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Targeting VEGF could do more harm than good in the eye

VEGF-A inhibitors could affect the ciliary body
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Preclinical studies have raised a potential red flag on anti-VEGF therapies, suggesting that increasingly aggressive use in eye disease could trip off side effects and even cause long-term damage.

When the researchers blocked VEGF-A in mice, they found changes to the ciliary body, which produces aqueous humor (the fluid that fills the front portion of the eye), linked with falling intraocular pressure. The research was published in Investigative Ophthalmology & Visual Science (IOVS).

A number of companies are developing VEGF-A inhibitors for eye disease or have launched them onto the market, for example Allergan ($AGN) and Molecular Partners' MP0260 in preclinical development for wet age-related macular degeneration (AMD), or Bayer and Regeneron's Eylea (VEGF Trap-Eye; aflibercept) and OSI Pharmaceuticals/Pfizer's ($PFE) Macugen (pegaptanib), both approved for wet AMD. Other indications include diabetic macular edema and retinopathy of prematurity.

While these effects on the ciliary body or associated adverse events haven't been seen in clinical trials or current use, the researchers are concerned that moves toward continuous delivery of the inhibitors--or the use of more potent inhibitors--could increase the risk, and suggest that these findings should perhaps change the direction of research.

"I am hoping that revealing the possible negative side effects of VEGF inhibition in the eye will motivate research into new ways to block edema and blood vessel growth in the eye that does not require continuous inhibition of intraocular VEGF," said Patricia D'Amore of Schepens Eye Research Institute/Massachusetts Eye and Ear.

- read the press release
- see the abstract

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