25
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Clinical Applications of the Photopic Negative Response to Optic Nerve and Retinal Diseases

      review-article
      *
      Journal of Ophthalmology
      Hindawi Publishing Corporation

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The photopic negative response (PhNR) in response to a brief flash is a negative-going wave following the b-wave of the cone electroretinogram (ERG) that is driven by retinal ganglion cells (RGCs). The function of RGCs is objectively evaluated by analysing the PhNR. We reviewed articles regarding clinical use of the PhNR. The PhNR was well correlated with the visual sensitivity obtained by standard automated perimetry and morphometric parameters of the inner retina and optic nerve head in optic nerve and retinal diseases. Moreover, combining the PhNR with focal or multifocal ERG techniques enables the objective assessment of local function of RGCs. The PhNR is therefore likely to become established as an objective functional test for optic nerve and retinal diseases involving RGC injury.

          Related collections

          Most cited references43

          • Record: found
          • Abstract: found
          • Article: not found

          A framework for comparing structural and functional measures of glaucomatous damage.

          While it is often said that structural damage due to glaucoma precedes functional damage, it is not always clear what this statement means. This review has two purposes: first, to show that a simple linear relationship describes the data relating a particular functional test (standard automated perimetry (SAP)) to a particular structural test (optical coherence tomography (OCT)); and, second, to propose a general framework for relating structural and functional damage, and for evaluating if one precedes the other. The specific functional and structural tests employed are described in Section 2. To compare SAP sensitivity loss to loss of the retinal nerve fiber layer (RNFL) requires a map that relates local field regions to local regions of the optic disc as described in Section 3. When RNFL thickness in the superior and inferior arcuate sectors of the disc are plotted against SAP sensitivity loss (dB units) in the corresponding arcuate regions of the visual field, RNFL thickness becomes asymptotic for sensitivity losses greater than about 10dB. These data are well described by a simple linear model presented in Section 4. The model assumes that the RNFL thickness measured with OCT has two components. One component is the axons of the retinal ganglion cells and the other, the residual, is everything else (e.g. glial cells, blood vessels). The axon portion is assumed to decrease in a linear fashion with losses in SAP sensitivity (in linear units); the residual portion is assumed to remain constant. Based upon severe SAP losses in anterior ischemic optic neuropathy (AION), the residual RNFL thickness in the arcuate regions is, on average, about one-third of the premorbid (normal) thickness of that region. The model also predicts that, to a first approximation, SAP sensitivity in control subjects does not depend upon RNFL thickness. The data (Section 6) are, in general, consistent with this prediction showing a very weak correlation between RNFL thickness and SAP sensitivity. In Section 7, the model is used to estimate the proportion of patients showing statistical abnormalities (worse than the 5th percentile) on the OCT RNFL test before they show abnormalities on the 24-2 SAP field test. Ignoring measurement error, the patients with a relatively thick RNFL, when healthy, will be more likely to show significant SAP sensitivity loss before statistically significant OCT RNFL loss, while the reverse will be true for those who start with an average or a relatively thin RNFL when healthy. Thus, it is important to understand the implications of the wide variation in RNFL thickness among control subjects. Section 8 describes two of the factors contributing to this variation, variations in the position of blood vessels and variations in the mapping of field regions to disc sectors. Finally, in Sections 7 and 9, the findings are related to the general debate in the literature about the relationship between structural and functional glaucomatous damage and a framework is proposed for understanding what is meant by the question, 'Does structural damage precede functional damage in glaucoma?' An emphasis is placed upon the need to distinguish between "statistical" and "relational" meanings of this question.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            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.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Ganglion cell contributions to the rat full-field electroretinogram.

              The purpose of this study was to determine what contributions are made to the rat full-field electroretinogram (ERG) by ganglion cells (GCs). To that end, the ERG was assessed longitudinally following optic nerve transection (ONTx). Additional studies were conducted using intravitreal injections of pharmacologically active substances. The ERG was recorded simultaneously from both eyes of anaesthetized adult Brown-Norway rats (ketamine: xylazine: acepromazine, 55: 5: 1 mg kg(-1)) using custom silver chloride electrodes. Stimuli were brief, white xenon discharges delivered via a Ganzfeld under dark-adapted and light-adapted conditions (150 cd m(-2)). ERGs were obtained 1, 2, 3, 4 and 9 weeks after ONTx (n = 8) or sham (n = 8) operations. ONTx reduced both positive and negative components of the scotopic threshold response (pSTR and nSTR). Scotopic ERG responses to brighter flashes, including a-waves, b-waves and oscillatory potentials (OPs) were unaffected by ONTx. ONTx reduced the photopic b-wave and OPs. TTX (6 microM) reduced the pSTR and nSTR, but not the scotopic a-wave, b-wave or OPs. TTX had dramatic effects on the photopic ERG, surpassing the effects of ONTx. TTX application 9 weeks post-ONTx had little additional effect on the STR. Inhibition of inner retinal responses using GABA (10 mM) or NMDA (0.8 mM) reduced the nSTR substantially. Similar results were obtained with antagonists of AMPA/KA ionotropic glutamate receptors 6-cyano-7-nitroquinoxaline-2,3(1H,4H)-dione (CNQX, 0.2 mM) or cis-2,3-piperidinedicarboxylic acid (PDA, 5 mm); however, both also reduced the scotopic b-wave by approximately 40 %. By contrast, the NMDA receptor antagonist D(-)-2-amino-7-phosphonoheptanoic acid (D-AP7, 0.2 mM) had no effect alone, but the combination of D-AP7 and CNQX completely abolished the STR. The results of this study indicate that: (1) both pSTR and nSTR components in the rat depend directly upon intact GC responses, and that amacrine cell contributions to these components are relatively small; (2) scotopic ERG response components to brighter flashes receive little influence from GCs; (3) the rat photopic ERG also reflects GC signals and may serve as an additional useful test of GC function; (4) TTX had dramatic effects on the rat photopic ERG that were not attributable to GC currents, but rather to voltage-gated sodium currents in amacrine or interplexiform cells; (5) a small residual negative STR persisted after ONTx that was likely to be generated by graded responses of third-order retinal cells, most likely amacrine cells.
                Bookmark

                Author and article information

                Journal
                J Ophthalmol
                J Ophthalmol
                JOP
                Journal of Ophthalmology
                Hindawi Publishing Corporation
                2090-004X
                2090-0058
                2012
                24 October 2012
                : 2012
                : 397178
                Affiliations
                Department of Ophthalmology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Iwate, Morioka 020-8505, Japan
                Author notes

                Academic Editor: Suresh Viswanathan

                Article
                10.1155/2012/397178
                3486014
                23133741
                23a6a8a3-3867-4b00-8daa-08c140c6e37e
                Copyright © 2012 Shigeki Machida.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 July 2012
                : 16 September 2012
                Categories
                Review Article

                Ophthalmology & Optometry
                Ophthalmology & Optometry

                Comments

                Comment on this article