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  1. Maheshwari S, Kanhangad V, Pachori RB, Bhandary SV, Acharya UR
    Comput Biol Med, 2019 Feb;105:72-80.
    PMID: 30590290 DOI: 10.1016/j.compbiomed.2018.11.028
    BACKGROUND AND OBJECTIVE: Glaucoma is a ocular disorder which causes irreversible damage to the retinal nerve fibers. The diagnosis of glaucoma is important as it may help to slow down the progression. The available clinical methods and imaging techniques are manual and require skilled supervision. For the purpose of mass screening, an automated system is needed for glaucoma diagnosis which is fast, accurate, and helps in reducing the burden on experts.

    METHODS: In this work, we present a bit-plane slicing (BPS) and local binary pattern (LBP) based novel approach for glaucoma diagnosis. Firstly, our approach separates the red (R), green (G), and blue (B) channels from the input color fundus image and splits the channels into bit planes. Secondly, we extract LBP based statistical features from each of the bit planes of the individual channels. Thirdly, these features from the individual channels are fed separately to three different support vector machines (SVMs) for classification. Finally, the decisions from the individual SVMs are fused at the decision level to classify the input fundus image into normal or glaucoma class.

    RESULTS: Our experimental results suggest that the proposed approach is effective in discriminating normal and glaucoma cases with an accuracy of 99.30% using 10-fold cross validation.

    CONCLUSIONS: The developed system is ready to be tested on large and diverse databases and can assist the ophthalmologists in their daily screening to confirm their diagnosis, thereby increasing accuracy of diagnosis.

  2. Raghavendra U, Gudigar A, Bhandary SV, Rao TN, Ciaccio EJ, Acharya UR
    J Med Syst, 2019 Jul 30;43(9):299.
    PMID: 31359230 DOI: 10.1007/s10916-019-1427-x
    Glaucoma is a type of eye condition which may result in partial or consummate vision loss. Higher intraocular pressure is the leading cause for this condition. Screening for glaucoma and early detection can avert vision loss. Computer aided diagnosis (CAD) is an automated process with the potential to identify glaucoma early through quantitative analysis of digital fundus images. Preparing an effective model for CAD requires a large database. This study presents a CAD tool for the precise detection of glaucoma using a machine learning approach. An autoencoder is trained to determine effective and important features from fundus images. These features are used to develop classes of glaucoma for testing. The method achieved an F - measure value of 0.95 utilizing 1426 digital fundus images (589 control and 837 glaucoma). The efficacy of the system is evident, and is suggestive of its possible utility as an additional tool for verification of clinical decisions.
  3. Acharya UR, Bhat S, Koh JEW, Bhandary SV, Adeli H
    Comput Biol Med, 2017 Sep 01;88:72-83.
    PMID: 28700902 DOI: 10.1016/j.compbiomed.2017.06.022
    Glaucoma is an optic neuropathy defined by characteristic damage to the optic nerve and accompanying visual field deficits. Early diagnosis and treatment are critical to prevent irreversible vision loss and ultimate blindness. Current techniques for computer-aided analysis of the optic nerve and retinal nerve fiber layer (RNFL) are expensive and require keen interpretation by trained specialists. Hence, an automated system is highly desirable for a cost-effective and accurate screening for the diagnosis of glaucoma. This paper presents a new methodology and a computerized diagnostic system. Adaptive histogram equalization is used to convert color images to grayscale images followed by convolution of these images with Leung-Malik (LM), Schmid (S), and maximum response (MR4 and MR8) filter banks. The basic microstructures in typical images are called textons. The convolution process produces textons. Local configuration pattern (LCP) features are extracted from these textons. The significant features are selected using a sequential floating forward search (SFFS) method and ranked using the statistical t-test. Finally, various classifiers are used for classification of images into normal and glaucomatous classes. A high classification accuracy of 95.8% is achieved using six features obtained from the LM filter bank and the k-nearest neighbor (kNN) classifier. A glaucoma integrative index (GRI) is also formulated to obtain a reliable and effective system.
  4. Maheshwari S, Pachori RB, Kanhangad V, Bhandary SV, Acharya UR
    Comput Biol Med, 2017 Sep 01;88:142-149.
    PMID: 28728059 DOI: 10.1016/j.compbiomed.2017.06.017
    Glaucoma is one of the leading causes of permanent vision loss. It is an ocular disorder caused by increased fluid pressure within the eye. The clinical methods available for the diagnosis of glaucoma require skilled supervision. They are manual, time consuming, and out of reach of common people. Hence, there is a need for an automated glaucoma diagnosis system for mass screening. In this paper, we present a novel method for an automated diagnosis of glaucoma using digital fundus images. Variational mode decomposition (VMD) method is used in an iterative manner for image decomposition. Various features namely, Kapoor entropy, Renyi entropy, Yager entropy, and fractal dimensions are extracted from VMD components. ReliefF algorithm is used to select the discriminatory features and these features are then fed to the least squares support vector machine (LS-SVM) for classification. Our proposed method achieved classification accuracies of 95.19% and 94.79% using three-fold and ten-fold cross-validation strategies, respectively. This system can aid the ophthalmologists in confirming their manual reading of classes (glaucoma or normal) using fundus images.
  5. Koh JEW, Ng EYK, Bhandary SV, Hagiwara Y, Laude A, Acharya UR
    Comput Biol Med, 2018 01 01;92:204-209.
    PMID: 29227822 DOI: 10.1016/j.compbiomed.2017.11.019
    Untreated age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma may lead to irreversible vision loss. Hence, it is essential to have regular eye screening to detect these eye diseases at an early stage and to offer treatment where appropriate. One of the simplest, non-invasive and cost-effective techniques to screen the eyes is by using fundus photo imaging. But, the manual evaluation of fundus images is tedious and challenging. Further, the diagnosis made by ophthalmologists may be subjective. Therefore, an objective and novel algorithm using the pyramid histogram of visual words (PHOW) and Fisher vectors is proposed for the classification of fundus images into their respective eye conditions (normal, AMD, DR, and glaucoma). The proposed algorithm extracts features which are represented as words. These features are built and encoded into a Fisher vector for classification using random forest classifier. This proposed algorithm is validated with both blindfold and ten-fold cross-validation techniques. An accuracy of 90.06% is achieved with the blindfold method, and highest accuracy of 96.79% is obtained with ten-fold cross-validation. The highest classification performance of our system shows the potential of deploying it in polyclinics to assist healthcare professionals in their initial diagnosis of the eye. Our developed system can reduce the workload of ophthalmologists significantly.
  6. Addoor KR, Krishna RA, Bhandary SV, Khanna R, Rao LG, Lingam KD, et al.
    Med J Malaysia, 2011 Mar;66(1):48-52.
    PMID: 23765143 MyJurnal
    In view of the alarming increase in the incidence of diabetes mellitus in Malaysia, we conducted a study to assess the awareness of complications of diabetes among the diabetics attending the peripheral clinics in Melaka. The study period was from January 2007 to December 2007. 351 patients were included in the study. 79.8% were aware of the complications of diabetes mellitus and 87.2% were aware that diabetes can affect the eyes. However, only 50% of the patients underwent an ophthalmological evaluation. Although awareness was good, the motivation to undergo the assessment was poor.
    Study site: Klinik Kesihatan Peringgit, Klinik Kommunity Ayer Keroh, Melaka, Malaysia
  7. Mookiah MR, Acharya UR, Fujita H, Tan JH, Chua CK, Bhandary SV, et al.
    Comput Biol Med, 2015 Nov 1;66:295-315.
    PMID: 26453760 DOI: 10.1016/j.compbiomed.2015.09.012
    Diabetic Macular Edema (DME) is caused by accumulation of extracellular fluid from hyperpermeable capillaries within the macula. DME is one of the leading causes of blindness among Diabetes Mellitus (DM) patients. Early detection followed by laser photocoagulation can save the visual loss. This review discusses various imaging modalities viz. biomicroscopy, Fluorescein Angiography (FA), Optical Coherence Tomography (OCT) and colour fundus photographs used for diagnosis of DME. Various automated DME grading systems using retinal fundus images, associated retinal image processing techniques for fovea, exudate detection and segmentation are presented. We have also compared various imaging modalities and automated screening methods used for DME grading. The reviewed literature indicates that FA and OCT identify DME related changes accurately. FA is an invasive method, which uses fluorescein dye, and OCT is an expensive imaging method compared to fundus photographs. Moreover, using fundus images DME can be identified and automated. DME grading algorithms can be implemented for telescreening. Hence, fundus imaging based DME grading is more suitable and affordable method compared to biomicroscopy, FA, and OCT modalities.
  8. Acharya UR, Sudarshan VK, Rong SQ, Tan Z, Lim CM, Koh JE, et al.
    Comput Biol Med, 2017 06 01;85:33-42.
    PMID: 28433870 DOI: 10.1016/j.compbiomed.2017.04.013
    An accurate detection of preterm labor and the risk of preterm delivery before 37 weeks of gestational age is crucial to increase the chance of survival rate for both mother and the infant. Thus, the uterine contractions measured using uterine electromyogram (EMG) or electro hysterogram (EHG) need to have high sensitivity in the detection of true preterm labor signs. However, visual observation and manual interpretation of EHG signals at the time of emergency situation may lead to errors. Therefore, the employment of computer-based approaches can assist in fast and accurate detection during the emergency situation. This work proposes a novel algorithm using empirical mode decomposition (EMD) combined with wavelet packet decomposition (WPD), for automated prediction of pregnant women going to have premature delivery by using uterine EMG signals. The EMD is performed up to 11 levels on the normal and preterm EHG signals to obtain the different intrinsic mode functions (IMFs). These IMFs are further subjected to 6 levels of WPD and from the obtained coefficients, eight different features are extracted. From these extracted features, only the significant features are selected using particle swarm optimization (PSO) method and selected features are ranked by Bhattacharyya technique. All the ranked features are fed to support vector machine (SVM) classifier for automated differentiation and achieved an accuracy of 96.25%, sensitivity of 95.08%, and specificity of 97.33% using only ten EHG signal features. Our proposed algorithm can be used in gynecology departments of hospitals to predict the preterm or normal delivery of pregnant women.
  9. Acharya UR, Mookiah MRK, Koh JEW, Tan JH, Bhandary SV, Rao AK, et al.
    Comput Biol Med, 2017 05 01;84:59-68.
    PMID: 28343061 DOI: 10.1016/j.compbiomed.2017.03.016
    The cause of diabetic macular edema (DME) is due to prolonged and uncontrolled diabetes mellitus (DM) which affects the vision of diabetic subjects. DME is graded based on the exudate location from the macula. It is clinically diagnosed using fundus images which is tedious and time-consuming. Regular eye screening and subsequent treatment may prevent the vision loss. Hence, in this work, a hybrid system based on Radon transform (RT), discrete wavelet transform (DWT) and discrete cosine transform (DCT) are proposed for an automated detection of DME. The fundus images are subjected to RT to obtain sinograms and DWT is applied on these sinograms to extract wavelet coefficients (approximate, horizontal, vertical and diagonal). DCT is applied on approximate coefficients to obtain 2D-DCT coefficients. Further, these coefficients are converted into 1D vector by arranging the coefficients in zig-zag manner. This 1D signal is subjected to locality sensitive discriminant analysis (LSDA). Finally, various supervised classifiers are used to classify the three classes using significant features. Our proposed technique yielded a classification accuracy of 100% and 97.01% using two and seven significant features for private and public (MESSIDOR) databases respectively. Also, a maculopathy index is formulated with two significant parameters to discriminate the three groups distinctly using a single integer. Hence, our obtained results suggest that this system can be used as an eye screening tool for diabetic subjects for DME.
  10. Hagiwara Y, Koh JEW, Tan JH, Bhandary SV, Laude A, Ciaccio EJ, et al.
    Comput Methods Programs Biomed, 2018 Oct;165:1-12.
    PMID: 30337064 DOI: 10.1016/j.cmpb.2018.07.012
    BACKGROUND AND OBJECTIVES: Glaucoma is an eye condition which leads to permanent blindness when the disease progresses to an advanced stage. It occurs due to inappropriate intraocular pressure within the eye, resulting in damage to the optic nerve. Glaucoma does not exhibit any symptoms in its nascent stage and thus, it is important to diagnose early to prevent blindness. Fundus photography is widely used by ophthalmologists to assist in diagnosis of glaucoma and is cost-effective.

    METHODS: The morphological features of the disc that is characteristic of glaucoma are clearly seen in the fundus images. However, manual inspection of the acquired fundus images may be prone to inter-observer variation. Therefore, a computer-aided detection (CAD) system is proposed to make an accurate, reliable and fast diagnosis of glaucoma based on the optic nerve features of fundus imaging. In this paper, we reviewed existing techniques to automatically diagnose glaucoma.

    RESULTS: The use of CAD is very effective in the diagnosis of glaucoma and can assist the clinicians to alleviate their workload significantly. We have also discussed the advantages of employing state-of-art techniques, including deep learning (DL), when developing the automated system. The DL methods are effective in glaucoma diagnosis.

    CONCLUSIONS: Novel DL algorithms with big data availability are required to develop a reliable CAD system. Such techniques can be employed to diagnose other eye diseases accurately.

  11. Acharya UR, Mookiah MR, Koh JE, Tan JH, Bhandary SV, Rao AK, et al.
    Comput Biol Med, 2016 08 01;75:54-62.
    PMID: 27253617 DOI: 10.1016/j.compbiomed.2016.04.015
    Posterior Segment Eye Diseases (PSED) namely Diabetic Retinopathy (DR), glaucoma and Age-related Macular Degeneration (AMD) are the prime causes of vision loss globally. Vision loss can be prevented, if these diseases are detected at an early stage. Structural abnormalities such as changes in cup-to-disc ratio, Hard Exudates (HE), drusen, Microaneurysms (MA), Cotton Wool Spots (CWS), Haemorrhages (HA), Geographic Atrophy (GA) and Choroidal Neovascularization (CNV) in PSED can be identified by manual examination of fundus images by clinicians. However, manual screening is labour-intensive, tiresome and time consuming. Hence, there is a need to automate the eye screening. In this work Bi-dimensional Empirical Mode Decomposition (BEMD) technique is used to decompose fundus images into 2D Intrinsic Mode Functions (IMFs) to capture variations in the pixels due to morphological changes. Further, various entropy namely Renyi, Fuzzy, Shannon, Vajda, Kapur and Yager and energy features are extracted from IMFs. These extracted features are ranked using Chernoff Bound and Bhattacharyya Distance (CBBD), Kullback-Leibler Divergence (KLD), Fuzzy-minimum Redundancy Maximum Relevance (FmRMR), Wilcoxon, Receiver Operating Characteristics Curve (ROC) and t-test methods. Further, these ranked features are fed to Support Vector Machine (SVM) classifier to classify normal and abnormal (DR, AMD and glaucoma) classes. The performance of the proposed eye screening system is evaluated using 800 (Normal=400 and Abnormal=400) digital fundus images and 10-fold cross validation method. Our proposed system automatically identifies normal and abnormal classes with an average accuracy of 88.63%, sensitivity of 86.25% and specificity of 91% using 17 optimal features ranked using CBBD and SVM-Radial Basis Function (RBF) classifier. Moreover, a novel Retinal Risk Index (RRI) is developed using two significant features to distinguish two classes using single number. Such a system helps to reduce eye screening time in polyclinics or community-based mass screening. They will refer the patients to main hospitals only if the diagnosis belong to the abnormal class. Hence, the main hospitals will not be unnecessarily crowded and doctors can devote their time for other urgent cases.
  12. Acharya UR, Mookiah MR, Koh JE, Tan JH, Noronha K, Bhandary SV, et al.
    Comput Biol Med, 2016 06 01;73:131-40.
    PMID: 27107676 DOI: 10.1016/j.compbiomed.2016.04.009
    Age-related Macular Degeneration (AMD) affects the central vision of aged people. It can be diagnosed due to the presence of drusen, Geographic Atrophy (GA) and Choroidal Neovascularization (CNV) in the fundus images. It is labor intensive and time-consuming for the ophthalmologists to screen these images. An automated digital fundus photography based screening system can overcome these drawbacks. Such a safe, non-contact and cost-effective platform can be used as a screening system for dry AMD. In this paper, we are proposing a novel algorithm using Radon Transform (RT), Discrete Wavelet Transform (DWT) coupled with Locality Sensitive Discriminant Analysis (LSDA) for automated diagnosis of AMD. First the image is subjected to RT followed by DWT. The extracted features are subjected to dimension reduction using LSDA and ranked using t-test. The performance of various supervised classifiers namely Decision Tree (DT), Support Vector Machine (SVM), Probabilistic Neural Network (PNN) and k-Nearest Neighbor (k-NN) are compared to automatically discriminate to normal and AMD classes using ranked LSDA components. The proposed approach is evaluated using private and public datasets such as ARIA and STARE. The highest classification accuracy of 99.49%, 96.89% and 100% are reported for private, ARIA and STARE datasets. Also, AMD index is devised using two LSDA components to distinguish two classes accurately. Hence, this proposed system can be extended for mass AMD screening.
  13. Mookiah MR, Acharya UR, Fujita H, Koh JE, Tan JH, Noronha K, et al.
    Comput Biol Med, 2015 Aug;63:208-18.
    PMID: 26093788 DOI: 10.1016/j.compbiomed.2015.05.019
    Age-related Macular Degeneration (AMD) is an irreversible and chronic medical condition characterized by drusen, Choroidal Neovascularization (CNV) and Geographic Atrophy (GA). AMD is one of the major causes of visual loss among elderly people. It is caused by the degeneration of cells in the macula which is responsible for central vision. AMD can be dry or wet type, however dry AMD is most common. It is classified into early, intermediate and late AMD. The early detection and treatment may help one to stop the progression of the disease. Automated AMD diagnosis may reduce the screening time of the clinicians. In this work, we have introduced LCP to characterize normal and AMD classes using fundus images. Linear Configuration Coefficients (CC) and Pattern Occurrence (PO) features are extracted from fundus images. These extracted features are ranked using p-value of the t-test and fed to various supervised classifiers viz. Decision Tree (DT), Nearest Neighbour (k-NN), Naive Bayes (NB), Probabilistic Neural Network (PNN) and Support Vector Machine (SVM) to classify normal and AMD classes. The performance of the system is evaluated using both private (Kasturba Medical Hospital, Manipal, India) and public domain datasets viz. Automated Retinal Image Analysis (ARIA) and STructured Analysis of the Retina (STARE) using ten-fold cross validation. The proposed approach yielded best performance with a highest average accuracy of 97.78%, sensitivity of 98.00% and specificity of 97.50% for STARE dataset using 22 significant features. Hence, this system can be used as an aiding tool to the clinicians during mass eye screening programs to diagnose AMD.
  14. Koh JEW, Acharya UR, Hagiwara Y, Raghavendra U, Tan JH, Sree SV, et al.
    Comput Biol Med, 2017 05 01;84:89-97.
    PMID: 28351716 DOI: 10.1016/j.compbiomed.2017.03.008
    Vision is paramount to humans to lead an active personal and professional life. The prevalence of ocular diseases is rising, and diseases such as glaucoma, Diabetic Retinopathy (DR) and Age-related Macular Degeneration (AMD) are the leading causes of blindness in developed countries. Identifying these diseases in mass screening programmes is time-consuming, labor-intensive and the diagnosis can be subjective. The use of an automated computer aided diagnosis system will reduce the time taken for analysis and will also reduce the inter-observer subjective variabilities in image interpretation. In this work, we propose one such system for the automatic classification of normal from abnormal (DR, AMD, glaucoma) images. We had a total of 404 normal and 1082 abnormal fundus images in our database. As the first step, 2D-Continuous Wavelet Transform (CWT) decomposition on the fundus images of two classes was performed. Subsequently, energy features and various entropies namely Yager, Renyi, Kapoor, Shannon, and Fuzzy were extracted from the decomposed images. Then, adaptive synthetic sampling approach was applied to balance the normal and abnormal datasets. Next, the extracted features were ranked according to the significances using Particle Swarm Optimization (PSO). Thereupon, the ranked and selected features were used to train the random forest classifier using stratified 10-fold cross validation. Overall, the proposed system presented a performance rate of 92.48%, and a sensitivity and specificity of 89.37% and 95.58% respectively using 15 features. This novel system shows promise in detecting abnormal fundus images, and hence, could be a valuable adjunct eye health screening tool that could be employed in polyclinics, and thereby reduce the workload of specialists at hospitals.
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