目的：评估视网膜静脉阻塞(RVO)后黄斑水肿患者眼内注射雷珠单抗的长期安全性和有效性。

　　设计：本研究为一项为期12个月的开放标签延长试验，在视网膜分支静脉阻塞研究(BRAVO)和视网膜中央静脉阻塞研究(CRUISE)之后评估雷珠单抗治疗这两类患者的有效性和安全性。

　　受试者：304例完成了BRAVO的患者和304例完成了CRUISE的患者。

　　方法：患者至少每3个月进行一次复查，如果他们符合预先设定的再治疗标准，就给予0.5 mg雷珠单抗眼内注射。

　　主要观察指标：主要结局是眼部和非眼部不良事件(AEs)的发生率与严重程度。主要的疗效结局包括从基线起最佳矫正视力(BCVA)字母评分(根据早期糖尿病视网膜病变研究协议)的变化和黄斑中央凹厚度。

　　结果：在完成了12个月研究的患者中，假注射液/0.5mg雷珠单抗组、0.3mg /0.5mg雷珠单抗组、0.5mg雷珠单抗组(不含第12个月的注射)的平均注射次数分别为2.0、2.4、2.1(分支RVO )和2.9、3.8、3.5(中央RVO )。研究中各治疗组的眼部和非眼部的严重AE(SAE)以及潜在的与全身血管内皮生长因子抑制相关的SAE的发生率分别为2%~9%和1%~6%。在分支RVO患者中，BCVA字母评分自基线至12个月时的平均变化分别为0.9(假注射液/0.5mg雷珠单抗组)、-2.3(0.3/0.5mg雷珠单抗组)和-0.7(0.5mg雷珠单抗组)。在中央RVO患者中，BCVA字母评分自基线至12个月时的平均变化分别为-4.2(假注射液/0.5mg雷珠单抗组)、-5.2(0.3/0.5mg雷珠单抗组)和-4.1(0.5mg雷珠单抗组)。

　　结论：本研究未发现长期使用雷珠单抗有新的安全性事件;潜在的与治疗相关的SAE发生率与之前的雷珠单抗试验结果一致。在治疗的第2年减少随访和雷珠单抗注射次数与中央RVO患者视力下降相关。但分支RVO患者的视力仍然保持稳定。结果表明，在视网膜静脉阻塞患者接受雷珠单抗治疗的第二年，随访和注射治疗应当个体化，平均而言，中央RVO患者的随访频率可能需要比每3个月一次更为频繁。

　　PURPOSE:To assess long-term safety and efficacy of intraocular ranibizumab injections in patients with macular edema after retinal vein occlusion (RVO).

　　DESIGN:Open-label extension trial of the 12-month Ranibizumab for the Treatment of Macular Edema following Branch Retinal Vein Occlusion: Evaluation of Efficacy and Safety (BRAVO) and Central Retinal Vein Occlusion Study: Evaluation of Efficacy and Safety (CRUISE) trials.

　　PARTICIPANTS:We included 304 patients who completed BRAVO and 304 patients who completed CRUISE.

　　METHODS:Patients were seen at least every 3 months and given an intraocular injection of 0.5 mg ranibizumab if they met prespecified retreatment criteria.

　　MAIN OUTCOME MEASURES:Primary outcomes were incidence and severity of ocular and nonocular adverse events (AEs). Key efficacy outcomes included mean change from baseline best-corrected visual acuity (BCVA) letter score by Early Treatment Diabetic Retinopathy Study protocol and central foveal thickness.

　　RESULTS:In patients who completed month 12, the mean number of injections (excluding month 12 injection) in the sham/0.5-, 0.3/0.5-, and 0.5-mg groups was 2.0, 2.4, and 2.1 (branch RVO) and 2.9, 3.8, and 3.5 (central RVO), respectively. The incidence of study eye ocular serious AEs (SAEs) and SAEs potentially related to systemic vascular endothelial growth factor inhibition across treatment arms was 2% to 9% and 1% to 6%, respectively. The mean change from baseline BCVA letter score at month 12 in branch RVO patients was 0.9 (sham/0.5 mg), -2.3 (0.3/0.5 mg), and -0.7 (0.5 mg), respectively. The mean change from baseline BCVA at month 12 in central RVO patients was -4.2 (sham/0.5 mg), -5.2 (0.3/0.5 mg), and -4.1 (0.5 mg), respectively.

　　CONCLUSIONS:No new safety events were identified with long-term use of ranibizumab; rates of SAEs potentially related to treatment were consistent with prior ranibizumab trials. Reduced follow-up and fewer ranibizumab injections in the second year of treatment were associated with a decline in vision in central RVO patients, but vision in branch RVO patients remained stable. Results suggest that during the second year of ranibizumab treatment of RVO patients, follow-up and injections should be individualized and, on average, central RVO patients may require more frequent follow-up than every 3 months.