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 journalArticle

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.

Original languageEnglish
Article numbereaat4544
JournalScience Translational Medicine
Volume10
Issue number466
DOIs
Publication statusPublished - 7 Nov 2018

Fingerprint

Retinal Drusen
Macular Degeneration
Disease Progression
Multimodal Imaging
Bruch Membrane
Retinal Pigment Epithelium
Durapatite
Optical Coherence Tomography
Basement Membrane
Minerals
Retina
Outcome Assessment (Health Care)

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

Cite this

Tan, A. C. S., Pilgrim, M. G., Fearn, S., Bertazzo, S., Tsolaki, E., Morrell, A. P., ... Curcio, C. A. (2018). Calcified nodules in retinal drusen are associated with disease progression in age-related macular degeneration. Science Translational Medicine, 10(466), [eaat4544]. https://doi.org/10.1126/scitranslmed.aat4544
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. / Calcified nodules in retinal drusen are associated with disease progression in age-related macular degeneration. In: Science Translational Medicine. 2018 ; Vol. 10, No. 466.
@article{4cd5b08551d748c39a9c48f8105d1520,
title = "Calcified nodules in retinal drusen are associated with disease progression in age-related macular degeneration",
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.",
author = "Tan, {Anna C.S.} and Pilgrim, {Matthew G.} and Sarah Fearn and Sergio Bertazzo and Elena Tsolaki and Morrell, {Alexander P.} and Miaoling Li and Messinger, {Jeffrey D.} and Rosa Dolz-Marco and Jianqin Lei and Nittala, {Muneeswar G.} and Sadda, {Srinivas R.} and Imre Lengyel and Freund, {K. Bailey} and Curcio, {Christine A.}",
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",
year = "2018",
month = "11",
day = "7",
doi = "10.1126/scitranslmed.aat4544",
language = "English",
volume = "10",
number = "466",

}

Tan, ACS, Pilgrim, MG, Fearn, S, Bertazzo, S, Tsolaki, E, Morrell, AP, Li, M, Messinger, JD, Dolz-Marco, R, Lei, J, Nittala, MG, Sadda, SR, Lengyel, I, Freund, KB & Curcio, CA 2018, 'Calcified nodules in retinal drusen are associated with disease progression in age-related macular degeneration', Science Translational Medicine, vol. 10, no. 466, eaat4544. https://doi.org/10.1126/scitranslmed.aat4544

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

In: Science Translational Medicine, Vol. 10, No. 466, eaat4544, 07.11.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Calcified nodules in retinal drusen are associated with disease progression in age-related macular degeneration

AU - Tan, Anna C.S.

AU - Pilgrim, Matthew G.

AU - Fearn, Sarah

AU - Bertazzo, Sergio

AU - Tsolaki, Elena

AU - Morrell, Alexander P.

AU - Li, Miaoling

AU - Messinger, Jeffrey D.

AU - Dolz-Marco, Rosa

AU - Lei, Jianqin

AU - Nittala, Muneeswar G.

AU - Sadda, Srinivas R.

AU - Lengyel, Imre

AU - Freund, K. Bailey

AU - Curcio, Christine A.

N1 - 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

PY - 2018/11/7

Y1 - 2018/11/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85056360136&partnerID=8YFLogxK

UR - http://stm.sciencemag.org/content/10/466/eaat4544

U2 - 10.1126/scitranslmed.aat4544

DO - 10.1126/scitranslmed.aat4544

M3 - Article

C2 - 30404862

AN - SCOPUS:85056360136

VL - 10

IS - 466

M1 - eaat4544

ER -

Tan ACS, Pilgrim MG, Fearn S, Bertazzo S, Tsolaki E, Morrell AP et al. Calcified nodules in retinal drusen are associated with disease progression in age-related macular degeneration. Science Translational Medicine. 2018 Nov 7;10(466). eaat4544. https://doi.org/10.1126/scitranslmed.aat4544