Validation of molecular and genomic biomarkers of retinal drug efficacy: use of ocular fluid sampling to evaluate VEGF.

The use of tissue- and cell-based methods in developing drugs for retinal diseases is inefficient. Consequently, many aspects of ocular drug therapy for retinal diseases are poorly understood. Biomarkers as prognostic indicators of change are needed to optimize the use of drugs. VEGF is considered an important target of drug therapy and VEGF levels in tissue are indicative of solid tumor growth. However, since many aspects of VEGF as a biomarker of ocular disease have not been validated, it has been difficult to ascertain without invasive procedures whether VEGF in the eye is a biomarker of response to drug therapy. Using published papers, registered clinical trials, and proteomic databases we assessed the earlier evidence for VEGF as an exploratory biomarker of proliferative and vasculopathic disease of the retina and asked whether the molecule has been rigorously validated in clinical trials. The emerging use of aqueous humor sampling has made it possible to explore biomarkers in oculo, and determine whether they are predictive of drug efficacy. We present data supporting the use of aqueous humor to validate drug-signaling pathways and biomarkers in the eye. In addition, we recommend convening a collaborative congress to help standardize the identification, validation, and use of biomarkers in retinal disease.