Eyeworld

56 | EYEWORLD | DECEMBER 2020 ATARACT C by Maxine Lipner Contributing Writer About the doctors Jeremy Keenan, MD Professor of Ophthalmology University of California, San Francisco San Francisco, California Nick Mamalis, MD Professor of Ophthalmology John A. Moran Eye Center University of Utah Salt Lake City, Utah Catherine Opere, PhD Professor of Pharmaceutical Sciences School of Pharmacy and Health Professions Creighton University Omaha, Nebraska tion or reversal has not worked. Dr. Opere's re- view included double-blinded clinical trials such as AREDS2 where both lutein and zeaxanthin were evaluated. 2 Both failed to demonstrate significant prophylactic action. In another study, 3 investigators followed patients in rural south India who received either 500 mg of vitamin C, 25 IU of vitamin A, and 400 IU of vitamin E, or placebo 3 times a week initially for 5 years, according to Jeremy Keenan, MD. "In the original trial, participants were examined for cataract progression with a slit lamp exam," he said. "No difference in cata- ract was observed after 5 years." Given that cataract progression is slow, the idea of this 15-year follow-up trial was that the antioxidant therapy might provide a later benefit. But this benefit was not observed. "The key finding is that about 15% of participants reported having cataract surgery over the 15 years of follow-up, with no difference between the antioxidant or placebo group," Dr. Keenan said. Based on this and other randomized trials, there's no compelling evidence that antioxidant vitamins prevent cataracts, he said. Dr. Mamalis pointed out that one of the issues may be a question of transporting the "medications" into the lens where these need to be. "If you're looking at a topical drop, that would have to not only penetrate the cornea and get into the anterior chamber but get into the crystalline lens itself," Dr. Mamalis said. Another reason this may not be translating from animals to humans is that it's much easier to The search for a pharmacologic cataract solution continued on page 58 A drop or pill that could forestall or even reverse cataract formation has been discussed and researched for years. It's an especially attractive options for patients in developing countries where surgery can be less available or less safe. A literature review found that in animals, cataracts have seemingly been forestalled with various agents. 1 A bevy of things, such as caro- tene, curcumin, resveratrol, flavonoids extracted from broccoli, propolis found in honey, onions, garlic, and saffron, have shown promise, at least in the lab, according to Catherine Opere, PhD. "When you look at the mechanism of many of these different herbs, the common theme was they increased intracellular antioxidants, they increased enzymes, and they decreased lipids and oxidation," Dr. Opere said. In animal studies, most "anti-cataract" pharmacotherapies have been prophylactic, Dr. Opere noted, adding that one of the pathways associated with aging, and thus age-related cataract formation, is oxidative stress, leading to a loss of lens solubility. Nick Mamalis, MD, pointed out that as the body ages, a lot of the proteins in the crystal- line lens end up crosslinking, and as a result, the lens becomes harder. "If you could come up with something that could prevent crosslinking, not only could you prevent the formation of cataracts, but you may also be able to prevent or delay the onset of presbyopia," he said. Antioxidants like vitamin C and vitamin E have been studied for this purpose, Dr. Opere said. "What's interesting about vitamin C is that when there's too much of it, it becomes toxic, and when there's too little, it's no good," Dr. Opere said. The same holds true for selenium, which in the right concentration is an antiox- idant, but if too much is given, it becomes a pro-oxidant and can induce a cataract in an animal. In animals, many of the substances re- viewed decrease lipid peroxidation and increase intracellular antioxidants, Dr. Opere explained. "If you drill down, that's the bottom line mecha- nism," she said. When it comes to in-human trials, a phar- macotherapeutic approach to cataract preven- Globe with a dense cataract Source: Nick Mamalis, MD

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