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Assessment of “non-recordable” electroretinograms by 9 Hz flicker stimulation under scotopic conditions

Documenta Ophthalmologica volume 124, pages 27–39 (2012)Cite this article

Abstract

To refine methods of electroretinographical (ERG) recording for the analysis of low retinal potentials under scotopic conditions in advanced retinal degenerative diseases. Standard Ganzfeld ERG equipment (Diagnosys LLC, Cambridge, UK) was used in 27 healthy volunteers (mean age 28 ± SD 8.5 years) to define the stimulation protocol. The protocol was then applied in clinical routine and 992 recordings were obtained from patients (mean age 40.6 ± 18.3 years) over a period of 5 years. A blue stimulus with a flicker frequency of 9 Hz was specified under scotopic conditions to preferentially record rod-driven responses. A range of stimulus strengths (0.0000012–6.32 scot. cd s/m² and 6–14 ms flash duration) was tested for maximal amplitudes and interference between rods and cones. Analysis of results was done by standard Fourier Transformation and assessment of signal-to-noise ratio. Optimized stimulus parameters were found to be a time-integrated luminance of 0.012 scot. cd s/m² using a blue (470 nm) flash of 10 ms duration at a repetition frequency of 9 Hz. Characteristic stimulus strength versus amplitude curves and tests with stimuli of red or green wavelength suggest a predominant rod-system response. The 9 Hz response was found statistically distinguishable from noise in 38% of patients with otherwise non-recordable rod responses according to International Society for Clinical Electrophysiology of Vision standards. Thus, we believe this protocol can be used to record ERG potentials in patients with advanced retinal diseases and in the evaluation of potential treatments for these patients. The ease of implementation in clinical routine and of statistical evaluation providing an observer-independent evaluation may further facilitate its employment.

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References

  1. Niwa Y, Kondo M, Ueno S, Nakamura M, Terasaki H, Miyake Y (2005) Cone and rod dysfunction in fundus albipunctatus with RDH5 mutation: an electrophysiological study. Invest Ophthalmol Vis Sci 46(4):1480–1485

    Article  PubMed  Google Scholar 

  2. DiLoreto DJ, Ison JR, Bowen GP, Cox C, del Cerro M (1995) A functional analysis of the age-related degeneration in the Fischer 344 rat. Curr Eye Res 14(4):303–310

    Article  PubMed  Google Scholar 

  3. Messias A, Zrenner E, Tzekov R, McGee D, Peters T, Wilhelm B, Baryluk A, Kubota R, Gekeler F (2010) Single doses of all-trans-N-retinylacetamide slow down the ERG amplitude recovery after bleaching in rats. Doc Ophthalmol 120(2):165–174

    Article  PubMed  Google Scholar 

  4. Karpe G (1945) Basis of clinical electroretinography. Acta Ophthalmol 24(suppl):1–118

    Google Scholar 

  5. Dalke C, Loster J, Fuchs H, Gailus-Durner V, Soewarto D, Favor J, Neuhauser-Klaus A, Pretsch W, Gekeler F, Shinoda K, Zrenner E, Meitinger T, de Angelis MH, Graw J (2004) Electroretinography as a screening method for mutations causing retinal dysfunction in mice. Invest Ophthalmol Vis Sci 45(2):601–609

    Article  PubMed  Google Scholar 

  6. Siqueira RC, Messias A, Voltarelli JC, Scott IU, Jorge R (2011) Intravitreal injection of autologous bone marrow-derived mononuclear cells for hereditary retinal dystrophy: a phase I trial. Retina. doi:10.1097/IAE.0b013e3181f9c242

  7. Kondo M, Ueno S, Piao CH, Miyake Y, Terasaki H (2008) Comparison of focal macular cone ERGs in complete-type congenital stationary night blindness and APB- treated monkeys. Vis Res 48(2):273–280

    Article  PubMed  CAS  Google Scholar 

  8. Viswanathan S, Frishman LJ, Robson JG, Harwerth RS, Smith EL (1999) The photopic negative response of the macaque electroretinogram is reduced by experimental glaucoma. Investig Ophthalmol Vis Sci 40:1124–1136

    CAS  Google Scholar 

  9. 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. Investig Ophthalmol Vis Sci 45(10):3827–3837

    Article  Google Scholar 

  10. Marmor MF, Arden GB, Nilsson SEG, Zrenner E (1989) Standard for clinical electroretinography. Arch Ophthalmol 107:816

    Article  Google Scholar 

  11. Marmor MF, Fulton AB, Holder GE, Miyake Y, Brigell M, Bach M (2009) ISCEV standard for full-field clinical electroretinography (2008 update). Doc Ophthalmol 118(1):69–77

    Article  PubMed  CAS  Google Scholar 

  12. Heckenlively JR, Arden GB (2006) Principles and Practice of Clinical Electrophysiology of Vision, vol, 2nd edn. MIT Press, Cambridge

    Google Scholar 

  13. Frishman LJ (1991) The scotopic threshold response. In: Heckenlively JR, Arden GB (eds) Principles and practice of clinical electrophysiology of vision. Mosby Year Book, St. Louis, pp 121–124

    Google Scholar 

  14. Frishman LJ, Steinberg RH (1990) Origin of negative potentials in the light-adapted ERG of cat retina. J Neurophysiol 63:1333

    PubMed  CAS  Google Scholar 

  15. Miyake Y, Yagasaki K, Horiguchi M, Kawase Y (1987) On- and off-responses in photopic electroretinogram in complete and incomplete types of congenital stationary night blindness. Jpn J Ophthalmol 31(1):81–87

    PubMed  CAS  Google Scholar 

  16. Sieving PA (1993) Photopic ON- and OFF-pathway abnormalities in retinal dystrophies. Trans Am Ophthalmol Soc 91:703–773

    Google Scholar 

  17. Zrenner E, Gouras P (1979) Blue-sensitive cones of the cat produce a rodlike electroretinogram. Investig Ophthalmol Vis Sci 18(10):1076–1081

    CAS  Google Scholar 

  18. Naka KI, Rushton WA (1968) S-potential and dark adaptation in fish. J Physiol 194(1):259–269

    PubMed  CAS  Google Scholar 

  19. Berson EL, Rosner B, Sandberg MA, Weigel-DiFranco C, Brockhurst RJ, Hayes KC, Johnson EJ, Anderson EJ, Johnson CA, Gaudio AR, Willett WC, Schaefer EJ (2010) Clinical trial of lutein in patients with retinitis pigmentosa receiving vitamin A. Arch Ophthalmol 128(4):403–411

    Article  PubMed  CAS  Google Scholar 

  20. Zrenner E, Bartz-Schmidt KU, Benav H, Besch D, Bruckmann A, Gabel VP, Gekeler F, Greppmaier U, Harscher A, Kibbel S, Koch J, Kusnyerik A, Peters T, Stingl K, Sachs H, Stett A, Szurman P, Wilhelm B, Wilke R (2011) Subretinal electronic chips allow blind patients to read letters and combine them to words. Proc Biol Sci 278(1711):1489–1497

    Article  PubMed  Google Scholar 

  21. Andréasson SO, Sandberg MA, Berson EL (1988) Narrow-band filtering for monitoring low-amplitude cone electroretinograms in retinitis pigmentosa. Am J Ophthalmol 105(5):500–503

    PubMed  Google Scholar 

  22. Henkes HE (1964) Recent advances in flicker-electroretinography. Documenta Ophthalmologica 18:307–314

    Article  PubMed  CAS  Google Scholar 

  23. Birch DG, Sandberg MA (1997) Submicrovolt full-field cone electroretinograms: artifacts and reproducibility. Documenta Ophthalmologica 92:269–280

    Article  CAS  Google Scholar 

  24. Berson EL, Sandberg MA, Rosner B, Birch DG, Hanson AH (1985) Natural course of retinitis pigmentosa over a three-year interval. Am J Ophthalmol 99(3):240–251

    PubMed  CAS  Google Scholar 

  25. Bach M, Meigen T (1999) Do’s and don’ts in Fourier analysis of steady-state potentials. Documenta Ophthalmologica 99:69–82

    Article  PubMed  CAS  Google Scholar 

  26. Meigen T, Bach M (2000) On the statistical significance of electrophysiological steady-state response. Documenta Ophthalmologica 98:207–232

    Article  Google Scholar 

  27. Sieving PA, Arnold EB, Jamison J, Liepa A, Coats C (1998) Submicrovolt flicker electroretinogram: cycle-by-cycle recording of multiple harmonics with statistical estimation of measurement Uncertainty. Investig Ophthalmol Vis Sci 39(8):1462–1469

    CAS  Google Scholar 

  28. Gekeler F, Messias A, Ottinger M, Bartz-Schmidt KU, Zrenner E (2006) Phosphenes electrically evoked with DTL electrodes: a study in patients with retinitis pigmentosa, glaucoma, and homonymous visual field loss and normal subjects. Invest Ophthalmol Vis Sci 47(11):4966–4974

    Article  PubMed  Google Scholar 

  29. Dawson WW, Trick GL, Litzkow CA (1979) Improved electrode for electroretinography. Invest Ophthalmol Vis Sci 18:988

    PubMed  CAS  Google Scholar 

  30. Dodt E (1951) Cone electroretinography by flicker. Nature 168:738

    Article  PubMed  CAS  Google Scholar 

  31. Regan D (1966) Some characteristics of average steady-state and transient responses evoked by modulated light. Electroencephalogr Clin Neurophysiol 20(3):238–248

    Article  PubMed  CAS  Google Scholar 

  32. Davson H (1990) Physiology of the eye, 5th edn. Macmillan Academic and Professional Ltd, London

    Google Scholar 

  33. Strasser T, Peters T, Jagle H, Zrenner E, Wilke R (2010) An integrated domain specific language for post-processing and visualizing electrophysiological signals in Java. Conf Proc IEEE Eng Med Biol Soc 2010:4687–4690

    PubMed  CAS  Google Scholar 

  34. Scholl HPN, Langrova H, Weber BHF, Zrenner E, A-S E (2001) Clinical electrophysiology of two rod pathways: normative values and clinical application. Graefe’s Arch Clin Exp Ophthalmol 239:71–80

    Article  CAS  Google Scholar 

  35. Lim S-H, Ohn Y-H (2005) Study of blue and red flash in dark-adapted electroretinogram. Korean J Ophthalmol 19(2):106–111

    Article  PubMed  Google Scholar 

  36. Weleber RG (1981) The effect of age on human cone and rod ganzfeld electroretinograms. Investig Ophthalmol Vis Sci 20(3):392–399

    CAS  Google Scholar 

  37. Gawande AA, Donovan WJ, Ginsburg AP, Marmor MF (1989) Photoaversion in retinitis pigmentosa. Br J Ophthalmol 73(2):115–120

    Article  PubMed  CAS  Google Scholar 

  38. Stockman A, Sharpe LT, Ruether K, Nordby K (1995) Two signals in the human rod visual system: a model based on electrophysiological data. Vis Neurosci 12:951–970

    Article  PubMed  CAS  Google Scholar 

  39. Cao D, Pokorny J, Grassi MA (2011) Isolated mesopic rod and cone electroretinograms realized with a four-primary method. Doc Ophthalmol 123(1):29–41

    Article  PubMed  Google Scholar 

  40. Bornschein H, Goodman G, Gunkel RD (1957) Temporal aspects of the human electroretinogram; a study of the implicit time-amplitude relationship of the B-wave. AMA Arch Ophthalmol 57(3):386–392

    Article  PubMed  CAS  Google Scholar 

  41. Berson EL, Gouras P, Hoff M (1969) Temporal aspects of the electroretinogram. Arch Ophthalmol 81(2):207–214

    Article  PubMed  CAS  Google Scholar 

  42. Cameron AM, Mahroo OAR, Lamb TD (2006) Dark adaptation of human rod bipolar cells measured from the b-wave of the scotopic electroretinogram. J Physiol 575(2):507–526

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank all subjects participated in the current study. For technical assistance with measurements of patients, we are very grateful to Mrs. Kramer, Mrs. Fuchs and Mrs. Haerer.

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Authors and Affiliations

  1. Centre for Ophthalmology, University of Tübingen, Schleichstraße 12-16, 72076, Tübingen, Germany

    Andreas Schatz & Florian Gekeler

  2. Institute for Ophthalmic Research, University of Tübingen, Schleichstraße 12-16, 72076, Tübingen, Germany

    Robert Wilke, Torsten Strasser & Eberhart Zrenner

  3. Graduate School of Biomedical Engineering, Bionic Vision Australia, The University of New South Wales, Botany Street, Randwick, NSW, 2050, Australia

    Robert Wilke

  4. Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, School of Medicine of Ribeirão Prêto, University of São Paulo, Ribeirão Prêto, Brazil

    Andre Messias

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  1. Andreas Schatz
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  2. Robert Wilke
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  4. Florian Gekeler
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Correspondence to Andreas Schatz.

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Andreas Schatz and Robert Wilke contributed equally to this work.

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Schatz, A., Wilke, R., Strasser, T. et al. Assessment of “non-recordable” electroretinograms by 9 Hz flicker stimulation under scotopic conditions. Doc Ophthalmol 124, 27–39 (2012). https://doi.org/10.1007/s10633-011-9302-1

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  • DOI: https://doi.org/10.1007/s10633-011-9302-1

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