Long-Term Stability of Anti-Vascular Endothelial Growth Factor (a-VEGF) Biologics Under Physiologically Relevant Conditions and Its Impact on the Development of Long-Acting Delivery Systems

The port delivery system with ranibizumab (PDS) is an investigational long-acting drug delivery system for the continuous release of ranibizumab, an anti-VEGF biologic, in the vitreous humor. The efficacy of the PDS implant relies on the maintenance of long-term drug stability under physiological conditions. Herein, the long-term stability of three anti-VEGF biologics - ranibizumab, bevacizumab and aflibercept - was investigated in phosphate buffered saline (PBS) at 37 °C for several months. Comparison of stability profiles shows that bevacizumab and aflibercept are increasingly prone to aggregation whereas ranibizumab undergoes minimal aggregation. Ranibizumab also shows the smallest loss in antigen binding capacity after long-term incubation in PBS. Even though the aggregated forms of bevacizumab and aflibercept bind to VEGF, the consequences of aggregation on immunogenicity, implant function and efficacy are unknown. These results highlight the importance of maintaining long-term drug stability under physiologically relevant conditions which is necessary for achieving efficacy with an in vivo continuous drug delivery device such as the PDS implant.     

雷珠单抗治疗视网膜分支静脉阻塞继发黄斑水肿过程中玻璃体的状态变化及其对疗效影响

目的 探讨雷珠单抗治疗视网膜分支静脉阻塞继发黄斑水肿（branch retinal vein occlusion-macular edema,BRVO-ME）过程中玻璃体状态的动态变化及其对疗效的影响。方法 回顾性分析2021年2—6月在中国科学技术大学附属第一医院眼科接受玻璃体腔注射雷珠单抗治疗的初诊BRVO-ME病人35例35眼,根据间接眼底镜,B超及光学相干断层扫描（optical coherence to-mography,OCT）结果对玻璃体状态进行评估,分为无PVD组17例,局限VMA组5例,广泛VMA组7例,完全PVD组6例。各组病人连续3月每月注射雷珠单抗1次,随访4个月以上,在每次注射1月后观察病人的玻璃体状态、黄斑厚度（central macular thick-ness,CMT）和最佳矫正视力（best corrected visual acuity,BCVA）。结果 35眼在治疗后BCVA和CMT均显著好转。各组病人在注药1次,2次,3次后的BCVA均差异无统计学意义。在第1次注药后,局限VMA组的CMT[452.00(433.50,591.50)μm]与无PV...     

糖尿病黄斑水肿应用玻璃体内注射雷珠单抗、曲安奈德的疗效分析

目的 比较玻璃体内注射雷珠单抗、曲安奈德在糖尿病黄斑水肿中的临床疗效.方法 收集本院2014年10月至2015年10月入院的80例糖尿病黄斑水肿患者,随机分为两组,雷珠单抗组患者给予雷珠单抗治疗,曲安奈德组患者给予曲安奈德治疗,比较两组患者治疗前后最佳矫正视力、RNV渗透面积、黄斑区中心视网膜厚度、眼压与并发症等.结果 雷珠单抗组患者BCVA为(0.556±0.155),显著高于曲安奈德组的(0.409±0.143);RNV渗透面积为(5.405±3.274),显著低于曲安奈德组的(8.332±4.058);雷珠单抗组患者CMT为(289.231±64.040) μm,显著低于曲安奈德组的(370.127±88.172)μm;雷珠单抗组患者治疗后眼压为(15.157±2.351) mmHg,显著低于曲安奈德组(17.264±3.197)mmHg;两组比较,t=4.4897、3.550、4.695、3.358,差异有统计学意义(P＜0.01).结论 玻璃体内注射雷珠单抗在糖尿病黄斑水肿中的临床疗效更为显著,安全性较高,具有借鉴性.     

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。     

Comparative role of intravitreal ranibizumab versus bevacizumab in choroidal neovascular membrane in age-related macular degeneration

Context:

Ranibizumab and bevacizumab are used widely for treating patients with choroidal neovascular membrane (CNVM) secondary to age-related macular degeneration (AMD).

Aims:

To determine and compare the efficacy and safety of intravitreal ranibizumab and bevacizumab in treatment of CNVM due to AMD.

Settings and Design:

Prospective comparative case series carried out in an eye institute and eye department of a hospital in Kolkata, India.

Materials and Methods:

One hundred and four eyes with CNVM due to AMD were randomized into two groups. Group A (n=54; 24 occult) received monthly intravitreal ranibizumab injections (0.5 mg in 0.05 ml) and Group B (n=50; 22 occult) received monthly bevacizumab injections (1.25 mg in 0.05 ml) for 3 consecutive months and then as per study criteria. Data analysis done using SPSS software. P-value of <0.05 was considered statistically significant.

Results:

The mean best corrected visual acuity (BCVA) in the ranibizumab group increased from 58.19 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at baseline to 64 ETDRS letters at month 3 (P<0.001). In bevacizumab group mean BCVA increased from 56.80 to 61.72 ETDRS letters at month 3 (P<0.001). At the end of 18 months, there was no statistically significant difference between groups A and B with respect to change in BCVA (P=0.563) or central macular thickness (CMT; P=0.281), as measured by optical coherence tomography (Stratus OCT 3000). No significant sight-threatening complications developed.

Conclusions:

Ranibizumab and bevacizumab are equally safe and efficacious in treating CNVM due to AMD.     

玻璃体腔注射治疗不同病程两组特发性脉络膜新生血管病变

目的 对比分析Ranibizumab玻璃体腔注射治疗两组不同病程的特发性脉络膜新生血管病变患者(ICNV)的疗效。方法 经眼底荧光素血管造影(FFA)及光相干断层扫描(OCT)检查,并结合临床表现确诊为特发性脉络膜新生血管病变的患者36例36眼,按病程分为A(病程＜3个月)、B(3个月≤病程<6个月)两组。所有患者均行常规玻璃体腔ranibizumab注射治疗。治疗前检查两组受检者最佳矫正视力BCVA(logMAR)、屈光度、眼压、散瞳查眼底、光学相干断层扫描(OCT)检查病灶与中心凹的位置关系以及CMT、FFA。治疗后每月检查两组受检者BCVA(logMAR)、眼压、散瞳查眼底、OCT查CMT,必要时重复造影确定是否需要眼内重复注射。对比两组治疗前和治疗后1、3、6个月时的BCVA(logMAR)、CMT、眼压,并统计6个月时的注射次数。结果 与治疗前相比,两组在治疗后的1、3、6个月随访时,BCVA及CMT均有明显改善, P<0.05。而两组间在治疗后的1、3、6个月随访时, BCVA及CMT的比较差异无统计学意义(P>0.05),但至随访6个月时,A组的注射次数(1.3±0.5)次少于B组(2.1±1.2) 次(P＜0.05)。结论 玻璃体腔注射ranibizumab能够快速有效的改善ICNV患者病情,发病早期治疗可以减少注射次数,降低注射风险并减少治疗的成本。