Medical Center Ophthalmology Associates, San Antonio, Texas 78240, USA.
Ophthalmology. 2012 Jun;119(6):1175-83. doi: 10.1016/j.ophtha.2011.12.016. Epub 2012 Feb 4.
To evaluate the long-term safety and efficacy of multiple intravitreal ranibizumab injections (Lucentis, Genentech, Inc., South San Francisco, CA) administered at the investigator's discretion in patients with choroidal neovascularization secondary to age-related macular degeneration.
An open-label, multicenter, extension study.
Patients who completed the controlled treatment phase of 1 of 3 prospective, randomized, 2-year clinical trials of ranibizumab were eligible for enrollment. Analyses were performed for 3 groups: (1) patients treated with ranibizumab in the initial study (ranibizumab treated-initial; n = 600); (2) patients randomized to control who crossed over to receive ranibizumab (ranibizumab treated-XO; n = 190); and (3) ranibizumab-naïve patients (ranibizumab untreated; n = 63).
Ranibizumab 0.5 mg was administered at the investigator's discretion. Adverse events (AEs) and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) assessments were conducted at study visits every 3 to 6 months.
Incidence and severity of AEs.
There was 1 occurrence of mild endophthalmitis per 3552 HORIZON injections in the ranibizumab treated-initial/ranibizumab treated-XO groups. There were no serious AE reports of lens damage, retinal tears, or rhegmatogenous retinal detachments in the study eyes. The proportion of patients with any single postdose intraocular pressure ≥30 mmHg was 9.2%, 6.6%, and 0%, and the proportion of patients with glaucoma was 3.2%, 4.2%, and 3.2% in the ranibizumab treated-initial, ranibizumab treated-XO, and ranibizumab untreated groups, respectively. Cataract AEs were less frequent in the ranibizumab untreated group: 6.3% versus 12.5% and 12.1% in the ranibizumab treated-initial and ranibizumab treated-XO groups, respectively. The proportion of patients with arterial thromboembolic events as defined by the Antiplatelet Trialists' Collaboration was 5.3% in the ranibizumab treated-initial and ranibizumab treated-XO groups, and 3.2% in the ranibizumab untreated group. At month 48 (2 years of HORIZON), the mean change in BCVA (ETDRS letters) relative to the initial study baseline was 2.0 in the ranibizumab treated-initial group versus -11.8 in the pooled ranibizumab treated-XO and ranibizumab untreated groups.
Multiple ranibizumab injections were well tolerated for ≥4 years. With less frequent follow-up leading to less treatment, there was an incremental decline of the visual acuity (VA) gains achieved with monthly treatment.
FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
评估在研究者的判断下多次玻璃体内注射雷珠单抗（罗氏，加利福尼亚州南旧金山）对年龄相关性黄斑变性所致脉络膜新生血管患者的长期安全性和疗效。
开放标签、多中心、扩展研究。
完成 3 项前瞻性、随机、2 年雷珠单抗临床试验对照治疗阶段的患者有资格参加。对 3 组患者进行了分析：（1）初始研究中接受雷珠单抗治疗的患者（雷珠单抗治疗-初始组；n = 600）；（2）随机分配至对照组但交叉接受雷珠单抗治疗的患者（雷珠单抗治疗-XO 组；n = 190）；和（3）雷珠单抗初治患者（雷珠单抗未治疗组；n = 63）。
研究者根据情况对患者进行雷珠单抗 0.5 mg 注射。每次访视时进行不良事件（AE）和早期治疗糖尿病视网膜病变研究（ETDRS）最佳矫正视力（BCVA）评估，访视时间为每 3 至 6 个月一次。
AE 的发生率和严重程度。
雷珠单抗治疗-初始/雷珠单抗治疗-XO 组每 3552 次 HORIZON 注射发生 1 例轻度眼内炎。在研究眼中未报告与晶状体损伤、视网膜裂孔或孔源性视网膜脱离相关的严重 AE。单次眼压≥30mmHg 的患者比例分别为 9.2%、6.6%和 0%，青光眼患者比例分别为 3.2%、4.2%和 3.2%，在雷珠单抗治疗-初始、雷珠单抗治疗-XO 和雷珠单抗未治疗组。雷珠单抗未治疗组的白内障 AE 发生率较低：雷珠单抗治疗-初始组为 12.5%，雷珠单抗治疗-XO 组为 12.1%，雷珠单抗未治疗组为 6.3%。抗血小板治疗者协作组定义的动脉血栓栓塞事件患者比例分别为雷珠单抗治疗-初始和雷珠单抗治疗-XO 组为 5.3%，雷珠单抗未治疗组为 3.2%。在 48 个月（2 年 HORIZON）时，与初始研究基线相比，雷珠单抗治疗-初始组的 BCVA（ETDRS 字母）平均变化为 2.0，而 pooled 雷珠单抗治疗-XO 和雷珠单抗未治疗组的平均变化为-11.8。
多次雷珠单抗注射至少耐受 4 年。由于随访次数减少导致治疗次数减少，每月治疗后视力（VA）获得的提高逐渐下降。
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