Real world evidence of use of anti-VEGF therapy in Denmark

Objective: This study evaluates real-world evidence regarding the frequency of anti-vascular-endothelial-growth-factor (VEGF) injections during the first year of therapy of treatment-naïve patients with neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME) and retinal vein occlusion (RVO) from the Danish National Patient Registry. There was a switch in anti-VEGF treatment for naïve nAMD patients during the study period, following the introduction of aflibercept, which was expected to reduce the injection frequency relative to ranibizumab due to a perception of prolonged treatment duration of aflibercept.

Methods: All treatment-naïve nAMD, DME or RVO patients who received an intravitreal injection in Denmark from 1 January 2012 to 31 July 2015 were eligible for inclusion. Patients were required to have been treated for at least one year and, for nAMD, to have received at least three injections during the first four months of treatment. Patients were allocated to half-year groupings (2012/1 to 2014/1) based on registration of their first intravitreal injection. Injection frequency during the first year of treatment was calculated for each group and t-tests investigated whether injection frequencies changed over time.

Results: In treatment naïve nAMD patients (n?=?500), the mean (SD) number of anti-VEGF injections increased significantly from 6.04 (1.71) in 2012/1 to 6.73 (1.62) in 2014/1 (p?=?.001; 2012/1 and 2012/2 vs. 2014/1) across all treatments. A similar trend was found for DME patients (n?=?76) from 2012/1 to 2014/1 and RVO patients (n?=?82) from 2012/2 to 2014/1, with mean injection frequencies increasing significantly from 5.14 (2.29) to 5.93 (1.98) (p?=?.007), and from 4.83 (1.21) to 6.08 (1.55) (p?=?.024), respectively. Post hoc sensitivity analysis also found a significant increase in injection frequency in nAMD patients who did not receive a loading phase (4.55 in 2012/1 and 5.05 in 2014/1; p?=?.006; n?=?616).

Conclusions: In contrast to the decrease in injection frequency predicted with a switch to aflibercept treatment for nAMD, our study showed that injection frequencies increased significantly from 2012 to 2014 in patients initiating therapy across the three diseases.     

Comparison of Systemic Adverse Events Associated with Intravitreal Anti-VEGF Injection: Ranibizumab versus Bevacizumab

The aim of this study was to compare the incidence of systemic adverse events in patients treated with intravitreal injections of bevacizumab or ranibizumab, and to evaluate whether compared to ranibizumab administration, bevacizumab constitutes a higher risk for systemic adverse events. A retrospective review was conducted for 916 consecutive patients treated with at least 1 intravitreal injection of bevacizumab or ranibizumab. Cox regression was performed to assess whether a variable had predictive value for occurrence of new systemic adverse events and to account for different follow-up times. A total of 702 patients were analyzed; 503 patients received bevacizumab alone, and 199 patients received ranibizumab alone. Systemic adverse events occurred in 10 of 702 patients (1.4%): 7 in the bevacizumab group (7/503; 1.4%) and 3 in the ranibizumab group (3/199; 1.5%). This difference was not statistically significant (Fisher''s exact test, P = 0.573). Cox proportional hazards analysis of 4 models did not reveal a covariate that significantly changed the hazard for systemic adverse events. In conclusion, compared to ranibizumab, bevacizumab may not increase the risk of systemic adverse events in patients receiving intravitreal injections.     

Interobserver variability for retreatment indications after Ranibizumab loading doses in neovascular age‐related macular degeneration

Purpose: To assess the interobserver variability (IOV) in indicating retreatment for neovascular Age‐related macular degeneration 4 weeks after three Ranibizumab loading doses using spectral domain OCT (SD‐OCT) as the primary objective diagnostic tool. Material and methods: Four observers decided for or against 4th Ranibizumab injection in 108 patients by six different rating rounds (RR) based on the SD‐OCT findings after the loading doses. Postoperative OCT images were supplemented consecutively with information from a chart review as the ‘patients subjective estimation of vision (SE)’, the course of best‐corrected visual acuity (BCVA) and the preoperative OCT as well as all information collectively. Agreement rates (AR) and Kappa statistics were calculated. Results: Based on post‐treatment OCT findings only (RR1), mean reinjection rate of all observers was 37.5%. Adding supplementary information, mean reinjection rate decreased to 20% when all information was available reflecting the ‘real’ situation (RR 6). Interobserver agreement rates varied from 66.7% to 90.7% depending on rating rounds and interobserver pairs. Mean AR and Kappa values (KV) were as following: AR 81.6%, KV 0.61 (RR1: ‘only post‐OP OCT’); AR 76.7%, KV 0.33 (RR2: post‐OP OCT + SE); AR 80.3%, KV 0.45 (RR3: post‐OP OCT + BCVA); AR 80.7%, KV 0.46 (RR4: pre‐ and post‐OP OCT); AR 82.2%, KV 0.49 (RR5: post‐OP OCT + SE + BCVA); and finally AR 83.6%, KV 0.47 (RR6: pre‐ and post‐OP OCT + SE + BCVA). The overall mean agreement rate was 80.9% with a Kappa of 0.47. Conclusion: IOV for indicating retreatment after three Ranibizumab loading doses reveals only moderate agreement in Kappa statistics, which seems to be too low considering the high costs for retreatments. More concise guidelines based on the post‐treatment OCT scans as the presumably most sensitive and noninvasive objective tool to follow choroidal neovascularization activity by judging the course of sub‐ and intraretinal fluid are necessary.     

Intravitreal ranibizumab (Lucentis®) in the treatment of retinal angiomatous proliferation (RAP)

Background  Retinal angiomatous proliferation (RAP) is a distinct variant of neovascular age-related macular degeneration (AMD). The aim of this study is to evaluate the functional and anatomic outcome after intravitreal ranibizumab (Lucentis) treatment in patients with RAP. Methods  Prospective study of consecutive patients with newly diagnosed or recurrent RAP treated with intravitreal ranibizumab at the Jules Gonin Eye Hospital between March 2006 and December 2007. Baseline and monthly follow-up visits included best-corrected visual acuity (BCVA), fundus exam and optical coherence tomography. Fluorescein and indocyanine green angiography were performed at baseline and repeated at least every 3 months. Results  Thirty-one eyes of 31 patients were treated with 0.5 mg of intravitreal ranibizumab for RAP between March 2006 and December 2007. The mean age of the patients was 82.6 years (SD:4.9). The mean number of intravitreal injections administered for each patient was 5 (SD: 2.4, range 3 to 12). The mean follow up was 13.4 months (SD: 3, range 10 to 22). The baseline mean logMAR BCVA was 0.72 (SD: 0.45) (decimal equivalent of 0.2). The mean logMAR BCVA was improved significantly (P < 0.0001) at the last follow-up to 0.45, SD: 0.3 (decimal equivalent 0.35). The visual acuity (VA) improved by a mean of 2.7 lines (SD 2.5). Mean baseline central macular thickness (CMT) was 376 μm, and decreased significantly to a mean of 224 μm (P < 0.001) at the last follow-up. Mean reduction of CMT was 152 μm (SD: 58). An average of 81.5% of the total visual improvement and 85% of the total CMT reduction occurred during the first post-operative month after one intravitreal injection of ranibizumab. During follow-up, an RPE tear occurred in one eye (3.2%) of the study group. No injection complications or systemic drug-related side-effects were noted during the follow-up period. Conclusions  Intravitreal ranibizumab injections appeared to be an effective and safe treatment for RAP, resulting in visual gain and reduction in macular thickness. Further long-term studies to evaluate the efficacy of intravitreal ranibizumab in RAP are warranted.     

VEGF在糖尿病性视网膜病变发病机制中的作用及抗VEGF治疗新进展

糖尿病性视网膜病变是世界新发致盲因素之一。血管内皮生长因子（ｖａｓｃｕｌａｒｅｎｄｏｔｈｅｌｉａｌｇｒｏｗｔｈｆａｃｔｏｒ,ＶＥＧＦ）是糖尿病性视网膜病变发病机制中的关键因子,成为近年研究的热点。近年来,抗ＶＥＧＦ药物成为新生血管性及血管性眼底疾病的重要治疗药物,本文就ＶＥＧＦ在糖尿病性视网膜病变病理进程中的作用及抗ＶＥＧＦ治疗新进展作一综述。     

玻璃体腔注射雷珠单抗联合GLP治疗BRVO-ME的临床观察

目的 研究视网膜分支静脉阻塞继发黄斑水肿(BRVO-ME)患者应用雷珠单抗玻璃体腔注射联合格栅样视网膜激光光凝术(GLP)治疗的临床效果。 方法 选取135例(135眼)BRVO-ME临床资料,随机分为单纯药物组(n=45)、单纯激光组(n=45)、联合治疗组(n=45),单纯药物组仅应用雷珠单抗玻璃体腔注射,单纯激光组仅应用GLP治疗,联合治疗组先予雷珠单抗玻璃体腔注射,间隔1周后应用GLP治疗。 结果 三组治疗3个月后最佳矫正视力(BCVA)水平对比,较治疗前差异有统计学意义(P<0.05),且联合治疗组治疗1、2、3个月后BCVA水平较同期单纯药物组、单纯激光组差异有统计学意义(P<0.05)。三组治疗3个月后黄斑中心凹视网膜厚度(CMT)水平对比,均较治疗前差异有统计学意义(P<0.05),且联合治疗1、2、3个月后CMT水平较同期单纯药物组、单纯激光组差异均有统计学意义(P<0.05)。 结论 玻璃体腔注射雷珠单抗联合GLP治疗BRVO-ME较单纯药物和单纯激光治疗,降低黄斑中心凹视网膜厚度、改善黄斑水肿、提高视力效果更明显,复发率更低,安全有效。     

The real life data of ranibizumab use among the diabetic macular edema patients in Turkey: Documenting the improvement with clinical optimization during three consecutive years

Purpose

To report the 12?month real life outcomes of ranibizumab treated diabetic macular edema (DME) patients.