A Bioengineering Approach to Myopia Control Tested in a Guinea Pig Model

Abstract

PurposeTo investigate the biocompatibility of an injectable hydrogel and its ability to control myopia progression in guinea pigs.MethodsThe study used a hydrogel synthesized from acrylated hyaluronic acid with a conjugated cell-binding peptide and enzymatically degradable crosslinker. Seven-day-old guinea pigs were first form deprived (FD) with diffusers for 1 week. One group was kept as an FD-only control; two groups received a sub-Tenon's capsule injection of either hydrogel or buffer (sham surgery) at the posterior pole of the eye. Form deprivation treatments were then continued for 3 additional weeks. Treatment effects were evaluated in terms of ocular axial length and refractive error. Safety was evaluated via intraocular pressure (IOP), visual acuity, flash electroretinograms (ERG), and histology.ResultsBoth hydrogel and sham surgery groups showed significantly reduced axial elongation and myopia progression compared to the FD-only group. For axial lengths, net changes in interocular difference (treated minus control) were 0.04 ± 0.06, 0.02 ± 0.09, and 0.24 ± 0.08 mm for hydrogel, sham, and FD-only groups, respectively (P = 0.0006). Intraocular pressures, visual acuities, and ERGs of treated eyes were not significantly different from contralateral controls. Extensive cell migration into the implants was evident. Both surgery groups showed noticeable Tenon's capsule thickening.ConclusionsSub-Tenon's capsule injections of both hydrogel and buffer inhibited myopia progression, with no adverse effects on ocular health. The latter unexpected effect warrants further investigation as a potential novel myopia control therapy. That the hydrogel implant supported significant cell infiltration offers further proof of its biocompatibility, with potential application as a tool for drug and cell delivery.

IMI – Interventions for Controlling Myopia Onset and Progression Report

“…Another more recent study involving a potentially more biocompatible, hyaluronic acid-based polymer and a guinea pig myopia model did show slowed elongation, but curiously, so did shaminjected eyes. 260 These promising results, along with the fact that the procedure used in this study may be modified to avoid the need for general anesthesia, argues for further investigations into this approach, starting with exploration of alternative materials and more extensive investigations into both potential benefits and potential adverse ocular effects.…”

IMI – Clinical Management Guidelines Report

“…269 If ocular pathologies such as retinal detachment and myopic maculopathy, associated with myopia progression, are due to the thinning of the sclera and the stresses created by the stretching of the eye, then there may be some role for strengthening the sclera. Although there have been attempts to strengthen the sclera via scleral reinforcement surgeries, 270 cross-linking, 271,272 and with injectables, 273 none of these methods have a long record of success in humans. Posterior scleral buckling has been reported in a large case series to slow axial elongation and to reduce vision loss, but it has yet to be duplicated by other researchers.…”

In Vivo Imaging of the Retina, Choroid, and Optic Nerve Head in Guinea Pigs

“…3 Furthermore, myopia poses an increased risk for the development of primary open angle glaucoma, 4–6 which results in nerve fiber layer thinning 7 and optic nerve head changes, including decreased minimum rim width 8 and increased Bruch’s membrane opening, 9 ultimately leading to permanent vision loss. Guinea pigs are becoming an increasingly popular model of myopia, 10–12 and may also represent a promising model of glaucoma. Guinea pig retinal physiology, both in vitro single cell recordings 13, 14 and in vivo electrophysiology, 15, 16 have previously been characterized.…”