The photopic negative response (PhNR): measurement approaches and utility in glaucoma

Visual electrophysiological testing continues to generate interest among glaucoma experts because of its potential help in clarifying disease pathophysiology and promoting early detection of glaucomatous damage. The photopic negative response (PhNR) is a slow negative component of the full-field electroretinogram that has been shown to provide specific information about retinal ganglion cells (RGCs) activity. The purpose of this article is to review the literature to explore the currently available measurement methods and the utility of PhNR in glaucoma diagnostic process.

We gathered publications related to the origins, types of stimuli used, measurements methods and applications of the PhNR of ERG in animal models and humans through a search of the literature cited in PubMed. Search terms were: "PhNR", "photopic negative response", "glaucoma", "glaucomatous optic neuropathy", "ERG", "electroretinogram".

The most reliable PhNR measurements are obtained using a red stimulus on a blue background, without requiring refractive correction, fixation monitoring, or ocular media transparency. Given its direct correlation with RGCs response, the PhNR measured as baseline-to-trough (BT) represents the most reliable parameter of evaluation. Glaucoma patients with evident perimetric defects show pathologic PhNR values. Even though the PhNR is promising in detecting early RGCs impairment, distinguishing between healthy subjects and suspect patients at risk of developing glaucomatous damage still remains challenging.

The PhNR is a useful additional tool to explore disorders that affect the innermost retina, including glaucoma and other forms of optic neuropathy. In particular, comparing reports of the standard examinations (optic disc assessment, OCT RNFL measurement, standard automated perimetry) with the results of electrophysiological tests may be helpful in solving clinical diagnostic and management dilemmas. On the one hand, the PhNR of the ERG can examine the parvocellular pathways; on the other hand, the steady-state pattern ERG optimized for glaucoma screening (PERGLA) can explore the magnocellular pathways. This could give ophthalmologists a useful feedback to identify early RGCs alterations suggestive of glaucoma, stratify the risk and potentially monitor disease progression.