Investigation of the Optic Nerve Head Morphology Influence to the Optic Nerve Head Biomechanics - Patient Specific Model.

Glaucoma is associated with damage and death of optic nerve fibers within the Lamina Cribrosa (LC) region of the Optic Nerve Head. The pathogenesis of the disease is unclear, and the anterior LC surface morphology of different individuals can be one of the possible contributor of glaucoma development and progression. The current study evaluates the relationship between the LC surface curvature and distribution of shear stresses on the LC surface. The patient-specific reconstructed ocular model was developed and analyzed in a finite element analysis software. In addition, the effect of elastic modulus of both sclera and LC on the shear stress was examined. Results showed that there is a correlation between the shear stress distribution and the curvature of the anterior LC surface. This finding highlights the potential significance of the LC morphology on the distribution of LC shear stress and require further investigation.

Investigation of the Optic Nerve Head Morphology Influence to the Optic Nerve Head Biomechanics - Population Specific Model.

Glaucoma is an eye disorder potentially leading to permanent blindness through the damage of optic nerves at the optic nerve head (ONH). As a critical region of optic nerve damage, the porous Lamina Cribrosa (LC) in the ONH plays a critical role in determining whether optic nerves passing through will experience apoptosis in response to shear stress. The primary cause of shear stress to the LC is the increase in intraocular pressure (IOP). Since morphology governs how mechanical stresses distributes, LC morphology could be an important factor in determining the risks of glaucoma development and progression. The current project aims at investigating how anterior LC surface morphology impacts its response to shear stress caused by IOP. Results of the current study show that steeper LC morphologies could be associated with increased average shear stress on the anterior LC surface. The effect of LC morphology was comparable to that of IOP. This highlights the potential significance of LC morphology on the distribution of IOP-induced shear stress and calls for further investigation in this area.

Characterization of Corneal Indentation Hysteresis.

Corneal indentation is adapted for the design and development of a characterization method for corneal hysteresis behavior - Corneal Indentation Hysteresis (CIH). Fourteen porcine eyes were tested using the corneal indentation method. The CIH measured in enucleated porcine eyes showed indentation rate and intraocular pressure (IOP) dependences. The CIH increased with indentation rate at lower IOP (<; 25 mmHg) and decreased with indentation rate at higher IOP (> 25 mmHg). The CIH was linear proportional to the IOP within an individual eye. The CIH was positively correlated with the IOP, corneal in-plane tensile stress and corneal tangent modulus (E). A new method based on corneal indentation for the measurement of Corneal Indentation Hysteresis in vivo is developed. To our knowledge, this is the first study to introduce the corneal indentation hysteresis and correlate the corneal indentation hysteresis and corneal tangent modulus.

Assessment of ocular biomechanics using dynamic ultra high-speed Scheimpflug imaging in keratoconic and normal eyes.

PURPOSE: To introduce several new ocular biomechanical parameters for comparison between keratoconic and normal eyes using an analysis method based on corneal dynamic deformation video recorded by corneal visualization Scheimpflug technology (Corvis ST; Oculus Optikgeräte GmbH, Wetzlar, Germany). METHODS: This comparative study comprised 52 keratoconic eyes of 43 patients with keratoconus and 52 normal eyes of 52 controls. An analysis method (PolyU [Labview 2009; National Instrument, Austin, TX]) was developed to introduce several new ocular biomechanical parameters and to compare the difference between keratoconic and normal eyes. The repeatability of the new parameters measurement was evaluated and compared with the Corvis ST measurement. Receiver operating characteristic curves were used to establish a cutoff value for the new biomechanical parameters. RESULTS: Intraclass correlation coefficients of the deformation amplitude, peak distance, corneal concave radius of curvature, maximum deformation area, maximum corneal inward velocity and outward velocity (Vin, max and Vout, max) were high in both the keratoconic and normal eyes (all intraclass correlation coefficients > 0.75). The measurement agreement of the PolyU analysis method and Corvis ST was good. Most of the biomechanical parameters of patients with keratoconus were significantly different from those of the controls. In the receiver operating characteristic analysis, the Vin, max was the best predictive parameter with an area under the curve of 0.79. CONCLUSIONS: The corneal deformation video recorded by the Corvis ST provides useful information for the study of ocular biomechanics. Most of the new ocular biomechanical parameters were significantly different between keratoconic and normal eyes. Further research is needed to develop more comprehensive clinical applications with these new ocular biomechanical parameters.

Comparative study of corneal tangent elastic modulus measurement using corneal indentation device.

The aim of this study is to examine the corneal tangent modulus measurement repeatability and performance of the corneal indentation device (CID). Twenty enucleated porcine eyes were measured and the eyes were pressurized using saline solution-filled manometer to 15 and 30 mmHg. Corneal tangent moduli measured using the CID were compared with those measured using high precision universal testing machine (UTM). The within-subject standard deviation (Sw), repeatability (2.77×Sw), coefficient of variation (CV) (Sw/overall mean), and intraclass correlation coefficient (ICC) were determined. The mean corneal tangent moduli measured using UTM and CID were 0.094±0.030 and 0.094±0.028 MPa at 15 mmHg, and 0.207±0.056 and 0.207±0.055 MPa at 30 mmHg, respectively, with a difference less than 0.13%. The 95% limit of agreement was between -0.009 and 0.009 MPa. The Sw, repeatability, CV and ICC of corneal tangent moduli measured by the CID were 0.006 MPa, 0.015 MPa, 4.3% and 0.993, respectively. The results showed that the corneal tangent moduli measured by the CID are repeatable and are in good agreement with the results measured by the high precision UTM.

Noninvasive measurement of scleral stiffness and tangent modulus in porcine eyes.

PURPOSE: We investigated an indentation technique to measure the scleral stiffness and tangent modulus of porcine eyes. METHODS: The scleral load-displacement responses were measured with a universal testing machine as a function of IOP in 15 porcine eyes ex vivo using a 5-mm diameter cylindrical flat-punch indenter. The scleral radius of curvature and scleral thickness were measured using a DSLR camera (Alpha 900) and a camera-mounted stereomicroscope (M205C), respectively. The relationships between scleral stiffness, tangent modulus, and IOP were examined. RESULTS: The mean local scleral radius of curvature and scleral thickness were 7.86 ± 0.49 and 1.03 ± 0.14 mm, respectively. The average scleral stiffness and scleral tangent modulus of porcine eyes were 0.13 ± 0.02 N/mm and 0.20 ± 0.04 MPa at 15 mm Hg, respectively. The scleral stiffness and scleral tangent modulus were correlated positively with IOP (scleral stiffness, 0.989 < r < 0.999, P < 0.001; scleral tangent modulus, 0.989 < r < 0.999, P < 0.001). CONCLUSIONS: The scleral indentation technique can provide a noninvasive approach to measure scleral stiffness and tangent modulus.

Individual-specific tonometry on porcine eyes.

Intraocular pressure (IOP) monitoring is important in the diagnosis and management of glaucoma. The measurement of IOP is affected by corneal properties, but the effect of corneal stiffness on IOP measurement is unaccounted for in pressure measurement instruments such as the Goldmann Applanation Tonometer (GAT). A new instrumented non-invasive indentation tonometry that can measure IOPIST, a corneal stiffness-corrected intraocular pressure is developed. The inter-individual corneal variations of 12 porcine eyes ex vivo were independently characterized; and their true intraocular pressure, IOPT's, were set using a manometer before indentation using the new indentation tonometry. Analyses of the load-displacement data showed that porcine corneal stiffness varied more than five times from 0.045 to 0.253N/mm. Analysis showed that, without individual stiffness correction, inter-individual variation of IOPGAT can vary up to 8mmHg from IOPT at 15mmHg; the error becomes larger at high IOPT. In comparison when corneal stiffness is accounted for, IOPIST has a significantly smaller error of 1.82±1.70mmHg for IOPT between 12 and 40mmHg than IOPGAT. The results showed that the new tonometry successfully accounted for inter-individual variations in IOP measurement.

Characterization of pressure reduction in coil-filled aneurysm under flow of human blood with and without anti-coagulant.

Filling aneurysms with embolization coils is a widely used part of the treatment to stop intracranial aneurysm from rupturing. However, the effect of coiling on aneurysmal pressure has not been established. In this study, the effect of intra-aneurysmal coiling on pressure reduction was characterized. Coil deployment in the aneurysm will disturb flow and may induce aneurysmal coagulation. These effects were experimentally examined in this study using silicone rubber saccular aneurysm models. Changes in aneurysmal blood pressure under pulsatile flow were characterized. With coils in the aneurysm, results showed that flow reduction of anti-coagulated blood in the aneurysm did not reduce aneurysmal pressure. Significant pressure reduction was observed only when the blood's coagulation ability is restored to normal. These results suggest that blood coagulation is pivotal to pressure reduction and concomitant with rupture risk reduction in treatments of aneurysm with coils.

Characterization of corneal tangent modulus in vivo.

PURPOSE: Intraocular pressure (IOP) measured using Goldmann Applanation Tonometry (GAT) changes with individual's corneal properties, but the method to measure the in vivo corneal material properties to account for individual variation in GAT IOP is not available. In this study, a new method to measure the IOP-dependent corneal tangent modulus in vivo is developed to address this research gap. METHODS: Instrumented indentation and analysis were developed to measure the corneal tangent modulus. The validity of the method and procedure was verified using model silicone eye pressurized to different IOP. In addition, 15 porcine eyes and 3 rabbit eyes were tested using the corneal indentation at different set intraocular pressure and different indentation rates. RESULTS: The results from silicone eye showed that the measured tangent modulus is in good agreement with the standard silicone rubber modulus. The results on the porcine eyes and rabbit eyes showed that the method can be used to measure corneal tangent modulus in vivo in the human range of intraocular pressure from 10 to 40 mmHg. CONCLUSIONS: An indentation method to measure the corneal tangent modulus in vivo was developed, and the IOP dependence of the corneal tangent modulus was characterized. The developed indentation method provides a new means to measure the in vivo corneal tangent modulus to account for individual and pressure variations in measurement of intraocular pressure.

Effect of age-stiffening tissues and intraocular pressure on optic nerve damages.

Age-stiffening of ocular tissues is statistically linked to glaucoma in the elderly. In this study, the effects of age-stiffening on the lamina cribrosa, the primary site of glaucomatous nerve damages, were modeled using computational finite element analysis. We showed that glaucomatous nerve damages and peripheral vision loss behavior can be phenomenologically modeled by shear-based damage criterion. Using this damage criterion, the potential vision loss for 30 years old with mild hypertension of 25 mmHg intraocular pressure (IOP) was estimated to be 4%. When the IOP was elevated to 35 mmHg, the potential vision loss rose to 45%; and age-stiffening from 35 to 60 years old increased the potential vision loss to 52%. These results showed that while IOP plays a central role in glaucomatous damages, age-stiffening facilitates glaucomatous damages and may be the principal factor that resulted in a higher rate of glaucoma in the elderly than the general population.

Partial contact indentation tonometry for measurement of corneal properties-independent intraocular pressure.

Inter-individual differences in corneal properties are ignored in existing methods for measuring intraocular pressure IOP, a primary parameter used in screening and monitoring of glaucoma. The differences in the corneal stiffness between individuals can be more than double and this difference would lead to IOP measurement errors up to 10 mmHg. In this study, an instrumented partial-contact indentation measurement and analysis method that can account for inter-individual corneal difference in stiffness is developed. The method was tested on 12 porcine eyes ex vivo and 7 rabbit eyes in vivo, and the results were compared to the controlled IOPs to determine the method's validity. Analyses showed that without corneal stiffness correction, up to 10 mmHg of measurement error was found between the existing approach and the controlled IOP. With the instrumented indentation and analysis method, less than 2 mmHg of differences were founded between the measured IOP and the controlled IOP. These results showed that instrumented partial-contact indentation can effectively account for inter-individual corneal variations in IOP measurement.