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Bressler, Susan B., MD*; Odia, Isoken, OD, MPH; Glassman, Adam R., MS; Danis, Ronald P., MD; Grover, Sandeep, MD§; Hampton, G. Robert, MD; Jampol, Lee M., MD**; Maguire, Maureen G., PhD††; Melia, Michele, ScM

doi: 10.1097/IAE.0000000000002302
Original Study

Purpose: To explore 5-year changes from baseline in diabetic retinopathy severity among eyes treated with ranibizumab for diabetic macular edema.

Methods: Diabetic retinopathy severity was assessed from study visits and annual fundus photographs among participants in Protocol I ( The proportion of eyes that improved at annual examinations and the cumulative probability of worsening through 5 years were estimated.

Results: Among 235 participants with nonproliferative diabetic retinopathy at baseline, there were 29%, 28%, and 32% of eyes with retinopathy improvement at 1, 3, and 5 years, respectively. Among 111 participants with proliferative diabetic retinopathy, corresponding improvement percentages were 38%, 35%, and 23%. The 5-year cumulative probability of worsening was 18% (95% CI: 14%–25%) among nonproliferative diabetic retinopathy eyes and 31% (95% CI: 23%–42%) among proliferative diabetic retinopathy eyes (P = 0.01). In Years 1, 3, and 5, the mean (SD) number of ranibizumab injections was 8.1 (2.5), 2.2 (2.6), and 1.8 (2.6) for nonproliferative diabetic retinopathy eyes, and 9.0 (2.8), 2.3 (2.9), and 1.7 (2.6) for proliferative diabetic retinopathy eyes, respectively. Proportions with improvement or rates of worsening did not change with time.

Conclusion: Individuals receiving ranibizumab therapy for diabetic macular edema may have favorable changes in DR severity throughout a 5-year period concomitant with sequential reduction in anti–vascular endothelial growth factor therapy.

In the Protocol I, individuals managed with ranibizumab therapy for diabetic macular edema had favorable changes in retinopathy severity at 5 years. Rates of improvement and worsening do not appear altered by a reduction in the number of intravitreous ranibizumab injections for diabetic macular edema during the later years.

*Wilmer Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland;

Jaeb Center for Health Research, Tampa, Florida;

Ophthalmology and Visual Sciences, University of Wisconsin, Madison, Wisconsin;

§Department of Ophthalmology, Jacksonville Health Science Center, University of Florida College of Medicine, Jacksonville, Florida;

Retina-Vitreous Surgeons of Central New York, PC, Syracuse, New York;

**Feinberg School of Medicine, Northwestern University, Chicago, Illinois; and

††Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania.

Reprint requests: Isoken Odia, OD, MPH, Jaeb Center for Health Research, 1530 Amberly Drive, Suite 350, Tampa, FL 33647; e-mail:

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, U.S. Department of Health and Human Services EY14231, EY23207, and EY18817.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

A complete list of all investigator financial disclosures can be found at

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, nor in the collection, management, analysis, or interpretation of the data, or in the preparation of the manuscript.

Genentech provided the ranibizumab for this study. As per the Industry Collaboration Guidelines (available at, the had complete control over the design of the protocol, ownership of the data, and all editorial content of presentations and publications related to the protocol. Genentech has provided funds restricted to clinical sites.

The study was completed at 52 sites within the United States; a published list of the investigators and staff participating in this protocol can be found in Ophthalmology 2010;117:1064–1077.e35 with a current list available at

© 2018 by Ophthalmic Communications Society, Inc.