Three-Dimensional Spectral-Domain Optical Coherence Tomography Data Analysis for Glaucoma Detection

Purpose: To develop a new three-dimensional (3D) spectral-domain optical coherence tomography (SD-OCT) data analysis method using a machine learning technique based on variable-size super pixel segmentation that efficiently utilizes full 3D dataset to improve the discrimination between early glaucomatous and healthy eyes. Methods: 192 eyes of 96 subjects (44 healthy, 59 glaucoma suspect and 89 glaucomatous eyes) were scanned with SD-OCT. Each SD-OCT cube dataset was first converted into 2D feature map based on retinal nerve fiber layer (RNFL) segmentation and then divided into various number of super pixels. Unlike the conventional super pixel having a fixed number of points, this newly developed variable-size super pixel is defined as a cluster of homogeneous adjacent pixels with variable size, shape and number. Features of super pixel map were extracted and used as inputs to machine classifier (LogitBoost adaptive boosting) to automatically identify diseased eyes. For discriminating performance assessment, area under the curve (AUC) of the receiver operating characteristics of the machine classifier outputs were compared with the conventional circumpapillary RNFL (cpRNFL) thickness measurements. Results: The super pixel analysis showed statistically significantly higher AUC than the cpRNFL (0.855 vs. 0.707, respectively, p = 0.031, Jackknife test) when glaucoma suspects were discriminated from healthy, while no significant difference was found when confirmed glaucoma eyes were discriminated from healthy eyes. Conclusions: A novel 3D OCT analysis technique performed at least as well as the cpRNFL in glaucoma discrimination and even better at glaucoma suspect discrimination. This new method has the potential to improve early detection of glaucomatous damage. © 2013 Xu et al

Gold nanorods as a contrast agent for Doppler optical coherence tomography

Purpose: To investigate gold nanorods (GNRs) as a contrast agent to enhance Doppler optical coherence tomography (OCT) imaging of the intrascleral aqueous humor outflow. Methods: A serial dilution of GNRs was scanned with a spectral-domain OCT device (Bioptigen, Durham, NC) to visualize Doppler signal. Doppler measurements using GNRs were validated using a controlled flow system. To demonstrate an application of GNR enhanced Doppler, porcine eyes were perfused at constant pressure with mock aqueous alone or 1.0×10 12 GNR/mL mixed with mock aqueous. Twelve Doppler and volumetric SD-OCT scans were obtained from the limbus in a radial fashion incremented by 30°, forming a circular scan pattern. Volumetric flow was computed by integrating flow inside non-connected vessels throughout all 12 scans around the limbus. Results: At the GNR concentration of 0.7×1012 GNRs/mL, Doppler signal was present through the entire depth of the testing tube without substantial attenuation. A well-defined laminar flow profile was observed for Doppler images of GNRs flowing through the glass capillary tube. The Doppler OCT measured flow profile was not statistically different from the expected flow profile based upon an autoregressive moving average model, with an error of -0.025 to 0.037 mm/s (p = 0.6435). Cross-sectional slices demonstrated the ability to view anterior chamber outflow ex-vivo using GNR-enhanced Doppler OCT. Doppler volumetric flow measurements were comparable to flow recorded by the perfusion system. Conclusions: GNRs created a measureable Doppler signal within otherwise silent flow fields in OCT Doppler scans. Practical application of this technique was confirmed in a constant pressure ex-vivo aqueous humor outflow model in porcine eyes. © 2014 Wang et al

Reproducibility of in-vivo OCT measured three-dimensional human lamina cribrosa microarchitecture

Purpose: To determine the reproducibility of automated segmentation of the three-dimensional (3D) lamina cribrosa (LC) microarchitecture scanned in-vivo using optical coherence tomography (OCT). Methods: Thirty-nine eyes (8 healthy, 19 glaucoma suspects and 12 glaucoma) from 49 subjects were scanned twice using swept-source (SS-) OCT in a 3.5x3.5x3.64 mm (400x400x896 pixels) volume centered on the optic nerve head, with the focus readjusted after each scan. The LC was automatically segmented and analyzed for microarchitectural parameters, including pore diameter, pore diameter standard deviation (SD), pore aspect ratio, pore area, beam thickness, beam thickness SD, and beam thickness to pore diameter ratio. Reproducibility of the parameters was assessed by computing the imprecision of the parameters between the scans. Results: The automated segmentation demonstrated excellent reproducibility. All LC microarchitecture parameters had an imprecision of less or equal to 4.2%. There was little variability in imprecision with respect to diagnostic category, although the method tends to show higher imprecision amongst healthy subjects. Conclusion: The proposed automated segmentation of the LC demonstrated high reproducibility for 3D LC parameters. This segmentation analysis tool will be useful for in-vivo studies of the LC. © 2014 Wang et al

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—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. 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 inter-parameter 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 8-10, 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 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 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 due to the effects of age on RNFL, macula and ONH OCT measurements should be considered when assessing eyes over time.National Institutes of Health (U.S.) (R01-EY13178-09)National Institutes of Health (U.S.) (R01-EY11289-23)National Institutes of Health (U.S.) (P30-EY008098

Intracameral dexamethasone reduces inflammation on the first postoperative day after cataract surgery in eyes with and without glaucoma

Purpose: To evaluate whether dexamethasone injected intracamerally at the conclusion of surgery can safely and effectively reduce postoperative inflammation and improve surgical outcomes in eyes with and without glaucoma. Methods: Retrospective chart review of 176 consecutive eyes from 146 patients receiving uncomplicated phacoemulsification (PE) (n = 118 total, 82 with glaucoma), glaucoma drainage device (GDD) (n = 35), combined PE/GDD (n = 11) and combined PE/endoscopic cyclophotocoagulation (n = 12). Ninety-one eyes from 76 patients were injected with 0.4 mg dexamethasone intracamerally at the conclusion of surgery. All eyes received standard postoperative prednisolone and ketorolac eyedrops. Outcomes were measured for four to eight weeks by subjective complaints, visual acuity (VA), slit-lamp biomicroscopy, intraocular pressure (IOP) and postoperative complications. Results: Dexamethasone significantly reduced the odds of having an increased anterior chamber (AC) cell score after PE (p = 0.0013). Mean AC cell score ± SD in nonglaucomatous eyes was 1.3 ± 0.8 in control and 0.8 ± 0.7 with dexamethasone; scores in glaucomatous eyes were 1.3 ± 0.7 in control and 0.9 ± 0.8 with dexamethasone. Treated nonglaucomatous eyes had significantly fewer subjective complaints after PE (22.2% vs 64.7% in control; p = 0.0083). Dexamethasone had no significant effects on VA, corneal changes, IOP one day and one month after surgery, or long-term complications. Conclusions: Intracameral dexamethasone given at the end of cataract surgery significantly reduces postoperative AC cells in eyes with and without glaucoma, and improves subjective reports of recovery in nonglaucomatous eyes. There were no statistically significant risks of IOP elevation or other complications in glaucomatous eyes. © 2009 Chang et al, publisher and licensee Dove Medical Press Ltd

Baerveldt tube shunts with trabectome surgery in a matched comparison to Baerveldt tube shunts

Baerveldt Tube Shunts (B) Bypass the conventional outflow system Are used in advanced glaucoma Have a lower complication rate and a slightly higher success rate than trabeculectomy Often experience a hypertensive phase in the postoperative period Two IOP drops are typically needed to achieve IOP goal Trabectome Surgery (AIT) Has a nearly 20 fold lower complication rate than tubes Most commonly used in mild to moderate glaucoma Hypothesis Compared with B, combining B+AIT will reduce IOP and IOP drops while blunting the hypertensive phase. The visual acuity after B+AIT is worse than after B during the postoperative period. The safety profiles of B+AIT and B are similar. Conclusion B+AIT and B have a similar IOP. B+AIT require fewer drops at every time point than B. B+AIT and B have a similar visual acuity. AIT can be used as an adjunct to B to decrease the need for IOP lowering drops

Design and Feasibility Assessment of a Retrospective Epidemiological Study of Coal-Fired Power Plant Emissions in the Pittsburgh Pennsylvania Region

Eighty-nine (89) percent of the electricity supplied in the 35-county Pittsburgh region (comprising parts of the states of Pennsylvania, Ohio, West Virginia, and Maryland) is generated by coal-fired power plants making this an ideal region in which to study the effects of the fine airborne particulates designated as PM{sub 2.5} emitted by the combustion of coal. This report demonstrates that during the period from 1999-2006 (1) sufficient and extensive exposure data, in particular samples of speciated PM{sub 2.5} components from 1999 to 2003, and including gaseous co-pollutants and weather have been collected, (2) sufficient and extensive mortality, morbidity, and related health outcomes data are readily available, and (3) the relationship between health effects and fine particulates can most likely be satisfactorily characterized using a combination of sophisticated statistical methodologies including latent variable modeling (LVM) and generalized linear autoregressive moving average (GLARMA) time series analysis. This report provides detailed information on the available exposure data and the available health outcomes data for the construction of a comprehensive database suitable for analysis, illustrates the application of various statistical methods to characterize the relationship between health effects and exposure, and provides a road map for conducting the proposed study. In addition, a detailed work plan for conducting the study is provided and includes a list of tasks and an estimated budget. A substantial portion of the total study cost is attributed to the cost of analyzing a large number of archived PM{sub 2.5} filters. Analysis of a representative sample of the filters supports the reliability of this invaluable but as-yet untapped resource. These filters hold the key to having sufficient data on the components of PM{sub 2.5} but have a limited shelf life. If the archived filters are not analyzed promptly the important and costly information they contain will be lost

Modeling hepatic fibrosis in African American and Caucasian American patients with chronic hepatitis C virus infection

Assessment of histological stage is an integral part of disease management in patients infected with the hepatitis C virus (HCV). The aim of this study was to develop a model incorporating objective clinical and laboratory parameters to estimate the probability of severe fibrosis ( i.e. , Ishak fibrosis ≥ 3) in previously untreated African American (AA) and Caucasian American (CA) patients with HCV genotype 1. The Ishak fibrosis scores of 205 CA and 194 AA patients enrolled in the Viral Resistance to Antiviral Therapy of Chronic Hepatitis C study (Virahep-C) were modeled using simple and multiple logistic regression. The model was then validated in an independent cohort of 461 previously untreated patients with HCV. The distribution of fibrosis scores was similar in the AA and CA patients as was the proportion of patients with severe fibrosis (35% vs. 39%, P = .47). After accounting for the number of portal areas in the biopsy, patient age, serum aspartate aminotransferase, alkaline phosphatase, and platelet count were independently associated with severe fibrosis in the overall cohort, and the relationship with fibrosis was similar in both the AA and CA subgroups. The area under the receiver operating characteristic curve (AUROC) of the Virahep-C model (0.837) was significantly better than in other published models ( P = .0003). The AUROC of the Virahep-C model was 0.851 in the validation population. In conclusion , a model consisting of widely available clinical and laboratory features predicted severe hepatic fibrosis equally well in AA and CA patients with HCV genotype 1 and was superior to other published models. The excellent performance of the Virahep-C model in an external validation cohort suggests the findings are replicable and potentially generalizable. (H EPATOLOGY 2006;44:925–935.)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55833/1/21335_ftp.pd

Biocompatible Reverse Thermal Gel Sustains the Release of Intravitreal Bevacizumab In Vivo

PURPOSE. We assessed the in vivo release profile of bevacizumab from and biocompatibility of poly(ethylene glycol)-poly-(serinol hexamethylene urethane), or ESHU, a thermoresponsive hydrogel administered intravitreally for drug delivery. METHODS. The technical feasibility of injection was assessed quantitatively via mechanical testing. For in vivo studies, New Zealand White rabbit eyes were injected intravitreally with 0.05 mL of either: ESHU dissolved in 25 mg/mL bevacizumab, ESHU dissolved in PBS, or 25 mg/mL bevacizumab. Clinical examination included IOP measurements and examination with indirect ophthalmoscopy for signs of inflammation. Additionally, eyes were examined histologically following euthanasia. To quantify bevacizumab release, aqueous humor samples were obtained via anterior chamber paracentesis and ELISA was used to determine the concentration of drug weekly. In vitro cytotoxicity testing also was performed using bovine corneal endothelial cells. RESULTS. The ESHU was injected easily through a 31-gauge needle, was well tolerated in vivo, and caused minimal cell death in vitro when compared to other common materials, such as silicone oil. The long-term presence of the gel did not affect IOP, and there was no evidence of inflammation histologically or through indirect observation. The ESHU sustained the release of bevacizumab for over 9 weeks and maintained a drug concentration that averaged 4.7 times higher than eyes receiving bolus bevacizumab injections. CONCLUSIONS. To our knowledge, this is the first report demonstrating sustained bevacizumab release in vivo from an intravitreally injected hydrogel formulation, suggesting that this delivery system may be a promising candidate for ocular drug delivery. Keywords: thermally responsive hydrogel, ocular drug delivery, sustained release, biocompatibility, injectable gel C horoidal neovascularization (CNV) is the hallmark of many blinding disorders, most notably wet age-related macular degeneration (AMD) and diabetic retinopathy. It is characterized by pathologic blood vessel growth, which originates in the choroid and progresses through the Bruch's membrane into the subretinal space. 1 These vessels are fragile and permeable, causing hemorrhage, retinal detachment, scarring, and ultimately, loss of central vision. Elevated levels of VEGF is a central cause of CNV. 2-4 Thus, intravitreal injection of anti-VEGF medications, such as bevacizumab (Avastin) or ranibizumab (Lucentis), has emerged as a leading treatment strategy. 10-13 Therefore, a delivery system that extends the presence of intravitreal drugs in the eye is highly desirable for reducing injection frequency and adverse effects, while maximizing therapeutic outcomes. A number of polymeric delivery systems have been considered by researchers for intravitreal drug delivery, including microparticles, which are well tolerated in the eye and are capable of delivering drugs over a longer period of time. 14,15 For example, microparticle-encapsulated or PEGylated bevacizumab is more effective than bevacizumab alone in treating CNV in rats

Characterization of Outer Retinal Morphology with HighSpeed, Ultrahigh-Resolution Optical Coherence Tomography

PURPOSE. To visualize, quantitatively assess, and interpret outer retinal morphology by using high-speed, ultrahigh-resolution (UHR) OCT. METHODS. Retinal imaging was performed in the ophthalmic clinic in a cross-section of 43 normal subjects with a 3.5-m, axial-resolution, high-speed, UHR OCT prototype instrument, using a radial scan pattern (24 images, 1500 axial scans). Outer retinal layers were automatically segmented and measured. High-definition imaging was performed with a 2.8-m axialresolution, high-speed, UHR OCT research prototype instrument, to visualize the finer features in the outer retina. RESULTS. Quantitative maps of outer retinal layers showed clear differences between the cone-dominated fovea and the roddominated parafovea and perifovea, indicating that photoreceptor morphology can explain the appearance of the outer retina in high-speed, UHR OCT images. Finer, scattering bands were visualized in the outer retina using high-definition imaging and were interpreted by comparison to known anatomy. CONCLUSIONS. High-speed UHR OCT enables quantification of scattering layers in the outer retina. An interpretation of these features is presented and supported by quantitative measurements in normal subjects and comparison with known anatomy. The thick scattering region of the outer retina previously attributed to the retinal pigment epithelium (RPE) is shown to consist of distinct scattering bands corresponding to the photoreceptor outer segment tips, RPE, and Bruch's membrane. These results may advance understanding of the outer retinal appearance in OCT images. The normative measurements may also aid in future investigations of outer retinal changes in age-related macular degeneration and other diseases. (Inves