DRUG INDUCED RETINAL DISORDERS IDENTIFIED THROUGH SPONTANEOUS REPORTING SYSTEM

ABSTRACT

Introduction: The retina is a highly specialized sense organ subjected to constant exposure to systemic toxins and oxidative stress. The frequency and etiology of drug-induced retinopathy, as well as the number of new potential drugs involved, are largely unknown. Objective: Describe the most frequent drug-induced retinal disorders and the drugs implicated gathered through the spontaneous report registry of the Spanish System of Pharmacovigilance (SSP). Methods: All spontaneous reported cases describing Retinal structural change, deposit and degeneration, Retinopathies not elsewhere classified, and Retinal bleeding and vascular disorders (excluded retinopathy) (MedDRA-HLT) in the SSP database from 1983 to January 2022 were selected. Medical devices and marketing authorisation holder cases were excluded. The variables studied were age and sex of the patients, characteristics of adverse drug reactions (ADRs) (seriousness, outcome) and suspect drugs (active substance, anatomical therapeutic chemical code, previous knowledge of drug-reaction association, rechallenge and existence of alternative causes). Results: Out of 175 spontaneous reports (0.1% of the spontaneous reports in the SSP database) that describe 210 ocular ADRs and/or adverse events, the most frequent (MedDRA-HLT) were retinal bleeding and vascular disorders (111, 52.9%), ocular structural change, deposit and degeneration (59, 28.1%) and vision disorders (12, 5.7%). For MedDRA-PT;retinal vein thrombosis (38, 18.1%), retinal detachment (22, 10.5%) and retinal hemorrhage (20, 9.5%). In only 8 cases (3.8%) drug administration was ophthalmic. Patient's median age was 57.65 (IQR 48-67.5) years;68.6% (120) were adults and 56.6% (99) were women. 153 reports (87.4%) were serious. 10.9% (19) cases resolved after withdrawal of the suspect drug and 12.6% (22) resolved with sequelae. A total of 220 drugs were suspected, of which 55 (25%) were COVID-19 vaccines -vector vaccine ChAdOx1 nCoV-19/AZD1222, Oxford-AstraZeneca (27) and mRNA vaccine BNT162b2, Pfizer- BioNTech (23)-, followed by sex hormones (21), immunostimulants (16) and antiprotozoals (14). Of the 175 reports, 56% (98) were poorly or unknown ADR associations. Alternative causes were excluded in 46 (26.3%) cases of which 12 (26%) were poorly or unknown ADR associations and no cases had a positive rechallenge. Conclusion: Our study shows that drug-induced retinopathy is an infrequent but serious complication. In the SSP database more than half of ADRs were retinal bleeding and vascular disorders. A quarter of the suspected drugs were new COVID-19 vaccines, followed by other drugs for which retinal disorders are well known. Although striking, it is important to contextualize this data in the current situation, considering the particularities of pharmacovigilance in vaccines, the massive rollout campaign and the nascent and evolving data on COVID-19 vaccines. Thus, further studies are needed to confirm such associations. Moreover, clinicians should be aware of drug-induced retinal disorders, even when not listed in the product information leaflet.