Oculometric biomarkers of visuomotor deficits in clinically asymptomatic patients with systemic lupus erythematosus undergoing long-term hydroxychloroquine treatment

Front Ophthalmol (Lausanne). 2024 Jul 22:4:1354892. doi: 10.3389/fopht.2024.1354892. eCollection 2024.

Abstract

Introduction: 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.

Methods: We measured oculomotor responses in a cohort of SLE patients on chronic HCQ therapy using a previously established behavioral task and analysis technique. 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).

Results: Significant visual and visuomotor deficits were found in 12 asymptomatic SLE patients on long-term HCQ therapy compared to a cohort of 17 age-matched 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 diagnosed mild toxicity, four oculometrics, all but fixation error and proportion smooth, remained significantly impaired compared to controls. 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.

Discussion: 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.

Keywords: pursuit eye movements; retinal function; saccadic eye movements; structure-function analysis; surveillance; visual motion processing.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by Ames Research Center Innovation Fund (LS), NASA Human Research Program (LS), NIH National Eye Institute (P30-026877) and Research to Prevent Blindness, Inc. (L-SL), NASA Grant 80NSSC19M0186 (KS), and NASA Ames Graduate Fellowship Award (TT). None of the funders had any technical or editorial influence on this study or manuscript. Furthermore, the authors declare that although this study received funding from Research to Prevent Blindness, Inc., this funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication.