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Charlotte E Joslin, Jacob K Kresovich, Norman P Blair, Mahnaz Shahidi; Identifying physiological biomarkers intermediating DME treatment. Invest. Ophthalmol. Vis. Sci. 2017;58(8):919.
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© ARVO (1962-2015); The Authors (2016-present)
Intravitreal anti-VEGF treatment (IVT) improves best corrected visual acuity (BCVA) and decreases central subfield thickness (CST) in diabetic macular edema. Pre-treatment mean arterial blood pressure and retinal arterial oxygen saturation (SO2A) significantly predicts IVT treatment outcomes (BCVA, CST), but mechanisms of IVT have not been elucidated. We examined pathophysiologic measurements as potential mechanisms through which IVT affects BCVA and CST in a prospective observational study.
We assessed nine biomarkers, BCVA and CST at baseline and follow-up in 50 eyes of 29 subjects with non-proliferative diabetic retinopathy (NPDR) or proliferative (PDR). We performed oximetry using a commercial scanning laser ophthalmoscope (Optos200TX) and measured retinal arterial and venous oxygen saturation of hemoglobin (SO2A, SO2V), central retinal artery and vein equivalents (CRAE, CRVE), retinal arterial and venous caliber (CalA, CalV), and oxygen extraction fraction (OEF). CST was measured with optical coherence tomography (Heidelberg) and BCVA with ETDRS protocols. We used multivariable mixed effect linear regression models with random intercepts, accounting for two eyes per subject, to assess the effects of treatment on each biomarker at longitudinal follow-up, adjusting for age, race, sex, prior IVT injections and DR diagnosis. We additionally assessed the adjusted cross-sectional effects of each biomarker on BCVA and CST at follow-up, further adjusting for lifetime IVT injections (Figure).
Median follow-up was 116 days. Twenty-six eyes received IVT after enrollment. In longitudinal analyses, compared to non-treated eyes, IVT was associated with a decreases in CRAE (β=-9.1, p= 0.09), SO2A (β=-10.4, p= 0.09), and OEF (β=-0.1, p= 0.01), and increases in SO2V (β=6.0, p=0.08). In cross-sectional analyses, for every unit change per biomarker, there was an associated change in CST (β=-2.0, p=0.01 for SO2V; β=130.4, p=0.02 for OEF; β=0.7, p=0.06 for CRVE; β=1.7, p=0.06 for CalV) and in BCVA (β=0.1, p=0.08 for CRAE; β=0.1, p=0.12 for SO2V).
Results suggest three biomarkers (SO2V, OEF and CRAE) are intermediaries between IVT and treatment outcomes. This study was limited by the small sample size; we therefore considered marginal results as meaningful. These results elucidate pathways through which IVT improves visual outcomes via pathophysiologic mechanisms.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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