Corneal confocal microscopy reveals neuroimmune alterations in drug-naïve patients with obsessive-compulsive disorder: a case-control study

Obsessive-compulsive disorder (OCD) has been associated with inflammatory and immunological mechanisms. Ocular imaging provides a noninvasive approach of investigating peripheral and neuroinflammatory processes. This study aimed to evaluate ocular inflammatory biomarkers in OCD using enhanced-depth imaging optical coherence tomography (EDI-OCT) and corneal confocal microscopy (CCM). Twenty-nine drug-naïve patients with OCD and 28 age- and sex-matched healthy controls underwent comprehensive ophthalmic assessment. Subfoveal choroidal thickness and the choroidal vascularity index (CVI) were measured using EDI-OCT; while dendritic cell (DC) density and subbasal nerve plexus (SBNP) parameters were quantified using CCM. Between-group comparisons were performed using nonparametric tests, and correlations with clinical severity were assessed using Spearman’s rank correlation coefficient (ρ). Subfoveal choroidal thickness did not differ between groups ( p = 0.787). CVI was higher in the OCD group ( p = 0.044), although the absolute difference was small. In contrast, CCM revealed marked corneal alterations: DC density was significantly increased (106.25 vs. 32.29 cells/mm²; p < 0.001), and SBNP parameters—including fiber density, length, and branching—were all significantly reduced (all p < 0.001). No significant associations were observed between corneal parameters and overall symptom severity, whereas CVI showed a modest positive correlation with obsession scores. This study provides the first evidence of corneal neuroinflammatory alterations in OCD using CCM. Increased DC density and reduced nerve fiber parameters suggest that CCM-derived measures may reflect neuroimmune alterations, whereas choroidal parameters appear less informative. These findings warrant validation in larger, longitudinal studies.