Fixed bimonthly aflibercept in naïve and switched neovascular age-related macular degeneration patients: one year outcomes

AIM: To determine real life clinical outcomes in poorly responsive and treatment-naïve neovascular age related macular degeneration (nvAMD) patients using bimonthly fixed dosing aflibercept regimen. METHODS: This was a retrospective study of 165 eyes with nvAMD started on aflibercept at Southampton Eye Unit between June 2013 and June 2014. Patients were either switched from pro re nata (PRN) ranibizumab/bevacizumab due to poor response (107 eyes), or treatment-naïve (58 eyes). Patients initially received 3-monthly intravitreal aflibercept injections followed by 2-monthly fixed doses. Clinic visits were scheduled at month 0, 4, 10 and 12. Mean change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline were assessed using the Wilcoxon signed-rank test. The proportion of patients maintaining BCVA (<15 letters loss) at 12mo was also evaluated. RESULTS: Mean BCVA change at month 12 was +3.29 and +4.67 letters in the switched and naïve aflibercept groups respectively (P<0.01). BCVA was maintained in 95.3% of switched and 96.6% of naïve patients. CRT at month 12 showed a decrease of -6.16 µm in the switched group and -35.36 µm in the naïve group (P<0.01). Patients previously treated with ranibizumab/bevacizumab had on average received 7.4 ranibizumab/bevacizumab injections over 12.6mo, attending 10 clinic visits. The fixed dosing aflibercept regimen required an average of 7.1 injections (naïve group), 7.5 injections (switched group) and 4 clinic visits per year. CONCLUSION: Fixed bimonthly aflibercept is effective in both treatment-naïve and poorly responsive nvAMD patients. Adopting a fixed dosing regimen can reduce patient burden without compromising on outcomes.     

Microstructural morphology and visual acuity outcome in eyes with epiretinal membrane before, during, and after membrane peeling in intraoperative optical coherence tomography assisted macular surgery

AIM: To measure the difference of intraoperative central macular thickness (CMT) before, during, and after membrane peeling and investigate the influence of intraoperative macular stretching on postoperative best corrected visual acuity (BCVA) outcome and postoperative CMT development. METHODS: A total of 59 eyes of 59 patients who underwent vitreoretinal surgery for epiretinal membrane was analyzed. Videos with intraoperative optical coherence tomography (OCT) were recorded. Difference of intraoperative CMT before, during, and after peeling was measured. Pre- and postoperatively obtained BCVA and spectral-domain OCT images were analyzed. RESULTS: Mean age of the patients was 70±8.13y (range 46-86y). Mean baseline BCVA was 0.49±0.27 logMAR (range 0.1-1.3). Three and six months postoperatively the mean BCVA was 0.36±0.25 (P=0.01 vs baseline) and 0.38±0.35 (P=0.08 vs baseline) logMAR respectively. Mean stretch of the macula during surgery was 29% from baseline (range 2%-159%). Intraoperative findings of macular stretching did not correlate with visual acuity outcome within 6mo after surgery (r=-0.06, P=0.72). However, extent of macular stretching during surgery significantly correlated with less reduction of CMT at the fovea centralis (r=-0.43, P<0.01) and 1 mm nasal and temporal from the fovea (r=-0.37, P=0.02 and r=-0.50, P<0.01 respectively) 3mo postoperatively. CONCLUSION: The extent of retinal stretching during membrane peeling may predict the development of postoperative central retinal thickness, though there is no correlation with visual acuity development within the first 6mo postoperatively.     

Peripheral retinal non-perfusion and treatment response in branch retinal vein occlusion

AIM: To evaluate the association between the size of peripheral retinal non-perfusion and the number of intravitreal ranibizumab injections in patients with treatment-naive branch retinal vein occlusion (BRVO) and macular edema. METHODS: A total of 53 patients with treatment-naive BRVO and macular edema were included. Each patient underwent a full ophthalmologic examination including optical coherence tomography (OCT) imaging and ultra wide-field fluorescein angiography (UWFA). Monthly intravitreal ranibizumab injections were applied according to the recommendations of the German Ophthalmological Society. Two independent, masked graders quantified the areas of peripheral retinal non-perfusion. RESULTS: Intravitreal injections improved best-corrected visual acuity (BCVA) significantly from 22.23±16.33 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters to 36.23±15.19 letters (P<0.001), and mean central subfield thickness significantly reduced from 387±115 µm to 321±115 µm (P=0.01). Mean number of intravitreal ranibizumab injections was 3.61±1.56. The size of retinal non-perfusion correlated significantly with the number of intravitreal ranibizumab injections (R=0.724, P<0.001). CONCLUSION: Peripheral retinal non-perfusion in patients with BRVO associates significantly with intravitreal ranibizumab injections in patients with BRVO and macular edema.     

Aflibercept for diabetic macular oedema: a Meta-analysis of randomized controlled trials

AIM: To evaluate the relative efficacy and safety of aflibercept for treatment of diabetic macular oedema (DMO). METHODS: A comprehensive search in MEDLINE, CENTRAL and EMBASE was undertaken for randomized controlled trials (RCTs) comparing intravitreal anti-vascular endothelial growth factor (anti-VEGF) versus another treatment. Primary outcome measures were proportion of patients with at least 15 letters of gain or loss on a logMAR visual acuity chart, and change in best corrected visual acuity (BCVA) and central macular thickness (CMT) from baseline. Safety outcomes were rates of death, thromboembolic events and any systemic or ocular serious adverse events. The final search was performed on November 2017. RESULTS: Four RCTs were included. Only one trial compared efficacy and safety of aflibercept with bevacizumab and ranibizumab over 1 or 2y. Three trials were included for Meta-analysis comprising 661 patients (331 in the aflibercept, and 330 in the photocoagulation group). Aflibercept was more efficacious compared to photocoagulation in the proportion of patients with at least 15 letters of improvement and worsening, and in improvement of BCVA and reduction in CMT at 1 or 2y. The safety estimates at 1 or 2y did not differ statistically. CONCLUSION: Aflibercept offers superior benefits over photocoagulation in improving and preserving vision, with no differences in safety. Further comparative effectiveness trials between aflibercept and other anti-VEGF agents will aid ophthalmologists in treatment decisions.     

Intravitreal bevacizumab (Avastin) therapy for persistent diffuse diabetic macular edema

PURPOSE: To evaluate the efficacy of bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) for the treatment of diabetic macular edema. METHODS: This prospective, consecutive, noncomparative case series included 51 consecutive patients (26 females and 25 males; mean age, 64 years) with diffuse diabetic macular edema. Inclusion criteria were determined independently of the size of edema, retinal thickness, visual acuity, age, metabolic control, type of diabetes, or previous treatments beyond a 6-month period. At each visit, patients underwent complete eye examination, including determination of best-corrected visual acuity, slit-lamp examination, intraocular pressure measurement, stereoscopic biomicroscopy of the macula, retinal thickness measurement by optical coherence tomography, fluorescein angiography, and fundus photography. After written informed consent was obtained, all patients were treated with a 0.05-mL injection containing 1.25 mg of bevacizumab. RESULTS: All patients completed 6 weeks of follow-up; 23 (45%) completed 12 weeks of follow-up. Sixteen patients (70%) had received at least two intravitreal injections. All patients had undergone previous treatments, such as focal laser therapy (35%), full-scatter panretinal laser therapy (37%), vitrectomy (12%), and intravitreal injection of triamcinolone (33%). The mean diameter of the foveal avascular zone was 503 micro m, with 49% with values of >500 micro m. At baseline, mean visual acuity +/- SD was 25.88 +/- 14.43 ETDRS letters (0.86 +/- 0.38 logMAR of Snellen letters). Mean central retinal thickness by optical coherence tomography +/- SD was 501 +/- 163 micro m (range, 252-1,031 micro m). Mean visual acuity +/- SD increased to 0.75 +/- 0.37 logMAR of Snellen letters at 6 weeks after injection (P = 0.001), with some regression to 0.84 +/- 0.41 logMAR of Snellen letters after 12 weeks. Changes in ETDRS letters were not significant throughout follow-up. Mean retinal thickness +/- SD decreased to 425 +/- 180 micro m at 2 weeks (P = 0.002), 416 +/- 180 micro m at 6 weeks (P = 0.001), and 377 +/- 117 micro m at 12 weeks (P = 0.001). Changes of retinal thickness and visual acuity correlated weakly (r = -0.480 and P = 0.03 at 6 weeks; r = -0.462 and P = 0.07 at 12 weeks). The increase of visual acuity after 6 weeks as measured by ETDRS charts could be predicted best by baseline visual acuity. No other factors investigated, such as age, thickness by optical coherence tomography, or previous treatments, were predictive for the increase in visual acuity. CONCLUSION: Even in cases of diffuse diabetic macular edema not responding to previous treatments such as photocoagulation, intravitreal injection of triamcinolone, or vitrectomy, improvement of visual acuity and decrease of retinal thickness could be observed after intravitreal injection of bevacizumab. Although our follow-up period was too short to provide specific treatment recommendations, the short-term results encourage further prospective studies with different treatment groups and longer follow-up.     

玻璃体腔注射曲氨奈德与Bevacizumab治疗非缺血性视网膜中央静脉阻塞继发黄斑水肿疗效比较

目的 比较玻璃体腔注射曲氨奈德(triamcinoloneacetonide,TA)与抗血管内皮生长因子单克隆抗体(Bevacizumab)治疗非缺血性视网膜中央静脉阻塞继发黄斑水肿(NI-CME)的临床疗效.方法 采用单中心非随机对照临床回顾性研究,共47例经眼科常规检查以及荧光素眼底血管造影(FFA)和光学相干断层扫描(OCT)检查确诊的NI-CME患者的47只眼纳入观察.患者被分成两组进行玻璃体腔注射TA(4mg/0.1m1)或Bevacizumab(1.25rag/0.05m1)治疗.TA组28例,注射次数1～2次,随诊时间(5.98 4±4.35)月.Bevacizumab组19例,注射次数1-3次,随诊时间(3.20±2.92)月.两组在术前年龄、病程、最佳矫正视力(BCVA)、中心视网膜厚度(CMT)方面均无统计学意义.比较治疗前和治疗后4、8、12周两组间以及各组内部的BCVA、CMT的改变.结果 两组间视力在4周(t=0.141,P=0.889)、8周(1=-1.637,p=0.127)、12周(t=-0.479,P=0.650)时均无统计学意义;CMT在4周(t=0.479,P=0.650)、8周(t=0.743,P=0.478)、12周(t=-1.979,P=0.083)时均无统计学意义.治疗后眼压明显升高仅见于TA组.结论 玻璃体腔注射TA或Bevacizumab治疗非缺血性视网膜中央静脉阻塞继发黄斑水肿,短期内均能明显改善视力,减轻黄斑水肿.此结果还需大样本、多中心的临床随机对照研究.     

Ranibizumab for treatment of choroidal neovascularization secondary to age-related macular degeneration

PURPOSE: To evaluate the short-term outcomes after intravitreal ranibizumab (Lucentis; Genentech, Inc., South San Francisco, CA) injection in patients with neovascular age-related macular degeneration. METHODS: A review of data for consecutive patients who received intravitreal ranibizumab injection was conducted. The main outcome measures were mean visual acuity and central macular thickness at 3 months compared with those at baseline. Response to ranibizumab therapy was evaluated with particular attention to prior treatment with bevacizumab (Avastin; Genentech, Inc.). RESULTS: Mean baseline visual acuity of 231 eyes of 231 patients was 20/152, and 189 patients (81.8%) had undergone prior treatment, with 153 (65.4%) having received intravitreal bevacizumab. Mean visual acuity at 3 months, available for 203 patients (88%), was 20/126 (P = 0.004). Mean visual acuity for 98 patients treated with bevacizumab within 3 months before ranibizumab injection was 20/100 at baseline and 20/98 at 3 months (P = 0.35). Mean baseline central macular thickness was 278 microm for all patients and improved to 211 microm at 3 months (P < 0.001). Macular thickness decrease was noted irrespective of previous bevacizumab therapy. CONCLUSION: Ranibizumab therapy was associated with significant improvements in mean visual acuity and central macular thickness for the group of all patients. Patients who had received bevacizumab treatment within 3 months before initiating ranibizumab treatment had stability of, but no improvement in, visual acuity.     

Intravitreal aflibercept in neovascular age-related macular degeneration previously treated with ranibizumab

AIM: To report the change in visual acuity and central macular thickness (CMT) following treatment with intravitreal aflibercept injections in patients with neovascular age-related macular degeneration (nAMD) with suboptimum response to ranibizumab. METHODS: This was a retrospective study. The inclusion criteria were patients with nAMD who responded poorly to ranibizumab. Patients then received either 3 consecutive aflibercept injections followed by PRN treatment or PRN alone. Primary endpoints were mean change in best-corrected visual acuity (BCVA) and CMT at 12mo. Secondary endpoints were number of injections and adverse events. RESULTS: Forty-nine eyes from 49 patients met the inclusion criteria and completed 12-month follow up on aflibercept. Thirty-eight eyes received 3 consecutive aflibercept injections followed by PRN treatment and 11 eyes received pro re nata (PRN) injections alone. At 12mo, mean BCVA improved by one letters (logMAR 0.56±0.31 to 0.54±0.34) and mean CMT decreased from 303.9±82.1 to 259.2±108.3 µm. Four percent of eyes gained 15 letters or more, 6% lost more than 15 letters and the remaining 90% had stable BCVA. The mean number of aflibercept injections was 6. There was one case of infectious endophthalmitis. CONCLUSION: Intravitreal aflibercept in patients with nAMD with a previous suboptimal response to ranibizumab resulted in an anatomical improvement in macular appearance at 12mo without a corresponding improvement in visual acuity.     

Evaluation of the Response to Ranibizumab Therapy following Bevacizumab Treatment Failure in Eyes with Diabetic Macular Edema

Background/Aims

Bevacizumab and ranibizumab are routinely used to treat diabetic macular edema (DME). We aim to evaluate the usefulness of switching to ranibizumab therapy following bevacizumab treatment failure in eyes with DME.

Methods

We performed a retrospective analysis of a consecutive group of patients with DME who received ranibizumab injections following the failure of bevacizumab injections. The injections were delivered following a pro re nata protocol every 4–6 weeks. The data collected included demographics, systemic and ophthalmic findings, as well as the central subfield thickness according to spectral-domain OCT.

Results

Eight eyes (5 patients) were included in the study. The median number of bevacizumab injections prior to the switch to ranibizumab was 4, and the median number of ranibizumab injections during the study was 2. The mean follow-up period was 541 ± 258 days. The mean central retinal thickness (CRT) (±SEM) was 539 ± 75 μm before the initiation of bevacizumab treatment, and 524 ± 43 μm after the last bevacizumab injection (p = 0.7). It reduced to 325 ± 26 μm following the ranibizumab injections (p = 0.0063). The best-corrected visual acuity (BCVA) improved in 4 eyes and remained stable in 4 eyes following the ranibizumab injections.

Conclusion

A ranibizumab therapy was effective in reducing the CRT in eyes that failed bevacizumab therapy. A BCVA improvement can also occur in these eyes. Switching between anti-vascular endothelial growth factor compounds may be beneficial in eyes with DME.Key Words: Ranibizumab, Bevacizumab, Diabetic macular edema, Treatment failure     

Six-year outcomes in neovascular age-related macular degeneration with ranibizumab

AIM: To evaluate the outcomes of (6y ranibizumab therapy in neovascular age-related macular degeneration (AMD). METHODS: HELIX was a retrospective, observational effectiveness study using medical records of patients treated in three clinics in Belgium. Patients had neovascular AMD and were initially treated with intravitreal ranibizumab (0.5 mg) between November 1, 2007 and October 31, 2008, had (6y of data available, and were treated on an ongoing, as-needed basis. Outcomes included best-corrected visual acuity (BCVA) and central retinal thickness (CRT). RESULTS: The sample consisted of 88 eyes from 69 patients. Mean age was 76.4±6.5y, most patients were female (62.3%). Most eyes (62.5%) were treatment-naive, 33 previously treated eyes had received predominantly other anti-vascular endothelial growth factor agents and verteporfin. Mean baseline BCVA was 57.4±12.7 ETDRS letters and CRT was 291.5±86.1 (m. On average, patients received 20.6±11.9 ranibizumab injections over the (6y. Intervals between injections were on average 12.7±16.1wk. Mean change in BCVA from baseline to last observation for the sample was less than one letter (-0.9±17.3 letters), with an average loss of -3.2±15.6 letters in previously treated eyes versus a gain of 0.6±18.4 letters in treatment-naïve eyes. When considering a loss of <15 letters over 6y as stabilization of disease, 75.9% of all eyes showed a positive (improvement or stabilization) outcome. Mean change in CRT from baseline to last observation for the sample was -26.9±148.4 (m with the greatest reduction observed in treatment-naive eyes. CONCLUSION: This retrospective study of 69 neovascular AMD patients treated for (6y with ranibizumab demonstrates long-term visual stabilization. In light of the natural evolution of the disease, these data confirm that ranibizumab is effective long-term under real-world conditions of heterogeneity of patients, clinicians, and centers.     

玻璃体腔注射曲安奈德与Bevacizumab治疗视网膜静脉阻塞性黄斑水肿疗效比较

目的 比较玻璃体腔注射曲安奈德(TA)与抗血管内皮生长因子单克隆抗体(Bevacizumab)治疗视网膜静脉阻塞性黄斑水肿(RVOME)的临床疗效.方法 共116例眼科常规检查以及荧光素眼底血管造影(FFA)和光学相干断层扫描(OCT)检查确诊的RVOME患者的116只眼纳入观察.患者被分成两组进行玻璃体腔注射TA(4mg,0.1ml)或Bevacizumab(1.25mg,0.05ml)治疗.TA组75例,Bevacizumab组41例,两组在术前年龄、病程、最佳矫正视力(BCVA)、中心视网膜厚度(CMT)方面均无显著差异.比较治疗前和治疗后4、8、12周两组间以及各组内部的BCVA、CMT的改变.结果 视力方面,与基线比较,TA组治疗后4周(P=0.000)、8周(P=0.000)、12周(P=0.000)时均有显著提高;Bevacizumab组治疗后4周(P=0.000)、8周(p=0.000)时显著提高,12周时有所回落(P=0.074).CMT方面,与基线比较,TA组治疗后4周(P=0.000)、8周(p=0.000)、12周(P=0.004)时,均有显著降低;Bevacizumab组治疗后4周(P=0.003)、8周(P=0.000)时显著降低,12周(P=0.205)时无显著差异.两组间比较,视力在4周(P=0.985)、8周(P=0.989)、12周(P=0.306)时均无显著差异;CMT在4周(P=0.075)、8周(P=0.453)、12周(P=0.583)时均无显著差异.治疗后眼压明显升高仅见于TA组.结论 玻璃体腔注射TA或bevacizumab治疗RVOME均能明显改善视力,减轻黄斑水肿.此结果还需大样本、多中心的临床随机对照研究.     

玻璃体腔注射雷珠单抗联合激光治疗视网膜黄斑分支静脉阻塞继发黄斑水肿

目的：观察玻璃体腔注射雷珠单抗联合激光治疗视网膜黄斑分支静脉阻塞( MBRVO)继发黄斑水肿的临床疗效。
　　方法：回顾性研究。临床确诊为MBRVO继发黄斑水肿的患者33例33眼纳入研究。玻璃体腔注射10 mg/mL雷珠单抗0.05mL(含雷珠单抗0.5mg)。治疗后每月复查,复查时发现视力下降和OCT检查发现黄斑水肿复发者再次重复注射雷珠单抗。复查发现出血明显吸收及OCT复查发现黄斑水肿明显消退者,在原水肿部位进行视网膜光凝。观察治疗前与治疗后6 mo最佳矫正视力、黄斑中心凹视网膜厚度( central macular thickness,CMT)、多焦视网膜电生理检查P1波的振幅密度及潜伏期的变化。
　　结果：治疗前BCVA经LogMAR转换后为0.68±0.35,治疗后6mo为0.34±0.23,与治疗前相比差异有统计学意义(P<0.01)。其中,21眼(64%)BCVA提高2行及以上者,9眼(27%)维持于就诊时水平,无视力下降者。治疗前平均CMT 为487.30±63.58μm,治疗后6mo CMT 降为238.84±52.66μm,与治疗前相比差异有统计学意义( P<0.01)。治疗后6 mo患者1环、2环、3环的P1波振幅密度均有提高,与治疗前相比差异均有统计学意义( P<0.01);治疗后6 mo患者1环、2环、3环的P1波潜伏期均有缩短,与治疗前相比差异均有统计学意义( P<0.05)。玻璃体腔注射后2眼出现结膜下出血。
　　结论：雷珠单抗联合局部视网膜光凝治疗视网膜黄斑分支静脉阻塞继发黄斑水肿可有效减轻黄斑水肿,显著提高患者视力,改善视功能。     

单次玻璃体腔注射雷珠单抗联合激光治疗视网膜分支静脉阻塞继发黄斑水肿

目的：观察单次玻璃体腔注射雷珠单抗联合激光光凝治疗视网膜分支静脉阻塞继发黄斑水肿的临床疗效。方法：回顾性系列病例研究。选择2014 年6月至2016 年12 月在台州市眼科医院经荧光素眼底血管造影确诊的视网膜分支静脉阻塞继发黄斑水肿的患者52例（52眼）,根据是否联合雷珠单抗治疗分为单纯激光组和联合治疗组,联合治疗组又根据接受雷珠单抗及激光治疗的先后顺序分为先激光组和后激光组。分别测量并记录患者治疗前,治疗后1、6 个月最佳矫正视力（BCVA）及黄斑中心凹厚度（CMT）。采用重复测量方差分析、单因素方差分析和配对t检验对数据进行统计学分析。结果：治疗前,治疗后1、6个月3组间BCVA总体差异有统计学意义（F=18.28,P=0.011）。治疗后1、6个月同一时间点3 组间BCVA比较,单纯激光组分别低于先激光组和后激光组（P < 0.01）。3 组治疗后6 个月BCVA较治疗前均有所提高,差异均有统计学意义（t=8.49、14.57、20.12,P < 0.01）。治疗前,治疗后1、6 个月3 组间CMT值总体差异有统计学意义（F=5.72,P=0.025）。治疗后1、6 个月同一时间点3 组间CMT值比较,单纯激光组分别大于先激光组和后激光组（P < 0.01）。3 组治疗后1、6 个月较治疗前CMT值均有所下降,差异均有统计学意义（P < 0.01）。结论：单次玻璃体腔注射雷珠单抗联合视网膜激光光凝治疗可有效减轻视网膜分支静脉阻塞继发黄斑水肿,提高患者的视力,其作用较单纯激光光凝治疗更加明显。     

Predictors of 1‐year visual outcome in neovascular age‐related macular degeneration following intravitreal ranibizumab treatment

Purpose: To describe predictors of visual outcome in patients treated with intravitreal ranibizumab for choroidal neovascularisation (CNV) in age‐related macular degeneration (AMD). Methods: Retrospective review of 279 patients with CNV in AMD who fulfilled MARINA/ANCHOR study eligibility criteria and were treated with repeated intravitreal injections of ranibizumab 0.5 mg in routine clinical practice, beginning with three initial injections at 4‐week intervals followed by individualized retreatment for the subsequent 9 months. Study parameters included best‐corrected visual acuity (BCVA) and morphological characteristics. Results: Mean BCVA relative to baseline was +4.7 (p < 0.0001), +4.2 (p < 0.0001)and ?0.4 (p > 0.667) Early Treatment Diabetic Retinopathy Study letters after 3, 6 and 12 months, respectively, after a mean of 5.1 injections when the proportion of patients with BCVA ≥70 letters had doubled compared with baseline. Predictive factors for BCVA ≤35 letters after 12 months were BCVA ≤35 letters at baseline and month 3 (p < 0.0001) while BCVA ≥70 letters at month 12 was associated with BCVA ≥70 letters at baseline and month 3 (p < 0.001) and with total lesion size <4 DA (p = 0.0147). Conclusion: Under a ranibizumab regimen with substantially fewer injections than with fixed four‐weekly injection regimens, BCVA was improved compared with the natural history of neovascular AMD, but did not achieve the visual gain observed in randomized clinical trials using fixed 4‐week retreatment. Visual acuity at month 3, after the initial fixed‐interval injections, was the strongest predictor of BCVA at month 12.     

雷珠单抗联合激光光凝治疗视网膜分支静脉阻塞继发黄斑水肿的疗效

目的：观察雷珠单抗玻璃体腔注射联合黄斑区激光光凝治疗视网膜分支静脉阻塞( branch retinal vein occlusion, BRVO)继发黄斑水肿的安全性及有效性。方法：临床确诊为BRVO继发黄斑水肿的病例患者44例44眼纳入研究,分为玻璃体腔注射雷珠单抗+黄斑区激光光凝组(联合组)和单纯黄斑区激光光凝组(光凝组)。所有患者均行最佳矫正视力、裂隙灯检查、眼底检查、非接触眼压计检查、荧光素眼底血管造影及光相干断层扫描检查。联合组所有患者均行常规玻璃体腔注射雷珠单抗0.05mL/0.5mg。出现黄斑水肿时,按需进行雷珠单抗玻璃体腔注射。玻璃体腔注射雷珠单抗后1wk,给予黄斑区激光光凝治疗。所有患者均随访6 mo。对比分析患眼治疗前后BCVA及CMT的变化情况以及有无并发症发生情况。结果：联合组疗效明显,视网膜厚度降低明显,视力提高快,视力及CMT 值均与治疗前比较差异有统计学意义(视力：t=5.781、7.496、7.341、7.836,均P=0.000;CMT：t=9.784、11.893、11.573、11.437,均P=0.000)。激光组激光治疗后1wk视力与治疗前比较差异无统计学意义( t=2.130,P=0.053),治疗后4、12、24wk视力改善与治疗前比较差异均有统计学意义( t=3.524、6.429、6.922, P=0.04、0.000、0.000)。联合组与激光组治疗后1、4、12、24 wk不同时间点视力比较差异有统计学意义( t=2.604、3.223、3.303、3.296,P=0.015、0.03、0.04、0.03)。联合组与激光组治疗后不同时间点CMT值变化差异有统计学意义( t =43.231、50.504、56.074、38.103,均 P =0.000)。随访期间未发生眼部并发症及全身不良反应。结论：雷珠单抗联合黄斑区激光光凝治疗BRVO继发黄斑水肿有良好的疗效及安全性。     

An optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration

PURPOSE: To evaluate an optical coherence tomography (OCT)-guided, variable-dosing regimen with intravitreal ranibizumab for the treatment of patients with neovascular age-related macular degeneration (AMD). DESIGN: Open-label, prospective, single-center, nonrandomized, investigator-sponsored clinical study. METHODS: In this two-year study, neovascular AMD patients with subfoveal choroidal neovascularization (CNV) (n = 40) and a central retinal thickness of at least 300 microm as measured by OCT were enrolled to receive three consecutive monthly intravitreal injections of ranibizumab (0.5 mg). Thereafter, retreatment with ranibizumab was performed if one of the following changes was observed between visits: a loss of five letters in conjunction with fluid in the macula as detected by OCT, an increase in OCT central retinal thickness of at least 100 microm, new-onset classic CNV, new macular hemorrhage, or persistent macular fluid detected by OCT at least one month after the previous injection of ranibizumab. RESULTS: At month 12, the mean visual acuity improved by 9.3 letters (P < .001) and the mean OCT central retinal thickness decreased by 178 microm (P < .001). Visual acuity improved 15 or more letters in 35% of patients. These visual acuity and OCT outcomes were achieved with an average of 5.6 injections over 12 months. After a fluid-free macula was achieved, the mean injection-free interval was 4.5 months before another reinjection was necessary. CONCLUSION: This OCT-guided, variable-dosing regimen with ranibizumab resulted in visual acuity outcomes similar to the Phase III clinical studies, but required fewer intravitreal injections. OCT appears useful for determining when retreatment with ranibizumab is necessary.     

雷珠单抗治疗BRVO-ME的临床疗效及视力预后相关因素分析

目的:分析雷珠单抗治疗视网膜分支静脉阻塞继发黄斑水肿(BRVO-ME)患者黄斑区视网膜结构和功能的改善情况,并探讨影响视力预后的相关因素。方法:前瞻性临床研究。选取2018-06/2019-05于我院眼科确诊的BRVO-ME患者25例25眼,均接受每月1次,连续3次玻璃体腔注射雷珠单抗治疗。分别于治疗前和第3次玻璃体腔注射1mo后检测最佳矫正视力(BCVA),并利用相干光断层扫描成像(OCT和OCTA)技术检测黄斑中心凹厚度(CMT),评估浅层视网膜毛细血管网的血管长度密度(VLD)、血管灌注密度(VPD)、中心凹无血管区面积(FAZ),通过多焦视网膜电流图(mf-ERG)分析一环和二环(中央凹)的N1、P1波潜伏期及P1波振幅密度。结果:治疗后,本组患者BCVA(LogMAR)较治疗前显著改善(0.323±0.086 vs 0.773±0.304,P<0.05);CMT显著降低(239.385±33.175μm vs 489.346±137.453μm,P<0.05),而VLD、VPD、FAZ均无明显变化(P>0.05);一环和二环N1波潜伏期、P1波潜伏期显著降低,且P1波振幅密度值显著提高(P<0.05)。Pearson相关性分析显示,年龄、治疗前BCVA、VLD、VPD、FAZ与治疗前后视力变化值具有显著相关性(均P<0.05)。结论:玻璃体腔内注射雷珠单抗治疗BRVO-ME可显著降低黄斑水肿,改善视力及黄斑区结构和功能,年龄、基线BCVA、黄斑区微结构参数可作为评估视力改善的预测指标。     

Intravitreal ranibizumab for macular oedema secondary to retinal vein occlusion: a retrospective study of 34 eyes

Purpose: To evaluate the efficacy and the safety of intravitreal ranibizumab injection (Lucentis) in eyes with macular oedema secondary to central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO). Methods: The files of consecutive patients (34 eyes, 15 CRVO, 19 BRVO) were retrospectively analysed. Intravitreal injections of 0.5 mg ranibizumab were administered; retreatment was based on acuity visual changes and optical coherence tomography findings. Patients received 2–4 injections (mean, 2.1). Mean follow‐up was 7 months. Results: After the first injection, mean best‐corrected visual acuity (BCVA) improved from 20/160 to 20/80 and mean central retinal thickness (CRT) decreased significantly from 549 to 301 μm (p < 0.01). For each injection, BCVA improvement was on average nine letters (p < 0.01) and macular oedema reduction was 195 μm CRT (p < 0.01). The decrease in CRT was similar in CRVO and BRVO, but the improvement in BCVA was larger in BRVO. No local or systemic adverse effect was detected. Final visual acuity was correlated to initial visual acuity and to visual acuity measured after the first injection. The change in CRT was correlated to the number of injections and to initial CRT. Conclusion: Intravitreal injections of ranibizumab appeared to be a safe and effective option in the treatment of macular oedema secondary to retinal vein occlusion. Nevertheless, because the natural course has demonstrated a possible improvement in vision in almost one quarter of affected eyes at 3 years, further controlled and prospective studies are necessary to compare this treatment to the natural course with a longer follow‐up.     

玻璃体注射雷珠单抗治疗老年性黄斑变性黄斑水肿与视网膜静脉阻塞性黄斑水肿的短期疗效观察

目的 观察玻璃体注射雷珠单抗治疗老年黄斑变性黄斑水肿（AMD-ME）与视网膜静脉阻塞性黄斑水肿（RVO-ME）的短期临床效果。设计 回顾性病例系列。研究对象 2015年10月至2016年7月确诊为AMD-ME 及RVO-ME 的患者共30例（30眼）,各15例（15眼）。方法 患眼接受玻璃体注射雷珠单抗（0.5 mg/0.05 ml）治疗,采用1+PRN的注射方法,比较治疗前和治疗后 1 天、1个月最佳矫正视力（BCVA）、眼压（IOP）、黄斑中心凹视网膜厚度（CMT）、注射后消除的水肿高度,评价每次随访时检查结果。主要指标 BCVA、CMT、消除的水肿高度、IOP。结果 AMD-ME组及RVO-ME 组注射雷珠单抗后1天、1个月的BCVA均较术前提高（P=0.000、0.000）。AMD-ME组 及RVO-ME 组每次治疗前和治疗后1个月CMT厚度均降低（P＝0.000、0.000）。治疗过程中患者眼压与治疗前比较并无明显变化 （P=0.096、0.066、0.213、0.088、0.240、0.337）。结论 玻璃体注射雷珠单抗治疗 AMD-ME 及 RVO-ME 在短期内均可减轻黄斑水肿和改善视力,两者治疗效果无明显差异。（眼科, 2017, 26： 120-124）     

Intravitreal bevacizumab (avastin) for central and hemicentral retinal vein occlusions: IBeVO study

PURPOSE: To evaluate the safety, visual acuity changes, and morphologic effects associated with intravitreal bevacizumab injections for the management of macular edema due to ischemic central or hemicentral retinal vein occlusion (RVO). METHODS: In this prospective, open-label study, 7 consecutive patients (7 eyes) with macular edema associated with ischemic central or hemicentral RVO were treated with intravitreal injections of 2.0 mg (0.08 mL) of bevacizumab at 12-week intervals. Standardized ophthalmic evaluation was performed at baseline and at weeks 1, 6, and 12 after each injection. Clinical evidence of toxicity and complications as well as changes in logarithm of minimum angle of resolution Early Treatment Diabetic Retinopathy Study best-corrected visual acuity (BCVA), central macular thickness (CMT) and total macular volume (TMV) shown by optical coherence tomography (OCT), and dye leakage shown by fluorescein angiography were evaluated. RESULTS: The median age of the 7 patients was 65 years (range, 58-74 years), and the median duration of symptoms before injection was 7 months (range, 2.5-16 months). At baseline, mean BCVA was 1.21 (Snellen equivalent, approximately 20/320) in the affected eye. Mean baseline CMT and TMV were 730.1 microm and 17.1 mm(3), respectively. Fluorescein leakage was observed in the macula and affected retinal quadrants in all seven eyes. Six patients completed the 25-week follow-up examination with reinjections performed at weeks 12 and 24. The most common adverse events were conjunctival hyperemia and subconjunctival hemorrhage at the injection site. At the last follow-up, mean BCVA in the affected eye was 0.68 (Snellen equivalent, 20/100(+1). No patient had a decrease in BCVA. Mean CMT and TMV at the 25-week follow-up were 260.3 microm and 9.0 mm(3), respectively; fluorescein leakage within the macula and affected retinal quadrants as compared with baseline was markedly reduced in all patients. Coupled with fluorescein angiographic findings, OCT data suggest a trend of macular edema recurrence between 6 weeks and 12 weeks after injection. CONCLUSIONS: Intravitreal bevacizumab injections of 2.0 mg at 12-week intervals were well tolerated and were associated with short-term BCVA stabilization or improvement and favorable macular changes in all patients with ischemic RVO and associated macular edema.