Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema

Abstract

Objective: To report expanded 2-year follow-up of a previously reported randomized trial evaluating 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 of 20/32 to 20/320 (approximate Snellen equivalent) and DME involving the fovea.

Methods: Continuation of procedures previously reported for the randomized trial.

Main outcome measures: Best-corrected visual acuity and safety at the 2-year visit.

Results: At the 2-year visit, compared with the sham + prompt laser group, the mean change in the visual acuity letter score from baseline was 3.7 letters greater in the ranibizumab + prompt laser group (95% confidence interval adjusted for multiple comparisons [aCI], -0.4 to +7.7), 5.8 letters greater in the ranibizumab + deferred laser group (95% aCI, +1.9 to +9.8), and 1.5 letters worse in the triamcinolone + prompt laser group (95% aCI, -5.5 to +2.4). After the 1- to 2-year visit in the ranibizumab + prompt or deferred laser groups, the median numbers of injections were 2 and 3 (potential maximum of 13), respectively. At the 2-year visit, the percentages of eyes with central subfield thickness ≥250 μm were 59% in the sham + prompt laser group, 43% in the ranibizumab + prompt laser group, 42% in the ranibizumab + deferred laser group, and 52% in the triamcinolone + prompt laser group. No systemic events attributable to study treatment were apparent. Three eyes in 3 (0.8%) of 375 participants had injection-related endophthalmitis in the ranibizumab groups, whereas elevated intraocular pressure and cataract surgery were more frequent in the triamcinolone + prompt laser group.

Conclusions: The expanded 2-year results reported are similar to results published previously and reinforce the conclusions originally reported: Ranibizumab should be considered for patients with DME and characteristics similar to those of the cohort in this clinical trial, including vision impairment with DME involving the center of the macula.

Figure 1. Completion of Follow-up for Study Eyes

One year completed visits include visits that occurred between 308 and 420 days (between 44 and 60 weeks) from randomization. Two year completed visits include visits that occurred between 616 and 840 days (between 88 and 120 weeks) from randomization. Ranib = Ranibizumab; Triam = Triamcinolone

Figure 2a. Mean Change in Visual Acuity at Follow-up Visits for Cohort that Completed 2-Year Visit

Values that were ±30 letters were assigned a value of 30. P values for difference in mean change in visual acuity from sham+prompt laser at the 104-week study visit: ranibizumab+prompt laser =0.03, ranibizumab+deferred laser <0.001, and triamcinolone+prompt laser groups = 0.35. Each visit week includes visits that are ±14 days, except at the 52-week visit which includes visits that occur between 308 and 420 days (between 44 and 60 weeks) from randomization and at the 104-week visit which includes visits that occur between 616 and 840 days (between 88 and 120 weeks) from randomization.

Figure 2b. Mean Change in Optical Coherence Tomography Central Subfield Retinal Thickening at Follow-up Visits for Cohort that Completed 2-Year Visit

P values for difference in mean change in optical coherence tomography (OCT) central subfield retinal thickness from sham+prompt laser at the 104-week visit: ranibizumab+prompt laser = 0.003, ranibizumab+deferred laser = 0.01, and triamcinolone+prompt laser = 0.37. Each visit week includes visits that are ±14 days, except at the 52-week visit which includes visits that occur between 308 and 420 days (between 44 and 60 weeks) from randomization and at the 104-week visit which includes visits that occur between 616 and 840 days (between 88 and 120 weeks) from randomization.

Figure 3. Mean Change in Visual Acuity at Follow-up Visits Using All Available Data

Values that were ±30 letters were assigned a value of 30. P values for difference in mean change in visual acuity from sham+prompt laser at the 104-week study visit: ranibizumab+prompt laser = 0.05, ranibizumab+deferred laser <0.001, and triamcinolone+prompt laser groups = 0.57. Each visit week includes visits that are ±14 days, except at the 52-week visit which includes visits that occur between 308 and 420 days (between 44 and 60 weeks) from randomization and at the 104-week visit which includes visits that occur between 616 and 840 days (between 88 and 120 weeks) from randomization.

Figure 4. Mean Change in Visual Acuity at Follow-up Visits among Eyes that were Pseudophakic at Baseline for Cohort that Completed 2-Year Visit

Values that were ±30 letters were assigned a value of 30. P values for difference in mean change in visual acuity from sham+prompt laser at the 104-week study visit: ranibizumab+prompt laser =0.83, ranibizumab+deferred laser = 0.15, and triamcinolone+prompt laser groups = 0.53. Each visit week includes visits that are ±14 days, except at the 52-week visit which includes visits that occur between 308 and 420 days (between 44 and 60 weeks) from randomization and at the 104-week visit which includes visits that occur between 616 and 840 days (between 88 and 120 weeks) from randomization.

Figure 5. Mean Change in Optical Coherence Tomography Central Subfield Retinal Thickening at Follow-up Visits for Eyes that Were Pseudophakic at Baseline for Cohort that Completed 2-Year Visit

P values for difference in mean change in optical coherence tomography (OCT) central subfield retinal thickness from sham+prompt laser at the 104-week visit: ranibizumab+prompt laser = 0.32, ranibizumab+deferred laser =0.68, and triamcinolone+prompt laser = 0.44. Each visit week includes visits that are ±14 days, except at the 52-week visit which includes visits that occur between 308 and 420 days (between 44 and 60 weeks) from randomization and at the 104-week visit which includes visits that occur between 616 and 840 days (between 88 and 120 weeks) from randomization. OCT = optical coherence tomography.

Figure 6. Cumulative Probability of Cataract Surgery through the 2-Year Study Visit for All Eyes Phakic at Baseline

Eyes pending a 2-year visit or who were lost to follow-up were censored at their last visit. N is the number of eyes phakic at baseline.