Calcified nodules in retinal drusen are associated with disease progression in age-related macular degeneration


Drusen are lipid-, mineral-, and protein-containing extracellular deposits that accumulate between the basal lamina of the retinal pigment epithelium (RPE) and Bruch’s membrane (BrM) of the human eye. They are a defining feature of age-related macular degeneration (AMD), a common sight-threatening disease of older adults. The appearance of heterogeneous internal reflectivity within drusen (HIRD) on optical coherence tomography (OCT) images has been suggested to indicate an increased risk of progression to advanced AMD. Here, in a cohort of patients with AMD and drusen, we show that HIRD indicated an increased risk of developing advanced AMD within 1 year. Using multimodal imaging in an independent cohort, we demonstrate that progression to AMD was associated with increasing degeneration of the RPE overlying HIRD. Morphological analysis of clinically imaged cadaveric human eye samples revealed that HIRD was formed by multilobular nodules. Nanoanalytical methods showed that nodules were composed of hydroxyapatite and that they differed from spherules and BrM plaques, other refractile features also found in the retinas of patients with AMD. These findings suggest that hydroxyapatite nodules may be indicators of progression to advanced AMD and that using multimodal clinical imaging to determine the composition of macular calcifications may help to direct therapeutic strategies and outcome measures in AMD.

Publication DOI:
Divisions: College of Engineering & Physical Sciences > School of Infrastructure and Sustainable Engineering > Chemical Engineering & Applied Chemistry
Additional Information: This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science Translational Medicine in Vol. 10, Issue 466, eaat4544 7 Nov 2018, DOI: 10.1126/scitranslmed.aat4544
Uncontrolled Keywords: Medicine(all)
Publication ISSN: 1946-6242
Full Text Link: http://discover ...
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
http://stm.scie ... 10/466/eaat4544 (Publisher URL)
PURE Output Type: Article
Published Date: 2018-11-07
Accepted Date: 2018-10-17
Authors: Tan, Anna C.S.
Pilgrim, Matthew G.
Fearn, Sarah
Bertazzo, Sergio
Tsolaki, Elena
Morrell, Alexander P.
Li, Miaoling
Messinger, Jeffrey D.
Dolz-Marco, Rosa
Lei, Jianqin
Nittala, Muneeswar G.
Sadda, Srinivas R.
Lengyel, Imre
Freund, K. Bailey
Curcio, Christine A.



Version: Accepted Version

| Preview

Export / Share Citation


Additional statistics for this record