Ocular adverse events associated with immune checkpoint inhibitors: a novel multidisciplinary management algorithm

Abstract

Ocular immune-related adverse events (IrAEs) associated with use of checkpoint inhibitors (CPIs) in cancer therapeutics are relatively rare, occurring in approximately 1% of treated patients. Recognition and early intervention are essential because the degree of tissue damage may be disproportionate to the symptoms, and lack of appropriate treatment risks permanent loss of vision. International guidelines on managing ocular IrAEs provide limited advice only. Importantly, local interventions can be effective and may avoid the need for systemic corticosteroids, thereby permitting the continuation of CPIs. We present a single institution case series of eight affected patients managed by our multidisciplinary team. Consistent with previously published series and case reports, we identified anterior uveitis as the most common ocular IrAE associated with CPIs requiring intervention. Based on our experience, as well as published guidance, we generated a simple algorithm to assist clinicians efficiently manage patients developing ocular symptoms during treatment with CPIs. In addition, we make recommendations for optimising treatment of uveitis and address implications for ongoing CPI therapy.

Ocular Inflammation Induced by Immune Checkpoint Inhibitors

“…This study adds 28 new cases of ocular IRAEs induced by ICPIs. Overall, these new cases were similar to those previously reported [ 14 , 16 , 22 , 25 , 26 , 37 , 41 , 50 ]. Indeed, most patients were aged around 60 years, with an overrepresentation of males (ratio = 1.9).…”

“…The literature review was also consistent with these findings. Yet, some authors have suggested an alternative hypothesis: melanoma itself would constitute a risk factor for ocular IRAEs, particularly for uveitis [ 11 , 26 ]. This hypothesis is supported by the known relationship between melanoma and ocular disorders or ocular IRAEs [ 13 , 14 , 23 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 ], which seem more frequent in patients treated for melanoma than those treated for other neoplasms.…”

“…While early data came from case reports or small case series [ 22 , 23 , 24 , 25 , 26 , 27 ], more recent papers are represented by large database analysis [ 10 , 14 , 17 , 19 , 20 , 28 , 29 , 30 ] which include a significant number of cases but do not have a sufficient level of detail to analyze the different eye disorders and their management. The aim of our study was therefore to describe ICPI-induced ocular IRAEs, more specifically the uveitis inflammatory involvement type, detailing the anatomical specificities, potential risk factors, management, and outcome, in relation to the outcome of the underlying tumor.…”

Immunotherapy-induced retinopathy mimicking cancer associated retinopathy

“…No ARAs panel or repeat ERG testing was done. 14 Young et al also reported a case of CAR associated with nivolumab and ipilimumab therapy for cervical cancer. However, details including presence of ARAs or abnormal ERG features were not described.…”

“…Shahzad et al also described a case of MAR in a monocular patient whose fellow eye was exenterated due to metastatic uveal melanoma. 14 Shortly after the first cycle of immunotherapy with nivolumab and ipilimumab (a checkpoint inhibitor that inhibits CTLA4), the patient developed severe photopsia. Following 9 weeks of treatment (3 cycles), the patient developed severe pneumonitis which was treated with oral prednisone and discontinuation of CPI therapy.…”