Researchers in the United Kingdom compared the 1-year safety and efficacy of intravitreal aflibercept to panretinal photocoagulation (PRP) for proliferative diabetic retinopathy (PDR).
Study design
This multicenter, randomized, phase 2b, single-masked, non-inferiority CLARITY trial (clinical efficacy and mechanistic evaluation of aflibercept for proliferative diabetic retinopathy) included 232 patients with type 1 or 2 diabetes and active PDR. All patients were treatment-naïve or had prior PRP. The cohort was randomized 1:1 to intravitreal aflibercept (2 mg/0.05 mL at baseline, 4 weeks, 8 weeks, and from 12 weeks as-needed) or standard PRP (single spot or multispot laser at baseline, every 2 weeks thereafter, and from 12 weeks as-needed) for 52 weeks.
The primary outcome was change in best-corrected visual acuity (BCVA) from baseline using a linear mixed-effect model that excluded fluctuations due to vitreous hemorrhage. The noninferiority margin was prespecified as -5 ETDRS letters.
Outcomes
At 1 year, investigators found that aflibercept monotherapy was both noninferior and superior to PRP. BCVA was significantly improved in both the intention-to-treat population (+3.9 letters, P<0.0001) and the per-protocol population (+4.0 letters, P<0.0001). This effect was achieved with a mean of 4 injections that included the mandated 3 loading injections, irrespective of the PDR risk status and previous treatment history.
Almost 90% of patients in the aflibercept group had no macular edema at 52 weeks compared with 71% of patients receiving PRP. Regression of retinal neovascularization was also favored in the aflibercept group by over 30% (P<0.0001).
There were no significant differences in safety concerns, but the aflibercept group had numerically fewer adverse effects in binocular visual acuity and visual fields. Patient satisfaction scores also revealed a preference for the anti-VEGF therapy in a clinical trial setting (P=0.02), further highlighting the advantages of aflibercept over PRP.
Clinical significance
Two randomized clinical trials have now reported successful outcomes with the use of anti-VEGF injections compared with PRP treatment, which was the standard of care for PDR for over 40 years. Two-year findings from the Diabetic Retinopathy Clinical Research Network’s (DRCR.net) Protocol S showed noninferiority of intravitreal ranibizumab compared with PRP for high-risk PDR.
The authors of the CLARITY study conclude that a longer-term phase 3 trial is needed. Though the results are impressive and could theoretically change clinical practice, the paradigm shift may be difficult to implement. PRP is generally viewed as a permanent treatment for PDR, and physicians may hesitate to introduce intravitreal injections as a monotherapy due to fears of noncompliance.