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  <front>
    <journal-meta />
    <article-meta>
      <title-group>
        <article-title>Application of convolution neural networks in eye fundus image analysis</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>N Y Ilyasova</string-name>
          <email>ilyasova.nata@gmail.com</email>
          <xref ref-type="aff" rid="aff0">0</xref>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>A S Shirokanev</string-name>
          <email>alexandrshirokanev@gmail.com</email>
          <xref ref-type="aff" rid="aff0">0</xref>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>I A Klimov</string-name>
          <email>klimov.ilya.05@gmail.com</email>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          <institution>Image Processing Systems Institute of RAS - Branch of the FSRC "Crystallography and Photonics" RAS</institution>
          ,
          <addr-line>Molodogvardejskaya street 151, Samara, Russia, 443001</addr-line>
        </aff>
        <aff id="aff1">
          <label>1</label>
          <institution>Samara National Research University</institution>
          ,
          <addr-line>Moskovskoe Shosse 34А, Samara, Russia, 443086</addr-line>
        </aff>
      </contrib-group>
      <pub-date>
        <year>2019</year>
      </pub-date>
      <fpage>74</fpage>
      <lpage>79</lpage>
      <abstract>
        <p>In this work, we proposed a new approach to analyzing eye fundus images that relies upon the use of a convolutional neural network (CNN). The CNN architecture was constructed, followed by network learning on a balanced dataset composed of four classes of images, composed of thick and thin blood vessels, healthy areas, and exudate areas. The learning was conducted on 12x12 images because an experimental study showed them to be optimal for the purpose. The test error was no higher than 4% for all sizes of the samples. Segmentation of eye fundus images was performed using the CNN. Considering that exudates are a primary target of laser coagulation surgery, the segmentation error was calculated on the exudate class, amounting to 5%. In the course of this research, the HSL color system was found to be most informative, using which the segmentation error was reduced to 3%.</p>
      </abstract>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>1. Introduction</title>
      <p>
        A severe consequence of diabetic retinopathy (DRP) is vision loss. DRP affects all parts of the retina,
leading to macular edema, which in turn causes fast worsening of eyesight [
        <xref ref-type="bibr" rid="ref1">1</xref>
        ]. The accurate and early
diagnosis alongside an adequate treatment can prevent the vision loss in more than 50 % of cases
[23]. There are a number of approaches to treating DRP, one of which involves laser photocoagulation
[
        <xref ref-type="bibr" rid="ref4">4</xref>
        ]. During this procedure, a number of retina areas where edema occurs are cauterized with a laser.
The procedure is conducted via coagulating near-edema zones. The development of diagnostic systems
enabling an automatic identification of the edema zone is currently a relevant task [
        <xref ref-type="bibr" rid="ref5">5</xref>
        ]. For the laser
coagulation procedure to be automated [
        <xref ref-type="bibr" rid="ref6 ref7">6, 7</xref>
        ], objects in the eye fundus image need to be classified [
        <xref ref-type="bibr" rid="ref10 ref11 ref8 ref9">8-11</xref>
        ],
which can be done in a number of ways [
        <xref ref-type="bibr" rid="ref12">12</xref>
        ].
      </p>
      <p>
        Convolutional neural networks are the choice of preference when dealing with object classification
[
        <xref ref-type="bibr" rid="ref13">13</xref>
        ]. Such is the conclusion members of the research community involved in medical image analysis
have come to in the course of their research. Techniques for medical data analysis are often among
research topics at international conferences and symposia. May 2006 has seen the publication of the
first issue of IEEE Transaction on. The first detailed review to be published on the use of deep
learning for medical image analysis appeared in 2017 [
        <xref ref-type="bibr" rid="ref5">5</xref>
        ]. Nowadays an active trend for the
development of digital medicine is seen.
      </p>
      <p>
        In Ref. [
        <xref ref-type="bibr" rid="ref14">14</xref>
        ], a classification model based on a convolutional neural network was used for
diagnosing the H. Pylori infection. In the work, an architecture specially tailored for a particular task
was utilized. The authors came to the conclusion that the particular disease was possible to diagnose
based on endoscopic images obtained using CNN. In Ref. [
        <xref ref-type="bibr" rid="ref15">15</xref>
        ], diagnosing an early-stage hypertension
retinopathy was discussed. The onset of the disease in the eye retina is prompted by blood hypertension.
The classifier proposed in Ref. [
        <xref ref-type="bibr" rid="ref15">15</xref>
        ] offered a 98.6 percent accuracy. In Ref. [
        <xref ref-type="bibr" rid="ref16">16</xref>
        ], a toolkit was
developed for the automated analysis of psoriasis-affected skin biopsy images, which is of considerable
significance in clinical treatment. The paper is a pioneering attempt into automatic segmentation of
psoriasis-affected skin biopsy images. The study resulted in a practical system based on the machine
analysis. CNN training on a prepared dataset was demonstrated, intended for further analysis of input
images.
      </p>
      <p>In this work, we study a class of eye fundus images with pathological changes that can be found at
different stages of the disease. Manifestations of the diabetic retinopathy include exudates, which
cause the retina thickening (Figure 1). In general, the image of an eye fundus with pathology contains
four classes of objects, such as thick and thin blood vessels, healthy areas and exudate zones.</p>
    </sec>
    <sec id="sec-2">
      <title>2. Training the convolutional neural network</title>
      <p>The initial data for analysis contained 11 training datasets of various size. All datasets were balanced
and in total contained 534 images. For the purposes of the present work, the CNN training was
conducted on four above-described classes of eye fundus images. The initial dataset consisted of 75
percent of training images and 25 percent of test images. To prevent overtraining, a control dataset
was also used. A 3x3 convolution kernel was chosen because it is optimal for 12x12 images. The CNN
architecture was constructed empirically so as the required accuracy of no less than 96 % is ensured.
Table 1 gives architecture of the empirically constructed convolutional neural network. With this
architecture, a recognition accuracy of 99.3% was attained, which is the best recognition result for the
four above-mentioned classes of images. Figure 2 depicts a plot for training the CNN model in each
training epoch.</p>
      <p>Layer
number
1
1
2
2
2
2
3</p>
      <p>Layers
Convolutional
Activation
Convolutional
Activation
Dropout
MaxPooling
Convolutional</p>
      <p>To attain a recognition certainty of 95 %, the CNN was put through 120 training runs on the initial
images of all sizes. Figure 3 shows an average training result for each image size.</p>
      <p>The results in Figure 2 show that the highest classification accuracy is attained for 12x12 images.</p>
    </sec>
    <sec id="sec-3">
      <title>3. Experimental study</title>
      <p>For the experiments, datasets were formed containing four above-described classes of 12x12 images,
using which the best result of CNN testing is achieved (Figure 3). In this study, the segmentation of
eye fundus images was conducted via deep learning. Shown in Fig. 4b is the result of CNN-aided
image segmentation. With a view of estimating the CNN-aided segmentation error, a manual
segmentation by an expert ophthalmologist was introduced as a reference image (Figure 4c). The
study was conducted on the exudates class, which had been singled out into a separate image (Figure
4d). The error of CNN-aided segmentation of the said exudate areas was calculated relative to the
expert estimate. The result of comparison of the exudation areas highlighted by CNN and the expert is
shown in Table 2. Using the data from Table 2, a CNN-aided segmentation error for the exudates was
defined as E = ( k + t ) NM and amounted to 7% (where N×M is the image size, k is the number of
expert-highlighted pixels that CNN failed to recognize as exudates, t is the number of exudate pixels
recognized by CNN but missing from the expert's image). The error of first kind, defined as E1 = l F ,
where l is the number of falsely recognized exudates classes and F is the total number of
exudatecontaining pixels in the expert's image, amounted to 5%.</p>
      <p>
        In the process of exudates area identification, color plays a key role. The segmentation error can be
significantly reduced by operating in particular color spaces. It has been established [
        <xref ref-type="bibr" rid="ref17">17</xref>
        ] that color
models YUV, RGB and HSL are most close to color perception of the human eye. However, the
models RGB and YUV have a number of hardware limitations with certain video-systems. In further
research, we used the HSL color model as the one that most adequately renders the color
characteristics of blood vessels and exudates. Figure 5 shows pathological areas highlighted by the
expert in different HSL color channels.
      </p>
      <p>Areas
Exudates area in the expert's image
Exudates area in the CNN-aided image
Total exudates area
Expert's exudates areas omitted by CNN
CNN-highlighted exudates areas missing in the expert's image</p>
      <p>Veracity of CNN-aided exudate highlighting has been confirmed by comparison of histograms of
CNN-aided and expert's images (Figure 4), which were superimposed for each corresponding channel
of HSL color system, with the expert-based histograms marked as green bars, and the CNN-based
histograms marked red (Figure 6). The expert-based histograms define an interval of values for the
affected fundus areas. From the histograms, the CNN-aided interval of exudates area is seen to be
narrower than that obtained based on expert's estimates. The histogram regions corresponding to the
false CNN-aided classification are within intervals shown by rectangles (Figure 6). Table 3 gives
segmentation errors calculated for each channel of the НSL color model. The data in Table 3 suggest
that the H channel is the most informative channel with the least segmentation error.
d) e) f)
Figure 5. Expert-highlighted affected fundus areas for the HSL color model for the channel (a) H, (b)
S, and (c) L; CNN-highlighted affected fundus areas for the HSL color model for the channel (d) H,
(e) S, and (f) L.</p>
      <p>Channel
Segmentation error for
the exudates class, %
c)
Figure 6. Image histograms obtained by using an expert opinion and CNN: а) Н channel, b) S
channel, and c) L channel.</p>
    </sec>
    <sec id="sec-4">
      <title>4. Conclusion</title>
      <p>In this work, a convolutional neural network (CNN) has been applied to the analysis of an eye fundus
image. CNN architecture has been constructed, allowing a testing error of no more than 4% to be
attained. Based on a 3x3 convolution kernel, CNN training was conducted on 12x12 images, thus
enabling the best result of CNN testing to be achieved. CNN-aided segmentation of the input image
conducted in this work has shown the CNN to be capable of identifying all training dataset classes
with high accuracy. The segmentation error was calculated on the exudates class, which is key for
laser coagulation surgery. The segmentation error on the exudates class was 7 %, with the error of first
kind being 5 %.</p>
      <p>In the study, we utilized the HSL color model because it renders color characteristics of eye blood
vessels and exudates most adequately. We have demonstrated the H channel to be most informative,
with the segmentation error amounting to 3 %.</p>
    </sec>
    <sec id="sec-5">
      <title>Acknowledgements</title>
      <p>This work was financially supported by the Russian Foundation for Basic Research under grant #
1929-01135, # 17-01-00972 and by the Ministry of Science and Higher Education within the State
assignment to the FSRC “Crystallography and Photonics” RAS.</p>
    </sec>
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