Electroretinography (ERG) testing has long been known to provide functional and objective information about the retina, which can often precede structural manifestation by several years.¹ Although primarily developed as a research tool to study cone and rod diseases, such as retinitis pigmentosa, it has in recent years been increasingly used in clinical evaluations of more common ocular disorders. Previously established ERG protocols inadequately addressed the clinical needs of many ophthalmologists, and subsequently many clinicians are now using modified ERG protocols to better monitor and treat patients.

Types of ERG

ERG studies typically assess retinal function using visual stimuli of either a temporally, phase-reversed pattern of constant total luminance or flashes of light. Pattern ERG (PERG) is so named because of the pattern of lines or checks that is used when testing the patient. Steady-state PERG is the use of fast-reversing, high-contrast, fine-grating stimuli and has shown particular value in discerning glaucomatous disease.² Recent research presented at the ARVO annual meeting demonstrated the repeatability of these PERG protocols.³

Full-field ERG (ffERG) is another protocol that uses a flash of light to stimulate different groups of retinal cells. ffERG primarily evaluates the functional integrity of the outer layer of the retina, including photoreceptors and bipolar cells. ffERG is altered primarily by conditions that diffusely affect retinal cell function, such as medications, systemic diseases, or retinal ischemia.

MULTILUMINANCE FLICKER ERG

For retina specialists, one of the most interesting and relevant modalities is multiluminance flicker ERG. Standard flicker ERG alternates flashes of light at a rate of 28 to 32 times per second, preferentially stimulating the cones, because the rods cannot recover quickly enough to respond to that level of cycling. Thus, flicker ERG predominantly tests retinal function by analyzing the synchronicity between cone cells. As such, it is an indirect measurement of retinal function.⁴

With multiluminance flicker ERG, the visual stimulus is presented at different luminance levels, starting with dim light and moving exponentially to brighter light intensities. The multiluminance ffERG objectively evaluates the cone function of the entire retina, providing important information about global retina ischemia and potential risk of neovascularization and proliferation.^4-6

For example, in a healthy patient, all cells will respond to each luminance with a similar speed and strength, producing a smooth arc graphically. However, in a patient with diabetic macular edema, there are patches of cells in the macula that are more diseased than others. If such a patient is provided a rapid flicker stimulus, the metabolically compromised cells will be unable to cycle quickly enough and may provide a delayed or less robust response compared with less perturbed cells.

The patient’s responses are then analyzed by algorithms and variations in magnitude and phase of the signal, which is related to the timing of the response to the stimulus. The graphic pattern that results allows the clinician to determine quickly the level of retinal dysfunction. The multiluminance flicker ERG affords a more quantifiable measurement of retinal function than the standard ffERG. This is useful for monitoring disease progression and response to therapy.

USES FOR RETINA SPECIALISTS

In the office of a retina specialist, multiluminance flicker ERG has the potential to be particularly useful in monitoring patients undergoing intravitreal anti-VEGF therapy for several common retinal diseases. Diabetic patients who have early nonproliferative retinopathy or who show no sign of retinopathy can generate a baseline multiluminance flicker ERG to determine if cellular decline can be detected prior to structural manifestations of the disease. Other patients can be tested prior to the initiation of therapy, be it pharmacologic, laser, or systemic therapy.

Clinicians who only perform OCT and FA to monitor progression and response lack data on global retinal function. For example, using only OCT and FA can provide quantifiable information on the degree of DME, but quantifiable information of retinal cell dysfunction would be lacking. Electroretinography provides noninvasive, objective, functional data about the retina that cannot be obtained with our current commonly used diagnostic modalities.

OBSTACLES TO OVERCOME

While the long history of reliability and repeatability of ERG testing is well known, many clinicians have yet to appreciate that the current platforms are accessible, efficient, and not difficult to perform. As with any technology that physicians are not accustomed to using in their clinic, it takes time to understand the true value of the diagnostic technique and its potential impact on your treatment decisions.

Repeatability in advanced disease is more complicated than repeatability in healthy eyes for any diagnostic. This is also true for ffERG. However, new tests awaiting publication show that not only are the results repeatable with healthy eyes but also in eyes with varying levels of retinal dysfunction. This is very important.

In addition, newer algorithms and software are constantly developed to further increase reliability. By necessity, the PERG you use in your office today will not be as good as the one you will have in your office in 1 to 2 years. This is a natural part of progression. However, each step increases the value of the technology and creates a path of data to demonstrate its worthiness.

Multiluminance ffERG is the next step in making ERG an indispensable tool for retina specialists. I find that it provides valuable information that I cannot acquire from any of my other diagnostic tools, and I am convinced that it will continue to revolutionize the way retina specialists practice. RP

REFERENCES

1. Banitt MR, Ventura LM, Feuer WJ, et al. Progressive loss of retinal ganglion cell function precedes structural loss by several years in glaucoma suspects. Invest Ophthalmol Vis Sci. 2013;54:2346-2352.
2. Mavilio A, Scrimieri F, Errico D. Can variability of pattern ERG signal help to detect retinal ganglion cells dysfunction in glaucomatous eyes? Biomed Res Int. 2015;2015:571314.
3. Resende AF, Waisbourd M, Gonzalez A, Hark LA, Mantravadi AV, Katz LJ. Test-retest repeatability of steady-state pattern electroretinogram and full-field electroretinogram. Presented at: annual meeting of the Association for Research in Vision and Ophthalmology; Seattle, WA; May 1, 2016.
4. Pescosolido N, Barbato A, Stefanucci A, Buomprisco G. Role of electrophysiology in the early diagnosis and follow-up of diabetic retinopathy. J Diabetes Res. 2015;2015:319692.
5. Kim SH, Lee SH, Bae JY, Cho JH, Kang YS. Electroretinographic evaluation in adult diabetics. Doc Ophthalmol. 1997-1998;94:201-213.
6. Domalpally A, Ip MS, Ehrlich JS. Effects of intravitreal ranibizumab on retinal hard exudate in diabetic macular edema: findings from the RIDE and RISE phase III clinical trials. Ophthalmology. 2015;122:779-786.