Abstract
Background/Objectives: To evaluate the modality-specific impact of cataracts on the detection of hydroxychloroquine retinopathy. Methods: In this retrospective cohort study, 202 eyes (101 patients) with confirmed HCQ retinopathy were included; analyses focused on 141 cataractous eyes from 72 patients. At each visit, the severity of cataracts in 141 eyes was graded using the Lens Opacities Classification System III (LOCS III), with clinically significant cataracts defined as a LOCS III grade ≥ 3. Screening was performed using swept source optical coherence tomography (OCT), ultrawide field fundus autofluorescence (FAF), and Humphrey visual field (HVF) tests. The detection rates of abnormalities on OCT, FAF, and HVF were compared between minimal (at the time of diagnosis or after cataract surgery) and maximal cataract severity as well as between eyes with clinically significant cataracts and others. Multivariate logistic regression was performed to identify the factors associated with the detection of retinopathy-associated abnormalities across each screening modality. Results: Of the 141 eyes with cataracts, 52 (36.9%) developed clinically significant opacities during the monitoring period, and 23 (16.3%) underwent cataract surgery. OCT detected ellipsoid zone disruptions in 100% of cataractous eyes, while visual fields revealed characteristic paracentral scotomas with comparable sensitivity regardless of cataract severity. In contrast, FAF sensitivity was significantly lower in eyes with clinically significant cataracts (61.5%) compared to those with mild cataracts (92.1%, p < 0.001). Sensitivities were also reduced at maximal versus minimal severity in eyes with clinically significant cortical opacities and nuclear opalescence (both p < 0.05). Multivariate analysis demonstrated that higher cortical opacity (odds ratio [OR] 0.43 per grade increase, 95% CI 0.22-0.85) and nuclear opalescence (OR 0.21, 95% CI 0.07-0.66) independently decreased FAF detection, whereas greater retinopathy severity was positively associated with detection on both FAF (OR 4.85, 95% CI 1.40-16.9) and HVF (OR 3.37, 95% CI 1.17-9.71). Conclusions: Cataracts impaired the FAF-based detection of hydroxychloroquine retinopathy, while OCT and HVF remained reliable despite significant lens opacities. Therefore, clinicians should consider cataract severity when interpreting FAF results and prioritize OCT and HVF assessments in patients with clinically significant cataracts.