Advances in topical immunotherapy are opening new possibilities for managing rare and challenging eye cancers, including ocular melanoma–related conditions. A recently published case series explores the use of compounded imiquimod 5% ointment as a potential treatment for diffuse conjunctival melanoma in situ (MIS) and ocular surface squamous neoplasia (OSSN)—two ocular surface malignancies with limited and often toxic treatment options.
Traditionally, management of conjunctival MIS, OSSN, and related ocular surface cancers relies on wide-margin surgical excision, often combined with topical chemotherapies such as mitomycin C (MMC) or 5-fluorouracil (5-FU). While these agents can be effective, they are also associated with significant ocular surface toxicity, discomfort, and long-term complications. As treatment paradigms across oncology shift toward immune-based approaches, researchers are increasingly interested in whether immunomodulatory therapies can offer safer, effective alternatives for delicate ocular tissues.
This small interventional case series followed five adult patients treated with a compounded ophthalmic formulation of imiquimod 5%, applied five days per week for a minimum of 12 weeks. The patients had diagnoses ranging from conjunctival intraepithelial neoplasia and squamous cell carcinoma to diffuse conjunctival melanoma in situ and primary acquired melanosis (PAM) adjacent to excised conjunctival melanoma. Importantly, imiquimod was compounded in a petrolatum-based ophthalmic ointment to remove irritants found in the commercially available cream, which is not approved for ophthalmic use.
The results are encouraging. After treatment, three patients achieved complete clinical and histological response, while two experienced partial response, including downgrading of disease severity on biopsy. Notably, one patient with diffuse conjunctival MIS showed complete histological resolution despite mild residual pigmentation on clinical exam. Another patient achieved complete resolution of PAM after extending treatment to 15 weeks.
Equally important for patients and clinicians concerned about safety, all reported adverse events were limited to the ocular surface or eyelids—such as conjunctivitis or irritation—and resolved within one to two weeks following a drug holiday or completion of therapy. No serious intraocular toxicities were identified.
While the authors emphasize that conclusions are limited by the small sample size, this study suggests that topical imiquimod may represent a promising, immune-based approach for select patients with ocular surface malignancies, including those related to ocular melanoma. Larger studies and longer-term follow-up are needed, but these findings offer hope for less toxic, eye-sparing treatment strategies in the future.
For the ocular melanoma community, research like this underscores the importance of continued innovation, clinical trials, and patient-centered approaches to rare eye cancers.