Scatter Photocoagulation Does Not Reduce Macular Edema or Treatment Burden in Patients with Retinal Vein Occlusion: The RELATE Trial

Abstract

Purpose: To determine whether scatter and grid laser photocoagulation (laser) adds benefit to ranibizumab injections in patients with macular edema from retinal vein occlusion (RVO) and to compare 0.5-mg with 2.0-mg ranibizumab.

Design: Randomized, double-masked, controlled clinical trial.

Participants: Thirty-nine patients with central RVO (CRVO) and 42 with branch RVO (BRVO).

Methods: Subjects were randomized to 0.5 mg or 2.0 mg ranibizumab every 4 weeks for 24 weeks and re-randomized to pro re nata ranibizumab plus laser or ranibizumab alone.

Main outcome measures: Mean change from baseline best-corrected visual acuity (BCVA) at week 24 for BCVA at weeks 48, 96, and 144 for second randomization.

Results: Mean improvement from baseline BCVA at week 24 was 15.5 and 15.8 letters in the 0.5-mg and 2.0-mg CRVO groups, and 12.1 and 14.6 letters in the 0.5-mg and 2.0-mg BRVO groups. For CRVO, but not BRVO, there was significantly greater reduction from baseline mean central subfield thickness (CST) in the 2.0-mg versus 0.5-mg group (396.1 vs. 253.5 μm; P = 0.03). For the second randomization in CRVO patients, there was no significant difference from week 24 BCVA in the ranibizumab plus laser versus the ranibizumab only groups at week 48 (-3.3 vs. 0.0 letters), week 96 (+0.69 vs. -1.6 letters), or week 144 (+0.4 vs. -6.7 letters), and a significant increase from week 24 mean CST at week 48 (+94.7 vs. +15.2 μm; P = 0.05) but not weeks 96 or 144. For BRVO, there was a significant reduction from week 24 mean BCVA in ranibizumab plus laser versus ranibizumab at week 48 (-7.5 vs. +2.8; P < 0.01) and week 96 (-2.0 vs. +4.8; P < 0.03), but not week 144, and there were no differences in mean CST change from week 24 at weeks 48, 96, or 144. Laser failed to increase edema resolution or to reduce the ranibizumab injections between weeks 24 and 144.

Conclusions: In patients with macular edema resulting from RVO, there was no short-term clinically significant benefit from monthly injections of 2.0-mg versus 0.5-mg ranibizumab injections and no long-term benefit in BCVA, resolution of edema, or number of ranibizumab injections obtained by addition of laser treatment to ranibizumab.

Figure 2.

Graphs comparing visual and anatomic outcomes after injections of 2.0 mg versus 0.5 mg ranibizumab in patients with macular edema resulting from retinal vein occlusion. Patients with macular edema resulting from (A and C) branch retinal vein occlusion (BRVO) or (B and D) central retinal vein occlusion (CRVO) were randomized to receive an injection of 2.0 or 0.5 mg ranibizumab every 4 weeks. There was no significant difference between the 2.0-mg and 0.5-mg groups in mean change from baseline best-corrected visual acuity (BCVA) measured in Early Treatment Diabetic Retinopathy Study letter score at any time point through the week 24 end point in patients with (A) BRVO or (B) CRVO. C, In patients with BRVO, there was no significant difference between the 2.0-mg and 0.5-mg groups in mean change from baseline central subfield thickness (CST) measured by spectral-domain optical coherence tomography at any time point through the week 24. D, However, patients with CRVO who received injection of 2.0 mg ranibizumab had a significantly greater reduction in mean CST at several time points (*P = 0.03, independent samples t test), including week 24. Error bars show the standard error of the mean.

Figure 3.

Graphs showing long-term visual outcomes in patients with macular edema resulting from retinal vein occlusion treated with a combination of ranibizumab and scatter and grid laser photocoagulation versus ranibizumab alone. Patients were re-randomized at week 24 to pro re nata (PRN) ranibizumab plus scatter and grid laser photocoagulation (laser + RBZ) or PRN ranibizumab alone RBZ alone. The graphs show the mean (±standard error of the mean) change from week 24 in best-corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study letter score at all time points through week 144 in patients with (A) macular edema resulting from branch retinal vein occlusion (BRVO) or (B) central retinal vein occlusion (CRVO). There was no significant difference between laser plus ranibizumab and ranibizumab only groups at week 144 in patients with BRVO or CRVO.

Figure 4.

Graphs showing long-term anatomic outcomes in patients with macular edema resulting from retinal vein occlusion treated with a combination of ranibizumab plus scatter and grid laser photocoagulation versus ranibizumab alone. The graphs show the mean (±standard error of the mean) change from week 24 central subfield thickness (CST) at all time points after re-randomized to pro re nata (PRN) ranibizumab plus scatter and grid laser photocoagulation (laser + RBZ) or PRN ranibizumab alone (RBZ alone). There was no significant difference between the laser + ranibizumab and ranibizumab only groups at week 144 in patients with (A) BRVO or (B) CRVO.