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      ISCEV extended protocol for the photopic negative response (PhNR) of the full-field electroretinogram

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          Abstract

          The International Society for Clinical Electrophysiology of Vision (ISCEV) Standard for full-field electroretinography (ERG) describes a minimum procedure, but encourages more extensive testing. This ISCEV extended protocol describes an extension to the ERG Standard, namely the photopic negative response (PhNR) of the light-adapted flash ERG, as a well-established technique that is broadly accepted by experts in the field. The PhNR is a slow negative-going wave after the b-wave that provides information about the function of retinal ganglion cells and their axons. The PhNR can be reduced in disorders that affect the innermost retina, including glaucoma and other forms of optic neuropathy. This document, based on existing literature, provides a protocol for recording and analyzing the PhNR in response to a brief flash. The protocol includes full-field stimulation, a frequency bandwidth of the recording in which the lower limit does not exceed 0.3 Hz, and a spectrally narrowband stimulus, specifically, a red flash on a rod saturating blue background. Suggested flash strengths cover a range up to and including the minimum required to elicit a maximum amplitude PhNR. This extended protocol for recording the PhNR provides a simple test of generalized retinal ganglion cell function that could be added to standard ERG testing.

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          The photopic negative response of the macaque electroretinogram: reduction by experimental glaucoma.

          To investigate the photopic flash electroretinograms (ERGs) of macaque monkeys in which visual field defects developed as a consequence of experimental glaucoma. Unilateral experimental glaucoma was induced in 10 monkeys by argon laser treatment of the trabecular meshwork. Visual field sensitivity was assessed behaviorally by static perimetry. Photopic ERGs were recorded to brief- (< or = 5 msec) and long-duration (200 msec) red ganzfeld flashes on a rod-suppressing blue-adapting background. Electroretinograms were recorded in four other monkeys, after intravitreal injection of tetrodotoxin (TTX; 3.8-8 p.M) to suppress action potentials of retinal ganglion and amacrine cells, and in six normal adult human subjects. Experimental glaucoma removed a cornea-negative response, the photopic-negative response (PhNR), from the ERG. The PhNR in control eyes was maximal approximately 60 msec after a brief flash, 100 msec after onset, and 115 msec after offset of the long-duration stimulus. The PhNR in experimental eyes was greatly reduced when the mean deviation of the visual field sensitivity was as little as -6 dB. As visual sensitivity declined further, the PhNR was reduced only slightly more. The a- and b-waves were unchanged, even when sensitivity decreased by more than 16 dB. Tetrodotoxin also selectively reduced the PhNR. The PhNR was observed in normal human ERGs. The cornea-negative PhNR of the photopic ERG depends on spiking activity and is reduced in experimental glaucoma when visual sensitivity losses are still mild. The PhNR most likely arises from retinal ganglion cells and their axons, but its slow timing raises the possibility that it could be mediated by glia. Regardless of the mechanism of its generation, the PhNR holds promise as an indicator of retinal function in early glaucomatous optic neuropathy.
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            The photopic negative response of the flash electroretinogram in primary open angle glaucoma.

            To determine whether the photopic negative response (PhNR) of the electroretinogram (ERG) is reduced in patients with primary open angle glaucoma (POAG). ERGs were recorded with DTL electrodes from 62 normal subjects (16 to 82 years), 18 POAG patients (47 to 83 years) and 7 POAG suspects (46 to 73 years) to brief flashes (<6 ms), and also in a few subjects to long (200 ms) red, full-field ganzfeld flashes delivered on a rod-saturating blue background. At the time of ERG measurements, the intraocular pressures of most of the patients were controlled medically. Visual field sensitivities were measured with the Humphrey C24-2 threshold test and optic nerve head cup-to-disc ratio (C/D) was determined by binocular indirect ophthalmoscopy. ERGs of normal subjects contained a slow negative potential following the a- and b-waves, the PhNR, that increased slightly in latency with age. The a- and b-wave amplitudes and implicit times of POAG patients were similar to age-matched controls. In contrast, their PhNRs were small or virtually absent. PhNR amplitudes were reduced even when visual sensitivity losses were small, and were correlated significantly (P < 0.05) with mean deviation (MD), corrected pattern SD (CPSD), and C/D across the population of POAG patients whose MD losses ranged from 1 to 13 dB, CPSDs from 0 to 11 dB and C/Ds from 0.6 to 0.9. PhNRs of most POAG suspects also were small. PhNR amplitudes in POAG patients are smaller than those of normal subjects. PhNR amplitudes are reduced when visual field sensitivity losses are mild and become even smaller as sensitivity losses increase. There is a potential role for the PhNR in early detection and possibly in monitoring the progression of glaucomatous damage.
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              Photopic negative response versus pattern electroretinogram in early glaucoma.

              Photopic negative response (PhNR) and pattern electroretinogram (PERG) are electrophysiological markers of retinal ganglion cell function; both are reduced in glaucoma. We compared PhNR and PERG in different stages of the disease. Eleven eyes with preperimetric glaucoma (glaucomatous optic disc with normal field); 18 with manifest glaucoma; and 26 normals were included. We obtained PhNR (flash strength from 0.1-4 cd·s/m(2)) and steady-state PERG and analyzed PhNR amplitude (baseline to 72 ms trough); PhNR/b-wave ratio; PERG amplitude; and PERG ratio (0.8°/16°). Identification of PhNR structure was only reliable ≥1 cd·s/m(2) flash strength; amplitude and receiver operating characteristics (ROC) area under curve (AUC) changed little from 1 to 4 cd·s/m(2). Both PhNR and PERG (amplitude and ratio) were reduced in preperimetric and more so in manifest glaucoma. AUCs based on PhNR/PERG amplitudes were not significantly different from chance in preperimetric glaucoma (AUCs 0.61/0.59), but were significant in manifest glaucoma (0.78/0.76); ratios were significant in both glaucoma groups (0.80/0.73 and 0.80/0.79). In spite of that, PhNR ratio and PERG ratio were not significantly correlated (r = 0.22 across all groups); an ROC based on a combination of both reached AUCs of 0.85/0.90 for preperimetric/manifest glaucoma. Both PhNR and PERG performed similarly to detect glaucoma; for both, ratios performed better than amplitudes. The PhNR has the advantage of not requiring clear optics and refractive correction; the PERG has the advantage of being recorded with natural pupils.
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                Author and article information

                Contributors
                1 713 743 1972 , Lfrishman@uh.edu
                Journal
                Doc Ophthalmol
                Doc Ophthalmol
                Documenta Ophthalmologica. Advances in Ophthalmology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0012-4486
                1573-2622
                31 May 2018
                31 May 2018
                2018
                : 136
                : 3
                : 207-211
                Affiliations
                [1 ]ISNI 0000 0004 1569 9707, GRID grid.266436.3, College of Optometry, , University of Houston, ; Houston, TX USA
                [2 ]ISNI 0000 0004 0571 7705, GRID grid.29524.38, Eye Hospital, , University Medical Centre Ljubljana, ; Ljubljana, Slovenia
                [3 ]ISNI 0000 0000 9935 6525, GRID grid.411668.c, Department of Ophthalmology, , University Hospital Erlangen, ; Erlangen, Germany
                [4 ]ISNI 0000 0001 2175 0319, GRID grid.185648.6, Department of Ophthalmology and Visual Sciences, Department of Bioengineering, , University of Illinois at Chicago, ; Chicago, IL USA
                [5 ]ISNI 0000 0001 2179 088X, GRID grid.1008.9, Department of Ophthalmology, Centre for Eye Research Australia, The Royal Victorian Eye and Ear Hospital, , University of Melbourne, ; Melbourne, VIC Australia
                [6 ]ISNI 0000 0001 2353 285X, GRID grid.170693.a, Department of Ophthalmology, , University of South Florida, ; Tampa, FL USA
                [7 ]College of Optometry, State University of New York, New York, NY USA
                Author information
                http://orcid.org/0000-0002-4226-5109
                Article
                9638
                10.1007/s10633-018-9638-x
                6061118
                29855761
                371ae0d6-bea9-4422-a9d8-5124a9caac53
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 7 May 2018
                : 9 May 2018
                Categories
                ISCEV Standards
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2018

                Ophthalmology & Optometry
                clinical standards,electroretinogram (erg),full-field erg,international society of clinical electrophysiology of vision (iscev),photopic negative response,phnr,optic neuropathy,glaucoma,retinal ganglion cells

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