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.
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.
|Weber, Isabell P; Yun, Seok Hyun; Scarcelli, Giuliano et al. (2017) The role of cell body density in ruminant retina mechanics assessed by atomic force and Brillouin microscopy. Phys Biol 14:065006|
|Yun, Seok Hyun; Kwok, Sheldon J J (2017) Light in diagnosis, therapy and surgery. Nat Biomed Eng 1:|
|Kwok, Sheldon J J; Kim, Moonseok; Lin, Harvey H et al. (2017) Flexible Optical Waveguides for Uniform Periscleral Cross-Linking. Invest Ophthalmol Vis Sci 58:2596-2602|
|Besner, Sebastien; Scarcelli, Giuliano; Pineda, Roberto et al. (2016) In Vivo Brillouin Analysis of the Aging Crystalline Lens. Invest Ophthalmol Vis Sci 57:5093-5100|
|Kim, Moonseok; Besner, Sebastien; Ramier, Antoine et al. (2016) Shear Brillouin light scattering microscope. Opt Express 24:319-28|
|Fiore, Antonio; Zhang, Jitao; Shao, Peng et al. (2016) High-extinction virtually imaged phased array-based Brillouin spectroscopy of turbid biological media. Appl Phys Lett 108:203701|
|Shao, Peng; Besner, Sebastien; Zhang, Jitao et al. (2016) Etalon filters for Brillouin microscopy of highly scattering tissues. Opt Express 24:22232-8|
|Zhang, Jitao; Fiore, Antonio; Yun, Seok-Hyun et al. (2016) Line-scanning Brillouin microscopy for rapid non-invasive mechanical imaging. Sci Rep 6:35398|
|Kwok, Sheldon J J; Kuznetsov, Ivan A; Kim, Moonseok et al. (2016) Selective two-photon collagen crosslinking in situ measured by Brillouin microscopy. Optica 3:469-472|
|Scarcelli, Giuliano; Besner, Sebastien; Pineda, Roberto et al. (2015) In vivo biomechanical mapping of normal and keratoconus corneas. JAMA Ophthalmol 133:480-2|
Showing the most recent 10 out of 12 publications