Scleral Cross-Linking in Form-Deprivation Myopic Guinea Pig Eyes Leads to Glaucomatous Changes

PURPOSE: To investigate the potential glaucomatous changes caused by scleral cross-linking (CXL) in a guinea pig form-deprivation (FD) myopia model. METHODS: Eighty 4-week-old tricolor guinea pigs were divided into four groups: FD only, genipin CXL only, FD plus CXL, and control. Refractive error, axial length (AL), intraocular pressure (IOP), and structural and vasculature optic disc changes in optical coherence tomography (OCT) and OCT angiography (OCTA) were measured at baseline and day 21. CXL efficacy was evaluated by scleral rigidity Young's modulus values. Histological and molecular changes in the anterior chamber angle, retina, and sclera were assessed. RESULTS: Baseline parameters were similar among groups (P > 0.05). The FD plus CXL group at day 21 had the least increase of AL (0.14 ± 0.08 mm) and highest IOP elevation (31.5 ± 3.6 mmHg) compared with the FD-only group (AL: 0.68 ± 0.17 mm; IOP: 22.2 ± 2.6 mmHg) and the control group (AL: 0.24 ± 0.09 mm; IOP: 17.4 ± 1.8 mmHg) (all P < 0.001). OCT and OCTA parameters of the optic disc in the FD plus CXL group at day 21 showed glaucomatous changes and decreased blood flow signals. Sclera rigidity increased in the CXL and FD plus CXL groups. Advanced glycation end products deposited extensively in the retina, choroid, and sclera of FD plus CXL eyes. CONCLUSIONS: CXL causes increased IOP and subsequent optic disc, anterior segment, and scleral changes while inhibiting myopic progression and axial elongation in FD guinea pig eyes. Therefore, applying CXL to control myopia raises safety concerns.