Clinical outcomes after switching treatment from intravitreal ranibizumab to aflibercept in neovascular age-related macular degeneration

Purpose

To describe the treatment response to aflibercept in patients with exudative age-related macular degeneration that showed insufficient or diminishing treatment effects under ranibizumab.

Methods

From December 2012 till June 2013 all patients receiving intravitreal injections of aflibercept after previous treatment with ranibizumab were collected in a database and retrospectively reviewed. Clinical data such as visual acuity or central subfield retinal thickness on optical coherence tomography (OCT) scans were analyzed for the time frame before, during, and shortly after the aflibercept injections. Of particular interest was the comparison of clinical features under ongoing ranibizumab treatment to the time during aflibercept treatment.

Results

Seventy-one eyes of 65 patients were included in the study. All eyes had previous ranibizumab injections in their medical history, the average number of which was nine (range 3-43). For the total group the mean visual acuity (VA) before the first ranibizumab injection was 0.54 logMAR, and after the last ranibizumab injection was 0.57 logMAR. Mean VA changed from 0.47 logMAR before the first aflibercept injection to 0.25 logMAR after the last aflibercept injection. Central subfield retinal thickness (CSRT) on OCT changed from a mean of 417.28 μm to 349.52 μm under ranibizumab treatment and from 338.76 μm to 272.00 μm under aflibercept treatment. Interestingly, 33 % of cases that did not show a functional improvement under ranibizumab therapy gained visual acuity after aflibercept treatment.

Conclusion

Aflibercept appears to be an effective choice for patients with neovascular age-related macular degeneration who were resistant to previous therapy of ranibizumab. The longevity of this effect still remains questionable.     

Rescue effects of intravitreal aflibercept in the treatment of neovascular age-related macular degeneration

We report the rescue results of intravitreal aflibercept in patients with treatment-resistant neovascular age-related macular degeneration (AMD). We retrospectively analyzed eyes with neovascular AMD resistant to posterior subtenon triamcinolone, intravitreal ranibizumab, and/or bevacizumab treatment in a tertiary medical center in middle Taiwan between December 2013 and October 2014. We then switched treatment to 2.0 mg aflibercept. The main outcome included changes in best-corrected visual acuity and central foveal thickness measured by optical coherence tomography during monthly follow-up. There were 204 patients with neovascular AMD, and the percentage of refractory cases was 1.96% (4 of 204 cases). Our study included five eyes of four patients that were resistant to multiple treatments and subsequently switched to aflibercept. The mean age was 71.25 ± 11.09 years (range 57–83 years). Treatments were on average 6.6 times previously. Upon switching to aflibercept treatment, the average central foveal thickness on optical coherence tomography was 505.6 ± 270.86 μm (range 150–815 μm). After aflibercept treatment, the average central foveal thickness was 192 ± 51.76 μm (range 149–274 μm). All patients showed anatomic improvement, and 80% of the eyes (4 of 5 eyes) had improved best-corrected visual acuity and 20% of the eyes (1 of 5 eyes) had stable visual acuity. Patients tolerated the treatment well without serious adverse events. This short-term study showed that intravitreal aflibercept was effective and safe in treatment-resistant neovascular AMD cases. However, analysis of more cases and long-term follow-ups are mandatory.     

Predictors of response after intravitreal bevacizumab injection for neovascular age-related macular degeneration

Purpose  

To identify fluorescein angiography (FA) and optical coherence tomography (OCT) characteristics predicting responses to intravitreal bevacizumab therapy in patients with neovascular age-related macular degeneration (AMD).     

Efficacy of intravitreal aflibercept in Japanese patients with exudative age-related macular degeneration

Purpose

To clarify the efficacy of aflibercept for treating exudative age-related macular degeneration (AMD).

Methods

We prospectively studied 47 eyes with AMD. Forty-seven patients (mean age 72.2 years) received three consecutive monthly intravitreal aflibercept injections followed by an injection every 2 months until 12 months. The primary outcome was the 12-month visual results compared with baseline; the secondary outcomes were the prevalence of geography atrophy (GA), a dry macula at month 12, and anatomic changes on optical coherence tomography.

Results

The mean logarithm of the minimum angle of resolution best-corrected visual acuity (BCVA) in 27 eyes with typical AMD and 20 eyes with polypoidal choroidal vasculopathy (PCV) significantly (p < 0.0001, p < 0.05, respectively) improved from 0.60 to 0.32 at baseline to 0.29 and 0.21 at month 12. At month 12, 22 (81.5 %) eyes with typical AMD and 17 (85 %) eyes with PCV had dry macula. The subfoveal choroidal thicknesses in typical AMD and PCV decreased significantly (p < 0.0001 for both comparisons) from 241 ± 118 and 294 ± 76 μ at baseline to 198 ± 104 and 244 ± 84 μ at month 12. Progressing or new GA was seen in three eyes with typical AMD and one eye with PCV; the mean change in the BCVA was significantly (p = 0.0026) worse at month 12. No other complications developed.

Conclusion

Intravitreal aflibercept significantly improved VA and anatomic changes in typical AMD and PCV over 12 months. Development of GA might be a risk for declining VA.

     

Choroidal structural changes determined by the binarization method after intravitreal aflibercept treatment in neovascular age-related macular degeneration

AIM: To assess the choroidal structural alterations after intravitreal injection of aflibercept in neovascular age-related macular degeneration (nAMD).METHODS: Fifty eyes with treatment-naïve nAMD were evaluated at baseline, 3rd, and 12th month. Fifty eyes of 50 healthy subjects were also included as controls. Choroidal thickness (CT) was measured in the subfoveal region. Total circumscribed choroidal area (CA), luminal area (LA), stromal area (SA), and choroidal vascularity index (CVI) was calculated using Image J.RESULTS: At baseline, subfoveal CT was increased in nAMD patients compared to controls (P=0.321). Eyes with nAMD had a significantly increased total circumscribed CA and SA (P=0.041, 0.005, respectively). The CVI was decreased (P=0.038). In the 3rd month, the subfoveal CT, LA, and CVI revealed a decrease (P=0.005, P=0.039, 0.043, respectively). In the 12th month, subfoveal CT, LA, and CVI were decreased in comparison to baseline measures (P<0.001, 0.006, 0.010, respectively).CONCLUSION: Significant structural alterations are found after intravitreal aflibercept treatment during the 12-month follow-up, in particular at the third month, in eyes with nAMD.     

Retinal pigment epithelial tears after intravitreal bevacizumab injection for neovascular age-related macular degeneration

PURPOSE: To study retinal pigment epithelium (RPE) tears after off-label intravitreal bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) injection for neovascular age-related macular degeneration. Eyes with a vascularized pigment epithelial detachment (PED) that developed an RPE tear were compared with eyes with a vascularized PED but without an RPE tear. METHODS: Nine retina specialists across the United States and in Europe participated in this retrospective case series. All eyes that received intravitreal bevacizumab injection for choroidal neovascularization (CNV) over 12 months (October 2005 to September 2006) were included. Eyes without all three confirmed tests (fluorescein angiography, fundus photography, and optical coherence tomography) were excluded from analysis. Statistical analyses were performed on multiple characteristics of eyes with a vascularized PED that did and did not develop an RPE tear. RESULTS: Among 2,785 intravitreal bevacizumab injections for 1,064 eyes, RPE tears were found in 22 eyes in 22 patients (2.2%). A vascularized PED was present in 21 of 22 eyes that developed an RPE tear (17.1% of PED eyes; 15, 100% occult CNV; 6, predominantly occult CNV). Mean interval from bevacizumab injections to RPE tears was 37.3 days. Mean follow-up time was 124.9 days. Mean subfoveal PED size was larger for eyes with tears than for those without tears (13.97 mm vs 9.9 mm, respectively; P = 0.01; odds ratio, 1.09). There was substantially smaller mean ratio of CNV size to PED size for eyes with tears than for those without tears (27.9% vs 67.6%, respectively; P = 0.005). Mean pre-bevacizumab injection best-corrected Snellen visual acuity was 20/162, and mean post-RPE tear best-corrected visual acuity was 20/160 (P = 0.48). CONCLUSION: Large PED size is a predictor for RPE tears, and a small ratio of CNV size to PED size (<50%) is more common in eyes with RPE tears. Vision may be preserved despite RPE tears.     

玻璃体腔注射康柏西普对湿性ARMD的疗效分析

目的：探讨玻璃体腔注射康柏西普对湿性年龄相关性黄斑变性(ARMD)的疗效及对脉络膜厚度的影响。

方法：回顾性研究。选取本院于2014-03/2017-12收治的213例345眼湿性ARMD患者,根据治疗方式不同分为两组,对照组(106眼176眼)行玻璃体腔注射曲安奈德治疗,观察组(107例169眼)行玻璃体腔注射康柏西普治疗。分析两组患者的疗效及脉络膜厚度变化。

结果：两组患者注射前BCVA、黄斑中央区厚度(CMT)均无差异(P>0.05)。观察组第3次注射后的BCVA优于对照组,且CMT值低于对照组(P<0.05)。两组患者间治疗前和治疗后1、3、6mo的中央视网膜厚度、脉络膜厚度无差异(P>0.05)。但两组患者治疗后6mo的中央视网膜厚度、脉络膜厚度显著低于治疗前和治疗后1、3mo(P<0.05)。经治疗后,观察组与对照组的并发症总发生率分别为5.7%、7.7%(P>0.05)。

结论：玻璃体腔注射康柏西普与注射曲安奈德的效果同样好,不仅可以改善和稳定患者视力,还能有效降低患者的中央视网膜厚度和脉络膜厚度,其疗效显著,安全性较高。     

Intravitreal aflibercept in neovascular age-related macular degeneration previously treated with ranibizumab

AIM: To report the change in visual acuity and central macular thickness (CMT) following treatment with intravitreal aflibercept injections in patients with neovascular age-related macular degeneration (nAMD) with suboptimum response to ranibizumab. METHODS: This was a retrospective study. The inclusion criteria were patients with nAMD who responded poorly to ranibizumab. Patients then received either 3 consecutive aflibercept injections followed by PRN treatment or PRN alone. Primary endpoints were mean change in best-corrected visual acuity (BCVA) and CMT at 12mo. Secondary endpoints were number of injections and adverse events. RESULTS: Forty-nine eyes from 49 patients met the inclusion criteria and completed 12-month follow up on aflibercept. Thirty-eight eyes received 3 consecutive aflibercept injections followed by PRN treatment and 11 eyes received pro re nata (PRN) injections alone. At 12mo, mean BCVA improved by one letters (logMAR 0.56±0.31 to 0.54±0.34) and mean CMT decreased from 303.9±82.1 to 259.2±108.3 µm. Four percent of eyes gained 15 letters or more, 6% lost more than 15 letters and the remaining 90% had stable BCVA. The mean number of aflibercept injections was 6. There was one case of infectious endophthalmitis. CONCLUSION: Intravitreal aflibercept in patients with nAMD with a previous suboptimal response to ranibizumab resulted in an anatomical improvement in macular appearance at 12mo without a corresponding improvement in visual acuity.     

Assessment of choriocapillaris/Sattler and Haller layer changes after intravitreal injection in eyes with neovascular age-related macular degeneration: aflibercept vs ranibizumab

Japanese Journal of Ophthalmology - To evaluate the changes in choriocapillaris (CC)/Sattler and Haller layer thicknesses in eyes with neovascular age-related macular degeneration (nAMD) after...     

Rapid response to intravitreal aflibercept in neovascular age-related macular degeneration after development of tachyphylaxis to bevacizumab and ranibizumab

This article reports a rapid response of intravitreal aflibercept for the treatment of a case of neovascular age-related macular degeneration that developed tachyphylaxis to bevacizumab and ranibizumab. An 80-year-old man with neovascular age-related macular degeneration became unresponsive to monthly treatment with bevacizumab or ranibizumab after initial responsiveness, to as-needed treatment with these antivascular endothelial growth factor drugs for 49 months. Subretinal fluid and pigment epithelial detachment had sustained in spite of 14 bevacizumab and seven ranibizumab injections prior to intravitreal aflibercept treatment. After only one injection of intravitreal aflibercept, a marked improvement was seen within 1 week. Complete drying of subretinal fluid and marked subsidence of pigment epithelial detachment were noted 4 weeks after the first aflibercept injection and sustained for three consecutive monthly injections. This case reveals that shifting to aflibercept may be an effective alternative treatment for neovascular age-related macular degeneration that becomes tachyphylactic to bevacizumab or ranibizumab.     

新生血管性年龄相关性黄斑变性患者玻璃体内注射抗血管内皮生长因子药物治疗进展

年龄相关性黄斑变性是引起50岁以上人群视力不可逆性损伤的主要原因之一，新生血管性年龄相关性黄斑变性（neovascular age-related macular degeneration,nAMD）也称湿性年龄相关性黄斑变性（wet age-related macular degeneration,wAMD），是其晚期阶段，可导致最严重的视力丧失。血管内皮生长因子（vascular endothelial growth factor,VEGF）是脉络膜新生血管和视网膜渗漏形成的主要因素，抗VEGF治疗是目前唯一实现多数患者视力改善并且停止疾病进展的治疗方法，因此玻璃体内注射抗VEGF药物已经成为wAMD一线治疗方法。用于临床治疗wAMD的抗VEGF药物主要有哌加他尼、贝伐单抗、雷珠单抗、阿柏西普和康柏西普。治疗方案有固定式、按需式以及治疗和延长式治疗方案。Brolucizumab和abicipar pegol是2种新的抗VEGF药物，正处于3期临床试验阶段。本文对以上药物治疗wAMD的研究进展进行综述。     

Short-term choroidal vascular changes after aflibercept therapy for neovascular age-related macular degeneration

Graefe's Archive for Clinical and Experimental Ophthalmology - The purpose of this study was to evaluate choroidal vascular changes in patients with neovascular age-related macular degeneration...     

Effect of aflibercept in patients with age-related macular degeneration

The purpose of this study was to evaluate the efficacy of standard induction therapy with intravitreal aflibercept (IVA) in patients with exudative age-related macular degeneration (AMD) at 6 months after completion of induction therapy. Eleven eyes with typical AMD (tAMD) and 13 eyes with polypoidal choroidal vasculopathy (PCV) received three monthly doses of IVA (2 mg/0.05 ml in weeks 0, 4, and 8) for treatment of exudative AMD. Best-corrected visual acuity (BCVA) was measured, and optical coherence tomography was performed at baseline and at each monthly visit until 6 months after IVA. Treatment failure was defined as persistent or recurrent AMD that presented with cystoid macular edema, serous retinal detachment, and pigment epithelium detachment. Mean logMAR BCVA was improved from 0.62 ± 0.46 at baseline to 0.54 ± 0.43 at 6 months after IVA (p < 0.05). The success rate was 95.8 % at 3 months and 75.0 % at 6 months after IVA. Failure of IVA was positively associated with the absence of PVD before treatment (r = 0.35) and with the AMD type (tAMD, r = 0.43) by univariate analysis. Cox proportional hazards analysis demonstrated that the absence of PVD before treatment was associated with an increased risk of failure of IVA (OR = 33.17, p = 0.0219). Three months of induction IVA achieved a high success rate in patients with AMD monitored for up to 6 months. Factors associated with failure of IVA were the absence of PVD and the presence of tAMD. Accordingly, continuation of IVA following induction therapy may be beneficial to manage AMD in patients with tAMD or those without PVD.     

Visual and anatomical outcomes following intravitreal aflibercept in eyes with recalcitrant neovascular age-related macular degeneration: 12-month results

Purpose

To describe the efficacy of intravitreal aflibercept on 12-month visual and anatomical outcomes in patients with neovascular age-related macular degeneration (AMD) recalcitrant to prior monthly intravitreal bevacizumab or ranibizumab.

Methods

Non-comparative case series of 21 eyes of 21 AMD patients with evidence of persistent exudation (intraretinal fluid/cysts, or subretinal fluid (SRF), or both) on spectral domain OCT despite ≥6 prior intravitreal 0.5 mg ranibizumab or 1.25 mg bevacizumab (mean 29.8±17.1 injections) over 31.6±17.4 months who were transitioned to aflibercept.

Results

At baseline, best-corrected visual acuity (BCVA) was 0.42±0.28 logarithm of minimum-angle of resolution (logMAR), central foveal thickness (CFT) was 329.38±102.67 μm and macular volume (MV) was 7.71±1.32 mm³. After 12 months of aflibercept (mean 10.2±1.2 injections), BCVA was 0.40±0.28 logMAR (P=0.5), CFT decreased to 292.71±91.35 μm (P=0.038) and MV improved to 7.33±1.27 mm³ (P=0.003). In a subset of 15 eyes with a persistent fibrovascular or serous pigment epithelial detachment (PED), mean baseline PED greatest basal diameter (GBD) was 2350.9±1067.6 μm and mean maximal height (MH) was 288.7±175.9 μm. At 12 months, GBD improved to 1896.3±782.3 μm (P=0.028), while MH decreased to 248.27±146.2 μm (P=0.002).

Conclusion

In patients with recalcitrant AMD, aflibercept led to anatomic improvement at 12 months, reduction in proportion of eyes with SRF and reduction in PED, while preserving visual acuity.     

Retinal pigment epithelium tears after intravitreal injection of bevacizumab (avastin) for neovascular age-related macular degeneration

BACKGROUND: Intravitreal bevacizumab (Avastin, Genentech, Inc., South San Francisco, CA) treatment of neovascular age-related macular degeneration (AMD) has become an important part of clinical retinal practice. We describe retinal pigment epithelium (RPE) tears that were noted after intravitreal injection of bevacizumab. METHODS: In this multimember, retrospective case series, data on eyes that developed RPE tears after intravitreal bevacizumab injection were collected and analyzed. Previous treatments, type of lesion, time to tear, and preinjection and final visual acuities were all compared. The total numbers of bevacizumab injections were available from all four institutions and compiled to estimate the incidence rate. RESULTS: Four retina centers administered a total of 1,455 intravitreal 1.25-mg bevacizumab injections for neovascular AMD during the 9-month study period. Twelve patients presented with RPE tears within 4 days to 8 weeks of injection (mean +/- SD, 24.3 +/- 15.2 days from injection to tear). In each case, the RPE tear was preceded by an RPE detachment, and all had a component of serous sub-RPE fluid. On the basis of our collective data, we estimate an incidence rate of approximately 0.8%. CONCLUSIONS: RPE tears can occur after intravitreal injection of bevacizumab. The low incidence of this adverse event should not preclude anti-vascular endothelial growth factor therapy counseling for patients with neovascular AMD, but eyes with serous RPE detachments appear to be most vulnerable to this adverse event.     

玻璃体腔内注射Bevacizumab治疗年龄相关性黄斑变性视野改变

目的 观察玻璃体腔内注射Bevacizumab(Avastin)治疗湿性年龄相关性黄斑变性(ARMD)术后各时间段的视野变化情况.方法 采用单中心随机临床研究方法.收集经间接眼底镜、荧光素眼底血管造影(FFA)以及光学相干断层扫描(OCT)检查确诊存在黄斑中心凹下脉络膜新生血管(CNV)的ARMD患者13例(15只眼),患眼最佳矫正视力均>0.1.患眼行Bevacizumab玻璃体腔内注射1.25mg(0.05ml),注射次数为6次,间隔6周至3个月,治疗后随访3～12个月,记录并分析术前及术后6周,3月,6月,12月的平均视觉敏感度(mean visual sensitivity,MS),平均缺损(mean defect,MD),缺损变异度(lose variance,Lv)的变化.结果 以0周注射为基准,第24周及48周MS值与注射前MS值相比有显著性差异(t值分别为2.91、3.69,P值均<0.05));第48周MD值与注射前MD值(7.97±3.97)dB差异有统计学意义(t值为1.35,P<0.05);各组LV值与注射前LV值比较差异无统计学意义.结论 多次玻璃体腔内注射Bevacizumab有利于改善湿性ARMD患者黄斑区视功能,主要体现在对视网膜平均敏感度以及平均缺损的改善上;重复4-6次注射后绝大多数湿性ARMD患者的视功能得到改善.