Retina Consultants of Texas (Retina Consultants of America), Houston, Texas.
Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas.
JAMA Ophthalmol. 2021 Sep 1;139(9):946-955. doi: 10.1001/jamaophthalmol.2021.2809.
Proactive treatment of nonproliferative diabetic retinopathy (NPDR) reduces the risk of progression to vision-threatening complications.
To evaluate vascular endothelial growth factor blockade therapy with intravitreal aflibercept injections in eyes with severe NPDR without diabetic macular edema (DME).
DESIGN, SETTING, AND PARTICIPANTS: The Study of the Efficacy and Safety of Intravitreal Aflibercept for the Improvement of Moderately Severe to Severe Nonproliferative Diabetic Retinopathy (PANORAMA) was a double-masked 100-week randomized clinical trial conducted in multiple centers worldwide. The study included 402 adults with Diabetic Retinopathy Severity Scale (DRSS) level 47 or 53 with no DME and best-corrected visual acuity of 20/40 or better.
Intravitreal injections of aflibercept, 2 mg, every 16 weeks after 3 initial monthly doses and one 8-week interval (aflibercept 2q16 group); intravitreal injections of aflibercept, 2 mg, every 8 weeks after 5 initial monthly doses, with pro re nata (PRN) dosing beginning at week 56 (aflibercept 2q8/PRN group); or sham injections (control group).
Proportions of eyes with a 2-step or greater improvement in DRSS level, vision-threatening complications, and center-involved DME from baseline to weeks 24, 52, and 100.
Among 402 participants (1 eye per participant), the mean (SD) age was 55.7 (10.5) years; 225 (56.0%) were male, and 310 (77.1%) were White. A total of 135 were randomized to the aflibercept 2q16 group, 134 to the aflibercept 2q8/PRN group, and 133 to the control group. At 24 weeks, treatment with aflibercept resulted in a 2-step or greater improvement in DRSS level in 157 of 269 eyes (58.4%) in the combined aflibercept groups vs 8 of 133 eyes (6.0%) in the control group (adjusted difference, 52.3%; 95% CI, 45.2%-59.5%; P < .001). At 52 weeks, 88 of 135 eyes (65.2%) in the aflibercept 2q16 group (adjusted difference, 50.1%; 95% CI, 40.1%-60.1%) and 107 of 134 eyes (79.9%) in the aflibercept 2q8/PRN group (adjusted difference, 64.8%; 95% CI, 55.8%-73.9%) compared with 20 of 133 eyes (15.0%) in the control group (P < .001 for both comparisons) showed a 2-step or greater improvement in DRSS level. Fewer eyes treated with aflibercept vs sham injections developed vision-threatening complications and/or center-involved DME through week 100 (22 of 135 eyes [16.3%] in the 2q16 group [adjusted difference, -34.2%; 95% CI, -44.6 to -23.8] and 25 of 134 eyes [18.7%] in the 2q8/PRN group [adjusted difference, -31.7%; 95% CI, -42.5 to -20.9] compared with 67 of 133 eyes [50.4%] in the control group; P < .001 for both comparisons). No new safety signals were identified.
In this study, significantly more eyes with moderately severe to severe NPDR that were treated with aflibercept showed a 2-step or greater improvement in DRSS level at 24, 52, and 100 weeks, and significantly fewer eyes treated with aflibercept vs sham developed vision-threatening complications and center-involved DME. Outcomes on the DRSS between year 1 and 2 emphasize the need for ongoing vascular endothelial growth factor suppression and adherence.
ClinicalTrials.gov Identifier: NCT02718326.
积极治疗非增殖性糖尿病性视网膜病变（NPDR）可降低进展为威胁视力的并发症的风险。
评估玻璃体内注射阿柏西普治疗严重 NPDR 而无糖尿病黄斑水肿（DME）的患者的疗效。
设计、地点和参与者：这项研究名为《改善中度至重度非增殖性糖尿病性视网膜病变的玻璃体内注射阿柏西普的疗效和安全性研究（PANORAMA）》，是一项在全球多个中心进行的双盲 100 周随机临床试验。该研究纳入了 402 名糖尿病视网膜病变严重程度评分（DRSS）为 47 级或 53 级、无 DME 且最佳矫正视力为 20/40 或更好的成年人。
玻璃体注射阿柏西普，2mg，前 3 个月每月注射 3 次，之后每 16 周注射 1 次（阿柏西普 2q16 组）；玻璃体注射阿柏西普，2mg，前 5 个月每月注射 5 次，之后每 8 周注射 1 次，8 周间隔后开始 PRN 治疗（阿柏西普 2q8/PRN 组）；或假注射（对照组）。
从基线到 24 周、52 周和 100 周，DRSS 水平提高 2 步或更多、威胁视力的并发症和中心性 DME 的比例。
在 402 名参与者（每个参与者 1 只眼）中，平均（SD）年龄为 55.7（10.5）岁；225 名（56.0%）为男性，310 名（77.1%）为白人。共 135 名被随机分配到阿柏西普 2q16 组，134 名被分配到阿柏西普 2q8/PRN 组，133 名被分配到对照组。在 24 周时，与对照组相比，联合阿柏西普组中 269 只眼中有 157 只（58.4%）的 DRSS 水平提高了 2 步或更多，而对照组中 133 只眼中只有 8 只（6.0%）（调整差异，52.3%；95%CI，45.2%-59.5%；P < .001）。在 52 周时，阿柏西普 2q16 组中 135 只眼中有 88 只（65.2%）（调整差异，50.1%；95%CI，40.1%-60.1%）和阿柏西普 2q8/PRN 组中 134 只眼中有 107 只（79.9%）（调整差异，64.8%；95%CI，55.8%-73.9%），而对照组中只有 133 只眼中有 20 只（15.0%）（均 P < .001）的 DRSS 水平提高了 2 步或更多。与 sham 注射相比，接受阿柏西普治疗的眼发生威胁视力的并发症和/或中心性 DME 的比例较低，直至 100 周（2q16 组中有 22 只眼[16.3%]，调整差异，-34.2%；95%CI，-44.6 至-23.8%，2q8/PRN 组中有 25 只眼[18.7%]，调整差异，-31.7%；95%CI，-42.5 至-20.9%），而对照组中有 67 只眼[50.4%]（均 P < .001）。没有发现新的安全信号。
在这项研究中，接受阿柏西普治疗的中度至重度 NPDR 患者的 DRSS 水平在 24、52 和 100 周时提高了 2 步或更多，接受阿柏西普治疗的眼发生威胁视力的并发症和中心性 DME 的比例明显较低。DRSS 在第 1 年和第 2 年的结果强调了持续抑制血管内皮生长因子和坚持治疗的必要性。
ClinicalTrials.gov 标识符：NCT02718326。
