Vitrectomy Outcomes in Eyes with Diabetic Macular Edema, Visual Loss, and Vitreomacular Traction Sponsored by the National Eye Institute, National Institutes of Health, U.S. Department of Health and Human Services. 1

2 Rationale: Vitrectomy for DME Rationale: Vitrectomy for DME  Case series report resolution of DME and improving VA  Most series not prospective, many in preOCT era  Possible positive impacts:  Anatomic resolution of vitreomacular tractional forces  Physiologic changes: improved oxygenation or beneficial changes in retinal microenvironment

3  Lack of investigator equipoise: surgery indicated in eyes with VMT and reduced VA  Cohort study: Prospective data collection, standardized protocol  Data provide reference for future surgical trials Rationale for Prospective Cohort Study

4 Overall Study Design Vitrectomy performed by the investigator’s usual routine. Vitrectomy performed by the investigator’s usual routine. Prospective Cohort Study At least one eye meeting all of the following criteria: DME on clinical exam BCVA letter score > 20/400 Presence of vitreomacular traction associated with macular edema OR judgment that edema will not to respond to focal/grid photocoagulation

6 Follow-up and Treatment Schedule  BCVA  OCT  7-field photos at 6 mos Vitrectomy Intraop/Postop Data and Complications Collected 3 Month Follow-Up 6 Month Follow-Up

7 Main Outcomes: 6 months  Visual acuity  Retinal thickening on OCT  Complications

ARVO Report: Primary Cohort   Investigator states that vitreomacular traction was reason for vitrectomy   Visual acuity 20/63 to 20/400   Central subfield >300 microns on OCT   Cataract extraction not performed during vitrectomy 8

9 Results

10  241 eyes enrolled and underwent vitrectomy for DME at 35 clinical sites  Indication for surgery VMIA: 227 eyes  87 eyes in primary cohort  Vitreomacular traction  VA 20/63 to 20/400  OCT CSF >300 microns  Cataract extraction not performed Study Enrollment

11  Primary Cohort (n=87) 98% at 3-month visit 96% at 6-month visit Visit Completion

12 Baseline Characteristics Primary Cohort (n=87) Median Age66 years Women (%)45% White (%)79% Diabetes Type (%): Type I /Type 216%/ 84% Median Visual Acuity20/100 Median OCT CSF thickness491 microns

13 Baseline Characteristics Continued Primary Cohort Retinopathy Severity NPDR 31% PDR 64% Pseudophakic57% Epiretinal Membranes Present No24% Probable22% Definite49%

14 Primary Cohort Status of vitreous on clinical examination Attached56% Partially attached32% Detached6% Uncertain6% Reasons for Vitrectomy Vitreomacular interface abnormality 100% Unresponsive to other therapies 31% Baseline Characteristics Continued

15 Surgery Characteristics Primary Cohort (n=87) Vitrectomy System 19/20 gauge40% 25 gauge49% Other10% Epiretinal Membrane Peeled61% ILM Removed54%

16 Primary Cohort (n=87) Agents Used to Improve Visualization 60% Triamcinolone34% ICG25% Other5% Laser Used55% PRP39% Focal5% Surgery Characteristics

17 Surgery Characteristics Continued Primary Cohort Cryotherapy Used8% Corticosteroids Used at Close64% Intravitreal43% Peribulbar/Subconj/Sub Tenon’s40% Posterior Capsulotomy Performed8% Epiretinal Membranes Present No39% Probable15% Definite46%

Visual Results: Vtx for DME   Anatomic: Median decrease in OCT CSF thickening of 153 microns 42% resolution of central DME (CSF≤250 microns) Two-thirds of eyes had 50% reduction or more   Functional: Visual acuity improved ≥ 10 letters (= 2 lines) in 37% at 6 months VA decreased ≥ 10 lines in 23% at 6 months

19 Primary Outcome: Primary Cohort Mean Retinal Thickness

20 Primary Outcome: Primary Cohort Change in Retinal Thickness

21 Primary Outcome: Primary Cohort Change in Visual Acuity

22 Primary Cohort Operative complications7% Any postoperative complications/AE – (%)18% Vitreous Hemorrhage6% Development of Vitreomacular Interface Abnormalities 2% Elevated IOP Requiring Treatment8% Retinal Detachment3% Retinal Tear0 Endophthalmitis1% Macular Ischemia0 Double Vision2% Other6% Complications 0-6 Months

23 Results  4/8 eyes with RD, endophthalmitis, or VH lost 10 or more letters at 6 months  For every 100 microns CSF decrease, improvement in VA 2.6 letters  CSF retinal thickness changes stabilize at 3 months after vitrectomy

Follow-up Analysis   1 year data on this cohort   Analysis of the entire cohort of patients with VMT: N=227   Impact on outcomes: pseudophakia, baseline VA, severity of retinopathy, ERM peeling, ILM peeling

25 Discussion

26 Conclusions: DME, Visual Loss, Vitreomac Traction   Marked anatomic improvement: 153 microns mean CSF decrease 43% <250 microns at 6 months Two-thirds > 50% improvement in CSF thickening 37% improved by 10 or more letters at 6 mo 22% declined by 10 or more letters at 6 mo

27 Study Limitations   Unknown how these cases would have fared without treatment   Judgment that indication for surgery was vitreomacular traction was made by the investigator, not a reading center   Variety of surgical maneuvers employed

28 Study Strengths   Standardized protocol across 35 diverse clinical sites in the U.S.   Little loss to follow-up through 6 months   “Real world” scenario: judgment of VMT made by experienced surgeons   Numbers allow subgroup analysis (n=227)   Provides a reference going forward

29 For further information and all DRCR Network financial disclosures, go to  35 clinical study sites  Subjects who volunteered to participate in this trial  DRCR Network Data and Safety Monitoring Committee  Juvenile Diabetes Research Foundation (JDRF)  DRCR Network investigators and staff Thank You Thank You