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

Anna C.S. Tan, Matthew G. Pilgrim, Sarah Fearn, Sergio Bertazzo, Elena Tsolaki, Alexander P. Morrell, Miaoling Li, Jeffrey D. Messinger, Rosa Dolz-Marco, Jianqin Lei, Muneeswar G. Nittala, Srinivas R. Sadda, Imre Lengyel*, K. Bailey Freund, Christine A. Curcio

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article numbereaat4544
JournalScience Translational Medicine
Issue number466
Publication statusPublished - 7 Nov 2018

Bibliographical note

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


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