Alex S. Huang

Clinical Results of Ab Interno Trabeculotomy Using the Trabectome in Patients with Pigmentary Glaucoma compared to Primary Open Angle Glaucoma

To evaluate outcomes of Trabectome on pigmentary glaucoma (PG) patients compared to matched controls with primary open angle glaucoma (POAG).

Aqueous Angiography: Real-Time and Physiologic Aqueous Humor Outflow Imaging.

Purpose Trabecular meshwork (TM) bypass surgeries attempt to enhance aqueous humor outflow (AHO) to lower intraocular pressure (IOP). While TM bypass results are promising, inconsistent success is seen. One hypothesis for this variability rests upon segmental (non-360 degrees uniform) AHO. We describe aqueous angiography as a real-time and physiologic AHO imaging technique in model eyes as a way to simulate live AHO imaging. Methods Pig (n = 46) and human (n = 6) enucleated eyes were obtained, orientated based upon inferior oblique insertion, and pre-perfused with balanced salt solution via a Lewicky AC maintainer through a 1mm side-port. Fluorescein (2.5%) was introduced intracamerally at 10 or 30 mm Hg. With an angiographer, infrared and fluorescent (486 nm) images were acquired. Image processing allowed for collection of pixel information based on intensity or location for statistical analyses. Concurrent OCT was performed, and fixable fluorescent dextrans were introduced into the eye for histological analysis of angiographically active areas. Results Aqueous angiography yielded high quality images with segmental patterns (p<0.0001; Kruskal-Wallis test). No single quadrant was consistently identified as the primary quadrant of angiographic signal (p = 0.06–0.86; Kruskal-Wallis test). Regions of high proximal signal did not necessarily correlate with regions of high distal signal. Angiographically positive but not negative areas demonstrated intrascleral lumens on OCT images. Aqueous angiography with fluorescent dextrans led to their trapping in AHO pathways. Conclusions Aqueous angiography is a real-time and physiologic AHO imaging technique in model eyes.

Aqueous Angiography in Living Nonhuman Primates Shows Segmental, Pulsatile, and Dynamic Angiographic Aqueous Humor Outflow

PURPOSE To evaluate the feasibility of safely performing aqueous angiography in intact eyes of living nonhuman primates (NHPs) for evaluating aqueous humor outflow and segmental patterns. DESIGN Cross-sectional, observational study. SUBJECTS Six nonhuman primates. METHODS Aqueous angiography was performed in 6 nonhuman primates. After anesthesia, an anterior chamber (AC) maintainer was placed through a temporal 1-mm side-port wound. Indocyanine green (ICG; 0.4%) or 2.5% fluorescein was introduced (individually or in sequence) into the eye with a gravity-driven constant-pressure system. Aqueous angiography images were obtained with a Spectralis HRA+OCT (Heidelberg Engineering GmbH, Heidelberg, Germany) suspended over the NHP eye using a custom-designed surgical boom arm. Concurrent anterior segment optical coherence tomography (OCT) was performed on distally angiographically positive and negative regions. MAIN OUTCOME MEASURES Angiographic patterns described by location, time-course, choice of tracer, and anterior-segment OCT. RESULTS Aqueous angiography in the living NHP eye demonstrated mostly stable angiographic patterns. With multimodal imaging, angiographically positive signal co-localized with episcleral veins as identified by infrared imaging and intrascleral lumens, as demonstrated by anterior segment OCT. Sequential aqueous angiography in individual eyes with ICG followed by fluorescein showed similar angiographic patterns. A pulsatile nature of aqueous angiographic outflow was sometimes observed. Aqueous angiographic patterns could also dynamically change. In some instances, positive angiographic flow suddenly arose in regions previously without an angiographic signal. Alternatively, an angiographic signal could suddenly disappear from regions in which an angiographic signal was initially documented. CONCLUSIONS Aqueous angiography in living NHPs demonstrated segmental and pulsatile patterns with a newly described ability to dynamically shift. These characteristics further the understanding of live aqueous humor outflow biology and may be useful in improving glaucoma surgeries aimed at trabecular meshwork bypass.

Aqueous Angiography-Mediated Guidance of Trabecular Bypass Improves Angiographic Outflow in Human Enucleated Eyes.

Purpose To assess the ability of trabecular micro-bypass stents to improve aqueous humor outflow (AHO) in regions initially devoid of AHO as assessed by aqueous angiography. Methods Enucleated human eyes (14 total from 7 males and 3 females [ages 52–84]) were obtained from an eye bank within 48 hours of death. Eyes were oriented by inferior oblique insertion, and aqueous angiography was performed with indocyanine green (ICG; 0.4%) or fluorescein (2.5%) at 10 mm Hg. With an angiographer, infrared and fluorescent images were acquired. Concurrent anterior segment optical coherence tomography (OCT) was performed, and fixable fluorescent dextrans were introduced into the eye for histologic analysis of angiographically positive and negative areas. Experimentally, some eyes (n = 11) first received ICG aqueous angiography to determine angiographic patterns. These eyes then underwent trabecular micro-bypass sham or stent placement in regions initially devoid of angiographic signal. This was followed by fluorescein aqueous angiography to query the effects. Results Aqueous angiography in human eyes yielded high-quality images with segmental patterns. Distally, angiographically positive but not negative areas demonstrated intrascleral lumens on OCT images. Aqueous angiography with fluorescent dextrans led to their trapping in AHO pathways. Trabecular bypass but not sham in regions initially devoid of ICG aqueous angiography led to increased aqueous angiography as assessed by fluorescein (P = 0.043). Conclusions Using sequential aqueous angiography in an enucleated human eye model system, regions initially without angiographic flow or signal could be recruited for AHO using a trabecular bypass stent.

Aqueous Angiography with Fluorescein and Indocyanine Green in Bovine Eyes

Purpose We characterize aqueous angiography as a real-time aqueous humor outflow imaging (AHO) modality in cow eyes with two tracers of different molecular characteristics. Methods Cow enucleated eyes (n = 31) were obtained and perfused with balanced salt solution via a Lewicky AC maintainer through a 1-mm side-port. Fluorescein (2.5%) or indocyanine green (ICG; 0.4%) were introduced intracamerally at 10 mm Hg individually or sequentially. With an angiographer, infrared and fluorescent images were acquired. Concurrent anterior segment optical coherence tomography (OCT) was performed, and fixable fluorescent dextrans were introduced into the eye for histologic analysis of angiographically positive and negative areas. Results Aqueous angiography in cow eyes with fluorescein and ICG yielded high-quality images with segmental patterns. Over time, ICG maintained a better intraluminal presence. Angiographically positive, but not negative, areas demonstrated intrascleral lumens with anterior segment OCT. Aqueous angiography with fluorescent dextrans led to their trapping in AHO pathways. Sequential aqueous angiography with ICG followed by fluorescein in cow eyes demonstrated similar patterns. Conclusions Aqueous angiography in model cow eyes demonstrated segmental angiographic outflow patterns with either fluorescein or ICG as a tracer. Translational Relevance Further characterization of segmental AHO with aqueous angiography may allow for intelligent placement of trabecular bypass minimally invasive glaucoma surgeries for improved surgical results.

Automated circumferential construction of first-order aqueous humor outflow pathways using spectral-domain optical coherence tomography

Abstract. The purpose was to create a three-dimensional (3-D) model of circumferential aqueous humor outflow (AHO) in a living human eye with an automated detection algorithm for Schlemm’s canal (SC) and first-order collector channels (CC) applied to spectral-domain optical coherence tomography (SD-OCT). Anterior segment SD-OCT scans from a subject were acquired circumferentially around the limbus. A Bayesian Ridge method was used to approximate the location of the SC on infrared confocal laser scanning ophthalmoscopic images with a cross multiplication tool developed to initiate SC/CC detection automated through a fuzzy hidden Markov Chain approach. Automatic segmentation of SC and initial CC’s was manually confirmed by two masked graders. Outflow pathways detected by the segmentation algorithm were reconstructed into a 3-D representation of AHO. Overall, only <1% of images (5114 total B-scans) were ungradable. Automatic segmentation algorithm performed well with SC detection 98.3% of the time and <0.1% false positive detection compared to expert grader consensus. CC was detected 84.2% of the time with 1.4% false positive detection. 3-D representation of AHO pathways demonstrated variably thicker and thinner SC with some clear CC roots. Circumferential (360 deg), automated, and validated AHO detection of angle structures in the living human eye with reconstruction was possible.

Swept-source OCT angiography imaging of the macular capillary network in glaucoma

Purpose To evaluate the macular capillary network density of superficial and deep retinal layers (SRL/DRL) by swept-source optical coherence tomography angiography (OCTA) in patients with primary open angle glaucoma (POAG) and to compare the results with those of normal subjects. Method In this prospective study, 24 eyes of 24 normal individuals and 24 eyes of 24 patients with mild to moderate POAG underwent fovea centred 6×6 mm cube macular OCTA imaging by a swept-source OCTA device (Triton, Topcon, Tokyo, Japan). Quantitative analysis of the retinal vasculature was performed by assessing vessel density (VD) as the ratio of the retinal area occupied by vessels at the SRL and DRL. Results The mean VD (ratio) at the SRL and DRL was statistically significantly lower in patients with POAG (SRL, p<0.001; DRL, p<0.001). In the SRL, the mean±SD VD ratio was 0.34±0.05 in patients with POAG and 0.40±0.02 in normal individuals (p<0.001). In the DRL, the mean (SD) ratio was 0.37±0.05 in patients with POAG and 0.43±0.02 in normal individuals (p<0.001). The mean VD at the SRL was significantly correlated with ganglion cell inner plexiform layer thickness (r=0.42, p=0.04) but not with visual field mean deviation (r=0.4, p=0.06) and retinal nerve fibre layer thickness (r=0.5, p=0.06). The mean VD at the DRL did not show significant correlation with any other glaucoma parameter (p>0.05). Conclusion The assessment of macular VD by swept-source OCTA may offer additional information for detection of glaucoma.

Unobtrusive and Continuous Monitoring of Alcohol-impaired Gait Using Smart Shoes

BACKGROUND Alcohol ingestion influences sensory-motor function and the overall well-being of individuals. Detecting alcohol-induced impairments in gait in daily life necessitates a continuous and unobtrusive gait monitoring system. OBJECTIVES This paper introduces the development and use of a non-intrusive monitoring system to detect changes in gait induced by alcohol intoxication. METHODS The proposed system employed a pair of sensorized smart shoes that are equipped with pressure sensors on the insole. Gait features were extracted and adjusted based on individuals gait profile. The adjusted gait features were used to train a machine learning classifier to discriminate alcohol-impaired gait from normal walking. In experiment of pilot study, twenty participants completed walking trials on a 12 meter walkway to measure their sober walking and alcohol-impaired walking using smart shoes. RESULTS The proposed system can detect alcohol-impaired gait with an accuracy of 86.2 % when pressure value analysis and person-dependent model for the classifier are applied, while statistical analysis revealed that no single feature was discriminative for the detection of gait impairment. CONCLUSIONS Alcohol-induced gait disturbances can be detected with smart shoe technology for an automated monitoring in ubiquitous environment. We demonstrated that personal monitoring and machine learning-based prediction could be customized to detect individual variation rather than applying uniform boundary parameters of gait.

Structural and functional imaging of aqueous humour outflow: a review

Maintaining healthy aqueous humour outflow (AHO) is important for intraocular cellular health and stable vision. Impairment of AHO can lead to increased intraocular pressure, optic nerve damage and concomitant glaucoma. An improved understanding of AHO will lead to improved glaucoma surgeries that enhance native AHO as well as facilitate the development of AHO‐targeted pharmaceuticals. Recent AHO imaging has evolved to live human assessment and has focused on the structural evaluation of AHO pathways and the functional documentation of fluid flow. Structural AHO evaluation is predominantly driven by optical coherence tomography, and functional evaluation of flow is performed using various methods, including aqueous angiography. Advances in structural and functional evaluation of AHO are reviewed with discussion of strengths, weaknesses and potential future directions.

Identifying predictors for postoperative clinical outcome in lumbar spinal stenosis patients using smart-shoe technology

BackgroundApproximately 33% of the patients with lumbar spinal stenosis (LSS) who undergo surgery are not satisfied with their postoperative clinical outcomes. Therefore, identifying predictors for postoperative outcome and groups of patients who will benefit from the surgical intervention is of significant clinical benefit. However, many of the studied predictors to date suffer from subjective recall bias, lack fine digital measures, and yield poor correlation to outcomes.MethodsThis study utilized smart-shoes to capture gait parameters extracted preoperatively during a 10 m self-paced walking test, which was hypothesized to provide objective, digital measurements regarding the level of gait impairment caused by LSS symptoms, with the goal of predicting postoperative outcomes in a cohort of LSS patients who received lumbar decompression and/or fusion surgery. The Oswestry Disability Index (ODI) and predominant pain level measured via the Visual Analogue Scale (VAS) were used as the postoperative clinical outcome variables.ResultsThe gait parameters extracted from the smart-shoes made statistically significant predictions of the postoperative improvement in ODI (RMSE =0.13, r=0.93, and p<3.92×10−7) and predominant pain level (RMSE =0.19, r=0.83, and p<1.28×10−4). Additionally, the gait parameters produced greater prediction accuracy compared to the clinical variables that had been previously investigated.ConclusionsThe reported results herein support the hypothesis that the measurement of gait characteristics by our smart-shoe system can provide accurate predictions of the surgical outcomes, assisting clinicians in identifying which LSS patient population can benefit from the surgical intervention and optimize treatment strategies.