Aggressive anti-VEGF therapy could impair proper ciliary body function, according to an animal study published in Investigative Ophthalmology & Visual Science.

In this study, investigators at Schepens Eye Research Institute/ Massachusetts Eye and Ear Infirmary evaluated the effect of sustained VEGF-A inhibition in a mouse model. They found that blocking VEGF-A expression led to nonpigmented epithelium thinning, pigmented epithelium vacuolization, capillary fenestration loss, thrombosis and a mean IOP decrease of nearly 3.5mm Hg––evidence of impaired ciliary body function.

“Very little is known about the factors that regulate the integrity and function of this tissue [the ciliary body] in the adult,” says lead author Patricia A. D’Amore, PhD, MBA, director of research and senior scientist at Schepens. “Our finding indicates that VEGF-A is at least one of the molecules that play a role in keeping the ciliary body healthy and functioning properly.”

Dr. D’Amore noted that current anti-VEGF administration techniques do not seem to interfere with ciliary body function. This includes the intravitreal administration of Lucentis (ranibizumab, Genentech/Roche), Eylea (aflibercept, Regeneron) and Avastin (bevacizumab, Genentech/Roche) that are used to treat neovascular AMD, diabetic retinopathy and macular edema.

“However, there is a move toward developing methods to continuously deliver anti-VEGF to the eye and to have drugs that are more potent inhibitors of VEGF,” she says. “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.”

Ford KM, Saint-Geniez M, Walshe TE, D’Amore PA. Expression and role of VEGF-a in the ciliary body. Invest Ophthalmol Vis Sci. 2012 Nov 7;53(12):7520-7.