Proliferative Diabetic Retinopathy Diagnosis Using Varying Scales Filter Banks and Double Layered Thresholding
Proliferative Diabetic Retinopathy Diagnosis Using Varying Scales Filter Banks and Double Layered Thresholding
Article
Proliferative Diabetic Retinopathy Diagnosis Using
Varying-Scales Filter Banks and Double-Layered Thresholding
Noor ul Huda 1 , Anum Abdul Salam 2 , Norah Saleh Alghamdi 3, * , Jahan Zeb 2
and Muhammad Usman Akram 2, *
1 Center for Advanced Studies in Telecommunications (CAST), COMSATS Institute of Information Technology,
Islamabad 45550, Pakistan; [email protected]
2 Computer and Software Engineering Department, College of Electrical and Mechanical Engineering ,
National University of Sciences and Technology, Islamabad 24090, Pakistan;
[email protected] (A.A.S.); [email protected] (J.Z.)
3 Department of Computer Sciences, College of Computer and Information Sciences,
Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia
* Correspondence: [email protected] (N.S.A.); [email protected] (M.U.A.)
Abstract: Diabetic retinopathy is one of the abnormalities of the retina in which a diabetic patient
suffers from severe vision loss due to an affected retina. Proliferative diabetic retinopathy (PDR) is the
final and most critical stage of diabetic retinopathy. Abnormal and fragile blood vessels start to grow
on the surface of the retina at this stage. It causes retinal detachment, which may lead to complete
blindness in severe cases. In this paper, a novel method is proposed for the detection and grading of
neovascularization. The proposed system first performs pre-processing on input retinal images to
enhance the vascular pattern, followed by blood vessel segmentation and optic disc localization. Then
various features are tested on the candidate regions with different thresholds. In this way, positive
and negative advanced diabetic retinopathy cases are separated. Optic disc coordinates are applied
for the grading of neovascularization as NVD or NVE. The proposed algorithm improves the quality
of automated diagnostic systems by eliminating normal blood vessels and exudates that might cause
hindrances in accurate disease detection, thus resulting in more accurate detection of abnormal blood
vessels. The evaluation of the proposed system has been carried out using performance parameters
Citation: Huda, N.u.; Salam, A.A.;
such as sensitivity, specificity, accuracy, and positive predictive value (PPV) on a publicly available
Alghamdi, N.S.; Zeb, J.; Akram, M.U.
standard retinal image database and one of the locally available databases. The proposed algorithm
Proliferative Diabetic Retinopathy
gives an accuracy of 98.5% and PPV of 99.8% on MESSIDOR and an accuracy of 96.5% and PPV of
Diagnosis Using Varying-Scales Filter
Banks and Double-Layered
100% on the local database.
Thresholding. Diagnostics 2023, 1, 0.
https://doi.org/ Keywords: image processing; biomedical imaging; diabetic retinopathy;
proliferative diabetic retinopathy; autonomous disease detection; fundus image analysis
Academic Editor: Firstname Lastname
arise near the optic disc. Even a small rise in blood pressure can cause hemorrhages in
this case. If bleeding appears in the vitreous humor it can affect the visual system. If this
bleeding becomes extensive, it results in a painless and rapid blackening of the vision.
Neovascularization [6] is divided into two types [7]:
• Neovascularization on disc (NVD): If the new vessel formation occurs within one disc
diameter of the optical disc then this is categorized as NVD or neovascularization on disc
• Neovascularization elsewhere (NVE): If new vessel formation occurs elsewhere on the
surface of the retina, then this is called neovascularization elsewhere (NVE).
Figure 1 highlights the classification of neovascularization. The article consists of five
sections. Section 2 of the paper describes the existing work and the main contributions
presented by the proposed method. The details of the proposed system are given in
Section 3. Section 4 shows the results and evaluation while Section 5 is composed of the
conclusion and future work.
2. Related Work
Several techniques have been proposed so far for the automated screening and detec-
tion of non-proliferative diabetic retinopathy and its stages [8–10], However, for detection
of PDR a very few work has been carried out. We have organized the related literature
based on two subcategories, i.e., PDR detection using machine learning techniques and
PDR detection using deep learning techniques.
information from the vessels. The vessels were extracted using a Gabor filter, and the result-
ing magnitude image was converted to a binary image. The resultant image was analyzed
using a fractal analysis box-counting method that identified vessel bundles near the optic
disc region, i.e., neovascularization in the optic disc region (NVD). Among ten images,
five with neovascularization had a fractal mean value of 1.66 and five images with no
neovascularization in the optic disc region resulted in a fractal mean value of 1.58. Saranya
et al. [15] used the fuzzy C-means (FCM) technique for blood vessel segmentation. They
used a set of features that included the gradient, gradient variation, gray-level coefficient of
variation, moment invariant-based features, and tortuosity for a k-nearest neighbor (KNN)
classifier. They achieved an accuracy of 96.5% on the DRIVE and MESSIDOR datasets. A
research methodology for the automated detection of neovascularization for PDR proposed
by Sohini Roy Chowdhury et al. [16] describes a technique to detect neovascularization
from fundus images and classify it as neovascularization in the optic disc region (NVD) or
neovascularization elsewhere (NVE). The green plane is extracted from the input image
and normalized in the [0 1] intensity range. The region of interest (ROI) is extracted for
both types of neovascularization, leading to vessel detection from both ROIs. Textural,
structural, and intensity-based features are used to classify NVD and NVE. The proposed
method was trained and tested on 40 images (30 normal, ten with PDR) from the STARE
database and 17 images from a local dataset. Accuracies of 87.6% and 92.1% were obtained
for NVD and NVE, respectively.
Lee et al. [17] proposed a new vessel-detection method that includes statistical texture
analysis (STA), high-order spectrum analysis (HOS), and fractional analysis. They used a
total of 137 images in their work and achieved an area under the curve of 99.3%. A method
based on the following-the-line approach for the segmentation of vessels was proposed by
R.A. Welikala et al. [18]. They used two-line approaches and two different sets of features
for the retraction of true abnormal blood vessels. They used 60 images from the MESSIDOR
dataset for evaluation purposes and classified these images on the basis of an SVM classifier.
They achieved an area under the curve (AUC) value of 0.96. Shuang Yu et al. [19] proposed
a novel technique for the automation of neovascularization in the optic disc region (NVD).
A fundus image is pre-processed followed by the application of a Gabor filter to extract
blood vessels. Twenty-one texture-based and vessel-based features are extracted to classify
an image as normal or NVD using support vector machines (SVM). Sixty-six retinal images
(15 NVD, 50 normal) were extracted from the globally available MESSIDOR, HRF, and
DIARETDB0 datasets to test and train the proposed technique. A sensitivity of 15/16 and
specificity of 47/50 were achieved using the proposed methodology.
In 2016 research was conducted by Diego F. G. Coelho [20] that aimed to detect
NVD from fundus images. In the proposed methodology, fundus images are analyzed by
calculating the gradient magnitude of the Fourier power spectrum followed by extraction
of the angular spread. Entropy and spatial variance are used to categorize an image as a
normal image or image with NVD using a linear statistical classifier. An accuracy of 100%
was achieved when the proposed technique was tested on ten images (five normal, five
NVD) extracted from the MESSIDOR database. Akram et al. [7] presented a method for the
detection of PDR. Their proposed method extracted a number of features based on vascular
patterns for the proper representation of normal and abnormal vessels. A modified m-
mediods-based classifier was used for the proper discrimination of abnormal vessels from
normal ones. Another machine-learning-based technique for automated NVD detection
was proposed by Shuang Yu et al. [21]. The proposed algorithm takes a fundus image and
extracts the ROI, i.e., the disc region. Vessels are extracted using multilevel Gabor filters. A
feature vector with 42 features (morphological and texture based) is extracted from both
normal and NVD images, followed by a reduction in size to eighteen. A reduced feature
vector was used to train and test 424 (134 NVD, 290 non-NVD) retinal fundus images. An
accuracy of 95.23% was observed.
Christodoulidis et al. [22] proposed a novel technique for the detection of NVD from
fundus images. The proposed research states that NVD detection from retinal fundus
Diagnostics 2023, 1, 0 4 of 18
images can be improved by adding a second-order statistical feature to the existing feature
set containing structural, vessel-based, and intensity-based features. The image is pre-
processed, followed by vessel detection. The vessel junctions are extracted by applying the
Tensor voting technique, which highlights the local maxima, indicating the junctions of
vessels. The suggested feature addition to the feature vector improved the sensitivity to 0.84.
Mona Leeza et al. [23] proposed an algorithm in 2019 to detect the severity level of diabetic
retinopathy using the bag-of-features approach. The algorithm is composed of five phases
starting from local feature extraction from retinal images using SURF. K-means clustering
is used to cluster the extracted features for dictionary generation. The algorithm proceeds
by max pooling to accumulate features followed by the construction of histograms of
oriented gradient (HoG). SVM and artificial neural networks are used to classify the retinal
image as normal, mild NPDR, moderate NPDR, severe NPDR, and PDR. The algorithm
resulted in 95.92% and 98.90% sensitivity and specificity, respectively. Research conducted
by Lei Zhang et al. [24] described another algorithm to screen for PDR using a modified
matched-filter approach. In the proposed technique, the result from Gaussian is proceeded
by subtraction of the mean to eliminate the false positives that occur due to step edge noise.
The accuracy of the algorithm was evaluated on the ZUEYE database, which resulted in an
accuracy of 95%.
utilized the pre-trained model for feature extraction followed by classification using SVM.
In addition to using pre-trained models separately, a combination of ResNet and GoogleNet
was proposed that yielded the highest accuracy of 0.9157.
Another algorithm [30] utilized ResNet to detect retinal neovascularization from
retinal fundus images. The proposed framework pre-processed the input image to enhance
the contrast and remove noise followed by training ResNet. The proposed model was
trained on 3662 retinal images from a local dataset containing healthy images (Label 0),
neovascularized images (Label 2), and diabetic retinopathy images (Label 1). Due to the
residual properties of ResNet, the model resulted in an accuracy of 0.88 on 1992 retinal
fundus images. A review conducted by Salamat et al. [6] summarized and comprehended
66 papers aiming to detect and classify diabetic retinopathy using various techniques.
The paper presented the past 8 years of research articles starting from 2019, indicating the
techniques used, the dataset, and the evaluation metrics along with the type of classification
or number of classes. The majority of the techniques presented in the review classified an
image into healthy or diseased without classifying it by the degree/severity of disease.
Our proposed method is an extension of [7]. Our method grades the PDR with-
out the use of a classifier and utilizes a simple feature-extraction approach to minimize
false-positive detection. The main issues with most of the algorithms mentioned are the
appearance of false-positive regions for abnormal blood vessels and evaluation on a very
small dataset. The proposed algorithm is novel in the sense that it addresses both NVD and
NVE. It uses a very robust method for the detection of optic disc coordinates. It gives al-
most no false detection, unlike other cases. The algorithm extracts optic disc and candidate
abnormal blood vessel regions using the vascular structure and filter bank, respectively.
Double-layered thresholds on the basis of pattern analysis for the detection of PDR are
applied, which grade the input retinal image as NVD or NVE.
Figure 2. Proposed flow diagram for the detection and grading of PDR.
3.1. Preprocessing
An automated assessment for pathologies of the retina initially requires the pre-
processing of a digital fundus image. An inverted green channel is used as it enhances the
vascular patterns against the dark background. All images are scaled to the same size, not
disturbing their aspect ratio. The dark background of the image is not really black as it
contains some of the lighter regions and an amount of noise. It is necessary, for the proper
extraction of the vascular pattern in the retina, to separate the noisy background from
the image. For this purpose, background segmentation is carried out. The method first
creates a binary mask for the background by using the mean and variance and then it elimi-
nates the small noisy pixel values from the background by using different morphological
operators [31]. Figure 3 shows the images after pre-processing.
capability. They also act as a filter for the background noise. In this work, 2D continuous
wavelet Gabor transform (CWT) is used. It is defined in (1):
Z
Tψ (b, θ, a) = Cψ−1/2 a exp ( jkb)ψ̂∗ ( ar−θ k) ĝ(k)d2 k (1)
√
where j = −1, and ψ̂∗ and ĝ denote a Fourier transform. The 2D Gabor wavelet is defined
as:
1
ψG (x) = exp( jk0 x) exp(− |Ax|2 ) (2)
2
1
ψ̂G (x) = (det( B))1/2 exp(− ( B(k − k0 )2 )) (3)
2
where k0 ∈ R2 is a vector that defines the frequency of the complex exponential, B = A−1
−1/2
ϵ 0
and A = with elongation ϵ ≥ 1 is a 2 × 2 positive definite diagonal matrix
0 1
that defines the wavelet anisotropy and its elongation in any desired direction.
The Gabor wavelet transform Mψ (b, a) is computed for each pixel position and its
scale value is considered. In addition, θ spans from 0o to 165o at steps of 10o and its
maximum is taken.
Mψ (b, a) = max | Tψ (b, θ, a)| (4)
Multilayered and adaptive thresholding techniques are applied to create a binary
mask for blood vessels after the completion of blood vessel enhancement [33]. The masking
process assigns 1 to all vessel pixels and 0 to all non-vessel pixels.
optic disc is segmented, where candidate regions are calculated using a Fourier transform
followed by morphological operations. If more than one candidate region appears, then
blood vessel segmentation is carried out to calculate the energy of each region. The region
with the maximum energy is marked as the OD [34]. Figure 5 shows the OD coordinates
after applying the algorithm.
The binary thresholded image that we obtain after the abnormal blood vessel extraction
contains both the lesions and the abnormal blood vessels. Neovascularization on disc (NVD)
is graded as the abnormal blood vessels detected at one disc distance (1dd) from the optic
disc coordinates. If D denotes the diameter of the disc then one disc diameter can be
calculated using:
1dd = D + ( D/2) (5)
By applying the one-disc distance, two filter masks are created, one for the NVD case
and the other for the NVE case. These masks are applied to the image for the extraction of
features. Figure 6 shows the filter masks and images to be further processed. True and false
objects in the binary image are first classified on the basis of the 0th moment of the image,
that is, the area of the candidate ROI. Let the characteristic function for the object in the
image be L( x, y). We define:
Figure 6. (A,C,E) show the filter mask, binary filtered image, and its map on the original green
channel for NVD, respectively. (B,D,F) show the filter mask, binary filtered image, and its map on
original green channel for NVE, respectively.
The first-order moment, i.e., the center of mass of the objects, is then calculated. Let
the center of mass be denoted by ( x̄, ȳ). Then:
RR
xL( x, y)
x̄ = R R (7)
L( x, y)
RR
yL( x, y)
ȳ = R R (8)
L( x, y)
where x and y are the coordinates of the image. The center of mass is then chosen as the
center of the window for the region of interest. Choosing an appropriate window size is
quite crucial. It is chosen to include all the abnormal blood vessels.
blood vessels have a high entropy value. If pk is the probability of occurrence of a grey
level k and M is the number of grey levels in the image, then entropy is calculated as:
M
H=− ∑ ( pk ) log2 ( pk ) (9)
k =1
• Energy: Energy is the sum of squares of all pixel intensities within a candidate region
of interest. The energy of the region containing the abnormal blood vessels lies in
between those of the regions that contain normal blood vessels and the bright lesions
or exudates. If g( x, y) is the pixel value in an image then the energy is calculated as:
• Homogeneity: Homogeneity returns a value that tells the closeness of the distribution
of elements. The homogeneity of abnormal blood vessels lies very close to that
of normal blood vessels but it is away from that of the lesions and exudates. The
abnormal blood vessels originate near normal vessels, while the exudates and bright
lesions can be found anywhere on the retina. The homogeneity is calculated as:
g(i, j)
H= ∑ 1 + |i − j | (11)
i,j
1
Mm ag =
nm ∑ G(i, j) (13)
i,j
The value for the feature sets is chosen inside a fixed window size for each candidate
ROI. The features and characteristics of newly grown vessels lie in between those of the
original vascular pattern and other false detection. Thus, thresholds are applied on both
the upper and lower bounds. After thresholding, there still remains some wrongly detected
Diagnostics 2023, 1, 0 12 of 18
candidate regions of interest, which can be called false-positive detection. A box plot
analysis is used for the further analysis and processing of false-positive detection.
3.6. Post-Processing
The regions that are obtained after ROI processing are grouped into two classes. One
contains the true positive, i.e., the region that actually has neovascularization, and the other
contains the false positive, which does not have neovascularization. A set of features is
applied to both classes. In this analysis, the size of the window for analysis of features is
kept adaptable to the size of the ROI. These features are as below:
1. Mean Intensity ( f 1 ): It is the mean value of pixels within the green plane of the
candidate region.
2. Maximum Intensity ( f 2 ): It is the maximum value of pixels within the green channel
of the candidate region.
3. Mean Skewness ( f 3 ): It is the measure of the lack of symmetry in a candidate region.
It is computed as:
∑ N ( gi − ḡ)3
skewness = i=1 (16)
( n − 1) s3
where g( x, y) is the candidate pixel value, g( x,¯ y) is the mean value pixels, s is the
standard deviation, and N is the number of pixels in the candidate region.
4. Entropy ( f 4 ): It is the value of all pixels in a candidate region and its neighboring
pixels. It is the measure of unpredictability in an ROI.
5. Energy ( f 5 ): It is the sum of the squares of all the pixel values of the green plane
inside a candidate region.
6. Mean Gradient ( f 6 ): It is the mean of the pixels of the edges detected using the Sobel
gradient within the candidate region.
7. Gradient Direction ( f 7 ): It is the standard deviation of the direction of the Sobel
gradient in a candidate region.
8. Mean Intensity of red plane ( f 8 ): It is the mean value of pixels within the red plane of
the candidate region.
9. Mean Intensity of blue plane ( f 9 ): It is the mean value of pixels within the blue plane
of the candidate region.
10. Mean Intensity lightness in LAB color space ( f 9 ): It is the mean value of pixels within
the lightness plane in the LAB color space of the candidate region.
A number of the features mentioned were tested on both sets of candidate ROIs, i.e.,
NVD and NVE. However, not all of them are useful in improving the accuracy of the cases.
Feature selection is very important in any automated system. To select good features for
applying further thresholds, box plots are analyzed. The box plot represents the data in
the form of blocks to show its lowest, highest, and median values [35]. The upper adjacent
limit is found by:
U pperlimit = Q3 + [1.5( Q3 − Q1 )] (17)
and the lower adjacent limit is found by:
where Q1 and Q3 are the first and third quartile, respectively. Figures 7 and 8 show the box
plot for useful NVD and NVE feature sets, respectively. The box plots are analyzed to find
the threshold values. After finding the features and threshold, each candidate region is
subjected to that feature set and the threshold is applied. If the feature value fulfills the
threshold then it is said to be a true detection; otherwise, it is removed.
Diagnostics 2023, 1, 0 13 of 18
Figure 7. Box plots of best features for NVE. (1) True detections, (2) false detections.
Figure 8. Box plots of best features for NVD. (1) True detections, (2) false detections.
4. Results
A dataset is a standard tool for the comparisons and evaluation of different algorithms.
It is very essential for the proper evaluation of medical image-processing-based algorithms.
We evaluated our algorithm on one globally available dataset (MESSIDOR) and one locally
available dataset.
MESSIDOR has been established to facilitate computer-aided diabetic retinopathy
detection [36]. The images in the dataset were acquired with a TopCon TRC NW6 Non-
mydriatic fundus camera with 45o FOV and resolutions of 1440 × 960, 2240 × 1488, and
2304 × 1536 with 8 bits per color plane. A total of 1200 images is contained in this dataset,
which is divided into three subsets of 400 images. Each subset is further divided into
Diagnostics 2023, 1, 0 14 of 18
four parts to facilitate thorough testing. An Excel file accompanies each set that contains
medical findings that are used for testing purposes. These images are graded into different
categories depending on the number, position, and presence of different lesions. Locally,
some data have been collected from the Armed Forces Institute of Ophthalmology (AFIO).
A total of 1200 images from the MESSIDOR database and 20 images from the AFIO database
is used for the evaluation of the proposed algorithm. A detailed description of the database
is given in Table 4.
In order to perform detailed testing, the algorithm is run on the whole database and
the results are verified with the help of an ophthalmologist. The results are compared with
the ground truth of the abnormal blood vessels marked by ophthalmologists. The results
are also verified with the ground truth attached to the database. A detailed evaluation of
the proposed system is also performed using different statistical evaluation parameters
such as sensitivity, specificity, accuracy, and PPV.
TP
Sensitivity = (19)
( TP + FN )
TN
Speci f icity = (20)
( TN + FP )
TP
PPV = (21)
( TP + FP )
( TP + TN )
Accuracy = (22)
( TP + TN + FP + FN )
where:
• TP are true positives, meaning abnormal blood vessel regions correctly classified as
abnormal.
• TN are true negatives, meaning normal blood vessel regions correctly classified an
normal.
• FP are false positives, meaning normal blood vessel regions wrongly classified as
abnormal.
• FN are false negatives, meaning abnormal blood vessel regions wrongly classified as
normal blood vessel regions.
Table 5 shows a comparison of the proposed system with existing methods for PDR de-
tection.
Table 5. Performance comparison of the proposed system with existing systems for abnormal blood
vessel detection.
Acc/F1
Sr. Method Number of Images Sen Spec
Score
1 Jelinek et al.[13] 27 images – – 0.90
Saranya et
2 50 images from MESSIDOR and DRIVE 0.96 0.89 0.96
al.[15]
3 Lee et al.[17] 137 images from MESSIDOR 0.96 0.99 0.98
Welikala et
4 60 images 0.91 0.92 0.96
al.[18]
5 Garima et al.[15] 799 images 0.95 0.83 0.96
Diagnostics 2023, 1, 0 15 of 18
Table 5. Cont.
Acc/F1
Sr. Method Number of Images Sen Spec
Score
8 Proposed 1200 images from MESIDOR 0.90 1 0.98
– 20 images from AFIO 0.80 1 0.95
Figure 9 illustrates the abnormal blood vessel detection results for the proposed
method. The validity of the proposed system is clearly highlighted. A large number of
images is used for the evaluation of the system. The improvement in results is because
of the accurate extraction of abnormal blood vessels and the optic disc for the detection
of sound feature selection and because of false ROI removal. Table 5 comprehends and
compares the results of various state-of-the-art frameworks with our proposed framework.
On the basis of accuracy, the proposed algorithm yields the highest accuracy on a large
dataset. Other algorithms achieving 0.98 accuracy lack thorough testing on a large dataset.
Moreover, unlike the majority of algorithms cited in the related literature, the proposed
framework not only highlights the diseased cases, but also categorizes them based on
the disease severity, also highlighting the diseased area. Moreover, instead of using deep
learning frameworks to obtain accurate results, our algorithm uses basic image-processing
techniques to reach the final conclusion, which makes it light and less data-hungry, since it
does require pre-training the model, thus giving accurate results even on a small dataset.
Figure 9. Results of grading of PDR: (a) graded as 1 and 2, (b) graded as 1, (c) graded as 1 and 2, (d)
graded as 0.
5. Conclusion
Proliferative diabetic retinopathy (PDR) is an advanced stage of diabetic retinopathy.
In this research, a computerized medical system for the screening of PDR is presented. The
proposed system performs an analysis of retinal images for grading PDR by analyzing box
plots for different sets of features. The proposed system carried out OD detection followed
by region-of-interest detection. The abnormal blood vessel detection stage created a binary
map of candidate regions using filter banks. A detailed feature set based on the properties
of these abnormal blood vessels is created for each candidate region and thresholds are
applied to detect all true abnormal blood vessel regions. A further set of features is then
applied with an adaptive window and the distribution pattern of true and false detection is
Diagnostics 2023, 1, 0 16 of 18
analyzed with box plots. By using the coordinates of the OD and the distance of abnormal
blood vessels from the optic disc, the system graded the input image into three categories,
i.e healthy, NVD, and NVE. The evaluation of the proposed system was performed on
the MESSIDOR and AFIO databases. For evaluation, the statistical measures sensitivity,
specificity, accuracy, and PPV were used. The results showed that the system achieved an
average accuracy of 98.5% and 96.5% for the MESSIDOR and AFIO databases, respectively,
while a PPV and specificity of 99.8% was achieved for both databases. This research’s
contributions are (i) a complete system for the grading of PDR, (ii) improved results by
addressing open issues such as the occurrence of false positives due to the similarity of
abnormal blood vessels to normal blood vessels, (iii) the use of two different techniques
for the extraction of a useful feature set, based on the properties of normal and abnormal
blood vessels, and (iv) the proposal of a method without the need for a classifier, which
saves the time required in training.
Author Contributions: Methodology, N.U.H, M.U.A., N.S.A., and A.A.S.; Validation, J.Z., M.U.A.,
and N.S.A.; Formal analysis, N.U.H.; Writing—original draft, N.U.H. and A.A.S.; Writing—review
and editing, M.U.A. and A.A.S.; Visualization, J.Z.; Supervision, M.U.A. and N.S.A.; Project admin-
istration, M.U.A. and N.S.A.; Funding acquisition, N.S.A. All authors have read and agreed to the
published version of the manuscript.
Funding: Princess Nourah bint Abdulrahman University Researchers Supporting Project number
(PNURSP2023R40), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
Institutional Review Board Statement:
Informed Consent Statement: Informed consent was obtained from all subjects involved in the study.
Data Availability Statement: The MESSIDOR dataset is available at https://www.adcis.net/en/
third-party/messidor/ (accessed on 29 June, 2023).
Conflicts of Interest: The authors declare no conflicts of interest.
Abbreviations
The following abbreviations are used in this manuscript:
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