Corneoscleral Shell Research Articles

A mechanical model of ocular bulb vibrations and implications for acoustic tonometry.

In this study, we propose a comprehensive mechanical model of ocular bulb vibrations and discuss its implications for acoustic tonometry. The model describes the eye wall as a spherical, pre-stressed elastic shell containing a viscoelastic material and accounts for the interaction between the elastic corneoscleral shell and the viscoelastic vitreous humor. We investigate the natural frequencies of the system and the corresponding vibration modes, expanding the solution in terms of scalar and vector spherical harmonics. From a quantitative point of view, our findings reveal that the eyebulb vibration frequencies significantly depend on IOP. This dependency has two origins: "geometric" stiffening, due to an increase of the pre-stress, and "material" stiffening, due to the nonlinearity of the stress-strain curve of the sclera. The model shows that the second effect is by far dominant. We also find that the oscillation frequencies depend on ocular rigidity, but this dependency is important only at relatively large values of IOP. Thus close to physiological conditions, IOP is the main determinant of ocular vibration frequencies. The vitreous rheological properties are found to mostly influence vibration damping. This study contributes to the understanding of the mechanical behavior of the eye under dynamic conditions and thus has implications for non-contact intraocular pressure measurement techniques, such as acoustic tonometry. The model can also be relevant for other ocular pathological conditions, such as traumatic retinal detachment, which are believed to be influenced by the dynamic behavior of the eye.

2D or not 2D? Mapping the in-depth inclination of the collagen fibers of the corneoscleral shell

The collagen fibers of the corneoscleral shell play a central role in the eye mechanical behavior. Although it is well-known that these fibers form a complex three-dimensional interwoven structure, biomechanical and microstructural studies often assume that the fibers are aligned in-plane with the tissues. This is convenient as it removes the out-of-plane components and allows focusing on the 2D maps of in-plane fiber organization that are often quite complex. The simplification, however, risks missing potentially important aspects of the tissue architecture and mechanics. In the cornea, for instance, fibers with high in-depth inclination have been shown to be mechanically important. Outside the cornea, the in-depth fiber orientations have not been characterized, preventing a deeper understanding of their potential roles. Our goal was to characterize in-depth collagen fiber organization over the whole corneoscleral shell. Seven sheep whole-globe axial sections from eyes fixed at an IOP of 50 mmHg were imaged using polarized light microscopy to measure collagen fiber orientations and density. In-depth fiber orientation distributions and anisotropy (degree of fiber alignment) accounting for fiber density were quantified over the whole sclera and in 15 regions: central cornea, peripheral cornea, limbus, anterior equator, equator, posterior equator, posterior sclera and peripapillary sclera on both nasal and temporal sides. Orientation distributions were fitted using a combination of a uniform distribution and a sum of π-periodic von Mises distributions, each with three parameters: primary orientation μ, fiber concentration factor k, and weighting factor a. To study the features of fibers that are not in-plane, i.e., fiber inclination, we quantified the percentage of inclined fibers and the range of inclination angles (half width at half maximum of inclination angle distribution). Our measurements showed that the fibers were not uniformly in-plane but exhibited instead a wide range of in-depth orientations, with fibers significantly more aligned in-plane in the anterior parts of the globe. We found that fitting the orientation distributions required between one and three π-periodic von Mises distributions with different primary orientations and fiber concentration factors. Regions of the posterior globe, particularly on the temporal side, had a larger percentage of inclined fibers and a larger range of inclination angles than anterior and equatorial regions. Variations of orientation distributions and anisotropies may imply varying out-of-plane tissue mechanical properties around the eye globe. Out-of-plane fibers could indicate fiber interweaving, not necessarily long, inclined fibers. Effects of small-scale fiber undulations, or crimp, were minimized by using tissues from eyes at high IOPs. These fiber features also play a role in tissue stiffness and stability and are therefore also important experimental information.

An Ex Vivo Pilot Study to Assess the Feasibility of 3D Printing of Orbital Implants in Horses.

Severe ophthalmic conditions such as trauma, uveitis, corneal damage, or neoplasia can lead to eye removal surgery. Poor cosmetic appearance resulting from the sunken orbit ensues. The aim of this study was to demonstrate the feasibility of manufacturing a custom-made 3D-printed orbital implant made of biocompatible material for the enucleated horse and usable in conjunction to a corneoscleral shell. Blender, a 3D-image software, was used for prototype design. Twelve cadaver heads of adult Warmbloods were collected from the slaughterhouse. On each head, one eye was removed via a modified transconjunctival enucleation while the contralateral eye was kept intact as control. Ocular measurements were collected on each enucleated eye with the help of a caliper and used for prototype sizing. Twelve custom-made biocompatible porous prototypes were 3D-printed in BioMed Clear resin using the stereolithography technique. Each implant was fixated into the corresponding orbit, within the Tenon capsule and conjunctiva. Heads were frozen and thin slices were then cut in the transverse plane. A scoring system based on four criteria (space for ocular prosthesis, soft-tissue-coverage, symmetry to the septum, and horizontal symmetry), ranging from A (proper fixation) to C (poor fixation), was developed to evaluate implantation. The prototypes reached our expectations: 75% of the heads received an A score, and 25% a B score. Each implant cost approximately 7.30€ and took 5 hours for 3D-printing. The production of an economically accessible orbital implant made of biocompatible porous material was successful. Further studies will help determine if the present prototype is usable in vivo.

Modeling the compliance of the human eye with elastic membranes based on a bionic approach.

Together with the corneoscleral shell the intraocular pressure maintains the shape of the human eyeball and thus ensures both mechanical and optical integrity, whereby the relationship between the intraocular volume and pressure is described by the so-called ocular compliance. The compliance of the human eye is of significance insituations where a variation of the intraocular volume leads to a change in pressure or vice versa, as this is the case in many clinical settings. In order to provide a framework and set-up for experimental investigations and testing this paper presents a bionic inspired approach to simulate the ocular compliance by using elastomeric membranes- based on physiological behaviour. For parameter studies and for validation, the numerical analysis with hyperelastic material models shows good agreement with reported compliance curves. In addition, the compliance curves of six different elastomeric membranes have been measured. The results show that the characteristics of the compliance curve of the human eye can be modeled within a 5 % range using the proposed elastomeric membranes. A set-up for experimental investigations is presented that allows the simulation of the compliance curve of the human eye without simplifications in terms of shape, geometry, and deformation behaviour.

Who bears the load? IOP-induced collagen fiber recruitment over the corneoscleral shell

Collagen is the main load-bearing component of cornea and sclera. When stretched, both of these tissues exhibit a behavior known as collagen fiber recruitment. In recruitment, as the tissues stretch the constitutive collagen fibers lose their natural waviness, progressively straightening. Recruited, straight, fibers bear substantially more mechanical load than non-recruited, wavy, fibers. As such, the process of recruitment underlies the well-established nonlinear macroscopic behavior of the corneoscleral shell. Recruitment has an interesting implication: when recruitment is incomplete, only a fraction of the collagen fibers is actually contributing to bear the loads, with the rest remaining “in reserve”. In other words, at a given intraocular pressure (IOP), it is possible that not all the collagen fibers of the cornea and sclera are actually contributing to bear the loads.To the best of our knowledge, the fraction of corneoscleral shell fibers recruited and contributing to bear the load of IOP has not been reported. Our goal was to obtain regionally-resolved estimates of the fraction of corneoscleral collagen fibers recruited and in reserve. We developed a fiber-based microstructural constitutive model that could account for collagen fiber undulations or crimp via their tortuosity. We used experimentally-measured collagen fiber crimp tortuosity distributions in human eyes to derive region-specific nonlinear hyperelastic mechanical properties. We then built a three-dimensional axisymmetric model of the globe, assigning region-specific mechanical properties and regional anisotropy. The model was used to simulate the IOP-induced shell deformation. The model-predicted tissue stretch was then used to quantify collagen recruitment within each shell region. The calculations showed that, at low IOPs, collagen fibers in the posterior equator were recruited the fastest, such that at a physiologic IOP of 15 mmHg, over 90% of fibers were recruited, compared with only a third in the cornea and the peripapillary sclera. The differences in recruitment between regions, in turn, mean that at a physiologic IOP the posterior equator had a fiber reserve of only 10%, whereas the cornea and peripapillary sclera had two thirds. At an elevated IOP of 50 mmHg, collagen fibers in the limbus and the anterior/posterior equator were almost fully recruited, compared with 90% in the cornea and the posterior sclera, and 70% in the peripapillary sclera and the equator. That even at such an elevated IOP not all the fibers were recruited suggests that there are likely other conditions that challenge the corneoscleral tissues even more than IOP. The fraction of fibers recruited may have other potential implications. For example, fibers that are not bearing loads may be more susceptible to enzymatic digestion or remodeling. Similarly, it may be possible to control tissue stiffness through the fraction of recruited fibers without the need to add or remove collagen.

Structural and biomechanical properties and trace elements composition of the corneoscleral eye shell in normal tension glaucoma

The results of comparative studies of the structural and biomechanical features of the corneoscleral eye shell in various clinical forms of glaucoma are presented. The article discusses how the systemic and local imbalance of trace elements that regulate collagen biosynthesis, the formation of cross-links in the connective tissue structures of the sclera, and the hydrodynamics of the intraocular fluid, affect the intraocular pressure level, and thereby the character of the development of glaucomatous lesions in normal tension glaucoma. Modern literature is shown to indicate the prospects for further research in this direction.

Determination of significant diagnostic criteria for the development of primary open-angle glaucoma based on a comprehensive statistical analysis of biomechanical and hemodynamic parameters of the eye

A complex statistical (correlation, discriminant, factorial) analysis of a set of parameters - biomechanical characteristics of the corneoscleral shell of the eye, hemodynamic parameters and perimetric indices, determined during examination of 110 eyes, including 69 eyes with various stages of primary open-angle glaucoma (POAG) and 41 eyes without ophthalmopathology – was carried out. Significantly correlated parameters characteristic of a particular stage of POAG were identified. The set of identified correlations characterizes progressive glaucoma damage as a process associated with a simultaneous change in the biomechanics of the eye shells and the scleral lamina cribrosa, as well as the blood supply to the choroid and retina, which, apparently, underlies the gradual deterioration of its photosensitivity and changes in the visual field. It was found that correlations within groups of patients with various stages of POAG change significantly with the progression of glaucomatous process, and, possibly, reflect the change in the contribution of biomechanical and hemodynamical disorders to the development of glaucomatous lesion at the corresponding stage of its development.

Age and Menopause Effects on Ocular Compliance and Aqueous Outflow

PurposeGlaucoma is the second leading cause of blindness worldwide. Recent work suggests that estrogen and the timing of menopause play a role in modulating the risk of developing glaucoma. Menopause is known to cause modest changes in intraocular pressure; yet, whether this change is mediated through the outflow pathway remains unknown. Menopause also affects tissue biomechanical properties throughout the body; however, the impact of menopause on ocular biomechanical properties is not well characterized.MethodsHere, we simultaneously assessed the impact of menopause on aqueous outflow facility and ocular compliance, as a measure of corneoscleral shell biomechanics. We used young (3–4 months old) and middle-aged (9–10 months old) Brown Norway rats. Menopause was induced by ovariectomy (OVX), and control animals underwent sham surgery, resulting in the following groups: young sham (n = 5), young OVX (n = 6), middle-aged sham (n = 5), and middle-aged OVX (n = 5). Eight weeks postoperatively, we measured outflow facility and ocular compliance.ResultsMenopause resulted in a 34% decrease in outflow facility and a 19% increase in ocular compliance (P = 0.011) in OVX animals compared with sham controls (P = 0.019).ConclusionsThese observations reveal that menopause affects several key physiological factors known to be associated with glaucoma, suggesting that menopause may contribute to an increased risk of glaucoma in women.

Full-field displacement measurement of corneoscleral shells by combining multi-camera speckle interferometry with 3D shape reconstruction

Changes in the biomechanical properties of the connective tissue of the eye occur with age and underlie the development of several ocular diseases, such as glaucoma, myopia, and keratoconus. The biomechanical dynamics of ocular connective tissue are measured by ex vivo inflation testing, in which intraocular pressure (IOP) is varied and optical methods are used to produce maps of corneal and scleral displacement. Current optical methods are limited by acquisition rate, occlusions, poor spatial resolution, and insufficient 3D mapping. We developed an interferometric optical method integrates four-camera electronic speckle pattern interferometry (ESPI) and a novel three-dimensional (3D) shape reconstruction process to measure shape and full-field mechanical deformations of corneal and scleral shells during ex vivo inflation testing. Each camera provides accurate measurements of the laser beam phase related to deformations of the specimen surface; a multi-view stereovision method generates the shape of the specimen and a functional form that links every pixel of a given camera to 3D points on the specimen's visible surface. In this way, dynamic deformations of the specimen are localized, with quantification of the time-dependent 3D displacements of the specimen at nanometric accuracy. The ESPI-3D system is suitable for analyzing scleral deformation and morphological changes caused by time-varying IOP.

Measurement of Ocular Compliance Using iPerfusion.

The pressure-volume relationship of the eye is determined by the biomechanical properties of the corneoscleral shell and is classically characterised by Friedenwald's coefficient of ocular rigidity or, alternatively, by the ocular compliance (OC), defined as dV/dP. OC is important in any situation where the volume (V) or pressure (P) of the eye is perturbed, as occurs during several physiological and pathological processes. However, accurately measuring OC is challenging, particularly in rodents. We measured OC in 24 untreated enucleated eyes from 12 C57BL/6 mice using the iPerfusion system to apply controlled pressure steps, whilst measuring the time-varying flow rate into the eye. Pressure and flow data were analysed by a “Discrete Volume” (integrating the flow trace) and “Step Response” method (fitting an analytical solution to the pressure trace). OC evaluated at 13 mmHg was similar between the two methods (Step Response, 41 [37, 46] vs. Discrete Volume, 42 [37, 48] nl/mmHg; mean [95% CI]), although the Step Response Method yielded tighter confidence bounds on individual eyes. OC was tightly correlated between contralateral eyes (R2 = 0.75, p = 0.0003). Following treatment with the cross-linking agent genipin, OC decreased by 40 [33, 47]% (p = 0.0001; N = 6, Step Response Method). Measuring OC provides a powerful tool to assess corneoscleral biomechanics in mice and other species.

Cyclic Pattern of Intraocular Pressure (IOP) and Transient IOP Fluctuations in Nonhuman Primates Measured with Continuous Wireless Telemetry

ABSTRACTPurpose: Most studies on intraocular pressure (IOP) to monitor IOP “fluctuations” in glaucoma patients have been performed with snapshot tonometry techniques that obtain IOP measurements at single time points weeks to months apart. However, IOP telemetry has shown that IOP varies from second-to-second due to blinks, saccades, and systolic vascular filling. The purpose of this study was to characterize the cyclic pattern of baseline IOP and transient IOP fluctuations in 3 nonhuman primates (NHPs).Methods: Bilateral IOP was measured using a proven implantable telemetry system and recorded 500 times per second, 24 hours a day, up to 451 continuous days in 3 male rhesus macaques aged 4 to 5 years old. The IOP transducers were calibrated every two weeks via anterior chamber cannulation manometry and all data were continuously corrected for signal drift via software, filtered for signal noise and dropout, and peaks and troughs were quantified and counted using a finite impulse response filter; waking hours were defined as 6:00–18:00 hours based on room light cycle.Results: Fourier transform analyses of baseline IOP and the hourly mean frequency of transient IOP fluctuations > 0.6 mmHg, 0.6–5 mmHg and > 5 mmHg above baseline during waking hours exhibited an approximate 16- to 91-day cyclic pattern in all NHPs. There were no measured environmental or experimental factors associated with this cyclical pattern.Conclusions: While the importance of the cyclic pattern identified in IOP and its fluctuations is unknown at this time, it is plausible that this pattern is relevant to both homeostasis and pathophysiology of the ONH, corneoscleral shell, and aqueous outflow pathways.

Advantages of dynamic bi-directional applanation tonometry in primary open-angle glaucoma diagnostics

Purpose. To study tonometry parameters features, measured by different methods, taking into account individual morphometric eye parameters and biomechanical properties of the corneoscleral shell in patients with the initial and the advanced stages of primary open angle glaucoma (POAG).Material and methods. 51 patients (99 eyes) aged 48–82, with the initial (45 eyes) and advanced stages (54 eyes) of POAG were examined. The control group consisted of 31 patients (62 eyes) aged 47–83 without ophthalmic pathology. In addition to standard ophthalmologic examination, tonometry was performed using the Ocular Response Analyzer (ORA, Reichert Inc., the USA).Results. The main tonometry parameters of ORA revealed significant differences between POAG patients and the control group. No significant difference in the central corneal thickness (CCT) was found between the POAG and the control group. Patients with I and II stages of glaucoma taken separately showed differences in CCT and tonometry parameters.Conclusion. Dynamic bi-directional applanation tonometry enables to take into account the changes in viscoelastic properties of the corneoscleral eye shell, and definitely has diagnostic advantages in examining patients with various stages of POAG.

Biomechanics of the corneoscleral shell and hemodynamics of the glaucomatous eye: is there a connection?

Purpose. To find the connection between the parameters of the corneoscleral shell and lamina cribrosa (LC) and hemodynamic parameters of the eyes with primary open angle glaucoma (POAG).Materials and methods. The study involved 111 eyes of 63 patients, including 41 eyes without ophthalmic pathology (control group, mean age M ± SD 66.9 ± 18.2 yrs), 22 eyes with the initial glaucoma stage (group 1, mean age 65.9 ± 11.3 yrs), 31 eyes with the developed glaucoma stage (group 2, mean age 69.2 ± 17.3 yrs), and 17 eyes with the advanced glaucoma stage (group 3, mean age 69,7 ± 7.3 yrs). LC parameters and the density of surface (SVL) and deep (DVL) vascular layers were measured using Spectralis OCT2 with an angiography module (Heidelberg Engineering, Germany) in the enhanced deep imaging (EDI) mode using AngioTool software. Corneal hysteresis (CH) and corneal resistance factor (CRF) were determined using ORA (Ocular Response Analyzer, Reichert, USA). The rigidity coefficient (E) of the corneoscleral shell was measured by a GlauTest-60 tonograph (Russia) operation in the differential tonometry mode. The elasticity coefficient (s) was determined by a modified differential tonometry technique. The rheographic index (RI) and pulse blood volume (PBV) were measured using transpalpebral rheoophthalmography.Results. A statistically significant correlation was revealed between CH and SVL (р = 0.005, r = 0.288), LC thickness and SVL and DVL (р = 0.001, r = 0.374 and р = 0.003, r = 0.397, respectively). A negative statistically significant correlation was found between E and RI (р = 0.000, r = -0.538) as well as between E and PBV (р = 0.001, r = -0.376). A similar correlation was revealed between s and theses parameters (RI and PBV; р = 0.027, r = -0.404 and р = 0.024, r = -0.410, respectively). E increase is accompanied by a decrease in the SVL density (р = 0.000, r = -0.376); besides, PBV is negatively correlated with the LC depth (р = 0.022, r = -0.257).Conclusion. In POAG, deteriorated blood supply of inner ocular shells (decreased RI, PBV, SVL and DVL density) correlates with (a) increased corneoscleral rigidity (manifested in the increase of rigidity and elasticity coefficients, and the decrease of CH), and (b) decreased LC thickness and its increased depth. Increased rigidity of the corneoscleral shell contributes to an LC posterior displacement. It must be concluded that LC thickness is a more sensitive biomechanical parameter that changes even in the initial stages of POAG and has a high diagnostic value.

Crimp around the globe; patterns of collagen crimp across the corneoscleral shell

Our goal was to systematically quantify the collagen crimp morphology around the corneoscleral shell, and test the hypothesis that collagen crimp is not uniform over the globe. Axial longitudinal cryosections (30 μm) of three sheep eyes, fixed at 0 mmHg IOP, were imaged using polarized light microscopy to quantify the local collagen in 8 regions: two corneal (central and peripheral) and six scleral (limbus, anterior-equatorial, equatorial, posterior-equatorial, posterior and peripapillary). Collagen crimp period (length of one wave), tortuosity (path length divided by end-to-end length), waviness (SD of orientation), amplitude (half the peak to trough distance), and conformity (width of contiguous similarly oriented bundles) were measured in each region. Measurements were obtained on 8216 collagen fiber bundles. When pooling measurements across the whole eye globe, the median crimp values were: 23.9 μm period, 13.2 μm conformity, 0.63 μm amplitude, 1.006 tortuosity, and 12.7° waviness. However, all parameters varied significantly across the globe. Median bundle periods in the central cornea, limbus, and peripapillary sclera (PPS) were 14.1 μm, 29.5 μm, and 22.9 μm, respectively. Median conformities were 20.8 μm, 14.5 μm, and 15.1 μm, respectively. Median tortuosities were 1.005, 1.007, and 1.007, respectively. Median waviness’ were 11.4°, 13.2°, and 13.2°, respectively. Median amplitudes were 0.35 μm, 0.87 μm, and 0.65 μm, respectively. All parameters varied significantly across the globe. All regions differed significantly from one another on at least one parameter. Regions with small periods had large conformities, and bundles with high tortuosity had high waviness and amplitude. Waviness, tortuosity, and amplitude, associated with nonlinear biomechanical behavior, exhibited “double hump” distributions, whereas period and conformity, representing tissue organization, were substantially different between sclera and cornea. Though the biomechanical implications and origin of the patterns observed remain unclear, our findings of well-defined patterns of collagen crimp across the corneoscleral shell, consistent between eyes, support the existence of mechanisms that regulate collagen characteristics at the regional or smaller levels. These results are experimental data necessary for more realistic models of ocular biomechanics and remodeling.

Тонометрия у пациентов с первичной открытоугольной глаукомой с учетом индивидуальных морфометрических показателей глаза и биомеханических свойств корнеосклеральной оболочки

Тонометрия у пациентов с первичной открытоугольной глаукомой с учетом индивидуальных морфометрических показателей глаза и биомеханических свойств корнеосклеральной оболочки

Влияние аналогов простагландинов на биомеханические показатели корнеосклеральной оболочки глаза при первичной открытоугольной глаукоме

, were measured for 57 patients, including 49 patients aged 51-75 (ave. 66.0 ± 1.7 years) with various stages of POAG and the control group of 8 patients aged 61-68 (ave. 63.7 ± 0.9 years) with no eye pathology (except for age-related cataract). All patients with POAG received hypotensive therapy. Of these, 24 patients received one of prostaglandin analogues (Glauprost) as monotherapy or in combination with beta-blockers and/or carbonic anhydrase inhibitors during no less than 3 months, and 25 patients only received hypotensive therapy beta-blockers and/or carbonic anhydrase inhibitors. The patients’ examination consisted of elastotonometry by Maklakov with three loads having different weights, modified Schiotz differential tonometry using a GlauTest 60 tonograph, measurement of corneal compensated intraocular pressure (IOPcc) and corneal hysteresis (CH) by Ocular Response Analyzer (ORA, Reichert, USA). Results. Coefficient К (2.45 ± 0.15) of patients with stage II POAG (mean age 65.0 ± 1.5 years) who did not use prostaglandin analogues was significantly higher (p < 0.05) than that of patients of the same age group (mean age 66.5 ± 1.8 years) with the same glaucoma stage who received Glauprost (К = 2.09 ± 0.17), which implies a higher risk of glaucoma progression. When prostaglandin analogues were used, CH level proved to be reliably (p < 0.05) higher (9.10 ± 0.4 mm Hg) as compared to patients who received no such therapy (8.14 ± 0.7 mm Hg): this is viewed as a favorable prognostic criterion for the POAG course. A less pronounced decrease of K and increase of CH after prostaglandin analogue instillations than in stage II POAG was also noted in patients with stage III POAG. Conclusion. Prostaglandin analogue Glauprost has a favorable impact on biomechanical parameters of the corneoscleral eye shell, especially in patients with stage II POAG. It lessens glaucoma progression risk induced by disturbed elastic properties of the cornea and the sclera and their ratio // Russian Ophthalmological Journal, 2017; 1: 15-9.

Non-invasive MRI Assessments of Tissue Microstructures and Macromolecules in the Eye upon Biomechanical or Biochemical Modulation.

The microstructural organization and composition of the corneoscleral shell (CSS) determine the biomechanical behavior of the eye, and are important in diseases such as glaucoma and myopia. However, limited techniques can assess these properties globally, non-invasively and quantitatively. In this study, we hypothesized that multi-modal magnetic resonance imaging (MRI) can reveal the effects of biomechanical or biochemical modulation on CSS. Upon intraocular pressure (IOP) elevation, CSS appeared hyperintense in both freshly prepared ovine eyes and living rat eyes using T2-weighted MRI. Quantitatively, transverse relaxation time (T2) of CSS increased non-linearly with IOP at 0–40 mmHg and remained longer than unloaded tissues after being unpressurized. IOP loading also increased fractional anisotropy of CSS in diffusion tensor MRI without apparent change in magnetization transfer MRI, suggestive of straightening of microstructural fibers without modification of macromolecular contents. Lastly, treatments with increasing glyceraldehyde (mimicking crosslinking conditions) and chondroitinase-ABC concentrations (mimicking glycosaminoglycan depletion) decreased diffusivities and increased magnetization transfer in cornea, whereas glyceraldehyde also increased magnetization transfer in sclera. In summary, we demonstrated the changing profiles of MRI contrast mechanisms resulting from biomechanical or biochemical modulation of the eye non-invasively. Multi-modal MRI may help evaluate the pathophysiological mechanisms in CSS and the efficacy of corneoscleral treatments.

Sclera as the target tissue in progressive myopia.

Introduction: The aim of the study was to study the eye corneoscleral shell and connective tissue (CT) system in children with acquired and congenital progressive myopia, and to identify the informative diagnostic criteria of weakened supporting function of the sclera. 155 children aged 9-17 were examined: 18 had emmetropia or hyperopia, 20--low, 32--moderate and 85--high myopia. 32 children had complicated myopia (CM) due to peripheral retinal degeneration (PRD). Corneal hysteresis (CH), scleral acoustic density (SAD), X-ray vertebral topography, plantography, joint hypermobility, serum cortisol (SC), and autonomic balance were measured. Corneal hysteresis, mmHg and SAD, rel. units (mean ± SE) were lower if myopia was higher: in low myopia, CH was 13.0 ± 0.3, in moderate myopia, 11.9 ± 0.3#, in high myopia, 10.7 ± 0.3#; SAD was resp. 215.9 ± 5.2, 204.9 ± 3.7# and 192.8 ± 5.8# (#: p < 0.05 with regard to low myopia). The lowest CH (10.3 ± 0.4) and SAD (186.5 ± 7.3) were found in acquired CM. Congenital myopia with PRD showed CH and SAD greater than in acquired CM (p < 0.05). Serum cortisol (nmol/L) in hyperopia was 335.8 ± 40.9 and dropped with higher myopia: in low myopia--290.7 ± 58.6, in moderate--250.9 ± 26.4, in high--243.9 ± 20.5. The lowest SC was found in acquired CM, consistent with CH and SAD. Connective tissue dysplasia progressed with higher myopia: it was found in 76.9% of children with low, 82.4% with moderate, 89.2% with high acquired myopia, and 91.7% with congenital myopia. Biomechanical defects of CT and hormonal imbalance were combined with vegetative nervous system (VNS) imbalance: in high myopia only 20.5% of children were eutonic, 61.5%--sympathicotonic and 17.5% parasympathicotonic. School age children with progressive myopia showed biomechanical abnormalities of the corneosclera, along with CT dysplasia, decreased SC and imbalanced VNS, more pronounced in acquired complicated myopia. Our findings contribute to the understanding of myopia pathogenesis and to the diagnostic/prognostic evaluation of myopic children, in particular when deciding whether sclera-strengthening intervention is needed.

Use and Misuse of Laplace's Law in Ophthalmology.

PurposeLaplace's Law, with its compactness and simplicity, has long been employed in ophthalmology for describing the mechanics of the corneoscleral shell. We questioned the appropriateness of Laplace's Law for computing wall stress in the eye considering the advances in knowledge of ocular biomechanics.MethodsIn this manuscript we recapitulate the formulation of Laplace's Law, as well as common interpretations and uses in ophthalmology. Using numerical modeling, we study how Laplace's Law cannot account for important characteristics of the eye, such as variations in globe shape and size or tissue thickness, anisotropy, viscoelasticity, or that the eye is a living, dynamic organ.ResultsWe show that accounting for various geometrical and material factors, excluded from Laplace's Law, can alter estimates of corneoscleral wall stress as much as 456% and, therefore, that Laplace's Law is unreliable.ConclusionsWe conclude by illustrating how computational techniques, such as finite element modeling, can account for the factors mentioned above, and are thus more suitable tools to provide quantitative characterization of corneoscleral biomechanics.

Magic angle-enhanced MRI of fibrous microstructures in sclera and cornea with and without intraocular pressure loading.

The structure and biomechanics of the sclera and cornea are central to several eye diseases such as glaucoma and myopia. However, their roles remain unclear, partly because of limited noninvasive techniques to assess their fibrous microstructures globally, longitudinally, and quantitatively. We hypothesized that magic angle-enhanced magnetic resonance imaging (MRI) can reveal the structural details of the corneoscleral shell and their changes upon intraocular pressure (IOP) elevation. Seven ovine eyes were extracted and fixed at IOP = 50 mm Hg to mimic ocular hypertension, and another 11 eyes were unpressurized. The sclera and cornea were scanned at different angular orientations relative to the main magnetic field inside a 9.4-Tesla MRI scanner. Relative MRI signal intensities and intrinsic transverse relaxation times (T2 and T2*) were determined to quantify the magic angle effect on the corneoscleral shells. Three loaded and eight unloaded tendon samples were scanned as controls. At magic angle, high-resolution MRI revealed distinct scleral and corneal lamellar fibers, and light/dark bands indicative of collagen fiber crimps in the sclera and tendon. Magic angle enhancement effect was the strongest in tendon and the least strong in cornea. Loaded sclera, cornea, and tendon possessed significantly higher T2 and T2* than unloaded tissues at magic angle. Magic angle-enhanced MRI can detect ocular fibrous microstructures without contrast agents or coatings and can reveal their MR tissue property changes with IOP loading. This technique may open up new avenues for assessment of the biomechanical and biochemical properties of ocular tissues in aging and in diseases involving the corneoscleral shell.