Regional differences in electroactive response of the sclera.

The sclera exhibits mechanical response when subjected to an external electric stimulation. The scleral electroactive response is a function of its charge density, mechanical properties, thickness, and strength of the applied electric voltage. The primary objective of the present work was to investigate the regional differences in the electroactive response of porcine sclera. To this end, we cut scleral strips in meridional directions from superior-temporal, superior-nasal, inferior-temporal, and inferior-nasal quadrants. In addition, we excised samples circumferentially from the posterior, equatorial, and anterior regions. The electroactive bending response of these samples was measured under 10 and 15 V in 0.15 M NaCl solution. The meridional samples were tested under two different configurations by clamping them either from their anterior or posterior end. It was observed that the scleral electroactive deformation increased with increasing the the electric voltage. Furthermore, regardless of the region from which meridional strips were excised, their electroactive response was considerably larger when they were clamped from their anterior end. Unlike meridional strips, the electroactive response of circumferential samples was significantly dependent on the location, that is, the average maximum bending angle of posterior samples was significantly larger than that of equatorial and anterior strips. The regionally different electroactive bending response of the sclera was discussed in terms of the variation in its biochemical and biomechanical properties throughout the eyeball.

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.

A direct fiber approach to model sclera collagen architecture and biomechanics.

Sclera collagen fiber microstructure and mechanical behavior are central to eye physiology and pathology. They are also complex, and are therefore often studied using modeling. Most models of sclera, however, have been built within a conventional continuum framework. In this framework, collagen fibers are incorporated as statistical distributions of fiber characteristics such as the orientation of a family of fibers. The conventional continuum approach, while proven successful for describing the macroscale behavior of the sclera, does not account for the sclera fibers are long, interwoven and interact with one another. Hence, by not considering these potentially crucial characteristics, the conventional approach has only a limited ability to capture and describe sclera structure and mechanics at smaller, fiber-level, scales. Recent advances in the tools for characterizing sclera microarchitecture and mechanics bring to the forefront the need to develop more advanced modeling techniques that can incorporate and take advantage of the newly available highly detailed information. Our goal was to create a new computational modeling approach that can represent the sclera fibrous microstructure more accurately than with the conventional continuum approach, while still capturing its macroscale behavior. In this manuscript we introduce the new modeling approach, that we call direct fiber modeling, in which the collagen architecture is built explicitly by long, continuous, interwoven fibers. The fibers are embedded in a continuum matrix representing the non-fibrous tissue components. We demonstrate the approach by doing direct fiber modeling of a rectangular patch of posterior sclera. The model integrated fiber orientations obtained by polarized light microscopy from coronal and sagittal cryosections of pig and sheep. The fibers were modeled using a Mooney-Rivlin model, and the matrix using a Neo-Hookean model. The fiber parameters were determined by inversely matching experimental equi-biaxial tensile data from the literature. After reconstruction, the direct fiber model orientations agreed well with the microscopy data both in the coronal plane (adjusted R2 = 0.8234) and in the sagittal plane (adjusted R2 = 0.8495) of the sclera. With the estimated fiber properties (C10 = 5746.9 MPa; C01 = -5002.6 MPa, matrix shear modulus 200 kPa), the model's stress-strain curves simultaneously fit the experimental data in radial and circumferential directions (adjusted R2's 0.9971 and 0.9508, respectively). The estimated fiber elastic modulus at 2.16% strain was 5.45 GPa, in reasonable agreement with the literature. During stretch, the model exhibited stresses and strains at sub-fiber level, with interactions among individual fibers which are not accounted for by the conventional continuum methods. Our results demonstrate that direct fiber models can simultaneously describe the macroscale mechanics and microarchitecture of the sclera, and therefore that the approach can provide unique insight into tissue behavior questions inaccessible with continuum approaches.

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.

Linear viscoelasticity of human sclera and posterior ocular tissues during tensile creep.

PURPOSE: Despite presumed relevance to ocular diseases, the viscoelastic properties of the posterior human eye have not been evaluated in detail. We performed creep testing to characterize the viscoelastic properties of ocular regions, including the sclera, optic nerve (ON) and ON sheath. METHODS: We tested 10 pairs of postmortem human eyes of average age 77 ± 17 years, consisting of 5 males and 5 females. Except for the ON that was tested in native shape, tissues were trimmed into rectangles. With physiologic temperature and constant wetting, tissues were rapidly loaded to tensile stress that was maintained by servo feedback as length was monitored for 1,500 sec. Relaxation modulus was computed using Prony series, and Deborah numbers estimated for times scales of physiological eye movements. RESULTS: Correlation between creep rate and applied stress level was negligible for all tissues, permitting description as linear viscoelastic materials characterized by lumped parameter compliance equations for limiting behaviors. The ON was the most compliant, and anterior sclera least compliant, with similar intermediate values for posterior sclera and ON sheath. Sensitivity analysis demonstrated that linear behavior eventually become dominant after long time. For the range of typical pursuit tracking, all tissues exhibit Debora numbers less than 75, and should be regarded as viscoelastic. With a 6.7 Deborah number, this is especially so for the ON during pursuit and convergence. CONCLUSIONS: Posterior ocular tissues exhibit creep consistent with linear viscoelasticity necessary for describing biomechanical behavior of the ON, its sheath, and sclera during physiological eye movements and eccentric ocular fixations. Running Head: Tensile Creep of Human Ocular Tissues.

Clinical Ocular Biomechanics: Where Are We after 20 Years of Progress?

Purpose: Ocular biomechanics is an assessment of the response of the structures of the eye to forces that may lead to disease development and progression, or influence the response to surgical intervention. The goals of this review are (1) to introduce basic biomechanical principles and terminology, (2) to provide perspective on the progress made in the clinical study and assessment of ocular biomechanics, and (3) to highlight critical studies conducted in keratoconus, laser refractive surgery, and glaucoma in order to aid interpretation of biomechanical parameters in the laboratory and in the clinic.Methods: A literature review was first conducted of basic biomechanical studies related to ocular tissue. The subsequent review of ocular biomechanical studies was limited to those focusing on keratoconus, laser refractive surgery, or glaucoma using the only two commercially available devices that allow rapid assessment of biomechanical response in the clinic.Results: Foundational studies on ocular biomechanics used a combination of computer modeling and destructive forces on ex-vivo tissues. The knowledge gained from these studies could not be directly translated to clinical research and practice until the introduction of non-contact tonometers that quantified the deformation response of the cornea to an air puff, which represents a non-destructive, clinically appropriate load. The corneal response includes a contribution from the sclera which may limit corneal deformation. Two commercial devices are available, the Ocular Response Analyzer which produces viscoelastic parameters with a customized load for each eye, and the Corvis ST which produces elastic parameters with a consistent load for every eye. Neither device produces the classic biomechanical properties reported in basic studies, but rather biomechanical deformation response parameters which require careful interpretation.Conclusions: Research using clinical tools has enriched our understanding of how ocular disease alters ocular biomechanics, as well as how ocular biomechanics may influence the pathophysiology of ocular disease and response to surgical intervention.

Finite element modeling of effects of tissue property variation on human optic nerve tethering during adduction.

Tractional tethering by the optic nerve (ON) on the eye as it rotates towards the midline in adduction is a significant ocular mechanical load and has been suggested as a cause of ON damage induced by repetitive eye movements. We designed an ocular finite element model (FEM) simulating 6° incremental adduction beyond the initial configuration of 26° adduction that is the observed threshold for ON tethering. This FEM permitted sensitivity analysis of ON tethering using observed material property variations in measured hyperelasticity of the anterior, equatorial, posterior, and peripapillary sclera; and the ON and its sheath. The FEM predicted that adduction beyond the initiation of ON tethering concentrates stress and strain on the temporal side of the optic disc and peripapillary sclera, the ON sheath junction with the sclera, and retrolaminar ON neural tissue. However, some unfavorable combinations of tissue properties within the published ranges imposed higher stresses in these regions. With the least favorable combinations of tissue properties, adduction tethering was predicted to stress the ON junction and peripapillary sclera more than extreme conditions of intraocular and intracranial pressure. These simulations support the concept that ON tethering in adduction could induce mechanical stresses that might contribute to ON damage.

Relative Contributions of Intraocular and Cerebrospinal Fluid Pressures to the Biomechanics of the Lamina Cribrosa and Laminar Neural Tissues.

Purpose: The laminar region of the optic nerve head (ONH), thought to be the site of damage to the retinal ganglion cell axons in glaucoma, is continuously loaded on its anterior and posterior surfaces by dynamic intraocular pressure (IOP) and orbital cerebrospinal fluid pressure (CSFP), respectively. Thus, translaminar pressure (TLP; TLP = IOP-CSFP) has been proposed as a glaucoma risk factor. Methods: Three eye-specific finite element models of the posterior human eye were constructed, including full 3D microstructures of the load-bearing lamina cribrosa (LC) with interspersed laminar neural tissues (NTs), and heterogeneous, anisotropic, hyperelastic material formulations for the surrounding peripapillary sclera and adjacent pia. ONH biomechanical responses were simulated using three combinations of IOP and CSFP loadings consistent with posture change from sitting to supine. Results: Results show that tensile, compressive, and shear stresses and strains in the ONH were higher in the supine position compared to the sitting position (P < 0.05). In addition, LC beams bear three to five times more TLP-driven stress than interspersed laminar NT, whereas laminar NT exhibit three to five times greater strain than supporting LC (P < 0.05). Compared with CSFP, IOP drove approximately four times greater stress and strain in the LC, NT, and peripapillary sclera, normalized per mm Hg pressure change. In addition, IOP drove approximately three-fold greater scleral canal expansion and anterior-posterior laminar deformation than CSFP per mm Hg (P < 0.05). Conclusions: Whereas TLP has been hypothesized to play a prominent role in ONH biomechanics, the IOP and CSFP effects are not equivalent, as IOP-driven stress, strain, and deformation play a more dominant role than CSFP effects.

Elevated IOP Alters the Material Properties of Sclera and Lamina Cribrosa in Monkeys.

Objective: Elevated intraocular pressure (IOP) has significant impacts on different stages in the progression of chronic glaucoma. In this study, we investigated changes in the material properties of sclera and lamina cribrosa (LC) in a nonhuman primate model with elevated IOP. Methods: Normal adult Tibetan macaques were selected for the construction of elevated IOP model. After 40 days of stable maintenance on the ocular hypertension, the binocular eyeballs were obtained for the measurement of macroscopic parameters of the eyeballs. Posterior scleral tissue strips were obtained in circumferential and axial directions, and thickness was measured, respectively. Biomechanical parameters were obtained with stress relaxation, creep, and tensile test. The nanoindentation test was performed on the LC and scleral tissue around optic nerve head (ONH) to obtain compressive modulus. Results: In the presence of elevated IOP, variations of the axial diameter of the eyeball were greater than those of the transverse diameter, and the mean scleral thickness around ONH was smaller in the experimental group than control group. The elastic modulus and stress relaxation modulus of sclera were larger, and the creep rate was lower in the experimental group than control group. In the control group, the elastic modulus and stress relaxation modulus of the circumferential sclera were larger in the axial direction, and creep rate was smaller. In the experimental group, there was no significant difference in biomechanical characteristics between the two directions. Compared to the control group, the compression modulus of the LC was smaller, and the compression modulus of sclera around ONH was larger in the experimental group. Conclusion: Elevated IOP alters the viscoelasticity and anisotropy of sclera and LC. These may contribute to reduction of the organizational resistance to external forces and decline in the ability of self-recovery.

Eye-specific 3D modeling of factors influencing oxygen concentration in the lamina cribrosa.

Our goal was to identify the factors with the strongest influence on the minimum lamina cribrosa (LC) oxygen concentration as potentially indicative of conditions increasing hypoxia risk. Because direct measurement of LC hemodynamics and oxygenation is not yet possible, we developed 3D eye-specific LC vasculature models. The vasculature of a normal monkey eye was perfusion-labeled post-mortem. Serial cryosections through the optic nerve head were imaged using fluorescence and polarized light microscopy to visualize the vasculature and collagen, respectively. The vasculature within a 450 µm-thick region containing the LC - identified from the collagen, was segmented, skeletonized, and meshed for simulations. Using Monte Carlo sampling, 200 vascular network models were generated with varying vessel diameter, neural tissue oxygen consumption rate, inflow hematocrit, and blood pressures (arteriole, venule, anterior boundary, and posterior boundary). Factors were varied over ranges of baseline ±20% with uniform probability. For each model we first obtained the blood flow, and from this the neural tissue oxygen concentration. ANOVA was used to identify the factors with the strongest influence on the minimum (10th percentile) oxygen concentration in the LC. The three most influential factors were, in ranked order, vessel diameter, neural tissue oxygen consumption rate, and arteriole pressure. There was a strong interaction between vessel diameter and arteriole pressure whereby the impact of one factor was larger when the other factor was small. Our results show that, for the eye analyzed, conditions that reduce vessel diameter, such as vessel compression due to elevated intraocular pressure or gaze-induced tissue deformation, may particularly contribute to decreased LC oxygen concentration. More eyes must be analyzed before generalizing.

Real-time imaging of optic nerve head collagen microstructure and biomechanics using instant polarized light microscopy.

Current tools lack the temporal or spatial resolution necessary to image many important aspects of the architecture and dynamics of the optic nerve head (ONH). We evaluated the potential of instant polarized light microscopy (IPOL) to overcome these limitations by leveraging the ability to capture collagen fiber orientation and density in a single image. Coronal sections through the ONH of fresh normal sheep eyes were imaged using IPOL while they were stretched using custom uniaxial or biaxial micro-stretch devices. IPOL allows identifying ONH collagen architectural details, such as fiber interweaving and crimp, and has high temporal resolution, limited only by the frame rate of the camera. Local collagen fiber orientations and deformations were quantified using color analysis and image tracking techniques. We quantified stretch-induced collagen uncrimping of lamina cribrosa (LC) and peripapillary sclera (PPS), and changes in LC pore size (area) and shape (convexity and aspect ratio). The simultaneous high spatial and temporal resolutions of IPOL revealed complex ONH biomechanics: i) stretch-induced local deformation of the PPS was nonlinear and nonaffine. ii) under load the crimped collagen fibers in the PPS and LC straightened, without torsion and with only small rotations. iii) stretch-induced LC pore deformation was anisotropic and heterogeneous among pores. Overall, with stretch the pores were became larger, more convex, and more circular. We have demonstrated that IPOL reveals details of collagen morphology and mechanics under dynamic loading previously out of reach. IPOL can detect stretch-induced collagen uncrimping and other elements of the tissue nonlinear mechanical behavior. IPOL showed changes in pore morphology and collagen architecture that will help improve understanding of how LC tissue responds to load.

Mechanical Deformation of Peripapillary Retina in Response to Acute Intraocular Pressure Elevation.

Elevated intraocular pressure (IOP) may cause mechanical injuries to the optic nerve head (ONH) and the peripapillary tissues in glaucoma. Previous studies have reported the mechanical deformation of the ONH and the peripapillary sclera (PPS) at elevated IOP. The deformation of the peripapillary retina (PPR) has not been well-characterized. Here we applied high-frequency ultrasound elastography to map and quantify PPR deformation, and compared PPR, PPS and ONH deformation in the same eye. Whole globe inflation was performed in ten human donor eyes. High-frequency ultrasound scans of the posterior eye were acquired while IOP was raised from 5 to 30 mmHg. A correlation-based ultrasound speckle tracking algorithm was used to compute pressure-induced displacements within the scanned tissue cross sections. Radial, tangential, and shear strains were calculated for the PPR, PPS, and ONH regions. In PPR, shear was significantly larger in magnitude than radial and tangential strains. Strain maps showed localized high shear and high tangential strains in PPR. In comparison to PPS and ONH, PPR had greater shear and a similar level of tangential strain. Surprisingly, PPR radial compression was minimal and significantly smaller than that in PPS. These results provide new insights into PPR deformation in response of IOP elevation, suggesting that shear rather than compression was likely the primary mode of IOP-induced mechanical insult in PPR. High shear, especially localized high shear, may contribute to the mechanical damage of this tissue in glaucoma.

Experimental and numerical analysis of electroactive characteristics of scleral tissue.

The sclera provides mechanical support to retina and protects internal contents of the eye against external injuries. The scleral extracellular matrix is mainly composed of collagen fibers and proteoglycans (PGs). At physiological pH, collagen molecules are neutral but PGs contain negatively charged glycosaminoglycan chains. Thus, the sclera can be considered as a polyelectrolyte hydrogel and is expected to exhibit mechanical response when subjected to electrical stimulations. In this study, we mounted scleral strips, dissected from the posterior part of porcine eyes, at the center of a custom-designed container between two electrodes. The container was filled with NaCl solution and the bending deformation of scleral strips as a function of the applied electric voltage was measured experimentally. It was found that scleral strips reached to an average bending angle of 3°, 10° and 23° when subjected to 5V, 10V, and 15V, respectively. We also created a chemo-electro-mechanical finite element model for simulating the experimental measurements by solving coupled Poisson-Nernst-Plank and equilibrium mechanical field equations. The scleral fixed charge density and modulus of elasticity were found by fitting the experimental data. The ion concentration distribution inside the domain was found numerically and was used to explain the underlying mechanisms for the scleral electroactive response. The numerical simulations were also used to investigate the effects of various parameters such as the electric voltage and fixed charge density on the scleral deformation under an electric field. STATEMENT OF SIGNIFICANCE: This manuscript investigates the electroactive response of scleral tissue. It demonstrates that the sclera deforms mechanically when subjected to electrical stimulations. A chemo-electro-mechanical model is also presented in order to numerically capture the electromechanical response of the sclera. This numerical model is used to explain the experimental observations by finding the ion distribution inside the tissue under an electric field. This work is significant because it shows that the sclera is an electroactive polyanionic hydrogel and it provides new information about the underlying mechanisms governing its mechanical and electrical properties.

Method for the biomechanical analysis of aqueous veins and perilimbal sclera by three-dimensional photoacoustic imaging and strain field calculation.

A method motivated by the eye's aqueous veins is described for the imaging and strain calculation within soft biological tissues. A challenge to the investigation of the biomechanics of the aqueous vein-perilimbal sclera tissue complex is resolution of tissue deformations as a function of intraocular pressure and the subsequent calculation of strain (a normalized measure of deformation). The method involves perfusion of the eye with a contrast agent during conduction of non-invasive, optical resolution photoacoustic microscopy. This imaging technique permits three-dimensional displacement measurements of tracked points on the inner walls of the veins which are used in a finite element model to determine the corresponding strains. The methods are validated against two standard strain measurement methods. Representative porcine globe perfusion experiments are presented that demonstrate the power of the method to determine complex strain fields in the veins dependent on intraocular pressure as well as vein anatomy. In these cases, veins are observed to move radially outward during increases in intraocular pressure and to possess significant spatial strain variation, possibly influenced by their branching patterns. To the authors' knowledge, these are the only such quantitative, data driven, calculations of the aqueous vein strains available in the open literature.

Lowering Intraocular Pressure: A Potential Approach for Controlling High Myopia Progression.

High myopia is among the most common causes of vision impairment, and it is mainly characterized by abnormal elongation of the axial length, leading to pathologic changes in the ocular structures. Owing to the close relationship between high myopia and glaucoma, the association between intraocular pressure (IOP) and high myopia progression has garnered attention. However, whether lowering IOP can retard the progression of high myopia is unclear. On reviewing previous studies, we suggest that lowering IOP plays a role in progressive axial length elongation in high myopia, particularly in pathologic myopia, wherein the sclera is more remodeled. Based on the responses of the ocular layers, we further proposed the potential mechanisms. For the sclera, lowering the IOP could inhibit the activation of scleral fibroblasts and then reduce scleral remodeling, and a decrease in the scleral distending force would retard the ocular expansion like a balloon. For the choroid, lowering IOP results in an increase in choroidal blood perfusion, thereby reducing scleral hypoxia and slowing down scleral remodeling. The final effect of these pathways is slowing axial elongation and the development of scleral staphyloma. Further animal and clinical studies regarding high myopia with varied degree of IOP and the changes of choroid and sclera during IOP fluctuation in high myopia are needed to verify the role of IOP in the pathogenesis and progression of high myopia. It is hoped that this may lead to the development of a prospective treatment option to prevent and control high myopia progression.

Effect of Topical Phenylephrine 2.5% on Episcleral Venous Pressure in Normal Human Eyes.

Purpose: Phenylephrine has been shown to affect intraocular pressure (IOP) but the mechanism of action is poorly understood. However, its action as a vasoconstrictor suggests possible effects on episcleral venous pressure (EVP). In this study, we evaluated the effect of phenylephrine on EVP and IOP in healthy subjects. Methods: Forty eyes of 20 subjects were included. Each subject received 3 drops of phenylephrine 2.5% in one eye at 1-minute intervals. The fellow eye served as control. Blood pressure, heart rate, and IOP and EVP of both eyes were measured at baseline, 15 minutes, and 60 minutes after instillation of phenylephrine. IOP was measured by pneumatonometry. EVP was assessed by using a computer-controlled episcleral venomanometer. Changes in IOP, EVP, blood pressure, and heart rate at 15 and 60 minutes were analyzed by paired t-tests. Results: IOP increased 15 minutes after instillation of phenylephrine in both treated (P = 0.001) and control eyes (P = 0.01) and returned to baseline at 60 minutes. The change in IOP at 15 minutes was not significantly different between the 2 groups. EVP in treated eyes was unchanged at 15 minutes (P = 0.8) but decreased significantly at 60 minutes (P < 0.001). In control eyes, there was no change in EVP at any time (P > 0.6). There were no significant changes from baseline in systolic and diastolic blood pressure and heart rate after instillation of phenylephrine. Conclusions: IOP elevation associated with topical phenylephrine is not caused by an increase in EVP in healthy subjects. Instead, EVP decreases with phenylephrine, but the mechanism remains to be determined.

Tensile Viscoelastic Properties of the Sclera after Glycosaminoglycan Depletion.

PURPOSE: Fibrillar collagen network and glycosaminoglycans (GAGs) are the primary components of extracellular matrix (ECM) of the sclera. The main goal of this study was to investigate the possible structural roles of GAGs in the scleral tensile properties as a function of preconditioning and displacement rate. METHODS: Four-step uniaxial stress-relaxation tests were used for characterizing the viscoelastic tensile response of the posterior porcine sclera with and without enzymatic GAG removal. The scleral strips were divided into different groups based on the displacement rate and the presence or absence of a preconditioning step in the loading protocol. The groups were (1) displacement rate of 0.2 mm/min without preconditioning, (2) displacement rate of 1 mm/min without preconditioning, (3) displacement rate of 0.2 mm/min with preconditioning, and (4) displacement rate of 1 mm/min with preconditioning. The peak stress, equilibrium stress, and the equilibrium elastic modulus were calculated for all specimens and compared against each other. RESULTS: Increasing the displacement rate from 0.2 mm/min to 1.0 mm/min was found to cause an insignificant change in the equilibrium stress and equilibrium elastic modulus of porcine scleral strips. Removal of GAGs resulted in an overall stiffer tensile behavior independent of the displacement rate in samples that were not preconditioned (P < .05). The behavior of preconditioned samples with and without GAG removal was not significantly different from each other. CONCLUSIONS: The experimental measurements of the present study showed that GAGs play an important role in the mechanical properties of the posterior porcine sclera. Furthermore, using a preconditioning step in the uniaxial testing protocol resulted in not being able to identify any significant difference in the tensile behavior of GAG depleted and normal scleral strips.

Sclera color in humans facilitates gaze perception during daytime and nighttime.

Species vary widely in the conspicuousness of their eye morphology and this could influence gaze perception. Eyes with conspicuous morphology can enhance gaze perception while eyes with camouflaged morphology may hinder gaze perception. While evidence suggests that conspicuous eye morphology enhances gaze perception, little is known about how environmental conditions affect this interaction. Thus, we investigated whether environmental light conditions affect gaze perception. Human subjects (Homo sapiens) were instructed to find direct-gaze faces within arrays of averted-gaze faces or to find averted-gaze faces within arrays of directed-gaze faces. The faces were displayed under conditions simulating nighttime or daytime conditions. Furthermore, the faces had naturally-colored sclera (white) or modified sclera (same color as the iris). Participants were fastest and most accurate in detecting faces during the daytime and nighttime conditions when the sclera were naturally-colored. Participants were worst at detecting faces with modified sclera during the nighttime conditions. These results suggest that eyes with conspicuous morphology enhance gaze perception during both daytime and nighttime conditions.

Large diameter scleral lens benefits for Asians with intractable ocular surface diseases: a prospective, single-arm clinical trial.

To report the efficacy and safety of large diameter scleral lenses and determine their suitability in Asian subjects with intractable ocular surface diseases. This prospective study enrolled intractable ocular surface diseases subjects with uncorrected visual acuity > counting finger but ≥ 0.3 logMAR and best-corrected visual acuity (BCVA) ≥ 0.3 logMAR, to fit large diameter scleral lenses for 12 weeks. 21 eyes (13 subjects) consisting ten eyes (47.6%) with persistent epithelial defects, 6 (28.6%) with graft-versus-host disease, 4 (19.0%) with Stevens-Johnson syndrome and one (4.8%) with severe dry eye were ultimately enrolled. Primary outcome measures were the visual acuity, corneal and conjunctival fluorescein staining, Ocular Surface Disease Index (OSDI), and National Eye Institute 25-Item Visual Function Questionnaire (NEI-VFQ-25). At week 12 with large diameter scleral lenses, BCVA improved from 0.77 logMAR to 0.27 logMAR (P < 0.001). High-grade corneal and conjunctival fluorescein staining proportion decreased from 61.90 to 14.29% and 52.38 to 9.52%, respectively (P = 0.0036 and 0.0063, respectively). OSDI and NEI-VFQ-25 improved from 67.89 to 34.69 and 51.40 to 64.48, respectively (P < 0.001). No adverse effects were observed. In Asians with intractable ocular surface diseases, large diameter scleral lens improves visual acuity and alleviates signs and symptoms of ocular surface diseases without any significant complications.Trial registration Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (Project No. HI12C0015 (A120018)). Clinical Trials.gov, NCT04535388. Registered 18 August 2020-Retrospectively registered, http://clinicaltrials.gov/ct2/show/NCT04535388 .

Ultrasonic elastography to assess biomechanical properties of the optic nerve head and peripapillary sclera of the eye.

PURPOSE: To quantitatively investigate both optic nerve head (ONH) and peripapillary sclera (PPS) biomechanical properties of porcine eyes through an ultrasonic elastography imaging system in response to both increasing and decreasing intraocular pressure (IOP). METHODS: The Young's modulus of the ONH and PPS were assessed using our high resolution ultrasonic imaging system which utilized a mechanical shaker to induce shear waves and an off-axis aligned 40 MHz needle transducer to track micron-level displacement along the direction of wave propagation. In this study, imaging on a total of 8 ex vivo porcine eyes preloaded with IOPs from 6 mmHg to 30 mmHg was performed. To have a better understanding of the effect of varying IOP on biomechanics, both increasing and decreasing IOPs were investigated. RESULTS: The increase of the Young's modulus of ONH (92.4 ± 13.9 kPa at 6 mmHg to 224.7 ± 71.1 kPa at 30 mmHg) and PPS (176.8 ± 14.3 kPa at 6 mmHg to 573.5 ± 64.4 kPa at 30 mmHg) following IOP elevation could be observed in the reconstructed Young's modulus of the shear wave elasticity (SWE) imaging while the B-mode structural images remained almost unchanged. In addition, for the same IOP level, both ONH and PPS have a tendency to be stiffer with decreasing IOP as compared to increasing IOP. CONCLUSIONS: Our results demonstrate the feasibility of using our ultrasonic elastography system to investigate the stiffness mapping of posterior eye with high resolution in both increasing and decreasing IOPs, making this technique potentially useful for glaucoma.