In Vivo Measurements of Prelamina and Lamina Cribrosa Biomechanical Properties in Humans.

Purpose: To develop and use a custom virtual fields method (VFM) to assess the biomechanical properties of human prelamina and lamina cribrosa (LC) in vivo. Methods: Clinical data of 20 healthy, 20 ocular hypertensive (OHT), 20 primary open-angle glaucoma, and 16 primary angle-closure glaucoma eyes were analyzed. For each eye, the intraocular pressure (IOP) and optical coherence tomography (OCT) images of the optic nerve head (ONH) were acquired at the normal state and after acute IOP elevation. The IOP-induced deformation of the ONH was obtained from the OCT volumes using a three-dimensional tracking algorithm and fed into the VFM to extract the biomechanical properties of the prelamina and the LC in vivo. Statistical measurements and P values from the Mann-Whitney-Wilcoxon tests were reported. Results: The average shear moduli of the prelamina and the LC were 64.2 ± 36.1 kPa and 73.1 ± 46.9 kPa, respectively. The shear moduli of the prelamina of healthy subjects were significantly lower than those of the OHT subjects. Comparisons between healthy and glaucoma subjects could not be made robustly due to a small sample size. Conclusions: We have developed a methodology to assess the biomechanical properties of human ONH tissues in vivo and provide preliminary comparisons in healthy and OHT subjects. Our proposed methodology may be of interest for glaucoma management.

In Vivo Three-Dimensional Lamina Cribrosa Strains in Healthy, Ocular Hypertensive, and Glaucoma Eyes Following Acute Intraocular Pressure Elevation.

Purpose: To compare in vivo lamina cribrosa (LC) strains (deformations) following acute IOP elevation in healthy, glaucoma, and ocular hypertensive subjects. Methods: There were 20 healthy, 20 high-tension primary open-angle glaucoma (POAG), 16 primary angle-closure glaucoma (PACG), and 20 ocular hypertensive (OHT; with normal visual fields) eyes studied. For each test eye, the optic nerve head was imaged three times (at baseline IOP, following an acute elevation of IOP to approximately 35 then 45 mm Hg using an ophthalmodynamomter) using optical coherence tomography (OCT). A three-dimensional (3D) strain-mapping algorithm was applied to both sets of baseline and IOP-elevated OCT volumes to extract IOP-induced 3D strains. Octant-wise LC strains were also extracted to study the pattern of local deformation. Results: The average LC strain in OHT subjects (3.96%) was significantly lower than that measured in healthy subjects (6.81%; P < 0.05). On average, POAG subjects experienced higher strain than the PACG subjects (4.05%), healthy subjects experienced higher strains than the POAG and PACG subjects, but these difference were not statistically significant. Local LC deformations showed lowest strain in the infero-temporal and temporal octant in the POAG and OHT subjects. Conclusions: We demonstrate measurable LC strains in vivo in humans as a response to acute IOP elevation. In this population, our data suggest that OHT LCs experience lower IOP-induced strains than healthy LCs.

Verification of a virtual fields method to extract the mechanical properties of human optic nerve head tissues in vivo.

We aimed to verify a custom virtual fields method (VFM) to estimate the patient-specific biomechanical properties of human optic nerve head (ONH) tissues, given their full-field deformations induced by intraocular pressure (IOP). To verify the accuracy of VFM, we first generated 'artificial' ONH displacements from predetermined (known) ONH tissue biomechanical properties using finite element analysis. Using such deformations, if we are able to match back the known biomechanical properties, it would indicate that our VFM technique is accurate. The peripapillary sclera was assumed anisotropic hyperelastic, while all other ONH tissues were considered isotropic. The simulated ONH displacements were fed into the VFM algorithm to extract back the biomechanical properties. The robustness of VFM was also tested against rigid body motions and noise added to the simulated displacements. Then, the computational speed of VFM was compared to that of a gold-standard stiffness measurement method (inverse finite element method or IFEM). Finally, as proof of principle, VFM was applied to IOP-induced ONH deformation data (obtained from one subject's eye imaged with OCT), and the biomechanical properties of the prelamina and lamina cribrosa (LC) were extracted. From given ONH displacements, VFM successfully matched back the biomechanical properties of ONH tissues with high accuracy and efficiency. For all parameters, the percentage errors were less than 0.05%. Our method was insensitive to rigid body motions and was also able to recover the material parameters in the presence of noise. VFM was also found 125 times faster than the gold-standard IFEM. Finally, the estimated shear modulus for the prelamina and the LC of the studied subject's eye were 33.7 and 63.5 kPa, respectively. VFM may be capable of measuring the biomechanical properties of ONH tissues with high speed and accuracy. It has potential in identifying patient-specific ONH biomechanical properties in the clinic if combined with optical coherence tomography.

In Vivo 3-Dimensional Strain Mapping Confirms Large Optic Nerve Head Deformations Following Horizontal Eye Movements.

PURPOSE: To measure lamina cribrosa (LC) strains (deformations) following abduction and adduction in healthy subjects and to compare them with those resulting from a relatively high acute intraocular pressure (IOP) elevation. METHODS: A total of 16 eyes from 8 healthy subjects were included. Among the 16 eyes, 11 had peripapillary atrophy (PPA). For each subject, both optic nerve heads (ONHs) were imaged using optical coherence tomography (OCT) at baseline (twice), in different gaze positions (adduction and abduction of 20°) and following an acute IOP elevation of approximately 20 mm Hg from baseline (via ophthalmodynamometry). Strains of LC for all loading scenarios were mapped using a three-dimensional tracking algorithm. RESULTS: In all 16 eyes, LC strains induced by adduction and abduction were 5.83% ± 3.78% and 3.93% ± 2.57%, respectively, and both significantly higher than the control strains measured from the repeated baseline acquisitions (P < 0.01). Strains of LC in adduction were on average higher than those in abduction, but the difference was not statistically significant (P = 0.07). Strains of LC induced by IOP elevations (on average 21.13 ± 7.61 mm Hg) were 6.41% ± 3.21% and significantly higher than the control strains (P < 0.0005). Gaze-induced LC strains in the PPA group were on average larger than those in the non-PPA group; however, the relationship was not statistically significant. CONCLUSIONS: Our results confirm that horizontal eye movements generate significant ONH strains, which is consistent with our previous estimations using finite element analysis. Further studies are needed to explore a possible link between ONH strains induced by eye movements and axonal loss in optic neuropathies.

In Vivo 3-Dimensional Strain Mapping of the Optic Nerve Head Following Intraocular Pressure Lowering by Trabeculectomy.

PURPOSE: To map the 3-dimensional (3D) strain of the optic nerve head (ONH) in vivo after intraocular pressure (IOP) lowering by trabeculectomy (TE) and to establish associations between ONH strain and retinal sensitivity. DESIGN: Observational case series. PARTICIPANTS: Nine patients with primary open-angle glaucoma (POAG) and 3 normal controls. METHODS: The ONHs of 9 subjects with POAG (pre-TE IOP: 25.3±13.9 mmHg; post-TE IOP: 11.8±8.6 mmHg) were imaged (1 eye per subject) using optical coherence tomography (OCT) (Heidelberg Spectralis, Heidelberg Engineering GmbH, Heidelberg, Germany) before (<21 days) and after (<50 days) TE. The imaging protocol was repeated for 3 controls in whom IOP was not altered. In each post-TE OCT volume, 4 tissues were manually segmented (prelamina, choroid, sclera, and lamina cribrosa [LC]). For each ONH, a 3D tracking algorithm was applied to both post- and pre-TE OCT volumes to extract IOP-induced 3D displacements at segmented nodes. Displacements were filtered, smoothed, and processed to extract 3D strain relief (the amount of tissue deformation relieved after TE). Strain relief was compared with measures of retinal sensitivity from visual field testing. MAIN OUTCOME MEASURES: Three-dimensional ONH displacements and strain relief. RESULTS: On average, strain relief (averaged or effective component) in the glaucoma ONHs (8.6%) due to TE was higher than that measured in the normal controls (1.07%). We found no associations between the magnitude of IOP decrease and the LC strain relief (P > 0.05), suggesting biomechanical variability across subjects. The LC displaced posteriorly, anteriorly, or not at all. Furthermore, we found linear associations between retinal sensitivity and LC effective strain relief (P < 0.001; high strain relief associated with low retinal sensitivity). CONCLUSIONS: We demonstrate that ONH displacements and strains can be measured in vivo and that TE can relieve ONH strains. Our data suggest a wide variability in ONH biomechanics in the subjects examined in this study. We further demonstrate associations between LC effective strain relief and retinal sensitivity.

Spectrally encoded extended source optical coherence tomography.

We have developed an extended source optical coherence tomography (SEES-OCT) technique in an attempt to improve signal strength for ophthalmic imaging. A line illumination with a visual angle of 7.9 mrad is produced by introducing a dispersive element in the infinity space of the sample arm. The maximum permissible exposure (MPE) of such an extended source is 3.1 times larger than that of a "standard" point source OCT, which corresponds to sensitivity improvement of 5 dB. The advantage of SEES-OCT in providing superior penetration depth over a point source system is demonstrated using swine eye tissues ex vivo.