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A Functional Regression Model of the Retinal Nerve Fiber Layer Thickness in Healthy Subjects.

ABSTRACT: Purpose:A new functional regression model is presented to explain the intersubject variability of the circumpapillary retinal nerve fiber layer (RNFL) thickness in healthy subjects. Methods:To evaluate the functional regression approach we used data from 202 healthy volunteers, divided equally into training samples (TS) and validation samples (VS). Covariates included RNFL, fovea distance, fovea angle, optic disk ratio, orientation and area provided by Fourier-domain-optical coherence tomography, age, and refractive error. Root mean square errors (RMSE) were calculated for each of the 256 sectors and for the 12 clock-hour sectors in the TS and VS and were compared to the RMSE of the previous model and the standard deviation of the raw data. Results:With the functional regression approach, we were able to explain on average 27.4% of the variation in the TS and 25.1% of the variation in the VS. The new model performed better compared to a multivariate linear regression model. It performed best in the superior-temporal and inferior-temporal clock-hour sectors where the percentage of RMSE reduction ranged between 26.3% and 44.1% for the TS and between 20.6% and 35.4% for the VS. Conclusions:The new functional regression approach improves on the multivariate linear regression model and allows an even larger reduction of the amount of intersubject variability, while at the same time using a substantially smaller number of parameters to be estimated. Translational Relevance:The demonstrated reduction of interindividual variation is expected to translate into an improved diagnostic separation between healthy and glaucomatous subjects, but this remains to be demonstrated in further studies.

SUBMITTER: Pereira I

PROVIDER: S-EPMC5777176 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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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.

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A Functional Regression Model of the Retinal Nerve Fiber Layer Thickness in Healthy Subjects.

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