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 either 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 through 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 vs. deferred laser groups respectively, there was vision loss of ≥10 letters in 9% vs. 8%, an improvement of ≥10 letters in 46% vs. 58%, and an improvement of >15 letters in 27% vs. 38% of participants. From baseline through 5 years, 56% of participants in the deferred group did not receive laser. The median number of injections was 13 vs. 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. While over half of eyes where 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.

Long-Term Outcome of Approved Pharmacotherapy for Diabetic Macular Edema: A Review of Randomized Controlled Trials in Fluocinolone Acetonide Implants, Dexamethasone Implants, Aflibercept and Ranibizumab

“…After three-year follow-up, the mean visual change was +9.7 letters in the ranibizumab with deferral laser, significantly better than +6.8 letters in the ranibizumab with prompt laser [3]. Although the five-year visual outcome revealed similar visual gains (+7.2 and +9.8 letters) were observed between the ranibizumab with prompt and deferral laser, better visual outcome was detected in the deferral laser (+17 letters) than in the prompt laser (+10 letters) in the subgroup with poor baseline vision [4]. Fewer cumulative ranibizumab injections were required in the ranibizumab with prompt laser group (median 13 injections) than in the ranibizumab with deferral laser group (median 17 injections).…”

“…The pathophysiology of macular edema involves both the presence of inflammation and angiogenic stimulant regarding vascular endothelial growth factor (VEGF) [1]. Intravitreal injections of anti-VEGF, including ranibizumab [2][3][4][5][6][7][8], bevacizuamb [9], pegaptanib [10], aflibercept [11] are proven to be effective for managing DME. Intravitreal injections of corticosteroids, potent anti-inflammatory agents, such as fluocinolone acetonide implants (Retisert) [12], fluocinolone acetonide inserts (Iluvein) [13,14], dexamethasone implants [15,16], and triamcinolone acetonide [2] have been shown to be beneficial to DME.…”

Aflibercept in diabetic macular edema: evaluating efficacy as a primary and secondary therapeutic option

“…Aflibercept in diabetic macular edema: evaluating efficacy as a primary and secondary therapeutic option Anti-vascular endothelial factors (anti-VEGFs) have become the standard of care in the treatment of diabetic macular edema (DME) after several randomized clinical trials (RCTs) established their efficacy compared with other treatment modalities such as laser therapy and steroids. [1][2][3] There are currently three anti-VEGF drugs that are available for clinical practice; aflibercept (Eylea, Regeneron Pharmaceuticals, Tarrytown, NY, USA), bevacizumab (Avastin, Genentech, South San Francisco, CA, USA), and ranibizumab (Lucentis, Genetech, South San Francisco, CA, USA). Aflibercerpt, previously known as VEGF Trap-EYE, is a 115-kDA recombinant fusion protein consisting of the VEGF binding domains of human VEGF receptors 1 and 2 fused to the Fc Domain of human immunoglobulin-G1.…”

“…5 Both ranibizumab (Lucentis) and bevacizumab (Avastin) have been studied extensively in several large randomized controlled trials in the treatment of DME. 1,2,6,7 Patients treated with both drugs have shown excellent visual gains, long term stability and improved anatomy compared with grid laser treatment and steroid injections, making them the first line treatment for visual loss associated with DME. 2 A study by Regnier et al 8 showed that the lifetime cost of treating patients with DME in the UK was £20 019 for ranibizumab PRN and £25 859 for aflibercept using a bimonthly dosing regimen.…”

“…1,2,6,7 Patients treated with both drugs have shown excellent visual gains, long term stability and improved anatomy compared with grid laser treatment and steroid injections, making them the first line treatment for visual loss associated with DME. 2 A study by Regnier et al 8 showed that the lifetime cost of treating patients with DME in the UK was £20 019 for ranibizumab PRN and £25 859 for aflibercept using a bimonthly dosing regimen. It also demonstrated that from a UK healthcare perspective ranibizumab provides greater health gains with lower overall costs than aflibercept.…”