Over the past five years, the retina has emerged as one of the most intensively studied organs in long COVID. Because the retina is the only part of the central nervous system that can be directly visualized non-invasively, many investigators view it as a “window” into systemic vascular and neurological injury.
The evidence now suggests that retinal abnormalities do occur in a subset of people following COVID-19, although the severity, persistence, and clinical significance vary considerably. Most people recover without permanent visual impairment, but measurable retinal changes may persist in some individuals, particularly after severe infection or in those with long COVID.
Proposed Mechanisms
Researchers believe retinal injury is multifactorial.
1. Microvascular injury
The retina contains one of the densest capillary networks in the body.
COVID-19 can produce:
- endothelial dysfunction
- microvascular inflammation
- platelet activation
- complement activation
- microthrombi
- impaired autoregulation
These changes may reduce retinal perfusion despite normal retinal arteries appearing on examination.
2. Persistent inflammation
Long COVID is associated with chronic elevation of inflammatory cytokines including:
- IL-6
- TNF-α
- interferons
- MCP-1
These inflammatory mediators may damage retinal neurons and retinal capillaries.
3. Direct viral persistence
Although controversial, SARS-CoV-2 RNA and viral proteins have been detected in ocular tissues in some studies.
Retinal cells express
- ACE2
- TMPRSS2
- Neuropilin-1
making direct infection biologically plausible.
Whether persistent virus actually drives chronic retinal disease remains unproven.
4. Neurodegeneration
The retina is neural tissue.
Damage to retinal ganglion cells may reflect similar injury occurring elsewhere in the brain.
This has generated enormous interest because retinal imaging may become a biomarker for neurological long COVID.
Structural Retinal Changes
Modern imaging uses:
- OCT (Optical Coherence Tomography)
- OCT Angiography (OCTA)
These detect microscopic retinal injury invisible on routine examination.
The most consistently reported findings include:
Retinal nerve fiber layer (RNFL)
Many studies report
- thinning
- localized loss
- delayed recovery
The RNFL consists of ganglion cell axons.
Damage here resembles mild neurodegeneration.
Recent longitudinal work found reductions in peripapillary retinal nerve fiber layer thickness that persisted one year after infection.
Ganglion Cell Layer (GCL)
Numerous studies demonstrate thinning of the:
- ganglion cell layer
- inner plexiform layer
These neurons transmit visual information directly to the optic nerve.
Loss may indicate neuronal injury rather than simple vascular disease.
Inner Nuclear Layer
Some investigators report paradoxical thickening.
This is believed to represent
- inflammation
- edema
- glial activation
rather than permanent tissue growth.
Outer Plexiform Layer
A 2025 study found the outer plexiform layer appeared especially vulnerable in patients with severe COVID-19, particularly those who experienced prolonged hypoxemia or intensive care treatment, suggesting ischemic injury.
Microvascular Changes
Perhaps the strongest evidence concerns retinal blood flow.
OCTA repeatedly demonstrates altered retinal microcirculation.
Common findings include
Reduced vessel density
Particularly involving
- superficial capillary plexus
- deep capillary plexus
Reduced vessel density suggests impaired capillary perfusion. Meta-analyses support these findings, although effect sizes are generally modest.
Enlarged Foveal Avascular Zone (FAZ)
The FAZ normally lacks blood vessels.
Following COVID, many studies show mild enlargement.
An enlarged FAZ usually reflects
- capillary dropout
- ischemia
- impaired perfusion
Capillary remodeling
Some studies report
- vessel tortuosity
- abnormal branching
- altered capillary density
These changes appear to correlate with disease severity.
Cotton Wool Spots
During acute COVID some patients develop
- cotton wool spots
- retinal hemorrhages
These represent localized infarction of retinal nerve fibers.
Fortunately,
most disappear within weeks.
Functional Changes
Structural abnormalities do not always produce symptoms.
However some patients report
- blurred vision
- difficulty reading
- reduced contrast sensitivity
- impaired dark adaptation
- photophobia
- visual fatigue
- fluctuating vision
Standard visual acuity may remain 20/20 despite measurable OCT abnormalities.
Long COVID
Researchers are increasingly focusing on patients with persistent symptoms.
Several OCT studies have shown
- thinner retinal ganglion cell layers
- reduced retinal vessel density
- persistent capillary abnormalities
months after infection.
These findings correlate in some studies with
- fatigue
- cognitive dysfunction
- autonomic symptoms
although causation has not been proven.
Severe COVID
Patients requiring
- ICU care
- mechanical ventilation
- ECMO
appear more likely to demonstrate retinal abnormalities.
These include
- reduced superficial capillary density
- enlarged FAZ
- retinal thinning
However, not all studies agree. One 2025 study of patients evaluated a median of 22 months after recovery found no persistent microvascular deficits, suggesting that substantial recovery may occur even after severe illness.
Can COVID Cause Macular Degeneration?
Current evidence indicates no convincing proof that COVID-19 directly causes age-related macular degeneration (AMD).
However COVID may
- worsen retinal ischemia
- accelerate existing vascular disease
- exacerbate diabetic retinopathy
- contribute to retinal vein occlusion in susceptible individuals
Patients already suffering retinal disease may therefore be more vulnerable.
Is the Retina a Biomarker for Brain Injury?
This is among the most exciting areas of research.
Because retinal ganglion cells are part of the central nervous system,
investigators are examining whether retinal imaging could become a biomarker for
- neuroinflammation
- cognitive dysfunction
- dementia risk
- long COVID neurological injury
Large longitudinal studies are underway.
Consensus of Current Evidence
The current literature supports several conclusions:
- There is good evidence that SARS-CoV-2 can produce measurable retinal structural and microvascular changes in some individuals.
- OCT and OCT angiography detect abnormalities more consistently than routine eye examinations.
- The most reproducible findings are mild thinning of inner retinal layers and reduced retinal capillary vessel density.
- Patients with severe COVID-19 and some with long COVID appear more likely to have persistent abnormalities.
- Results across studies are heterogeneous, and some well-designed studies show recovery or no lasting changes, indicating that retinal injury is not universal.
Footnotes
- Marinho PM, Marcos AAA, Romano AC, Nascimento H, Belfort R Jr. Retinal abnormalities, including cotton wool spots and retinal microhemorrhages, were among the first ocular findings described in patients with COVID-19, suggesting retinal microvascular involvement.
- Kaim M, Kır MB, Uzun F, Findik H. Quantitative OCT analysis demonstrated thinning of the retinal ganglion cell layer in recovered COVID-19 patients, supporting the hypothesis that SARS-CoV-2 may induce mild neurodegenerative retinal changes.
- Mou K, Gao Y, Zhang Y, et al. In one of the first prospective longitudinal studies using pre-infection baseline imaging, swept-source OCT and OCT angiography demonstrated persistent reductions in retinal nerve fiber layer thickness, ganglion cell-inner plexiform layer thickness, and superficial vascular plexus density one year after infection.
- Schreiberová Z, Genzor S, Mudroch T, et al. Long-term retinal oximetry and OCT angiography demonstrated that some patients recover without persistent microvascular abnormalities nearly two years after severe COVID-19, illustrating heterogeneity of long-term retinal outcomes.
- Tzamalis A, Foti M, Georgiadou M, Tsaftaridis N, Ziakas N. Systematic review evidence indicates retinal vein occlusion and retinal artery occlusion remain uncommon but appear to occur more frequently following SARS-CoV-2 infection than expected by chance alone.
- Modern OCT angiography consistently identifies subtle reductions in retinal capillary vessel density despite normal clinical examination, emphasizing the sensitivity of advanced retinal imaging.
- The retina is increasingly regarded as a readily accessible extension of the central nervous system, permitting non-invasive evaluation of neurovascular injury associated with long COVID.
- Current evidence supports endothelial dysfunction, complement activation, inflammatory cytokines, platelet activation, and microvascular thrombosis as principal mechanisms of retinal injury following SARS-CoV-2 infection.
- Despite increasing evidence of retinal abnormalities, no definitive causal relationship has been established between COVID-19 and age-related macular degeneration; instead, COVID-19 may exacerbate pre-existing retinal vascular disease in susceptible individuals.
- Ophthalmic societies now recognize OCT and OCT angiography as valuable modalities for evaluating persistent visual symptoms in patients with long COVID because conventional funduscopic examination may appear normal.
References
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- Kaim M, Kır MB, Uzun F, Findik H. Evaluation of Retinal and Optic Nerve Parameters in Recovered COVID-19 Patients: Potential Neurodegenerative Impact on the Ganglion Cell Layer. Diagnostics (Basel). 2025;15(10):1195.
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