Comparison of choroidal biomarkers and scleral thickness in keratoconus in relation to corneal cross-linking.

PURPOSE: To investigate whether corneal collagen cross-linking (CXL) is associated with measurable remodeling of extra-corneal tissues in KC, by comparing choroidal and scleral structural biomarkers between treatment-naïve and CXL-treated eyes. METHODS: This is a single center, cross-sectional, observational study. Anterior scleral thickness (ST) was quantified using swept-source anterior segment optical coherence tomography (AS-OCT; CASIA2, Tomey, Japan). Ocular biomechanical parameters were measured with the Ocular Response Analyzer (ORA; Reichert, Germany). Subfoveal choroidal thickness (SFCT), peripapillary choroidal thickness (PPCT) were assessed with spectral-domain OCT (SPECTRALIS HRA-OCT, Heidelberg Engineering, Germany). Choroidal vascularity index (CVI) and total choroidal area (TCA) were computed using a validated semi-automated algorithm. A subgroup analysis compared treated and untreated fellow eyes in unilateral CXL cases. RESULTS: 65 keratoconic eyes of 65 patients were recruited – 35 treatment-naïve versus 30 post–epithelium-off cross-linking (≥ 6 months post-treatment). CXL-treated eyes exhibited significantly greater Sub-Foveal Choroidal Thickness (SFCT) (421.1 ± 81.9 μm vs. 352.9 ± 81.9 μm; p = 0.016), mean Peripapillary Choroidal Thickness (PPCT) (238.0 ± 72.9 μm vs. 199.5 ± 65.3 μm; p = 0.038), and mean Total Choroidal Area (TCA) (1.45 ± 0.32 mm² vs. 1.29 ± 0.27 mm²; p = 0.046) compared with treatment-naïve eyes, whereas Choroidal Vascularity Index (CVI) and Scleral Thickness (ST) showed no significant differences (p > 0.05). In unilateral cases, treated eyes demonstrated consistent increases in SFCT, TCA, and PPCT relative to fellow untreated eyes (p < 0.05). PPE alterations occurred exclusively in the CXL group (16.7%). Multivariate regression analysis identified previous CXL as the only independent factor associated with increased SFCT (β = 0.340, p = 0.040). CONCLUSIONS: CXL appears to be associated with thicker choroids in keratoconic eyes, independent of biomechanical or scleral thickness variations. These findings support the hypothesis that CXL might be linked to subclinical remodeling of deeper ocular layers, potentially affecting choroidal-scleral fluid dynamics. Further prospective longitudinal studies with larger cohorts and multimodal assessment are warranted to clarify the mechanisms, time course, and long-term implications of choroidal changes following CXL.