Retinal Degeneration, CME and Optic Atrophy Strongly Associated with Plaquenil Use

This graph from the study shows time to onset of ocular adverse events associated with chloroquine and hydroxychloroquine.  Photo: Li X,et al. Front Pharmacol. 2025;16:1498814. Click image to enlarge. Hydroxychloroquine (HCQ) and chloroquine are cornerstone therapies for the treatment of systemic lupus erythematosus, as they help reduce disease activity and prevent disease progression. However, recent in-depth investigations into the safety profiles of these agents have highlighted some concerning ocular complications. Notably, systemic administration of these drugs, particularly in the treatment of dermatological conditions, has been associated with a range of serious ocular adverse effects. Prolonged use of chloroquine and hydroxychloroquine can result in irreversible damage to the retinal pigment epithelium and the photoreceptor complex. Researchers in China recently evaluated the risk of adverse events associated with chloroquine and HCQ in patients with lupus, using data from the FDA Adverse Event Reporting System (FAERS). They identified several potential new and unexpected adverse event signals, offering valuable insights for clinical risk monitoring and management. The most frequently reported ocular conditions were cataract, macular degeneration and glaucoma. Disproportionality analysis demonstrated strong associations between HCQ/chloroquine use and retinal degeneration, cystoid macular edema (CME) and optic atrophy.“Although the precise mechanisms by which HCQ and chloroquine induce retinal changes remain incompletely understood, it is known that both drugs extensively accumulate in ocular pigmented tissues, particularly within the retinal pigment epithelium, where they bind tightly to melanin,” the study authors wrote in their paper, which was published in Frontiers in Pharmacology.Between 2004 and 2024, the FAERS database recorded a total of 2,575 adverse event reports related to HCQ or chloroquine use in patients with lupus, of which 437 involved ocular adverse events. In this study, baseline demographic characteristics revealed that ocular adverse events were significantly more frequent among female patients than male patients (271 cases vs. 30 cases) and that middle-aged patients (18 to 64 years, n = 220, 50.34%) were more prone to ocular adverse events compared to elderly patients (>65 years, n = 44, 10.07%).The study’s results revealed significant differences in the time to onset among different types of ocular adverse events following initial drug exposure. Cataract exhibited the shortest mean onset time, averaging 125.5 days, suggesting that the lens may be particularly sensitive to the pharmacological effects of chloroquine and HCQ, with damage manifesting within a relatively short period. Retinal degeneration had the longest with 937.5 days.“This study provides real-world pharmacovigilance evidence supporting a substantial risk of ocular adverse events associated with HCQ/chloroquine use,” the researchers concluded. “Further mechanistic and prospective studies are warranted to elucidate the underlying pathophysiological pathways and to confirm these associations.”Click here for the journal source.  Li X, Zhang SQ, Wang KR, et al. Chloroquine and hydroxychloroquine-related ocular adverse events in SLE treatment: A real-world disproportionality analysis based on FDA adverse event reporting system (FAERS). Front Pharmacol. 2025;16:1498814. This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.