Current descriptions of retinal thickness across normal age cohorts are mostly limited to global analyses, thus overlooking spatial variation across the retina and limiting spatial analyses of retinal and optic nerve disease. This retrospective cross-sectional study uses location-specific cluster analysis of 8 × 8 macular average grid-wise thicknesses to quantify topographical patterns and rates of normal, age-related changes in all individual retinal layers of 253 eyes of 253 participants across various age cohorts (n = 23–69 eyes per decade). Most retinal layers had concentric spatial cluster patterns except the retinal nerve fibre layer (RNFL) which displayed a nasal, asymmetric radial pattern. Age-related thickness decline mostly occurred after the late 4th decade, described by quadratic regression models. The ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), and outer nuclear layer + Henle’s fibre layer (ONL+HFL) were significantly associated with age (p < 0.0001 to < 0.05), demonstrating similar rates of thickness decline (mean pooled slope =  − 0.07 µm/year), while the IS/OS had lesser mean pooled thickness slopes for all clusters (− 0.04 µm/year). The RNFL, OPL, and RPE exhibited no significant age-related thickness change, and the RNFL were significantly associated with sex. Analysis using spatial clusters compared to the ETDRS sectors revealed more extensive spatial definition and less variability in the former method. These spatially defined, clustered normative data and age-correction functions provide an accessible method of retinal thickness analysis with more spatial detail and less variability than the ETDRS sectors, potentially aiding the diagnosis and monitoring of retinal and optic nerve disease.

Purpose: To examine changes in retinal vasculature and ganglion cell layer (GCL) thickness in intermediate age-related macular degeneration (AMD) using optical coherence tomography angiography (OCTA). Methods: Zeiss Cirrus Angioplex OCTA 6 3 6 mm scans and a macula 512 3 128 cube scans of the central retina were taken of 63 eyes with intermediate AMD and 51 control eyes. For OCTA scans, the superficial and deep capillary plexus were automatically segmented and vascular density quantified as total number of pixels contributing to the blood flow signal detectable by OCTA. Images were then skeletonized and vessel length, diameter index, morphology, and branching complexity determined. Foveal avascular zone (FAZ) characteristics and GCL thickness were extracted from in-built Angioplex software. Results: Vascular density was significantly reduced in the superficial capillary plexus of AMD eyes compared with normal eyes, particularly in the superior quadrant (42.4% 6 1.6% vs. 43.2% 6 1.4%; P , 0.05). A nonsignificant reduction was also seen in the deep capillary plexus (P ¼ 0.06). Total vessel length and average vessel diameter were all significantly decreased in AMD eyes suggesting density changes were related to decreased vessel number and caliber. Vascular complexity and number of branch points was significantly decreased in the deep capillary plexus (P , 0.05) suggesting loss or significantly reduced flow of vessels. Average GCL thickness was also significantly reduced in the AMD eyes (P , 0.05). No significant changes in FAZ parameters were observed in AMD eyes. Conclusions: This study suggests intermediate AMD affects both the quantity and morphology of inner retinal vasculature and may be associated with changes in inner retinal structure. This work builds upon the notion that AMD pathogenesis may extends beyond the outer retina. Translational Relevance: Better understanding of retinal vascular changes in AMD can provide insights in the development of treatment and prevention protocols for these diseases.

Nivison-Smith L. Macula ganglion cell thickness changes display location-specific variation patterns in intermediate age-related macular degeneration. Invest Ophthalmol Vis Sci. 2020;61(3):2. https://doi.org/10.1167/iovs.61.3.2 PURPOSE.The purpose of this study was to examine changes in the ganglion cell layer (GCL) of individuals with intermediate age-related macular degeneration (AMD) using grid-wise analysis for macular optical coherence tomography (OCT) volume scans. We also aim to validate the use of age-correction functions for GCL thickness in diseased eyes. METHODS.OCT macular cube scans covering 30°× 25°were acquired using Spectralis spectral-domain OCT for 87 eyes with intermediate AMD, 77 age-matched normal eyes, and 254 non-age-matched normal eyes. The thickness of the ganglion cell layer (GCL) was defined after segmentation at 60 locations across an 8 × 8 grid centered on the fovea, where each grid location covered 0.74 mm 2 (approximately 3°× 3°) within the macula. Each GCL location of normal eyes (n = 77) were assigned to a specific iso-ganglion cell density cluster in the macula, based on patterns of age-related GCL thickness loss. Analyses were then performed comparing AMD GCL grid-wise data against corresponding spatial clusters, and significant AMD GCL thickness changes were denoted as values outside the 95% distribution limits. RESULTS.Analysis of GCL thickness changes revealed significant differences between spatial clusters, with thinning toward the fovea, and thickening toward the peripheral macula. The direction of GCL thickness changes in AMD were associated more so with thickening than thinning in all analyses. Results were corroborated by the application of GCL thickness age-correction functions.CONCLUSIONS. GCL thickness changed significantly and nonuniformly within the macula of intermediate AMD eyes. Further characterization of these changes is critical to improve diagnoses and monitoring of GCL-altering pathologies.

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.

Purpose To examine individual retinal layers’ location-specific patterns of thicknesses in intermediate age-related macular degeneration (iAMD) using optical coherence tomography (OCT). Methods OCT macular cube scans were retrospectively acquired from 84 iAMD eyes of 84 participants and 84 normal eyes of 84 participants propensity-score matched on age, sex, and spherical equivalent refraction. Thicknesses of 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 layers (IS/OS), and retinal pigment epithelium to Bruch's membrane (RPE-BM) were calculated across an 8 × 8 grid (total 24° × 24° area). Location-specific analysis was performed using cluster (normal) and grid (iAMD) -to-cluster (normal) comparisons. Results In iAMD versus normal eyes, the central RPE-BM was thickened (mean difference ± SEM up to 27.45% ± 7.48%, P < 0.001; up to 7.6 SD-from-normal), whereas there was thinned outer (OPL, ONL +HFL , and non-central RPE-BM, up to −6.76% ± 2.47%, P < 0.001; up to −1.6 SD-from-normal) and inner retina (GCL and IPL, up to −4.83% ± 1.56%, P < 0.01; up to −1.7 SD-from-normal) with eccentricity-based effects. Interlayer correlations were greater against the ONL +HFL (mean |r| ± SEM 0.19 ± 0.03, P = 0.14 to < 0.0001) than the RPE-BM (0.09 ± 0, P = 0.72 to < 0.0001). Conclusions Location-specific analysis suggests altered retinal anatomy between iAMD and normal eyes. These data could direct clinical diagnosis and monitoring of AMD toward targeted locations.