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A New Class of Biomarkers in the Vitreous With Potential for Predicting the Treatment Timing and Monitoring Response

Geetanjali Davuluri, MD; Virginia Espina, MS; Emanuel F. Petricoin III, PhD; Mark Ross, PhD; Jianghong Deng, BS; Lance A. Liotta, MD, PhD; Bert M. Glaser, MD

Arch Ophthalmol. 2009;127(5):613-621.

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.

Author Affiliations: National Retina Institute, Towson, Maryland (Drs Davuluri and Glaser); and George Mason University, Manassas, Virginia (Mss Espina and Deng and Drs Petricoin, Ross, and Liotta).

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