SUBRETINAL DRUSENOID DEPOSITS IN NON-NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: Morphology, Prevalence, Topography, and Biogenesis Model
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In Brief Purpose: To characterize the morphology, prevalence, and topography of subretinal drusenoid deposits, a candidate histological correlate of reticular pseudodrusen, with reference to basal linear deposit (BlinD), a specific lesion of age-related macular degeneration, and to propose a biogenesis model for both lesion. Methods: Donor eyes with median death-to-preservation of 2:40 hours were postfixed in osmium tannic acid paraphenylenediamine and prepared for macula-wide high-resolution digital sections. Annotated thicknesses of 21 chorioretinal layers were determined at standard locations in sections through the fovea and the superior perifovea. Results: In 22 eyes of 20 white donors (83.1 ± 7.7 years), SDD appeared as isolated or confluent drusenoid dollops punctuated by tufts of retinal pigment epithelium apical processes and associated with photoreceptor perturbation. Subretinal drusenoid deposits and BlinD were detected in 85 and 90% of non-neovascular age-related macular degeneration donors, respectively. Subretinal drusenoid deposit was thick (median, 9.4 μm) and more abundant in the perifovea than in the fovea (P < 0.0001). BlinD was thin (median, 2.1 μm) and more abundant in the fovea than in the perifovea (P < 0.0001). Conclusion: Subretinal drusenoid deposits and BlinD prevalence in age-related macular degeneration eyes are high. Subretinal drusenoid deposits organized morphology, topography, and impact on surrounding photoreceptors imply specific processes of biogenesis. Contrasting topographies of subretinal drusenoid deposits and BlinD suggest relationships with differentiable aspects of rod and cone physiology, respectively. A 2-lesion 2-compartment biogenesis model incorporating outer retinal lipid homeostasis is presented. The largest series of eyes devoted to histological characterization of subretinal drusenoid deposit, a candidate correlate of reticular pseudodrusen, shows that it is a stereotyped extracellular lesion that is as prevalent in age-related macular degeneration eyes as basal linear deposit. A 2-lesion 2-compartment biogenesis model invoking photoreceptor lipid homeostasis is proposed.
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The absence of basal linear deposits in Klc1−/− retina is to be expected, given that basal linear deposits form mostly in the fovea, a small central region of the macula that contains only cone photoreceptors, which is not present in a mouse retina.
“This difference is to be expected, given that basal linear deposits form mostly in the fovea (Curcio et al., 2013), a small central region of the macula that contains only cone photoreceptors (Osterberg, 1935), which is not present in a mouse retina.”
From Microtubule motors transport phagosomes in the RPE, and lack of KLC1 leads to AMD-like pathogenesis (2015) · cites this paper as Curcio et al., 2013
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The Onion Sign in Neovascular Age-Related Macular Degeneration Represents Cholesterol Crystals
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Spotlight on reticular pseudodrusen
Rabiolo, A., Sacconi, R., Cicinelli, M. V., Querques, L., Bandello, F. M., & Querques, G. (2017) · Clinical ophthalmology · doi:10.2147/opth.s130165 · Cited by 69 · see citing works
Risk Factors Associated With Reticular Pseudodrusen Versus Large Soft Drusen
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Reduction of Retinal Sensitivity in Eyes With Reticular Pseudodrusen
Ooto, S., Ellabban, A. A., Ueda‐Arakawa, N., Oishi, A., Tamura, H., Yamashiro, K., Tsujikawa, A., & Yoshimura, N. (2013) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2013.06.036 · Cited by 65 · see citing works
- Authors
- Curcio, C. A., Messinger, J. D., Sloan, K. R., McGwin, G., Medeiros, N. E., & Spaide, R. F.
- Affiliations
- University of Alabama at Birmingham (US)
- Vitreous Retina Macula Consultants of New York (US)
- Corresponding author
- Curcio, Christine A.
- Messinger, Jeffrey D.
- Venue
- Retina
- Published
- 2013-02
- Volume
- 33
- Issue
- 2
- Pages
- 265-276
- ISSN
- 0275-004X (ISSN-L)
- PMC
- PMC3870202
- OpenAlex
- W2045011938
- Cited by
- 384
- References
- 86
- Citations by year
- 2026: 25 · 2025: 15 · 2024: 27 · 2023: 18 · 2022: 35 · 2021: 28 · 2020: 28 · 2019: 27 · 2018: 37 · 2017: 32 · 2016: 32 · 2015: 35 · 2014: 36 · 2013: 9
- FWCI
- 23.94
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Retina (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Eye Institute (R01EY006109, EY06109)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
- Keywords
- subretinal drusenoid deposits, reticular pseudodrusen, non-neovascular age-related macular degeneration, retinal pigment epithelium, perifovea, fovea
- MeSH terms
- Aged, 80 and over, Female, Fovea Centralis, Humans, Male, Models, Biological, Tissue Donors, Retinal Drusen, Eye Diseases, Hereditary, Prevalence, Bruch Membrane, Topography, Medical, White People, Retinal Pigment Epithelium, Geographic Atrophy
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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