Imiquimod Treatment for Conjunctival Melanoma In Situ or Ocular Surface Squamous Neoplasia.

Importance: There are limited effective treatment options for diffuse conjunctival melanoma in situ (MIS), diffuse conjunctival intraepithelial neoplasia, and squamous cell carcinoma. There is a need for a more effective treatment with less ocular adverse effects than mitomycin C for MIS and 5-fluorouracil for ocular surface squamous neoplasia (OSSN). Objective: To evaluate the outcomes of compounded imiquimod 5% in ophthalmic petrolatum-based ointment for diffuse conjunctival MIS or OSSN. Design, Setting, and Participants: This was an interventional case series study at a tertiary referral center conducted from June 2024 to March 2025. Patients with a histological diagnosis of either conjunctival intraepithelial neoplasia (CIN), conjunctival squamous cell carcinoma, conjunctival MIS, or conjunctival melanoma with adjacent clinical primary acquired melanosis (PAM) were included in the study. Exposures: Compounded imiquimod 5% ointment applied to the conjunctival surface 5 days per week for 12 weeks at a minimum (range, 12-15 weeks) along with a topical antibiotic. Main Outcomes and Measures: Histological resolution of MIS or OSSN. Results: This case series included 5 patients (mean [SD] age, 77.4 [6] years; 4 female [80%]). At 12 weeks of treatment, there was complete clinical and histological response of CIN with moderate dysplasia, partial histological response (downgrade from squamous cell carcinoma to CIN with moderate dysplasia), and no histological recurrence of positive margins of squamous cell carcinoma excision. At 12 weeks of treatment, there was partial clinical response of diffuse MIS with mild persistence of epithelial pigmentation at the corneal limbus at the 7-o'clock position; however, there was complete histological response in the areas of initial map biopsy. At 15 weeks of treatment, there was complete clinical and histological response of PAM. Of the 5 patients, all experienced ophthalmic adverse events only affecting the ocular surface and eyelids. All ocular surface adverse events resolved within 1 to 2 weeks of drug holiday or completing treatment. Conclusions and Relevance: Study results suggest that, although definitive safety and efficacy cannot be determined across only 5 cases, compounded imiquimod 5% ointment may be a safe and effective approach to manage diffuse conjunctival MIS or OSSN. Longer-term follow-up with larger number of cases is warranted.