Kozak Igor, Do Diana V, Lai Hongxin, Ogidigben Miller J, López Francisco J
Department of Ophthalmology and Vision Science at The University of Arizona, Tucson, AZ.
Department of Opthalmology, Moorfields Eye Hospital Centre, Abu Dhabi, United Arab Emirates.
Ophthalmol Sci. 2025 May 26;5(5):100833. doi: 10.1016/j.xops.2025.100833. eCollection 2025 Sep-Oct.
Time in range (TIR) is a novel end point that assesses the time during which an outcome remains within a predetermined range. Because the range includes normal parameters, it is indicative of clinically meaningful benefit. The MEAD trial comprised two 3-year randomized, multicenter, sham-controlled, phase III clinical studies that evaluated the efficacy and safety of dexamethasone intravitreal implant (DEX-I) in patients with diabetic macular edema. Dexamethasone intravitreal implant significantly improved best-corrected visual acuity (BCVA) and central retinal thickness (CRT) compared with sham treatment. We present a post hoc analysis of the MEAD trial to investigate TIR benefit across various thresholds of BCVA and CRT with DEX-I versus sham.
Post hoc analysis of results from the randomized, multicenter, sham-controlled, phase III MEAD trial (NCT00168337 and NCT00168389).
Adults with type 1 or 2 diabetes mellitus and fovea-involved macular edema associated with diabetic retinopathy.
Intravitreal injection of DEX-I 0.7 mg or sham procedure.
Time in range during year 1 was evaluated using BCVA thresholds of ≥69, ≥51, ≥59, and ≥64 letters, and CRT thresholds of <300, <353, <446, and <551 μm (the latter cutoffs being quartile [Q] 1, Q2, and Q3 of pooled baseline BCVA and CRT, respectively).
Dexamethasone intravitreal implant 0.7 mg was associated with a statistically significant longer TIR versus sham at the BCVA ≥69-letter threshold (15.0 vs. 9.1 weeks, respectively; 0.001) and the CRT <300 μm threshold (18.5 vs. 8.3 weeks, respectively; 0.001). Dexamethasone intravitreal implant was also associated with longer TIR versus sham at thresholds of BCVA ≥59 (greater than or equal to Q2) and ≥64 letters (greater than or equal to Q3) and CRT <353 μm (less than Q1), <446 μm (less than Q2), and <551 μm (less than Q3) (all 0.001).
Patients receiving intravitreal DEX-I 0.7 mg had a longer time with BCVA above the driving threshold and below the normal limit of CRT during year 1 of the MEAD trial versus those who received sham. These results suggest that patients treated with dexamethasone experience a longer time with clinically meaningful outcomes than with sham, such as being able to drive or regaining normal structural retinal features.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
血糖在目标范围内时间（TIR）是一种新的终点指标，用于评估某一结果维持在预定范围内的时间。由于该范围包含正常参数，它表明具有临床意义的获益。MEAD试验包括两项为期3年的随机、多中心、假手术对照的III期临床研究，评估了地塞米松玻璃体内植入物（DEX-I）治疗糖尿病性黄斑水肿患者的疗效和安全性。与假手术治疗相比，地塞米松玻璃体内植入物显著改善了最佳矫正视力（BCVA）和中心视网膜厚度（CRT）。我们对MEAD试验进行了一项事后分析，以研究DEX-I与假手术相比，在不同BCVA和CRT阈值下的TIR获益情况。
对随机、多中心、假手术对照的III期MEAD试验（NCT00168337和NCT00168389）的结果进行事后分析。
患有1型或2型糖尿病且患有与糖尿病视网膜病变相关的累及黄斑中心凹的黄斑水肿的成年人。
玻璃体内注射0.7毫克DEX-I或假手术操作。
使用BCVA阈值≥69、≥51、≥59和≥64字母，以及CRT阈值<300、<353、<446和<551微米（后一组临界值分别为汇总基线BCVA和CRT的四分位数[Q]1、Q2和Q3）评估第1年的血糖在目标范围内时间。
在BCVA≥69字母阈值（分别为15.0周和9.1周；P<0.001）和CRT<300微米阈值（分别为18.5周和8.3周；P<0.001）时，0.7毫克地塞米松玻璃体内植入物与假手术相比，在统计学上具有显著更长的血糖在目标范围内时间。在BCVA≥59（大于或等于Q2）和≥64字母（大于或等于Q3）以及CRT<353微米（小于Q1）、<446微米（小于Q2）和<551微米（小于Q3）的阈值下，地塞米松玻璃体内植入物与假手术相比也具有更长的血糖在目标范围内时间（均P<0.001）。
在MEAD试验的第1年，接受0.7毫克玻璃体内DEX-I治疗的患者，其BCVA高于驾驶阈值且CRT低于正常限度的时间比接受假手术的患者更长。这些结果表明，与假手术相比，接受地塞米松治疗的患者具有临床意义的结果持续时间更长，例如能够驾驶或恢复视网膜正常结构特征。
在本文末尾的脚注和披露中可找到专有或商业披露信息。
