Efficacy and safety of faricimab for neovascular age-related macular degeneration: a systematic review and network meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of faricimab compared with other anti-vascular endothelial growth factor (anti-VEGF) agents in treating neovascular age-related macular degeneration (nAMD) patients. METHODS AND ANALYSIS: A systematic review (SR) was conducted up to January 2023. Network meta-analyses (NMA) were performed, including sensitivity and subgroup analyses for naïve population. Outcomes included changes in visual acuity (Early Treatment of Diabetic Retinopathy Study [ETDRS] letters), anatomical changes, frequency of injections and adverse events. The Cochrane Collaboration guidelines and the Confidence in Network Meta-Analysis framework were used for the SR and the certainty of evidence, respectively. RESULTS: From 4128 identified records through electronic databases and complementary searches, 63 randomised controlled trials (RCTs) met the eligibility criteria, with 42 included in the NMA. Faricimab showed a significant reduction in the number of annual injections compared with most fixed and flexible anti-VEGF treatment regimens, while showing no statistically significant differences in visual acuity through ETDRS letter gain, demonstrating a comparable efficacy. Retinal thickness results showed comparable efficacy to other anti-VEGF agents, and inferior only to brolucizumab. Results also showed that more patients treated with faricimab were free from post-treatment retinal fluid compared with aflibercept every 8 weeks, and both ranibizumab and bevacizumab, in the fixed and pro re nata (PRN) assessed schedules. Faricimab showed a comparable safety profile regarding the risk of ocular adverse events and serious ocular adverse events (SOAE), except for the comparison with brolucizumab quarterly, in which faricimab showed a significant reduction for SOAE risk. CONCLUSION: Faricimab showed a comparable clinical benefit in efficacy and safety outcomes, with a reduction in annual injections compared with fixed and flexible anti-VEGF drug regimens, representing a valuable treatment option for nAMD patients. PROSPERO REGISTRATION NUMBER: CRD42023394226.

Antiangiogenic activity of a bevacizumab-loaded polyurethane device in animal neovascularization models.

PURPOSE: To evaluate the antiangiogenic activity of bevacizumab-loaded polyurethane using two animal models of neovascularization. METHODS: The percentage of blood vessels was evaluated in a chicken chorioallantoic membrane model (n=42) and in the rabbit cornea (n=24) with neovascularization induced by alkali injury. In each model, the animals were randomly divided into the groups treated with the bevacizumab-loaded polyurethane device, phosphate-buffered-saline (negative control) and bevacizumab commercial solution (positive control). Clinical examination, as well as histopathological and immunohistochemical evaluation, were performed in the rabbit eyes. Microvascular density in hot spot areas was determined in semi-thin sections of corneal tissue by hematoxylin-eosin staining and factor VIII immunohistochemistry. Immunohistochemical analysis was also performed to evaluate VEGF expression. RESULTS: In the evaluated models, the use of bevacizumab (Avastin®) and the bevacizumab-loaded polyurethane device led to similar results with regard to inhibition of neovascularization. In the chorioallantoic membrane model, the bevacizumab-loaded polyurethane device reduced angiogenesis by 50.27% when compared to the negative control group. In the rabbit model of corneal neovascularization, the mean density of vessels/field was reduced by 46.87% on analysis of factor VIII immunohistochemistry photos in the bevacizumab-loaded polyurethane device group as compared to the negative control (PBS) sections. In both models, no significant difference could be identified between the bevacizumab-loaded polyurethane device and the positive control group, leading to similar results with regard to inhibition of neovascularization. CONCLUSIONS: The present study shows that the bevacizumab-loaded polyurethane device may release bevacizumab and inhibit neovascularization similarly to commercial bevacizumab solution in the short-term.

The macular threshold protocol of the Humphrey visual field analyzer: a superior functional outcome of intravitreal bevacizumab for the treatment of neovascular age-related macular degeneration / Desfecho funcional superior da eficácia do tratamento com bevacizumab intravítreo em degeneração macular relacionada à idade, por meio do protocolo de limiar macular do campímetro de Humphrey

PURPOSE: To evaluate the decibel loss on the Macular threshold protocol of the Humphrey visual field as a reliable functional outcome of the intravitreal bevacizumab treatment. METHODS: Thirteen patients were evaluated at baseline and on the week 6 for best corrected visual acuity, optical coherence tomography central macular thickness and decibel loss on Macular threshold protocol of the Humphrey visual field after 1.25 mg intravitreal injection of bevacizumab. The outcomes were analyzed separately and in correlation using the Wilcoxon signed ranks test. RESULTS: The improvement of the optical coherence tomography and the Macular threshold protocol of the Humphrey visual field from baseline to week 6 were significant with p=0.032 and p=0.003, respectively. The visual acuity did not show a significant improvement. The correlation of the visual acuity and Macular threshold protocol of the Humphrey visual field was significant at baseline (p=0.041) and on week 6 (p=0.019). CONCLUSION: The Macular threshold protocol of the Humphrey visual field significantly improved despite the fact that the best corrected visual acuity did not. The Macular threshold protocol of the Humphrey visual field correlated with the visual acuities significantly. The optical coherence tomography was significant to demonstrate improvement but did not correlate with best corrected visual acuity and Macular threshold protocol of the Humphrey visual field. These findings suggest that the Macular threshold protocol of the visual field may be a more reliable tool for evaluation of global macular function after intravitreal bevacizumab treatment.

OBJETIVO: Avaliar se a perda de decibéis no protocolo macular do campímetro de Humphrey (PMCH) é um resultado funcional confiável para o tratamento com bevacizumab intravítreo. MÉTODOS: Treze pacientes foram avaliados na visita de base e na semana 6 após a injeção intravítrea de 1,25 mg de bevacizumab realizando a melhor acuidade visual corrigida, espessura macular central na tomografia de coerência óptica e análise da perda de decibéis no PMCH. Estes desfechos foram analisados separadamente e em correlação usando o teste Wicoxon signed ranks. RESULTADOS: A melhora da espessura central no OCT e do PMCH na semana 6 em relação a visita de base foi significante com p=0,032 e p=0,003 respectivamente. A acuidade visual não mostrou uma melhora estatisticamente significante. A correlação entre a acuidade visual e o PMCH foi significante na visita de base (p=0,041) e na visita de 6 semanas (p=0,019). CONCLUSÃO: O PMCH melhorou significantemente apesar do fato de que a melhor acuidade visual corrigida não apresentou tal melhora. O PMCH correlacionou-se com a acuidade visual de forma estatisticamente significativa. O OCT foi significativo para demonstrar melhora porém não se correlacionou com o PMCH e com a acuidade visual. Estes achados sugerem que o PMCH pode ser uma ferramenta mais confiável na avaliação da função macular global após injeção intravítrea de bevacizumab.