Eye disorders

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Glaucoma
Search date May 2010 Rajiv Shah and Richard P L Wormald ABSTRACT
INTRODUCTION: Glaucoma is characterised by progressive optic neuropathy and peripheral visual field loss. It affects 1% to 2% of white people aged over 40 years and accounts for 8% of new blind registrations in the UK. The main risk factor for glaucoma is raised intraocular pressure, but 40% of people with glaucoma have normal intraocular pressure and only 10% of people with raised intraocular pressure are at risk of optic-nerve damage. Glaucoma is more prevalent, presents earlier, and is more difficult to control in black people than in white populations. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for established primary open-angle glaucoma, ocular hypertension, or both? What are the effects of lowering intraocular pressure in people with normal-tension glaucoma? What are the effects of treatment for acute angle-closure glaucoma? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 12 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: laser trabeculoplasty (alone or plus topical medical treatment), topical medical treatments, and surgical trabeculectomy.

QUESTIONS What are the effects of treatments for established primary open-angle glaucoma, ocular hypertension, or both?. . 3 What are the effects of lowering intraocular pressure in people with normal-tension glaucoma?. . . . . . . . . . . 13 What are the effects of treatment for acute angle-closure glaucoma?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 INTERVENTIONS IN PRIMARY OPEN-ANGLE GLAUCOMA, OCULAR HYPERTENSION, OR BOTH Likely to be beneficial Laser trabeculoplasty plus topical medical treatment (more effective than no initial treatment at reducing progression of glaucoma; in people with primary openangle glaucoma) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Topical medical treatment (in people with primary openangle glaucoma, ocular hypertension, or both) . . . . 5 Trade off between benefits and harms Surgical trabeculectomy (in people with primary openangle glaucoma, ocular hypertension, or both) . . . 10 Unknown effectiveness Laser trabeculoplasty in people with primary open-angle glaucoma (currently uncertain compared with surgical trabeculectomy or topical medical treatments) . . . . . 8 LOWERING INTRAOCULAR PRESSURE IN NORMALTENSION GLAUCOMA Unknown effectiveness Medical treatment in people with normal-tension glaucoma (currently uncertain as insufficient data of adequate quality) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 Key points Glaucoma is characterised by progressive optic neuropathy and peripheral visual field loss. It affects 1% to 2% of white people aged over 40 years and accounts for 8% of new blind registrations in the UK. The main risk factor for glaucoma is raised intraocular pressure (IOP), but up to 40% of people with glaucoma have normal IOP and only about 10% of people with raised IOP are at risk of optic-nerve damage. Unknown effectiveness Laser treatment (iridotomy or iridoplasty; currently uncertain compared with surgical or medical treatments) New . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 Footnote *No placebo-controlled RCTs, but a strong consensus that treatments are effective Surgical treatment in people with normal-tension glaucoma (currently uncertain as insufficient data of adequate quality) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 IN ACUTE ANGLE-CLOSURE GLAUCOMA Likely to be beneficial Medical treatment* (any route; in acute angle-closure glaucoma) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 Surgical treatment* (any type; in acute angle-closure glaucoma) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

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Clinical Evidence 2011;06:703

Eye disorders

Glaucoma
Glaucoma is more prevalent, presents earlier, and is more difficult to control in black people (especially those of West African descent) than in white populations. Blindness from glaucoma results from gross loss of visual field or loss of central vision and, when the optic nerve is vulnerable, can progress quickly without treatment. Lowering IOP by laser trabeculoplasty plus topical medical treatment may be more effective at reducing progression of glaucoma in people with primary open-angle or pseudoexfoliation glaucoma, compared with no treatment. Topical medical treatment may reduce the risk of developing glaucoma in people with ocular hypertension, compared with placebo. We don't know whether topical medical treatment, laser trabeculoplasty, or surgical trabeculectomy is more effective at maintaining visual fields and acuity in primary open-angle glaucoma. Surgery may increase the risk of developing cataracts. We don't know whether reducing IOP with medical treatment alone or in combination with other treatments including surgery is more effective than no treatment at reducing progression of visual field loss in people with normal-tension glaucoma. There is a consensus that medical and surgical treatments are beneficial in people with acute angle-closure glaucoma, although we don't know this for sure because it is unethical to withhold pressure-lowering treatment. The consensus about how laser treatments compare with medical or surgical treatments in people with acute angleclosure glaucoma is currently uncertain, and more high-quality evidence is needed. DEFINITION Glaucoma is a group of diseases characterised by progressive optic neuropathy. It is usually bilateral but asymmetrical, and may occur at any intraocular pressure (IOP). All forms of glaucoma show optic-nerve damage (cupping, pallor, or both) associated with peripheral visual field loss. Primary open-angle glaucoma occurs in people with an open anterior chamber drainage angle and no secondary identifiable cause. Knowledge of the natural history of these conditions is incomplete, but it is thought that the problem starts with an IOP that is too high for the optic nerve. However, in a large proportion of people with glaucoma (about 40% at first testing) IOP is within the statistically defined normal range. The term normal-tension glaucoma is often used to describe this condition. It exhibits the same clinical picture as primary open-angle glaucoma with some additional risk factors. The division between the two conditions is an artificial one based on IOP, but they are really two diseases at different ends of a spectrum. The term "ocular hypertension" (OHT) generally applies to eyes with an IOP greater than the statistical upper limit of normal (about 21 mmHg). A thicker cornea leads to an overestimate of the IOP. Conversely, a thinner cornea may lead to underestimation of IOP and may be a risk factor for progression from OHT to glaucoma. Only a relatively small proportion of eyes with raised IOP have an optic nerve that is vulnerable to its effects (about 10%). Previously, trialists were anxious about withholding active treatment in overt primary open-angle glaucoma, and so several placebo or no-treatment trials selected people just with OHT. Trials comparing treatments often include both people with primary open-angle glaucoma and people with OHT, but in these the outcome is usually IOP alone. Acute angle-closure glaucoma is glaucoma resulting from a rapid and severe rise in IOP caused by physical obstruction of the anterior chamber drainage angle. Subacute and chronic angle-closure glaucoma also occur, but are not considered in this review. Glaucoma occurs in 1% to 2% of white people aged over 40 years, rising to 5% at 70 years. Primary open-angle glaucoma accounts for two-thirds of those affected, and normal-tension glaucoma for [1] [2] about one quarter. Glaucoma is more prevalent, presents at a younger age with higher IOPs, is more difficult to control, and is the main irreversible cause of blindness in black populations, es[1] [3] pecially those of West African origin. Glaucoma-related blindness is responsible for 8% of [4] new blind registrations in the UK. Angle-closure glaucoma occurs at about one tenth of the frequency of open-angle glaucoma in white Europeans but is more common in Chinese people and Native American people especially the Inuit.

INCIDENCE/ PREVALENCE

AETIOLOGY/ The major risk factor for developing primary open-angle glaucoma is raised IOP. In one RCT (90 RISK FACTORS people with IOP >22 mmHg, another glaucoma risk factor, and normal visual fields; mean age 5556 years), three baseline risk factors were identified to be independently associated with glau[5] comatous field loss. These were higher IOP (P = 0.047; IOP per mmHg), suspect discs [6] (P = 0.007), and older age (P = 0.034; age per year). Lesser risk factors include family history and ethnic origin. The relationship between systemic blood pressure and IOP may be an important determinant of blood flow to the optic-nerve head and, as a consequence, may represent a risk [6] factor for glaucoma. Systemic hypotension, vasospasm (including Raynaud's disease and migraine), and a history of major blood loss have been reported as risk factors for normal-tension [7] glaucoma in hospital-based studies. Risk factors for acute angle-closure glaucoma include family history, female sex, being long-sighted, and cataracts. One systematic review (search date 1999, 6 observational studies, 594,662 people with mydriasis) found no evidence supporting the
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Eye disorders

Glaucoma
theory that routine pupillary dilatation with short-acting mydriatics was a risk factor for acute angle[8] closure glaucoma. PROGNOSIS Advanced visual field loss is found in about 20% of people with primary open-angle glaucoma at [9] [10] diagnosis and is an important prognostic factor for glaucoma-related blindness. Blindness from glaucoma is caused initially by loss of the peripheral visual field and ultimately by loss of central vision. Once early field defects have appeared, and where the IOP is greater than 30 mmHg, [11] untreated people may lose the remainder of the visual field in 3 years or less. As the disease progresses, people with glaucoma have difficulty moving from a bright room to a darker room, and judging steps and kerbs. Progression of visual field loss is often slower in normal-tension glaucoma. Acute angle glaucoma leads to rapid loss of vision, initially from corneal oedema and subsequently from ischaemic optic neuropathy. Once optic-nerve damage has occurred, it cannot be repaired.

AIMS OF To prevent progression of visual field loss and to minimise adverse effects of treatment. INTERVENTION OUTCOMES Disease progression: onset or progression of glaucoma; visual acuity; visual fields. Optic disc cupping and IOP are surrogate outcomes, which we do not report in this review. However, some RCTs have reported combined outcomes including these measures. In these cases, we have reported these surrogate outcomes as part of the combined outcome reported. Adverse effects of treatment. Clinical Evidence search and appraisal May 2010. The following databases were used to identify studies for this systematic review: Medline 1966 to May 2010, Embase 1980 to May 2010, and The Cochrane Database of Systematic Reviews, May 2010 (1966 to date of issue). An additional search within The Cochrane Library was carried out for the Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA). When editing this review we used The Cochrane Database of Systematic Reviews 2010, Issue 3. We also searched for retractions of studies included in the review. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the contributor for additional assessment, using predetermined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews of RCTs and RCTs in any language, at least single blinded, and containing >20 individuals of whom >80% were followed up. There was no minimum length of follow-up required to include studies. We excluded all studies described as "open", "open label", or not blinded unless blinding was impossible. We included systematic reviews of RCTs and RCTs where harms of an included intervention were studied applying the same study design criteria for inclusion as we did for benefits. In addition we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the MHRA, which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table, p 21 ). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com). What are the effects of treatments for established primary open-angle glaucoma, ocular hypertension, or both? LASER TRABECULOPLASTY PLUS TOPICAL MEDICAL TREATMENT (IN PEOPLE WITH PRIMARY OPEN-ANGLE GLAUCOMA, OCULAR HYPERTENSION, OR BOTH). . . . . . . . . . . .

METHODS

QUESTION

OPTION

For GRADE evaluation of interventions for Glaucoma, see table, p 21 . Lowering intraocular pressure by laser trabeculoplasty plus topical medical treatment may be more effective at reducing progression of glaucoma in people with primary open-angle or pseudoexfoliation glaucoma, compared with no treatment.

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Eye disorders

Glaucoma
Benefits and harms Laser trabeculoplasty plus topical medical treatment versus no treatment: [12] [13] We found one systematic review (search date 2007, 1 RCT, 255 people) comparing topical medical treatment (betaxolol hydrochloride) plus laser trabeculoplasty versus no treatment. Disease progression Laser trabeculoplasty plus topical medical treatment compared with no treatment Laser trabeculoplasty plus topical betaxolol hydrochloride may be more effective than no initial treatment at reducing the proportion of people with progression of glaucoma (defined by objective visual field changes, optic disc changes in 1 or both eyes, or both) at 6 years in people aged 50 to 80 years with newly detected primary open-angle glaucoma or pseudoexfoliation glaucoma, who were previously untreated (low-quality evidence). Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours

Progression of glaucoma
[13]

RCT

255 people aged 50 to 80 years with newly detected primary open-angle glaucoma or pseudoexfoliation glaucoma, previously untreated In review
[12]

Progression of glaucoma (defi- P = 0.007 nite visual field and optic disc defect progression) , measured at 6 years 58/129 (45%) with laser trabeculoplasty plus topical betaxolol hydrochloride 78/126 (62%) with no treatment Progression of glaucoma was defined by objective visual field changes, optic disc changes in 1 or both eyes of the person, or both Latanoprost eye drops were also allowed in both groups if the intraocular pressure exceeded 25 mmHg at 2 consecutive visits in the treatment group or exceeded 35 mmHg in the no-treatment control group laser trabeculoplasty plus topical betaxolol hydrochloride

[13]

RCT

255 people aged 50 to 80 years with newly detected primary open-angle glaucoma or pseudoexfoliation glaucoma, previously untreated In review
[12]

Median time to progression 66 months with laser trabeculoplasty plus topical betaxolol hydrochloride 48 months with no treatment Progression of glaucoma was defined by objective visual field changes, optic disc changes in 1 or both eyes of the person, or both Latanoprost eye drops were also allowed in both groups if the intraocular pressure exceeded 25 mmHg at 2 consecutive visits in the treatment group or exceeded 35 mmHg in the no-treatment control group

Significance not assessed

Adverse effects Laser trabeculoplasty plus topical medical treatment compared with no treatment Laser trabeculoplasty plus topical betaxolol hydrochloride may be associated with a more rapid development of lens opacities (low-quality evidence).

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Eye disorders

Glaucoma
Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours Lens opacities
[13]

RCT

255 people aged 50 to 80 years with newly detected primary open-angle glaucoma or pseudoexfoliation glaucoma, previously untreated In review
[12]

Speed of onset of lens opacities with laser trabeculoplasty plus topical betaxolol hydrochloride with no treatment Absolute results reported graphically Latanoprost eye drops were also allowed in both groups if the intraocular pressure exceeded 25 mmHg at 2 consecutive visits in the treatment group or exceeded 35 mmHg in the no-treatment control group

P = 0.002

no treatment

Laser trabeculoplasty plus topical medical treatment versus topical medical treatment alone: We found no RCTs. Further information on studies Comment: The review found no evidence comparing selective laser trabeculoplasty, or newer topical medical [12] treatments including prostaglandin analogues, brimonidine, or carbonic anhydrase inhibitors. Clinical guide: Guidelines for open-angle glaucoma: There are now numerous national and international guidelines for the diagnosis and management of open-angle glaucoma, including the American Academy of Ophthalmology's Preferred Practice Pattern, last updated in 2005, and Canadian, Japanese, European, and Asian Pacific guidelines, to name but a few. The extent to which these are formally evidence based is variable; the only systematically derived evidence-based guidance was published by NICE in April 2009 and is now going through the implementation phase in the UK (for details, see clinical guide under comment on topical medical treatments, p 5 ). OPTION TOPICAL MEDICAL TREATMENT (IN PEOPLE WITH PRIMARY OPEN-ANGLE GLAUCOMA, OCULAR HYPERTENSION, OR BOTH). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

For GRADE evaluation of interventions for Glaucoma, see table, p 21 . Topical medical treatment may reduce the risk of developing glaucoma in people with ocular hypertension compared with placebo. We don't know whether topical medical treatment is more effective than laser trabeculoplasty, p 8 or surgical trabeculectomy, p 10 at maintaining visual fields and acuity in primary open-angle glaucoma. Topical medical treatments may be associated with uncommon but potentially serious systemic adverse effects including exacerbation of chronic obstructive airways disease after use of non-selective topical beta-blockers. Benefits and harms

Topical medical treatment versus placebo or no treatment: [14] We found two systematic reviews (search dates 2004, 5 RCTs, 2326 people; and 2007, 10 RCTs, 3648 people [15] ) comparing topical medical treatments versus placebo or no treatment.The reviews identified 5 RCTs in common; however, they used different meta-analyses and applied different inclusion/exclusion criteria. Of the 10 RCTs identified
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Eye disorders

Glaucoma
by the second review, 5 were identified and one was excluded (inadequate control group [comparing eyes rather [14] than people]) by the first review. Disease progression Compared with placebo or no treatment Topical medical treatment (beta-blockers, dorzolamide, or unspecified) may be more effective at reducing the proportion of people with ocular hypertension who develop visual field loss (lowquality evidence). Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
[15]

Disease progression
[14]

Systematic review

2326 people with ocular hypertension 5 RCTs in this analysis

Proportion of people with visu- HR 0.56 al field loss, deterioration of 95% CI 0.3 to 0.81 optic disc, or both , over 5 to 10 years P = 0.01 81/1159 (7%) with topical medical Many of the identified RCTs had treatment high withdrawal rates 151/1161 (13%) with control Included RCTs compared timolol, betaxolol, or various topical medical treatments versus placebo or no treatment topical medical treatment

[15]

Systematic review

3648 people main- Proportion of people with visu- OR 0.62 ly with ocular hyper- al field defect progression , 2 95% CI 0.47 to 0.81 tension to 3 years 10 RCTs in this analysis Some RCTs also included people with open-angle glaucoma, pseudoexfoliation syndrome, and pigment dispersion syndrome 89/1822 (5%) with topical medical treatment 140/1826 (8%) with placebo or no treatment Included RCTs compared any topical medical treatment (betablockers, dorzolamide, or unspecified) versus placebo or no treatment topical medical treatment

[15]

Systematic review

935 people mainly with ocular hypertension

Proportion of people with visu- OR 0.67 al field defect progression , 2 95% CI 0.45 to 1.00 to 3 years Result was of borderline signifi8 RCTs in this 45/460 (10%) with beta-blockers cance analysis 64/466 (14%) with placebo or no See further information on studies Subgroup analysis treatment for comment on separate subAnalysis of betagroup analyses of individual betablockers (betaxolol blockers (betaxolol and timolol), and timolol) as a and dorzolamide group Some RCTs also included people with open-angle glaucoma, pseudoexfoliation syndrome, and pigment dispersion syndrome

beta-blockers

[16]

RCT

African-American people

Proportion of people develop- HR 0.50 ing primary open-angle glauco95% CI 0.28 to 0.90 ma , over a median of 6.5 years Subgroup analysis P = 0.02 17/203 (8%) with topical medical Separate report of treatment longer-term data from an RCT identi- 33/205 (16%) with placebo [15] fied by review

topical medical treatment

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Eye disorders

Glaucoma
Adverse effects Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours

Withdrawal because of adverse effects

[15]

Systematic review

People mainly with Proportion of people who ocular hypertenwithdrew owing to adverse efsion fects Subgroup analysis with beta-blockers Analysis of betablockers Some RCTs also included people with open-angle glaucoma, pseudoexfoliation syndrome, and pigment dispersion syndrome with placebo or no treatment Absolute results not reported

OR 0.95 95% CI 0.40 to 2.26

Not significant

[17]

RCT

1081 people with ocular hypertension In review

[15]

Proportion of people who withdrew owing to adverse effects 116/536 (22%) with dorzolamide 51/541 (9%) with placebo

OR 2.54 95% CI 1.83 to 3.53 placebo

Ocular adverse effects

[17]

RCT

1081 people with ocular hypertension In review

[15]

Ocular adverse effects (includ- Significance not assessed ing burning or stinging) when using the drops 23% of visits with dorzolamide 7% of visits with placebo Absolute numbers not reported

No data from the following reference on this outcome. Topical medical treatment alone versus topical medical treatment plus laser trabeculoplasty: See option on laser trabeculoplasty plus topical medical treatment in people with primary open-angle glaucoma, ocular hypertension, or both, p 3 . Topical medical treatment alone versus laser trabeculoplasty: See option on laser trabeculoplasty in people with primary open-angle glaucoma, ocular hypertension, or both, p 8. Topical medical treatment versus surgical trabeculectomy: See option on surgical trabeculectomy in people with primary open-angle glaucoma, ocular hypertension, or both, p 10 . ........................................................... 7
[14]

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Eye disorders

Glaucoma
Further information on studies
[15]

Subgroup analyses of individual beta-blockers versus placebo or no treatment found no significant difference in visual field defect progression between groups. A single RCT comparing dorzolamide versus placebo in [17] people with OHT, included in the meta-analysis, also found no significant difference in visual field progression between groups. Studies may have been underpowered to detect a difference between groups.

Comment: Harms of topical medical treatment One non-systematic review assessing systemic adverse effects of topical medical treatments found that they were uncommon but may be serious, including exacerbation of COPD after use of non[18] selective topical beta-blockers. It found that non-selective topical beta-blockers can also cause systemic hypotension and reduction in resting heart rate. One RCT (80 people) assessing harms of prostaglandin analogues compared 5 interventions: bimatoprost, latanoprost, travoprost, unoprostone, and placebo. It found that bimatoprost, latanoprost, and travoprost all significantly increased aqueous flare (breakdown of blood aqueous barrier) from baseline over 6 months compared with [19] unoprostone (P <0.02) and placebo (P <0.001 for difference among groups). Clinical guide: Guidelines for open-angle glaucoma: There are now numerous national and international guidelines for the diagnosis and management of open-angle glaucoma, including the American Academy of Ophthalmology's Preferred Practice Pattern, last updated in 2005, and Canadian, Japanese, European, and Asian Pacific guidelines, to name but a few. The extent to which these are formally evidence based is variable; the only systematically derived evidence-based guidance was published by NICE in April 2009 and is now going through the implementation phase in the UK. The NICE systematic review (search date 2008) used the same reviews and RCTs referred to in this Clinical Evidence review, and so we have not included its findings separately. However, it also performed its own systematic review and economic analyses on additional questions not covered by this Clinical Evidence review, in order to provide guidance on treatment thresholds for ocular hypertension and open-angle glaucoma. These are based on modelling risk factors for conversion and progression using age, intraocular pressure, and central corneal thickness in three bands or strata for each. The economic methodology is not explicit but was done according to standard [20] NICE methodology. Economic modelling provided the basis for recommending prostaglandin analogues as first-line treatment in most age groups with open-angle glaucoma and ocular hypertension, except for some groups for whom topical beta-blockers are recommended. It is also recommended that surgery is offered to people in whom two topical agents are insufficient to control the disease. Other important recommendations include ensuring the patient is fully informed of their diagnosis and prognosis, and understands the treatments offered. OPTION LASER TRABECULOPLASTY (IN PEOPLE WITH PRIMARY OPEN-ANGLE GLAUCOMA, OCULAR HYPERTENSION, OR BOTH) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

For GRADE evaluation of interventions for Glaucoma, see table, p 21 . We don't know whether laser trabeculoplasty is more effective than topical medical treatment, p 5 or surgical trabeculectomy, p 10 at maintaining visual fields and acuity in primary open-angle glaucoma. Benefits and harms

Laser trabeculoplasty versus surgical trabeculectomy: See option on surgical trabeculectomy in people with primary open-angle glaucoma, ocular hypertension, or both, p 10 . Laser trabeculoplasty versus topical medical treatment: We found one systematic review (search date 2007, 4 RCTs) comparing initial laser trabeculoplasty versus initial medical treatment in people with newly diagnosed open-angle glaucoma (majority with primary open-angle glaucoma, [12] some with pseudoexfoliation syndrome and pigment dispersion syndrome). BMJ Publishing Group Ltd 2011. All rights reserved.

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Eye disorders

Glaucoma
Disease progression Compared with topical medical treatment We don't know how initial laser trabeculoplasty and topical medical treatment compare at reducing visual field defect progression at 2 years in people with primary open-angle glaucoma (very low-quality evidence). Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours

Disease progression
[12]

Systematic review

353 people with Visual field loss progression , RR 0.70 newly diagnosed at 2 years 95% CI 0.42 to 1.16 open-angle glauco23/311 (7%) eyes with laser trama beculoplasty 2 RCTs in this 33/313 (11%) eyes with topical analysis medical treatment Most people had Analysis of eyes rather than peoprimary open-angle ple; see further information on glaucoma; some studies for additional detail had pseudoexfoliation syndrome and Topical medical preparations pigment dispersion used included pilocarpine and syndrome timolol One RCT included in the metaanalysis allowed medication change during the trial; see further information on studies

Not significant

Adverse effects Compared with topical medical treatment Initial laser trabeculoplasty may be associated with higher incidence of peripheral anterior synechiae compared with initial medical treatment (moderate-quality evidence). Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours

Peripheral anterior synechiae

[12]

Systematic review

353 people with Peripheral anterior synechiae RR 11.5 newly diagnosed 84/311 (27%) eyes with laser 95% CI 5.63 to 22.09 open-angle glaucotrabeculoplasty ma 8/313 (3%) eyes with topical 2 RCTs in this medical treatment analysis Analysis of eyes rather than peoMost people had ple; see further information on primary open-angle studies for additional detail glaucoma; some had pseudoexfolia- Topical medical preparations tion syndrome and used included pilocarpine and pigment dispersion timolol syndrome One RCT included in the metaanalysis allowed medication change during the trial; see further information on studies

topical medical treatment

Further information on studies

[12]

Details of included RCTs The first RCT (271 people, 542 eyes) compared argon laser trabeculoplasty versus [22] timolol. The second included RCT (82 people, 82 eyes) compared argon laser trabeculoplasty versus pilocarpine. Additional medications The review reported uncertainty about additional medications or interventions [22] allowed in one RCT. One RCT allowed the addition of medication or change in medication during the trial according to a stepped regimen (timolol, dipivefrine, low-dose pilocarpine, high-dose pilocarpine, timolol plus high-dose pilocarpine, or dipivefrine plus high-dose pilocarpine) on the basis of confirmed increased intraocular pressure, deterioration in visual field, optic disc, or systemic adverse effects. The analysis was by intention to

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treat; however, only 20% of people in the laser trabeculoplasty and 15% of the people in the timolol group had not received additional treatments at median 3 years' follow-up. Comment: The review reported no evidence comparing selective laser trabeculoplasty or newer topical medical [12] treatments including prostaglandin analogues, brimonidine, or carbonic anhydrase inhibitors. Clinical guide: Guidelines for open-angle glaucoma: There are now numerous national and international guidelines for the diagnosis and management of open-angle glaucoma, including the American Academy of Ophthalmology's Preferred Practice Pattern, last updated in 2005, and Canadian, Japanese, European, and Asian Pacific guidelines, to name but a few. The extent to which these are formally evidence based is variable; the only systematically derived evidence-based guidance was published by NICE in April 2009 and is now going through the implementation phase in the UK (for details, see clinical guide under comment on topical medical treatments, p 5 ). OPTION SURGICAL TRABECULECTOMY (IN PEOPLE WITH PRIMARY OPEN-ANGLE GLAUCOMA, OCULAR HYPERTENSION, OR BOTH). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

For GRADE evaluation of interventions for Glaucoma, see table, p 21 . We don't know whether surgical trabeculectomy is more effective than laser trabeculoplasty, p 8 or topical medical treatment, p 5 at maintaining visual fields and acuity in primary open-angle glaucoma. Surgery may increase the risk of developing cataracts. Surgical trabeculectomy has been reported to be associated with a reduction in central vision. Benefits and harms

Surgical trabeculectomy versus topical medical treatment: We found one systematic review (search date 2007, 4 RCTs, 888 people with primary, pseudoexfoliative, and pig[21] mentary open-angle glaucoma) comparing surgical versus topical medical treatment. The earliest RCT identified by the review was initiated in 1968 and the surgical treatment was a Scheie's procedure, which is no longer done as a surgical procedure for glaucoma. Therefore, we present results for only the remaining three RCTs. Disease progression Compared with topical medical treatment We don't know how surgical trabeculectomy and topical medical treatment compare at preventing visual field loss or deterioration of visual acuity scores in people with primary, pseudoexfoliative, and pigmentary open-angle glaucoma (low-quality evidence). Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours

Visual field loss

[21]

102 people Data from 1 RCT

Systematic review

Visual field loss , at 2 to 5 years 25/40 (63%) with topical medical treatment 34/48 (71%) with surgical trabeculectomy

OR 0.69 95% CI 0.29 to 1.67 Not significant

[21]

607 people Data from 1 RCT

Systematic review

Visual field loss , at 2 to 5 years with topical medical treatment with surgical trabeculectomy Absolute results not reported

OR 0.74 95% CI 0.54 to 1.01 Not significant

[21]

107 people Data from 1 RCT

Systematic review

Proportion of people with visu- OR 2.56 al field loss progressed by at 95% CI 1.12 to 5.83 least 1 stage of visual field severity , at mean of 4.6 years 27/57 (47%) with topical medical treatment

primary trabeculectomy

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Ref (type) Population Outcome, Interventions
13/50 (26%) with primary trabeculectomy

Results and statistical analysis

Effect size

Favours

Visual acuity
[21]

107 people Data from 1 RCT

Systematic review

Mean visual acuity scores , at 4 to 5 years with topical medical treatment with surgical treatment Absolute results not reported

OR 1.48 95% CI 0.58 to 3.51 Not significant

[21]

102 people Data from 1 RCT

Systematic review

Mean visual acuity scores , at 4 to 5 years with surgical treatment with medical treatment Absolute results not reported

Reported as not significant P value not reported Not significant

[21]

607 people Data from 1 RCT

Systematic review

Defined visual acuity loss (loss OR 0.50 of about 2 Snellen lines) 95% CI 0.33 to 0.75 with surgical treatment OR adjusted for age, race, history with medical treatment of diabetes, and time in study Absolute results not reported The treatment effect remained significant after adjustment for cataract surgery; OR 0.47, 95% CI 0.31 to 0.74

topical medical treatment

Adverse effects Compared with topical medical treatment Surgical trabeculectomy increases the risk of developing cataracts and the risk of requiring cataract surgery in people with primary, pseudoexfoliative, and pigmentary open-angle glaucoma (high-quality evidence). Ref (type) Cataracts
[21]

Population

Outcome, Interventions

Results and statistical analysis

Effect size

Favours

819 people 3 RCTs in this analysis

Cataracts 57/403 (14%) with surgical trabeculectomy 24/416 (6%) with topical medical treatment

OR 2.69 95% CI 1.64 to 4.42 topical medical treatment

Systematic review

[21]

607 people Data from 1 RCT

Systematic review

Proportion of people requiring HR 2.72 cataract surgery , at up to 3 95% CI 1.51 to 4.89 years with primary trabeculectomy with topical medical treatment Absolute results not reported topical medical treatment

Surgical trabeculectomy versus laser trabeculoplasty: [23] [24] We found two RCTs. In one RCT, racetreatment interactions were found to be significant for the primary [25] outcome measures, and therefore results were analysed by race. We also identified a 10-year follow-up of the [23] RCT, but it is not reported here because of high loss to follow-up (loss of 30% of black people and 20% of white people). -

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Eye disorders

Glaucoma
Disease progression Surgical trabeculectomy compared with laser trabeculoplasty We don't know how surgical trabeculectomy and laser trabeculoplasty compare at preventing deterioration of vision (measured by visual acuity and visual field) at 5 to 7 years in people with newly diagnosed primary open-angle glaucoma or advanced glaucoma (low-quality evidence). Ref (type) Vision
[23]

Population

Outcome, Interventions

Results and statistical analysis

Effect size

Favours

RCT

451 black people with advanced glaucoma

Improved vision (both visual P <0.01 acuity and visual field) , after 7 years

Subgroup analysis with initial laser trabeculoplasty Total population of 776 people (789 eyes) with advanced glaucoma with initial surgical trabeculectomy Absolute results reported graphically Initial surgical trabeculectomy was followed by laser trabeculoplasty and repeat surgical trabeculectomy as required Initial laser trabeculoplasty was followed by surgical trabeculectomy as required
[23]

initial laser trabeculoplasty

RCT

325 white people with advanced glaucoma

Improved vision (both visual Reported as not significant acuity and visual field) , after 7 P value not reported years

Subgroup analysis with initial laser trabeculoplasty Total population of 776 people (789 eyes) with advanced glaucoma with initial surgical trabeculectomy Absolute results reported graphically Initial surgical trabeculectomy was followed by laser trabeculoplasty and repeat surgical trabeculectomy as required Initial laser trabeculoplasty was followed by surgical trabeculectomy as required
[24]

Not significant

RCT 3-armed trial

186 people with Visual acuity , after 5 years Reported as no significant differnewly diagnosed ence among groups with topical medical treatment primary open-angle (pilocarpine timolol a sympa- P value not reported glaucoma thomimetic) with laser trabeculoplasty with surgical trabeculectomy Absolute results reported graphically Not significant

Adverse effects No data from the following reference on this outcome. Further information on studies BMJ Publishing Group Ltd 2011. All rights reserved. [23] [24]

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Eye disorders

Glaucoma
Comment: Harms of surgical trabeculectomy: Surgical trabeculectomy is associated with a reduction in central vision. In one observational study, [26] 83% of people lost two lines of Snellen visual acuity. Clinical guide: Guidelines for open-angle glaucoma: There are now numerous national and international guidelines for the diagnosis and management of open-angle glaucoma, including the American Academy of Ophthalmology's Preferred Practice Pattern, last updated in 2005, and Canadian, Japanese, European, and Asian Pacific guidelines, to name but a few. The extent to which these are formally evidence based is variable; the only systematically derived evidence-based guidance was published by NICE in April 2009 and is now going through the implementation phase in the UK (for details, see clinical guide under comment on topical medical treatments, p 5 ). QUESTION What are the effects of lowering intraocular pressure in people with normal-tension glaucoma? MEDICAL TREATMENT IN PEOPLE WITH NORMAL-TENSION GLAUCOMA . . . . . . . . . . . . . .

OPTION

For GRADE evaluation of interventions for Glaucoma, see table, p 21 . We don't know whether reducing intraocular pressure with medical treatment alone or in combination with other treatments including surgery is more effective than no treatment at reducing progression of visual field loss in people with normal-tension glaucoma. We found no direct information from RCTs about medical treatment (any route other than topical) in people with normal-tension glaucoma. Benefits and harms

Topical medical treatment versus placebo or no treatment: We found one systematic review (search date 2004, 2 RCTs, 400 people with either primary open-angle or normal[14] tension glaucoma). Disease progression Compared with placebo or no treatment Topical medical treatment may be more effective than placebo at reducing the proportion of people with glaucoma progression at 5 to 6 years in people with normal-tension or primary openangle glaucoma, although subgroup analysis in people with normal-tension glaucoma alone found no significant difference between groups. Treatment to reduce intraocular pressure by 30% (using drugs, trabeculectomy, or both) may be more effective than no treatment at reducing progression of visual field loss at 8 years in people with normaltension glaucoma (very low-quality evidence). Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours

Glaucoma progression
[14]

Systematic review

400 people with ei- Glaucoma progression , at 5 to HR 0.65 ther primary open- 6 years 95% CI 0.49 to 0.87 angle or normal80/195 (41%) with interventions tension glaucoma P = 0.003 including topical medical treat2 RCTs in this ment analysis 109/205 (53%) with no treatment See further information on studies for details of interventions evaluated in RCTs in meta-analysis

interventions including topical medical treatment

[14]

Systematic review

274 people with normal-tension glaucoma 2 RCTs in this analysis Subgroup analysis

Glaucoma progression 49/134 (37%) with interventions including topical medical treatment 63/143 (44%) with no treatment

HR 0.70 95% CI 0.48 to 1.02 The subgroup analysis is likely to have been underpowered to detect a clinically important difference between groups Not significant

See further information on studies Total population in- for details of interventions evalucluded people with ated in RCTs in meta-analysis

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Eye disorders

Glaucoma
Ref (type) Population
primary open-angle glaucoma

Outcome, Interventions

Results and statistical analysis

Effect size

Favours

Vision
[28]

RCT

140 people (140 eyes) with normaltension glaucoma who had a 30% reduction in intraocular pressure with treatment Data from 1 RCT

Progression of visual field loss RR 0.32 (after a 30% reduction in in95% CI 0.15 to 0.70 traocular pressure) , after 8 years NNT 5 7/61 (12%) eyes with topical 95% CI 3 to 9 medical treatment or trabeculectomy

28/79 (35%) eyes with no treatSubgroup analysis ment Companion paper See further information on studies [27] to 1 RCT iden- for definition of progression of vi[14] tified by review; sual field loss see further information on studies for additional details

topical medical treatment or trabeculectomy

Adverse effects Ref (type) Cataracts

[27]

Population

Outcome, Interventions

Results and statistical analysis

Effect size

Favours

RCT

145 people with normal-tension glaucoma In review

[14]

Cataract formation , after 8 years 23/66 (35%) with interventions including topical medical treatment 11/79 (14%) with no treatment See further information on studies for details on interventions assessed

P = 0.0011 Subgroup analysis found that the excess risk of cataract formation was confined to those people treated surgically (P = 0.0001)

no treatment

Topical medical treatment versus surgical treatment: We found no systematic review or RCTs comparing topical medical treatment versus surgical treatment in people with normal-tension glaucoma. Further information on studies
[14]

Details of identified RCTs One RCT compared topical medical treatment (betaxolol) plus laser trabeculoplasty [13] versus no treatment. The second RCT compared treatments to lower intraocular pressure by 30% (medical [27] or surgical treatment [all allowed treatments not defined], or both) versus no treatment. Further information The original RCT included 145 people with normal-tension glaucoma. This companion paper reported visual field progression from a new baseline once a 30% reduction in intraocular pressure had [28] been achieved in the treated group. Progression of visual field loss was defined as deepening of an existing scotoma, a new or expanded field defect coming close to central vision, or a fresh scotoma in a previously normal part of the visual field.
[27]

[28]

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Eye disorders

Glaucoma
Comment: We found no direct information about medical treatment (any route other than topical) in people [13] [14] with normal-tension glaucoma. The RCT (255 people) included in the review, comparing topical medical treatments plus laser trabeculoplasty versus no treatment, is also reported in the option on laser trabeculoplasty plus topical medical treatment in people with primary open-angle [27] [14] glaucoma, p 8 . The RCT (145 people) included in the review and the companion paper [28] comparing medical or surgical treatment versus no treatment is also described in the option on surgical treatment in people with normal-tension glaucoma, p 15 . The RCT suggested that the overall favourable effect of intraocular pressure-lowering treatment using drugs or surgery compared with no treatment was evident only when the cataract-inducing effect of trabeculectomy was removed. Not all cases of normal-tension glaucoma progress when untreated (40% had not progressed [27] at 5 years). SURGICAL TREATMENT IN PEOPLE WITH NORMAL-TENSION GLAUCOMA . . . . . . . . . . . .

OPTION

For GRADE evaluation of interventions for Glaucoma, see table, p 21 . We don't know whether reducing intraocular pressure with medical treatment alone or in combination with other treatments including surgery is more effective than no treatment at reducing progression of visual field loss in people with normal-tension glaucoma. Benefits and harms

Surgical treatment versus no treatment: [14] [27] We found one systematic review (search date 2004), which identified one RCT. Disease progression Surgical treatment compared with placebo or no treatment Treatment to reduce intraocular pressure by 30% (using trabeculectomy, drugs, or both) may be more effective than no treatment at reducing progression of visual field loss at 8 years in people with normal-tension glaucoma (very low-quality evidence). Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours

Disease progression
[27]

RCT

145 people (145 Progression of visual field loss P = 0.21 eyes) with normal- , after 5 years tension glaucoma 22/66 (33%) eyes with treatment [14] In review 31/79 (39%) eyes with no treatment In the intervention arm, the treatment was given to lower intraocular pressure by 30%; treatment was medical or surgical (all allowed treatments not defined), or both

Not significant

[28]

RCT

140 people (140 eyes) with normaltension glaucoma who had a 30% reduction in intraocular pressure with treatment Subgroup analysis

Progression of visual field loss RR 0.32 (after a 30% reduction in in95% CI 0.15 to 0.70 traocular pressure) , after 8 years NNT 5 7/61 (12%) with trabeculectomy or topical medical treatment 28/79 (35%) with no treatment 95% CI 3 to 9 trabeculectomy or topical medical treatment

See further information on studies Companion paper for definition of progression of vi[27] to 1 RCT iden[14] sual field loss tified by review; see further information on studies for additional details

Adverse effects Surgical treatment compared with placebo or no treatment Treatment to reduce intraocular pressure by 30% (using trabeculectomy, drugs, or both) may be associated with increased cataract formation at 8 years in people with normal-

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Eye disorders

Glaucoma
tension glaucoma, the excess risk of cataract formation being confined to the subgroup of people who were treated surgically (very low-quality evidence). Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours

Cataract formation
[27]

RCT

145 people (145 Cataract formation , after 8 eyes) with normal- years tension glaucoma 23/66 (35%) eyes with interven[14] In review tions including surgical treatment 11/79 (14%) eyes with no treatment In the intervention arm, the treatment was given to lower intraocular pressure by 30%; treatment was medical or surgical (all allowed treatments not defined), or both

P = 0.0011 Subgroup analysis found that the excess risk of cataract formation was confined to those people treated surgically (P = 0.0001) no treatment

Surgical treatment versus topical medical treatment: See option on medical treatment in people with normal-tension glaucoma, p 13 . Further information on studies Comment: The RCT comparing topical medical or surgical treatment versus no treatment is also described in the option on medical treatment in people with normal-tension glaucoma, p 13 . The RCT suggested that the overall favourable effect of intraocular pressure-lowering treatment using medical treatment or surgery compared with no treatment was evident only when the cataract-inducing effect of trabeculectomy was removed. Not all cases of normal-tension glaucoma progress when untreated [27] (40% had not progressed at 5 years). What are the effects of treatment for acute angle-closure glaucoma? MEDICAL TREATMENT (ACUTE ANGLE-CLOSURE GLAUCOMA) . . . . . . . . . . . . . . . . . . . . . .
[27]

QUESTION OPTION

For GRADE evaluation of interventions for Glaucoma, see table, p 21 . There is a consensus that medical treatments are beneficial in people with acute angle-closure glaucoma, although we don't know this for sure because it is unethical to withhold pressure-lowering treatment. We found no direct evidence from RCTs about whether medical treatments (any route) are better than no active treatment. RCTs comparing pilocarpine with placebo are considered unethical. Benefits and harms

Medical treatment: We found one systematic review (search date 2002), which identified no RCTs assessing our outcomes of interest.
[29]

Further information on studies

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Eye disorders

Glaucoma
Comment: Clinical guide: RCTs comparing pilocarpine with placebo are considered unethical. There is a consensus that medical treatment with pressure-lowering drugs (especially those that can be given parenterally, such as iv acetazolamide) are effective in acute angle-closure glaucoma. We found no evidence from RCTs to support or challenge this view. SURGICAL TREATMENT (ACUTE ANGLE-CLOSURE GLAUCOMA) . . . . . . . . . . . . . . . . . . . .

OPTION

For GRADE evaluation of interventions for Glaucoma, see table, p 21 . There is a consensus that surgical treatments are beneficial in people with acute angle-closure glaucoma, although we don't know this for sure because it is unethical to withhold pressure-lowering treatment. We found no direct information from RCTs about whether surgical treatments (any type) are better than no active treatment. Benefits and harms

Surgical procedure versus no treatment: [29] We found one systematic review (search date 2002), which identified no RCTs (see comment). Surgical peripheral iridectomy versus Nd:YAG laser iridotomy: [29] We found one systematic review (search date 2002, 1 RCT that met Clinical Evidence inclusion criteria). Disease progression Surgical peripheral iridectomy compared with Nd:YAG laser iridotomy We don't know whether surgical iridectomy is more effective than laser iridotomy at preventing deterioration of visual acuity at 3 years in people with uniocular acute angle-closure glaucoma (low-quality evidence). Ref (type) Vision
[7]

Population

Outcome, Interventions

Results and statistical analysis

Effect size

Favours

RCT

48 people with Visual acuity , after 3 years Reported as not significant uniocular acute an0.30 logMAR units with peripheral P value not reported gle-closure glaucoiridectomy ma 0.57 logMAR units with Nd:YAG [29] In review laser iridotomy

Not significant

Adverse effects No data from the following reference on this outcome. Further information on studies Comment: Surgical peripheral iridectomy: further information on harms Surgical iridectomy involves an open operation on the eye, with risk of serious complications including intraocular infection or haemorrhage. We found no published evidence quantifying these risks. .......................................................... 17
[29]

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Eye disorders

Glaucoma
Clinical guide: Surgical peripheral iridectomy is a long-established treatment for angle-closure glaucoma whether acute, subacute, or chronic; the principle being the relief of relative pupil block with accumulation of aqueous humour behind the iris shallowing the anterior chamber and occluding the drainage angle. Consensus suggests that surgical treatments are effective in the treatment of acute angleclosure glaucoma. Management of acute angle-closure glaucoma is aimed at restoring flow of aqueous humour to the anterior chamber angle and adjacent trabecular meshwork. OPTION LASER TREATMENT (IRIDOTOMY OR IRIDOPLASTY) (ACUTE ANGLE-CLOSURE GLAUCOMA). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . New

For GRADE evaluation of interventions for Glaucoma, see table, p 21 . The consensus about how laser treatments compare with medical or surgical treatments in people with acute angle-closure glaucoma is currently uncertain, and more high-quality evidence is needed. We found no direct information from RCTs about whether laser treatments are better than no active treatment. Benefits and harms

Laser treatment versus no treatment or versus medical treatment: We found one systematic review (search date 2002), which identified no RCTs meeting Clinical Evidence inclusion [29] criteria. We found no subsequent RCTs in people with acute angle-closure glaucoma that reported on our outcomes of interest as primary outcomes (see comment). Laser treatment versus surgical treatment: See benefits and harms of surgical treatment in acute angle-closure glaucoma, p 17 . Further information on studies Comment: One RCT (64 people, 73 eyes with first presentation of acute primary angle-closure glaucoma) compared argon laser peripheral iridoplasty versus conventional systemic medical treatment (acetazolamide [iv followed by oral] plus potassium [oral]). All people also received topical pilocarpine plus topical timolol before randomisation. This RCT did not report on our outcomes of interest for this Clinical Evidence review as primary outcomes. However, we have included a brief comment from this RCT on reducing intraocular pressure, despite it being a surrogate outcome, because of the importance of relieving an acute attack in acute angle-closure glaucoma. The RCT found that laser trabeculoplasty significantly reduced intraocular pressure compared with standard medical treatment at 15 minutes, 30 minutes, and 1 hour after treatment. However, it found no significant [30] difference between groups after 2 hours. Nd:YAG laser iridotomy: further information on harms Nd:YAG laser iridotomy is associated with haemorrhage from the iris, pressure spikes, and corneal [31] oedema. Nd:YAG and argon laser iridotomy can produce focal, non-progressive lens opacity. [32] In one non-RCT, iris haemorrhage was more common with the Nd:YAG laser, but pupil distortion, [33] iritis, and late blockage were more common with the argon laser. One non-RCT found that the mean number of laser burns required to penetrate the iris was 6 with [33] the Nd:YAG laser and 73 with the argon laser.

GLOSSARY
Drainage angle Area in the anterior chamber of the eye where the iris meets the sclera, and where fluid from the aqueous humour drains by the trabecular meshwork. Laser iridotomy Involves making a hole in the base of the iris (without opening the eye) using either an argon or Nd:YAG laser.
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Glaucoma
Surgical iridectomy Opening the eye at the corneal limbus and removing a triangle of tissue from the base of the iris. Argon laser iridoplasty A procedure that involves placing circumferential argon laser burns (approximately 1620 burns) in the peripheral iris to induce a contraction and pulling away of the peripheral iris from the drainage angle with the aim of opening the angle. High-quality evidence Further research is very unlikely to change our confidence in the estimate of effect. Low-quality evidence Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Moderate-quality evidence Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Very low-quality evidence Any estimate of effect is very uncertain.

SUBSTANTIVE CHANGES
Laser treatment in acute angle-closure glaucoma New option added. Categorised as Unknown effectiveness, as we found insufficient RCT evidence to assess the effects of this intervention. Surgical trabeculectomy in people with primary open-angle glaucoma, ocular hypertension, or both Search [21] updated for an already included systematic review. No new evidence added. Categorisation unchanged (Tradeoff between benefits and harms). Topical medical treatment (in people with primary open-angle glaucoma, ocular hypertension, or both) Search [21] updated for an already included systematic review. No new evidence added. Categorisation unchanged (Likely to be beneficial).

REFERENCES
1. Sommer A, Tielsch JM, Katz J, et al. Relationship between intraocular pressure and primary open angle glaucoma among white and black Americans. Arch Ophthalmol 1991;109:10901095.[PubMed] Coffey M, Reidy A, Wormald R, et al. Prevalence of glaucoma in the west of Ireland. Br J Ophthalmol 1993;77:1721.[PubMed] Leske MC, Connell AM, Wu SY, et al. Incidence of open-angle glaucoma: the Barbados Eye Studies. The Barbados Eye Studies Group. Arch Ophthalmol 2001;119:8995.[PubMed] Government Statistical Service. Causes of blindness and partial sight amongst adults. London, UK: HMSO, 1988. Araie M, Azuma I, Kitazawa Y. Influence of topical betaxolol and timolol on visual field in Japanese open-angle glaucoma patients. Jpn J Ophthalmol 2003;47:199207. [PubMed] Tielsch JM, Katz J, Quigley HA, et al. Diabetes, intraocular pressure, and primary open-angle glaucoma in the Baltimore Eye Survey. Ophthalmology 1995;102:4853.[PubMed] Fleck BW, Wright E, Fairley EA. A randomised prospective comparison of operative peripheral iridectomy and Nd:YAG laser iridotomy treatment of acute angle closure glaucoma: 3 year visual acuity and intraocular pressure control outcome. Br J Ophthalmol 1997;81:884888.[PubMed] Pandit RJ, Taylor R. Mydriasis and glaucoma: exploding the myth. A systematic review. Diabet Med 2000;17:693699.[PubMed] Sheldrick JH, Ng C, Austin DJ, et al. An analysis of referral routes and diagnostic accuracy in cases of suspected glaucoma. Ophthalmic Epidemiol 1994;1:3138.[PubMed] Fraser S, Bunce C, Wormald R, et al. Deprivation and late presentation of glaucoma: case-control study. BMJ 2001;322:639643.[PubMed] Jay JL, Murdoch JR. The rates of visual field loss in untreated primary open angle glaucoma. Br J Ophthalmol 1993;77:176178.[PubMed] Rolim de Moura C, Paranhos A Jr, Wormald R. Laser trabeculoplasty for open angle glaucoma. In: The Cochrane Library, Issue 3, 2010. Chichester, UK: John Wiley & Sons, Ltd. Search date 2007.[PubMed] Heijl A, Leske MC, Bengtsson B, et al. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol 2002;120:12681279.[PubMed] Maier PC, Funk J, Schwarzer G, et al. Treatment of ocular hypertension and open angle glaucoma: meta-analysis of randomised controlled trials. BMJ 2005;331:134.[PubMed] Vass C, Hirn C, Sycha T, et al. Medical interventions for primary open angle glaucoma and ocular hypertension. In: The Cochrane Library, Issue 3, 2010. Chichester, UK: John Wiley & Sons, Ltd. Search date 2007.[PubMed] Higginbotham EJ, Gordon MO, Beiser JA, et al. The Ocular Hypertension Treatment Study: topical medication delays or prevents primary open-angle glaucoma in African American individuals. Arch Ophthalmol 2004;122:813820.[PubMed] Miglior S, Zeyen T, Pfeiffer N, et al. Results of the European Glaucoma Prevention Study. Ophthalmology 2005;112:366375.[PubMed] 28. 20. 18. 19. Diamond JP. Systemic adverse effects of topical ophthalmic agents: implications for older patients. Drugs Aging 1997;11:352360.[PubMed] Arcieri ES, Santana A, Rocha FN, et al. Blood-aqueous barrier changes after the use of prostaglandin analogues in patients with pseudophakia and aphakia: a 6month randomized trial. Arch Ophthalmol 2005;123:186192.[PubMed] National Institute for Health and Clinical Evidence. Glaucoma: diagnosis and management of chronic open angle glaucoma and ocular hypertension. NICE guideline CG85. April 2009. Available at http://guidance.nice.org.uk/CG85 (last accessed 11 May 2011). Burr J, Azuara-Blanco A, Avenell A. Medical versus surgical interventions for open angle glaucoma. In: The Cochrane Library, Issue 3, 2010. Chichester, UK: John Wiley & Sons, Ltd. Search date 2007.[PubMed] Glaucoma Laser Trial Research Group. The glaucoma laser trial (GLT) and glaucoma laser trial follow-up study: 7. Results. Am J Ophthalmol 1995;120:718731.[PubMed] The AGIS investigators. The Advanced Glaucoma Intervention Study (AGIS): 4. Comparison of treatment outcomes within race. Seven-year results. Ophthalmology 1998;105:11461164.[PubMed] Migdal C, Gregory W, Hitchings R. Long-term functional outcome after early surgery compared with laser and medicine in open-angle glaucoma. Ophthalmology 1994;101:16511657.[PubMed] The AGIS investigators. The Advanced Glaucoma Intervention Study (AGIS): 13. Comparison of treatment outcomes within race: 10-year results. Ophthalmology 2004;111:651664.[PubMed] Costa VP, Smith M, Spaeth GL, et al. Loss of visual acuity after trabeculectomy. Ophthalmology 1993;100:599612.[PubMed] Collaborative Normal-tension Glaucoma Study Group. The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. Am J Ophthalmol 1998;126:498505.[PubMed] Collaborative Normal-tension Glaucoma Study Group. Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Am J Ophthalmol 1998;126:487497.[PubMed] Saw SM, Gazzard G, Friedman DS. Interventions for angle-closure glaucoma: an evidence-based update. Ophthalmology 2003;110:18691878.[PubMed] Lam DS, Lai JS, Tham CC, et al. Argon laser peripheral iridoplasty versus conventional systemic medical therapy in treatment of acute primary angle-closure glaucoma: a prospective, randomized, controlled trial. Ophthalmology 2002;109:15911596.[PubMed] Fleck BW, Dhillon B, Khanna V, et al. A randomised, prospective comparison of Nd:YAG laser iridotomy and operative peripheral iridectomy in fellow eyes. Eye (Lond) 1991;5:315321.[PubMed] Pollack IP, Robin AL, Dragon DM, et al. Use of the neodymium:YAG laser to create iridotomies in monkeys and humans. Trans Am Ophthalmol Soc 1984;82:307328.[PubMed] Moster MR, Schwartz LW, Spaeth GL, et al. Laser iridectomy. A controlled study comparing argon and neodymium:YAG. Ophthalmology 1986;93:2024.[PubMed] 2. 3.

4. 5.

21.

22.

6.

23.

7.

24.

8. 9.

25.

26. 27.

10. 11. 12.

13.

29. 30.

14.

15.

31.

16.

32.

17.

33.

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Rajiv Shah Ophthalmic Surgeon Department of Ophthalmology St Vincent's Hospital Sydney Australia Richard P L Wormald Consultant Ophthalmic Surgeon Moorfields Eye Hospital London UK
Competing interests: RS has received honoraria for speaking and has been to sponsored meetings with Alcon and Allergan. RPLW has received honoraria for speaking and attending meetings from various pharmaceutical companies producing treatments for glaucoma including Alcon, Allergan, and Pfizer, and is a co-author of several systematic reviews cited in this review, as well as two studies cited in the background section. We would like to acknowledge the previous contributors of this review, including Jeremy Diamond and Colm O'Brien.

Disclaimer
The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.

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Glaucoma
GRADE Important outcomes Studies (Participants)
[13]

Evaluation of interventions for Glaucoma.

Adverse effects, Disease progression Outcome Comparison Type of evidence Quality Consistency Directness Effect size 0 GRADE Low Comment Quality point deducted for incomplete reporting of results. Directness point deducted for composite outcome Quality point deducted for incomplete reporting of results. Directness point deducted for multiple interventions used Quality point deducted for methodological weaknesses (high withdrawal rates). Directness point deducted for composite outcome Quality points deducted for incomplete reporting of results and analysis flaws. Directness point deducted for multiple interventions used Quality points deducted for incomplete reporting of results and analysis flaws. Directness point deducted for multiple interventions used. Effect-size points added for RR >5 Quality point deducted for incomplete reporting of results. Consistency point deducted for different results between studies Quality point deducted for incomplete reporting of results. Effect-size point added for OR >2 Quality point deducted for incomplete reporting of results. Directness point deducted for different results in different populations Quality points deducted for incomplete reporting of intervention and unclear outcome measurement. Directness points deducted for inclusion of people with primary open-angle glaucoma and inclusion of multiple interventions Quality points deducted for sparse data and incomplete reporting of intervention. Directness point deducted for inclusion of multiple interventions Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for subgroup analysis Quality points deducted for sparse data and incomplete reporting of results

What are the effects of treatments for established primary open-angle glaucoma, ocular hypertension, or both? 1 (255) Disease progression Adverse effects Laser trabeculoplasty plus topical medical treatment versus no treatment Laser trabeculoplasty plus topical medical treatment versus no treatment Topical medical treatment versus placebo or no treatment Laser trabeculoplasty versus topical medical treatment Laser trabeculoplasty versus topical medical treatment 4 1 0 1

1 (255)

[13]

Low

10 (3648)
[16]

[14]

[15]

Disease progression Disease progression Adverse effects

Low

2 (624 eyes)
[22]

[12]

Very low

2 (624 eyes)
[22]

[12]

+2

Moderate

3 (802)

[21]

Disease progression Adverse effects Disease progression

Surgical trabeculectomy versus topical medical treatment Surgical trabeculectomy versus topical medical treatment Surgical trabeculectomy versus laser trabeculoplasty

Low

at least 2 (at least [21] 819) 2 (962)

[23] [24]

4 4

1 1

0 0

0 1

+1 0

High Low

What are the effects of lowering intraocular pressure in people with normal-tension glaucoma? 2 (400)
[14] [27]

Disease progression

Topical medical treatment versus placebo or no treatment

Very low

1 (145)

[14]

[27]

Disease progression Adverse effects

Surgical treatment versus no treatment Surgical treatment versus no treatment

Very low

1 (145)

[14]

[27]

Very low

What are the effects of treatment for acute angle-closure glaucoma? 1 (48)
[29]

Disease progression

Surgical peripheral iridectomy versus Nd:YAG laser iridotomy

Low

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Eye disorders

Glaucoma
Important outcomes Studies (Participants) Outcome Comparison Type of evidence Adverse effects, Disease progression Quality Consistency Directness Effect size GRADE Comment

We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasirandomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.

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