Compounded Imiquimod has Potential Role in Treatment of Ocular Surface Malignancies: JAMA
USA: Researchers have found in a small case series that a compounded form of imiquimod, a topical immune-response modifier, showed promising effectiveness in treating ocular surface malignancies. The therapy appeared relatively safe, though the sample size was limited. Currently, these malignancies are typically managed surgically or with off-label topical agents like 5-fluorouracil or mitomycin C, which can be toxic to the ocular surface.
A new case series published in JAMA Ophthalmology by R. Christopher Bowen from the Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, and colleagues, highlights the potential role of compounded imiquimod 5% ointment in addressing difficult-to-treat ocular surface neoplasms. These conditions—including conjunctival melanoma in situ (MIS) and ocular surface squamous neoplasia (OSSN)—are rare but challenging malignancies with limited effective and well-tolerated nonsurgical therapies.
The investigators conducted an interventional case series at a tertiary referral center between June 2024 and March 2025. Five adults with histologically confirmed conjunctival intraepithelial neoplasia, conjunctival squamous cell carcinoma, conjunctival MIS, or conjunctival melanoma associated with primary acquired melanosis (PAM) were enrolled.
Each patient applied compounded imiquimod 5% ointment, formulated in an ophthalmic petrolatum base, five days a week for at least 12 weeks. Some continued treatment up to 15 weeks. A topical antibiotic was also provided to reduce infectious risk.
Despite the small sample size, the outcomes were encouraging:
- Three of the five patients achieved complete clinical and histological resolution after 12 weeks of imiquimod therapy.
- Two patients showed partial responses, indicating meaningful but incomplete improvement.
- Complete clearance was observed in cases of conjunctival intraepithelial neoplasia (CIN) with moderate dysplasia.
- One squamous cell carcinoma case showed partial downgrading to CIN with moderate dysplasia.
- No histological recurrence was seen at previously positive surgical margins.
- Patients with conjunctival melanoma in situ (MIS) had partial clinical improvement, while biopsy-confirmed areas demonstrated full histologic resolution.
- A patient with primary acquired melanosis (PAM) showed complete clinical and histological clearance after 15 weeks of treatment.
- No serious adverse events occurred during treatment.
- All five patients experienced mild to moderate ocular surface or eyelid irritation.
- These adverse effects resolved within one to two weeks after taking a drug holiday or completing therapy, indicating good overall tolerability.
Although the findings point toward a potentially valuable alternative for patients with diffuse or recurrent disease, the authors caution against overinterpretation. With only five cases, definitive conclusions regarding safety, long-term outcomes, or comparative effectiveness cannot be drawn. The study’s limited scale also prevents assessment of variability in response across different tumor types and levels of disease severity.
Still, these early observations support further research. Larger cohorts with extended follow-up will be needed to verify the durability of responses and to determine whether imiquimod can serve as a practical, less toxic nonsurgical option for conjunctival MIS and OSSN. As current treatments often involve significant ocular surface toxicity or surgical morbidity, the possibility of a topical therapy with favorable tolerability opens an important avenue for future investigation.
Reference:
Bowen RC, Bryar PJ, Gerami P. Imiquimod Treatment for Conjunctival Melanoma In Situ or Ocular Surface Squamous Neoplasia. JAMA Ophthalmol. Published online November 26, 2025. doi:10.1001/jamaophthalmol.2025.4669
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