Simha Arathi, Aziz Kanza, Braganza Andrew, Abraham Lekha, Samuel Prasanna, Lindsley Kristina B
Christian Medical College, Department of Ophthalmology, Vellore, India, 632001.
Johns Hopkins University School of Medicine, Wilmer Eye Institute, Baltimore, Maryland, USA, 21287.
Cochrane Database Syst Rev. 2020 Feb 6;2(2):CD007920. doi: 10.1002/14651858.CD007920.pub3.
Neovascular glaucoma (NVG) is a potentially blinding, secondary glaucoma. It is caused by the formation of abnormal new blood vessels, which prevent normal drainage of aqueous from the anterior segment of the eye. Anti-vascular endothelial growth factor (anti-VEGF) medications are specific inhibitors of the primary mediators of neovascularization. Studies have reported the effectiveness of anti-VEGF medications for the control of intraocular pressure (IOP) in NVG.
To assess the effectiveness of intraocular anti-VEGF medications, alone or with one or more type of conventional therapy, compared with no anti-VEGF medications for the treatment of NVG.
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register); MEDLINE; Embase; PubMed; and LILACS to 22 March 2019; metaRegister of Controlled Trials to 13 August 2013; and two additional trial registers to 22 March 2019. We did not use any date or language restrictions in the electronic search for trials.
We included randomised controlled trials (RCTs) of people treated with anti-VEGF medications for NVG.
Two review authors independently assessed the search results for trials, extracted data, and assessed risk of bias, and the certainty of the evidence. We resolved discrepancies through discussion.
We included four RCTs (263 participants) and identified one ongoing RCT. Each trial was conducted in a different country: China, Brazil, Egypt, and Japan. We assessed the trials to have an unclear risk of bias for most domains due to insufficient information. Two trials compared intravitreal bevacizumab combined with Ahmed valve implantation and panretinal photocoagulation (PRP) with Ahmed valve implantation and PRP. We did not combine these two trials due to substantial clinical and statistical heterogeneity. One trial randomised participants to receive an injection of either an intravitreal anti-VEGF medication or placebo at the first visit, followed by non-randomised treatment according to clinical findings after one week. The last trial randomised participants to PRP with and without ranibizumab, but details of the study were unavailable for further analysis. Two trials that examined IOP showed inconsistent results. One found inconclusive results for mean IOP between participants who received anti-VEGF medications and those who did not, at one month (mean difference [MD] -1.60 mmHg, 95% confidence interval [CI] -4.98 to 1.78; 40 participants), and at one year (MD 1.40 mmHg, 95% CI -4.04 to 6.84; 30 participants). Sixty-five percent of the participants with anti-VEGF medications achieved IOP ≤ 21 mmHg, versus 60% without anti-VEGF medications. In another trial, those who received anti-VEGF medications were more likely to reduce their IOP than those who did not receive them, at one month (MD -6.50 mmHg, 95% CI -7.93 to -5.07; 40 participants), and at one year (MD -12.00 mmHg, 95% CI -16.79 to -7.21; 40 participants). Ninety-five percent of the participants with anti-VEGF medications achieved IOP ≤ 21 mmHg, versus 50% without anti-VEGF medications. The certainty of a body of evidence was low for this outcome due to limitations in the design and inconsistency of results between studies. Post-operative complications included anterior chamber bleeding (3 eyes) and conjunctival hemorrhage (2 participants) in the anti-VEGF medications group, and retinal detachment and phthisis bulbi (1 participant each) in the control group. The certainty of evidence is low due to imprecision of results and indirectness of evidence. No trial reported the proportion of participants with improvement in visual acuity, proportion of participants with complete regression of new iris vessels, or the proportion of participants with relief of pain and resolution of redness at four- to six-week, or one-year follow-up.
AUTHORS' CONCLUSIONS: Currently available evidence is uncertain regarding the long-term effectiveness of anti-VEGF medications, such as intravitreal ranibizumab or bevacizumab or aflibercept, as an adjunct to conventional treatment in lowering IOP in NVG. More research is needed to investigate the long-term effect of these medications compared with, or in addition to, conventional surgical or medical treatment in lowering IOP in NVG.
新生血管性青光眼（NVG）是一种具有潜在致盲性的继发性青光眼。它由异常新生血管的形成引起，这些新生血管阻碍了眼前段房水的正常引流。抗血管内皮生长因子（抗VEGF）药物是新生血管形成主要介质的特异性抑制剂。研究报告了抗VEGF药物在控制NVG眼压（IOP）方面的有效性。
评估眼内抗VEGF药物单独使用或与一种或多种传统疗法联合使用，与不使用抗VEGF药物相比，治疗NVG的有效性。
我们检索了截至2019年3月22日的Cochrane中心对照试验注册库（CENTRAL，其中包含Cochrane眼科和视力试验注册库）、MEDLINE、Embase、PubMed和LILACS；截至2013年8月13日的对照试验元注册库；以及另外两个试验注册库至2019年3月22日。在电子检索试验时，我们未使用任何日期或语言限制。
我们纳入了接受抗VEGF药物治疗NVG患者的随机对照试验（RCT）。
两位综述作者独立评估试验的检索结果，提取数据，并评估偏倚风险和证据的确定性。我们通过讨论解决分歧。
我们纳入了四项RCT（263名参与者），并确定了一项正在进行的RCT。每项试验在不同国家进行：中国、巴西、埃及和日本。由于信息不足，我们评估这些试验在大多数领域的偏倚风险不明确。两项试验比较了玻璃体内注射贝伐单抗联合艾哈迈德瓣膜植入和全视网膜光凝（PRP）与艾哈迈德瓣膜植入和PRP。由于存在大量临床和统计异质性，我们未合并这两项试验。一项试验将参与者随机分为在首次就诊时接受玻璃体内抗VEGF药物注射或安慰剂注射，然后在一周后根据临床结果进行非随机治疗。最后一项试验将参与者随机分为接受PRP联合或不联合雷珠单抗治疗，但该研究的详细信息无法用于进一步分析。两项检查眼压的试验结果不一致。一项试验发现，接受抗VEGF药物治疗的参与者与未接受抗VEGF药物治疗的参与者在1个月时的平均眼压结果无定论（平均差值[MD] -1.60 mmHg，95%置信区间[CI] -4.98至1.78；40名参与者），在1年时（MD 1.40 mmHg，95% CI -4.04至6.84；30名参与者）。接受抗VEGF药物治疗的参与者中有65%眼压≤21 mmHg，而未接受抗VEGF药物治疗的参与者中这一比例为60%。在另一项试验中，接受抗VEGF药物治疗的参与者在1个月时（MD -6.50 mmHg，95% CI -7.93至-5.07；40名参与者）和1年时（MD -12.00 mmHg，95% CI -16.79至-7.21；40名参与者）比未接受抗VEGF药物治疗的参与者更有可能降低眼压。接受抗VEGF药物治疗的参与者中有95%眼压≤21 mmHg，而未接受抗VEGF药物治疗的参与者中这一比例为50%。由于设计上的局限性和研究结果之间的不一致性，该结果的证据确定性较低。抗VEGF药物治疗组的术后并发症包括前房出血（3只眼）和结膜出血（2名参与者），对照组包括视网膜脱离和眼球痨（各1名参与者）。由于结果的不精确性和证据的间接性，证据的确定性较低。没有试验报告在4至6周或1年随访时视力改善的参与者比例、新生虹膜血管完全消退的参与者比例或疼痛缓解和眼红消退的参与者比例。
目前可得的证据对于抗VEGF药物（如玻璃体内注射雷珠单抗、贝伐单抗或阿柏西普）作为传统治疗辅助手段降低NVG眼压的长期有效性尚不确定。需要更多研究来调查与传统手术或药物治疗相比，或在传统治疗基础上，这些药物降低NVG眼压的长期效果。
