To evaluate patients with glaucoma or those suspected of having glaucoma, we rely on clinical observations as well as structural examinations using the slit lamp, fundus photography, and optical coherence tomography (OCT). We also employ more subjective tests, such as Snellen visual acuity and visual fields, to acquire subjective functional analyses.

Electrophysiologic testing of the neurovisual pathways is another testing method that provides an analysis of the functional integrity of the visual pathways from the retina to the visual cortex of the brain via the optic nerves. Traditionally reserved for research facilities due to their complexity, visually evoked potentials (VEP) and electroretinography (ERG) have become a more common part of clinical examination in the office setting. Both VEP and ERG (available from Diopsys), when used in conjunction with clinical examinations, can provide insights that can better direct treatment.

Glaucoma is a disease that affects the retinal ganglion cells. The American Academy of Ophthalmology defines glaucoma as an optic neuropathy. It is not defined by intraocular pressure (IOP). The only characteristic all patients with glaucoma have in common is the loss of retinal ganglion cell function. Electrophysiology testing is an additional complementary test to manage the glaucoma patient. In this article, I discuss 4 reasons I believe that VEP and ERG testing are useful tools for physicians evaluating patients with glaucoma.

1. Electrophysiologic testing, such as VEP and ERG, is the only objective functional testing we have to evaluate the integrity of the visual system.

Visual fields are subjective, and although indicative of function, visual field changes don’t occur until there is a loss of 50% of the retinal nerve fibers, so visual field changes come relatively late in the progression of the disease.¹

Optical coherence tomography is an objective structural test. While OCT can measure changes in the retinal nerve fiber layer (RNFL), it gives no information about function. Changes in the RNFL can be detected earlier than visual field changes; however, structural loss implies that cellular loss has already occurred.

Tonometry is an objective measure, but it tells us nothing about function, and it can be influenced by a variety of structural factors, such as corneal thickness.

2. Visually evoked potentials and ERG provide ancillary and/or alternative, objective measures of visual function for subclinical vision disorders.

These tools can also be used when the diagnosis is questionable — for example, in patients who have borderline findings, present with atypical signs or symptoms for the disease in question, require differentiation of comorbidities, or are unable to provide a reliable, subjective responses to tests that assess visual function (acuity, contrast sensitivity, and perimetry).

The VEP test records the integrity of the entire visual pathway to the visual cortex using light or pattern stimuli. Use of this technology allows the specialist to decipher ophthalmic disorders of the visual pathway from posterior pathway manifestations (retrobulbar) that cause visual disturbances. This includes visual evaluation for detection and management of ophthalmic disorders of the neuro-ophthalmic pathway (eg, amblyopia). Visually evoked potentials are also an alternative to psychophysical tests of vision function (acuity, perimetry, and contrast sensitivity) for patients who are unable to provide a reliable response to evaluate visual function (eg, those with speech, physical, or mental deficits), as well as a sensitive marker for systemic or traumatic disorders and occurrences that affect vision (eg, infectious, neoplastic, autoimmune, vascular, endocrine, neurological, toxic, and traumatic). This flash stimulus is particularly beneficial when patients have poor vision (finger counting) or when the visual pathway function needs to be evaluated through an opacity (eg, cataract).

Similarly, ERG is used for many of the same reasons as VEP, but where the concern is limited to the retina. Electroretinography uses various types of stimuli, full-field flash or pattern, to elicit responses from the photoreceptors (rods and/or cones) with light or the retinal ganglion cells function using patterns. Both stimuli techniques have been in use since the 1980s, with pattern ERG accepted by the AAO for glaucoma suspects for early detection of glaucomatous vision loss. A preponderance of historical and current evidence also explains the ability of pattern ERG (pERG) to detect ganglion cell dysfunction prior to vision loss on perimetry and/or retinal ganglion cell layer (structural) loss. It is well known that intervention at earlier stages can prevent cell death (apoptosis), thereby minimizing preventable and correctable vision impairment.

Pattern ERG testing can be used together with VEP tests to help clinicians differentiate between retinal and optic nerve disorders, as well as to improve sensitivity and specificity in diagnosing neuropathies and maculopathies when used in conjunction with other tests. It is a means of objectively detecting the early stages of disease and is independent of patient response, so it can clarify results of subjective functional tests and pinpoint the origin of abnormalities to the retina or optic nerve for more timely treatment.

3. Electrophysiologic testing, in particular pERG, can objectively detect changes in retinal ganglion cell function before other structural or functional tests.

Peer-reviewed studies indicate pERG is the only clinically effective, objective procedure to evaluate early glaucomatous damage at a level where retinal ganglion cell function can be restored, prior to structural damage of the retinal nerve fiber layer and subsequent visual field loss.^2-8

Glaucoma is most often identified by changes in a patient’s visual field test, but structural changes can also be observed via OCT of the optic nerve head and the RNFL. However, recent studies have shown that this structural damage is preceded by damage to the retinal ganglion cells that causes them to lose their autoregulatory ability. A recent study showed that pattern ERG signals were able to anticipate an equivalent loss of RNFL as seen on OCT by a mean of 8 years.²

A separate study found that the low-contrast VEP protocol was able to identify patients with structural abnormalities consistent with glaucoma, who also had normal achromatic perimetry.⁹ This allows clinicians to identify patients whose visual field tests are normal but still can benefit from treatment. As in most diseases, glaucoma treatment is most effective when started early. Detection of failing retinal ganglion cells before they are irretrievably lost could open new possibilities for glaucoma therapy.

While the most common test for glaucoma is measuring IOP, clinicians also use OCT imaging, visual field tests, and other means of analysis. However, there are still patients with a normal RNFL appearance and unexplained scores on visual field examination. VEP and ERG testing provide an objective means of evaluating a patient’s neurovisual pathway. This additional information can make the difference in diagnosis and treatment decisions.

4. Pattern ERG can help determine whether a patient with elevated IOP should be treated for glaucoma.

Although elevated IOP is an identified risk factor for glaucoma, only about 10% of individuals with elevated IOP will actually develop glaucoma. As reported in the Ocular Hypertension Treatment Study (OHTS), there are approximately 3 to 6 million people in the United States with elevated IOP, most of whom will never develop glaucoma. However, many (the OHTS estimated at least 1.5 million people in 2002) with elevated IOP and no glaucoma damage are receiving treatment, many with pressure-lowering medications.¹⁰

Objective measures of retinal ganglion cell function using pERG allows the physician to distinguish the 10% of individuals who will develop glaucoma and, therefore, require medication from the 90% of patients with elevated IOP who have healthy retinal function and a high probability of not developing the disease. This presents a considerable opportunity for more appropriate treatment plans and a potential reduction in the unnecessary costs of overprescribing expensive, risky medications to patients who don’t need them.

Finally, another published study clearly supports the use of pERG as a measure of retinal ganglion cell function in patients with open-angle glaucoma. The study demonstrates the utility of pERG in detecting an improvement in RGC function if there is a significant clinical reduction in IOP.¹¹ It also demonstrates that (1) pERG is an accepted method to measure retinal ganglion cell function, (2) pERG is used to evaluate patients with glaucoma, and (3) detection and treatment of glaucoma in the early stages may be amenable to reversal of retinal ganglion cell loss when treated appropriately.

A Helpful Tool

As more clinicians recognize the value of electrophysiologic testing in the diagnosis and treatment of glaucoma treatment, it will become a more common part of clinical examination in the office setting. GP

References

1. Harwerth RS, Quigley HA. Visual field defects and retinal ganglion cell losses in human glaucoma patients. Arch Ophthalmol. 2006;124(6):853-859. doi:10.1001/archopht.124.6.853.
2. Banitt MR, Ventura LM, Feuer WJ, Savatovsky E, Luna G, Shif O, 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.
3. Derr PH, et al. Evaluation of pre-perimetric glaucoma patients using short duration transient visual evoked potentials (SD-tVEP). Presented at the Association for Research in Vision and Ophthalmology annual conference. May 2014, Orlando, FL.
4. Electrophysiology in the diagnosis of glaucoma that confirms use of PERG in glaucoma. In: Grehn F, Stamper R, eds. Glaucoma. 2009.
5. Xu S, Meyer D, Yoser S, Mathews D, Elfervig JL. Pattern visual evoked potential in the diagnosis of functional visual loss. Ophthalmology. 2001;108(1):76-80.
6. Bode SF, Jehle T, Bach M. Pattern electroretinogram in glaucoma suspects: new findings from a longitudinal study. Invest Ophthalmol Vis Sci. 2011;52(7):4300-4306.
7. Pfeiffer N, Tillmon B, Bach M. Predictive value of the pattern electroretinogram in high-risk ocular hypertension. Invest Ophthalmol Vis Sci. 1993;34(5):1710-1715.
8. Bach M, Unsoeld AS, Philippin H, et al. Pattern ERG as an early glaucoma indicator in ocular hypertension: a long-term, prospective study. Invest Ophthalmol Vis Sci. 2006;47(11):4881-4887.
9. Pillai C, Ritch R, Derr P, et al. Sensitivity and specificity of short duration transient evoked potentials (SD-tVEP) in discriminating normal from glaucomatous eyes. Invest Ophthalmol Vis Sci. 2013;54(4):2847-2852.
10. Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120(6):701-713.
11. Karaśkiewicz J, Penkala K, Mularczyk M, Lubiński W. Evaluation of retinal ganglion cell function after intraocular pressure reduction measured by pattern electroretinogram in patients with primary open-angle glaucoma. Doc Ophthalmol. 2017;134(2):89-97.

Mark A. Latina, MD, is an associate clinical professor at the New England Medical Center, Tufts University School of Medicine, in Boston, Massachusetts. Dr. Latina invented selective laser trabeculoplasty. He reports consultancy to Diopsys.