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SUBRETINAL DRUSENOID DEPOSITS IN NON-NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: Morphology, Prevalence, Topography, and Biogenesis Model
Open accessAbstract
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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“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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Human photoreceptor topography
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Self-citationTopography of ganglion cells in human retina
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Self-citationThe Wisconsin Age-related Maculopathy Grading System
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ApoE-Directed Therapeutics Rapidly Clear β-Amyloid and Reverse Deficits in AD Mouse Models
Cramer, P. E., Cirrito, J. R., Wesson, D. W., Lee, C. Y. D., Karlo, J. C., Zinn, A. E., Casali, B. T., Restivo, J. L., Goebel, W. D., James, M. J., et al. (2012) · Science · doi:10.1126/science.1217697 · Cited by 1,050
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“Fewer than half subserve lipid metabolism.(68) Brain cerebrospinal fluid, embryologically equivalent to the subretinal space, also harbors HDL-like lipoproteins containing apoE.”
BackgroundAgeing and degeneration in the macular region: A clinico-pathological study
Sarks, S. H. (1976) · British Journal of Ophthalmology · doi:10.1136/bjo.60.5.324 · Cited by 891
Evolution of geographic atrophy of the retinal pigment epithelium
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Age-related Macular Degeneration Histopathologic Studies
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Reticular Pseudodrusen Are Subretinal Drusenoid Deposits
Zweifel, S. A., Spaide, R. F., Curcio, C. A., Malek, G., & Imamura, Y. (2009) · Ophthalmology · doi:10.1016/j.ophtha.2009.07.014 · Cited by 494
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Optical coherence tomography angiography
Spaide, R. F., Fujimoto, J. G., Waheed, N. K., Sadda, S. R., & Staurenghi, G. (2017) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2017.11.003 · Cited by 1,861
Self-citationAge-related macular degeneration
Mitchell, P., Liew, G., Gopinath, B., & Wong, T. Y. (2018) · The Lancet · doi:10.1016/s0140-6736(18)31550-2 · Cited by 1,511
Consensus Definition for Atrophy Associated with Age-Related Macular Degeneration on OCT
Sadda, S. R., Guymer, R. H., Holz, F. G., Schmitz-Valckenberg, S., Curcio, C. A., Bird, A. C., Blodi, B. A., Bottoni, F. G., Chakravarthy, U., Chew, E. Y., et al. (2017) · Ophthalmology · doi:10.1016/j.ophtha.2017.09.028 · Cited by 932
Self-citationImmunology of age-related macular degeneration
Ambati, J., Atkinson, J. P., & Gelfand, B. D. (2013) · Nature reviews. Immunology · doi:10.1038/nri3459 · Cited by 606
Age-Related Macular Degeneration: Genetics and Biology Coming Together
Fritsche, L. G., Fariss, R. N., Stambolian, D. E., Abecasis, G. R., Curcio, C. A., & Swaroop, A. (2014) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-090413-025610 · Cited by 546
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Metadata
- 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
- Health Sciences › Medicine › Ophthalmology › 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
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