The photopic negative response of the flash ERG: changes in experimental glaucoma in monkeys and clinical applications in humans

The flash electroretinogram (ERG), which can be recorded noninvasively at the cornea, has commonly been used to assess photoreceptor and bipolar cell activity, reflected in the initial negative (a-wave) and positive (b-) waves respectively of the response to a brief flash. In this study we measured light-adapted (photopic) flash ERGs using red flashes on a rod saturating blue background, and discovered a negative-going wave after the b-wave which we called the photopic negative response (PhNR). Pharmacological studies in monkeys indicated that the PhNR arises from the spiking activity of inner retinal neurons proximal to bipolar cells, predominantly retinal ganglion cells. We measured the PhNR in monkeys with experimental glaucoma and human patients with primary open angle glaucoma (POAG), pathologies that eventually destroy ganglion cells. PhNR amplitudes were already significantly reduced (P<0.5) relative to controls in monkey eyes with experimental glaucoma and in POAG patients when visual sensitivity losses, assessed using perimetry, were mild (mean deviation of less than -6dB). PhNR amplitudes also were reduced in glaucoma suspects. These findings suggest promise for the PhNR for early detection of glaucomatous damage.