Five-Year Outcomes of Ranibizumab With Prompt or Deferred Laser Versus Laser or Triamcinolone Plus Deferred Ranibizumab for Diabetic Macular Edema

Abstract

Purpose To compare long-term vision and anatomic effects of ranibizumab with prompt or deferred laser vs laser or triamcinolone + laser with very deferred ranibizumab in diabetic macular edema (DME). Design Randomized clinical trial. Methods Eight hundred and twenty-eight study eyes (588 [67%] completed the 5-year visit), at 52 sites, with visual acuity 20/32 to 20/320 and DME involving the central macula were randomly assigned to intravitreous ranibizumab (0.5 mg) with either (1) prompt or (2) deferred laser; (3) sham injection + prompt laser; or (4) intravitreous triamcinolone (4 mg) + rompt laser. The latter 2 groups could initiate ranibizumab as early as 74 weeks from baseline, for persistent DME with vision impairment. The main outcome measures were visual acuity, optical coherence central subfield thickness, and number of injections through 5 years. Results At 5 years mean (± standard deviation) change in Early Treatment Diabetic Retinopathy Study visual acuity letter scores from baseline in the ranibizumab + eferred laser (N = 111), ranibizumab + rompt laser (N = 124), laser/very deferred ranibizumab (N = 198), and triamcinolone + laser/very deferred ranibizumab (N = 125) groups were 10 ± 13, 8 ± 13, 5 ± 14, and 7 ± 14, respectively. The dif-ference (95% confidence interval) in mean change be-tween ranibizumab + eferred laser and laser/very deferred ranibizumab and triamcinolone D laser/very deferred ranibizumab was 4.4 (1.2-7.6, P = .001) and 2.8 (−0.9 to 6.5, P = .067), respectively, at 5 years. Conclusions Recognizing limitations of follow-up available at 5 years, eyes receiving initial ranibizumab therapy for center-involving DME were likely have better long-term vision improvements than eyes managed with laser or triamcinolone + aser followed by very deferred ranibizumab for persistent thickening and vision impairment.

Ranibizumab for the Treatment of Diabetic Macular Oedema in the Real-World Clinical Setting in Portugal: A Multicentre Study

“…As for systemic events, there were 2 patients who suffered a myocardial infarction. These adverse events are in accordance with reports from major studies [15, 16]. However, it is a reminder that caution is advisable with regard to anti-VEGF therapy in a population with significant cardiovascular risk factors.…”

“…The DRCR.net Protocol I at 5 years reports that eyes that had received very deferred ranibizu­mab did not achieve the same long-term improvement when compared with ranibizumab therapy as a first-line treatment strategy [16]. Chronic DME and laser-related structural damage could also cause irreversible vision loss from retinal atrophy, neural cell loss, and other permanent structural changes [16]. Therefore, the chronicity of DME in some of our patients and thus the relative “delay” in starting IVR are important factors further contributing to the lower functional gain in our series.…”

Role of Inflammation in Diabetic Retinopathy:Therapeutic Targets

“…Triamcinolone is as effective in reducing central retinal thickness in patients with DME as ranibizumab, although the effectiveness gradually diminishes due to increased rates of cataract formation. However, triamcinolone plus laser in pseudophakic DME patients was found to be superior to laser alone and equivalent to ranibizumab; it may be an effective treatment in anti-VEGF nonresponders 10,63 . In addition to triamcinolone injections, dexamethasone intravitreal implants and fluocinolone acetonide intravitreal inserts have shown substantial benefit in improving visual acuity in DME patients 64,65 .…”

Effect of Leaking Foveal Microaneurysms on the Treatment of Center-Involving Diabetic Macular Edema: A Pilot Study

“…Anti-VEGF agents have been well demonstrated to provide superior vision recovery over other treatments, such as focal/grid laser by the Early Treatment Diabetic Retinopathy Study (ETDRS) group [3, 7, 8] or steroids [3, 9]. Consequently, we have been developing an adjunct therapy to minimize the required numbers of injections and maximize the adherence and benefit of anti-VEGF treatment in DME patients.…”