Keratoconus is the most common corneal degeneration in the US, affecting about 1 in 2000 people with a mean onset age of 15.4 years. The organization of collagen fibers in the cornea provides the mechanical strength that is essential to support the load and form the normal corneal shape. In keratoconus, the microstructural changes in the cornea disrupt the mechanical stability. Keratoconus explants showed disrupted collagen orientation and decreased mechanical modulus. Current diagnosis relies on indirect factors such as age and corneal geometrical features and thus far has failed to allow definitive diagnosis of early-stage progressive keratoconus. The proposed research will use recently developed Brillouin microscopy to test the hypothesis that spatially localized degeneration of mechanical stability is a critical driver of keratoconus progression. The first specific aim will improve the accuracy and speed of the current Brillouin instrument to enable comprehensive mechanical mapping of the cornea from patients with subclinical, mild, and advanced keratoconus. The second specific aim will determine the correlation between various biomechanical metrics derived from the in vivo measurements and the rate of progression of morphological changes. The third specific aim will derive model-based diagnostic metrics that are quantitatively related to corneal mechanical instability and correlated with the clinical data. The proposed study is expected to have high impacts on the clinical management of keratoconus patients by providing biomechanical metrics in vivo that will allow objective assessment of the rate of progression of keratoconus prospectively in early stages and enable clinicians to make objective, timely decision for optimal treatments of progressive keratoconus. Moreover, the research will accelerate the translation of the Brillouin technology to the clinic.

Public Health Relevance

This application is relevant to public health because it will lead to a novel diagnostic instrument and metrics to identify progressive keratoconus more accurately in earlier stages than currently possible. This improvement will help patients receive timely optimized treatments. Therefore, the proposed research is relevant to the NIH's mission of fostering innovative research strategies to increase the nation's ability to improve the treatment of disease.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY025454-02
Application #
9070594
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Mckie, George Ann
Project Start
2015-06-01
Project End
2019-05-31
Budget Start
2016-06-01
Budget End
2017-05-31
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
Yun, Seok Hyun; Kwok, Sheldon J J (2017) Light in diagnosis, therapy and surgery. Nat Biomed Eng 1:
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Shao, Peng; Besner, Sebastien; Zhang, Jitao et al. (2016) Etalon filters for Brillouin microscopy of highly scattering tissues. Opt Express 24:22232-8
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Scarcelli, Giuliano; Polacheck, William J; Nia, Hadi T et al. (2015) Noncontact three-dimensional mapping of intracellular hydromechanical properties by Brillouin microscopy. Nat Methods 12:1132-4

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