Retinal Biomarkers Reveal Vascular Changes in Long COVID
Manjot K Gill, MD, MS, FASRS, FRCS(C), discusses how reduced retinal capillary perfusion may provide insights into Long COVID’s neurological effects and potential treatment approaches.
A new prospective cohort study has found that non-hospitalized patients with neurological post-acute sequelae of Long COVID exhibit a significant reduction in deep capillary plexus vessel length density (DCP VLD) compared to healthy controls. Researchers used optical coherence tomography angiography (OCT-A) to analyze retinal microvascular changes, finding a statistically significant decrease in DCP VLD (p = .005).
The study included 30 Long COVID patients (60 eyes) and 44 healthy controls (80 eyes). Participants had tested positive for SARS-CoV-2, experienced neurological symptoms for at least six weeks, and had not been hospitalized for COVID-19. OCT-A imaging segmented the full retinal slab into superficial and deep capillary plexuses, with vessel density and vessel length density measured using ImageJ software. Findings indicate that Long COVID affects the smallest blood vessels, which may contribute to neurological symptoms. Researchers used linear mixed-effects models to control for age and sex, applying statistical adjustments via the Benjamini–Hochberg procedure.
The Retina as a Window into Systemic Disease
In our interview with Manjot K. Gill, MD, MS, FASRS, FRCS(C), professor of ophthalmology and medical education at Northwestern Medicine, she discussed the study’s findings, “Our study was designed to determine whether the retina—the tissue that lines the back of the eye—could be used as a marker for blood vessel health elsewhere in the body,” Gill said. “There’s a growing field called oculomics, where we use the retina as a biomarker for systemic disease. In our study, we examined a population of Long COVID patients who had persistent neurological symptoms. We imaged their retinas and compared their blood vessels to those of control patients with very similar age and gender profiles. This study is one of the first of its kind.”
The results showed a preferential reduction in capillary blood flow in the deep layers of the retina among Long COVID patients. Gill and her team hypothesize that this reduction in small-caliber blood vessels may reflect similar vascular changes in the brain, which could contribute to the persistent neurological symptoms seen in Long COVID,“This really is a first-of-its-kind study because we examined a well-defined population of non-hospitalized Long COVID patients,” Gill said. “It is also the first to demonstrate a physiological effect in this group, which may provide important insights into the underlying causes of Long COVID.”
Implications for Long COVID Diagnosis and Treatment
Although this study is a pilot investigation, the findings could inform future approaches to Long COVID diagnosis and treatment. Gill and her team are now launching a larger follow-up study to track patients over time, assess whether these findings are reproducible, and examine whether reductions in retinal blood flow correlate with symptom severity, “This could help predict which patients are at risk, track their recovery, and correlate these findings with other biomarkers of Long COVID,” Gill said. “Eventually, once treatments become available, we hope to use this marker of reduced perfusion in the eye to gauge patients’ responses to therapy.”
Further research may explore how these methods apply to other vascular changes throughout the body. “This study provides the first indication that a physiological change is occurring in Long COVID patients, and these findings in the eye may reflect similar vascular changes elsewhere in the body. We are launching a follow-up study to track these patients and see whether retinal perfusion changes improve or worsen alongside their symptoms. Hopefully, this will allow us to establish another marker that can be correlated with other biomarkers of Long COVID.”
With many individuals experiencing prolonged symptoms after COVID-19 infection, identifying physiological markers like retinal perfusion changes may help improve diagnosis, monitoring, and treatment of this condition.
