Biomechanics of the Anterior Human Corneal Tissue Investigated with Atomic Force Microscopy

Lombardo, Marco; Lombardo, Giuseppe; Carbone, Giovanni; Santo, Maria P. De; Barberi, R.; Serrao, Sebastiano

doi:10.1167/iovs.11-8720

Cited by 64 publications

(69 citation statements)

References 56 publications

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“…1 These mechanical properties stem from the constituent components of the cornea and therefore are governed by factors such as the extracellular matrix and the organization of collagen fibers. 2 The assessment of corneal biomechanical properties has a number of potential clinical applications such as improving the accuracy of IOP measurements, 3,4 the diagnosis of keratoconus (KC), 5 assessing the biomechanical effects of corneal collagen crosslinking (CXL), 6 and assessing the risk of post-LASIK ectasia. 7,8 Recently, the CorVis ST (CST; Oculus, Wetzlar, Germany) was introduced as a clinical tool for the assessment of corneal biomechanical properties in vivo.…”

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confidence: 99%

Quantitative Analysis of Corneal Energy Dissipation and Corneal and Orbital Deformation in Response to an Air-Pulse in Healthy Eyes

Vellara

Ali

Gokul

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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Citation: Vellara HR, Ali NQ, Gokul A, Turuwhenua J, Patel DV, McGhee CNJ. Quantitative analysis of corneal energy dissipation and corneal and orbital deformation in response to an airpulse in healthy eyes. Invest Ophthalmol Vis Sci. 2015;56:6941-6947. DOI:10.1167/iovs.15-17396 PURPOSE. To examine and evaluate ocular biomechanical metrics and additionally derived corneal and orbital components using a noncontact Scheimpflug-based tonometer (CorVis ST) in a population of healthy eyes. METHODS.A total of 152 eyes of 152 participants were examined by slit-lamp biomicroscopy, corneal tomography, and the CorVis ST (CST). This determined the distribution of outputs from the CST, such as deformation amplitude (DA), and additionally derived parameters, including maximum corneal deformation (MCD), maximum orbital deformation (MOD), and corneal energy dissipation (CED).RESULTS. The mean age of participants was 35.88 6 13.8 years. Deformation amplitude significantly correlated with age (r ¼ 0.24, P ¼ 0.002) but not sex or ethnicity (P > 0.05). Multiple linear regression analysis revealed significant correlations between DA and age (r ¼ 0.19, P ¼ 0.006) and DA and IOP (r ¼ À0.59, P < 0.001). Age correlated with MCD (r ¼ 0.20, P ¼ 0.01), MOD (r ¼ 0.18, P ¼ 0.03), and CED (r ¼ 0.39, P < 0.001). Males had a lower MOD than females (0.24 vs. 0.26 mm, respectively, P ¼ 0.01); however, there were no differences in MCD or CED between sexes (P > 0.05). There were no significant differences between ethnicities for MCD, MOD, and CED (P > 0.05). Multiple linear regression analysis revealed significant correlations between MCD and IOP (r ¼ À0.65, P < 0.001), CED and age (r ¼ 0.41, P < 0.001), CED and IOP (r ¼ 0.28, P ¼ 0.001), and between CED and central corneal thickness (CCT) (r ¼ À0.36, P < 0.001).CONCLUSIONS. The isolation of the corneal component (MCD) should be used when analyzing deformation characteristics in diseases that only affect the cornea. This study establishes a baseline for a population of healthy eyes. Future publications will identify differences in MCD, MOD, and CED between healthy and diseased populations.

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confidence: 99%

Quantitative Analysis of Corneal Energy Dissipation and Corneal and Orbital Deformation in Response to an Air-Pulse in Healthy Eyes

Vellara

Ali

Gokul

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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“…In order to avoid any bias due to changes in the hydration state during the experiment, the corneal tissues were kept in 20% dextran solution overnight before AFM testing. [15][16][17][36][37][38][39] Based on the studies by Hamaoui et al 36 and according to our standardized study protocol, [15][16][17] it was found that 20% dextran solution was effective in avoiding tissue swelling and maintaining corneal hydration during experimentation of riboflavin/UV-A corneal cross-linking. In this study, we indented less than 3 lm anterior stromal depth (which corresponds to the less hydrated part of the cornea; <1% total stromal thickness), and the changes of hydration as well as of indented stroma were therefore considered negligible.…”

Section: 27-29mentioning

confidence: 94%

“…[15][16][17] The mechanical properties of the anterior corneal stroma were measured using an AFM (Multimode 8 Atomic Force Microscope with Nanoscope V controller; Bruker Italy Srl, Milano, Italy) in the force spectroscopy mode according to standardized protocol used in previous studies. 15,17 Measurements were performed at 278C with the specimens immersed in 20% dextran solution, using phosphorus-doped rectangular silicon cantilevers of nominal elastic constant between 20 and 80 N/m (TESPA; Bruker Italia Srl). Dextran was used as imaging medium in order to keep the tissues at the same osmolarity as overnight storage.…”

Section: Afm Data Acquisitionmentioning

confidence: 99%

“…[15][16][17]20,21 The optical sensitivity and spring constant of each cantilever were determined for accurate measurement of the elastic modulus. Optical sensitivity was measured as the slope of the force curve taken in 20% dextran solution when the tip was in contact with a rigid surface such as a mica sheet.…”

Section: Afm Data Analysismentioning

confidence: 99%

“…In previous studies, [15][16][17] we have shown the reliability of atomic force microscopy (AFM) to probe the biomechanical properties of human corneal tissues and to evaluate the changes induced by riboflavin/UV-A corneal cross-linking on the elastic and viscoelastic properties of the anterior stroma at the submicroscopic level. The results were consistent with the notion that riboflavin/UV-A corneal cross-linking induces the formation of additional cross-linking bonds between stromal proteoglycan core proteins and collagen, as postulated by other authors.…”

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Biomechanical Strengthening of the Human Cornea Induced by Nanoplatform-Based Transepithelial Riboflavin/UV-A Corneal Cross-Linking

Labate

Lombardo

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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Citation: Labate C, Lombardo M, Lombardo G, De Santo MP. Biomechanical strengthening of the human cornea induced by nanoplatformbased transepithelial riboflavin/UV-A corneal cross-linking. Invest Ophthalmol Vis Sci. 2017;58:179-184. DOI: 10.1167/iovs.16-20813 PURPOSE. The purpose of this study was to investigate the biomechanical stiffening effect induced by nanoplatform-based transepithelial riboflavin/UV-A cross-linking protocol using atomic force microscopy (AFM).METHODS. Twelve eye bank donor human sclerocorneal tissues were investigated using a commercial atomic force microscope operated in force spectroscopy mode. Four specimens underwent transepithelial corneal cross-linking using a hypotonic solution of 0.1% riboflavin with biodegradable polymeric nanoparticles of 2-hydroxypropyl-b-cyclodextrin plus enhancers (trometamol and ethylenediaminetetraacetic acid) and UV-A irradiation with a 10 mW/cm 2 device for 9 minutes. After treatment, the corneal epithelium was removed using the Amoils brush, and the Young's modulus of the most anterior stroma was quantified as a function of scan rate by AFM. The results were compared with those collected from four specimens that underwent conventional riboflavin/UV-A corneal cross-linking and four untreated specimens. RESULTS.The average Young's modulus of the most anterior stroma after the nanoplatformbased transepithelial and conventional riboflavin/UV-A corneal cross-linking treatments was 2.5 times (P < 0.001) and 1.7 times (P < 0.001) greater than untreated controls respectively. The anterior stromal stiffness was significantly different between the two corneal crosslinking procedures (P < 0.001). The indentation depth decreased after corneal cross-linking treatments, ranging from an average of 2.4 6 0.3 lm in untreated samples to an average of 1.2 6 0.1 lm and 1.8 6 0.1 lm after nanoplatform-based transepithelial and conventional crosslinking, respectively.CONCLUSIONS. The present nanotechnology-based transepithelial riboflavin/UV-A corneal crosslinking was effective to improve the biomechanical strength of the most anterior stroma of the human cornea.

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Non‐invasive optical method for real‐time assessment of intracorneal riboflavin concentration and efficacy of corneal cross‐linking

Lombardo

Villari

Micali

et al. 2018

Journal of Biophotonics

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Keratoconus is the primary cause of corneal transplantation in young adults worldwide. Riboflavin/UV-A corneal cross-linking may effectively halt the progression of keratoconus if an adequate amount of riboflavin enriches the corneal stroma and is photo-oxidated by UV-A light for generating additional cross-linking bonds between stromal proteins and strengthening the biomechanics of the weakened cornea. Here we reported an UV-A theranostic prototype device for performing corneal cross-linking with the ability to assess corneal intrastromal concentration of riboflavin and to estimate treatment efficacy in real time. Seventeen human donor corneas were treated according to the conventional riboflavin/UV-A corneal cross-linking protocol. Ten of these tissues were probed with atomic force microscopy in order to correlate the intrastromal riboflavin concentration recorded during treatment with the increase in elastic modulus of the anterior corneal stroma. The intrastromal riboflavin concentration and its consumption during UV-A irradiation of the cornea were highly significantly correlated (R = 0.79; P = .03) with the treatment-induced stromal stiffening effect. The present study showed an ophthalmic device that provided an innovative, non-invasive, real-time monitoring solution for estimating corneal cross-linking treatment efficacy on a personalized basis.

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Biomechanics of the Anterior Human Corneal Tissue Investigated with Atomic Force Microscopy

Cited by 64 publications

References 56 publications

Quantitative Analysis of Corneal Energy Dissipation and Corneal and Orbital Deformation in Response to an Air-Pulse in Healthy Eyes

Quantitative Analysis of Corneal Energy Dissipation and Corneal and Orbital Deformation in Response to an Air-Pulse in Healthy Eyes

Biomechanical Strengthening of the Human Cornea Induced by Nanoplatform-Based Transepithelial Riboflavin/UV-A Corneal Cross-Linking

Non‐invasive optical method for real‐time assessment of intracorneal riboflavin concentration and efficacy of corneal cross‐linking

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