High-Density Optical Coherence Tomography Analysis Provides Insights Into Early/Intermediate Age-Related Macular Degeneration Retinal Layer Changes
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Purpose: To topographically map all of the thickness differences in individual retinal layers between early/intermediate age-related macular degeneration (AMDearly/AMDint) and normal eyes and to determine interlayer relationships. Methods: Ninety-six AMDtotal (48 AMDearly and 48 AMDint) 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-mm2) grid thicknesses were custom extracted for comparison between AMDtotal 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: AMDtotal 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.
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High-density OCT thickness analysis has shown that the central RPE-BrM complex is thicker in intermediate AMD than early AMD, likely due to the build-up of lipoprotein-related lipids.
“High-density OCT thickness analysis has shown that the central RPE–BrM complex is thicker in intermediate AMD than early AMD, likely due to the build-up of lipoprotein-related lipids [95].”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [95]
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Retinal Sensitivity Using Microperimetry in Age-Related Macular Degeneration in an Amish Population
Nittala, M. G., Velaga, S. B., Hariri, A. H., Pfau, M., Birch, D. G., Haines, J. L., Pericak‐Vance, M. A., Stambolian, D. E., & Sadda, S. R. (2019) · Ophthalmic surgery, lasers & imaging retina · doi:10.3928/23258160-20190905-15 · Cited by 12 · see citing works
Camacho, P., Dutra-Medeiros, M., Salgueiro, L., et al. (2021) · Journal of Ophthalmic and Vision Research · doi:10.18502/jovr.v16i3.9435 · Cited by 9 · see citing works
Development of a High-Density Spatially Localized Model of the Human Retina
Khou, V., Kalloniatis, M., Tong, J., et al. (2020) · Investigative Ophthalmology & Visual Science · Cited by 3 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 3
- [18]Trinh M, Kalloniatis M, Nivison-Smith L. Location-specific patterns of inner retinal thinning in intermediate age-related macular degeneration. Invest Ophthalmol Vis Sci. 2021; 62: 305. PMC8525852 34661608
- [37]Heidelberg Engineering GmbH. SPECTRALIS®. Glaucoma Module Premium Edition. User Manual Software Version 6.7. Heidelberg, Germany: Heidelberg Engineering GmbH; 2016.
- [46]Vichi M. Data Science: Innovative Developments in Data Analysis and Clustering. Cham, Switzerland: Springer Nature; 2017.
Cited by
Sorted by citations
Hammadi, S., Tzoumas, N., Ferrara, M., Meschede, I. P., Lo, K., Harris, C., Lako, M., & Steel, D. H. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12082870 · Cited by 44 · see citing works
- Authors
- Trinh, M., Kalloniatis, M., Alonso-Caneiro, D., & Nivison-Smith, L.
- Affiliations
- UNSW Sydney (AU)
- Contact Lens and Visual Optics Laboratory, Queensland University of Technology, Brisbane, Queensland, Australia
- Centre for Eye Health, University of New South Wales, Sydney, New South Wales, Australia
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2022-05-27
- Volume
- 63
- Issue
- 5
- Pages
- 36
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- PMC
- PMC9150835
- OpenAlex
- W4281688793
- Cited by
- 29
- References
- 104
- Citations by year
- 2026: 8 · 2025: 1 · 2024: 10 · 2023: 7 · 2022: 3
- FWCI
- 4.69
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Investigative Ophthalmology & Visual Science (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Griffith Research Online (submittedVersion, cc-by-nc-nd)
- Funders
- Medical Research Council
- National Health and Medical Research Council (1174385, 1186915)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Keywords
- age-related macular degeneration, retinal layer thickness, retinal nerve fiber layer, ganglion cell layer, inner nuclear layer, outer nuclear layer, retinal pigment epithelium, Bruch's membrane, retinal topography
- MeSH terms
- Humans, Macular Degeneration, Retina, Retrospective Studies, Tomography, Optical Coherence, Retinal Pigment Epithelium
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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