Comment on: Immune checkpoint inhibitor therapy for treatment of periocular Merkel cell carcinoma – Exploring ocular side effects

Dear Editor,

I read with interest the systematic review by Folk et al.[1] on immune checkpoint inhibitor therapy for periocular Merkel cell carcinoma (MCC). The review is timely and clinically important as periocular disease presents unique therapeutic challenges in which oncologic control must be balanced against eyelid function, ocular protection, and cosmetic outcome.[1] The authors are to be commended for consolidating the limited periocular literature and for highlighting the encouraging activity of pembrolizumab and avelumab in this setting.

At the same time, the small number of reported cases, the retrospective nature of the available evidence, and the short follow-up warrant cautious interpretation of the observed response rates.[1] In my view, the safety discussion would be strengthened by explicitly acknowledging ocular immune-related adverse events, particularly pembrolizumab-associated Vogt–Koyanagi–Harada (VKH)-like syndrome.[2] Such cases have been reported with bilateral intraocular inflammation, serous retinal detachment, and choroidal involvement, emphasizing that immune checkpoint blockade can produce clinically significant posterior segment toxicity even when antitumor efficacy is preserved.[2]

Nivolumab, an anti-PD-1 immune checkpoint inhibitor also mentioned in their article, is known to occasionally trigger immune-related adverse events, including cases of bilateral anterior uveitis.[3] Patients frequently present with visual changes and anterior chamber inflammation, which typically resolve once the immunotherapy is discontinued and prompt topical or systemic corticosteroid therapy is initiated.[3] Our team also has managed cases of bilateral granulomatous uveitis that responded to topical steroids without requiring the cessation of nivolumab and additional immunosuppression to control the inflammation.

This point is especially relevant in periocular malignancies, where ophthalmic surveillance is essential and where treatment interruption may have complex oncologic implications.[1,4] In my own experience, pembrolizumab-associated VKH-like inflammation was characterized by bilateral granulomatous panuveitis with indocyanine green angiographic evidence of choroidal involvement, and the diagnosis was best established through multimodal imaging. The inflammatory episode could be controlled with corticosteroid therapy, underscoring that prompt recognition and collaborative management may allow preservation of both vision and ongoing cancer treatment. Data from the Mayo Clinic experience similarly showed that ophthalmic immune-related adverse events are uncommon and are often manageable without discontinuation of therapy.[4] More severe uveitic presentations require individualized decisions regarding continuation of immunotherapy.[4] I therefore suggest that future studies of periocular MCC treated with immune checkpoint inhibitors should include standardized ophthalmic follow-up, multimodal imaging, and explicit reporting of ocular toxicity to better define the balance between efficacy and safety.[1,2,4]