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Mixed results seen with anti-VEGF therapy for children's retinal diseases

Article

Anti-vascular endothelial growth factor treatment of the pediatric retinal diseases-familial exudative vitreoretinopathy and retinopathy of prematurity-using pegaptanib sodium showed mixed results, with a marked decrease in exudation in the former but no effect in preventing retinal detachment in the latter.

Key Points

Las Vegas-Anti-vascular endothelial growth factor (VEGF) treatment of the pediatric retinal diseases-familial exudative vitreoretinopathy (FEVR) and retinopathy of prematurity (ROP)-using pegaptanib sodium (Macugen, Eyetech Pharmaceuticals) showed mixed results, with a marked decrease in exudation in the former but no effect in preventing retinal detachment in the latter, said Michael T. Trese, MD.

FEVR

In the treated eyes, all had reduced exudation 4 weeks after the injection that continued for several months. "There was a recognizable pattern of resolution of the exudation and no toxicity from the drug was observed," he said.

Dr. Trese demonstrated the pattern of resolution of the exudation in the treated eyes. "Clearing started at the periphery and moved toward the center," he explained.

Interestingly, the IOP in these eyes seemed to increase more than in eyes with age-related macular degeneration that were treated with pegaptanib. One of the eyes required a paracentesis.

Only two of the eyes in the study received a second injection of pegaptanib 6 months after the first injection. Three of the first four eyes that received an injection had vitreous bleeds that varied in size from small to large. Two of these eyes underwent vitrectomy. All three eyes had an improvement in visual acuity and preretinal vessels, and a large reduction in exudation. "We did not see any obvious involution of the preretinal vessels using pegaptanib," Dr. Trese stated.

ROP

"This disease is a self-limited retinal vascular disease that can lead to tractional and exudative retinal detachment. ROP is driven largely by VEGF and off-regulated by endogenous VEGF-beta, which is produced at the infant's due date," Dr. Trese explained.

VEGF has several functions in retinal vascular disease, but three of the primary ones are promotion of permeability, support of neovascularization, and suppression of genetically programmed endothelial cell apoptosis. "Those cells can contribute to the tractional component of retinal detachment," he said.

VEGF has a strong role in retinal detachment. "The exudative component is due to permeability, and the tractional component seems to be due to cell boluses that are being acted on by endogenous VEGF-beta at the due date," he explained.

Most studies of ROP have been conducted in animal eyes. Dr. Trese reported on a series of 27 human eyes that he and his colleagues studied; 22 eyes had ROP, and five were control eyes. The five eyes underwent surgery for cataract. All ROP samples from the eyes were obtained at the time of vitreous surgery between 37 and 45 weeks postmenstrual age; all isoforms of VEGF were measured in the samples.

"We found that there were extremely high levels of VEGF that exceeded 3,500 pg/ml," he said.

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