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Two case reports of breastfeeding mothers on high doses of methadone and a literature review reveal that minimal transmission of methadone into breast milk occurs regardless of the mother's methadone dose. The current American Academy of Pediatrics recommendations that only women in drug treatment programs on less than 20 mg/day of methadone be advised to breastfeed should be reconsidered. [ABSTRACT FROM AUTHOR]

Gene-based burden tests are a popular and powerful approach for analysis of exome-wide association studies. These approaches combine sets of variants within a gene into a single burden score that is then tested for association. Typically, a range of burden scores are calculated and tested across a range of annotation classes and frequency bins. Correlation between these tests can complicate the multiple testing correction and hamper interpretation of the results. We introduce a method called the sparse burden association test (SBAT) that tests the joint set of burden scores under the assumption that causal burden scores act in the same effect direction. The method simultaneously assesses the significance of the model fit and selects the set of burden scores that best explain the association at the same time. Using simulated data, we show that the method is well calibrated and highlight scenarios where the test outperforms existing gene-based tests. We apply the method to 73 quantitative traits from the UK Biobank, showing that SBAT is a valuable additional gene-based test when combined with other existing approaches. This test is implemented in the REGENIE software., Competing Interests: Declaration of interests All authors are current employees and/or stockholders of Regeneron Pharmaceuticals., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Subretinal injection is the preferred delivery technique for various novel ocular therapies and is widely used because of its precision and efficient delivery of gene and cell therapies; however, choosing an injection point and defining delivery parameters to target a specified retinal location and area is an inexact science. We provide an overview of the key factors that play important roles during subretinal injections to refine the technique, enhance patient outcomes, and minimise risks. We describe the role of anatomical and physical variables that affect subretinal bleb propagation and shape and their impact on retinal integrity. We highlight the risks associated with subretinal injections and consider strategies to mitigate reflux and retinal trauma. Finally, we explore the emerging field of robotic assistance in improving intraocular manouvrability and precision to facilitate the injection procedure., Competing Interests: Declaration of Competing Interest This manuscript is a review paper, has not been published and is not under consideration for publication elsewhere. We have no conflicts of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Summary: We describe a novel technique modification of subretinal injection to reduce the risk of foveal dehiscence during subretinal tissue plasminogen activator delivery for submacular haemorrhage, using a perfluorocarbon liquid filled vitreous cavity and an eccentric injection point, with a viscous fluid injector system controlled injection., Purpose: To describe a novel method of subretinal injection to reduce the risk of foveal dehiscence during subretinal tissue plasminogen activator delivery for submacular hemorrhage., Method: Description of technique with illustrative case description and details of four cases treated. The subretinal injection is delivered under a perfluorocarbon liquid bubble filling 80% of the vitreous cavity. An eccentric injection point is used and the tissue plasminogen activator injected under a pneumatically controlled viscous fluid injection system with a 38-g polyimide cannula and low injection pressure., Results: Four cases have been treated with controlled subretinal injection extending under the fovea without dehiscence, including one case with apparent preexisting foveal dehiscence and a preretinal clot., Conclusion: The technique allows the creation of a low more diffuse subretinal bleb compared with without perfluorocarbon liquid, minimizing hydraulic stress on the fovea during injection and could be applied to other subretinal injection scenarios where the fovea is at risk of hydraulic blowout. Further experience of the technique is needed to validate this initial report.

In this study, hyperpolarized 13 C MRI (HP- 13 C MRI) was used to investigate changes in the uptake and metabolism of pyruvate with age. Hyperpolarized 13 C-pyruvate was administered to healthy aging individuals (N = 35, ages 21-77) and whole-brain spatial distributions of 13 C-lactate and 13 C-bicarbonate production were measured. Linear mixed-effects regressions were performed to compute the regional percentage change per decade, showing a significant reduction in both normalized 13 C-lactate and normalized 13 C-bicarbonate production with age: - 7 % ± 2 % per decade for 13 C-lactate and - 9 % ± 4 % per decade for 13 C-bicarbonate. Certain regions, such as the right medial precentral gyrus, showed greater rates of change while the left caudate nucleus had a flat 13 C-lactate versus age and a slightly increasing 13 C-bicarbonate versus age. The results show that both the production of lactate (visible as 13 C-lactate signal) as well as the consumption of monocarboxylates to make acetyl-CoA (visible as 13 C-bicarbonate signal) decrease with age and that the rate of change varies by brain region., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Purpose: The study presents an averaged anterior eye geometry model combined with a localised material model that is straightforward, appropriate and amenable for implementation in finite element (FE) modelling., Methods: Both right and left eye profile data of 118 subjects (63 females and 55 males) aged 22-67 years (38.5 ± 7.6) were used to build an averaged geometry model. Parametric representation of the averaged geometry model was achieved through two polynomials dividing the eye into three smoothly connected volumes. This study utilised the collagen microstructure x-ray data of 6 ex-vivo healthy human eyes, 3 right eyes and 3 left eyes in pairs from 3 donors, 1 male and 2 females aged between 60 and 80 years, to build a localised element-specific material model for the eye., Results: Fitting the cornea and the posterior sclera sections to a 5th-order Zernike polynomial resulted in 21 coefficients. The averaged anterior eye geometry model recorded a limbus tangent angle of 37° at a radius of 6.6 mm from the corneal apex. In terms of material models, the difference between the stresses generated in the inflation simulation up to 15 mmHg in the ring-segmented material model and localised element-specific material model were significantly different (p < 0.001) with the ring-segmented material model recording average Von-Mises stress 0.0168 ± 0.0046 MPa and the localised element-specific material model recording average Von-Mises stress 0.0144 ± 0.0025 MPa., Conclusions: The study illustrates an averaged geometry model of the anterior human eye that is easy to generate through two parametric equations. This model is combined with a localised material model that can be used either parametrically through a Zernike fitted polynomial or non-parametrically as a function of the azimuth angle and the elevation angle of the eye globe. Both averaged geometry and localised material models were built in a way that makes them easy to implement in FE analysis without additional computation cost compared to the limbal discontinuity so-called idealised eye geometry model or ring-segmented material model., (© 2023 The Authors.)

Proteoglycans (PGs) are minor extracellular matrix proteins, and their contributions to the mechanobiology of complex ligaments such as the cranial cruciate ligament (CCL) have not been determined to date. The CCLs are highly susceptible to injuries, and their extracellular matrix comprises higher PGs content than the other major knee ligaments. Hence these characteristics make CCLs an ideal specimen to use as a model in this study. This study addressed the hypothesis that PGs play a vital role in CCL mechanobiology by determining the biomechanical behaviour at low strain rates before and after altering PGs content. For the first time, this study qualitatively investigated the contribution of PGs to key viscoelastic characteristics, including strain rate dependency, hysteresis, creep and stress relaxation, in canine CCLs. Femur-CCL-tibia specimens ( n = 6 pairs) were harvested from canine knee joints and categorised into a control group, where PGs were not depleted, and a treated group, where PGs were depleted. Specimens were preconditioned and cyclically loaded to 9.9 N at 0.1, 1 and 10%/min strain rates, followed by creep and stress relaxation tests. Low tensile loads were applied to focus on the toe-region of the stress-strain curves where the non-collagenous extracellular matrix components take significant effect. Biochemical assays were performed on the CCLs to determine PGs and water content. The PG content was ∼19% less in the treated group than in the control group. The qualitative study showed that the stress-strain curves in the treated group were strain rate dependent, similar to the control group. The CCLs in the treated group showed stiffer characteristics than the control group. Hysteresis, creep characteristics (creep strain, creep rate and creep compliance), and stress relaxation values were reduced in the treated group compared to the control group. This study suggests that altering PGs content changes the microstructural organisation of the CCLs, including water molecule contents which can lead to changes in CCL viscoelasticity. The change in mechanical properties of the CCLs may predispose to injury and lead to knee joint osteoarthritis. Future studies should focus on quantitatively identifying the effect of PG on the mechanics of intact knee ligaments across broader demography., Competing Interests: 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., (Copyright © 2022 Readioff, Geraghty, Kharaz, Elsheikh and Comerford.)

Walking on compliant substrates requires more energy than walking on hard substrates but the biomechanical factors that contribute to this increase are debated. Previous studies suggest various causative mechanical factors, including disruption to pendular energy recovery, increased muscle work, decreased muscle efficiency and increased gait variability. We test each of these hypotheses simultaneously by collecting a large kinematic and kinetic dataset of human walking on foams of differing thickness. This allowed us to systematically characterize changes in gait with substrate compliance, and, by combining data with mechanical substrate testing, drive the very first subject-specific computer simulations of human locomotion on compliant substrates to estimate the internal kinetic demands on the musculoskeletal system. Negative changes to pendular energy exchange or ankle mechanics are not supported by our analyses. Instead we find that the mechanistic causes of increased energetic costs on compliant substrates are more complex than captured by any single previous hypothesis. We present a model in which elevated activity and mechanical work by muscles crossing the hip and knee are required to support the changes in joint (greater excursion and maximum flexion) and spatio-temporal kinematics (longer stride lengths, stride times and stance times, and duty factors) on compliant substrates.

Knee joint ligaments provide stability to the joint by preventing excessive movement. There has been no systematic effort to study the effect of OA and ageing on the mechanical properties of the four major human knee ligaments. This study aims to collate data on the material properties of the anterior (ACL) and posterior (PCL) cruciate ligaments, medial (MCL) and lateral (LCL) collateral ligaments. Bone-ligament-bone specimens from twelve cadaveric human knee joints were extracted for this study. The cadaveric knee joints were previously collected to study ageing and OA on bone and cartilage material properties; therefore, combining our previous bone and cartilage data with the new ligament data from this study will facilitate subject-specific whole-joint modelling studies. The bone-ligament-bone specimens were tested under tensile loading to failure, determining material parameters including yield and ultimate (failure) stress and strain, secant modulus, tangent modulus, and stiffness. There were significant negative correlations between age and ACL yield stress ( p = 0.03 ), ACL failure stress ( p = 0.02 ), PCL secant ( p = 0.02 ) and tangent ( p = 0.02 ) modulus, and LCL stiffness ( p = 0.046 ). Significant negative correlations were also found between OA grades and ACL yield stress ( p = 0.02 ) and strain ( p = 0.03 ), and LCL failure stress ( p = 0.048 ). However, changes in age or OA grade did not show a statistically significant correlation with the MCL tensile parameters. Due to the small sample size, the combined effect of age and the presence of OA could not be statistically derived. This research is the first to report tensile properties of the four major human knee ligaments from a diverse demographic. When combined with our previous findings on bone and cartilage for the same twelve knee cadavers, the current ligament study supports the conceptualisation of OA as a whole-joint disease that impairs the integrity of many peri-articular tissues within the knee. The subject-specific data pool consisting of the material properties of the four major knee ligaments, subchondral and trabecular bones and articular cartilage will advance knee joint finite element models., Competing Interests: 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., (Copyright © 2022 Peters, Geraghty, Bates, Akhtar, Readioff and Comerford.)

Body fat distribution is a major, heritable risk factor for cardiometabolic disease, independent of overall adiposity. Using exome-sequencing in 618,375 individuals (including 160,058 non-Europeans) from the UK, Sweden and Mexico, we identify 16 genes associated with fat distribution at exome-wide significance. We show 6-fold larger effect for fat-distribution associated rare coding variants compared with fine-mapped common alleles, enrichment for genes expressed in adipose tissue and causal genes for partial lipodystrophies, and evidence of sex-dimorphism. We describe an association with favorable fat distribution (p = 1.8 × 10 -09 ), favorable metabolic profile and protection from type 2 diabetes (~28% lower odds; p = 0.004) for heterozygous protein-truncating mutations in INHBE, which encodes a circulating growth factor of the activin family, highly and specifically expressed in hepatocytes. Our results suggest that inhibin βE is a liver-expressed negative regulator of adipose storage whose blockade may be beneficial in fat distribution-associated metabolic disease., (© 2022. The Author(s).)

We report a case of Streptococcus mutans multivalvular infective endocarditis complicated by aortic root abscess and septic emboli in a 19-year-old male with a bicuspid aortic valve. This case illustrates the progression of untreated subacute bacterial endocarditis and highlights the importance of ongoing clinical suspicion for infective endocarditis in patients with underlying valvular defects., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The peritumoral region (PTR) of glioblastoma (GBM) appears as a T2W-hyperintensity and is composed of microscopic tumor and edema. Infiltrative low grade glioma (LGG) comprises tumor cells that seem similar to GBM PTR on MRI. The work here explored if a radiomics-based approach can distinguish between the two groups (tumor and edema versus tumor alone)., Methods: Patients with GBM and LGG imaged using a 1.5 T MRI were included in the study. Image data from cases of GBM PTR, and LGG were manually segmented guided by T2W hyperintensity. A set of 91 first-order and texture features were determined from each of T1W-contrast, and T2W-FLAIR, diffusion-weighted imaging sequences. Applying filtration techniques, a total of 3822 features were obtained. Different feature reduction techniques were employed, and a subsequent model was constructed using four machine learning classifiers. Leave-one-out cross-validation was used to assess classifier performance., Results: The analysis included 42 GBM and 36 LGG. The best performance was obtained using AdaBoost classifier using all the features with a sensitivity, specificity, accuracy, and area of curve (AUC) of 91%, 86%, 89%, and 0.96, respectively. Amongst the feature selection techniques, the recursive feature elimination technique had the best results, with an AUC ranging from 0.87 to 0.92. Evaluation with the F-test resulted in the most consistent feature selection with 3 T1W-contrast texture features chosen in over 90% of instances., Conclusions: Quantitative analysis of conventional MRI sequences can effectively demarcate GBM PTR from LGG, which is otherwise indistinguishable on visual estimation., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Studying the biomechanical properties of biological tissue is crucial to improve our understanding of disease pathogenesis. The biomechanical characteristics of the cornea, sclera and the optic nerve head have been well addressed with an extensive literature and an in-depth understanding of their significance whilst, in comparison, knowledge of the retina and choroid is relatively limited. Knowledge of these tissues is important not only to clarify the underlying pathogenesis of a wide variety of retinal and vitreoretinal diseases, including age-related macular degeneration, hereditary retinal dystrophies and vitreoretinal interface diseases but also to optimise the surgical handling of retinal tissues and, potentially, the design and properties of implantable retinal prostheses and subretinal therapies. Our aim with this article is to comprehensively review existing knowledge of the biomechanical properties of retina, internal limiting membrane (ILM) and the Bruch's membrane-choroidal complex (BMCC), highlighting the potential implications for clinical and surgical practice. Prior to this we review the testing methodologies that have been used both in vitro, and those starting to be used in vivo to aid understanding of their results and significance.

Purpose: The peritumoral region (PTR) in glioblastoma (GBM) represents a combination of infiltrative tumor and vasogenic edema, which are indistinguishable on magnetic resonance imaging (MRI). We developed a radiomic signature by using imaging data from low grade glioma (LGG) (marker of tumor) and PTR of brain metastasis (BM) (marker of edema) and applied it on the GBM PTR to generate probabilistic maps., Methods: 270 features were extracted from T1-weighted, T2-weighted, and apparent diffusion coefficient maps in over 3.5 million voxels of LGG (36 segments) and BM (45 segments) scanned in a 1.5T MRI. A support vector machine classifier was used to develop the radiomics model from approximately 50% voxels (downsampled to 10%) and validated with the remaining. The model was applied to over 575,000 voxels of the PTR of 10 patients with GBM to generate a quantitative map using Platt scaling (infiltrative tumor vs. edema)., Results: The radiomics model had an accuracy of 0.92 and 0.79 in the training and test set, respectively (LGG vs. BM). When extrapolated on the GBM PTR, 9 of 10 patients had a higher percentage of voxels with a tumor-like signature over radiological recurrence areas. In 7 of 10 patients, the areas under curves (AUC) were > 0.50 confirming a positive correlation. Including all the voxels from the GBM patients, the infiltration signature had an AUC of 0.61 to predict recurrence., Conclusion: A radiomic signature can demarcate areas of microscopic tumors from edema in the PTR of GBM, which correlates with areas of future recurrence.

Purpose: To investigate the stress-strain behaviour of 9 soft contact lens materials, that are commonly used in the market, under uniaxial compression loading., Methods: Seven types of hydrogel and two types of silicone-hydrogel soft contact lens materials were hydrated in phosphate-buffered saline (PBS) solution then subjected to uniaxial compression loads. The load rate was set to 16.0 N/min starting with two consecutive initial 5.0 N loading cycles followed by three relaxation periods of 4.0 min within which there were two more 5.0 N loading cycles and eventually, a full loading cycle that stopped at a load of 49.0 N. The load and contraction data obtained experimentally were analysed to derive the stress-strain behaviour. Finite Element (FE) analysis was then utilised to evaluate the performance of soft contact lenses on the human eye and handling lenses off the eye., Results: Unlike tensile tests, all tested materials showed nonlinear behaviour when tested under compression. When fitted to first-order Ogden hyperelastic model, parameter μ was found to be varying in the range 0.12 to 0.74 MPa and material parameter α was found to be varying in the range 8.2 to 20.326 among the nine tested materials. Compression modulus of elasticity was 2.2 times higher than the tensile modulus of elasticity on average. FE simulation with nonlinear Ogden constitutive model showed a limited change (8%~12%) in the optical performance when compared to other material models, however, it predicted higher stress when the lens was simulated under bending during off-eye handling., Conclusions: Compression tests revealed slightly nonlinear behaviour when materials were strained under compression stress down to 15% ~ 30% of their nominal heights. Considering the physiological compression loading range of 8 mmHg, secant moduli of elasticity were 1.5% to 6.9% higher than the tension moduli of elasticity depending on the material. Tensile-based moduli of elasticity could be used in FE analysis as a step towards simulating the optical performance of soft contact lenses on-eye. However, nonlinear compression-based material models are recommended for FE analysis of soft contact lenses when lens-handling is investigated off-eye., Competing Interests: The authors have read the journal’s policy and have the following competing interests: LW is a paid employee of Ultravision CLPL, which also provided raw materials for this study. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

Ligaments including the cruciate ligaments support and transfer loads between bones applied to the knee joint organ. The functions of these ligaments can get compromised due to changes to their viscoelastic material properties. Currently there are discrepancies in the literature on the viscoelastic characteristics of knee ligaments which are thought to be due to tissue variability and different testing protocols. The aim of this study was to characterise the viscoelastic properties of healthy cranial cruciate ligaments (CCLs), from the canine knee (stifle) joint, with a focus on the toe region of the stress-strain properties where any alterations in the extracellular matrix which would affect viscoelastic properties would be seen. Six paired CCLs, from skeletally mature and disease-free Staffordshire bull terrier stifle joints were retrieved as a femur-CCL-tibia complex and mechanically tested under uniaxial cyclic loading up to 10 N at three strain rates, namely 0.1%, 1% and 10%/min, to assess the viscoelastic property of strain rate dependency. The effect of strain history was also investigated by subjecting contralateral CCLs to an ascending (0.1%, 1% and 10%/min) or descending (10%, 1% and 0.1%/min) strain rate protocol. The differences between strain rates were not statistically significant. However, hysteresis and recovery of ligament lengths showed some dependency on strain rate. Only hysteresis was affected by the test protocol and lower strain rates resulted in higher hysteresis and lower recovery. These findings could be explained by the slow process of uncrimping of collagen fibres and the contribution of proteoglycans in the ligament extracellular matrix to intra-fibrillar gliding, which results in more tissue elongations and higher energy dissipation. This study further expands our understanding of canine CCL behaviour, providing data for material models of femur-CCL-tibia complexes, and demonstrating the challenges for engineering complex biomaterials such as knee joint ligaments., Competing Interests: The authors declare that they have no competing interests., (© 2020 Readioff et al.)

It is limiting to use conventional methods when characterising material properties of complex biological tissues with inhomogeneous and anisotropic structure, such as the anterior cruciate ligament (ACL) in the knee joint. This study aims to develop and utilise a three-dimensional digital image correlation method (3D DIC) for the purpose of determining material properties of femur-ACL-tibia complex across the surface without any contact between the tissue and the loading equipment. A full-field (360° view) 3D DIC test setup consisting of six digital single-lens reflex cameras was developed and ACL specimens from skeletally mature dog knee joints were tested. The six cameras were arranged into three pairs and the cameras within each pair were positioned with 25° in between to obtain the desired stereovision output. The test setup was calibrated twice: first to obtain the intrinsic and extrinsic parameters within camera pairs, and second to align the 3D surfaces from each camera pair in order to generate the full view of the ACLs. Using the undeformed 3D surfaces of the ligaments, ACL-specific finite element models were generated. Longitudinal deformation of ligaments under tensile loads obtained from the 3D DIC, and this was analysed to serve as input for the inverse finite element analysis. As a result, hyperelastic coefficients from the first-order Ogden model that characterise ACL behaviour were determined with a marginal error of <1.5%. This test setup and methodology provides a means to accurately determine inhomogeneous and anisotropic material properties of ACL. The methodology described in this study could be adopted to investigate other biological and cultured tissues with complex structure. STATEMENT OF SIGNIFICANCE: Determining the material properties of soft tissues with complex anatomical structure, such as the anterior cruciate ligament (ACL), is important to better understand their contribution to musculoskeletal biomechanics. Current conventional methods for characterising material properties of the ACL are often limited to a contact measurement approach, however an improved understanding of the mechanics of this complex tissue is vital in terms of preventing injury and developing novel therapies. This article reports the development and utilisation of non-contact optical methodology involving full-field three-dimensional digital image correlation and finite element analysis to accurately investigate material properties of the ACL, in a controlled environment. This technique reduces inaccuracies due to specimen clamping and more importantly considers the inhomogeneous nature of the examined tissue., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

In-office needle arthroscopy offers the potential advantage of reduced injury to intervention time, without the need for advanced imaging. It is particularly appropriate for those with contraindications to advanced imaging and also may reduce the risk of incorrect diagnoses in those situations in which imaging is associated with low sensitivity/specificity. The purpose of this article is to provide a standardized diagnostic approach to needle arthroscopy of the shoulder., (© 2020 by the Arthroscopy Association of North America. Published by Elsevier.)

The complexity of inverse finite element modelling methods used in ocular biomechanics research has significantly increased in recent years in order to produce material parameters that capture microscale tissue behaviour. This study presents a more accessible method for researchers to optimise sclera material parameters for use in finite element studies where macroscale sclera displacements are required. Five human donor sclerae aged between 36 and 72 years were subjected to cycles of internal pressure up to 61 mmHg using a custom-built inflation rig. Displacements were measured using a laser beam and two cameras through a digital image correlation algorithm. Specimen-specific finite element models incorporating regional thickness variation and sclera surface topography were divided into six circumferential regions. An inverse finite element procedure was used to optimise Ogden material parameters for each region. The maximum root mean squared (RMS) error between the numerical and experimental displacements within individual specimens was 17.5 µm. The optimised material parameters indicate a gradual reduction in material stiffness (as measured by the tangent modulus) from the equator to the posterior region at low-stress levels up to 0.005 MPa. The variation in stiffness between adjacent regions became gradually less apparent and statistically insignificant at higher stresses. The study demonstrated how inflation testing combined with inverse modelling could be used to effectively characterise regional material properties capable of reproducing global sclera displacements. The material properties were found to vary between specimens, and it is expected that age could be a contributing factor behind this variation., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The micromechanical behaviour of the cornea is important for understanding and modelling of many ocular disorders. Whereas inflation testing has been utilised to determine the bulk mechanical properties of the cornea under physiological pressures, micromechanical testing has been limited to unpressurised corneal samples. In this study the micromechanical properties of pressurised porcine corneas were determined using oscillatory nanoindentation coupled with a custom inflation method. Inflation was conducted in phosphate buffered saline (PBS) and tissue culture (TC) solutions. The shear storage modulus (G') and shear loss modulus (G") was determined for corneas inflated corneas with PBS and TC. Central corneal thickness (CCT) was monitored during the inflation (0-60 mmHg). Elastic modulus (E) was also calculated and quantitatively mapped for corneas. The results showed that G' at 15 mmHg was 86.18 ± 16 kPa and 88.86 + 13.54 kPa inflated by PBS and TC respectively. These values increased 3.2 times in an approximate linear relationship to 60 mmHg. G″ at 15 mmHg was 12.5 ± 2.5 kPa and 13.54 + 1.9 kPa inflated by PBS and TC respectively. G″ increased 1.9 times in an approximate linear relationship to 60 mmHg. No significant change was noticed in viscoelastic properties of corneas inflated by TC for 4 h whereas 4 h of hydration on PBS affected the mechanical properties. The central corneal region was found to be stiffer than in peripheral region. Mapping of elasticity revealed a symmetrical distribution of properties that varied with inflation. Our method has potential for measurement of viscoelastic properties of corneas in conditions where there have been localised changes in mechanical properties such as keratoconus., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the variation in the optical power achieved following soft contact lens eye fitting for spherical and cylindrical lenses with differing hydrogel material properties., Methods: Uniaxial tensile tests were performed on four hydrogel materials 77% water-content (w-c) hydrogel, 74% w-c blue silicone hydrogel, 74% w-c clear silicone hydrogel, and 64% w-c clear hydrogel (shortly referred to as H77p0, SiH74p5-blue, SiH74p5-clear, and H64p0-clear), under loading conditions that would be expected in vivo. Finite element models of the cornea and contact lens interaction were generated using spherical and cylindrical lenses with powers varying from -10 to +20 D; overall diameters of either 13.5, 14.0, or 14.5 mm; and with material properties matching those determined through experimental testing., Results: The moduli of elasticity for each of the tested hydrogel materials were 0.195 ± 0.027 MPa, 0.277 ± 0.019 MPa, 0.279 ± 0.01 MPa, and 0.457 ± 0.013 MPa for H77p0, SiH74p5-blue, SiH74p5-clear, and H64p0 respectively. The calculated values of effective power change (EPC) showed strong negative correlations with lens power. This was particularly apparent in the higher end of the lens power spectrum (over +5 D), where each of the materials demonstrated a highly linear reduction in EPC with increased lens power., Conclusions: Soft contact lenses composed of a stiffer hydrogel are far more resilient to changes in EPC across the lower end of the lens power spectrum (-10 to +5 D). Beyond this range, the material choice does not have a significant effect on the EPC.

The biceps tendon is a common pain generator in the shoulder. Long head of the biceps tendon pathology occurs in a variety of different ways. There are several different treatment options available to address the long head of the biceps. With advances in arthroscopy, all-arthroscopic tenodesis is becoming a more popular choice to address biceps tendon pathology. We describe an all-arthroscopic technique, termed "the loop-lock," for performing a biceps tenodesis., (© 2019 Published by Elsevier on behalf of the Arthroscopy Association of North America.)

The Consortium for Mouse Cell Line Authentication was formed to validate Short Tandem Repeat (STR) markers for intraspecies identification of mouse cell lines. The STR profiling method is a multiplex polymerase chain reaction (PCR) assay comprised of primers targeting 19 mouse STR markers and two human STR markers (for interspecies contamination screening). The goals of the Consortium were to perform an interlaboratory study to-(1) validate the mouse STR markers to uniquely identify mouse cell lines (intraspecies identification), (2) to provide a public database of mouse cell lines with the National Institute of Standards and Technology (NIST)-validated mouse STR profiles, and (3) to publish the results of the interlaboratory study. The interlaboratory study was an international effort that consisted of 12 participating laboratories representing institutions from academia, industry, biological resource centers, and government. The study was based on 50 of the most commonly used mouse cell lines obtained from the American Type Culture Collection (ATCC). Of the 50 mouse cell lines, 18 had unique STR profiles that were 100% concordant (match) among all Consortium laboratory members, and the remaining 32 cell lines had discordance that was resolved readily and led to improvement of the assay. The discordance was due to low signal and interpretation issues involving artifacts and genotyping errors. Although the total number of discordant STR profiles was relatively high in this study, the percent of labs agreeing on allele calls among the discordant samples was above 92%. The STR profiles, including electropherogram images, for NIST-validated mouse cell lines will be published on the NCBI BioSample Database (https://www.ncbi.nlm.nih.gov/biosample/). Overall, the interlaboratory study showed that the multiplex PCR method using 18 of the 19 mouse STR markers is capable of discriminating at the intraspecies level between mouse cell lines. Further studies are ongoing to refine the assay including (1) development of an allelic ladder for improving the accuracy of allele calling and (2) integration of stutter filters to identify true stutter., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: NIST was awarded a patent by the United States Patent Office (9,556,482 B2) for mouse cell line authentication. For full disclosure, this technology is licensed to IDEXX BioAnalytics and ATCC for commercialization; both companies have authorship on this manuscript. NIST and the inventors have received payments and will potentially receive royalties. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Purpose: To evaluate the impact of soft contact lens eye-fit on optical power by computational modelling and to produce correction maps for reversing this impact during the design process., Methods: Finite element models of spherical and toric hydrogel contact lenses at varying nominal powers of -20 D to +20 D, base curves radii (R1b) of 8.2, 8.5, 8.8 mm, and overall diameters (d3) of 14.5, 15.0, 15.5 mm were generated. Lenses were fitted to computational eye models generated with human eyes' topography data. Combined eye-lens simulations were run under the boundary conditions of the tears' surface tension between the contact lens and the eye in addition to the eyelid blink pressure. Lens optical zone power changes were calculated through computational light-ray tracing methods following each simulation., Results: Effective power changes (EPC) were affected negatively for all toric simulated lenses with power varying from -20 D to +20 D. Spherical lenses demonstrated similar behaviour, however with some positive EPC over the power range from -20 D to -10 D for spherical power (SPH) lenses. EPC assessment was between +0.25 D and -0.5 D for most lenses, however, lenses with prescriptions from +10 D to +20 D incurred EPC outside this range. The spherical lenses showed a maximum effective power change of +1.046 ± 0.338 D (Average Eye), and a minimum of -3.278 ± 0.731 D (Steep Eye). Similarly, the toric lenses showed a maximum of +1.501 ± 0.338 D (Average Eye), and a minimum of -3.514 ± 0.731 D (Steep Eye). EPC trends, along with minimum and maximum power, generally increased negatively as nominal lens prescription increased positively. Contact lens base curve selection affected the assessed effective power change for both spherical and toric lenses. The effect from lens total diameter for spherical lenses was less substantial than that for toric lenses., Conclusions: This study considered the impact of soft contact lens design parameters on effective optical power changes (EPC) after eye-fit. Spherical lenses experienced more EPC of clinical significance (>0.25 D) than toric lenses. Both types of lenses, spherical and toric (simple astigmatism), demonstrated similar trends in EPC on fitting from -20 D to +20 D, with lenses in the extremely positive and the extremely negative prescriptions demonstrating the highest EPCs. The lens base curve impacted the extent of EPC observed, with flatter base curves experiencing less power change. Diameter proved to impact toric lenses more than spherical ones, however generally the diameter has less effect on power change than base curve selection., Competing Interests: The authors have read the journal's policy and the authors of this manuscript have the following competing interests: AA was a paid employee of an Innovate UK Knowledge Transfer Partnership Programme Grant till November 2017. AS, CEO of Eaglet Eye BV, and both IF and RS, the clinicians in Eaglet Eye BV, may use the figures in this manuscript to improve the performance of the Eye Surface Profiler (ESP). All other authors declare no potential financial or non-financial competing interests including employment, consultancy, patents, products in development, or marketed products. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

There has been a lot of interest in accurately characterising corneal biomechanical properties under intraocular pressure (IOP) to help better understand ocular pathologies that are associated with elevated IOP. This study investigates the novel use of Line-Field Optical Coherence Tomography (LF-OCT) as an elastographic tool for accurately measuring mechanical properties of porcine corneas based on volumetric deformation following varying IOPs. A custom-built LF-OCT was used to measure geometrical and corneal surface displacement changes in porcine corneas under a range of IOPs, from 0-60 mmHg. Corneal thickness, elastic properties and hysteresis were calculated as a function of pressure. In addition, the effects of hydration were explored. We found that the elastic modulus increased in a linear fashion with IOP. Corneal thickness was found to reduce with IOP, decreasing 14% from 0 to 60 mmHg. Prolonged hydration in phosphate buffered saline (PBS) was found to significantly increase the elastic modulus and corneal hysteresis. Our study demonstrates that LF-OCT can be used to accurately measure the elastic properties based on volumetric deformation following physiological pressures. Furthermore, we show that prolonged hydration in PBS has a significant effect on the measured corneal properties.

Purpose: To evaluate the effect of freezing and thawing on the biomechanical properties of ex-vivo porcine ocular tissue., Methods: Thirty-six porcine eyes (18 pairs) were obtained fresh from a local abattoir and split into two groups of nine pairs to study the effect of storage at -20 °C and -80 °C. A randomly-selected eye from each pair (Control Group, CG) was tested fresh while the fellow eyes were frozen for 14 days, either at -20 °C and -80 °C (Frozen Group, FG) before thawing and testing. Seventy-two strips were extracted from the corneas and scleras of eye globes and subjected to uniaxial tension tests under loads up to 1.0 N. Following five preconditioning cycles, the load and elongation data obtained experimentally were analysed to derive the tissue's stress-strain and tangent modulus-strain behaviour., Results: Corneal tissue subjected to freezing at -20 °C exhibited significant increases in tangent modulus (mechanical stiffness) by 13 ± 17% (p = 0.003) at 1% strain and 14 ± 12% (p < 0.001) at 2% strain. In contrast, the increases in corneal stiffness at -80 °C were insignificant (6 ± 14%, p = 0.099 at 1% strain, 6 ± 15%, p = 0.091 at 2% strain). The corresponding increases in tangent modulus in the sclera were all insignificant (for -20 °C: 4 ± 14%, p = 0.265 at 1% strain, 3 ± 9%, p = 0.186 at 2% strain; for -80 °C: 3 ± 18%, p = 0.537 at 1% strain and 3 ± 18%, p = 0.491 at 2% strain)., Conclusions: The study provided evidence that freezing and thawing led to insignificant changes in ocular tissue stiffness except in corneal tissue that was frozen at -20 °C., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: To compare a biomechanically corrected intraocular pressure (bIOP) algorithm provided by the dynamic Scheimpflug analyzer (Corvis ST) with Goldmann applanation tonometry IOP (Goldmann IOP) and standard dynamic Scheimpflug analyzer IOP measurements before and after laser in situ keratomileusis (LASIK) and refractive lenticule extraction small-incision lenticule extraction (SMILE) surgeries., Setting: Smile Eye Clinic, Munich, Germany, and University of Liverpool, Liverpool, United Kingdom., Design: Retrospective case series., Methods: Patients scheduled for LASIK and patients scheduled for small-incision lenticule extraction for myopia or myopic astigmatism were included. The preoperative and postoperative evaluations included Goldmann, Scheimpflug tomography, and dynamic Scheimpflug analyzer IOP measurements., Results: The study comprised 14 patients in the LASIK group and 22 patients in the small-incision lenticule extraction group. Preoperative Goldmann IOP and Scheimpflug analyzer IOP values showed significant positive correlation with central corneal thickness (CCT) (P = .05 for LASIK; P = .003 for small-incision lenticule extraction). No significant correlation was found between bIOP and CCT (P > .05). After both surgeries, there were significant decreases in Goldmann IOP (-3.2 mm Hg ± 3.4 [SD] and -3.2 ± 2.1 mm Hg, respectively; both P < .001) and Scheimpflug analyzer IOP (-3.7 ± 2.1 mm Hg and -3.3 ± 2.0 mm Hg, respectively, both P < .001) compared with preoperative readings, whereas bIOP did not differ significantly (0.1 ± 2.1 mm Hg and 0.8 ± 1.8 mm Hg, respectively; P = .80 and P = .273, respectively)., Conclusions: The bIOP readings before and after LASIK and small-incision lenticule extraction were neither significantly different nor correlated with CCT. In contrast, both Goldmann IOP and Scheimpflug analyzer IOP had significant reductions postoperatively and showed significant correlation with CCT preoperatively., (Copyright © 2018 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

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, J 0 and J 45 (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 J 0 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 J 45 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.

Purpose: To develop a novel diffusion-weighted magnetic resonance spectroscopy (DW-MRS) technique in conjunction with J-resolved spatially localized spectroscopy (JPRESS) to measure the apparent diffusion coefficients (ADCs) of brain metabolites beyond N-acetylaspartic acid (NAA), creatine (Cr), and choline (Cho) at 3T. This technique will be useful to probe tissue microstructures in vivo, as the various metabolites have different physiological characteristics., Methods: Two JPRESS spectra were collected (high b-value and low b-value), and the ADCs of 16 different metabolites were estimated. Two analysis pipelines were developed: 1) a 2D pipeline that uses ProFit software to extract ADCs from metabolites not typically accessible at 3T and 2) a 1D pipeline that uses TARQUIN software to extract the metabolite concentrations from each line in the 2D dataset, allowing for scaling as well as validation., Results: The ADCs of 16 different metabolites were estimated from within six subjects in parietal white matter. There was excellent agreement between the results obtained from the 1D and 2D pipelines for NAA, Cr, and Cho., Conclusion: The proposed technique provided consistent estimates for the ADCs of NAA, Cr, Cho, glutamate + glutamine, and myo-inositol in all subjects and additionally glutathione and scyllo-inositol in all but one subject. Magn Reson Med 78:1235-1245, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

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.

Background: Minimally invasive diagnostic procedures such as needle-core biopsy and fine-needle aspiration provide adequate material for molecular analyses. Advances in precision oncology are trending toward the interrogation of limited amounts of genomic material to guide clinical and therapeutic decisions. The aim of this study was to investigate the minimum cellularity needed on cytologic smears for the identification of clinically relevant variants with next-generation sequencing (NGS)., Methods: Thirty cases of cytologically diagnosed, resection-proven primary lung adenocarcinoma were identified. Nineteen of the 30 cases were known to harbor actionable variants. One Diff-Quik (DQ)-stained slide and 1 Papanicolaou (Pap)-stained slide were selected from each case. Cases were categorized as containing fewer than 100 tumor cells, 100 to 500 tumor cells, or more than 500 tumor cells. NGS was performed on the Ion Torrent platform., Results: NGS was successfully performed on all cell blocks and on 90% of the smears. Paired DQ and Pap smears showed similar cellularity, and cases that differed in cellularity were within 1 category of each other. The cases with more than 100 tumor cells had a 93% success rate; this was significantly different from the situation for cases with fewer than 100 tumor cells, which were successfully sequenced only 67% of the time. Overall, NGS was able to provide clinically relevant information for 83% of DQ smears and for 90% of Pap smears tested., Conclusions: The data show a significantly higher likelihood of successful NGS with cytologic smears with more than 100 tumor cells. There was a trend for a higher NGS success rate with Pap smears versus DQ smears. Cancer Cytopathol 2017;125:398-406. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Introduction: Urothelial carcinoma (UCC) of the bladder is the most common malignancy of the urinary tract. The performance of urine cytology (UCy) after radical cystectomy (RC) and urinary diversion is quite variable and there is no consensus regarding its role in post-treatment surveillance. The goal of this study is to retrospectively review the diagnostic value of positive (suspicious or positive for malignancy) diverted urine cytology (DUCy) in the detection of urinary tract recurrence of UCC., Materials and Methods: A retrospective 10-year (January 2005 to January 2015) computerized search for all DUCy specimens was conducted. All suspicious (Susp) or positive for malignant cells (PMC) ThinPrep cases were identified and retrospectively reviewed. Clinical, surgical, and pathological follow-up for patients with Susp or PMC UCy were tabulated and analyzed., Results: During the 10-year-period, 1,525 DUCy cases from 408 patients were identified. Of these, 25 cases (1.64%) from 10 patients were called either Susp (13; 0.85%) or PMC (12; 0.79%). The 25 DUCy cases occurred within a mean of 20 months post-RC. Out of 10 patients, 9 had a concurrent biopsy or a subsequent resection of the recurrent site. Of these 9 patients, 8 (89%) had subsequent biopsy or resection, which showed recurrent UCC. In 5/8 patients, positive DUCy was the very first manifestation of recurrence, which was subsequently confirmed by imaging or histology., Conclusion: It is our experience that patients with positive UCy after RC have a high likelihood of recurrent UCC and should be counseled and managed accordingly. Diagn. Cytopathol. 2016;44:975-979. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

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.

Backgroud: To evaluate the symmetry of corneal biomechanical metrics, measured using an ocular response analyzer (ORA) and self-built corneal inflation test platform, in bilateral rabbit corneas and to investigate their relationship with physical intraocular pressure (IOPp)., Methods: Twenty fresh enucleated eyes from ten rabbits were used for ex vivo whole ocular globe inflation. IOP was increased from 7.5 to 37.5 mmHg with 7.5 mmHg steps and biomechanical metrics were acquired using the ORA. At least 3 examinations were performed at each pressure stage. Two biomechanical metrics, corneal hysteresis (CH) and corneal resistance factor (CRF) were recorded and analyzed as a function of IOPp. Corneal specimens were then excised from the intact ocular globe and tested under inflation conditions up to 45.7 mmHg posterior pressure. The experimental pressure-deformation data was analyzed using an inverse modeling procedure to derive the stress-strain behavior of the cornea., Results: A comparison of corneal shape parameters showed no statistically significant difference (P > 0.05) between bilateral eyes. Similarly, there were no statistically significant differences in values of CH, CRF and corneal stiffness (as measured by the tangent modulus, Et) between bilateral eyes (CH: F = 0.94, P = 0.54; CRF: F = 4.42, P = 0.35; Et: F = 3.15, P = 0.12) at different pressure levels. IOPp was highly correlated with CRF while the relationship with CH was less pronounced., Conclusions: An obvious interocular symmetry in biomechanical metrics is found in this research. IOP has been shown to have important influences on the value of CRF provided by ORA.

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., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

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.