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      Short-Term Changes in the Photopic Negative Response Following Intraocular Pressure Lowering in Glaucoma

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          Abstract

          Purpose

          To evaluate the short-term changes in inner retinal function using the photopic negative response (PhNR) after intraocular pressure (IOP) reduction in glaucoma.

          Methods

          Forty-seven participants with glaucoma who were commencing a new or additional IOP-lowering therapy (treatment group) and 39 participants with stable glaucoma (control group) were recruited. IOP, visual field, retinal nerve fiber layer thickness, and electroretinograms (ERGs) were recorded at baseline and at a follow-up visit (3 ± 2 months). An optimized protocol developed for a portable ERG device was used to record the PhNR. The PhNR saturated amplitude ( V max ), V max ratio, semi-saturation constant ( K), and slope of the Naka–Rushton function were analyzed.

          Results

          A significant percentage reduction in IOP was observed in the treatment group (28 ± 3%) compared to the control group (2 ± 3%; P < 0.0001). For PhNR V max , there was no significant interaction ( F 1,83 = 2.099, P = 0.15), but there was a significant difference between the two time points ( F 1,83 = 5.689, P = 0.019). Post hoc analysis showed a significant difference between baseline and 3 months in the treatment group (mean difference, 1.23 µV; 95% confidence interval [CI], 0.24–2.22) but not in the control group (0.30 µV; 95% CI, 0.78–1.38). K and slope were not significantly different in either group. Improvement beyond test–retest variability was seen in 17% of participants in the treatment group compared to 3% in the control group ( P = 0.007, χ 2 test).

          Conclusions

          The optimized protocol for measuring the PhNR detected short-term improvements in a proportion of participants following IOP reduction, although the majority showed no change.

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          Most cited references40

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          Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial.

          Treatments for open-angle glaucoma aim to prevent vision loss through lowering of intraocular pressure, but to our knowledge no placebo-controlled trials have assessed visual function preservation, and the observation periods of previous (unmasked) trials have typically been at least 5 years. We assessed vision preservation in patients given latanoprost compared with those given placebo.
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            ISCEV extended protocol for the photopic negative response (PhNR) of the full-field electroretinogram

            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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              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

                Journal
                Invest Ophthalmol Vis Sci
                Invest. Ophthalmol. Vis. Sci
                iovs
                IOVS
                Investigative Ophthalmology & Visual Science
                The Association for Research in Vision and Ophthalmology
                0146-0404
                1552-5783
                07 August 2020
                August 2020
                : 61
                : 10
                : 16
                Affiliations
                [1 ]Glaucoma Research Unit, Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia
                [2 ]Ophthalmology, Department of Surgery, The University of Melbourne, Melbourne, Australia
                [3 ]Royal Victorian Eye and Ear Hospital, Melbourne, Australia
                [4 ]Centre for Vision Research, Duke-NUS Medical School, Singapore, Singapore
                [5 ]Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore
                Author notes
                Correspondence: Jessica Tang, Glaucoma Research Unit, Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Level 7, Peter Howson Wing, 32 Gisborne St, East Melbourne, VIC 3002, Australia; j.tang8@ 123456student.unimelb.edu.au .
                Article
                IOVS-19-28324
                10.1167/iovs.61.10.16
                7441296
                32766747
                3805bf28-c72d-46c7-975f-b99bf54b141b
                Copyright 2020 The Authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 16 June 2020
                : 29 August 2019
                Page count
                Pages: 7
                Categories
                Glaucoma
                Glaucoma

                electroretinography,glaucoma,pressure lowering,photopic negative response

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