topical cyclosporine in the treatment of allergic conjunctivitis

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surface diseases.10,11 Randomized controlled trials (RCTs)reported to date have shown varying results in the efcacy andsafety of cyclosporine in treating allergic conjunctivitis.12,13

Moreover, the sample sizes of individual trials were small.Inview oftheconicting evidence, we conducted a systematicreview and meta-analysis of RCTs on topical cyclosporineversus placebo in treatingallergic conjunctivitis to evaluatethetreatment efcacy and safety of topical cyclosporine.

Methods

Search Strategy

We searched MEDLINE and EMBASE via the OVID platform, theCochrane Central Register of Controlled Trials, ClinicalTrials.gov(www.clinicaltrials.gov), and the World Health OrganizationInternational Clinical Trials Registry Platform for RCTs thatevaluated topical cyclosporine versus placebo for allergicconjunctivitis. We used the Cochrane highly sensitive searchstrategy14 and combined our search terms as described inAppendix1 (available athttp://aaojournal.org). We manually searched thereferences of all potentially relevant articles to identify studiesnot found by the electronic searches. We did not apply anylanguage restrictions. The nal search was performed on August10, 2012, for all databases.

Inclusion and Exclusion Criteria

Two reviewers (K.H.W. and S.S.R.) independently assessed thetitles and abstracts to identify those that fullled the inclusion

criteria: RCTs; included patients from all age groups with allergicconjunctivitis, which includes the spectrum of seasonal or peren-nial allergic conjunctivitis, VKC, AKC and giant papillary

conjunctivitis; compared cyclosporine versus placebo; and exam-ined at least one of the following outcomes: composite signs score,composite symptoms score, usage of steroid eye drops, andoccurrence of adverse events, including stinging or burningsensation. We included only those trials that dened and tabulatedtheir own composite scores. Typically, the composite signs scorewas determined by averaging the scores of at least one of thefollowing signs: hyperemia, swelling, papillae and giant papillaeon the tarsal conjunctiva, hyperemia and edema of the bulbarconjunctiva, or corneal involvement. Similarly, the compositesymptoms score was calculated in the same manner by averagingthe scores of at least one of the individual symptoms: redness,tearing, burning, discomfort, foreign body sensation, discharge,and photophobia. We excluded studies that did not quantify thesigns and symptoms, studies that did not use a placebo or vehicle

eye drops as a control, or studies that presented data on patient sub-groups only.

Data Extraction

Two reviewers (K.H.W. and L.J.C.) independently performed thedata extraction that met the inclusion criteria. We used a customizedform to record the author of study, year of publication, location oftrials, sample size, mean age, gender, duration of follow-up, inter-ventions, and outcome measures. The extracted outcomes werebased on the data from the double-masked (participants andoutcome assessors), placebo-controlled phase of the respectivestudies. Outcomes at a follow-up time point, rather than the change

Potentially relevant articlesidentified: 556

MEDLINE: 205

EMBASE: 300

CENTRAL: 14

Clinical Trials: 33

WHO ICTRP: 4

Duplicates: 119

Titles and Abstracts

screened: 437

Articles obtained for full

text review: 21

Not eligible: 416

Study excluded: 14

Non-RCTs: 7

Unqualified interventions: 3

Unqualified outcome measures: 4

Eligible RCTs: 7

Figure 1. Flow chart showing selection of publications for inclusion in this meta-analysis. CENTRAL Cochrane Central Register of Controlled Trials;

RCT randomized control trial; WHO ICTRP World Health Organization International Clinical Trials Registry Platform.

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from baseline, were extracted and analyzed.15,16 In studies that useda scale where the scores of signs and symptoms decreased with

severity, we reversed the values of our extracted data to ensure thescales in our meta-analysis point in a unied direction (i.e., a highernumerical value means more severe signs and symptoms). We ob-tained standard deviations and standard errors from P valuesfollowing methods outlined in the Cochrane Handbook forSystematic Reviews of Interventions.16 We interpolated outcomemeasures fromgures if the numerical values were not reported inthe texts. The results presented are based on participants whocompleted the follow-up in individual studies.

Assessment of Risk of Bias

We assessed therisk of bias of included studies using the Cochranerisk of bias tool.17 We evaluated random sequence generation andallocation concealment (selection bias), masking of participants

and personnel (performance bias), masking of outcomeassessment (detection bias), incomplete outcome data (attritionbias), and selection reporting (reporting bias). We graded eachdomain as: low, unclear, and high risk of bias according to thecriteria outlined in the Cochrane Handbook for SystematicReview of Interventions.17 Two reviewers (K.H.W. and S.S.R.)independently assessed the risk of bias and resolveddiscrepancies by discussion.

Statistical Analysis

We used Review Manager software version 5.2 (The NordicCochrane Centre, The Cochrane Collaboration, Copenhagen,Denmark) for meta-analyses. We analyzed the scores of compositesigns and symptoms and the reduction in steroid eye drop use as

continuous variables, whereas the side effects were used asdichotomous variables. Notably, all the included studies reporteda composite score of signs and symptoms, but each study tabulatedits own composite score differently using a combination of signsand symptoms. For this reason, we used the standardized meandifference as the summary measure to analyze results on a uniformscale. Standardized mean difference expresses the size of theintervention effect in each study with respect to the variabilitywithin that study and is reported in units of standard deviation.Because the absolute value is difcult to interpret on its own, itshould be interpreted together with the P value and condenceinterval (CI).15 We used standardized mean difference for scores ofcomposite signs and symptoms, mean differences for reduction of

steroid eye drops use, and the Mantel-Haenszel odds ratio foroccurrence of adverse events, namely stinging or burning

sensation.Statistical heterogeneity of the included studies was analyzedusing the Cochrane Q-statistics chi-square test and I2 statistic. Ifsignicant heterogeneity was observed between studies, a randomeffects model was used for pooling the data; otherwise, a xedeffects model was used. We conducted a sensitivity analysis toexamine the inuence of each individual study on the overall meta-analysis estimate.17

Results

We identied 556 titles and abstracts through our literature searchand retrieved 21 articles for a full text review. We included7RCTsin this systematic review and meta-analysis (Fig 1).12,13,18e22

Study Characteristics

Table 1 shows the characteristics of the included trials. Weincluded 7 studies, with a total of 153 participants and 306 eyes.Two studies were conducted in Italy, and 1 study each wasconducted in the United States, the United Kingdom, Australia,Turkey, and India. A total of 53 patients from 3 studies wereassigned randomly to receive topical cyclosporine in 1 eye,whereas the fellow eye was treated with placebo (paired-eyedesign).18e20 In the remaining 4 studies, 51 patients in total wereassigned randomly to receive topical cyclosporine in both eyes,whereas 49 patients in total received placebo in botheyes, and theoutcomes were evaluated on a patient basis.12,13,21,22 Sample sizesranged from 9 to 35. More than 70% of the participants were male.The follow-up periods of ranged from 2 to 16 weeks. Theconcentration of topical cyclosporine was 2% or 0.05%.

Risk of Bias in Included Studies

Figures 2 and 3 (available at http://aaojournal.org) summarizethe risk of bias assessment of included studies. For selectionbias, 4 studies used a computer-generated randomization sc-heme.12,13,21,22 Two studies provided sufcient details on themethod of allocation concealment by having the allocation codingkept by a person who was independent of the trial.12,22 Forperformance and detection biases, all except one study19 weredouble-masked (participants and outcome assessors) and placebo-controlled trials. Masking was achieved by using identical unit

Table 1. Characteristics of included trials

Study (Year) CountryPts/Eyes

(n)

Mean Age (Yr) SD Male/FemaleFU(wk)

Conc.of CsA

Regimen;duration

Completion of FU

CsA Placebo CsA Placebo CsA Placebo

Daniell (2006)13 Australia 35/70 26.218 26.2 16.3 15/2 13/5 12 0.05% 4 times/day; 3 mo 17/20 18/20Kilic (2006)18 Turkey 20/40* 7.9 2.2 12/8 2 2% 5 times/day; 2 wk N/AAkpek (2004)21 US/UK 20/40 42.3 10.6 42.9 17.8 6/4 6/4 4 0.05% 6 times/day; 2 wk and

4 times/day; 2wk10/10 10/12

Pucci (2002)19

Italy 24/48* 8.4 1.6 16/8 2 2% 4 times/day; 2 wk N/AGupta (2001)22 India 24/48 10.8 3.5 10.6 4.6 10/2 12/0 16 2% 4 times/day; 4 mo 12/12 12/12Hingorani (1998)12 UK 21/42 33.9 13.5 35.7 13.8 8/4 4/5 12 2% 4 times/day; 3 mo 12/12 9/9Secchi(1990)20 Italy 9/18* 11.2 7.2 N/A 15 days 2% 4 times/day; 15 days 9/9

Conc. concentration; CsA cyclosporine; FU follow-up; mo months, N/A data not available; Pts patient; SD standard deviation;US United States; UKUnited Kingdom; wk weeks; Yryears*53 patients were randomly assigned to receive topical cyclosporine in one eye, whereas the fellow eye was treated with placebo. 17-19 Of the remainingpatients, 51 were randomly assigned to receive topical cyclosporine in both eyes, and 49 patients were randomly assigned to receive placebo in both eyes.20-23

For the latter group, the outcomes were evaluated on a patient-basis.

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bottles to hold the study treatment. We judged attrition bias to be oflow risk in 4 studies where reasons for and the numbers ofparticipants who exited the study werereported clearly and wereunlikely to affect the outcome.12,13,20,22 We could not comment onthe risk of selective reporting because we did not have access to thestudy protocols, but all outcomes described in respective method-

ologies were reported. None of the studies were judged to be athigh risk of bias in any domain.

Outcome Measures

The meta-analytical results for the 4 outcomes are summarized inFigures 4e7. All of the 7 studies reported scores for composite signsand symptoms. Statistically signicant heterogeneity was detectedin the outcomes except for the reduction in steroid eye drop use.

Topical cyclosporine was associated withlower compositescoresof signs and symptoms of allergic conjunctivitis as compared withplacebo. The pooled standardized mean difference was 1.21 (95%CI, 1.80 to 0.62; I2 71%;Fig 4) and 0.84 (95% CI, 1.51to 0.16; I2 80%; Fig 5), respectively. Of the 3 studies thatrecruited patients with steroid-dependent allergic conjunctivitis, 2reported reduction in steroid eye drop use. The pooled meandifference was 61.2 (95% CI, 101.6 to 20.7; I2 58%;Fig 6)steroid eye drops per week in participants who had supplemented.

Six studies reported adverse effects. Three studies did notobserve any stinging or burning sensation on instillation of thecyclosporine or placebo eye drops. Topical cyclosporine did notshow a higher observable rate of burning or stinging sensation(odds ratio, 2.56; 95% CI, 0.19e35.06; I2 73%; Fig 7). Oursensitivity analysis by omitting one study a time did not changethe results (data not shown).

Discussion

The present systematic review and meta-analysis found thattopical cyclosporine is effective in alleviating the signs andsymptoms of allergic conjunctivitis and reducing the use of

topical steroid eye drops in steroid-dependent patients, whilemaintaining similar safety prole as compared with placebo.

Scores of Composite Signs and Symptoms

The outcomes that quantied the treatment efcacy aresubjective. The signs were graded by the clinicians onophthalmologic examination and the symptoms were self-reported. Although these measurements are subjective andan information bias is likely, clinical decisions usually arebased on such ndings in history taking and physical exam-ination. Thus, we regard this methodology to evaluate theoutcome as acceptable and conclude that patients treated withtopical cyclosporine, regardless of the dose and treatment

regimen, demonstrated greater improvement in the manifes-tations of allergic conjunctivitis as compared with placebo.

Reduction in Steroid Eye Drop Use

The trial of Hingorani et al12 reported that topicalcyclosporine allowed patients with steroid-dependent AKCto wean off topical corticosteroid, whereas the trial ofDaniell et al13 revealed no statistically signicant differencebetween the steroid and placebo groups in patients with

Figure 4. Graph showing the effect of topical cyclosporine (CsA) versus placebo on the combined outcome score of composite signs. CI condence

interval; IV inverse variance; SD standard deviation; Std. standardized.

Figure 5. Graph showing the effect of topical cyclosporine (CsA) versus placebo on the combined outcome in score of composite symptoms. CI

condence interval; IV inverse variance; SD standard deviation; Std. standardized.


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AKC or VKC. In these trials, the amount of steroid use wasmodulated during the course of study, but the extent ofmodulation varied and depended on the clinicianssubjective assessment of the patients clinical response,which inevitably introduces information bias. The differentforms of steroid were adjusted by a factor to allowcomparison of their relative potencies.23 Although oursummary statistics showed a signicant reduction in steroideye drop use, interpretation should be made with cautionbecause the number of included studies and participants forthis outcome is small. Furthermore, the 2 trials useddifferent concentrations of cyclosporine 2% and 0.05%,which could explain in part why reduction in steroid eyedrop use was observed in the study of Hingorani et al12 thatused a higher concentration. Moreover, the study ofHingorani et al12 included AKC patients exclusively,whereas that of Daniell et al13 included both AKC and VKCpatients, which suggests that topical cyclosporine may havea role in reducing steroid eye drop use in AKC patients only.

Safety

The present study found that the safety prole of topical

cyclosporine is comparable with that of placebo whenstinging and burning sensation are used as indicators ofsafety outcomes. Stinging and burning are the most commonadverse effects associated with topical cyclosporine in phase3 studies of cyclosporine in dry eye patients.24,25 Theseadverse effects may be attributed to the vehicle (e.g., olive,maize, or castor oil) used to dissolve cyclosporine. A large-

scale multicenter RCT that examined topical cyclosporine indry eye patients showed that despite the occurrences ofadverse effects, only 2.4% of the patients in the cyclosporinegroup discontinued the study because of intolerabilitycompared with 1.7% of the patients in the placebo groupover 6 months.25 Another phase 3 study of the safetyevaluation of ophthalmic cyclosporine in dry eye patientsreported that the participants continued their assignedmedication with no serious treatment-related adverseeffects over a mean follow-up of 19.8 months.24 Thecomments on the safety of topical cyclosporine drawnfrom our systematic review and meta-analysis are consis-tent with those from these large-scale clinical trials, sug-gesting that cyclosporine could be a safe and well-toleratedtreatment for allergic conjunctivitis.

Limitations and Perspectives

Quality of the Evidence. Our search was limited to studiespublished in indexed journals and trial registers. Theincluded trials also vary in terms of population, the types ofallergic conjunctivitis, dosage and regime of cyclosporine,measurement of clinical outcomes, follow-up period, and

qualities.Patients across the included studies had different forms of

allergic conjunctivitis (AKC, VKC, or both), which could beone source of clinical heterogeneity. However, both AKC andVKC are subsets ofallergic conjunctivitis with similar patho-physiologic features.26 Thus, we believe that the heterogeneitythat resulted from their pooling had a minimal impact on the

Figure 6. Graph showing the effect of topical cyclosporine (CsA) versus placebo on the combined outcome of reduction in steroid eye drops use. CI condence interval; IV inverse variance; SD standard deviation.

Figure 7. Graph showing the effect of topical cyclosporine (CsA) versus placebo on the combined outcome of stinging or burning sensation. There were 3

studiesdAkpek et al,21 Daniell et al,13 and Kilic and Gurler18dreporting that no side effects were detected; however, results of these studies were not

included in the pooled analysis. CI condence interval; df degrees of freedom; M-H Mantel-Haenszel.


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outcomes. Another possible source includes the differentconcentration of topical cyclosporine used. A study suggestedthat 1% cyclosporine may be the minimal effective treatmentregimen to control the manifestations of VKC,27 whereas forAKC, the lowest concentration commercially available,0.05% cyclosporine (Restasis; Allergan, Inc, Irvine, CA), wasshown to be effective.21 Therefore, any concentration higherthan 0.05% should be included for analysis.

The study design could be a source of methodologicheterogeneity. Three studies included patients whocontinued their usual topical steroid therapy during thetrial.12,13,21 Two studies had a washout period free ofdrugs,18,22 whereas the remaining2 studies stopped all drugsbefore the start of the trial.19,20 The addictive benet oftopical cyclosporine to the patients usual treatment may leadto an overestimation of its efcacy. Adequate randomizationwithin the original trials can balance the effect of suchheterogeneities. Moreover, the use of a standardized meandifference as an outcome measure also addressed intra-studyvariability. Another source of heterogeneity might haveresulted from the varied criteria for dening the scales of

allergic signs and symptoms across the included studies.Finally, the periods of the double-masked controlled phasesvaried across the studies (2e16 weeks), making the long-term efcacy and safety yet to be determined.

Implications for Practice.Our meta-analysis supportsthe use of topical cyclosporine for treating allergicconjunctivitis. It is more effective than placebo in alleviatingthe overall signs and symptoms. The stinging and burningsensation of topical cyclosporine is similar to that ofplacebo. Topical cyclosporine also has been shown to havea role in weaning off steroid eye drops in steroid-dependentpatients. Nevertheless, the clinical and methodologicheterogeneities across the studies suggest that the overallefcacy of topical cyclosporine should be appreciated with

caution. Further RCTs with larger sample sizes providingsufcient statistical power to detect even a small differencein the treatment effects, standardized study designsincluding the use of precisely dened grading for theseverity of individual signs and symptoms, unied follow-up schedules, and different concentrations of cyclosporineare warranted to determine the short- and long-term efcacyand safety and the minimal effective dosage of topicalcyclosporine in treating allergic conjunctivitis.

References

1. Calonge M. Classication of ocular atopic/allergic disordersand conditions: an unsolved problem. Acta Ophthalmol ScandSuppl 1999;(228):103.

2. von Mutius E, Martinez FD, Fritzsch C, et al. Prevalence ofasthma and atopy in two areas of West and East Germany. AmJ Respir Crit Care Med 1994;149:35864.

3. Abelson MB, Smith L, Chapin M. Ocular allergic disease:mechanisms, disease sub-types, treatment. Ocul Surf 2003;1:12749.

4. Ono SJ, Abelson MB. Allergic conjunctivitis: update onpathophysiology and prospects for future treatment. J AllergyClin Immunol 2005;115:11822.

5. Belfort R, Marbeck P, Hsu CC, Freitas D. Epidemiologicalstudy of 134 subjects with allergic conjunctivitis. Acta Oph-thalmol Scand Suppl 2000;(230):3840.

6. Leonardi A, De Dominicis C, Motterle L. Immunopatho-genesis of ocular allergy: a schematic approach to differentclinical entities. Curr Opin Allergy Clin Immunol 2007;7:42935.

7. Leonardi A. Emerging drugs for ocular allergy. Expert OpinEmerg Drugs 2005;10:50520.

8. Bielory L. Ocular allergy treatment. Immunol Allergy ClinNorth Am 2008;28:189224, vii.

9. Bonini S, Bonini S, Lambiase A, et al. Vernal keratocon-junctivitis revisited: a case series of 195 patients with long-term followup. Ophthalmology 2000;107:115763.

10. Power WJ, Mullaney P, Farrell M, Collum LM. Effect oftopical cyclosporin A on conjunctival T cells in patients withsecondary Sjgrens syndrome. Cornea 1993;12:50711.

11. el-Asrar AM, Tabbara KF, Geboes K, et al. An immunohis-tochemical study of topical cyclosporine in vernal keratocon-junctivitis. Am J Ophthalmol 1996;121:15661.

12. Hingorani M, Moodaley L, Calder VL, et al. A randomized,placebo-controlled trial of topical cyclosporin A in steroid-dependent atopic keratoconjunctivitis. Ophthalmology 1998;105:171520.

13. Daniell M, Constantinou M, Vu HT, Taylor HR. Rando-mised controlled trial of topical ciclosporin A in steroiddependent allergic conjunctivitis. Br J Ophthalmol 2006;90:4614.

14. Lefebvre C, Manheimer E, Glanville J, Cochrane InformationRetrieval Methods Group. 6.4.11: search lters. In: Higgins JP,Altman DG, eds. Cochrane Handbook for Systematic Reviewsof Interventions Version 5.1.0 [updated March 2011]. TheCochrane Collaboration; 2011. Available at: http://handbook.cochrane.org/. Accessed March 4, 2013.

15. Deeks JJ,Higgins JP,Altman DG,Cochrane Statistical MethodsGroup. Analysing data and undertaking meta-analyses. In:Higgins JP, Altman DG, eds. Cochrane Handbook for System-atic Reviews of Interventions Version 5.1.0 [updated March

2011]. The Cochrane Collaboration; 2011. Available at:http://handbook.cochrane.org/. Accessed March 4, 2013.

16. Higgins JP, Deeks JJ. 7.7.3: data extraction for continuousoutcomes. In: Higgins JP, Altman DG, eds. Cochrane Hand-book for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration; 2011.Available at: http://handbook.cochrane.org/. Accessed March4, 2013.

17. Higgins JP, Altman DG, Sterne JA, Cochrane StatisticalMethods Group, Cochrane Bias Methods Group. Assessingrisk of bias in included studies. In: Higgins JP, Altman DG,eds. Cochrane Handbook for Systematic Reviews of Inter-ventions Version 5.1.0 [updated March 2011]. The CochraneCollaboration; 2011. Available at: http://handbook.cochrane.org/. Accessed March 4, 2013.

18. Kilic A, Gurler B. Topical 2% cyclosporine A in preservative-free articial tears for the treatment of vernal keratoconjunc-tivitis. Can J Ophthalmol 2006;41:6938.

19. Pucci N, Novembre E, Cianferoni A, et al. Efcacy and safetyof cyclosporine eyedrops in vernal keratoconjunctivitis. AnnAllergy Asthma Immunol 2002;89:298303.

20. Secchi AG, Tognon MS, Leonardi A. Topical use of cyclo-sporine in the treatment of vernal keratoconjunctivitis. Am JOphthalmol 1990;110:6415.

21. Akpek EK, Dart JK, Watson S, et al. A randomized trial oftopical cyclosporin 0.05% in topical steroid-resistant atopickeratoconjunctivitis. Ophthalmology 2004;111:47682.


2202
http://handbook.cochrane.org/http://handbook.cochrane.org/http://handbook.cochrane.org/http://handbook.cochrane.org/http://handbook.cochrane.org/http://handbook.cochrane.org/http://handbook.cochrane.org/http://handbook.cochrane.org/http://handbook.cochrane.org/http://handbook.cochrane.org/http://handbook.cochrane.org/http://handbook.cochrane.org/http://handbook.cochrane.org/http://handbook.cochrane.org/


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22. Gupta V, Sahu PK. Topical cyclosporin A in the manage-ment of vernal keratoconjunctivitis. Eye (Lond) 2001;15:3941.

23. Jaanus SD. Anti-inammatory drugs. In: Bartlett JD,Jaanus SD, eds. Clinical Ocular Pharmacology. 2nd ed.Boston: Butterworths; 1989:16397.

24. Barber LD, Pugfelder SC, Tauber J, Foulks GN. Phase IIIsafety evaluation of cyclosporine 0.1% ophthalmic emulsionadministered twice daily to dry eye disease patients for up to 3

years. Ophthalmology 2005;112:17904.

25. Sall K, Stevenson OD, Mundorf TK, Reis BL; CsA Phase 3Study Group. Two multicenter, randomized studies of the ef-cacy andsafety of cyclosporineophthalmic emulsionin moderateto severe dry eye disease. Ophthalmology 2000;107:6319.

26. Wong NN. Vernal vs. atopic keratoconjunctivitis. Clin Eye VisCare 1999;11:136.

27. Spadavecchia L, Fanelli P, Tesse R, et al. Efcacy of 1.25%and 1% topical cyclosporine in the treatment of severe vernalkeratoconjunctivitis in childhood. Pediatr Allergy Immunol

2006;17:52732.

Footnotes and Financial Disclosures

Originally received: June 23, 2012.

Final revision: March 25, 2013.

Accepted: March 27, 2013.

Available online: June 4, 2013. Manuscript no. 2012-918.1 Department of Ophthalmology and Visual Sciences, Prince of Wales

Hospital, Shatin, New Territories, Hong Kong, China.2 Department of Ophthalmology and Visual Sciences, The Chinese

University of Hong Kong, Hong Kong, China.

Financial Disclosure(s):

The author(s) have no proprietary or commercial interest in any materials

discussed in this article.

Correspondence:

Dr. Alvin L. Young, MMedSc(Hons), FRCSI, Department of Ophthal-

mology and Visual Sciences, The Chinese University of Hong Kong, Prince

of Wales Hospital, Shatin, New Territories, Hong Kong, China. E-mail:

[email protected].


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