This study demonstrated that the novel waveform-derived indices provided by ORA have important role in the detection of early keratoconus. Furthermore, the results showed that the p1area, p2area, h1, h2, dive1, mslew1, aspect1, aplhf, dslope1, and CRF had a high degree of sensitivity and specificity in detecting early keratoconus Goebels et al.
Elham et al. They found that some parameters, such as CCT, the highest concavity radius, and DA, were significantly different between healthy corneas and keratoconus.
Studies on the corneal biomechanical properties of keratoconic eyes with different severity grades showed that both ORA and Corvis ST allowed for good differentiation between healthy eyes and keratoconic eyes with different severity grades Koh et al. Since forme fruste keratoconus eyes lacked any, or presented with very subtle changes in geometrical parameters, many built-in parameters of these devices cannot be utilized for diagnosing forme fruste keratoconus patients because of their strong correlation with corneal geometrical parameters Shen et al.
Thus, parameters directly describing the mechanical meaning could help in understanding the corneal biomechanical changes in early keratoconus patients better. In this study, both the corneal elastic modulus and S TSC were smaller in clinical keratoconus patients, which was an observation that agreed with our previous study Wang et al.
However, there was no significant difference between healthy subjects and forme fruste keratoconus patients for S TSC.
In our last study, the corneal elastic modulus was calculated, and this value was found to be less correlated with IOP than S TSC and corneal geometrical parameters Qin et al. Corneal elastic modulus showed better predictability AUC was 0. The LSD test and ROC curve analysis showed that the corneal elastic modulus was significantly smaller in the forme fruste keratoconus patients than in healthy patients. The results of the present study confirmed that the changes in corneal biomechanical properties arose in early keratoconus before the evident corneal geometry changes Kozobolis et al.
In this study, the built-in parameters provided by Corvis ST Software were also compared between forme fruste keratoconus patients and healthy subjects, and the results showed that A1T was the best predictive parameter with an AUC of 0. A1T has been found to be an important parameter to reflect corneal biomechanical properties, while it was strongly correlated with IOP Wang et al.
In this study, there was no significant difference in IOP among the three groups, and the sensitivity and specificity of the A1T were similar to those of the corneal elastic modulus, which may demonstrate that A1T can reflect corneal elastic properties under normal IOP. The corneal elastic modulus showed better predictability in diagnosing keratoconus compared with the Corvis built-in parameters. The keratoconus diagnosis model combining E, DCR parameters, and corneal Pentacam parameters by the BP neural network showed a more accurate diagnostic efficiency of Besides, the ROC curve analysis results showed that the predicted value provided by BP neural network is more sensitive to FFKC than to TBI and CBI, while additional work based on more clinical data should be done in the future for clinical applications because of the limited amount of sample in this study.
One of the limitations was that the sample number in this study is small. More subjects may be necessary to verify the results of this study. Another limitation was that the parameters related to corneal viscoelasticity were not applied to detect forme fruste keratoconus patients from healthy subjects.
Although the corneal elastic modulus showed better identifiability of forme fruste keratoconus, a great number of researchers have believed that corneal viscoelasticity is also important to diagnose KC. Thus, further study should be carried out to determine corneal viscoelastic parameters from Corvis measurements and to apply the outcome to detect KC by combining the results of this study in the future. In conclusion, the corneal elastic modulus was calculated and compared in healthy subjects, forme fruste keratoconus patients, and clinical keratoconus patients.
The corneal elastic modulus showed improved predictability in detecting forme fruste keratoconus patients compared with normal apparently healthy subjects, which might be used as an additional parameter for keratoconus diagnosis. Further study is needed to generate more accurate methods to diagnose forme fruste keratoconus patients when also combined with corneal biomechanical and corneal topography parameters.
The studies involving human participants were reviewed and approved by the Ethics Committee of the Beijing Tongren Hospital. LT and XQ contributed equally to this work. All authors read and approved the final manuscript. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors, and the reviewers.
Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. National Center for Biotechnology Information , U. Journal List Front Bioeng Biotechnol v. Front Bioeng Biotechnol.
Published online Dec Author information Article notes Copyright and License information Disclaimer. This article was submitted to Biomechanics, a section of the journal Frontiers in Bioengineering and Biotechnology. Received Aug 29; Accepted Nov 8.
The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice.
No use, distribution or reproduction is permitted which does not comply with these terms. Associated Data Data Availability Statement The raw data supporting the conclusion of this article will be made available by the authors, without undue reservation. Keywords: forme fruste keratoconus, clinical keratoconus, corneal visualization Scheimpflug technology, corneal elastic modulus, dynamic corneal response parameters.
Introduction Keratoconus KC presents as a progressive, non-inflammatory disease with a strong genetic component in which the cornea thins locally and forms into a conical shape. Methods Subjects and measurements Fifty clinical keratoconus patients 50 eyes , 36 forme fruste keratoconus patients 36 eyes , and 50 healthy subjects 50 eyes were enrolled in the study. Th The elevation of the back surface at the thinnest location Kmax Maximum keratometry from the anterior corneal surface Pachymin Pachymetry at the thinnest point.
Open in a separate window. Determination of corneal elastic modulus The method to evaluate the corneal elastic modulus has been proposed in our previous study Qin et al. Backpropagation neural network Establishment Based on the one-way ANOVA results, we combined some sensitive topometric and tomographic parameters in Pentacam of keratoconus B.
Discussion Keratoconus KC is a progressive, non-inflammatory ectatic corneal disorder in which the normal cornea thins locally and forms into a conical shape. Data Availability Statement The raw data supporting the conclusion of this article will be made available by the authors, without undue reservation. Ethics Statement The studies involving human participants were reviewed and approved by the Ethics Committee of the Beijing Tongren Hospital.
Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
References Ahearne M. Cornea 39 , — Biomechanics and Wound Healing in the Cornea. Eye Res. Biomechanical Properties of Human and Porcine Corneas.
Determination of the Modulus of Elasticity of the Human Cornea. Case Reports. Your browser does not support the video tag. Thanks to the corneal biomechanics, it is possible to measure what was previously not measurable.
This raises keratoconus diagnosis and glaucoma screening to a new level. Crucial for this: the perfect combination of biomechanical analysis, tonometry and pachymetry. What do I need biomechanics for? Watch our video to find out in only 3 minutes! In this study including more than eyes the accuracy was higher than 98 percent 2. Moreover, the clinical use of this index in case of subclinical or forme fruste keratoconus was proven in another publication.
Many of these cases could be detected by the CBI, even though no topographic or tomographic abnormalities could be observed 3. These case examples support the hypothesis that biomechanical changes occur before morphological changes are present. Cynthia J. Roberts, William J. The detection of early or subclinical forms of corneal ectasia is gaining more attention as these cases are supposed to be at high-risk for developing iatrogenic ectasia after laser vision correction.
In addition, an early detection of the disease is also important in order to perform corneal cross-linking before the vision was already affected. Currently, screening for subclinical ectasia is mainly done by corneal tomography or corneal topography. Unfortunately, based on these methods a significant amount of cases remains unrecognized, this could represent a high risk when performing refractive surgery in these normal appearing cases.
Biomechanical analysis offers a new tool to optimize the screening and to detect cases that are at high risk despite having a normal topography and normal tomography. Based on a so-called random forest algorithm — a modern machine learning approach — an overall risk score is provided to evaluate ectasia susceptibility.
A random forest algorithm consists of different uncorrelated decision trees — each using tomographic and biomechanical parameters. Each tree makes a classification being either normal or ectasia based on the input variables. The TBI finally represents the percentage, how many trees the cornea classified as normal and how many as abnormal.
In a validation study this index had the highest accuracy for the detection of subclinical keratoconus compared to all other tested methods including corneal topography and tomography 1. Pre-operatively, several screening methods exist in order to analyse the risk for developing ectasia after Laser Vision Correction. However, until now limited possibilities exist to evaluate ectasia risk post-operatively.
This is an aid for clinical decisions such as corneal crosslinking or laser touch-ups. It enables you to analyze the progression, related to a baseline measurement. Another important feature is to verify the success of treatment after corneal crosslinking. Progression of keratoconus must be detected at a very early stage if a severe loss of vision is to be prevented.
Intraocular pressure measurement will not indicate any elevated risk for glaucoma and also the optic nerve head might appear relatively normal.
In Europe up to 30 percent of primary open angle glaucoma patients have a normal intraocular pressure, in Asia the incidence of NTG is even higher. It has been shown recently that biomechanical properties can serve as an independent risk factor for NTG as the corneas of NTG patients are more deformable than age-matched healthy controls 1. Acta Ophthalmol.
The understanding of corneal biomechanical properties is an area of intensive research over the last decade now. Several experts all over the world have contributed to the understanding of the biomechanical behaviour of the cornea. Others have worked on new methods to measure biomechanical properties in vivo or ex vivo. Corneal cross-linking has been established which is based on the alteration of the biomechanical properties.
In the following section experts in the different field summarize parts of their work. Eberhard Spoerl, PhD is one of the inventors of corneal cross-linking. Since is head of the laboratory for biomechanics in the Technical University of Dresden and is investigating the biomechanical properties of the eye ball along with testing methods to stiffen the cornea.
In the following document he describes basic concepts of biomechanical properties such as the concept of elasticity and ways to measure stress strain curves ex-vivo. Download: Stress-strain measurements by strip extensiometry Prof.
Eberhard Spoerl, PhD. A visco-elastic material exhibits both elastic and viscous properties. The cornea is such a visco-elastic material. Elastic properties are mainly driven by collagen fibres, the viscous properties by the matrix between the fibres consisting of proteoglycans that cause friction.
The capability of a body to change its shape when a force is applied and to return into its original shape when the influence of the force is removed. Honey for example has a much higher viscosity than water. In opposite to elastic materials viscous material are not deformed reversible when an external force is applied, but move continuously under shear or tensile stress and do not return to their original shape.
Viscosity is a measure of its resistance against progressive deformation by shear stress or tensile stress. At a molecular level, viscosity is caused by the interaction or friction between molecules.
The higher the friction between different layers of the material the more force is needed keep the material flowing. Biomechanical properties of the cornea can be measured ex vivo in tensile tests or inflation tests.
The change in length can be plotted as a function of the applied force. In order to obtain properties independent from the shape of the material the change in length is normalized to the original length L 0. The ratio between change in length and original length is called strain. The force is also normalized to the cross sectional area on which the fore is applied. The ratio between force and cross sectional area is called stress.
In a spring the relationship between stress and strain is linear. The cornea exhibits a hyper-elastic behaviour which means that with increasing strain more force is needed to deform the cornea.
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