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

doi:10.1126/scitranslmed.aat4544

Research ArticleRetinal Disease

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

Anna C. S. Tan¹,²,³,⁴,*,
Matthew G. Pilgrim⁵,⁶,*,
Sarah Fearn⁷,
Sergio Bertazzo⁸,
Elena Tsolaki⁸,
Alexander P. Morrell⁹,
Miaoling Li¹⁰,
Jeffrey D. Messinger¹⁰,
Rosa Dolz-Marco¹,²,
Jianqin Lei¹¹,
Muneeswar G. Nittala¹¹,
Srinivas R. Sadda¹¹,¹²,
Imre Lengyel ⁵,¹³,†,‡,
K. Bailey Freund¹,²,¹⁴,‡ and
Christine A. Curcio¹⁰,‡

¹Vitreous Retina Macula Consultants of New York, New York, NY 10022, USA.
²LuEsther T. Mertz Retinal Research Center, Manhattan, Eye, Ear and Throat Hospital, New York, NY 10075, USA.
³Singapore National Eye Center/Singapore Eye Research Institute Singapore, Singapore 168751, Singapore.
⁴Duke-NUS Singapore, Singapore 168751, Singapore.
⁵UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
⁶Division of Biomaterials and Tissue Engineering, UCL Eastman Dental Institute, University College London, London WC1X 8LD, UK.
⁷Department of Materials, Imperial College London, London SW7 2AZ, UK.
⁸Department of Medical Physics and Biomedical Engineering, University College London, Malet Place Engineering Building, London WC1E 6BT, UK.
⁹Material Physics, Aston University, Aston Express Way, Birmingham B4 7ET, UK.
¹⁰Department of Ophthalmology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 32594-0019, USA.
¹¹Doheny Image Reading Center, Doheny Eye Institute, Los Angeles, CA 90033, USA.
¹²Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
¹³Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen’s University Belfast, Belfast BT9 7BL, UK.
¹⁴Department of Ophthalmology, New York University Langone School of Medicine, New York, NY 10016, USA.

↵†Corresponding author. Email: i.lengyel{at}qub.ac.uk

↵* These authors contributed equally to this work.
↵‡ Co-senior authors.

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Science Translational Medicine 07 Nov 2018:
Vol. 10, Issue 466, eaat4544
DOI: 10.1126/scitranslmed.aat4544

Anna C. S. Tan

Vitreous Retina Macula Consultants of New York, New York, NY 10022, USA.

LuEsther T. Mertz Retinal Research Center, Manhattan, Eye, Ear and Throat Hospital, New York, NY 10075, USA.

Singapore National Eye Center/Singapore Eye Research Institute Singapore, Singapore 168751, Singapore.

Duke-NUS Singapore, Singapore 168751, Singapore.

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Matthew G. Pilgrim

UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.

Division of Biomaterials and Tissue Engineering, UCL Eastman Dental Institute, University College London, London WC1X 8LD, UK.

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Sarah Fearn

Department of Materials, Imperial College London, London SW7 2AZ, UK.

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Sergio Bertazzo

Department of Medical Physics and Biomedical Engineering, University College London, Malet Place Engineering Building, London WC1E 6BT, UK.

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Elena Tsolaki

Department of Medical Physics and Biomedical Engineering, University College London, Malet Place Engineering Building, London WC1E 6BT, UK.

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Alexander P. Morrell

Material Physics, Aston University, Aston Express Way, Birmingham B4 7ET, UK.

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Miaoling Li

Department of Ophthalmology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 32594-0019, USA.

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Jeffrey D. Messinger

Department of Ophthalmology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 32594-0019, USA.

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Rosa Dolz-Marco

Vitreous Retina Macula Consultants of New York, New York, NY 10022, USA.

LuEsther T. Mertz Retinal Research Center, Manhattan, Eye, Ear and Throat Hospital, New York, NY 10075, USA.

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Jianqin Lei

Doheny Image Reading Center, Doheny Eye Institute, Los Angeles, CA 90033, USA.

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Muneeswar G. Nittala

Doheny Image Reading Center, Doheny Eye Institute, Los Angeles, CA 90033, USA.

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Srinivas R. Sadda

Doheny Image Reading Center, Doheny Eye Institute, Los Angeles, CA 90033, USA.

Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.

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Imre Lengyel

UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.

Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen’s University Belfast, Belfast BT9 7BL, UK.

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For correspondence: i.lengyel@qub.ac.uk

K. Bailey Freund

Vitreous Retina Macula Consultants of New York, New York, NY 10022, USA.

LuEsther T. Mertz Retinal Research Center, Manhattan, Eye, Ear and Throat Hospital, New York, NY 10075, USA.

Department of Ophthalmology, New York University Langone School of Medicine, New York, NY 10016, USA.

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Christine A. Curcio

Department of Ophthalmology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 32594-0019, USA.

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Imaging AMD progression

Age-related macular degeneration (AMD) is the leading cause of vision impairment in older individuals. About 20% of those who develop AMD will progress to vision loss. Reliable methods to identify patients at risk of progression to late stage AMD are lacking. Tan et al. used multimodal imaging, histological analysis and nano-analytical measurements to show that calcified nodules in the retina were associated with AMD progression. The authors found that these nodules were composed of hydroxyapatite and could be distinguished from other types of calcifications. The results suggest that multimodal imaging might help to guide therapeutic approaches and outcome measures in patients at risk of progressing to advanced AMD.

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

Imaging AMD progression

Science Translational Medicine

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