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      Pattern Electroretinogram Detects Localized Glaucoma Defects

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          Abstract

          Purpose

          We evaluated the clinical ability of pattern electroretinogram (PERG) to detect functional losses in the affected hemifield of open-angle glaucoma patients with localized perimetric defects.

          Methods

          Hemifield (horizontally-defined) steady-state PERGs (h-PERGs) were recorded in response to 1.7 c/deg alternating gratings from 32 eyes of 29 glaucomatous patients with a perimetric, focal one-hemifield defect, 10 eyes of 10 glaucomatous patients with a diffuse perimetric defect, and 18 eyes of 18 age-matched normal subjects. Standard automated perimetry (SAP) and spectral-domain optical coherence tomography (SD-OCT) for retinal nerve fiber layer (RNFL) thickness also were performed. h-PERG amplitudes and ratios, calculated corresponding hemifield perimetric deviations, as well as hemiretina RNFL thicknesses were analyzed.

          Results

          h-PERG amplitudes, perimetric deviations, and RNFL thicknesses showed losses ( P < 0.001) when comparing affected with unaffected hemifields of localized glaucomatous eyes. No differences were found in h-PERG amplitudes between hemifields of normal or diffuse glaucomatous eyes. h-PERG amplitude ratios (affected/unaffected hemifield) in localized glaucoma were lower ( P < 0.001) than the ratios from normal or diffuse glaucomatous eyes. The areas under the receiver operating characteristic curves for h-PERG amplitude ratios, comparing localized-defect glaucomatous eyes with normal or diffuse glaucomatous eyes, were 0.93 and 0.91, respectively.

          Conclusions

          h-PERG assessment showed good diagnostic accuracy to confirm localized glaucomatous defects detected perimetrically. This test may be particularly useful in cognitively impaired patients or young/nonverbal patients unable to provide reliable visual fields.

          Translational Relevance

          h-PERG provides a sensitive objective measure to confirm focal losses detected with SAP and/or RNFL thickness analysis.

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          Most cited references39

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          Glaucomatous damage of the macula.

          There is a growing body of evidence that early glaucomatous damage involves the macula. The anatomical basis of this damage can be studied using frequency domain optical coherence tomography (fdOCT), by which the local thickness of the retinal nerve fiber layer (RNFL) and local retinal ganglion cell plus inner plexiform (RGC+) layer can be measured. Based upon averaged fdOCT results from healthy controls and patients, we show that: 1. For healthy controls, the average RGC+ layer thickness closely matches human histological data; 2. For glaucoma patients and suspects, the average RGC+ layer shows greater glaucomatous thinning in the inferior retina (superior visual field (VF)); and 3. The central test points of the 6° VF grid (24-2 test pattern) miss the region of greatest RGC+ thinning. Based upon fdOCT results from individual patients, we have learned that: 1. Local RGC+ loss is associated with local VF sensitivity loss as long as the displacement of RGCs from the foveal center is taken into consideration; and 2. Macular damage is typically arcuate in nature and often associated with local RNFL thinning in a narrow region of the disc, which we call the macular vulnerability zone (MVZ). According to our schematic model of macular damage, most of the inferior region of the macula projects to the MVZ, which is located largely in the inferior quadrant of the disc, a region that is particularly susceptible to glaucomatous damage. A small (cecocentral) region of the inferior macula, and all of the superior macula (inferior VF), project to the temporal quadrant, a region that is less susceptible to damage. The overall message is clear; clinicians need to be aware that glaucomatous damage to the macula is common, can occur early in the disease, and can be missed and/or underestimated with standard VF tests that use a 6° grid, such as the 24-2 VF test. Copyright © 2012 Elsevier Ltd. All rights reserved.
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            Number of ganglion cells in glaucoma eyes compared with threshold visual field tests in the same persons.

            To compare the number of retinal ganglion cells (RGCs) topographically mapped with specific visual field threshold test data in the same eyes among glaucoma patients. Seventeen eyes of 13 persons with well-documented glaucoma histories and Humphrey threshold visual field tests (San Leandro, CA) were obtained from eye banks. RGC number was estimated by histologic counts of retinal sections and by counts of remaining axons in the optic nerves. The locations of the retinal samples corresponded to specific test points in the visual field. The data for glaucoma patients were compared with 17 eyes of 17 persons who were group matched for age, had no ocular history, and had normal eyes by histologic examination. The mean RGC loss for the entire retina averaged 10.2%, indicating that many eyes had early glaucoma damage. RGC body loss averaged 35.7% in eyes with corrected pattern SD probability less than 0.5%. When upper to lower retina RGC counts were compared with their corresponding visual field data within each eye, a 5-dB loss in sensitivity was associated with 25% RGC loss. For individual points that were abnormal at a probability less than 0.5%, the mean RGC loss was 29%. In control eyes, the loss of RGCs with age was estimated as 7205 cells per year in persons between 55 and 95 years of age. In optic nerves from glaucoma subjects, smaller axons were significantly more likely to be present than larger axons (R2 = 0.78, P<0.001). At least 25% to 35% RGC loss is associated with statistical abnormalities in automated visual field testing. In addition, these data corroborate previous findings that RGCs with larger diameter axons preferentially die in glaucoma.
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              Retinal ganglion cell atrophy correlated with automated perimetry in human eyes with glaucoma.

              We measured the number and size of retinal ganglion cells from six human eyes with glaucoma. In each, the histologic findings were correlated with visual field results. Five age-matched normal eyes were studied for comparison. In general, there were fewer remaining large ganglion cells in retinal areas with atrophy. In the perifoveal area, however, no consistent pattern of cell loss by size was found. Our estimates suggest that visual field sensitivity in automated testing begins to decline soon after the initial loss of ganglion cells. Throughout the central 30 degrees of the retina, 20% of the normal number of cells were gone in locations with a 5-dB sensitivity loss, and 40% cell loss corresponded to a 10-dB decrease. There were some remaining ganglion cells in areas that had 0-dB sensitivity in the field test.
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                Author and article information

                Journal
                Transl Vis Sci Technol
                Transl Vis Sci Technol
                tvst
                Transl Vis Sci Technol
                TVST
                Translational Vision Science & Technology
                The Association for Research in Vision and Ophthalmology
                2164-2591
                September 2018
                13 September 2018
                : 7
                : 5
                : 6
                Affiliations
                [1]1Institute of Ophthalmology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia
                [2]2Institute of Ophthalmology, Università Cattolica del Sacro Cuore, Roma, Italia
                Author notes
                [*]

                TS and AG contributed equally to this study.

                Correspondence: Tommaso Salgarello, Institute of Ophthalmology, Fondazione Policlinico Universitario A. Gemelli IRCCS - Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, I-00168, Roma, Italy. e-mail: tommaso.salgarello@ 123456policlinicogemelli.it
                Article
                tvst-07-04-15 TVST-17-0676
                10.1167/tvst.7.5.6
                6136848
                30221072
                a304f1e8-27b8-4f10-a62b-a4a45d18ff18
                Copyright 2018 The Authors

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

                History
                : 15 December 2017
                : 19 June 2018
                Categories
                Articles

                glaucoma,localized defect,electroretinogram,hemifield,hemiretina

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