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Automatic detection Non-proliferative Diabetic Retinopathy using
image processing techniques
RajuS. Maher1
, Dr. Mukta Dhopeshwarkar2
1
Research Scholar Department of Computer Science & IT, Dr. Babasaheb Ambedkar Marathwada University,
Aurangabad, India
2
Assistant ProfessorDepartment of Computer Science & IT, Dr. Babasaheb Ambedkar Marathwada University,
Aurangabad, India
ABSTRACT
Diabetes is a chronic disease that is reaching epidemic proportions worldwide. There are currently more than
190 million people with diabetes worldwide. The World Health Organization (WHO) estimates that this will rise
to 221 million by the year 2010, largely due to population growth, ageing, urbanization and a sedentary lifestyle.
Diabetes is currently the fourth main cause of death in most developed countries. In Singapore, the prevalence
of diabetes in our population is 8.2% according to the 2004 National Health Survey. This is expected to grow as
our population age.
Diabetic Retinopathy, if not well managed and controlled, can progress steadily to devastating
complications like blindness. At present, various analyses on complicated interaction between hereditary and
environmental factors are being undertaken regarding the onset of diabetes. The development of diabetic
complication has become a major concern regarding the prognosis of diabetic patients.
Diabetes Retinopathy is one of the most common diseases that people get affected by over the years. By doing
this paper, we hope to detect the stages of Diabetic Retinopathy as early as possible so as to prevent and cure
more Singaporeans from falling prey to this disease
Keywords: Diabetes Retinopathy, World Health Organization (WHO), fundus Images.
I. INTRODUCTION
Diabetic retinopathy is a vascular disorder
occurring due to the combination of micro-vascular
leakage and micro-vascular occlusion within the
retina. It is primarily classified into Non-Proliferative
Diabetic Retinopathy (NPDR) and Proliferative
Diabetic Retinopathy (PDR) [1].It is a major public
health problem and diabetic-related eye diseases are
the commonest cause of vision defects and blindness
in the world. The appearance of microaneurysms,
hemorrhages and exudates represent to certain extent
the degree of severity of the disease. Typically there
are no salient symptoms in the early stages of
diabetic retinopathy, but the number and severity
predominantly increase with the time. Non
proliferative diabetic retinopathy is the most common
and may arise at any point in time after the onset of
diabetes. Ophthalmologists detect these changes by
examining the patient's retina and look for spots of
bleeding, lipid exudation, or areas of retinal swelling
[1][2].Many techniques have been employed to
perform exudates detection. A complete comparative
analysis of the most recent techniques is made on [2].
Identification and recording of the following
abnormalities (see Figure 1.1) will aid in the accurate
assessment of retinopathy severity
Fig. 1.1: Anatomical and pathological features in
colour retinal image [1].
Microaneurysms: These are the earliest clinical
abnormality to be noticed in the eye. These are local
swelling of retina capillary and usually appear in
isolation or in clusters. Their size ranges from 10 to
100 microns and are dark red spots that look like tiny
hemorrhages. The number of microaneurysms
increases as the degree of retinal involvement
progresses [3].
Hemorrhages: Intra-retinal hemorrhages appear
when capillaries or microaneurysms rupture and
some blood leaks out of these vessels. In Figure 1.1
hemorrhages can be seen as red flame shaped regions
RESEARCH ARTICLE OPEN ACCESS
Raju Maheret al. Int. Journal of Engineering Research and Applications www.ijera.com
ISSN: 2248-9622, Vol. 6, Issue 1, (Part - 3) January 2016, pp.122-127
www.ijera.com 123|P a g e
Hard exudates: Hard exudates represent leak of
fluid that is rich in fat and protein from surrounding
capillaries and microaneurysms within the retina.
These are one of the main characteristics of diabetic
retinopathy and appear as random yellowish patches
of varying sizes, and shapes.
Soft exudates: These are often called cotton wool
spots and are more often seen in advanced
retinopathy. These abnormalities usually appear as
little fluffy round or oval areas in the retina with a
whitish colour, usually adjacent to an area of
hemorrhage. Cotton wool spots come about due to
the swelling of the surface layer of the retina in the
absence of normal blood flow through the retinal
vessels. The nerve fibers are injured in a particular
location resulting in swelling and appearance of a
cotton wool spot [3]. Proliferative diabetic
retinopathy, the advanced stage retinopathy develops
in more than 50 percent cases after about 25 years of
onset of the disease. Therefore, it is more common in
patients with juvenile onset diabetes. The hallmark of
PDR is the growth of new blood vessels in the areas
where normal capillaries have already closed. These
new blood vessels are abnormal and fragile. They
grow along the retina and along the surface of the
clear, vitreous gel that fills the inside of the eye. By
themselves, these blood vessels do not cause
symptoms or vision loss. However, they have thin,
fragile walls that leak blood resulting in severe vision
loss and even blindness can be the end result.early
screening and identification of patients with diabetic
retinopathy will help to prevent loss of vision.
Therefore an automated detection and treatment of
diabetic retinopathy in an early stage can prevent the
blindness [4].Diabetes Retinopathy in simple words
is damage to the blood vessels in the retina. A retina
is a light sensitive tissue at the back of the eye. A
healthy retina is required for good vision. It is caused
when blood vessels swell and leak fluid and
abnormal blood vessels are formed on the surface of
the retina. Diabetic Retinopathy is not easily noticed
at first but overtime the condition gets worst and even
cause vision loss. Diabetic Retinopathy is said to
affect both eyes. In my project, this disease is
classified into 3 stages. The three stages are normal,
non-proliferative Diabetic Retinopathy (NPDR), and
Proliferative Diabetic Retinopathy (PDR) as shown
below. Figure (1.1) (b-d) shows the optical image of
three stages of NPDR. They are mild Diabetic
Retinopathy, moderate Diabetic Retinopathy, and
severe Diabetic Retinopathy [4, 6].
1. Diabetic Retinopathy
Diabetic Retinopathy is a common complication
of diabetes mellitus, characterized by macular edema
and frequently accompanied by lipid exudation.
Diabetic Retinopathy, defined as retinopathy within
one disc diameter of the center of the macula is the
major cause of vision loss. One of the morphological
characteristics of diabetic retinopathy clinical signs is
the onset of retinal hard exudates, which are
manifested as whitish- yellowish changes. They are
most frequently localized in the area of the macular
region, surrounding the zones of retinal edema,
although they can also be noticed in other
localizations at the posterior pole of the eye fundus.
They are a dominant feature in both exudative and
mixed types of diabetic maculopathy. If they are very
apparent and affect the center of macular region
called fovea centralis, visual function is significantly
and irrevocably damaged as shown in Figure 2.1.
Diabetic maculopathy comprises of two aspects: First
is the macular edema in which fluid and lipoproteins
accumulate within the retina. Second is the macular
ischaemia in which there is closure of perifoveal
capillaries demonstrable on fundus fluorescein
angiography. It is not known to what extent macular
ischaemia contributes to the visual lossattributable to
diabetic maculopathy and this work is limited to the
automatic detection of macular edema and its severity
stages.
Fig. 2.1: Normal vision (left) and same scene
viewed by person with diabetic retinopathy (right)
[Courtesy: http://www.nei.neh.gov].
2. Non-Proliferative Diabetic Retinopathy
This color retinal photograph demonstrates non-
proliferative diabetic retinopathy. The image is
centered on the macula (the part of the retina
responsible for central fine vision) with part of the
optic nerve seen on the left of the photo (left eye).
There are hemorrhages within the retinal tissue on the
right side of the photograph. (Click image for full
size image.)The doctor looks for small spots of
bleeding or areas of retinal swelling due to fluid
leakage. Sometimes, fatty material leaks from
damaged vessels and collects in the retina as deposits
called exudates. The ophthalmologist will often take
color photos of the back of the eye to document the
retinal changes. Non–proliferative diabetic
retinopathy is further sub–divided into mild,
moderate, and severe depending on the number and
amounts of bleeding and leaking areas.Frequently,
especially if there is reduced vision, the
ophthalmologist may elect to investigate the retinal
changes further with a special diagnostic test know as
a fluorescein angiogram. This test involves injecting
a yellow dye into an arm vein and photographing the
back of the eye as the dye passes through the retinal
Raju Maheret al. Int. Journal of Engineering Research and Applications www.ijera.com
ISSN: 2248-9622, Vol. 6, Issue 1, (Part - 3) January 2016, pp.122-127
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circulation. This test is especially useful for
identifying areas of blood vessel damage and
abnormal leakage from them. The test does not
involve the use of X–rays. Patients should be aware
that their urine will be bright yellow for a day or two
following the injection.Fluorescein angiogram of the
same patient shown above. The retinal vessels are
filled with the fluorescent dye. Hemorrhages appear
as dark spots in the angiogram and correspond to
those seen in the color photo. On the right side of the
image, there is damage to retinal blood vessels which
no longer fill with the dye. This is called an area of
non–perfusion, also called retinal ischemia.Optical
Coherence Tomography (OCT) is another test that is
commonly obtained in order to assess fluid
accumulation (macular edema) in the retina in
patients with diabetes. OCT can demonstrate areas of
retinal thickening and can be a useful tool in
assessing a patient’s response to a
treatment.Proliferative diabetic retinopathy (PDR) is
a more advanced form of diabetic retinopathy and a
major cause of visual loss in diabetic patients.
Patients at risk for this complication require frequent
eye exams and often immediate treatment once the
disorder is recognized.As retinal blood vessels
become damaged and close off in diabetic
retinopathy due to the cumulative effects of diabetes,
the peripheral portions of the retinal circulation begin
to close down causing the retina to become oxygen
deficient or ischemic. This process is known as
retinal ischemia and is believed to be the first step in
the development of proliferative diabetic retinopathy.
Presumably, the ischemic (nutrient–starved) retina
releases a chemical message or growth factor which
leads to the growth of new abnormal blood vessels
(neovascularization) in the eye. These abnormal
vessels often grow on the surface of the retina, at the
optic nerve, or in the front of the eye on the iris.
Color retinal photograph centered on the optic
nerve (left eye). This picture demonstrates
proliferative diabetic retinopathy. Abnormal vessels
(neovascularization) are growing from the nerve over
the retinal surface and into the vitreous jelly (the
clear substance which fills the eye).
3. Drawing of Proliferative Diabetic Retinopathy
Unfortunately, neovascularization is never good
for the eye. The new vessels cannot replace the flow
of necessary nutrients and, instead, can cause many
problems such as vitreous hemorrhage (bleeding into
the gel which fills the eye), traction retinal
detachment, and uncontrolled glaucoma (high
pressure in the eye). These problems occur because
new vessels are fragile and are prone to bleed. As
they grow within the eye associated scar tissue may
exert traction on adjacent structures. This pulling
may produce a distortion of the retina and even lead
to a retinal detachment. When the vessels grow in the
front of the eye on the colored iris (iris
neovascularization) they can clog the fluid outflow
channels and cause the pressure in the eye to become
very high. This is called neovascular or
rubeoticglaucoma. Color retinal photograph centered
on the optic nerve (left eye). This picture
demonstrates proliferative diabetic retinopathy.
Abnormal vessels (neovascularization) are growing
from the nerve over the retinal surface and into the
vitreous gel. Some of these vessels have bled into the
vitreous (vitreous hemorrhage).Color retinal
photograph centered on the optic nerve (left eye)[5].
This picture demonstrates proliferative diabetic
retinopathy. Abnormal vessels (neovascularization)
are growing from the nerve over the retinal surface
and into the vitreous gel. Some of these vessels have
bled into the vitreous (vitreous hemorrhage).Color
retinal photograph demonstrating severe proliferative
diabetic retinopathy. Abnormal vessels (neovascu-
larization) are growing from the nerve over the
retinal surface producing a fractional retinal
detachment. In advanced cases of proliferative
diabetic retinopathy such as this, a surgical treatment
known as a vasectomy may be required to flatten the
retina.Oftentimes these abnormal blood vessels will
grow and the patient will have no symptoms and
normal vision. However, these blood vessels are very
fragile and can suddenly break open and bleed. When
these blood vessels bleed, blood spills out into the
normally clear vitreous gel that fills the central
hollow part of the eye. This can result in a rapid and
sudden decrease in vision. This type of bleeding is
termed a Vitreous Hemorrhage. The change in vision
from a vitreous hemorrhage can run the spectrum
from a few floaters, to cobwebs, to cloudy vision, or
to complete loss of vision.Like a bruise, a Vitreous
Hemorrhage will usually be absorbed by the body
over the course of several weeks to months, resulting
in some improvement in vision. However, sometimes
the blood does not clear on its own and surgery is
necessary to remove the blood–filled vitreous gel.
This surgery is called a Vasectomy and will be
described in a later section.If caught in its early
stages, proliferative diabetic retinopathy can
sometimes be arrested with pan retinal
photocoagulation or the injection of an off–label
medication into the eye.
II. IMAGE DATABASE AND
PREPROCESSING
The digital colour retinal images required for the
development of automatic system for retinopathy
detection are provided by the Department of
Ophthalmology, Kasturba Medical College (KMC),
and Manipal. The images are captured by a Zeiss FF
450IR fundus camera (Figure 3.1). A modified digital
backunit (Sony 3CCD colour video camera) is
connected to the fundus camera to convert the fundus
Raju Maheret al. Int. Journal of Engineering Research and Applications www.ijera.com
ISSN: 2248-9622, Vol. 6, Issue 1, (Part - 3) January 2016, pp.122-127
www.ijera.com 125|P a g e
image into a digital image. The digital images are
processed and saved on the hard drive of a Windows
based computer with a resolution of 768 x 576 in 24
bit JPEG format. This consists of 8-bits of Red,
Green and Blue (RGB) layers with 256 levels each.
The images are linked to the patient data using the
Visupac software, which is a patient database [4].
The images are usually obtained from the posterior
pole’s view including the optic disc and macula. A
total of over 300 images are captured by the
ophthalmologists. Out of those images only 148
images are considered for testing the system after
consulting with the expert ophthalmologist. Images
of the patients treated by laser are not considered in
the work [6][9][10][11]..
Fig.3.1 Zeiss FF 450IR fundus camera.
Apart from the KMC database, two publicly
available retinal databases called DRIVE and STARE
are used for testing the retinal vessel segmentation
method and DIARETDB1 standard database is used
for testing exudate detection method. The details of
these databases are as follows. The STARE
Database: There are twenty retinal fundus slides and
their ground truth images in the STARE (Structured
Analysis of Retina) database. The images are
digitized slides captured by a TopCon TRV-50
fundus camera with 35 degree field of view. Each
slide was digitized to produce a 605 x 700 pixel
image with 24-bits per pixel. All the twenty images
were carefully labeled by hand to produce ground
truth vessel segmentation by an expert. Figure 3.2
shows an example of an image from the database.
The DRIVE Database: The second image database is
referred as the DRIVE (Digital Retinal Images for
Vessel Extraction). The database consists of 40
colour fundus photographs and their ground truth
images [5] [7].
Fig. 3.2: Retinal image from STARE database (left),
hand labeled ground truth vessel segmentation (right).
All images in DRIVE database are digitized
using a Cannon CR5 non-mydriatic 3CCD camera
with a 45 degree field of view. Each image is
captured using 24-bits per pixel at the image size of
565×584. These images were labeled by hand, to
produce ground truth vessel segmentation and Figure
3.3 shows one such image [9][10][11]..
1. Database
Database: The DAIRETDB1 database consists of
89 colour fundus images of which 84 contain at least
mild non proliferative signs of the diabetic
retinopathy (see Figure 3.4), and five are considered
as normal which do not contain any signs of the
diabetic retinopathy according to all the experts
participated in the evaluation. Images were captured
with the same 50 degree field-of-view digital fundus
camera with varying imaging controlled by the
system in the Kuopio university hospital, Finland.
The image ground truth provided along with the
database is based on expert selected findings related
to the diabetic retinopathy and normal fundus
structures. Special software was used to inspect the
fundus images and annotate the findings as hard
exudates, hemorrhages and microaneurysms
[8][9][10][11].
Fig. 3.4: Example of abnormal fundus image from
DIARETDB1 database (left), and Ground truth of
hard exudates (right).
2. Preprocessing
Patient movement, poor focus, bad positioning,
reflections, inadequate illumination can cause a
significant proportion of images to be of such poor
quality as to interfere with analysis. In approximately
10% of the retinal images, artifacts are significant
enough to impede human grading. Preprocessing of
such images can ensure adequate level of success in
the automated abnormality detection. In the retinal
images there can be variations caused by the factors
including differences in cameras, illumination,
acquisition angle and retinal pigmentation. First step
in the preprocessing is to attenuate such image
variations by normalizing the colour of the original
retinal image against a reference image. Few of the
retinal images acquired using standard clinical
protocols often exhibit low contrast. Also, retinal
images typically have a higher contrast in the center
of the image with reduced contrast moving outward
Raju Maheret al. Int. Journal of Engineering Research and Applications www.ijera.com
ISSN: 2248-9622, Vol. 6, Issue 1, (Part - 3) January 2016, pp.122-127
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from the center. For such images, a local contrast
enhancement method is applied as a second
preprocessing step. Finally it is required to create a
fundus mask for each image to facilitate
segmentation of lesions and anatomical structures in
later stages. The pre-processing steps are explained in
detail in the following subsections [9][10].
3. Colour Normalization
Colour normalization is necessary due to the
significant intra-image and inter-image variability in
the colour of the retina in different patients. There
can also be, differences in skin pigmentation, aging
of the patient and iris colour between different
patients that affect the colour of the retinal image.
Colour normalization method is applied to make the
images invariant with respect to the background
pigmentation variation between individuals. The
colour normalization is performed using histogram
matching. In histogram matching a processed image
can have a shape of the histogram as specified by the
user. This is done by modifying the image values
through a histogram transformation operator which
maps a given initial intensity distribution into a
desired distribution using the histogram equalization
technique as an intermediate stage. Let Ps(s) and
Pd(s) represent the standard image and desired image
probability density functions, respectively.
4. Fundus Mask Detection
The mask is a binary image with the same
resolution as that of fundus image whose positive
pixels correspond to the foreground area. It is
important to separate the fundus from its background
so that the further processing is only performed for
the fundus and not interfered by pixels belonging to
the background. In a fundus mask, pixels belonging
to the fundus are marked with ones and the
background of the fundus with zeros. The fundus can
be easily separated from the background by
converting the original fundus image from the RGB
to HSI colour system where a separate channel is
used to represent the intensity values of the image.
The intensity channel image is thresholded by a low
threshold value as the background pixels are typically
significantly darker than the fundus pixels. A median
filter of size 5×5 is used to remove any noise from
the created fundus mask and the edge pixels are
removed by morphological erosion with a structuring
element of size 5×5. Figure 3.5 (b) shows the
example of the fundus mask [9][10][11].
Fig. 3.5: Automatic fundus masks generation. (a)
Input image; (b) Automatically generated fundus
mask.
III. CONCLUSION
To develop an automatic retinal image
processing system, the first important thing is to
obtain an effective database. To realize this and also
for facilitating comparison with the existing methods,
four sets of Retinal databases are used. Details of the
fundus camera and image properties of each of these
databases are explained.
In any retinal image database, there will be some
images with non-uniform illumination and poor
contrast. There can also be difference in the colour of
the fundus due to retinal pigmentation among
different patients. These images are preprocessed
before they can be subjected to anatomical and
pathological structure detection. Colour
normalization is performed to attenuate colour
variations in the image by normalizing the colour of
the original retinal image against a reference image.
In order to correct non uniform illumination and to
improve contrast of an image, contrast-limited
adaptive histogram equalization is employed. On
application of this method, the image quality is
significantly improved with the increase in contrast.
Each fundus camera has a mask of different shape
and size according to its settings. By automatically
detecting the fundus mask a lesion detection
algorithm or vessel detection algorithm can process
only the pixels of the fundus leaving out the
background pixels. The following Chapters will
explain the methods used to detect anatomical and
pathological structures in retinal image leading to the
development of automatic system for the
identification of severity levels in diabetic
maculopathy.
REFERENCES
[1] Raju Maher, Sangramsing Kayte, Dr. Mukta
D “Review of Automated Detection for
Diabetes Retinopathy Using Fundus
Images” International Journal of Advanced
Research in Computer Science and Software
Engineering Volume 5, Issue 3, March
2015.
[2] RajuSahebrao Maher, Sangramsing N
Kayte, Sandip T Meldhe and Mukta
Raju Maheret al. Int. Journal of Engineering Research and Applications www.ijera.com
ISSN: 2248-9622, Vol. 6, Issue 1, (Part - 3) January 2016, pp.122-127
www.ijera.com 127|P a g e
Dhopeshwarkar. Article: Automated
Diagnosis Non-proliferative Diabetic
Retinopathy in Fundus Images using
Support Vector Machine. International
Journal of Computer Applications
125(15):7-10, September 2015. Published by
Foundation of Computer Science (FCS),
NY, USA
[3] Raju Maher, Sangramsing Kayte,
Dnyaneshwar Panchal, PankajSathe, Sandip
Meldhe " A Decision Support System for
Automatic Screening of Non-Proliferative
Diabetic Retinopathy" International Journal
of Emerging Research in Management
&Technology ISSN: 2278-9359 (Volume-4,
Issue-10) October 2015
[4] RajuSahebrao Maher, Dnyaneshwar S.
Panchal, Sangramsing Kayte, Dr. Mukta
Dhopeshwarkar "Automatic Identification of
Varies Stages of Diabetic Retinopathy Using
Retinal Fundus Images"-International
Journal of Advanced Research in Computer
Science and Software Engineering Volume
5, Issue 9, September 2015 ISSN: 2277
128X
[5] http://www.nei.nih.gov/health/diabetic/retin
opathy.asp
[6] Diabetic Retinopathy-Early Detection Using
Image Processing Techniques
[7] Diseases and Surgery of the Macula, Retina,
and Vitreous Diabetic Eye Disease By John
H. Drouilhet, M.D., FACS.
[8] DIARETDB0: Evaluation Database and
Methodology for Diabetic Retinopathy
Algorithms
[9] Sangramsing N. Kayte, Bharatratna P.
Gaikwad, "Design and Development of
Non-Proliferative Diabetic Retinopathy
Detection Technique using Image Features
Extraction Techniques “National
Conference in Advances in computing
(NCAC’13), 05-06 March 2013
[10] Acharaya, U.R., Ng, E.Y.K., Tan, J.H., Sree,
S.V. and Ng, K.H. (2012) An integrated
index for the identification of diabetic
retinopathy stages using texture parameters.
Jour- nal of Medical Systems, 36, 2011-
2020.
[11] Raju Maher, Charansing N. Kayte,
“Automated Screening of Diabetic
Retinopathy Using Image Processing”,
IOSR Journal of Pharmacy and Biological
Sciences, Volume 10, Issue 6 Ver. III (Nov -
Dec. 2015), PP 54-63.
[12] Gonzalez, R.C. and Woods, R.E. (2008)
Digital image processing. 3rd Edition,
Prentice Hall, Upper Saddle River.
[13] Andjelkovic, J., Zivic, N., Reljin, B.,
Celebic, V. and Sa- lom I. (2008)
Application of multifractal analysis on me-
dical images. Wseas Transactions on
Information Science and Applications.

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Automatic detection Non-proliferative Diabetic Retinopathy using image processing techniques

  • 1. Raju Maheret al. Int. Journal of Engineering Research and Applications www.ijera.com ISSN: 2248-9622, Vol. 6, Issue 1, (Part - 3) January 2016, pp.122-127 www.ijera.com 122|P a g e Automatic detection Non-proliferative Diabetic Retinopathy using image processing techniques RajuS. Maher1 , Dr. Mukta Dhopeshwarkar2 1 Research Scholar Department of Computer Science & IT, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, India 2 Assistant ProfessorDepartment of Computer Science & IT, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, India ABSTRACT Diabetes is a chronic disease that is reaching epidemic proportions worldwide. There are currently more than 190 million people with diabetes worldwide. The World Health Organization (WHO) estimates that this will rise to 221 million by the year 2010, largely due to population growth, ageing, urbanization and a sedentary lifestyle. Diabetes is currently the fourth main cause of death in most developed countries. In Singapore, the prevalence of diabetes in our population is 8.2% according to the 2004 National Health Survey. This is expected to grow as our population age. Diabetic Retinopathy, if not well managed and controlled, can progress steadily to devastating complications like blindness. At present, various analyses on complicated interaction between hereditary and environmental factors are being undertaken regarding the onset of diabetes. The development of diabetic complication has become a major concern regarding the prognosis of diabetic patients. Diabetes Retinopathy is one of the most common diseases that people get affected by over the years. By doing this paper, we hope to detect the stages of Diabetic Retinopathy as early as possible so as to prevent and cure more Singaporeans from falling prey to this disease Keywords: Diabetes Retinopathy, World Health Organization (WHO), fundus Images. I. INTRODUCTION Diabetic retinopathy is a vascular disorder occurring due to the combination of micro-vascular leakage and micro-vascular occlusion within the retina. It is primarily classified into Non-Proliferative Diabetic Retinopathy (NPDR) and Proliferative Diabetic Retinopathy (PDR) [1].It is a major public health problem and diabetic-related eye diseases are the commonest cause of vision defects and blindness in the world. The appearance of microaneurysms, hemorrhages and exudates represent to certain extent the degree of severity of the disease. Typically there are no salient symptoms in the early stages of diabetic retinopathy, but the number and severity predominantly increase with the time. Non proliferative diabetic retinopathy is the most common and may arise at any point in time after the onset of diabetes. Ophthalmologists detect these changes by examining the patient's retina and look for spots of bleeding, lipid exudation, or areas of retinal swelling [1][2].Many techniques have been employed to perform exudates detection. A complete comparative analysis of the most recent techniques is made on [2]. Identification and recording of the following abnormalities (see Figure 1.1) will aid in the accurate assessment of retinopathy severity Fig. 1.1: Anatomical and pathological features in colour retinal image [1]. Microaneurysms: These are the earliest clinical abnormality to be noticed in the eye. These are local swelling of retina capillary and usually appear in isolation or in clusters. Their size ranges from 10 to 100 microns and are dark red spots that look like tiny hemorrhages. The number of microaneurysms increases as the degree of retinal involvement progresses [3]. Hemorrhages: Intra-retinal hemorrhages appear when capillaries or microaneurysms rupture and some blood leaks out of these vessels. In Figure 1.1 hemorrhages can be seen as red flame shaped regions RESEARCH ARTICLE OPEN ACCESS
  • 2. Raju Maheret al. Int. Journal of Engineering Research and Applications www.ijera.com ISSN: 2248-9622, Vol. 6, Issue 1, (Part - 3) January 2016, pp.122-127 www.ijera.com 123|P a g e Hard exudates: Hard exudates represent leak of fluid that is rich in fat and protein from surrounding capillaries and microaneurysms within the retina. These are one of the main characteristics of diabetic retinopathy and appear as random yellowish patches of varying sizes, and shapes. Soft exudates: These are often called cotton wool spots and are more often seen in advanced retinopathy. These abnormalities usually appear as little fluffy round or oval areas in the retina with a whitish colour, usually adjacent to an area of hemorrhage. Cotton wool spots come about due to the swelling of the surface layer of the retina in the absence of normal blood flow through the retinal vessels. The nerve fibers are injured in a particular location resulting in swelling and appearance of a cotton wool spot [3]. Proliferative diabetic retinopathy, the advanced stage retinopathy develops in more than 50 percent cases after about 25 years of onset of the disease. Therefore, it is more common in patients with juvenile onset diabetes. The hallmark of PDR is the growth of new blood vessels in the areas where normal capillaries have already closed. These new blood vessels are abnormal and fragile. They grow along the retina and along the surface of the clear, vitreous gel that fills the inside of the eye. By themselves, these blood vessels do not cause symptoms or vision loss. However, they have thin, fragile walls that leak blood resulting in severe vision loss and even blindness can be the end result.early screening and identification of patients with diabetic retinopathy will help to prevent loss of vision. Therefore an automated detection and treatment of diabetic retinopathy in an early stage can prevent the blindness [4].Diabetes Retinopathy in simple words is damage to the blood vessels in the retina. A retina is a light sensitive tissue at the back of the eye. A healthy retina is required for good vision. It is caused when blood vessels swell and leak fluid and abnormal blood vessels are formed on the surface of the retina. Diabetic Retinopathy is not easily noticed at first but overtime the condition gets worst and even cause vision loss. Diabetic Retinopathy is said to affect both eyes. In my project, this disease is classified into 3 stages. The three stages are normal, non-proliferative Diabetic Retinopathy (NPDR), and Proliferative Diabetic Retinopathy (PDR) as shown below. Figure (1.1) (b-d) shows the optical image of three stages of NPDR. They are mild Diabetic Retinopathy, moderate Diabetic Retinopathy, and severe Diabetic Retinopathy [4, 6]. 1. Diabetic Retinopathy Diabetic Retinopathy is a common complication of diabetes mellitus, characterized by macular edema and frequently accompanied by lipid exudation. Diabetic Retinopathy, defined as retinopathy within one disc diameter of the center of the macula is the major cause of vision loss. One of the morphological characteristics of diabetic retinopathy clinical signs is the onset of retinal hard exudates, which are manifested as whitish- yellowish changes. They are most frequently localized in the area of the macular region, surrounding the zones of retinal edema, although they can also be noticed in other localizations at the posterior pole of the eye fundus. They are a dominant feature in both exudative and mixed types of diabetic maculopathy. If they are very apparent and affect the center of macular region called fovea centralis, visual function is significantly and irrevocably damaged as shown in Figure 2.1. Diabetic maculopathy comprises of two aspects: First is the macular edema in which fluid and lipoproteins accumulate within the retina. Second is the macular ischaemia in which there is closure of perifoveal capillaries demonstrable on fundus fluorescein angiography. It is not known to what extent macular ischaemia contributes to the visual lossattributable to diabetic maculopathy and this work is limited to the automatic detection of macular edema and its severity stages. Fig. 2.1: Normal vision (left) and same scene viewed by person with diabetic retinopathy (right) [Courtesy: http://www.nei.neh.gov]. 2. Non-Proliferative Diabetic Retinopathy This color retinal photograph demonstrates non- proliferative diabetic retinopathy. The image is centered on the macula (the part of the retina responsible for central fine vision) with part of the optic nerve seen on the left of the photo (left eye). There are hemorrhages within the retinal tissue on the right side of the photograph. (Click image for full size image.)The doctor looks for small spots of bleeding or areas of retinal swelling due to fluid leakage. Sometimes, fatty material leaks from damaged vessels and collects in the retina as deposits called exudates. The ophthalmologist will often take color photos of the back of the eye to document the retinal changes. Non–proliferative diabetic retinopathy is further sub–divided into mild, moderate, and severe depending on the number and amounts of bleeding and leaking areas.Frequently, especially if there is reduced vision, the ophthalmologist may elect to investigate the retinal changes further with a special diagnostic test know as a fluorescein angiogram. This test involves injecting a yellow dye into an arm vein and photographing the back of the eye as the dye passes through the retinal
  • 3. Raju Maheret al. Int. Journal of Engineering Research and Applications www.ijera.com ISSN: 2248-9622, Vol. 6, Issue 1, (Part - 3) January 2016, pp.122-127 www.ijera.com 124|P a g e circulation. This test is especially useful for identifying areas of blood vessel damage and abnormal leakage from them. The test does not involve the use of X–rays. Patients should be aware that their urine will be bright yellow for a day or two following the injection.Fluorescein angiogram of the same patient shown above. The retinal vessels are filled with the fluorescent dye. Hemorrhages appear as dark spots in the angiogram and correspond to those seen in the color photo. On the right side of the image, there is damage to retinal blood vessels which no longer fill with the dye. This is called an area of non–perfusion, also called retinal ischemia.Optical Coherence Tomography (OCT) is another test that is commonly obtained in order to assess fluid accumulation (macular edema) in the retina in patients with diabetes. OCT can demonstrate areas of retinal thickening and can be a useful tool in assessing a patient’s response to a treatment.Proliferative diabetic retinopathy (PDR) is a more advanced form of diabetic retinopathy and a major cause of visual loss in diabetic patients. Patients at risk for this complication require frequent eye exams and often immediate treatment once the disorder is recognized.As retinal blood vessels become damaged and close off in diabetic retinopathy due to the cumulative effects of diabetes, the peripheral portions of the retinal circulation begin to close down causing the retina to become oxygen deficient or ischemic. This process is known as retinal ischemia and is believed to be the first step in the development of proliferative diabetic retinopathy. Presumably, the ischemic (nutrient–starved) retina releases a chemical message or growth factor which leads to the growth of new abnormal blood vessels (neovascularization) in the eye. These abnormal vessels often grow on the surface of the retina, at the optic nerve, or in the front of the eye on the iris. Color retinal photograph centered on the optic nerve (left eye). This picture demonstrates proliferative diabetic retinopathy. Abnormal vessels (neovascularization) are growing from the nerve over the retinal surface and into the vitreous jelly (the clear substance which fills the eye). 3. Drawing of Proliferative Diabetic Retinopathy Unfortunately, neovascularization is never good for the eye. The new vessels cannot replace the flow of necessary nutrients and, instead, can cause many problems such as vitreous hemorrhage (bleeding into the gel which fills the eye), traction retinal detachment, and uncontrolled glaucoma (high pressure in the eye). These problems occur because new vessels are fragile and are prone to bleed. As they grow within the eye associated scar tissue may exert traction on adjacent structures. This pulling may produce a distortion of the retina and even lead to a retinal detachment. When the vessels grow in the front of the eye on the colored iris (iris neovascularization) they can clog the fluid outflow channels and cause the pressure in the eye to become very high. This is called neovascular or rubeoticglaucoma. Color retinal photograph centered on the optic nerve (left eye). This picture demonstrates proliferative diabetic retinopathy. Abnormal vessels (neovascularization) are growing from the nerve over the retinal surface and into the vitreous gel. Some of these vessels have bled into the vitreous (vitreous hemorrhage).Color retinal photograph centered on the optic nerve (left eye)[5]. This picture demonstrates proliferative diabetic retinopathy. Abnormal vessels (neovascularization) are growing from the nerve over the retinal surface and into the vitreous gel. Some of these vessels have bled into the vitreous (vitreous hemorrhage).Color retinal photograph demonstrating severe proliferative diabetic retinopathy. Abnormal vessels (neovascu- larization) are growing from the nerve over the retinal surface producing a fractional retinal detachment. In advanced cases of proliferative diabetic retinopathy such as this, a surgical treatment known as a vasectomy may be required to flatten the retina.Oftentimes these abnormal blood vessels will grow and the patient will have no symptoms and normal vision. However, these blood vessels are very fragile and can suddenly break open and bleed. When these blood vessels bleed, blood spills out into the normally clear vitreous gel that fills the central hollow part of the eye. This can result in a rapid and sudden decrease in vision. This type of bleeding is termed a Vitreous Hemorrhage. The change in vision from a vitreous hemorrhage can run the spectrum from a few floaters, to cobwebs, to cloudy vision, or to complete loss of vision.Like a bruise, a Vitreous Hemorrhage will usually be absorbed by the body over the course of several weeks to months, resulting in some improvement in vision. However, sometimes the blood does not clear on its own and surgery is necessary to remove the blood–filled vitreous gel. This surgery is called a Vasectomy and will be described in a later section.If caught in its early stages, proliferative diabetic retinopathy can sometimes be arrested with pan retinal photocoagulation or the injection of an off–label medication into the eye. II. IMAGE DATABASE AND PREPROCESSING The digital colour retinal images required for the development of automatic system for retinopathy detection are provided by the Department of Ophthalmology, Kasturba Medical College (KMC), and Manipal. The images are captured by a Zeiss FF 450IR fundus camera (Figure 3.1). A modified digital backunit (Sony 3CCD colour video camera) is connected to the fundus camera to convert the fundus
  • 4. Raju Maheret al. Int. Journal of Engineering Research and Applications www.ijera.com ISSN: 2248-9622, Vol. 6, Issue 1, (Part - 3) January 2016, pp.122-127 www.ijera.com 125|P a g e image into a digital image. The digital images are processed and saved on the hard drive of a Windows based computer with a resolution of 768 x 576 in 24 bit JPEG format. This consists of 8-bits of Red, Green and Blue (RGB) layers with 256 levels each. The images are linked to the patient data using the Visupac software, which is a patient database [4]. The images are usually obtained from the posterior pole’s view including the optic disc and macula. A total of over 300 images are captured by the ophthalmologists. Out of those images only 148 images are considered for testing the system after consulting with the expert ophthalmologist. Images of the patients treated by laser are not considered in the work [6][9][10][11].. Fig.3.1 Zeiss FF 450IR fundus camera. Apart from the KMC database, two publicly available retinal databases called DRIVE and STARE are used for testing the retinal vessel segmentation method and DIARETDB1 standard database is used for testing exudate detection method. The details of these databases are as follows. The STARE Database: There are twenty retinal fundus slides and their ground truth images in the STARE (Structured Analysis of Retina) database. The images are digitized slides captured by a TopCon TRV-50 fundus camera with 35 degree field of view. Each slide was digitized to produce a 605 x 700 pixel image with 24-bits per pixel. All the twenty images were carefully labeled by hand to produce ground truth vessel segmentation by an expert. Figure 3.2 shows an example of an image from the database. The DRIVE Database: The second image database is referred as the DRIVE (Digital Retinal Images for Vessel Extraction). The database consists of 40 colour fundus photographs and their ground truth images [5] [7]. Fig. 3.2: Retinal image from STARE database (left), hand labeled ground truth vessel segmentation (right). All images in DRIVE database are digitized using a Cannon CR5 non-mydriatic 3CCD camera with a 45 degree field of view. Each image is captured using 24-bits per pixel at the image size of 565×584. These images were labeled by hand, to produce ground truth vessel segmentation and Figure 3.3 shows one such image [9][10][11].. 1. Database Database: The DAIRETDB1 database consists of 89 colour fundus images of which 84 contain at least mild non proliferative signs of the diabetic retinopathy (see Figure 3.4), and five are considered as normal which do not contain any signs of the diabetic retinopathy according to all the experts participated in the evaluation. Images were captured with the same 50 degree field-of-view digital fundus camera with varying imaging controlled by the system in the Kuopio university hospital, Finland. The image ground truth provided along with the database is based on expert selected findings related to the diabetic retinopathy and normal fundus structures. Special software was used to inspect the fundus images and annotate the findings as hard exudates, hemorrhages and microaneurysms [8][9][10][11]. Fig. 3.4: Example of abnormal fundus image from DIARETDB1 database (left), and Ground truth of hard exudates (right). 2. Preprocessing Patient movement, poor focus, bad positioning, reflections, inadequate illumination can cause a significant proportion of images to be of such poor quality as to interfere with analysis. In approximately 10% of the retinal images, artifacts are significant enough to impede human grading. Preprocessing of such images can ensure adequate level of success in the automated abnormality detection. In the retinal images there can be variations caused by the factors including differences in cameras, illumination, acquisition angle and retinal pigmentation. First step in the preprocessing is to attenuate such image variations by normalizing the colour of the original retinal image against a reference image. Few of the retinal images acquired using standard clinical protocols often exhibit low contrast. Also, retinal images typically have a higher contrast in the center of the image with reduced contrast moving outward
  • 5. Raju Maheret al. Int. Journal of Engineering Research and Applications www.ijera.com ISSN: 2248-9622, Vol. 6, Issue 1, (Part - 3) January 2016, pp.122-127 www.ijera.com 126|P a g e from the center. For such images, a local contrast enhancement method is applied as a second preprocessing step. Finally it is required to create a fundus mask for each image to facilitate segmentation of lesions and anatomical structures in later stages. The pre-processing steps are explained in detail in the following subsections [9][10]. 3. Colour Normalization Colour normalization is necessary due to the significant intra-image and inter-image variability in the colour of the retina in different patients. There can also be, differences in skin pigmentation, aging of the patient and iris colour between different patients that affect the colour of the retinal image. Colour normalization method is applied to make the images invariant with respect to the background pigmentation variation between individuals. The colour normalization is performed using histogram matching. In histogram matching a processed image can have a shape of the histogram as specified by the user. This is done by modifying the image values through a histogram transformation operator which maps a given initial intensity distribution into a desired distribution using the histogram equalization technique as an intermediate stage. Let Ps(s) and Pd(s) represent the standard image and desired image probability density functions, respectively. 4. Fundus Mask Detection The mask is a binary image with the same resolution as that of fundus image whose positive pixels correspond to the foreground area. It is important to separate the fundus from its background so that the further processing is only performed for the fundus and not interfered by pixels belonging to the background. In a fundus mask, pixels belonging to the fundus are marked with ones and the background of the fundus with zeros. The fundus can be easily separated from the background by converting the original fundus image from the RGB to HSI colour system where a separate channel is used to represent the intensity values of the image. The intensity channel image is thresholded by a low threshold value as the background pixels are typically significantly darker than the fundus pixels. A median filter of size 5×5 is used to remove any noise from the created fundus mask and the edge pixels are removed by morphological erosion with a structuring element of size 5×5. Figure 3.5 (b) shows the example of the fundus mask [9][10][11]. Fig. 3.5: Automatic fundus masks generation. (a) Input image; (b) Automatically generated fundus mask. III. CONCLUSION To develop an automatic retinal image processing system, the first important thing is to obtain an effective database. To realize this and also for facilitating comparison with the existing methods, four sets of Retinal databases are used. Details of the fundus camera and image properties of each of these databases are explained. In any retinal image database, there will be some images with non-uniform illumination and poor contrast. There can also be difference in the colour of the fundus due to retinal pigmentation among different patients. These images are preprocessed before they can be subjected to anatomical and pathological structure detection. Colour normalization is performed to attenuate colour variations in the image by normalizing the colour of the original retinal image against a reference image. In order to correct non uniform illumination and to improve contrast of an image, contrast-limited adaptive histogram equalization is employed. On application of this method, the image quality is significantly improved with the increase in contrast. Each fundus camera has a mask of different shape and size according to its settings. By automatically detecting the fundus mask a lesion detection algorithm or vessel detection algorithm can process only the pixels of the fundus leaving out the background pixels. The following Chapters will explain the methods used to detect anatomical and pathological structures in retinal image leading to the development of automatic system for the identification of severity levels in diabetic maculopathy. REFERENCES [1] Raju Maher, Sangramsing Kayte, Dr. Mukta D “Review of Automated Detection for Diabetes Retinopathy Using Fundus Images” International Journal of Advanced Research in Computer Science and Software Engineering Volume 5, Issue 3, March 2015. [2] RajuSahebrao Maher, Sangramsing N Kayte, Sandip T Meldhe and Mukta
  • 6. Raju Maheret al. Int. Journal of Engineering Research and Applications www.ijera.com ISSN: 2248-9622, Vol. 6, Issue 1, (Part - 3) January 2016, pp.122-127 www.ijera.com 127|P a g e Dhopeshwarkar. Article: Automated Diagnosis Non-proliferative Diabetic Retinopathy in Fundus Images using Support Vector Machine. International Journal of Computer Applications 125(15):7-10, September 2015. Published by Foundation of Computer Science (FCS), NY, USA [3] Raju Maher, Sangramsing Kayte, Dnyaneshwar Panchal, PankajSathe, Sandip Meldhe " A Decision Support System for Automatic Screening of Non-Proliferative Diabetic Retinopathy" International Journal of Emerging Research in Management &Technology ISSN: 2278-9359 (Volume-4, Issue-10) October 2015 [4] RajuSahebrao Maher, Dnyaneshwar S. Panchal, Sangramsing Kayte, Dr. Mukta Dhopeshwarkar "Automatic Identification of Varies Stages of Diabetic Retinopathy Using Retinal Fundus Images"-International Journal of Advanced Research in Computer Science and Software Engineering Volume 5, Issue 9, September 2015 ISSN: 2277 128X [5] http://www.nei.nih.gov/health/diabetic/retin opathy.asp [6] Diabetic Retinopathy-Early Detection Using Image Processing Techniques [7] Diseases and Surgery of the Macula, Retina, and Vitreous Diabetic Eye Disease By John H. Drouilhet, M.D., FACS. [8] DIARETDB0: Evaluation Database and Methodology for Diabetic Retinopathy Algorithms [9] Sangramsing N. Kayte, Bharatratna P. Gaikwad, "Design and Development of Non-Proliferative Diabetic Retinopathy Detection Technique using Image Features Extraction Techniques “National Conference in Advances in computing (NCAC’13), 05-06 March 2013 [10] Acharaya, U.R., Ng, E.Y.K., Tan, J.H., Sree, S.V. and Ng, K.H. (2012) An integrated index for the identification of diabetic retinopathy stages using texture parameters. Jour- nal of Medical Systems, 36, 2011- 2020. [11] Raju Maher, Charansing N. Kayte, “Automated Screening of Diabetic Retinopathy Using Image Processing”, IOSR Journal of Pharmacy and Biological Sciences, Volume 10, Issue 6 Ver. III (Nov - Dec. 2015), PP 54-63. [12] Gonzalez, R.C. and Woods, R.E. (2008) Digital image processing. 3rd Edition, Prentice Hall, Upper Saddle River. [13] Andjelkovic, J., Zivic, N., Reljin, B., Celebic, V. and Sa- lom I. (2008) Application of multifractal analysis on me- dical images. Wseas Transactions on Information Science and Applications.