CHAPTER - 1

INTRODUCTION
Medical imaging has revolutionized the medicine by providing costefficient healthcare and effective diagnosis in all major disease areas.
Medical imaging allows scientists and physicians to understand
potential life-saving information using less invasive techniques.
In medical imaging the quality of the image acquisition and the
image interpretation determines the accuracy of diagnosis. Computers
have a huge impact on the acquisition of medical images. They
perform multi-pronged functions like controlling imaging hardware,
performing reconstruction, post-processing of the image data and
storing the scans. In contrast, the role of computers in the
interpretation

of

medical

images

has

so

far

been

limited.

Interpretation remains an almost exclusively human domain.

Recent years have witnessed pioneering work in the area of medical
imaging. Applications that can interpret an image are being developed,
which in turn can aid a physician in detecting possible subtle
abnormalities. The computer indicates places in the image that
require extra attention from the physician because they could be
abnormal. These technologies are called Computer Aided Diagnosis
(CAD). Studies on CAD systems show that CAD can be helpful to
improve diagnostic accuracy of physicians and lighten the burden of

increasing workload. The most established CAD applications in

medical fields are the use of automated systems in mammography,
chest computed tomography and radiography.
This thesis describes components of an automatic system that can
aid in the detection of diabetic retinopathy. Diabetic retinopathy is an
eye disease and a general complication of diabetes that causes vision
loss, if left undiagnosed at the initial stage. As the number of diabetes
affected people is increasing worldwide, the need for automated
detection methods of diabetic retinopathy will increase as well. To
automatically detect diabetic retinopathy, a computer has to interpret
and analyze digital images of the retina.
The Fundus Image Analysis system described in this thesis is
developed to assist ophthalmologists diagnosis by providing second
opinion and also functions as an automatic tool for the mass
screening of diabetic retinopathy. Colour fundus images are used by
ophthalmologists to study eye diseases like diabetic retinopathy.
Extraction of the normal features like optic disk, fovea and blood
vessels; and abnormal features like exudates, cottonwool spots,
microaneurysms and hemorrhages from colour fundus images are
used in fundus image analysis system for comprehensive analysis and
grading of diabetic retinopathy. This CAD system also provides the
spatial distribution of abnormalities based on fovea such that an
ophthalmologist can make a detailed diagnosis.

This introductory Chapter presents some background information

on the anatomy of the eye, diabetic retinopathy, and diabetic
retinopathy screening.

1.1. ANATOMY OF THE EYE

The human eye functions like a camera. Human eye receives light,
converting it into an electric signal and transmitting the same to the
brain with the help of optic nerve where the electrical signal is
converted into vision. Figure 1.1 illustrates the cross-section of
human eye and points out its major components. Amongst the various
ocular structures, only the anatomical parts of the retina are
explained which are more appropriate to this research work.
Light enters the human eye through the pupil and is directed on
the retina that is similar to a camera film. Like film, the retina is
comprised of several layers with different functions. The first layer
that receives light is called the nerve fiber layer. The majority of the
retinal blood vessels are under this layer which nourishes the internal
parts of the retina. The outermost layer contains millions of
photoreceptors responsible for receiving light rays, converting them
into electrical impulses. These electrical impulses are transformed into
images when they are transmitted to the brain.
The outlying parts of the retina are responsible for peripheral
vision. Macula is the central area of the retina, temporal to the optic
disk. It is responsible to have fine central vision and colour vision.
The center of macula is called fovea. This region of the retina is the

Fig1.1. A Cross Section of the Human Eye

most sensitive region. The diameter of the macula is about 4 to 5 mm,

which enable us in appreciating details and performing tasks, like
reading.
Optic disk (or optic nerve head) is the bright yellowish disk, from
which, blood vessels and optic nerve fibres emerge. Optic disk
transmits electrical impulses from the retina to the brain and it is
about 3mm nasal to fovea. It measures 1.5 to 2 mm in diameter.
The retinal blood vessels are originated from the central retinal
artery and vein that lie in the optic nerve head. These blood vessels
nourish the internal parts of retina and radiate out from the optic
disk. Fig.1.2 shows a typical normal retina image with highlighted
areas of macula, fovea, optic disk and blood vessels.

Fig.1.2. A Typical Retinal Image from the Left Eye Showing Retinal
Vasculature, Optic Disk, Macula and Fovea.

1.2. DIABETIC RETINOPATHY

Diabetic retinopathy is the prime cause of vision loss amongst the
working age population of the developing and the developed countries.
Diabetic patients are 25 times more probable to become blind than
non-diabetic patients [1]. Diabetic retinopathy is a complication of
diabetes to the retina. Both the forms of diabetes i.e. diabetes mellitus
and diabetes insepidous, leads to diabetic retinopathy eventually after
some time. It is a very asymptomatic disease in the early stages and it
could lead to permanent vision loss if untreated for long time. The
problem here is the patients may not know about it until it reaches
advanced stages. Once it reaches advanced stages vision loss becomes

inevitable. As diabetic retinopathy is the third major cause of

blindness particularly in India, there is an immediate requirement to
develop efficient diagnosis methods for this problem. The age of onset
and the duration of the diabetes are the two most important issues
that determine the incidence of diabetic retinopathy. Among the
patients below the age of 30 years, when first diagnosed with diabetes,
the prevalence is 17% during the first 5 years. This increases to 97%
after 15 years of diabetes [2]. Amongst the patients above the age of
30 years at the onset of diabetes, 20% have showed signs of
retinopathy immediately after presentation and this increased to 78%
after 15 years of diabetes [3].
Diabetic retinopathy occurs because of microangiopathy which in
turn affects the retinal precapillary arterioles, capillaries and venules.
It is caused by microvascular leakages from the breakdown of the
internal blood-retinal barrier and microvascular occlusion. Due to the
progressive damage of the microvascular system, loss of vision and
blindness can occur as shown in Fig. 1.3.
Microaneurysms are the first clinically noticeable signs of diabetic
retinopathy. They appear as small red dots of 10 to 100 microns
diameter. Microaneurysms exist normally temporal to the macula
(Fig. 1.4(a)). Microaneurysms arise due to high sugar levels in the
blood which causes the walls of tiny blood vessels to distend.
As the disease progresses, microaneurysms will be ruptured. This
results in retinal hemorrhages either superficially or in deeper layers
of the retina (Fig. 1.4(a)). As the retinal blood vessels become more

Fig.1.3. Effect of Diabetic Retinopathy on Vision (a) Without

Retinopathy (b) With Retinopathy

damaged

and

permeable,

their

number

will

increase.

Retinal

hemorrhages look either as small red dots or blots identical to

microaneurysms or as larger flame-shaped hemorrhages.
The vessels besides leaking blood also cause the leakage of lipids
and proteins paving way for the appearance of small bright dots called
exudates (Fig. 1.4(b)). They are seen on the retina as typical bright,
reflective white or cream coloured lesions that indicate increased
blood vessel permeability and an allied risk of retinal edema. If this
takes place on the macula region vision may be lost.
As the disease advances further, multiple small patches of the
retina become ischemic deprived of blood. These ischemic regions are
observable on the retina as fluffy whitish blobs called cottonwool spots
(Fig. 1.4(c)). As a response to the development of ischemic areas, the
eye starts growing new blood vessels to provide more oxygen to the
retina. These newly grown blood vessels, called Neovascularization,

(a)

(b)

(c)

Fig.1.4. Abnormal Diabetic Retinopathy Images (a) An Image

Containing Microaneurysms and Hemorrhages (b) Diabetic
Retinopathy with Retinal Exudates in Macula Region (c) Diabetic
Retinopathy with Cottonwool Spots.

are delicate and weak having a greater risk of rupturing. These newly
developed blood vessels cause large hemorrhages than normal vessels.

1.3. SCREENING FOR DIABETIC RETINOPATHY

According to recent reports incidence of diabetes is about 12 to
14% in the urban population of India of which over 20% of patients
are likely to be suffering from diabetic retinopathy [4]. In the rural
population, the prevalence of diabetes is about 5%. Early detection of
diabetic retinopathy and treatment can prevent visual impairment and
most of the patients can be saved from vision loss. Screening is an
effective way for early detection of diabetic retinopathy. Studies have
revealed that people who suffer from diabetes benefit from regularly
attending a screening session [5-7]. In this screening session the
retinas of both eyes are examined by an ophthalmologist and if
diabetic retinopathy is detected the patient can be followed up.
Examples of large scale screening programs conducted in India are
Telescreening for Diabetic Retinopathy: Taking eye care to rural
south India and Comprehensive diabetic retinopathy Project [8].
Traditionally the retina is observed either directly using an
ophthalmoscope or indirectly via digital photographs that are taken by
a fundus camera. The ophthalmoscope is a small portable instrument
containing a light source and a set of lenses. A digital fundus camera
is a low power microscope with a camera attached and designed to
photograph the interior layers of the eye. For large scale screening, it

has been shown that fundus images are more reliable than
ophthalmoscope in the detection of diabetic retinal lesions [912].
Digital fundus photography allows instantaneous examination of the
retina as and when necessary with a quick storage, access to the
images and decoupling of the acquisition and interpretation stages of
the screening.
In order to identify diabetic retinopathy at the beginning stages,
screening should be done periodically. Moreover, majority of the
diabetic population is living in the vast rural India, so large numbers
of screening camps are needed. This large scale repeated mass
screenings lead to generation of numerous fundus images that are to
be evaluated. It requires lot of time and many technicians, which are
currently not available. Typically, 90% of the images thus generated in
such scenario would be normal. Hence a fully automated, computer
based diabetic retinopathy recognition systems which can filter out
many of these normal images will save the time and reduce the
number of retinal images that are to be examined by the physicians.
With rapid development of technology, latest techniques for
screening are available which include digital photographic and
computerized techniques for detection and assessment of retinopathy.
A computer might be employed to make a selection of the images
stored on the central server. Possible suspect images (patients) could
be shown to the ophthalmologist while certainly normal images could
be stored immediately. This could potentially lower the total workload

of

the

ophthalmologists.

This

thesis

mainly

focuses

on

the

development of an automated Fundus Image Analysis system for such

a pre-selection of retinal images in diabetic retinopathy screening.

1.4. AIMS AND OBJECTIVES

The main aim of this research is to develop reliable and accurate
image processing and pattern recognition methods for automatic
fundus image analysis to aid ophthalmologists diagnosis and to be
used as an automatic tool for the mass screening of diabetic
retinopathy. Given a low quality colour fundus image, the proposed
fundus image analysis system should extract the fundal landmark
features such as the optic disk, fovea and the retinal blood vessels as
reference coordinates before the system can achieve more complex
tasks of identifying pathological entities such as hard exudates,
cottonwool spots, hemorrhages and microaneurysms. The system
must be able to do it all the time irrespective of variability in colour,
illumination levels and amount of noise. It would be good if the
algorithms of the system are fast and computationally light.
The objectives of this research work are
To Segment Retinal Blood Vessel Tree - This is a must for the
identification of optic disk and for the elimination of vascular
structures from the search of possible non-vascular lesions.

 To Identify the Position of the Optic Disk - It provides the main

landmark of the retinal coordinates and to exclude it from the set
of possible lesions.
To Detect the Contour of the Optic Disk - To assess the progress
of eye disease and treatment results.
To Identify Fovea, Vascular Arcade and to Establish Polar
Fundal Coordinate System Centered on Fovea - This co-ordinate
system will be helpful to the ophthalmologists to analyze the
severity of diabetic retinopathy.
To

Detect

Bright

Lesions

such

as

Hard

Exudates

and

Cottonwool Spots The bright lesions are the visible sign of

diabetic retinopathy and indicators of co-existent retinal edema.
Automated

early

detection

of

bright

lesions

can

assist

ophthalmologists prevent the spread of the disease more effectively.

To

Detect

Red

Lesions

such

as

Microaneurysms

and

Hemorrhages As red lesions are the first clinically observable

lesions indicating diabetic retinopathy, their detection is critical for
a diabetic retinopathy screening system.

1.5. FUNDUS IMAGE ANALYSIS SYSTEM

To accomplish the above mentioned aims and objectives a Fundus
Image Analysis system is developed in this thesis which is as shown in
Fig. 1.5. The input colour retinal image is analysed automatically and
a comprehensive assessment of the severity of diabetic retinopathy
and macular edema is derived after analysis. The proposed fundus

Input:
Colour Fundus Image

Blood Vessel
Segmentation

Optic Disc Localization

and Contour Detection

Fovea
Detection

Detection of
Exudates and
Cottonwool spots

Detection of
Microaneurysms
and Hemorrhages

Diagnosis of
Diabetic Retinopathy

Output
Fig.1.5. Fundus Image Analysis System

image analysis system consists of six main components. The binary

vasculature extracted by the blood vessel segmentation component is
used in optic disk detection, fovea detection and red lesion detection.
The optic disk localization and contour detection component finds the
location and boundary of the optic disk. The location and the
boundary of the optic disk are used to detect fovea and bright lesions.

The location of optic disk is employed to remove any spurious bright

lesion detections on the optic disk. The fovea detection component
detects vascular arcade, macula and fovea. Based on the location of
fovea a fundal coordinate system is set up that is used to find the
severity of diabetic retinopathy. The bright lesion detection component
detects exudates and cottonwool spots. The red lesion detection
component

identifies

microaneurysms

and

hemorrhages.

The

outcomes of these two components are used in diagnosis of diabetic

retinopathy component. The fundus image analysis system grades
diabetic retinopathy and macular edema based on the detection of
these lesions and this system also provides the spatial distribution of
abnormalities based on fovea such that an ophthalmologist can make
a detailed diagnosis.

1.6. ORGANIZATION OF THE THESIS

The thesis is organized in nine chapters including Introduction in
Chapter 1. In Chapter 2, the literature corresponding to retinal image
analysis systems and algorithms is reviewed.
Chapter

describes

the

proposed

method

for

automated

segmentation of blood vessels in fundus images. A method based on

relative local entropy is presented to segment the blood vessels.
Chapter 4 presents the proposed methods for localization and
contour detection of the optic disk in a fundus image. Two methods
are investigated to localize the optic disk. First method is based on
finding vessel branch which has maximum number of blood vessels

and the second method employs principal component analysis to

localize the optic disk. Geometric active contour model with new
variational formulation is applied to detect a more accurate optic disk
boundary.
Chapter 5 explains the proposed approach used for localization of
macula and fovea. Using the segmented vessel network as input,
vascular arcade and horizontal raphe of the retina are determined.
Then macula and centre of macula (fovea) are localized from the
horizontal raphe. Finally, a fundal coordinate system is established
centered on fovea.
An automatic bright lesion detection system is proposed in
Chapter 6. The colour retinal image is preprocessed using local
contrast enhancement technique to enhance the contrast of the
retinal image.

As optic disk appears similar to hard exudates it is

eliminated using the entropy feature. Spatially Weighted Fuzzy CMeans (SWFCM) clustering is applied to extract candidate bright
lesions. Then true bright lesions are classified from bright non-lesions
using K-Nearest Neighbourhood (KNN) and Support Vector Machine
(SVM) classifiers. A blood vessel segmentation algorithm based on
SWFCM clustering is also presented in this chapter.
Chapter 7 presents the proposed automatic red lesion detection
system. The candidate red lesions are extracted based on a hybrid
approach combining mathematical morphology based segmentation
and detection using matched filtering and relative local entropy based

thresholding. Next, true red lesions are separated from red nonlesions using KNN and SVM classifiers.
In Chapter 8, the proposed fundus image analysis system is
presented. This system is evaluated and compared to existing diabetic
retinopathy screening systems. Finally, Chapter 9 summarizes the
principal contributions of this research work. Suggestions for future
work are also presented in the concluding remarks.