在体角膜生物力学性能评估前沿:应力应变指数SSI及其现状

目的探究新型角膜生物力学参数-应力应变指数SSI评估主流角膜屈光手术和角膜胶原交联术CXL的生物力学响应的有效性。方法临床收集行TPRK、FS-LASIK和SMILE手术的近视患者62、80和60例,行CXL的圆锥角膜KC患者55例。于术前和术后(近视患者:1、3及6月;KC患者:6、12月)行Corvis ST可视化生物力学分析仪测量,获取SSI和主要在体角膜生物力学性能参数DCRs。统计学分析手术前后SSI的变化及其与角膜厚度CCT、眼内压IOP和其他DCRs的相关性。

Consideration of corneal biomechanics in the diagnosis and management of keratoconus: is it important?

Keratoconus is a bilateral,non-inflammatory,degenerative corneal disease.The occurrence and development of keratoconus is associated with corneal thinning and conical protrusion,which causes irregular astigmatism.With the disruption of the collagen organization,the cornea loses its shape and function resulting in progressive visual degradation.Currently,corneal topography is the most important tool for the diagnosis of keratoconus,which may lead to false negatives among the patient population in the subclinical phase.However,it is now hypothesised that biomechanical destabilisation of the cornea may take place ahead of the topographic evidence of keratoconus,hence possibly assisting with disease diagnosis and management.This article provides a review of the definition,diagnosis,and management strategies for keratoconus based on corneal biomechanics.

Human adipose derived stem cells are superior to human osteoblasts (HOB) in bone tissue engineering on a collagen-fibroin-ELR blend

The ultrastructure of the bone provides a unique mechanical strength against compressive, torsional andtensional stresses. An elastin-like recombinamer (ELR) with a nucleation sequence for hydroxyapatitewas incorporated into films prepared from a collagen-silk fibroin blend carrying microchannel patternsto stimulate anisotropic osteogenesis. SEM and fluorescence microscopy showed the alignment ofadipose-derived stem cells (ADSCs) and the human osteoblasts (HOBs) on the ridges and in the groovesof microchannel patterned collagen-fibroin-ELR blend films. The Young's modulus and the ultimatetensile strength (UTS) of untreated films were 0.58 ± 0.13 MPa and 0.18 ± 0.05 MPa, respectively. After 28days of cell culture, ADSC seeded film had a Young's modulus of 1.21 ± 0.42 MPa and UTS of0.32 ± 0.15 MPa which were about 3 fold higher than HOB seeded films. The difference in Young'smodulus was statistically significant (p: 0.02). ADSCs attached, proliferated and mineralized better thanthe HOBs. In the light of these results, ADSCs served as a better cell source than HOBs for bone tissueengineering of collagen-fibroin-ELR based constructs used in this study. We have thus shown theenhancement in the tensile mechanical properties of the bone tissue engineered scaffolds by usingADSCs.

Fast segmentation of anterior segment optical coherence tomography images using graph cut

Background:Optical coherence tomography(OCT)is a non-invasive imaging system that can be used to obtain images of the anterior segment.Automatic segmentation of these images will enable them to be used to construct patient specific biomechanical models of the human eye.These models could be used to help with treatment planning and diagnosis of patients.Methods:A novel graph cut technique using regional and shape terms was developed.It was evaluated by segmenting 39 OCT images of the anterior segment.The results of this were compared with manual segmentation and a previously reported level set segmentation technique.Three different comparison techniques were used:Dice’s similarity coefficient(DSC),mean unsigned surface positioning error(MSPE),and 95%Hausdorff distance(HD).A paired t-test was used to compare the results of different segmentation techniques.Results:When comparison with manual segmentation was performed,a mean DSC value of 0.943±0.020 was achieved,outperforming other previously published techniques.A substantial reduction in processing time was also achieved using this method.Conclusions:We have developed a new segmentation technique that is both fast and accurate.This has the potential to be used to aid diagnostics and treatment planning.

角膜生物力学检测方法介绍

力学问题贯穿于生物体的整个生命过程,对生物体中的力学问题进行定量分析,产生了生物学和物理学的交叉学科——生物力学;其研究重点是生理学、医学有关的力学问题.随着医疗检查诊断技术的发展,人们逐渐认识到眼生物力学性能的重要性.角膜生物力学性能测量在角膜疾病诊断、角膜屈光手术效果预测及眼内压测量等方面都具有非常重要的意义.角膜组织主要由致密交错的胶原纤维束和细胞外基质组成,其生物力学特征颇为复杂,表现为非线弹性、各向异性、黏弹性、区域差异性和年龄相关性等特征.生物力学性能测量的关键是找寻描述生物组织力学特性的本构方程,方程内包含的参量为本构参量,包括应力、应变和弹性模量等.根据测量时生物材料初始状态的差异,角膜生物力学性能参数的测量方法可分为离体和在体测量2种.虽然在体测量具有更为广阔的临床应用前景,然而当前在体测量技术并不成熟.临床常用仪器ORA和Corvis无法提供本构参量,尚不能作为眼生物学性能测量的标准实验手段.笔者就目前国际上常见几种离体测量技术的原理及发展做了详细介绍,以方便相关研究者更好地进行选择,这其中包括：轴向拉伸试验、基于薄壳理论的简单离体角膜膨胀试验、基于逆向建模技术的离体角膜膨胀试验和同样基于逆向建模技术的离体全眼球膨胀试验.将切成条状的角膜试件固定于材料试验机进行单向或双向拉伸,获取本构参量,是为轴向拉伸试验.最早用于角膜生物力学性能的测量,此方法设备简单,容易操作,但对角膜的生理结构破坏较大,测量值存在不小的误差.基于薄壳理论的简单离体角膜膨胀试验：将完整分离的角膜试件固定于填充有液体的前房模拟装置,模拟眼内压对角膜后表面施压并实时记录角膜形变;根据薄壳理论推导公式计算得到角膜组织的本构关系方程.离体角膜膨胀试验保持了角膜组织结构的完整性和提供更接近于角膜生理状态的施力方式,但仍存在破坏角巩膜连续解剖结构、机械固定方式导致应力集中等缺点.因薄壳理论的球形角膜结构和均质性生物力学性能假设限制了膨胀试验结果的精确性,通过构建具有个性化几何特征的角膜有限元生物力学模型,模拟角膜在眼内压力作用下的形变过程,将膨胀试验测量所得眼内压和角膜形变关系曲线作为目标曲线,不断调整本构方程系数使得模拟的角膜形变曲线和目标曲线逐渐逼近,反复迭代运算得到角膜组织本构参量的最优化结果,称为基于逆向建模技术的离体角膜嘭胀试验,具有较好的试验测量精度和可重复性.离体全眼球膨胀试验延续了角巩膜完整的曲面形状和采取接近眼球生理的施力方式,是相对最接近角膜生理状态的测量方法,但该试验也存在设备制作复杂、操作繁琐等缺点.如能在试验过程中提供接近生理状态的眼球支撑方式,解决角巩膜随眼内压力变化过程形变数据的准确提取等技术难题,有望实现对角巩膜组织区域差异性、各向异性及黏弹性等生物力学特征的一体化定量测量分析,具有非常广阔的应用前景.

Ex vivo testing of intact eye globes under inflation conditions to determine regional variation of mechanical stiffness

Background:The eye globe exhibits significant regional variation of mechanical behaviour.The aim of this present study is to develop a new experimental technique for testing intact eye globes in a form that is representative of in vivo conditions,and therefore suitable for determining the material properties of the complete outer ocular tunic.Methods:A test rig has been developed to provide closed-loop control of either applied intra-ocular pressure or resulting apical displacement;measurement of displacements across the external surface of the eye globe using high-resolution digital cameras and digital image correlation software;prevention of rigid-body motion and protection of the ocular surface from environmental drying.The method has been demonstrated on one human and one porcine eye globe,which were cyclically loaded.Finite element models based on specimen specific tomography,free from rotational symmetry,were used along with experimental pressure-displacement data in an inverse analysis process to derive the mechanical properties of tissue in different regions of the eye’s outer tunic.Results:The test method enabled monitoring of mechanical response to intraocular pressure variation across the surface of the eye globe.For the two eyes tested,the method showed a gradual change in the sclera’s stiffness from a maximum at the limbus to a minimum at the posterior pole,while in the cornea the stiffness was highest at the centre and lowest in the peripheral zone.Further,for both the sclera and cornea,the load–displacement behaviour did not vary significantly between loading cycles.Conclusions:The first methodology capable of mechanically testing intact eye globes,with applied loads and boundary conditions that closely represent in vivo conditions is introduced.The method enables determination of the regional variation in mechanical behaviour across the ocular surface.

In vivo study of corneal responses to increased intraocular pressure loading

Background:The cornea is responsible for two-thirds of the eye's refractive power which is a function of the shape and refractive index.The aim of this present study is to examine human eyes in vivo for corneal shape changes in response to short-term elevation in intraocular pressure.Methods:Videokeratographic and tonometric assessments at baseline were compared with the same assessments when intraocular pressure was elevated to approximately double(199±22%)the baseline levels using ophthalmodynamometer applanation of the sclera.Composite maps of the cornea and limbus were created by combining topographical assessments for central,nasal,temporal,inferior and superior fixation.Numerical finiteelement simulations were custom built for each subject and the stiffness distribution across corneal surface modified to achieve matches between simulated and experimental data.Results:The stiffness distributions required to achieve simulation-experimental matches showed a consistent trend with the 2.5 mm annulus bounded by the limbus showing a mean stiffness reduction of 47.3±10.8%compared with the central cornea(P=0.001).Conclusions:Corneal structure appears to provide the central cornea with a greater stiffness compared with the peripheral cornea and associated greater tolerance to elevation in intraocular pressure,consistent with the need for stable corneal refraction and vision.The method adopted to examine corneal biomechanical performance in vivo may have applications in additional studies.

Unintended changes in ocular biometric parameters during a 6-month follow-up period after FS-LASIK and SMILE

Background:Corneal refractive surgery has become reliable for correcting refractive errors,but it can induce unintended ocular changes that alter refractive outcomes.This study is to evaluate the unintended changes in ocular biometric parameters over a 6-month follow-up period after femtosecond laser-assisted laser in situ keratomileusis(FS-LASIK)and small incision lenticule extraction(SMILE).Methods:156 consecutive myopic patients scheduled for FS-LASIK and SMILE were included in this study.Central corneal thickness(CCT),mean curvature of the corneal posterior surface(K_(pm)),internal anterior chamber depth(IACD)and the length from corneal endothelium to retina(ER)were evaluated before and after surgery over a 6-month period.Results:Both the FS-LASIK and SMILE groups(closely matched at the pre-surgery stage)experienced flatter Kpm,shallower IACD and decreased ER 1 week post-surgery(P<0.01),and these changes were larger in FS-LASIK than in SMILE group.During the 1 week to 6 months follow up period,K_(pm),IACD and ER remained stable unlike CCT which increased significantly(P<0.05),more in the FS-LASIK group.Conclusions:During the follow up,the posterior corneal surface became flatter and shifted posteriorly,the anterior chamber depth and the length from the corneal endothelium to retina decreased significantly compared with the pre-surgery stage.These unintended changes in ocular biometric parameters were greater in patients undergoing FS-LASIK than SMILE.The changes present clear challenges for IOL power calculations and should be considered to avoid affecting the outcome of cataract surgery.

Biomechanical diagnostics of the cornea

Corneal biomechanics has been a hot topic for research in contemporary ophthalmology due to its prospective applications in diagnosis,management,and treatment of several clinical conditions,including glaucoma,elective keratorefractive surgery,and different corneal diseases.The clinical biomechanical investigation has become of great importance in the setting of refractive surgery to identify patients at higher risk of developing iatrogenic ectasia after laser vision correction.This review discusses the latest developments in the detection of corneal ectatic diseases.These developments should be considered in conjunction with multimodal corneal and refractive imaging,including Placido-disk based corneal topography,Scheimpflug corneal tomography,anterior segment tomography,spectral-domain optical coherence tomography(SD-OCT),very-high-frequency ultrasound(VHF-US),ocular biometry,and ocular wavefront measurements.The ocular response analyzer(ORA)and the Corvis ST are non-contact tonometry systems that provide a clinical corneal biomechanical assessment.More recently,Brillouin optical microscopy has been demonstrated to provide in vivo biomechanical measurements.The integration of tomographic and biomechanical data into artificial intelligence techniques has demonstrated the ability to increase the accuracy to detect ectatic disease and characterize the inherent susceptibility for biomechanical failure and ectasia progression,which is a severe complication after laser vision correction.

Accuracy and reliability of orthogonal polynomials in representing corneal topography

Fitting of corneal topography data to analytical surfaces has been necessary in many clinical and experimental applications,yet absolute superiority of fitting methods was still unclear,and their overfitting risks were not well studied.This study aimed to evaluate the accuracy and reliability of orthogonal polynomials as fitting routines to represent corneal topography.Four orthogonal polynomials,namely,Zernike polynomials(ZPs),pseudo-Zernike polynomials(PZPs),Gaussian-Hermite polynomials(GHPs)and Orthogonal Fourier-Mellin polynomials(OFMPs),were employed to fit anterior and posterior corneal topographies collected from 200 healthy and 174 keratoconic eyes using Pentacam topographer.The fitting performance of these polynomials were compared,and the potential overfitting risks were assessed through a prediction exercise.The results showed that,except for low orders,the fitting performance differed little among polynomials with orders
10 regarding surface reconstruction(RMSEs~0.3μm).Anterior surfaces of normal corneas were fitted more efficiently,followed by those of keratoconic corneas,then posterior corneal surfaces.The results,however,revealed an alarming fact that all polynomials tended to overfit the data beyond certain orders.GHPs,closely followed by ZPs,were the most robust in predicting unmeasured surface locations;while PZPs and especially OFMPs overfitted the surfaces drastically.Order 10 appeared to be optimum for corneal surfaces with 10-mm diameter,ensuring accurate reconstruction and avoiding overfitting.The optimum order however varied with topography diameters and data resolutions.The study concluded that continuing to use ZPs as fitting routine for most topography maps,or using GHPs instead,remains a good choice.Choosing polynomial orders close to the topography diameters(millimeters)is generally suggested to ensure both reconstruction accuracy and prediction reliability and avoid overfitting for both normal and complex(e.g.,keratoconic)corneal surfaces.

Review of in-vivo characterisation of corneal biomechanics

The study of corneal biomechanics in vivo has been evolving fast in recent years.While an organised corneal structure is necessary for its transparency,resistance to occasional external insults and bearing the intraocular pressure(IOP),which several clinically relevant events can disturb.This review focuses on three techniques that are available for clinical use,namely the Ocular Response Analyzer(Reichert Ophthalmic Instruments,Buffalo,NY,USA),the Corvis ST(Oculus Optikgerate GmbH,Wetzlar,Germany)and the Brillouin Optical Scattering System(Intelon Optics Inc.,Lexington,MA,USA).The principles and the main parameters of each device are discussed along with their strategies to improve accuracy in the IOP measurement,corneal ectasia diagnosis,evaluation of corneal cross-linking procedures,and planning of corneal refractive surgeries.

Review of ex-vivo characterisation of corneal biomechanics

The evaluation of the corneal biomechanical behaviour has important clinical applications.To name a few,the accuracy of the intraocular pressure measurement,the study of corneal ectatic diseases and the assessment and optimisation of corneal surgical procedures are all highly influenced by corneal biomechanics.Over the last 45 years different ex-vivo methods were developed to study corneal biomechanical behaviour.Different tissue maintenance,support,loading systems,as well as different monitoring strategies of corneal deformations were employed.In this review,the most important and commonly used methods are outlined,including strip extensiometry,inflation,compression,indentation and tissue separation testing.Their particularities,applications,pros and cons and main applications are discussed.