## 2 Materials and Methods  
The current study, examining treatment-naive patients affected by RA, was prospectively carried out at the Department of Ophthalmology of the G. B Bietti Foundation in Rome. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Fondazione Bietti- IFO (Project identification code: N.114/21/FB). Each patient was carefully informed about the purpose of the research and provided signed consent to all procedures and data analysis. The study adopted inclusion and exclusion criteria as follows: Recent diagnosis of \"definite RA\", based on 2010 Rheumatoid Arthritis Classification Criteria. Patients were included with a score greater than 6 with regard to the following four main criteria: joint involvement, serology, acute-phase response measure, and symptom duration [26]; no previous or current treatment related to RA; no concomitant systemic disorders, including diabetes, cardiovascular diseases, and hypertension; no previous or concomitant ocular disease able to confound the appropriate examination, including media opacity and pathologic myopia, especially any type of retinal disorder; and no history of ocular surgery. Moreover, patients with a spherical refractor error over 4.00 dioptres or a cylindrical refractor error over 2.00 dioptres were excluded to restrict the influence of axial length on proper OCTA assessment. All RA patients underwent a comprehensive ophthalmological examination, including assessment of best-corrected visual acuity (BCVA) on standard ETDBS LogMAR charts at 4 m, slit lamp examination, tonometry, dilated fundus examination, structural and angiographic optical coherence tomography (OCT/OCTA) evaluation, and static visual field examination, at the baseline and after a one-year follow-up. OCTA technology enables the retinal and subretinal vascular networks to be reconstructed by encoding the source signal derived from the movement of erythrocytes inside the vessels; the trajectory of the vascular flows thus makes it possible to create a map of the vascular network. The retinal microvascular network imaging was analyzed by OCTA (Optovue XR Avanti, Fremont, CA, USA) and performed on all patients. The scans were centered on the fovea and the images acquired with the 6 \(\times\) 6 mm protocol. After acquisition, the internal software automatically delineates the superficial capillary plexus (SCP) and deep capillary plexus (DCP). The AngioVue software detects the SCP as the layer included between approximately 3 \(\upmu\)m below the internal limiting membrane and 15 \(\upmu\)m below the inner plexiform layer, while the DCP lies 15 to 70 \(\upmu\)m below the inner plexiform layer. SCP and DCP vessel density (VD), central foveal thickness (CFT) and foveal avascular zone (FAZ) values were collected. In more detail, the VD of the global area, foveal area (circle 1 mm in diameter centered on the fovea), and parafoveal region (between two concentric circles of 1 mm diameter and 3 mm diameter) of the SCP and DCP were calculated, providing specific values for the temporal, nasal, superior and inferior regions of the parafoveal area. Poor quality OCTA scans (signal strength below index 50, motion artefacts, and inappropriate segmentation) were excluded from the analysis. Structural analysis was performed at the baseline examination and at the one-year follow-up to establish the normal retinal architecture and if necessary identify anatomical changes related to HCQ toxicity, especially outer nuclear layer damage. Each scan was evaluated by two independent retinal specialists; uncertain cases were collectively discussed and categorized. Static visual field examination was performed by automated visual field testing, using a Humphrey computerized visual field device (Carl Zeiss Meditec Inc., Dublin, CA, USA), after applying refractive correction appropriate for the test distance. Central visual field testing was done using a 10-2 threshold central test program, which scans a 10 degree area at intervals of 2 degrees.