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

Optical coherence tomography in Alzheimer's disease. A meta-analysis

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder, which is likely to start as mild cognitive impairment (MCI) several years before the its full-blown clinical manifestation. Optical coherence tomography (OCT) has been used to detect a loss in peripapillary retina nerve fiber layer (RNFL) and a reduction in macular thickness and volume of people affected by MCI or AD. Here, we performed an aggregate meta-analysis combining results from different studies. METHODS AND FINDINGS: Data sources were case-control studies published between January 2001 and August 2014 (identified through PubMed and Google Scholar databases) that examined the RNFL thickness by means of OCT in AD and MCI patients compared with cognitively healthy controls. RESULTS: 11 studies were identified, including 380 patients with AD, 68 with MCI and 293 healthy controls (HC). The studies suggest that the mean RNFL thickness is reduced in MCI (weighted mean differences in μm, WMD = -13.39, 95% CI: -17.34 to -9.45, p = 0.031) and, even more so, in AD (WMD = -15.95, 95% CI: -21.65 to -10.21, p<0.0001) patients compared to HC. RNFL in the 4 quadrants were all significantly thinner in AD superior (superior WMD = -24.0, 95% CI: -34.9 to -13.1, p<0.0001; inferior WMD = -20.8, 95% CI: -32.0 to -9.7, p<0.0001; nasal WMD = -14.7, 95% CI: -23.9 to -5.5, p<0.0001; and temporal WMD = -10.7, 95% CI: -19.9 to -1.4, p<0.0001); the same significant reduction in quadrant RNFL was observed in MCI patients compared with HC (Inferior WMD = -20.22, 95% CI: -30.41 to -10.03, p = 0.0001; nasal WMD = -7.4, 95% CI: -10.08 to -4.7, p = 0.0000; and temporal WMD = -6.88, 95% CI: -12.62 to -1.13, p = 0.01), with the exception of superior quadrant (WMD = -19.45, 95% CI: -40.23 to 1.32, p = 0.06). CONCLUSION: Results from the meta-analysis support the important role of OCT for RNFL analysis in monitoring the progression of AD and in assessing the effectiveness of purported AD treatments

Optical Coherence Tomography Angiography Vessel Density in Healthy, Glaucoma Suspect, and Glaucoma Eyes.

PurposeThe purpose of this study was to compare retinal nerve fiber layer (RNFL) thickness and optical coherence tomography angiography (OCT-A) retinal vasculature measurements in healthy, glaucoma suspect, and glaucoma patients.MethodsTwo hundred sixty-one eyes of 164 healthy, glaucoma suspect, and open-angle glaucoma (OAG) participants from the Diagnostic Innovations in Glaucoma Study with good quality OCT-A images were included. Retinal vasculature information was summarized as a vessel density map and as vessel density (%), which is the proportion of flowing vessel area over the total area evaluated. Two vessel density measurements extracted from the RNFL were analyzed: (1) circumpapillary vessel density (cpVD) measured in a 750-μm-wide elliptical annulus around the disc and (2) whole image vessel density (wiVD) measured over the entire image. Areas under the receiver operating characteristic curves (AUROC) were used to evaluate diagnostic accuracy.ResultsAge-adjusted mean vessel density was significantly lower in OAG eyes compared with glaucoma suspects and healthy eyes. (cpVD: 55.1 ± 7%, 60.3 ± 5%, and 64.2 ± 3%, respectively; P &lt; 0.001; and wiVD: 46.2 ± 6%, 51.3 ± 5%, and 56.6 ± 3%, respectively; P &lt; 0.001). For differentiating between glaucoma and healthy eyes, the age-adjusted AUROC was highest for wiVD (0.94), followed by RNFL thickness (0.92) and cpVD (0.83). The AUROCs for differentiating between healthy and glaucoma suspect eyes were highest for wiVD (0.70), followed by cpVD (0.65) and RNFL thickness (0.65).ConclusionsOptical coherence tomography angiography vessel density had similar diagnostic accuracy to RNFL thickness measurements for differentiating between healthy and glaucoma eyes. These results suggest that OCT-A measurements reflect damage to tissues relevant to the pathophysiology of OAG

The Relationship of the Clinical Disc Margin and Bruch's Membrane Opening in Normal and Glaucoma Subjects.

PurposeWe tested the hypotheses that the mismatch between the clinical disc margin (CDM) and Bruch's membrane opening (BMO) is a function of BMO area (BMOA) and is affected by the presence of glaucoma.MethodsA total of 45 normal eyes (45 subjects) and 53 glaucomatous eyes (53 patients) were enrolled and underwent radial optic nerve head (ONH) imaging with spectral domain optical coherence tomography. The inner tip of the Bruch's membrane (BM) and the clinical disc margin were marked on radial scans and optic disc photographs, and were coregistered with custom software. The main outcome measure was the difference between the clinical disc area (CDA) and BMOA, or CDA-BMOA mismatch, as a function of BMOA and diagnosis. Multivariate regression analyses were used to explore the influence of glaucoma and BMOA on the mismatch.ResultsGlobal CDA was larger than BMOA in both groups but the difference was statistically significant only in the normal group (1.98 ± 0.37 vs. 1.85 ± 0.45 mm2, P = 0.02 in the normal group; 1.96 ± 0.38 vs. 1.89 ± 0.56 mm2, P = 0.08 in the glaucoma group). The sectoral CDA-BMOA mismatch was smaller in superotemporal (P = 0.04) and superonasal (P = 0.05) sectors in the glaucoma group. The normalized CDA-BMOA difference decreased with increasing BMOA in both groups (P &lt; 0.001). Presence or severity of glaucoma did not affect the CDA-BMOA difference (P &gt; 0.14).ConclusionsClinical disc area was larger than BMOA in normal and glaucoma eyes but reached statistical significance only in the former group. The CDA-BMOA mismatch diminished with increasing BMOA but was not affected by presence of glaucoma. These findings have important clinical implications regarding clinical evaluation of the ONH

Neuroprotection in a Novel Mouse Model of Multiple Sclerosis

The authors acknowledge the support of the Barts and the London Charity, the Multiple Sclerosis Society of Great Britain and Northern Ireland, the National Multiple Sclerosis Society, USA, notably the National Centre for the Replacement, Refinement & Reduction of Animals in Research, and the Wellcome Trust (grant no. 092539 to ZA). The siRNA was provided by Quark Pharmaceuticals. The funders and Quark Pharmaceuticals had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Visual pathway function and structure in Wolfram syndrome: Patient age, variation and progression

Background/aimsTo report alterations in visual acuity and visual pathway structure over an interval of 1–3 years in a cohort of children, adolescents and young adults who have Wolfram syndrome (WFS) and to describe the range of disease severity evident in patients with WFS whose ages differed by as much as 20 years at first examination.MethodsAnnual, prospective ophthalmological examinations were performed in conjunction with retinal nerve fibre layer (RNFL) analysis. Diffusion tensor MRI-derived fractional anisotropy was used to assess the microstructural integrity of the optic radiations (OR FA).ResultsMean age of the 23 patients with WFS in the study was 13.8 years (range 5–25 years). Mean log minimum angle resolution visual acuity was 0.66 (20/91). RNFL thickness was subnormal in even the youngest patients with WFS. Average RNFL thickness in patients with WFS was 57±8 µ or ~40% thinner than that measured in normal (94±10 µ) children and adolescents (P&lt;0.01). Lower OR FA correlated with worse visual acuity (P=0.006). Subsequent examinations showed declines (P&lt;0.05) in visual acuity, RNFL thickness and OR FA at follow-up intervals of 12–36 months. However, a wide range of disease severity was evident across ages: some of the youngest patients at their first examination had deficits more severe than the oldest patients.ConclusionThe genetic mutation of WFS causes damage to both pregeniculate and postgeniculate regions of the visual pathway. The damage is progressive. The decline in visual pathway structure is accompanied by declines of visual function. Disease severity differs widely in individual patients and cannot be predicted from their age.</jats:sec

Peripapillary and macular choroidal thickness in glaucoma.

PurposeTo compare choroidal thickness (CT) between individuals with and without glaucomatous damage and to explore the association of peripapillary and submacular CT with glaucoma severity using spectral domain optical coherence tomography (SD-OCT).MethodsNinety-one eyes of 20 normal subjects and 43 glaucoma patients from the UCLA SD-OCT Imaging Study were enrolled. Imaging was performed using Cirrus HD-OCT. Choroidal thickness was measured at four predetermined points in the macular and peripapillary regions, and compared between glaucoma and control groups before and after adjusting for potential confounding variables.ResultsThe average (± standard deviation) mean deviation (MD) on visual fields was -0.3 (±2.0) dB in controls and -3.5 (±3.5) dB in glaucoma patients. Age, axial length and their interaction were the most significant factors affecting CT on multivariate analysis. Adjusted average CT (corrected for age, axial length, their interaction, gender and lens status) however, was not different between glaucoma patients and the control group (P=0.083) except in the temporal parafoveal region (P=0.037); nor was choroidal thickness related to glaucoma severity (r=-0.187, P=0.176 for correlation with MD, r=-0.151, P=0.275 for correlation with average nerve fiber layer thickness).ConclusionsChoroidal thickness of the macular and peripapillary regions is not decreased in glaucoma. Anatomical measurements with SD-OCT do not support the possible influence of the choroid on the pathophysiology of glaucoma