Subthreshold micropulse laser versus intravitreal anti-VEGF for diabetic macular edema patients with relatively better visual acuity

AIM: To compare the effects of yellow (577 nm) subthreshold micropulse laser (SML) and intravitreal (IV) anti-vascular endothelial growth factor (VEGF) treatment in patients with diabetic macular edema (DME) with relatively better visual acuity [best corrected visual acuity (BCVA) ≤0.15 logMAR]. METHODS: The medical records of 76 eyes of 47 patients underwent IV (0.5 mg) anti-VEGF injection or SML for the DME with relatively better BCVA were reviewed. The IV group received three consecutive monthly IV anti-VEGF injections, then were retreated as needed. The laser treatment group was treated at baseline and 3mo, and then retreated at 6 and 9mo if needed. All participants were followed up for one year. The mean BCVA and mean central macular thickness (CMT) values changes over the follow-up were evaluated. RESULTS: Twenty-four and 23 patients were assigned to the SML and IV subgroups, respectively. The mean number of treatments was 3.64±0.76 in SML group and 5.85±1.38 in IV group (P<0.05). The subgroups were similar with regard to the mean BCVA score at baseline and at the 1st and 3rd months, but the score of SML group was better than that of IV group at the 6th, 9th, and 12th months (P<0.05). The decrease in the mean CMT values from baseline values was higher in SML group at the 6th, 9th, and 12th months (P<0.05). CONCLUSION: Yellow SML treatment is superior to IV anti-VEGF injection in DME patients with relatively better BCVA for increasing visual acuity and decreasing CMT at 6, 9, and 12mo. SML can be a good alternative first-line therapy for DME with BCVA ≤0.15 logMAR.     

玻璃体腔内注射抗VEGF对糖尿病性黄斑水肿患者脉络膜厚度的影响

目的:使用光学相干断层扫描(OCT)研究累及中心凹的糖尿病性黄斑水肿(DME)患者玻璃体腔内注射雷珠单抗或阿柏西普后中心凹下脉络膜厚度的变化。方法:纳入本院确诊累及中心凹的DME患者17例,其中玻璃体腔内注射雷珠单抗0.5mg/0.05mL患者9例,玻璃体腔内注射阿柏西普2mg/0.05mL患者8例,所有患者均接受每月1次,共3次治疗。使用增强深度成像-光学相干层析成像(EDI-OCT)观察两组患者治疗前和治疗后1mo中心凹下脉络膜厚度、视力和视网膜中央厚度的变化情况。结果:两组患者通过3次玻璃体腔注射抗VEGF后,中心凹下脉络膜厚度和视网膜中央厚度明显较治疗前变薄,视力较治疗前明显改善(均P<0.05),而两组间中心凹下脉络膜厚度、视网膜中央厚度和视力比较均无差异(均P>0.05)。治疗前中心凹下脉络膜厚度与视力改善之间无明显相关性(r_s=-0.269,P=0.296)。治疗后脉络膜厚度变化与视力改善、视网膜中央厚度变化以及患者年龄之间均无明显相关性(均P>0.05)。结论:玻璃体腔内注射雷珠单抗和阿柏西普均可以使累及中心凹的DME患者中央凹下脉络膜和视网膜中央厚度变薄并显著改善视力。     

Systemic safety of anti-VEGF drugs: a commentary

Introduction: VEGF is a mediator of angiogenesis. Thus, concerns have been expressed following the use of VEGF inhibitors for the treatment of neovascular age-related macular degeneration (nAMD). Ranibizumab, and more recently aflibercept, are VEGF inhibitors licensed for the treatment of nAMD. Bevacizumab is also used but unlicensed for this application.

Areas covered: A non-systematic review of nAMD trials was undertaken to investigate four outcomes: all-cause mortality, all systemic serious adverse events (SSAEs), arteriothrombotic events (ATEs) and gastrointestinal (GI) complications. Differences in event rates with injections of ranibizumab compared to bevacizumab, aflibercept, photodynamic therapy (PDT) and sham were explored and quantified using fixed-effect meta-analyses.

Expert opinion: Anti-VEGF agents can influence vascular health; however, the data suggest no difference in the risk of an ATE or death between anti-VEGF agents. Clinical trials are limited in their size and eligibility criteria and databases of patients treated in routine practice should also be scrutinized.     

糖尿病黄斑水肿的治疗进展

糖尿病性视网膜病变( diabetic retinopathy,DR)是一种严重的致盲性眼病,糖尿病黄斑水肿( diabetic lacular edela,DME)可发生在DR的任一时期,常常引起不易逆转的视力丧失,随着发病机制研究的不断深入,在运用传统激光治疗的同时,新兴的抗炎、抗VEGF药物治疗已取得很大进展,微创技术的革新为手术治疗亦提供更大便利,多种治疗方式的联合应用,也成为治疗的主要趋势。我们对目前DME的主要治疗进展进行综述。     

One-year outcomes of Aflibercept for refractory diabetic macular edema in Bevacizumab nonresponders

Purpose:A sub-population of patients with diabetic macular edema (DME) responds less effectively to off-label use of Bevacizumab. Approval of Aflibercept for DME has offered Bevacizumab nonresponders an alternative therapeutic option. Herein, we investigate the anatomical and functional changes associated with Aflibercept treatment in Bevacizumab nonresponders with chronic DME in a Canadian setting.Methods:A retrospective study of eyes with persistent DME that were switched to Aflibercept due to nonresponse following ≥6 consecutive monthly Bevacizumab injections was performed. Anatomical and functional changes and the predictors of response were assessed using patients'' characteristics prior to receiving their first (baseline) and seventh consecutive Aflibercept injections (follow-up).Results:Twenty-four eyes were included, with a mean age of 63.9 ± 10.7 years, an average of 16.8 ± 8.5 Bevacizumab injections prior to switching to Aflibercept, and mean follow-up duration of 11.8 ± 1.7 months following switching to Aflibercept. Best-corrected visual acuity (BCVA) improved significantly from 0.49 ± 0.13 to 0.41 ± 0.11 logMAR (P < 0.001) and central subfield thickness (CST) decreased by 119.4 μm from 409.4 ± 85.8 μm to 290.0 ± 64.5 μm (P < 0.001), with 50% of eyes showing complete anatomical response. Worse BCVA and higher CST at baseline predicted greater vision improvements (P = 0.001 and P = 0.035, respectively) while a larger decrease in CST was associated with greater baseline CST (P = 0.001) and better glycemic control (P = 0.039).Conclusion:Our data from a real-world clinical setting highlight the efficacy of Aflibercept as an alternative therapeutic option for DME recalcitrant to Bevacizumab, with potential additional benefit to those with worse vision, greater CST, and better glycemic control at baseline.     

联合方案治疗BRVO-ME远期疗效的Meta分析

目的:评价视网膜激光光凝联合玻璃体腔注射雷珠单抗与单纯雷珠单抗治疗视网膜分支静脉阻塞继发黄斑水肿(BRVO-ME)的远期疗效及安全性。方法:系统检索Embase、The Cochrane Library、PubMed、中国期刊全文数据库(CNKI)、万方数据库(Wanfang Database)、维普中文科技期刊数据库(VIP)关于激光和雷珠单抗治疗BRVO-ME的随机对照临床研究文献,对纳入研究进行风险评估、提取数据指标。采用RevMan 5.3软件进行数据分析,采用漏斗图评价发表偏倚。结果:共纳入7项研究,641眼。激光联合雷珠单抗组和单纯雷珠单抗组患者的最佳矫正视力(BCVA)在治疗后12mo[WMD=0.00,95%CI(-0.13,0.14),P=0.95]和24mo[WMD=0.05,95%CI(-0.12,0.22),P=0.57]变化均无明显差异。两组在治疗12mo[WMD=-7.67,95%CI(-54.58,39.24),P=0.75]和24mo[WMD=12.21,95%CI(-81.68,106.09),P=0.80]黄斑中心凹厚度的变化无明显差异。两组在12、24mo的雷珠单抗注药次数及最终不良事件发生情况方面亦无统计学差异。结论:激光联合雷珠单抗相较单纯雷珠单抗治疗BRVO-ME,在视力和黄斑中心凹厚度方面的远期结果无明显差异,在雷珠单抗的注药次数和安全性方面也无较大差距。     

玻璃体腔注射贝伐单抗治疗慢性CSC的长期疗效观察

目的：探讨玻璃体腔注射贝伐单抗(IVB)治疗慢性中心性浆液性脉络膜视网膜病变(central serous chorioretinopathy,CSC)的安全性和长期临床疗效。

方法：我们给予6例6眼慢性CSC患者玻璃体腔注射1.25mg/0.05mL IVB治疗。5例患者在第一次注射后3mo接受了第二次相同剂量的注射。注射后1,3,6,12,24mo时随访观察。观察指标包括治疗前后的最佳矫正视力、眼压、OCT、眼底荧光素造影(FFA)。

结果：第一次玻璃体腔注射IVB后,2例患者视网膜下液(SRF)完全吸收,但其中1例在随访至3mo复发; 3例患者SRF有小幅度上升或下降; 1例患者的SRF先上升后明显下降; 再次进行IVB后,3例患者SRF完全吸收,其他的3例患者SRF无明显变化。但是SRF的吸收与视力的变化并不是同步的。治疗前后1,2a患者的视力变化在统计学上没有显著性差异。随访期间所有患者眼压均在正常范围,无一例出现眼内炎。

结论：玻璃体腔注射IVB对于治疗慢性CSC患者是安全的,对促进SRF的吸收有一定效果,但从长期结果来看,IVB对于慢性CSC患者的远期视力预后无明显作用。     

Intravitreal ranibizumab for the treatment of choroidal neovascularisation secondary to angioid streaks

Aims

To assess the medium to long-term efficacy and safety of intravitreal ranibizumab for the treatment of choroidal neovascularisation (CNV) secondary to angioid streaks (AS).

Methods

A total of 12 eyes of nine patients treated with intravitreal ranibizumab (0.5 mg in 0.05 ml) for CNV secondary to AS were retrospectively identified. Efficacy of treatment was determined by changes in best-corrected LogMAR visual acuity (BCVA) and optical coherence tomography. Changes with respect to baseline BCVA were defined as improved or reduced with a gain or loss of more than 10 letters, respectively, or stable if remaining within 10 letters.

Results

Over a mean follow-up of 21.75 months (range: 1–54), patients received mean 5.75 (range: 2–15) intravitreal ranibizumab injections per affected eye. BCVA improved in three eyes (25%), stabilised in eight eyes (66.67%), and deteriorated in one eye (8.33%). There was no significant change in central retinal thickness (CRT) over the follow-up period (P=0.1072). No drug-related systemic side effects were recorded.

Conclusion

The long-term treatment of CNV secondary to AS with intravitreal ranibizumab showed a stabilisation in CRT and an improvement or stabilisation of BCVA. The absence of systemic side effects was reassuring. Further long-term prospective studies are required to validate these findings.     

Retinopathy of prematurity: overview of new global problem

Retinopathy of prematurity (ROP) is a disease characterized by abnormal retinal vasculature in preterm infants. It is an important cause of visual disability in premature infants and although the incidence varies among different countries it is increasing as advances in neonatal care result in improved survival. Oxygen, growth factors like vascular endothelial growth factor, and poor postnatal growth play a significant role in the pathogenesis of ROP. Targeting lower oxygen saturation is associated with a reduction in ROP, but with increased mortality. Screening for ROP varies between centres and countries but generally it includes preterm infants (less than 32 weeks’ gestation) and/or those with a birth weight of less than 1500g. ROP has been recently reclassified as type-1-needing treatment and type-2 ROP needing observation, based on the benefits and treatment efficacy. Laser therapy and anti-VEGF are the two main treatments. Recent reports suggest that anti-VEGF therapy may have better visual outcomes (myopia) and a better safety profile. ROP is a global disease of prematurity and understanding the pathogenesis, course of ROP, preventive strategies, treatment options and outcomes are essential for all healthcare professionals caring for preterm babies. This short article describes the evidence for screening, prevention and treatment options and looks ahead to possible advances in the near future.     

Anti-angiogenic therapies in cancer clinical trials

Strategies involving vasculature have widely been acknowledged to have therapeutic potential in the management of cancer and other diseases. Based on a large body of evidence from preclinical studies and early clinical trials there is considerable optimism that anti-angiogenesis and vascular targeting will be a major clinical therapy. This review considers some 30 anti-angiogenic and vascular targeting agents that are currently in cancer clinical trials and highlights specific problems relating to the assessment of the activity of these agents in patients, trial design, potential toxicities and resistance mechanisms.