Age-related macular degeneration (AMD) is a disease of the retinal pigment epithelium characterized by the appearance of protein/lipid deposits (drusen), geographic atrophy and neovascularization. Techniques currently used for diagnostic imaging of AMD include indocyanine green dye or fluorescein angiography, autofluorescence imaging and optical coherence tomography (OCT). OCT images depict optical backscatter, caused by variation in local optical refractive index. The high resolution provided by OCT has proved invaluable for imaging structural changes associated with AMD. Nevertheless, our understanding of the pathobiology of this disease is uncertain. The development of high-resolution retinal/choroidal imaging modalities not dependent upon optical scattering offers a potential means for gaining new insights into the AMD disease process, early diagnosis and clinical management. In this project we propose to develop and test means for imaging the elastic properties of the retina/choroid by detection of minute displacements generated within these structures induced by acoustic radiation force. Such elastic changes at the level of Bruch's membrane and the choroid would be expected as a consequence of drusen deposition and altered microvascular patterns. Furthermore, tissue elastic changes are also known to be associated with the development of neovascularization. A capacity to image elastic alteration may provide a means to visualize precursors to pathologic changes associated with AMD disease progression. We propose to image the retina/choroid with high speed, high-resolution, enhanced-depth OCT and to observe minute displacements occurring upon exposure to acoustic radiation force at safe, diagnostic levels. We will utilize two techniques: acoustic radiation force impulse (ARFI) imaging, in which displacements are induced by a brief (order of 1 msec) impulse, and vibro-acoustography, in which displacements are induced by low-frequency (order of 1 kHz) vibrations induced by interaction of two ultrasound sources of slightly different frequency. Studies will be conducted with tissue phantoms, rabbit eyes, in a primate model of AMD and finally normal and AMD human subjects in which we will demonstrate alterations in retinal/choroidal elastic properties associated with specific pathologic conditions including drusen, geographic atrophy, and neovascularization.

Public Health Relevance

The aim of this project is improved imaging and early diagnosis of age-related macular degeneration (AMD), a major cause of blindness. Current imaging techniques such as optical coherence tomography (OCT) allow detailed display of retinal anatomy, but cannot probe tissue elastic properties which may be altered as part of the disease process. We will utilize OCT to image the response of the retina and choroid to compressional pulses or vibrations induced by ultrasound in animal models and subjects with AMD to image retinal/choroidal elasticity and relate this property to the presence of drusen, disease progression and response to treatment.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY021529-03
Application #
8616071
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Greenwell, Thomas
Project Start
2012-02-01
Project End
2016-01-31
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10032
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