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- Visual Electrophysiology Aids Early Diagnosis, Treatment Monitoring, Disease Tracking
Electrophysiologic testing has long been valued for the information it can provide; however, it has remained largely untapped due to the difficulty of administering the tests. With the advent of an office-based system, testing is now efficient and accurate, allowing not only early detection of pathologies but also the improved patient management that comes with being able to track and evaluate disease progression and treatment efficacy. This article reviews common clinical uses of electrophysiologic testing and explores the ways in which it can aid in early disease detection and progression tracking.
Electrophysiologic testing can provide objective measurement of how the visual system are functioning. This type of testing can relay information about cells that are dysfunctional but not yet dead. Treatment interventions can then be used to help to improve the function of these cells, and this improvement will then be reflected in subsequent electrophysiology results. This enables the clinician to track treatment and disease progression over time.
Several electrophysiologic testing modalities and their utility in different disease entities are discussed in the following sections.
Pattern electroretinography (pERG) is an objective, functional test of retinal ganglion cells. It has been shown to detect abnormalities from glaucoma up to 8 years earlier than structural tests.1 This is a potentially significant benefit, as early diagnosis can lead to more effective treatment and the ability to slow progression of the disease, preserving the health of cells responsible for vision.
pERG is particularly useful in early detection of disease in glaucoma suspects.2 Early glaucoma affects the ganglion cells in the inner layer of the retina. Clinical diagnosis is commonly based on elevated intraocular pressure (IOP), optic nerve cupping, retinal nerve fiber layer defects, and visual field defects. However, IOP is not always high enough to warrant concern, and once the optic nerve has cupped the disease has become advanced. With pERG, cell dysfunction can be detected while there is still time to initiate successful treatment (Figure 1).
When a stimulus of alternating horizontal bars is presented to the central retina using pERG testing, responses to several hundred stimuli can be averaged to obtain a measurable signal. This provides valuable information on ganglion cell function, making pERG ideal as a specific test for recognition of early glaucoma.3Diabetic Retinopathy
Electrophysiologic abnormalities of the retina in diabetic retinopathy (DR) can often be detected with pERG before the development of overt clinical retinopathy. DR, a severe complication of diabetes, is the product of damage to the retinal microvasculature. If not detected early enough, DR can result in a number of adverse conditions, including decrease in visual acuity and sudden vision loss. It has been widely documented that abnormalities occur in the retina and visual pathways well before structural changes may be clinically detected. Optical coherence tomography and invasive tests such as fluorescein angiography, are useful to detect DR changes. However, pERG has been shown to have high sensitivity in detecting preclinical abnormalities,4,5 and it can evaluate the efficacy of treatments on functional recovery while optimizing patient convenience and comfort.6,7Plaquenil Toxicity
The toxicity of hydroxychloroquine (Plaquenil [Concordia] and generics), a medication used in the treatment of malaria and inflammatory disorders such as rheumatoid arthritis and lupus, may cause structural problems in the outer retina and retinal pigment epithelium. This damage can be minimized with early detection. Because pERG is sensitive to functional abnormalities, it can be useful in detecting toxicity retinopathy.8 Once treatment is under way, the test can be repeated to track improvement.
Full-Field ElectroretinographyCone-involved dysfunctions
Full-field electroretinography (ffERG) measures generalized dysfunction in response to stimulus of the entire retina. Flicker ffERG specifically elicits responses from the cone cells. This modality is useful in evaluating hereditary conditions such as retinitis pigmentosa9 and other conditions such as retinal vascular occlusions and other cone-involved dysfunctions. Due to the intensity of the flash stimulus, ffERG is helpful in tracking disease progression and monitoring treatment efficacy in moderate to severe retinopathies. It is also useful for performing objective, functional testing in patients with media opacities, as the full-field light stimulus can penetrate through to the retina (Figure 2).
Visual Evoked Potential
Visual evoked potential (VEP) measures visual function from the retina to the visual cortex. Abnormal response time or strength may indicate ocular damage, optic nerve impairment, or neurological diseases such as optic neuritis due to multiple sclerosis. Detecting these abnormalities early can help prevent greater damage or disease progression and blindness. Because the test is objective and does not require a response from the patient, it is also ideal for children, nonverbal patients, and patients with communication issues.Optic Neuritis
Often associated with multiple sclerosis, optic neuritis is an inflammation of the optic nerve. Optical coherence tomography can provide useful information for clinical and subclinical detection, but VEP is the preferred test (Figure 3) because it tends to have higher sensitivity, especially for detecting past optic neuritis.10 VEP is also more sensitive for detecting optic pathway damage than visual acuity or optic nerve appearance.11Amblyopia
Early detection is crucial with any pathology, and this is especially the case with amblyopia because the latent potential of vision improvement is key when determining a course of treatment. Amblyopia is caused by dysfunction in the lateral geniculate body and visual cortex.12-16 Because VEP detects abnormal changes in the visual cortex by measuring electrical changes, the test is beneficial for both diagnosis and treatment prognosis assessment. Treatment efficacy can also be tracked, as increases in the amplitude on VEP appear to reflect vision improvement during treatment.17Traumatic Brain Injury
Traumatic brain injuries (TBIs), caused by blunt or penetrating trauma to the head, may stem from a number of causes, including injuries sustained in sports, military action, and vehicular accidents. Individuals with TBI can experience a wide range of vision-related problems along with associated symptoms such as blurry vision, impaired reading, and motion hypersensitivity. VEP is an extremely useful tool in the diagnosis and prognosis of TBI, as well as in the assessment of therapeutic efficacy. With this objective test, the patient cannot inadvertently or intentionally inhibit the results. This allows ocular and visual dysfunctions to be documented without prejudice.18
Additionally, VEP can be used to assess patients with visual attention deficit, nonverbal patients, and patients with attention deficit hyperactivity disorder, and it allows objective evaluation of visual interventions including an attentional element.19 n
Visual electrophysiology is a reliable, objective and useful test in the assessment of patients with several eye diseases and as stated by the American Academy of Ophthalmology it can be useful in the evaluation of glaucoma suspects.
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. The Glaucoma Suspect. Basic and Clinical Science Course, Glaucoma. San Francisco: American Academy of Ophthalmology; 2015-2016.
3. Azarmina M. Full-field versus multifocal electroretinography. J Ophthalmic Vis Res. 2013;8(3):191-192.
4. Caputo S, Di Leo MAS, Falsini B, et al. Evidence for early impairment of macular function with pattern ERG in type I diabetic patients. Diabetes Care. 1990;13(4):412-418.
5. Parisi V, Uccioli L. Visual electrophysiological responses in persons with type 1 diabetes. Diabetes Metab Res Rev. 2001;17(1):12-18.
6. Ozkiriş A. Pattern electroretinogram changes after intravitreal bevacizumab injection for diabetic macular edema. Doc Ophthalmol. 2010;120(3):243-250.
7. Ozkiris A, Evereklioglu C, Oner A, Erkiliç K. Pattern electroretinogram for monitoring the efficacy of intravitreal triamcinolone injection in diabetic macular edema. Doc Ophthalmol. 2004;109(2):139-145.
8. Neubauer AS, Stiefelmeyer S, Berninger T, Arden GB, Rudolph G. The multifocal pattern electroretinogram in chloroquine retinopathy. Ophthalmic Res. 2004;36(2):106-113.
9. Gerth C, Wright T, Heon E, Westall C. Assessment of central retinal function in patients with advanced retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2007;48(3):1312-1318.
10. Naismith RT, Tutlam NT, Xu J, et al. Optical coherence tomography is less sensitive than visual evoked potentials in optic neuritis. Neurology. 2009;73(1):46-52.
11. Kelly JP, Leary S, Khanna P, Weiss AH. Longitudinal measures of visual function, tumor volume, and prediction of visual outcomes after treatment of optic pathway gliomas. Ophthalmology. 2012;119(6):1231-1237.
12. Sokol S. Pattern visual evoked potentials: their use in pediatric ophthalmology. Int Ophthalmol Clin. 1980;20:251-268.
13. Arden GB, Barnard WM, Mushin AS. Visually evoked responses in amblyopia. Br J Ophthalmol. 1974;58:183-192.
14. Sokol S. Abnormal evoked potential latencies in amblyopia. Br J Ophthalmol. 1983;67:310-314.
15. Yin ZQ, Fang QX. The simultaneously recorded of PERG and PVEP in amblyopic children. Chin J Ophthalmol. 1989;5:312-315.
16. Yu M, Brown B, Edwards MH. Investigation of multifocal visual evoked potential in anisometropic and esotropic amblyopes. Invest Ophthalmol Vis Sci. 1998;39:2033-2040.
17. Oner A, Coskun M, Evereklioglu C, Dogan H. Pattern VEP is a useful technique in monitoring the effectiveness of occlusion therapy in amblyopic eyes under occlusion therapy. Doc Ophthalmol. 2004;109:223-227.
18. Ciuffreda KJ, Ludlam DP. Objective diagnostic and interventional vision test protocol for the mTBI population. Optometry. 2011;82(6):337-339.
19. Yadav NK, Ciuffreda KJ. Objective assessment of visual attention in mild traumatic brain injury (mTBI) using visual-evoked potentials (VEP). Brain Inj. 2015;29(3):352-365.
Robert J. Noecker, MD, MBA
• Private practice at Ophthalmic Consultants of Connecticut, in Fairfield
• Assistant clinical professor of ophthalmology at Yale University, New Haven, Connecticut
• (203) 366-8000; firstname.lastname@example.org
• Financial disclosure: consultant to Diopsys
Alberto González García, MD
• Neuro-ophthalmologist, Research Director at Diopsys and Chairman of Diopsys Scientific Advisory Board
• (973) 244-0622; email@example.com