The History of Electrophysiology

These objective tests can provide valuable information.

By Jerome Sherman, OD

Visual electrophysiology has been available as a diagnostic tool for decades, but until recently, the complexity of the systems necessary to perform tests like visual evoked potential (VEP) and pattern electroretinography (PERG) typically limited these investigations to research settings. PERG and VEP test the retina and neurovisual pathways and are capable of objectively determining if there are functional abnormalities that indicate present, or even future, structural damage. These tests are greatly beneficial in the early detection of a number of diseases, but older systems were often difficult to access and complicated to operate. It has been only in recent years that devices like the Nova ERG (Diopsys) and VEP Vision Testing System (Diopsys) have made it possible to conduct these tests easily in office settings.

History of Electrophysiology

When I graduated from optometry school and joined the faculty at SUNY in 1970, I studied under William M. Ludlam, OD, the first optometrist to use VEP.1 The system we used was not commercially available. It was rather intricate, included multiple components, and required the use of a Faraday cage, a shield used to block electromagnetic fields. The testing showed great promise, but the process was daunting and complex, not something that could be recreated in a clinical setting.

In the mid-1970s, a meteorologist and science reporter for WNBC in New York, Frank Field, OD, did a story on VEP. As part of the piece, his crew filmed me at SUNY examining a nonverbal little girl with Down syndrome. By analyzing her brainwaves with a scalp electrode, we were able to determine her refractive error, her visual acuity in each eye, and her binocularity. The publicity led to numerous referrals to SUNY of nonverbal patients of all ages.

Then, in 1979, Optometry, the journal of the American Optometric Association, decided to dedicate its golden anniversary edition to advanced diagnostic procedures in optometry. VEP was featured on the cover, along with an illustration of the Nicolet device, which was the only system in use at the time. VEP was a brand-new technology to most optometrists and ophthalmologists, and in that issue, we were able to detail the possible applications for which this test could be used.2

In 1982, I published an article describing another new technology, PERG, in which I reported that responses from the eye and brain could be measured simultaneously by performing PERG and VEP at the same time.3 The key finding was that a patient with one severed optic nerve could still generate a PERG. This suggested that components of the PERG originate not only from ganglionic (optic nerve) structures, but also from preganglionic structures.

Interestingly, the widest spread use for electrophysiology at the time was by neurologists for the diagnosis of multiple sclerosis (MS).4-8 Because we did not have computed tomography or magnetic resonance imaging at that time, neurologists used VEP to test for delayed responses, which could indicate an optic nerve problem due to MS.8 VEP delays were also associated with conditions such as Parkinson disease,9 spinocerebellar degeneration,10 vitamin B12 deficiency,11-13 Friedreich ataxia,14 and diabetic retinopathy.15

During the 1980s, we conducted research on different types of diseases and retinal abnormalities and how they affect VEP.16-18 One study focused on central serous choroidopathy, a common retinal problem.18 We found that VEPs of patients with this condition are significantly delayed, which mimics MS. We demonstrated that macular diseases can cause large VEP delays, and that it is important to first rule out retinal problems before diagnosing MS based on a VEP delay.

Electrode Advances

Figure 1. Early electrodes proved cumbersome and increased the risk of corneal damage.

Although my 1982 publication demonstrated that PERGs were clinically useful,3 noninvasive electrodes did not exist at that time. The electrodes available were not only finicky, but also uncomfortable for patients and required contact with the eye. The ones used at the time typically included contact lenses, generally with silver disks that sat over the cornea.19-26 Later electrode models incorporated soft contact lenses,27-30 gold foil,31 and microfiber.32 Although these were somewhat more comfortable, most of them were still invasive and increased the risk of corneal damage (Figure 1).

Figrue 2. Recent advances have allowed patients to wear electrodes that do not require corneal contact, increasing comfort and all but eliminating risk of corneal damage secondary to physical contact.

A major breakthrough occurred with the advent of the ERG-Electrode (Diopsys). This slim, noninvasive electrode sits just below the eye, eliminating the need for contact with the cornea (Figure 2). Its efficacy is equivalent or superior to previous electrodes, without the risk factors inherent in earlier models.33 As it does not require contact with the eye, it is comfortable for patients and ideal for children and disabled patients who often do not tolerate a contact lens electrode well.34

Simplifying a Complex System

Past systems were technically sound and provided valuable information; however, they were incredibly complicated. The technology behind electrophysiology continued to improve, and in recent years, Diopsys simplified the system as a whole, creating a device that could be used in the office by technicians, with disposable electrodes that sit comfortably under the eye and results that are color-coded help to deliver high quality test results efficiently.

Other available systems include the Visual Evoked Response Imaging System, or VERIS (Electro-Diagnostic Imaging), developed in 1987.35 Designed primarily for researchers, the original system was excellent, in my opinion, especially for scientific uses. However, it was complicated, expensive, and not user-friendly. Tomey and Konan also have systems capable of running various electrophysiologic tests.

Improved Diagnostics and Tracking

VEP and PERG have each been shown to identify decreased visual function, even when visual field tests are normal. In addition to the conditions already mentioned, delayed VEPs can also indicate the presence of diseases such as optic neuritis,36 amblyopia,37-40 and brain trauma41—even in nonverbal or otherwise impaired patients.42

PERG has been shown to detect glaucoma several years earlier than structural tests, including optical coherence tomography (OCT).43 This is a significant benefit because it allows treatment to be initiated before permanent damage occurs. This test is also useful in detecting early abnormalities in diabetic retinopathies;44-46 it can aid in tracking treatment efficacy;47,48 and it is useful in instances of suspected toxic retinopathy.49

Electrophysiology: What’s Next?

As a concerned clinician, teacher, and researcher, I try to do as much as possible to provide the best care for my patients. Electrophysiology has afforded me the opportunity to obtain objective, functional information about the eye and visual pathways that, when added to other tests like OCT and visual field, provides a fuller picture with which to diagnosis and treat my patients more accurately. It has been exciting to participate in the evolution of this technology, and I look forward to what the future holds.

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2. Sherman J. Visual evoked potential (VEP): basic concepts and clinical applications. J Am Optom Assoc. 1979;50(1):19-30.

3. Sherman J. Simultaneous pattern-reversal electroretinograms and visual evoked potentials in diseases of the macula and optic nerve. Ann N Y Acad Sci. 1982;388:214-226.

4. Richey ET, Kooi KA, Tourtellotte WW. Visually evoked responses in multiple sclerosis. J Neurol Neurosurg Psychiatry. 1971;34(3):275-280.

5. Halliday AM, McDonald WI, Mushin J. Delayed visual evoked response in optic neuritis. Lancet. 1972;1(7758):982-985.

6. Halliday AM, McDonald WI, Mushin J. Visual evoked response in diagnosis of multiple sclerosis. Br Med J. 1973;4(5893):661-664.

7. Cohen SN, Syndulko K, Tourtellotte WW. Clinical applications of visual evoked potentials in neurology. Bull Los Angeles Neurol Soc. 1982;47:13-29.

8. Regan D. Evoked Potentials in Psychology, Sensory Physiology and Clinical Medicine. New York, NY: John Wiley and Sons; 1972.

9. Bodis-Wollner I, Yahr MD. Measurements of visual evoked potentials in Parkinson’s disease. Brain. 1978;101(4):661-671.

10. Bird TD, Crill WB. Pattern reversal visual evoked potentials in the hereditary ataxias and spinal degenerations. Ann Neurol. 1981;9(3):243-250.

11. Troncoso J, Mancall EL, Schatz NJ. Visual evoked responses in pernicious anemia. Arch Neurol. 1979;36(3):168-169.

12. Bodis-Wollner I, Korczyn A. Dissociated sensory loss and visual evoked potentials in a patient with pernicious anemia. Mt Sinai J Med. 1980;47(6):579-582.

13. Krumholz A, Weiss HD, Goldstein PJ, Harris KC. Evoked responses in vitamin B12 deficiency. Ann Neurol. 1981;9(4):407-409.

14. Kirkham TH, Coupland SG. An electroretinal and visual evoked potential study in Friedreich’s ataxia. Can J Neurol Sci. 1981;8(4):289-294.

15. Puvanendran K, Devathasan G, Wong PK. Visual evoked responses in diabetes. J Neurol Neurosurg Psychiatry. 1983;46(7):643-647.

16. Bass SJ, Bodis-Wollner I, Nath S, Sherman J. Visual evoked potentials in macular disease. Invest Ophthalmol Vis Sci. 1985;26(8):1071-1074.

17. Davis ET, Schnider CM, Sherman J. Normative data and control studies of flash VEP’s for comparison to a clinical population. Am J Optom Physiol Opt. 1987;64(8):579-592.

18. Sherman J, Bass SJ, Noble KG, Nath S, Sutija V. Invest Ophthalmol Vis Sci. 1986;27(2):214-221.

19. Riggs LA. Continuous and reproducible records of electric activity of the human retina. Proc Soc Exp Biol Med. 1941;48:204-207.

20. Schubert G. Bornschein H. Beitrag zur analyse des menschlichen elektroretinogramms. Ophthalmologica. 1952;123(6):396-413.

21. Gouras P. Electroretinography: Some basic principles. Invest Ophthalmol. 1970;9(8):557-569.

22. Karpe G. Basis of clinical electroretinography. Acta Ophthalmol.1945;24(suppl):1-118.

23. Burian HM, Allen L. A speculum contract lens electrode for electronretinography. Electroencephalogr Clin Neurophysiol. 1954;6(3):509-511.

24. Jacobson JH. A new contact lends electrode for clinical electroretinography. AMA Arch Ophthalmol. 1955;54(6):940.

25. Henkes HE, Van Balen ATM. Techniques of recording of the hitherto unrecordable ERG in the human eye. Presented at the ERG symposium at Luhacorice, Belgium. Acta Fac Med Univ Brunensis. 1960;4:21-28.

26. Sundmark E. The contract glass in human electroretinography. Acta Ophthalmmol Suppl. 1959;52(suppl):1-40.

27. Dawson WW, Zimmerman TJ, Houde WL. A method of more comfortable electroretinography. Arch Ophthalmol. 1974;91:1-2.

28. Schoessler JP, Jones R. A new corneal electrode for electroretinography. Vision Res. 1975;15(2):299-301.

29. Galloway NR. Ophthalmic electrodiagnosis (Major Problems in Ophthalmology S.). London, WB Saunders Co. 1975.

30. Bloom BH, Sokol S. A corneal electrode for patterned stimulus electroretinography. Am J Ophthalmol. 1977;83(2):272-275.

31. Arden GB, Carter RM, Hogg C, et al. A gold foil electrode: Extending the horizons for clinical electroretinography. Invest Ophthalmol. 1979;18(4):421-426.

32. Dawson WW, Trick GL, Litzgow CA. Improved electrode for electroretinography. Invest Ophthalmol Vis Sci. 1979;18(9):988-991.

33. Shengelia A. et al. Evaluation of pattern ERG responses using various electrodes. Invest Ophthalmol Vis Sci. 2016;57:3943.

34. Brodie S. Tips and tricks for successful electroretinography in children. Curr Opin Ophthalmol. 2014;25(5):366–373.

35. Sutter, EE. Noninvasive testing methods: Multifocal electrophysiology. Kansas City, MO. Encyclopedia of the Eye. 2010;3:142-160.

36. Naismith RT, Tutlam NT, Xu J, et al. Optical coherence tomography is less sensitive than visual evoked potentials in optic neuritis. Neurology. 2009;73:46–52.

37. Sokol S. Pattern visual evoked potentials: their use in pediatric ophthalmology. Int Ophthalmol Clin. 1980;20:251-268.

38. Arden GB, Barnard WM, Mushin AS. Visually evoked responses in amblyopia. Br J Ophthalmol.1974;58(3):183-192.

39. Sokol S. Abnormal evoked potential latencies in amblyopia. Br J Ophthalmol. 1983;67(5):310–314.

40. Yin ZQ, Fang QX. The simultaneously recorded of PERG and PVEP in amblyopic children. Chin J Ophthalmol. 1989;5:312–315.

41. Ciuffreda KJ, Ludlam DP. Objective diagnostic and interventional vision test protocol for the mild traumatic brain injury population. Optometry. 2011;82(6):337-339.

42. 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.

43. 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(3):2346-2352.

44. Caputo S, Di Leo MA, 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.

45. Parisi V, Uccioli L. Visual electrophysiological responses in persons with type 1 diabetes. Diabetes Metab Res Rev. 2001;17:12-18.

46. Ventura LM, Golubev I, Feuer WJ, Porciatti V. The PERG in diabetic glaucoma suspects with no evidence of retinopathy. J Glaucoma. 2010;19(4):243–247.

47. Ozkiriş A. Pattern electroretinogram changes after intravitreal bevacizumab injection for diabetic macular edema. Doc Ophthalmol. 2010;120(3):243–250.

48. 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.

49. Neubauer AS, Stiefelmeyer S, Berninger T, et al. The multifocal pattern electroretinogram in chloroquine retinopathy. Ophthalmic Res. 2004;36(2):106-113.

Jerome Sherman, OD
• distinguished teaching professor, clinical optometric science department, SUNY College of Optometry, New York; private practice, Omni Eye Services and Somers Eye Center, New Jersey and New York
• financial disclosure: consultant, Diopsys