Biological and Methodological Variability in Retinal Nerve Fiber Layer OCT: The Framingham Heart Study.

ABSTRACT

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 (ß =  - 0.19 microns/year, [95% confidence interval {CI} - 0.29, - 0.09]), female gender (ß = +1.48 microns vs. male, [95% CI 0.09, 2.86]), axial length (ß =  - 1.24 microns/mm of greater length, [95% CI - 1.80, - 0.67]), and SS (ß = +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 (ß = +0.02 per micron increase, [95% CI 0.01, 0.03]), and lower SS (ß = +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 (ß = +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.