Linear dichroism of the retinal nerve fiber layer expressed with Mueller matrices

An electro-optic device is used that permits the measurement of polarized absorption spectra (linear dichroism). The change of the polarization state of a light beam brought about by passage through the optic elements of a dichrograph are described mathematically by a transformation of the Stokes vector. The polarization or absorption properties of the optical elements are described by the Mueller matrices. The dichroic properties of sheep retina and cornea are studied in vitro.     

Nonlinear analysis of static axisymmetric deformation of the human cornea

This paper presents a simple mechanics model for analyzing the stresses, strains and displacements of the human cornea under the action of the intraocular pressure. The analysis is performed under the assumptions that when the cornea undergoes small displacements the stress–strain constitutive relation includes an isotropic, linear material of ground substance and an orthotropic, nonlinear material of collagen fibrils. The present results highlight the influence of corneal geometry and its local microstructural organisation on the corneal overall mechanical properties.     

Differences between real and predicted corneal shapes after aspherical corneal ablation

We study the differences between real and expected corneal shapes, using an aspherical ablation algorithm with a known equation and avoiding the limitation imposed by most studies of refractive surgery in which the ablation equations are not known. We have calculated the theoretical corneal shape predicted by this algorithm, comparing this shape with the real corneal topography. The results indicate that the deviations that appear in the corneal shape are significant for visual performance and for the correction of eye aberrations. If we include in this analysis the effect of reflection losses and nonnormal incidence on the cornea, we can reduce corneal differences, but they will remain significant. These results confirm that it is essential to minimize corneal differences to achieve effective correction in refractive surgery.     

Application of structural analysis to the mechanical behaviour of the cornea.

Structural engineering analysis tools have been used to improve the understanding of the biomechanical behaviour of the cornea. The research is a multi-disciplinary collaboration between structural engineers, mathematical and numerical analysts, ophthalmologists and clinicians. Mathematical shell analysis and nonlinear finite-element modelling have been used in conjunction with laboratory experiments to study the behaviour of the cornea under different loading states and to provide improved predictions of the mechanical response to disease and injury. The initial study involved laboratory tests and mathematical back analysis to determine the corneal material properties and topography. These data were then used to facilitate the construction of accurate finite-element models that are able to reliably trace the performance of cornea upon exposure to disease, injury or elevated intra-ocular pressure. The models are being adapted to study the response to keratoconus (a disease causing loss of corneal tissue) and to tonometry procedures, which are used to measure the intra-ocular pressure. This paper introduces these efforts as examples of the application of structural engineering analysis tools and shows their potential in the field of corneal biomechanics.     

Comparative study of corneal strip extensometry and inflation tests.

Strip extensometry tests are usually considered less reliable than trephinate inflation tests in studying corneal biomechanics. In spite of the evident simplicity of strip extensometry tests, several earlier studies preferred inflation tests in determining the constitutive relationship of the cornea and its other material properties, such as Young's modulus and the hysteresis behaviour. In this research, the deficiencies of the strip tests are discussed and a mathematical procedure presented to take account of these deficiencies when obtaining the corneal material properties. The study also involves testing 10 pairs of porcine corneas using both strip extensometry and trephinate inflation techniques and the results are subjected to mathematical back analysis in order to determine the stress-strain behaviour. The behaviour obtained from the strip extensometry tests and using the new mathematical analysis procedure is shown to match closely the inflation test results.     

Synthesis, characterization, and in vitro evaluation of a hydrogel-based corneal onlay

Blindness due to opacity of the cornea is treated by corneal transplantation with donor tissue. Due to the limited supply of suitable donor corneas, the need for synthetic corneal equivalents is clear. Herein we report the design and in vitro characterization of a hydrogel-based implant; this implant will serve as a permanent, transparent, space-filling onlay with a two-layer design that mimics the native corneal stratification to support surface epithelialization and foster integration with the surrounding tissue. The top layer of the implant was composed of a 2-hydroxyethylmethacrylate hydrogel containing methacrylic acid as the co-monomer (HEMA-co-MAA) with tunable dimensions and compressive modulus ranging from 700-1000 kPa. The bottom layer, which constitutes the bulk of the implant and is designed to provide integration with the corneal stroma, is a dendrimer hydrogel with high water content and compressive modulus ranging from 500-1200 kPa. Both hydrogels were found to possess optical and diffusion properties similar to those of the human cornea. In addition, composite implants with uniform and structurally sound interfaces were formed when the gels were sequentially injected and cross-linked in the same mold. HEMA-co-MAA hydrogels were covalently modified with type I collagen to enable corneal epithelial cell adhesion and spreading that was dependent upon the collagen coating density but independent of hydrogel stiffness. Similarly, dendrimer hydrogels supported the adhesion and spreading of corneal fibroblasts upon modification with the adhesion ligand arginine-glycine-aspartic acid (RGD). Fibroblast adhesion was not dependent upon dendrimer hydrogel stiffness for the formulations studied and, after in vitro culture for 4 weeks, fibroblasts remained able to adhere to and conformally coat the hydrogel surface. In conclusion, the tunable physical properties and structural integrity of the laminated interface suggests that this design is suitable for further study. The judicious tuning of material properties and inclusion of bioactive moieties is a promising strategy for promotion of implant epithelialization and tissue integration.     

Property-based design: optimization and characterization of polyvinyl alcohol (PVA) hydrogel and PVA-matrix composite for artificial cornea

Each approach for artificial cornea design is toward the same goal: to develop a material that best mimics the important properties of natural cornea. Accordingly, the selection and optimization of corneal substitute should be based on their physicochemical properties. In this study, three types of polyvinyl alcohol (PVA) hydrogels with different polymerization degree (PVA1799, PVA2499 and PVA2699) were prepared by freeze-thawing techniques. After characterization in terms of transparency, water content, water contact angle, mechanical property, root-mean-square roughness and protein adsorption behavior, the optimized PVA2499 hydrogel with similar properties of natural cornea was selected as a matrix material for artificial cornea. Based on this, a biomimetic artificial cornea was fabricated with core-and-skirt structure: a transparent PVA hydrogel core, surrounding by a ringed PVA-matrix composite skirt that composed of graphite, Fe-doped nano hydroxyapatite (n-Fe-HA) and PVA hydrogel. Different ratio of graphite/n-Fe-HA can tune the skirt color from dark brown to light brown, which well simulates the iris color of Oriental eyes. Moreover, morphologic and mechanical examination showed that an integrated core-and-skirt artificial cornea was formed from an interpenetrating polymer network, no phase separation appeared on the interface between the core and the skirt.     

眼球系统中关键屈光元件的光学模型研究

角膜和晶状体是人眼光学系统中两个关键的屈光元件,为了理解眼内各介质和整个眼球的屈光状态以及视网膜上的成像,有利于眼科临床方面的应用,需要分别对二者进行光学特性模型的分析与研究。根据角膜和晶状体的光学特性,应用光学设计软件Zemax和有关的数学工具,从光学成像角度,分别对角膜和晶状体模型进行研究:基于结合人眼光学模型的角膜双二次曲面模型的建立方法,统计分析了我国人眼实测角膜参数的数据;通过对晶状体折射率分布特点的分析,分别在轴向和径向上进行了综合分析。最后给出了符合我国人眼特点的角膜面型的统计数值,完善了我国人眼角膜光学模型的建立;获得了形式简单且能够表示晶状体折射率分布一般特征的梯度渐变模型表达式。基于收集的我国人眼实测数据的角膜面型模型和晶状体梯度渐变形式的折射率模型,为解决人眼光学系统研究中的关键问题提供了新的方案和思路。     

Fabrication and characters of a corneal endothelial cells scaffold based on chitosan

A novel chitosan-based membrane that made of hydroxyethyl chitosan, gelatin and chondroitin sulfate was used as a carrier of corneal endothelial cells. The characteristics of the blend membrane including transparency, equilibrium water content, ion and glucose permeability were determined. The results showed that the optical transparency of the membrane was as good as the natural human cornea. The water content of this scaffold was 81.32% which was remarkably close to the native cornea. The membrane had a good ion permeability and its glucose permeability was even higher than natural human cornea. The cultured rabbit corneal endothelial cells formed a monolayer on the membrane. The results demonstrated that the membrane was suitable for corneal endothelial cells to attach and grow on it. In addition, the membranes in vivo could be degraded steadily with less inflammation and showed a good histocompatibility. These results demonstrated that the hydroxyethyl chitosan-chondroitin sulfate-gelatin blend membrane can potentially be used as a carrier for corneal endothelial cell transplantation.     

Measurements of the corneal birefringence with a liquid-crystal imaging polariscope

An imaging polariscope has been used to analyze the spatially resolved polarization properties of living human corneas. The apparatus is a modified double-pass setup, incorporating a liquid-crystal modulator in the analyzer pathway. Keeping the incident polarization state fixed (first passage), we recorded a series of three images of the pupil's plane corresponding to independent polarization states of the analyzer unit. Azimuth and retardation at each point of the cornea were calculated from those images. Results show that the magnitude of retardation increases along the radius toward the periphery of the cornea. Left-right eye symmetry in retardation was also found. Maps of azimuth indicate that the direction of the corneal slow axis is nasally downward.     

Preparation and properties of a chitosan-based carrier of corneal endothelial cells

A novel chitosan-based membrane that was made of hydroxypropyl chitosan, gelatin and chondroitin sulfate was used as a carrier of corneal endothelial cells. The characteristics of the blend membrane, such as transparency, equilibrium water content, permeability, mechanical properties, protein absorption ability, hydrophilicity and surface morphology, were determined. To study the effects of the membrane on cell attachment and growth, rabbit corneal endothelial cells were cultured on this artificial membrane. The biodegradability and biocompatibility of the blend membrane were in vivo evaluated by its implantation into the muscle of the rats. Glucose permeation results demonstrated that the blend membrane had higher glucose permeability than natural human cornea. Scanning electron microscopy (SEM) analysis of the membranes demonstrated that no fibrils were observed. As a result, the optical transparency of the membrane was as good as the natural human cornea. The average value of tensile strength of the membrane was 13.71 MPa for dry membrane and 1.48 MPa for wet membrane. The value of elongation at break of the wet was 45.64%. The cultured rabbit corneal endothelial cells formed a monolayer on the blend membrane which demonstrated that the membrane was suitable for corneal endothelial cells to attach and grow. In addition, the membranes in vivo showed a good bioabsorption property. The mild symptoms of inflammation at sites of treatment could be resolved as the implant was absorbed by the host. The results of this study demonstrated that the hydroxypropyl chitosan-chondroitin sulfate-gelatin blend membrane can potentially be used as a carrier for corneal endothelial cell transplantation.     

Transverse depth-dependent changes in corneal collagen lamellar orientation and distribution

It is thought that corneal surface topography may be stabilized by the angular orientation of out-of plane lamellae that insert into the anterior limiting membrane. In this study, micro-focus X-ray scattering data were used to obtain quantitative information about lamellar inclination (with respect to the corneal surface) and the X-ray scatter intensity throughout the depth of the cornea from the centre to the temporal limbus. The average collagen inclination remained predominantly parallel to the tissue surface at all depths. However, in the central cornea, the spread of inclination angles was greatest in the anterior-most stroma (reflecting the increased lamellar interweaving in this region), and decreased with tissue depth; in the peripheral cornea inclination angles showed less variation throughout the tissue thickness. Inclination angles in the deeper stroma were generally higher in the peripheral cornea, suggesting the presence of more interweaving in the posterior stroma away from the central cornea. An increase in collagen X-ray scatter was identified in a region extending from the sclera anteriorly until about 2 mm from the corneal centre. This could arise from the presence of larger diameter fibrils, probably of scleral origin, which are known to exist in this region. Incorporation of this quantitative information into finite-element models will further improve the accuracy with which they can predict the biomechanical response of the cornea to pathology and refractive procedures.     

Modelling the gravitational sag of the cornea and the subsequent quality of the refracted image

This paper presents model asymmetries in the topography of the human cornea arising from linear gravitational distributions of the intraocular pressure. Equations for the corneal radius of curvature were used to provide an indication of the gravitational sag of the cornea when the head is in an upright position. In such case, corneal astigmatism is found along the optic axis of the eye. Ray paths inclined at a particular angle to the optic axis produce images (spot diagrams) which show a significant reduction in corneal astigmatism.     

Corneal Critical Barrier against the Penetration of Dexamethasone and Lomefloxacin Hydrochloride: Evaluation by the Activation Energy for Drug Partition and Diffusion in Cornea

The cornea is a solid barrier against drug permeation. We searched the critical barrier of corneal drug permeation using a hydrophobic drug, dexamethasone (DM), and a hydrophilic drug, lomefloxacin hydrochloride (LFLX). The activation energies for permeability of DM and LFLX across the intact cornea were 88.0 and 42.1 kJ/mol, respectively. Their activation energies for permeability across the cornea without epithelium decreased to 33.1 and 16.6 kJ/mol, respectively. The results show that epithelium is the critical barrier on the cornea against the permeation of a hydrophobic drug of DM as well as a hydrophilic drug of LFLX. The activation energy of partition for DM (66.8 kJ/mol) was approximately 3-fold larger than that of diffusion (21.2 kJ/mol). The results indicate that the partition for the hydrophobic drug of DM to the corneal epithelium is the primary barrier. Thermodynamic evaluation of activation energy for the drug permeation parameters is a good approch to investigate the mechanism of drug permeability.     

Corneal critical barrier against the penetration of dexamethasone and lomefloxacin hydrochloride: evaluation by the activation energy for drug partition and diffusion in cornea

The cornea is a solid barrier against drug permeation. We searched the critical barrier of corneal drug permeation using a hydrophobic drug, dexamethasone (DM), and a hydrophilic drug, lomefloxacin hydrochloride (LFLX). The activation energies for permeability of DM and LFLX across the intact cornea were 88.0 and 42.1 kJ/mol, respectively. Their activation energies for permeability across the cornea without epithelium decreased to 33.1 and 16.6 kJ/mol, respectively. The results show that epithelium is the critical barrier on the cornea against the permeation of a hydrophobic drug of DM as well as a hydrophilic drug of LFLX. The activation energy of partition for DM (66.8 kJ/mol) was approximately 3-fold larger than that of diffusion (21.2 kJ/mol). The results indicate that the partition for the hydrophobic drug of DM to the corneal epithelium is the primary barrier. Thermodynamic evaluation of activation energy for the drug permeation parameters is a good approch to investigate the mechanism of drug permeability.     

Penetration enhancers and ocular bioadhesives: two new avenues for ophthalmic drug delivery

This review is focused on the two avenues of development that promise a major impact on future ocular drug therapeutics: bioadhesives, including hydrogels and other agents like carbopols, polyacrylic acids, chitosan, etc., and penetration enhancers, including different surfactants, calcium chelators, etc. The capacity of some polymers to adhere to the mucin coat covering the conjunctiva and the corneal surface of the eye forms the basis for ocular mucoadhesion. These systems markedly prolong the residence time of a drug in the conjunctival sac, since clearence is now controlled by the much slower rate of mucus turnover rather than the tear turnover rate. But improving the corneal drug retention alone is inadequate in bringing about a significant improvement of drug bioavailability. Another approach consists of transiently increasing the pentration characteristics of the cornea with appropriate substances, known as penetration enhancers or absorption promoters. The main aim of this article is to give an insight into the potential application of mucoadhesives and corneal penetration enhancers for the conception of innovative opthalmic delivery appraoches, to decrease the systemic side effects, and create a more focused effect, which may be achieved with lower doses of the drug. Ophthalmic formulations based on these mucoadhesives and penetration enhancers are simple to manufacture and exhibit an excellent tolerance when administered into the cornea. The use of the former considerably prolongs the corneal contact time and the use of the latter increases the rate and amount of drug transport. The various corneal epithelial barriers along with the major routes of transport of drugs are discussed. The article includes a list of the various substances in use or under investigation for the aforementioned properties, along with their mechanisms of action. A fair appraisal of the subject with regard to these two therapeutic approaches and any expected ill effects has been made.     

Conditions for polarization elements to be dichroic and birefringent

The polarization of light when it passes through optical media can change as a result of change in the amplitude (dichroism) or phase shift (birefringence) of the electric vector. The anisotropic properties of media can be determined from these two optical features. We derive the conditions required for polarization elements to be dichroic and birefringent. Our derivation starts from commonly accepted assumptions for dichroism and birefringence. Our main conclusions are that (i) the generalized Jones matrix for dichroic elements has in general nonorthogonal eigenpolarizations and (ii) in the general case, the birefringent and dichroic properties of polarization elements have no direct association with the corresponding phase and dichroic polar forms derived in the polar decomposition of the polarization elements' Jones matrices.     

Visco-elastic and thermal-induced damaging in time-dependent reshaping of human cornea after conductive keratoplasty

With the aim of investigating the role played by both the radiofrequency-induced thermal damaging and the viscoelasticity of the tissue in human cornea surface reshaping—time dependent key factors for the success of the surgical outcome in the short-term post-intervention period—the Conductive Keratoplasty (CK, a surgical technique used for the correction of farsightedness) has been simulated with reference to the protocol adopted for moderate hyperopia. By means of a transient thermal analysis, the amount of the local thermal-induced tissue damaging has been computed in order to remap the constitutive properties of the corneal tissue. Successively, a mechanical non-linear analysis has been performed for predicting the corneal curvature around the optical zone during the post-surgery period. The study aims to contribute some firm thermo-mechanical roots to better understand the corneal tissue response to thermal insults and its reshaping predictability in a long period.     

Effect of the sterilization method on the properties of Bombyx mori silk fibroin films

We have compared the effects of different sterilization techniques on the properties of Bombyx mori silk fibroin thin films with the view to subsequent use for corneal tissue engineering. The transparency, tensile properties, corneal epithelial cell attachment and degradation of the films were used to evaluate the suitability of certain sterilization techniques including gamma-irradiation (in air or nitrogen), steam treatment and immersion in aqueous ethanol. The investigations showed that gamma-irradiation, performed either in air or in a nitrogen atmosphere, did not significantly alter the properties of films. The films sterilized by gamma-irradiation or by immersion in ethanol had a transparency greater than 98% and tensile properties comparable to human cornea and amniotic membrane, the materials of choice in the reconstruction of ocular surface. Although steam-sterilization produced stronger, stiffer films, they were less transparent, and cell attachment was affected by the variable topography of these films. It was concluded that gamma-irradiation should be considered to be the most suitable method for the sterilization of silk fibroin films, however, the treatment with ethanol is also an acceptable method.     

Numerical model of optical coherence tomographic vibrography imaging to estimate corneal biomechanical properties

Most techniques measuring corneal biomechanics in vivo are biased by side factors. We demonstrate the ability of optical coherence tomographic (OCT) vibrography to determine corneal material parameters, while reducing current prevalent restrictions of other techniques (such as intraocular pressure (IOP) and thickness dependency). Modal analysis was performed in a finite-element (FE) model to study the oscillation response in isolated thin corneal flaps/eye globes and to analyse the dependency of the frequency response function on: corneal elasticity, viscoelasticity, geometry (thickness and curvature), IOP and density. The model was verified experimentally in flaps from three bovine corneas and in two enucleated porcine eyes using sound excitation (100–110 dB) together with a phase-sensitive OCT to measure the frequency response function (range 50–510 Hz). Simulations showed that corneal vibration in flaps is sensitive to both, geometrical and biomechanical parameters, whereas in whole globes it is primarily sensitive to corneal biomechanical parameters only. Calculations based on the natural frequency shift revealed that flaps of the posterior cornea were 0.8 times less stiff than flaps from the anterior cornea and cross-linked corneas were 1.6 times stiffer than virgin corneas. Sensitivity analysis showed that natural vibration frequencies of whole globes were nearly independent from corneal thickness and IOP within the physiological range. OCT vibrography is a promising non-invasive technique to measure corneal elasticity without biases from corneal thickness and IOP.