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Abstract

Introduction: Cerebral small vessel disease (CSVD) is a major vascular contributor to cognitive impairment and dementia. CSVD affects the deep and subcortical cerebral white matter.1,2 The retinal nerve fiber layer (RNFL) and cerebral white matter share a common embryological origin, with RNFL ganglion cell axons structurally analogous to cerebral white matter tracts.3,4 This connection creates an opportunity to investigate whether structural changes in the RNFL reflect pathological changes in the cerebral white matter.3,5,6 While most studies examining the relationship between RNFL and CSVD focus on specific comorbidities (e.g., patients with stroke or with cognitive impairment)2,6,7,8, this study analyzed a cohort that includes both cognitively healthy participants and those with cognitive impairment. Our aim was to assess whether RNFL thickness is associated with CSVD regardless of comorbidities.

Methods: We analyzed 49 participants from the Rio Grande Valley South Texas Alzheimer’s Disease Center who underwent optical coherence tomography (OCT) and brain magnetic resonance imaging. We excluded one case of self-reported closed-angle glaucoma. RNFL measurements included thickness of the superior, nasal, inferior, and temporal quadrants, and the total average of all four quadrants. Left and right eye measurements were averaged. CSVD was defined by the presence of (i) extensive white matter hyperintensities (WMH) on T2-fluid attenuated inversion recovery sequences; (ii) lacunes on T1-weighed sequences, and (iii) cerebral microbleeds defined as round voids on gradient echo sequences. The comparison of RNFL thickness between individuals with and without CSVD was performed using the t-Student test. Associations between RNFL and WMH were examined using multivariable logistic regression adjusted for age, sex, body mass index, and OCT scan quality.

Results: The mean age was 67.4±11.9 years; 65.3% women and 83.7% Hispanic. The average OCT scan quality was 28.9±4.35. Inferior RNFL was thinner in participants with lacunes compared to those without (110.5±32.6µm vs. 133.3±18.7µm; P=0.015). Individuals with extensive WMH had thinner global and inferior RNFL compared to those without (global RNFL, 85.6±14.1µm vs. 101.1±11.7µm; inferior RNFL quadrant, 104.1±30.1µm vs. 132.8±19.7µm). No significant differences were found in the temporal, superior, or nasal quadrants, or in relation to cerebral microbleeds. In adjusted regression models, some associations lost significance, likely due to small CSVD sample size (n=6 for lacunes, n=4 for WMH). However, we observed each unit decrease in inferior RNFL thickness (µm) was associated with greater odds ratios (OR) of having lacunes (ORs ranged from 1.09 [95% confidence interval, 1.01-1.18] to 1.10 [confidence interval, 1.01-1.17]; P≤0.026).

Conclusion: Inferior RNFL thinning was associated with the presence of WMH and lacunes. Larger studies using continuous quantification of CSVD and multimodal imaging are needed to determine the relevance of using noninvasive technologies, such as the OCT, for detecting retinal structural changes that may reflect underlying neurodegenerative pathology.

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Associations Between Retinal Nerve Fiber Layer Thickness and Cerebral Small Vessel Disease

Introduction: Cerebral small vessel disease (CSVD) is a major vascular contributor to cognitive impairment and dementia. CSVD affects the deep and subcortical cerebral white matter.1,2 The retinal nerve fiber layer (RNFL) and cerebral white matter share a common embryological origin, with RNFL ganglion cell axons structurally analogous to cerebral white matter tracts.3,4 This connection creates an opportunity to investigate whether structural changes in the RNFL reflect pathological changes in the cerebral white matter.3,5,6 While most studies examining the relationship between RNFL and CSVD focus on specific comorbidities (e.g., patients with stroke or with cognitive impairment)2,6,7,8, this study analyzed a cohort that includes both cognitively healthy participants and those with cognitive impairment. Our aim was to assess whether RNFL thickness is associated with CSVD regardless of comorbidities.

Methods: We analyzed 49 participants from the Rio Grande Valley South Texas Alzheimer’s Disease Center who underwent optical coherence tomography (OCT) and brain magnetic resonance imaging. We excluded one case of self-reported closed-angle glaucoma. RNFL measurements included thickness of the superior, nasal, inferior, and temporal quadrants, and the total average of all four quadrants. Left and right eye measurements were averaged. CSVD was defined by the presence of (i) extensive white matter hyperintensities (WMH) on T2-fluid attenuated inversion recovery sequences; (ii) lacunes on T1-weighed sequences, and (iii) cerebral microbleeds defined as round voids on gradient echo sequences. The comparison of RNFL thickness between individuals with and without CSVD was performed using the t-Student test. Associations between RNFL and WMH were examined using multivariable logistic regression adjusted for age, sex, body mass index, and OCT scan quality.

Results: The mean age was 67.4±11.9 years; 65.3% women and 83.7% Hispanic. The average OCT scan quality was 28.9±4.35. Inferior RNFL was thinner in participants with lacunes compared to those without (110.5±32.6µm vs. 133.3±18.7µm; P=0.015). Individuals with extensive WMH had thinner global and inferior RNFL compared to those without (global RNFL, 85.6±14.1µm vs. 101.1±11.7µm; inferior RNFL quadrant, 104.1±30.1µm vs. 132.8±19.7µm). No significant differences were found in the temporal, superior, or nasal quadrants, or in relation to cerebral microbleeds. In adjusted regression models, some associations lost significance, likely due to small CSVD sample size (n=6 for lacunes, n=4 for WMH). However, we observed each unit decrease in inferior RNFL thickness (µm) was associated with greater odds ratios (OR) of having lacunes (ORs ranged from 1.09 [95% confidence interval, 1.01-1.18] to 1.10 [confidence interval, 1.01-1.17]; P≤0.026).

Conclusion: Inferior RNFL thinning was associated with the presence of WMH and lacunes. Larger studies using continuous quantification of CSVD and multimodal imaging are needed to determine the relevance of using noninvasive technologies, such as the OCT, for detecting retinal structural changes that may reflect underlying neurodegenerative pathology.

 

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