Belfast, Ireland—Anti-vascular endothelial growth factor (anti-VEGF) monotherapy is inadequate in patients with age-related macular degeneration (AMD). However, by adding an anti-platelet-derived growth factor (anti-PDGF) drug to the anti-VEGF regimen, treatment is enhanced by preventing the development of fibrosis thus improving visual outcomes, according to Usha Chakravarthy, MBBS, PhD.
There are three important aspects of the therapeutic responses observed with anti-VEGF monotherapy for treating neovascular AMD, reported Dr. Chakravarthy, professor of ophthalmology and visual sciences, Royal Victoria Hospital and Queens University of Belfast, Northern Ireland.
“The long-term outcomes with monotherapy are disappointing,” said Dr. Chakravarthy. “The visual acuity changes are not explained by amelioration of exudative manifestations, (and) finally, fibrosis and atrophy are key mediators of the poor outcomes.”
Published evidence has shown a steady decline in vision over time even with persistent anti-VEGF monotherapy.
In the Inhibition of VEGF in the Age-Related Choroidal Neovascularization clinical trial, patient were divided into groups as responders, intermediate responders, and non-responders. When retinal thickness was measured, the visual acuity responses were found to be similar, which indicated that the visual acuity is a poor measure. Further, in the Comparison of Age-Related Macular Degeneration Treatment Trials, fibrosis developed in about 50% of patients.
“For many years, many have recognized that development of atrophy and fibrosis is associated with poor outcomes in patients with AMD,” Dr. Chakravarthy added.
Myofibroblasts are the culprit cells in this process that mediate fibrosis and contraction and they develop from pericytes, macrophases, and epithelial cells when in the presence of PDGF.
“PDGF antagonism prevents migration of these cells and prevents myofibroblasts from laying down fibrosis on their scaffolding,” she explained.