Multiparameter correction equation for Goldmann applanation tonometry.

PURPOSE: To develop a correction factor to improve the accuracy of intraocular pressure (IOP) measurements made by the Goldmann applanation tonometer (GAT), which considers the combined effects of variations in central corneal thickness (CCT), central anterior curvature (R), age, and the IOP level itself. METHODS: Nonlinear numerical simulations based on the finite element method were used to represent corneal behavior under the effect of IOP and external tonometric pressure. The simulations considered various biomechanical corneal properties including the cornea's nonuniform thickness, elliptical topography, weak stromal interlamellar cohesion, low epithelial and endothelial stiffness, and hyperelastic and hysteretic material behavior. The simulations were used to model the GAT procedure on corneas to obtain a correction equation based on the values of CCT, R, age, and IOP measured using GAT (IOPG). The efficiency of the equation in reducing the effects of corneal parameters on IOPG measurements was also assessed using an independent clinical database. RESULTS: The individual effects of variations in CCT, R, and age were estimated at 1.66 mm Hg/100 µ of CCT, 0.89 mm Hg/1 mm of R, and 0.12 mm Hg/decade of age. The correction equation reduced the association between clinical IOP measurements and corneal parameters with r2 reducing from 11.8 to 0.02%. CONCLUSIONS: The GAT correction factor can consider the combined effect of variations in corneal thickness, curvature, age, and IOP. The factor could significantly reduce the reliance of IOPG measurements on corneal stiffness parameters.

Regional variation in the biomechanical properties of the human sclera.

The study aimed to determine the variation in thickness and biomechanical properties between the different regions of the human sclera. Thickness measurements were carried out along eight meridian lines extending from the posterior pole to limbus in 36 human donor scleras aged 52-96 years. Strip specimens were extracted from areas close to the limbus, equator and posterior pole, and tested under cycles of uniaxial tension. Two strain rates were considered to assess the viscoelasticity effects on the regional variation in material behaviour. The results were used to derive the stress-strain behaviour of each specimen and to calculate the tangent modulus at each stress level. The scleras had a variable thickness from maximum at the posterior pole to minimum close to the equator, and increasing again towards the limbus. All scleral specimens demonstrated nonlinear behaviour with an initially low tangent modulus (a measure of stiffness) increasing gradually under higher stresses. With reference to specific stress levels, the behaviour comparisons between regions showed a gradual growth in material tangent stiffness with progression from the posterior region towards the limbus. The viscoelasticity of the tissue, which was evident with significant increases in stress (157-203%) and tangent modulus (30.3-38.8%) with strain rate rise (from 8% to 200% per min), was associated with reductions in the regional variation in stiffness. The considerable variation in biomechanical behaviour found in this study should be useful in improving the accuracy of representing the sclera's real-life conditions in numerical simulations.

Assessment of the ocular response analyzer as a tool for intraocular pressure measurement.

The ocular response analyzer (ORA) is a new indentation tonometer that subjects the cornea to an increasing then decreasing air pulse, and uses the corresponding two applanation pressures P1 and P2 to estimate the intraocular pressure (IOP). The present study aims to improve the accuracy of IOP estimation through representative numerical simulation of the ORA procedure. A parametric study has been carried out to consider the effect of corneal thickness, curvature, age, and true IOP on the P1 and P2 measurements. Based on the obtained database of input and output parameters, an equation has been suggested relating the P1 and P2 measurements to the value of IOP. The equation is intended to make IOP estimates independent of corneal stiffness, which varies with size and age. The equation has been tested against a clinical data set obtained at Moorfields Eye Hospital involving 144 subjects, and found to produce IOP estimates that are less dependent on corneal size and age than published equations.

Mechanical anisotropy of porcine cornea and correlation with stromal microstructure.

An experimental study was conducted to determine the variation of biomechanical properties with anatomical orientation in porcine corneas. Strip specimens extracted from fresh porcine corneas were subjected to cycles of uniaxial tension while monitoring their behaviour. The specimens were extracted from either the superior-inferior (vertical), temporal-nasal (horizontal) or diagonal direction. Comparisons of behaviour were limited to specimens taken from the same animal to avoid the natural variation of biomechanical properties in corneas from different animals. The specimens were subjected to three different strain rates to check if the behaviour comparisons were affected by the cornea's viscoelasticity. Overall, vertical and horizontal specimens were found to have almost the same behaviour, and both were marginally stiffer than diagonal specimens (by 2-8%). This almost isotropic biomechanical behaviour was compatible with earlier indications of similar collagen fibril densities in the three main orientations of porcine corneas.

Numerical study of the effect of corneal layered structure on ocular biomechanics.

PURPOSE: The study aimed to improve the accuracy of corneal numerical simulation by adopting a better representation of the corneal layered structure. The study considered both the shear and tensile behavior of the interface surfaces between stromal lamellae, and assessed the effect of modeling the cornea's three main layers-the epithelium, stroma, and endothelium with their respective material properties. METHODS: Twelve human donor corneas were tested to determine the behavior of the stroma under surface shear. Numerical models were then built to consider the stromal inter-lamellar adhesion, which included the shear behavior determined experimentally and the tensile behavior available in the literature. They also adopted the distinctive material properties of the epithelium, stroma, and endothelium. The numerical models simulated corneal behavior under intraocular pressure elevation, concentric anterior pressure, and the conditions under tonometry with the Goldmann applanation tonometer. RESULTS: The stress-strain shear behavior of stromal tissue followed an exponential pattern, with an initial low stiffness increasing gradually under higher stresses. This behavior was adopted in the numerical simulation to set the level of adhesion between stromal layers. Considering that the stromal inter-lamellar adhesion and the distinctive material properties of corneal layers had a significant effect in simulating the response to concentrated anterior pressures, which cause bending of corneal tissue, this was almost unnecessary when predicting the effect of intraocular pressure, which put the cornea under membrane tension. CONCLUSIONS: The corneal layered structure affects the results of numerical simulations especially in problems where the cornea is subjected to bending effects.

Goldmann tonometry correction factors based on numerical analysis.

With the world's aging population, it is expected that the number of people affected by glaucoma, the second most common cause of irreversible blindness, will increase considerably. Current knowledge on glaucoma progression relates elevation of the intraocular pressure (IOP) to optic nerve damage and hence visual impairment. For this reason, IOP measurement in tonometry has become an essential part of routine eye examinations needed for the diagnosis and management of the disease. The accuracy of the current reference standard in tonometry, the Goldmann applanation tonometer, is known to be affected by the natural variations in corneal thickness, curvature, and material properties. Earlier studies attempted to quantify these effects and produced correction factors that considered the variations in each one of these parameters separately, and no guidance was given as to how to combine the effects of variations in more than one parameter. The present research attempted to address this gap by conducting a multidimensional numerical study that considered variations in thickness, curvature, material properties, and IOP, and used the results to develop a single correction equation that considered these parameters simultaneously. The results of the analysis and the correction equation were validated successfully against the outcome of earlier clinical and mathematical studies on the effect of individual parameters, and the correction equation was presented in a simple form suitable for clinical application.

Biomechanical properties of human and porcine corneas.

The suitability of porcine corneas as approximate models for human corneas in mechanical property characterisation studies is experimentally assessed. Thirty seven human donor corneas and thirty four ex-vivo porcine corneas were tested under inflation conditions to determine their short-term stress-strain behaviour and long-term creep behaviour up to 2.8 h (10,000 s). Vertical strips extracted from further 12 human corneas and 10 porcine corneas were subjected to stress-relaxation tests for up to 20 min at different stress levels. Human and porcine corneas were observed to have almost the same form of behaviour under short and long-term loading. They both exhibited non-linear stress-strain behaviour and reacted to sustained loading in a similar fashion. However, human corneas were significantly stiffer than porcine corneas. They also crept less under long-term loading and could sustain their stress state for longer compared to porcine corneas. These differences, in addition to others identified earlier in relation to corneal mechanical anisotropy, cast doubt on the suitability of porcine corneas as models for human corneas in mechanical studies.

Experimental assessment of corneal anisotropy.

PURPOSE: To determine the variation of corneal biomechanical properties with anatomical orientation. METHODS: Strip specimens extracted from fresh porcine corneas were tested under uniaxial tension with strain rates representing static and dynamic loading conditions. The specimens were extracted from the vertical, horizontal, and 45 degrees diagonal directions. The load elongation results were used to derive the stress-strain behavior of each specimen. The average behavior for specimens taken in each anatomical direction was determined along with the effect of strain rate. Specimens from a small number of human corneas were included in the study to verify the findings. RESULTS: Specimens extracted from the vertical direction of porcine and human corneas demonstrated the highest strength (fracture stress) followed by horizontal then diagonal specimens. Vertical specimens were 10% to 20% stronger than horizontal specimens in porcine and human corneas. At low strain rates (1%/min), vertical specimens displayed similar stiffness (resistance to deformation) to horizontal specimens but greater stiffness than diagonal specimens. On increasing the strain rate to 500%/min, the stiffness behavior matched that of strength with vertical specimens being 10% to 20% stiffer than horizontal specimens in porcine and human corneas. CONCLUSIONS: The corneal anisotropic behavior is compatible with the preferential orientation of stromal fibrils in the vertical and horizontal directions. Quantifying the effect of this nonuniform fibril organization on corneal anisotropic behavior will be useful in developing numerical models of the cornea for applications where its integrity is compromised such as in simulating refractive surgery procedures.

Assessment of the epithelium's contribution to corneal biomechanics.

Determining the epithelium's contribution to corneal biomechanics is important for the predictive numerical simulation of corneal biomechanical behaviour in which the cornea's five main layers are represented separately. Twenty-four corneal buttons were tested under posterior inflation conditions while monitoring their behaviour using non-contact methods. The corneas were divided into two groups of 12; one with and one without the epithelium. Control of specimen hydration, temperature and pressure application rate, and limiting the programme to specimens within a small age range resulted in a narrow scatter of test results. On average, intact specimens were able to carry slightly more pressure at the same deformation, and experienced less average stress for the same strain, compared with specimens without the epithelium. These results indicated that the stiffness of the epithelium was considerably lower than that of the stroma, and might therefore be ignored in numerical simulation studies.

Greater knowledge gain with structured than student-directed learning in Child Health: cluster randomized trial.

The aim of this study was to detect a difference in knowledge gain between students receiving structured versus student-directed learning for the two-week Child Health outpatient module. A total of 138 phase 3 (year 4) medical students in 10 two-week paediatric outpatient blocks at the Department of Child Health, University of Dundee, Scotland, were randomized to student-directed or structured learning between January and December 2002. Pre- and post-course tests were administered at the start and the end of the attachment; 129 students sat both tests. Results are presented as mean scores with standard deviations or 95% confidence intervals (CI) in parentheses. The primary outcome measure was gain in knowledge of the Child Health core curriculum that is covered in the outpatient setting. Although pre-course scores were similar (student-directed 25.3 (7.3); structured 24.8 (7.5)) the structured approach resulted in higher post-course scores in comparison with the student-directed approach (student-directed 41.8 (9.4); structured 53.8 (8.8); p < 0.01). Knowledge gain showed significant differences between the two learning approaches (student-directed 16.5 (3.7); structured 29.1 (3.8), difference = 12.6 (95% CI 11.3 to 13.9)). Low pre-course scores or gender did not affect knowledge gain. In the Child Health outpatient setting, the 'traditional' structured approach led to significantly greater knowledge gain in comparison with the 'novel' student-directed approach. The findings emphasize the importance of careful evaluation of novel medical education strategies before their implementation in medical schools, and the need for further research to define the effective methods for delivering medical education in Child Health.