Retina Image Analysis

• Project name: Retina Image Analysis

• Tutor: Michael Beyeler (michael.beyeler@unil.ch)

• Slides: File:Retina image analysis.pptx

                                     Retina Image Analysis                                        
                      Participant : Alexandre Jann, Maylis Touya, Paola Zanchi
                                Teaching Assistant:  Michael Beyeler

Introduction

With an estimated number of 17.9 million death per year, cardiovascular diseases are the first cause of death (WHO). More people die annually from these diseases than from any other cause. Cardiovascular disease is a group of disorder of the heart and the blood vessels. It includes different types of disorders such as strokes, heart attack, coronary heart disease, cerebrovascular disease, thromboembolic disease, rheumatic heart disease, cardiomyopathy, and other conditions. Out of all cardiovascular diseases death, 85% are due to heart attacks and strokes. Many factors must be taken in account for the development of cardiovascular disease. High blood pressure is a very predominant factor that account for about 13% of the deaths. Tobacco and diabetes have also an impact as well as lack of exercise, obesity, and poor diet. Prevention of the cardiovascular disease and identification at early stages can prevent premature deaths. These diseases usually take place in low- and middle-income countries (75% of cardiovascular disease death). This is mainly because those countries often do not have the benefit of integrated primary health care programs for early detection and treatment of people with risk factors as there is for the people in high-income countries.

The eye fundus is the interior surface of the eye opposite the lens. It is supplied by two distinct vascular systems: arteries and veins. With fundus photography, a special fundus camera points through the pupil to the back of the eye and takes pictures. Color images provide documentation of the ocular fundus. The resulting images can be spectacular and help the doctor to find, watch and treat disease. An eye fundus is a less invasive physical exam, which allows us to see well the conditions of the blood vessels in a very short amount of time. It seems that it can be a very good exam and can maybe replace the actuals vascular exams that are invasive and take a long time to be made.

With this project, we wanted to know if we can link tortuosity of the blood vessel in the eyes with cardiovascular diseases by using programming and bioinformatics.

This project is quite interesting because it allows us to have a mathematical insight into the determination of diseases and comorbidity risks. Moreover, since an eye fundus is a less invasive physical exam, allowing us to see well the conditions of the blood vessels in a very short amount of time, it seems that it can be a very good exam, and maybe can replace the actuals vascular exams that are invasive and take a long time to be made. As said before, a very high number of cardiovascular diseases can be avoided thanks to prevention and early detection, so with this project, detection could be easier for the patients and the doctor as well and show efficient results.

Problematic / Hypothesis

Can we predict the risk of cardiovascular disease from the tortuosity of blood vessels in the eye?

Material and Methods

Material

Eye Fundus Snapshot

Eye fundus snapshots are easy to take. Eye fundus examination is used for screening for vision problems and via the health status of the retina, macula and blood vessels. This can be done in people of any age. To carry out this examination, it is necessary to use ophthalmic drops that permit to dilate the pupils and increase the angle of observation and therefore allow better visualization of the eye fundus with the different structures present: retina, retinal vasculature, optic disc, macula, and posterior pole. Images are produced using a low-power microscope attached to a camera (1). Let's note that a fundus camera or retinal camera is a specialized low power microscope with an attached camera designed to photograph the interior surface of the eye, including the retina, retinal vasculature, optic disc, macula, and posterior pole (i.e. the fundus). Your eyes will be dilated before the procedure. Widening (dilating) a patients pupil increases the angle of observation. This allows the technicians to image a much greater area and have a clearer view of the back of the eye. Based on the reflected light effect, it is then possible to obtain an image [1]. In colour fundus photography, the image intensities represent the amount of reflected red (R), green (G), and blue (B) wavebands, as determined by the spectral sensitivity of the sensor. The capture lasts only a few minutes per eye, is not painful and non-invasive. The use of eye drops (eye drops) does not show any health impairment. The only side effects that have been perceived and are that sometimes it is possible to see phenomena of ocular dryness, foreign body sensation, and watery eyes.[2]

Here, you can find a video (2) showing the step by step of this procedure.

UKBioBank

UK biobak here

Method

ARIA

It is a software originally used for measuring the tortuosity of a plant's roots. In fact, ARIA stands for Automatic Root Image Analysis, and has been shown at first in this paper [3]. Here, it has been used to measure the tortuosity of blood vessels in fundus images.

Tortuosity measurement :

Distance Factor Formula

First method

We used the density factor (called DF) to calculate the tortuosity of the blood vessels. It consists of the ratio between the length of a line and the length between its first and last point of measurement. As shown on the right, we can see that the formula is pretty simple and easy to manipulate.

The formula for the distance ratio (DF) with the total length of the path of the segment (numerator) divided by the length of the segment between it's first and last point (denominator).

Second Methods

We also tried to

Statistical tools :

We used the quantile method to determine the outliers of our DF: all the DFs that were above the 4rth quantile were set as irrelevant, and thus deleted from the dataset. As shown on the right, we can again see that the formula of the quantile method is pretty simple and easy to manipulate and understand. As you can see, the calculated value was used as a threshold in order to remove all of the outliers: as said earlier every value above this one was set as an outlier and thus deleted.

Formula in order to calculate the threshold value above which the outliers will be defined

Results

Firstly, by plotting each point found by ARIA and adapting their diameter to the one found by the software, we managed to find that there are some fundus that are way more tortuous than other, just by looking at them and by looking at their plotted blood vessels.

References

Papers [ between square brackets ]

1. Michael Abràmoff, Christine N. Kay, Chapter 6 - Image Processing, Editor(s): Stephen J. Ryan, SriniVas R. Sadda, David R. Hinton, Andrew P. Schachat, SriniVas R. Sadda, C.P. Wilkinson, Peter Wiedemann, Andrew P. Schachat, Retina (Fifth Edition), W.B. Saunders, 2013, Pages 151-176, ISBN 9781455707379,https://doi.org/10.1016/B978-1-4557-0737-9.00006-0.
2. Oliverio, Giovanni William et al. “Safety and Tolerability of an Eye Drop Based on 0.6% Povidone-Iodine Nanoemulsion in Dry Eye Patients.” Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics vol. 37,2 (2021): 90-96. doi:10.1089/jop.2020.0085
3. Pace J, Lee N, Naik HS, Ganapathysubramanian B, Lübberstedt T (2014) "Analysis of Maize (Zea mays L.) Seedling Roots with the High-Throughput Image Analysis Tool ARIA (Automatic Root Image Analysis)". PLOS ONE 9(9): e108255. https://doi.org/10.1371/journal.pone.0108255
4. Cheung, Carol Yim-Lui et al. “Retinal vascular tortuosity, blood pressure, and cardiovascular risk factors.” Ophthalmology vol. 118,5 (2011): 812-8. doi:10.1016/j.ophtha.2010.08.045
5. Strandberg, Timo E, and Kaisu Pitkala. “What is the most important component of blood pressure: systolic, diastolic or pulse pressure?.” Current opinion in nephrology and hypertension vol. 12,3 (2003): 293-7. doi:10.1097/00041552-200305000-00011

Websites and Videos (between simple brackets)

1. Internet Site of the University of British Columbia : Color Fundus Photography
2. Video : "Fundus Photography step by step" by the Fundus Photography Channel

Why was this project a challenge?

This project was a huge challenge because of the time: there was a lot of things to say and to explore and not a lot of time to explore everything we had in mind. Also, the COVID pandemic was a huge problem because of the distance between everyone and sometimes temperamental computers. But in the end, after countless hours on this project, we finally managed to upload results that we were proud of.

PDF Files of our work

You can find the PDF of our work on R here for the small dataset.

You can find our R script here.

You can find our intermediate presentation here.

You can find our final PDF report here.

You can find our final presentation here.