A non-invasive approach for early diagnosis of retinal diseases | HCLTech

A non-invasive approach for early diagnosis of retinal diseases

A non-invasive approach for early diagnosis of retinal diseases
May 18, 2021

Retina

Retina is a thin layer of tissue on the inside back wall of your eye.  It contains millions of light sensitive cells (cones and rods) and other nerve cells that receive and organize visual information. Retina sends this information to the brain enabling us to see.

Retinal diseases which when diagnosed at an early stage can be treated and vision loss can be avoided.

Retinitis pigmentosaRetinal diseases can affect any part of your retina, causing visual symptoms. Untreated, some can cause severe vision loss and blindness. Some of the retinal diseases are:

  • Macular degeneration
  • Retinoblastoma
  • Diabetic Retinopathy
  • Retinal ischaemia

These diseases when diagnosed at an early stage can be treated and vision loss can be avoided. Hence, early diagnosis of these diseases plays an important role.

Existing methodologies for diagnosis

 Electroretinography: In this procedure, the patient’s retina is stimulated by a flash light and the retina’s electrical response to light is captured by electrodes placed on the eye. The information from the electrodes transfers to a monitor and gets displayed as electrical signals which can be analyzed for diagnosis

RatinaRatina

In this approach, the drawbacks include electrodes placed directly on the cornea, which makes it invasive, and the electrodes used are very expensive.

Fluorescein angiography: In this procedure, fluorescent dye is injected into bloodstream to highlight the blood vessels for photography.

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This is also an invasive approach and dye injection results in eye infection.

Fundus Photography: In this procedure, the interior surface of the eye is photographed by a specialized low power microscope with an attached camera.

Here the equipment used for photography is sophisticated, expensive, and requires highly trained personnel for operation and interpretation of results.

Proposed approach – A non-invasive electrophysiology test for retinal disorders

Idea description

The retina of the patient’s eye is stimulated by a light stimulus (flickering LED). The electrical response of the retina to the light is captured by surface electrodes (Ag/AgCl) placed in contact with the skin close to the eye. These electrodes obtain electrical signals generated by the retina in response to light stimulus.

The acquired electrical signals are processed using various pre-processing methods by a signal processing software and then the latency - the time interval between actuation of stimulus and maximal response (peak) of the acquired signal which is an indication of degree of retinal disorder is calculated. This elapsed time calculation is analyzed for diagnosing retinal disorders.

Methodology:

  • Electrode placement
  •  External stimulus (flashes of light) to the retina
  •  Signal acquisition, pre-processing, and processing
  •  Feature extraction (peak response)
  •  Algorithm to calculate latency
  •  Interpretation of results

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Electrode placement

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  • The electrodes are Ag/AgCl surface which are used predominantly for acquisition of bio-electric signals (ECG, EEG, EGG).
  • Three electrodes (two active and one ground) are placed in contact with the skin close to the eye. One active electrode is placed along the side of one eye and the other placed beneath the lower eyelid. The ground electrode is placed on the center of the forehead. Ground electrode is a must to prevent electric shock to the patient while acquiring electric signals.
  • The return electrical signals generated by the retina in response to the light stimulus are acquired with the help of these electrodes.

External Stimulus:

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  • An external stimulus is used to stimulate the retina in order to generate electrical signals.
  • This stimulus can be series of light from a light-emitting diode spaced for about 30 ms or reversal of black and white boxes of a checker board or stimulus of other frequencies. As retina is a part of the eye which converts light signals to electrical signals the stimulus should be a flickering light which can trigger retina to produce electrical signals.
  • LIGHT STIMULI – A single bright LED white light flickering at a time interval of 30 milliseconds gives the desired response from retina.

FluroFluro

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  • The electrical signals (analog signals) from the retina in response to the external stimulus which are acquired using the surface electrodes is of micro volt which cannot be used for display or analysis. Hence, to increase the voltage of the acquired signals, an amplifier with high gain is used.
  • A biomedical amplifier with a gain of 1000, high input impedance (>10 mega ohms) and high tolerance of noise and output offsets for accurate reproduction of the signal is designed.
  • A bandpass filter with the upper and lower cut off frequencies of 0.5Hz, 40Hz is designed to obtain signal in this frequency range and to eliminate noise.
  • The amplified, filtered signals are then given as input to a data acquisition card which then converts analog to digital signals and then transferred to LABVIEW (Signal processing software installed in a laptop).
  • Digital signals are processed again to filter any noise by LABVIEW.

Feature extraction:

  • The processed digital signal is plotted as a function of amplitude vs time period.
  •  Fast Fourier transform of the plotted signal is obtained.
  • The desired feature i.e. the peak of the digitized signal is extracted

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B wave implicit time - latency

From the feature extracted, the latency – time interval between the onset of the stimulus and the peak of the return signal i.e. (maximal response of the obtained signal) is calculated. This latency is the diagnostic measure for retinal disorders.

Various trials with normal subjects are performed by this procedure and the latency i.e. the time interval between the actuation of stimulus and normal response is calculated from the digitized signals.

A threshold value of latency is set from trials done with normal subjects as normal latency period.

The time delay in the latency compared to the threshold set indicates delay in generation of electrical signals by retina which due to impaired blood flow gives an indication of retinal disorders. The time delay from the normal latency period gives an indication of the degree of retinal disorder

The greater the time delay, greater will be the possibility of severe retinal disorders.

Procedure

  1. Make patient sit in a comfortable position.
  2. Clean the skin close to the eye where electrodes are to be placed for proper acquisition of signals.
  3. Place three surface Ag/AgCl electrodes as per the below mentioned pattern:
    • One active electrode - place along the side of one eye
    • Another active electrode - place beneath the lower eyelid and
    • Ground electrode - place on the center of the forehead
  4. Make the patient watch a flash light (flickering LED stimulus) in a dark environment. No other light should hit the patient’s eye.
  5. The signals acquired from the electrodes are plotted as function of amplitude vs time after various levels of preprocessing which are displayed in the monitor.
  6. Latency value of the patient’s retina and normal latency value is displayed and whether the patients result positive for retinal disorders and the severity is displayed based on the difference between the normal value and the actual value of latency for patient’s retinal response is finally displayed in the monitor.
  7. Take a printout of the final result and consult a doctor with this report for actual diagnosis of the retinal disorder.

Advantages

  1. Surface electrodes (Ag/AgCl) used are very low in price, easily available, placed in the skin around the eye. Hence this approach becomes non-invasive, easily affordable to all classes of people.
  2. Instead of invasive and expensive methodologies for initial diagnosis, this approach can be used as a preliminary test in eye clinics to actually check for the presence of abnormal retinal behavior. If results are positive, later the patient can go for an advanced and expensive test to diagnose the kind and severity of retinal disorder.
  3. Since the approach is non-invasive, it can be used to test children and old age people.
  4. This can be further developed to a pocket friendly device with results displayed in mobile app which allows patients to perform test in their homes.
  5. No need of highly trained personnel for performing the test since handling of the approach is easy.

References

  1. Retinal diseases - The American Society of Retina Specialists (asrs.org)
  2. http://www.ese.upenn.edu/detkin/software/Labview/daqlvOverview. (sdsu.edu)
  3. The ERG and Sites and Mechanisms of Retinal Disease, Adaptation, and Development - Advances in Photoreception - NCBI Bookshelf (nih.gov)
  4. ERG Activities | EERA (eera-ecer.de)
  5. DESIGN OF PORTABLE LED VISUAL STIMULUS AND SSVEP ANALYSIS FOR VISUAL FATIGUE REDUCTION AND IMPROVED ACCURACY | Request PDF (researchgate.net)

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