REVISION – Early Reperfusion Therapy with Alteplase for Recovery of Vision in Acute Central Retinal Artery Occlusion: A Phase III Double-Blind Randomized Placebo-Controlled Trial

Abstract

Purpose : Non-arteritic central retinal artery occlusion (CRAO) is a neurovascular-ophthalmological emergency leading to severe and permanent vision loss in the affected eye in 95% of the cases. This phase III trial aims to evaluate intravenous alteplase’s efficacy and safety in treating acute CRAO, with a focus on achieving functional recovery within a 4.5-hour window post-symptom onset. Secondary objectives include safety assessments and identifying predictive biomarkers.

Methods : Employing a double-blind randomized placebo-controlled design, this multicentric trial consists of interventional (t ≤ 4.5h) and observational arms (t ≤ 12 h). The interventional study employs intravenous alteplase or placebo within the 4.5-hour window, with endpoints including best corrected visual acuity (BCVA) assessment, visual field analysis, optical coherence tomography (OCT), optical coherence tomography angiography (OCT-A), fluorescein angiography at specific time points. Safety assessments encompass various parameters, including intracranial hemorrhage, adverse events, and mortality. Exploratory endpoints seek to identify predictive biomarkers correlating with treatment response and visual outcomes.

Results : The trial outcomes are centered on assessing the efficacy and safety of intravenous alteplase in acute CRAO. Primary endpoints include functional recovery (logMAR ≤ 0.5, normal to mild vision impairment according to the WHO ICD-11 classification) within the affected eye, measured by BCVA assessment, at specific time intervals. Secondary endpoints cover a wide array of visual recovery metrics, safety evaluations, and exploratory analyses to identify potential prognostic biomarkers.

Conclusions : This prospective randomized placebo-controlled trial aims to provide insights into the efficacy, safety, and potential prognostic markers associated with intravenous alteplase therapy in acute non-arteritic central retinal artery occlusion. The outcomes of this study could significantly impact the management and treatment strategies for this visually devastating condition of acute CRAO.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.