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

ISCEV extended protocol for the photopic negative response (PhNR) of the full-field... Doc Ophthalmol (2018) 136:207–211 https://doi.org/10.1007/s10633-018-9638-x ISCEV STANDARDS ISCEV extended protocol for the photopic negative response (PhNR) of the full-field electroretinogram . . . . Laura Frishman Maja Sustar Jan Kremers J. Jason McAnany . . Marc Sarossy Radouil Tzekov Suresh Viswanathan Received: 7 May 2018 / Accepted: 9 May 2018 / Published online: 31 May 2018 The Author(s) 2018 Abstract The International Society for Clinical information about the function of retinal ganglion cells Electrophysiology of Vision (ISCEV) Standard for and their axons. The PhNR can be reduced in disorders full-field electroretinography (ERG) describes a min- that affect the innermost retina, including glaucoma imum procedure, but encourages more extensive and other forms of optic neuropathy. This document, testing. This ISCEV extended protocol describes an based on existing literature, provides a protocol for extension to the ERG Standard, namely the photopic recording and analyzing the PhNR in response to a negative response (PhNR) of the light-adapted flash brief flash. The protocol includes full-field stimula- ERG, as a well-established technique that is broadly tion, a frequency bandwidth of the recording in which accepted by experts in the field. The PhNR is a slow the lower limit does not exceed 0.3 Hz, and a negative-going wave after the b-wave that provides spectrally narrowband stimulus, specifically, a red L. Frishman (&) R. Tzekov College of Optometry, University of Houston, Houston, Department of Ophthalmology, University of South TX, USA Florida, Tampa, FL, USA e-mail: Lfrishman@uh.edu S. Viswanathan M. Sustar College of Optometry, State University of New York, Eye Hospital, University Medical Centre Ljubljana, New York, NY, USA Ljubljana, Slovenia J. Kremers Department of Ophthalmology, University Hospital Erlangen, Erlangen, Germany J. J. McAnany Department of Ophthalmology and Visual Sciences, Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, USA M. Sarossy Department of Ophthalmology, Centre for Eye Research Australia, The Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, VIC, Australia 123 208 Doc Ophthalmol (2018) 136:207–211 flash on a rod saturating blue background. Suggested Patient population flash strengths cover a range up to and including the minimum required to elicit a maximum amplitude This protocol for recording the PhNR can be used for PhNR. This extended protocol for recording the PhNR testing patients in whom inner retinal integrity, and provides a simple test of generalized retinal ganglion specifically signaling by retinal ganglion cells and cell function that could be added to standard ERG their axons, may be compromised due to ganglion cell testing. pathology or limitations in the input to the ganglion cells. For example, since 2000, reduced PhNR ampli- Keywords Clinical standards  Electroretinogram tudes have been reported in patients with glaucoma (ERG)  Full-field ERG  International Society of [3–6], optic atrophy [7, 8], central retinal artery Clinical Electrophysiology of Vision (ISCEV)  occlusion [9, 10], ischemic optic neuropathy [11], diabetic retinopathy [12], and idiopathic intracranial Photopic negative response  PhNR  Optic neuropathy  Glaucoma  Retinal ganglion cells hypertension [13]. In some cases, the protocol may be useful for monitoring treatment effects in eyes with ocular hypertension or glaucoma [14]. Abnormal potassium (K ) channel activity or other dysfunction Introduction of retinal glia may also be reflected in PhNR recordings [15]. This is because generation of the The International Society for Clinical Electrophysiol- PhNR, which has a slow time course (Fig. 1), is ogy of Vision (ISCEV) Standard for full-field elec- thought to involve glial K currents that serve to troretinography (ERG) describes a minimum set of remove the excess K released into extracellular space tests, but encourages the use of additional ERG during activation of retinal ganglion cells [16]. protocols for clinical ERG testing [1]. This extended protocol describes the photopic negative response (PhNR) of the flash ERG, as a specialized procedure Technical issues which is well established and broadly accepted by experts in the field. The protocol was prepared by the The electrodes and electronic recording equipment for authors in accordance with ISCEV procedures (http:// this PhNR protocol are as described in the ISCEV www.iscev.org/standards/index.html.) and was Standard for full-field ERG [1]. The present protocol approved by the ISCEV Board of Directors on March assumes full-field stimulation, while acknowledging 25, 2018. that focal stimulation has been shown to be effective in assessing inner retinal function [17]. For the frequency bandwidth of the recording, the ISCEV Standard Scope and applications suggests a minimum range of 0.3–300 Hz. For PhNR recordings, the bottom limit of the filtering could be The photopic negative response (PhNR) of the light- lower to minimize distortion and possible attenuation adapted (LA) electroretinogram (ERG) is a negative- of the slow negative wave. For spectral characteristics going wave that occurs after the b-wave in response to of the stimulus, whereas the ISCEV Standard recom- a brief flash. The PhNR reflects generalized activity of mends ‘‘visibly white’’ (broadband) stimuli, narrow- retinal ganglion cells and their axons [2], and its band stimuli are recommended for recording the amplitude can be reduced early in diseases that affect PhNR. Specifically, a long-wavelength (red) flash on the innermost retina. The PhNR also occurs in a rod saturating short-wavelength (blue) background response to long-duration flashes, following the b- yields a larger amplitude PhNR than broadband wave at light onset and d-wave at light offset [3], but stimuli. LED-based stimulators typically provide a most publications to date have described brief flashes. 20-nm half-height bandwidth for the red and blue Only the brief flash PhNR will be addressed in this LEDs. The recommendation for narrowband stimuli is protocol. based on the outcome of studies that compared PhNR amplitudes using broad- vs narrowband stimuli in nonhuman primates [18] and in glaucoma patients 123 Doc Ophthalmol (2018) 136:207–211 209 Calibration The stimulus strength for the brief flashes can be specified in photopic candela seconds per meter -2 squared (phot cd s m ); the background in phot -2 cd m . A spectroradiometer (or spectrometer) is required to determine the spectral characteristics of chromatic flashes. Care should be taken to measure a range of flash luminances as some Ganzfeld stimula- tors use different combinations and banks of LEDs for different luminance ranges, and these may have different wavelength specifications. It is useful also to confirm that the background is strong enough to saturate rod photoreceptors, for example, about 100 -2 scot cd m . Blue backgrounds will saturate the rods while minimizing the photopic stimulus strength and hence the adapting effect of the background on cone- driven responses. Protocol specifications The procedures for patient preparation and recording are as specified by the ISCEV Standard for the light- adapted ERG, including pupil dilation and 10 min of light adaptation if the patient was dark adapted for other testing prior to recording the light-adapted ERG. Other specifications are listed below; (a) The chromatic characteristics of the stimuli. Fig. 1 Illustration of the light-adapted ERG of a healthy Background: steady, blue LED (450–485 nm); -2 subject (35 years.) in response to a brief red LED flash (660 nm) 100 scot cd m ; equivalent to * 10 phot at each of four flash strengths, on a blue background (460 nm) of -2 -2 cd m . Light flash: red LED (630–660 nm). 10 cd m . Figure shows PhNR amplitude measurements from (b) Flash strengths and background luminance. baseline to PhNR trough (BT) and from b-wave peak to PhNR -2 trough (PT). Adapted from Ref. [26] (the Association for Flash: \ 5 ms; 1.0–2.5 phot cd s m , or the Research in Vision and Ophthalmology is the copyright holder) stimulus strength that produces the largest PhNR amplitude, but does not exceed the initial [6, 18, 19], and more generally on a review of the stimulus strength producing amplitude satura- literature which shows that most studies in patients tion, or lead to the decline in response amplitude have used red LED flashes on blue LED backgrounds. associated with the photopic hill [21, 22]. The It should be noted that other narrowband combinations dynamic range of the stimulus response func- using blue flashes on yellow or orange backgrounds tion generally ranges from * 0.01 to have also been reported to be effective for eliciting a -2 [ 2.0 phot cd s m . robust PhNR [19, 20]. (c) Frequency of flash presentation. Inter-flash interval: 1 s. Some studies have used an interval of 500 ms, but this may not allow enough time for PhNR to fully recover to baseline. 123 210 Doc Ophthalmol (2018) 136:207–211 (d) Recording bandwidth. The low-frequency filter PhNR amplitudes can be greater than that of a- and b- should be 0.3 Hz or lower; the high-frequency waves [21–24]. filter, a minimum of 300 Hz. (e) Signal averaging. There should be sufficient repetitions to provide good signal-to-noise Reporting ratio, and many studies have used 20 trials or more. At least 8–10 trials or more are necessary Reporting of results of PhNR testing should include for lower stimulus strengths if a range of stimuli measurements of the a-wave, b-wave, and PhNR and a are used that include weak stimuli, fewer may computation of the PhNR: b-wave ratio. This helps to be necessary for saturated responses. Artifact determine whether the origin of any change in PhNR rejection should be used if available. If single amplitude is at the retinal ganglion cells themselves or responses are saved, noisy responses can be a more distal location in the retina. The choice of removed during off-line analysis before method for measuring PhNR amplitude is open to the averaging. study and the site, but for comparison with other studies, inclusion of the BT measure is advised. Some studies have compared the sensitivity of the ratio of PhNR to b-wave amplitude (i.e., PhNR normalized to Response evaluation b-wave) versus the simple BT measure for detecting glaucoma, and results were mixed [5, 25]. Caution is As shown in Fig. 1, the PhNR amplitude can be needed as the ratio measure could be misleading in measured from baseline to the minimum point in the diseases where the b-wave is abnormal. trough (BT). It also can be measured from the peak of the b-wave to the maximum amplitude in trough (PT). Acknowledgements We would like to thank Anthony G. Alternatively, PhNR amplitude can be measured at a Robson for his advice and careful editing, and the members of ISCEV in particular, Michael F. Marmor for their valuable fixed time, for example, at 65–75 ms after the flash in discussion during the consultation period. the trough of the response (not shown). Using a fixed time could be helpful when responses in diseased eyes are small and the trough is difficult to locate. Note that Compliance with ethical standards the PT measurement is largely dominated by the b- wave amplitude, and a change in b-wave amplitude Conflict of interest The authors declare that they have no conflict of interest. reflecting a change in bipolar cell function must be considered when interpreting a change in PhNR Statement of human rights This article does not contain any amplitude. When measuring the PhNR, it may also studies with human participants performed by any of the be necessary to take account of the i-wave, or i-waves, authors. positive deflection(s) of Off pathway origin [11] in the Statement on the welfare of animals This article does not falling limb of the b-wave, and/or later in the trough contain any studies with animals performed by any of the (Fig. 1). For responses to the suggested narrowband authors. stimuli, such as those used for responses in Fig. 1, the Informed consent This article does not contain any studies maximum trough amplitude generally occurs after the with human participants performed by any of the authors. initial i-wave. Given the slow nature of the response, and the variety of amplitude criteria that have been Open Access This article is distributed under the terms of the used, peak time of the PhNR is generally not reported. Creative Commons Attribution 4.0 International License (http:// creativecommons.org/licenses/by/4.0/), which permits unre- The PhNR is moderately affected by age, so, for the stricted use, distribution, and reproduction in any medium, particular measure(s) chosen, appropriate age- provided you give appropriate credit to the original matched normative data should be used [3, 22]. author(s) and the source, provide a link to the Creative Com- Comparisons of longitudinal findings in patients to mons license, and indicate if changes were made. normal test-retest repeatability of PhNR amplitudes are also important, as the test–retest variability of 123 Doc Ophthalmol (2018) 136:207–211 211 Appendix: Justification for the protocol details optic neuropathies: comparison with primate ERGs after pharmacologic blockade of inner retina. Invest Ophthalmol Vis Sci 45:3827–3837 A systematic literature review was performed using 12. Chen H, Zhang M, Huang S, Wu D (2008) The photopic PubMed to find publications that reported use of the negative response of flash ERG in nonproliferative diabetic retinopathy. Doc Ophthalmol 117:129–135 PhNR from the period 1999–2017. The committee 13. Moss HE, Park JC, McAnany JJ (2015) The photopic neg- identified the relevant references to include in the ative response in idiopathic intracranial hypertension. reference list, discussed the methods used in the Invest Ophthalmol Vis Sci 56:3709–3714 references to record PhNRs, and came to a consensus 14. Niyadurupola N, Luu CD, Nguyen DQ, Geddes K, Tan GX et al (2013) Intraocular pressure lowering is associated with on those to include in the extended protocol. an increase in the photopic negative response (PhNR) amplitude in glaucoma and ocular hypertensive eyes. Invest Ophthalmol Vis Sci 54:1913–1919 15. Thompson DA, Feather S, Stanescu HC, Freudenthal B, References Zdebik AA et al (2011) Altered electroretinograms in patients with KCNJ10 mutations and EAST syndrome. 1. McCulloch DL, Marmor MF, Brigell MG, Hamilton R, J Physiol 589:1681–1689 Holder GE et al (2015) ISCEV Standard for full-field clin- 16. Raz-Prag D, Grimes WN, Fariss RN, Vijayasarathy C, ical electroretinography (2015 update). Doc Ophthalmol Campos MM et al (2010) Probing potassium channel 130:1–12 function in vivo by intracellular delivery of antibodies in a 2. Viswanathan S, Frishman LJ, Robson JG, Harwerth RS, rat model of retinal neurodegeneration. Proc Natl Acad Sci Smith EL 3rd (1999) The photopic negative response of the U S A 107:12710–12715 macaque electroretinogram: reduction by experimental 17. Machida S, Toba Y, Ohtaki A, Gotoh Y, Kaneko M et al glaucoma. Invest Ophthalmol Vis Sci 40:1124–1136 (2008) Photopic negative response of focal electoretino- 3. Viswanathan S, Frishman LJ, Robson JG, Walters JW grams in glaucomatous eyes. Invest Ophthalmol Vis Sci (2001) The photopic negative response of the flash elec- 49:5636–5644 troretinogram in primary open angle glaucoma. Invest 18. Rangaswamy NV, Shirato S, Kaneko M, Digby BI, Robson Ophthalmol Vis Sci 42:514–522 JG et al (2007) Effects of spectral characteristics of ganzfeld 4. Colotto A, Falsini B, Salgarello T, Iarossi G, Galan ME et al stimuli on the photopic negative response (PhNR) of the (2000) Photopic negative response of the human ERG: ERG. Invest Ophthalmol Vis Sci 48:4818–4828 losses associated with glaucomatous damage. Invest Oph- 19. Kremers J, Jertila M, Link B, Pangeni G, Horn FK (2012) thalmol Vis Sci 41:2205–2211 Spectral characteristics of the PhNR in the full-field flash 5. Machida S, Gotoh Y, Toba Y, Ohtaki A, Kaneko M et al electroretinogram of normals and glaucoma patients. Doc (2008) Correlation between photopic negative response and Ophthalmol 124:79–90 retinal nerve fiber layer thickness and optic disc topography 20. Drasdo N, Aldebasi YH, Chiti Z, Mortlock KE, Morgan JE in glaucomatous eyes. Invest Ophthalmol Vis Sci et al (2001) The s-cone PHNR and pattern ERG in primary 49:2201–2207 open angle glaucoma. Invest Ophthalmol Vis Sci 6. Sustar M, Cvenkel B, Brecelj J (2009) The effect of 42:1266–1272 broadband and monochromatic stimuli on the photopic 21. Binns AM, Mortlock KE, North RV (2011) The relationship negative response of the electroretinogram in normal sub- between stimulus intensity and response amplitude for the jects and in open-angle glaucoma patients. Doc Ophthalmol photopic negative response of the flash electroretinogram. 118:167–177 Doc Ophthalmol 122:39–52 7. Gotoh Y, Machida S, Tazawa Y (2004) Selective loss of the 22. Joshi NR, Ly E, Viswanathan S (2017) Intensity response photopic negative response in patients with optic nerve function of the photopic negative response (PhNR): effect of atrophy. Arch Ophthalmol 122:341–346 age and test-retest reliability. Doc Ophthalmol 135:1–16 8. Miyata K, Nakamura M, Kondo M, Lin J, Ueno S et al 23. Mortlock KE, Binns AM, Aldebasi YH, North RV (2010) (2007) Reduction of oscillatory potentials and photopic Inter-subject, inter-ocular and inter-session repeatability of negative response in patients with autosomal dominant optic the photopic negative response of the electroretinogram atrophy with OPA1 mutations. Invest Ophthalmol Vis Sci recorded using DTL and skin electrodes. Doc Ophthalmol 48:820–824 121:123–134 9. Machida S, Gotoh Y, Tanaka M, Tazawa Y (2004) Pre- 24. Tang J, Edwards T, Crowston JG, Sarossy M (2014) The dominant loss of the photopic negative response in central test–retest reliability of the photopic negative response retinal artery occlusion. Am J Ophthalmol 137:938–940 (PhNR). Transl Vis Sci Technol 3:1 10. Shinoda K, Yamada K, Matsumoto CS, Kimoto K, Nakat- 25. Preiser D, Lagreze WA, Bach M, Poloschek CM (2013) suka K (2008) Changes in retinal thickness are correlated Photopic negative response versus pattern electroretinogram with alterations of electroretinogram in eyes with central in early glaucoma. Invest Ophthalmol Vis Sci 54:1182–1191 retinal artery occlusion. Graefes Arch Clin Exp Ophthalmol 26. Wang J, Cheng H, Hu YS, Tang RA, Frishman LJ (2012) 246:949–954 The photopic negative response of the flash electroretino- 11. Rangaswamy NV, Frishman LJ, Dorotheo EU, Schiffman gram in multiple sclerosis. Invest Ophthalmol Vis Sci JS, Bahrani HM et al (2004) Photopic ERGs in patients with 53:1315–1323 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Documenta Ophthalmologica Springer Journals

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

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Doc Ophthalmol (2018) 136:207–211 https://doi.org/10.1007/s10633-018-9638-x ISCEV STANDARDS ISCEV extended protocol for the photopic negative response (PhNR) of the full-field electroretinogram . . . . Laura Frishman Maja Sustar Jan Kremers J. Jason McAnany . . Marc Sarossy Radouil Tzekov Suresh Viswanathan Received: 7 May 2018 / Accepted: 9 May 2018 / Published online: 31 May 2018 The Author(s) 2018 Abstract The International Society for Clinical information about the function of retinal ganglion cells Electrophysiology of Vision (ISCEV) Standard for and their axons. The PhNR can be reduced in disorders full-field electroretinography (ERG) describes a min- that affect the innermost retina, including glaucoma imum procedure, but encourages more extensive and other forms of optic neuropathy. This document, testing. This ISCEV extended protocol describes an based on existing literature, provides a protocol for extension to the ERG Standard, namely the photopic recording and analyzing the PhNR in response to a negative response (PhNR) of the light-adapted flash brief flash. The protocol includes full-field stimula- ERG, as a well-established technique that is broadly tion, a frequency bandwidth of the recording in which accepted by experts in the field. The PhNR is a slow the lower limit does not exceed 0.3 Hz, and a negative-going wave after the b-wave that provides spectrally narrowband stimulus, specifically, a red L. Frishman (&) R. Tzekov College of Optometry, University of Houston, Houston, Department of Ophthalmology, University of South TX, USA Florida, Tampa, FL, USA e-mail: Lfrishman@uh.edu S. Viswanathan M. Sustar College of Optometry, State University of New York, Eye Hospital, University Medical Centre Ljubljana, New York, NY, USA Ljubljana, Slovenia J. Kremers Department of Ophthalmology, University Hospital Erlangen, Erlangen, Germany J. J. McAnany Department of Ophthalmology and Visual Sciences, Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, USA M. Sarossy Department of Ophthalmology, Centre for Eye Research Australia, The Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, VIC, Australia 123 208 Doc Ophthalmol (2018) 136:207–211 flash on a rod saturating blue background. Suggested Patient population flash strengths cover a range up to and including the minimum required to elicit a maximum amplitude This protocol for recording the PhNR can be used for PhNR. This extended protocol for recording the PhNR testing patients in whom inner retinal integrity, and provides a simple test of generalized retinal ganglion specifically signaling by retinal ganglion cells and cell function that could be added to standard ERG their axons, may be compromised due to ganglion cell testing. pathology or limitations in the input to the ganglion cells. For example, since 2000, reduced PhNR ampli- Keywords Clinical standards  Electroretinogram tudes have been reported in patients with glaucoma (ERG)  Full-field ERG  International Society of [3–6], optic atrophy [7, 8], central retinal artery Clinical Electrophysiology of Vision (ISCEV)  occlusion [9, 10], ischemic optic neuropathy [11], diabetic retinopathy [12], and idiopathic intracranial Photopic negative response  PhNR  Optic neuropathy  Glaucoma  Retinal ganglion cells hypertension [13]. In some cases, the protocol may be useful for monitoring treatment effects in eyes with ocular hypertension or glaucoma [14]. Abnormal potassium (K ) channel activity or other dysfunction Introduction of retinal glia may also be reflected in PhNR recordings [15]. This is because generation of the The International Society for Clinical Electrophysiol- PhNR, which has a slow time course (Fig. 1), is ogy of Vision (ISCEV) Standard for full-field elec- thought to involve glial K currents that serve to troretinography (ERG) describes a minimum set of remove the excess K released into extracellular space tests, but encourages the use of additional ERG during activation of retinal ganglion cells [16]. protocols for clinical ERG testing [1]. This extended protocol describes the photopic negative response (PhNR) of the flash ERG, as a specialized procedure Technical issues which is well established and broadly accepted by experts in the field. The protocol was prepared by the The electrodes and electronic recording equipment for authors in accordance with ISCEV procedures (http:// this PhNR protocol are as described in the ISCEV www.iscev.org/standards/index.html.) and was Standard for full-field ERG [1]. The present protocol approved by the ISCEV Board of Directors on March assumes full-field stimulation, while acknowledging 25, 2018. that focal stimulation has been shown to be effective in assessing inner retinal function [17]. For the frequency bandwidth of the recording, the ISCEV Standard Scope and applications suggests a minimum range of 0.3–300 Hz. For PhNR recordings, the bottom limit of the filtering could be The photopic negative response (PhNR) of the light- lower to minimize distortion and possible attenuation adapted (LA) electroretinogram (ERG) is a negative- of the slow negative wave. For spectral characteristics going wave that occurs after the b-wave in response to of the stimulus, whereas the ISCEV Standard recom- a brief flash. The PhNR reflects generalized activity of mends ‘‘visibly white’’ (broadband) stimuli, narrow- retinal ganglion cells and their axons [2], and its band stimuli are recommended for recording the amplitude can be reduced early in diseases that affect PhNR. Specifically, a long-wavelength (red) flash on the innermost retina. The PhNR also occurs in a rod saturating short-wavelength (blue) background response to long-duration flashes, following the b- yields a larger amplitude PhNR than broadband wave at light onset and d-wave at light offset [3], but stimuli. LED-based stimulators typically provide a most publications to date have described brief flashes. 20-nm half-height bandwidth for the red and blue Only the brief flash PhNR will be addressed in this LEDs. The recommendation for narrowband stimuli is protocol. based on the outcome of studies that compared PhNR amplitudes using broad- vs narrowband stimuli in nonhuman primates [18] and in glaucoma patients 123 Doc Ophthalmol (2018) 136:207–211 209 Calibration The stimulus strength for the brief flashes can be specified in photopic candela seconds per meter -2 squared (phot cd s m ); the background in phot -2 cd m . A spectroradiometer (or spectrometer) is required to determine the spectral characteristics of chromatic flashes. Care should be taken to measure a range of flash luminances as some Ganzfeld stimula- tors use different combinations and banks of LEDs for different luminance ranges, and these may have different wavelength specifications. It is useful also to confirm that the background is strong enough to saturate rod photoreceptors, for example, about 100 -2 scot cd m . Blue backgrounds will saturate the rods while minimizing the photopic stimulus strength and hence the adapting effect of the background on cone- driven responses. Protocol specifications The procedures for patient preparation and recording are as specified by the ISCEV Standard for the light- adapted ERG, including pupil dilation and 10 min of light adaptation if the patient was dark adapted for other testing prior to recording the light-adapted ERG. Other specifications are listed below; (a) The chromatic characteristics of the stimuli. Fig. 1 Illustration of the light-adapted ERG of a healthy Background: steady, blue LED (450–485 nm); -2 subject (35 years.) in response to a brief red LED flash (660 nm) 100 scot cd m ; equivalent to * 10 phot at each of four flash strengths, on a blue background (460 nm) of -2 -2 cd m . Light flash: red LED (630–660 nm). 10 cd m . Figure shows PhNR amplitude measurements from (b) Flash strengths and background luminance. baseline to PhNR trough (BT) and from b-wave peak to PhNR -2 trough (PT). Adapted from Ref. [26] (the Association for Flash: \ 5 ms; 1.0–2.5 phot cd s m , or the Research in Vision and Ophthalmology is the copyright holder) stimulus strength that produces the largest PhNR amplitude, but does not exceed the initial [6, 18, 19], and more generally on a review of the stimulus strength producing amplitude satura- literature which shows that most studies in patients tion, or lead to the decline in response amplitude have used red LED flashes on blue LED backgrounds. associated with the photopic hill [21, 22]. The It should be noted that other narrowband combinations dynamic range of the stimulus response func- using blue flashes on yellow or orange backgrounds tion generally ranges from * 0.01 to have also been reported to be effective for eliciting a -2 [ 2.0 phot cd s m . robust PhNR [19, 20]. (c) Frequency of flash presentation. Inter-flash interval: 1 s. Some studies have used an interval of 500 ms, but this may not allow enough time for PhNR to fully recover to baseline. 123 210 Doc Ophthalmol (2018) 136:207–211 (d) Recording bandwidth. The low-frequency filter PhNR amplitudes can be greater than that of a- and b- should be 0.3 Hz or lower; the high-frequency waves [21–24]. filter, a minimum of 300 Hz. (e) Signal averaging. There should be sufficient repetitions to provide good signal-to-noise Reporting ratio, and many studies have used 20 trials or more. At least 8–10 trials or more are necessary Reporting of results of PhNR testing should include for lower stimulus strengths if a range of stimuli measurements of the a-wave, b-wave, and PhNR and a are used that include weak stimuli, fewer may computation of the PhNR: b-wave ratio. This helps to be necessary for saturated responses. Artifact determine whether the origin of any change in PhNR rejection should be used if available. If single amplitude is at the retinal ganglion cells themselves or responses are saved, noisy responses can be a more distal location in the retina. The choice of removed during off-line analysis before method for measuring PhNR amplitude is open to the averaging. study and the site, but for comparison with other studies, inclusion of the BT measure is advised. Some studies have compared the sensitivity of the ratio of PhNR to b-wave amplitude (i.e., PhNR normalized to Response evaluation b-wave) versus the simple BT measure for detecting glaucoma, and results were mixed [5, 25]. Caution is As shown in Fig. 1, the PhNR amplitude can be needed as the ratio measure could be misleading in measured from baseline to the minimum point in the diseases where the b-wave is abnormal. trough (BT). It also can be measured from the peak of the b-wave to the maximum amplitude in trough (PT). Acknowledgements We would like to thank Anthony G. Alternatively, PhNR amplitude can be measured at a Robson for his advice and careful editing, and the members of ISCEV in particular, Michael F. Marmor for their valuable fixed time, for example, at 65–75 ms after the flash in discussion during the consultation period. the trough of the response (not shown). Using a fixed time could be helpful when responses in diseased eyes are small and the trough is difficult to locate. Note that Compliance with ethical standards the PT measurement is largely dominated by the b- wave amplitude, and a change in b-wave amplitude Conflict of interest The authors declare that they have no conflict of interest. reflecting a change in bipolar cell function must be considered when interpreting a change in PhNR Statement of human rights This article does not contain any amplitude. When measuring the PhNR, it may also studies with human participants performed by any of the be necessary to take account of the i-wave, or i-waves, authors. positive deflection(s) of Off pathway origin [11] in the Statement on the welfare of animals This article does not falling limb of the b-wave, and/or later in the trough contain any studies with animals performed by any of the (Fig. 1). For responses to the suggested narrowband authors. stimuli, such as those used for responses in Fig. 1, the Informed consent This article does not contain any studies maximum trough amplitude generally occurs after the with human participants performed by any of the authors. initial i-wave. Given the slow nature of the response, and the variety of amplitude criteria that have been Open Access This article is distributed under the terms of the used, peak time of the PhNR is generally not reported. Creative Commons Attribution 4.0 International License (http:// creativecommons.org/licenses/by/4.0/), which permits unre- The PhNR is moderately affected by age, so, for the stricted use, distribution, and reproduction in any medium, particular measure(s) chosen, appropriate age- provided you give appropriate credit to the original matched normative data should be used [3, 22]. author(s) and the source, provide a link to the Creative Com- Comparisons of longitudinal findings in patients to mons license, and indicate if changes were made. normal test-retest repeatability of PhNR amplitudes are also important, as the test–retest variability of 123 Doc Ophthalmol (2018) 136:207–211 211 Appendix: Justification for the protocol details optic neuropathies: comparison with primate ERGs after pharmacologic blockade of inner retina. Invest Ophthalmol Vis Sci 45:3827–3837 A systematic literature review was performed using 12. Chen H, Zhang M, Huang S, Wu D (2008) The photopic PubMed to find publications that reported use of the negative response of flash ERG in nonproliferative diabetic retinopathy. Doc Ophthalmol 117:129–135 PhNR from the period 1999–2017. The committee 13. Moss HE, Park JC, McAnany JJ (2015) The photopic neg- identified the relevant references to include in the ative response in idiopathic intracranial hypertension. reference list, discussed the methods used in the Invest Ophthalmol Vis Sci 56:3709–3714 references to record PhNRs, and came to a consensus 14. Niyadurupola N, Luu CD, Nguyen DQ, Geddes K, Tan GX et al (2013) Intraocular pressure lowering is associated with on those to include in the extended protocol. an increase in the photopic negative response (PhNR) amplitude in glaucoma and ocular hypertensive eyes. Invest Ophthalmol Vis Sci 54:1913–1919 15. Thompson DA, Feather S, Stanescu HC, Freudenthal B, References Zdebik AA et al (2011) Altered electroretinograms in patients with KCNJ10 mutations and EAST syndrome. 1. McCulloch DL, Marmor MF, Brigell MG, Hamilton R, J Physiol 589:1681–1689 Holder GE et al (2015) ISCEV Standard for full-field clin- 16. Raz-Prag D, Grimes WN, Fariss RN, Vijayasarathy C, ical electroretinography (2015 update). Doc Ophthalmol Campos MM et al (2010) Probing potassium channel 130:1–12 function in vivo by intracellular delivery of antibodies in a 2. Viswanathan S, Frishman LJ, Robson JG, Harwerth RS, rat model of retinal neurodegeneration. Proc Natl Acad Sci Smith EL 3rd (1999) The photopic negative response of the U S A 107:12710–12715 macaque electroretinogram: reduction by experimental 17. Machida S, Toba Y, Ohtaki A, Gotoh Y, Kaneko M et al glaucoma. Invest Ophthalmol Vis Sci 40:1124–1136 (2008) Photopic negative response of focal electoretino- 3. Viswanathan S, Frishman LJ, Robson JG, Walters JW grams in glaucomatous eyes. Invest Ophthalmol Vis Sci (2001) The photopic negative response of the flash elec- 49:5636–5644 troretinogram in primary open angle glaucoma. Invest 18. Rangaswamy NV, Shirato S, Kaneko M, Digby BI, Robson Ophthalmol Vis Sci 42:514–522 JG et al (2007) Effects of spectral characteristics of ganzfeld 4. Colotto A, Falsini B, Salgarello T, Iarossi G, Galan ME et al stimuli on the photopic negative response (PhNR) of the (2000) Photopic negative response of the human ERG: ERG. Invest Ophthalmol Vis Sci 48:4818–4828 losses associated with glaucomatous damage. Invest Oph- 19. Kremers J, Jertila M, Link B, Pangeni G, Horn FK (2012) thalmol Vis Sci 41:2205–2211 Spectral characteristics of the PhNR in the full-field flash 5. Machida S, Gotoh Y, Toba Y, Ohtaki A, Kaneko M et al electroretinogram of normals and glaucoma patients. Doc (2008) Correlation between photopic negative response and Ophthalmol 124:79–90 retinal nerve fiber layer thickness and optic disc topography 20. Drasdo N, Aldebasi YH, Chiti Z, Mortlock KE, Morgan JE in glaucomatous eyes. Invest Ophthalmol Vis Sci et al (2001) The s-cone PHNR and pattern ERG in primary 49:2201–2207 open angle glaucoma. Invest Ophthalmol Vis Sci 6. Sustar M, Cvenkel B, Brecelj J (2009) The effect of 42:1266–1272 broadband and monochromatic stimuli on the photopic 21. Binns AM, Mortlock KE, North RV (2011) The relationship negative response of the electroretinogram in normal sub- between stimulus intensity and response amplitude for the jects and in open-angle glaucoma patients. Doc Ophthalmol photopic negative response of the flash electroretinogram. 118:167–177 Doc Ophthalmol 122:39–52 7. Gotoh Y, Machida S, Tazawa Y (2004) Selective loss of the 22. Joshi NR, Ly E, Viswanathan S (2017) Intensity response photopic negative response in patients with optic nerve function of the photopic negative response (PhNR): effect of atrophy. Arch Ophthalmol 122:341–346 age and test-retest reliability. Doc Ophthalmol 135:1–16 8. Miyata K, Nakamura M, Kondo M, Lin J, Ueno S et al 23. Mortlock KE, Binns AM, Aldebasi YH, North RV (2010) (2007) Reduction of oscillatory potentials and photopic Inter-subject, inter-ocular and inter-session repeatability of negative response in patients with autosomal dominant optic the photopic negative response of the electroretinogram atrophy with OPA1 mutations. Invest Ophthalmol Vis Sci recorded using DTL and skin electrodes. Doc Ophthalmol 48:820–824 121:123–134 9. Machida S, Gotoh Y, Tanaka M, Tazawa Y (2004) Pre- 24. Tang J, Edwards T, Crowston JG, Sarossy M (2014) The dominant loss of the photopic negative response in central test–retest reliability of the photopic negative response retinal artery occlusion. Am J Ophthalmol 137:938–940 (PhNR). Transl Vis Sci Technol 3:1 10. Shinoda K, Yamada K, Matsumoto CS, Kimoto K, Nakat- 25. Preiser D, Lagreze WA, Bach M, Poloschek CM (2013) suka K (2008) Changes in retinal thickness are correlated Photopic negative response versus pattern electroretinogram with alterations of electroretinogram in eyes with central in early glaucoma. Invest Ophthalmol Vis Sci 54:1182–1191 retinal artery occlusion. Graefes Arch Clin Exp Ophthalmol 26. Wang J, Cheng H, Hu YS, Tang RA, Frishman LJ (2012) 246:949–954 The photopic negative response of the flash electroretino- 11. Rangaswamy NV, Frishman LJ, Dorotheo EU, Schiffman gram in multiple sclerosis. Invest Ophthalmol Vis Sci JS, Bahrani HM et al (2004) Photopic ERGs in patients with 53:1315–1323

Journal

Documenta OphthalmologicaSpringer Journals

Published: May 31, 2018

References

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