Search

Author(s): Christopher, Mark; Belghith, Akram; Weinreb, Robert N; Bowd, Christopher; Goldbaum, Michael H; Saunders, Luke J; Medeiros, Felipe A; Zangwill, Linda M | Abstract: Purpose:To apply computational techniques to wide-angle swept-source optical coherence tomography (SS-OCT) images to identify novel, glaucoma-related structural features and improve detection of glaucoma and prediction of future glaucomatous progression. Methods:Wide-angle SS-OCT, OCT circumpapillary retinal nerve fiber layer (cpRNFL) circle scans spectral-domain (SD)-OCT, standard automated perimetry (SAP), and frequency doubling technology (FDT) visual field tests were completed every 3 months for 2 years from a cohort of 28 healthy participants (56 eyes) and 93 glaucoma participants (179 eyes). RNFL thickness maps were extracted from segmented SS-OCT images and an unsupervised machine learning approach based on principal component analysis (PCA) was used to identify novel structural features. Area under the receiver operating characteristic curve (AUC) was used to assess diagnostic accuracy of RNFL PCA for detecting glaucoma and progression compared to SAP, FDT, and cpRNFL measures. Results:The RNFL PCA features were significantly associated with mean deviation (MD) in both SAP (R2 = 0.49, P l 0.0001) and FDT visual field testing (R2 = 0.48, P l 0.0001), and with mean circumpapillary RNFL thickness (cpRNFLt) from SD-OCT (R2 = 0.58, P l 0.0001). The identified features outperformed each of these measures in detecting glaucoma with an AUC of 0.95 for RNFL PCA compared to an 0.90 for mean cpRNFLt (P = 0.09), 0.86 for SAP MD (P = 0.034), and 0.83 for FDT MD (P = 0.021). Accuracy in predicting progression was also significantly higher for RNFL PCA compared to SAP MD, FDT MD, and mean cpRNFLt (P = 0.046, P = 0.007, and P = 0.044, respectively). Conclusions:A computational approach can identify structural features that improve glaucoma detection and progression prediction.

The goal of this study was to determine if glaucomatous progression in suspect eyes can be predicted from baseline confocal scanning laser ophthalmoscope (CSLO) and standard automated perimetry (SAP) measurements analyzed with relevance vector machine (RVM) classifiers.Two hundred sixty-four eyes of 193 participants were included. All eyes had normal SAP results at baseline with five or more SAP tests over time. Eyes were labeled progressed (n = 47) or stable (n = 217) during follow-up based on SAP Guided Progression Analysis or serial stereophotograph assessment. Baseline CSLO-measured topographic parameters (n = 117) and baseline total deviation values from the 24-2 SAP test-grid (n = 52) were selected from each eye. Ten-fold cross-validation was used to train and test RVMs using the CSLO and SAP features. Receiver operating characteristic (ROC) curve areas were calculated using full and optimized feature sets. ROC curve results from RVM analyses of CSLO, SAP, and CSLO and SAP combined were compared to CSLO and SAP global indices (Glaucoma Probability Score, mean deviation and pattern standard deviation).The areas under the ROC curves (AUROCs) for RVMs trained on optimized feature sets of CSLO parameters, SAP parameters, and CSLO and SAP parameters combined were 0.640, 0.762, and 0.805, respectively. AUROCs for CSLO Glaucoma Probability Score, SAP mean deviation (MD), and SAP pattern standard deviation (PSD) were 0.517, 0.513, and 0.620, respectively. No CSLO or SAP global indices discriminated between baseline measurements from progressed and stable eyes better than chance.In our sample, RVM analyses of baseline CSLO and SAP measurements could identify eyes that showed future glaucomatous progression with a higher accuracy than the CSLO and SAP global indices. (ClinicalTrials.gov numbers, NCT00221897, NCT00221923.).

PURPOSE.To determine whether combining structural (optical coherence tomography, OCT) and functional (standard automated perimetry, SAP) measurements as input for machine learning classifiers (MLCs; relevance vector machine, RVM; and subspace mixture of Gaussians, SSMoG) improves diagnostic accuracy for detecting glaucomatous eyes compared with using each measurement method alone. METHODS.Sixty-nine eyes of 69 healthy control subjects (average age, 62.0, SD 9.7 years; visual field mean deviation [MD], !0.70, SD 1.41 dB) and 156 eyes of 156 patients with glaucoma (average age, 66.4, SD 10.2 years; visual field MD,!3.12, SD 3.43 dB) were imaged with OCT (Stratus OCT, Carl Zeiss Meditec, Inc., Dublin, CA) and tested with SAP (Humphrey Field Analyzer II with Swedish Interactive Thresholding Algorithm, SITA; Carl Zeiss Meditec, Inc.) within 3 months of each other. RVM and SSMoG MLCs were trained and tested on OCT-determined RNFL thickness measurements from 32 sectors ("11.25° each) obtained in the circumpapillary area under the instrument-defined measurement ellipse and SAP pattern deviation values from 52 points from the 24-2 grid, independently and in combination. Tenfold cross-validation was used to train and test classifiers on unique subsets of the full 225-eye data set, and areas under the receiver operating characteristic curve (AUROC) for the classification of eyes in the test set were generated. AUROC results from classifiers trained on OCT and SAP alone and those trained on OCT and SAP in combination were compared. In addition, these results were compared to currently available OCT measurements (mean retinal nerve fiber layer [RNFL] thickness, inferior RNFL thickness, and superior RNFL thickness) and SAP indices (MD and pattern standard deviation [PSD]). RESULTS.The AUROCs for RVM trained on OCT parameters alone, SAP parameters alone and OCT and SAP parameters combined were 0.809, 0.815, and 0.845, respectively. The AUROCs for SSMoG trained on OCT parameters alone, SAP parameters alone, and OCT and SAP parameters combined were 0.817, 0.841, and 0.869, respectively. Combining techniques using both RVM and SSMoG significantly improved on MLC analysis of OCT, but not SAP, measurements alone. Classification performance using RVM and SSMoG was statistically similar. C ONCLUSIONS.RVM and SSMoG Bayesian MLCs trained on OCT and SAP data can successfully discriminate between healthy and early glaucomatous eyes. Combining OCT and SAP measurements using RVM and SSMoG increased diagnostic performance marginally compared with MLC analysis of data obtained using each technology alone. (Invest Ophthalmol Vis Sci.2008;49:945‐953) DOI:10.1167/iovs.07-1083

Machine learning classifiers (MLCs) are computational methods that enable machines to learn from experience. MLCs are effective in a variety of applications and classification problems in glaucoma, including visual field interpretation,1-7 diagnosis of glaucoma through structural measures,8-14 identification of patterns of visual field loss,15,16 and detection of glaucomatous progression.17-20 MLCs trained to identify patients with glaucomatous optic neuropathy (GON) from standard automated perimetry (SAP) of visual fields have been shown to be as sensitive as traditional Statpac-like analysis at specificities of 90% and greater.2 As with all new methods, however, further optimization of the performance of the MLCs would be advantageous. One approach to optimizing the analysis of visual fields has been to group visual field locations. Mapping the visual field into clusters of related locations has been used to clarify the structure–function relationship21-24 and to aid in the detection of glaucomatous progression by reducing the effect of long-term variability.25-27 Clustering may also serve as a dimension–reduction tool to optimize MLCs and to increase our understanding of the visual field regional relationships. However, it is not clear whether there is an advantage to selecting one map over the others or whether dimension reduction with structure-derived clusters compares favorably with mathematical dimension-reduction. In the present study we compared the sensitivity and specificity of two MLCs trained separately on three clustering schemes to determine (1) whether MLC ability to categorize healthy and GON eyes can be optimized by training with clustered data; (2) which MLC, visual field mapping scheme or MLC/map combination achieves the highest performance; and (3) how structure-derived schemes compare to the mathematical dimension-reducing scheme.

PURPOSE. To determine whether topographical measurements of the parapapillary region analyzed by machine learning classifiers can detect early to moderate glaucoma better than similarly processed measurements obtained within the disc margin and to improve methods for optimization of machine learning classifier feature selection. METHODS. One eye of each of 95 patients with early to moderate glaucomatous visual field damage and of each of 135 normal subjects older than 40 years participating in the longitudinal Diagnostic Innovations in Glaucoma Study (DIGS) were included. Heidelberg Retina Tomograph (HRT; Heidelberg Engineering, Dossenheim, Germany) mean height contour was measured in 36 equal sectors, both along the disc margin and in the parapapillary region (at a mean contour line radius of 1.7 mm). Each sector was evaluated individually and in combination with other sectors. Gaussian support vector machine (SVM) learning classifiers were used to interpret HRT sector measurements along the disc margin and in the parapapillary region, to differentiate between eyes with normal and glaucomatous visual fields and to compare the results with global and regional HRT parameter measurements. The area under the receiver operating characteristic (ROC) curve was used to measure diagnostic performance of the HRT parameters and to evaluate the cross-validation strategies and forward selection and backward elimination optimization techniques that were used to generate the reduced feature sets. RESULTS. The area under the ROC curve for mean height contour of the 36 sectors along the disc margin was larger than that for the mean height contour in the parapapillary region (0.97 and 0.85, respectively). Of the 36 individual sectors along the disc margin, those in the inferior region between 240° and 300°, had the largest area under the ROC curve (0.85‐ 0.91). With SVM Gaussian techniques, the regional parameters showed the best ability to discriminate between normal eyes and eyes with glaucomatous visual field damage, followed by the global parameters, mean height contour measures along the disc margin, and mean height contour measures in the parapapillary region. The area under the ROC curve was 0.98, 0.94, 0.93, and 0.85, respectively. Cross-validation and optimization techniques demonstrated that good discrimination (99% of peak area under the ROC curve) can be obtained with a reduced number of HRT parameters. CONCLUSIONS. Mean height contour measurements along the disc margin discriminated between normal and glaucomatous eyes better than measurements obtained in the parapapillary region. (Invest Ophthalmol Vis Sci. 2004;45:3144 ‐3151) DOI

PURPOSE To determine whether Heidelberg Retina Tomograph (HRT; Heidelberg Engineering, Dossenheim, Germany) classification techniques and investigational support vector machine (SVM) analyses can detect optic disc abnormalities in glaucoma-suspect eyes before the development of visual field abnormalities. METHODS Glaucoma-suspect eyes (n = 226) were classified as converts or nonconverts based on the development of repeatable (either two or three consecutive) standard automated perimetry (SAP)-detected abnormalities over the course of the study (mean follow-up, approximately 4.5 years). Hazard ratios for development of SAP abnormalities were calculated based on baseline classification results, follow-up time, and end point status (convert, nonconvert). Classification techniques applied were HRT classification (HRTC), Moorfields Regression Analysis, forward-selection optimized SVM (SVM fwd) and backward elimination-optimized SVM (SVM back) analysis of HRT data, and stereophotograph assessment. RESULTS Univariate analyses indicated that all classification techniques were predictors of the development of two repeatable abnormal SAP results, with hazards ratios (95% confidence interval [CI]) ranging from 1.32 (1.00-1.75) for HRTC to 2.0 (1.48-2.76) for stereophotograph assessment (all P < or = 0.05). Only SVM (SVM fwd and SVM back) analysis of HRT data and stereophotograph assessment were univariate predictors of the development of three repeatable abnormal SAP results, with hazard ratios (95% CI) ranging from 1.73 (1.16-2.82) for SVM fwd to 1.82 (1.19-3.12) for SVM back (both P < 0.007). Multivariate analyses including each classification technique individually in a model with age, baseline SAP pattern standard deviation [PSD], and baseline IOP indicated that all classification techniques except HRTC (P = 0.06) were predictors of the development of two repeatable abnormal SAP results with hazards ratios ranging from 1.30 (0.99, 1.73) for HRTC to 1.90 (1.37, 2.69) for stereophotograph assessment. Only SVM (SVM fwd and SVM back) analysis of HRT data and stereophotograph assessment were significant predictors of the development of three repeatable abnormal SAP results in multivariate analyses; hazard ratios of 1.57 (1.03, 2.59) and 1.70 (1.18, 2.51), respectively. SAP PSD was a significant predictor of two repeatable abnormal SAP results in multivariate models with all classification techniques, with hazard ratios ranging from 3.31 (1.39, 7.89) to 4.70 (2.02, 10.93) per 1-dB increase. CONCLUSIONS HRT classifications techniques and stereophotograph assessment can detect optic disc topography abnormalities in glaucoma-suspect eyes before the development of SAP abnormalities. These data support strongly the importance of optic disc examination for early glaucoma diagnosis.