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Relationship between stimulus size and different components of the electroretinogram (ERG) elicited by flashed stimuli

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Abstract

Purpose

To investigate how light stimulus conditions of varying spatial sizes affect components of the flash and long-flash electroretinogram (ERG) in normal subjects.

Method

Three stimulus conditions were generated by a Ganzfeld stimulator: a white flash on white background (WoW), a red flash on a blue background (RoB) and an L+M-cone isolating on–off (long flash) stimulus (Cone Iso). ERGs were recorded from six subjects (5 M, 1 F) with DTL electrodes to full-field (FF), 70°, 60°, 50°, 40°, 30° and 20° diameter circular stimuli. Amplitudes and peak times for a-, b-, d- and i-wave, and PhNR were examined. PhNR amplitudes were estimated in two different ways: from baseline (fB) and from preceding b-wave peak (fP).

Results

With decreasing stimulus size, amplitudes for all ERG waveform components attenuated and peak times increased, although the effect varied across different components. An exponential fit described the relationship between amplitudes and size of stimulated retinal area well for most components and conditions (R2= 0.75-0.99), except for PhNR(fB) (R2= − 0.16–0.88). For peak times, an exponential decay function also fitted the data well (R2= 0.81–0.97), except in a few cases where the exponential constant was too small and a linear regression function was applied instead (a-wave Cone Iso, b- and i-wave WoW). The exponential constants for RoB amplitudes (b-wave, PhNR(fB), PhNR(fP)) were larger compared to their counterparts under WoW (p < 0.05), while there was no difference between the constants for a-wave amplitudes and peak times and for PhNR peak times. The exponential constants of amplitudes vs. area under WoW and Cone Iso were remarkably similar, while under RoB PhNR(fB) showed larger constants compared to either a- or b-wave (p < 0.05).

Conclusion

ERG components change in a predictable way with stimulus size and spectral characteristics of the stimulus under these conditions. This predictability could allow a modified version of these sets of stimuli to be tested for clinical applicability.

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References

  1. Robson JG, Saszik SM, Ahmed J et al (2003) Rod and cone contributions to the a-wave of the electroretinogram of the macaque. J Physiol 547:509–530. https://doi.org/10.1113/jphysiol.2002.030304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Bush RA, Sieving PA (1994) A proximal retinal component in the primate photopic ERG a-wave. Invest Ophthalmol Vis Sci 35:635–645

    CAS  PubMed  Google Scholar 

  3. Ueno S, Kondo M, Niwa Y et al (2004) Luminance dependence of neural components that underlies the primate photopic electroretinogram. Invest Ophthalmol Vis Sci 45:1033–1040. https://doi.org/10.1167/iovs.03-0657

    Article  PubMed  Google Scholar 

  4. Dong CJ, Hare WA (2000) Contribution to the kinetics and amplitude of the electroretinogram b-wave by third-order retinal neurons in the rabbit retina. Vision Res 40:579–589. https://doi.org/10.1016/s0042-6989(99)00203-5

    Article  CAS  PubMed  Google Scholar 

  5. Rufiange M, Rousseau S, Dembinska O et al (2002) Cone-dominated ERG luminance-response function: the Photopic Hill revisited. Documenta Ophthalmol Adv Ophthalmol 104:231–248

    Article  Google Scholar 

  6. Rosolen SG, Rigaudière F, LeGargasson J-F et al (2004) Comparing the photopic ERG i-wave in different species. Veterinary Ophthalmol 7:189–192. https://doi.org/10.1111/j.1463-5224.2004.04022.x

    Article  Google Scholar 

  7. Rangaswamy NV, Frishman LJ, Dorotheo EU et al (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. https://doi.org/10.1167/iovs.04-0458

    Article  PubMed  Google Scholar 

  8. Viswanathan S, Frishman LJ, Robson JG et al (2001) The photopic negative response of the flash electroretinogram in primary open angle glaucoma. Invest Ophthalmol Vis Sci 42:514–522

    CAS  PubMed  Google Scholar 

  9. Colotto A, Falsini B, Salgarello T et al (2000) Photopic negative response of the human ERG: losses associated with glaucomatous damage. Invest Ophthalmol Vis Sci 41:2205–2211

    CAS  PubMed  Google Scholar 

  10. Gotoh Y, Machida S, Tazawa Y (2004) Selective loss of the photopic negative response in patients with opticnerve atrophy. Arch Ophthalmol 122:341–346. https://doi.org/10.1001/archopht.122.3.341

    Article  PubMed  Google Scholar 

  11. 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

    Article  PubMed  Google Scholar 

  12. Rangaswamy NV, Shirato S, Kaneko M et al (2007) Effects of spectral characteristics of ganzfeld stimuli on the photopic negative response (PhNR) of the ERG. Invest Ophthalmol Vis Sci 48:4818–4828. https://doi.org/10.1167/iovs.07-0218

    Article  PubMed  PubMed Central  Google Scholar 

  13. Frishman L, Sustar M, Kremers J et al (2018) ISCEV extended protocol for the photopic negative response (PhNR) of the full-field electroretinogram. Doc Ophthalmol 136:207–211. https://doi.org/10.1007/s10633-018-9638-x

    Article  PubMed  PubMed Central  Google Scholar 

  14. Kremers J, Jertila M, Link B et al (2012) Spectral characteristics of the PhNR in the full-field flash electroretinogram of normals and glaucoma patients. Doc Ophthalmol 124:79–90. https://doi.org/10.1007/s10633-011-9304-z

    Article  PubMed  Google Scholar 

  15. Tsai TI, Jacob MM, McKeefry D et al (2016) Spatial properties of L- and M-cone driven incremental (On-) and decremental (Off-) electroretinograms: evidence for the involvement of multiple post-receptoral mechanisms. J Opt Soc Am A Opt Image Sci Vis 33:A1–A11. https://doi.org/10.1364/josaa.33.0000a1

    Article  PubMed  Google Scholar 

  16. de Graaf B, Wertheim AH (1988) The perception of object motion during smooth pursuit eye movements: adjacency is not a factor contributing to the Filehne illusion. Vision Res 28:497–502. https://doi.org/10.1016/0042-6989(88)90172-1

    Article  PubMed  Google Scholar 

  17. Miyake Y (1998) Focal macular electroretinography. Nagoya J Med Sci 61:79–84

    CAS  PubMed  Google Scholar 

  18. Machida S, Toba Y, Ohtaki A et al (2008) Photopic negative response of focal electoretinograms in glaucomatous eyes. Invest Ophthalmol Vis Sci 49:5636–5644. https://doi.org/10.1167/iovs.08-1946

    Article  PubMed  Google Scholar 

  19. Machida S, Tamada K, Oikawa T et al (2010) Sensitivity and specificity of photopic negative response of focal electoretinogram to detect glaucomatous eyes. Br J Ophthalmol 94:202–208. https://doi.org/10.1136/bjo.2009.161166

    Article  CAS  PubMed  Google Scholar 

  20. Kinoshita J, Takada S, Iwata N et al (2016) Comparison of photopic negative response (PhNR) between focal macular and full-field electroretinograms in monkeys. Documenta Ophthalmologica. Adv Ophthalmol 132:177–187. https://doi.org/10.1007/s10633-016-9538-x

    Article  Google Scholar 

  21. Martin PR, Grünert U (1992) Spatial density and immunoreactivity of bipolar cells in the macaque monkey retina. J Compar Neurol 323:269–287. https://doi.org/10.1002/cne.903230210

    Article  CAS  Google Scholar 

  22. Dawson WW, Trick GL, Litzkow CA (1979) Improved electrode for electroretinography. Invest Ophthalmol Vis Sci 18:988–991

    CAS  PubMed  Google Scholar 

  23. Kremers J (2003) The assessment of L- and M-cone specific electroretinographical signals in the normal and abnormal human retina. Prog Retinal Eye Res 22:579–605

    Article  Google Scholar 

  24. Estévez O, Spekreijse H (1982) The “silent substitution” method in visual research. Vision Res 22:681–691. https://doi.org/10.1016/0042-6989(82)90104-3

    Article  PubMed  Google Scholar 

  25. Donner KO, Rushton WA (1959) Retinal stimulation by light substitution. J Physiol 149:288–302. https://doi.org/10.1113/jphysiol.1959.sp006340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Shapiro AG, Pokorny J, Smith VC (1996) Cone-rod receptor spaces with illustrations that use CRT phosphor and light-emitting-diode spectra. J Opt Soc Am A Opt Image Sci Vision 13:2319–2328

    Article  CAS  Google Scholar 

  27. Aher AJ, McKeefry DJ, Parry NRA et al (2018) Rod- versus cone-driven ERGs at different stimulus sizes in normal subjects and retinitis pigmentosa patients. Documenta Ophthalmologica. Adv Ophthalmol 136:27–43. https://doi.org/10.1007/s10633-017-9619-5

    Article  Google Scholar 

  28. Meigen T, Bach M (1999) On the statistical significance of electrophysiological steady-state responses. Documenta Ophthalmologica. Adv Ophthalmol 98:207–232

    Article  CAS  Google Scholar 

  29. Ortiz G, Drucker D, Hyde C et al (2020) The photopic negative response of the Light-adapted 3.0 ERG in clinical settings. Doc Ophthalmol 140:115–128. https://doi.org/10.1007/s10633-019-09723-5

    Article  PubMed  Google Scholar 

  30. Nagra M, Gilmartin B, Thai NJ et al (2017) Determination of retinal surface area. J Anat 231:319–324. https://doi.org/10.1111/joa.12641

    Article  PubMed  PubMed Central  Google Scholar 

  31. Drasdo N, Fowler CW (1974) Non-linear projection of the retinal image in a wide-angle schematic eye. Br J Ophthalmol 58:709–714. https://doi.org/10.1136/bjo.58.8.709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Dacey DM (1993) The mosaic of midget ganglion cells in the human retina. J Neurosci 13:5334–5355

    Article  CAS  Google Scholar 

  33. Hoffmann EM, Zangwill LM, Crowston JG et al (2007) Optic disk size and glaucoma. Survey Ophthalmol 52:32–49. https://doi.org/10.1016/j.survophthal.2006

    Article  Google Scholar 

  34. Victor JD, Shapley RM (1979) The nonlinear pathway of Y ganglion cells in the cat retina. J Gen Physiol 74:671–689. https://doi.org/10.1085/jgp.74.6.671

    Article  CAS  PubMed  Google Scholar 

  35. Yeh T, Lee BB, Kremers J (1995) Temporal response of ganglion cells of the macaque retina to cone-specific modulation. J Opt Soc Am A Opt Image Sci Vis 12:456–464. https://doi.org/10.1364/josaa.12.000456

    Article  CAS  PubMed  Google Scholar 

  36. Curcio CA, Allen KA (1990) Topography of ganglion cells in human retina. J Comp Neurol 300:5–25. https://doi.org/10.1002/cne.903000103

    Article  CAS  PubMed  Google Scholar 

  37. Curcio CA, Millican CL, Allen KA et al (1993) Aging of the human photoreceptor mosaic: evidence for selective vulnerability of rods in central retina. Invest Ophthalmol Vis Sci 34:3278–3296

    CAS  PubMed  Google Scholar 

  38. Jacob MM, Pangeni G, Gomes BD et al (2015) The spatial properties of L- and M-cone inputs to electroretinograms that reflect different types of post-receptoral processing. PLoS ONE 10:e0121218. https://doi.org/10.1371/journal.pone.0121218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Murray IJ, Parry NR, Kremers J et al (2004) Photoreceptor topography and cone-specific electroretinograms. Vis Neurosci 21:231–235. https://doi.org/10.1017/s0952523804213268

    Article  CAS  PubMed  Google Scholar 

  40. Rodrigues AR, FilhoMda S, Silveira LC et al (2010) Spatial distributions of on- and off-responses determined with the multifocal ERG. Doc Ophthalmol 120:145–158. https://doi.org/10.1007/s10633-009-9205-6

    Article  PubMed  Google Scholar 

  41. Martins CMG, Tsai T, Barboni MTS et al (2016) The influence of stimulus size on heterochromatic modulation electroretinograms. J Vision 16:13. https://doi.org/10.1167/16.8.13

    Article  Google Scholar 

  42. Masri R (2019) Neurons of the primate retina: a qualitative and quantitative analysis, in save sight institute and discipline of ophthalmology. University of Sydney, Sydney

    Google Scholar 

  43. Grunert U, Martin PR (2020) Cell types and cell circuits in human and non-human primate retina. Prog Retin Eye Res. https://doi.org/10.1016/j.preteyeres.2020.100844

    Article  PubMed  Google Scholar 

  44. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Shapley RM, Victor JD (1978) The effect of contrast on the transfer properties of cat retinal ganglion cells. J Physiol 285:275–298. https://doi.org/10.1113/jphysiol.1978.sp012571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Lee BB, Wehrhahn C, Westheimer G et al (1995) The spatial precision of macaque ganglion cell responses in relation to vernier acuity of human observers. Vision Res 35:2743–2758. https://doi.org/10.1016/0042-6989(95)00015-r

    Article  CAS  PubMed  Google Scholar 

  47. Viswanathan S, Frishman LJ, Robson JG et al (1999) The photopic negative response of the macaque electroretinogram: reduction by experimental glaucoma. Invest Ophthalmol Vis Sci 40:1124–1136

    CAS  PubMed  Google Scholar 

  48. Morny EKA, Patel K, Votruba M et al (2019) The relationship between the photopic negative response and retinal ganglion cell topography. Invest Ophthalmol Vis Sci 60:1879–1887. https://doi.org/10.1167/iovs.18-25272

    Article  PubMed  Google Scholar 

  49. Kondo M, Piao CH, Tanikawa A et al (2000) Amplitude decrease of photopic ERG b-wave at higher stimulus intensities in humans. Jpn J Ophthalmol 44:20–28. https://doi.org/10.1016/s0021-5155(99)00172-0

    Article  CAS  PubMed  Google Scholar 

  50. Sustar M, Hawlina M, Brecelj J (2006) ON- and OFF-response of the photopic electroretinogram in relation to stimulus characteristics. Documenta Ophthalmologica. Adv Ophthalmol 113:43–52. https://doi.org/10.1007/s10633-006-9013-1

    Article  Google Scholar 

  51. Kondo M, Kurimoto Y, Sakai T et al (2008) Recording focal macular photopic negative response (PhNR) from monkeys. Invest Ophthalmol Vis Sci 49:3544–3550. https://doi.org/10.1167/iovs.08-1798

    Article  PubMed  Google Scholar 

  52. Kondo M, Miyake Y, Horiguchi M et al (1998) Recording multifocal electroretinogram on and off responses in humans. Invest Ophthalmol Vis Sci 39:574–580

    CAS  PubMed  Google Scholar 

  53. Hood DC, Bach M, Brigell M et al (2012) ISCEV standard for clinical multifocal electroretinography (mfERG) (2011 edition). Doc Ophthalmol 124:1–13. https://doi.org/10.1007/s10633-011-9296-8

    Article  PubMed  Google Scholar 

  54. Hood DC, Seiple W, Holopigian K et al (1997) A comparison of the components of the multifocal and full-field ERGs. Vis Neurosci 14:533–544. https://doi.org/10.1017/s0952523800012190

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We would like to thank Brian Vohnsen for careful reading and comments on the manuscript.

Funding

M.N. was supported by the Research, Innovation, and Scholarly Endeavors Program’s Scholarly Student Excellent Award, at the University of South Florida Morsani College of Medicine. J.K. and A.A. are supported by the German Research Council (DFG; Grant#: KR1317/13-2). The sponsors had no role in the design or conduct of this research.

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Correspondence to Radouil Tzekov.

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Nittmann, M.G., Aher, A.J., Kremers, J. et al. Relationship between stimulus size and different components of the electroretinogram (ERG) elicited by flashed stimuli. Doc Ophthalmol 142, 213–231 (2021). https://doi.org/10.1007/s10633-020-09797-6

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