Abstract
Purpose :
One billion people will be at risk of blindness by 2050 from high myopia, however limited treatment options are available. Changes occur at the optic nerve head that mimic those found in glaucoma, and underlying causes are thought to relate to scleral fibroblast overactivation and increased intraocular pressure levels which can be modified by rho associated kinase inhibitors (ROCKi). The current study assessed the efficacy of ROCK inhibitors at influencing the development of high myopia.
Methods :
High myopia was induced in 2 week-old guinea pigs using a variation of form deprivation (FDHM) in one eye over a 2 week period. In Experiment 1, animals simultaneously received daily sub-tenons injections of 0.1% (100 μM) Y-27632 dihydrochloride (Sigma) in saline (n=11), saline alone (n=9) or no injections in the deprived eye. In Experiment 2, eyedrops (ripasudil hydrochloride hydrate, 0.4% w/v, Glanatec, KOWA, n=10) or bion tears (n=9) were simultaneously administered in the deprived eye twice each day. Cycloplegic autorefraction, high-frequency ultrasound, keratometry and tonometry were used to measures refractive error, ocular distances, corneal power, and intraocular pressure respectively.
Results :
In Experiment 1, FDHM animals that were not injected developed -9.0D of myopia arising from increased ocular growth. Both injected groups also developed significant relative myopia (Saline+FDHM: -10.2D, ROCKi+FDHM: -12.2D) partly from increased corneal power combined with relative increases in thickness of the ocular components measured on-axis. In Experiment 2, both control and drug eyedrop groups also developed significant relative myopia (-7.1D and -8.2D respectively). ROCK inhibitors significantly reduced intraocular pressure and noticeably improved wound healing at the injection site.
Conclusions :
Since ROCK inhibitors were ineffective at reducing myopia development despite reduction in intraocular pressure, it suggests that inhibitory effects previously noted for topical latanoprost may not arise from its effects on intraocular pressure reduction. Additionally, it suggests that modification of scleral fibroblasts with anterior application of ROCK inhibitors has a tendency to exacerbate myopia development.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.