Abstract
Purpose
To assess the test–retest reliability of the multifocal photopic negative response (mfPhNR) of normal human subjects.
Methods
Multifocal electroretinograms were recorded from one eye of 61 healthy adult subjects on two separate days using a Visual Evoked Response Imaging System software version 4.3 (EDI, San Mateo, California). The visual stimulus delivered on a 75-Hz monitor consisted of seven equal-sized hexagons each subtending 12° of visual angle. The m-step exponent was 9, and the m-sequence was slowed to include at least 30 blank frames after each flash. Only the first slice of the first-order kernel was analyzed. The mfPhNR amplitude was measured at a fixed time in the trough from baseline (BT) as well as at the same fixed time in the trough from the preceding b-wave peak (PT). Additionally, we also analyzed BT normalized either to PT (BT/PT) or to the b-wave amplitude (BT/b-wave). The relative reliability of test–retest differences for each test location was estimated by the Wilcoxon matched-pair signed-rank test and intraclass correlation coefficients (ICC). Absolute test–retest reliability was estimated by Bland–Altman analysis.
Results
The test–retest amplitude differences for neither of the two measurement techniques were statistically significant as determined by Wilcoxon matched-pair signed-rank test. PT measurements showed greater ICC values than BT amplitude measurements for all test locations. For each measurement technique, the ICC value of the macular response was greater than that of the surrounding locations. The mean test–retest difference was close to zero for both techniques at each of the test locations, and while the coefficient of reliability (COR—1.96 times the standard deviation of the test–retest difference) was comparable for the two techniques at each test location when expressed in nanovolts, the %COR (COR normalized to the mean test and retest amplitudes) was superior for PT than BT measurements. The ICC and COR were comparable for the BT/PT and BT/b-wave ratios and were better than the ICC and COR for BT but worse than PT.
Conclusion
mfPhNR amplitude measured at a fixed time in the trough from the preceding b-wave peak (PT) shows greater test–retest reliability when compared to amplitude measurement from baseline (BT) or BT amplitude normalized to either the PT or b-wave amplitudes.
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References
Viswanathan S, Frishman LJ, Robson JG, Harwerth RS, Smith EL 3rd (1999) The photopic negative response of the macaque electroretinogram: reduction by experimental glaucoma. Invest Ophthalmol Vis Sci 40:1124–1136
Colotto A, Falsini B, Salgarello T, Iarossi G, Galan ME, Scullica L (2000) Photopic negative response of the human ERG: losses associated with glaucomatous damage. Invest Ophthalmol Vis Sci 41:2205–2211
Viswanathan S, Frishman LJ, Robson JG, Walters JW (2001) The photopic negative response of the flash electroretinogram in primary open angle glaucoma. Invest Ophthalmol Vis Sci 42:514–522
Rangaswamy NV, Frishman LJ, Dorotheo EU, Schiffman JS, Bahrani HM, Tang RA (2004) Photopic ERGs in patients with optic neuropathies: comparison with primate ERGs after pharmacologic blockade of inner retina. Invest Ophthalmol Vis Sci 45:3827–3837
Gotoh Y, Machida S, Tazawa Y (2004) Selective loss of the photopic negative response in patients with optic nerve atrophy. Arch Ophthalmol 122:341–346
Machida S, Gotoh Y, Tanaka M, Tazawa Y (2004) Predominant loss of the photopic negative response in central retinal artery occlusion. Am J Ophthalmol 137:938–940
Chen H, Wu D, Huang S, Yan H (2006) The photopic negative response of the flash electroretinogram in retinal vein occlusion. Doc Ophthalmol 113:53–59
Chen H, Zhang M, Huang S, Wu D (2008) The photopic negative response of flash ERG in nonproliferative diabetic retinopathy. Doc Ophthalmol 117:129–135
Moon CH, Hwang SC, Kim BT, Ohn YH, Park TK (2011) Visual prognostic value of optical coherence tomography and photopic negative response in chiasmal compression. Invest Ophthalmol Vis Sci 52:8527–8533
McFarlane M, Wright T, Stephens D, Nilsson J, Westall CA (2012) Blue flash ERG PhNR changes associated with poor long-term glycemic control in adolescents with type 1 diabetes. Invest Ophthalmol Vis Sci 53:741–748
Wang J, Cheng H, Hu YS, Tang RA, Frishman LJ (2012) The photopic negative response of the flash electroretinogram in multiple sclerosis. Invest Ophthalmol Vis Sci 53:1315–1323
Kirkiewicz M, Lubinski W, Penkala K (2016) Photopic negative response of full-field electroretinography in patients with different stages of glaucomatous optic neuropathy. Doc Ophthalmol 132:57–65
Machida S, Gotoh Y, Toba Y, Ohtaki A, Kaneko M, Kurosaka D (2008) Correlation between photopic negative response and retinal nerve fiber layer thickness and optic disc topography in glaucomatous eyes. Invest Ophthalmol Vis Sci 49:2201–2207
Kondo M, Kurimoto Y, Sakai T, Koyasu T, Miyata K, Ueno S, Terasaki H (2008) Recording focal macular photopic negative response (PhNR) from monkeys. Invest Ophthalmol Vis Sci 49:3544–3550
Machida S, Toba Y, Ohtaki A, Gotoh Y, Kaneko M, Kurosaka D (2008) Photopic negative response of focal electoretinograms in glaucomatous eyes. Invest Ophthalmol Vis Sci 49:5636–5644
Machida S, Tamada K, Oikawa T, Yokoyama D, Kaneko M, Kurosaka D (2010) Sensitivity and specificity of photopic negative response of focal electoretinogram to detect glaucomatous eyes. Br J Ophthalmol 94:202–208
Machida S, Tamada K, Oikawa T, Gotoh Y, Nishimura T, Kaneko M, Kurosaka D (2011) Comparison of photopic negative response of full-field and focal electroretinograms in detecting glaucomatous eyes. J Ophthalmol 2011:2011
Machida S, Kaneko M, Kurosaka D (2015) Regional variations in correlation between photopic negative response of focal electoretinograms and ganglion cell complex in glaucoma. Curr Eye Res 40:439–449
Tamada K, Machida S, Yokoyama D, Kurosaka D (2009) Photopic negative response of full-field and focal macular electroretinograms in patients with optic nerve atrophy. Jpn J Ophthalmol 53:608–614
Tamada K, Machida S, Oikawa T, Miyamoto H, Nishimura T, Kurosaka D (2010) Correlation between photopic negative response of focal electroretinograms and local loss of retinal neurons in glaucoma. Curr Eye Res 35:155–164
Kaneko M, Machida S, Hoshi Y, Kurosaka D (2015) Alterations of photopic negative response of multifocal electroretinogram in patients with glaucoma. Curr Eye Res 40:77–86
Kato F, Miura G, Shirato S, Sato E, Yamamoto S (2015) Correlation between N2 amplitude of multifocal ERGs and retinal sensitivity and retinal nerve fiber layer thickness in glaucomatous eyes. Doc Ophthalmol 131:97–206
Golemez H, Yildirim N, Ozer A (2016) Is multifocal electroretinography an early predictor of glaucoma? Doc Ophthalmol 132:27–37
Mortlock KE, Binns AM, Aldebasi YH, North RV (2010) Inter-subject, inter-ocular and inter-session repeatability of the photopic negative response of the electroretinogram recorded using DTL and skin electrodes. Doc Ophthalmol 121:123–134
Tang J, Edwards T, Crowston JG, Sarossy M (2014) The test–retest reliability of the photopic negative response (PhNR). Transl Vis Sci Technol 3:1
Holm S (1979) A simple sequentially rejective multiple test procedure. Scand J Stat 6:65–70
Portney LG, Watkins C (2001) Foundations of clinical research: applications to practice. Prentice Hall Health, Upper Saddle
Cicchetti DV (1994) Guidelines, criteria, and rules of thumb for evaluating normed and standardized assessment instruments in psychology. Psychol Assess 6:284–290
Bland JM, Altman DG (1986) Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1:307–310
Fortune B, Bui BV, Cull G, Wang L, Cioffi GA (2004) Inter-ocular and inter-session reliability of the electroretinogram photopic negative response (PhNR) in non-human primates. Exp Eye Res 78:83–93
Kundra H, Park JC, McAnany JJ (2016) Comparison of photopic negative response measurements in the time and time-frequency domains. Doc Ophthalmol 133:91–98
Preiser D, Lagreze WA, Bach M, Poloschek CM (2013) Photopic negative response versus pattern electroretinogram in early glaucoma. Invest Ophthalmol Vis Sci 54:1182–1191
Wu Z, Hadoux X, Fan Gaskin JC, Sarossy MG, Crowston JG (2016) Measuring the photopic negative response: viability of skin electrodes and variability across disease severities in glaucoma. Transl Vis Sci Technol 5:13
Acknowledgements
The authors would like to acknowledge the assistance of Dr. Usha Govindarajulu with some of the statistical analysis included in this study.
Funding
Funding was provided by National Eye Institute (Grant No. T35EY013937)
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
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Informed consent was obtained from all individual participants included in the study.
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Van Alstine, A.W., Viswanathan, S. Test–retest reliability of the multifocal photopic negative response. Doc Ophthalmol 134, 25–36 (2017). https://doi.org/10.1007/s10633-016-9569-3
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DOI: https://doi.org/10.1007/s10633-016-9569-3