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Architecture for Automatic GLaucoma

Diagnosis and Its Genetic Association Study through Medical Image InformAtics

(AGLAIA)Jimmy Liu Jiang1, Zhang Zhuo1, Wong Wing Kee1, Tan Ngan Meng1, Yin Feng Shou1, Lee Benghai1, Cheng Jun1, Wong Tien Yin2

1: Institute for Infocomm Research, Agency for Science, Technology and Research (A*STAR), Singapore2: Singapore Eye Research Institute

AGLAIA Single statement

A system for the automated detection of glaucoma from multiple image features of retinal images with possible genetic analysis.

Glaucoma Has No Cure!

Glaucoma Irreversible loss of optic nerves Leading to blindness 5.7 million glaucoma blind (total 38 million blind in the

world)

BUT: glaucoma can be slowed if detected early Vision loss (functional) Optic nerve damage (imaging)

Optic Nerve Damage Precedes Vision Loss

No Glaucoma Early Late Stage

Nerve Damaged Severe

Vision Loss

Optic Nerve

Pictures from NIH

Measure Optic Nerve Damage from Retinal Image - CDR CDR (Cup to Disc Ratio) value is an

important indicator for Glaucoma

Automatic CDR measurement Saving clinician’s time Results reproducible Ideal for mass screening

DiscCup

Step 1: Disc segmentation

Step 2: Boundary smoothing of the detected disc

Step 3: Cup segmentation

Step 4: Boundary smoothing of the detected cup

Step 5: Intelligent Fusion

AGLAIA

AGLAIA Framework

Fundus imageFundus image

Genome data

Genome data

Clinical dataClinical data

Intelligentfusion

Glaucoma riskanalysis Report

GWAS

CDR

HemorrhageNotching

PPA KinkRim

Asymmetry

Clinical dataClinical data

MINING

Gradeability Disc Size

Tilted Disc

ISNT RuleVessel Pattern

RNFL

Fundus imageFundus image

Genome data

Genome data

Clinical dataClinical data

Intelligentfusion

Glaucoma riskanalysis Report

GWAS

CDR

HemorrhageNotching

PPA KinkRim

Asymmetry

Clinical dataClinical data

MINING

Gradeability Disc Size

Tilted Disc

ISNT RuleVessel Pattern

RNFL

13 Image cues used in AGLAIAAGLAIA aims to provide a multi-modality system that captures globally a range of

parameter that is indicative of early glaucoma damage. AGLAIA will automatically measure and assess the following features objectively and quantitatively, features which are currently evaluated subjectively by glaucoma specialist in clinical practice: Cup-to-disc ratio (CDR) – further refinement will be made based on initial algorithms

developed in ARGALI Disc hemorrhage (DH) Thinning of the NRR (NeuroRetinal Rim) Notching of the NRR Compliance of NRR width by ‘ISNT Rule’ (inferior≥superior≥nasal≥temporal) Inter-eye asymmetry Parapapillary atrophy (PPA) Blood vessel pattern analysis Blood vessel kink analysis Tilted Disc - quantify the degree of tilting based on the disc contour Disc Size - automatically classify disc size to "large, medium or small" categories based on

automatic disc measurement Gradeability – analyze the image and determine gradeability Check the presence of RNFL (Retinal Nerve Fiber Layer) defect.

Image Datasets

Datasets used for testing Retinal Vessel and Glaucoma Subtype Study

(RVGSS) 65 glaucoma images

Singapore Indian Chinese Cohort (SICC) 224 non-glaucoma images

Clinical CDR provided

Test Result Summary

Specificity 0.88

Sensitivity 0.95

Average absolute CDR error (wrt clinical CDR) 0.14

AGLAIA Market Potential

The Technology can be readily implemented in currently available instruments for ocular screening without extensive modifications.

The Technology could potentially be of interest to ocular instrument makers to incorporate the Technology into their equipment, and to health institutions such as clinics and hospitals for glaucoma screening.

AGLALI CDR Absolute Error Distribution

Error Interval

Receiver Operating Characteristic (ROC) Curve

AUC Sensitivity Specificity ICC Maximum Std. Deviation

0.94 0.954 0.88 0.553 0.65 0.12