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Documenta Ophthalmologica

, Volume 139, Issue 3, pp 185–195 | Cite as

Test–retest repeatability of the pattern electroretinogram and flicker electroretinogram

  • Arthur F. Resende
  • Carina T. Sanvicente
  • Hamoon Eshraghi
  • Alberto Garcia
  • Kassandra Pickel
  • Qiang Zhang
  • Michael Waisbourd
  • L. Jay KatzEmail author
Original Research Article
  • 66 Downloads

Abstract

Purpose

To evaluate the repeatability of the steady-state pattern electroretinogram (PERG) and full-field flicker electroretinogram (Flicker ERG) protocols, delivered by the office-based Neuro Optic Vision Assessment (NOVA)™ testing platform, in healthy subjects.

Methods

Healthy individuals underwent PERG (16° and 24°) and Flicker ERG [fixed luminance (FL) and multi-luminance (ML)] testing protocols. Test–retest repeatability of protocols was calculated using intra-class correlation coefficients (ICC). Reference values of the parameters of the aforementioned tests were also calculated.

Results

The ICCs for the PERG parameters ranged from 0.793 to 0.911 (p < 0.001). The ICCs for the Flicker ERG parameters ranged from 0.968 to 0.994 (p < 0.001). A linear regression analysis was applied to assess the impact of age on ERG responses. Age had a significant impact on all PERG parameters (16° or 24°). The phase response of the FL Flicker ERG significantly decreased with age (β = − 0.837, p ≤ 0.001). The FL Flicker ERG Magnitude was also impacted with a significant quadratic effect of age (β = − 0.0047, p = 0.0004). Similarly, the Phase Area Under the Curve (Phase AUC) of the ML Flicker ERG significantly declined with age (β = − 0.007, p = 0.009), and the impact on the Magnitude AUC was significant as well, with a negative quadratic age effect.

Conclusions

The PERG and Flicker ERG protocols, delivered by an office-based testing platform, were shown to have good-to-excellent test–retest repeatability when tests were performed in the same order and in immediate succession.

Keywords

Steady-state pattern electroretinogram Flicker electroretinogram Repeatability Electrophysiology Reference database 

Notes

Funding

This study was funded by Dyopsis Inc. Dr. Alberto Garcia, MD works as Chief Medical Officer at Diopsys Inc. Ms. Kassandra Pickel, MPH worked as a Research Associate at Diopsys Inc. during this manuscript’s preparation. The Wills Eye Hospital Glaucoma Research Center has received funding from Diopsys Inc. to conduct this study.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Statement of human rights

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.

Statement on the welfare of animals

This manuscript does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    Csaky K, Ferris F 3rd, Chew EY et al (2018) Report from the NEI/FDA endpoints workshop on age-related macular degeneration and inherited retinal diseases. Investig Ophthalmol Vis Sci 58:3456–3463.  https://doi.org/10.1167/iovs.17-22339 CrossRefGoogle Scholar
  2. 2.
    Weinreb RN, Kaufman PL (2011) Glaucoma research community and FDA look to the future, II: NEI/FDA glaucoma clinical trial design and endpoints symposium: measures of structural change and visual function. Investig Ophthalmol Vis Sci 52:7842–7851CrossRefGoogle Scholar
  3. 3.
    Nair P, Aiello LP, Gardner TW et al (2016) Report from the NEI/FDA diabetic retinopathy clinical trial design and endpoints workshop. Investig Ophthalmol Vis Sci 57:5127–5142.  https://doi.org/10.1167/iovs.16-20356 CrossRefGoogle Scholar
  4. 4.
    Weinreb RN, Kaufman PL (2009) The glaucoma research community and FDA look to the future: a report from the NEI/FDA CDER glaucoma clinical trial design and endpoints symposium. Investig Ophthalmol Vis Sci 50:1497–1505.  https://doi.org/10.1167/iovs.08-2843 CrossRefGoogle Scholar
  5. 5.
    Csaky KG, Richman EA, Ferris IIIFL (2008) Report from the NEI/FDA ophthalmic clinical trial design and endpoints symposium. Investig Ophthalmol Vis Sci 49:479–489.  https://doi.org/10.1167/iovs.07-1132 CrossRefGoogle Scholar
  6. 6.
    Chew SS, Kerr NM, Wong AB et al (2016) Anxiety in visual field testing. Br J Ophthalmol 100:1128–1133.  https://doi.org/10.1136/bjophthalmol-2015-307110 CrossRefPubMedGoogle Scholar
  7. 7.
    Bach M, Brigell MG, Hawlina M et al (2013) ISCEV standard for clinical pattern electroretinography (PERG): 2012 update. Doc Ophthalmol 126:1–7.  https://doi.org/10.1007/s10633-012-9353-y CrossRefPubMedGoogle Scholar
  8. 8.
    McCulloch DL, Marmor MF, Brigell MG et al (2015) ISCEV standard for full-field clinical electroretinography (2015 update). Doc Ophthalmol 130:1–12.  https://doi.org/10.1007/s10633-014-9473-7 CrossRefGoogle Scholar
  9. 9.
    Wilsey LJ, Fortune B (2016) Electroretinography in glaucoma diagnosis. Curr Opin Ophthalmol 27:118–124.  https://doi.org/10.1097/icu.0000000000000241 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Porciatti V (2015) Electrophysiological assessment of retinal ganglion cell function. Exp Eye Res 141:164–170.  https://doi.org/10.1016/j.exer.2015.05.008 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Harwerth RS, Carter-Dawson L, Smith EL 3rd et al (2004) Neural losses correlated with visual losses in clinical perimetry. Invest Ophthalmol Vis Sci 45:3152–3160.  https://doi.org/10.1167/iovs.04-0227 CrossRefPubMedGoogle Scholar
  12. 12.
    Hood DC, Kardon RH (2007) A framework for comparing structural and functional measures of glaucomatous damage. Prog Retin Eye Res 26:688–710.  https://doi.org/10.1016/j.preteyeres.2007.08.001 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Quigley HA, Dunkelberger GR, Green WR (1989) Retinal ganglion cell atrophy correlated with automated perimetry in human eyes with glaucoma. Am J Ophthalmol 107:453–464CrossRefGoogle Scholar
  14. 14.
    Lasta M, Pemp B, Schmidl D et al (2013) Neurovascular dysfunction precedes neural dysfunction in the retina of patients with type 1 diabetes. Invest Ophthalmol Vis Sci 54:842–847.  https://doi.org/10.1167/iovs.12-10873 CrossRefPubMedGoogle Scholar
  15. 15.
    Shunsuke Y, Shu K, Shinji U et al (2015) Flicker electroretinograms before and after intravitreal ranibizumab injection in eyes with central retinal vein occlusion. Acta Ophthalmol 93:e465–e468.  https://doi.org/10.1111/aos.12674 CrossRefGoogle Scholar
  16. 16.
    Zele AJ, Feigl B, Kambhampati PK et al (2015) A method for estimating intrinsic noise in electroretinographic (ERG) signals. Doc Ophthalmol 131:85–94.  https://doi.org/10.1007/s10633-015-9510-1 CrossRefPubMedGoogle Scholar
  17. 17.
    Derr PH, Gonzalez Garcia AO, Urgiles C et al (2014) Steady state pattern electroretinography (ssPERG) in age-related macular degeneration (AMD) compared to controls. Investig Ophthalmol Vis Sci 55:3973Google Scholar
  18. 18.
    Urgiles C, Tello C, Derr PH et al (2014) Evaluation of steady state pattern electroretinography (ssPERG) in discriminating normal from glaucoma suspect and glaucomatous eyes. Investig Ophthalmol Vis Sci 55:5609Google Scholar
  19. 19.
    Mavilio A, Scrimieri F, Errico D (2015) Can variability of pattern ERG signal help to detect retinal ganglion cells dysfunction in glaucomatous eyes? Biomed Res Int 2015:571314.  https://doi.org/10.1155/2015/571314 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Banitt MR, Ventura LM, Feuer WJ et al (2013) Progressive loss of retinal ganglion cell function precedes structural loss by several years in glaucoma suspects. Investig Ophthalmol Vis Sci 54:2346–2352.  https://doi.org/10.1167/iovs.12-11026 CrossRefGoogle Scholar
  21. 21.
    Cicchetti D (1994) Guidelines, criteria, and rules of thumb for evaluating normed and standardized assessment instrument in psychologyGoogle Scholar
  22. 22.
    Wolak ME, Fairbairn DJ, Paulsen YR (2012) Guidelines for estimating repeatability. Methods Ecol Evol 3:129–137.  https://doi.org/10.1111/j.2041-210X.2011.00125.x CrossRefGoogle Scholar
  23. 23.
    Fleiss JL (1999) Reliability of measurement. In: Fleiss JL (ed) The design and analysis of clinical experiments. Wiley, pp. 1–32Google Scholar
  24. 24.
    Bowd C, Tafreshi A, Vizzeri G et al (2009) Repeatability of pattern electroretinogram measurements using a new paradigm optimized for glaucoma detection. J Glaucoma 18:437–442.  https://doi.org/10.1097/IJG.0b013e31818c6f44 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Asakawa K, Amino K, Iwase M et al (2017) New mydriasis-free electroretinogram recorded with skin electrodes in healthy subjects. Biomed Res Int 2017:8539747.  https://doi.org/10.1155/2017/8539747 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Fredette MJ, Anderson DR, Porciatti V, Feuer W (2008) Reproducibility of pattern electroretinogram in glaucoma patients with a range of severity of disease with the new glaucoma paradigm. Ophthalmology 115:957–963.  https://doi.org/10.1016/j.ophtha.2007.08.023 CrossRefPubMedGoogle Scholar
  27. 27.
    Jacobi PC, Miliczek KD, Zrenner E (1993) Experiences with the international standard for clinical electroretinography: normative values for clinical practice, interindividual and intraindividual variations and possible extensions. Doc Ophthalmol 85:95–114CrossRefGoogle Scholar
  28. 28.
    Birch DG, Anderson JL (1992) Standardized full-field electroretinography: normal values and their variation with age. Arch Ophthalmol 110:1571–1576.  https://doi.org/10.1001/archopht.1992.01080230071024 CrossRefPubMedGoogle Scholar
  29. 29.
    Parvaresh MM, Ghiasian L, Ghasemi Falavarjani K et al (2009) Normal values of standard full field electroretinography in an Iranian population. J Ophthalmic Vis Res 4:97–101PubMedPubMedCentralGoogle Scholar
  30. 30.
    Porciatti V, Ventura LM (2004) Normative data for a user-friendly paradigm for pattern electroretinogram recording. Ophthalmology 111:161–168.  https://doi.org/10.1016/j.ophtha.2003.04.007 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Coupland SG, Wu D (2006) International multicenter normative ERG database using the ISCEV standard. Investig Ophthalmol Vis Sci 47:1669CrossRefGoogle Scholar
  32. 32.
    Trick GL, Nesher R, Cooper DG, Shields SM (1992) The human pattern ERG: alteration of response properties with aging. Optom Vis Sci 69:122–128CrossRefGoogle Scholar
  33. 33.
    Palmowski-Wolfe AM, Woerdehoff U (2005) A comparison of the fast stimulation multifocal-ERG in patients with an IOL and control groups of different age. Doc Ophthalmol 111:87–93.  https://doi.org/10.1007/s10633-005-4506-x CrossRefPubMedGoogle Scholar
  34. 34.
    Amarasekera DC, Resende AF, Waisbourd M (2018) Steady-state pattern electroretinogram and short-duration transient visual evoked potentials in glaucomatous and healthy eyes. Clin Exp Opthalmol 46:54–61.  https://doi.org/10.1111/ceo.13006 CrossRefGoogle Scholar
  35. 35.
    Ventura LM, Golubev I, Feuer WJ, Porciatti V (2010) The PERG in diabetic glaucoma suspects with no evidence of retinopathy. J Glaucoma 19:243–247.  https://doi.org/10.1097/IJG.0b013e3181a990ea CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Pescosolido N, Barbato A (2015) Role of electrophysiology in the early diagnosis and follow-up of diabetic retinopathy. J Diabetes Res 2015:319692.  https://doi.org/10.1155/2015/319692 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Tzekov R, Arden GB (1999) The electroretinogram in diabetic retinopathy. Surv Ophthalmol 44:53–60CrossRefGoogle Scholar
  38. 38.
    Parisi V, Uccioli L (2001) Visual electrophysiological responses in persons with type 1 diabetes. Diabetes Metab Res Rev 17:12–18CrossRefGoogle Scholar
  39. 39.
    Parisi V, Uccioli L, Parisi L et al (1998) Neural conduction in visual pathways in newly-diagnosed IDDM patients. Electroencephalogr Clin Neurophysiol Potentials Sect 108:490–496.  https://doi.org/10.1016/S0168-5597(98)00026-4 CrossRefGoogle Scholar
  40. 40.
    Riva CE, Logean E, Falsini B (2005) Visually evoked hemodynamical response and assessment of neurovascular coupling in the optic nerve and retina. Prog Retin Eye Res 24:183–215.  https://doi.org/10.1016/j.preteyeres.2004.07.002 CrossRefPubMedGoogle Scholar
  41. 41.
    Nguyen TT, Kawasaki R, Kreis AJ et al (2009) Correlation of light-flicker-induced retinal vasodilation and retinal vascular caliber measurements in diabetes. Investig Ophthalmol Vis Sci 50:5609–5613.  https://doi.org/10.1167/iovs.09-3442 CrossRefGoogle Scholar
  42. 42.
    Garhofer G, Zawinka C, Resch H et al (2004) Reduced response of retinal vessel diameters to flicker stimulation in patients with diabetes. Br J Ophthalmol 88:887–891.  https://doi.org/10.1136/bjo.2003.033548 CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Mandecka A, Dawczynski J, Blum M et al (2007) Influence of flickering light on the retinal vessels in diabetic patients. Diabetes Care 30:3048–3052.  https://doi.org/10.2337/dc07-0927 CrossRefPubMedGoogle Scholar
  44. 44.
    Bresnick GH, Korth K, Groo A, Palta M (1984) Electroretinographic oscillatory potentials predict progression of diabetic retinopathy. Preliminary report. Arch Ophthalmol 102:1307–1311CrossRefGoogle Scholar
  45. 45.
    Kim SH, Lee SH, Bae JY et al (1997) Electroretinographic evaluation in adult diabetics. Doc Ophthalmol 94:201–213CrossRefGoogle Scholar
  46. 46.
    Nagy BV, Barboni MT, Martins CM et al (2014) Human flicker electroretinography using different temporal modulations at mesopic and photopic luminance levels. Doc Ophthalmol 129:129–138.  https://doi.org/10.1007/s10633-014-9452-z CrossRefPubMedGoogle Scholar
  47. 47.
    Domalpally A, Ip MS, Ehrlich JS (2015) Effects of intravitreal ranibizumab on retinal hard exudate in diabetic macular edema: findings from the RIDE and RISE phase III clinical trials. Ophthalmology 122:779–786.  https://doi.org/10.1016/j.ophtha.2014.10.028 CrossRefPubMedGoogle Scholar
  48. 48.
    Writing Committee for the Diabetic Retinopathy Clinical Research N (2015) Panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial. JAMA 314:2137–2146.  https://doi.org/10.1001/jama.2015.15217 CrossRefGoogle Scholar
  49. 49.
    Pedersen KB, Møller F, Sjølie AK, Andréasson S (2010) Electrophysiological assessment of retinal function during 6 months of bevacizumab treatment in neovascular age-related macular degeneration. Retina 30:1025–1033.  https://doi.org/10.1097/IAE.0b013e3181cafc8f CrossRefPubMedGoogle Scholar
  50. 50.
    Holm K, Schroeder M, Lovestam Adrian M (2015) Peripheral retinal function assessed with 30-Hz flicker seems to improve after treatment with Lucentis in patients with diabetic macular oedema. Doc Ophthalmol 131:43–51.  https://doi.org/10.1007/s10633-015-9495-9 CrossRefPubMedGoogle Scholar
  51. 51.
    Yasuda S, Kachi S, Ueno S et al (2015) Flicker electroretinograms before and after intravitreal ranibizumab injection in eyes with central retinal vein occlusion. Acta Ophthalmol 93:e465–e468.  https://doi.org/10.1111/aos.12674 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Arthur F. Resende
    • 1
  • Carina T. Sanvicente
    • 1
  • Hamoon Eshraghi
    • 2
  • Alberto Garcia
    • 3
  • Kassandra Pickel
    • 3
  • Qiang Zhang
    • 4
  • Michael Waisbourd
    • 5
  • L. Jay Katz
    • 1
    Email author
  1. 1.Glaucoma Research CenterWills Eye HospitalPhiladelphiaUSA
  2. 2.St. Luke’s University HospitalBethlehemUSA
  3. 3.Diopsys Inc.Pine BrookUSA
  4. 4.Vickie and Jack Farber Vision Research CenterWills Eye HospitalPhiladelphiaUSA
  5. 5.Division of Ophthalmology, Sackler Faculty of MedicineTel-Aviv Medical CenterTel-AvivIsrael

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