EyeWorld Asia-Pacific March 2021 Issue

FEATURE 10 EWAP MAR C H 2021 by Maxine Lipner Contributing Writer Contact information Keenan: Jeremy.Keenan@ucsf.edu Mamalis: nick.mamalis@hsc.utah.edu Opere: CatherineOpere@creighton.edu This article originally appeared in the December 2020 issue of EyeWorld . It has been slightly modified and appears here with permission from the ASCRS Ophthalmic Services Corp. The search for a pharmacologic cataract solution 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 carotene, 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 crystalline 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 antioxidant, 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 reviewed decrease lipid peroxidation and increase intracellular antioxidants, Dr. Opere explained. “If you drill down, that’s the bottom line mechanism,” she said. When it comes to in-human trials, a pharmacotherapeutic approach to cataract prevention or reversal has not worked. Dr. Opere’s review 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 cataract 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, Globe with a dense cataract Source: Nick Mamalis, MD