The Prevention of Postvitrectomy Cataracts With Antioxidant Biogel

An update on basic science research

SHLOMIT SCHAAL, MD, PhD • AGUSTINA PALACIO, MD • MARTIN O’TOOLE, PhD • TONGALP TEZEL, MD

The low oxygen tension around the lens (8.7 mm Hg)¹ helps to protect natural lens proteins and lipids from oxidative damage.^2,3 The vitreous gel serves as a natural barrier for lens oxidation, decreasing the oxygen concentration from the retina toward the lens.^4,5

Surgical removal of vitreous gel during vitrectomy results in an efflux of oxygen inside the eye through diffusion from the retina-choroid complex and/or ion-assisted transport of oxygen through the vitreous humor, resulting in increased oxygen-related damage to the crystalline lens.^6-8 As a result, it is well known to retina surgeons that more than half of phakic patients develop secondary cataracts within two years after vitrectomy.^1,9 Moreover, increased reactive oxygen species in the anterior chamber of the postvitrectomy eye has recently been shown to damage the trabecular meshwork, thereby leading to postvitrectomy glaucoma and irreversible damage to the optic nerve.^10,11

At the University of Louisville, researchers have developed an injectable, biocompatible photopolymerizable gel to create an oxygen barrier that can be applied onto the crystalline lens during vitrectomy surgery to help maintain its relative hypoxic native environment.¹² The gel is a mixture of polymers and antioxidant compounds that was designed to be applied easily to the posterior surface of the natural lens as a viscous liquid and then photopolymerized in situ during vitrectomy surgery to remain on the lens as a protective hydrogel, preventing the formation of vitrectomy-induced lens opacities.^8,13

Because there has been growing evidence that preservation of the natural lens may protect against postvitrectomy glaucoma, this gel may also serve to protect against postvitrectomy optic nerve damage, because it may preserve the natural crystalline lens.

ENGINEERED TO WORK

This material was specifically engineered to meet the following requirements: (1) it has the same refractive index as the lens to avoid any refractive error; (2) it is completely transparent to avoid any scattering or transmission defects of light; (3) it is permeable to ions and fluids so as not to interfere with aqueous circulation; (4) it is sufficiently elastic not to interfere with the accommodative ability of the human lens; (5) it has the surface energy not to allow protein adhesion or cell growth on the polymer surface; (6) it has viscoelastic properties to allow for injection via a 25-gauge needle; and (7) it has the ability to withhold oxygen and thus seal the lens semipermanently/permanently without the need for frequent intravitreal injections or drops to replenish any chemical. The gel formulation was optimized and changed over the research period to achieve optimal results.

The gel is loaded with a slow-release antioxidant particle formulation to provide antioxidant capacity to the lens in the absence of vitreous. The gel itself, due to its porous nature, can physically impede the diffusion of oxygen through the gel and may serve as a reservoir for absorbing oxygen.

The biogel proved to be biocompatible with porcine lenses in ex-vivo studies and significantly delayed the development of lenticular opacities without any apparent side effects. Lenses cultured with the gel showed greater resistance to oxidative damage and showed significantly less cataract formation than control lenses (Figure 1).

Figure 1. Gel protected lenses (left) remained clear in ex-vivo vitrectomy mimicking hyperoxic conditions, while control lenses under similar conditions (right) became cataractous.

Measurement of PO₂ within the gel near the lens capsule revealed that the gel maintained the lens at 8.3 mm Hg PO₂, and lenses cultured with the gel showed no detrimental effects for up to one month. The longevity of the lenses encased in gel suggests that the flow of nutrients and circulation of the media to the lens were unimpeded by the gel.

In-vivo testing of the gel formulation in 15 pigs over the last year proved to prevent cataract formation successfully in the eyes for up to 12 months (and counting) following vitrectomy (Figure 2). No inflammation, increases in IOP, lens dislocation, or harmful adverse effects were noted during the clinical and electrophysiological exams. No toxicity to the lens, cornea, or retina was detected in the histological sections of the treated eyes. No changes in ocular refraction were noted.

Figure 2. Three months after vitrectomy lenses were extracted and studied. Gel protected lenses (left) remained clear in-vivo post vitrectomy, while control lenses under similar conditions (right) became cataractous. Oxygen-induced cataract changes are shown as cortical lenticular bubbles (right).

The gel proved to be biocompatible, nonimmunogenic, and well tolerated. The porcine surgical model has shown promising results, revealing that formulated biogel could possibly prevent oxygen-induced cataract formation after vitrectomy surgery. Dr. Schaal recently presented the latest progress of this research in a talk at the ARVO annual meeting in Denver, CO, in May 2015.¹⁴

CONCLUSION

Research in this area is ongoing, with the generous support of the Coulter Foundation grant. The objective is to determine the precise mechanism of action of this novel cataract-preventing biogel and to establish the most effective way to administer the gel during vitrectomy surgery. Animal studies in large numbers are under way to calculate the actual success rate in preventing postvitrectomy cataracts. RP

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