Treatment of Conjunctival and Corneal Epithelial Neoplasia with Retinoic Acid and Topical Interferon Alfa-2b: Long-term Follow-up

Objective: To evaluate the long-term recurrence rate of conjunctival and corneal intraepithelial neoplasia (CIN) treated with retinoic acid and topical interferon alfa-2b.

Design: Retrospective, noncomparative, interventional case series.

Participants: A total of 89 eyes of 89 patients from 1 institution who were treated between September 2003 and February 2010 for CIN lesions used topical interferon alfa 1 million IU/ml drops 4 times daily and retinoic acid 0.01% once every second day.

Methods: Diagnosis was made by biopsy and impression cytology. Patients' notes and clinical photographs were reviewed, and data were analyzed. All eyes were monitored for the possibility of recurrence with a minimum of 1 year of follow-up from the time of documented clinical resolution.

Main Outcome Measures: All eyes were monitored for the possibility of recurrence with a minimum of 1 year of follow-up from the time of documented clinical resolution.

Results: Complete clinical resolution of the CIN lesions was achieved in 87 of the 89 eyes treated (97.75%). Two of the 89 eyes treated (2.25%) had only a partial response to treatment; of these 2 patients, 1 was taking cyclosporine for keratitis sicca. For the 87 eyes with complete response, resolution occurred after a mean of 1.69 months (range, 19 days to 6.5 months). Mean follow-up after clinical resolution (tumor-free period) was 51.5 months (range, 11-84 months). Four of the 87 patients with complete response developed a mild allergic papillary conjunctivitis that settled on halving the interferon dose to 0.5 million IU drops and reducing the frequency to 3 times daily. Side effects were limited to 1 case of epithelial microcysts and 1 case of marginal keratitis.

Conclusions: In this group of patients observed with CIN lesions, combination treatment of topical retinoic acid and interferon alfa-2b was effective in treating lesions with minimal self-limited side effects with faster and greater resolution and a longer tumor-free period compared with studies using interferon alfa-2b alone. We hypothesize that topical all-trans retinoic acid and interferon alfa-2b may act synergistically. We believe that combination treatment of interferon alfa-2b and retinoic acid may offer a superior alternative to interferon alfa-2b alone in treating CIN.