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Original Investigation |

Persistent Macular Thickening After Ranibizumab Treatment for Diabetic Macular Edema With Vision Impairment

Susan B. Bressler, MD1; Allison R. Ayala, MS2; Neil M. Bressler, MD1,3; Michele Melia, ScM2; Haijing Qin, MS2; Frederick L. Ferris III, MD4,5; Christina J. Flaxel, MD6; Scott M. Friedman, MD7; Adam R. Glassman, MS2; Lee M. Jampol, MD8; Michael E. Rauser, MD9 ; for the Diabetic Retinopathy Clinical Research Network
[+] Author Affiliations
1Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland
2Jaeb Center for Health Research, Tampa, Florida
3Editor, JAMA Ophthalmology
4National Eye Institute, National Institutes of Health, Bethesda, Maryland
5Viewpoint Editor, JAMA Ophthalmology
6Oregon Health & Science University, Portland
7Florida Retina Consultants, Lakeland
8Feinberg School of Medicine, Northwestern University Medical School, Chicago, Illinois
9Loma Linda University Health Care, Loma Linda, California
JAMA Ophthalmol. 2016;134(3):278-285. doi:10.1001/jamaophthalmol.2015.5346.
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Importance  The prevalence of persistent diabetic macular edema (DME) after months of anti–vascular endothelial growth factor therapy and its effect on visual acuity are unknown.

Objective  To assess subsequent outcomes of eyes with DME persisting for 24 weeks after initiating treatment with 0.5 mg of ranibizumab.

Design, Setting, and Participants  We performed post hoc, exploratory analyses of a randomized clinical trial from March 20, 2007, through January 29, 2014, from 117 of 296 eyes (39.5%) randomly assigned to receive ranibizumab with persistent DME (central subfield thickness ≥250 μm on time domain optical coherence tomography) through the 24-week visit.

Interventions  Four monthly intravitreous injections of ranibizumab and then as needed per protocol.

Main Outcomes and Measures  Cumulative 3-year probabilities of chronic persistent DME (failure to achieve a central subfield thickness <250 μm and at least a 10% reduction from the 24-week visit on at least 2 consecutive study visits) determined by life-table analyses, and at least 10 letter (≥2 line) gain or loss of visual acuity among those eyes.

Results  The probability of chronic persistent DME among eyes with persistent DME at the 24-week visit decreased from 100% at the 32-week visit to 81.1% (99% CI, 69.6%-88.6%), 55.8% (99% CI, 42.9%-66.9%), and 40.1% (99% CI, 27.4%-52.4%) at the 1-, 2-, and 3-year visits, respectively. At 3 years, visual acuity improved in eyes with and without chronic persistent DME through the follow-up period, respectively, by a mean of 7 letters and 13 letters from baseline. Among 40 eyes with chronic persistent edema through 3 years, 17 (42.5%) (99% CI, 23.1%-63.7%) gained 10 letters or more from baseline, whereas 5 (12.5%) (99% CI, 2.8%-31.5%) lost 10 letters or more from baseline.

Conclusions and Relevance  These data suggest less than half of eyes treated for DME with intravitreous ranibizumab have persistent central-involved DME through 24 weeks after initiating treatment. Among the 40% that then have chronic persistent central-involved DME through 3 years, longer-term visual acuity outcomes appear to be slightly worse than in the 60% in which DME does not persist. Nevertheless, when following the treatment protocol used in this trial among eyes with vision impairment from DME, long-term improvement in visual acuity from baseline is typical and substantial (≥2-line) loss of visual acuity is likely uncommon through 3 years, even when central-involved DME chronically persists.

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Probability of Chronic Persistent Diabetic Macular Edema (DME)

An event is defined as a central subfield thickness less than 250 µm and a 10% or greater reduction relative to the 24-week study visit on at least 2 consecutive study visits subsequent to the 24-week visit.

aFive participants excluded from 104- or 156-week cross-sectional analyses as noted in the eFigure in the Supplement due to insufficient visits or lost to follow-up are not censored in the time to event analysis because of meeting the definition of no longer chronic persistent DME by 52 weeks.

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