Andrew R. Berneshawi ¹ Kimia Seyedmadani ^2,3 Mark R. Anderson ^4,5 Rahul Goel ^5,6 Terence L. Tyson ⁵ Yasemine M. Akay ³ Metin Akay ³ Loh-Shan B. Leung ¹ Leland S. Stone ^5*

• ¹ Department of Ophthalmology, School of Medicine, Stanford University, Palo Atlo, California, United States
• ² Johnson Space Center, National Aeronautics and Space Administration, Houston, Texas, United States
• ³ Department of Biomedical Engineering, Cullen College of Engineering, University of Houston, Houston, Texas, United States
• ⁴ ASRC Federal Analytical Service (United States), Huntsville, Alabama, United States
• ⁵ Human Systems Integrations Division, Ames Research Center, National Aeronautics and Space Administration, Moffett Field, California, United States
• ⁶ San José State University Research Foundation, Moffett Field, United States

This study examines a set of oculomotor measurements, or "oculometric" biomarkers, as potential early indicators of visual and visuomotor deficits due to retinal toxicity in asymptomatic Systemic Lupus Erythematosus (SLE) patients on long-term hydroxychloroquine (HCQ) treatment. The aim is to identify subclinical functional impairments that are otherwise undetectable by standard clinical tests and to link them to structural retinal changes. We measured oculomotor responses in a cohort of SLE patients on chronic HCQ therapy using a previously established behavioral task and analysis technique. Significant visual and visuomotor deficits were found in 12 asymptomatic SLE patients on long-term HCQ therapy compared to a cohort of 17 agematched healthy controls. Notably, six oculometrics were significantly different. The median initial pursuit acceleration was 22%, steady-state pursuit gain 16%, proportion smooth 7%, and target speed responsiveness 31% lower, while catch-up saccade amplitude was 46% and fixation error 46% larger. Excluding the two patients with early clinical signs of toxicity, four oculometrics, all but fixation error and proportion smooth, remained significantly impaired compared to controls. We also examined the relationship between oculometrics, OCT measures of retinal thickness, and standard clinical perimetry measures of visual function in our patient group using Bivariate Pearson Correlation and a Linear Mixed-Effects Model (LMM). Across our population of 12 patients (24 retinae), we found that pursuit latency, initial acceleration, steady-state gain, and fixation error were linearly related to retinal thickness even when age was accounted for, while standard measures of clinical function (Mean Deviation and Pattern Standard Deviation) were not. Our data show that specific oculometrics are sensitive early biomarkers of functional deficits in SLE patients on HCQ that could be harnessed to assist in the early detection of HCQ-induced retinal toxicity and other visual pathologies, potentially providing early diagnostic value beyond standard visual field and OCT evaluations.