Anti-inflammatory and dry eye benefits of accelerated epi-off corneal cross-linking in pediatric keratoconus with allergic ocular surface disease and elevated MMP-9

Purpose: To assess the functional and ocular surface anti-inflammatory outcomes of epithelium-off accelerated corneal cross-linking (ACXL) in adolescents with progressive keratoconus associated with allergic ocular surface disease and dry eye disease (DED) characterized by elevated tear matrix metalloproteinase-9 (MMP-9) concentrations. Methods: Prospective interventional case series of 30 eyes from 15 patients (mean age 16.41 ± 2.36 years; Krumeich stage II) undergoing epi-off ACXL. Outcomes at baseline and 1, 3, 6, and 12 months included corrected distance visual acuity (CDVA), maximum keratometry (Kmax), minimum corneal thickness (MCT), computerized non-invasive tear break-up time (cBUT), Ocular Surface Disease Index (OSDI), and tear MMP-9 (point-of-care test). In vivo qualitative confocal microscopy (IVCM) investigation provided supportive imaging. Paired t-tests were used and results reported with 95% confidence intervals (CI). Results: CDVA improved to 0.09 logMAR at 12 months (≈ 0.81 decimal; 95% CI: 0.10-0.08 logMAR; P < 0.001). Kmax decreased from 55.00 to 53.75 D (95% CI: 53.55-53.95 D; Δ =  - 1.25 D; P < 0.001), indicating ectasia stabilization. cBUT increased from 10.11 to 14.41 s (95% CI: 14.11-14.71; P < 0.01). OSDI decreased to 12.15 (95% CI: 11.65-12.65). Tear MMP-9 levels diminished from 64.79 to 16.15 ng/mL (P < 0.0001) and the proportion < 38.6 ng/mL reached 86.7% of the study cohort at 12 months. IVCM documented disappearance of inflammatory infiltrates. No postoperative persistent adverse events occurred. Conclusions: Epi-off ACXL stabilized ectasia, improving visual and ocular surface outcomes, markedly lowering tear MMP-9 levels. Although exploratory, these findings are consistent with a potential ocular surface anti-inflammatory and neuromodulatory role of ACXL, meriting validation in studies involving inflammatory DED beyond keratoconus.