Completers and non-completers differed in racial/ethnicity distribution, with a higher proportion of the completers being white and a higher proportion of non-completers (who had the potential to complete the study before it was closed) being Hispanic (, available at www.archophthalmol.com
). In all three treatment groups, baseline visual acuity was similar in completers and non-completers. However, visual acuity during follow up on average was about 4 letters worse in non-completers (who had the potential for 3 year follow up) through their last completed visit compared with the completers (P=0.01). Visual acuity during follow up appeared to be similar in completers and the non-completers who did not have the potential for 3-year follow up (P=0.15).
Baseline Characteristics Comparing Completers and Non-completers*
Among the eyes with three-year follow up, the mean number of treatments with the assigned treatment regimen during the three years of follow up were 3.1 in the laser group, 4.2 in the 1 mg triamcinolone group, and 4.1 in the 4 mg triamcinolone group. There were no cases of endophthalmitis following any of the 1898 injections during the entire study. During the third year of follow up, 20 (17%), 22 (24%), and 28 (29%) of eyes in the three treatment groups, respectively, were treated once with the assigned treatment regimen, 8 (7%), 9 (10%), and 21 (21%) were treated twice, and 1 (1%), 8 (9%), and 4 (4%) were treated three times.
Among the 3-year completers, 7 (6%) in the laser group received the 4 mg triamcinolone study drug at some point during the 3 years of follow up, 21 (23%) in the 1 mg triamcinolone group received focal/grid photocoagulation, and 20 (20%) in the 4 mg triamcinolone group received focal/grid photocoagulation. Other treatments for DME (primarily vitrectomy, nonstudy triamcinolone [Kenalog], and bevacizumab) were received by 15 (13%), 16 (17%), and 11 (11%) of eyes in the three treatment groups, respectively.
Effect of Treatment on Visual Acuity
Between two years and three years of follow up, visual acuity improved more often than it worsened in all three treatment groups. Among eyes with visual acuity at two years that was worse than 20/32, about twice as many in each treatment group improved 10 or more letters than worsened 10 or more letters from 2 to 3 years (, available at www.archophthalmol.com
Change in Visual Acuity from 2 Years to 3 Years Stratified by 2 Year Visual Acuity*
At 3 years, visual acuity outcomes slightly favored the laser group compared with the two triamcinolone groups (), with the differences between groups at 3 years being of similar magnitude to the differences at 2 years (). The mean change in the visual acuity letter score from baseline to 3 years was +5 in the laser group and 0 in the two triamcinolone groups (for the 3 2-group comparisons, mean difference adjusted for baseline visual acuity and prior macular photocoagulation: laser-1mg = +5.6 [95% confidence interval +0.8 to +10.4], laser-4mg = +4.7 [95% confidence interval 0.0 to +9.5] 1mg-4mg = −0.8 [95% confidence interval −6.0 to +4.3]). Using multiple imputation to handle missing data for eyes without 3-year follow up, mean change in the letter score was +2, 0, and −1, respectively and using the last observation carried forward method, mean change in the letter score was +1, −1, and −2, respectively. For the subjects with two study eyes, the mean paired difference in the change in the visual acuity letter score at 3 years was +9.3 (95% confidence interval +2.1 to +16.4) for the laser-1 mg subjects (N=29) and +4.6 (95% confidence interval −6.2 to +15.5) for the laser-4 mg triamcinolone subjects (N=27), in each case favoring the laser group.
Change in Visual Acuity and Retinal Thickness from Baseline to 3 Years*
Mean visual acuity at each visit according to treatment group. Figure 1A: Includes all available data from all randomized eyes. Figure 1B: Includes all available data from the cohort of eyes that completed the 3 year visit.
Among the completers of the 3-year visit, 51 (44%) in the laser group, 23 (25%) in the 1 mg group, and 37 (38%) in the 4 mg group had improvement in the visual acuity letter score of 10 or more from baseline to 3 years and 14 (12%), 24 (26%), and 22 (22%), respectively had worsening of 10 or more letters. For comparison, from baseline to 2 years among the completers of the 3-year visit, the percentages were 33%, 18%, and 32%, respectively improving and 12%, 29%, and 27%, respectively, worsening.
Results of treatment group comparisons were similar when limited to eyes that were either pseudophakic or had minimal lens changes by clinician assessment at 3 years. The mean change in the visual acuity letter score from baseline to 3 years was +5 in the laser group (N=79), +2 in the 1 mg triamcinolone group (N=61), and 0 in the 4 mg triamcinolone group (N=90).
Effect of Treatment on Retinal Thickening
Similar to the visual acuity results, more eyes in all three treatment groups had a decrease in OCT central subfield thickness from year two to year three than had an increase (, available at www.archophthalmol.com
). At three years, central subfield thickness was <250 microns in 75 (67%) eyes in the laser group, 37 (43%) in the 1 mg triamcinolone group, and 45 (51%) in the 4 mg triamcinolone group ().
Change in Central Subfield Thickness from 2 Years to 3 Years Stratified by 2 Year Central Subfield Thickness*
Glaucoma and Cataract
Four eyes in the 4 mg triamcinolone group had a procedure for glaucoma prior to the 2-year visit (1 had laser trabeculoplasty and 3 had glaucoma surgery), but there were no additional cases of glaucoma surgery in any treatment group during the third year of follow up. At 3 years, mean intraocular pressure was 16±3 mm Hg in the laser group, 17±3 mm Hg in the 1 mg triamcinolone group, and 16±4 mm Hg in the 4 mg triamcinolone group, with 6 (5%), 14 (15%), and 10 (10%) having an intraocular pressure ≥21 mm Hg. Intraocular pressure lowering medications were being used in 3 (3%), 2 (2%), and 12 (12%) eyes, respectively. Among completers of the 3-year visit, an intraocular pressure increase of ≥10 mm Hg occurred at any visit between baseline and 2 years in 4 (3%) eyes in the laser group, 16 (17%) in the 1 mg triamcinolone group, and 30 (31%) in the 4 mg triamcinolone group, and occurred at any visit between baseline and 3 years in 4%, 18%, and 33%, respectively.
Among phakic eyes at baseline, the three-year cumulative probability of cataract surgery was 31% in the laser group, 46% in the 1 mg group, and 83% in the 4 mg group (P<0.001 for all pairwise comparisons). Excluding eyes in the laser group that received triamcinolone, the cumulative probability was 27%. The timing of the cataract surgery is depicted in .
Cumulative probability of cataract surgery for all eyes phakic at baseline. The “# eyes at risk” indicates the number of eyes still in follow up at the beginning of the interval.