Panretinal Photocoagulation vs Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy

Abstract

IMPORTANCE Panretinal photocoagulation (PRP) is standard treatment for reducing severe visual loss from proliferative diabetic retinopathy (PDR). However, PRP can damage the retina, resulting in peripheral vision loss or worsening diabetic macular edema (DME). OBJECTIVE Compare ranibizumab versus PRP for PDR. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial (55 U.S. sites) assessing non-inferiority of ranibizumab compared with PRP for vision outcomes; 305 adults with PDR enrolled February-December 2012 (mean age 52, 44% female, 52% white). Both eyes enrolled for 89 participants totaling 394 study eyes. The final 2-year visit was completed January 2015. INTERVENTIONS Ranibizumab group (N=191 eyes): intravitreous 0.5-mg ranibizumab and, PRP if treatment failed; ranibizumab as needed for DME. PRP group (N=203 eyes): PRP; ranibizumab as needed for DME. MAIN OUTCOMES AND MEASURES Primary: mean visual acuity change at 2 years (5-letter non-inferiority margin; intention-to-treat analysis). Secondary: visual acuity area under the curve, peripheral visual field loss, DME development, neovascularization, vitrectomy, and safety. RESULTS Mean visual acuity letter improvement at 2 years was +2.8 in the ranibizumab group versus +0.2 in the PRP group (difference +2.2, 95% confidence interval [CI]: −0.5 to +5.0, non-inferiority P<0.001). Mean treatment group difference in visual acuity area under the curve over 2 years was +4.2 (95% CI: +3.0 to +5.4, P<0.001). Visual field sensitivity loss was worse (mean dB difference 372; 95% CI: 213 to 531, P<0.001), vitrectomy more frequent (15% versus 4%, difference 9%, 95% CI: 4% to 15%, P<0.001), and DME development more frequent (28% versus 9%, difference 19%, 95% CI: 10% to 28%, P<0.001) in the PRP versus ranibizumab group, respectively. Eyes with neither active nor regressed neovascularization at 2 years was similar (35% [ranibizumab group] versus 30% [PRP group], difference 3%, 95% CI: −7% to 12%, P=0.58). One eye (ranibizumab group) developed endophthalmitis. No significant differences between groups in rates of major cardiovascular events were identified. CONCLUSION Among eyes with PDR, treatment with ranibizumab resulted in visual acuity that was non-inferior to (not worse than) PRP treatment at two years. Although longer term follow-up is needed, ranibizumab may be a reasonable treatment alternative, at least through 2 years, for patients with PDR.

The RELATION study: efficacy and safety of ranibizumab combined with laser photocoagulation treatment versus laser monotherapy in NPDR and PDR patients with diabetic macular oedema

“…DRCR.net studies have shown the combination to be noninferior to PRP alone in improvement of VA after 2 years of treatment (Writing Committee for the Diabetic Retinopathy Clinical Research Network et al. 2015). Although numerically higher improvement in BCVA was noted in the COMBI versus LASER group in our study, the sample size was too low to draw any robust conclusions.…”

“…2013; Writing Committee for the Diabetic Retinopathy Clinical Research Network et al. 2015), it may be hypothesized that higher mean BCVA gains might have been observed in the RELATION study if it had completed the planned full 12 months. The United States Food and Drug Administration has recently approved ranibizumab for the treatment of all forms of DR (Genentech Press Release 2017).…”

The Role of Anti-vascular Endothelial Growth Factor Agents in the Management of Retinopathy of Prematurity

“…65,66 There are currently four anti-VEGF agents on the market delivered as intravitreal injections: pegaptanib, ranibizumab, aflibercept, and bevacizumab. While bevacizumab is not currently approved for intravitreal use, its off label use has been well tolerated and quite effective in treating the entities described above for over 10 years.…”

Screening for Diabetic Retinopathy

“…Diabetic retinopathy is the leading cause of new cases of blindness in the US and the most common cause of blindness in North Carolina. With timely laser treatment and intravitreal anti-vascular endothelial growth factor (VEGF) therapy, severe vision loss from diabetic retinopathy can be reduced by 90% [2][3][4]. However, because early diabetic retinopathy is usually asymptomatic, the only avenue for patients to present in a timely fashion is through early screening.…”