1. The Diabetic Retinopathy Clinical Research Network
Intravitreous Anti-VEGF vs. Vitrectomy
for Vitreous Hemorrhage from PDR
(Protocol AB)
Protocol Chair: Andrew N. Antoszyk, MD

2. Background
Vitreous hemorrhage due to PDR is a frequent cause of vision loss in patients with diabetes.
No recent, definitive evidence to guide how to:
Optimize VA outcomes, or
Optimize time to maximal visual recovery
Major question of interest:
Once intervention is desired, what is the relative safety and efficacy of currently available therapies? 2

3. Anti-VEGF for VH in PDR Rationale
Data supporting anti-VEGF use for VH + PDR:
In DRCR.net Protocol N, a difference in rates of vitrectomy at 4 months with anti-VEGF compared with saline-treated eyes was not identified BUT
Ranibizumab treated eyes showed some biological effects suggesting benefits:
Higher probability of completing PRP (44% vs 31% by 16 weeks P = 0.05)
Greater average VA improvement (22 vs. 16 letters, P = 0.04)
Reduced rate of recurrent hemorrhage (6% vs. 17%, P = 0.01)
Photo of vitreous hemorrhage 3

4. Vitrectomy for VH in PDR Rationale
Newer surgical techniques allow smaller incisions, faster operating times, and fewer associated adverse events
DRIVE UK study: Eyes with “simple VH” of at least 3 months duration had better outcomes than eyes with TRD or other diabetic pathology
85% (51) had >3 line gain in VA
Mean gain of 42 ± 27 ETDRS letters
8.3% (5) had repeat vitrectomy
3 for non-clearing VH; 2 for RD
Gupta B, Sivaprasad S, Wong R, et al. Visual and anatomical outcomes following vitrectomy for
complications of diabetic retinopathy: the DRIVE UK study. Eye (Lond) Apr;26(4):510-6. 4

5. Study Objectives
Evaluate and compare VA outcomes over time for the following regimens:
Prompt vitrectomy + PRP
Intravitreous anti-VEGF (Aflibercept) injections
Characterize the follow-up course for the two treatment regimens, including:
Post-operative complications for the vitrectomy group
Number of injections needed and percent requiring vitrectomy in the aflibercept group 5

6. Study Design 200 eyes (1 per pt) that meets the following criteria:
Multi-Center Randomized Clinical Trial
200 eyes (1 per pt) that meets the following criteria:
Vitreous hemorrhage
causing vision impairment,
presumed to be from PDR, and
requiring intervention (vitrectomy or anti-VEGF).
Vitrectomy +
PRP
Anti-VEGF
Primary Outcome: Visual Acuity Area Under the Curve (AUC) over 6 Months*
Total Duration: 2 Years 6
*Note: Publication not planned until 2-year results available

7. Additional Key Outcomes
Although 6M VA AUC is “primary”, long-term outcomes are also important:
Mean VA at 1, 3 months and annual visits
VA AUC at annual visits
Percent 20/20 and 20/40 or better and 20/200 or worse at annual visits
Rates of recurrent VH on clinical exam
Productivity from WPAI questionnaire
Treatment and follow-up costs
WPAI Work Productivity Assessment

8. Major Inclusion/Exclusion Criteria
VA 20/32 or worse but at least light perception
No anti-VEGF treatment within 2 months prior to vitreous hemorrhage onset
No prior vitrectomy
Note: Prior PRP is not a requirement nor an exclusion
No rhegmatogenous retinal detachment and no traction retinal detachment involving or threatening the fovea
Patient is able and willing to undergo vitrectomy within 2 weeks (no contraindication to surgery)

9. Follow-Up and Treatment Overview
Outcome assessment visits for both groups
Every 3 months in the first year
Every 4 months in the second year
Anti-VEGF Treatment
Visits every 4 weeks for 6 months and then as needed
Injections required in the Anti-VEGF Group through week 12 and then as needed according to criteria
Both groups may receive anti-VEGF for DME
Vitrectomy
Within 2 weeks of randomization in the Vitrectomy Group
If needed in anti-VEGF group according to criteria

10. Referrals We Need Your Help!
Please consider any eyes with vitreous hemorrhage due to diabetic retinopathy causing vision impairment
Study participants must be willing to be randomized to vitrectomy or aflibercept injections and continue follow-up for 2 years

11. Thank You on Behalf of Diabetic Retinopathy Clinical Research Network (DRCR.net)
Dedicated to multicenter clinical research of diabetic retinopathy, macular edema and associated disorders. 11