An Oral Antioxidant Formulation Delaying and Potentially Reversing Canine Diabetic Cataract: A Placebo-controlled Double-masked Pilot Study

Background: The majority of dogs with diabetes mellitus develop blinding mature cataracts through the action of the enzyme aldose reductase producing sorbitol with osmotic action drawing water into the lens thus causing opacification. Here we evaluate the use of OcuGLOTM a formulation including the aldose reductase inhibitor alpha lipoic acid, grapeseed extract, carotenoids, omega-3-fatty acids, and coenzyme Q10 in the prevention of canine diabetic cataract in a prospective placebo-controlled double-masked study. Materials and methods: Dogs with diabetes mellitus but as yet without the development of blinding diabetic cataracts were given either OcuGLOTM or a placebo containing antioxidant vitamins. Dogs were examined monthly and their degree of lens opacification documented photographically using a Genesis D fundus camera at +10D. Time to progression of lens opacification was documented and compared between the OcuGLOTM group and the placebo group, using Kaplan Meier survival curve statistics. Results: Mean time without change in lens opacification was 278 ± 184 days with OcuGLO RxTM and 77 ± 40 days in the placebo group this difference being statistically significant at p=0.0005. Twelve of 15 dogs taking the placebo developed significantly increased lens opacification while 5 of 15 dogs taking OcuGLO RxTM developed significant cataract. of these five dogs four animals did not receive daily OcuGLO RxTM as directed due to unrelated concurrent illness or owner non-compliance. The remaining dog progressed despite Ocu-GLO RxTM administration. In two dogs, diabetic cataract was reversed with regained vision on Ocu-GLO RxTM. Discussion: This small preliminary study demonstrates that oral Ocu-GLO RxTM has beneficial effects in delaying cataract formation in dogs with diabetes mellitus. We look forward to further studies with larger case populations but note that the statistical significance reached between placebo and supplement-treated group, even with a small study population, demonstrates the efficacy of this commercially available dietary supplement. Introduction Cataract formation is a widely recognised complication of diabetes mellitus in the dog [1]. Lens opacification in diabetes is suggested to occur through three mechanisms. The first and most important in the dog is the accumulation of polyols, sugar alcohols and most particularly sorbitol, produced through the action of the enzyme aldose reductase (AR) and resulting in an osmotic stress and ingress of fluid into the lens, causing cataract [2]. While this development of lens opacity is generally considered to be rapid, changing a clear lens to a mature cataract within hours or days, and occurring bilaterally symmetrically in both eyes, these assumptions may not necessarily be correct, formed through the fact that most ophthalmologists will only see diabetic dogs when they have become blind. In fact, initial changes in lens opacity prior to the development of mature cataract may occur in diabetic dogs with equatorial vacuoles and cortical opacities occurring in a substantial number of cases, and not necessarily occurring bilaterally symmetrically. Similar changes are seen in dogs fed galactose [3], but the cataract formation may be more severe in this experimental model, since the osmoticon produced by AR from galactose, galacticol, is not further metabolised to fructose by an enzyme equivalent to sorbitol dehydrogenase. Inhibition of aldose reductase has been shown to prevent galactose and diabetic cataract in a number of experimental models [4-6], and in some cases reversal of diabetic cataract on use of sorbinil, an aldose reductase inhibitor, has been reported [7]. The other two mechanisms involve non-enzymatic glycation of lens proteins [8] and oxidative stress [9], which may itself occur through the competition between AR and glutathione reductase for NADPH leading to a depletion in reduced glutathione (GSH), a key intralenticular antioxidant. The part played by these mechanisms in the canine lens is at present unknown. It has already been demonstrated that administration of the topical AR inhibitor Kinostat appears to inhibit the development of cataracts in diabetic dogs, but this product is not as yet commercially