Doc Ophthalmol (2018) 136:1–26 https://doi.org/10.1007/s10633-017-9621-y ISCEV STANDARDS ISCEV guide to visual electrodiagnostic procedures Anthony G. Robson . Josefin Nilsson . Shiying Li . Subhadra Jalali . Anne B. Fulton . Alma Patrizia Tormene . Graham E. Holder . Scott E. Brodie Received: 15 December 2017 / Accepted: 18 December 2017 / Published online: 3 February 2018 Ó The Author(s) 2018. This article is an open access publication Abstract Clinical electrophysiological testing of the mfERG), the electrooculogram (EOG) and the corti- visual system incorporates a range of noninvasive tests cal-derived visual evoked potential (VEP). The guide- and provides an objective indication of function line outlines the basic principles of testing. Common relating to different locations and cell types within clinical presentations and symptoms are described the visual system. This document developed by the with illustrative examples and suggested investigation International Society for Clinical Electrophysiology strategies. of Vision provides an introduction to standard visual electrodiagnostic procedures in widespread use Keywords ISCEV standards Á Clinical including the full-field electroretinogram (ERG), the electrophysiology Á Electrooculogram (EOG) Á pattern electroretinogram (pattern ERG or PERG), the Electroretinogram (ERG) Á Pattern ERG Á Multifocal multifocal electroretinogram (multifocal ERG or ERG (mfERG) Á Visual evoked potential (VEP) Á Optic neuropathy Á Maculopathy Á Retinopathy A. G. Robson (&) Á G. E. Holder Department of Electrophysiology, Moorfields Eye A. B. Fulton Hospital, 162 City Road, London, UK Department of Ophthalmology, Boston Children’s e-mail: anthony.robson@moorfields.nhs.uk Hospital, Boston, USA A. G. Robson Á G. E. Holder A. P. Tormene Institute of Ophthalmology, University College London, Department of Neurosciences, Ophthalmic Clinic, Padova London, UK University, Padova, Italy J. Nilsson G. E. Holder Department of Clinical Neurophysiology, Sahlgrenska National University of Singapore, National University University Hospital, Go¨teborg, Sweden Hospital, Singapore City, Singapore S. Li S. E. Brodie Southwest Hospital, Southwest Eye Hospital, Third The Mount Sinai Hospital, New York Eye and Ear Military Medical University, Chongqing Institute of Infirmary of Mount Sinai, New York, USA Retina, Chongqing, China S. Jalali Srimati Kanuri Santhamma Centre for Vitreoretinal Diseases, Jasti V. Ramanamma Childrens’ Eye Care Centre, L V Prasad Eye Institute, Hyderabad, India 123 2 Doc Ophthalmol (2018) 136:1–26 Introduction Fig. 1 Representative full-field and pattern ERGs in a normal c subject (a), in a case of macular dystrophy (b), cone-rod dystrophy (c), rod-cone dystrophy with relative sparing of Clinical electrophysiological testing of the visual macular function (d), complete CSNB (e), incomplete CSNB system incorporates a range of tests based upon the (f) and birdshot retinochoroidopathy (BRC) before treatment recording of electrical potentials evoked by visual (g) and after treatment illustrating full recovery of the ERG and stimuli, using electrodes situated on the surface of the PERG (h). Recordings showed a high degree of inter-ocular symmetry except in BRC (data from other eye are not shown). eyes, the peri-orbital skin or scalp. The tests are Note there is a 20-ms pre-stimulus delay in all single flash ERG noninvasive and provide an objective indication of recordings. Two responses for each stimulus condition are function relating to different locations and cell types superimposed to illustrate reproducibility. Broken lines replace within the visual system. This document developed by blink artefacts occurring after the ERGs, for clarity the International Society for Clinical Electrophysiol- ogy of Vision (ISCEV) provides an introduction to physiologic implications of abnormal responses. Users standard visual electrodiagnostic procedures in wide- should consult the relevant standard or extended pro- spread use and describes the common clinical indica- tocol for detailed testing protocols. tions for which these tests are applicable. Detailed specifications for each procedure may be found in the The full-field ERG appropriate ISCEV standards [1–5]. The basic princi- ples of electrodiagnostic testing are outlined in this The ISCEV standard full-field ERGs (Fig. 1a) are document, but the document is not intended to be global responses of the retina to brief flashes of light prescriptive or to address every clinical scenario and is and provide an assessment of generalized retinal not a mandate for specific procedures on individual function under light- and dark-adapted conditions. A patients. Clinical electrophysiological testing has the ganzfeld (German for ‘‘whole field’’) stimulator, greatest utility when performed in conjunction with which provides a uniformly illuminated field, is used clinical assessment by specialist eye care profession- to deliver a range of flash stimuli that evenly als. Clinical context is essential to enable appropriate illuminate the maximal area of retina. The ERGs are clinical management. recorded with electrodes in contact with the cornea or This guideline describes the basic methods and conjunctiva or with skin electrodes attached to the underlying principles of testing for each of the lower eyelids. Several types of corneal electrode may standard tests including the full-field flash elec- be used including contact lens, fiber, jet and gold foil troretinogram (ERG), the pattern electroretinogram electrodes. The pupils are dilated to maximize retinal (pattern ERG or PERG), the multifocal electroretino- illumination and to minimize inter-subject and inter- gram (mfERG), the electrooculogram (EOG) and the visit variability. Reliable interpretation of recordings cortical-derived visual evoked potential (VEP). The requires comparison with electrode-specific and age- principal focus is to place these tests in clinical matched normative data. The normal test–retest vari- context. Common clinical presentations and symp- ability of ERG parameters is also an important toms are described with illustrative examples and consideration if used to monitor disease progression suggested investigation strategies. or the safety or efficacy of treatments. The ISCEV standard protocol includes dark- adapted (DA) recordings after 20-min dark adaptation The electrophysiological tests to flash strengths of 0.01, 3.0 and 10.0 cd s m-2 (DA 0.01; DA 3.0; DA 10.0). The weak flash (DA 0.01) ISCEV publishes and regularly updates standards for ERG arises in the inner retinal rod bipolar cells and is clinical tests of the visual system. The most recent the only standard test that selectively monitors rod publications are listed on the ISCEV Web site www. system function. Abnormality of the DA 0.01 ERG iscev.org/standards and are freely accessible. In can be caused by either rod photoreceptor dysfunction addition to these basic tests, extended protocols may or selective dysfunction occurring post-phototrans- support differential diagnosis or functional monitor- duction or at the level of the inner retinal rod bipolar ing. Below is a brief description of normal waveforms cells. The DA 3.0 (standard flash) and DA 10.0 (strong resulting from the ISCEV standard tests and the flash) ERGs have input from both rod and cone 123 Doc Ophthalmol (2018) 136:1–26 3 123 4 Doc Ophthalmol (2018) 136:1–26 Fig. 1 continued 123 Doc Ophthalmol (2018) 136:1–26 5 systems, but the DA rod system contribution domi- the retinal periphery and there is minimal contribution nates in a normal retina. Approximately the first 8 ms from the macula. Electrophysiological assessment of of the cornea-negative a-wave reflects rod hyperpo- macular function requires the use of different tech- larizations, and as the a-wave in the DA 10.0 ERG is of niques such as the pattern ERG or multifocal ERG. shorter peak time and larger than in the DA 3.0 ERG, it provides a better measure of rod photoreceptor The pattern ERG function. The subsequent cornea-positive b-wave arises largely in the rod On-bipolar cells and reflects The ISCEV standard PERG is derived largely from the function that is post-phototransduction. Thus, the DA macular retinal ganglion cells and complements the strong flash ERG enables localization of dysfunction full-field ERG, in differentiating between maculopa- to the rod photoreceptors (a-wave reduction and thy and generalized retinopathy. PERG also enables a concomitant b-wave reduction) or to a level that is more meaningful evaluation of a VEP, to exclude a post-phototransduction or inner retinal (sparing of the macular cause of VEP abnormality and to provide an a-wave with b-wave reduction). The DA oscillatory additional assessment of retinal ganglion cell involve- potentials (OPs) are small high-frequency components ment (see below). The PERG is recorded to an normally visible on the rising limb of the DA 3.0 and alternating high-contrast checkerboard using a corneal DA 10.0 ERG b-waves and are thought to reflect electrode. PERGs are attenuated by poor refraction amacrine cell signaling. Reduction in the OPs is often and ocular media opacity, and care must be taken to associated with other ERG abnormalities but may optimize the optical quality of the checkerboard occur selectively in some disorders. The cone system stimulus; for this reason, contact lens electrodes are contribution to both DA ERG a- and b-waves is minor not suitable. in a normal retina but can be of greater significance in The transient PERG has two major components of patients with disease primarily or exclusively affect- diagnostic value: a positive polarity P50 and a ing the rod system. negative polarity N95 (Figs. 1a and 2). Both compo- Standard light-adapted (LA) ERGs provide two nents reflect macular retinal ganglion cell function, but measures of generalized cone system function; both there is an additional more distal retinal contribution are obtained to a flash strength of 3.0 cd s m-2, after a to the P50 component. Both P50 and N95 depend on standard period of 10-min light adaptation in the the function of the macular cones, and P50 reduction Ganzfeld with a constant background luminance of and/or delay can characterize macular dysfunction.