sensitivity
Trim-and-fllmethod L0 L0 L0
Numberofimputed 5 0 0
studies
Resultingoutcome (1.55(1.182.02) 3.18(1.825.55) 1.46(1.241.73)
95%CI)
Aswithheterogeneityafewstatisticaltestshavebeendevelopedtoexaminetheextentof
potentialpublicationbiaswithinameta-analysis(Table10.3).Twomainstatisticaltestsare
appliedtotheresults,theseare:
Eggers small study effects:Aformaltestforpublicationbias.Thetestinvolvesregression
ofthez-scoresupontheinverseofthestandarderrorandtheinterceptoftheregressionline
isusedtomeasureasymmetry(aroundthestandardisedpooledvalue,0)whichisregarded
asasignofpublicationbias.
Trim-and-fll method: usesfunnelplotsymmetryasanindicatorforpublicationbiasand
estimatesthenumberofstudiesthathavenocounterpartontheothersideofthesymmetry
axis.Thesestudiesareremoved(trimmed)andanewsymmetry-axisiscalculated.Theprocedure
isrepeateduntilthereisnoasymmetryfound.Finally,thetrimmedstudiesareputbackinthe
funnelplottogetherwithhypotheticalcounterpartsandnewcombinedempiricalvaluescanbe
calculatedwithbothoriginalandimputedstudiesincluded.
Thep-valueforstudiesexaminingaccidentalfallsandvisualimpairmentislessthan5%
indicatingthatpublicationbiasispresentwithinthismeta-analyses,whilepublicationbias
fortheVFL/Glaucomaandhipfracturestudiesappearstoolow(pvaluesaregreaterthan5%).
Theeffectofthispublicationbiascanbeseenwiththetrim-and-fllmethod,whichindicatesthat
thetreatmenteffectshouldhaveaRRofapproximately1.55forpeoplewithavisualimpairment.
To some extent
publication bias will
always be present
within a meta-
analysis, the problem
is then to estimate
how large and what
effect the bias has on
the result.
Centre for Eye Research Australia
97 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
10. Appendix 1: Meta-Analysis -
falls and hip fractures
10.5: ADDI1IONAL SUOk1IVL LI1LkA1UkL
Anumberofadditionalarticleswerefoundduringtheliteraturesearchprocess,whichcould
notbeincludedwithinthemeta-analysisbecauseofincompleteorthelackofquantitative
informationrequired.TheseadditionalarticlesareshowninTable10.4.
TABLE 10.4: NON-QUANTITATIVE SUPPORTING LITERATURE
Visual Impairment Increased Risk Source
Visualimpairment Risk of frst, multiple and injurious falls: Arfkenetal,1994
wasnotsignifcantlyassociatedwith
visualimpairment
Visualimpairment Risk of fallwasnotsignifcantly Campbelletal,1989
(nospecifcdefnitionprovided) associatedwithvisualimpairment
60/60(facerecognition) ORofhip fracture=3.1 deBoeretal,2004*
Blindness/poorvision Risk of fall: wassignifcantlyassociated Gaebleretal,1993
(nospecifcdefnition withblindnessandpoorvision
provided)
Poorvision(nospecifc Risk of wrist fracturewaslowerinthe Haboubietal,1991
defnitionprovided) groupwithpoorvision
Best(corrected)VA Risk of fall: signifcantdifferencebetween Jacketal,1995
of<6/18 lowvisionofpatientsattendingforfalls
comparedwiththoseattendingforother
medicalproblems
Patientsdiagnosedwith: Risk of fall: amongpatientswithdiabetic Kameletal,2000
refractiveerrors,cataracts, retinopathyandglaucomathevision
glaucoma,diabetic questionnairehada100%sensitivityin
retinopathyand/orAMD identifyingpatientswithahistoryoffalls
ParticipantsoftheBeaver Risk of fall and hip fracture: was Kleinetal,1998
DamEyeStudy: signifcantlyassociatedwithVAinthe
VAbasedmeasures over60s,intheunder60sriskwasonly
associatedwithsomevisionmeasures
<6/12 ORofmultiple falls=1.75 Koski,1998*
Poordistancevision ORofmultiple falls=2.3 Koski,1998*
LowcontrastVAand Risk of multiple falls signifcantly Lordetal,1994
contrastsensitivity increasedinsubjectswithpoorVA
and/oralowabilitytoperceivecontrast
Blindness(nospecifc Risk of second hip fracturewas Saxenaetal,2000
defnitionprovided) signifcantlyincreasedintheblind/and
thosewithlowvision
Visuallyimpairedandblind Risk of fall: theblinddemonstrateda Tobisetal,1990
(nostrongerdefnitions higherriskthanthedeafornon-
provided) impairedpopulations
*Notenoughinformationcouldbeobtainedfromtheabstractstobeincludedinthemeta-analysis

98
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Centre for Eye Research Australia
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Centre for Eye Research Australia
This report was prepared jointly by the Centre
for Eye Research Australia and Access Economics
Pty Limited.
We acknowledge particularly the expert input
and prior research of
Professor Hugh Taylor AC
Centre for Eye Research Australia and
University of Melbourne
Professor Jonathan Crowston
Centre for Eye Research Australia and
University of Melbourne
Associate Professor Jill Keeffe OAM
Centre for Eye Research Australia and
University of Melbourne
Ms Lynne Pezzullo
Access Economics Pty Ltd
Ms Penny Taylor
Access Economics Pty Ltd
Mr Peter Moore
Access Economics Pty Ltd

Acknowledgments and Disclaimer
While every effort has been made to ensure the accuracy of this document, the uncertain nature of economic data,
forecasting and analysis means that Access Economics Pty Limited is unable to make any warranties in relation to the
information contained herein. Access Economics Pty Limited, its employees and agents disclaim liability for any loss or
damage which may arise as a consequence of any person relying on the information contained in this document.
Publication of this work has been made possible by an unrestricted grant from Allergan who had no part in the direction
or fndings contained in this report.
Centre for Eye Research Australia, University of Melbourne, Australia, February 2008.
Centre for Eye Research Australia
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The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model 105
Tunne l Vi s i on
The Economic Impact of
Primary Open Angle Glaucoma -
A Dynamic Economic Model
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Centre for Eye Research Australia
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