ORIGINAL ARTICLE

Clinical and laboratory study of ocular rosacea in

northern Greece
E. Lazaridou,
,
* C. Fotiadou,

N.G. Ziakas,

C. Giannopoulou,

Z. Apalla,

D. Ioannides

First Departments of

Dermatology-Venereology and

Ophthalmology, Aristotle University Medical School, Thessaloniki, Greece
*Correspondence: Dr E. Lazaridou. E-mail: bethlaz@med.auth.gr
Abstract
Background The prevalence of ophthalmic involvement in rosacea is probably higher than previously presumed
and varies considerably among several studies.
Objective This study aimed to determine the incidence of ocular disease among a population of rosacea patients
in Northern Greece, to objectively determine the presence of eye dryness in rosacea patients with and without
clinical ophthalmic involvement and correlate the severity of ocular disease with the severity of cutaneous rosacea.
Methods One hundred patients with rosacea were assessed for the stage of their disease and examined for ocular
symptoms and signs. In 24 of them the tear break up time (TBUT) and Schirmer test were performed in each eye,
along with 24 controls.
Results A total of 33 patients (33%) were positive for ophthalmic ndings. The most frequent symptoms and signs
were burning sensation and tearing, and conjunctivitis and blepharitis, respectively. Eleven patients with ophthalmic
manifestations had mild to moderate erythematotelangiectatic rosacea, 17 had moderate papulopustular rosacea
and four exhibited ndings of phymatous rosacea. The total mean value of patients Schirmer tests was signicantly
lower compared with the healthy controls (P < 0.0001). Mean TBUT was shorter in the rosacea group than that in
the age-matched controls (P < 0.0001).
Conclusion Ocular involvement in rosacea is a common phenomenon with eye dryness being an early sign. Tear
function tests, like Schirmer test and TBUT, although not specic, could contribute to the screening and early
diagnosis of the disease, to prevent the potential development of sight-threatening conditions.
Received: 1 November 2010; Accepted: 12 January 2011
Conict of interest
None declared.
Funding sources
No funding sources supported this work.
Introduction
Rosacea is a chronic cutaneous disorder of unknown origin with
a central face distribution.
1,2
It is considered a syndrome that
encompasses various combinations of primary (ushing, ery-
thema, papules, pustules, telangiectasia) and secondary features
(burning or stinging, plaques, dry appearance, oedema, peripheral
locations, phymatous changes and ocular manifestations).
3,4
The
standard classication system for rosacea that was developed by
the National Rosacea Expert Committee denes four subtypes of
the disease: 1. Erythematotelangiectatic, 2. Papulopustular, 3. Phy-
matous and 4. Ocular rosacea.
3
The evolution from one subtype
to another is possible but does not occur in each case.
3,4
The prevalence of ophthalmic involvement in rosacea is probably
higher than previously presumed but it varies considerably between
ophthalmic anddermatological studies.
5,6
Inmost cases, ocular signs
and symptoms are preceded by cutaneous ones, although the latter
are not prerequisite for the diagnosis of ocular rosacea.
6,7
Interest-
ingly, in a study by Lempert et al., patients undergoing surgery
for chalazionwere 45 times more likely to suffer fromrosacea.
8
The ocular manifestations of rosacea usually involve one or
more of the following symptoms and signs: foreign body sensa-
tion, burning or stinging, dryness, itching, light sensitivity, blurred
vision, tearing, redness, interpalpebral conjunctival hyperemia, tel-
angiectasias of the conjunctiva and lid margin erythema, irregular-
ities and telangiectasias.
911
Ophthalmic complications such as
blepharitis, conjunctivitis, meibohmian gland dysfunction, styes,
chalazia, supercial punctate keratitis and iritis may also occur.
912
Vision-threatening aspects of the disease are rare and include con-
ditions such as marginal corneal inltrates and ulceration or even
corneal neovascularization, thinning and perforation.
9,13
2011 The Authors
JEADV 2011, 25, 14281431 Journal of the European Academy of Dermatology and Venereology 2011 European Academy of Dermatology and Venereology
DOI: 10.1111/j.1468-3083.2011.03995.x JEADV
The above mentioned manifestations are not specic for rosacea
alone.
14
Many ophthalmologic diseases share the same signs and
symptoms and this makes the need for diagnostic or at least indic-
ative tests quite urgent.
The precise aetiopathogenetic mechanism for the cutaneous
as well as the ophthalmic component of the disease remains
unknown.
1315
The current knowledge is that rosacea is an inam-
matory disorder. There are studies that conrm the inammatory
nature of ocular rosacea by documenting elevated tear levels of
IL-a and matrix metalloproteinase-9 in rosacea patients.
16,17
Bar-
ton et al., also observed high levels of TNF-a at the ocular surface
of these patients. All these are unexpected ndings for normal
eye.
17
The close relationship between ocular and cutaneous
inammation in rosacea is demonstrated by Bamford et al. in a
study that revealed that patients with stye during childhood had
a predisposition for rosacea development during adulthood.
18
Demodex folliculorum mites most probably represent a contribut-
ing cofactor to the inammatory reaction seen in both cutaneous
and ocular disease.
19,20
Our study was designed to: (i) determine the incidence of ocu-
lar disease among a population of rosacea patients, in Northern
Greece, (ii) apply two tear function tests Schirmer and tear
break-up time test (TBUT) to objectively determine the presence
of eye dryness in rosacea patients with and without clinical symp-
toms and signs from the eyes and compare the results with the
general population and (iii) correlate the severity of ocular disease
with the severity of cutaneous rosacea.
Patients and methods
The study was conducted during a 4-year period and included 100
patients with rosacea who attended the First Department of Der-
matology of the Aristotle University of Thessaloniki (AUTH) and
a control group of 24 healthy individuals, matched for age and
gender. The control group comprised individuals with no skin dis-
ease who visited our department for screening examinations (i.e.
screening of naevi).
Inclusion criteria were (i) written informed consent provided
by the two studied groups, (ii) diagnosis of rosacea, based on the
clinical criteria stated by the Expert National Rosacea Society
Committee (presence of one or more of the following primary
features concentrated on the central areas of the face: ushing,
permanent erythema, papules and pustules and telangiectasia) and
the histological ndings.
At rst visit gender, age and gender for both patients and
controls were recorded. At the same time, the clinical stage of
rosacea was determined according to the standard classica-
tion system reported by the Expert National Rosacea Society
Committee.
All patients were questioned and examined for ocular symp-
toms and signs. Twenty-four of them were referred, along with the
controls, to the First Department of Ophthalmology of the AUTH,
to perform the TBUT and Schirmer test in each eye.
The tear lm break-up test was performed with a uorescein-
enhanced tear lm, which was rst moistened with sterile saline
and then placed to the inferior bulbar surface of the conjunctiva
in each eye of the patient. All patients were asked to blink one or
two times in order to stabilize the tear lm before estimating the
tear lm break-up, with the help of a broad spectrum cobalt-blue
light viewed through a yellow lter. The tear break-up time was
dened as the time taken from blink until the appearance of the
rst randomly distributed dark spots or streaks within the uores-
cein-enhanced tear lm. The tear break-up time was considered
normal if it was 10 s.
The Schirmer test was performed with a sterile Schirmer test
lm, inserted between the inner surface of the lower eyelid and the
bulbar surface of the conjunctiva for 5 min. Tear secretion was
assessed after the removal of the strip by measuring the size of the
wet area in millimetres. The test was considered within normal
limits if it was 5 mm, although a Schirmer test 10 mm is a
threshold that many authors consider as the beginning of eye
dryness.
Statistical analysis of all results was carried out using the Fishers
exact and Wilcoxon tests.
Results
In a total of 100 patients, 37 men and 63 women with rosacea
were studied with a mean age of 58 years. All patients were
referred to our dermatological department for their cutaneous
manifestations of rosacea but they were asked and examined for
ocular symptoms and signs as well. The number of patients that
exhibited each one of the ocular manifestations is shown in
Table 1.
A total of 33 patients (33%) were positive for ophthalmic nd-
ings. The most frequent symptoms were burning sensation and
tearing (10 and 5 patients, respectively) and the most frequent
signs were conjunctivitis and blepharitis (18 and 12 patients
respectively). Eleven patients with ophthalmic manifestations had
mild to moderate erythematotelangiectatic rosacea, 17 had moder-
ate papulopustular rosacea and four exhibited ndings of phyma-
tous rosacea.
Table 1 Number of patients and ocular manifestations
Ophthalmic symptoms Patients
number
Ophthalmic
signs
Patients
number
Burning sensation 10 Conjunctivitis 18
Tearing 5 Blepharitis 12
Dry eyes 2 Eyelid swelling 1
Light sensitivity 3 Chalazion 1
Number of patients
with ophthalmic symptoms
17
Number of patients
with ophthalmic signs
25
Number of patients
with ophthalmic
signs and or symptoms
33
2011 The Authors
JEADV 2011, 25, 14281431 Journal of the European Academy of Dermatology and Venereology 2011 European Academy of Dermatology and Venereology
Study of ocular rosacea in northern Greece 1429
Tear function tests were performed in 24 of 100 rosacea patients,
12 women and 12 men. It is important to note that 14 of these
patients complained about eye problems whereas the other 10 were
asymptomatic. These tests were also applied to 24 healthy controls
(12 women and 12 men) without any ophthalmic or skin disease.
The results of Schirmer test are given in Table 2. Pathologic
Schirmer test values (i.e. <5 mm) were not found in any subject
(patient or control). Nevertheless, the rosacea group had a total
mean value of 12.9 mm, which was considerably lower compared
with the controls (21.5 mm). This difference proved to be statisti-
cally signicant (P < 0.0001, Wilcoxon statistical test). There was
also a statistically signicant difference between the mean Schirmer
test values of male patients and male controls (P < 0.0001), female
patients and female controls (P < 0.0001), as well as between male
and female patients (P < 0.0186). At the same time, the difference
between male and female healthy controls was not signicant
(P = 0.577). Among rosacea patients 62.5% had a Schirmer test
score 10 mm compared with 20.8% of controls (P = 0.0086,
Fisher test).
Mean TBUT was shorter in the rosacea group (8.6 s) than in
the age-matched controls (14.4 s) and this difference was statisti-
cally signicant (P < 0.0001, Wilcoxon test) (Table 3). In addition
to that, mean TBUT between male patients and male controls as
well as between female patients and controls showed a statistically
signicant difference. At the same time no signicant difference in
the mean TBUT scores was revealed, between male and female
patients. TBUT score <10 s is considered abnormal, as it is dened
above. The majority of rosacea patients (87.5%) had mean TBUT
scores lower than 10 s, whereas this was the case for only 20.8%
of the healthy controls. This pronounced difference is statistically
signicant (P < 0.0001, Fisher test).
Discussion
Rosacea is a chronic cutaneous disorder that causes high psycho-
logical strain in those affected, but has no serious adverse effects
on vital functions other than the rare but possible development of
sight-threatening conditions. Nevertheless, ocular rosacea is often
overlooked by both doctors and patients, since the latter may not
associate it with the cutaneous disease.
14
On this basis, the early
diagnosis of ocular involvement by clinical evaluation and tear
function tests may prevent major complications such as corneal
vascularization and perforation.
The incidence of ocular manifestations in our rosacea popula-
tion was 33%, while other studies have given results varying from
658%.
5
A very recent study by Bakar et al. presented 72% of
ophthalmic involvement in rosacea patients.
21
This variation prob-
ably reects the difference among study populations and the means
by which the disease is diagnosed each time. The real prevalence of
ocular rosacea is probably underestimated because the ophthalmic
disease usually remains undiagnosed as patients focus their atten-
tion to the aesthetic appearance of their face and not to other
symptoms. This fact strains the need for a detailed history about
eye complaints as well as for a careful evaluation of the clinical con-
dition of eyelid margins and conjuctiva.
22
The exact timing of the
rst manifestations of ocular disease remains unknown. In most
cases, cutaneous ndings appear earlier than ophthalmic ones.
The most frequent ocular symptoms in our study were burning
sensation and tearing (10% and 5%, respectively), whereas the
most common signs were conjunctivitis (18%) and blepharitis
(12%). These ndings are consistent with the ndings reported in
previous studies.
6,10,13,15,2228
However, in contrast to other stud-
ies, serious conditions like supercial punctual keratitis or even
corneal neovascularization, thinning and perforation were not
observed.
6,7,11,13
Moreover, the severity of ocular disease was not
proportional to the gravity of cutaneous rosacea, a nding that is
in agreement with a study conducted by Michel and Calibel
5
Other limited studies correlate the severity of ocular rosacea, either
with a tendency to strong ushing or with the presence of multiple
telangiectasias.
1,26
Tear function tests (i.e. Schirmer test and TBUT) were per-
formed in 24 out of 100 patients of our study, as well as in 24
healthy controls, to determine the presence and gravity of eye dry-
ness in our population. Although all Schirmer test results were
above the limit of 5 mm, which is considered normal, the total
mean value of patients Schirmer tests was 12.9 mm, which is sig-
nicantly lower compared with the 21.5 mm score of the healthy
controls. These results are indicative of the fact that rosacea
patients exhibit higher level of dryness in their eyes when
compared with healthy controls. Moreover, our study showed that
this total mean value was even lower in male rosacea patients
compared with female ones and thus male rosacea patients may
Table 2 Results of Schirmer test
Rosacea patients* Healthy controls
Men Women Men Women
R.E L.E R.E L.E R.E L.E R.E L.E
10.5
mm
11.1
mm
14.9
mm
15.1
mm
20.0
mm
22.0
mm
21.8
mm
22.8
mm
*Total mean value: 12.9 mm.
Total mean value: 21.5 mm.
L.E, left eye; R.E, right eye.
Table 3 Tear break up time mean values
Rosacea patients* Healthy controls
Men Women Men Women
R.E L.E R.E L.E R.E L.E R.E L.E
7.8 s 8.1 s 9.4 s 9.3 s 14.3 s 14.9 s 14.9 s 14.4 s
*Total mean value: 8.6 s.
Total mean value: 14.4 s.
L.E, left eye; R.E, right eye.
2011 The Authors
JEADV 2011, 25, 14281431 Journal of the European Academy of Dermatology and Venereology 2011 European Academy of Dermatology and Venereology
1430 Lazaridou et al.
probably show a greater tendency for dry eyes compared with
female patients. A Schirmer test value <10 mm is considered by
many authors as the clinical threshold of eye dryness. According
to this denition 62.5% of our rosacea patients fullled this crite-
rion, which is a very high proportion when compared with the
20.8% of healthy controls. These ndings are consistent with those
of previous studies and they delineate the fact that rosacea, very
often, is characterized by eye dryness.
13,15,29
The mean value of TBUT was signicantly shorter in the patient
group (8.6 s) compared with that of the healthy controls group
(14.4 s). In addition to that, a great proportion of patients, reach-
ing 87.5%, exhibited TBUT values 10 s compared with the
20.8% of healthy controls with TBUT values under this threshold.
As these ratios are in accordance with similar ndings published
in the past, they strengthen the opinion that eye dryness is a com-
mon problem for rosacea patients.
13,15,21,25,30
Most of the ocular symptoms and signs in rosacea are related to
dry eye, a condition possibly produced by a disturbance in any of
the components that form the preocular tear lm. Rosacea is
closely associated with the dysfunction and inammation of the
meibomian glands.
17,30
These glands are considered as differenti-
ated sebaceous glands, which are the target of inammation in
rosacea. Meibomian gland dysfunction causes an abnormal lipid
composition of the tear lm, which leads to thickened secretions,
lower tear break-up time and consequently dryness of the ocular
surface.
13,15,21,27
This dysfunction could be secondary, either to
increased glandular production of free fatty acids due to bacterial
lipases or to hyperemia because of facial and angular venous dila-
tation.
16,24,31
As a conclusion, ocular involvement in rosacea is a common
phenomenon that affects patients probably through inammatory
pathways. Eye dryness due to meibomian gland dysfunction is
usually the rst clinical sign of the ophthalmic disease and is more
evident in male than female patients. Our study showed that the
severity of ocular rosacea is not associated with the severity of the
cutaneous component of the disorder. Tear function tests, like
Schirmer test and TBUT, although not specic, could contribute
to the screening and early diagnosis of the disease to prevent the
potential development of sight-threatening conditions. It is clear
that rosacea patients need a multidisciplinary approach that
includes an evaluation by both dermatologists and ophthalmolo-
gists.
References
1 Buecher SA. Rosacea: an update. Dermatology 2005; 210: 100108.
2 Powell FC. Rosacea. N Engl J Med 2005; 352:793803.
3 Wilkin J, Dahl M, Detmar M et al. Standard classication of rosacea:
Report of the National Rosacea Society Expert Committee on the classi-
cation and staging of Rosacea. J Am Acad Dermatol 2002; 46: 584587.
4 Wilkin J, Dahl M, Detmar M et al. Standard grading system for rosacea:
Report of the National Rosacea Society Expert Committee on the
classication and staging of Rosacea. J Am Acad Dermatol 2004; 50:
907912.
5 Michel JL, Calibel F. Frequency, severity and treatment of ocular
rosacea during cutaneous disease. Ann Dermatol Venereol 2003; 130:
2024.
6 Ghanem VC, Mehra N, Wong S, Mannis M. The prevalence of ocular
signs in acne rosacea: comparing patients from ophthalmology and
dermatology clinics. Cornea 2003; 22: 230233.
7 Akpek EK, Merchant A, Pinar V, Foster CS. Ocular rosacea: patient
characteristics and follow-up. Ophthalmology 1997; 104: 18631867.
8 Lempert SL, Jenkins MS, Brown SI. Chalazia and rosacea. Arch Oph-
thalmol 1979; 97: 16521653.
9 Kligman A. Ocular rosacea. Current concepts and therapy. Arch Derma-
tol 1997; 133: 8990.
10 Jenkins MA, Brown SI, Lempert SL et al. Ocular rosacea. Am J Ophthal-
mol 1979; 88: 618622.
11 Meschig R, Melnik B, Plewig G. Ophthalmological complications of
rosacea. In: Marks R, Plewig G eds. Acne and Related Disorders. Martin
Dunitz, London, 1989: 321325.
12 Bernardes TF, Bonoli AA. Blepharitis. Semin Ophthalmol 2010; 25:7983.
13 Yaylali V, Ozyurt C. Comparison of tear function tests and impression
cytology with the ocular ndings in acne rosacea. Eur J Ophthalmol
2002; 12: 1117.
14 Tanzi EL, Weinberg JM. The ocular manifestations of Rosacea. Cutis
2001; 68: 112114.
15 Gudmundsen KJ, ODonell BF, Powell FC. Schirmer testing for dry eyes
in patients with rosacea. J Am Acad Dermatol 1992; 26: 211214.
16 Stone DU, Chodosh J. Ocular rosacea: an update on pathogenesis and
therapy. Curr Opinion Ophthalmol 2004; 15: 499502.
17 Barton K, Monroy DC, Nava A, Pugfelder SC. Inammatory cytokines
in the tears of patients with ocular rosacea. Ophthalmology 1997; 104:
18681874.
18 Bamford JT, Gessert CE, Renier CM et al. Childhood stye and adult
rosacea. J Am Acad Dermatol 2006; 55: 951955.
19 Lazaridou E, Apalla Z, Sotiraki S, Ziakas NG, Fotiadou C, Ioannides D.
Clinical and laboratory study of rosacea in northern Greece. J Eur Acad
Dermatol Venereol 2010; 24: 410414.
20 Li J, OReilly N, Sheha H et al. Correlation between ocular Demodex
infestation and serum immunoreactivity to Bacillus proteins in patients
with facial rosacea. Ophthalmology 2010; 117: 870877.
21 Bakar O, Demircay Z, Toker E, Cakir S. Ocular signs, symptoms and
tear function tests of papulopustular rosacea patients receiving azithro-
mycin. J Eur Acad Dermatol Venereol 2009; 23: 544549.
22 Crawford GH, Pelle MT, James WD. Rosacea: etiology, pathogenesis,
and subtype classication. J Acad Dermatol 2004; 51: 327341.
23 Lemp MA, Mahmood MA, Weiler HH. Association of rosacea and
keratoconjunctivitis sicca. Arch Ophthalmol 1984; 102: 556557.
24 Plewig G, Kligman AM. Acne and Rosacea, 3rd edn. Springer-Verlag,
Berlin Heidelberg New York, 2000: 460461.
25 Quarterman MJ, Johnson DW, Abele DC, Lesher JL Jr, Hull DS, Davis
LS. Ocular rosacea. Signs, symptoms, and tear studies before and after
treatment with doxycycline. Arch Dermatol 1997; 133: 4954.
26 Keshtcar-Jafari A, Akhyani M, Ehsani AH et al. Correlation of the
severity of cutaneous rosacea with ocular rosacea. Indian J Dermatol
Venereol Leprol 2009; 75: 405406.
27 Afonso AA, Monroy D, Stern ME et al. Correlation of tear uorescein
clearance and Schirmer test scores with ocular irritation symptoms.
Ophthalmology 1999; 4: 803810.
28 Hoting E, Paul E, Plewig G. Treatment of rosacea with isotretinoin.
Int J Dermatol 1986; 25: 10381043.
29 Kocak-Altintas AG, Kocak-Midillioglu I, Gul U et al. Impression cytol-
ogy and ocular characteristics in ocular rosacea. Eur J Ophthalmol 2003;
13: 351359.
30 McCulley JP, Sciallis GF. Meibomian keratoconjunctivitis. Am J Oph-
thalmol 1997; 84: 788793.
31 Chamaillard M, Mortemousque B, Boralevi F et al. Cutaneous and
ocular signs of childhood Rosacea. Arch Dermatol 2008; 144: 167171.
2011 The Authors
JEADV 2011, 25, 14281431 Journal of the European Academy of Dermatology and Venereology 2011 European Academy of Dermatology and Venereology
Study of ocular rosacea in northern Greece 1431
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