A Hydrogel Vitreous Substitute that Releases Antioxidant

Abstract

Current experimental vitreous substitutes only replace the physical functions of the natural vitreous humor. Removal of the native vitreous disrupts oxygen homeostasis in the eye, causing oxidative damage to the lens that likely results in cataract formation. Neither current clinical treatments nor other experimental vitreous substitutes consider the problem of oxidative stress after vitrectomy. To address this problem, biomimetic hydrogels are prepared by free radical polymerization of poly(ethylene glycol) methacrylate and poly(ethylene glycol) diacrylate. These hydrogels have similar mechanical and optical properties to the vitreous. The hydrogels are injectable through small‐gauge needles and demonstrate in vitro biocompatibility with human retinal and lens epithelial cells. The hydrogels and added vitamin C, an antioxidant, show a synergistic effect in protecting ocular cells against reactive oxygen species, which fulfills a chemical function of the natural vitreous. These hydrogels have the potential to prevent post‐vitrectomy cataract formation and reduce the cost of additional surgeries.

Macro- and Microscale Properties of the Vitreous Humor to Inform Substitute Design and Intravitreal Biotransport

“…17,34,59 Only a handful of hydrogel vitreous substitutes (n = 13) have similar storage and loss moduli to those reported for the human vitreous humor (less than 20 Pa). 34,59,[62][63][64]69,73,76,81,84,110,128,129 In contrast, a majority of the previously proposed vitreous substitutes have modulus values that are orders of magnitude higher than those of the reported human vitreous humor. While the in vivo results for some of these hydrogel vitreous substitutes were promising for short-and intermediate-term applications (less than 1 or 2 years), it is unknown whether the high modulus of these stiff gels would have long-term adverse effects on ocular tissues.…”

“…However, stiff hydrogels can be difficult to inject through a small gauge needle into the vitreous chamber. The storage and loss moduli of synthetic hydrogels 34,[59][60][61][62]69,73,74,76,[81][82][83] (G' = 1203 ± 755 Pa, n = 18 and G" = 373 ± 330 Pa, n = 12) and semisynthetic hydrogels [92][93][94]97,98,[100][101][102]104 (G' = 1330 ± 1090 Pa, n = 9 and G" = 291 ± 223 Pa, n = 9) are approximately two orders of magnitude higher, while natural hydrogels' 37,110 (G' = 99.4 ± 53.4 Pa, n = 3 and G" = 51.5 ± 48.5 Pa, n = 2) are about one order of magnitude higher compared to the human vitreous [15][16][17] (G' = 5.09 ± 1.86 Pa, n = 3 and G" = 1.81 ± 0.98 Pa, n = 3). Hydrogels with different mechanisms of injection into the eye also have a wide variation in storage and loss moduli ( Table 5 and Figure 4B).…”

“…Hydrogels with different mechanisms of injection into the eye also have a wide variation in storage and loss moduli ( Table 5 and Figure 4B). Hydrogel vitreous substitutes with direct injection mechanism 59,62,73,76,[81][82][83]94,110 (G' = 49.9 ± 31.3 Pa, n = 9 and G" = 26.3 ± 21.8 Pa, n = 9) have the closest modulus to the human vitreous, followed by thermogelling/in situ crosslinking hydrogels 37,96,100,101 (G' = 136 ± 33.1 Pa, n = 4 and G" = 28.9 ± 23.8 Pa, n = 4). The moduli of hydrogels with in situ crosslinking 34,69,93,97,98,104 (G' = 1626 ± 1031 Pa, n = 13 and G" = 338 ± 332 Pa, n = 6) or thermogelling 60,61,74,102 (G' = 2946 ± 2360 Pa, n = 4 and G" = 1206 ± 937 Pa, n = 4) mechanisms are, on average, more than two orders of magnitude higher than those of the natural human vitreous.…”

“…Hydrogel vitreous substitutes loaded with antioxidants such as ascorbic acid have recently been reported to reduce reactive oxygen species activity for lens cells, potentially preventing or reducing the incidence of cataract formation. 59 Glutathione, another antioxidant found at high concentrations in the ocular lens, [155][156][157] has recently been used in conjunction with ascorbate in a hydrogel vitreous substitute and was shown to curtail the potential cytotoxicity of ascorbate, prolong its antioxidant activity, and improve its stability in an aqueous environment. 158 These developments provide a novel avenue for ophthalmologists to better treat and control vitreoretinal and other ocular diseases while reducing the frequency of therapeutic administration for patients.…”

Scleral Buckling with Viscoelastics or Gas Injection for Bulging Retinal Detachments: A Retrospective Cohort Study

“…Comparing phacoemulsification surgery (PE) with viscosurgical devices (OVDs) and without OVD, best-corrected visual acuity (BCVA) values were significantly different on the day following surgery (0.41 ± 0.26 and 0.54 ± 0.34 logMAR) in OVD and non-OVD groups, respectively, although both groups had similar values at 6 months postoperatively [12]. e density and refractive index of a viscoelastic agent are basically close to those of the vitreous [13][14][15]. Recently, local dry vitrectomy combined with segmental scleral buckling and viscoelastic tamponade was evaluated for treating partial rhegmatogenous retinal detachment (RRD) with local vitreous traction, and postoperative visual acuities showed improvement or remained stable in the totality of patients, with no major complications besides transient mild intraocular pressure increased in 3 of 11 patients [16].…”