1. What’s New in Diabetic Eye Disease? A.Paul Chous, MA, OD, FAAO, CDE Specializing in Diabetes Eye Care & Education Tacoma, WA

9. DRCR.net Protocol T Head to Head Comparison of the 3 anti-VEGF therapies for center-involved DME One Year analysis showed Aflibercept (Eylea) yielded 5-7 additional ETDRS letters compared to bevacizumab (Avastin) & ranibizumab (Lucentis) when baseline VA was 20/50 or worse –Fewer pts needed rescue laser –1 fewer injection Few adverse events in all 3 groups –No difference for serious events, hospitalization or death N Engl J Med 2015; 372:1193-1203

10. Protocol T – Two Year Analysis No significant difference between Eylea and Lucentis at 2 yrs irrespective of baseline VA (+2 ETDRS letters with aflibercept) Eylea was superior to Avastin (+ 5 letters) Eylea patients were 20% less likely to need rescue laser Lucentis patients were 2X more likely to have an APTC event Ophthalmology Feb 27, 2016

12. Anti-VEGF is Effective Against DR, including PDR DRCR.net Protocol S showed anti-VEGF (Lucentis®) is non-inferior to PRP – Less DME & better visual field with Lucentis Decision should be individualized – PRP still the ‘Gold Standard,’ esp if patient is less likely to return for f/u S S JAMA 2015 Nov 4; 314(20):2137-46

14. Novel Potential Strategies Against DR and DME Being Investigated Blockade of epigenetic damage to mitochondrial DNA underlying DR/DME Stem cell therapy to prevent vascular hyper-permeability Inhibition of angiogenic factors upstream from VEGF (HIF, iNOS)

17. Peripheral Lesions Identified on Ultrawide Field Imaging Predict Increased Risk of Diabetic Retinopathy Progression over 4 Years. Ophthalmology. 2015 Feb 19. Eyes with Predominantly Peripheral DR Lesions (PPL)  3.2 X more likely to have a 2-step ETDRS severity progression  4.7 X more likely to develop PDR  After ALL Adjustments (4 yrs -200 eyes)

18. Fibrates & Retinopathy Simvistatin + Fenofibrate therapy lowers the risk of DR progression by 35% (and need for laser by 31%) compared to simvistatin alone in pts with T2DM and high cardiovascular risk (n = 2856) Consistent with FIELD Study showing reduced progression of DR and need for laser Tx Lancet 2007 370(9600):687-97 ACCORD Eye Study, N Engl J Med. 2010 Jul 15;363(3):233-44 Add-on Fenofibrate lowers risk of DR progression in T2DM

19. Fenofibrate Approved first-line therapy for NPDR in Australian adults with T2DM NNT = 14 for prevention of CSME/PDR Decreases total macular volume in DME Ophthalmic Epidemiol. 2014 Oct;21(5):307-17 Ophthalmology. 2014 Aug 26. Curr Med Chem. 2013;20(26):3258-66 Diabetologia 2014; DOI: 10.1007/s00125-014-3344-3.

20. Diabetes & DR Affect Visual Function  Snellen visual acuity is a 150+ yr old test that does not always reflect real world visual function  DM/DR also impair: color perception, contrast sensitivity, visual field sensitivity Diabet Med. 2011 Jul;28(7):865-71 Acta Opthalmol 2005; 82(5):574-80 Graefes Arch Clin Exp Ophthalmol. 2001 Sep;239(9):643-8 BJO 1996;80: 209-13 IOVS 1997; 38(9): 1819-24 Diabetes Care 1992; 15(5):620-25 Graefes Arch Clin Exp Ophthalmol.1996 May;234(5):300- 5

22. 6 month placebo-controlled RCCT of adults with T1DM or T2DM > 5 years 6 month placebo-controlled RCCT of adults with T1DM or T2DM > 5 years No DR (2:1) and mild-moderate NPDR (1:1) No DR (2:1) and mild-moderate NPDR (1:1) Daily use of a multi-component nutritional supplement Daily use of a multi-component nutritional supplement Pre- and post- analysis of CSF, MPOD, color vis., macular perimetry, OCT, A1c, lipids, 25(OH) vit. D, TNF- , hsCRP Pre- and post- analysis of CSF, MPOD, color vis., macular perimetry, OCT, A1c, lipids, 25(OH) vit. D, TNF- , hsCRP Di abetes V isual Fu nction S upplement S tudy (DiVFuSS) Brit J Ophthalmol. Feb;100(2):227-34

24. Test Formula Zeaxanthin & Lutein Benfotiamine Alpha Lipoic Acid Vitamin D Vitamins C & E Mixed Tocopherols/Tocotrienols Resveratrol Green Tea Curcuminoids N-Acetyl Cysteine Grape Seed Extract CoQ10 Zinc Oxide EPA/DHA Pycnogenol

25. Mean Change/SD in visual function measures, serum lipids, hsCRP, TNF- , glycohemoglobin, foveal thickness and symptoms of diabetic peripheral neuropathy with 95% p-Values Δ from baseline Suppl v. Plac p-Value Color Error Score -20.55+24.37 +7.5+22.01 <0.0002 5-2 MD (db) +2.78+9.83 -0.75+0.98 <0.0001 MPOD (du) +0.09+0.05 -0.01+0.03 < 0.0001 LDL-C (mg/dl) -7.61+16.08 +0.82+10.15 0.01 HDL-C (mg/dl) +3.82+6.24 -1.61+5.31 0.0004 TGs (mg/dl) -10.46+28.48 +2.39 +11.56 0.01 hsCRP (mg/L) -2.14+3 -0.28+1.83 0.01 TNF-a (pg/ml) +0.78+5.04 +0.56+2.79 0.88 HbA1c (%) -0.1+0.4 +0.1+0.4 0.06 Foveal Thickness (  m) 2.66+11.25 0.34+3.48 0.35 DPNSS -30.7% +10.7% 0.0024 Fisher’s Exact Test