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      Brillouin microscopy: assessing ocular tissue biomechanics

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          Abstract

          Purpose of review

          Assessment of corneal biomechanics has been an unmet clinical need in ophthalmology for many years. Many researchers and clinicians have identified corneal biomechanics as source of variability in refractive procedures and one of the main factors in keratoconus. However, it has been difficult to accurately characterize corneal biomechanics in patients. The recent development of Brillouin light scattering microscopy heightens the promise of bringing biomechanics into the clinic. The aim of this review is to overview the progress and discuss prospective applications of this new technology.

          Recent findings

          Brillouin microscopy uses a low-power near-infrared laser beam to determine longitudinal modulus or mechanical compressibility of tissue by analyzing the return signal spectrum. Human clinical studies have demonstrated significant difference in the elastic properties of normal corneas versus corneas diagnosed with mild and severe keratoconus. Clinical data have also shown biomechanical changes after corneal cross-linking treatment of keratoconus patients. Brillouin measurements of the crystalline lens and sclera have also been demonstrated.

          Summary

          Brillouin microscopy is a promising technology under commercial development at present. The technique enables physicians to characterize the biomechanical properties of ocular tissues.

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          Most cited references54

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          Introduction of Two Novel Stiffness Parameters and Interpretation of Air Puff-Induced Biomechanical Deformation Parameters With a Dynamic Scheimpflug Analyzer.

          To investigate two new stiffness parameters and their relationships with the dynamic corneal response (DCR) parameters and compare normal and keratoconic eyes.
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            Corneal biomechanical properties in normal, post-laser in situ keratomileusis, and keratoconic eyes.

            To compare the biomechanical properties of normal, post-laser in situ keratomileusis (LASIK), and keratoconic corneas evaluated by corneal hysteresis and the corneal resistance factor measured with the Reichert Ocular Response Analyzer (ORA). Instituto Oftalmológico de Alicante, Vissum, Alicante, Spain. Two hundred fifty eyes were divided into 3 groups: normal (control group), post-LASIK, and keratoconus. The corneal biomechanical properties were measured with the ORA, which uses a dynamic bidirectional applanation process. The main outcome measures were intraocular pressure, corneal hysteresis, and the corneal resistance factor. The control group had 165 eyes; the LASIK group, 65 eyes; and the keratoconus group, 21 eyes. In the control group, the mean corneal hysteresis value was 10.8 mm Hg +/- 1.5 (SD) and the mean corneal resistance factor, 11.0 +/- 1.6 mm Hg. The corneal hysteresis value was lower in older eyes, and the difference between the youngest age group (9 to 14 years) and oldest age group (60 to 80 years) was statistically significant (P = .01, t test). One month after LASIK, corneal hysteresis and the corneal resistance factor decreased significantly, from 10.44 to 9.3 mm Hg and from 10.07 to 8.13 mm Hg, respectively. In the keratoconus group, the mean corneal hysteresis was 7.5 +/- 1.2 mm Hg and the mean corneal resistance factor, 6.2 +/- 1.9 mm Hg. There were statistically significant differences in both biomechanical parameters between keratoconic eyes and post-LASIK eyes (P<.001, t test). The corneal hysteresis and corneal resistance factor values were significantly lower in keratoconic eyes than in post-LASIK eyes. Future work is needed to determine whether these differences are useful in detecting keratoconus when other diagnostic tests are equivocal.
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              Brillouin optical microscopy for corneal biomechanics.

              The mechanical properties of corneal tissue are linked to prevalent ocular diseases and therapeutic procedures. Brillouin microscopy is a novel optical technology that enables three-dimensional mechanical imaging. In this study, the feasibility of this noncontact technique was tested for in situ quantitative assessment of the biomechanical properties of the cornea. Brillouin light-scattering involves a spectral shift proportional to the longitudinal modulus of elasticity of the tissue. A 532-nm single-frequency laser and a custom-developed ultrahigh-resolution spectrometer were used to measure the Brillouin frequency. Confocal scanning was used to perform Brillouin elasticity imaging of the corneas of whole bovine eyes. The longitudinal modulus of the bovine corneas was compared before and after riboflavin corneal collagen photo-cross-linking. The Brillouin measurements were then compared with conventional stress-strain mechanical test results. High-resolution Brillouin images of the cornea were obtained, revealing a striking depth-dependent variation of the elastic modulus across the cornea. Along the central axis, the Brillouin frequency shift varied gradually from 8.2 GHz in the epithelium to 7.5 GHz near the endothelium. The coefficients of the down slope were measured to be approximately 1.09, 0.32, and 2.94 GHz/mm in the anterior, posterior, and innermost stroma, respectively. On riboflavin collagen cross-linking, marked changes in the axial Brillouin profiles (P < 0.001) were noted before and after cross-linking. Brillouin imaging can assess the biomechanical properties of cornea in situ with high spatial resolution. This novel technique has the potential for use in clinical diagnostics and treatment monitoring.
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                Author and article information

                Journal
                Curr Opin Ophthalmol
                Curr Opin Ophthalmol
                COOPH
                Current Opinion in Ophthalmology
                Lippincott Williams & Wilkins
                1040-8738
                1531-7021
                July 2018
                07 June 2018
                : 29
                : 4
                : 299-305
                Affiliations
                [a ]Harvard Medical School and Wellman Center for Photomedicine, Massachusetts General Hospital
                [b ]Intelon Optics Inc., Zero Emerson Place, Boston Massachusetts, USA
                Author notes
                Correspondence to Seok Hyun Yun, Professor and Patricia and Scott Eston MGH Research Scholar, Massachusetts General Hospital, 65 Landsdowne St. UP-525, Cambridge, MA 02139, USA. Tel: +1 617 768 8704; e-mail: syun@ 123456mgh.harvard.edu
                Article
                ICU290405 00006
                10.1097/ICU.0000000000000489
                6012042
                29771749
                c1dd715b-8de3-4ff3-8c34-c49141ae1b3b
                Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

                History
                Categories
                REFRACTIVE SURGERY: Edited by Jimmy K. Lee
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                biomechanics,brillouin spectroscopy,cornea,keratoconus,refractive surgery

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