Should We WAVE Goodbye to Laser?

Saraniya Sathiamoorthi; Sophie J. Bakri, MD


August 01, 2017

Peripheral Laser for Recalcitrant Macular Edema Owing to Retinal Vein Occlusion: The WAVE Trial

Wykoff CC, Ou WC, Wang R, et al
Ophthalmology. 2017;124:919-921

Study Summary

The WAVE study was a 1-year, prospective, randomized, phase 4 trial that evaluated the role of targeted retinal photocoagulation (TRP) in reducing the ranibizumab injection burden in patients with retinal vein occlusion (RVO).

Eligible patients had a history of ischemic central or branch RVO with persistent or recurrent cystoid macular edema (CME) even after undergoing two or more consecutive monthly anti-vascular endothelial growth factor (VEGF) injections. Study participants were also required to have areas of retinal nonperfusion on wide-field fluorescein angiography that were amenable to TRP.

Once enrolled, patients (n = 30) were randomly assigned in a 1:4 ratio to receive ranibizumab monotherapy (n = 6) or combination therapy with ranibizumab and TRP (n = 24). All patients received six monthly ranibizumab injections, with an additional allowance of six monthly injections as clinically needed. The combination therapy cohort received TRP 1 week after the first ranibizumab injection, with additional TRP after the fourth month if indicated.

Primary outcome measures were mean changes from baseline of best corrected visual acuity and number of injections administered. Secondary outcome measures included mean changes in central retinal thickness and safety analyses.

The investigators found no additional benefits associated with TRP among primary or secondary outcome measures. There were no significant differences between the monotherapy and combination therapy groups in terms of mean gains in best corrected visual acuity or central retinal thickness after 1 year. Treatment burden was similar between the monotherapy and combination therapy groups; the mean total number of injections administered was 9.5 and 8.8, respectively, and 3.7 and 3.1 injections were given in the last 6 months. No safety signals were identified.


Despite its small sample size, the WAVE trial was a well-designed study. First, by requiring all patients to receive the same number of ranibizumab injections in the initial 6 months (with the addition of TRP in the combination therapy cohort), results could be better compared at the 6-month mark. In addition, by selecting patients with ischemic RVO and CME after two or more anti-VEGF injections, the investigators reduced the confounding that can occur when treatment-naive patients are included.

The investigators labeled these patients as having persistent or recurrent CME and most likely to benefit from TRP. However, it is unclear whether the edema, though persistent, had significantly improved from baseline, or whether it was entirely unaffected by the anti-VEGF injections. In addition, very little is currently known about the proper timing of TRP and whether patients who had had at least 2 months of macular edema would have benefited at all.

This study is important in answering a common clinical question: Does peripheral laser to areas of retinal ischemia help reduce macular edema, improve vision, and reduce injection burden in patients with RVO? In summary, the WAVE trial, along with the similar RELATE trial,[1] provides evidence against the use of adjunctive TRP to treat CME in patients with RVO.


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