Ocular adverse events associated with immune checkpoint inhibitors, a scoping review

Abstract

Introduction Immune checkpoint inhibitors (ICIs) have become an important part of the treatment of multiple cancers, especially for advanced melanoma and non-small cell lung cancer. Some tumors are capable of escaping immunosurveillance by stimulating checkpoints on T-cells. ICIs prevent activation of these checkpoints and thereby stimulate the immune system and indirectly the anti-tumor response. However, the use of ICIs is associated with various adverse events. Ocular side effects are rare but may have a major impact on the quality of life of the patient. Methods A comprehensive literature search of the medical databases Web of Science, Embase and PubMed was performed. Articles that provided a comprehensive description of a case report containing 1) cancer patient(s) treated with (a combination of) immune checkpoint inhibitors, and 2) assessed occurrence of ocular adverse events, were included. A total of 290 case reports were included. Results Melanoma (n = 179; 61.7%) and lung cancer (n = 56; 19.3%) were the most frequent reported malignancies. The primary used ICIs were nivolumab (n = 123; 42.5%) and ipilimumab (n = 116; 40.0%). Uveitis was most the common adverse event (n = 134; 46.2%) and mainly related to melanoma. Neuro-ophthalmic disorders, including myasthenia gravis and cranial nerve disorders, were the second most common adverse events (n = 71; 24.5%), mainly related to lung cancer. Adverse events affecting the orbit and the cornea were reported in 33 (11.4%) and 30 cases (10.3%) respectively. Adverse events concerning the retina were reported in 26 cases (9.0%). Conclusion The aim of this paper is to provide an overview of all reported ocular adverse events related to the use of ICIs. The insights retrieved from this review might contribute to a better understanding of the underlying mechanisms of these ocular adverse events. Particularly, the difference between actual immune-related adverse events and paraneoplastic syndromes might be relevant. These findings might be of great value in establishing guidelines on how to manage ocular adverse events related to ICIs.

Immunotherapy-induced adverse events in metastatic renal cell carcinoma: A case of rapid response and complex challenges

“…A literature review reveals a paucity of cases detailing Vogt-Koyanagi-Harada (VKH)-like syndrome associated with nivolumab, highlighting the uniqueness of this case. 1 Mechanisms of immune checkpoint inhibitor (ICI)-induced panuveitis, similar to VKH, are thought to involve a T-cell mediated attack on melanocytes, which are present in the uveal tract of the eye, 2 with most cases reported representing adverse ocular events to immunotherapy in the context of metastatic melanoma.…”

Diagnosing and Managing Uveitis Associated with Immune Checkpoint Inhibitors: A Review

“…Martens et al (2023) also described a strong discrepancy between anterior and panuveitis, and intermediate uveitis. Among 134 reported cases, they found ICI-induced anterior uveitis accounted for 45%, panuveitis 42% (of which 22% were VKH-like), posterior 4%, and intermediate 6% [128]. A review of uveitis manifestations documented in phase I-III trials showed comparable results [71].…”

Bilateral Vitiligo-Like Depigmentation of Choroid and Retinal Pigment Epithelium Associated with Ipilimumab-Nivolumab Therapy for Metastatic Cutaneous Melanoma

“…Ipi/Nivo work synergistically to enhance host T-cell defenses by inhibiting cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) and programmed cell death protein 1 (PD1), respectively, and are used as first-line therapy for metastatic melanoma [ 3 , 4 ]. Many types of inflammatory ocular adverse events have been reported with Ipi/Nivo combination therapy, including uveitis, retinal inflammation, retinal vasculitis, and Vogt-Koyanagi-Harada-like syndrome [ 5 ]. Furthermore, choroidal involvement with checkpoint inhibitor-related toxicity can present with birdshot chorioretinopathy, choroidal thinning, and choroidal effusions [ 5 ].…”

“…Many types of inflammatory ocular adverse events have been reported with Ipi/Nivo combination therapy, including uveitis, retinal inflammation, retinal vasculitis, and Vogt-Koyanagi-Harada-like syndrome [ 5 ]. Furthermore, choroidal involvement with checkpoint inhibitor-related toxicity can present with birdshot chorioretinopathy, choroidal thinning, and choroidal effusions [ 5 ]. Herein, we report a novel finding of vitiligo-like loss of pigmentation in the retinal pigment epithelium (RPE) and choroid in a patient with multi-metastatic cutaneous melanoma being treated with ipilimumab and nivolumab.…”