We have developed and validated a comprehensive multivariate model that may be used to create a narrower range of normative RNFL data, which could improve diagnostic separation between early glaucoma and healthy subjects. This, however, remains to be demonstrated in future studies.
We characterized the age-related changes of the intra-retinal layers measured with spectral-domain optical coherence tomography (SD-OCT; Cirrus high-definition OCT [Carl Zeiss Meditec]. The Singapore Epidemiology of Eye Diseases is a population-based, cross-sectional study of Chinese, Malays and Indians living in Singapore. Iowa Reference Algorithms (Iowa Institute for Biomedical Imaging) were used for intra-retinal layer segmentation and mean thickness of 10 intra-retinal layers rescaled with magnification correction using axial length value. Linear regression models were performed to investigate the association of retinal layers with risk factors. After excluding participants with history of diabetes or ocular diseases, high-quality macular SD-OCT images were available for 2,047 participants (44–89 years old). Most of the retinal layers decreased with age except for foveal retinal nerve fiber layer (RNFL) and the inner/outer segments of photoreceptors where they increased with age. Men generally had thicker retinal layers than women. Chinese have the thickest RNFL and retinal pigment epithelium amongst the ethnic groups. Axial length and refractive error remained correlated with retinal layers in spite of magnification correction. Our data show pronounced age-related changes in retinal morphology. Age, gender, ethnicity and axial length need be considered when establishing OCT imaging biomarkers for ocular or systemic disease.
Background/AimsTo compensate the retinal nerve fibre layer (RNFL) thickness assessed by spectral-domain optical coherence tomography (SD-OCT) for anatomical confounders.MethodsThe Singapore Epidemiology of Eye Diseases is a population-based study, where 2698 eyes (1076 Chinese, 704 Malays and 918 Indians) with high-quality SD-OCT images from individuals without eye diseases were identified. Optic disc and macular cube scans were registered to determine the distance between fovea and optic disc centres (fovea distance) and their respective angle (fovea angle). Retinal vessels were segmented in the projection images and used to calculate the circumpapillary retinal vessel density profile. Compensated RNFL thickness was generated based on optic disc (ratio, orientation and area), fovea (distance and angle), retinal vessel density, refractive error and age. Linear regression models were used to investigate the effects of clinical factors on RNFL thickness.ResultsRetinal vessel density reduced significantly with increasing age (1487±214 µm in 40–49, 1458±208 µm in 50–59, 1429±223 µm in 60–69 and 1415±233 µm in ≥70). Compensation reduced the variability of RNFL thickness, where the effect was greatest for Chinese (10.9%; p<0.001), followed by Malays (6.6%; p=0.075) and then Indians (4.3%; p=0.192). Compensation reduced the age-related RNFL decline by 55% in all participants (β=−3.32 µm vs β=−1.50 µm/10 years; p<0.001). Nearly 62% of the individuals who were initially classified as having abnormally thin RNFL (outside the 99% normal limits) were later reclassified as having normal RNFL.ConclusionsRNFL thickness compensated for anatomical parameters reduced the variability of measurements and may improve glaucoma detection, which needs to be confirmed in future studies.
Using our model of the circumpapillary retinal vessel distribution, 70% of the RNFL thickness is influenced by RVD. On average, 7% of the interindividual variance of the RNFL thickness may be explained by RVD. A normative database that takes into account the circumpapillary blood vessels might slightly improve the diagnostic power of RNFL measurement.
Although reaching an improvement in some sectors, rotation of RNFL measurements according to the DFA on average does not reduce intersubject variability of RNFL. However, adjusting for RVD reduced the variance significantly. The results reinforce our work in assessing RVD as an important anatomical factor responsible for intersubject variability in RNFL measurements.
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