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Insights for mfVEPs from perimetry using large spatial frequency-doubling and near frequency-doubling stimuli in glaucoma

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To compare two forms of perimetry that use large contrast-modulated grating stimuli in terms of: their relative diagnostic power, their independent diagnostic information about glaucoma and their utility for mfVEPs. We evaluated a contrast-threshold mfVEP in normal controls using the same stimuli as one of the tests.


We measured psychophysical contrast thresholds in one eye of 16 control subjects and 19 patients aged 67.8 ± 5.65 and 71.9 ± 7.15, respectively, (mean ± SD). Patients ranged in disease severity from suspects to severe glaucoma. We used the 17-region FDT-perimeter C20-threshold program and a custom 9-region test (R9) with similar visual field coverage. The R9 stimuli scaled their spatial frequencies with eccentricity and were modulated at lower temporal frequencies than C20 and thus did not display a clear spatial frequency-doubling (FD) appearance. Based on the overlapping areas of the stimuli, we transformed the C20 results to 9 measures for direct comparison with R9. We also compared mfVEP-based and psychophysical contrast thresholds in 26 younger (26.6 ± 7.3 y, mean ± SD) and 20 older normal control subjects (66.5 ± 7.3 y) control subjects using the R9 stimuli.


The best intraclass correlations between R9/C20 thresholds were for the central and outer regions: 0.82 ± 0.05 (mean ± SD, p ≤ 0.0001). The areas under receiver operator characteristic plots for C20 and R9 were as high as 0.99 ± 0.012 (mean ± SE). Canonical correlation analysis (CCA) showed significant correlation (r = 0.638, p = 0.029) with 1 dimension of the C20 and R9 data, suggesting that the lower and higher temporal frequency tests probed the same neural mechanism(s). Low signal quality made the contrast-threshold mfVEPs non-viable. The resulting mfVEP thresholds were limited by noise to artificially high contrasts, which unlike the psychophysical versions, were not correlated with age.


The lower temporal frequency R9 stimuli had similar diagnostic power to the FDT-C20 stimuli. CCA indicated the both stimuli drove similar neural mechanisms, possibly suggesting no advantage of FD stimuli for mfVEPs. Given that the contrast-threshold mfVEPs were non-viable, we used the present and published results to make recommendations for future mfVEP tests.

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  1. 1.

    Medeiros FA, Sample PA, Weinreb RN (2004) Frequency doubling technology perimetry abnormalities as predictors of glaucomatous visual field loss. Am J Ophthalmol 137:865–871

  2. 2.

    Kim TW, Zangwill LM, Bowd CB, Sample PA, Shah N, Weinreb RN (2007) Retinal nerve fiber layer damage as assessed by optical coherence tomography in eyes with a visual field defect detected by frequency doubling ecthnology perimetry but not by standard automated perimetry. Ophthalmology 114:1053–1057

  3. 3.

    Liu S, Lam S, Weinreb RN, Ye C, Cheung CY, Lai G, Lam DS, Leung CK (2011) Comparison of standard automated perimetry, frequency-doubling technology perimetry, and short-wavelength automated perimetry for detection of glaucoma. Invest Ophthalmol Vis Sci 52(10):7325–7331. https://doi.org/10.1167/iovs.11-7795

  4. 4.

    Tafreshi A, Sample PA, Liebmann JM, Girkin CA, Zangwill LM, Weinreb RN, Lalezary M, Racette L (2009) Visual function-specific perimetry to identify glaucomatous visual loss using three different definitions of visual field abnormality. Invest Ophthalmol Vis Sci 50(3):1234–1240. https://doi.org/10.1167/iovs.08-2535

  5. 5.

    Maddess T, Henry GH (1992) Performance of nonlinear visual units in ocular hypertension and glaucoma. Clin Vis Sci 7(5):371–383

  6. 6.

    Petrusca D, Grivich MI, Sher A, Field GD, Gauthier JL, Greschner M, Shlens J, Chichilnisky EJ, Litke AM (2007) Identification and characterization of a Y-like primate retinal ganglion cell type. J Neurosci 27(41):11019–11027. https://doi.org/10.1523/JNEUROSCI.2836-07.2007

  7. 7.

    Crook JD, Peterson BB, Packer OS, Robinson FR, Gamlin PD, Troy JB, Dacey DM (2008) The smooth monostratified ganglion cell: evidence for spatial diversity in the Y-cell pathway to the lateral geniculate nucleus and superior colliculus in the macaque monkey. J Neurosci 28(48):12654–12671. https://doi.org/10.1523/JNEUROSCI.2986-08.2008

  8. 8.

    Crook JD, Peterson BB, Packer OS, Robinson FR, Troy JB, Dacey DM (2008) Y-cell receptive field and collicular projection of parasol ganglion cells in macaque monkey retina. J Neurosci 28(44):11277–11291. https://doi.org/10.1523/JNEUROSCI.2982-08.2008

  9. 9.

    White AJ, Sun H, Swanson WH, Lee BB (2002) An examination of physiological mechanisms underlying the frequency-doubling illusion. Invest Ophthalmol Vis Sci 43(11):3590–3599

  10. 10.

    Swanson WH, Sun H, Lee BB, Cao D (2011) Responses of primate retinal ganglion cells to perimetric stimuli. Invest Ophthalmol Vis Sci 52(2):764–771. https://doi.org/10.1167/iovs.10-6158

  11. 11.

    Marx MS, Podos SM, Bodis-Wollner I, Lee PY, Wang RF, Severin C (1988) Signs of early damage in glaucomatous monkey eyes: low spatial frequency losses in the pattern ERG and VEP. Exp Eye Res 46(2):173–184

  12. 12.

    Johnson MA, Drum BA, Quigley HA, Sanchez RM, Dunkelberger GR (1989) Pattern-evoked potentials and optic nerve fiber loss in monocular laser-induced glaucoma. Invest Ophthalmol Vis Sci 30(5):897–907

  13. 13.

    Rosli Y, Bedford SM, Maddess T (2009) Low spatial frequency channels and the spatial frequency doubling illusion. Invest Ophthal Vis Sci 50:1956–1963. https://doi.org/10.1167/iovs.08-1810

  14. 14.

    Kulikowski JJ, Maddess T (1998) Apparent finess of compound gratings. In: Invest. Ophthal. Vis. Sci., Ft. Lauderdale, USA, p 405

  15. 15.

    Maddess T, James AC, Goldberg I, Wine S, Dobinson J (2000) Comparing a parallel PERG, automated perimetry and frequency doubling thresholds. Invest Ophthalmol Vis Sci 41:3827–3832

  16. 16.

    Rosli Y, Maddess T, Dawel A, James AC (2009) Multifocal frequency-doubling pattern visual evoked responses to dichoptic stimulation. Clin Neurophys 120:2100–2108

  17. 17.

    Abdullah SN, Aldahlawi N, Vaegan Boon MY, Maddess T (2012) Effect of contrast, region number and viewing distance on multifocal steady-state visual evoked potentials (MSVs). Invest Ophthalmol Vis Sci 53:5527–5535

  18. 18.

    Abdullah SN, Sanderson G, James AC, Vaegan Maddess T (2014) Visual evoked potential and psychophysical contrast thresholds in glaucoma. Doc Ophthalmol 128:111–120

  19. 19.

    Ruseckaite R, Maddess T, Danta G, James AC (2006) Frequency doubling illusion VEPs and automated perimetry in multiple sclerosis. Doc Ophthalmol 113:29–41

  20. 20.

    Johnson CA, Samuels S (1997) Screening for glaucomatous visual field loss with frequency doubling perimetry. Invest Ophthalmol Vis Sci 38:413–425

  21. 21.

    Maddess T, Goldberg I, Dobinson J, Wine S, Welsh AH, James AC (1999) Testing for glaucoma with the spatial frequency doubling illusion. Vis Res 39:4258–4273

  22. 22.

    Abdullah SN, Vaegan, Boon MY, Maddess T (2012) Contrast-response functions of the multifocal steady-state VEP (MSV). Clin Neurophys 123:1865–1871

  23. 23.

    Campbell FW, Green DG (1965) Optical and retinal factors affecting visual resolution. J Physiol 181(3):576–593

  24. 24.

    Horner DG, Dul MW, Swanson WH, Liu T, Tran I (2013) Blur-resistant perimetric stimuli. Optom Vis Sci 90(5):466–474. https://doi.org/10.1097/OPX.0b013e31828fc91d

  25. 25.

    Henson DB (2000) Strategies used in examining the visual field. Visual Fields. Reed Educational and Professional Publishing Ltd, Oxford, pp 23–41

  26. 26.

    Cubbidge R (2005) Threshold strategies. In: Doshi S, Harvey W (eds) Eyes essential, visual fields, First edn. Elsevier Butterworth-Heinemann, Oxford, pp 24–35

  27. 27.

    Vaegan Rahman AMA, Sanderson GF (2008) Glaucoma affects steady state VEP contrast thresholds before psychophysics. Optom Vis Sci 85(7):547–558

  28. 28.

    Bland JM, Altman DG (1986) Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1(8476):307–310

  29. 29.

    Swanson WH, Malinovsky VE, Dul MW, Malik R, Torbit JK, Sutton BM, Horner DG (2014) Contrast sensitivity perimetry and clinical measures of glaucomatous damage. Optom Vis Sci 91(11):1302–1311. https://doi.org/10.1097/OPX.0000000000000395

  30. 30.

    Hanley JA, McNeil BJ (1982) The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 143(1):29–36. https://doi.org/10.1148/radiology.143.1.7063747

  31. 31.

    Maddess T (2011) The influence of sampling errors on test-retest variability in perimetry. Invest Ophthalmol Vis Sci 52:1014–1022

  32. 32.

    Maddess T (2014) Modelling the relative influence of fixation and sampling errors on test-retest-variability in perimetry. Graefes Arch Ophthalmol 252:1611–1619

  33. 33.

    Gardiner SK, Swanson WH, Goren D, Mansberger SL, Demirel S (2014) Assessment of the reliability of standard automated perimetry in regions of glaucomatous damage. Ophthalmology 121(7):1359–1369. https://doi.org/10.1016/j.ophtha.2014.01.020

  34. 34.

    Numata T, Maddess T, Matsumoto C, Okuyama S, Hashimoto S, Nomoto H, Shinomura Y (2017) Exploring test-retest variability using high-resolution perimetry. Trans Vis Sci Tech 6(5(8)):1–9. https://doi.org/10.1167/tvst.6.5.8

  35. 35.

    Johnson CA, Sample PA, Cioffi GA, Liebmann JR, Weinreb RN (2002) Structure and function evaluation (SAFE): I. Criteria for glaucomatous visual field loss using standard automated perimetry (SAP) and short wavelength automated perimetry (SWAP). Am J Ophthalmol 134(2):177–185

  36. 36.

    Weber J, Dobek K (1986) What is the most suitable grid for computer perimetry in glaucoma patients? Ophthalmologica 192(2):88–96

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This paper is dedicated to our late colleague Gordon F Sanderson. We are grateful for the very constructive comments of the reviewers.


This research was supported by the Australian Research Council through the ARC Centre of Excellence in Vision Science (CE0561903) and intramural funding from the Australian National University.

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Correspondence to Ted Maddess.

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Conflict of interest

Some readers will know that Maddess held the patents for the FDT/Matrix perimeters; however, those patents lapsed in 2015 and Maddess retains no interest in those Carl Zeiss products. Indeed, the R9 method of the paper might be seen as a competitor of FDT. Maddess has a small holding in and is on the advisory board of, EyeCo Pty Ltd, which is developing treatments for retina oedema and dry macular degeneration. He could also earn royalty income from patents assigned to Konan Medical USA Inc for a pupillography based perimetry system, but which has no features like R9 or FDT. R9 could be seen as a competitor to that potential product. Author SNA declares that she has no conflict of interest. Author GFS is deceased. Author MAH declares that he has no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the University of New South Wales and the University of Otago; and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the University of New South Wales and the University of Otago; and with the 1964 Helsinki declaration and its later amendments.

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Abdullah, S.N., Sanderson, G.F., Husni, M.A. et al. Insights for mfVEPs from perimetry using large spatial frequency-doubling and near frequency-doubling stimuli in glaucoma. Doc Ophthalmol (2020). https://doi.org/10.1007/s10633-020-09750-7

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  • Glaucoma
  • Frequency doubling
  • Perimetry
  • Neural mechanisms
  • Multifocal VEPs