Tear inflammatory protein changes after orthokeratology lens system replacement in wearers with corneal punctate staining: a pilot pre-post exploratory study Research Article

<title>Abstract</title> <p>Background Corneal punctate staining is common during orthokeratology follow-up and may reflect epithelial stress or inflammatory activity at the lens-tear-cornea interface. Temporary discontinuation of lens wear is often considered for clinically meaningful staining, but some wearers and their guardians are reluctant to interrupt overnight orthokeratology. This exploratory prospective study evaluated tear inflammatory protein profiles in orthokeratology wearers with corneal punctate staining and examined clinical and proteomic changes after lens system replacement. Methods Twenty long-term Alpha Ortho-K wearers were included in the final analysis: 12 without corneal punctate staining and 8 with clinically meaningful staining and complete paired follow-up data. Wearers in the staining group underwent lens system replacement from Alpha Ortho-K to Menicon Z Night Ortho-K as part of clinical management and were followed for 3 months. Corneal staining was graded using the Cornea and Contact Lens Research Unit scale, and tear inflammatory protein assays were measured using the Olink Target 96 Inflammation Panel. Baseline cross-sectional and within-participant paired comparisons were performed. Results At baseline, the staining group included five wearers with CCLRU Grade 2 staining and three with Grade 3 staining. At the 3-month follow-up, all eight wearers improved to Grade 0, with no recorded changes in lens care solution, wearing schedule, or topical medication use. In the paired analysis, 13 inflammatory protein assays remained significant after false discovery rate correction, and all showed lower levels after lens system replacement. Conclusions Orthokeratology-related corneal punctate staining was accompanied by nominal cross-sectional differences in tear inflammatory protein assays. Among selected wearers who continued overnight orthokeratology, lens system replacement was associated with within-participant improvement in corneal staining and reductions in multiple tear inflammatory protein assays, particularly those related to chemokine signaling and innate immune activity. Larger controlled studies are needed to confirm these findings, assess causality, and evaluate clinical generalizability. Trial registration: Chinese Clinical Trial Registry, ChiCTR2500106186. Registered July 17, 2025.</p>