March 2026

OPHTHALMOLOGY

CASE SERIES EVALUATES COMPOUNDED IMIQUIMOD FOR OCULAR SURFACE CANCERS

A Northwestern Medicine case series published in JAMA Ophthalmology reports promising early outcomes using compounded imiquimod 5% ophthalmic ointment to treat conjunctival melanoma in situ (MIS) and ocular surface squamous neoplasia (OSSN), rare conditions that are often difficult to manage with existing therapies.

Diffuse ocular surface malignancies can be challenging to treat surgically and are commonly managed with topical chemotherapies such as mitomycin C and 5‑fluorouracil, both of which are associated with significant ocular toxicity. The study explored whether a reformulated, ophthalmic‑specific version of imiquimod, an immune response modifier widely used in dermatologic oncology, could offer effective tumor control with fewer ocular side effects.

Overview
The interventional case series included five adult patients treated at a tertiary referral center between June 2024 and March 2025. Diagnoses included conjunctival intraepithelial neoplasia, squamous cell carcinoma, conjunctival MIS and primary acquired melanosis.

Patients received compounded imiquimod 5% ointment in a petrolatum‑based formulation designed to remove irritating excipients found in commercial imiquimod cream. The medication was applied to the conjunctival surface five nights per week for at least 12 weeks, with topical antibiotics used prophylactically. Post-treatment biopsies assessed histologic response.

Key Findings
Tumor response:
  • Three of five patients achieved complete histologic response.
  • Two patients achieved partial response, including downgrading of disease severity.
Safety:
  • All patients experienced mild, reversible ocular surface adverse effects, such as conjunctivitis.
  • No serious ocular complications, including keratitis, limbal stem cell deficiency, uveitis or vision threatening toxicity, were observed.
Vision outcomes:
  • Visual acuity remained stable overall, with no clinically meaningful treatment related decline.

Clinical Significance
Imiquimod activates innate and adaptive immune pathways through toll‑like receptor signaling, promoting tumor cell apoptosis and immune‑mediated clearance. While it is not FDA‑approved for ophthalmic use, this study is the first to report outcomes using a compounded ophthalmic formulation for conjunctival MIS and OSSN.

Although limited by small sample size and short follow‑up, the findings suggest that compounded imiquimod 5% ointment may be a safe and effective alternative or adjunct for patients with diffuse, nonresectable ocular surface disease. 
R. Chris Bowen, MD, Director of Ocular Oncology Service and Assistant Professor of Ophthalmology at Northwestern Medicine
Paul J. Bryar, MD, Vice Chair of Clinical Operations in the Department of  Ophthalmology and Professor of Ophthalmology and Pathology at Northwestern Medicine
Pedram Gerami, MD, IDP Foundation Professor of Skin Cancer Research and Professor of Dermatology, Pathology and Pediatrics at Northwestern Medicine

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