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

Tan, ACS; Pilgrim, MG; Fearn, S; Bertazzo, S; Tsolaki, E; Morrell, AP; Li, M; ... Curcio, CA; + view all (2018) Calcified nodules in retinal drusen are associated with disease progression in age-related macular degeneration. Science Translational Medicine , 10 (466) , Article eaat4544. 10.1126/scitranslmed.aat4544. Green open access

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Abstract

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.

Type: Article
Title: Calcified nodules in retinal drusen are associated with disease progression in age-related macular degeneration
Open access status: An open access version is available from UCL Discovery
DOI: 10.1126/scitranslmed.aat4544
Publisher version: https://doi.org/10.1126/scitranslmed.aat4544
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Chemical Engineering
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng
URI: https://discovery.ucl.ac.uk/id/eprint/10064623
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