Electroretinogram (ERG) Testing

The electroretinogram (ERG) measures the electrical activity of the retina in response to light stimuli, analogous to an electrocardiogram (EKG) for the heart. The eye’s retina converts light into an electrical signal that is sent via nerves to the brain. These retina processes can be monitored via an ERG by measuring the voltage between an electrode placed near or on the surface of the cornea and a second electrode placed on the temple. A third electrode (ground) is used to reduce electrical interference from power lines and cell phones. In the RETeval Sensor Strip, all three electrodes are combined in one convenient sticker.

Flash ERG (RETeval®, RETevet and UTAS)
Full-field retinal stimulation is achieved with a ganzfeld that delivers a light stimulus that looks the same in all directions. Thus, the whole retina responds to the stimulation. By changing the color, intensity, and frequency of the light, it is possible to preferentially obtain responses from rods, cones, ON and OFF bipolar cells and ganglion cells. The patient’s gaze direction isn’t critical and they do not need to be refracted.

Pattern ERG (UTAS)
The pattern electroretinogram (pERG) is performed using an alternating checkerboard stimulus on a monitor. The responses are much smaller in amplitude than those of the flash ERG. The pattern ERG is most commonly used as a testing method for glaucoma as it reflects the activity of ganglion cells and structures closely dependent upon ganglion cell integrity. Gaze direction is important because only a portion of the retina is stimulated. Patient refraction is critical, as the contrast of the checkerboard provides the stimulation.

Multi-Focal ERG (UTAS)
The multi-focal electroretinogram (mfERG) is obtained as the result of the stimulation with alternating black & white hexagonal pattern from a monitor. Multi-focal ERG results are presented either as a 3-dimensional ERG “map” or as an array of waveforms obtained through the software’s algorithm. This technique allows for the measurements of the retinal function in localized portions of the retina. Gaze direction is critical, as the test (which takes several minutes) attempts to isolate the response of different parts of the retina. Patient refraction is less important in than pERG, because the stimulus is a luminance-based rather than contrast-based.

 

ISCEV Standard flash ERG Protocol
In 2015, the International Society for Clinical Electrophysiology of Vision (ISCEV) published the latest version of a standardized ERG testing protocol. The standard describes six tests, each designed to evaluate different areas or functions of the retina.

  1. Dark-adapted 0.01 ERG
    In a dark-adapted eye, a dim flash of 0.01 cd·s/m2 elicits a positive response waveform dominated by the rod bipolar and Müller cells.
  2. Dark-adapted 3 ERG
    In a dark-adapted eye, a standard flash of 3 cd·s/m2 elicits a response from both the rod and cone pathways. Because the eye has roughly 10 times more rods than cones, the response is primarily from the rod pathway. The photoreceptor response is visible as the early negative portion called the a-wave while the following positive portion called the b-wave results from the bipolar response in the retina.
  3. Dark-adapted 10 ERG (combined response with enhanced a-waves reflecting photoreceptor function).
    In a dark-adapted eye, a bright flash of 10 cd·s/m2 elicits a response from both the rod and cone pathways. The a-wave is more clearly defined than in the 3 ERG, and the brighter flash allows the assessment of photoreceptor function in the presence of obstacle such as a cataract.
  4. Dark-adapted Oscillatory Potentials (OPs)
    The oscillatory potentials (OPs) are high-frequency wavelets seen on the ascending-edge of the b-wave. The OPs originate from amacrine and ganglion cell function.
  5. Light-adapted 3 ERG
    In a light-adapted eye, a standard flash of 3 cd·s/m2 elicits an early a-wave indicative of cone function followed by a positive b-wave indicative of bipolar function.
  6. Light-adapted 30 Hz Flicker ERG
    In a light-adapted eye, a flicker ERG elicits a response from cone bipolar cells. The flicker ERG, especially the implicit time, has been shown to be a sensitive measurement in patients with ischemic diseases such as diabetic retinopathy and CRVO.

Other Flash ERG Protocols

Below is a list of a few commonly-used protocols that are not part of the ISCEV standard.

  • Photopic negative response (PhNR)
    The red flash on a blue background photopic negative response test was designed to highlight the response from the retinal ganglion cells, which is the negative response after the b-wave. This test is simpler to perform than pattern ERG/VEP for glaucoma because you don’t have to refract the patient and gaze direction is less important.
  • S-Cone
    The s-cone test uses a blue stimulus to highlight the response from the s-cones, which is useful in detecting enhanced s-cone syndrome.
  • Long flash (on-off)
    By using a long-duration stimulus rather than a brief flash, the response from the on bipolar cells are distinguished from the off bipolar cells and so diseases that differentially effect one cell type can be more easily discriminated, for example, complete versus incomplete CSNB.

User-Defined Protocols

UTAS

The software allows the user to personalize the testing procedure depending on the subject, parameter evaluated or experimental endpoint. For instance, the flash can be set as dim as (-75 dB, or 0.00000008 cd·s/m2), and as bright as (30 dB, or 2500 cd·s/m2). Custom protocols are easily developed through the software’s user interface.

RETeval and RETevet
Protocols are written in the lua programming language, allowing for unprecedented control of testing such as randomizing presentation order, precision timing, and changing future steps based on the results of earlier steps. Stimuli can be specified in terms of luminance or by doing real-time compensation for pupil size, in terms of retinal illuminance. Brief flash, rectangular, triangular, and sinusoidal light waveforms can be generated. Contact LKC support for assistance in developing custom protocols suited for your needs.