Effect of Faricimab versus Aflibercept on Hyperreflective Foci in Patients with Diabetic Macular Edema from the YOSEMITE/RHINE Trials

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science Pub Date : 2025-04-19 DOI:10.1016/j.xops.2025.100798

Usha Chakravarthy FRCOphth, PhD , Varun Chaudhary MD, FRCS(C) , Srinivas R. Sadda MD , Colin S. Tan FRCOphth, FRCSEd (Ophth) , Stela Vujosevic MD, PhD , Sascha Fauser MD , Kara Gibson PhD , Carl Glittenberg MD , Nancy Holekamp MD, FASRS , Ben Lanza PhD , Andreas Maunz PhD , Jeffrey R. Willis MD, PhD , Rishi P. Singh MD

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Abstract

Purpose

To compare the effect of faricimab, a dual angiopoietin-2 (Ang-2) and VEGF-A inhibitor, with aflibercept on resolution of hyperreflective foci (HRF) in patients with diabetic macular edema (DME).

Design

A post hoc analysis of the randomized, double-masked, noninferiority YOSEMITE/RHINE (NCT03622580/NCT03622593) phase III trials.

Participants

Adults with vision loss due to center-involving DME.

Methods

A deep learning–based algorithm was used to automatically quantify HRF in spectral-domain OCT volume scans from YOSEMITE/RHINE. Study eyes were randomized to faricimab 6.0 mg every 8 weeks (Q8W; n = 519), faricimab 6.0 mg according to a personalized treat-and-extend (T&E)–based regimen (n = 524), and aflibercept 2.0 mg Q8W (n = 502). Hyperreflective foci were defined as hyperreflective objects up to 50 μm in diameter and assessed within the 1.0-mm and 3.0-mm–diameter ETDRS rings and by location within the inner and outer retina.

Main Outcome Measures

Hyperreflective foci volume and count at baseline and over time through week 48 in the inner, outer, and total retina, 1-mm and 3-mm diameters; time to absence of HRF at 2 consecutive visits in the inner and outer retina, 1-mm diameter over 48 weeks.

Results

Adjusted mean HRF volumes at week 48 were lower for faricimab Q8W (104.1 picoliter [pL]) and faricimab T&E (110.1 pL) compared with aflibercept (180.3 pL; nominal P < 0.001 for both) in the inner retina, 1-mm diameter. In the inner retina, 3-mm diameter adjusted mean HRF volumes at week 48 were lower for faricimab Q8W (763.9 pL) and faricimab T&E (777.2 pL) compared with aflibercept (1030.6 pL; nominal P < 0.001 for both). Similar results were obtained for volumes in the outer retina and for HRF counts. In the inner retina, 1-mm diameter, the 25th percentile for time to absence of HRF count at 2 consecutive visits was achieved 8 weeks earlier with faricimab Q8W and faricimab T&E versus aflibercept.

Conclusions

Greater HRF reductions were achieved with faricimab versus aflibercept, supporting the therapeutic potential of dual Ang-2/VEGF-A inhibition to suppress disease activity in DME.

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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来自YOSEMITE/RHINE试验的Faricimab与afliberept对糖尿病性黄斑水肿患者高反射灶的影响

目的比较faricimab（血管生成素-2 （ang2）和VEGF-A双重抑制剂）与afliberept对糖尿病黄斑水肿（DME）患者高反射灶（hyperreflective focal， HRF）消退的影响。设计一项随机、双盲、非低效性的YOSEMITE/RHINE (NCT03622580/NCT03622593) III期试验的事后分析。受试者为因二甲醚引起的视力丧失的成年人。方法采用基于深度学习的算法自动量化YOSEMITE/RHINE的光谱域OCT体积扫描的HRF。研究眼每8周随机服用法昔单抗6.0 mg (Q8W；n = 519), faricimab 6.0 mg (n = 524), aflibercept 2.0 mg Q8W （n = 502）。高反射焦点被定义为直径达50 μm的高反射物体，并在直径1.0 mm和3.0 mm的ETDRS环内以及视网膜内外的位置进行评估。主要观察指标：视网膜内、外和总直径为1 mm和3 mm的过反射灶体积和计数在基线时和在第48周内；48周内1毫米直径的内、外视网膜连续2次就诊至HRF消失的时间。结果48周时，faricimab Q8W （104.1 picoll [pL]）和faricimab T&；E （110.1 picoll [pL]）的调整后平均HRF体积低于afliberept (180.3 pL；名义P <；0.001)内视网膜，直径1毫米。在视网膜内，法昔单抗Q8W （763.9 pL）和法昔单抗T&；E （777.2 pL）在第48周的3毫米直径调整后的平均HRF体积低于阿伯西ept (1030.6 pL；名义P <；两者均为0.001)。外视网膜的体积和HRF计数也得到了类似的结果。在直径为1毫米的内视网膜中，法昔单抗Q8W和法昔单抗T&；E与afliberceept相比，在连续2次就诊时HRF计数消失时间的第25百分位数在8周前达到。结论：法利西单抗比阿非利西普更能降低HRF，支持双重抑制Ang-2/VEGF-A抑制DME疾病活性的治疗潜力。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。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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