High-Density Optical Coherence Tomography Analysis Provides Insights Into Early/Intermediate Age-Related Macular Degeneration Retinal Layer Changes

Abstract

Purpose To topographically map all of the thickness differences in individual retinal layers between early/intermediate age-related macular degeneration (AMD early /AMD int ) and normal eyes and to determine interlayer relationships. Methods Ninety-six AMD total (48 AMD early and 48 AMD int ) and 96 normal eyes from 192 participants were propensity-score matched by age, sex, and refraction. Retrospective optical coherence tomography (OCT) macular cube scans were acquired, and high-density (60 × 60 0.01-mm 2 ) grid thicknesses were custom extracted for comparison between AMD total and normal eyes corrected for confounding. Resultant “normal differences” underwent cluster, interlayer correlation, and dose–response analyses for the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer + Henle's fiber layer (ONL +HFL ), inner and outer segment (IS/OS) thickness, and retinal pigment epithelium (RPE) to Bruch's membrane (BM) thickness. Results AMD total inner retinal clusters demonstrated extensively thinned RNFL, GCL, IPL, and paracentral INL and thickened INL elsewhere, with normal difference means ranging from −8.13 µm (95% confidence interval [CI], −11.12 to −5.13) to 1.58 µm (95% CI, 1.07–2.09) ( P < 0.0001 to P < 0.05). Outer retinal clusters displayed thinned paracentral OPL/ONL +HFL , central IS/OS, and peripheral RPE–BM and thickened central RPE–BM, with means ranging from −1.31 µm (95% CI, −2.06 to −0.55) to 2.99 µm (95% CI, 0.97–5.01] ( P < 0.0001 to P <0.05). Effect sizes (−2.56 to 9.93 SD), cluster sizes, and eccentricity effects varied. All interlayer correlations were negligible to moderate regardless of AMD severity. Only the RPE–BM was partly thicker with greater AMD severity (up to 5.44 µm; 95% CI, 4.88–6.00; P < 0.01). Conclusions From the early stage, AMD eyes demonstrate thickness differences compared to normal with unique topographies across all retinal layers. Poor interlayer correlations highlight that the outer retina inadequately reflects complete retinal health. The clinical importance of OCT assessment across all individual retinal layers in early/intermediate AMD requires further investigation.

Macular outer nuclear layer, ellipsoid zone and outer photoreceptor segment band thickness, axial length and other determinants

“…Correspondingly, the number of retinal photoreceptors and retinal ganglion cells (as measured by the optic nerve fibers) increased with larger retinal surface area, i.e., with a larger globe size, in a histomorphometric study 31 . The observations of the physiological associations of the thickness of the ONL, EZ and POS with other parameters such as age, axial length and disc-fovea distance may be useful for the assessment of associations between the thickness of these structures and diseases, such as age-related macular degeneration, as shown in a recent study by Trinh et al and by Zekavat et al 32,33 .…”

Characterisation of the normal human ganglion cell–inner plexiform layer using widefield optical coherence tomography

“…57 Given previous reports of variable, non-linear rates of age-related change in GCL thickness from the central to peripheral macula, 13,14,32 further investigations of whether similar trends occur in GCIPL measurements captured over the central 55° × 45° are warranted. Cluster analysis enables location-agnostic identification of subsets of data demonstrating similar statistical characteristics and has been previously applied to describe patterns of age-related change in visual field, corneal, OCT and OCT angiography parameters, 32,52,[58][59][60][61][62][63] and visual field progression in glaucoma. [64][65][66][67] In this study, we used similar approaches to identify locations demonstrating similar ageing properties of GCIPL captured using widefield OCT, and those that were suitable to pool together in subsequent analyses to redistribute measurement variability.…”

High sampling resolution optical coherence tomography reveals potential concurrent reductions in ganglion cell‐inner plexiform and inner nuclear layer thickness but not in outer retinal thickness in glaucoma

“…For each participant in the glaucoma cohort, quantitative, location‐specific differences in GCIPL, INL and ORC thicknesses relative to a matched subgroup of the healthy cohort were calculated across the entire scan area. Deriving deviations in retinal thickness from a demographic‐matched healthy subgroup was performed to reduce interindividual variability, opposed to adjustment of absolute retinal thickness measurements using coefficients derived from multiple linear regression analyses, as non‐linear models have been previously applied to describe age‐related changes in the GCL, INL and ORC 22,26,28,50 . These models suggest accelerated decline in retinal thickness with increasing age, and therefore applying linear correction factors may overestimate retinal thickness measurements in older participants.…”

“…Rather, predefined statistical criteria are applied to determine the optimal number of clusters from hierarchical cluster results, and in this study, two distinct criteria were implemented. First, to avoid excessive complexity and therefore overassignment due to the volume of data input to the clustering algorithm, the Bayesian information criterion based on the likelihood function was applied as a starting point for the maximum number of suitable clusters 50,57 . Data were then classified according to this number of clusters from hierarchical cluster analysis results, and d’ was calculated for each cluster pair, based on the mean ( x ) and standard deviation ( σ ) for each cluster 28,55 :…”

“…Deriving deviations in retinal thickness from a demographicmatched healthy subgroup was performed to reduce interindividual variability, opposed to adjustment of absolute retinal thickness measurements using coefficients derived from multiple linear regression analyses, as nonlinear models have been previously applied to describe age-related changes in the GCL, INL and ORC. 22,26,28,50 These models suggest accelerated decline in retinal thickness with increasing age, and therefore applying , with foveal centres marked with red crosses. Maps were rotated such that the optic disc to fovea tilt was 0°, to enable interindividual structural comparisons.…”