雷珠单抗临床应用新进展概述

雷珠单抗(ranibizumab)是第二代人源化抗血管内皮生长因子(VEGF)重组鼠单克隆抗体片段,能与所有活性形式的VEGF-A结合,防止其与VEGFR1及VEGFR2结合,从而减少血管内皮细胞增殖和降低血管通透性,抑制新生血管生成。近年来,其临床应用范围不断扩大,新的观察结果和观点、理念不断涌现。现将近年来雷珠单抗在眼科临床应用的最新进展作一综述。     

阿柏西普和雷珠单抗治疗糖尿病性黄斑水肿的疗效

目的:比较阿柏西普和雷珠单抗治疗糖尿病性黄斑水肿(DME)的疗效。方法:前瞻性随机对照试验。纳入2020-06/2021-09于我院确诊的非增殖期糖尿病视网膜病变合并DME的患者35例60眼,均采用3+PRN方案行玻璃体腔注射治疗,其中17例30眼接受阿柏西普治疗(阿柏西普组),18例30眼接受雷珠单抗治疗(雷珠单抗组)。随访12mo,观察两组患者中心凹厚度(CMT)和最佳矫正视力(BCVA)情况,记录玻璃体腔注射次数和并发症发生情况。结果:治疗后1、3、6、12mo,阿柏西普组CMT和BCVA均明显优于雷珠单抗组(均P<0.001)。随访期间,阿柏西普组玻璃体腔注射次数少于雷珠单抗组(4.23±0.86次vs 6.40±0.97次,P<0.05),两组患者均未出现药物相关不良反应、眼内感染、血管栓塞等严重并发症。结论:阿柏西普和雷珠单抗治疗DME均具有明确的疗效和安全性,相较于雷珠单抗,阿柏西普可能是DME患者更有效和方便的治疗选择。     

微脉冲激光联合雷珠单抗玻璃体腔内注射治疗非缺血型BRVO继发黄斑水肿

目的：探讨微脉冲激光联合雷珠单抗玻璃体腔内注射治疗非缺血型视网膜分支静脉阻塞(BRVO)继发黄斑水肿(ME)的疗效。方法：选取2020-01/2022-03在我院接受治疗的非缺血型BRVO继发ME患者200例200眼作为本次研究对象,按照随机数字表法分为对照组(100例100眼)和观察组(100例100眼)。其中对照组给予雷珠单抗玻璃体腔内注射治疗,观察组给予微脉冲激光联合雷珠单抗玻璃体腔内注射治疗。比较两组最佳矫正视力(BCVA)、黄斑中心凹视网膜厚度(CMT)、黄斑中心凹下脉络膜厚度(SFCT)、总注药次数、黄斑区渗漏以及并发症发生情况。结果：治疗后两组患者的BCVA均改善,且观察组治疗后1、3、6、12mo的BCVA优于对照组(均P&#x0026;#x003C;0.05)。治疗后两组患者的CMT、SFCT均降低,且观察组治疗后1、3、6、12mo的CMT、SFCT低于对照组(均P&#x0026;#x003C;0.05)。观察组治疗期间总注药次数明显少于对照组(4.06±1.12次 vs 5.32±1.15次,t=5.852,P&#x0026;#x003C;0.001)。对照组和观察组治疗后12mo的渗漏率分别为69.0%、27.0%,两组比较有差异(χ2=35.337,P&#x0026;#x003C;0.001)。对照组和观察组患者的并发症发生率分别为11.0%、5.0%,两组比较无差异(χ2=2.446,P=0.118)。结论：微脉冲激光联合雷珠单抗玻璃体腔内注射治疗非缺血型BRVO继发ME的临床效果显著,能够提高患者的视力,改善ME,减少雷珠单抗总用药次数,且不会增加并发症发生率,安全系数高。     

Effects of Vitreomacular Traction on Ranibizumab Treatment Response in Eyes with Neovascular Age-related Macular Degeneration

PurposeTo investigate the effects of vitreomacular traction (VMT) on ranibizumab treatment response for neovascular age-related macular degeneration (AMD).MethodsA retrospective review of 85 eyes of 85 patients newly diagnosed with neovascular AMD was conducted. Patients were eligible if they had received more than three consecutive monthly ranibizumab (0.50 mg) treatments and ophthalmic evaluations. Patients were classified into a VMT (+) group or VMT (-) group according to optical coherence tomography imaging. Best corrected visual acuity and central retinal thickness (CRT) measurements were obtained at three and six months after initial injection.ResultsOne month after the third injection, mean visual acuity (VA) increases of 6.36 and 9.87 letters were observed in the VMT (+) and VMT (-) groups, respectively. The corresponding mean CRT values decreased by 70.29 µm and 121.68 µm, respectively. A total 41 eyes were identified as eligible for a subsequent fourth injection; 71.1% of patients (27 eyes) in the VMT (+) group but only 29.8% of patients in the VMT (-) group needed a subsequent fourth injection. Follow-up was extended to six months for 42 of the 85 enrolled patients (49.4%). The trends in VA and optical coherence tomography were found to be maintained at six-month follow-up.ConclusionsVA and CRT appeared to be more improved after ranibizumab treatment in the VMT (-) group compared to the VMT (+) group. VMT might antagonize the effect of ranibizumab treatment in a subpopulation of AMD patients.     

Factors affecting visual acuity after one year of follow up after repeated intravitreal ranibizumab for macular degeneration

Aim

Providing intravitreal ranibizumab therapy for neovascular age related macular degeneration (nARMD) is a source of increasing strain for many UK eye departments. Whilst most units attempt to adhere to the product licence of following up patients at four weekly intervals; delays in follow up appointments can and do occur. We aim to see if mean follow up intervals during the maintenance phase are correlated with visual outcomes at one year and perform a multivariate analysis of patient factors in a bit to understand the factors affecting visual acuity outcomes.

Method

A continuously updated prospective audit of patients receiving ranibizumab therapy at the Royal Gwent Hospital was accessed and a coefficient of determination and Spearman’s rank test undertaken to see whether mean follow up delays resulted in visual acuity penalties after nine months of maintenance. Multivariate analysis using ANOVA was then undertaken to examine in more detail the various factors affecting visual acuity outcomes.

Results

805 eyes of 708 patients were included in the study. Mean follow up intervals varied between 28.0 and 96.3 days over the first six treatments of the maintenance phase (mean 49.2 – SD 10.7) with a mean change in visual acuity from baseline of +7.1 letters at 12 weeks and +4.6 letters at 52 weeks. There was a negative correlation seen between visual acuity gains after nine months of the maintenance phase and increasing clinic follow up times although Spearman’s rank analysis demonstrated a correlation coefficient of only −0.078, which was not statistically significant. Variability in follow up appointments resulting in worse outcomes was however significant (p < 0.01), as was increasing age at presentation (p = 0.04). Smoking was found to decrease age of presentation by six years (74.2 years vs 80.0 years). The adjusted R² for the whole analysis was 0.44.

Conclusion

Wide variation in follow up intervals was associated with a worse visual acuity outcome although longer mean follow up interval was not. Smokers presented at a significantly younger age than non-smokers or ex-smokers. This was a large study with an adjusted R² of 0.44. The results are relevant to other macular degeneration service providers around the world.     

抗VEGF治疗在眼科的临床意义及研究进展

目前许多抗血管内皮生长因子(VEGF)药物被用于治疗各种眼科疾病,尤其在血管增生性眼病的治疗中扮演着重要角色,这些药物能够明显抑制新生血管且减轻水肿提高患者视力,但其长期治疗效果需要更长远的随访和研究。本文就抗VEGF在眼科的应用及研究进展进行综述,为临床应用和深入研究提供参考。     

雷珠单抗眼用注射液治疗高度近视脉络膜新生血管的疗效分析

〔摘 要〕 目的：探究雷珠单抗眼用注射液治疗高度近视脉络膜新生血管（CNV）的治疗效果。 方法：回顾性分析 2018 年1 月至 2019 年 12 月期间暨南大学附属广州红十字会医院收治的 29 例（33 眼）高度近视 CNV 患者临床资料,所有患者均接受雷珠单抗眼用注射液治疗,患者均随访 1 年,比较患者治疗前后不同时间段最佳矫正视力（BCVA）、黄斑中心视网膜厚度（CRT）。 结果： 所有患者平均注射（1.85 ± 0.46）针。治疗后 1 年随访中,治疗后 2 周患者 BCVA 较治疗前提高,治疗后 3 个月后 BCVA 逐渐稳定;治疗后不同时间点 BCVA 均较治疗前提高,差异具有统计学意义（P ＜ 0.05）。治疗后患者 CRT 水平较治疗前低,并持续下降至治疗后 3 个月后 CRT 水平逐渐稳定;治疗后不同时间点 CRT 水平均治疗前低,差异具有统计学意义（P ＜ 0.05）。 结论：对高度近视 CNV 患者应用雷珠单抗眼用注射液治疗,可改善其视力水平,降低黄斑中心视网膜厚度。     

Acute generalised exanthematous pustulosis following intravitreal Ranibizumab

Acute generalised exanthematous pustulosis, or AGEP, is a well documented cutaneous drug reaction. It typically occurs within 48 hours of oral antibiotics, but can be caused by other medications and, occasionally, after viral infections. We present a case of AGEP following intravitreal injection of Ranibizumab, a monoclonal antibody vascular endothelial growth factor inhibitor.     

Significance of monitoring vascular endothelial growth factor,monocyte chemoattractant protein-1 and Interleukin-8 in diabetic macular edema towards early identification of nonresponders to ranibizumab therapy

Purpose:Identification of nonresponders prior to anti-vascular endothelial growth factor (anti-VEGF) therapy would help in the judicious clinical management of diabetic macular edema (DME) patients. Thus, a systematic study was initiated to identify nonresponding DME patient population undergoing ranibizumab treatment to figure out additional inflammatory components that may contribute to their nonresponsiveness to anti-VEGF therapy.Methods:A total of 40 patients recruited to this investigator-initiated trial received intravitreal ranibizumab monthly for 3 months. The fourth- and fifth-month injections were according to PRN protocol and the sixth-month injection was mandatory. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and VEGF in aqueous humor were measured for all the patients. Patients were grouped into responders/nonresponders on the formulated criteria and the levels of key pro-inflammatory cytokines were also measured between the two groups at baseline, 2 month and 5 months using cytometric bead array (CBA).Results:Eleven patients were categorized (29.72%) as responders and 10 patients (27.02%) as nonresponders. Nonresponders showed poorer BCVA (P = 0.024, 0.045, and 0.048 for 4, 5, and 6 months) and higher CMT (P = 0.021, 0.0008 and <0.0001 for baseline, 1, 2, 3, 4, 5, and 6 months) compared to responders. The cytokines IL-8, MCP-1 were significantly up regulated (P = 0.0048 and 0.029 for MCP-1 and IL-8) in nonresponders.Conclusion:Elevated MCP-1 and IL-8 levels found in the nonresponders could be used as a prognostic marker to identify these groups of patients and can help in developing alternative treatment options along with anti-VEGF therapy.