Retinal vessel multifractals predict pial collateral status in patients with acute ischemic stroke

Adnan Khan, Patrick De Boever, Nele Gerrits, Naveed Akhtar, Maher Saqqur, Georgios Ponirakis, Hoda Gad, Ioannis N. Petropoulos, Ashfaq Shuaib, James E. Faber, Saadat Kamran, Rayaz A. Malik

Abstract

Pial collateral blood flow is a major determinant of the outcomes of acute ischemic stroke. This study was undertaken to determine whether retinal vessel metrics can predict the pial collateral status and stroke outcomes in patients.

Introduction

Acute ischemic stroke is the second most common cause of death, and survivors are left with significant disability [1]. Ischemic stroke typically occurs due to occlusion of a cerebral artery or an embolus from the heart or neck vessels [2]. Irrespective of the cause of ischemia, adequate pial collateral flow can offset the severity of ischemic brain injury [3]. In experimental studies of stroke, the infarct volume correlated more strongly with collateral number, diameter and penetrating arteriole number than with middle cerebral artery territory [4].

The pial collateral circulation is a network of leptomeningeal arteries that cross-connect the outer-most branches of adjacent arterial trees [5], but their extent is determined by genetic and environmental factors that vary widely in the population [6]. Rarefaction of collaterals is associated with ageing and multiple cardiovascular risk factors [7]. Indeed, individuals with ischemic stroke and poor pial collaterals sustain larger infarcts, respond poorly to reperfusion, have increased risk for and severity of intracerebral hemorrhage and suffer increased morbidity and mortality [8–11]. In this respect, the identification of patients with poor pial collaterals may allow risk stratification and targeted strategies to reduce risk factors associated with rarefaction of collaterals in patients at risk of acute ischemic stroke.

Materials and methods

Thirty-five patients with MCA occlusion and 21 age-matched healthy control participants were recruited. Exclusion criteria included patients with stroke secondary to non-vascular disorder, intracerebral hemorrhage, a known history of ocular trauma or surgery, high refractive error and glaucoma.

Acute ischemic stroke was confirmed clinically and radiologically using American Heart Association (AHA) criteria [19].

Results

Thirty-five patients with acute ischemic stroke were age-matched with twenty-one healthy controls (48.1 ± 10.6 vs 44.3 ± 10.6 yrs., p = 0.200). Patients with acute ischemic stroke were classified into those with poor (n = 15) and good (n = 20) pial collaterals.

Discussion

This translational study demonstrates increased retinal vessel multifractal dimensions in patients with acute ischemic stroke and poor pial collaterals and presents a retinal vessel classifier that differentiates patients with poor from good pial collaterals. Patients with acute ischemic stroke and worse pial collateral scores have evidence of a larger infarct volume and higher modified Rankin scale score and NIHSS at discharge [35]. In contrast, a good pial collateral status is associated with lower rates of symptomatic intracranial hemorrhage and mortality in patients with acute ischemic stroke following reperfusion [36]. We also show that patients with poor pial collaterals had a higher modified Rankin score and NIHSS at admission. However, standard risk factors for stroke e.g., age, hypertension, lipids and HbA1c did not differ between patients with good and poor pial collaterals.

Citation: Khan A, De Boever P, Gerrits N, Akhtar N, Saqqur M, Ponirakis G, et al. (2022) Retinal vessel multifractals predict pial collateral status in patients with acute ischemic stroke. PLoS ONE 17(5): e0267837. https://doi.org/10.1371/journal.pone.0267837

Editor: Aurel Popa-Wagner, Essen University Medical School, GERMANY

Received: September 19, 2021; Accepted: April 16, 2022; Published: May 5, 2022.

Copyright: © 2022 Khan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: The data used for statistical analysis in this study is available at (https://doi.org/10.6084/m9.figshare.16574498.v1).”

Funding: Supported by Qatar National Research Fund Grant BMRP20038654. The funders had no role in study design, data collection, analysis and interpretation, and decision to prepare the manuscript and the publication process.”

Competing interests: The authors have declared that no competing interests exist.