Time-in-Range Analysis of Responses after Intravitreal Dexamethasone Therapy in Eyes with Diabetic Macular Edema

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science Pub Date : 2025-05-26 DOI:10.1016/j.xops.2025.100833

Igor Kozak MD, PhD , Diana V. Do MD , Hongxin Lai PhD , Miller J. Ogidigben PhD , Francisco J. López MD, PhD

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Abstract

Purpose

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.

Design

Post hoc analysis of results from the randomized, multicenter, sham-controlled, phase III MEAD trial (NCT00168337 and NCT00168389).

Participants

Adults with type 1 or 2 diabetes mellitus and fovea-involved macular edema associated with diabetic retinopathy.

Intervention

Intravitreal injection of DEX-I 0.7 mg or sham procedure.

Main Outcome Measures

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).

Results

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; P < 0.001) and the CRT <300 μm threshold (18.5 vs. 8.3 weeks, respectively; P < 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 P < 0.001).

Conclusions

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.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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糖尿病性黄斑水肿患者玻璃体内地塞米松治疗后反应的时间范围分析

目的范围内时间（TIR）是一种新的终点，用于评估结果保持在预定范围内的时间。由于范围包括正常参数，因此它指示临床有意义的益处。MEAD试验包括两项为期3年的随机、多中心、假对照的III期临床研究，评估地塞米松玻璃体内植入物（DEX-I）治疗糖尿病黄斑水肿患者的疗效和安全性。与假手术相比，地塞米松玻璃体内植入可显著改善最佳矫正视力（BCVA）和中央视网膜厚度（CRT）。我们提出了一项MEAD试验的事后分析，以调查不同阈值的BCVA和CRT与DEX-I相比的TIR益处。设计随机、多中心、假对照、III期MEAD试验（NCT00168337和NCT00168389）结果的事后分析。研究对象为1型或2型糖尿病伴糖尿病视网膜病变的黄斑水肿患者。干预：玻璃体内注射DEX-I 0.7 mg或假手术。采用BCVA阈值≥69、≥51、≥59和≥64个字母，以及CRT阈值为<；300、<353、<；446和<；551 μm（后一阈值分别为合并基线BCVA和CRT的四分位数[Q] 1、Q2和Q3）评估第一年范围内的时间。结果在BCVA≥69个字母阈值时，地塞米松玻璃体内植入0.7 mg与假手术相比，TIR更长（分别为15.0周与9.1周），具有统计学意义；P & lt;0.001)和CRT <；300 μm阈值（18.5 vs. 8.3周）；P & lt;0.001)。在BCVA≥59（大于或等于Q2）和≥64个字母（大于或等于Q3）和CRT <；353 μm（小于Q1）， <446 μm（小于Q2）和<；551 μm（小于Q3）阈值时，地塞米松玻璃体内植入物与假手术相比TIR更长(均P <；0.001)。结论在MEAD试验的第1年，玻璃体内注射DEX-I 0.7 mg的患者BCVA高于驱动阈值、低于CRT正常阈值的时间较假手术组更长。这些结果表明，与假手术相比，接受地塞米松治疗的患者获得临床有意义的结果的时间更长，例如能够驱动或恢复正常的视网膜结构特征。财务披露专有或商业披露可在本文末尾的脚注和披露中找到。

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