Crosslinking of guinea pig sclera by WST-D/NIR as a treatment to arrest myopia

Abstract

Purpose : Myopia, or near-sightedness, is expected to affect half of the world population by 2050 and is the major cause of blindness in working-age adults. Despite the increasing prevalence and major health burden, there is still no treatment for pathologic myopia. A new promise for myopic patients is collagen crosslinking, which restores mechanical strength to the weakened parts of the eye. This research investigates scleral collagen crosslinking by administering the photosensitizer agent WST11 with dextran (WST-D) to the sclera, followed by activation with near-infrared (NIR) transpupillary irradiation as a potential treatment to arrest pathological myopia.

Methods : To develop this treatment, ex vivo optimization of WST-D/NIR collagen crosslinking in guinea pig sclera was performed. Untreated, WST-D–treated, and saline/NIR–treated guinea pig eyes served as controls. The in vivo safety and efficacy of WST-D/NIR treatment were investigated in 6-month-old guinea pigs. The eyes were extracted immediately after the treatment. The safety was assessed by monitoring the penetration depth of WST-D into the ocular tissue and a thermostability assay was used as an indirect measure of crosslinking efficacy.

Results : Incubation of guinea pig eyes with WST-D for 30 minutes limited the penetration of WST11 to the sclera, without entering the choroid or retina. Transpupillary illumination of the sclera immediately after WST-D incubation resulted in effective stiffening. The effect was greatly reduced when using NIR irradiation 24 hours after WST-D incubation, suggesting the WST-D had largely cleared from the sclera. The extent of stiffening appeared proportional to the applied energy by the NIR irradiation, whereby 10 mW/cm² for 30 min appeared optimal for safety and efficacy.

Conclusions : The penetration depth of WST-D can be limited to the sclera and irradiation with NIR light significantly increased the stiffness of the tissue. These results provide a proof-of-concept and valuable insights into the parameters needed to reach optimal stiffening of the sclera and will be used to prepare for clinical translation.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.