December 2020

CATARACT

The search for a pharmacologic cataract solution


by Maxine Lipner Contributing Writer


Globe with a dense cataract
Source: Nick Mamalis, MD

 

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, 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 treat animals at a relatively young age, whereas in humans, cataract development is lifelong, though often does not become visually significant until age 60 or 70. Dr. Mamalis said any in-human study would need to show that flexibility and clarity are maintained long term.
Dr. Opere is hopeful that a pharmacological approach could someday be successful. “I think we have to go back to the drawing board and figure out why this is not translating and what we should do differently,” she said. “There’s a lot of potential. I think we shouldn’t give up.”

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

References

1. Heruye SH, et al. Current trends in the pharmacotherapy of cataracts. Pharmaceuticals (Basel). 2020;13:15.
2. Age-Related Eye Disease Study 2 Research Group. Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA. 2013;309:2005–2015.
3. Srinivasan M, et al. Antioxidant vitamins for cataracts: 15-year follow-up of a randomized trial. Ophthalmology. 2020;127:986–987.

Relevant disclosures

Keenan
: None
Mamalis: None
Opere: None

Contact

Keenan
: Jeremy.Keenan@ucsf.edu
Mamalis: nick.mamalis@hsc.utah.edu
Opere: CatherineOpere@creighton.edu
 

From JCRS

Modeling Medicare cataract surgery volume in 2020 and estimating pandemic-related backlog
The impact of the COVID-19 pandemic on ophthalmic practices has been significant, but just how the shutdown in the spring will affect overall 2020 cataract surgical volumes has yet to be realized.
An epidemiologic study published in the Journal of Cataract & Refractive Surgery (JCRS) sought to model cataract surgery volume in 2020 with the impact of the pandemic in mind. It also sought to estimate the backlog of surgeries that was created when most stopped performing elective surgery throughout the country.
Using data from 2008–2018, the study authors first estimated an overall Medicare cataract surgery volume for 2020—3.7 million cases—assuming the pandemic shutdown didn’t happen. They then assumed that cataract surgery volume was normal and 100% in January and February 2020. They used practice patterns from Shruti Aggarwal, MD, first author of the study, to establish the volume between March and April and assumed that elective surgeries restarted in May. The return of elective surgeries was below typical volume, and the researchers modeled this using a stochastic Monte Carlo simulation of a Gompertz function, which they wrote “is a sigmoid curve with a rapid acceleration phase followed by a plateau phase.” They forecasted post-shutdown volumes under an optimistic (90% growth velocity) and pessimistic (50% growth velocity) scenario. The authors were primarily interested in determining how many surgeries would need to be performed to reach 90% pre-pandemic volume estimates. The backlog estimate was created by adding the number of cases that were deferred in the shutdown to those that were created during the post-shutdown ramp-up period.
The authors wrote that higher ramp-up velocities in general might be possible in ophthalmology but noted the impact and variability different state regulations would have. Even with a significant ramp-up speed, the authors estimated a significant residual backlog.
“In both scenarios, the size of the surgical cataract case backlog at 2-year post-suspension (May 2022) would be tremendous: 1,080,000 cases in the optimistic scenario, and 1,550,000 cases in the pessimistic scenario,” the study authors wrote.
“Our analysis reveals that even under optimistic conditions, the backlog would be greater than 1 million surgical cataract cases at 2 years post-suspension,” they wrote later in the conclusion. “Even in the backlog minimization sensitivity analysis with all ideal conditions, it would take 9 months to catch up on the backlog.”
The authors detailed how getting through this backlog would require increased surgery levels beyond pre-pandemic rates, which they said puts an emphasis on the need for efficiency in relationships with medical colleagues, surgical planning, postop visits, and considering immediately sequential bilateral cataract surgery.

Reference

Aggarwal S, et al. COVID-19 and cataract surgery backlog in Medicare beneficiaries. J Cataract Refract Surg. 2020;46:1530–1533.
The search for a pharmacologic cataract solution The search for a pharmacologic cataract solution
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