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

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.