Randomized Trial Evaluating Ranibizumab Plus Prompt or Deferred Laser or Triamcinolone Plus Prompt Laser for Diabetic Macular Edema
Objective
Evaluate intravitreal 0.5 mg ranibizumab or 4 mg triamcinolone combined with focal/grid laser compared with focal/grid laser alone for treatment of diabetic macular edema (DME).
Design
Multicenter, randomized clinical trial.
Participants
A total of 854 study eyes of 691 participants with visual acuity (approximate Snellen equivalent) of 20/32 to 20/320 and DME involving the fovea.
Methods
Eyes were randomized to sham injection + prompt laser (n=293), 0.5 mg ranibizumab + prompt laser (n=187), 0.5 mg ranibizumab + deferred (≥24 weeks) laser (n=188), or 4 mg triamcinolone + prompt laser (n=186). Retreatment followed an algorithm facilitated by a web-based, real-time data-entry system.
Main Outcome Measures
Best-corrected visual acuity and safety at 1 year.
Results
The 1-year mean change (±standard deviation) in the visual acuity letter score from baseline was significantly greater in the ranibizumab + prompt laser group (+9±11, P<0.001) and ranibizumab + deferred laser group (+9±12, P<0.001) but not in the triamcinolone + prompt laser group (+4±13, P=0.31) compared with the sham + prompt laser group (+3±13). Reduction in mean central subfield thickness in the triamcinolone + prompt laser group was similar to both ranibizumab groups and greater than in the sham + prompt laser group. In the subset of pseudophakic eyes at baseline (n=273), visual acuity improvement in the triamcinolone + prompt laser group appeared comparable to that in the ranibizumab groups. No systemic events attributable to study treatment were apparent. Three eyes (0.8%) had injection-related endophthalmitis in the ranibizumab groups, whereas elevated intraocular pressure and cataract surgery were more frequent in the triamcinolone + prompt laser group. Two-year visual acuity outcomes were similar to 1-year outcomes.
Conclusions
Intravitreal ranibizumab with prompt or deferred laser is more effective through at least 1 year compared with prompt laser alone for the treatment of DME involving the central macula. Ranibizumab as applied in this study, although uncommonly associated with endophthalmitis, should be considered for patients with DME and characteristics similar to those in this clinical trial. In pseudophakic eyes, intravitreal triamcinolone + prompt laser seems more effective than laser alone but frequently increases the risk of intraocular pressure elevation.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found after the references.
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Manuscript no. 2010-112.
The most recently published list of the DRCR.net investigators and staff who participated in this study is available at www.drcr.net.
Correspondence: Protocol I Correspondence, Jaeb Center for Health Research, 15310 Amberly Drive, Suite 350, Tampa, FL 33647. E-mail: drcrstat4@jaeb.org
This article contains online-only material. The following should appear online-only: Table 1, Table 2, Table 3, Table 4, Table 6, Table 7, Table 9, Table 10, Table 12, Table 13, Table 14, Table 16, Table 18, Table 19; Figure 1, Figure 2, Figure 5, Figure 7, Figure 8; .
Financial Disclosure(s): 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, and EY018817.
The funding organization (National Institutes of Health) participated in oversight of the conduct of the study and review of the manuscript but not directly in the design or conduct of the study; the collection, management, analysis, or interpretation of the data; or the preparation of the manuscript. Genentech provided the ranibizumab for the study, and Allergan, Inc., provided the triamcinolone for the study. In addition, Genentech and Allergan, Inc., provided funds to the DRCR.net to defray the study's clinical site costs. As described in the DRCR.net Industry Collaboration Guidelines (available at www.drcr.net), the DRCR.net had complete control over the design of the protocol, the ownership of the data, and all editorial content of presentations and publications related to the protocol. A complete list of all DRCR.net investigator financial disclosures can be found at www.drcr.net.
The lead author(s) have made the following disclosure(s): Scott M. Friedman: Sirion Therapeutics (S), MacuSight (S), Pfizer (S), Vitreoretinal Technologies (S), Allergan (S), EMMES Corporation (S). Ingrid U. Scott: Genentech (C). Lloyd P. Aiello: Genentech (C). Susan B. Bressler: GlaxoSmithKline (C). Frederick L. Ferris III; Bausch & Lomb (P).
Neil M. Bressler:
Grants to investigators at The Johns Hopkins University are negotiated and administered by the institution (e.g., the School of Medicine) that receives the grants, typically through the Office of Research Administration. Individual investigators who participate in the sponsored project(s) are not directly compensated by the sponsor but may receive salary or other support from the institution to support their effort on the projects(s).
Dr. Neil M. Bressler is Principal Investigator of grants at The Johns Hopkins University sponsored by the following entities (not including the National Institutes of Health): Allergan, Bausch & Lomb, Carl Zeiss Meditec, EMMES Corporation, Genentech, Lumenis, Notal Vision Ltd.,* Novartis, QLT, Regeneron, Steba Biotech, Abbott Medical Optics, ForSight Labs, LLC, and Genzyme Corporation. Dr. Susan B. Bressler's consulting arrangement with Notal Vision in connection with Dr. Neil M. Bressler's role as principal investigator on a Notal Vision-sponsored research grant has been reviewed and managed by The Johns Hopkins University School of Medicine in accordance with its conflict of interest policy.
PII: S0161-6420(10)00243-5
doi:10.1016/j.ophtha.2010.02.031
© 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
