title: Automated drusen detection in retinal images using analytical modelling algorithms.
abstract: BACKGROUND
  Drusen are common features in the ageing macula associated with exudative Age-Related Macular Degeneration (ARMD). They are visible in retinal images and their quantitative analysis is important in the follow up of the ARMD. However, their evaluation is fastidious and difficult to reproduce when performed manually.
  
  
  METHODS
  This article proposes a methodology for Automatic Drusen Deposits Detection and quantification in Retinal Images (AD3RI) by using digital image processing techniques. It includes an image pre-processing method to correct the uneven illumination and to normalize the intensity contrast with smoothing splines. The drusen detection uses a gradient based segmentation algorithm that isolates drusen and provides basic drusen characterization to the modelling stage. The detected drusen are then fitted by Modified Gaussian functions, producing a model of the image that is used to evaluate the affected area.Twenty two images were graded by eight experts, with the aid of a custom made software and compared with AD3RI. This comparison was based both on the total area and on the pixel-to-pixel analysis. The coefficient of variation, the intraclass correlation coefficient, the sensitivity, the specificity and the kappa coefficient were calculated.
  
  
  RESULTS
  The ground truth used in this study was the experts' average grading. In order to evaluate the proposed methodology three indicators were defined: AD3RI compared to the ground truth (A2G); each expert compared to the other experts (E2E) and a standard Global Threshold method compared to the ground truth (T2G).The results obtained for the three indicators, A2G, E2E and T2G, were: coefficient of variation 28.8 %, 22.5 % and 41.1 %, intraclass correlation coefficient 0.92, 0.88 and 0.67, sensitivity 0.68, 0.67 and 0.74, specificity 0.96, 0.97 and 0.94, and kappa coefficient 0.58, 0.60 and 0.49, respectively.
  
  
  CONCLUSIONS
  The gradings produced by AD3RI obtained an agreement with the ground truth similar to the experts (with a higher reproducibility) and significantly better than the Threshold Method. Despite the higher sensitivity of the Threshold method, explained by its over segmentation bias, it has lower specificity and lower kappa coefficient. Therefore, it can be concluded that AD3RI accurately quantifies drusen, using a reproducible method with benefits for ARMD evaluation and follow-up.
authors.affiliation: Center of Technologies and Systems, Uninova, Campus da FCT-UNL, 2829-516 Caparica, Portugal. atbdm@fct.unl.pt
authors.forename: André D
authors.initials: AD
authors.lastname: Mora
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Vieira
authors.forename: Ayyakkannu
authors.initials: A
authors.lastname: Manivannan
authors.forename: José M
authors.initials: JM
authors.lastname: Fonseca
mesh_terms: D000465:Algorithms; D003941:Diagnostic Techniques, Ophthalmological; D005654:Fundus Oculi; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008266:Macula Lutea / Q000473:pathology; D008268:Macular Degeneration / Q000175:diagnosis* / Q000473:pathology*; D008954:Models, Biological; D015203:Reproducibility of Results; D015593:Retinal Drusen / Q000175:diagnosis*; D012680:Sensitivity and Specificity