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.

Simulating Outcomes of Cataract Surgery: Important Advances in Ophthalmology.

As the human eye ages, the crystalline lens stiffens (presbyopia) and opacifies (cataract), requiring its replacement with an artificial lens [intraocular lens (IOL)]. Cataract surgery is the most frequently performed surgical procedure in the world. The increase in IOL designs has not been paralleled in practice by a sophistication in IOL selection methods, which rely on limited anatomical measurements of the eye and the surgeon's interpretation of the patient's needs and expectations. We propose that the future of IOL selection will be guided by 3D quantitative imaging of the crystalline lens to map lens opacities, anticipate IOL position, and develop fully customized eye models for ray-tracing-based IOL selection. Conversely, visual simulators (in which IOL designs are programmed in active elements) allow patients to experience prospective vision before surgery and to make more informed decisions about which IOL to choose. Quantitative imaging and optical and visual simulations of postsurgery outcomes will allow optimal treatments to be selected for a patient undergoing modern cataract surgery.

Isolated human crystalline lens three-dimensional shape: A comparison between Indian and European populations.

There have been many studies on lens properties in specific populations (e.g. in China, Europe, Singapore, etc.) some of which suggest there may be differences between populations. Differences could be caused by ethnic or environmental influences or experimental procedures. The purpose of this study is to evaluate if any differences exist between Indian and European populations in the central geometric and full shape properties of human lenses. Two custom-developed spectral domain optical coherence tomography systems were used to acquire the crystalline lens geometry: one in India (69 lenses from 59 donors) and the other in Spain (24 lenses from 19 donors). The steps for obtaining accurate 3-D models from optical coherence tomography raw images comprised of image segmentation, fan and optical distortion correction, tilt removal and registration. The outcome variables were lens equatorial diameter, lens thickness, anterior and posterior lens thicknesses and their ratio, central radius of curvature of the anterior and posterior lens surfaces, lens volume and lens surface area. A mixed effects model by maximum likelihood estimation was used to evaluate the effect of age, population and their interaction (age*population) on lens parameters. After adjusting for age, there were no population differences observed in anterior and posterior radii of curvature, equatorial diameter, lens thickness, anterior and posterior lens thicknesses and their ratio, volume and surface area (all p ≥ 0.08). There was also no effect of the interaction term on anterior and posterior radii of curvature, equatorial diameter, lens thickness, anterior and posterior lens thicknesses and their ratio, volume and surface area (all p ≥ 0.06). All central geometric and full shape parameters appeared to be comparable between the European and Indian populations. This is the first study to compare geometric and full shape lens parameters between different populations in vitro.

Crystalline lens gradient refractive index distribution in the guinea pig.

PURPOSE: The crystalline lens undergoes morphological and functional changes with age and may also play a role in eye emmetropisation. Both the geometry and the gradient index of refraction (GRIN) distribution contribute to the lens optical properties. We studied the lens GRIN in the guinea pig, a common animal model to study myopia. METHODS: Lenses were extracted from guinea pigs (Cavia porcellus) at 18 days of age (n = 4, three monolaterally treated with negative lenses and one untreated) and 39 days of age (n = 4, all untreated). Treated eyes were myopic (-2.07 D on average) and untreated eyes hyperopic (+3.3 D), as revealed using streak retinoscopy in the live and cyclopeged animals. A custom 3D spectral domain optical coherence tomography (OCT) system (λ = 840 nm, Δλ = 50 nm) was used to image the enucleated crystalline lens at two orientations. Custom algorithms were used to estimate the lens shape and GRIN was modelled with four variables that were reconstructed using the OCT data and a minimisation algorithm. Ray tracing was used to calculate the optical power and spherical aberration assuming a homogeneous refractive index or the estimated GRIN. RESULTS: Guinea pig lenses exhibited nearly parabolic GRIN profiles. When comparing the two age groups (18- and 39 day-old) there was a significant increase in the central thickness (from 3.61 to 3.74 mm), and in the refractive index of the surface (from 1.362 to 1.366) and the nucleus (from 1.443 to 1.454). The presence of GRIN shifted the spherical aberration (-4.1 µm on average) of the lens towards negative values. CONCLUSIONS: The guinea pig lens exhibits a GRIN profile with surface and nucleus refractive indices that increase slightly during the first days of life. GRIN plays a major role in the lens optical properties and should be incorporated into computational guinea pig eye models to study emmetropisation, myopia development and ageing.

In Situ Synthesis of Polyurethane Scaffolds with Tunable Properties by Controlled Crosslinking of Tri-Block Copolymer and Polycaprolactone Triol for Tissue Regeneration.

Mimicking the mechanical properties of native tissues is a critical criterion for an ideal tissue engineering scaffold. However, most biodegradable synthetic materials, including polyester-based polyurethanes (PUs), consist of rigid polyester chains and have high crystallinity. They typically lack the elasticity of most human tissues. In this study, a new type of biodegradable PU with excellent elasticity was synthesized based on the controlled crosslinking of poly(ester ether) triblock copolymer diols and polycaprolactone (PCL) triols using urethane linkages. Three-dimensional (3D) porous scaffolds with a defined geometry, tunable microstructures, and adjustable mechanical properties were synthesized in situ using an isocyanate-ended copolymer, a tri-armed PCL, and a chain extender. The mechanical properties of the scaffolds can be easily tuned by changing the ratio of reactants, varying the solution concentration, or using a porogen. Notably, all of these scaffolds, although mostly made of rigid PCL chains, showed remarkable elasticity and cyclical properties. With an optimized molecular design, a maximum recovery rate of 99.8% was achieved. This was because the copolymer provided molecular flexibility while the long chain crosslinking of PCL triol hindered crystallization, thus making the PU behave like an amorphous elastic material. Moreover, the in vitro cell culture of 3T3 fibroblasts and MG63 osteoblast-like cells confirmed the biocompatibility of these PU scaffolds and revealed that scaffolds with different stiffnesses can stimulate the proliferation of different types of cells. All of these attributes make PU scaffolds extremely suitable for the regeneration of tissues that experience dynamic loading.

Design and Synthesis of P(AAm-co-NaAMPS)-Alginate-Xanthan Hydrogels and the Study of Their Mechanical and Rheological Properties in Artificial Vascular Graft Applications.

Cardiovascular diseases (CVDs) are the number one cause of mortality among non-communicable diseases worldwide. Expanded polytetrafluoroethylene (ePTFE) is a widely used material for making artificial vascular grafts to treat CVDs; however, its application in small-diameter vascular grafts is limited by the issues of thrombosis formation and intimal hyperplasia. This paper presents a novel approach that integrates a hydrogel layer on the lumen of ePTFE vascular grafts through mechanical interlocking to efficiently facilitate endothelialization and alleviate thrombosis and restenosis problems. This study investigated how various gel synthesis variables, including N,N'-Methylenebisacrylamide (MBAA), sodium alginate, and calcium sulfate (CaSO4), influence the mechanical and rheological properties of P(AAm-co-NaAMPS)-alginate-xanthan hydrogels intended for vascular graft applications. The findings obtained can provide valuable guidance for crafting hydrogels suitable for artificial vascular graft fabrication. The increased sodium alginate content leads to increased equilibrium swelling ratios, greater viscosity in hydrogel precursor solutions, and reduced transparency. Adding more CaSO4 decreases the swelling ratio of a hydrogel system, which offsets the increased swelling ratio caused by alginate. Increased MBAA in the hydrogel system enhances both the shear modulus and Young's modulus while reducing the transparency of the hydrogel system and the pore size of freeze-dried samples. Overall, Hydrogel (6A12M) with 2.58 mg/mL CaSO4 was the optimal candidate for ePTFE-hydrogel vascular graft applications due to its smallest pore size, highest shear storage modulus and Young's modulus, smallest swelling ratio, and a desirable precursor solution viscosity that facilitates fabrication.

Estimation of Crystalline Lens Material Properties From Patient Accommodation Data and Finite Element Models.

Purpose: The mechanical properties of the crystalline lens are related to its optical function of accommodation, and their changes with age are one of the potential causes for presbyopia. We estimated the mechanical parameters of the crystalline lens using quantitative optical coherence tomography (OCT) imaging and wavefront sensing data from accommodating participants and computer modeling. Methods: Full-lens shape data (from quantitative swept-source OCT and eigenlens representation) and optical power data (from Hartmann-Shack wavefront sensor) were obtained from 11 participants (22-30 years old) for relaxed accommodation at infinity and -4.5 D accommodative demand. Finite element models of lens, capsular bag, zonulae, and ciliary body were constructed using measured lens geometry and literature data, assuming a 60-mN radial force. An inverse modeling scheme was used to determine the shear moduli of the nucleus and cortex of the lens, such that the simulated deformed (maximally stretched) lens matched the participant's lens at -4.5 D. Results: The shear moduli of the nucleus and cortex were 1.62 ± 1.32 and 8.18 ± 5.63 kPa, on average, respectively. The shear modulus of the nucleus was lower than that of the cortex for all participants evaluated. The average of the two moduli per participant was statistically significantly correlated with age (R2 = 0.76, P = 0.0049). Conclusions: In vivo imaging and mechanical modeling of the crystalline lens allow estimations of the crystalline lens' mechanical properties. Differences between nuclear and cortical moduli and their dependency with age appear to be critical in accommodative function and likely in its impairment in presbyopia.

Effect of fixational eye movements in corneal topography measurements with optical coherence tomography.

There is an increasing interest in applying optical coherence tomography (OCT) to quantify the topography of ocular structures. However, in its most usual configuration, OCT data is acquired sequentially while a beam is scanned through the region of interest, and the presence of fixational eye movements can affect the accuracy of the technique. Several scan patterns and motion correction algorithms have been proposed to minimize this effect, but there is no consensus on the ideal parameters to obtain a correct topography. We have acquired corneal OCT images with raster and radial patterns, and modeled the data acquisition in the presence of eye movements. The simulations replicate the experimental variability in shape (radius of curvature and Zernike polynomials), corneal power, astigmatism, and calculated wavefront aberrations. The variability of the Zernike modes is highly dependent on the scan pattern, with higher variability in the direction of the slow scan axis. The model can be a useful tool to design motion correction algorithms and to determine the variability with different scan patterns.

Estimation of the full shape of the crystalline lens from OCT: validation using stretched donor lenses.

Quantifying human crystalline lens geometry as a function of age and accommodation is important for improved cataract and presbyopia treatments. In previous works we presented eigenlenses as a basis of 3-D functions to represent the full shape of the crystalline lens ex vivo. Also, we presented the application of eigenlenses to estimate the full shape of the lens in vivo from 3-D optical coherence tomography (OCT) images, where only the central part of the lens -visible through the pupil- is available. The current work presents a validation of the use of eigenlenses to estimate in vivo the full shape of dis-accommodated lenses. We used 14 ex vivo crystalline lenses from donor eyes (11-54 y/o) mounted in a lens stretcher, and measured the geometry and the power of the lenses using a combined OCT and ray tracing aberrometry system. Ex vivo, the full extent of the lens is accessible from OCT because the incident light is not blocked by the iris. We measured in non-stretched (fully accommodated) and stretched (mimicking in vivo dis-accommodated lenses) conditions. Then, we simulated computationally in vivo conditions on the obtained ex vivo lenses geometry (assuming that just the portion of the lens within a given pupil is available), and estimated the full shape using eigenlenses. The mean absolute error (MAE) between estimated and measured lens' diameters and volumes were MAE = 0.26 ± 0.18 mm and MAE = 7.0 ± 4.5 mm3, respectively. Furthermore, we concluded that the estimation error between measured and estimated lenses did not depend on the accommodative state (change in power due to stretching), and thus eigenlenses are also useful for the full shape estimation of in vivo dis-accommodated lenses.

Estimation of the full shape of the crystalline lens in-vivo from OCT images using eigenlenses.

Quantifying the full 3-D shape of the human crystalline lens is important for improving intraocular lens power or sizing calculations in treatments of cataract and presbyopia. In a previous work we described a novel method for the representation of the full shape of the ex vivo crystalline lens called eigenlenses, which proved more compact and accurate than compared state-of-the art methods of crystalline lens shape quantification. Here we demonstrate the use of eigenlenses to estimate the full shape of the crystalline lens in vivo from optical coherence tomography images, where only the information visible through the pupil is available. We compare the performance of eigenlenses with previous methods of full crystalline lens shape estimation, and demonstrate an improvement in repeatability, robustness and use of computational resources. We found that eigenlenses can be used to describe efficiently the crystalline lens full shape changes with accommodation and refractive error.

Variable coastal hypoxia exposure and drivers across the southern California Current.

Declining oxygen is one of the most drastic changes in the ocean, and this trend is expected to worsen under future climate change scenarios. Spatial variability in dissolved oxygen dynamics and hypoxia exposures can drive differences in vulnerabilities of coastal ecosystems and resources, but documentation of variability at regional scales is rare in open-coast systems. Using a regional collaborative network of dissolved oxygen and temperature sensors maintained by scientists and fishing cooperatives from California, USA, and Baja California, Mexico, we characterize spatial and temporal variability in dissolved oxygen and seawater temperature dynamics in kelp forest ecosystems across 13° of latitude in the productive California Current upwelling system. We find distinct latitudinal patterns of hypoxia exposure and evidence for upwelling and respiration as regional drivers of oxygen dynamics, as well as more localized effects. This regional and small-scale spatial variability in dissolved oxygen dynamics supports the use of adaptive management at local scales, and highlights the value of collaborative, large-scale coastal monitoring networks for informing effective adaptation strategies for coastal communities and fisheries in a changing climate.

Estimation of scleral mechanical properties from air-puff optical coherence tomography.

We introduce a method to estimate the biomechanical properties of the porcine sclera in intact eye globes ex vivo, using optical coherence tomography that is coupled with an air-puff excitation source, and inverse optimization techniques based on finite element modeling. Air-puff induced tissue deformation was determined at seven different locations on the ocular globe, and the maximum apex deformation, the deformation velocity, and the arc-length during deformation were quantified. In the sclera, the experimental maximum deformation amplitude and the corresponding arc length were dependent on the location of air-puff excitation. The normalized temporal deformation profile of the sclera was distinct from that in the cornea, but similar in all tested scleral locations, suggesting that this profile is independent of variations in scleral thickness. Inverse optimization techniques showed that the estimated scleral elastic modulus ranged from 1.84 ± 0.30 MPa (equatorial inferior) to 6.04 ± 2.11 MPa (equatorial temporal). The use of scleral air-puff imaging holds promise for non-invasively investigating the structural changes in the sclera associated with myopia and glaucoma, and for monitoring potential modulation of scleral stiffness in disease or treatment.

Eigenlenses: a new model for full crystalline lens shape representation and its applications.

The crystalline lens is an important optical element in the eye, responsible for focusing, and which experiences significant changes throughout life. The shape of the lens is usually studied only in the optical area (central 4 to 6 mm). However, for a great number of applications, a description of the full shape of the crystalline lens is required. We propose a new method for the representation of the full shape of the crystalline lens, constructed from 3-dimensional optical coherence tomography images of 133 isolated crystalline lenses (0-71 y/o), which we have called eigenlenses. The method is shown to be compact and accurate to describe not only the full shape of the crystalline lens, but also the optical zone in comparison with other methods. We also demonstrate its application to the extrapolation of the full shape of the crystalline lens from in-vivo optical images of the anterior segment of the eye, where only the central part of the lens visible through the pupil is available, and in the generation (synthesis) of realistic full lenses of a given age. The method has critical applications, among others, in improving and evaluating myopia and presbyopia treatments.

Corneal Collagen Ordering After In Vivo Rose Bengal and Riboflavin Cross-Linking.

Purpose: Photoactivated cornea collagen cross-linking (CXL) increases corneal stiffness by initiating formation of covalent bonds between stromal proteins. Because CXL depends on diffusion to distribute the photoinitiator, a gradient of CXL efficiency with depth is expected that may affect the degree of stromal collagen organization. We used second harmonic generation (SHG) microscopy to investigate the differences in stromal collagen organization in rabbit eyes after corneal CXL in vivo as a function of depth and time after surgery. Methods: Rabbit corneas were treated in vivo with either riboflavin/UV radiation (UVX) or Rose Bengal/green light (RGX) and evaluated 1 and 2 months after CXL. Collagen fibers were imaged with a custom-built SHG scanning microscope through the central cornea (350 µm depth, 225 × 225 µm en face images). The order coefficient (OC), a metric for collagen organization, and total SHG signal were computed for each depth and compared between treatments. Results: OC values of CXL-treated corneas were larger than untreated corneas by 27% and 20% after 1 month and 38% and 33% after 2 months for the RGX and UVX, respectively. RGX OC values were larger than UVX OC values by 3% and 5% at 1 and 2 months. The SHG signal was higher in CXL corneas than untreated corneas, both at 1 and 2 months after surgery, by 18% and 26% and 1% and 10% for RGX and UVX, respectively. Conclusions: Increased OC corresponded with increased collagen fiber organization in CXL corneas. Changes in collagen organization parallel reported temporal changes in cornea stiffness after CXL and also, surprisingly, are detected deeper in the stroma than the regions stiffened by collagen cross-links.

Age-Related Changes to the Three-Dimensional Full Shape of the Isolated Human Crystalline Lens.

Purpose: Studying the full shape crystalline lens geometry is important to understand the changes undergone by the crystalline lens leading to presbyopia, cataract, or failure of emmetropization, and to aid in the design and selection of intraocular lenses and new strategies for correction. We used custom-developed three-dimensional (3-D) quantitative optical coherence tomography (OCT) to study age-related changes in the full shape of the isolated human crystalline lens. Methods: A total of 103 ex vivo human isolated lenses from 87 subjects (age range, 0-56 years) were imaged using a 3-D spectral-domain OCT system. Lens models, constructed after segmentation of the surfaces and distortion correction, were used to automatically quantify central geometric parameters (lens thickness, radii of curvatures, and asphericities of anterior and posterior surfaces) and full shape parameters (lens volume, surface area, diameter, and equatorial plane position). Age-dependencies of these parameters were studied. Results: Most of the measured parameters showed a biphasic behavior, statistically significantly increasing (radii of curvature, lens volume, surface area, diameter) or decreasing (asphericities, lens thickness) very fast in the first two decades of life, followed by a slow but significant increase after age 20 years (for all the parameters except for the posterior surface asphericity and the equatorial plane position, that remained constant). Conclusions: Three-dimensional quantitative OCT allowed us to study the age-dependency of geometric parameters of the full isolated human crystalline lens. We found that most of the lens geometric parameters showed a biphasic behavior, changing rapidly before age 20 years and with a slower linear growth thereafter.

Multi-meridian corneal imaging of air-puff induced deformation for improved detection of biomechanical abnormalities.

Corneal biomechanics play a fundamental role in the genesis and progression of corneal pathologies, such as keratoconus; in corneal remodeling after corneal surgery; and in affecting the measurement accuracy of glaucoma biomarkers, such as the intraocular pressure (IOP). Air-puff induced corneal deformation imaging reveals information highlighting normal and pathological corneal response to a non-contact mechanical excitation. However, current commercial systems are limited to monitoring corneal deformation only on one corneal meridian. Here, we present a novel custom-developed swept-source optical coherence tomography (SSOCT) system, coupled with a collinear air-puff excitation, capable of acquiring dynamic corneal deformation on multiple meridians. Backed by numerical simulations of corneal deformations, we propose two different scan patterns, aided by low coil impedance galvanometric scan mirrors that permit an appropriate compromise between temporal and spatial sampling of the corneal deformation profiles. We customized the air-puff module to provide an unobstructed SSOCT field of view and different peak pressures, air-puff durations, and distances to the eye. We acquired multi-meridian corneal deformation profiles (a) in healthy human eyes in vivo, (b) in porcine eyes ex vivo under varying controlled IOP, and (c) in a keratoconus-mimicking porcine eye ex vivo. We detected deformation asymmetries, as predicted by numerical simulations, otherwise missed on a single meridian that will substantially aid in corneal biomechanics diagnostics and pathology screening.

Fabrication of triple-layered vascular grafts composed of silk fibers, polyacrylamide hydrogel, and polyurethane nanofibers with biomimetic mechanical properties.

Mimicking the mechanical properties of native tissue is an important requirement for tissue engineering scaffolds. Blood vessels are subject to repetitive dilation and contraction and possess a special nonlinear mechanical property due to their triple-layered structure. Fabrication of vascular grafts consisting of bioresorbable materials with biomimetic mechanical properties is an urgent demand, as well as a critical challenge. Inspired by the configuration and function of collagen and elastin in native blood vessels, a new type of triple-layered vascular graft (TLVG) was developed in this study. The TLVGs were composed of braided silk as the inner layer, polyacrylamide (PAM) hydrogel as the middle layer, and electrospun thermoplastic polyurethane (TPU) as the outer layer. The woven-structured silk fibers were able to mimic the properties of the loosely distributed collagen fibers, while the highly elastic PAM hydrogel and TPU nanofibers mimicked the elasticity of elastin in the blood vessel. With this specially designed microstructure and combination of rigid and elastic materials, the TLVGs successfully mimicked the nonlinear mechanical property of native blood vessels. Moreover, TLVGs possess sufficient suture retention strength for surgical implantation. The introduction of a PAM hydrogel layer effectively solved the leaking issue for conventional porous vascular grafts and greatly enhanced the burst pressure. In addition, all materials used have high biocompatibility to human endothelial cells, which indicates that the developed TLVGs have high potential to be used as readily available vascular grafts.

Morphological changes of human crystalline lens in myopia.

Ocular biometric parameters, including full shape crystalline lens, were assessed in myopes and emmetropes using 3-D optical coherence tomography. The anterior chamber depth, the radius of the curvature of the anterior cornea, anterior lens, and posterior lens, lens thickness, lens equatorial diameter, surface area, equatorial position, volume, and power, were evaluated as functions of refractive errors and axial lengths while controlling for age effects. The crystalline lens appears to change with myopia consistent with lens thinning, equatorial, and capsular stretching while keeping constant volume. Axial elongation appears counteracted by a crystalline lens power reduction, while corneal power remains unaffected.

Highly Stretchable and Biocompatible Strain Sensors Based on Mussel-Inspired Super-Adhesive Self-Healing Hydrogels for Human Motion Monitoring.

Integrating multifunctionality such as adhesiveness, stretchability, and self-healing ability on a single hydrogel has been a challenge and is a highly desired development for various applications including electronic skin, wound dressings, and wearable devices. In this study, a novel hydrogel was synthesized by incorporating polydopamine-coated talc (PDA-talc) nanoflakes into a polyacrylamide (PAM) hydrogel inspired by the natural mussel adhesive mechanism. Dopamine molecules were intercalated into talc and oxidized, which enhanced the dispersion of talc and preserved catechol groups in the hydrogel. The resulting dopamine-talc-PAM (DTPAM) hydrogel showed a remarkable stretchability, with over 1000% extension and a recovery rate over 99%. It also displayed strong adhesiveness to various substrates, including human skin, and the adhesion strength surpassed that of commercial double-sided tape and glue sticks, even as the hydrogel dehydrated over time. Moreover, the DTPAM hydrogel could rapidly self-heal and regain its mechanical properties without needing any external stimuli. It showed excellent biocompatibility and improved cell affinity to human fibroblasts compared to the PAM hydrogel. When used as a strain sensor, the DTPAM hydrogel showed high sensitivity, with a gauge factor of 0.693 at 1000% strain, and was capable of monitoring various human motions such as the bending of a finger, knee, or elbow and taking a deep breath. Therefore, this hydrogel displays favorable attributes and is highly suitable for use in human-friendly biological devices.

Quantization of collagen organization in the stroma with a new order coefficient.

Many optical and biomechanical properties of the cornea, specifically the transparency of the stroma and its stiffness, can be traced to the degree of order and direction of the constituent collagen fibers. To measure the degree of order inside the cornea, a new metric, the order coefficient, was introduced to quantify the organization of the collagen fibers from images of the stroma produced with a custom-developed second harmonic generation microscope. The order coefficient method gave a quantitative assessment of the differences in stromal collagen arrangement across the cornea depths and between untreated stroma and cross-linked stroma.