April 2009




An ounce of prevention ...

by Matt Young EyeWorld Contributing Editor

Could antioxidants someday cause this kind of tool—and the rest of your phaco kit—to go out of fashion? Source: Takayuki Akahoshi, M.D.

Phacoemulsification—the technique Charles Kelman, M.D., introduced in 1967 to emulsify the lens nucleus with ultrasonic waves, whereby eliminating cataracts without a large incision—remains unchallenged today as the gold standard. But could there be another, better standard out there? Scientific research is beginning to point to cataract prevention as a serious alternative to a cataract cure. Specifically, researchers are looking at sodium pyruvate as a topical agent to prevent cataracts from ever forming by protecting against oxidative stress. “The compound penetrates the cornea in measurable amounts, the levels observed being adequate to offer protection against oxidative stress,” wrote Shambhu D. Varma, Ph.D., Department of Ophthalmology and Visual Sciences, University of Maryland School of Medicine, Baltimore, in the December 2008 issue of Ophthalmologica. Other antioxidants exist, as does systemic intake of sodium pyruvate, but Dr. Varma noted the potential toxicity of such agents and usage. Although much research remains, cataract prevention is no longer a matter that is being taken lightly.

An agent of change?

Dr. Varma and colleagues looked at 37 patients slated for cataract surgery, instilling one drop of 5% sodium pyruvate in the scheduled eye two hours pre-op. The agent was applied in an artificial tear, and drops were applied four times at 10-minute intervals. At the beginning of surgery, an aqueous sample was withdrawn. “The level of pyruvate in the aqueous samples of patients that did not receive pyruvate eye drops accounted for only 0.145 +/– 0.06 mM,” Dr. Varma reported. “In the group given pyruvate, the levels rose to 0.525 +/– 0.22, 0.525 +/– 0.14 and 0.35 +/– 0.16 mM for patients aged 14–18, 30–45 and 50–72 years, respectively. This increase obviously represents true pyruvate that actually penetrated from that contained in the eye drop preparation.” The concentration is also likely to be non-toxic. “Being highly water soluble, it can also be easily compounded with most other common additives in the eye drop such as the components of the commonly used buffers and the preservatives,” Dr. Varma reported. The same cannot be said of other agents. “Previous studies have demonstrated that many antioxidants are anti-cataractogenic, such as flavonoids, ascorbate, vitamin E and pyruvate,” Dr. Varma noted. “However, these compounds, except pyruvate, can also become pro-oxidant, and consequently, can become toxic, especially in the presence of trace metals.”

Further, pyruvate has the potential to be especially effective as an antioxidant preventing cataracts. “Pyruvate, apart from being endogenously derived with no known toxicity, has the advantage of its dual mode of action—as a reactive oxygen species scavenger as well as a metabolic agonist,” Dr. Varma reported. “Hence, in addition to scavenging reactive oxygen species, it is capable of overcoming the metabolic inhibition known to be associated with aging as well as diabetes. In addition, it also inhibits protein glycation, another important contributing factor in cataract formation.”

Already, other research has shown pyruvate as efficacious in reducing cataract risk. In the April 1999 issue of Free Radical Research, Dr. Varma demonstrated the efficacy of systemic pyruvate in attenuating cataract formation in rats. Rats were fed a diet of 30% galactose and developed nuclear lens opacity within 30 days. “This was delayed if the diet and water contained, in addition, 2% sodium pyruvate,” Dr. Varma noted. “The incidence of cataract in [the pyruvate] group was 0% at day 30 and only 25% at day 55.”

Meanwhile, in the October 2007 issue of the Journal of Ocular Pharmacology and Therapeutics, Dr. Varma found that ultraviolet cataracts in rat lens organ culture studies were prevented by pyruvate. “A protective effect of this keto acid against UV-induced tissue damage has been shown for the first time, suggesting its clinical usefulness against UV irradiation–induced pathologies,” Dr. Varma reported. Dr. Varma suggests the time is right to pursue clinical trials with pyruvate. “It should be feasible to carry out clinical trials with this compound aimed at preventing and treating intraocular diseases such as cataracts and diabetic retinopathy induced by intraocular generation of reactive oxygen species and consequent oxidative stress,” Dr. Varma wrote in Ophthalmologica.

Despite the advances in cataract prevention, Mohan Rajan, M.D., medical director, Rajan Eye Care Hospital, Chennai, India, says antioxidants will only be able to delay the onset of cataract, not prevent it completely. “We did a study on this at the University of Madras [Chennai],” Dr. Rajan said. That research found that systemic antioxidants halted lens opacities from progressing but didn’t decrease the existing cataract, he said. “Oxidative stress is one of the factors in cataract development, but cataract is multifactorial,” Dr. Rajan said. Instead, Dr. Rajan is confident that either phacoemulsification or extracapsular cataract extraction will be able to reduce the backlog of cataract surgery patients.

Editors’ note: Dr. Varma has no financial interests related to this study. Dr. Rajan has no financial interests related to his comments.

Contact information

Rajan: +65 6254 6330, rajaneye@vsnl.com
Varma: 410-706-3395, svarm001@umaryland.edu

An ounce of prevention ... An ounce of prevention ...
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