Three versus five intravitreal aflibercept injections as the initial loading phase in the treatment of diabetic macular edema: one-year results / Três versus cinco injeções intravítreas de aflibercept como carga inicial do tratamento de edema macular diabético: resultados de um ano

ABSTRACT Purpose: To compare the efficacy of three initial monthly intravitreal aflibercept injections followed by pro re nata (3+PRN) dosing versus five initial monthly intravitreal aflibercept injections followed by pro re nata (5+PRN) dosing in patients with diabetic macular edema. Methods: A total of 60 treatment-naïve patients with macular edema who underwent intravitreal aflibercept injections (2 mg/0.05 mL) with at least one year of follow-up were analyzed in this retrospective and comparative study. The patients were divided into two groups according to the number of intravitreal aflibercept injections administered in the loading phase. The 3+PRN group comprised 27 patients, whereas the 5+PRN group comprised 33 patients. The visual and anatomical outcomes were compared between the two groups at baseline and at 3, 6, 9, and 12 months. Results: Both 3+PRN and 5+PRN, showed statistically significant improvements in the best-corrected visual acuity and central macular thicknesse throughout the study period (p<0.001 and, p<0.001, respectively). There were no significant differences between the two groups in terms of changes in the best-corrected visual acuity and central macular thickness (p=0.453 and, p=0.784, respectively). The mean number of intravitreal aflibercept injections was significantly greater in the 5+PRN group (6.1 ± 0.8) than in the 3+PRN group (3.9 ± 0.8) (p<0.001). Conclusion: The 3+PRN and 5+PRN regimens showed similar 12-month visual and anatomical outcomes following treatment with intravitreal aflibercept injections in patients with macular edema.

RESUMO Objetivo: Comparar a eficácia de três injeções intravítreas mensais iniciais de aflibercept, seguidas de dosagem de pro re nata (3+PRN) versus cinco injeções mensais iniciais intravítreas de aflibercept, seguidas de doses de pro re nata (5 + PRN) em pacientes com edema macular diabético. Métodos: Foram analisados neste estudo retrospectivo e comparativo 60 pacientes que não receberam tratamento prévio com edema macular e foram submetidos a injeções intravítreas de aflibercept (2 mg/0,05 mL) com pelo menos um ano de acompanhamento. Os pacientes foram divididos em dois grupos de acordo com o número de injeções intravítreas de aflibercept administradas na fase inicial. O grupo 3+PRN compreendeu 27 pacientes, enquanto o grupo 5+PRN compreendeu 33 pacientes. Os resultados visuais e anatômicos foram comparados entre os dois grupos no período inicial e aos 3, 6, 9 e 12 meses. Resultados: Tanto os grupos 3+PRN quanto 5+PRN mostraram melhoras estatisticamente significativas na acuidade visual melhor corrigida e na espessura macular central ao longo do período de estudo (p<0,001 e p <0,001, respectivamente). Não houve diferenças significativas entre os dois grupos em termos de alterações na acuidade visual melhor corrigida e na espessura macular central (p=0,453 e p=0,784, respectivamente). O número médio de injeções intravítreas de aflibercept foi significativamente maior no grupo 5+PRN (6,1 ± 0,8) do que no grupo 3+PRN (3,9 ± 0,8) (p <0,001). Conclusão: Os regimes 3+PRN e 5+PRN mostraram resultados visuais e anatômicos semelhantes em 12 meses após o tratamento com injeções intravítreas de aflibercept em pacientes com edema macular.

Aflibercept versus dexametasona en edema macular secundario a la oclusión de la vena central de la retina / Aflibercept versus dexamethasone for macular edema secondary to central retinal vein occlusion

INTRODUCCIÓN El edema macular es una complicación frecuente de la oclusión de la vena central de la retina que clínicamente provoca deterioro de la agudeza visual. Los tratamientos más utilizados son el implante de dexametasona y los fármacos anti factor del crecimiento endotelial vascular, destacando aflibercept dentro de estos. Sin embargo, no existe consenso acerca de qué tratamiento constituye la mejor alternativa. MÉTODOS Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un meta análisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES Identificamos dos revisiones sistemáticas que en conjunto incluyeron cuatro estudios primarios, todos ensayos aleatorizados. Concluimos que no es posible establecer si aflibercept es superior a dexametasona en términos de mejora de agudeza visual y seguridad, debido a que la certeza de la evidencia existente ha sido evaluada como muy baja.

INTRODUCTION Macular edema is a frequent complication of central retinal vein occlusion that might lead to deterioration of visual acuity. The most commonly used treatments are dexamethasone implant and anti-vascular endothelial growth factor drugs, being aflibercept one of the most commonly used them. However, there is no consensus about which treatment constitute the best alternative. METHODS We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS We identified two systematic reviews that included four primary studies overall, all randomized trials. We concluded that it is not possible to establish whether aflibercept is superior to dexamethasone in terms of improvement of visual acuity and safety, because the certainty of the existing evidence has been evaluated as very low.

Efficacy of aflibercept on exudative age-related macular degeneration in patients exhibiting complete ranibizumab resistance and tachyphylaxis / Eficácia do aflibercept em pacientes portadores de degeneração macular relacionada à idade exsudativa com resistência completa e taquifilaxia ao ranibizumab

ABSTRACT Purpose: The present study compared the efficacy of aflibercept for neovascular age-related macular degeneration (NV-AMD) in patients with complete ranibizumab resistance and tachyphylaxis. Methods: Forty-four eyes of 38 neovascular age-related macular degeneration patients were evaluated. Eyes were divided into a complete resistance group (n=23 eyes) and tachyphylaxis group (n=21 eyes). Results: After three injections, eight (38.1%) patients in the tachyphylaxis group and nine (39.1%) in the complete resistance group presented with macular dryness. After the first injection of aflibercept, the mean visual acuity improved significantly in the tachyphylaxis group (p=0.018) but remained unchanged in the complete resistance group (p=0.37). There was a non-significant trend towards improved mean visual acuity in both groups after the second and third injections relative to the acuity at the final visit for ranibizumab treatment. In the tachyphylaxis group, the presence of subfoveal pigmented epithelium detachment (PED) decreased significantly after intravitreal aflibercept treatment. Conclusions: Although treatment with aflibercept yielded generally positive anatomical results in both groups, no significant increase in visual acuity was achieved.

RESUMO Objetivo: O presente estudo comparou a eficácia do aflibercept na degeneração macular neovascular relacionada à idade (NV-AMD) com de resistência completa ao ranibizumab e taquifilaxia ao ranibizumab. Método: Quarenta e quatro olhos de 38 pacientes com degeneração macular neovascular relacionada à idade foram inscritos. Eles foram divididos em dois grupos: grupo de resistência completa (n=23 olhos) e grupo taquifilaxia (n=21 olhos). Resultados: Depois de três injeções, 8 (38,1%) olhos no grupo de taquifilaxia e 9 (39,1%) olhos no grupo de resistência completa, apresentaram mácula seca. Após a primeira injeção de aflibercept, a acuidade visual média melhorou significativamente no grupo taquifilaxia (p=0,018) e manteve-se inalterada no grupo de resistência completa (p=0,37). Houve uma tendência de melhora da acuidade visual média em ambos os grupos após a segunda e terceira injeções em comparação com a última visita do tratamento com ranibizumab, mas isso não foi estatisticamente significativo. A presença de descolamento do epitélio pimentado subfoveal (PED) em olhos com taquifilaxia ao ranibizumab diminuiu significativamente após o tratamento aflibercept intravítreo. Conclusões: Embora o tratamento com aflibercept tenha mostrado resultados anatômicos positivas em ambos os grupos, não foi obtida melhora significativa da acuidade visual.

Sterile Inflammation after Intravitreal Injection of Aflibercept in a Korean Population

PURPOSE: To report the frequency and clinical features of sterile inflammation after intravitreal aflibercept injection in a Korean population. METHODS: A single-center, retrospective study was performed in patients who received intravitreal aflibercept from July 2013 through January 2015. RESULTS: A total of four cases of post-injection sterile inflammation were identified from 723 aflibercept injections in 233 patients. Patients presented 1 to 13 days after intravitreal aflibercept injection (mean, 5 days). The mean baseline visual acuity was 20 / 60, which decreased to 20 / 112 at diagnosis but ultimately recovered to 20 / 60. Three cases had inflammatory cells in the anterior chamber (mean, 2.25+; range, 0 to 4+), and all cases had vitritis (mean, 3+; range, 2+ to 4+). No patients had pain. Only one patient underwent anterior chamber sampling (culture negative) and injection of antibiotics. Three of four patients were treated with a topical steroid, and all experienced improvement in their symptoms and signs of inflammation. CONCLUSIONS: The overall incidence of sterile inflammation after intravitreal aflibercept injection in a Korean population was 4 of 723 injections (0.55%), or 4 of 233 patients (1.79%). Sterile inflammation after intravitreal aflibercept injection typically presents without pain, and the visual outcomes are generally favorable.

Aflibercept Treatment for Neovascular Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy Refractory to Anti-vascular Endothelial Growth Factor

PURPOSE: To report the results of switching treatment to vascular endothelial growth factor (VEGF) Trap-Eye (aflibercept) in neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) refractory to anti-VEGF (ranibizumab and bevacizumab). METHODS: This is a retrospective study involving 32 eyes from 29 patients; 18 were cases of neovascular AMD and 14 were cases of PCV. The best-corrected visual acuity (BCVA) and central macular thickness (CMT) of spectral-domain optical coherence tomography were evaluated. RESULTS: BCVA and CMT improved from 0.58 to 0.55 (p = 0.005) and from 404 to 321 microm (p < 0.001), respectively, after switching to aflibercept. The 14 eyes that received 6 or more aflibercept injections remained stable at 0.81 to 0.81 and 321 to 327 microm (p = 1.0, 0.29), respectively, after 3 aflibercept injections. The 10 eyes that received 3 or more bevacizumab injections after 3 or more aflibercept injections worsened, from 0.44 to 0.47 and from 332 to 346 microm (p = 0.06, 0.05), respectively. The results showed similar improvement of BCVA and CMT in neovascular AMD and PCV. CONCLUSIONS: Aflibercept seems to be effective for improvement and maintenance of BCVA and CMT for neovascular AMD and PCV refractory to anti-VEGF. Switching from aflibercept back to bevacizumab treatment may not be a proper strategy.

Combined blockade of HER2 and VEGF exerts greater growth inhibition of HER2-overexpressing gastric cancer xenografts than individual blockade

Gastric cancer overexpressing the human epidermal growth factor 2 (HER2) protein has a poor outcome, although a combination of chemotherapy and the anti-HER2 antibody trastuzumab has been approved for the treatment of advanced gastric cancer. Vascular endothelial growth factor (VEGF) expression in gastric cancer is correlated with recurrence and poor prognosis; however, the anti-VEGF antibody bevacizumab has shown limited efficacy against gastric cancer in clinical trials. In this study, we evaluated the antitumor effects of trastuzumab; VEGF-Trap binding to VEGF-A, VEGF-B and placental growth factor (PlGF); and a combination of trastuzumab and VEGF-Trap in a gastric cancer xenograft model. Although trastuzumab and VEGF-Trap each moderately inhibited tumor growth, the combination of these agents exerted greater inhibition compared with either agent alone. Immunohistochemical analyses indicated that the reduction in tumor growth was associated with decreased proliferation and increased apoptosis of tumor cells and decreased tumor vascular density. The combined treatment resulted in fewer proliferating tumor cells, more apoptotic cells and reduced tumor vascular density compared with treatment with trastuzumab or VEGF-Trap alone, indicating that trastuzumab and VEGF-Trap had additive inhibitory effects on the tumor growth and angiogenesis of the gastric cancer xenografts. These data suggest that trastuzumab in combination with VEGF-Trap may represent an effective approach to treating HER2-overexpressing gastric cancer.