EyeArt + EyePACS: Automated Retinal Image Analysis For Diabetic Retinopathy Screening in a Telemedicine System

Telemedicine frameworks are key to screening the large, ever-growing diabetic population for preventable blindness due to diabetic retinopathy (DR). Integrating fully-automated screening systems in telemedicine frameworks will make DR screening more efficient, cost-effective, reproducible, and accessible. In this paper, we present the integration of EyeArt, an automated DR screening system, into EyePACS, a telemedicine system for DR screening used in diverse screening settings. EyeArt in- corporates novel image processing and analysis algorithms for assessing image gradability; enhancing images based on median filtering; detecting interest regions and localizing lesions based on multi-scale morphological analysis; and DR screening and thus achieves robustness to the large image variability seen in a telemedicine system such as EyePACS. EyeArt is implemented as a scalable, high-throughput cloud-based system to enable large-scale DR screening. We evaluate the safety and performance of EyeArt on a dataset with 434,023 images from 54,324 patient cases obtained from EyePACS. On this dataset, EyeArt’s screening sensitivity is 90% at specificity 60.8% and the area under the receiver operating characteristic curve (AUROC) is 0.883. In a setup where trained human graders review patient cases recommended for referral by EyeArt with low confidence, a workload reduction of 62% is possible. Therefore, EyeArt can be safely integrated into large real world telemedicine DR screening programs such as EyePACS helping reduce workload and increase efficiency and thus help in reducing vision loss due to DR through early detection and treatment

Comparison of Drusen Area Detected by Spectral Domain Optical Coherence Tomography and Color Fundus Imaging

Citation: Yehoshua Z, Gregori G, Sadda SR, et al. Comparison of drusen area detected by spectral domain optical coherence tomography and color fundus imaging. Invest Ophthalmol Vis Sci. 2013;54;4:24294: -24344: . DOI:10.1167 PURPOSE. To compare the measurements of drusen area from manual segmentation of color fundus photographs with those generated by an automated algorithm designed to detect elevations of the retinal pigment epithelium (RPE) on spectral domain optical coherence tomography (SD-OCT) images. METHODS. Fifty eyes with drusen secondary to nonexudative age-related macular degeneration were enrolled. All eyes were imaged with a high-definition OCT instrument using a 200 3 200 A-scan raster pattern covering a 6 mm 3 6 mm area centered on the fovea. Digital color fundus images were taken on the same day. Drusen were traced manually on the fundus photos by graders at the Doheny Image Reading Center, whereas quantitative OCT measurements of drusen were obtained by using a fully automated algorithm. The color fundus images were registered to the OCT data set and measurements within corresponding 3-and 5-mm circles centered at the fovea were compared. . The mean differences between color images and the SD-OCT (color À SD-OCT) were 0.36 (60.93) (P ¼ 0.008) for the 3-mm circle and 1.26 (61.38) (P < 0.001) for the 5-mm circle measurements. Intraclass correlation coefficients of agreements for 3-and 5-mm measurements were 0.599 and 0.540, respectively. RESULTS. The mean areas (6SD [range CONCLUSIONS. There was only fair agreement between drusen area measurements obtained from SD-OCT images and color fundus photos. Drusen area measurements on color fundus images were larger than those with SD-OCT scans. This difference can be attributed to the fact that the OCT algorithm defines drusen in terms of RPE deformations above a certain threshold, and will not include small, flat drusen and subretinal drusenoid deposits. The two approaches provide complementary information about drusen

OCT Signs of Early Atrophy in Age-Related Macular Degeneration: Interreader Agreement: Classification of Atrophy Meetings Report 6.

PURPOSE: To determine the interreader agreement for incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA) and complete RPE and outer retinal atrophy (cRORA) and their related features in age-related macular degeneration (AMD). DESIGN: Interreader agreement study. PARTICIPANTS: Twelve readers from 6 reading centers. METHODS: After formal training, readers qualitatively assessed 60 OCT B-scans from 60 eyes with AMD for 9 individual features associated with early atrophy and performed 7 different annotations to quantify the spatial extent of OCT features within regions of interest. The qualitative and quantitative features were used to derive the presence of iRORA and cRORA and also in an exploratory analysis to examine if agreement could be improved using different combinations of features to define OCT atrophy. MAIN OUTCOME MEASURES: Interreader agreement based on Gwet's first-order agreement coefficient (AC1) for qualitatively graded OCT features and classification of iRORA and cRORA, and smallest real difference (SRD) for quantitatively graded OCT features. RESULTS: Substantial or better interreader agreement was observed for all qualitatively graded OCT features associated with atrophy (AC1 = 0.63-0.87), except for RPE attenuation (AC1 = 0.46) and disruption (AC1 = 0.26). The lowest SRD for the quantitatively graded horizontal features was observed for the zone of choroidal hypertransmission (± 190.8 μm). Moderate agreement was found for a 3-category classification of no atrophy, iRORA, and cRORA (AC1 = 0.53). Exploratory analyses suggested a significantly higher level of agreement for a 3-category classification using (1) no atrophy; (2) presence of inner nuclear layer and outer plexiform layer subsidence, or a hyporeflective wedge-shaped band, as a less severe atrophic grade; and (3) the latter plus an additional requirement of choroidal hypertransmission of 250 μm or more for a more severe atrophic grade (AC1 = 0.68; P = 0.013). CONCLUSIONS: Assessment of iRORA and cRORA, and most of their associated features, can be performed relatively consistently and robustly. A refined combination of features to define early atrophy could further improve interreader agreement

Automated Diabetic Retinopathy Image Assessment Software: Diagnostic Accuracy and Cost-Effectiveness Compared with Human Graders.

OBJECTIVE: With the increasing prevalence of diabetes, annual screening for diabetic retinopathy (DR) by expert human grading of retinal images is challenging. Automated DR image assessment systems (ARIAS) may provide clinically effective and cost-effective detection of retinopathy. We aimed to determine whether ARIAS can be safely introduced into DR screening pathways to replace human graders. DESIGN: Observational measurement comparison study of human graders following a national screening program for DR versus ARIAS. PARTICIPANTS: Retinal images from 20 258 consecutive patients attending routine annual diabetic eye screening between June 1, 2012, and November 4, 2013. METHODS: Retinal images were manually graded following a standard national protocol for DR screening and were processed by 3 ARIAS: iGradingM, Retmarker, and EyeArt. Discrepancies between manual grades and ARIAS results were sent to a reading center for arbitration. MAIN OUTCOME MEASURES: Screening performance (sensitivity, false-positive rate) and diagnostic accuracy (95% confidence intervals of screening-performance measures) were determined. Economic analysis estimated the cost per appropriate screening outcome. RESULTS: Sensitivity point estimates (95% confidence intervals) of the ARIAS were as follows: EyeArt 94.7% (94.2%-95.2%) for any retinopathy, 93.8% (92.9%-94.6%) for referable retinopathy (human graded as either ungradable, maculopathy, preproliferative, or proliferative), 99.6% (97.0%-99.9%) for proliferative retinopathy; Retmarker 73.0% (72.0 %-74.0%) for any retinopathy, 85.0% (83.6%-86.2%) for referable retinopathy, 97.9% (94.9%-99.1%) for proliferative retinopathy. iGradingM classified all images as either having disease or being ungradable. EyeArt and Retmarker saved costs compared with manual grading both as a replacement for initial human grading and as a filter prior to primary human grading, although the latter approach was less cost-effective. CONCLUSIONS: Retmarker and EyeArt systems achieved acceptable sensitivity for referable retinopathy when compared with that of human graders and had sufficient specificity to make them cost-effective alternatives to manual grading alone. ARIAS have the potential to reduce costs in developed-world health care economies and to aid delivery of DR screening in developing or remote health care settings

Correlation between retinal sensitivity and cystoid space characteristics in diabetic macular edema

Purpose: To evaluate the correlation between retinal sensitivity and cystoid space characteristics in eyes with diabetic macular edema (DME). Materials and Methods: Prospective cross-sectional study of 22 subjects with DME (32 treatment-naïve eyes). All study subjects underwent complete ophthalmic examination, including slit-lamp biomicroscopy and dilated fundus examination. All subjects underwent spectral domain optical coherence tomography (SD-OCT) and microperimetry (MP). Intraretinal cystoid space (ICS) volume was generated after manual delineation of cystoid space boundaries using the three-dimensional-OCT software. Various SD-OCT parameters, including retinal thickness, retinal volume, cystoid space volume, cystoid space intensity, and outer retinal structure integrity, were correlated with MP parameters and best-corrected visual acuity (BCVA). Results: Subject′s mean age was 57 ± 9 years. The mean logarithm of minimum angle of resolution BCVA was 0.4 ± 0.2. The intraclass correlation coefficient for inter- and intra-grader assessment of cystoid space volume by manual delineation was 0.99 and 0.99, respectively. Mean total ICS volume was 0.4 ± 0.4 mm 3 and for the foveal center, subfield was 0.1 ± 0.1 mm 3 . Mean retinal sensitivity was 12.89 ± 10 dB; however, foveal retinal sensitivity was 12.3 ± 11.1 dB. We found no significant correlation between BCVA and total cystoid space volume (r = 0.33, P = 0.06). Correlation between total retinal sensitivity and total ICS was negative and nonsignificant (r = −0.17, P = 0.36). Correlation between foveal retinal sensitivity and foveal cystoid space intensity was moderate and marginally significant (r = −0.43, P = 0.05). Conclusion: Total cystoid space volume was not significantly correlated with BCVA or total retinal sensitivity in subjects with DME. Foveal cystoid space optical intensity was negatively correlated with foveal retinal sensitivity. These findings suggest further investigation of cystoid space characteristics in the setting of DME may be of value

Choroidal thickness in non-ocular Behçet's disease – A spectral-domain OCT study

Purpose: To evaluate choroidal thickness in patients with non-ocular Behçet's disease (BD) using spectral domain optical coherence tomography (SD-OCT) and to compare the results to normal eyes. Methods: In this retrospective observational comparative study, we collected OCT and clinical data from the charts of 4 patients (7 eyes) with BD who had been referred for a screening eye exam and had a normal ocular examination. Data from 9 healthy volunteers (17 eyes) were collected as age-matched controls. The choroid was manually segmented from volume OCT scans using custom Doheny Image Reading Center OCT grading software (3D-OCTOR). Main outcome measures were choroidal thickness and intensity were compared between eyes of patients with BD and those of healthy controls. Results: Eyes of patients with non-ocular BD had significantly thinner mean central subfield choroidal thickness (227.5 ± 56.93 versus 306.85 ± 17.85, P = 0.04) and central subfield choroidal volume (0.18 ± 0.04 vs 0.24 ± 0.02, P = 0.005). There was no significant difference in mean choroidal thickness in the whole ETDRS grid or in mean choroidal intensity in the central subfield and the whole ETDRS grid between eyes of patients with non-ocular BD and those of controls. Conclusion: This study demonstrates that BD may have subclinical manifestations in the choroid, resulting in thinning of the choroid relative to normal eyes, even without overt signs of ocular involvement. Keywords: Choroidal thickness, Behçet's disease, Spectral domain optical coherence tomography, Choroidal intensity, Choroidal reflectivit

ASSOCIATION OF DRUSEN VOLUME WITH CHOROIDAL PARAMETERS IN NONNEOVASCULAR AGE-RELATED MACULAR DEGENERATION

The choroid is thought to be relevant to the pathogenesis of nonneovascular age-related macular degeneration, but its role has not yet been fully defined. In this study, we evaluate the relationship between the extent of macular drusen and specific choroidal parameters, including thickness and intensity. Spectral domain optical coherence tomography images were collected from two distinct, independent cohorts with nonneovascular age-related macular degeneration: Amish (53 eyes of 34 subjects) and non-Amish (40 eyes from 26 subjects). All spectral domain optical coherence tomography scans were obtained using the Cirrus HD-OCT with a 512 × 128 macular cube (6 × 6 mm) protocol. The Cirrus advanced retinal pigment epithelium analysis tool was used to automatically compute drusen volume within 3 mm (DV3) and 5 mm (DV5) circles centered on the fovea. The inner and outer borders of the choroid were manually segmented, and the mean choroidal thickness and choroidal intensity (i.e., brightness) were calculated. The choroidal intensity was normalized against the vitreous and nerve fiber layer reflectivity. The correlation between DV and these choroidal parameters was assessed using Pearson and linear regression analysis. A significant positive correlation was observed between normalized choroidal intensity and DV5 in the Amish (r = 0.42, P = 0.002) and non-Amish (r = 0.33, P = 0.03) cohorts. Also, DV3 showed a significant positive correlation with normalized choroidal intensity in both the groups (Amish: r = 0.30, P = 0.02; non-Amish: r = 0.32, P = 0.04). Choroidal thickness was negatively correlated with normalized choroidal intensity in both Amish (r = -0.71, P = 0.001) and non-Amish (r = -0.43, P = 0.01) groups. Normalized choroidal intensity was the most significant constant predictor of DV in both the Amish and non-Amish groups. Choroidal intensity, but not choroidal thickness, seems to be associated with drusen volume in Amish and non-Amish populations. These observations suggest that choroidal parameters beyond thickness warrant further study in the setting of age-related macular degeneration

Risk Factors for Progression of Age-Related Macular Degeneration: Population-Based Amish Eye Study

Objective: To evaluate the optical coherence tomography (OCT)-based risk factors for progression to late age-related macular degeneration (AMD) in a population-based study of elderly Amish. Methods: A total of 1332 eyes of 666 consecutive subjects who completed a 2-year follow-up visit were included in this multicenter, prospective, longitudinal, observational study. Imaging features were correlated with 2-year incidence of late AMD development. Odds ratios for imaging features were estimated from logistic regression. Baseline OCT images were reviewed for the presence of drusen volume ≥0.03 mm3 in the central 3 mm ring, intraretinal hyperreflective foci (IHRF), hyporeflective drusen cores (hDC), subretinal drusenoid deposits (SDD), and drusenoid pigment epithelium detachment (PED). Subfoveal choroidal thickness, drusen area, and drusen volume within 3 and 5 mm circles centered on the fovea were also assessed. Results: Twenty-one (1.5%) of 1332 eyes progressed to late AMD by 2 years. The mean age of the study subjects was 65 ± 10.17 (±SD) years and 410 subjects were female. Univariate logistic regression showed that drusen area and volume in both 3 mm and 5 mm circles, subfoveal choroidal thickness, drusen volume ≥ 0.03 mm3 in the 3 mm ring, SDD, IHRF, and hDC were all associated with an increased risk for development of late AMD. The multivariate regression model identified that drusen volume in the 3 mm ring (OR: 2.59, p = 0.049) and presence of IHRF (OR: 57.06, p < 0.001) remained as independent and significant risk factors for progression to late AMD. Conclusions: This population-based study confirms previous findings from clinic-based studies that high central drusen volume and IHRF are associated with an increased risk of progression to late AMD. These findings may be of value in risk-stratifying patients in clinical practice or identifying subjects for early intervention clinical trials

CHOROIDAL VASCULARITY INDEX AND CHOROIDAL THICKNESS IN EYES WITH RETICULAR PSEUDODRUSEN

To evaluate choroidal vascularity index (CVI), choroidal thickness, choroidal volume, and choroidal intensity in subjects with nonneovascular age-related macular degeneration (NNVAMD) with and without reticular pseudodrusen (RPD). We included 60 eyes of 35 subjects with NNVAMD (including 30 eyes of 18 subjects with RPD) and 30 eyes of 17 age-matched healthy individuals from the ongoing Amish Eye study. The choroid was segmented from dense volume spectral domain optical coherence tomography scans and choroidal thickness (microns), choroidal intensity (log units), and choroidal volume (mm) from the entire macula (6 × 6 mm) were computed. A central horizontal B-scan was binarized and the luminal and stromal portions of the choroid were segmented. Choroidal vascularity index (%) was calculated as the ratio of luminal area to total choroid area. Choroidal parameters were compared between the groups by pairwise comparisons using the Student's t-test. The CVI was significantly lower in healthy eyes compared to those with RPD (53.43 ± 8.51 vs. 54.76 ± 4.83, P < 0.001). The CVI was also significantly lower in NNVAMD eyes without RPD compared to those with RPD (50.09 ± 7.51 vs. 54.76 ± 4.83, P = 0.006). There was no difference in CVI between healthy eyes and NNVAMD eyes without RPD (P = 0.84). Choroidal thickness and choroidal volume were significantly higher in NNVAMD without RPD (P < 0.05); and significantly lower in NNVAMD with RPD (P < 0.05) when compared with normal eyes. Choroidal intensity was significantly higher in NNVAMD with RPD when compared with normal eyes (P = 0.02) and NNVAMD eyes without RPD (P = 0.001). Multiple choroidal parameters reflecting the status of the choroidal vasculature and stroma seem to be altered in eyes with RPD compared with both normal eyes and NNVAMD eyes without RPD. These findings may provide insights into the pathophysiology of RPD