Residual edema evaluation with ranibizumab 0.5 mg and 2.0 mg formulations for diabetic macular edema (REEF study)

Abstract

Purpose To compare the efficacy of ranibizumab 0.5-mg and 2.0-mg intravitreal injections for persistent diabetic macular edema (DME) previously treated with bevacizumab. Methods In all, 43 patients with residual center-involved DME following intravitreal bevacizumab were included in this 12-month prospective, nonrandomized, multicenter study. Enrolled patients received three monthly ranibizumab 0.5-mg injections. At month 3, patients with residual macular edema switched to three monthly injections of ranibizumab 2.0-mg. Assessments included monthly visual acuity and spectraldomain optical coherence tomography. Results Mean visual acuity improved by þ 6.4 letters at month 3 and þ 8.8 letters at month 6. Mean central subfield thickness (CST) decreased by -113 mm at month 3 and -165 mm at month 6. Before enrollment, 29/43 (67.4%) patients showed o10% CST reduction following monthly bevacizumab treatment. After three monthly ranibizumab 0.5-mg injections, 22/29 (75.9%) patients showed 410% reduction in CST, whereas 6 showed o10% reduction. Of these six, three (50%) showed 410% reduction in CST after switching to three monthly ranibizumab 2.0-mg doses. No serious adverse events were observed to month 6. Conclusion Ranibizumab 0.5-mg or 2.0-mg may improve visual and anatomic outcomes in patients with DME who demonstrated minimal or no response to bevacizumab therapy. Moreover, increased dosage of ranibizumab (2.0-mg) may provide additional benefit over ranibizumab 0.5-mg in some patients. However, 2.0-mg ranibizumab is not currently commercially licensed or available.

Treatment strategies for refractory diabetic macular edema: switching anti-VEGF treatments, adopting corticosteroid-based treatments, and combination therapy

“…Moreover, the 6/29 (20%) patients that did not respond adequately with ranibizumab 0.5 mg (CSFT reduction <10%) were switched to higher doses of three monthly 2.0 mg ranibizumab injections, which resulted in CSFT reduction >10% in 3 of 6 patients. Of note, the 2.0 mg dose of ranibizumab is not commercially available at this time [34].…”

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

“…37,38 This is in contrast to AMD where the effect of switching between anti-VEGFs in resistant cases has been studied extensively. [39][40][41][42][43][44][45] Switching to both aflibercept and ranibizumab has been attempted, with resistant cases usually showing variable degrees of improvement, making this strategy a reasonable option in cases of AMD.…”

Diabetic macular oedema: pathophysiology, management challenges and treatment resistance

“…These studies, summarised in Table 1, are heterogeneous in their design, inclusion and exclusion criteria and follow-up, making comparison difficult. However, there seems to be a universal anatomical improvement after switching from bevacizumab to ranibizumab [94][95][96]. and there may be a benefit in switching from either of these drugs to aflibercept [97][98][99].…”

“…The Residual Edema Evaluation with Ranibizumab 0.5 mg and 2.0 mg Formulations for Diabetic Macular Edema (REEF) study (ClinicalTrials.gov: NCT01292798) examined the effects of 0.5 mg and 2.0 mg ranibizumab on visual and anatomical outcomes for patients with bevacizumab-resistant DMO [95]. All participants were started on a 0.5 mg dose, which was increased to 2.0 mg if there was residual DMO after 3 months.…”