The future of canine glaucoma therapy.

Canine glaucoma is a group of disorders that are generally associated with increased intraocular pressure (IOP) resulting in a characteristic optic neuropathy. Glaucoma is a leading cause of irreversible vision loss in dogs and may be either primary or secondary. Despite the growing spectrum of medical and surgical therapies, there is no cure, and many affected dogs go blind. Often eyes are enucleated because of painfully high, uncontrollable IOP. While progressive vision loss due to primary glaucoma is considered preventable in some humans, this is mostly not true for dogs. There is an urgent need for more effective, affordable treatment options. Because newly developed glaucoma medications are emerging at a very slow rate and may not be effective in dogs, work toward improving surgical options may be the most rewarding approach in the near term. This Viewpoint Article summarizes the discussions and recommended research strategies of both a Think Tank and a Consortium focused on the development of more effective therapies for canine glaucoma; both were organized and funded by the American College of Veterinary Ophthalmologists Vision for Animals Foundation (ACVO-VAF). The recommendations consist of (a) better understanding of disease mechanisms, (b) early glaucoma diagnosis and disease staging, (c) optimization of IOP-lowering medical treatment, (d) new surgical therapies to control IOP, and (e) novel treatment strategies, such as gene and stem cell therapies, neuroprotection, and neuroregeneration. In order to address these needs, increases in research funding specifically focused on canine glaucoma are necessary.

Glaucoma Structural and Functional Progression in American and Korean Cohorts.

PURPOSE: To compare the rate of glaucoma structural and functional progression in American and Korean cohorts. DESIGN: Retrospective longitudinal study. PARTICIPANTS: Three hundred thirteen eyes from 189 glaucoma and glaucoma suspects, followed up for an average of 38 months. METHODS: All subjects were examined semiannually with visual field (VF) testing and spectral-domain optical coherence tomography. All subjects had 5 or more reliable visits. MAIN OUTCOME MEASUREMENTS: The rates of change of retinal nerve fiber layer (RNFL) thickness, cup-to-disc (C/D) ratios, and VF mean deviation (MD) were compared between the cohorts. Variables affecting the rate of change for each parameter were determined, including ethnicity, refraction, baseline age and disease severity, disease subtype (high- vs. normal-tension glaucoma), clinical diagnosis (glaucoma vs. glaucoma suspect), and the interactions between variables. RESULTS: The Korean cohort predominantly demonstrated normal-tension glaucoma, whereas the American cohort predominantly demonstrated high-tension glaucoma. Cohorts had similar VF parameters at baseline, but the Korean eyes had significantly thicker mean RNFL and larger cups. Korean glaucoma eyes showed a faster thinning of mean RNFL (mean, -0.71 µm/year vs. -0.24 µm/year; P < 0.01). There were no detectable differences in the rate of change between the glaucoma cohorts for C/D ratios and VF MD and for all parameters in glaucoma suspect eyes. Different combinations of the tested variables significantly impacted the rate of change. CONCLUSIONS: Ethnicity, baseline disease severity, disease subtype, and clinical diagnosis should be considered when comparing glaucoma progression studies.

Visualization of the conventional outflow pathway in the living human eye.

PURPOSE: We sought to visualize the aqueous outflow system in 3 dimensions (3D) in living human eyes, and to investigate the use of commercially available spectral-domain optical coherence tomographic (SD-OCT) systems for this purpose. DESIGN: Prospective, observational study. PARTICIPANTS: One randomly determined eye in each of 6 normal healthy subjects was included. TESTING: We performed 3D SD-OCT imaging of the aqueous humor outflow structures with 2 devices: The Cirrus HD-OCT and the Bioptigen SDOIS. MAIN OUTCOME MEASURES: We created 3D virtual castings of Schlemm's canal (SC) and more distal outflow structures from scan data from each device. RESULTS: Virtual casting of the SC provided visualization of more aqueous vessels branching from SC than could be located by interrogating the 2-dimensional (2D) image stack. Similarly, virtual casting of distal structures allowed visualization of large and small aqueous outflow channel networks that could not be appreciated with conventional 2D visualization. CONCLUSIONS: The outflow pathways from SC to the superficial vasculature can be identified and tracked in living human eyes using commercially available SD-OCT.

3D visualization of aqueous humor outflow structures in-situ in humans.

Aqueous humor (AH) exiting the eye via the trabecular meshwork and Schlemm's canal (SC) passes through the deep and intrascleral venous plexus (ISVP) or directly through aqueous veins. The purpose of this study was to visualize the human AH outflow system 360° in three dimensions (3D) during active AH outflow in a virtual casting. The conventional AH outflow pathways of 7 donor eyes were imaged with a modified Bioptigen spectral-domain optical coherence tomography system (Bioptigen Inc, USA; SuperLum LTD, Ireland) at a perfusion pressure of 20 mmHg (N = 3), and 10 mmHg (N = 4). In all eyes, 36 scans (3 equally distributed in each clock hour), each covering a 2 × 3 × 2 mm volume (512 frames, each 512 × 1024 pixels), were obtained. All image data were black/white inverted, and the background subtracted (ImageJ 1.40 g, http://rsb.info.nih.gov/ij/). Contrast was adjusted to isolate the ISVP. SC, collector channels, the deep and ISVP, and episcleral veins were observed throughout the limbus. Aqueous veins could be observed extending into the episcleral veins. Individual scan ISVP castings were rendered and assembled in 3D space in Amira 4.1 (Visage Imaging Inc. USA). A 360-degree casting of the ISVP was obtained in all perfused eyes. The ISVP tended to be dense and overlapping in the superior and inferior quadrants, and thinner in the lateral quadrants. The human AH outflow pathway can be imaged using SD-OCT. The more superficial structures of the AH outflow pathway present with sufficient contrast as to be optically isolated and cast in-situ 360° in cadaver eye perfusion models. This approach may be useful as a model in future studies of human AH outflow.

Development, Validation, and Innovation in Ophthalmic Laser-Based Imaging: Report From a US Food and Drug Administration-Cosponsored Forum.

In April 2019, the US Food and Drug Administration, in conjunction with 11 professional ophthalmic, vision science, and optometric societies, convened a forum on laser-based imaging. The forum brought together the Food and Drug Administration, clinicians, researchers, industry members, and other stakeholders to stimulate innovation and ensure that patients in the US are the first in the world to have access to high-quality, safe, and effective medical devices. This conference focused on the technology, clinical applications, regulatory issues, and reimbursement issues surrounding innovative ocular imaging modalities. Furthermore, the emerging role of artificial intelligence in ophthalmic imaging was reviewed. This article summarizes the presentations, discussion, and future directions.

Automated volumetric evaluation of stereoscopic disc photography.

PURPOSE: To develop a fully automated algorithm (AP) to perform a volumetric measure of the optic disc using conventional stereoscopic optic nerve head (ONH) photographs, and to compare algorithm-produced parameters with manual photogrammetry (MP), scanning laser ophthalmoscope (SLO) and optical coherence tomography (OCT) measurements. METHODS: One hundred twenty-two stereoscopic optic disc photographs (61 subjects) were analyzed. Disc area, rim area, cup area, cup/disc area ratio, vertical cup/disc ratio, rim volume and cup volume were automatically computed by the algorithm. Latent variable measurement error models were used to assess measurement reproducibility for the four techniques. RESULTS: AP had better reproducibility for disc area and cup volume and worse reproducibility for cup/disc area ratio and vertical cup/disc ratio, when the measurements were compared to the MP, SLO and OCT methods. CONCLUSION: AP provides a useful technique for an objective quantitative assessment of 3D ONH structures.

In vitro simulation of the first technique for non-invasive measurement of volumetric ophthalmic artery blood flow in humans.

BACKGROUND AND OBJECTIVE: To evaluate the accuracy, reproducibility, and variability of volumetric flow measurements taken by color Doppler imaging ultrasound, using an in vitro "phantom" model to simulate the ophthalmic artery. MATERIALS AND METHODS: An agar flow phantom with two wall-less lumens was constructed to simulate the ophthalmic artery. Velocity and volumetric flow measurements were taken for various flow rates and ultrasound probe positions. The measurements were analyzed for accuracy, reproducibility, and variability. RESULTS: Velocity measurements were more accurate than flow measurements (8 of 24 vs 3 of 24 accurate trials). The average coefficient of variation for volumetric blood flow was 11.4% (n = 120). Volumetric flow significantly correlated with velocity (R(2) = 0.408, n = 600, P < .001). The highest correlation was achieved using the large lumen with the probe held at 75 degrees , offset to the flow (R(2) = 0.862, n = 75). CONCLUSION: Based on an in vitro model, non-invasive color Doppler imaging recordings of volumetric flow measurements in the ophthalmic artery significantly correlated with velocity and higher correlations were found using the larger lumens, although the data showed a lack of high accuracy in measurements of flow and velocity.

Effects of age on optical coherence tomography measurements of healthy retinal nerve fiber layer, macula, and optic nerve head.

PURPOSE: To determine the effects of age on global and sectoral peripapillary retinal nerve fiber layer (RNFL), macular thicknesses, and optic nerve head (ONH) parameters in healthy subjects using optical coherence tomography (OCT). DESIGN: Retrospective, cross-sectional observational study. PARTICIPANTS: A total of 226 eyes from 124 healthy subjects were included. METHODS: Healthy subjects were scanned using the Fast RNFL, Fast Macula, and Fast ONH scan patterns on a Stratus OCT (Carl Zeiss Meditec, Dublin, CA). All global and sectoral RNFL and macular parameters and global ONH parameters were modeled in terms of age using linear mixed effects models. Normalized slopes were also calculated by dividing the slopes by the mean value of the OCT parameter for interparameter comparison. MAIN OUTCOME MEASURES: Slope of each OCT parameter across age. RESULTS: All global and sectoral RNFL thickness parameters statistically significantly decreased with increasing age, except for the temporal quadrant and clock hours 8 to 10, which were not statistically different from a slope of zero. Highest absolute slopes were in the inferior and superior quadrant RNFL and clock hour 1 (superior nasal). Normalized slopes showed a similar rate in all sectors except for the temporal clock hours (8-10). All macular thickness parameters statistically significantly decreased with increasing age, except for the central fovea sector, which had a slight positive slope that was not statistically significant. The nasal outer sector had the greatest absolute slope. Normalized macular slope in the outer ring was similar to the normalized slopes in the RNFL. Normalized inner ring had shallower slope than the outer ring with a similar rate in all quadrants. Disc area remained nearly constant across the ages, but cup area increased and rim area decreased with age, both of which were statistically significant. CONCLUSIONS: Global and regional changes caused by the effects of age on RNFL, macula, and ONH OCT measurements should be considered when assessing eyes over time. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Visualization of 3-D high speed ultrahigh resolution optical coherence tomographic data identifies structures visible in 2D frames.

Optical coherence tomography has allowed unprecedented visualization of ocular structures, but the identity of some visible objects within slices remains unknown. This study reconstructs a number of those objects in 3D space, allowing their identification by observation of their 3D morphology. In the case mottling deep within image slices through the optic disc, C-mode imaging provided visualization of the appearance and distribution of laminar pores. In the case of white spots and streaks sometimes observed in image slices through the cornea, C-mode imaging contoured to the path of those white spots allowed their visual identification as nerves extending radially into the cornea from the limbus. White spots observed in ultra-high resolution retinal image slices were identified as blood within retinal capillaries. C-mode contour-corrected imaging of three dimensional structures provided the identification of previously unidentified structures visible in cross-sectional image slices.

Comparison of StratusOCT and Cirrus HD-OCT imaging in macular diseases.

BACKGROUND AND OBJECTIVE: The Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) device is a spectral-domain optical coherence tomography system that allows faster data acquisition than the previous generation StratusOCT (Carl Zeiss Meditec, Dublin, CA), which is a time-domain device. The authors compared images from both units to determine the clinical usefulness of spectral-domain optical coherence tomography technology in patients with macular diseases. PATIENTS AND METHODS: Six consecutive patients were imaged with both the Cirrus HD-OCT and the StratusOCT devices and the images were compared. RESULTS: Cirrus HD-OCT images were typically more useful than StratusOCT images for assessing fine architectural details in macular pathology. The Cirrus HD-OCT software also facilitated a better understanding of three-dimensional data volumes. CONCLUSIONS: Commercially available spectral-domain optical coherence tomography is a clinically useful tool for visualizing and understanding macular diseases and offers benefits not inherent in previous generation machines.

Automated assessment of the optic nerve head on stereo disc photographs.

PURPOSE: To develop automated software for optic nerve head (ONH) quantitative assessment from stereoscopic disc photographs and to evaluate its performance in comparison with human expert assessment. METHODS: A fully automated system, including three-dimensional ONH modeling, disc margin detection, cup margin detection, and calculation of stereometric ONH parameters, was developed and tested. One eye each from 54 subjects (23 healthy, 17 suspected glaucoma, and 14 glaucoma) was enrolled. The majority opinion of three experts defined disc and cup margins on the disc photographs was used for comparison. Seven ONH parameters, disc area, rim area, rim volume, cup area, cup volume, cup-to-disc (C/D) area ratio, and vertical C/D ratio, were computed based on both machine- and expert-defined margins and compared between the methods. RESULTS: All automated ONH measurements showed good correlation with the expert defined margins (Pearson r = 0.90, disc area; 0.56, rim area; 0.78, rim volume; 0.88, cup area; 0.93, cup volume; 0.69, C/D area ratio; and 0.67, vertical C/D ratio; all P or= 0.21). The mean or median of automatically defined disc and cup areas was significantly higher than the subjective assessment (disc area P = 0.0001, t-test; cup area P = 0.036, Wilcoxon signed ranks test), although they had high correlation coefficients. The software failed to detect the disc margin for all the disc photographs with peripapillary atrophy. CONCLUSIONS: The automated ONH analysis method provides an objective and quantitative ONH evaluation using widely available stereo disc photographs.

Optical coherence tomography scan circle location and mean retinal nerve fiber layer measurement variability.

PURPOSE: To investigate the effect on optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness measurements of varying the standard 3.4-mm-diameter circle location. METHODS: The optic nerve head (ONH) region of 17 eyes of 17 healthy subjects was imaged with high-speed, ultrahigh-resolution OCT (hsUHR-OCT; 501 x 180 axial scans covering a 6 x 6-mm area; scan time, 3.84 seconds) for a comprehensive sampling. This method allows for systematic simulation of the variable circle placement effect. RNFL thickness was measured on this three-dimensional dataset by using a custom-designed software program. RNFL thickness was resampled along a 3.4-mm-diameter circle centered on the ONH, then along 3.4-mm circles shifted horizontally (x-shift), vertically (y-shift) and diagonally up to +/-500 microm (at 100-microm intervals). Linear mixed-effects models were used to determine RNFL thickness as a function of the scan circle shift. A model for the distance between the two thickest measurements along the RNFL thickness circular profile (peak distance) was also calculated. RESULTS: RNFL thickness tended to decrease with both positive and negative x- and y-shifts. The range of shifts that caused a decrease greater than the variability inherent to the commercial device was greater in both nasal and temporal quadrants than in the superior and inferior ones. The model for peak distance demonstrated that as the scan moves nasally, the RNFL peak distance increases, and as the circle moves temporally, the distance decreases. Vertical shifts had a minimal effect on peak distance. CONCLUSIONS: The location of the OCT scan circle affects RNFL thickness measurements. Accurate registration of OCT scans is essential for measurement reproducibility and longitudinal examination (ClinicalTrials.gov number, NCT00286637).

Repeated, noninvasive, high resolution spectral domain optical coherence tomography imaging of zebrafish embryos.

PURPOSE: To demonstrate a new imaging method for high resolution spectral domain optical coherence tomography (SD-OCT) for small animal developmental imaging. METHODS: Wildtype zebrafish that were 24, 48, 72, and 120 h post fertilization (hpf) and nok gene mutant (48 hpf) embryos were imaged in vivo. Three additional embryos were imaged twice, once at 72 hpf and again at 120 hpf. Images of the developing eye, brain, heart, whole body, proximal yolk sac, distal yolk sac, and tail were acquired. Three-dimensional OCT data sets (501 x 180 axial scans) were obtained as well as oversampled frames (8,100 axial scans) and repeated line scans (180 repeated frames). Scan volumes ranged from 750 x 750 microm to 3 x 3 mm, each 1.8 mm thick. Three-dimensional data sets allowed construction of C-mode slabs of the embryo. RESULTS: SD-OCT provided ultra-high resolution visualization of the eye, brain, heart, ear, and spine of the developing embryo as early as 24 hpf, and allowed development to be documented in each of these organ systems in consecutive sessions. Repeated line scanning with averaging optimized the visualization of static and dynamic structures contained in SD-OCT images. Structural defects caused by a mutation in the nok gene were readily observed as impeded ocular development, and enlarged pericardial cavities. CONCLUSIONS: SD-OCT allowed noninvasive, in vivo, ultra-high resolution, high-speed imaging of zebrafish embryos in their native state. The ability to measure structural and functional features repeatedly on the same specimen, without the need to sacrifice, promises to be a powerful tool in small animal developmental imaging.

Comparison of parameters from Heidelberg Retina Tomographs 2 and 3.

PURPOSE: To compare stereometric parameters and classification results from the Heidelberg Retina Tomograph version 2 (HRT2); HRT3; and HRT3 Glaucoma Probability Score (GPS), an automated method of obtaining optic nerve head analysis without the need for manual definition of disc margin. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: Five hundred four eyes from 281 consecutive subjects (glaucoma, glaucoma suspect, and healthy) evaluated in a glaucoma clinic. METHODS: All participants had HRT2 scanning of the optic nerve head. Inclusion criteria were scans with good centration and focus, even illumination, an overall quality score by HRT3 of acceptable or better, and standard deviation < 50 mum. A Bland-Altman analysis was used for the comparison of HRT2 and HRT3. From these results, calibration equations were determined to permit conversion of the measurements between devices. The agreement between HRT2 and HRT3 Moorfields regression analysis (MRA) and HRT3 GPS classification methods was measured using kappa statistics. MAIN OUTCOME MEASURES: Heidelberg Retina Tomograph version 2 and HRT3 stereometric parameters, MRA, and global GPS. RESULTS: There was a statistically significant difference between HRT2 and HRT3 global disc area, rim area, cup area, rim volume, cup volume, height variation contour, and retinal nerve fiber layer cross-sectional area stereometric parameters. All of those parameters were smaller using HRT3, due to a manufacturer-reported horizontal scaling error of 4% in HRT2 that was corrected in HRT3. kappas for agreement were 0.60 between classifications (within normal limits, borderline, and outside normal limits) of MRA by HRT2 and HRT3 and 0.47 between HRT3 MRA and GPS. CONCLUSIONS: The HRT3 generally provided smaller stereometric disc measurements than HRT2. There was no clear conversion between HRT3 and GPS parameters, as the 2 methods for measuring the stereometric parameters differ.

Improved visualization of glaucomatous retinal damage using high-speed ultrahigh-resolution optical coherence tomography.

PURPOSE: To test if improving optical coherence tomography (OCT) resolution and scanning speed improves the visualization of glaucomatous structural changes as compared with conventional OCT. DESIGN: Prospective observational case series. PARTICIPANTS: Healthy and glaucomatous subjects in various stages of disease. METHODS: Subjects were scanned at a single visit with commercially available OCT (StratusOCT) and high-speed ultrahigh-resolution (hsUHR) OCT. The prototype hsUHR OCT had an axial resolution of 3.4 mum (3 times higher than StratusOCT), with an A-scan rate of 24 000 hertz (60 times faster than StratusOCT). The fast scanning rate allowed the acquisition of novel scanning patterns such as raster scanning, which provided dense coverage of the retina and optic nerve head. MAIN OUTCOME MEASURES: Discrimination of retinal tissue layers and detailed visualization of retinal structures. RESULTS: High-speed UHR OCT provided a marked improvement in tissue visualization as compared with StratusOCT. This allowed the identification of numerous retinal layers, including the ganglion cell layer, which is specifically prone to glaucomatous damage. Fast scanning and the enhanced A-scan registration properties of hsUHR OCT provided maps of the macula and optic nerve head with unprecedented detail, including en face OCT fundus images and retinal nerve fiber layer thickness maps. CONCLUSION: High-speed UHR OCT improves visualization of the tissues relevant to the detection and management of glaucoma.

Comparison of optic disc margin identified by color disc photography and high-speed ultrahigh-resolution optical coherence tomography.

OBJECTIVE: To determine the correspondence between optic disc margins evaluated using disc photography (DP) and optical coherence tomography (OCT). METHODS: From May 1, 2005, through November 10, 2005, 17 healthy volunteers (17 eyes) had raster scans (180 frames, 501 samplings per frame) centered on the optic disc taken with stereo-optic DP and high-speed ultrahigh-resolution OCT (hsUHR-OCT). Two image outputs were derived from the hsUHR-OCT data set: an en face hsUHR-OCT fundus image and a set of 180 frames of cross-sectional images. Three ophthalmologists independently and in a masked, randomized fashion marked the disc margin on the DP, hsUHR-OCT fundus, and cross-sectional images using custom software. Disc size (area and horizontal and vertical diameters) and location of the geometric disc center were compared among the 3 types of images. RESULTS: The hsUHR-OCT fundus image definition showed a significantly smaller disc size than the DP definition (P <.001, mixed-effects analysis). The hsUHR-OCT cross-sectional image definition showed a significantly larger disc size than the DP definition (P <.001). The geometric disc center location was similar among the 3 types of images except for the y-coordinate, which was significantly smaller in the hsUHR-OCT fundus images than in the DP images. CONCLUSION: The optic disc margin as defined by hsUHR-OCT was significantly different than the margin defined by DP.

Ultrahigh-resolution spectral domain optical coherence tomography imaging of the lamina cribrosa.

Study of the structure of the lamina cribrosa is critical in glaucoma research. The purpose of this study is to determine the optimal spectral domain optical coherence tomography imaging protocol for the digital isolation and display of the lamina cribrosa. Three-dimensional datasets centered on the lamina cribrosa were obtained with 200 X 200 to 512 X 512 A-scan densities. The effect of scan density and c-mode slab thickness was subjectively compared. Increasing slab thickness reduced the sharpness of visible prelamina and lamina cribrosa structures. In retrolamina structures, thin slabs provided good visualization, but increased slab size increased the visibility of deeper structures. Scan times as short as 2.3 seconds (256 X 256 A-scans) degraded visualization of the shape of the optic nerve head. The optical scan protocol for lamina cribrosa imaging appears to be a 3 x 3 mm 200 X 200 A-scan volume with the lamina cribrosa positioned near direct current.

Dye dependent differences in arteriovenous passage times: a comparison of indocyanine green and fluorescein sodium dye analysis.

BACKGROUND AND OBJECTIVE: To evaluate the difference in arteriovenous passage time calculated from retinal angiograms using indocyanine green and fluorescein sodium dye in healthy individuals. PATIENTS AND METHODS: Examinations of eight healthy individuals (mean age +/- standard deviation: 27.3 +/- 4.2 years) who had four consecutive ophthalmic visits that were 2 weeks apart were analyzed. Indocyanine green and fluorescein angiography were performed sequentially (with the indocyanine green angiography occurring first) using scanning laser ophthalmoscopy. Arteriovenous passage times were calculated offline using digital angiogram video analysis. RESULTS: Mean arteriovenous passage times calculated from indocyanine green angiography (1.417 +/- 0.136 seconds) recordings were significantly shorter than fluorescein sodium times (2.539 +/- 0.421 seconds) (P < .0001) and intra-group variability was similar. There were no significant correlations between indocyanine green and fluorescein sodium arteriovenous passage times. CONCLUSION: Arteriovenous passage times calculated using indocyanine green and fluorescein angiography are not interchangeable.

Measuring and interpreting ocular blood flow and metabolism in glaucoma.

There is a growing body of evidence suggesting that vascular dysfunction is related to several prominent ophthalmic diseases, including glaucoma. The vast majority of studies providing data on ocular circulation and disease pathophysiology use a relatively small number of complicated ocular blood flow imaging techniques. Although these imaging technologies are not commonly used in clinical settings, understanding the medical literature characterizing ocular blood flow requires familiarity with their methodology and function. This review highlights the imaging technologies most commonly used to investigate ocular blood flow, including color Doppler imaging, confocal scanning laser ophthalmoscopic angiography with fluorescein and indocyanine green dye, Canon laser blood flowmetry, scanning laser Doppler flowmetry, and retinal photographic oximetry. Each imaging technique's ability to define vascular function and reveal pathology is discussed as are limitations inherent to each technology. The ultimate goal of this review is to provide the physician with a clinically relevant foundation for differentiating the various ocular blood flow outcome measures often presented in the literature and determine how they are related to ocular health and disease.

Perilimbal sclera mechanical properties: Impact on intraocular pressure in porcine eyes.

There is extensive knowledge on the relationship of posterior scleral biomechanics and intraocular pressure (IOP) load on glaucomatous optic neuropathy; however, the role for biomechanical influence of the perilimbal scleral tissue on the aqueous humor drainage pathway, including the distal venous outflow system, and IOP regulation is not fully understood. The purpose of this work is to study the outflow characteristics of perfused porcine eyes relative to the biomechanical properties of the perilimbal sclera, the posterior sclera and the cornea. Enucleated porcine eyes from eleven different animals were perfused with surrogate aqueous at two fixed flow rates while monitoring their IOP. After perfusion, mechanical stress-strain and relaxation tests were conducted on specimens of perilimbal sclera, posterior sclera, and cornea from the same perfused eyes. Statistical analysis of the data demonstrated a strong correlation between increased tangent modulus of the perilimbal sclera tissues and increased perfusion IOP (R2 = 0.74, p = 0.0006 at lower flow rate and R2 = 0.71, p = 0.0011 at higher flow rate). In contrast, there were no significant correlations between IOP and the tangent modulus of the other tissues (Posterior sclera: R2 = 0.17 at lower flow rate and R2 = 0.30 at higher flow rate; cornea: R2 = 0.02 at lower flow rate and R2<0.01 at higher flow rate) nor the viscoelastic properties of any tissue (R2 ≤ 0.08 in all cases). Additionally, the correlation occurred for IOP and not net outflow facility (R2 ≤ 0.12 in all cases). These results provide new evidence that IOP in perfused porcine eyes is strongly influenced by the tangent modulus, sometimes called the tissue stiffness, of the most anterior portion of the sclera, i.e. the limbus.