Activated VEGF receptor shed into the vitreous in eyes with wet AMD: A new class of biomarkers in the vitreous with potential for predicting the treatment timing and monitoring response

Objective: To examine whether phosphorylated vascular endothelial growth factor (VEGF) receptors shed into the vitreous reflect the ongoing retinal and choroidal signal pathway activity in wet age-related macular degeneration (AMD). Methods: Vitreous samples obtained immediately prior to anti-VEGF injection from 11 patients with choroidal neovascularization were analyzed using reverse-phase microarrays. Two patients had samples collected at the time of injection and 1 month later. Samples from 5 patients were collected prior to vitrectomy for macular hole, epiretinal membrane, or retinal detachment. Results: Phosphorylated forms of VEGF receptor (VEGFR Y996 and Y1175), platelet-derived growth factor receptor β (PDGFRβ Y716 and Y751), and c-KIT (Y703) were present in the vitreous. A significant difference in PDGFRβ Y751 (P<.002), VEGFR Y996 (P<.04), and VEGFR Y1175 (P<.006), but not c-KIT Y703 (P<.05) or PDGFRβ Y716 (P<.96), was noted for the responders to treatment (n=5) compared with nonresponders (n=6) and controls (n=5). Conclusions: Vitreous levels of activated receptors constitute a new class of biomarkers. Activated forms of VEGF and PDGF receptors, previously not known to exist in the vitreous, correlate with response to anti-VEGF therapy. These findings could provide the basis for the development of individualized treatment and discovery of new therapeutic targets.