Simultaneous Inhibition of Angiopoietin-2 and Vascular Endothelial Growth Factor-A with Faricimab in Diabetic Macular Edema: BOULEVARD Phase 2 Randomized Trial.

PURPOSE: The phase 2 BOULEVARD trial compared safety and efficacy of faricimab, a novel bispecific antibody targeting angiopoietin-2 and vascular endothelial growth factor-A (VEGF-A), with ranibizumab in patients with diabetic macular edema (DME). DESIGN: The BOULEVARD trial (ClinicalTrials.gov identifier, NCT02699450) was a prospective, randomized, active comparator-controlled, double-masked, multicenter, phase 2 study conducted at 59 sites in the United States. PARTICIPANTS: The trial enrolled patients 18 years of age or older with center-involving DME, best-corrected visual acuity (BCVA) of 73 to 24 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, and central subfield thickness (CST) of 325 µm or more. METHODS: Anti-VEGF treatment-naïve patients were randomized 1:1:1 to intravitreal 6.0 mg faricimab, 1.5 mg faricimab, or 0.3 mg ranibizumab, and patients previously treated with anti-VEGF were randomized 1:1 to 6.0 mg faricimab or 0.3 mg ranibizumab. Patients were dosed monthly for 20 weeks, followed by an observation period up to week 36 to assess durability. MAIN OUTCOME MEASURES: The prespecified primary outcome measure was mean change in BCVA from baseline at week 24 for faricimab versus ranibizumab in treatment-naïve patients. Key secondary and exploratory outcome measures included CST, Diabetic Retinopathy Severity Scale (DRSS) score, and durability as assessed by time to re-treatment. RESULTS: The trial enrolled 229 patients (168 treatment-naïve and 61 previously treated with anti-VEGF). In treatment-naïve patients, 6.0 mg faricimab, 1.5 mg faricimab, and 0.3 mg ranibizumab resulted in mean improvements of 13.9, 11.7, and 10.3 ETDRS letters from baseline, respectively. The 6.0-mg faricimab dose demonstrated a statistically significant gain of 3.6 letters over ranibizumab (P = 0.03). In both patient populations, faricimab resulted in dose-dependent reductions in CST, improvements in DRSS score, and longer time to re-treatment during the observation period compared with ranibizumab. Faricimab showed no new or unexpected safety signals. CONCLUSIONS: The BOULEVARD trial met its primary end point; faricimab demonstrated statistically superior visual acuity gains versus ranibizumab at week 24 in treatment-naïve patients. Central subfield thickness reduction, DRSS score improvement, and extended durability outcomes support the primary outcome. These findings suggest the benefit of simultaneous inhibition of angiopoietin-2 and VEGF-A with faricimab for patients with DME.

Fibrovascular ingrowth at sclerotomy sites in vitrectomized diabetic eyes with recurrent vitreous hemorrhage: ultrasound biomicroscopy findings.

PURPOSE: To evaluate the frequency of fibrovascular ingrowth (FVIG) at sclerotomy sites in vitrectomized eyes of diabetic patients with postoperative vitreous hemorrhage referred for ultrasound biomicroscopy (UBM). DESIGN: Retrospective observational case series. PARTICIPANTS: Twenty-six eyes of 23 diabetic patients with recurrent, nonclearing postoperative vitreous hemorrhage subsequent to pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR). METHODS: Ultrasound biomicroscopy evaluation of all sclerotomy sites in patients referred for postoperative nonclearing or recurrent vitreous hemorrhage after PPV for PDR. Correlation with intraoperative findings was obtained in eyes undergoing revision of the vitrectomy. Eight eyes underwent repeat UBM after revision of the vitrectomy, and changes at previous sclerotomy sites were evaluated. MAIN OUTCOME MEASURES: Ultrasound biomicroscopy images at each sclerotomy site were classified into 3 categories: none (grade 0), minor (grade 1), and major (grade 2). The UBM characteristics of each category were defined by the examiner. Logistic regression analysis was performed to identify prognostic factors associated with development of FVIG in the study patients. RESULTS: Grade 1 or 2 FVIG was detected in 85% of cases, and grade 2 FVIG was identified in >/=1 sclerotomy site in 58% of cases. Grade 1 or 2 FVIG was detected in 56% of microvitrector sites, 41% of infusion sites, and 61% of light port sites. Ten patients underwent repeat vitrectomy because of recurrent nonclearing vitreous hemorrhage and UBM images showing FVIG. Inspection of the sclerotomy site confirmed the UBM findings in every case. Eight of these patients underwent follow-up UBM evaluation subsequent to the repeat vitrectomy. In 6 of the 8 patients, follow-up UBM showed no residual FVIG. CONCLUSIONS: Ultrasound biomicroscopy showed FVIG in a high proportion of eyes that experienced recurrent nonclearing vitreous hemorrhage after PPV for PDR. Ultrasound biomicroscopy is capable of detecting and characterizing FVIG at sclerotomy sites and may aid in reoperative planning.

Photodynamic therapy with verteporfin for subretinal neovascularization secondary to bilateral idiopathic acquired juxtafoveolar telangiectasis.

The clinical course of a patient treated with multiple sessions of photodynamic therapy (PDT) with verteporfin for subretinal neovascularization secondary to bilateral idiopathic acquired juxtafoveolar telangiectasis is described. The patient presented with subfoveal subretinal neovascularization in one eye secondary to bilateral idiopathic acquired juxtafoveolar telangiectasis. The visual acuity improved from 5/40 to 20/60 and fluorescein angiography documented near-complete closure of the subretinal neovascularization within 2 weeks following the initial session of PDT. The visual acuity decreased to 20/200 and fluorescein angiography documented reperfusion of the neovascular membrane 6 weeks later. Four additional sessions of PDT were administered during the next 13 months with similar results. This case indicates that PDT for subretinal neovascularization due to bilateral idiopathic acquired juxtafoveolar telangiectasis may achieve partial short-term neovascular membrane closure and improvement in visual acuity.