Laser therapy versus intravitreal injection of anti-VEGF agents in monotherapy of ROP:a Meta-analysis

AIM:To compare the efficacy and safety between laser therapy and anti-vascular endothelial growth factor(VEGF)agents intravitreal injection monotherapy in type-1 retinopathy of prematurity(ROP)and aggressive posterior retinopathy of prematurity(APROP).METHODS:A systematic literature search was performed in PubMed,Cochrane Library,and Embase for original comparable studies.We included studies that compare laser therapy and intravitreal injections of anti-VEGF agents monotherapy in ROP regardless of languages and publication types.RESULTS:Complication incidence was significantly higher in laser therapy group(OR:0.38;95%CI:0.19-0.75;P=0.005).Spherical equivalent(SE)was higher in laser therapy[weighted mean difference(WMD):2.40,95%CI:0.88-3.93;P=0.002].The time between treatment and retreatment was longer in laser therapy group(WMD:8.45,95%CI:5.35-11.55;P<0.00001).Recurrence incidence(OR:0.97;95%CI:0.45-2.09;P=0.93)and retreatment incidence(OR:1.24;95%CI:0.56-2.73;P=0.59)were similar in two approaches.Subgroup analysis between type-1 ROP and APROP was not significant except SE reported in the included studies(P<0.0001).CONCLUSION:This Meta-analysis outcome indicates anti-VEGF agents are as effective as laser treatment,and safer than laser in type-1 ROP and APROP.The degree of myopia in APROP is higher than type-1 ROP.More randomized controlled trials in large sample size should be conducted in the future.     

抗VEGF与激光治疗1型早产儿视网膜病变的Meta分析

目的:系统评价抗VEGF与激光治疗1型早产儿视网膜病变(ROP)的疗效分析。方法:通过计算机检索PubMed、EMbase、CBM、The Cochrane Library、WanFang Data、CNKI和VIP数据库,收集比较抗VEGF与激光用于治疗1型ROP疗效的随机对照试验(RCT),检索时限均从建库至2020-01-06,按照纳入与排除标准提取资料,行质量评价后,采用RevMan 5.3软件进行Meta分析。结果:共纳入6个RCT。Meta分析结果显示:抗VEGF与激光组相比,复发率无差异[RR=0.94,95%CI(0.17~5.23),P=0.94];亚组分析Ⅰ区有差异[RR=0.17,95%CI(0.05~0.62),P=0.007];Ⅱ区无差异[RR=2.20,95%CI(0.07~73.48),P=0.66]。与激光组相比,再治疗率无差异[RR=2.36,95%CI(0.70~7.99),P=0.17],亚组分析Ⅰ区无差异[RR=0.33,95%CI(0.01~7.50),P=0.49];Ⅱ区有差异[RR=13,95%CI(1.84~92.01),P=0.01]。两者不良反应发生率无差异[RR=0.87,95%CI(0.54~1.40),P=0.57]。结论:激光和抗VEGF疗效相当,但在降低Ⅰ区复发率方面抗VEGF则更有优势,降低Ⅱ区再治疗率方面激光更有优势。     

玻璃体腔注射贝伐单抗和雷珠单抗治疗1型ROP疗效的Meta分析

目的:评价玻璃体腔注射贝伐单抗(IVB)和雷珠单抗(IVR)治疗1型早产儿视网膜病变(ROP)的疗效。方法:通过检索PubMed、Embase、Web of Science、the Cochrane Library、CQVIP、CBM、OVID、中国知网和万方数据库,检索时间为建库至2020-04-01。纳入所有比较IVB和IVR治疗ROP疗效的研究。由两位研究员进行独立的数据提取和质量评估。使用Review Manager 5.3软件进行统计分析。本研究观察的主要结局指标为再治疗率,次要结局指标包括:完全血管化比例和等效球镜度。结果:共纳入了8篇病例对照研究,共885眼。与IVB治疗组相比,IVR治疗组有更高的再治疗率(OR=0.55,95%CI:0.34~0.88,P<0.05)及更低的等效球镜度数(WMD=-1.44,95%CI:-2.28~-0.00,P<0.05),对于完全血管化比例,两组比较无差异(OR=2.15,95%CI:0.80~0.576,P>0.05)。结论:IVR和IVB治疗1型ROP均可以完成视网膜的完全血管化,但两种治疗方法各有优势,IVR对于儿童屈光的影响较小,但在降低再发率方面其作用较IVB差。     

Comparison of conbercept and ranibizumab for the treatment efficacy of diabetic macular edema: a Meta-analysis and systematic review

AIM: To evaluate the efficacy of intravitreal injection of conbercept (IVC) and ranibizumab (IVR) in patients with diabetic macular edema. METHODS: Reviewers have searched 12 databases, including PubMed, Medline, EMBASE, Web of Science, Springer, ScienceDirect, OVID, Cochrane Library, ClinicalTrials.gov, cqVIP, WanFangdata and China National Knowledge Infrastructure (CNKI), up to December 28, 2018. RevMan 5.3 (Cochrane Library Software, Oxford, UK) was employed for statistical analysis. Fixed and random effects models were applied to assess heterogeneity. Odds ratio (OR) was applied for dichotomous variables; weighted mean difference (WMD) was applied for continuous variables. The confidence interval (CI) was set at 95%. Central macular thickness (CMT) and best-corrected visual acuity (BCVA) were employed to analyze the improvement of DME patients. Inclusion criteria for picking out studies were retrospective studies and randomized controlled trials (RCTs) that compared IVC and IVR for the treatment of diabetic macular edema. RESULTS: Four retrospective studies and five RCTs were included with a total of 609 patients. No statistically significant difference was observed in mean CMT and mean BCVA in the baseline parameters [BCVA (WMD: -0.48; 95%CI: -1.06 to 0.10; P=0.1), CMT (WMD: -0.83; 95%CI: -15.15 to 13.49; P=0.91). No significant difference was found in the improvement of BCVA and adverse event (AE) in IVC group, compared with IVR group after treatment of loading dosage [the 1st month BCVA (WMD: 0.01; 95%CI: -0.26 to 0.27; P=0.96), the 3rd month BCVA (WMD: -0.04; 95%CI: -0.14 to 0.06; P=0.46); the 6th month BCVA (WMD: -0.24; 95%CI: -1.62 to 1.14; P=0.73)], AE (OR: 0.84; 95%CI: 0.38 to 1.84; P=0.66)]. A slight difference was found in the effectiveness rate (OR: 1.70; 95%CI: 0.97 to 2.96; P=0.06), There were statistically significant differences between IVC and IVR treatment in terms of CMT [1st month CMT (WMD: -19.88; 95%CI: -27.94 to -11.82; P<0.001), 3rd month CMT (WMD: -23.31; 95%CI: -43.30 to -3.33; P=0.02), 6th month CMT (WMD: -74.74; 95%CI: -106.22 to -43.26; P<0.001)]. CONCLUSION: Pooled evidence suggests that both IVC and IVR are effective in the therapy of diabetic macular edema and affirms that IVC presents superiority over IVR therapy in regard of CMT in patients with diabetic macular edema, but no statistically significant difference with regard to visual improvement. Relevant RCTs with longer-term follow-up are necessary to back up our conclusion.     

Efficiency and safety of laser photocoagulation with or without intravitreal ranibizumab for treatment of diabetic macular edema: a systematic review and Meta-analysis

AIM: To compare the therapeutic effect and safety of laser photocoagulation along with intravitreal ranibizumab (IVR) versus laser therapy in treatment of diabetic macular edema (DME). METHODS: Pertinent publications were identified through comprehensive searches of PubMed, EMBASE, Web of Science, Cochrane Library, and ClinicalTrials.gov to identify randomized clinical trials (RCTs) comparing IVR+laser to laser monotherapy in patients with DME. Therapeutic effect estimates were determined by weighted mean differences (WMD) of change from baseline in best corrected visual acuity (BCVA) and central retinal thickness (CRT) at 6, 12, or 24mo after initial treatment, and the risk ratios (RR) for the proportions of patients with at least 10 letters of improvement or reduction at 12mo. Data regarding major ocular and nonocular adverse events (AEs) were collected and analyzed. The Review Manager 5.3.5 was used. RESULTS: Six RCTs involving 2069 patients with DME were selected for this Meta-analysis. The results showed that IVR+laser significantly improved BCVA compared with laser at 6mo (WMD: 6.57; 95% CI: 4.37-8.77; P<0.00001), 12mo (WMD: 5.46; 95% CI: 4.35-6.58; P<0.00001), and 24mo (WMD: 3.42; 95% CI: 0.84-5.99; P=0.009) in patients with DME. IVR+laser was superior to laser in reducing CRT at 12mo from baseline with statistical significance (WMD: -63.46; 95% CI: -101.19 to -25.73; P=0.001). The pooled RR results showed that the proportions of patients with at least 10 letters of improvement or reduction were in favor of IVR+laser arms compared with laser (RR: 2.13; 95% CI: 1.77-2.57; P<0.00001 and RR: 0.37; 95% CI: 0.22-0.62; P=0.0002, respectively). As for AEs, the pooled results showed that a significantly higher proportion of patients suffering from conjunctival hemorrhage (study eye) and diabetic retinal edema (fellow eye) in IVR+laser group compared to laser group (RR: 3.29; 95% CI: 1.53-7.09; P=0.002 and RR: 3.02; 95% CI: 1.24-7.32; P=0.01, respectively). The incidence of other ocular and nonocular AEs considered in this Meta-analysis had no statistical difference between IVR+laser and laser alone. CONCLUSION: The results of our analysis show that IVR+laser has better availability in functional (improving BCVA) and anatomic (reducing CRT) outcomes than laser monotherapy for the treatment of DME. However, the patients who received the treatment of IVR+laser may get a higher risk of suffering from conjunctival hemorrhage (study eye) and diabetic retinal edema (fellow eye).     

抗血管内皮生长因子治疗糖尿病黄斑水肿患者短期疗效影响因素分析

目的　观察抗血管内皮生长因子（VEGF）玻璃体内注射治疗糖尿病黄斑水肿（DME）患者短期疗效的影响因素。方法　回顾性分析。纳入接受玻璃体内注射抗VEGF药物的DME患者67例67眼,采集患者一般信息、全身病史及相关血液学检测指标（血糖、血常规、血脂、生化、肾功能等）、眼部病史及眼科相关检查结果［视力、眼压、眼底彩色照相、OCT相关影像学指标、荧光素眼底血管造影（FFA）等］。采用单因素及二元logistic回归分析进行数据统计。结果　将单因素分析结果中有统计学差异的指标纳入二元logistic回归分析,结果显示,基线1 mm黄斑中心视网膜体积小（OR=0.001,95%CI为0.001~0.036）、1 mm 黄斑中心视网膜厚度薄（OR=0.994,95%CI 为0.988~1.000）、白细胞计数低（OR=0.561,95%CI为0.332~0.948）、血红蛋白浓度高（OR=1.076,95%CI为1.021~1.135）、红细胞计数高（OR=11.798,95%CI为 1.854~75.078）、视力下降时间长（OR=2.008,95%CI为 1.053~3.830）、基线最佳矫正视力低（OR=0.274,95%CI为 0.093~0.804）是DME患者抗VEGF治疗后短期疗效不佳的独立影响因素。结论　DME患者基线时视功能与眼部解剖结构以及全身情况可能影响抗VEGF治疗的短期疗效。     

Clinical efficacy of intravitreal corticoid as an adjunctive therapy to anti-VEGF treatment of neovascular age-related macular degeneration: a Meta-analysis

AIM: To evaluate the efficacy and safety of intravitreal corticoid as an adjunctive therapy to anti-vascular endothelial growth factor (VEGF) treatment of neovascular age-related macular degeneration (nvAMD). METHODS: Four databases including PubMed, Embase, Cochrane Library, and the clinicaltrials.gov were comprehensively searched for studies comparing intravitreal corticoid plus anti-VEGF (IVC/IVA) vs anti-VEGF monotherapy (IVA) in patients with nvAMD. GRADE profiler was used to assess the quality of outcomes. Best-corrected visual acuity (BCVA), central macular thickness (CMT) and adverse events including the occurrence of severe elevation of intraocular pressure (IOP) and the progress of cataract were extracted from the eligible studies. Review Manager (RevMan) 5.3 was used to analyze the data. RESULTS: There was no statistic difference of mean change in BCVA at 6 and 12mo between IVC/IVA and IVA group [95% confidence interval (CI): -2.28 to 4.24, P=0.55; 95%CI: -3.01 to 8.70, P=0.34]. No statistic difference was found in the change of CMT between two groups at 6mo time point (95%CI: -17.98 to 16.42, P=0.93) while the CMT reduction in IVC/IVA group was significantly more obvious than IVA group at 12mo time point [mean difference (MD)=-44.08, 95%CI: -80.52 to -7.63, P=0.02]. The risk of occurrence of severe elevation of IOP in the IVC/IVA group was higher than that in the IVA group (95%CI: 1.92 to 9.48; P=0.0004). Cataract progression risk was calculated no statistic difference between two groups (95%CI: 0.74 to 4.66; P=0.18). CONCLUSION: No visual or anatomical benefits are observed in IVC/IVA group at 6mo. At 12mo, the CMT of the IVC/IVA group is significantly lower than that of the IVA group. Risk of severe elevation of IOP is significantly higher when treated by IVC/IVA.     

玻璃体注射Bevacizumab治疗26例Ⅰ区早产儿视网膜病变

目的：评价玻璃体注射 bevacizumab 治疗26例Ⅰ区早产儿视网膜病变(retinopathy of prematurity,ROP)的治疗效果。方法：通过回顾性研究,对2013-09/2014-10确诊为Ⅰ区阈值期 ROP 并行玻璃体注射 bevacizumab 治疗的26例患儿分三组(阈值前期Ⅰ型 ROP、阈值期 ROP、急进型后极部早产儿视网膜病变-APROP),进行术后效果分析比较。结果：治疗Ⅰ区高危性阈值期 ROP 患儿26例52眼。其中阈值前期Ⅰ型 ROP 3例6眼,阈值期 ROP 15例30眼, APROP 8例16眼。治疗阈值期Ⅰ型 ROP、阈值期 ROP 和APROP 的一次手术治愈率分别为100%(6/6)、60%(18/30)和75%(12/16),三组之间手术治愈率无统计学差异(P>0.05)。
　　结论：玻璃体腔内注射 bevacizumab 治疗Ⅰ区 ROP 的临床疗效明确,比传统光凝术治疗具有一定优越性,可作为 I区 ROP 的一线治疗方法。     

Combination of Intravitreal Ranibizumab and Laser Photocoagulation for Aggressive Posterior Retinopathy of Prematurity

Purpose

To report on 2 cases of aggressive posterior retinopathy of prematurity (ROP) treated with intravitreal ranibizumab (Lucentis^®) and laser photocoagulation.

Methods

Two premature females, born at 25 and 26 weeks’ gestation with a birth weight of 530 and 550 g, respectively, with aggressive posterior ROP received combined treatment with laser photocoagulation and intravitreal ranibizumab (0.3 mg [30 µl]) to each eye. Structural outcomes were evaluated by indirect ophthalmoscopy and documented by retinography.

Results

An intravitreal injection was made at 34 weeks of postmenstrual age in the first case, followed by laser photocoagulation 1 week later. There was a partial regression of ROP with treatment. Five weeks later, neovascularization regrowth with bleeding in both eyes (intraretinal and subhyaloid) occurred and retreatment with combined therapy was performed. In the second case, single therapy with laser photocoagulation was made at 34 weeks of postmenstrual age. In spite of the confluent photocoagulation in the avascular area, progression to 4A ROP stage occurred 1 week later. Both eyes were retreated 1 week later with intravitreal ranibizumab and laser photocoagulation. Treatment resulted in ROP regression in both cases. There were no signs of systemic or ocular adverse side effects.

Conclusion

The cases presented show that combination therapy of indirect laser photocoagulation and intravitreal ranibizumab can be effective in the management of aggressive posterior ROP. Further investigation on anti-VEGF safety in premature infants is necessary. Additional studies are needed to define the role of anti-VEGF in ROP treatment.Key Words: Retinopathy of prematurity, Laser photocoagulation, Ranibizumab, Anti-VEGF therapy     

玻璃体切除术前注射抗VEGF类药物治疗PDF的疗效及安全性的Meta分析

目的:探究增殖性糖尿病视网膜病变(proliferative diabetic retinopathy,PDR)患者行玻璃体切除术治疗前玻璃体腔内注射抗VEGF类药物的有效性与安全性.方法:全面检索EMbase、The Cochrane Library、Pubmed、中国生物医学文摘数据库(CBM)、万方数据库(WanFang Database)、中国期刊全文数据库(CNKI)等数据库,检索时限均从建库至2017-01,语种不限,检索文献类型为随机对照试验;采用Jadad量表及Cochrane协作网提供的风险偏倚评估工具评价所纳入研究的质量,采用GRADEpro软件对各评价指标的参数进行循证医学质量评价;采用漏斗图检测所纳入文献的发表偏倚;最后采用Review Manager 5.3软件行Meta分析.结果:最终纳入发表时间介于2008/2016的16篇随机对照试验文献.共包含923例患眼,其中493例患眼进入PPV联合术前玻璃体腔内注射anti-VEGF组(试验组),430例患眼进入单纯行PPV组(对照组).Meta分析结果显示:(1)试验组术中出血的发生概率明显低于对照组[OR=0.06,95%CI(0.02~0.15),P<0.01],两组之间的差异具有统计学意义.(2)试验组手术持续时间明显短于对照组[WMD=-29.13,95%CI(-36.95~-21.30),P<0.01],两组之间的差异具有统计学意义.(3)试验组术后早期[OR=0.29,95%CI(0.19~0.44),P<0.01]及晚期[OR=0.34,95%CI(0.20~0.58),P<0.01]玻璃体出血的概率均低于对照组,两组之间的差异均具有统计学意义.(4)试验组术后最佳矫正视力水平不优于对照组[WMD=-0.51(LogMAR),95%CI(-1.10~0.08),P=0.09],两组之间的差异无统计学意义.(5)试验组术中医源性视网膜破裂发生概率低于对照组[OR=0.24,95%CI(0.14,0.40),P<0.01],两组之间的差异具有统计学意义.(6)在纳入的16篇文献共493例试验组患眼中,无1例报道出现与注射anti-VEGF类药物相关的明显眼内及全身不良反应.结论:PDR患者行玻璃体切除术治疗前玻璃体腔内注射抗VEGF类药物是安全、有效的治疗措施,能够显著减少术中及术后并发症的发生概率,改善患者的整体治疗效果.其具体的实施方案,如注射药物的剂量、玻璃体腔内注射与手术的间隔时间等,还有待进一步的探索与完善.     

Anti-vascular endothelial growth factor in the management of retinopathy of prematurity: A survey among the members of Indian Retinopathy of Prematurity Society

Purpose:To report the results of the survey for the role of anti-VEGF in the management of retinopathy of prematurity (ROP) among the members of Indian ROP (iROP) society.Methods:A questionnaire was designed in English using Google forms and its link was circulated to the members of the iROP society on their mobile numbers. The survey included questions pertaining to demographics, anti-VEGF agents, injection technique, post-injection follow-up, and documentation pertaining to their ROP practice. Anonymous responses were obtained and analyzed for individual questions.Results:226 members of the society were contacted and 157 responded (69.4%) to the survey. 137 (87.2%) respondents used anti-VEGF in the management of ROP. Aggressive posterior ROP (APROP) was the most common indication (78, 52.7%). The procedure was carried out in the main operation room (102, 70.3%) simultaneously for both the eyes (97; 68%) under topical anesthesia (134; 86.4%) by most of the respondents. One-hundred thirteen (77.9%) respondents used half of the adult dose, irrespective of the agent used; however, more than half of them preferred bevacizumab (85, 54%). 53 (36.3%) respondents followed up infants as per disease severity rather than a fixed schedule while only 33 (23%) performed photo documentation. 151 (96.2%) respondents felt the need for guidelines regarding the usage of anti-VEGF in ROP.Conclusion:There is an increase in the trend towards the use of anti-VEGF in the management of severe ROP, particularly APROP. However, there are considerable variations among the ROP practitioners regarding the agent, dosage, follow-up schedule, and documentation, suggesting the need for uniform guidelines.     

Influence of polymorphisms in VEGF, ACE, TNF and GST genes on the susceptibility to retinopathy of prematurity among Chinese infants

AIM: To investigate common polymorphisms in VEGF, ACE, TNF and GST genes with retinopathy of prematurity (ROP) risk among Chinese infants. METHODS: Nine polymorphisms in the above genes were genotyped on 724 advanced cases of ROP and 878 prematurely-born infants of low birth weight who were without any ophthalmologic disease. The frequencies of the polymorphisms were compared between cases and controls to identify the association present, if any. RESULTS: Of the nine polymorphisms, only two showed significant associations: ACE insertion deletion (ID) polymorphism (P=0.031) and TNF -308G/A polymorphism (P<0.001). The former was associated with a reduced ROP risk [ID genotype, adjusted OR (aOR): 0.603, 95%CI: 0.427-0.893, P=0.034; DD genotype, aOR: 0.468, 95%CI: 0.229-0.626, P=0.002], while the latter showed an increased risk (GA genotype, aOR: 1.956, 95%CI: 1.396-2.465, P<0.001; AA genotype, aOR: 2.809, 95%CI: 1.802-4.484, P<0.001). The association was also noted at the allele level (ACE D allele aOR: 0.698, 95%CI: 0.294-0.883, P<0.001; TNF -308A allele aOR: 1.776, 95%CI: 1.446-2.561, P<0.001). CONCLUSION: The ACE ID polymorphism can protect against ROP development while the TNF -308G/A can increase the risk of the disease among Chinese infants.     

玻璃体腔注射抗VEGF药物治疗早产儿视网膜病变的研究进展

早产儿视网膜病变(ROP)是发生于早产儿的一种未成熟视网膜血管增殖性眼病，是一种严重的儿童致盲性眼病。视网膜激光光凝术是治疗ROP的经典方法，然而激光治疗是破坏性的，尤其是在ROP Ⅰ区病变的情况下，视网膜激光光凝治疗会引起严重的并发症。研究表明，血管内皮细胞生长因子(VEGF)在ROP发生及发展过程中具有关键作用，而玻璃体腔注射抗VEGF药物不仅能有效控制ROP，并且为视网膜继续发育争取了机会。本文就玻璃体腔内注射抗VEGF药物治疗ROP的治疗指征、药物筛选、注射部位、给药剂量、疗效观察以及并发症对其进行综述。     

Quantitative analysis of retinal intermediate and deep capillary plexus in patients with retinal deep vascular complex ischemia

AIM: To evaluate the efficacy and safety of intravitreal corticoid as an adjunctive therapy to anti-VEGF treatment of neovascular age-related macular Degeneration (nvAMD). METHODS: Four databases including PubMed, Embase, Cochrane Library, and the clinicaltrials.gov were comprehensively searched for studies comparing intravitreal corticoid plus anti-VEGF (IVC/IVA) vs anti-VEGF monotherapy (IVA) in patients with nvAMD. GRADE profiler was used to assess the quality of outcomes. Best-corrected visual acuity (BCVA), central macular thickness (CMT) and adverse events including the occurrence of severe elevation of intraretinal pressure (IOP) and the progress of cataract were extracted from the eligible studies. Review Manager (RevMan) 5.3 was used to analyze the data. RESULTS: There was no statistic difference between mean change in BCVA at 6mo and 12mo (95% CI: -2.28 to 4.24, P=0.55). Mean change of CMT at 6mo and 12mo: no statistically significant difference were found in CMT at this time point (95% CI:-17.98 to 16.42, P=0.93). Occurrence of severe elevation of IOP: the risk in the IVC/IVA group was higher than that in the IVA group (95% CI: 1.92 to 9.48; P=0.0004). Cataract progression events: no statistic difference was found (95% CI: 0.74 to 4.66; P=0.18). CONCLUSION: No visual or anatomical benefits are observed in IVC/IVA group at 6mo. At 12mo, the CMT of the IVC/IVA group is significantly lower than that of the IVA group. Risk of severe elevation of IOP is significantly higher when treated by IVC/IVA.     

抗血管内皮生长因子玻璃体内注射治疗不同区域早产儿视网膜病变的疗效观察

目的 观察抗血管内皮生长因子(vascular endothelial growth factor,VEGF)治疗不同区域早产儿视网膜病变的临床效果.方法 回顾性分析2013年4月至2014年4月在郑州儿童医院行玻璃体内注射抗VEGF药物的早产儿视网膜病变患儿24例(46眼),分为Ⅰ区病变组15例(28眼),Ⅱ区病变组9例(18眼).所有患者均在全身麻醉下行玻璃体内注射抗VEGF药物雷珠单抗,对患儿术后眼底进展情况进行观察,分析两组首次注射治愈和进展情况以及并发症发生情况.结果 两组间的出生孕周、出生体质量相比,差异均无统计学意义(均为P ＞0.05);手术矫正孕周相比,差异有统计学意义(P=0.001).24例(46眼)中,首次注射治愈21眼,病情继续发展25眼,治愈率为45.65％,治疗到治愈的时间间隔为2～12个月.Ⅰ区病变组首次注射治愈9眼,治愈率为32.14％,进展率为67.86％;Ⅱ区病变18眼中12眼首次注射治愈,6眼病情继续进展,治愈率为66.67％,进展率为33.34％.两组首次注射治愈率相比,差异有统计学意义(x2=5.263,P=0.022),Ⅰ区病变的首次注射治愈率明显低于Ⅱ区病变.两组进展率相比,差异有统计学意义(x2=-2.269,P=0.023),Ⅰ区病变的进展率明显高于Ⅱ区病变.随访中未发现与玻璃体内注射有关的白内障、眼内炎、视网膜裂孔等出现,仅有2例出现角膜水肿,4例出现结膜下出血,均未做特殊处理自愈.结论 玻璃体内注射抗VEGF药物对于Ⅰ区、Ⅱ区病变均有效,Ⅰ区病变手术成功率低,再次手术的几率大,但可为再次手术创造时间和条件.     

湖北地区早产儿视网膜病变筛查结果及相关因素分析

目的 了解湖北地区早产儿视网膜病变（ROP）的发病情况以及相关影响因素。方法 2009年7月至2011年5月对出生胎龄＜37周的313例早产儿的626只眼采用双目间接检眼镜和二代广角数码视网膜成像系统（RetcamⅡ）进行了ROP筛查。其中,男性200例, 女性113例。出生体重890～3500 g,平均出生体重（1977.37±497.03） g。出生胎龄26～37周,平均出生胎龄（33.13±2.44）周。根据筛查结果分为ROP组和无ROP组。所有ROP患儿均随访至视网膜完全血管化;如视网膜未能完全血管化则随访至视网膜情况稳定或进行激光光凝治疗。同时对两组间性别、出生胎龄、出生体重、妊娠年龄、分娩方式、试管婴儿、多胎妊娠、孕期吸氧、宫内缺氧、子痫、先兆流产、婴儿吸氧史、呼吸窘迫综合征、缺血缺氧性脑病、黄疸、蓝光照射治疗等相关因素进行统计学分析。结果313例626只眼中,ROP组52例87只眼,分别占早产儿人数及眼数的16.61%和13.90%。其中,急进性后部型ROP 2只眼;1期38只眼;2期36只眼;3期11只眼。无ROP组261人539只眼,分别占受检早产儿人数及眼数的83.39%和86.10%。接受激光光凝治疗20只眼。统计学分析结果显示,ROP组和无ROP组在出生胎龄（t=-4.348）、出生体重（t=-3.966）、婴儿吸氧史(χ2=9.05;比值比=3.403,95%可信区间1.475~7.854)间比较,差异有统计学意义（P＜0.05）。性别、妊娠年龄、分娩方式、试管婴儿、多胎妊娠、孕期吸氧、宫内缺氧、子痫、先兆流产、呼吸窘迫综合征、缺血缺氧性脑病、黄疸、蓝光照射治疗两组比较,差异无统计学意义（P＞0.05）。结论湖北地区ROP发生率为16.61％;出生胎龄、出生体重、婴儿吸氧史是影响ROP发病率的重要影响因素。     

Overflow phenomenon in serum lutein after supplementation: a systematic review supported with SNPs analyses

Lutein, a type of carotenoids, is found to delay the onset and progression of age-related macular degeneration (AMD). Several lutein supplementation studies showed that after an initial increase, lutein serum levels demonstrated a subsequent decrease despite continuous supplementation. In this systematic literature review, this obscure phenomenon was tried to be explained. The subsequent drop in lutein levels was postulated due to down-regulation of lutein receptors scavenger receptor class B type I (SR-BI) in the gastrointestinal tract, upregulation of lutein degrading enzyme β-carotene dioxygenase (BCDO2), or perhaps a combination of both. Some single nucleotides polymorphisms (SNPs) that could have influence on the occurrence of this phenomenon. To date, an exact scientific explanation for this phenomenon has not been established. Further research is needed to investigate this phenomenon in depth to reach an irrefutable explanation, giving that lutein is proven to be effective in delaying the onset and progression of AMD and its metabolism in the human body becomes of equal importance.     

【In Press】Effect of anti-VEGF treatment on retinopathy of prematurity in Zone II Stage 3+

AIM: To assess the effect of intravitreal ranibizumab injection for retinopathy of prematurity (ROP) in Zone II Stage 3+. METHODS: Data was collected from ROP patients with Zone II Stage 3+ who had intravitreal ranibizumab injections between October 2014 and January 2017 at the department of Ophthalmology in our hospital. No prior laser or other intravitreal therapy was done. Fundus examination was performed prior to the intervention and at each follow-up visit. Gestational age at birth, birth weight, sex, ROP zone, ROP stage, post menstrual age (PMA) at treatment, and follow-up period were recorded. The final clinical status of the retina was noted for each patient. The primary outcome measures included ROP recurrences requiring re-treatment, complete or incomplete peripheral vascularization RESULTS: Eighty-six eyes of 46 premature infants with Zone II Stage 3+ROP were enrolled in the study. The mean gestational age at birth was 28.18±1.67wk (range: 25 to 33wk) and the mean birth weight was 1070.57±226.85 g (range: 720.00 to 1650.00 g). The mean PMA at treatment was 38.32±2.99wk (range: 32.29 to 46.00wk). Seventy-one eyes (82.56%) were treated successfully with intravitreal ranibizumab as monotherapy. Fifteen eyes (17.44%) developed recurrent disease. The mean interval between the treatment and retreatment was 5.96±3.22wk (range: 1.86 to 11.71wk). All eyes vascularized into zone III at the end of the study and among them 62 eyes (72.1%) achieved complete vascularization. CONCLUSION: Intravitreal ranibizumab injection is an effective treatment in patients with zone II stage 3+ ROP. More patients with longer follow-up duration are mandatory to confirm the safety and efficacy of this treatment.     

Chronic ocular GVHD: limbal and conjunctival stem cell allografts from the same hematopoietic stem cell donor

AIM: To investigate common polymorphisms in VEGF, ACE, TNF and GST genes with retinopathy of prematurity (ROP) risk among Chinese infants. METHODS: Nine polymorphisms in the above genes were genotyped on 724 advanced cases of ROP and 878 prematurely-born infants of low birth weight who were without any ophthalmologic disease. The frequencies of the polymorphisms were compared between cases and controls to identify the association present, if any. RESULTS: Of the nine polymorphisms, only two showed significant associations: ACE ID polymorphism (P=0.031) and TNF -308G/A polymorphism (P<0.001). The former was associated with a reduced ROP risk (ID genotype, adjusted OR (aOR): 0.603, 95%CI: 0.427-0.893, P=0.034; DD genotype, aOR: 0.468, 95%CI: 0.229-0.626, P=0.002), while the latter showed an increased risk (GA genotype, aOR: 1.956, 95%CI: 1.396-2.465, P<0.001; AA genotype, aOR: 2.809, 95%CI: 1.802-4.484, P<0.001). The association was also noted at the allele level (ACE D allele aOR: 0.698, 95%CI: 0.294-0.883, P<0.001; TNF -308A allele aOR: 1.776, 95%CI: 1.446-2.561, P<0.001). CONCLUSION: The ACE ID polymorphism can protect against ROP development while the TNF -308G/A can increase the risk of the disease among Chinese infants.     

Pharmakologische Therapie der Fr��hgeborenenretinopathie

Mandatory screening performed by an experience ophthalmologist remains the most important pillar in the management of retinopathy of prematurity (ROP). The current gold standard for treatment of proliferative ROP is still panretinal laser photocoagulation, depending on severity, in combination with vitreoretinal surgery if necessary. The first case series of off-label intravitreal anti-VEGF treatment are encouraging. In addition to intravitreal anti-VEGF therapy, other treatment concepts such as supplementation with IGF-1 or omega-3 fatty acids also represent interesting pharmacological approaches to the management of ROP. However, larger controlled trials are required to validate the benefits and safety of these systemic treatment approaches.