Biomechanical Properties Of Sclera Research Articles

Biomechanical and microstructural changes in posterior myopic Guinea pig

The biomechanical and microstructural properties of the posterior sclera are drivers of myopia progression to high/pathologic myopia, a leading cause of blindness, affecting over 2.3 billion people worldwide. We investigated the effect of myopia on mechanical properties of the posterior sclera in guinea-pig (GP) eyes using scanning-acoustic-microscopy (SAM) with 3-μm spatial resolution. Form-deprivation (FD) was used to induce myopia in the right eyes of six GPs between 4 and 12 days of age, and 6-μm-thick scleral cryosections were scanned using a custom-made SAM. Bulk modulus (K) parameter-maps were estimated from SAM radiofrequency echo signals. We studied the effects of myopia on SAM maps in the nasal versus temporal regions of the posterior sclera. In the induced myopia eyes, K-values in the nasal region were 0.126 GPa lower than that in the temporal region (p = 0.009), whereas in the control eye, K did not significantly differ between regions (p > 0.07). Scleral biomechanical properties changed depending on eye region and induced myopia level. These results demonstrate that SAM-maps are important to elucidate myopia pathogenesis, providing insight to the location and timing of scleral stiffness reduction, as reflected in lower K-values in myopic eyes. [Work supported by the NIH grant R01GM143388 (J.M.), UON grant G2100649 (S.M.), and NMRC CIRG19nov-0030 (Q.V.H.).]

Poster Session: Estimation of scleral biomechanical properties from air-puff-coupled optical coherence tomography.

Progression of myopia is usually accompanied by axial overgrowth of the eyeball, which affects scleral biomechanics (BM). To study scleral biomechanics, we propose the use of air-puff deformation swept-source OCT imaging. Air-puff deformation imaging was performed at different sites of ex vivo porcine (n=5) and rabbit (n=3) eyes, (<24hr postmortem): Nasal/temporal equatorial and posterior sclera (NE, NP, TE, TP), superior (S) and inferior (I) sclera, and cornea (C). Intraocular pressure was kept at 15mmHg. Deformation data were used as input to inverse finite element model (FEM) algorithms to reconstruct BM properties. Experimental deformation amplitudes showed dependence on the animal model, with porcine scleras exhibiting greater inter-site variation (displacement of S, I was up to four times greater than that of N, T), while rabbit scleras exhibited at most 40% of displacement differences between all sites. Both models showed significant (p<.001) differences in the temporal deformation profile between sclera and (C), but similarities in all scleral locations, suggesting that the scleral temporal profile is independent of scleral thickness variations. The FEM estimated an elastic modulus of 1.84 ± 0.30 MPa (I) to 6.04 ± 2.11 MPa (TE) for the porcine sclera. The use of scleral air-puff imaging is promising for noninvasive investigation of structural changes in the sclera associated with myopia and for monitoring possible modulation of scleral stiffness with myopia treatment.

Altered Structure and Function of Murine Sclera in Form-Deprivation Myopia.

The sclera is believed to biomechanically influence eye size, facilitating the excessive axial elongation that occurs during myopigenesis. Here, we test the hypothesis that the sclera will be remodeled and exhibit altered biomechanics in the mouse model of form-deprivation (FD) myopia, accompanied by altered retinoid concentrations, a potential signaling molecule involved in the process. Male C57 Bl/6J mice were subjected to unilateral FD (n = 44 eyes), leaving the contralateral eye untreated (contra; n = 44). Refractive error and ocular biometry were measured in vivo prior to and after 1 or 3 weeks of FD. Ex vivo measurements were made of scleral biomechanical properties (unconfined compression: n = 24), scleral sulfated glycosaminoglycan (sGAG) content (dimethylmethylene blue: n = 18, and immunohistochemistry: n = 22), and ocular all-trans retinoic acid (atRA) concentrations (retina and RPE+choroid+sclera, n = 24). Age-matched naïve controls were included for some outcomes (n = 32 eyes). Significant myopia developed after 1 (-2.4 ± 1.1 diopters [D], P < 0.001) and 3 weeks of FD (-4.1 ± 0.7 D, P=0.025; mean ± standard deviation). Scleral tensile stiffness and permeability were significantly altered during myopigenesis (stiffness = -31.4 ± 12.7%, P < 0.001, and permeability = 224.4 ± 205.5%, P < 0.001). Total scleral sGAG content was not measurably altered; however, immunohistochemistry indicated a sustained decrease in chondroitin-4-sulfate and a slower decline in dermatan sulfate. The atRA increased in the retinas of eyes form-deprived for 1 week. We report that biomechanics and GAG content of the mouse sclera are altered during myopigenesis. All scleral outcomes generally follow the trends found in other species and support a retina-to-sclera signaling cascade underlying mouse myopigenesis.

Advances in preventing myopia by scleral collagen crosslinking

<p indent="0mm">The prevention of myopia is crucial due to its increasing prevalence globally. Myopia development is associated with scleral remodeling and reduced scleral biomechanical properties. Scleral collagen crosslinking is a new, effective approach to prevent myopia clinically, including photo-crosslinking by light irradiation (ultraviolet A and riboflavin scleral collagen crosslinking, and blue light and riboflavin scleral collagen crosslinking) and crosslinking by biological crosslinkers (genipin, carbohydrate, FARs, and Tgases). This article summarizes the relevant research on the application scheme, validity, and safety of scleral collagen crosslinking to prevent myopia.

Corneal and scleral biomechanics in ophthalmic diseases: An updated review

Corneal and scleral biomechanical properties have important implications in the maintenance of normal ocular morphology and function. The cornea and sclera compose the outermost layer of the eyeball, forming a sphere with a certain degree of intraocular pressure, and are therefore under dynamic loading conditions. Recently, several major ophthalmic conditions have been shown to be linked to corneal and scleral biomechanical properties, such as ametropia, corneal pathologies, ocular surface disease, and glaucoma. A profound understanding of corneal and scleral biomechanics is essential to clarifying disease pathogenesis, improving diagnostic ability, and developing treatment strategies. This review aims to highlight the role of corneal and scleral biomechanics in ophthalmology and its clinical translation. Specifically, advances and prospects in corneal and scleral biomechanics and possible associated diseases are addressed.

Safety and Long-term Scleral Biomechanical Stability of Rhesus Eyes after Scleral Cross-linking by Blue Light

ABSTRACT Purpose: To assess the safety and long-term scleral biomechanical stability of rhesus eyes after blue light scleral CXL by investigating the biomechanical and microstructural changes. Methods: Seven rhesus monkeys (14 eyes) were observed in this study. All right eyes received blue light scleral CXL at the superior temporal equatorial sclera, and the left eyes served as controls. Biological ocular parameters were followed up to 1 year after scleral CXL. Stress-strain measurements of three rhesus sclera were measured, three rhesus retinas were examined histologically by H&E and TUNEL staining. And the microstructure of both the sclera and retina were observed by transmission electron microscopy at 1 year. Results: As for the retinal thickness, choroidal thickness, flow density of retinal superficial vascular networks and flash electroretinography (f-ERG) results, no significant differences were observed between the paired eyes at 1 year (P >.05). At the same time, the scleral collagen fibril distribution was much tighter, and the scleral biomechanical properties were significantly increased in the experimental eyes. However, apoptotic cells and retinal ultrastructural changes could still be found in the retina of the experimental eyes. Conclusion: This study demonstrates that blue light scleral CXL could effectively increase the scleral stiffness of the rhesus eye for at least 1 year, but ultrastructural change was still observed in the retina of scleral CXL eye. Therefore, the long-term intraocular safety of the blue light scleral CXL technique for preventing myopia progression should be investigated further.

Dome-shaped maculopathy: a review.

First described by Gaucher and associates in 2008 in eyes with high myopia, dome-shaped maculopathy (DSM) is an anterior convex protrusion of the macula towards the vitreous cavity observable on OCT. This seems to be related to a localized scleral thickness, which might be the result of regional variation in the scleral bio-mechanical properties and the process of emmetropization causing asymmetric scleral growth. The presence of DSM can be associated with an increased risk of complications. The clinical spectrum ranges from being asymptomatic to metamorphopsia and mild-to-moderate gradual visual loss over years. Visual impairment in DSM results from retinal pigment epithelial changes, sub-foveal serous detachment, retinoschisis and myopic choroidal neovascularization. In this review, we compile and review the available information on the pathophysiology, nomenclature, classification, clinical features including imaging, differential diagnosis, complications associated with DSM and the gaps in our understanding of this entity thus far.

Pulsed and continuous accelerated scleral cross-linking using riboflavin and ultraviolet A irradiation for the prevention of myopia progression in a guinea pig model

Objective To evaluated the effect of oral administration of riboflavin combined with pulsed and continuous light accelerated scleral cross-linking on the histological and biomechanical properties of sclera in a guinea pig model to control the progression of myopia. Methods Thirty 4-week-old guinea pigs were divided into 5 groups, or the control group, non cross-linking group, conventional cross-linking group, pulse light cross-linking group and continuous light cross-linking group with 6 guinea pigs in each group.Three cross-linking groups were administered 0.1% riboflavin solution with vitamin C by gavage from 3 days before modeling to modeling process.The conventional cross-linking group underwent cross-linking with 1 hour of (ultraviolet A (UVA) exposure at 0.67 mW/cm2, the pulse light cross-linking group received a pulsed-light accelerated crosslinking for 8 minuctes (1 second on/1 second off) of UVA exposure at 10 mW/cm2, and the continuous light accelerated cross-linking group was crosslinked with continuous-light accelerated crosslinking at 10 mW/cm2 for 4 minuctes.The same procedure was conducted on the non cross-linking group without UVA irradiation and 0.1% riboflavin solution before modeling and modeling process.No any intervene was carried out in the control group.Retinoscopy and the axial length measurement were performed before and after experiment.The animals were euthanized 2 weeks after experiment and then biomechanical and histopathological examinations of scleras were conducted.The use and care of the animals complied with Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission. Results Myopia models were established with an increased axial length and myopic diopter 2 weeks after myopic modeling process.Axial length in the non cross-linking group was longer than that of the control group at 2 weeks, with a siginificant difference between them (P<0.01). The myopic Diopter in the non cross-linking group was significantly increased in comprasion with the control group at 2 weeks (P<0.01). Compared with myopic eyes in the non cross-linking groups, axial length, diopter and strain assessment values were decreased significantly in three scleral cross-linking groups (all at P<0.01). The sclera ultimate load and stress assessment in the conventinal cross-lingking group, pulse light cross-linking group, continuous light cross-linking group were significantly higher than those in the non-cross-linking group Max stress: [2.20±0.03], [2.67±0.05], [2.41±0.04]Mpa vs.[1.30±0.02]Mpa; Max load: [1.92±0.03], [2.33±0.28], [1.91±0.03]P vs.[1.54±0.06]P) (all at P<0.01). Collagenous tissue of the scleras in the pulse light cross-linking group and continious ligh cross-linking group was similar in appearance to the control group.In addition, MMP2 expression of pulse light cross-linking group and continuous light cross-linking group was significantly increased, and TIMP-2 expression showed a reduce. Conclusions Pulsed and continuous light accelerated scleral cross-linking using oral administration of riboflavin and riboflavin UVA irradiation can effectively prevent the myopia development by increasing scleral biomechanical strength in guinea pig. Key words: Riboflavin; Ultraviolet A; Scleral cross-linking; Myopia; Guinea

Riboflavin and ultraviolet A irradiation for the prevention of progressive myopia in a guinea pig model

In this study, we evaluated the effect of oral administration of riboflavin combined with whole-body ultraviolet A (UVA) irradiation on the biochemical and biomechanical properties of sclera in a guinea pig model to control the progression of myopia. Experimental groups were administered 0.1% riboflavin solution with or without vitamin C by gavage from 3 days before myopic modeling and during the modeling process. Guinea pigs underwent 30 min of whole-body UVA irradiation after each gavage for 2 weeks. For control groups, guinea pigs were administered vitamin C and underwent either whole-body UVA irradiation without 0.1% riboflavin solution or whole-body fluorescent lamp irradiation with or without 0.1% riboflavin solution. Resultantly, myopia models were established with an increased axial length and myopic diopter. Compared with myopic eyes in the control groups, the net increase in axial length, diopter and strain assessment decreased significantly, and the net decrease in sclera thickness, ultimate load, and stress assessment decreased significantly in experimental groups. MMP-2 expression showed a lower net increase, while TIMP-2 expression showed a lower net decrease. In addition, hyperplasia of scleral fibroblasts was more active in myopic eyes of experimental groups. Overall, our results showed that oral administration of riboflavin with whole-body UVA irradiation could increase the strength and stiffness of sclera by altering the biochemical and biomechanical properties, and decreases in axial elongation and myopic diopter are greater in the guinea pig myopic model.

Anatomical differences of the protein profile in the rabbit sclera during growth

We aimed to investigate the proteome changes in anatomical regions of sclera during growth and development of the rabbit. Sclera from New Zealand white rabbits of three ages (1 month, 2 months and 6 months) was dissected into three segments - anterior, equatorial, and posterior. A total of 36 samples were divided into groups by age and anatomical region. Tryptic digests of total proteins were analyzed by liquid chromatography followed by tandem mass spectrometry (LC-MS/MS). Label-free quantification based on spectral counts was used to determine the relative protein abundance and identify proteins with statistically significant differences between age groups or anatomical regions of the sclera. Western blotting was performed to validate some of the differentially expressed proteins. A total of 840 non-redundant proteins was identified in the sclera at different ages and regions with protein and peptide false discovery rate (FDR) at ≤1.0% and ≤0.1%, respectively. Differentially expressed proteins were identified by comparing age or anatomical region. Among these, periostin showed decreasing abundance with age, while myocilin, latent-transforming growth factor beta-binding protein 2, hyaluronan, proteoglycan link protein 1 and selenbp1 showed increasing abundance with age. In mature rabbits, alcohol dehydrogenase showed region-related differences in the sclera. Periostin showed an age-related decrease while selenbp1 showed an age-related increase in abundance in the anterior region. Vitronectin and extracellular superoxide dismutase had greater expression with age in the equatorial and posterior regions, respectively. The age related differential expression of periostin and selenbp1 was confirmed by western blotting. In conclusion, the protein profile of sclera showed age- and region-related differences. The differential protein profiles provide a baseline for understanding changes in the protein expression in the young and mature rabbit that appears to show regional changes. The changes observed in the present study add to the existing knowledge about regional alterations in biomechanical properties of sclera during growth.

Influence of Age on Ocular Biomechanical Properties in a Canine Glaucoma Model with ADAMTS10 Mutation.

Soft tissue often displays marked age-associated stiffening. This study aims to investigate how age affects scleral biomechanical properties in a canine glaucoma model with ADAMTS10 mutation, whose extracellular matrix is concomitantly influenced by the mutation and an increased mechanical load from an early age. Biomechanical data was acquired from ADAMTS10-mutant dogs (n = 10, 21 to 131 months) and normal dogs (n = 5, 69 to 113 months). Infusion testing was first performed in the whole globes to measure ocular rigidity. After infusion experiments, the corneas were immediately trephined to prepare scleral shells that were mounted on a pressurization chamber to measure strains in the posterior sclera using an inflation testing protocol. Dynamic viscoelastic mechanical testing was then performed on dissected posterior scleral strips and the data were combined with those reported earlier by our group from the same animal model (Palko et al, IOVS 2013). The association between age and scleral biomechanical properties was evaluated using multivariate linear regression. The relationships between scleral properties and the mean and last measured intraocular pressure (IOP) were also evaluated. Our results showed that age was positively associated with complex modulus (p<0.001) and negatively associated with loss tangent (p<0.001) in both the affected and the normal groups, suggesting an increased stiffness and decreased mechanical damping with age. The regression slopes were not different between the groups, although the complex modulus was significantly lower in the affected group (p = 0.041). The posterior circumferential tangential strain was negatively correlated with complex modulus (R = -0.744, p = 0.006) showing consistent mechanical evaluation between the testing methods. Normalized ocular rigidity was negatively correlated with the last IOP in the affected group (p = 0.003). Despite a mutation that affects the extracellular matrix and a chronic IOP elevation in the affected dogs, age-associated scleral stiffening and loss of mechanical damping were still prominent and had a similar rate of change as in the normal dogs.

Ultrasonic Measurement of Scleral Cross-Sectional Strains During Elevations of Intraocular Pressure: Method Validation and Initial Results in Posterior Porcine Sclera

Scleral biomechanical properties may be important in the pathogenesis and progression of glaucoma. The goal of this study is to develop and validate an ultrasound method for measuring cross-sectional distributive strains in the sclera during elevations of intraocular pressure (IOP). Porcine globes (n = 5) were tested within 24 hs postmortem. The posterior scleral shells were dissected and mounted onto a custom-built pressurization chamber. A high-frequency (55-MHz) ultrasound system (Vevo660, VisualSonics Inc., Toronto) was employed to acquire the radio frequency data during scans of the posterior pole along both circumferential and meridian directions. The IOP was gradually increased from 5 to 45 mmHg. The displacement fields were obtained from correlation-based ultrasound speckle tracking. A least-square strain estimator was used to calculate the strains in both axial and lateral directions. Experimental validation was performed by comparing tissue displacements calculated from ultrasound speckle tracking with those induced by an actuator. Theoretical analysis and simulation experiments were performed to optimize the ultrasound speckle tracking method and evaluate the accuracy and signal-to-noise ratio (SNR) in strain estimation. Porcine sclera exhibited significantly larger axial strains (e.g., -5.1 ± 1.5% at 45 mmHg, meridian direction) than lateral strains (e.g., 2.2 ± 0.7% at 45 mmHg, meridian direction) during IOP elevations (P's < 0.01). The strain magnitudes increased nonlinearly with pressure increase. The strain maps displayed heterogeneity through the thickness. The lateral strains were significantly smaller in the circumferential direction than the meridian direction at 45 mmHg (P < 0.05). Experimental validation showed that the ultrasound speckle tracking method was capable of tracking displacements at the accuracy of sub-micron to micron. Theoretical analysis predicted the dependence of the strain estimation SNR on the strain level, as well as signal processing parameters such as kernel size. Simulation results showed that ultrasound speckle tracking had a high accuracy for estimating strains of 1-5% and a high SNR for strains of 0.5-5%. A new experimental method based on ultrasound speckle tracking has been developed for obtaining cross-sectional strain maps of the posterior sclera. This method provides a useful tool to examine distributive strains through the thickness of the sclera during elevations of IOP.

Acute intraocular pressure after intravitreal injections, what is the mecanism?

AbstractPurpose To evaluate the mechanism of acute intraocular hypertension after intravitreal injections (IVI) of anti‐VEGF therapies.Methods A prospective study was performed to evaluate the IOP increase immediately after IVI of 0,05ml ranibizumab in 50 patients. We have also studied the correlation between IOP immediately after IVI and axial length, then with lens status. Moreover we have analysed the anterior chamber anatomic changes (anterior chamber volume and irido corneal angle), measures were taken before and 5mn after IVI by scheimpflug camera from Oculyzer® (Alcon).Results The IOP peak immediately after IVI was higher than 45 mmHg in 67,3% of patients. It was transient, decreasing after 15mn and returning to baseline in all patient after 45 mn. We found no statistically significant difference between pseudophakic eyes (n=30) and phakic eyes (n=20, p=0.80). No correlation was found between the axial length and the IOP spike (r=0.042, p=0,85). The mean change for the anterior chamber volume (ACV) is mild (0,33 mm3).The ACV increased in pseudophakic eyes (+15,64 mm3, +7,7%), but decreased in the phakic eyes (‐7,24 mm3, ‐4,4%). The mean change for irido corneal angle (ICA) is not significant (‐1,61°), it decreases in phakic eyes (‐2,97°, ‐7,2%) versus a quite neutral effect in pseudophakic eyes (+0,78°, + 1,5%).Conclusion The IOP spike is not correlated either with axial lengh or with lens status. ACV and ICA variations are different according to the lens status but remains mild. These results enhance the importance of the scleral biomechanical properties, and highlight an unpredictable peak. This could be an argument to propose a systematic prophylactic hypotensive treatment before IVI.

Biomechanical changes in the sclera of monkey eyes exposed to chronic IOP elevations.

To characterize scleral biomechanics in both eyes of eight monkeys in which chronic intraocular pressure (IOP) elevation was induced in one eye. Each posterior sclera was mounted on a pressurization apparatus, IOP was elevated from 5 to 45 mm Hg while the 3D displacements of the scleral surface were measured by speckle interferometry. Finite element (FE) models of each scleral shell were constructed that incorporated stretch-induced stiffening and multidirectionality of the collagen fibers. FE model predictions were then iteratively matched to experimental displacements to extract unique sets of scleral biomechanical properties. For all eyes, the posterior sclera exhibited inhomogeneous, anisotropic, nonlinear biomechanical behavior. Biomechanical changes caused by chronic IOP elevation were complex and specific to each subject. Specifically: (1) Glaucomatous eyes in which the contralateral normal eyes displayed large modulus or thickness were less prone to biomechanical changes; (2) glaucomatous scleral modulus associated with an IOP of 10 mm Hg decreased (when compared with that of the contralateral normal) after minimal chronic IOP elevation; (3) glaucomatous scleral modulus associated with IOPs of 30 and 45 mm Hg increased (when compared with that of the contralateral normal) after moderate IOP elevation; and (4) FE-based estimates of collagen fiber orientation demonstrated no change in the glaucomatous eyes. Significant stiffening of the sclera follows exposure to moderate IOP elevations in most eyes. Scleral hypercompliance may precede stiffening or be a unique response to minimal chronic IOP elevation in some eyes. These biomechanical changes are likely to be the result of scleral extracellular matrix remodeling.

Biaxial mechanical testing of human sclera

The biomechanical environment of the optic nerve head (ONH), of interest in glaucoma, is strongly affected by the biomechanical properties of sclera. However, there is a paucity of information about the variation of scleral mechanical properties within eyes and between individuals. We thus used biaxial testing to measure scleral stiffness in human eyes. Ten eyes from 5 human donors (age 55.4±3.5 years; mean±SD) were obtained within 24 h of death. Square scleral samples (6 mm on a side) were cut from each ocular quadrant 3–9 mm from the ONH centre and were mechanically tested using a biaxial extensional tissue tester (BioTester 5000, CellScale Biomaterials Testing, Waterloo). Stress–strain data in the latitudinal (toward the poles) and longitudinal (circumferential) directions, here referred to as directions 1 and 2, were fit to the four-parameter Fung constitutive equation W= c( e Q −1), where Q = c 1 E 11 2 + c 2 E 22 2 + 2 c 3 E 11 E 22 and W, c’s and E ij are the strain energy function, material parameters and Green strains, respectively. Fitted material parameters were compared between samples. The parameter c 3 ranged from 10 −7 to 10 −8, but did not contribute significantly to the accuracy of the fitting and was thus fixed at 10 −7. The products c⁎ c 1 and c⁎ c 2, measures of stiffness in the 1 and 2 directions, were 2.9±2.0 and 2.8±1.9 MPa, respectively, and were not significantly different (two-sided t-test; p=0.795). The level of anisotropy (ratio of stiffness in orthogonal directions) was 1.065±0.33. No statistically significant correlations between sample thickness and stiffness were found (correlation coefficients=−0.026 and −0.058 in directions 1 and 2, respectively). Human sclera showed heterogeneous, near-isotropic, nonlinear mechanical properties over the scale of our samples.

Effects of Scleral Stiffness Properties on Optic Nerve Head Biomechanics

The biomechanical environment within the optic nerve head, important in glaucoma, depends strongly on scleral biomechanical properties. Here we use a range of measured nonlinear scleral stress-strain relationships in a finite element (FE) model of the eye to compute the biomechanical environment in the optic nerve head at three levels of intraocular pressure (IOP). Three stress-strain relationships consistent with the 5th, 50th and 95th percentiles of measured human scleral stiffness were selected from a pool of 30 scleral samples taken from 10 eyes and implemented in a generic FE model of the eye using a hyperelastic five-parameter Mooney-Rivlin material model. Computed strains within optic nerve head tissues depended strongly on scleral properties, with most of this difference occurring between the compliant and median scenarios. Also, the magnitudes of strains were found to be substantial even at normal IOP (up to 5.25% in the lamina cribrosa at 15 mmHg), being larger than previously reported values even at normal levels of IOP. We conclude that scleras that are "weak", but still within the physiologic range, will result in appreciably increased optic nerve head strains and could represent a risk factor for glaucomatous optic neuropathy. Estimations of the deformation at the optic nerve head region, particularly at elevated IOP, should take into account the nonlinear nature of scleral stiffness.

Modeling individual-specific human optic nerve head biomechanics. Part II: influence of material properties

Biomechanical factors acting within the optic nerve head (ONH) likely play a role in the loss of vision that occurs in glaucoma. In a companion paper (Sigal et al. 2008), we quantified the biomechanical environment within individual-specific ONH models reconstructed from human post mortem eyes. Our goal in this manuscript was to use finite element modeling to investigate the influence of tissue material properties on ONH biomechanics in these same individual-specific models. A sensitivity analysis was carried out by simulating the effects of changing intraocular pressure on ONH biomechanics as tissue mechanical properties were systematically varied over ranges reported in the literature. This procedure was repeated for each individual-specific model described in the companion paper (Sigal et al. 2008). The outcome measures of the analysis were first and third principal strains, as well as the derived quantity of maximum shear strain, in ONH tissues. Scleral stiffness had by far the largest influence in ONH biomechanics, and this result was remarkably consistent across ONH models. The stiffnesses of the lamina cribrosa and pia mater were also influential. These results are consistent with those obtained using generic ONH models. The compressibility of the pre-laminar neural tissue influenced compressive and shearing strains. Overall, tissue material properties had a much greater influence on ONH biomechanics than did tissue geometry, as assessed by comparing results between our individual-specific models. Material properties of ONH tissues, particularly of the peripapillary sclera, play a dominant role in the mechanical response of an ONH to acute changes in IOP and may be important in the pathogenesis of glaucoma. We need to better understand inter-individual differences in scleral biomechanical properties and whether they are clinically important.

An experimental study on collagen content and biomechanical properties of sclera after posterior sclera reinforcement

Background The development of pathological myopia is associated with reduced scleral collagen accumulation, scleral thinning, and loss of scleral tissue, in both humans and animal models. Posterior scleral reinforcement (PSR) was considered as an effective way for treating pathological myopia. Yet it is not well understood the possible role of collagen on the sclera reinforcement mechanisms in the PSR surgery. Methods PSR surgery was performed on the normal adult New Zealand white rabbits eyes. Human sclera was used as reinforcement materials. At 1, 2, 3, 6, 9 months after the PSR surgery, scleral hydroxyproline (Hyp) synthesis and collagen fibers arrangement were determined by enzymolysic hydrolysis assay and histological morphology technique. An Instron test machine was used to investigate the elastic modulus of sclera. Findings It was found that the elastic modulus and Hyp content of reinforced sclera were lower at first month after surgery, and then gradually up to physiological level in the following months. Those two indexes were close to that of the normal control groups at 9 months. Interpretation These findings indicate that sclera elastic modulus was associated with both change of Hyp content and collagen fibers arrangement after PSR. The therapeutic effect of PSR surgery was confirmed not only from biological but also biomechanical aspects.

Factors Influencing Optic Nerve Head Biomechanics

The biomechanical environment within the optic nerve head (ONH) may play a role in retinal ganglion cell loss in glaucomatous optic neuropathy. This was a systematic analysis in which finite element methods were used to determine which anatomic and biomechanical factors most influenced the biomechanical response of the ONH to acute changes in IOP. Based on a previously described computational model of the eye, each of 21 input factors, representing the biomechanical properties of relevant ocular tissues, the IOP, and 14 geometric factors were independently varied. The biomechanical response of the ONH tissues was quantified through a set of 29 outcome measures, including peak and mean stress and strain within each tissue, and measures of geometric changes in ONH tissues. Input factors were ranked according to their aggregated influence on groups of outcome measures. The five input factors that had the largest influence across all outcome measures were, in ranked order: stiffness of the sclera, radius of the eye, stiffness of the lamina cribrosa, IOP, and thickness of the scleral shell. The five least influential factors were, in reverse ranked order: retinal thickness, peripapillary rim height, cup depth, cup-to-disc ratio, and pial thickness. Factor ranks were similar for various outcome measure groups and factor ranges. The model predicts that ONH biomechanics are strongly dependent on scleral biomechanical properties. Acute deformations of ONH tissues, and the consequent high levels of neural tissue strain, were less strongly dependent on the action of IOP directly on the internal surface of the ONH than on the indirect effects of IOP on the sclera. This suggests that interindividual variations in scleral properties could be a risk factor for the development of glaucoma. Eye size and lamina cribrosa biomechanical properties also have a strong influence on ONH biomechanics.