Intravitreal Ranibizumab for diabetic macular edema with prompt versus deferred laser treatment: 5-year randomized trial results

Abstract

Objective: To report 5-year results from a previously reported trial evaluating intravitreal 0.5 mg ranibizumab with prompt versus deferred (for ≥24 weeks) focal/grid laser treatment for diabetic macular edema (DME).

Design: Multicenter, randomized clinical trial.

Participants: Among participants from the trial with 3 years of follow-up who subsequently consented to a 2-year extension and survived through 5 years, 124 (97%) and 111 (92%) completed the 5-year visit in the prompt and deferred groups, respectively.

Methods: Random assignment to ranibizumab every 4 weeks until no longer improving (with resumption if worsening) and prompt or deferred (≥24 weeks) focal/grid laser treatment.

Main outcome measures: Best-corrected visual acuity at the 5-year visit.

Results: The mean change in visual acuity letter score from baseline to the 5-year visit was +7.2 letters in the prompt laser group compared with +9.8 letters in the deferred laser group (mean difference, -2.6 letters; 95% confidence interval, -5.5 to +0.4 letters; P = 0.09). At the 5-year visit in the prompt versus deferred laser groups, there was vision loss of ≥10 letters in 9% versus 8%, an improvement of ≥10 letters in 46% versus 58%, and an improvement of ≥15 letters in 27% versus 38% of participants, respectively. From baseline to 5 years, 56% of participants in the deferred group did not receive laser. The median number of injections was 13 versus 17 in the prompt and deferral groups, including 54% and 45% receiving no injections during year 4 and 62% and 52% receiving no injections during year 5, respectively.

Conclusions: Five-year results suggest focal/grid laser treatment at the initiation of intravitreal ranibizumab is no better than deferring laser treatment for ≥24 weeks in eyes with DME involving the central macula with vision impairment. Although more than half of eyes in which laser treatment is deferred may avoid laser for at least 5 years, such eyes may require more injections to achieve these results when following this protocol. Most eyes treated with ranibizumab and either prompt or deferred laser maintain vision gains obtained by the first year through 5 years with little additional treatment after 3 years.

Figure 1. Mean Change in Visual Acuity at Follow-up Visits

Open triangle (Prompt) = Ranibizumab + prompt laser treatment; closed square (Deferred) = Ranibizumab + deferred laser treatment. Visual acuity change truncated to ±30 letters. Results were similar without truncation (data not shown). Difference in mean change in visual acuity at 5 years from longitudinal model: P value adjusted for baseline visual acuity = 0.09; P value adjusted for baseline visual acuity and other potential confounders = 0.15.

Figure 2. Mean Change in Visual Acuity at Follow-up Visits Limited to the Cohort that Completed the Five-year Visit

Open triangle (Prompt) = Ranibizumab + prompt laser treatment; closed square (Deferred = Ranibizumab + deferred laser treatment. Visual acuity change truncated to ±30 letters. Difference in mean change in visual acuity at 5 years from longitudinal model: P value adjusted for baseline visual acuity = 0.12; P value adjusted for baseline visual acuity and other potential confounders = 0.36.

Figure 3. Mean Change in Visual Acuity at Follow-up Visits Stratified by Baseline Visual Acuity Subgroup

Open triangle (Prompt) = Ranibizumab + prompt laser treatment; closed square (Deferred) = Ranibizumab + deferred laser treatment. Visual acuity change truncated to ±30 letters. P value for interaction of treatment group with baseline visual acuity over 5 years from longitudinal model =0.004.

Figure 4. Proportion of Eyes With Visual Acuity Letter Score ≥69 (Approximate Snellen Equivalent 20/40 or Better) at Follow-up Visits

Open triangle (Prompt) = Ranibizumab + prompt laser treatment; closed square (Deferred) = Ranibizumab + deferred laser treatment.

Figure 5. Proportion of Eyes With Visual Acuity Letter Score ≤38 (Approximate Snellen Equivalent 20/200 or Worse) at Follow-up Visits

Open triangle (Prompt) = Ranibizumab + prompt laser treatment; closed square (Deferred) = Ranibizumab + deferred laser treatment.

Figure 6. Mean Change in Optical Coherence Tomography Central Subfield Retinal Thickening at Follow-up Visits

Open triangle (B) = Ranibizumab + prompt laser treatment; closed square (C) = Ranibizumab + deferred laser treatment. Difference in mean change in OCT central subfield thickness at 5 years from longitudinal model: P value adjusted for baseline CSF thickness and visual acuity = 0.48; P value adjusted for baseline CSF thickness and visual acuity and other potential confounders = 0.53.