Charles A. Reisman

Automated layer segmentation of macular OCT images using dual-scale gradient information

A novel automated boundary segmentation algorithm is proposed for fast and reliable quantification of nine intra-retinal boundaries in optical coherence tomography (OCT) images. The algorithm employs a two-step segmentation schema based on gradient information in dual scales, utilizing local and complementary global gradient information simultaneously. A shortest path search is applied to optimize the edge selection. The segmentation algorithm was validated with independent manual segmentation and a reproducibility study. It demonstrates high accuracy and reproducibility in segmenting normal 3D OCT volumes. The execution time is about 16 seconds per volume (480x512x128 voxels). The algorithm shows potential for quantifying images from diseased retinas as well.

Automated segmentation of outer retinal layers in macular OCT images of patients with retinitis pigmentosa

To provide a tool for quantifying the effects of retinitis pigmentosa (RP) seen on spectral domain optical coherence tomography images, an automated layer segmentation algorithm was developed. This algorithm, based on dual-gradient information and a shortest path search strategy, delineates the inner limiting membrane and three outer retinal boundaries in optical coherence tomography images from RP patients. In addition, an automated inner segment (IS)/outer segment (OS) contour detection method based on the segmentation results is proposed to quantify the locus of points at which the OS thickness goes to zero in a 3D volume scan. The segmentation algorithm and the IS/OS contour were validated with manual segmentation data. The segmentation and IS/OS contour results on repeated measures showed good within-day repeatability, while the results on data acquired on average 22.5 months afterward demonstrated a possible means to follow disease progression. In particular, the automatically generated IS/OS contour provided a possible objective structural marker for RP progression.

Improving Glaucoma Detection Using Spatially Correspondent Clusters of Damage and by Combining Standard Automated Perimetry and Optical Coherence Tomography

PURPOSE To improve the detection of glaucoma, techniques for assessing local patterns of damage and for combining structure and function were developed. METHODS Standard automated perimetry (SAP) and frequency-domain optical coherence tomography (fdOCT) data, consisting of macular retinal ganglion cell plus inner plexiform layer (mRGCPL) as well as macular and optic disc retinal nerve fiber layer (mRNFL and dRNFL) thicknesses, were collected from 52 eyes of 52 healthy controls and 156 eyes of 96 glaucoma suspects and patients. In addition to generating simple global metrics, SAP and fdOCT data were searched for contiguous clusters of abnormal points and converted to a continuous metric (pcc). The pcc metric, along with simpler methods, was used to combine the information from the SAP and fdOCT. The performance of different methods was assessed using the area under receiver operator characteristic curves (AROC scores). RESULTS The pcc metric performed better than simple global measures for both the fdOCT and SAP. The best combined structure-function metric (mRGCPL&SAP pcc, AROC = 0.868 ± 0.032) was better (statistically significant) than the best metrics for independent measures of structure and function. When SAP was used as part of the inclusion and exclusion criteria, AROC scores increased for all metrics, including the best combined structure-function metric (AROC = 0.975 ± 0.014). CONCLUSIONS A combined structure-function metric improved the detection of glaucomatous eyes. Overall, the primary sources of value-added for glaucoma detection stem from the continuous cluster search (the pcc), the mRGCPL data, and the combination of structure and function.

Optical Coherence Tomography in the UK Biobank Study – Rapid Automated Analysis of Retinal Thickness for Large Population-Based Studies

Purpose To describe an approach to the use of optical coherence tomography (OCT) imaging in large, population-based studies, including methods for OCT image acquisition, storage, and the remote, rapid, automated analysis of retinal thickness. Methods In UK Biobank, OCT images were acquired between 2009 and 2010 using a commercially available “spectral domain” OCT device (3D OCT-1000, Topcon). Images were obtained using a raster scan protocol, 6 mm x 6 mm in area, and consisting of 128 B-scans. OCT image sets were stored on UK Biobank servers in a central repository, adjacent to high performance computers. Rapid, automated analysis of retinal thickness was performed using custom image segmentation software developed by the Topcon Advanced Biomedical Imaging Laboratory (TABIL). This software employs dual-scale gradient information to allow for automated segmentation of nine intraretinal boundaries in a rapid fashion. Results 67,321 participants (134,642 eyes) in UK Biobank underwent OCT imaging of both eyes as part of the ocular module. 134,611 images were successfully processed with 31 images failing segmentation analysis due to corrupted OCT files or withdrawal of subject consent for UKBB study participation. Average time taken to call up an image from the database and complete segmentation analysis was approximately 120 seconds per data set per login, and analysis of the entire dataset was completed in approximately 28 days. Conclusions We report an approach to the rapid, automated measurement of retinal thickness from nearly 140,000 OCT image sets from the UK Biobank. In the near future, these measurements will be publically available for utilization by researchers around the world, and thus for correlation with the wealth of other data collected in UK Biobank. The automated analysis approaches we describe may be of utility for future large population-based epidemiological studies, clinical trials, and screening programs that employ OCT imaging.

Association of Retinal Nerve Fiber Layer Thinning With Current and Future Cognitive Decline: A Study Using Optical Coherence Tomography

Importance Identifing potential screening tests for future cognitive decline is a priority for developing treatments for and the prevention of dementia. Objective To examine the potential of retinal nerve fiber layer (RNFL) thickness measurement in identifying those at greater risk of cognitive decline in a large community cohort of healthy people. Design, Setting, and Participants UK Biobank is a prospective, multicenter, community-based study of UK residents aged 40 to 69 years at enrollment who underwent baseline retinal optical coherence tomography imaging, a physical examination, and a questionnaire. The pilot study phase was conducted from March 2006 to June 2006, and the main cohort underwent examination for baseline measures from April 2007 to October 2010. Four basic cognitive tests were performed at baseline, which were then repeated in a subset of participants approximately 3 years later. We analyzed eyes with high-quality optical coherence tomography images, excluding those with eye disease or vision loss, a history of ocular or neurological disease, or diabetes. We explored associations between RNFL thickness and cognitive function using multivariable logistic regression modeling to control for demographic as well as physiologic and ocular variation. Main Outcomes and Measures Odds ratios (ORs) for cognitive performance in the lowest fifth percentile in at least 2 of 4 cognitive tests at baseline, or worsening results on at least 1 cognitive test at follow-up. These analyses were adjusted for age, sex, race/ethnicity, height, refraction, intraocular pressure, education, and socioeconomic status. Results A total of 32 038 people were included at baseline testing, for whom the mean age was 56.0 years and of whom 17 172 (53.6%) were women. A thinner RNFL was associated with worse cognitive performance on baseline assessment. A multivariable regression controlling for potential confounders showed that those in the thinnest quintile of RNFL were 11% more likely to fail at least 1 cognitive test (95% CI, 2.0%-2.1%; P = .01). Follow-up cognitive tests were performed for 1251 participants (3.9%). Participants with an RNFL thickness in the 2 thinnest quintiles were almost twice as likely to have at least 1 test score be worse at follow-up cognitive testing (quintile 1: OR, 1.92; 95% CI, 1.29-2.85; P < .001; quintile 2: OR, 2.08; 95% CI, 1.40-3.08; P < .001). Conclusions and Relevance A thinner RNFL is associated with worse cognitive function in individuals without a neurodegenerative disease as well as greater likelihood of future cognitive decline. This preclinical observation has implications for future research, prevention, and treatment of dementia.

RETINAL NERVE FIBER LAYER THINNING ASSOCIATED WITH POOR COGNITIVE FUNCTION AMONG A LARGE COHORT, THE UK BIOBANK

ASSOCIATEDWITH POOR COGNITIVE FUNCTION AMONG A LARGE COHORT, THE UK BIOBANK Fang Ko, John Gallacher, Zaynah Muthy, Kay-tee Khaw, Charles A. Reisman, Qi Yang, Catey Bunce, Peng T. Khaw, Nicholas G. Strouthidis, Paul J. Foster, Praveen J. Patel, the UK Biobank Eye and Vision Consortium, and the Dementias Platform UK, NIHR Biomedical Research Centre, Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, United Kingdom; 2 University of Oxford, Oxford, United Kingdom; 3 University of Cambridge, Cambridge, United Kingdom; Topcon Advanced Biomedical Imaging Laboratory, Oakland, NJ, USA; NIHR Biomedical Research Centre, Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, United Kingdom; 6 Singapore Eye Research Institute, Singapore, Singapore; 7 University of Sydney, Sydney, Australia. Contact e-mail: fangkomail@gmail.com

The development of a reference database with the Topcon 3D OCT-1 Maestro

Importance The paper presents the range for measurements taken with a new spectral domain optical coherence tomography (OCT) device to establish a reference database for discrimination purposes. Objective To report the range of thickness values for the new Topcon Maestro 3D OCT device with 2 scan size settings: the 12×9 mm wide field and 6×6 mm scans. Design Prospective, multicenter cohort study conducted at 7 clinical sites across the USA. Setting Primary eyecare clinics within academic, hospital, and private practice locations. Participants Healthy volunteers; all enrolled participants underwent a complete ophthalmological examination to confirm healthy ocular status prior to being enrolled in the study. Main outcome measure Average and 1st, 5th, 95th, and 99th percentile ranges for OCT parameters Early Treatment Diabetic Retinopathy Study macula full retinal thickness, ganglion cell + inner plexiform layer thickness (GCL + IPL), ganglion cell complex (GCC) thickness, circumpapillary retinal nerve fiber layer (cpRNFL) thickness. Results Three hundred and ninety-nine eyes of 399 subjects were included in the analysis. Mean (SD) age was 46.3 (16.3) years (range 18–88 years). Forty-three percent of the subjects were male. Mean (SD) measurements (in μm) for the 12×9 mm wide scan were as follows: foveal thickness=237.079 (20.899), GCL + IPL=71.363 (5.924), GCC=105.949 (8.533), cpRNFL=104.720 (11.829); measurements for the 6×6 mm scans were as follows: foveal thickness=234.000 (20.657), GCL + IPL=71.726 (5.880), GCC=106.698 (9.094), cpRNFL=104.036 (11.341). Conclusion The overall normal thickness values reported with Topcon 3D OCT-1 Maestro were like those studies with OCT from different manufactures. The reference limits at the 1st, 5th, 95th, and 99th percentile points establish the thresholds for the quantitative comparison of the cpRNFL and the macula in the human retina to a database of known healthy subjects.

Introduction to Swept Source OCT

Optical coherence tomography (OCT), first introduced in 1991, is an enabling optical, noninvasive imaging modality that provides cross-sectional visualization of biological tissues with resolutions one to two orders of magnitude better than conventional ultrasound [1]. Because the eye is optically accessible for visible and near-infrared light, ophthalmic OCT has been the most successful clinical application from the invention of OCT with an unparalleled combination of axial resolution (1–10 μm) and penetration depth (1–2 mm in tissue). This chapter presents a brief introduction of OCT, including the early time-domain OCT (TD-OCT) and the more recent Fourier-domain OCT (FD-OCT), which can be characterized into the two forms of spectral-domain OCT (SD-OCT) and swept source OCT (SS-OCT). Since the commercial launch of SD-OCT in 2006 by multiple manufacturers, including the world’s first Topcon 3D OCT-1000, the significant practical advantages of both higher speed and higher sensitivity of SD-OCT over TD-OCT [2–4] have led to a widespread use of OCT instruments in ophthalmology [5]. On the other hand, SS-OCT, which employs the state-of-the-art high-speed wavelength tuning laser (swept source) as well as digital data acquisition and processing technology, offers further advantages of overcoming the signal roll-off observed for SD-OCT at a deeper range along with an unprecedented A-scan rate for wider field-of-view structural OCT and OCT angiography imaging [6, 7]. With advances in commercial wavelength tuning lasers, the first clinical 1 μm SS-OCT machine, Topcon DRI OCT-1 Atlantis, became commercially available for retinal imaging in 2012 [8].

Evaluation of Cultured Corneal Epithelial Cells and Epithelial Thickness by Full-Field Optical Coherence Tomography

The growth process of cultured corneal epithelial cells has been evaluated by full-field optical coherence tomography. Three different layers of the epithelium were discriminated and the thickness of corneal epithelium was quantitatively measured.