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
SN - 1946-6234
VL - 10
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 466
M1 - eaat4544
ER -