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Girard, M. J. A.

Publications and source records attributed to Girard, M. J. A..

11 recordsLinked to original sources

Bruch's Membrane Contributes to the Structural Integrity of the Human Eye

PurposeTo investigate the contribution of the Bruchs membrane and sclera tissues to the overall structural integrity of the ocular wall. MethodsTwenty-three human globes were subjected to biomechanical testing. A piece of sclera measuring 5 x 5 mm was carefully removed at the nasal region, 2 mm away from the optic nerve head. The intraocular pressure was increased at approximately 1 mmHg/s until Bruchs membrane-uvea-retina-tissue layer (BMUR) ruptured. Next, strips of sclera and Bruchs membrane-choriocapillaris (BMC) complex were isolated from the superior fundus region. Uniaxial tension tests were performed at a strain rate of 0.01/s and sampling rate of 15 Hz. The tangent moduli of the BMC and sclera at 0.01, 0.02 and 0.03 strains were compared. ResultsThe rupture pressure of the BMUR was 98.1 {+/-} 21.4 mmHg. The tangent moduli of the BMC at 0.01, 0.02 and 0.03 strains were 2.96 {+/-} 1.44 MPa, 7.68 {+/-} 1.78 MPa and 9.43 {+/-} 2.11 MPa, respectively, and the tangent moduli of the sclera at 0.01, 0.02 and 0.03 strains were 1.09 {+/-} 0.80 MPa, 2.72 {+/-} 1.67 MPa and 5.69 {+/-} 3.27 MPa, respectively. ConclusionThe BMUR was able to sustain relatively high IOP before rupturing. The uniaxial tensile tests showed that the BMC tangent moduli were about 3 times of those of the sclera at strains of 0.01 and 0.02. Although the sclera is approximately 47 times thicker, the BMC is still likely to make a significant contribution (3.51% to 7.42% at strain <0.03) to the overall structural strength of the ocular wall.

bioengineering↗

Iris Crypts Could Reduce the Chance of Angle Closure: A Computational Biomechanics Study Derived from Clinical and Human Iris Data

PurposeTo investigate the effect of crypts during pupil constriction and dilation on the potential for angle closure by performing finite element analysis using clinical and experimental data on human tissues. MethodsA computational model was developed to determine the influence of small crypts (surface area of [~]0.015 mm2) and large crypts (surface area of 0.300 mm2) on the anterior chamber angles during pupil dilation. The model needed permeability data from human subjects, hence 21 enucleated human eyes (72 hours post-mortem) were procured and subjected to a flow set-up previously reported. Finally, 66 subjects were recruited to measure pupil constriction and dilation levels from optical coherence tomography (OCT) videos. ResultsThe hydraulic permeability of the human iris stroma was determined to be 2.55 {+/-} 1.93 x 10-5 mm2/Pa{middle dot}s. The average iris constriction and dilation durations were 0.710 {+/-} 0.213 seconds and 1.24 {+/-} 0.401 seconds, respectively, with pupil diameter changes of 1.16 {+/-} 0.39 mm and 0.75 {+/-} 0.27 mm, respectively. The computational models had starting anterior chamber angles of 51.30{degrees} and final anterior chamber angles of 26.81{degrees} once steady state has been reached. In an extreme case with decreased anterior border layer (ABL) permeability, the anterior chamber angle narrowed to 12.37{degrees}, but the presence of crypts kept the angle above 20.36{degrees}, highlighting the potential of crypts in preventing angle closure. ConclusionsOur findings on the biomechanics of crypts in the iris may drive the development of novel treatments by altering ABL morphology, providing an alternative bypass for angle closure prevention in high-risk patients.

bioengineering↗

Iris Morphological and Biomechanical Factors Influencing Angle Closure During Pupil Dilation

PurposeTo use finite element (FE) analysis to assess what morphological and biomechanical factors of the iris and of the anterior chamber are more likely to influence angle narrowing during pupil dilation. MethodsThe study consisted of 1,344 FE models comprising of the cornea, sclera, lens and iris (stroma, sphincter and dilator tissues) to simulate pupil dilation and to assess changes in angle. For each model, we varied the following parameters: anterior chamber depth (ACD = 2 -4 mm) and width (ACW = 10-12 mm), iris convexity (IC = 0-0.3 mm), thickness (IT = 0.3-0.5 mm), stiffness (E = 4-24 kPa) and Poissons ratio (v = 0-0.3), and simulated pupil dilation. We evaluated for the change in anterior chamber angle ({bigtriangleup}{angle}) and the final dilated anterior chamber angles ({angle}f) from baseline to dilation for each parameter. ResultsThe final dilated AC angles decreased with a smaller ACD ({angle}f = 53.4{degrees}{+/-}12.3{degrees} to 21.3{degrees}{+/-}14.9{degrees}), smaller ACW ({angle}f = 48.2{degrees}{+/-}13.5{degrees} to 26.2{degrees}{+/-}18.2{degrees}), larger IT ({angle}f = 52.6{degrees}{+/-}12.3{degrees} to 24.4{degrees}{+/-}15.1{degrees}), larger IC ({angle}f = 45.0{degrees}{+/-}19.2{degrees} to 33.9{degrees}{+/-}16.5{degrees}), larger E ({angle}f = 40.3{degrees}{+/-}17.3{degrees} to 37.4{degrees}{+/-}19.2{degrees}) and larger v ({angle}f = 42.7{degrees}{+/-}17.7{degrees} to 34.2{degrees}{+/-}18.1{degrees}). The change in AC angle increased with larger ACD ({bigtriangleup}{angle} = 9.37{degrees}{+/-}11.1{degrees} to 15.4{degrees}{+/-}9.3{degrees}), smaller ACW ({bigtriangleup}{angle} = 7.4{degrees}{+/-}6.8{degrees} to 16.4{degrees}{+/-}11.5{degrees}), larger IT ({bigtriangleup}{angle} = 5.3{degrees}{+/-}7.1{degrees} to 19.3{degrees}{+/-}10.2{degrees}), smaller IC ({bigtriangleup}{angle} = 5.4{degrees}{+/-}8.2{degrees} to 19.5{degrees}{+/-}10.2{degrees}), larger E ({bigtriangleup}{angle} = 10.9{degrees}{+/-}12.2{degrees} to 13.1{degrees}{+/-}8.8{degrees}) and larger v ({bigtriangleup}{angle} = 8.1{degrees}{+/-}9.4{degrees} to 16.6{degrees}{+/-}10.4{degrees}). ConclusionsThis parametric study offered valuable insights into the factors that could influence angle closure. The morphology of the iris (IT and IC) and its innate biomechanical behavior (E and v) were crucial in influencing the way the iris deformed during dilation, and angle closure was further exacerbated by decreased AC biometry (ACD and ACW).

bioengineering↗

How Myopia and Glaucoma Influence the Biomechanical Susceptibility of the Optic Nerve Head

PurposeWe aimed to assess optic nerve head (ONH) deformations following acute intraocular pressure (IOP) elevations and horizontal eye movements (adduction and abduction) in control eyes, highly myopic (HM) eyes, HM eyes with glaucoma (HMG), and eyes with pathologic myopia alone (PM) or PM with staphyloma (PM+S). MethodsWe studied 282 eyes, comprising of 99 controls, 51 HM, 35 HMG, 21 PM and 75 PM+S eyes. For each eye, we imaged the ONH using spectral-domain optical coherence tomography (OCT) under the following conditions: (1) primary gaze, (2) 20{degrees} adduction, (3) 20{degrees} abduction and (4) primary gaze with acute IOP elevation (to ~35 mmHg) achieved through ophthalmodynamometry. For each OCT volume, we automatically segmented the ONH tissues using deep learning. We performed digital volume correlation (DVC) analysis to compute IOP- and gaze-induced ONH displacements and effective strains (i.e. local deformations). All biomechanical quantities were compared across groups. ResultsUnder IOP elevation, we found that HM eyes exhibited significantly lower strains (3.9 {+/-} 2.4 %) than PM eyes (6.9 {+/-} 5.0%, p < 0.001), HMG eyes (4.7 {+/-} 1.8%, p = 0.04) and PM+S eyes (7.0 {+/-} 5.2%, p < 0.001). Under adduction, we found that HM eyes exhibited significantly lower strains (4.8% {+/-} 2.7%) than PM+S eyes (6.0 {+/-} 3.1%, p = 0.02). We also found significant associations between axial length (or refractive error) and strains - eyes with higher axial length and greater myopia were associated with higher strains. IOP-induced strains were also positively correlated with adduction-induced strains. ConclusionWe found that HMG eyes experienced significantly higher strains under IOP elevations as compared to HM eyes. Additionally, PM+S eyes experienced highest ONH strains as compared to other groups under all biomechanical loads. Our preliminary findings suggest the possibility of using a simple biomechanical test to tease out the susceptibility of HM eyes to further develop glaucoma and/or staphyloma.

bioengineering↗

The Structural Layers of the Porcine Iris Exhibit Inherently Different Biomechanical Properties

PurposeTo isolate the structural components of the ex vivo porcine iris tissue and to determine their biomechanical properties. MethodsThe porcine stroma and dilator tissues were separated, and their dimensions were assessed using optical coherence tomography (OCT). The stroma underwent flow test (n = 32) to evaluate for permeability using Darcys Law ({Delta}P = 2000 Pa, A = 0.0391 mm2), and both tissues underwent stress relaxation experiments ({varepsilon} = 0.5 with initial ramp of {delta}{varepsilon} = 0.1) to evaluate for their viscoelastic behaviours (n = 28). Viscoelasticity was characterised by the parameters {beta} (half width of the Gaussian distribution), {tau}m(mean relaxation time constant), E0 (instantaneous modulus) and E{infty} (equilibrium modulus). ResultsFor the stroma, the hydraulic permeability was 9.49 {+/-} 3.05 x 10-6 mm2/Pa{middle dot}s, and the viscoelastic parameters were {beta} = 2.50 {+/-} 1.40, and {tau}m = 7.43 {+/-} 4.96 s, with the two moduli calculated to be E0= 14.14 {+/-} 6.44 kPa and E{infty} = 6.08 {+/-} 2.74 kPa. For the dilator tissue, the viscoelastic parameters were {beta} = 2.06 {+/-} 1.33 and {tau}m = 1.28 {+/-} 1.27 s, with the two moduli calculated to be E0 = 9.16 {+/-} 3.03 kPa and E{infty} = 5.54 {+/-} 1.98 kPa. ConclusionWe have established a new protocol to evaluate the biomechanical properties of the structural layers of the iris. Overall, the stroma was permeable and exhibited smaller moduli than those of the dilator muscle. An improved characterisation of iris biomechanics may form the basis to further our understanding of angle closure glaucoma.

bioengineering↗

Differing Associations between Optic Nerve Head Strains and Visual Field Loss in Normal- and High-Tension Glaucoma Subjects

PurposeTo study the associations between optic nerve head (ONH) strains under intraocular pressure (IOP) elevation with retinal sensitivity in glaucoma subjects. DesignClinic based cross-sectional study. Participants229 subjects with primary open angle glaucoma (subdivided into 115 high tension glaucoma (HTG) subjects and 114 normal tension glaucoma (NTG) subjects). MethodsFor one eye of each subject, we imaged the ONH using spectral-domain optical coherence tomography (OCT) under the following conditions: (1) primary gaze and (2) primary gaze with acute IOP elevation (to approximately 33 mmHg) achieved through ophthalmodynamometry. A 3-dimensional (3D) strain-mapping algorithm was applied to quantify IOP-induced ONH tissue strain (i.e. deformation) in each ONH. Strains in the pre-lamina tissue (PLT)and the retina, the choroid, the sclera and the lamina cribrosa (LC) were associated (using linear regression) with measures of retinal sensitivity from the 24-2 Humphrey visual field test (Carl Zeiss Meditec, Dublin, CA, USA). This was done globally, then locally according to the regionalization scheme of Garway-Heath et al. Main Outcome MeasuresAssociations between ONH strains and values of retinal sensitivity from visual field testing. ResultsFor HTG subjects, we found that (1) there were significant negative linear associations between ONH strains and retinal sensitivity (p<0.001) (on average, a 1% increase in ONH strains corresponded to a decrease in retinal sensitivity of 1.1 dB), (2) high strain regions co-localized with anatomically-mapped regions of high visual field loss, (3) the strongest negative associations were observed in the superior region and in the PLT. In contrast, for NTG subjects, no significant associations between strains and retinal sensitivity were observed except in the supero-temporal region of the LC. ConclusionWe found significant negative associations between IOP-induced ONH strains and retinal sensitivity in a relatively large glaucoma cohort. Specifically, HTG subjects who experienced higher ONH strains were more likely to exhibit lower retinal sensitivities. Interestingly, this trend was in general less pronounced in NTG subjects, which could suggest a distinct pathophysiology between the two glaucoma subtypes.

bioengineering↗

Adduction Induces Large Optic Nerve Head Deformations in Subjects with Normal Tension Glaucoma

Purpose: To assess optic nerve head (ONH) deformations and strains during adduction, abduction, and intraocular pressure (IOP) elevation in subjects with high-tension glaucoma (HTG) and normal-tension glaucoma (NTG). Design: Clinic-based cross-sectional study. Participants: 114 HTG subjects and 114 NTG subjects. Methods. We recruited 228 subjects (114 subjects with HTG [pre-treatment IOP > 21mmHg] and 114 with NTG [pre-treatment IOP < 21mmHg]). For each subject, we imaged the ONH using spectral-domain optical coherence tomography (OCT) under the following conditions: (1) primary gaze, (2) 20 degree adduction, (3) 20 degree abduction, and (4) primary gaze with acute IOP elevation (to approximately 33 mmHg) achieved through ophthalmodynamometry. For each OCT volume, we automatically segmented the prelaminar tissue (PLT), the choroid, the sclera and the lamina cribrosa (LC) using a deep learning algorithm. We also digitally aligned the OCT volumes obtained from (2)-(4) to the primary gaze volume (1) before performing digital volume correlation (DVC) analysis to quantify IOP- and gaze-induced ONH tissues three-dimensional displacements and effective strain (a local measure of tissue deformation) for all scenarios. Main Outcome Measures: Three-dimensional ONH displacements and strains. Results: Across all subjects, adduction generated high effective strain (4.2 {+/-} 1.4%) in the ONH tissues with no significant difference (p>0.05) with those induced by IOP elevation (4.5 {+/-} 1.5%); while abduction generated significantly lower (p = 0.014) effective strain (3.8 {+/-} 1.1%). Interestingly, the LC of HTG subjects exhibited significantly higher effective strain than those of NTG subjects under IOP elevation (HTG:4.6 {+/-} 1.7% vs NTG:4.1 {+/-} 1.5%, p = 0.047). Conversely, the LC tissue of NTG subjects exhibited significantly higher effective strain than those of HTG subjects under adduction (NTG: 4.9 {+/-} 1.9% vs HTG: 4.0 {+/-} 1.4%, p = 0.041). Conclusion: We found that adduction produced comparable strains and displacements as IOP elevation. We also found that NTG subjects experienced higher strains due to adduction than HTG subjects, while HTG subjects experienced higher strain due to IOP elevation than NTG subjects - and that these differences were most pronounced in the LC tissue.

bioengineering↗

Changes in Iris Stiffness and Permeability in Primary Angle Closure Glaucoma

PurposeTo evaluate the biomechanical properties of the iris by evaluating iris movement during pupil constriction and to compare such properties between healthy and primary angle-closure glaucoma (PACG) subjects. MethodsA total of 140 subjects were recruited for this study. In a dark room, the anterior segments of one eye per subject were scanned using anterior segment optical coherence tomography (AS-OCT, SS-1000 CASIA, Tomey Corporation, Nagoya, Japan) imaging during induced pupil constriction with an external white light source of 1700 lux. Using a custom segmentation code, we automatically isolated the iris segments from the AS-OCT images, which were then discretized and transformed into a three-dimensional point cloud. For each iris, a finite element (FE) mesh was constructed from the point cloud, and an inverse FE simulation was performed to match the clinically observed iris constriction in the AS-OCT images. Through this optimization process, we were able to identify the elastic modulus and permeability of each iris. ResultsFor all 140 subjects (95 healthy and 45 PACG of Indian/Chinese ethnicity, Age: 60.2{+/-}8.7 for PACG subjects and 57.7{+/-}10.1 for healthy subjects), the simulated deformation pattern of the iris during pupil constriction matched well with OCT images. We found that the iris stiffness was higher in PACG than in healthy controls (24.5{+/-}8.4 kPa vs 17.1{+/-}6.6 kPa with 40 kPa of active stress specified in the sphincter region; p < 0.001), whereas iris permeability was lower (0.41{+/-}0.2 mm2/kPa.s vs 0.55{+/-}0.2 mm2/kPa.s; p = 0.142). ConclusionThis study suggests that the biomechanical properties of the iris in PACG are different from those in healthy controls. An improved understanding of the biomechanical behavior of the iris may have implications for the understanding and management of angle-closure glaucoma.

bioengineering↗

Gaze-evoked deformations of the optic nerve head in thyroid eye disease

PurposeTo assess gaze evoked deformations of the optic nerve head (ONH) in thyroid eye disease (TED), using computational modelling and optical coherence tomography (OCT). MethodsMultiple finite element models were constructed: One model of a healthy eye, and two models mimicking effects of TED; one with proptosis and another with extraocular tissue stiffening. Two additional hypothetical models had extraocular tissue softening or no extraocular tissue at all. Horizontal eye movements were simulated in these models. OCT images of the ONH of 10 healthy volunteers and 1 patient with TED were taken in primary gaze. Additional images were recorded in the same subjects performing eye movements in adduction and abduction. The resulting ONH deformation in the models and human subjects was measured by recording the tilt angle (relative antero-posterior deformation of the Bruchs membrane opening). Effective stress was measured in the peripapillary sclera of the models. ResultsIn our computational models the eyes with proptosis and stiffer extraocular tissue had greater gaze-evoked deformations than the healthy eye model, while the models with softer or no extraocular tissue had lesser deformations, in both adduction and abduction. Scleral stress correlated with the tilt angle measurements. In healthy subjects, the mean tilt angle was 1.46{degrees} {+/-} 0.25 in adduction and -0.42{degrees} {+/-} 0.12 in abduction. The tilt angle measured in the subject with TED was 5.37{degrees} in adduction and -2.21{degrees} in abduction. ConclusionsComputational modelling and experimental observation suggest that TED can cause increased gaze-evoked deformations of the ONH.

bioengineering↗

Effect of Changing Heart Rate on the Ocular Pulse and Dynamic Biomechanical Behavior of the Optic Nerve Head

PurposeTo study the effect of changing heart rate on the ocular pulse and the dynamic biomechanical behaviour of the optic nerve head (ONH) using a comprehensive mathematical model.\n\nMethodsIn a finite element model of a healthy eye, a biphasic choroid consisted of a solid phase with connective tissues and a fluid phase with blood, and the lamina cribrosa (LC) was viscoelastic as characterized by a stress-relaxation test. We applied arterial pressures at 18 ocular entry sites (posterior ciliary arteries) and venous pressures at four exit sites (vortex veins). In the model, the heart rate was varied from 60 bpm to 120 bpm (increment: 20 bpm). We assessed the ocular pulse amplitude (OPA), pulse volume, ONH deformations and the dynamic modulus of the LC at different heart rates.\n\nResultsWith an increasing heart rate, the OPA decreased by 0.04 mmHg for every 10 bpm increase in heart rate. The ocular pulse volume decreased linearly by 0.13 {micro}L for every 10 bpm increase in heart rate. The storage modulus and the loss modulus of the LC increased by 0.014 MPa and 0.04 MPa, respectively, for every 10 bpm increase in heart rate.\n\nconclusionsIn our model, the OPA, pulse volume, and ONH deformations decreased with an increasing heart rate, while the LC became stiffer. The effects of blood pressure / heart rate changes on ONH stiffening may be of interest for glaucoma pathology.\n\nSupportSingapore Ministry of Education, Academic Research Fund, Tier 2 (R-397-000-280-112).\n\nCommercial relationshipNone

bioengineering↗

Optic Nerve Tortuosity and Globe Proptosis in Normal and Glaucoma Subjects

PurposeTo assess the difference in optic nerve tortuosity during eye movements and globe proptosis between primary open angle glaucoma and normal subjects using orbital magnetic resonance imaging.\n\nMethods10 Chinese subjects matched for age, ethnicity and refractive errors were recruited, including five normal controls and five patients with primary open angle glaucoma. All subjects underwent magnetic resonance imaging to assess their optic nerves and globes for three eye positions: primary gaze, adduction and abduction. Optic nerve tortuosity (optic nerve length divided by the distance between two ends) and globe proptosis (maximum distance between cornea and interzygomatic line) were measured from magnetic resonance imaging images.\n\nResultsIn adduction, the tortuosity of normal eyes was significantly larger than that of the glaucomatous eyes. Optic nerve tortuosity in adduction in the control and glaucoma groups were 1.004{+/-}0.003 (mean {+/-} standard deviation) and 1.001{+/-}0.001, respectively (p=0.037). Globe proptosis (primary gaze) in glaucoma subjects (19.14{+/-}2.11 mm) was significantly higher than that in control subjects (15.32{+/-}2.79 mm; p = 0.046).\n\nConclusionsIn this sample, subjects with glaucoma exhibited more taut optic nerves and more protruding eye globes compared to normal eyes. This may impact optic nerve head deformations in anatomically predisposed patients.\n\nPrecisEyes with glaucoma have tauter optic nerves compared with normal eyes, which may exert more force on the optic nerve head tissues during eye movements.

pathology↗