20140110090111_0170

资料来自互联网，仅供科研和教学使用，使用者请于24小时内自行删除

ORIGINAL ARTICLE

Clinical and laboratory study of ocular rosacea innorthern 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: [email protected]

AbstractBackground 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 findings. 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 findings of phymatous rosacea. The total mean value of patients’ Schirmer tests was significantly

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 specific, 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

Conflict of interestNone declared.

Funding sourcesNo funding sources supported this work.

IntroductionRosacea 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 (flushing, 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 classification system for rosacea that was developed by

the National Rosacea Expert Committee defines 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 and dermatological studies.5,6 In most 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 chalazion were 4–5 times more likely to suffer from rosacea.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.9–11 Ophthalmic complications such as

blepharitis, conjunctivitis, meibohmian gland dysfunction, styes,

chalazia, superficial punctate keratitis and iritis may also occur.9–12

Vision-threatening aspects of the disease are rare and include con-

ditions such as marginal corneal infiltrates and ulceration or even

corneal neovascularization, thinning and perforation.9,13

ª 2011 The Authors

JEADV 2011, 25, 1428–1431 Journal of the European Academy of Dermatology and Venereology ª 2011 European Academy of Dermatology and Venereology

DOI: 10.1111/j.1468-3083.2011.03995.x JEADV


The above mentioned manifestations are not specific 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.13–15 The current knowledge is that rosacea is an inflam-

matory disorder. There are studies that confirm the inflammatory

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 findings for normal

eye.17 The close relationship between ocular and cutaneous

inflammation 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 inflammatory 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 methodsThe 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: flushing,

permanent erythema, papules and pustules and telangiectasia) and

the histological findings.

At first 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 classifica-

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 film break-up test was performed with a fluorescein-

enhanced tear film, which was first 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 film before estimating the

tear film break-up, with the help of a broad spectrum cobalt-blue

light viewed through a yellow filter. The tear break-up time was

defined as the time taken from blink until the appearance of the

first randomly distributed dark spots or streaks within the fluores-

cein-enhanced tear film. The tear break-up time was considered

normal if it was ‡10 s.

The Schirmer test was performed with a sterile Schirmer test

film, 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 Fisher’s

exact and Wilcoxon tests.

ResultsIn 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 find-

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 findings of phyma-

tous rosacea.

Table 1 Number of patients and ocular manifestations

Ophthalmic symptoms Patientsnumber

Ophthalmicsigns

Patientsnumber

Burning sensation 10 Conjunctivitis 18

Tearing 5 Blepharitis 12

Dry eyes 2 Eyelid swelling 1

Light sensitivity 3 Chalazion 1

Number of patientswith ophthalmic symptoms

17

Number of patientswith ophthalmic signs

25

Number of patientswith ophthalmicsigns and ⁄ or symptoms

33

ª 2011 The Authors


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 significant (P < 0.0001, Wilcoxon statistical test). There was

also a statistically significant 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 significant

(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 significant (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

significant difference. At the same time no significant difference in

the mean TBUT scores was revealed, between male and female

patients. TBUT score <10 s is considered abnormal, as it is defined

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

significant (P < 0.0001, Fisher test).

DiscussionRosacea 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

6–58%.5 A very recent study by Bakar et al. presented 72% of

ophthalmic involvement in rosacea patients.21 This variation prob-

ably reflects 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

first manifestations of ocular disease remains unknown. In most

cases, cutaneous findings 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 findings are consistent with the findings reported in

previous studies.6,10,13,15,22–28 However, in contrast to other stud-

ies, serious conditions like superficial 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 finding that is

in agreement with a study conducted by Michel and Calibel5

Other limited studies correlate the severity of ocular rosacea, either

with a tendency to strong flushing 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-

nificantly 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

10.5mm

11.1mm

14.9mm

15.1mm

20.0mm

22.0mm

21.8mm

22.8mm

*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.

ª 2011 The Authors


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 definition 62.5% of our rosacea patients fulfilled this crite-

rion, which is a very high proportion when compared with the

20.8% of healthy controls. These findings 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 significantly 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 findings 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 film. Rosacea is

closely associated with the dysfunction and inflammation of the

meibomian glands.17,30 These glands are considered as differenti-

ated sebaceous glands, which are the target of inflammation in

rosacea. Meibomian gland dysfunction causes an abnormal lipid

composition of the tear film, 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 inflammatory

pathways. Eye dryness due to meibomian gland dysfunction is

usually the first 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 specific, 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.

References1 Buecher SA. Rosacea: an update. Dermatology 2005; 210: 100–108.

2 Powell FC. Rosacea. N Engl J Med 2005; 352:793–803.

3 Wilkin J, Dahl M, Detmar M et al. Standard classification of rosacea:

Report of the National Rosacea Society Expert Committee on the classi-

fication and staging of Rosacea. J Am Acad Dermatol 2002; 46: 584–587.

4 Wilkin J, Dahl M, Detmar M et al. Standard grading system for rosacea:

Report of the National Rosacea Society Expert Committee on the

classification and staging of Rosacea. J Am Acad Dermatol 2004; 50:

907–912.

5 Michel JL, Calibel F. Frequency, severity and treatment of ocular

rosacea during cutaneous disease. Ann Dermatol Venereol 2003; 130:

20–24.

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: 230–233.

7 Akpek EK, Merchant A, Pinar V, Foster CS. Ocular rosacea: patient

characteristics and follow-up. Ophthalmology 1997; 104: 1863–1867.

8 Lempert SL, Jenkins MS, Brown SI. Chalazia and rosacea. Arch Oph-

thalmol 1979; 97: 1652–1653.

9 Kligman A. Ocular rosacea. Current concepts and therapy. Arch Derma-

tol 1997; 133: 89–90.

10 Jenkins MA, Brown SI, Lempert SL et al. Ocular rosacea. Am J Ophthal-

mol 1979; 88: 618–622.

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: 321–325.

12 Bernardes TF, Bonfioli AA. Blepharitis. Semin Ophthalmol 2010; 25:79–83.

13 Yaylali V, Ozyurt C. Comparison of tear function tests and impression

cytology with the ocular findings in acne rosacea. Eur J Ophthalmol

2002; 12: 11–17.

14 Tanzi EL, Weinberg JM. The ocular manifestations of Rosacea. Cutis

2001; 68: 112–114.

15 Gudmundsen KJ, O’Donell BF, Powell FC. Schirmer testing for dry eyes

in patients with rosacea. J Am Acad Dermatol 1992; 26: 211–214.

16 Stone DU, Chodosh J. Ocular rosacea: an update on pathogenesis and

therapy. Curr Opinion Ophthalmol 2004; 15: 499–502.

17 Barton K, Monroy DC, Nava A, Pflugfelder SC. Inflammatory cytokines

in the tears of patients with ocular rosacea. Ophthalmology 1997; 104:

1868–1874.

18 Bamford JT, Gessert CE, Renier CM et al. Childhood stye and adult

rosacea. J Am Acad Dermatol 2006; 55: 951–955.

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: 410–414.

20 Li J, O’Reilly N, Sheha H et al. Correlation between ocular Demodex

infestation and serum immunoreactivity to Bacillus proteins in patients

with facial rosacea. Ophthalmology 2010; 117: 870–877.

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: 544–549.

22 Crawford GH, Pelle MT, James WD. Rosacea: etiology, pathogenesis,

and subtype classification. J Acad Dermatol 2004; 51: 327–341.

23 Lemp MA, Mahmood MA, Weiler HH. Association of rosacea and

keratoconjunctivitis sicca. Arch Ophthalmol 1984; 102: 556–557.

24 Plewig G, Kligman AM. Acne and Rosacea, 3rd edn. Springer-Verlag,

Berlin Heidelberg New York, 2000: 460–461.

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: 49–54.

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: 405–406.

27 Afonso AA, Monroy D, Stern ME et al. Correlation of tear fluorescein

clearance and Schirmer test scores with ocular irritation symptoms.

Ophthalmology 1999; 4: 803–810.

28 Hoting E, Paul E, Plewig G. Treatment of rosacea with isotretinoin.

Int J Dermatol 1986; 25: 1038–1043.

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: 351–359.

30 McCulley JP, Sciallis GF. Meibomian keratoconjunctivitis. Am J Oph-

thalmol 1997; 84: 788–793.

31 Chamaillard M, Mortemousque B, Boralevi F et al. Cutaneous and

ocular signs of childhood Rosacea. Arch Dermatol 2008; 144: 167–171.

ª 2011 The Authors


Study of ocular rosacea in northern Greece 1431


This document is a scanned copy of a printed document. No warranty is given about the accuracy of the copy.

Users should refer to the original published version of the material.

20140110090111_0170

Documents