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Bert M Glaser, Travis M Poulsen, Joshua C Hines, Stephanie M Ecker; The Difference in Response After 3 months of Anti-VEGF in wet AMD Correlates with Differences in Vitreous Protein Biomarkers. Invest. Ophthalmol. Vis. Sci. 2014;55(13):568.
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© ARVO (1962-2015); The Authors (2016-present)
To understand the biochemical pathways that may explain differences in wet AMD patient response to anti-VEGF treatment. To achieve this goal, the vitreous proteome of eyes undergoing 3 months of therapy that gained 5 or more ETDRS letters was compared eyes that lost ETDRS letters.
We studied 167 eyes with wet AMD that either gained >5 letters or lost vision during the first 3 months of treatment. Of the 167 eyes, 57 gained ≥5 letters. Best Corrected ETDRS visual acuity was measured at each visit. From the 167 study eyes, a total of 414 in-office vitreous samples were collected just prior to anti-VEGF therapy over the 3 months. Each vitreous sample was assessed via Reverse Phase Protein Microarray technology for levels of 45 proteins known to be important in the progression of wet AMD. The pathways studied included Angiogenesis, Inflammation, Apoptosis/Survival, Oxidative Stress, and Hypoxia, protein levels represent mean values over 3 months.
Seven proteins showed a significant (P< 0.05) difference in expression between eyes that gained ≥5 letters versus those that lost letters. The most significant difference was in the levels of TGF-β (P= 0.0002). TGF-β had a higher expression level in eyes that lost vision. Interestingly, the other six proteins that showed significant expression differences were all higher in eyes that gained ≥5 letters. These proteins were MMP-14 (P= 0.0004), AMPK α1 S485 (P= 0.0005), BCL2 Thr56 (P= 0.0007), TIMP2 (P= 0.0076), PDGFRβ Y716 (P= 0.0086) and PDGFRβ Y751 (P= 0.0409).
This study demonstrates significant differences in the vitreous proteome of eyes that gain vision during the first 3 months of anti-VEGF therapy versus those that lose vision during the same period. These results suggest that eyes that have better response to anti-VEGF have a more angiogenic “footprint” compared to a pathway with high levels of TGF-β in eyes with vision loss. These results show the potential for TGF-β or a related cytokine to be a therapeutic target for eyes that are losing vision during anti-VEGF treatment.
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