Non-Hospitalized Long COVID Patients Exhibit Reduced Retinal Capillary Perfusion: A Prospective Cohort Study

Clayton E. Lyons; Jonathan Alhalel; Anna Busza; Emily Suen; Nathan Gill; Nicole Decker; Stephen Suchy; Zachary Orban; Millenia Jimenez; Gina Perez Giraldo; Igor J. Koralnik; Manjot K. Gill

doi:10.3390/jimaging11020062

Non-Hospitalized Long COVID Patients Exhibit Reduced Retinal Capillary Perfusion: A Prospective Cohort Study

Clayton E. Lyons, Jonathan Alhalel, Anna Busza, Emily Suen, Nathan Gill, Nicole Decker, Stephen Suchy, Zachary Orban, Millenia Jimenez, Gina Perez Giraldo, Igor J. Koralnik, Manjot K. Gill^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

The mechanism of post-acute sequelae of SARS-CoV-2 (PASC) is unknown. Using optical coherence tomography angiography (OCT-A), we compared retinal foveal avascular zone (FAZ), vessel density (VD), and vessel length density (VLD) in non-hospitalized Neuro-PASC patients with those in healthy controls in an effort to elucidate the mechanism underlying this debilitating condition. Neuro-PASC patients with a positive SARS-CoV-2 test and neurological symptoms lasting ≥6 weeks were included. Those with prior COVID-19 hospitalization were excluded. Subjects underwent OCT-A with segmentation of the full retinal slab into the superficial (SCP) and deep (DCP) capillary plexus. The FAZ was manually delineated on the full slab in ImageJ. An ImageJ macro was used to measure VD and VLD. OCT-A variables were analyzed using linear mixed-effects models with fixed effects for Neuro-PASC, age, and sex, and a random effect for patient to account for measurements from both eyes. The coefficient of Neuro-PASC status was used to determine statistical significance; p-values were adjusted using the Benjamani–Hochberg procedure. Neuro-PASC patients (N = 30; 60 eyes) exhibited a statistically significant (p = 0.005) reduction in DCP VLD compared to healthy controls (N = 44; 80 eyes). The sole reduction in DCP VLD in Neuro-PASC may suggest preferential involvement of the smallest blood vessels.

Original language	English (US)
Article number	62
Journal	Journal of Imaging
Volume	11
Issue number	2
DOIs	https://doi.org/10.3390/jimaging11020062
State	Published - Feb 2025

Funding

This research was funded by an Unrestricted Departmental Grant from Research to Prevent Blindness and a grant from the Illinois Society to Prevent Blindness.

Keywords

long COVID
optical coherence tomography angiography (OCT-A)
retina
vessel density (VD)
vessel length density (VLD)

ASJC Scopus subject areas

Radiology Nuclear Medicine and imaging
Computer Vision and Pattern Recognition
Computer Graphics and Computer-Aided Design
Electrical and Electronic Engineering

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/jimaging11020062

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title = "Non-Hospitalized Long COVID Patients Exhibit Reduced Retinal Capillary Perfusion: A Prospective Cohort Study",

abstract = "The mechanism of post-acute sequelae of SARS-CoV-2 (PASC) is unknown. Using optical coherence tomography angiography (OCT-A), we compared retinal foveal avascular zone (FAZ), vessel density (VD), and vessel length density (VLD) in non-hospitalized Neuro-PASC patients with those in healthy controls in an effort to elucidate the mechanism underlying this debilitating condition. Neuro-PASC patients with a positive SARS-CoV-2 test and neurological symptoms lasting ≥6 weeks were included. Those with prior COVID-19 hospitalization were excluded. Subjects underwent OCT-A with segmentation of the full retinal slab into the superficial (SCP) and deep (DCP) capillary plexus. The FAZ was manually delineated on the full slab in ImageJ. An ImageJ macro was used to measure VD and VLD. OCT-A variables were analyzed using linear mixed-effects models with fixed effects for Neuro-PASC, age, and sex, and a random effect for patient to account for measurements from both eyes. The coefficient of Neuro-PASC status was used to determine statistical significance; p-values were adjusted using the Benjamani–Hochberg procedure. Neuro-PASC patients (N = 30; 60 eyes) exhibited a statistically significant (p = 0.005) reduction in DCP VLD compared to healthy controls (N = 44; 80 eyes). The sole reduction in DCP VLD in Neuro-PASC may suggest preferential involvement of the smallest blood vessels.",

keywords = "long COVID, optical coherence tomography angiography (OCT-A), retina, vessel density (VD), vessel length density (VLD)",

author = "Lyons, {Clayton E.} and Jonathan Alhalel and Anna Busza and Emily Suen and Nathan Gill and Nicole Decker and Stephen Suchy and Zachary Orban and Millenia Jimenez and {Perez Giraldo}, Gina and Koralnik, {Igor J.} and Gill, {Manjot K.}",

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year = "2025",

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doi = "10.3390/jimaging11020062",

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T1 - Non-Hospitalized Long COVID Patients Exhibit Reduced Retinal Capillary Perfusion

T2 - A Prospective Cohort Study

AU - Lyons, Clayton E.

AU - Alhalel, Jonathan

AU - Busza, Anna

AU - Suen, Emily

AU - Gill, Nathan

AU - Decker, Nicole

AU - Suchy, Stephen

AU - Orban, Zachary

AU - Jimenez, Millenia

AU - Perez Giraldo, Gina

AU - Koralnik, Igor J.

AU - Gill, Manjot K.

PY - 2025/2

Y1 - 2025/2

N2 - The mechanism of post-acute sequelae of SARS-CoV-2 (PASC) is unknown. Using optical coherence tomography angiography (OCT-A), we compared retinal foveal avascular zone (FAZ), vessel density (VD), and vessel length density (VLD) in non-hospitalized Neuro-PASC patients with those in healthy controls in an effort to elucidate the mechanism underlying this debilitating condition. Neuro-PASC patients with a positive SARS-CoV-2 test and neurological symptoms lasting ≥6 weeks were included. Those with prior COVID-19 hospitalization were excluded. Subjects underwent OCT-A with segmentation of the full retinal slab into the superficial (SCP) and deep (DCP) capillary plexus. The FAZ was manually delineated on the full slab in ImageJ. An ImageJ macro was used to measure VD and VLD. OCT-A variables were analyzed using linear mixed-effects models with fixed effects for Neuro-PASC, age, and sex, and a random effect for patient to account for measurements from both eyes. The coefficient of Neuro-PASC status was used to determine statistical significance; p-values were adjusted using the Benjamani–Hochberg procedure. Neuro-PASC patients (N = 30; 60 eyes) exhibited a statistically significant (p = 0.005) reduction in DCP VLD compared to healthy controls (N = 44; 80 eyes). The sole reduction in DCP VLD in Neuro-PASC may suggest preferential involvement of the smallest blood vessels.

AB - The mechanism of post-acute sequelae of SARS-CoV-2 (PASC) is unknown. Using optical coherence tomography angiography (OCT-A), we compared retinal foveal avascular zone (FAZ), vessel density (VD), and vessel length density (VLD) in non-hospitalized Neuro-PASC patients with those in healthy controls in an effort to elucidate the mechanism underlying this debilitating condition. Neuro-PASC patients with a positive SARS-CoV-2 test and neurological symptoms lasting ≥6 weeks were included. Those with prior COVID-19 hospitalization were excluded. Subjects underwent OCT-A with segmentation of the full retinal slab into the superficial (SCP) and deep (DCP) capillary plexus. The FAZ was manually delineated on the full slab in ImageJ. An ImageJ macro was used to measure VD and VLD. OCT-A variables were analyzed using linear mixed-effects models with fixed effects for Neuro-PASC, age, and sex, and a random effect for patient to account for measurements from both eyes. The coefficient of Neuro-PASC status was used to determine statistical significance; p-values were adjusted using the Benjamani–Hochberg procedure. Neuro-PASC patients (N = 30; 60 eyes) exhibited a statistically significant (p = 0.005) reduction in DCP VLD compared to healthy controls (N = 44; 80 eyes). The sole reduction in DCP VLD in Neuro-PASC may suggest preferential involvement of the smallest blood vessels.

KW - long COVID

KW - optical coherence tomography angiography (OCT-A)

KW - retina

KW - vessel density (VD)

KW - vessel length density (VLD)

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M1 - 62

ER -

Non-Hospitalized Long COVID Patients Exhibit Reduced Retinal Capillary Perfusion: A Prospective Cohort Study

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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