Investigating Retinal Microvascular Changes Using OCT-Angiography: The Role of Oxidative Stress and Endothelial Dysfunction in Hypertensive Nephropathy.
Malvasi M, Salomone L, et al. • Medicina (Kaunas, Lithuania) • 2026
These exploratory findings suggest a possible association among increased renal vascular resistance, oxidative stress, and localized retinal structural alterations in patients with essential hypertension, supporting the hypothesis of an eye-kidney-redox interplay.
Key Findings
Results
Higher renal resistive index (RRI) values were associated with localized macular thinning and reduced optic nerve head perfusion metrics in hypertensive patients.
The study enrolled 32 patients with essential hypertension (64 eyes) in a cross-sectional exploratory design.
Associations were found between RRI and localized macular thinning, not global OCT/OCTA parameters.
Reduced optic nerve head perfusion metrics were observed in association with higher RRI values.
No significant differences were observed in most global OCT/OCTA parameters, indicating changes were localized rather than diffuse.
Results
Patients with RRI values at or above the 75th percentile showed significantly increased hydrogen peroxide levels compared to those below this threshold.
The comparison was made between patients with RRI ≥ 75th percentile versus those below.
The difference in hydrogen peroxide levels was statistically significant (p = 0.004).
Hydrogen peroxide was used as a systemic oxidative stress biomarker.
This finding links higher renal vascular resistance with greater systemic oxidative stress.
Results
Patients with RRI values at or above the 75th percentile demonstrated significantly reduced nitric oxide bioavailability.
Reduced nitric oxide bioavailability was statistically significant at p = 0.033 in patients with RRI ≥ 75th percentile.
Nitric oxide bioavailability served as an indicator of endothelial dysfunction.
This reduction coexisted with elevated hydrogen peroxide levels, suggesting concurrent oxidative stress and endothelial impairment.
Nitric oxide reduction supports the hypothesis of redox imbalance contributing to microvascular damage.
Results
Thinning of selected inner macular sectors was observed in patients with higher RRI values.
Macular thinning was localized to specific inner macular sectors rather than representing a global change.
This sectorial thinning coexisted with elevated oxidative stress markers in the high-RRI group.
The finding suggests that detailed sectorial OCT analysis may detect subclinical changes missed by conventional global measurements.
The pattern supports a structural retinal correlate of systemic microvascular injury.
Results
A trend toward reduced optic nerve head flow index was observed in patients with higher RRI, suggesting early microvascular impairment.
The reduction in optic nerve head flow index was described as a trend, not reaching formal statistical significance.
This finding was noted as potentially representing early microvascular impairment that may not be detected by conventional global OCT measurements.
Optic nerve head perfusion was assessed using OCTA imaging.
The authors indicated this warrants investigation in larger prospective studies.
Methods
The study used optical coherence tomography angiography (OCTA) to evaluate retinal microvascular parameters alongside renal Doppler ultrasonography for RRI assessment.
32 patients with essential hypertension underwent comprehensive ophthalmic examination including OCT and OCTA imaging.
Renal Doppler ultrasonography was performed for RRI assessment.
Systemic oxidative stress biomarkers including hydrogen peroxide and nitric oxide bioavailability were evaluated.
The cross-sectional exploratory design analyzed associations between renal, ocular, and biochemical parameters.
64 eyes total were examined (both eyes of each of the 32 patients).
Background
The retinal and renal microcirculations share common pathogenic mechanisms, making retinal imaging a potential non-invasive biomarker of hypertensive microvascular injury.
Arterial hypertension is identified as a major cause of systemic microvascular damage involving target organs such as the kidneys and retina.
The authors propose an 'eye-kidney-redox interplay' as a conceptual framework for their findings.
Advanced retinal imaging, particularly detailed sectorial OCT analysis, is proposed as a complementary non-invasive tool for early detection of subclinical microvascular damage.
The study suggests retinal imaging may provide non-invasive biomarkers of hypertensive microvascular injury without requiring invasive renal assessment.
What This Means
This research suggests that in people with high blood pressure, the health of small blood vessels in the kidney and the eye may be closely linked through a shared process involving oxidative stress and impaired blood vessel function. The study examined 32 hypertensive patients using specialized eye imaging technology (OCT and OCTA) alongside kidney blood flow measurements and blood tests for markers of oxidative stress. When kidney blood vessel resistance was higher (measured by the renal resistive index), patients also tended to show localized thinning in specific areas of the retina and reduced blood flow to the optic nerve, along with higher levels of a harmful molecule called hydrogen peroxide and lower levels of nitric oxide — a molecule that helps keep blood vessels healthy.
Importantly, these retinal changes were subtle and localized, meaning they would not have been detected by standard global measurements of retinal thickness. Only when researchers looked at specific sectors of the retina did patterns emerge that corresponded with worse kidney blood vessel health and more oxidative stress. This suggests that detailed, sector-by-sector analysis of retinal images could serve as a non-invasive window into the health of small blood vessels throughout the body, potentially catching damage earlier than conventional tests.
This research suggests the concept of an 'eye-kidney-redox interplay' — where changes in kidney vessels, eye vessels, and the body's oxidative balance all reflect and possibly reinforce each other in hypertension. If confirmed in larger studies, retinal imaging might one day help clinicians identify patients at risk for kidney and cardiovascular complications earlier and non-invasively. The authors caution that this was a small exploratory study and that larger prospective studies are needed before these findings can be applied clinically.
Malvasi M, Salomone L, Azzara I, Cammisotto V, Castellani V, Pignatelli P, et al.. (2026). Investigating Retinal Microvascular Changes Using OCT-Angiography: The Role of Oxidative Stress and Endothelial Dysfunction in Hypertensive Nephropathy.. Medicina (Kaunas, Lithuania). https://doi.org/10.3390/medicina62081526