1. OCULAR FEATURES OF VERNAL KERATOCONJUNCTIVITIS IN CHILDREN REQUIRING TRABECULECTOMY WITH MITOMYCIN-C FOR STEROID-INDUCED GLAUCOMA CORDELIA CHAN FRCSEd MARCUS ANG MMed DONALD TAN FRCOphth FINANCIAL DISCLOSURES CORDELIA CHAN Consultant, Carl Zeiss Meditec (Travel Sponsorship) MARCUS ANG Nil DONALD TAN Patents / Royalty, NetWork Medical Products The authors have no financial interest in the subject matter of this poster

2. VERNAL KERATOCONJUNCTIVITIS Vernal keratoconjunctivitis (VKC) is a severe form of ocular allergy that affects mostly children and young adults, with a prevalence of up to 5- 15% amongst children The disease is often chronic and persistent in the tropical climates in Asia, unlike the seasonal exacerbations seen in temperate climates The chronic forms in Asians eyes may be at high risk of permanent visual impairment from corneal scarring, cataract formation and glaucoma secondary to corticosteroid therapy

3. STEROID RESPONSE IN VKC “Steroid response” in VKC can lead to a secondary open-angle glaucoma, which may persist even after corticosteroid therapy is discontinued and the IOP normalizes Patients with VKC receiving corticosteroid therapy have been reported to be associated with a 2-7% incidence of glaucoma

4. PURPOSE We analysed cases of severe VKC with corticosteroid-induced glaucoma in our Asian population, and describe from these cases the clinical profile of patients requiring trabeculectomy with mitomycin-C (MMC). The risk factors for trabeculectomy as well as the disease patterns and intraocular pressure control following surgery are highlighted

5. MATERIALS AND METHODS A retrospective case-controlled review of medical records of all cases of VKC seen in a single Center from 1 Jan 03 to 31 Dec 08. Data was entered into standardized data collection forms designed specifically for the study The disease severity was graded based on the definition by Bonini et al. Clinical grade 3 and 4 (“severe” and “very severe”) were included in the study –Bonini S, Sacchetti M, Mantelli F, Lambiase A. Clinical grading of vernal keratoconjunctivitis. Curr Opin Allergy Clin Immunol 2007 Oct;7(5):436-41. Corticosteroid-induced glaucoma was diagnosed if eyes had more than two recordings of increased IOP > 21mmHg on Goldmann applanation tonometry, and glaucomatous optic nerve head changes or glaucomatous visual field defects on Humphrey 24-2 full threshold testing The clinical profile of steroid responders with failed medical therapy requiring trabeculectomy with MMC (0.02%, applied for 3-5min), and their outcomes following surgery were documented.

6. RESULTS A total of 171 patients with severe VKC were reviewed, of which 36 patients (21.0%) were found to have corticosteroid- induced glaucoma 6 patients (8 eyes) (16.7%) of these steroid responders underwent trabeculectomy with MMC after failed medical therapy SUMMARY PROFILE OF PATIENTS REQUIRING TRABECULECTOMY WITH MMC Mean age: 9.3 years (+/-4.5) Sex: All male Mean maximum IOP: 38.8mmHg (+/-7.9) Mean increase in IOP from baseline: 29.0mmHg (+/-8.2) All had severe topical steroid dependent disease. 1 patient was given a short-course of oral steroids All required two or more IOP lowering eyedrops pre-operatively Mean duration of disease at time of trabeculectomy: 7.2 years

7. PATIENTS REQUIRING TRABECULECTOMY WITH MMC Patient (Age/Sex /Race) Systemic atopic disease and /or family history of atopy Duration of disease (years) at time of surgery No. of Recurren ces Peak IOP (mmHg) Duration of steroid use (Weeks) Main steroid used No. of anti- glaucoma medications Type of Surgery Mean Clinical grade of VKC Pre- operative Mean Clinical grade of VKC Post- operative P-value 4/M/c Y43359D2 R Trabeculectomy / MMC L: 3.934 R: 4.000 L: 1.000 R: 0.932 0.014 5/M/i Y 3 123118D3 R & L Trabeculectomy / MMC L: 3.666 R: 4.000 L: 1.000 R: 1.022 0.035 7/M/i Y43427D2 L Trabeculectomy / MMC L: 4.000 R: 0.534 L: 1.000 R: 0.534 0.001 7/M/c Y663472D3 R Trabeculectomy / MMC L: 3.332 R: 3.668 L: 3.668 R: 0.932 0.001 13/M/c Y9105330D2 R & L Trabeculectomy / MMC L: 3.668 R: 3.934 L: 0.934 R: 0.934 0.030 14/M/c Y683839PF2 L Trabeculectomy / MMC L: 3.268 R: 3.934 L: 0.866 R: 3.868 0.001 Demographics: Age= Presenting Age, M=Male, c= Chinese, i=Indian, m=Malay; Medical history: Y=Yes, N=No; Main steroid used: D=Dexamethasone 0.1% Topical, PF= Predforte 1.0% Topical; Clinical grade of VKC: Based on modified clinical grading by Bonini et al 8 weeks pre-operatively and duration of post-operative period.

8. RISK FACTORS FOR TRABECULECTOMY VKC patients with steroid response requiring trabeculectomy with MMC were compared with those treated medically This was performed with age and gender-adjusted logistic regression Risk factors: –Longer duration of steroid use (OR 1.1; 95%CI, 1.0-1.3; p=0.035) –Higher peak IOP (OR1.3; 95%CI, 1.0-1.5; p=0.017) –Greater increase in IOP from baseline (OR 1.3; 95%CI, 1.0-1.5; p=0.011) Multivariate analysis revealed this to be the most significant risk factor –Other factors eg type of steroid used, type of VKC (ie limbal, tarsal, mixed), corneal involvement or neovascularization were not found to be significant

9. POST-TRABECULECTOMY OUTCOMES Significant improvement in severity of VKC post-trabeculectomy in all 8 eyes, with reduced dependence on topical steroids Mean clinical grade of improvement 2.1; 95% CI, 1.3-3.0; p<0.001 7 eyes had successful IOP control following trabeculectomy Mean IOP post-trabeculectomy : 9.74mmHg (+/- 4.1) 1 eye had trabeculectomy failure 18 months post-surgery. Repeat trabeculectomy with MMC was performed. Successful after 4 months to date VKC PATTERNS IOP CONTROL Mean follow-up period post-trabeculectomy: 22.5 months (+/-15.3)

10. DISCUSSION The risk of corticosteroid-induced glaucoma in Asian eyes with VKC may be higher due to the chronicity of the disease and the long-term use of topical steroids, as in the patients in our study Our study found important risk factors for trabeculectomy in these cases to be longer duration of topical steroid use, higher peak IOP and greater increase in IOP from baseline The limitations of our study are its small numbers and retrospective nature

11. DISCUSSION Mitomycin C is an antibiotic-anticancer agent that inhibits DNA, RNA and protein synthesis and has a long-term effect on cell proliferation. It induces prolonged localised inhibition of Tenon’s fibroblasts, thus reducing trabeculectomy bleb scarring. Its usefulness when applied topically in VKC has been described In our study, following trabeculectomy with MMC, all eyes saw significant improvement in the ocular surface requiring minimal or no use of topical steroids for control of VKC symptoms We postulate that the application of 0.02% MMC directly to the bare sclera in the superior fornix during trabeculectomy induces significant long-term inhibition of fibroblast and inflammatory cells in the ocular surface, resulting in an improvement in the signs and symptoms of VKC in our patients

12. CONCLUSIONS Prolonged duration of topical steroid use and greater increase in IOP from baseline are significant risk factors for severe steroid response requiring trabeculectomy in Asian patients with severe forms of VKC Significant improvement in the signs and symptoms of VKC is seen in eyes following trabeculectomy with MMC. This could be related to the after-effects of MMC on the ocular surface. This supports the usefulness of MMC in the management of severe, refractory forms of VKC A Presentation by the Singapore National Eye Center Singapore National Eye Centre