Lateral Resolution of a Commercial Optical Coherence Tomography Instrument.

Purpose: The lateral resolution of an optical coherence tomography (OCT) instrument was considered to be equal to the illumination spot size on the retina. To evaluate the potential lateral resolution of the Spectralis OCT, an instrument calculated to have a 14 µm resolution. Methods: The lateral point spread function (PSF) was evaluated using diamond abrasive powder 0 to 1 µm in diameter in silicone elastomer and a validated target with 800 nm FeO particles in urethane. The amplitude transfer function was calculated from human OCT images. Finally, resolution was measured using the 1951 USAF target. Results: Measurement of the lateral PSF from 1215 diamond particle images yielded a full-width half maximum (FWHM) to be 5.11 µm and for 732 FeO particles, 4.9 µm. From the amplitude transfer function, the FWHM of the diffraction limited PSF was calculated to be 5.0 µm. The USAF target imaging showed a lateral resolution of 4.6 µm. Conclusions: Although a calculation of the spot size of the illumination beam was reported in the past as the lateral resolution of the OCT instrument, the actual lateral resolution is better by a factor of at least 2.5 times. The clinically used A-scan spacing was derived from the calculated, and not the true resolution, and results in under sampling. This set of findings likely apply to all commercial clinical instruments. Translational Relevance: The scan density parameters of past and present commercial OCT instruments were based on earlier translational concepts, which now appear to have been incorrect.

Association of ambient air pollution with age-related macular degeneration and retinal thickness in UK Biobank.

AIM: To examine the associations of air pollution with both self-reported age-related macular degeneration (AMD), and in vivo measures of retinal sublayer thicknesses. METHODS: We included 115 954 UK Biobank participants aged 40-69 years old in this cross-sectional study. Ambient air pollution measures included particulate matter, nitrogen dioxide (NO2) and nitrogen oxides (NOx). Participants with self-reported ocular conditions, high refractive error (< -6 or > +6 diopters) and poor spectral-domain optical coherence tomography (SD-OCT) image were excluded. Self-reported AMD was used to identify overt disease. SD-OCT imaging derived photoreceptor sublayer thickness and retinal pigment epithelium (RPE) layer thickness were used as structural biomarkers of AMD for 52 602 participants. We examined the associations of ambient air pollution with self-reported AMD and both photoreceptor sublayers and RPE layer thicknesses. RESULTS: After adjusting for covariates, people who were exposed to higher fine ambient particulate matter with an aerodynamic diameter <2.5 µm (PM2.5, per IQR increase) had higher odds of self-reported AMD (OR=1.08, p=0.036), thinner photoreceptor synaptic region (ß=-0.16 µm, p=2.0 × 10-5), thicker photoreceptor inner segment layer (ß=0.04 µm, p=0.001) and thinner RPE (ß=-0.13 µm, p=0.002). Higher levels of PM2.5 absorbance and NO2 were associated with thicker photoreceptor inner and outer segment layers, and a thinner RPE layer. Higher levels of PM10 (PM with an aerodynamic diameter <10 µm) was associated with thicker photoreceptor outer segment and thinner RPE, while higher exposure to NOx was associated with thinner photoreceptor synaptic region. CONCLUSION: Greater exposure to PM2.5 was associated with self-reported AMD, while PM2.5, PM2.5 absorbance, PM10, NO2 and NOx were all associated with differences in retinal layer thickness.

Correction: Genetic variation affects morphological retinal phenotypes extracted from UK Biobank optical coherence tomography images.

[This corrects the article DOI: 10.1371/journal.pgen.1009497.].

Genetic variation affects morphological retinal phenotypes extracted from UK Biobank optical coherence tomography images.

Optical Coherence Tomography (OCT) enables non-invasive imaging of the retina and is used to diagnose and manage ophthalmic diseases including glaucoma. We present the first large-scale genome-wide association study of inner retinal morphology using phenotypes derived from OCT images of 31,434 UK Biobank participants. We identify 46 loci associated with thickness of the retinal nerve fibre layer or ganglion cell inner plexiform layer. Only one of these loci has been associated with glaucoma, and despite its clear role as a biomarker for the disease, Mendelian randomisation does not support inner retinal thickness being on the same genetic causal pathway as glaucoma. We extracted overall retinal thickness at the fovea, representative of foveal hypoplasia, with which three of the 46 SNPs were associated. We additionally associate these three loci with visual acuity. In contrast to the Mendelian causes of severe foveal hypoplasia, our results suggest a spectrum of foveal hypoplasia, in part genetically determined, with consequences on visual function.

Relationships between retinal layer thickness and brain volumes in the UK Biobank cohort.

BACKGROUND AND PURPOSE: Current methods to diagnose neurodegenerative diseases are costly and invasive. Retinal neuroanatomy may be a biomarker for more neurodegenerative processes and can be quantified in vivo using optical coherence tomography (OCT), which is inexpensive and noninvasive. We examined the association of neuroretinal morphology with brain MRI image-derived phenotypes (IDPs) in a large cohort of healthy older people. METHODS: UK Biobank participants aged 40 to 69 years old underwent comprehensive examinations including ophthalmic and brain imaging assessments. Macular retinal nerve fibre layer (mRNFL), macular ganglion cell-inner plexiform layer (mGCIPL), macular ganglion cell complex (mGCC) and total macular thicknesses were obtained from OCT. Magnetic resonance imaging (MRI) IDPs assessed included total brain, grey matter, white matter and hippocampal volume. Multivariable linear regression models were used to evaluate associations between retinal layers thickness and brain MRI IDPs, adjusting for demographic factors and vascular risk factors. RESULTS: A total of 2131 participants (mean age 55 years; 51% women) with both gradable OCT images and brain imaging assessments were included. In multivariable regression analysis, thinner mGCIPL, mGCC and total macular thickness were all significantly associated with smaller total brain (p < 0.001), grey matter and white matter volume (p < 0.01), and grey matter volume in the occipital pole (p < 0.05). Thinner mGCC and total macular thicknesses were associated with smaller hippocampal volume (p < 0.02). No association was found between mRNFL and the MRI IDPs. CONCLUSIONS: Markers of retinal neurodegeneration are associated with smaller brain volumes. Our findings suggest that retinal structure may be a biomarker providing information about important brain structure in healthy older adults.

Retinal asymmetry in multiple sclerosis.

The diagnosis of multiple sclerosis is based on a combination of clinical and paraclinical tests. The potential contribution of retinal optical coherence tomography (OCT) has been recognized. We tested the feasibility of OCT measures of retinal asymmetry as a diagnostic test for multiple sclerosis at the community level. In this community-based study of 72 120 subjects, we examined the diagnostic potential of the inter-eye difference of inner retinal OCT data for multiple sclerosis using the UK Biobank data collected at 22 sites between 2007 and 2010. OCT reporting and quality control guidelines were followed. The inter-eye percentage difference (IEPD) and inter-eye absolute difference (IEAD) were calculated for the macular retinal nerve fibre layer (RNFL), ganglion cell inner plexiform layer (GCIPL) complex and ganglion cell complex. Area under the receiver operating characteristic curve (AUROC) comparisons were followed by univariate and multivariable comparisons accounting for a large range of diseases and co-morbidities. Cut-off levels were optimized by ROC and the Youden index. The prevalence of multiple sclerosis was 0.0023 [95% confidence interval (CI) 0.00229-0.00231]. Overall the discriminatory power of diagnosing multiple sclerosis with the IEPD AUROC curve (0.71, 95% CI 0.67-0.76) and IEAD (0.71, 95% CI 0.67-0.75) for the macular GCIPL complex were significantly higher if compared to the macular ganglion cell complex IEPD AUROC curve (0.64, 95% CI 0.59-0.69, P = 0.0017); IEAD AUROC curve (0.63, 95% CI 0.58-0.68, P < 0.0001) and macular RNFL IEPD AUROC curve (0.59, 95% CI 0.54-0.63, P < 0.0001); IEAD AUROC curve (0.55, 95% CI 0.50-0.59, P < 0.0001). Screening sensitivity levels for the macular GCIPL complex IEPD (4% cut-off) were 51.7% and for the IEAD (4 µm cut-off) 43.5%. Specificity levels were 82.8% and 86.8%, respectively. The number of co-morbidities was important. There was a stepwise decrease of the AUROC curve from 0.72 in control subjects to 0.66 in more than nine co-morbidities or presence of neuromyelitis optica spectrum disease. In the multivariable analyses greater age, diabetes mellitus, other eye disease and a non-white ethnic background were relevant confounders. For most interactions, the effect sizes were large (partial ω2 > 0.14) with narrow confidence intervals. In conclusion, the OCT macular GCIPL complex IEPD and IEAD may be considered as supportive measurements for multiple sclerosis diagnostic criteria in a young patient without relevant co-morbidity. The metric does not allow separation of multiple sclerosis from neuromyelitis optica. Retinal OCT imaging is accurate, rapid, non-invasive, widely available and may therefore help to reduce need for invasive and more costly procedures. To be viable, higher sensitivity and specificity levels are needed.

Ambient Air Pollution Associations with Retinal Morphology in the UK Biobank.

Purpose: Because air pollution has been linked to glaucoma and AMD, we characterized the relationship between pollution and retinal structure. Methods: We examined data from 51,710 UK Biobank participants aged 40 to 69 years old. Ambient air pollution measures included particulates and nitrogen oxides. SD-OCT imaging measured seven retinal layers: retinal nerve fiber layer, ganglion cell-inner plexiform layer, inner nuclear layer, outer plexiform layer + outer nuclear layer, photoreceptor inner segments, photoreceptor outer segments, and RPE. Multivariable regression was used to evaluate associations between pollutants (per interquartile range increase) and retinal thickness, adjusting for age, sex, race, Townsend deprivation index, body mass index, smoking status, and refractive error. Results: Participants exposed to greater particulate matter with an aerodynamic diameter of <2.5 µm (PM2.5) and higher nitrogen oxides were more likely to have thicker retinal nerve fiber layer (ß = 0.28 µm; 95% CI, 0.22-0.34; P = 3.3 × 10-20 and ß = 0.09 µm; 95% CI, 0.04-0.14; P = 2.4 × 10-4, respectively), and thinner ganglion cell-inner plexiform layer, inner nuclear layer, and outer plexiform layer + outer nuclear layer thicknesses (P < 0.001). Participants resident in areas of higher levels of PM2.5 absorbance were more likely to have thinner retinal nerve fiber layer, inner nuclear layer, and outer plexiform layer + outer nuclear layers (ß = -0.16 [95% CI, -0.22 to -0.10; P = 5.7 × 10-8]; ß = -0.09 [95% CI, -0.12 to -0.06; P = 2.2 × 10-12]; and ß = -0.12 [95% CI, -0.19 to -0.05; P = 8.3 × 10-4], respectively). Conclusions: Greater exposure to PM2.5, PM2.5 absorbance, and nitrogen oxides were all associated with apparently adverse retinal structural features.

Comparison of Associations with Different Macular Inner Retinal Thickness Parameters in a Large Cohort: The UK Biobank.

PURPOSE: To describe and compare associations with macular retinal nerve fiber layer (mRNFL), ganglion cell complex (GCC), and ganglion cell-inner plexiform layer (GCIPL) thicknesses in a large cohort. DESIGN: Cross-sectional study. PARTICIPANTS: We included 42 044 participants in the UK Biobank. The mean age was 56 years. METHODS: Spectral-domain OCT macular images were segmented and analyzed. Corneal-compensated intraocular pressure (IOPcc) was measured with the Ocular Response Analyzer (Reichert, Corp., Buffalo, NY). Multivariable linear regression was used to examine associations with mean mRNFL, GCC, and GCIPL thicknesses. Factors examined were age, sex, ethnicity, height, body mass index (BMI), smoking status, alcohol intake, Townsend deprivation index, education level, diabetes status, spherical equivalent, and IOPcc. MAIN OUTCOME MEASURES: Thicknesses of mRNFL, GCC, and GCIPL. RESULTS: We identified several novel independent associations with thinner inner retinal thickness. Thinner inner retina was associated with alcohol intake (most significant for GCIPL: -0.46 µm for daily or almost daily intake compared with special occasion only or never [95% confidence interval (CI), 0.61-0.30]; P = 1.1×10-8), greater social deprivation (most significant for GCIPL: -0.28 µm for most deprived quartile compared with least deprived quartile [95% CI, -0.42 to -0.14]; P = 6.6×10-5), lower educational attainment (most significant for mRNFL: -0.36 µm for less than O level compared with degree level [95% CI, -0.45 to 0.26]; P = 2.3×10-14), and nonwhite ethnicity (most significant for mRNFL comparing blacks with whites: -1.65 µm [95% CI, -1.86 to -1.43]; P = 2.4×10-50). Corneal-compensated intraocular pressure was associated most significantly with GCIPL (-0.04 µm/mmHg [95% CI, -0.05 to -0.03]; P = 4.0×10-10) and was not associated significantly with mRNFL (0.00 µm/mmHg [95% CI, -0.01 to 0.01]; P = 0.77). The variables examined explained a greater proportion of the variance of GCIPL (11%) than GCC (6%) or mRNFL (7%). CONCLUSIONS: The novel associations we identified may be important to consider when using inner retinal parameters as a diagnostic tool. Associations generally were strongest with GCIPL, particularly for IOP. This suggests that GCIPL may be the superior inner retinal biomarker for macular pathophysiologic processes and especially for glaucoma.

Associations with photoreceptor thickness measures in the UK Biobank.

Spectral-domain OCT (SD-OCT) provides high resolution images enabling identification of individual retinal layers. We included 32,923 participants aged 40-69 years old from UK Biobank. Questionnaires, physical examination, and eye examination including SD-OCT imaging were performed. SD OCT measured photoreceptor layer thickness includes photoreceptor layer thickness: inner nuclear layer-retinal pigment epithelium (INL-RPE) and the specific sublayers of the photoreceptor: inner nuclear layer-external limiting membrane (INL-ELM); external limiting membrane-inner segment outer segment (ELM-ISOS); and inner segment outer segment-retinal pigment epithelium (ISOS-RPE). In multivariate regression models, the total average INL-RPE was observed to be thinner in older aged, females, Black ethnicity, smokers, participants with higher systolic blood pressure, more negative refractive error, lower IOPcc and lower corneal hysteresis. The overall INL-ELM, ELM-ISOS and ISOS-RPE thickness was significantly associated with sex and race. Total average of INL-ELM thickness was additionally associated with age and refractive error, while ELM-ISOS was additionally associated with age, smoking status, SBP and refractive error; and ISOS-RPE was additionally associated with smoking status, IOPcc and corneal hysteresis. Hence, we found novel associations of ethnicity, smoking, systolic blood pressure, refraction, IOPcc and corneal hysteresis with photoreceptor thickness.

The Relationship Between Ambient Atmospheric Fine Particulate Matter (PM2.5) and Glaucoma in a Large Community Cohort.

Purpose: Glaucoma is more common in urban populations than in others. Ninety percent of the world's population are exposed to air pollution above World Health Organization (WHO) recommended limits. Few studies have examined the association between air pollution and glaucoma. Methods: Questionnaire data, ophthalmic measures, and ambient residential area air quality data for 111,370 UK Biobank participants were analyzed. Particulate matter with an aerodynamic diameter < 2.5 µm (PM2.5) was selected as the air quality exposure of interest. Eye measures included self-reported glaucoma, intraocular pressure (IOP), and average thickness of macular ganglion cell-inner plexiform layer (GCIPL) across nine Early Treatment Diabetic Retinopathy Study (ETDRS) retinal subfields as obtained from spectral-domain optical coherence tomography. We examined the associations of PM2.5 concentration with self-reported glaucoma, IOP, and GCIPL. Results: Participants resident in areas with higher PM2.5 concentration were more likely to report a diagnosis of glaucoma (odds ratio = 1.06, 95% confidence interval [CI] = 1.01-1.12, per interquartile range [IQR] increase P = 0.02). Higher PM2.5 concentration was also associated with thinner GCIPL (ß = -0.56 µm, 95% CI = -0.63 to -0.49, per IQR increase, P = 1.2 × 10-53). A dose-response relationship was observed between higher levels of PM2.5 and thinner GCIPL (P < 0.001). There was no clinically relevant relationship between PM2.5 concentration and IOP. Conclusions: Greater exposure to PM2.5 is associated with both self-reported glaucoma and adverse structural characteristics of the disease. The absence of an association between PM2.5 and IOP suggests the relationship may occur through a non-pressure-dependent mechanism, possibly neurotoxic and/or vascular effects.

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.

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.

Associations with Retinal Pigment Epithelium Thickness Measures in a Large Cohort: Results from the UK Biobank.

PURPOSE: To describe associations of ocular and systemic factors with retinal pigment epithelium (RPE)-Bruch's membrane (BM) complex thickness as measured by spectral-domain (SD) optical coherence tomography (OCT). DESIGN: Multisite community-based study. This research has been conducted using the UK Biobank Resource. PARTICIPANTS: Sixty-seven thousand three hundred eighteen people 40 to 69 years old received questionnaires, physical examination, and eye examination, including macular SD OCT. Systematic selection process identified 34 652 eyes with high-quality SD OCT images from normal individuals for analysis. METHODS: We included people with no self-reported ocular disease, diabetes, or neurologic disorders; visual acuity of ≥20/25; refraction between -6 diopters (D) to 6 D, and IOP of 6 to 21 mmHg. Only high-quality, well-centered SD OCT images with central, stable fixation were included. Descriptive statistics, t tests, and regression analyses were performed. Multivariate regression modeling was used to adjust for covariates and to identify relationships between RPE-BM thickness and ocular and systemic features. MAIN OUTCOME MEASURES: Retinal pigment epithelium-BM thickness, as measured by SD OCT segmentation using Topcon Advanced Boundary Segmentation at 9 Early Treatment of Diabetic Retinopathy Study subfields. RESULTS: Mean RPE-BM thickness was 26.3 µm (standard deviation, 4.8 µm) at central subfield. Multivariate regression with age stratification showed that RPE thinning became apparent after age 45. Among those aged ≤45, RPE-BM was significantly thicker among those of black or mixed/other race (+3.61 and +1.77 µm vs. white, respectively; P < 0.001) and higher hyperopia (+0.4 µm/D; P < 0.001), but not for other variables considered. Among those age >45, RPE-BM was significantly thinner with older age (-0.10 µm/year; P < 0.001), Asian ethnicity (-0.45 µm vs. white; P = 0.02), taller height (-0.02 µm/cm; P < 0.001), higher IOP (-0.03 µm/mmHg; P < 0.001), and regular smoking (-0.27 µm vs. nonsmokers; P = 0.02). In contrast, RPE-BM was significantly thicker among black or mixed/other race (+3.29 µm and +0.81 µm vs. white, respectively; P < 0.001) and higher hyperopia (+0.28 µm/D; P < 0.001). There was no significant association with sex or Chinese ethnicity. CONCLUSIONS: We describe novel findings of RPE-BM thickness in normal individuals, a structure that varies with age, ethnicity, refraction, IOP, and smoking. The significant association with IOP is especially interesting and may have relevance for the etiology of glaucoma, while the association between age and smoking may have relevance for the etiology of age-related macular degeneration.

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.

Spectral-Domain Optical Coherence Tomography Imaging in 67 321 Adults: Associations with Macular Thickness in the UK Biobank Study.

PURPOSE: To derive macular thickness measures and their associations by performing rapid, automated segmentation of spectral-domain optical coherence tomography (SD OCT) images collected and stored as part of the UK Biobank (UKBB) study. DESIGN: Large, multisite cohort study in the United Kingdom. Analysis of cross-sectional data. PARTICIPANTS: Adults from the United Kingdom aged 40 to 69 years. METHODS: Participants had nonmydriatic SD OCT (Topcon 3D OCT-1000 Mark II; Topcon GB, Newberry, Berkshire, UK) performed as part of the ocular assessment module. Rapid, remote, automated segmentation of the images was performed using custom optical coherence tomography (OCT) image analysis software (Topcon Advanced Boundary Segmentation [TABS]; Topcon GB) to generate macular thickness values. We excluded people with a history of ocular or systemic disease (diabetes or neurodegenerative diseases) and eyes with reduced vision (<0.1 logarithm of the minimum angle of resolution) or with low SD OCT signal-to-noise ratio and low segmentation success certainty. MAIN OUTCOME MEASURES: Macular thickness values across 9 Early Treatment of Diabetic Retinopathy Study (ETDRS) subfields. RESULTS: The SD OCT scans of 67 321 subjects were available for analysis, with 32 062 people with at least 1 eye meeting the inclusion criteria. There were 17 274 women and 14 788 men, with a mean (standard deviation [SD]) age of 55.2 (8.2) years. The mean (SD) logarithm of the minimum angle of resolution visual acuity was -0.075 (0.087), and the refractive error was -0.071 (+1.91) diopters (D). The mean (SD) central macular thickness (CMT) in the central 1-mm ETDRS subfield was 264.5 (22.9) µm, with 95% confidence limits of 220.8 and 311.5 µm. After adjusting for covariates, CMT was positively correlated with older age, female gender, greater myopia, smoking, body mass index (BMI), and white ethnicity (all P < 0.001). Of note, macular thickness in other subfields was negatively correlated with older age and greater myopia. CONCLUSIONS: We report macular thickness data derived from SD OCT images collected as part of the UKBB study and found novel associations among older age, ethnicity, BMI, smoking, and macular thickness.

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.

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.

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.