Persistent Macular Thickening Following Intravitreous Aflibercept, Bevacizumab, or Ranibizumab for Central-Involved Diabetic Macular Edema With Vision Impairment

Abstract

Prevalence of persistent central-involved diabetic macular edema (DME) through 24 weeks of anti-vascular endothelial growth factor therapy and its longer-term outcomes may be relevant to treatment. OBJECTIVE To assess outcomes of DME persisting at least 24 weeks after randomization to treatment with 2.0-mg aflibercept, 1.25-mg bevacizumab, or 0.3-mg ranibizumab. DESIGN, SETTING, AND PARTICIPANTS Post hoc analyses of a clinical trial, the DRCR.net Protocol T among 546 of 660 participants (82.7%) meeting inclusion criteria for this investigation. INTERVENTIONS Six monthly intravitreous anti-vascular endothelial growth factor injections (unless success after 3 to 5 injections); subsequent injections or focal/grid laser as needed per protocol to achieve stability. MAIN OUTCOMES AND MEASURES Persistent DME through 24 weeks, probability of chronic persistent DME through 2 years, and at least 10-letter (Ն 2-line) gain or loss of visual acuity. RESULTS The mean age of participants was 60 years, 363 (66.5%) were white, and 251 (46.0%) were women. Persistent DME through 24 weeks was more frequent with bevacizumab (118 of 180 [65.6%]) than aflibercept (60 of 190 [31.6%]) or ranibizumab (73 of 176 [41.5%]) (aflibercept vs bevacizumab, P < .001; ranibizumab vs bevacizumab, P < .001; and aflibercept vs ranibizumab, P = .05). Among eyes with persistent DME through 24 weeks (n = 251), rates of chronic persistent DME through 2 years were 44.2% with aflibercept, 68.2% with bevacizumab (aflibercept vs bevacizumab, P = .03), and 54.5% with ranibizumab (aflibercept vs ranibizumab, P = .41; bevacizumab vs ranibizumab, P = .16). Among eyes with persistent DME through 24 weeks, proportions with vs without chronic persistent DME through 2 years gaining at least 10 letters from baseline were 62% of 29 eyes vs 63% of 30 eyes (P = .88) with aflibercept, 51% of 70 vs 55% of 31 (P = .96) with bevacizumab, and 45% of 38 vs 66% of 29 (P = .10) with ranibizumab. Only 3 eyes with chronic persistent DME lost at least 10 letters. CONCLUSIONS AND RELEVANCE Persistent DME was more likely with bevacizumab than with aflibercept or ranibizumab. Among eyes with persistent DME, eyes assigned to bevacizumab were more likely to have chronic persistent DME than eyes assigned to aflibercept. These results suggest meaningful gains in vision with little risk of vision loss, regardless of anti-vascular endothelial growth factor agent given or persistence of DME through 2 years. Caution is warranted when considering switching therapies for persistent DME following 3 or more injections; improvements could be owing to continued treatment rather than switching therapies. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT011627249

Serum pro‐inflammatory factors as predictors of persistent diabetic macular oedema with limited anatomic response to anti‐VEGF: association with intravitreal injection treatment profiles in real‐world setting

“…Additionally, it is important to note that while our results were achieved following a treatment strategy applied in a real‐world clinical setting, our rate of persistent DME after 6 months of BVZ treatment (62% of cases) was very similar to that reported in a post hoc analysis of Protocol T (65.6% of cases) (Bressler et al. ). Such DRCR.net analysis revealed that there is a tendency for persistent DME to improve with continued anti‐VEGF treatment, yet it is important to notice that with BVZ, 68.2% of cases still had macular thickening after 24 months of treatment and while aflibercept fared better, there was still a very significant percentage of these cases with persistent oedema (44.2%) at 24 months.…”

“…Additionally, depending on the chosen anti‐VEGF agent, it is estimated that up to 65% of cases may have persistent DME, despite six monthly intravitreal injections (IVI; Bressler et al. ). Such results suggest that, notwithstanding the prominent role of VEGF in vasopermeability, other pathogenic pathways may contribute to persistent disruption of the inner blood‐retinal barrier (BRB).…”

Guidance for anti-VEGF intravitreal injections during the COVID-19 pandemic

“…In general, patients with neovascular age-related macular degeneration (especially those in the first 2 years of treatment), neovascular glaucoma, new cases with significant vision loss, new central retinal vein occlusion cases, and monocular or quasi-monocular patients (only one eye > 20/40) should be prioritized and their treatment schedules maintained. Patients with DME and branch retinal vein occlusion are less likely to suffer irreversible vision loss in the short term [18,19], and postponement of appointments for nonmonocular patients may be considered (except for patients with significant vision loss from recent DME and patients in the acute phase of retinal vein occlusion). However, prolonged treatment postponement (> 4-6 months) should be avoided and the situation should be reassessed within 2-3 months depending on the stage of the pandemic and the confinement measures in place in each individual country.…”

<p>The Evolving Treatment of Diabetic Retinopathy</p>

“…Despite the effectiveness of the current anti-VEGF agents in reducing progression of diabetic retinopathy and DME, protocol T of the DRCR Network demonstrated the incidence of persistent DME at 24 weeks to be 65.6% for bevacizumab, 31.6% for aflibercept, and 41.5% for ranibizumab. 266 In clinical practice, an analysis of Medicare claims data indicates that approximately 50% of DME patients will have persistent edema after 1 year of anti-VEGF treatment. 267 These rates of persistent DME in conjunction with the concomitant need for continuous monitoring call into question the long-term sustainability of such strategies.…”