Neuroprotection for Nonarteritic Central Retinal Artery Occlusion: Lessons from Acute Ischemic Stroke

Abstract

Nonarteritic central retinal artery occlusion (NA-CRAO) is a variant of acute ischemic stroke (AIS) and is a cause of sudden severe loss of vision. There are guidelines by the American Heart Association and the American Stroke Association for the care of CRAO patients. This review explores the basis of retinal neuroprotection for CRAO and its potential for improving the outcome of NA-CRAO. Recently, there have been significant advances in research into the use of neuroprotection to treat retinal diseases, including retinal detachment, age-related macular degeneration, and inherited retinal diseases. Also, neuroprotective research in AIS has been extensive, and newer drugs tested, including Uric acid, Nerinetide, and Otaplimastat, with promising results. Progress in cerebral neuroprotection after AIS offers hope for retinal neuroprotection after CRAO; and a possibility of extrapolating research findings from AIS into CRAO. Combining neuroprotection and thrombolysis can extend the therapeutic window for NA-CRAO treatment and potentially improve outcomes. Experimented neuroprotection for CRAO includes Angiopoietin (Comp Ang1), KUS 121, Gene therapy (XIAP), and hypothermia. Efforts in the field of neuroprotection for NA-CRAO should focus on better imaging to delineate the penumbra after an acute episode of NA-CRAO (using a combination of high-definition optical coherence angiography and electrophysiology). Also, research should explore details of pathophysiologic mechanisms involved in NA-CRAO, allowing for further neuroprotective intervention, and closing the gap between preclinical and clinical neuroprotection.

Macular Imaging

“…PAM can simultaneously image anatomical, functional, molecular, flow dynamic, and metabolic contrasts in vivo [148]. PAM has been used for macular blood flow imaging in retina vaso-occlusive diseases [149]. Of interest is that PAM has been integrated with adaptive optics for highresolution retina imaging [150].…”

Intravenous Thrombolysis for Central Retinal Artery Occlusion: A Look at the Literature for the Emergency Medicine Physician

“…Yet another review by Janská et al concluded, "It seems that the IVT efficacy and safety can be confirmed" [31]. Okonkwo et al made a case for neuroprotective strategies in patients with CRAO, and on the subject of IVT state "...intravenous (IV) thrombolysis (IV-tPA) in CRAO though controversial, could hold some promise for a category of patients who can have treatment early and perhaps suffer from incomplete arterial occlusion" [32]. A 2023 Cochrane review, which looked at six RCTs, totaling 223 participants with acute nonarteritic CRAO, could not provide a strong recommendation for IVT in CRAO [11].…”

Retinal artery occlusion - Experimental and epidemiological studies

“…29 New trials are currently ongoing. 31 The lack of proven beneficial effect of thrombolysis to date supports the point of view from Hayreh, a prominent clinical scientist in ophthalmology and vascular diseases of the eye specifically. Based on studies showing e.g.…”

“…34 In contrast, neuroprotective treatments for RAO have received less attention. This new approach to treatment of RAO adopted from stroke was however very recently pointed out by Okonkwo et al 31 In their paper, they specifically highlighted the potential of developing neuroprotective therapies for RAO, further emphasized by the absence of effective revascularizing treatments.…”

“…An essential requirement for the development of effective treatment is to understand the molecular mechanisms underlying retinal damage in RAO. 31 However, the exact molecular events leading to retinal cell damage and loss of vision from RAO-induced ischemia are unclear. To date, a limited number of studies on animal models of RAO have been performed with identification of preselected molecules suggested to be involved, but no major protein analyses have yet been performed.…”