PURPOSE To evaluate the efficacy and safety of ranibizumab 0.5 mg in adult patients with macular edema (ME) resulting from any cause other than diabetes, retinal vein occlusion, or neovascular age-related macular degeneration. DESIGN A phase 3, 12-month, double-masked, randomized, sham-controlled, multicenter study. PARTICIPANTS One hundred seventy-eight eligible patients aged ≥18 years. METHODS Patients were randomized 2:1 to receive either ranibizumab 0.5 mg (n = 118) or sham (n = 60) at baseline and month 1. From month 2, patients in both arms received open-label individualized ranibizumab treatment based on disease activity. A preplanned subgroup analysis was conducted on the primary end point on 5 predefined baseline ME etiologies (inflammatory/post-uveitis, pseudophakic or aphakic, central serous chorioretinopathy, idiopathic, and miscellaneous). MAIN OUTCOME MEASURES Changes in best-corrected visual acuity (BCVA; Early Treatment Diabetic Retinopathy Study letters) from baseline to month 2 (primary end point) and month 12 and safety over 12 months. RESULTS Overall, 156 patients (87.6%) completed the study. The baseline characteristics were well balanced between the treatment arms. Overall, ranibizumab showed superior efficacy versus sham from baseline to month 2 (least squares mean BCVA, +5.7 letters vs. +2.9 letters; 1-sided P = 0.0111), that is, a treatment effect (TE) of +2.8 letters. The mean BCVA gain from baseline to month 12 was 9.6 letters with ranibizumab. The TE at month 2 was variable in the 5 predefined etiology subgroups, ranging from >5-letter gain to 0.5-letter loss. The safety findings were consistent with the well-established safety profile of ranibizumab. CONCLUSIONS The primary end point was met and ranibizumab showed superiority in BCVA gain over sham in treating ME due to uncommon causes, with a TE of +2.8 letters versus sham at month 2. At month 12, the mean BCVA gain was high (9.6 letters) in the ranibizumab arm; however, the TE was observed to be variable across the different etiology subgroups, reaching a >1-line TE in BCVA in patients with ME resulting from inflammatory conditions/post-uveitis or after cataract surgery. Overall, ranibizumab was well tolerated with no new safety findings up to month 12.

中文翻译：

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雷尼单抗0.5 mg治疗因罕见原因引起的黄斑水肿的疗效和安全性：PROMETHEUS十二个月的研究结果。

目的评估兰尼单抗0.5 mg对除糖尿病，视网膜静脉阻塞或新血管性年龄相关性黄斑变性以外的任何原因引起的黄斑水肿（ME）成年患者的疗效和安全性。设计A期3个月，12个月，双重掩盖，随机，假手术控制的多中心研究。参加者178名年龄≥18岁的合格患者。方法患者在基线和第1个月被随机以2：1的比例接受0.5 mg雷尼珠单抗（n = 118）或假（n = 60）接受治疗。从第2月开始，两组患者均根据疾病活动接受开放标签的个体化雷珠单抗治疗。在5种预定义的基线ME病因（炎症/葡萄膜炎，假晶状体或无晶状体，中央浆液性脉络膜视网膜病变，特发性，和其他）。主要观察指标从基线到第2个月（主要终点），第12个月和第12个月的最佳矫正视力（BCVA；早期治疗糖尿病性视网膜病变研究信函）的变化以及12个月内的安全性。结果总体上，有156例患者（占87.6％）完成了研究。治疗组之间的基线特征很好地平衡。总体而言，从基线到第二个月，兰尼单抗显示出优于假手术的功效（最小二乘均值BCVA，+ 5.7个字母对+2.9个字母； 1面P = 0.0111），即，治疗效果（TE）为+2.8个字母。雷尼单抗从基线到第12个月的平均BCVA增益为9.6个字母。第二个月的TE在5个预定义的病因亚组中是可变的，范围从> 5字母增加到0.5字母减少。安全性发现与兰尼单抗的公认安全性一致。结论达到了主要终点，由于罕见原因，兰尼单抗在治疗ME方面显示出BCVA增值优于假手术，在第2个月的TE与假手术相比为+2.8个字母，在第12个月，平均BCVA增高（9.6个字母）。 ）在兰尼单抗手臂中; 然而，观察到TE在不同病因亚组之间是可变的，在ME患者中，由炎症状况/葡萄膜炎后或白内障手​​术引起的TE中，TE> 1行TE。总体而言，兰尼单抗的耐受性良好，直到第12个月都没有新的安全性发现。在第2个月时，伪造为8个字母，而在假时为12个月。然而，观察到TE在不同病因亚组之间是可变的，在ME患者中，由炎症状况/葡萄膜炎后或白内障手​​术引起的TE中，TE> 1行TE。总体而言，兰尼单抗的耐受性良好，直到第12个月都没有新的安全性发现。在第2个月时，伪造为8个字母，而在假时为12个月。然而，观察到TE在不同病因亚组之间是可变的，在ME患者中，由炎症状况/葡萄膜炎后或白内障手​​术引起的TE中，TE> 1行TE。总体而言，兰尼单抗的耐受性良好，直到第12个月都没有新的安全性发现。