Wykoff Charles C, Do Diana V, Goldberg Roger A, Dhoot Dilsher S, Lim Jennifer I, Du Weiming, Silva Fabiana Q, Desai Rutvi, Moini Hadi, Reed Kimberly, Berliner Alyson J, Vitti Robert, Clark W Lloyd
Retina Consultants of Texas; Retina Consultants of America; Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas.
Byers Eye Institute, Stanford University, Palo Alto, California.
Ophthalmol Retina. 2023 Oct 27. doi: 10.1016/j.oret.2023.10.016.
Identify baseline systemic and ocular characteristics associated with nonproliferative diabetic retinopathy (NPDR) worsening, and the impact of intravitreal aflibercept injection (IAI) on these associations.
Post hoc analysis of PANORAMA.
Patients with moderately severe to severe NPDR enrolled in the prospective PANORAMA phase 3 trial.
Associations between baseline systemic and ocular factors with events indicative of NPDR worsening at Week 100 were evaluated by multivariable analysis in sham-treated eyes. NPDR worsening was defined as development of (1) vision-threatening complications (VTCs; comprising PDR and/or anterior segment neovascularization), (2) center-involved diabetic macular edema (CI-DME), or (3) ≥ 2-step Diabetic Retinopathy Severity Scale (DRSS) worsening. Impact of IAI on identified baseline factors was evaluated using univariable analysis in combined IAI groups.
Baseline systemic and ocular factors associated with events indicative of NPDR worsening at Week 100. The cumulative incidence and risk of developing such events at Week 100 among sham versus IAI-treated eyes.
Using multivariable analyses among sham-treated eyes, 5 baseline factors associated with increased risk of NPDR worsening were identified: fluorescein leakage, retinal nonperfusion area, thicker central subfield thickness, eosinophil level, and proteinuria. Considering baseline fluorescein leakage area as a prognostic indicator in detail, the risk of developing VTCs alone, VTCs and/or CI-DME, or ≥ 2-step DRSS worsening increased with increasing fluorescein leakage area in the sham group (all P < 0.05). Considering baseline retinal nonperfusion area as a prognostic indicator in detail, the risk of developing VTCs alone, CI-DME alone, or VTCs and/or CI-DME increased with increasing baseline retinal nonperfusion area in the sham group (all P < 0.05). In contrast, among IAI-treated eyes, increasing baseline fluorescein leakage or retinal nonperfusion areas did not increase the risks of NPDR worsening.
Within the PANORAMA trial, increased areas of fluorescein leakage and retinal nonperfusion at baseline were identified as key ocular biomarkers associated with events indicative of NPDR worsening among sham-treated patients. IAI treatment appeared to mitigate the effect of these baseline risk factors and reduced the likelihood of NPDR worsening.
确定与非增殖性糖尿病视网膜病变（NPDR）恶化相关的基线全身和眼部特征，以及玻璃体内注射阿柏西普（IAI）对这些关联的影响。
对PANORAMA试验的事后分析。
参加前瞻性PANORAMA 3期试验的中度至重度NPDR患者。
在接受假治疗的眼中，通过多变量分析评估基线全身和眼部因素与100周时提示NPDR恶化事件之间的关联。NPDR恶化定义为出现以下情况：（1）威胁视力的并发症（VTCs；包括增殖性糖尿病视网膜病变和/或眼前节新生血管形成），（2）累及中心凹的糖尿病性黄斑水肿（CI-DME），或（3）糖尿病视网膜病变严重程度量表（DRSS）恶化≥2级。在联合IAI组中使用单变量分析评估IAI对已确定的基线因素的影响。
与100周时提示NPDR恶化事件相关的基线全身和眼部因素。假治疗组与IAI治疗组在100周时发生此类事件的累积发生率和风险。
在接受假治疗的眼中进行多变量分析，确定了5个与NPDR恶化风险增加相关的基线因素：荧光素渗漏、视网膜无灌注区、中心子野厚度增加、嗜酸性粒细胞水平和蛋白尿。详细将基线荧光素渗漏面积作为预后指标，在假治疗组中，单独发生VTCs、VTCs和/或CI-DME或DRSS恶化≥2级的风险随着荧光素渗漏面积的增加而增加（所有P<0.05）。详细将基线视网膜无灌注区作为预后指标，在假治疗组中，单独发生VTCs、单独发生CI-DME或VTCs和/或CI-DME的风险随着基线视网膜无灌注区的增加而增加（所有P<0.05）。相比之下，在接受IAI治疗的眼中，基线荧光素渗漏或视网膜无灌注区增加并未增加NPDR恶化的风险。
在PANORAMA试验中，基线荧光素渗漏和视网膜无灌注面积增加被确定为与假治疗患者中提示NPDR恶化事件相关的关键眼部生物标志物。IAI治疗似乎减轻了这些基线风险因素的影响，并降低了NPDR恶化的可能性。
