On the recovery of the stress-free configuration of the human cornea

Purpose: The geometries used to conduct numerical simulations of the biomechanics of the human cornea are reconstructed from images of the physiological configuration of the system, which is not in a stress-free state because of the interaction with the surrounding tissues. If the goal of the simulation is a realistic estimation of the mechanical engagement of the system, it is mandatory to obtain a stress-free configuration to which the external actions can be applied. Methods: Starting from a unique physiological image, the search of the stress-free configuration must be based on methods of inverse analysis. Inverse analysis assumes the knowledge of one or more geometrical configurations and, chosen a material model, obtains the optimal values of the material parameters that provide the numerical configurations closest to the physiological images. Given the multiplicity of available material models, the solution is not unique. Results: Three exemplary material models are used in this study to demonstrate that the obtained, non-unique, stress-free configuration is indeed strongly dependent on both material model and on material parameters. Conclusion: The likeliness of recovering the actual stress-free configuration of the human cornea can be improved by using and comparing two or more imaged configurations of the same cornea.

Modeling the eye as a window on the body

Systemic pathologies such as diabetes and hypertension affect different organs and systems in the body. However, the first signs of these pathologies often emerge as alterations in visual and structural functions in the eye. As a consequence, the ophthalmologist is often the first physician to make a diagnosis of systemic diseases. In fact, the eye represents a unique organ where signs of systemic diseases may be assessed with non-invasive techniques.

Test-retest reproducibility of atomic force microscopy measurements of human trabecular meshwork stiffness

Purpose: The purpose of the present study was to quantify test-retest reproducibility of measurements of stiffness of the human trabecular meshwork (HTM) by atomic force microscopy (AFM). Methods: Eleven 40 μm radial limbal cryostat sections from a fresh human donor rim were mounted on charged slides and rehydrated at room temperature. Stiffness at four TM locations (anterior to posterior along Schlemm’s canal) was measured by AFM. At each location, a 6 x 6 grid was sampled. Indentation points were evenly distributed over a 20 μm x 20 μm area, with a rate of one load/unload cycle per second. Measurements were then repeated for calculation of test-retest variability. Results: The test-retest coefficients of variation for the four measurement locations (anterior to posterior) were 24.39, 25.28, 12.74, and 14.26%, respectively, with a notable drop in the two posterior locations compared to the anterior. The test-retest coefficient for the sections was 19.17%. For the entire eye, the test-retest coefficient of variation for the measurement of the TM stiffness was 17.13%. Young’s moduli consistently decreased from anterior to posterior location. Conclusions: Wide regional variation suggests that single value does little to fully describe the complex array of TM stiffness levels within the eye, and future studies of TM stiffness assessed by AFM should include multiple tissue samples from each eye, with documentation of the anterior-posterior location of each measurement.

Effect of iStent Trabecular Micro-Bypass device on outflow system morphology

Purpose: Rigorous clinical testing has established that Schlemm’s canal cross-sectional area (SC-CSA) is reduced in glaucomatous eyes. However, to date, it is unclear whether trabecular bypass procedures impact the morphology of the proximal aqueous outflow tract, or if the introduction of a local region of low outflow resistance adversely affects SC-CSA elsewhere, specifically presenting as SC diminution. This study quantifies changes in the morphology of the distal outflow pathway after iStent Trabecular Micro-Bypass stent (Glaukos Corp, Laguna Hills, CA, USA) implantation in living eyes by anterior segment optical coherence tomography (OCT). Design: This was a prospective observational study. Subjects: This study included six patients (eight eyes) with primary-open angle glaucoma. Methods: Patients underwent iStent placement in the nasal anterior chamber angle quadrant. OCT imaging was obtained of both nasal and temporal eye quadrants before and after surgery. For each SC parameter, an average of ten consecutive, evenly spaced measurements were manually obtained over a 1 mm segment of SC on FIJI ImageJ. Linear mixed effects modeling quantified the effect of the iStent on these parameters. Main outcome measures: Main outcome measures were changes in SC-CSA, inner-to-outer wall distance (IOD), and trabecular meshwork (TM) thickness following iStent placement. Results: Following iStent placement, total SC-CSA increased an average of 1,039.12 μm2 (P = 0.05). Individually, there were no significant changes in SC-CSA in the nasal or temporal quadrants. Total SC-IOD and nasal SC-IOD increased an average of 2.35 μm (P = 0.01) and 2.96 μm (P = 0.04), respectively. There were no significant changes in temporal quadrant SC-IOD. There were no significant changes in TM thickness in either quadrant. Conclusions: Implantation of the iStent Trabecular Micro-Bypass stent significantly increases SC-IOD in the nasal quadrant at the location of implant, with no evidence of SC diminution in the temporal quadrant. It remains unclear how these observations relate to the surgical efficacy of trabecular bypass procedures.

Effects of the hand-grip test on retinal vascular and structural parameters measured by optical coherence tomography in healthy subjects

Purpose: To examine the relationship between the cardiovascular status and variations in optical coherence tomography (OCT)-derived parameters of the peripapillary and macular tissues, and macular vascular flow area measured by optical coherence tomography angiography (OCTA) in healthy subjects. Design: Prospective, open-label, non-randomized clinical study. Methods: Twenty one eyes of 21 healthy subjects were analyzed using a swept-source device, including OCT and OCTA acquisitions. Cardiovascular changes were investigated by performing a practical hand-grip test (HGT). Blood pressure, heart rate, OCT and OCTA structural and vascular changes were measured and analyzed before and after the HGT-induced exercise. Results: The mean patient age was 34.0 (± 15.2) years. While both diastolic and systolic blood pressures increased significantly aft er exercise (p < 0.001 and p = 0.003, respectively), the heart rate did not show a significant increment (p = 0.182). OCT structural parameters of the optic nerve did not change significantly. Instead, a significant redistribution of choroidal thickness (CT) was observed in the macular region, with a significant reduction (-6.5%, p = 0.001) in the outer-nasal macular sector after exercise. OCTA acquisitions did not show changes in the vascular density of both the superficial retinal layer and deep retinal layer. Conclusions: We demonstrated that HGT-induced exercise can moderately elevate blood pressure without detectable effects on OCTA-derived parameters in healthy young subjects. Moreover, it produced a significant redistribution of CT. Further studies are needed to better explain the possible role of HGT in the characterization of the pathophysiology of ocular diseases associated with abnormalities of the vascular function such as glaucoma, age-related macular degeneration, and diabetic retinopathy.

Increasing protected data accessibility for age-related cataract research using a semi-automated honest broker

Ophthalmology researchers are becoming increasingly reliant on protected data sets to find new trends and enhance patient care. However, there is an inherent lack of trust in the current healthcare community ecosystem between the data custodians (i.e., health care organizations and hospitals) and data consumers (i.e., researchers and clinicians). This typically results in a manual governance approach that causes slow data accessibility for researchers due to concerns such as ensuring auditability for any authorization of data consumers, and assurance to ensure compliance with health data security standards. In this paper, we address this issue of long-drawn data accessibility by proposing a semi-automated “honest broker” framework that can be implemented in an online health application. The framework establishes trust between the data consumers and the custodians by: 1. improving the eiciency in compliance checking for data consumer requests using a risk assessment technique; 2. incorporating auditability for consumers to access protected data by including a custodian-in-the-loop only when essential; and 3. increasing the speed of large-volume data actions (such as view, copy, modify, and delete) using a popular common data model. Via an ophthalmology case study involving an age-related cataract research use case in a community cloud testbed, we demonstrate how our solution approach can be implemented in practice to improve timely data access and secure computation of protected data for ultimately achieving data-driven eye health insights.

Image processing-based model for tortuosity measurement of retinal blood vessels

Purpose: The study of retinal blood vessel morphology is of great importance in retinal image analysis. The retinal blood vessels have a number of distinct features such as width, diameter, tortuosity, etc. In this paper, a method is proposed to measure the tortuosity of retinal blood vessels obtained from retinal fundus images. Tortuosity is a situation in which blood vessels become tortuous, that is, curved or non-smooth. It is one of the earliest changes that occur in blood vessels in some retinal diseases. Hence, its detection at an early stage can prevent the progression of retinal diseases such as diabetic retinopathy, hypertensive retinopathy, retinopathy of prematurity, etc. The present study focuses on the measurement of retinal blood vessel tortuosity for the analysis of hypertensive retinopathy. Hypertensive retinopathy is a condition in which the retinal vessels undergo changes and become tortuous due to long term high blood pressure. Early recognition of hypertensive retinopathy signs remains an important step in determining the target-organ damage and risk assessment of hypertensive patients. Hence, this paper attempts to estimate tortuosity using image-processing techniques that have been tested on artery and vein segments of retinal images. Design: Image processing-based model designed to measure blood vessel tortuosity. Methods: In this paper, a novel image processing-based model is proposed for tortuosity measurement. This parameter will be helpful for analyzing hypertensive retinopathy. To test the eff ectiveness of the system in determining tortuosity, the method is first applied on a set of synthetically generated blood vessels. Then, the method is repeated on blood vessel (both artery and vein) segments extracted from retinal images collected from publicly available databases and on images collected from a local eye hospital. The blood vessel segment images that are used in the method are binary images where blood vessels are represented by white pixels (foreground), while black pixels represent the background. Vessels are then classified into normal, moderately tortuous, and severely tortuous by following the analysis performed on the images in the Retinal Vessel Tortuosity Data Set (RET-TORT) obtained from BioIm Lab, Laboratory of Biomedical Imaging (Padova, Italy). This database consists of 30 artery segments and 30 vein segments, which were manually ordered on the basis of increasing tortuosity by Dr. S. Piermarocchi, a retinal specialist belonging to the Department of Ophthalmology of the University of Padova (Italy). The artery and vein segments with the fewest number of turns are given a low tortuosity ranking, while those with the greatest number of turns are given a high tortuosity ranking by the expert. Based on this concept, our proposed method defines retinal image segments as normal when they present the fewest number of twists/turns, moderately tortuous when they present more twists/turns than normal but fewer than severely tortuous vessels, and severely tortuous when they present a greater number of twists/turns than moderately tortuous vessels. On implementing our image processing-based method on binary blood vessel segment images that are represented by white pixels, it is found that the vessel pixel (white pixels) count increases with increasing vessel tortuosity. That is, for normal blood vessels, the white pixel count is less compared to moderately tortuous and severely tortuous vessels. It should be noted that the images obtained from the different databases and from the local hospital for this experiment are not hypertensive retinopathy images. Instead, they are mostly normal eye images and very few of them show tortuous blood vessels. Results: The results of the synthetically generated vessel segment images from the baseline for the evaluation of retinal blood vessel tortuosity. The proposed method is then applied on the retinal vessel segments that are obtained from the DRIVE and HRF databases, respectively. Finally, to evaluate the capability of the proposed method in determining the tortuosity level of the blood vessels, the method is tested with a standard tortuous database, namely, the RET-TORT database. The results are then compared with the tortuosity level mentioned in the database. It was found that our method is able to classify blood vessel images as normal, moderately tortuous, and severely tortuous, with results closely matching the clinical ordering provided by the expert in the RET-TORT database. Subjective evaluation was also performed by research scholars and postgraduate students to cross-validate the results. Conclusion: The close correlation between the tortuosity evaluation using the proposed method and the clinical ordering of retinal vessels as provided by the retinal specialist in the RET-TORT database shows that, although simple, this method can evaluate the tortuosity of vessel segments effectively.

Predicting infusion pressure during pars plana vitrectomy: a physically based model

Purpose: Intraocular pressure (IOP) during pars plana vitrectomy (PPV) decreases as aspiration generates flow, a phenomenon known as head loss. Since direct measurement of the IOP during surgery is impractical, currently, available compensating systems infer IOP by measuring infusion flow rate and estimating corresponding pressure drop. The purpose of the present paper is to propose and validate a physically based algorithm of the infusion pressure drop as a function of flow. Methods: Complete infusion lines (20G, 23G, 25G and 27G) were set up and primed. The infusion bottle was set at incremental heights and flow rate measured 10 times and recorded as mean Å} SD. Overall head loss (OHL) was defined, according to hydraulics laws, as the sum of frictional head loss (FHL; i.e., pressure drop due to friction along tubing) and exit head loss (EHL). The latter is equal to the kinetic energy of the exiting flow through the trocar (FKE = V2/2g). A 2nd degree polynomial equation (i.e., ΔP = aQ2 + bQ, where ΔP is the pressure drop, or OHL, and Q is the volumetric flow) was derived for each gauge and compared to experimental data 2nd order polynomial best-fit curve. Results: Ninety-seven percent of the pressure values for all gauges predicted using the derived equation fell within 2 SD of the mean difference yielding a Bland-Altman statistical significance when compared to 91% of best fit curve. Conclusion: The derived equations accurately predicted the head loss for each given infusion line gauge and can help infer IOP during PPV.

A model for tear film dynamics during a realistic blink

Each time one blinks, a stable tear film (TF) must reestablish itself on the ocular surface to ensure the function and health of the eye. Although the formation of the TF has been extensively studied both experimentally and theoretically, the influence of the lid dynamics on the TF formation is still not fully understood. Experimental instrumentation does not yet have the capability to estimate the TF thickness in vivo over the entire front of the eye, especially near the lids during a blink, where the eyelashes obstruct the view of the ocular surface. Additionally, a realistic blinking eyeshaped domain presents challenges in approximating themotion of the TF in theoretical studies. In thiswork,we overcome these theoretical challenges by implementing a moving overset grid method to study the influence of the lid motion on the formation of TF.

Peripapillary non-flow area measurement for the measurement of progressive localized glaucomatous perfusion damage

Purpose: To investigate the applicability of peripapillary non-flow area (PNFA) measurement in the radial peripapillary capillaries (RPC) layer for the measurement of progressive localized glaucomatous perfusion damage. Methods: A research soft ware version of the Angiovue /RTVue-XR OCT (Optovue, Fremont, CA, USA) was used to measure localized PNFA progression by clicking on a predefined peripapillary non-perfusion area on prospectively acquired images. Capillary vessel density (VD) in the corresponding peripapillary sector was also measured. High-quality peripapillary Angiovue OCT VD images of an open-angle glaucoma population prospectively imaged for 2 to 2.5 years (5 or 6 visits at 6-month intervals) were investigated. Eyes with both localized PNFA at baseline and statistically significant peripapillary VD progression in the hemifield of the PNFA were selected for the analysis. Results: Four eyes of four patients were eligible. In three eyes, the Octopus visual field cluster mean defect in the cluster spatially corresponding to the area of the PNFA progressed significantly (P < 0.01) at a rate of 1.5 to 3.4 dB/year. In two eyes, neither PNFA nor sector VD showed significant correlation with the follow-up time. In one eye, significant negative correlation for sector VD (r = -0.841, P = 0.036) and almost significant positive correlation for PNFA (r = 0.803, P = 0.055) was found, while in another eye significant positive correlation for PFNA (r = 0.875, P = 0.022) but no correlation for sector VD was found. Conclusion: Our results suggest that PNFA measurement in the RPC layer is a potentially useful tool for the measurement of progression of localized glaucomatous capillary perfusion damage in open-angle glaucoma eyes with localized peripapillary non-perfusion.