Comprehensive Quantitative Analysis of Structural and Vascular Alterations in Retinal and Choroidal Layers in Patients Treated with Hydroxychloroquine

• Long-term HCQ use reduces outer retinal layer thickness. • Choroidal thickness and choriocapillaris flow are decreased. • Deep capillary plexus density declines with treatment duration. • OCTA metrics may serve as candidate imaging markers of subclinical HCQ-related changes. : To quantitatively assess retinal and choroidal thicknesses, as well as microvascular alterations, using spectral-domain optical coherence tomography (SD-OCT) and optical coherence tomography angiography (OCTA) in hydroxychloroquine (HCQ) users. : Eighty-one eyes of 81 patients receiving HCQ for rheumatoid arthritis or Sjögren’s syndrome were included. Patients were categorized as high-risk (treatment ≥5 years) or low-risk (treatment <5 years) users. SD-OCT, OCTA, and visual fields were obtained. Outer retinal layer and choroidal thicknesses, retinal vascular densities, and choriocapillaris flow areas were assessed, and their correlations with cumulative HCQ dose and treatment duration were analyzed. : Outer nuclear layer (ONL), outer plexiform layer (OPL), and retinal pigment epithelium (RPE) thicknesses in several macular regions were significantly lower in long-term than in short-term HCQ users (p<0.05). Choroidal thickness and choriocapillaris flow area were also significantly reduced in long-term users (p<0.05). Additionally, deep capillary plexus (DCP) vascular density was lower at several locations in the long-term group. HCQ treatment duration and cumulative dose showed significant negative correlations with DCP vascular density, choriocapillaris flow area, choroidal thickness, and ONL thickness (p<0.05 for each). Long-term HCQ use was associated with thinning of the ONL, OPL, RPE, and choroid, accompanied by reduced DCP vascular density and choriocapillaris flow area. These structural and microvascular parameters correlated negatively with treatment duration and cumulative HCQ dose, suggesting subclinical alterations related to cumulative HCQ exposure.