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

Abstract

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.

Figure

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. ^a Five 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.