ObjectiveTo evaluate whether there are changes in cone cells in patients with pre-clinical hydroxychloroquine (HCQ) retinopathy using an adaptive optics (AO) retinal camera. MethodsA retrospective case-control study. From May 2020 to July 2020, 46 patients who were treated in Department of Rheumatism and Immunology, Hainan Hospital of PLA General Hospital with rheumatic immune diseases were included. All patients had a history of HCQ use and no obvious abnormality was found in fundus examination; 105 healthy people with similar demographic characteristics without a history of hydroxychloroquine were recruited as the control group were included. All subjects received the routine ophthalmological examination including best corrected visual auity (BCVA), spectral-domain optical coherence tomography (SD-OCT), Fundus autofluorescence (FAF), visual field, endoscopy of the cornea, and the measurement of axial length (AL). The BCVA was performed with the Snellen visual acuity chart, and the result was converted to logarithmic minimum angle of resolution (logMAR) visual acuity for statistic. Among the 46 cases, 6 cases were males and 40 cases were females. Age was (42.02±13.81) years old; logMAR BCVA was 0.063±0.015; AL was (23.95±0.726) mm. Visual field, macular SD-OCT, FAF examination showed no abnormality. The average cumulative dose of HCQ was 522.60 (6-1 728) g. rtx1 AO retinal camera was used to collect fundus images of subjects in four quadrants above the retina, nasal side, lower side and temporal side with 3°centrifugation from the fovea in both eyes. The cone density, cone spacing, cone arrangement regularity and the proportion of the nearest cones with 6 (nn=6) were measured in the four quadrants. The density of cone cells between the left and right eyes in case group and control group were compared by paired t test. The density and spacing of cone cells in each quadrant were compared by t test of two independent samples. ResultsCompared with the control group, the cone cell density in the four quadrants of the left eye and the nasal, superior and inferior sides of the right eye in the case group was significantly decreased, and the difference was statistically significant (t=4.247, 2.107, 4.884, 2.254, 2.643, 4.445, 4.116; P＜0.05). The cone spacing in the nasal and temporal sides of the left eye of the patients in the case group was significantly larger than that in the control eye, with statistical significance (t=2.750, 3.318; P＜0.05). Compared with the control group, the regulatign of cone cell arrangement in the left temporal side of the right and left eye in the case group were significantly reduced, the difference was statistically significant (P=0.002, 0.011). The proportion of nn=6 in the inferior and temporal sides of the right eye decreased significantly in the case group, and the difference was statistically significant (P=0.006, 0.032). ConclusionAO retinal imaging can detect the changes of cone cells in the early clinical stage of HCQ retinopathy.