ERG: Alive and well in clinical practice

Stanford, CA-Electrodiagnostic testing remains a critical and important tool for analyzing visual function in patients with retinal disease.

Michael F. Marmor, MD, professor of ophthalmology, Stanford University School of Medicine, Stanford, CA, emphasized that electrophysiologic testing is still very powerful and useful, and described the role of this technology in clinical practice.

"While anatomic examinations are improving constantly, anatomy does not equal function," Dr. Marmor said. "Functional testing provides information that anatomic testing does not."

Fundus examinations alone do not necessarily provide full information, as he pointed out with the case of a patient in whom the fundus appearance was relatively normal. The electroretinogram (ERG) was flat, however, and the patient had retinitis pigmentosa. Another example was a patient with no foveal pit present on optical coherence tomography (OCT). Yet, the patient had 20/25 visual acuity and a normal multifocal ERG (mfERG).

Electrodiagnostic testing is also important for going beyond subjective tests of visual function, such as visual acuity, visual fields, and dark adaptometry.

"These tests may be affected by factors such as attention and testing skills that fall short of the ideal," he said.

"The ERG and mfERG provide objective measures of retinal function," Dr. Marmor said. "They can distinguish rods and cones, the inner retina from the outer retina, and the macula from the periphery. Special ERG tests even can isolate problems such as damage to the blue-sensitive cones (S cones) or the ganglion cells."

Pearls and caveats

He offered some pearls and caveats regarding ERGs:

• The amplitude of the ERG reflects the spatial extent of cellular damage, whereas the ERG implicit time is a sensitive indicator of diffuse pathology of the retinal cells, i.e., "sick" cells.

• A negative ERG waveform indicates that the photoreceptors are functioning, whereas the inner retina is not, such as seen in schisis or inner retinal artery occlusion or severe ischemia from a central retinal vein or artery occlusion.

• Be aware of test-retest variability. ERG amplitude can vary from 30% to 50% on retesting depending on myriad factors.

• The full-field ERG does not measure the macula, because 90% of cones and even more rods are not in the macula.

• A flat ERG is diagnostic of trouble, but not of any specific disease.

Multifocal ERG

The mfERG is a powerful tool for evaluating macular function.

During this test, a pattern of flickering lights flashes on and off to stimulate the retina, and computer analysis determines which ERG signals emanate from particular points in the macula.

An mfERG commonly provides three displays. The most direct is a trace array of small ERG responses at different loci in the macula from the fovea to 20º eccentricity. The computer also can generate a three-dimensional plot and average the responses in rings around the center. The ring display, according to Dr. Marmor, is helpful for diseases that are concentric, such as a central maculopathy or a bull's-eye lesion.

The sensitivity can be enhanced by comparing the ratios of various rings to each other, e.g., in screening for hydroxychloroquine toxicity.

ERG and mfERG applications

The ERG and mfERG distinguish between a maculopathy and a peripheral retinal disorder. The tests are invaluable for evaluating patients with unexplained visual loss, and can distinguish between age-related maculopathy and cone dystrophy, he said. They define the nature of functional disorders, such as night blindness or color vision difficulties, and can sort out differences between rod dysfunction, cone dysfunction, congenital color deficiency, or optic nerve disease. The ERG is more sensitive than fluorescein angiography in predicting neovascularization after central retinal vein occlusion. It can measure retinal viability in eyes with opaque media that cannot be examined anatomically.

ERG for occult maculopathy

In older patients, Dr. Marmor said, ERG testing is useful to discover occult maculopathy or a cone dystrophy and to provide evidence of autoimmune retinopathy that may be associated with cancer.

"Another major use of ERGs is that the technology is an objective way to follow the effects of pharmaceutical agents for both treatment efficacy and toxicity. As new therapies are discovered for intrinsic retinal disease, such as gene therapy and stem cell replacement, functional testing with the ERG will be critical to show if and how well the retina is working," he said.

Dr. Marmor concluded, "The ERG is alive and well and should have a role in clinical practice."