Brolucizumab 19.8mg/0.165ml solution for injection pre-filled syringes

Polypoidal choroidal vasculopathy (PCV) represents a distinct subtype of neovascular age-related macular degeneration (nAMD). PCV is currently managed using intravitreal anti-vascular endothelial growth factor (VEGF) agents such as brolucizumab and aflibercept. This meta-analysis compares the effectiveness of brolucizumab and aflibercept in PCV patients. We systematically searched four electronic databases to identify eligible studies. Data extraction and pooling were performed utilizing the mean difference (MD) or rate ratio (RR) through the generic inverse variance method, with significance determined by a p-value < 0.05 between intervention subgroups. The generic inverse variance analysis method was applied with the employment of the random-effect model when data were heterogeneous. We retrieved 44 studies, 35 were included in the meta-analysis. The analysis compared the efficacy of aflibercept and brolucizumab in patients with nAMD over 3-6 months and 12 months. For best-corrected visual acuity (BCVA), the MD between aflibercept and brolucizumab were -0.11 versus -0.06 at 3-6 months and -0.11 versus -0.04 at 12 months, with no substantial differences (p = 0.58 and p = 0.08, respectively). Regarding polypoidal regression, RR after aflibercept use was 53% versus 70% for brolucizumab at 3-6 months and 47% versus 61% at 12 months, with no significant differences (p = 0.19 and p = 0.31, respectively). In terms of central retinal thickness (CRT), the MDs for aflibercept versus brolucizumab were -129.03 versus -143.93 at 3-6 months and -129.72 versus -145.32 at 12 months, without significant differences (p = 0.62 for both). For central choroidal thickness (CCT) and central foveal thickness (CFT), no significant differences were found between the two interventions at either time point. However, for central macular thickness, brolucizumab demonstrated superiority over aflibercept at 12 months (MD = -119.29 versus -215.00, p < 0.0001). In conclusion, our meta-analysis comparing aflibercept and brolucizumab in PCV revealed no significant differences in BCVA, polypoidal regression, CRT, CCT, and CFT at 6 or 12 months. Overall, both drugs demonstrated comparable efficacy in managing PCV.

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Background: Laser Speckle Flowgraphy (LSFG) is a non-invasive imaging technology that quantitatively evaluates retinal and choroidal blood flow by analyzing speckle patterns generated by laser light scattering. This systematic review summarizes the application of LSFG in two major degenerative retinal diseases: age-related macular degeneration (AMD) and diabetic retinopathy (DR). Methods: A comprehensive literature search (2010-2025) was conducted in PubMed, Cochrane Library and EMBASE according to PRISMA guidelines. Twenty-three studies including a total of 974 eyes (191 AMD, 783 DR) were analyzed. Results: In AMD, LSFG detected baseline reductions in choroidal and retinal perfusion in non-exudative disease, often extending beyond atrophic regions. Anti-VEGF injections produced acute reductions in MBR, particularly with brolucizumab, with partial recovery over time; drug-specific differences suggest a potential impact on geographic atrophy progression. In DR, LSFG revealed early microvascular dysfunction even in asymptomatic eyes. Retinal and choroidal MBR and blowout score correlated with HbA1c, DR severity, and inflammatory mediators. Intravitreal anti-VEGF therapy consistently reduced retinal and choroidal MBR and RFV, while conventional panretinal photocoagulation decreased choroidal flow and vascular caliber more robustly than patterned laser, reflecting oxygenation-driven VEGF modulation. Low baseline MBR predicted higher central macular thickness and reduced therapeutic response in diabetic macular edema. Conclusions: LSFG provides reproducible, rapid, and non-invasive quantitative insights into ocular hemodynamics across degenerative retinal diseases. Its integration into multimodal imaging may facilitate early diagnosis, support personalized management, and assist in the prognostic assessment of retinal and choroidal vascular disorders.

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IntroductionNeovascular age-related macular degeneration (nAMD) is a leading cause of irreversible vision loss in older adults. Intravitreal anti-vascular endothelial growth factor (VEGF) agents-including Aflibercept, Ranibizumab, Bevacizumab, Brolucizumab, and Faricimab-are the mainstay of therapy. However, their comparative efficacy and safety remain uncertain. This study aimed to compare the visual and systemic outcomes of these agents to inform clinical decision-making.MethodsA systematic search of PubMed, Embase, Scopus, and Web of Science from inception to September 2025 identified randomized controlled trials (RCTs) and observational studies comparing at least two anti-VEGF agents in nAMD. Eligible studies reported outcomes of best-corrected visual acuity (BCVA) change, visual gain ≥ 15 letters, mortality, or arteriothrombotic events. Risk of bias was assessed using Cochrane Risk of Bias 2 (RoB 2) and Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tools. A frequentist network meta-analysis estimated mean differences (MD) and odds ratios (OR) with 95 % confidence interval (CI). The protocol was registered in PROSPERO (CRD42025631298).ResultsSixteen studies involving 6758 participants (follow-up 3-24 months) met the inclusion criteria. For BCVA improvement, Aflibercept had the highest surface under the cumulative ranking curve (SUCRA) ranking (0.80), although all agents showed similar mean differences that were not statistically significant: aflibercept (MD 0.80; 95 % CI -1.20-2.80), Ranibizumab (0.64; -1.87-3.15), Bevacizumab (0.60; -2.02-3.22), Faricimab (2.20; -0.69-5.09), and Brolucizumab (4.20; -5.97-14.36). The larger point estimate for Brolucizumab reflects imprecision rather than superior visual efficacy. Mortality was lowest with Aflibercept (risk ratio (RR) 0.76; 95% CI 0.41-1.55). For arteriothrombotic events, no statistically significant differences were observed between anti-VEGF agents. Comparisons between Aflibercept and Bevacizumab (RR 1.11; 95% CI 0.60-2.07), aflibercept and Ranibizumab (RR 0.77; 95% CI 0.49-1.21), and Bevacizumab and Ranibizumab (RR 0.88; 95% CI 0.60-1.30) showed wide confidence intervals, reflecting substantial imprecision. Certainty of evidence (GRADE) ranged from moderate to low.ConclusionAll anti-VEGF agents stabilize or improve vision in nAMD. Aflibercept may provide the most favorable efficacy-safety balance, Faricimab offers promising durability, and Brolucizumab demonstrates large visual gains with potential safety concerns. Further head-to-head and long-term real-world studies are needed to optimize individualized treatment strategies.

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Diabetic macular edema (DME) is a leading cause of vision loss, with anti-vascular endothelial growth factor (VEGF) agents as standard therapy. However, comparative efficacy and safety remain debated. To evaluate anti-VEGF agents' efficacy/safety in DME by drug class, dosing, and baseline severity. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant meta-analysis of 21 studies (2010-2024) was conducted. Random-effects models pooled mean differences (MD) for visual acuity (VA) and central retinal thickness. Subgroup analyses assessed anti-VEGF types, dosing regimens, and baseline severity. Aflibercept showed superior VA gains in severe DME (+8.2 letters; 95% CI: 6.1-10.3) compared with bevacizumab (+3.7 letters). Faricimab demonstrated non-inferiority to ranibizumab with extended dosing (every 16 weeks; +10.1 letters). Bevacizumab biosimilars were cost-effective but required more injections. Brolucizumab was associated with a higher risk of intraocular inflammation (RR = 2.1, 95% CI: 1.6-2.6). Monthly regimens outperformed PRN (MD: +2.5 letters, p < 0.001). Aflibercept remains optimal for severe DME, while faricimab reduces treatment burden. Safety and cost considerations favor individualized therapy. Heterogeneity was extremely high (I² = 97.19%), indicating substantial variability in treatment effects across studies, only partially explained by differences in drug class, dosing regimens, and baseline severity. This high heterogeneity underscores the need for personalized treatment approaches and cautious interpretation of pooled estimates.

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ObjectivesTo evaluate the cost-effectiveness of VEGF inhibitors, ranibizumab, aflibercept, bevacizumab, brolucizumab, pegaptanib, and conbercept for wAMD treatment.MethodsA systematic search was conducted in PubMed, Cochrane, and SpringerLink databases to identify cost-effectiveness analyses and cost-utility analyses related to wAMD treatment. Eligible studies were assessed using Drummond's 10-point checklist to evaluate methodological quality. The extracted data included intervention costs, quality-adjusted life-years, and incremental cost-effectiveness ratios.ResultsTwenty-two studies met the inclusion criteria. Bevacizumab and brolucizumab were frequently reported as cost-effective alternatives, offering comparable or superior visual outcomes at lower costs than ranibizumab or aflibercept. Pegaptanib was consistently less cost-effective. Findings for ranibizumab versus aflibercept varied by treatment regimen and analytic assumptions. Across studies, cost-effectiveness estimates were influenced by model perspective, time horizon, exclusion of adverse events, and single-eye modeling. A further limitation is that in contexts of non-inferior efficacy, small incremental quality-adjusted life-years differences may artificially inflate incremental cost-effectiveness ratios, potentially overstating the costs relative to benefits.ConclusionsDecision making in wAMD treatment requires more thorough economic evaluations that incorporate standardized methodologies and lengthy cost assessments.

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