Brendan Geraghty

Characterization of age-related variation in corneal biomechanical properties

An experimental study has been conducted to determine the stress–strain behaviour of human corneal tissue and how the behaviour varies with age. Fifty-seven well-preserved ex vivo donor corneas aged between 30 and 99 years were subjected to cycles of posterior pressure up to 60 mm Hg while monitoring their behaviour. The corneas were mechanically clamped along their ring of scleral tissue and kept in physiological conditions of temperature and hydration. The tissue demonstrated hyper-elastic pressure-deformation and stress–strain behaviour that closely matched an exponential trend. Clear stiffening (increased resistance to deformation) with age was observed in all loading cycles, and the rate of stiffness growth was nonlinear with bias towards older specimens. With a strong statistical association between stiffness and age (p < 0.05), it was possible to develop generic stress–strain equations that were suitable for all ages between 30 and 99 years. These equations, which closely matched the experimental results, depicted corneal stiffening with age in a form suitable for implementation in numerical simulations of ocular biomechanical behaviour.

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 scleras real-life conditions in numerical simulations.

Age-related variations in the biomechanical properties of human sclera

This study examined age-related changes in biomechanical behaviour in the anterior, equatorial and posterior regions of the human sclera (white of the eye). Circumferential strip specimens were extracted from areas close to the limbus, equator and posterior pole in 45 donor scleras ranging in age between 51 and 84 years. The strips were subjected to cycles of uniaxial tension loading at a strain rate of 8% per minute while monitoring their load-deformation behaviour. All specimens demonstrated nonlinear behaviour with an initially low tangent modulus (a measure of material stiffness) increasing under higher stresses. The average ratios between the tangent modulus at a high stress of 1 MPa and that at a low stress of 0.05 MPa were 11.2±1.7, 12.0±1.7 and 12.4±1.5 for anterior, equatorial and posterior specimens, respectively. Stiffening was observed with age in all regions, but it was statistically significant only in the anterior region (P<0.01). Anterior specimens showed the largest stiffness growth with advancing age in both the initial, matrix regulated phase of behaviour (0.32 MPa/decade), and the final, collagen regulated phase (3.97 MPa/decade), followed by equatorial (0.27 and 2.15 MPa/decade) then posterior specimens (0.14 and 0.26 MPa/decade). The stress-strain behaviour of scleral tissue exhibits increasing stiffness with higher age. In addition to a regional variation of material stiffness, the rate of stiffness growth with age also varies between regions.

Evaluation of the relationship of corneal biomechanical metrics with physical intraocular pressure and central corneal thickness in ex vivo rabbit eye globes

The relationship of corneal biomechanical metrics provided by the Ocular Response Analyzer (ORA) and Corvis ST (CVS) with physical intraocular pressure (IOPp) and central corneal thickness (CCT) was evaluated. Thirty fresh enucleated eyes of 30 rabbits were used in ex vivo whole globe inflation experiments. IOPp was measured with a pressure transducer and increased from 7.5 to 37.5 mmHg in steps of 7.5 mmHg while biomechanical data was acquired using the ORA and CVS. At least 3 examinations were performed at each pressure level, where CCT and twelve biomechanical metrics were recorded and analyzed as a function of IOPp. The biomechanical metrics included corneal hysteresis (CH) and corneal resistance factor (CRF), obtained by the ORA. They also included the applanation times (A1T, A2T), lengths (A1L, A2L) and velocities (A1V, A2V), in addition to the highest concavity time (HCT), peak distance (PD), radius (HR) and deformation amplitude (DA), obtained by the CVS. The variation of CCT and the twelve biomechanical metrics for the 30 rabbit eyes tested across the 5 pressure stages considered (inter-pressure differences) were statistically significant (P = 0.00). IOPp was highly to moderately correlated with most biomechanical metrics, especially CRF, A1T, A1V, A2V, PD and DA, while the relationships with CH, A2T, A1L and HCT were poor. IOP has important influences on most corneal biomechanical metrics provided by CVS and ORA. Two biomechanical metrics A1V and HR were influenced by CCT after correcting for the effect of IOP in most pressure stages, while the correlation with others were weak. Comparisons of research groups based on ORA and CVS with different IOPs and CCTs may lead to possible misinterpretations if both or one of which are not considered in the analysis.

Nanoscale characterization of the biomechanical properties of collagen fibrils in the sclera

We apply the PeakForce Quantitative Nanomechanical Property Mapping (PFQNM) atomic force microscopy mode for the investigation of regional variations in the nanomechanical properties of porcine sclera. We examine variations in the collagen fibril diameter, adhesion, elastic modulus and dissipation in the posterior, equatorial and anterior regions of the sclera. The mean fibril diameter, elastic modulus and dissipation increased from the posterior to the anterior region. Collagen fibril diameter correlated linearly with elastic modulus. Our data matches the known macroscopic mechanical behavior of the sclera. We propose that PFQNM has significant potential in ocular biomechanics and biophysics research.

Repeatability of corneal elevation maps in keratoconus patients using the tomography matching method

To assess repeatability of corneal tomography in successive measurements by Pentacam in keratoconus (KC) and normal eyes based on the Iterative Closest Point (ICP) algorithm. The study involved 143 keratoconic and 143 matched normal eyes. ICP algorithm was used to estimate six single and combined misalignment (CM) parameters, the root mean square (RMS) of the difference in elevation data pre (PreICP-RMS) and post (PosICP-RMS) tomography matching. Corneal keratometry, expressed in the form of M, J0 and J45 (power vector analysis parameters), was used to evaluate the effect of misalignment on corneal curvature measurements. The PreICP-RMS and PosICP-RMS were statistically higher (P < 0.01) in KC than normal eyes. CM increased significantly (p = 0.00), more in KC (16.76 ± 20.88 μm) than in normal eyes (5.43 ± 4.08 μm). PreICP-RMS, PosICP-RMS and CM were correlated with keratoconus grade (p < 0.05). Corneal astigmatism J0 was different (p = 0.01) for the second tomography measurements with misalignment consideration (−1.11 ± 2.35 D) or not (−1.18 ± 2.35 D), while M and J45 kept similar. KC corneas consistently show higher misalignments between successive tomography measurements and lower repeatability compared with healthy eyes. The influence of misalignment is evidently clearer in the estimation of astigmatism than spherical curvature. These higher errors appear correlated with KC progression.

Evaluating the repeatability of corneal elevation through calculating the misalignment between Successive topography measurements during the follow up of LASIK

The study aims to evaluate, using the Iterative Closest Point (ICP) algorithm, the repeatability of successive corneal elevation measurements taken post-LASIK. Two topography maps of 98 LASIK participants were recorded preoperatively (Pre), 1 month (Pos1M) and 3 months postoperatively (Pos3M). Elevation of the second measurement was fitted to the first measurement by calculating using ICP, and correcting for, both translational and rotational misalignment components. The RMS of elevation differences between anterior corneal measurements were statistically significant post-LASIK compared to preoperation (P < 0.05). A misalignment ratio used to describe the weighting of the elevation difference caused by misalignment relative to the total difference remained stable (0.40 and 0.23 for anterior and posterior corneal surfaces, respectively) in different periods. The study also considered the combined misalignment parameter (CM), which represents the total effect of all individual misalignment components on the repeatability of corneal topography maps. CM was significantly greater post-LASIK relative to pre-LASIK (P < 0.05). Overall, the contribution of misalignment to the total difference between successive corneal measurements remained stable pre and post operation, while the combined effect of refractive error correction and optical diameter appeared to have a significant influence on the elevation repeatability in the early stages of the follow up period.

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.

Role of Corneal Biomechanics in the Diagnosis and Management of Keratoconus

Keratoconus, the occurrence and development of which is associated with corneal thinning and conical protrusion causing irregular astigmatism, is a bilateral non-inflammatory degenerative corneal disease. With the disruption of the collagen organisation, the cornea loses its shape and function resulting in progressive visual degradation. Currently, corneal topography remains the most important tool for the diagnosis of keratoconus. However, this approach may lead to false negatives among the patient population in the subclinical phase. It is now hypothesised that biomechanical destabilisation of the cornea may take place ahead of the topographic evidence of keratoconus. Therefore, accurate characterisation of in vivo biomechanical properties could possibly be used to assist with diagnosis and management, particularly in the early stages of the disease. This chapter provides a summary of the definition, diagnosis and management strategies for keratoconus based on corneal biomechanics.

Age-Related Variation in the Biomechanical and Structural Properties of the Corneo-Scleral Tunic

With increasing age, the mechanical performance of the cornea and sclera is impaired due to structural changes in the major structural proteins, namely collagens , proteoglycans and elastin. In addition, the level of hydration in the ocular tunic decreases over time. These structural changes profoundly impact on the biomechanical properties of the corneo-scleral tunic. This chapter focuses on the structural and biomechanical changes that occur in the corneo-scleral tunic with age. The techniques that are utilized in order to determine the mechanical properties of both the cornea and sclera are discussed, and a comprehensive review of studies which have characterized age-related changes in ocular biomechanics are presented. The cornea is found to increase in stiffness with age and all the characteristics of viscoelastic behavior (creep , stress-relaxation and hysteresis) decrease with age. Similarly, the stiffness of the sclera increases markedly with age although the reported magnitude of stiffening varies significantly from one study to another. This may be related to variations amongst the different techniques that have been utilized. Increased stiffening in the cornea and the sclera with age is strongly associated with the increase in collagen crosslinking that occurs as part of the natural aging process.