NIR Light Through the Pupil Crosslinks Sclera Without Surgery in Guinea Pigs

Progressive myopia is a worsening global health crisis linked to scleral thinning and biomechanical weakening. Current interventions—spectacle lenses, atropine, posterior scleral reinforcement—slow but do not reverse the underlying collagen matrix degradation. Scleral crosslinking has emerged as a promising strategy to directly address this weakness, but existing light-activated methods require invasive surgery to reach the sclera with UVA light, and chemical crosslinking agents lack spatial specificity and carry risks of retinal toxicity and inflammation.

This study explored WST11, a bacteriochlorophyll-derived photosensitizer already approved in Europe for vascular-targeted photodynamic therapy of prostate cancer, formulated with dextran (WST-D) and activated by 753 nm NIR light. The NIR wavelength can safely penetrate through the pupil and anterior eye structures to reach the posterior sclera without surgery. Adding dextran increases the viscosity of the formulation, restricting WST11 diffusion and preventing it from reaching the choroid or retina.

In ex vivo experiments, 2%, 5%, and 10% dextran concentrations were tested. Only 10% dextran reliably confined WST11 to the outer half of the posterior sclera during a 30-minute incubation, with a diffusion coefficient of 1.90 × 10⁻⁹ cm²/s. A thermal degradation assay—measuring the temperature at which 50% of scleral tissue shrinks (T50)—was used to quantify crosslinking efficacy. All WST-D plus NIR combinations tested produced significantly higher T50 values than untreated controls. The peak result came from 30 minutes of WST-D incubation followed by 10 mW/cm² NIR for 30 minutes (ΔT50: 6.8, p=0.0006). Notably, eyes from older guinea pigs (5–6 months) responded more strongly than younger ones, a finding consistent with age-related differences in baseline collagen cross-link density and scleral composition.

The optimized parameters were then applied in vivo in 6-month-old guinea pigs. Following transpupillary NIR delivery, both the equatorial sclera (ΔT50: 3.7, p<0.0001) and posterior sclera (ΔT50: 3.4, p=0.01) showed significant crosslinking compared to untreated controls. The in vivo ΔT50 values were somewhat lower than ex vivo findings, likely reflecting the dilution effect of the living aqueous environment and the constraints of in vivo WST-D delivery through the pupil rather than direct posterior incubation.

The approach has several notable advantages: NIR light is non-phototoxic at the wavelengths used, the treatment is non-surgical, WST11 has an established clinical safety profile, and dextran-mediated diffusion control adds spatial targeting. The age-dependent efficacy finding is an important caveat, indicating that treatment protocols may need to be personalized. Future studies should assess whether WST-D/NIR crosslinking can slow axial elongation in myopia-induced animal models and evaluate long-term biocompatibility.