Visual Electrophysiology Tests for Glaucoma Continue to Improve

In 2024, the International Society for Clinical Electrophysiology of Vision (ISCEV) updated the pattern electroretinography (PERG) test standard, which can be used to test for glaucoma. Meanwhile, the results of a study evaluating a proposed modified photopic negative response (PhNR) test offer the promise of glaucoma testing with unprecedented sensitivity and specificity. These developments will contribute to more accurate glaucoma patient management decisions.  

Improving early diagnosis while avoiding overtreatment 

According to the U.S. Centers for Disease Control and Prevention (CDC), glaucoma affects about three million people in the U.S. and is the second leading cause of blindness worldwide. Notably, about half of the people with glaucoma don’t know they have it.  

There is no cure for glaucoma, but there are treatments to slow it down, using eye drops, oral medicine, or laser surgery to reduce eye pressure. On the one hand, patients diagnosed early with the condition stand to benefit the most from these treatments. On the other hand, specialists caution about overtreating glaucoma.  

In a recent interview published in Eyenet Magazine, one specialist on a panel explained that, in cases where glaucoma is moving slowly, some patients may be better off avoiding treatment. The challenge for glaucoma specialists is determining the proper diagnosis and prognosis from a broad set of test modalities. 

Glaucoma testing today 

Glaucoma testing typically begins with tonometry to measure intra-ocular pressure and may be followed by standard automated perimetry to assess visual field impairments. When glaucoma is suspected, follow-up evaluations include inspecting the optic disc for nerve damage and optical coherence tomography (OCT) imaging to measure retinal fiber layer thinning.  

Visual electrophysiology complements the diagnostic tool set. It is the only test capable of objectively assessing the function of retinal ganglion cells (RGCs), facilitating both diagnosis and prognosis.   

Updated ISCEV standard for PERG 

Within visual electrophysiology, the PERG test measures biomarkers relevant to glaucoma. The ISCEV standard mentions that PERG is an established clinical method of assessing macular and RGC function. The ISCEV updated the PERG standard in 2024, replacing the 2013 version. This mature standard has been expanded with new guidance on large stimulus fields, combined testing of PERG and pattern visually evoked potentials, and more.   

However, the standard highlights the importance of steady fixation, proper refractive correction, and clear ocular media to achieve a strong PERG signal. Furthermore, PERG examines only the RGCs at the center of the retina, which are typically involved only in the later stages of glaucoma development.  

Advantages of PhNR over PERG tests for glaucoma 

In 2018, the ISCEV published the photopic negative response (PhNR) test protocol as an extension of the full-field electroretinography (ERG) test. The PhNR is another test that objectively measures the functional health of RGCs.  

The advantage of PhNR over PERG is that test results are mostly independent of visual fixation, corrective refraction, or ocular media transparency. And since PhNR is an extension of a full-field ERG test, it provides, within the same test, an assessment of the full-field photoreceptor and bipolar cells. In addition, PhNR tests most RGCs at the center and on the periphery of the retina, where the early onset of glaucoma is likely to manifest, facilitating early detection.  

Improving the sensitivity and specificity of PhNR tests 

Promising results of a study to evaluate a proposed new test protocol for PhNR were published in October 2024. The protocol’s proposed improvements included a systematic method of objectively removing test artifacts due to eye muscle activity, which adds noise to the measurement. Improvements were achieved with electrical filtering, a waveform rejection criterion, and increased stimulus frequency.  

This modified PhNR protocol significantly reduced intra- and inter-subject data variability, achieving unprecedented sensitivity and specificity. This development represents an important step toward providing ophthalmologists with an objective functional test that will enable them to accurately distinguish patients who require treatment from those who don’t. This test can help improve earlier detection and minimize overtreatment of glaucoma.