The Diabetic Retinopathy Clinical Research Network Dedicated to multicenter clinical research of diabetic retinopathy, macular edema and associated Supported through a cooperative agreement from the National Eye Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services EY14231, EY14229, EY018817 

DRCR.net Overview Objective: The development of a collaborative network to facilitate multicenter clinical research on diabetic retinopathy, diabetic macular edema and associated conditions. Funding: National Eye Institute-sponsored cooperative agreement initiated September 2002. Current award 2009-2013

Priority Initiatives Involvement of community-based practices, as well as “academic” or university-based centers. Collaborate with industry to facilitate investigations and pursue opportunities otherwise not possible and to do so in a manner consistent with the Network’s dedication to academic integrity and optimal clinical trial performance.

Organization: Clinical Sites of the Network Overall Network Participation (as of 11/29/11) 252 sites submitted application for Network 884 total Investigators; 2715 additional personnel Current Participation 116 active sites; 8 pending sites 75 community based sites 342 Investigators 873 additional personnel 38 States & 1 country

DRCR Network Protocols A through H with Enrollment Completed 2003 to 2007 # of Subjects A: Pilot Study of Laser Photocoagulation for DME 263 B: Randomized Trial Comparing Intravitreal Triamcinolone Acetonide and Laser Photocoagulation for DME 693 C: Temporal Variation in OCT Measurements of DME 114 D: Evaluation of Vitrectomy for DME 241 E: Pilot Study of Peribulbar Triamcinolone Acetonide for DME 113 F: Observational Study of the Development of DME Following Scatter Laser Photocoagulation 155 G: Subclinical Diabetic Macular Edema Study 68 H: Phase 2 Randomized Trial of Bevacizumab for DME 121 5

DRCR Network Protocols with Enrollment From 2008 to 2011 (as of 11/29/11) # of Subjects I: Laser-Ranibizumab-Triamcinolone Study for DME* 691 J: Laser-Ranibizumab-Triamcinolone Study for DME + PRP*** 333 K: The Course of Response to Focal Photocoagulation for DME*** 128 L: Autorefraction and E-ETDRS Measurements in DME*** 490 M: Diabetes Education Study** 1172 N: Intravitreal Ranibizumab for Vitreous Hemorrhage from PDR Study* 261 O: Comparison of Time Domain OCT & Spectral Domain OCT in DME** 1145 P: Pilot Study of Individuals with DME Undergoing Cataract Surgery*** 68 Q: Individuals with Diabetes without DME Undergoing Cataract Surgery*** 317 * Enrollment done/in active follow-up; **Recruiting; ***Enrollment/follow-up done

DRCR Network Protocols with Enrollment From 2008 to 2011 (as of 8/8/11) # of Subjects R: NSAIDs in Eyes with Non Central Involved DME** 11 DRCR Network Participant Total Since 2003 6384 * Enrollment done/in active follow-up; **Recruiting; ***Enrollment/follow-up done

Active Studies

Major Eligibility Criteria Protocol I: Intravitreal Ranibizumab or Triamcinolone Acetonide in Combination with Laser Photocoagulation for Diabetic Macular Edema Objective To evaluate the safety and efficacy of intravitreal anti-VEGF treatment in combination with focal laser photocoagulation, intravitreal anti-VEGF treatment alone, and intravitreal corticosteroids in combination with focal laser photocoagulation in eyes with center-involved DME Major Eligibility Criteria Diabetic macular edema involving the center of the macula (OCT central subfield thickness ≥ 250 microns) responsible for visual acuity of 20/32 or worse Enrollment (3/07 – 12/08) Total enrolled: 691 subjects/854 eyes at 52 sites Diabetic Retinopathy Clinical Research Network. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010 June;117(6):1064-1077.e35.  

Protocol M: Effect of Diabetes Education during Ophthalmology Visits on Diabetes Control Objective To assess whether glycemic control (assessed with HbA1c measurement) in individuals with type 1 or type 2 diabetes can be improved with a point-of-care measurement of HbA1c in the ophthalmologist’s office combined with a personalized risk assessment for diabetic retinopathy and other complications of diabetes Major Eligibility Criteria Diagnosis of diabetes mellitus (type 1 or type 2) Patient is not eligible if patient has a known HbA1c <7.5% within prior 6 months Enrollment (Ongoing) Total enrolled: 1172 subjects at 42 sites (as of 11/29/11)

Protocol N: An Evaluation of Intravitreal Ranibizumab for Vitreous Hemorrhage Due to Proliferative Diabetic Retinopathy Objective To determine if intravitreal injections of ranibizumab decrease the proportion of eyes in which vitrectomy is performed compared with saline injections in eyes presenting with vitreous hemorrhage from proliferative diabetic retinopathy Major Eligibility Criteria Study eye with Vitreous hemorrhage causing vision impairment, presumed to be from proliferative diabetic retinopathy, and precluding completion of panretinal photocoagulation Immediate vitrectomy not required Enrollment (6/10 – 10/11) Total enrolled: 261 subjects at 61 sites

Protocol O: Comparison of Time Domain OCT and Spectral Domain OCT Retinal Thickness Measurement in Diabetic Macular Edema Objective To compare thickness measurements between Zeiss TD Stratus OCT and selected SD OCT machines (Zeiss Cirrus, Heidelberg Spectralis, Topcon 3D-OCT, and Optovue RTVue), estimating a conversion factor between TD OCT and SD OCT To assess and compare the reproducibility of the selected SD OCT machines utilizing their respective software analysis algorithms Major Eligibility Criteria DME in at least one eye (OCT central subfield thickness ≥250 microns) Enrollment (Ongoing) Total enrolled: 1145 subjects at 39 sites (as of 11/29/11)

Protocol R: A Phase II Evaluation of Topical NSAIDs in Eyes with Non Central Involved DME Objective To assess the effects of topical NSAIDs on macular retina volume compared with placebo in eyes with non-central DME To assess the effects of topical NSAIDs on central subfield thickness and to compare the progression of non-central DME to central DME as determined by OCT and stereoscopic fundus photographs Major Eligibility Criteria Best corrected E-ETDRS VA letter score ≥74 Definite retinal thickening due to DME within 3000 µm of the center of the macula but not involving the central subfield No focal/grid laser within the last 6 months or other treatment for DME within the last 4 months No anticipated need to treat DME during the course of the study unless the eye meets the criteria for treatment Enrollment (Ongoing) Total enrolled: 29 subjects at 12 sites in run-in phase; of which, 11 are randomized in full trial (as of 11/29/11)

Protocols In Development Prompt Panretinal Photocoagulation Versus Intravitreal Ranibizumab with Deferred Panretinal Photocoagulation for Proliferative Diabetic Retinopathy Protocol T – Intravitreal Bevacizumab Compared with Intravitreal Ranibizumab for Diabetic Macular Edema