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Retinal nerve fiber layer thickness predicts CSF amyloid/tau before cognitive decline.

ABSTRACT: BACKGROUND:Alzheimer's disease (AD) pathology precedes symptoms and its detection can identify at-risk individuals who may benefit from early treatment. Since the retinal nerve fiber layer (RNFL) is depleted in established AD, we tested whether its thickness can predict whether cognitively healthy (CH) individuals have a normal or pathological cerebrospinal fluid (CSF) Aß42 (A) and tau (T) ratio. METHODS:As part of an ongoing longitudinal study, we enrolled CH individuals, excluding those with cognitive impairment and significant ocular pathology. We classified the CH group into two sub-groups, normal (CH-NAT, n = 16) or pathological (CH-PAT, n = 27), using a logistic regression model from the CSF AT ratio that identified >85% of patients with a clinically probable AD diagnosis. Spectral-domain optical coherence tomography (OCT) was acquired for RNFL, ganglion cell-inner plexiform layer (GC-IPL), and macular thickness. Group differences were tested using mixed model repeated measures and a classification model derived using multiple logistic regression. RESULTS:Mean age (± standard deviation) in the CH-PAT group (n = 27; 75.2 ± 8.4 years) was similar (p = 0.50) to the CH-NAT group (n = 16; 74.1 ± 7.9 years). Mean RNFL (standard error) was thinner in the CH-PAT group by 9.8 (2.7) ?m; p < 0.001. RNFL thickness classified CH-NAT vs. CH-PAT with 87% sensitivity and 56.3% specificity. CONCLUSIONS:Our retinal data predict which individuals have CSF biomarkers of AD pathology before cognitive deficits are detectable with 87% sensitivity. Such results from easy-to-acquire, objective and non-invasive measurements of the RNFL merit further study of OCT technology to monitor or screen for early AD pathology.

SUBMITTER: Asanad S

PROVIDER: S-EPMC7259639 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Retinal nerve fiber layer thickness predicts CSF amyloid/tau before cognitive decline.

Asanad Samuel S Fantini Michele M Sultan William W Nassisi Marco M Felix Christian M CM Wu Jessica J Karanjia Rustum R Ross-Cisneros Fred N FN Sagare Abhay P AP Zlokovic Berislav V BV Chui Helena C HC Pogoda Janice M JM Arakaki Xianghong X Fonteh Alfred N AN Sadun Alfredo A AA Harrington Michael G MG

PloS one 20200529 5

<h4>Background</h4>Alzheimer's disease (AD) pathology precedes symptoms and its detection can identify at-risk individuals who may benefit from early treatment. Since the retinal nerve fiber layer (RNFL) is depleted in established AD, we tested whether its thickness can predict whether cognitively healthy (CH) individuals have a normal or pathological cerebrospinal fluid (CSF) Aß42 (A) and tau (T) ratio.<h4>Methods</h4>As part of an ongoing longitudinal study, we enrolled CH individuals, excludi ...[more]

PMID: 32469871

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Project description:PURPOSE:To investigate the role of sex on retinal nerve fiber layer (RNFL) thickness at 768 circumpapillary locations based on OCT findings. DESIGN:Population-based cross-sectional study. PARTICIPANTS:We investigated 5646 eyes of 5646 healthy participants from the Leipzig Research Centre for Civilization Diseases (LIFE)-Adult Study of a predominantly white population. METHODS:All participants underwent standardized systemic assessments and ocular imaging. Circumpapillary RNFL (cRNFL) thickness was measured at 768 points equidistant from the optic nerve head using spectral-domain OCT (Spectralis; Heidelberg Engineering, Heidelberg, Germany). To control ocular magnification effects, the true scanning radius was estimated by scanning focus. Student t test was used to evaluate sex differences in cRNFL thickness globally and at each of the 768 locations. Multivariable linear regression and analysis of variance were used to evaluate individual contributions of various factors to cRNFL thickness variance. MAIN OUTCOME MEASURES:Difference in cRNFL thickness between males and females. RESULTS:Our population consisted of 54.8% females. The global cRNFL thickness was 1 ?m thicker in females (P < 0.001). However, detailed analysis at each of the 768 locations revealed substantial location specificity of the sex effects, with RNFL thickness difference ranging from -9.98 to +8.00 ?m. Females showed significantly thicker RNFLs in the temporal, superotemporal, nasal, inferonasal, and inferotemporal regions (43.6% of 768 locations), whereas males showed significantly thicker RNFLs in the superior region (13.2%). The results were similar after adjusting for age, body height, and scanning radius. The superotemporal and inferotemporal RNFL peaks shifted temporally in females by 2.4° and 1.9°, respectively. On regions with significant sex effects, sex explained more RNFL thickness variance than age, whereas the major peak locations and interpeak angle explained most of the RNFL thickness variance unexplained by sex. CONCLUSIONS:Substantial sex effects on cRNFL thickness were found at 56.8% of all 768 circumpapillary locations, with specific patterns for different sectors. Over large regions, sex was at least as important in explaining the cRNFL thickness variance as was age, which is well established to have a substantial impact on cRNFL thickness. Including sex in the cRNFL thickness norm could therefore improve glaucoma diagnosis and monitoring.

Project description:ObjectiveTo evaluate the distribution of macula and circumpapillary retina nerve fiber layer (cpRNFL) thickness and other associated factors among grade-1 primary school children in Lhasa using spectral-domain optical coherence tomography (SD-OCT).MethodologyOCT assessment was conducted on 1856 grade-1 students from 7 primary schools in Lhasa, Tibet following a successful random stratified sampling of the students. Each child underwent comprehensive general and ocular examinations as well as an SD-OCT detection (12 × 9 mm, 3D wide scan mode, Topcon 3D OCT-1) to assess the thickness of the macula, ganglion cell-inner plexiform layer (GCIPL), ganglion cell complex (GCC), and cpRNFL. Multivariate and correlation analyses were performed to evaluate the association of the demographic and ocular variables.ResultsThe average age of the 1762 (94.43%) students who underwent OCT assessment was 6.83 ± 0.46 years. Among them, 984 (53.02%) were boys. The number of students who had macular, cpRNFL, and optic disc scans completed and with adequate image quality were 1412 (82.2%), 1277 (74.4%), and 1243 (72.4%), respectively. The average macula full retinal thickness (FRT), GCIPL, GCC, and cpRNFL thickness of the students was 279.19 ± 10.61 μm, 76.41 ± 4.70 μm, 108.15 ± 6.15 μm, and 112.33 ± 13.5 μm, respectively. Multivariate regression and correlation analysis further revealed that boys and girls had significant differences in their average cpRNFL thickness. Moreover, GCC and GCIPL thickness was negatively correlated with IOP but positively correlated with the body mass index. The thickness of all the layers of the macula and cpRNFL were positively correlated with spherical equivalent. Further to this, the average macular FRT, GCIPL, and GCC thicknesses were positively correlated with cpRNFL global thickness.ConclusionThis study describes the normal distribution of macular retina, cpRNFL, and optic disc parameters in grade-1 Tibetan children in Lhasa. It contributes to the establishment of a normative ophthalmology database of Tibetan children, and advances the ability of OCT in ophthalmic disorder diagnosis during long-term monitoring in plateau.

Project description:PurposeCircumpapillary retinal nerve fiber layer thickness (RNFLT) measurement aids in the clinical diagnosis of glaucoma. Spectral domain optical coherence tomography (SD-OCT) machines measure RNFLT and provide normative color-coded plots. In this retrospective study, we investigate whether normative percentiles of RNFLT (pRNFLT) from Spectralis SD-OCT improve prediction of glaucomatous visual field loss over raw RNFLT.MethodsA longitudinal database containing OCT scans and visual fields from Massachusetts Eye & Ear glaucoma clinic patients was generated. Reliable OCT-visual field pairs were selected. Spectralis OCT normative distributions were extracted from machine printouts. Supervised machine learning models compared predictive performance between pRNFLT and raw RNFLT inputs. Regional structure-function associations were assessed with univariate regression to predict mean deviation (MD). Multivariable classification predicted MD, pattern standard deviation, MD change per year, and glaucoma hemifield test.ResultsThere were 3016 OCT-visual field pairs that met the reliability criteria. Spectralis norms were found to be independent of age, sex, and ocular magnification. Regional analysis showed significant decrease in R2 from pRNFLT models compared to raw RNFLT models in inferotemporal sectors, across multiple regressors. In multivariable classification, there were no significant improvements in area under the curve of receiver operating characteristic curve (ROC-AUC) score with pRNFLT models compared to raw RNFLT models.ConclusionsOur results challenge the assumption that normative percentiles from OCT machines improve prediction of glaucomatous visual field loss. Raw RNFLT alone shows strong prediction, with no models presenting improvement by the manufacturer norms. This may result from insufficient patient stratification in tested norms.Translational relevanceUnderstanding correlation of normative databases to visual function may improve clinical interpretation of OCT data.

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Retinal nerve fiber layer thickness predicts CSF amyloid/tau before cognitive decline.

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Retinal nerve fiber layer thickness predicts CSF amyloid/tau before cognitive decline.

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