Oxygen may be the culprit in nuclear cataract

By Laszlo Dosa

WASHINGTON, DC - A new understanding of the role of oxygen in post-surgical cataract formation should lead to a better understanding of how cataracts form and how they might be prevented, David C. Beebe PhD told a Research to Prevent Blindness seminar.

He explained that the natural lens exists normally in a very low oxygen environment and the vitreous appears to have a sheltering role, keeping the oxygen away from the lens.
When the vitreous body liquefies prematurely, as in high myopia or vitrectomy, nuclear cataracts can develop and progress.

Dr Beebe cited research indicating that patients repeatedly exposed to high levels of oxygen over a long period of time would develop nuclear cataracts. Work at his own laboratory and others has shown that oxygen is toxic to the lens.

"We believe that as oxygen diffuses from the blood vessels in the retina, it uses up oxygen at a very high level. So if the vitreous gel is present in the eye, the oxygen levels are high only very close to the source - the retinal vessels.

"We also know that people who have vitrectomies are at a very high risk of developing nuclear cataracts," Dr Beebe said.
He believes this oxygen hypothesis is a reasonable explanation for why people get cataracts after vitrectomy.

He predicts that if retinal surgery could be performed without vitrectomy, post-vitrectomy nuclear cataracts would not occur.
There is clinical support for this idea. For example, in one study, pre-retinal membranes removed without vitrectomy did not lead to post-vitrectomy cataract or myopic shift after two years of follow-up, he noted.

Dr Beebe predicts that, as may be the case after vitrectomy, when the vitreous body breaks down, circulation will start in the eye and carry oxygen from the retina to the lens. Consequently, patients who lose much of their vitreous to breakdown will be at risk from developing cataract.
In a study reported earlier this year at the annual meeting of the Association for Research in Vision and Ophthalmology (ARVO), Dr Beebe and colleagues evaluated whether liquefaction of the vitreous gel was related to maturity-onset nuclear cataract.

An analysis of 83 donor lenses confirmed that increased vitreous liquefaction was associated with increased age-related nuclear cataract.
The study showed a statistically significant association between the amount of vitreous breakdown and the extent of cataract.

"This is the first time that we've been able to connect changes in the environment around the lens to cataracts. It gives us an understanding of the potential mechanisms that lead from changes in the eye to cataract formation.
"We have known of no other mechanism to understand each step in the process that would lead from a particular change in the body to a cataract.
"So, the idea that breakdown of the vitreous body or its destruction during vitrectomy leads to cataract is the first time we've really had a causal chain of events, Dr Beebe told EuroTimes.

Stuart J. McKinnon MD, PhD said he found Dr Beebe's hypothesis interesting and sensible. He added that he would like to see more data on oxygen concentration in various parts of the eye.

"I would like to see the researchers show that there is a difference in oxygen concentration after vitrectomy, that it is actually higher around the lens and then perhaps to artificially create a condition where more oxygen is around the lens investigate whether or not that would produce a cataract," Dr McKinnon.
He noted that the research suggests the possibility of using an oxygen-scavenging molecule to prevent cataracts in that situation.

Moreover, there are similar implications in other areas of ophthalmic surgery, such as glaucoma filtration, where changing the normal physiology can alter the way the lens behaves and can induce cataracts.
Dr Beebe agreed there is a need to better understand the mechanism of the disease before therapies can be designed for its prevention.

The current study at least suggests that preservation or replacement of the vitreous gel might protect patients from nuclear cataract.
"I think the advances we are making, if verified by other studies, will lead to a better understanding of the mechanism of the disease. We feel that others will certainly take this up and look at ways to prevent the process," he said.



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