1/25/2018. Case Management Strategies in Diabetic Retinopathy. Case Study #1: Severe DME. DDOS: 3/31/2016 Va 20/400. Disclosures

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Andra Hunter
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Case Management Strategies in Diabetic Retinopathy Disclosures No

intraocular Bevacizumab (Avastin) for Diabetic Retinopathy Sundeep

3/31/2016 Va 20/400 55 year old DM Type II male presents 3/2016.

1 Case Management Strategies in Diabetic Retinopathy Disclosures No financial conflict of interest Will discuss off label use of intraocular Bevacizumab (Avastin) for Diabetic Retinopathy Sundeep Dev, MD VRS Update Course 2018 Case Study #1: Severe DME DDOS: 3/31/2016 Va 20/ year old DM Type II male presents 3/2016. Diagnosed with Diabetes in HA1c: 6.8 now. Was 12 when diagnosed. BP WNL. Medical HX: Anemia Decreased VA OU x 1 month VA OD: 20/400 OS: 20/100 DOS: 3/31/2106 Va 20/100 DOS: 3/31/2016 Early FA OD Early FA OS 1

DOS: 3/31/2016 DOS: 3/31/2016 Late FA OD Late FA OS Management options Diffuse Central DME /very severe NPDR/peripheral ischemia Systemic management BS, BP, Lipid control, Fluid retention/renal

Diffuse DME Best results with anti-vegf therapy - 1 st line therapy Seems to be particularly helpful in DME cases with significant peripheral non perfusion Neovascularization - Exquisitely sensitive

3 mg) RIDE/RISE ($1150) Aflibercept (Eylea) VIVID/VISTA ($2000) Dexamaethasone implant (Ozurdex) MEAD ($1400) Fluocinolone implant (Iluvien) FAME($9300) Off label therapy Bevacizumab (Avastin) DRCR.

2 DOS: 3/31/2016 DOS: 3/31/2016 Late FA OD Late FA OS Management options Diffuse Central DME /very severe NPDR/peripheral ischemia Systemic management BS, BP, Lipid control, Fluid retention/renal status, anemia Focal/Grid laser not very effective for diffuse edema. ETDRS <15% with CSME get improvement in VA Anti-VEGF best option Steroid rescue therapy What is the best initial option? Diffuse DME Best results with anti-vegf therapy - 1 st line therapy Seems to be particularly helpful in DME cases with significant peripheral non perfusion Neovascularization - Exquisitely sensitive to anti-vegf with nearly 100% response Macular Edema Current Pharmacologic options FDA Approved therapy Ranibizumab (Lucentis 0.3 mg) RIDE/RISE ($1150) Aflibercept (Eylea) VIVID/VISTA ($2000) Dexamaethasone implant (Ozurdex) MEAD ($1400) Fluocinolone implant (Iluvien) FAME($9300) Off label therapy Bevacizumab (Avastin) DRCR.net ($70) Intravitreal Triamcinolone (Triessence) - $150 Ranibizumab (Lucentis) for DME 1 st drug to be approved for DME RIDE/RISE trials: 759 patients Evaluated 0.3 mg vs. 0.5 mg (AMD dose) vs. sham/laser FDA approved 0.3 mg dose for DME 8/2012 (no difference from results with 0.5 mg dose) 2

3 Mean BCVA Maintained During OLE* RIDE RISE Pooled Ranibizumab for DME Mean BCVA (ETDRS Letters) 85 Sham/ OLE* Sham Control RBZ 0.5 mg Crossover PRN RBZ 0.5 mg 80 Sham/crossover RBZ 0.3 mg 75 RBZ 0.5 mg Month Patients, n Sham/crossover RBZ 0.3 mg RBZ 0.5 mg Patients in the RIDE/RISE trials that switched from sham to Lucentis after 2 years never achieved same vision benefit Benefit seems to be best within 12 months of diagnosis *Data become unstable after Month 54 due to the low number of patients at that point. Treatment during core study. Observed data. OLE = open-label extension; RBZ = ranibizumab. Boyer DS, et al. Ophthalmology. 2015;122: e1. Secondary Endpoint: Mean Change in OCT CFT Over Time RIDE RISE Pooled Ranibizumab for DME longer term Mean Change in CFT (µm) Day 7 Month RISE/RIDE extension beyond month 36 patients maintained vision and anatomic benefit with PRN dosing and fewer injections (mean 4.5 injections over next 14.1 months) 1-25% didn t require further injections Sham (n=257) RBZ 0.3 mg (n=250) RBZ 0.5 mg (n=252) Last observation carried forward imputation method was used. Vertical bars are ±1 SE of the mean. CFT is defined as center point thickness. Independent review of OCT performed at the University of Wisconsin Fundus Photograph Reading Center. Brown DM, et al. Ophthalmology. 2013;120: Ophthalmology 2015;122: Ranibizumab for DME DRCR Protocol I 5 year results of Lucentis for DME with prompt or deferred laser Most eyes treated with Lucentis and either prompt or deferred laser maintain vision gains obtained in first year through 5 years with little additional Rx over last 3 years 9 injections year injections year injections year 3 Almost zero by year 5 Ranibizumab for DME PRN dosing RESTORE - 12 month randomized trial and open label 24 month extension 3 monthly loading doses and then PRN treatment showed efficacy in maintaining visual and anatomic benefit 1 Ophthalmology 2015;122: Ophthalmology 2013;120:

outcomes Payne JF, et al. Ophthalmology 2017; 124:74-81.

4 Ranibizumab for DME - TREX TREX-DME study: Treat and extend dosing of Ranibizumab 0.3 mg resulted in similar visual and anatomic outcomes as monthly dosing at 1 year TREX cohort had mean of 10 injections in 1 st year Adding FA guided laser to this algorithm did not further improve outcomes Payne JF, et al. Ophthalmology 2017; 124: Eylea (Aflibercept) for DME Two Phase 3 trials of total 862 patients VIVID and VISTA-DME 2 yr then PRN open label extension (OLE) to 3 years 2 mg monthly vs. 2 mg monthly for 5 months then q 2 months vs laser Recommended dose by FDA 7/29/14: 2 mg dose monthly for 5 months then q 2 months Label update 5/2016: some patients will benefit from monthly dosing Heier JS, Ophthalmol 2016; 123: Eylea for DME ENDURANCE STUDY 12 month extension study following 36 month VISTA trial Vision gains maintained with a reduced frequency of injections (mean of 4.5 injections) in year 4 with a PRN approach 30% needed no injections No reduction in injection burden was observed after macular laser application What about Bevacizumab? Bevacizumab (Avastin) - off label, compounded at pharmacy commonly used due to huge cost savings. Which agent to choose for our patient? Wycoff CC, et al. AJO 2017; 173:

5 DRCR.net Protocol T Comparative trial of Avastin, Lucentis and Eylea for center involved DME (n=660) Year 1: q 4 week exam and retreatment if improvement or worsened by >5 letters or OCT CST by > 10%. PRN once acheived 20/20 and CST normal (250 um or less) Laser at 6 mo if persistent edema and vision/oct stable for 2 consecutive injections Year 2: visits could be extended to 16 wks. ReRx if vision or OCT worsened Mean Change in Visual Acuity Over 2 Years Full Cohort Week 52 Week 104 Bevacizumab Ranibizumab Aflibercept Week Treatment Group Comparison Aflibercept vs. Bevacizumab P = 0.02 Aflibercept vs. Ranibizumab P = 0.47 Ranibizumab vs. Bevacizumab P = 0.11 ~50% of Cohort Mean Change in Visual Acuity Baseline Visual Acuity 20/32 to 20/40 Week 52 Week 104 Mean Change in OCT CST Over 2 Years Baseline Visual Acuity 20/32 to 20/40 Week 52 Week 104 Bevacizumab Bevacizumab Ranibizumab Aflibercept Ranibizumab Week Treatment Group Comparison Aflibercept vs. Bevacizumab P = 0.51 Aflibercept vs. Ranibizumab P = 0.51 Ranibizumab vs. Bevacizumab P = 0.31 Aflibercept Ranibizumab/Aflibercept resulted in singificant OCT CST improvement vs. Bevacizumab ~50% of Cohort Mean Change in Visual Acuity Baseline Visual Acuity 20/50 or Worse Week 52 Week 104 Mean Change in OCT CST Over 2 Years Baseline Visual Acuity 20/50 or Worse Week 52 Week 104 Bevacizumab Bevacizumab Ranibizumab Ranibizumab Aflibercept Aflibercept Week Treatment Group Comparison Aflibercept vs. Bevacizumab P = 0.02 Aflibercept vs. Ranibizumab P = 0.18 Ranibizumab vs. Bevacizumab P = Year Treatment Group Comparison: Aflibercept vs. Bevacizumab P = 0.01 Aflibercept vs. Ranibizumab P = 0.18 Ranibizumab vs. Bevacizumab P =

Results: DME Treatment: # anti-vegf injections DME Treatment: Adjunctive Laser Aflibercept Bevacizumab Ranibizumab Global P-value Aflibercept Bevacizumab Ranibizumab Global P-value # of injections:

046 Over 2 Years 15 (11, 17) 16 (12, 20) 15 (11, 19) 0.08 Over 2 Years 41% 64% 52% <0.001 Note: 98% of protocol required re-injections were given over 2 years.

differences become less significant at year 2 Jampol LM, et al. JAMA Ophthalmol 2016; 134(12): 1429-1434 (The source of the data is from the DRCR.

6 Results: DME Treatment: # anti-vegf injections DME Treatment: Adjunctive Laser Aflibercept Bevacizumab Ranibizumab Global P-value Aflibercept Bevacizumab Ranibizumab Global P-value # of injections: Median (25 th, 75 th percentile) At least one focal/grid laser Year 1 9 (8, 11) 10 (8, 12) 10 (8, 11) Year 1 37% 56% 46% <0.001 Year 2 5 (2, 7) 6 (2, 9) 6 (2, 9) 0.32 Year 2 20% 31% 27% Over 2 Years 15 (11, 17) 16 (12, 20) 15 (11, 19) 0.08 Over 2 Years 41% 64% 52% <0.001 Note: 98% of protocol required re-injections were given over 2 years. Conclusions All 3 agents reduce OCT thickness but bevacizumab appears to be less effective than aflibercept and ranibizumab Aflibercept appears to give the most rapid improvement at 1 year and differences become less significant at year 2 Jampol LM, et al. JAMA Ophthalmol 2016; 134(12): (The source of the data is from the DRCR.net, but the analyses, content and conclusions presented have not been reviewed or approved by DRCR.net.) DRCR.net Protocol T: My take Anti-VEGF clearly best treatment for center involved and diffuse edema All agents are effective Lucentis/Eylea give better results especially in more severe cases with worse vision ( <20/50) Eylea results in more rapid improvement in severe cases in year 1, no significant difference by year 2 Lucentis is cheaper than Eylea ($1150 vs. $2000) If quiet, PRN ok - recurrence less risky as in AMD Case by case basis cost and insurance a factor Avastin may be good enough /20/100 D1st visit 3/31/2016, VA 20/400 DOS: 4/7/ week After Eylea x 1 OD. Treated OS VA OD: 20/60 VA OS: 20/100 6

7 DOS: 4/28/2016 After Eylea OU x 1 VA OD: 20/50 PH: 20/40+ VA OS: 20/60 DOS: 5/26/2016 After Eylea OU x 2. Patient started Simvastatin. VA OD: 20/60 VA OS: 20/50 DOS: 6/30/2016 After Eylea OU x 3 VA OD: 20/60 VA OS: 20/60 DOS: 8/4/2016 After Eylea OU x 4 VA OD: 20/30 VA OS: 20/30 DOS: 9/8/2016 After Eylea OU x 5 VA OD: 20/25 VA OS: 20/50 2 PH: 20/40 DOS: 11/16/17 After Eylea OU x 16 VA OD: 20/25 VA OS: 20/20 7

OCT - Predicting Visual Acuity Disruption of ellipsoid zone (IS/OS junction) correlates with poorer visual outcomes Increased

5 injections CASE Study #2 : Severe PDR with mild DME 29 year old Type I diabetic male with complaints of blurry decreased VA

8 OCT - Predicting Visual Acuity Disruption of ellipsoid zone (IS/OS junction) correlates with poorer visual outcomes Increased Disorganization of retinal inner layers length (DRIL) - poorer visual outcomes Balaratnasingam C et al; Ophthalmol 2016; 123: Lee; same; /125 rapidly improved to 20/40 in 3 injections Ellipsoid layer disruption and DRIL 20/400 to 20/150 with 5 injections CASE Study #2 : Severe PDR with mild DME 29 year old Type I diabetic male with complaints of blurry decreased VA OU and floaters OD. Blood sugars poorly controlled with HA1c unknown and LBS 350 at initial visit of 5/18/2017. Medical HX: Hypertension; Kidney Disease Patient is a daily smoker VA OD: 20/40 OS: 20/100 present DOS: 5/18/2017 Mild VH DOS: 5/18/2017 8

DOS: 5/18/17 (Initial visit) Early FA OD: 20/40 Early FA OS:

Management options Severe PDR, large NVE, significant

leakage, and mild vitreous hemorrhage with early traction

laser risk of worsening DME/diffuse leak Focal laser followed

compliance critical Anti-VEGF followed by PRP Laser Vitrectomy

loss by 50% (DRS) Complications of treatment Decreased night

9 DOS: 5/18/17 (Initial visit) Early FA OD: 20/40 Early FA OS: 20/100 Late FA OD: DOS: 5/18/2017 Late FA OS: DOS: 5/18/17 Management options Severe PDR, large NVE, significant peripheral and macular non-perfusion with mild DME but diffuse leakage, and mild vitreous hemorrhage with early traction Systemic management BP, BS, Renal status, smoking Immediate PRP laser risk of worsening DME/diffuse leak Focal laser followed by PRP laser diffuse leakage/ischemia Anti-VEGF monotherapy compliance critical Anti-VEGF followed by PRP Laser Vitrectomy / PRP Laser high risk in young diabetic Panretinal Photocoagulation: It works! Panretinal Photocoagulation Reduces incidence of severe vision loss by 50% (DRS) Complications of treatment Decreased night vision Decreased peripheral vision Decreased accommodation Worse macular edema/decreased acuity Progression of disease Pre-laser Post-laser 9

10 PDR today: DRCR.net Protocol S Ranibizumab vs. PRP for PDR: Ranibizumab had: Change in VA from baseline no worse than PRP (noninferiority trial) Superior mean VA over the course of 2 yrs Better mean VF outcomes Decreased need for vitrectomies Decreased development of central DME PRP rarely given for failure or futility of ranibizumab DRCR.net Protocol S Patient centered Oucomes Work productivity loss (WPAIQ) was 15.6% less (p=.005) with Ranibizumab at 1 year and 2.9% less (p=.54) at 2 years vs. PRP group 97% Ranibizumab patients were 20/40 or better in 1 eye at 2 years compared to 87% PRP group (p=.005) No other differences found using NEI- VFQ-25 Beaulieu WT, Bressler NM,et al. AJO 2016; 170: Potential Impact of DME presence when treating PDR Presence of DME may influence the benefit of Ranibizumab over PRP When DME is present and treatment with anti-vegf agent is planned, PRP may be unnecessary in most cases, if patient can be compliant with follow-up 6 monthly initial injections, mean number of injections was about 50% less in year 2 Long term impact: unknown - A hybrid approach is likely the safest DRCR.net Protocol S Conclusions PRP has been effective for 40 years and remains an effective therapy today Ranibizumab is an effective alternative to PRP for atleast 2 years Ranibizumab may be first choice when DME is present No substantial safety concerns for atleast 2 years need longer term data No reason to believe other anti-vegf drugs wouldn t also be effective Cost First year drug cost alone: Ranibizumab ~ $13,800 1 st year Aflibercept ~ $18000-$24000 Bevacizumab ~ $900 Frequent exams Benefit: Excellent drying of macula VA improvement 7-11 letters DRCR.net Protocol S: My take Individualize approach: what the patient wants, systemic status, compliance ability, other eye, presence of DME, degree of retinopathy, vision Anti-VEGF for DME/PDR Also prefer anti-vegf for aggressive PDR without edema to quiet down first Would still most often gradually integrate PRP and may require less intense PRP Most often use atleast one injection prior to PRP to try to prevent DME development even in cases where long term treatment not planned 10

11 DOS: 5/18/2017, Va 20/40 DOS: 5/18/2017, Va 20/100 DME /lipid Watch for TRD NVE/PRH/Mild traction Large NVE, Mild edema DOS: 5/25/ wk s/p Avastin x 1 OS, 20/70 DOS: 6/1/2017, 1 week After Avastin x 1 OD Pre Avastin Post Avastin 1 week VA OD: 20/40 VA OS: 20/70 NVE rapid regression Edema better Traction stable Edema improving DOS: 6/22/2017 After Avastin x 1 OU LBS: 112 VA OD: 20/30 VA OS: 20/60 DOS: 7/27/17 After Avastin x 2 OU LBS & HA1c: Unknown VA OD: 20/25 VA OS: 20/50 Stable Recurrent NVE at 5 weeks with Pre retinal heme Edema better NVE regressed / PRH stable 11

DOS: 8/24/2017 After Avastin x 3 OU LBS: 192 VA OD: 20/80 VA OS: 20/60 DOS: 11/16/2017 After Avastin x 6 OU: PRP planned OU VA OD: 20/40 VA OS: 20/60 Edema gone No edema Vitreous heme as NVE lifts

12 DOS: 8/24/2017 After Avastin x 3 OU LBS: 192 VA OD: 20/80 VA OS: 20/60 DOS: 11/16/2017 After Avastin x 6 OU: PRP planned OU VA OD: 20/40 VA OS: 20/60 Edema gone No edema Vitreous heme as NVE lifts off and PRH disperses NVE lifting off/less traction NVE regressed/prh resolving Diabetic Retinopathy 2/2015 Lucentis approved to treat DR in patients with DME > 2 step improvements in DR stage seen as early as 3 months 3/25/15 - Eylea approved to treat DR in patients with DME Both shown to reduce progression and improve grade of retinopathy ANDROID STUDY Evaluate change in peripheral perfusion using UWFA after treatment with Aflibercept (Eylea) in patients with PDR and CRVO Eylea q mo for 12 months vs. q mo for 6 months then q 2 mo for 6 mo Both groups followed to month 18 with PRN UWFA - 55% reduction in area of peripheral non-perfusion by 12 months in both groups At Month 18 with PRN, 50% maintained benefit without injections, 50% regressed Heier J, presented at AAO Retina 10/2016 Summary: When to use anti-vegf Anti-VEGF therapy for Diffuse DME/DR: largest chance of vision improvement Prevents worsening DR and actually improves grade of retinopathy and reverses ischemia while treating DME Low risk of vision loss from DR while on therapy Highly effective for NV compliance more critical Long term sustained benefit injection burden seems to decrease over time Very low risk of complications (ATE, endophthalmitis) When is anti-vegf not appropriate Poor compliance Sick patients Significant active traction Consequences of failing to return for anti-vegf treatment for PDR can be disastrous perform PRP soon 12

CASE #3: DME and Cataract surgery 59 year old Diabetic female LBS: Unknown HA1c: 9.

OS>OD that is cloudy and foggy x 1 year. Dense cataracts OS>OD.

Early FA OD. No view OS due to dense cataract.

Mod-severe NPDR (difficult to grade) with central DME OS, ERM OS, minimal DME OD, Dense cataracts,

13 CASE #3: DME and Cataract surgery 59 year old Diabetic female LBS: Unknown HA1c: 9.0 Medical HX: Diabetic only Posterior Synechiae of Iris suggest possible past iritis Decreased vision OS>OD that is cloudy and foggy x 1 year. Dense cataracts OS>OD. VA 20/60 and 20/400 Minimal cysts DOS: 7/29/2017, VA 20/60 DOS: 7/29/2017, VA 20/400 DOS: 7/29/2017 Early FA OD. No view OS due to dense cataract. Poor view: ERM/central edema/lipid Mild leakage Management options Post-Cataract surgery Diabetic CME Mod-severe NPDR (difficult to grade) with central DME OS, ERM OS, minimal DME OD, Dense cataracts, possible uveitis history. Cataract surgery main issue with vision and needed to manage retina, but CE alone is high risk to worsen DR Anti-VEGF monotherapy Anti-VEGF followed by Laser Steroid implants Vitrectomy, membrane stripping 13

Perioperative Anti-VEGF therapy in DR May prevent worsening DME when CE needed Leaking MA

central DME after CE shown in DRCR Protocol Q in these cases) Very helpful to quiet

1 OS (7/29/2017) s/p CE OS on 8/15/17. Avastin given OU.

14 Perioperative Anti-VEGF therapy in DR May prevent worsening DME when CE needed Leaking MA s without edema high risk with CE Anti-VEGF often can prevent worsening (increased risk of central DME after CE shown in DRCR Protocol Q in these cases) Very helpful to quiet neovascularization pre- Vitrectomy and pre- cataract surgery DOS: 9/2/2017 After Avastin x 1 OS (7/29/2017) s/p CE OS on 8/15/17. Avastin given OU. VA OD: 20/50 VA OS: 20/150 PH: 20/70+2 DOS: 9/30/2016 After Avastin OS x 2; OD x 1 s/p CE OD on 9/19/16. Avastin OU given. VA OD: 20/80 PH: 20/30 VA OS: 20/125 PH: 20/60 DOS: 10/28/2016 After Avastin x 2 OD DOS: 10/28/16 After Avastin x 3 OS DOS 10/28/16 After Avastin OS x 3; OD x 2 Early FA OD: Early FA OS: 14

DOS 10/28/16 After Avastin OS x 3; OD x 2 Management options Late FA OD: Late FA OS: s/p CE OU controlled focal edema OD, persistent central edema OS with ERM using Bevacizumab Options: Continue

are known to decrease inflammation, reduce breakdown of the blood-retinal barrier, and have antiangiogenic properties. 1.

Post cataract surgery CME/DME usually cystoid in pattern to suggest inflammatory cause Dexamethasone implant office injection 3 year study for DME (MEAD study) Mean 4 treatments in 3 years Study 1:

15 DOS 10/28/16 After Avastin OS x 3; OD x 2 Management options Late FA OD: Late FA OS: s/p CE OU controlled focal edema OD, persistent central edema OS with ERM using Bevacizumab Options: Continue Bevacizumab Switch to Ranibizumab or Aflibercept Steroid implants Vitrectomy, membrane stripping Focal laser OD, possible OS as adjunct When to use steroids Ozurdex for DME- approved 6/2014 Steroids are known to decrease inflammation, reduce breakdown of the blood-retinal barrier, and have antiangiogenic properties. 1. Diffuse DME with no anatomic response to anti-vegf suspect inflammatory role 2. Vitrectomized eye requiring very frequent anti-vegf therapy implants work best 3. Post cataract surgery CME/DME usually cystoid in pattern to suggest inflammatory cause Dexamethasone implant office injection 3 year study for DME (MEAD study) Mean 4 treatments in 3 years Study 1: 21% vs sham 12% gain > 3 lines Study 2: 18% vs sham 10% gain > 3 lines 42% needed IOP lowering therapy. Surgery not usually needed, resolves by 6 months 68% cataract formation Anterior migration if torn posterior capsule Iluvien for DME- approved 2/ year study for DME 1 injection of implant lasting 3 years Steroid challenge prior recommended Combined results of 2 trials: 28.7% treated vs. 16.2% control had a > 3 line improvement 36 mo. Improvement seen at 3 weeks and sustained through month % sustained IOP rise, 5% needed glaucoma surgery 15

combination Ranibizumab with Dexamethasone (same visit q 3 mo) DRCR.

16 DRCR.net Protocol U (2017) 6 month Evaluation of Combination Dexamethasone + Ranibizumab vs. Ranibizumab Alone for Persistent Central-Involved DME Following Anti-VEGF Therapy Persistent DME/reduced Va despite Ranibizumab x 3m Randomize Continued Ranibizumab vs. combination Ranibizumab with Dexamethasone (same visit q 3 mo) DRCR.net Protocol U (2017) Mean VA improvement by 6 months was no better in the dexamethasone + ranibizumab group than in the sham + ranibizumab group (mean 3 letters) On average, there was a greater reduction in retinal thickness in the dexamethasone + ranibizumab group (-110 vs -62 um) Study was not sufficiently sized to determine whether treatment response might differ by lens status, but trend towards more improvement in pseudophakic eyes vs. phakic eyes 29% Any Increase in IOP in combination group vs. 0% Ranibizumab alone. (15% > 30, 20% required drops) Ranibizumab for DME: Early and Long Term Responses Of the 40% with poor responses early with Ranibizumab alone, 28% did get some additional improvement over time Need to personalize Rx Consider steroid use in poor responders Still those in Ranibizumab group with deferred laser had best results compared to Ranibizumab plus prompt laser and Triamcinolone plus laser with deferred Ranibizumab DRCR.net Protocol I study Gonzalez VH, et al. AJO 2016; 172: Protocol I: EARLY Analysis DOS: 12/9/2016 After Avastin x 4 OS x 3 OD HA1c: 8.0. Ozurdex implant OS VA OD: 20/30 VA OS: 20/70 PH: 20/50 DOS: 1/12/2017 After Ozurdex #1 OS, Avastin x 4 OD Scheduled Laser OU and ERM removal surgery OS VA OD: 20/40 VA OS: 20/100 PH: 20/50 Other treatments for Macular Edema Vitrectomy Diffuse macular edema caused by posterior hyaloid thickening and/or ERM Leakage results from direct vitreoretinal traction DRCR Protocol D after vitrectomy for DME/VMT edema reduced in most eyes % Va improvement,13-31% worse Va Several smaller studies have shown variable visual improvement Ophthalmology 2010;117:

DOS: 2/16/2017 s/p Avastin/Ozurdex/Laser & ERM removal OS; s/p Avastin/ Laser x 1 OD VA OD: 20/40 VA OS: 20/40 DOS: 6/23/2017 After Ozurdex #2 OS; Added Avastin plus 2 nd laser OD VA OD: 20/25 VA OS:

17 DOS: 2/16/2017 s/p Avastin/Ozurdex/Laser & ERM removal OS; s/p Avastin/ Laser x 1 OD VA OD: 20/40 VA OS: 20/40 DOS: 6/23/2017 After Ozurdex #2 OS; Added Avastin plus 2 nd laser OD VA OD: 20/25 VA OS: 20/40 PH: 20/30 DOS: 12/1/2017 After Ozudex x 2 OS and 1 more Avastin and 2 nd Laser OD. Ozurdex OS given at today s visit? Iluvien next step VA OD: 20/25 VA OS: 20/60 Summary Management of DR as it develops Screening of patients at risk systemic control Anti-VEGF therapy first line for central/diffuse edema. Focal laser for focal non-central DME Try steroid implants for refractory cases/vitrectomized eyes Anti-VEGF and gradual PRP for PDR - compliance Vitrectomy (often with preoperative anti-vegf) for advanced complications Thanks for attending!!! 17

Diabetic Retinopathy Update 2017

Diabetic Retinopathy Update 2017 Basis for DR management standards for past 40 years Diabetic Retinopathy Study (DRS) 1971-1989 and Early Treatment of Diabetic Retinopathy Study (ETDRS) 1979-1990 Sundeep