As an objective measure of global retinal function, flicker electroretinography (ERG) testing, also referred to as light-induced vision response, has several potential applications in ophthalmology. These include helping to establish a diagnosis, following patients over time and guiding treatment decisions.
However, as its use is sometimes associated with esoteric disease states, it may be underused. Additionally, because there is often a need to refer patients to a specialised centre for testing and interpretation, there may be a perception that the technique is impractical for routine clinical practice.
The availability of office-based platforms might change the perceived clinical utility of flicker ERG testing. Tabletop, cart-based and suitcase-sized testing units capable of different types of electrophysiology testing put the full range of services found in specialised centres into the hands of every eye-care specialist.
Some of these units automatically generate a report that informs the clinician about irregularities and any change since the previous test. To facilitate interpretation, the test results are colour-coded on the basis of validated reference ranges. Thus, it is not necessary to fully appreciate all the nuances of testing in order to have an extremely useful testing modality in one’s practice.
Importantly, electrophysiology testing has applications in disease entities that eye-care specialists see on a daily basis, as well as more specialised uses. This article will review several potential uses for flicker ERG to demonstrate how electrophysiology testing might impact routine clinical practice.
What is flicker ERG?
Office-based flicker ERG systems operate in a similar manner to conventional systems: a mini-Ganzfeld stimulator held over the eye is used for either fixed- or multi-luminance testing to measure cone and and associated bipolar cell function (Figure 1). As the stimulus is presented, the signal response is recorded by a sensor placed at the lid margin.
Because it provides a sum of the central retina’s response, flicker ERG is extremely useful as a quantitative biomarker of retinal disease and has potential to demonstrate either deterioration or improvement in function. Multi-luminance flicker ERG tests at six different luminance levels, generating a curve of retinal response; fixed-luminance flicker ERG measures the variability and consistency of the response.
These are the same testing features one would expect from conventional electrophysiology; however, unlike earlier systems that use a contact lens to generate a measurement, office-based systems are non-contact and are thus much more patient-friendly.
The Diopsys platform also offers flash ERG software options, which allow the peripheral retinal function (i.e., the rod system) to be tested. This is useful in inherited retinal dystrophies and autoimmune disease.
ERG differs from other tests routinely used in the clinic. Whereas fundus photography and visual field testing are subjective measures of structure and function, respectively, and optical coherence tomography (OCT) provides objective information about the retina structure, ERG is the only test used in ophthalmology that provides objective data about the function of the retina. Because it is extremely sensitive in detecting subtle changes in signal, its output often delivers information that is actionable and relevant for making decisions about treatment.
Inconclusive and indeterminate OCT findings
Flicker ERG testing becomes particularly useful when there are unexplained retina findings; for example, a patient with sudden onset of blurred vision or loss of vision. In such a patient, OCT may depict oedema or thickening, but is often inconclusive because macular oedema or cysts may have a number of causes. A delay in ERG response without reduction in size in that setting, meanwhile, suggests that either an ischaemic or inflammatory entity is present, or there may be an altered immune system response.
OCT is of limited utility in the setting of media opacity, whereas flicker ERG is useful in all but the most dense cataracts or vitreous opacities.1,2 An inability to view the fundus can have several implications.
For example, it can be difficult to determine if macular disease or atrophy is present, in which case the prospects for visual recovery after a cataract operation are unknown. If the ERG is normal despite an inability to see or image the retina, there is a reasonable chance that removing the cataract will be successful.
In the setting of very dense cataracts, the platforms offered by the company Diopsys provide another option. It may be possible to use the Ganzfeld stimulus to perform a flash visual-evoked potential (VEP), which is less affected by lens media opacity. Absence of response on flash VEP is indicative of an abnormality, and asymmetrical findings might indicate unilateral abnormalities.
In many cases, responses on flash VEP can be tracked against validated findings from normative databases, although subtle changes on flash VEP or findings that are not well outside of normative data should be interpreted with caution. Nevertheless, the ability to use this test with on-board software (by Diopsys) demonstrates the overall utility of in-office electrophysiology testing in specific settings.
In patients with diabetic retinopathy (DR), flicker ERG and steady-state pattern ERG (ssPERG) both have a role. Flicker ERG has been shown to help detect subtle retina changes in eyes with DR, thus facilitating early diagnosis.3,4 Changes on flicker ERG correlate with DR stages, meaning the technique is useful for prognostic purposes.5,6
Studies also show that flicker ERG can detect changes in global retinal function following intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents for treatment of diabetic macular oedema in the presence of DR.7 This makes it possible to adjust therapy over time based on an individual’s response.
Whereas flicker ERG demonstrates the activity of the cone and bipolar cells, ssPERG shows responses from the retinal ganglion cells. Thus, flicker ERG is a measure of global retina function and ssPERG is more focused on the central 12° of the macula.
ssPERG is extremely relevant in managing DR cases in which visual acuity findings suggest functional deficits that do not correlate with OCT images. It has been demonstrated that ssPERG may detect preclinical abnormalities secondary to diabetic eye disease.8
Because of its ability to assess function in retina ganglion cells, ssPERG also has utility for patients with concomitant glaucoma.7,8 ssPERG has a role in detecting responses to various forms of treatment of diabetic macular oedema, including corticosteroid and anti-VEGF injections.3, 10-12
Central retinal vein occlusion
In cases of central retinal vein occlusion (CRVO), flicker ERG parameters worsen as retinal volume and thickness increase, suggesting a strong correlation with OCT findings.13,14 Moreover, flicker ERG can predict which eyes are at risk of developing ischaemia and neovascularisation.15,16
There is also a role for monitoring the effect of treatment with anti-VEGF agents using flicker ERG, and with multi-luminous flicker ERG in particular.17 In many cases, oedema may resolve on OCT without gain in visual acuity, and so it can be difficult to discern whether treatment is having an effect.
In that setting, monitoring the latency of response on multi-luminous flicker ERG will help determine if more treatment is warranted. Conversely, if OCT continues to show oedema, flicker ERG may indicate functional improvement despite a lack of structural improvement.
Finally, there is a subset of patients for whom OCT depicts improvement but whose visual acuity does not return; in this situation, flicker ERG is ultimately helpful in counselling patients about their visual prognosis and assessing whether further treatment will provide any benefit.
Electrophysiology testing has several indications that are relevant to routine clinical practice, as the examples herein illustrate. Office-based platforms allow the eye-care practitioner access to forms of testing that have previously been restricted to conventional electrophysiology. Above and beyond the cited examples, they also have great utility in, for example, paediatric patients with unexplained vision loss.
Because the various forms of testing available on office-based electrophysiology systems can determine abnormalities in every part of the visual pathway, these systems have significant potential applications, for both the diagnosis and management of these conditions, and for making informed treatment decisions.
Dr Peter Good
Dr Good is a consultant neurophysiologist employed at the Birmingham and Midland Eye Centre and BMI The Priory Hospital. He has no financial interest in the subject matter.
1. Ratanapakorn T, et al. Effect of cataract on electroretinographic response. J Med Assoc Thai. 2010;93:1196-1199.
2. Foerster MH, Li XX. Evaluation of the central retina and optic nerve function in media opacities. Doc Ophthalmol. 1986;63:101-106.
3. Pescosolido N, et al. Role of electrophysiology in the early diagnosis and follow-up of diabetic retinopathy. J Diabetes Res. 2015:319692.
4. Holopigian K, et al. Evidence for photoreceptor changes in patients with diabetic retinopathy. Invest Ophthalmol Vis Sci. 1997;38:2355-2365.
5. Tzekov R, Arden GB. The electroretinogram in diabetic retinopathy. Surv Ophthalmol. 1999;44:53-60.
6. Kim SH, et al. Electroretinographic evaluation in adult diabetics. Doc Ophthalmol. 1997-1998;94:201-213.
7. Holm K, Schroeder M, LÃ¶vestam Adrian M. Peripheral retinal function assessed with 30-Hz flicker seems to improve after treatment with Lucentis in patients with diabetic macular oedema. Doc Ophthalmol. 2015;131:43-51.
8. Caputo S, et al. Evidence for early impairment of macular function with pattern ERG in type I diabetic patients. Diabetes Care. 1990;13:412-418.
9. Ventura LM, et al. The PERG in diabetic glaucoma suspects with no evidence of retinopathy. J Glaucoma. 2010;19:243-247.
10. Vesti E, Trick GL. Diabetes can alter the interpretation of visual dysfunction in ocular hypertension. Ophthalmology. 1996;103:1419-1425.
11. Ozkiris A. Pattern electroretinogram changes after intravitreal bevacizumab injection for diabetic macular edema. Documenta Ophthalmologica. 2010;120:243-250.
12. Ozkiris A, et al. Pattern electroretinogram for monitoring the efficacy of intravitreal triamcinolone injection in diabetic macular edema. Doc Ophthalmol. 2004;109:139-145.
13. Nowacka B, et al. The macular function and structure in patients with diabetic macular edema before and after ranibizumab treatment. Doc Ophthalmol. 2016;132:111-122.
14. Noma H, et al. Association of electroretinogram and morphological findings in branch retinal vein occlusion with macular edema. Doc Ophthalmol. 2011;123:83-91.
15. Noma H, et al. Association of electroretinogram and morphological findings in central retinal vein occlusion with macular edema. Clin Ophthalmol. 2014;8:191-197.
16. Larsson J, AndrÃ©asson S. Photopic 30 Hz flicker ERG as a predictor for Rubeosis in central retinal vein occlusion. Br J Ophthalmol. 2001;85:683-685.
17. Yasuda S, et al. Electroretinograms and level of aqueous vascular endothelial growth factor in eyes with hemicentral retinal vein occlusion or branch retinal vein occlusion. Jpn J Ophthalmol. 2014;58:232-236.