Ocular toxicities associated with anticancer therapies: Are we missing something in the blind spot?

Abstract

e15001 Background: Ocular toxicities are common challenges associated with anticancer agents, including small molecules, antibody-drug conjugates (ADC), targeted antibodies, particularly those targeting Epidermal Growth Factor Receptor (EGFR), Mitogen-activated protein kinase (MEK) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4). This subject suffers from a paucity of consensus guidelines, especially drug class versus severity of toxicity versus ocular anatomy. The aim of this paper is to examine the ocular side effects of various classes of anticancer therapies. Methods: Approved anticancer drugs known to be associated with ocular toxicity were reviewed as of Dec-2021. US FDA Labels were reviewed, as were further publications on said drugs. Ocular toxicities were then classified based on the anatomy of the eye, class of drug and drug target, severity and the recommended surveillance and management. Results: The most common ocular toxicities were mild including “visual disturbances” and conjunctivitis. Severe toxicities were reported as well, including corneal ulceration, retinal vascular occlusion, optic neuritis, and even cortical blindness. Our review clearly indicates that each class of drugs has a distinct ocular toxicity pattern, including the precise segment of the eye involved, severity and pattern of manifestation. Drug related toxicity involving the anterior segment tends to be of lesser severity, whereas posterior segment toxicity is more severe, and, as such, may result in treatment interruptions. Molecular-pathway-specific toxicity patterns were noted. EGFR inhibitors were associated with corneal-ulceration and microcysts. MEK inhibitor-associated retinopathy (MEKAR) is documented, and drugs (e.g. Trametinib) increase the risk of retinal detachment and retinal vascular occlusion. We noted a pattern of Monoclonal Antibodies (e.g. Cetuximab) having lower adverse events than the small molecule (e.g. Gefitinib) having the similar pathway of action. ADCs (12 US FDA approved) are known to affect various ocular tissues, commonly involving the ocular surface, with intra-class differences. Conclusions: Our review highlights the need for an ophthalmic referral at baseline, prior to initiating anticancer drugs known to cause ocular toxicities. Cancer patients need consensus-based multidisciplinary global standardized algorithms for surveillance, early diagnosis and management of ocular toxicities associated with anticancer therapies.

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“…The retinal layer thickness ratio remained unchanged, and no significant amplitude differences were observed between the ADC and control groups in the ERG and OptoMotry tests. However, some studies have reported ocular toxicity results associated with ADCs [ 127 , 128 , 129 , 130 ]. Although the exact mechanisms underlying the ocular toxicity of ADCs remain unclear, increased adverse reactions have been observed, particularly with maytansinoid- and MMAF-containing ADCs [ 130 ].…”