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Biological and Methodological Variability in Retinal Nerve Fiber Layer OCT: The Framingham Heart Study
Louay Almidani1, Jasdeep Sabharwal1, Anoush Shahidzadeh2
1Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Objective:
To explore participant-level biological attributes and scan-level methodological attributes associated with retinal nerve fiber layer (RNFL) thickness variability in a population-based sample of elderly United States adults.
Design:
Cross-sectional analysis using data from the Framingham Heart Study.
Participants:
One thousand three hundred forty-seven eyes from 825 participants with ≥1 OCT scan and axial length data were included.
Methods:
Three or more successive RNFL scans of each eye of each participant were obtained in a single session. Multivariable linear mixed models were employed to explore the associations between average RNFL thickness with participant-level biological attributes (age, gender, race, ethnicity, and axial length) and scan-level attributes (signal strength [SS]) as independent variables in the whole population as well as a subsample of adults with no self-reported history of glaucoma. Similar analyses were designed to assess methodological variability with average within-eye standard deviation (SD) for repeated scans as the dependent variable.
Main Outcomes Measures:
(1) Biological variability: average RNFL thickness, and (2) methodological variability: average within-participant SD across repeated scans.
Results:
Age (β = 0.19 microns/year, [95% confidence interval {CI}: 0.29, 0.09]), female gender (β = +1.48 microns vs. male, [95% CI: 0.09, 2.86]), axial length (β = 1.24 microns/mm of greater length, [95% CI: 1.80, 0.67]), and SS (β = +1.62 microns/1 unit greater SS, [95% CI: 1.16, 2.09]) were significantly associated with RNFL thickness, while race and ethnicity were not (P > 0.05). In analyses designed to assess methodological variability, higher RNFL thickness (β = +0.02 per micron increase, [95% CI: 0.01, 0.03]), and lower SS (β = +0.19 per 1 unit lower SS, [95% CI: 0.10, 0.27]) were significantly associated with greater RNFL variability. In adults with no self-reported history of glaucoma (n of eyes = 1165, n of participants = 712), female gender was not associated with RNFL, while African American race was associated with thicker RNFL (β = +4.65 microns vs. Whites, [95% CI: 1.28, 8.03]).
Conclusions:
Retinal nerve fiber layer thickness is lower with older age, male gender, greater axial length, lower SS, and Whites (as compared with African Americans) without self-reported glaucoma. Measurement variability (SD) is higher with greater RNFL thickness and lower SS. Understanding these biological and methodological variations is important to aid in OCT interpretation.
Financial Disclosures:
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
