Topical Cataract Tx: Preclinical Results Offer Promise

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An international team of researchers—using mice that had cataracts associated with crystallin protein mutations—found that a top­ical oxysterol compound may improve lens transparency and refractive index contours in some lenses, further paving the way toward a topical treatment for cataracts.¹

In some mice—but not all—the researchers noted a “dramatic improve­ment in the eyes that had the com­pound instilled. This suggests that the compound may be effective for some cataracts but not all,” said coauthor Barbara Pierscionek, PhD, at Anglia Ruskin University in Chelmsford, United Kingdom. She added, “Given that cataracts have a multitude of causes, it is not surprising that different treatments may be needed for different types [of cataracts]. The exciting find­ing was that, at least for some cataracts, this treatment appears to work.”

The oxysterol compound, VP1-001 (also known as 25-hydroxy-cholesterol), had been previously suggested as a potential anticataract agent. However, Dr. Pierscionek said, until now, no one had tested whether the compound could restore the optics of the eye.

NEXT STEPS. Studies are needed to clarify method of action and assess effects in humans.

Study specifics. Wild-type and knock-in mutant mice were used in the experiments. Twenty-six mice received topical treatment with VP1-001 (ViewPoint Therapeutics) in one eye and vehicle in the other; nine mice were untreated controls. The research­ers used slit-lamp biomicroscopy to analyze the lens and provide apparent cataract grades. X-ray phase tomog­raphy measurements were used to calculate refractive index in the lenses of 64 postmortem mouse eyes.

Results. All told, 61% of the mice of all genotypes showed an improvement in refractive index profiles following treatment. This was supported by a re­duction in apparent lens opacity grade by 1.0 in 46% of the mice.

Next steps. Additional studies will seek to clarify the oxysterol’s mecha­nism of action, and clinical trials are needed to determine if the results can be replicated in humans, Dr. Pierscionek said. “Ultimately, if this treat­ment works, we could revolutionize the way in which cataracts are treated and may be able to reduce the need for surgery.” The findings also may aid in treating conditions that have second­ary manifestations in the lens, such as diabetes.

—Patricia Weiser, PharmD

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1 Wang K et al. Invest Ophthalmol Vis Sci. 2022;63(5):15.

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Relevant financial disclosures—Dr. Pierscionek: National Natural Science Foundation of China: S; NIH: S; SPring-8 Synchrotron: S.

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