Effects of poly(2-hydroxyethyl methacrylate) and poly(vinyl-pyrrolidone) hydrogel implants on myopic and normal chick sclera.

There has been generally little attention paid to the utilization of biomaterials as an anti-myopia treatment. The purpose of this study was to investigate whether polymeric hydrogels, either implanted or injected adjacent to the outer scleral surface, slow ocular elongation. White Leghorn (Gallus gallus domesticus) chicks were used at 2 weeks of age. Chicks had either (1) a strip of poly(2-hydroxyethyl methacrylate) (pHEMA) implanted monocularly against the outer sclera at the posterior pole, or (2) an in situ polymerizing gel [main ingredient: poly(vinyl-pyrrolidone) (PVP)] injected monocularly at the same location. Some of the eyes injected with the polymer were fitted with a diffuser or a -10D lens. In each experiment, ocular lengths were measured at regular intervals by high frequency A-scan ultrasonography, and chicks were sacrificed for histology at staged intervals. No in vivo signs of either orbital or ocular inflammation were observed. The pHEMA implant significantly increased scleral thickness by the third week, and the implant became encapsulated with fibrous tissue. The PVP-injected eyes left otherwise untreated, showed a significant increase in scleral thickness, due to increased chondrocyte proliferation and extracellular matrix deposition. However, there was no effect of the PVP injection on ocular elongation. In eyes wearing optical devices, there was no effect on either scleral thickness or ocular elongation. These results represent "proof of principle" that scleral growth can be manipulated without adverse inflammatory responses. However, since neither approach slowed ocular elongation, additional factors must influence scleral surface area expansion in the avian eye.

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

Purpose: To investigate the biocompatibility of an injectable hydrogel and its ability to control myopia progression in guinea pigs. Methods: The 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. Results: Both 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. Conclusions: Sub-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.

Scleral reinforcement through host tissue integration with biomimetic enzymatically degradable semi-interpenetrating polymer network.

Enzymatically degradable semi-interpenetrating polymer networks (edsIPNs) were explored for their biocompatibility and ability to promote new scleral tissue growth, as a means of reinforcing the posterior wall of the eye. The edsIPNs comprised thermoresponsive poly(N-isopropylacrylamide-co-acrylic acid), customizable peptide crosslinkers cleavable by matrix metalloproteinases, and interpenetrating linear poly(acrylic acid)-graft-peptide chains to engage with cell surface receptors. Rheological studies revealed an increase in stiffness at body temperature; the complex shear modulus |G*| was 14.13 +/- 6.13 Pa at 22 degrees C and 63.18 +/- 12.24 Pa at 37 degrees C, compatible with injection at room temperature. Primary chick scleral fibroblasts and chondrocytes cultured on edsIPN increased by 15.1- and 11.1-fold, respectively, over 11 days; both exhibited delayed onset of exponential growth compared with the cells plated on tissue culture polystyrene. The edsIPN was delivered by retrobulbar injection (100 microL) to nine 2-week-old chicks to assess biocompatibility in vivo. Ocular axial dimensions were assessed using A-scan ultrasonography over 28 days, after which eyes were processed for histological analysis. Although edsIPN injections did not affect the rate of ocular elongation, the outer fibrous sclera showed significant thickening. The demonstration that injectable biomimetic edsIPNs stimulate scleral fibrous tissue growth represents proof-of-principle for a novel approach for scleral reinforcement and a potential therapy for high myopia.