Author Response on: Immune checkpoint inhibitor therapy for treatment of periocular merkel cell carcinoma: A systematic review of clinical outcomes and safety

We thank the author for this letter and thoughtful comments regarding our systematic review of immune checkpoint inhibitor (ICI) therapy for treatment of periocular Merkel cell carcinoma (MCC). We appreciate the clinical insights highlighted in this response and recognition of the inherent challenge in managing periocular MCC.

We agree that current evidence for use of ICI therapy in treatment of periocular MCC remains limited. As noted in our review, the available literature consists primarily of small case series and reports, with relatively short follow-up durations, which may limit our ability to definitively evaluate efficacy and safety. The author of this letter raises an important point regarding adverse events associated with ICIs. Although our review focused primarily on oncologic and periocular outcomes reported within the published periocular MCC literature, we agree that ophthalmic toxicities should be discussed in the setting of expanding clinical ICI use. Of note, ICI-related ocular adverse effects were not observed or specifically reported in the periocular MCC cases included in our review,[1,2,3,4,5,6,7] which limited our ability to comment on their incidence or clinical management in this patient population. This may also reflect the overall rarity of ophthalmic immune-related adverse events, which the author also notes.

Nevertheless, pembrolizumab-associated Vogt–Koyanagi–Harada-like syndrome,[8] nivolumab-associated uveitis,[9] and other inflammatory ocular complications have been rarely reported in patients treated with ICIs for different malignancies and demonstrate that immune checkpoint blockade may result in clinically significant adverse ocular findings if not promptly recognized and treated.[10,11] This does not necessarily require cessation of ICI but rather may potentially be managed with local inflammation control, although other infectious conditions should be ruled out given the relative immunocompromised state. Moreover, it is important to recognize other potential effects of treatment with ICIs, including pseudoprogression and hyperprogression.[12,13] Management should be individualized according to oncologic status and guided by extensive patient discussion on therapeutic benefits and potential risks of ICIs, including rare but possible ocular adverse effects.

We agree with the author’s recommendation for standardized ophthalmic surveillance in patients treated with ICIs as well as improved patient and physician education of potential ocular complications to facilitate expeditious referral if these rare effects occur; we also agree that future study directions should include specific documentation of ocular toxicities or lack thereof. As ICIs become increasingly integrated into the treatment approach of various malignancies, recognition and evaluation of ocular adverse effects and long-term follow-up will be important for defining the risk potential of these therapies. Such future studies may additionally help identify which patients may be at increased risk for ocular complications while maintaining effective oncologic treatment.

We thank the author for highlighting this important aspect of ICI therapy and for contributing additional clinical perspective that complements the findings of our review.