Retinal Microvasculature Changes in Long-Term Consumption of Hydroxychloroquine Publisher Pubmed



Ghassemi F ; Fardad S ; Salari F ; Masoumi A ; Ghasemi D ; Faghihi H ; Zarei M ; Mohebbi M ; Yaseri M ; Ebrahimiadib N
Source: Scientific Reports Published:2026

Abstract

To evaluate retinal microvascular and structural changes in patients undergoing hydroxychloroquine (HCQ) therapy using optical coherence tomography angiography (OCTA) in patients without clinical retinopathy. This prospective cross-sectional study enrolled both eyes of 59 age-matched control cases (Group 1) with 118 eyes from 59 HCQ-treated patients (27 with < 60 months of treatment [Group 2], 32 with ≥ 60 months [Group 3]) at Farabi Hospital (2020–2022). All participants underwent a comprehensive ophthalmic evaluation, including spectral-domain OCTA (Optovue RTVue XR Avanti). The inner, mid- and outer retinal layer thicknesses (IRT, MRT, ORT) and superficial, deep retinal vascular densities and choroidal vascular densities (SVD, DVD, CVD) were analyzed using ETDRS grids. We employed generalized estimating equations with a Bonferroni correction to compare groups. The Group 3 (≥ 60-month consumption of HCQ) demonstrated significant reductions in foveal inner retinal thickness (IRT) (43.25 ± 7.07 vs. 48.84 ± 8.71 μm, p = 0.002) and parafoveal outer retinal thickness (ORT) (146.14 ± 6.77 vs. 151.8 ± 9.94 μm, p = 0.002) compared to controls. OCTA analysis showed that foveal DVD and CVD were lower in Group 3 compared with Group 1, whereas parafoveal DVD was increased in Group 3. Moreover, Group 2 cases indicated choroidal changes compared with the control group. Duration and cumulative dose of HCQ consumption negatively correlated with foveal SVD and IRT, alongside a positive correlation with parafoveal DVD and FAZ. GEE regression revealed that longer treatment duration and higher cumulative dose were independently associated with reduced foveal IRT (β=-0.002, p = 0.03; β=-0.013, p = 0.046), reduced foveal SVD (β=-0.002, p = 0.003; β=-0.014, p = 0.006), and an enlarged FAZ area (β = 0.161, p = 0.039). OCTA suggests possible progressive retinal microvascular attenuation in HCQ therapy, with alterations observed after 60 months of treatment despite normal functional testing. Parafoveal DVD seems to be a key feature, underscoring the potential for OCTA’s utility in monitoring HCQ retinopathy. © The Author(s) 2026.