Evaluation of microvascular changes in rheumatoid arthritis patients receiving hydroxychloroquine by optical coherence tomography angiography

Background Hydroxychloroquine (HCQ) is widely used in rheumatoid arthritis (RA) and can cause irreversible toxic retinopathy, typically after long-term exposure. Current screening guidelines rely mainly on spectral-domain OCT and visual fields, which may detect damage relatively late. Optical coherence tomography angiography (OCTA) allows noninvasive, depth-resolved assessment of macular microvasculature and may reveal earlier changes. Objective To evaluate early macular microvascular changes using OCTA in low-risk RA patients during the first 6 months of HCQ therapy. Patients and methods In this prospective cohort study, 32 RA patients (64 eyes) starting HCQ (400 mg/day; ≤5 mg/kg/day; cumulative dose <1000 g) underwent comprehensive ophthalmic examination and swept-source OCTA at baseline and 6 months. Superficial capillary plexus (SCP) foveal and parafoveal vessel density (VD) were quantified in foveal, quadrant, and whole parafoveal regions. Superficial and deep foveal avascular zone (sFAZ, dFAZ) areas, central foveal thickness, and subfoveal choroidal thickness (CT) were also measured. Results There was a significant reduction in the means SCP foveal VD ( P =0.017), and whole parafoveal VD at SCP level ( P =0.002), with significant inferotemporal parafoveal decline ( P ≤0.045) and superficial FAZ area showed significant reduction ( P <0.001) at post 6 months HCQ therapy examination compared with the means at baseline examination. whereas deep FAZ, central foveal thickness, and choroidal thickness showed no significant change (all P >0.05). Conclusions In low-risk RA patients early in the course of HCQ therapy, OCTA detected subtle macular microvascular alterations despite preserved visual function and macular thickness. These findings support the use of OCTA as a sensitive adjunct to conventional screening for HCQ-related retinal toxicity, potentially helping clinicians monitor patients and stratify their risk of retinal damage. While these early changes appear reversible and do not require drug discontinuation, they necessitate close follow-up according to the 2016 American Academy of Ophthalmology recommendations for screening HCQ retinopathy. However, it remains unclear whether these microvascular changes are primarily drug-induced or secondary to RA-associated microangiopathy.