1. Update on Prevention, Diagnosis & Treatment of Diabetic Macular Edema (DME) Part 2 A. Paul Chous, MA, OD, FAAO Specializing in Diabetes Eye Care & Education Tacoma, WA Adjunct Instructor, Nova Southeastern University College of Optometry Principal Investigator for the Diabetes Visual Function Supplement Study (DiVFuSS)

2. Vitreous Sensory Retina Retinal Pigment Epithelium Choroid Small, perifoveal cyst within sensory retina Asymptomatic with 20/20 vision OCT Allows histological examination OCT Allows histological examination of retinal anatomy in vivo of retinal anatomy in vivo

3. Diabetic Macular Edema (DME) Normal MaculaDME with Cysts in Fovea 20/200 vision

4. Treatment of DME Improve metabolic control Improve metabolic control Grid and focal laser photocoagulation Grid and focal laser photocoagulation Anti-VEGF injections Anti-VEGF injections Corticosteroids Corticosteroids Combination Therapy Combination Therapy

5. Macular Laser Therapy The “Gold Standard” for treatment of DME from 1985 to 2012 The “Gold Standard” for treatment of DME from 1985 to 2012 Stabilizes, but does not generally improve vision Stabilizes, but does not generally improve vision Reduces the risk of doubling of the visual angle (going from 20/100 to 20/200 vision) by 50% if/when the patient has CSME Reduces the risk of doubling of the visual angle (going from 20/100 to 20/200 vision) by 50% if/when the patient has CSME ETDRS Research Group. Ophthalmology, 1991

6. Anti-VEGF Drugs for DME Multiple studies have shown that vascular endothelial growth factor (VEGF) inhibitor agents are superior to laser Multiple studies have shown that vascular endothelial growth factor (VEGF) inhibitor agents are superior to laser IMPROVE VISION & retinal thickeningIMPROVE VISION & retinal thickening Three drugs now used by retinal specialists: Avastin™ (bevacizumab off- label); Lucentis™ (ranibizumab); Eylea™ (aflibercept) Three drugs now used by retinal specialists: Avastin™ (bevacizumab off- label); Lucentis™ (ranibizumab); Eylea™ (aflibercept) Macugen™ (pegaptinib) is rarely used due to lower efficacyMacugen™ (pegaptinib) is rarely used due to lower efficacy

8. Anti-VEGF Treatment Protocols Retina specialists have different anti-VEGF agent preferences (Avastin is 1/20 th the cost!) Retina specialists have different anti-VEGF agent preferences (Avastin is 1/20 th the cost!) Protocols usually begin with monthly dosing to dry out macula and assess patient response Protocols usually begin with monthly dosing to dry out macula and assess patient response If patient responds to therapy and is stable after initial series of injections, there may be an attempt to extend interval between injections (treat and extend) If patient responds to therapy and is stable after initial series of injections, there may be an attempt to extend interval between injections (treat and extend) Patient responses are highly individual Patient responses are highly individual

9. Ranibizumab: Sustained Improvement in Visionwith Ongoing Anti-VEGF Therapy Mean change in BCVA from baseline (pooled) Severe VA loss (15 letters) significantly reducedSevere VA loss (15 letters) significantly reduced Rapid improvements in vision & anatomy maintained for 3 yearsRapid improvements in vision & anatomy maintained for 3 years RISE and RIDE Research Group. Ophthalmology. 2013;120:2013-2022.