title: Ocular Adverse Events Associated with Antibody-Drug Conjugates in Human Clinical Trials.
abstract: This article reviews ocular adverse events (AEs) reported in association with administration of antibody-drug conjugates (ADCs) in human clinical trials. References reporting ocular toxicity or AEs associated with ADCs were collected using online publication searches. Articles, abstracts, or citations were included if they cited ocular toxicities or vision-impairing AEs with a confirmed or suspected association with ADC administration. Twenty-two references were found citing ocular or vision-impairing AEs in association with ADC administration. All references reported use of ADCs in human clinical trials for treatment of various malignancies. The molecular target and cytotoxic agent varied depending on the ADC used. Ocular AEs affected a diversity of ocular tissues. The most commonly reported AEs involved the ocular surface and included blurred vision, dry eye, and corneal abnormalities (including microcystic corneal disease). Most ocular AEs were not severe (≤ grade 2) or dose limiting. Clinical outcomes were not consistently reported, but when specified, most AEs improved or resolved with cessation of treatment or with ameliorative therapy. A diverse range of ocular AEs are reported in association with administration of ADCs for the treatment of cancer. The toxicologic mechanism(s) and pathogenesis of such events are not well understood, but most are mild in severity and reversible. Drug development and medical professionals should be aware of the clinical features of these events to facilitate early recognition and intervention in the assessment of preclinical development programs and in human clinical trials.
authors.affiliation: 1 Ocular Services On Demand (OSOD), LLC , Madison, Wisconsin.
authors.forename: Joshua Seth
authors.initials: JS
authors.lastname: Eaton
authors.affiliation: 1 Ocular Services On Demand (OSOD), LLC , Madison, Wisconsin.|2 Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison , Madison, Wisconsin.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Miller
authors.affiliation: 3 Department of Ophthalmology and Vision Sciences, School of Medicine, University of California , Davis, Sacramento, California.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Mannis
authors.affiliation: 1 Ocular Services On Demand (OSOD), LLC , Madison, Wisconsin.|3 Department of Ophthalmology and Vision Sciences, School of Medicine, University of California , Davis, Sacramento, California.|4 Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California , Davis, Davis, California.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Murphy
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry; D002986:Clinical Trials as Topic; D015195:Drug Design; D005128:Eye Diseases / Q000139:chemically induced* / Q000503:physiopathology; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D018796:Immunoconjugates