1. Topical Cyclosporine 0.05% as a Long-Term Monotherapy for Atopic Keratoconjunctivitis Jonathan H. Tzu, M.D ¹, * ; C. Asli Utine, M.D ¹,², * Michael Stern, Ph.D ³, ** ; Esen K. Akpek, M.D¹, ***

2. * The authors have no financial interest in the subject matter of this poster * * The author is a full-time, salaried employee of Allergan Inc., Irvine, CA. *** The author’s institution has received grant support from Allergan Inc. From the Ocular Surface Diseases and Dry Eye Clinic, The Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland.

3. Purpose: To evaluate the long-term effectiveness of topical cyclosporine as a monotherapy for atopic keratoconjunctivitis (AKC)

4. Patients: Ten patients with moderate to severe AKC. Intervention: Topical cyclosporine A (CsA) 0.05% eyedrops (Restasis, Allergan Inc.) were used, as a monotherapy; 6 times daily during day 1 to day 28, followed by 4 times daily during day 29 to day 56 of the study. The patients were challenged by withdrawing the therapy between day 57 to day 63.

5. Day 1 - Patients with active symptoms of AKC started on cyclosporine 0.05% six times daily - initial signs and symptoms/visual acuity recorded Day 28 - Patients switched to cyclosporine 0.05% four times daily - signs and symptoms recorded Day 56 - Cyclosporine 0.05% stopped - signs and symptoms recorded Day 63 - Cyclosporine 0.05% restarted and adjusted based on clinical severity, up to 8 times daily - signs and symptoms recorded Long term follow up - 12 month minimum - signs/visual acuity/steroid usage are recorded

6. Follow-up All continuing patients were instructed to self- treat with topical CsA at a dosing ranging from twice to 6 times daily depending on the activity of the disease. Other treatments such as artificial tears, tacrolimus ointment for lid disease, or systemic cyclosporine for significant atopic dermatitis were allowed. Follow-up examinations were performed at 3 month intervals or more frequently as necessary. The study was terminated once the last patient completed a follow-up period of at least 12 months.

7. Main Outcome Measures Symptoms (itching, tearing, discomfort, mucous discharge, and photophobia) and signs (bulbar conjunctival hyperemia, upper tarsal conjunctival papillae, punctate keratitis, corneal neovascularization, cicatrizing conjunctivitis, and blepharitis) of AKC were assessed on the day of enrollment, on days 28, 56, 63 and at subsequent follow-up visits. Additionally, occurrence of flare-up of the AKC requiring topical steroid use and progression of the disease findings over the long-term follow-up were recorded.

8. Results: All patients experienced significant improvement of their symptoms and signs during the first two months of the study. All patients had a clinically significant relapse when examined at the end of the 1 week “withdrawal” period. Two patients relocated and were lost to follow-up. One patient was non- compliant and continued the treatment only for 7 months. During the treatment period (median of 21.5 months, cumulatively, 17.5 patient-years), a total of only two flare-up episodes (two patients) were noted requiring topical steroids. Both were associated with either a decrease in the dose of CsA eyedrops or brief discontinuation of the therapy by the patient. The one non-compliant patient was treated with topical steroids by a local physician and was noted to have worsening of his disease with decrease of vision from corneal findings at 24 months of follow-up. No side effects or progression of the disease were noted in the 7 patients who were able to continue with the treatment.

9. Patient CharacteristicNumber of Patients (n = 10) Median age of presentation (range)41 (21 - 50) Male/female5/5 Median years with known diagnosis of AKC (range) 4 (2-10) Median follow-up (range)21.5 months (2 - 58) With known AKC on presentation3 Extraocular atopy Eczema10 Asthma3 Allergic rhinitis4 Family history of atopy5 Other ocular comorbidities Keratoconus3 Recurrent bacterial conjunctivitis2 Steroid-induced glaucoma1 Herpes simplex keratitis3

10. Conclusion: In this small prospective case series, long- term continuous use of cyclosporine 0.05% eyedrops alone seemed to prevent topical steroid-requiring acute flare-ups associated with atopic keratoconjunctivitis, and halted the natural progression of the disease.