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Bert M. Glaser, Stephanie M. Ecker, Joshua C. Hines; Treat and Extend Therapy Cause Significant Changes to the Vitreous Proteome in Patients with Wet AMD. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2926.
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Currently there is no data that can guide the choice among several anti-VEGF treatment protocols for wet AMD. Several studies suggest that vitreous biomarkers may reflect response to treatments. Herein, patients under one common treatment protocol termed "Treat and Extend" therapy (TER) are studied to discover the vitreous biomarker differences in those who experience vision stability compared to others who have progression of vision loss.
A total of 42 in-office vitreous aspirates were taken before and after 21 TER extended treatment follow-up intervals, which was determined by the patient’s OCT response. The patients were split into two groups, depending on VA change during the extended follow-up interval. Patients were considered minimally affected if their VA decreased by less than 10 ETDRS letters; a decrease of more than 10 letters was considered progressive VA loss. A total of 37 biomarkers were evaluated using reverse phase protein microarray technology.
Patients who had minimally affected VA during the extended follow-up interval had a significant increase in expression levels of 8 proteins that point to an increase in AKT/PI3K regulation of nitric oxide. The proteins include AKT T308 (P= 0.0322), eNOS S1177 (P= 0.0288), PDGFRβ Y716 (P= 0.0210) and VEGFR2 Y996 (P= 0.0425). A protein-protein interaction pathway analysis was confirmatory. In the group with progressive VA loss, there was no change in expression of any of the biomarkers. As an additional contrast protein-protein interaction pathway analysis in the group with progressive VA loss showed oxidative stress induced activation of MAPK signaling pathway.
Eight protein biomarkers significantly increase during the extend period in eyes that had minimal vision loss, suggesting that anti-VEGF treatment was depressing the levels before the treatment suspension. However, in the patients who had VA progression, the same 8 proteins have no change in expression level, suggesting that the two different VA responses are being affected by two different signaling pathways. The identification of these biomarkers has the potential to allow individualization of TER protocols for each patient before additional vision loss occurs.
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