Documenta Ophthalmologica

, Volume 130, Issue 3, pp 197–209 | Cite as

Structural and functional changes in glaucoma: comparing the two-flash multifocal electroretinogram to optical coherence tomography and visual fields

  • Anna A. Ledolter
  • Matthias Monhart
  • Andreas Schoetzau
  • Margarita G. Todorova
  • Anja M. Palmowski-Wolfe
Original Research Article

Abstract

Purpose

To correlate multifocal electroretinogram (mfERG) findings in the macular area of glaucoma patients with automated perimetry (visual fields) and with optical coherence tomography (OCT).

Methods

A two-global flash mfERG (VERIS™) was recorded in 20 eyes with primary open-angle glaucoma. The root mean square was calculated, and three response epochs were analysed: the direct component (15–45 ms) and two induced components (IC-1 at 45–75 ms and IC-2 at 75–105 ms). The central 10° of the mfERG was compared to the central 10° of the OCT and of the visual field. Responses grouped in a superior and in an inferior semicircle, extending between 10° and 20°, were also compared to the corresponding areas of the OCT and of the visual fields. In addition, the area of the papillomacular bundle was also analysed separately.

Results

In glaucoma patients, mfERG responses showed a significant positive association with retinal thickness in the central 10° for IC2 (p = 0.001) and a trend for IC1 (p = 0.066). A significant association was found between the central IC1 and IC2 of the mfERG and corresponding perimetric sensitivities expressed in linear units (p < 0.01). The OCT showed a positive association with visual field sensitivities (p < 0.05) in all areas examined (p < 0.05). Separation of the papillomacular bundle area did not improve structure–function association further.

Conclusions

In our study, mfERG showed a statistically significant correlation with perimetric sensitivity measured in linear units and with structural macular changes detected with time-domain OCT.

Keywords

Optical coherence tomography Multifocal ERG Global flash multifocal ERG Glaucoma Structure–functional relations Visual field 

Notes

Acknowledgments

This work was supported by Swiss National Science Foundation (SNSF) 32003B-135219 (A.M.P.); LHW Stiftung Lichtenstein (A.M.P.).

Conflict of interest

The author(s) have no proprietary or commercial interest in any materials discussed in the article.

References

  1. 1.
    Gupta N, Yücel YH (2007) Glaucoma as a neurodegenerative disease. Curr Opin Ophthalmol 18(2):110–114CrossRefPubMedGoogle Scholar
  2. 2.
    Werkmeister RM, Cherecheanu AP, Garhofer G, Schmidl D, Schmetterer L (2013) Imaging of retinal ganglion cells in glaucoma: pitfalls and challenges. Cell Tissue Res 353(2):261–268CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    Wang MHD, Hood DC, Cho JS, Ghadiali Q, De Moraes CG, Zhang X, Ritch R, Liebmann JM (2009) Measurement of local retinal ganglion cell layer thickness in patients with glaucoma using frequency-domain optical coherence tomography. Arch Ophthalmol 127(7):875–881CrossRefPubMedCentralPubMedGoogle Scholar
  4. 4.
    Atkin A, Bodis-Wollner I, Wolkstein M, Moss A, Podos SM (1979) Abnormalities of central contrast sensitivity in glaucoma. Am J Ophthalmol 88(2):205–211CrossRefPubMedGoogle Scholar
  5. 5.
    Adams AJ, Heron G, Husted R (1987) Clinical measures of central vision function in glaucoma and ocular hypertension. Arch Ophthalmol 105(6):782–787CrossRefPubMedGoogle Scholar
  6. 6.
    Lahav K, Levkovitch-Verbin H, Belkin M, Glovinsky Y, Polat U (2011) Reduced mesopic and photopic foveal contrast sensitivity in glaucoma. Arch Ophthalmol 129(1):16–22CrossRefPubMedGoogle Scholar
  7. 7.
    Fujimoto JG, Drexler W, Schuman JS, Hitzenberger CK (2009) Optical coherence tomography (OCT) in ophthalmology: introduction. Opt Express 17(5):3978–3979CrossRefPubMedGoogle Scholar
  8. 8.
    Parikh RS, Parikh SR, Thomas R (2010) Diagnostic capability of macular parameters of Stratus OCT 3 in detection of early glaucoma. Br J Ophthalmol 94(2):197–201CrossRefPubMedGoogle Scholar
  9. 9.
    Hood DC, Raza AS, de Moraes CG, Odel JG, Greenstein VC, Liebmann JM, Ritch R (2011) Initial arcuate defects within the central 10° in glaucoma. Invest Ophthalmol Vis Sci 52(2):940–946CrossRefPubMedCentralPubMedGoogle Scholar
  10. 10.
    Kanadani FN, Hood D, Grippo T, Wangsupadilok B, Harizman N, Greenstein VC, Liebmann JM, Ritch R (2006) Structural and functional assessment of the macular region in patients with glaucoma. Br J Ophthalmol 90:1393–1397CrossRefPubMedCentralPubMedGoogle Scholar
  11. 11.
    Hood DC, Raza AS, de Moraes CGV, Johnson CA, Liebmann JM, Ritch R (2012) The nature of macular damage in glaucoma as revealed by averaging optical coherence tomography data. Trans Vis Sci Tech 1(1):3:1–3:15CrossRefGoogle Scholar
  12. 12.
    Kim NR, Hong S, Kim JH, Rho SS, Seong GJ, Kim CY (2013) Comparison of macular ganglion cell complex thickness by Fourier-domain OCT in normal tension glaucoma and primary open-angle glaucoma. J Glaucoma 22(2):133–139CrossRefPubMedGoogle Scholar
  13. 13.
    Hare W, Ton H, Woldemussie E, Ruiz G, Feldmann B, Wijono M (1999) Electrophysiological and histological measures of retinal injury in chronic ocular hypertensive monkeys. Eur J Ophthalmol 9(Suppl 1):30–33Google Scholar
  14. 14.
    Raz D, Seeliger MW, Geva AB, Percicot CL, Lambrou GN, Ofri R (2002) The effect of contrast and luminance on mfERG responses in a monkey model of glaucoma. Invest Ophthalmol Vis Sci 43(6):2027–2035PubMedGoogle Scholar
  15. 15.
    Frishman LJ, Saszik S, Harwerth RS, Viswanathan S, Li Y, Smith EL III, Robson JG, Barnes G (2000) Effects of experimental glaucoma in macaques on the multifocal ERG. Multifocal ERG in laser-induced glaucoma. Doc Ophthalmol 100(2–3):231–251CrossRefPubMedGoogle Scholar
  16. 16.
    Luo X, Patel NB, Harwerth RS, Frishman LJ (2011) Loss of the low-frequency component of the global-flash multifocal electroretinogram in primate eyes with experimental glaucoma. Invest Ophthalmol Vis Sci 52(6):3792–3804CrossRefPubMedCentralPubMedGoogle Scholar
  17. 17.
    Luo X, Patel NB, Rajagopalan LP, Harwerth RS, Frishman LJ (2014) Relation between macular retinal ganglion cell/inner plexiform layer thickness and multifocal electroretinogram measures in experimental glaucoma. Invest Ophthalmol Vis Sci 55(7):4512–4524CrossRefPubMedCentralPubMedGoogle Scholar
  18. 18.
    Todorova MG, Palmowski-Wolfe AM (2011) MfERG responses to long-duration white stimuli in glaucoma patients. Doc Ophthalmol 122(2):87–97CrossRefPubMedGoogle Scholar
  19. 19.
    Sutter EE, Bearse MA, Shimada Y, Li Y (1999) A multifocal ERG protocol for testing retinal ganglion cell function. Invest Ophthalmol Vis Sci S15Google Scholar
  20. 20.
    Palmowski AM, Allgayer R, Heinemann-Vernaleken B, Ruprecht KW (2002) Multifocal ERG (MFERG) with a special multiflash stimulation technique in open angle glaucoma. Ophthalmic Res 34:83–89CrossRefPubMedGoogle Scholar
  21. 21.
    Palmowski-Wolfe AM, Todorova MG, Orguel S, Flammer J, Brigell M (2007) The ‘two global flash’ mfERG in high and normal tension primary open-angle glaucoma. Doc Ophthalmol 114:9–19CrossRefPubMedGoogle Scholar
  22. 22.
    Fortune B, Bearse MAJ, Cioffi GA, Johnson CA (2002) Selective loss of an oscillatory component from temporal retinal multifocal ERG responses in glaucoma. Invest Ophthalmol Vis Sci 43:2638–2647PubMedGoogle Scholar
  23. 23.
    Chu PHW, Chan HHL, Yiu-Fai Ng, Brown B, Siu AW, Beale BA, Gilger BC, Wongd F (2008) Porcine global flash multifocal electroretinogram: possible mechanisms for the glaucomatous changes in contrast response function. Vis Res 48:1726–1734CrossRefPubMedGoogle Scholar
  24. 24.
    Kramer SA, Ledolter AA, Todorova MG, Schötzau A, Orgül S, Palmowski-Wolfe AM (2013) The 2-global flash mfERG in glaucoma: attempting to increase sensitivity by reducing the focal flash luminance and changing filter settings. Doc Ophthalmol 126(1):57–67CrossRefPubMedGoogle Scholar
  25. 25.
    Hori N, Komori S, Yamada H, Sawada A, Nomura Y, Mochizuki K, Yamamoto T (2012) Assessment of macular function of glaucomatous eyes by multifocal electroretinograms. Doc Ophthalmol 4(125):235–247CrossRefGoogle Scholar
  26. 26.
    Talamini CL, Raza AS, Dale EA, Greenstein VC, Odel JG, Hood DC (2011) Abnormal multifocal ERG findings in patients with normal-appearing retinal anatomy. Doc Ophthalmol 123(3):187–192CrossRefPubMedGoogle Scholar
  27. 27.
    Villoslada P, Cuneo A, Gelfand J, Hauser SL, Green A (2012) Color vision is strongly associated with retinal thinning in multiple sclerosis. Mult Scler 18(7):991–999CrossRefPubMedGoogle Scholar
  28. 28.
    Garway-Heath DF, Holder GE, Fitzke FW, Hitchings RA (2002) Relationship between electrophysiological, psychophysical, and anatomical measurements in glaucoma. Invest Ophthalmol Vis Sci 43:2213–2220PubMedGoogle Scholar
  29. 29.
    Hood D, Kardon R (2007) A framework for comparing structural and functional measures of glaucomatous damage. Prog Retin Eye Res 26(6):688–710CrossRefPubMedCentralPubMedGoogle Scholar
  30. 30.
    De Moraes CG, Liebmann JM, Ritch R, Hood DC (2012) Clinical use of multifocal visual-evoked potentials in a glaucoma practice: a prospective study. Doc Ophthalmol 125(1):1–9CrossRefPubMedCentralPubMedGoogle Scholar
  31. 31.
    Dale EA, Hood DC, Greenstein VC, Odel JG (2010) A comparison of multifocal ERG and frequency domain OCT changes in patients with abnormalities of the retina. Doc Ophthalmol 120:175–186CrossRefPubMedCentralPubMedGoogle Scholar
  32. 32.
    Malik R, Swanson WH, Garway-Heath DF (2012) Structure-function relationship’ in glaucoma: past thinking and current concepts. Clin Exp Ophthalmol 40(4):369–380CrossRefGoogle Scholar
  33. 33.
    Hood D, Harizman N, Kanadani FN, Grippo TM, Baharestani S, Greenstein VC, Liebmann JM, Ritch R (2007) Retinal nerve fibre thickness measured with optical coherence tomography accurately detects confirmed glaucomatous damage. Br J Ophthalmol 91:905–907CrossRefPubMedCentralPubMedGoogle Scholar
  34. 34.
    Medeiros FA, Zangwill LM, Bowd C, Vessani RM, Susanna R Jr, Weinreb RN (2005) Evaluation of retinal nerve fiber layer, optic nerve head, and macular thickness measurements for glaucoma detection using optical coherence tomography. Am J Ophthalmol 139:44–55CrossRefPubMedGoogle Scholar
  35. 35.
    Weijland A, Fankhauser F, Bebie H, Flammer J (2004) Automated perimetry. Visual field digest, 5th edn. Haag-Streit AG, Switzerland, p 61Google Scholar
  36. 36.
    Palmowski-Wolfe A (2012) Can the OCT replace functional tests such as the mfERG? Invest Ophthalmol Vis Sci 53(10):6129CrossRefPubMedGoogle Scholar
  37. 37.
    Lee K, Lee J, Na J, Kook M (2013) Usefulness of macular thickness derived from spectral-domain optical coherence tomography (SD-OCT) in the detection of glaucoma progression. Invest Ophthalmol Vis Sci 54(3):1941–1949CrossRefPubMedGoogle Scholar
  38. 38.
    Drasdo N, Millican CL, Katholi CR, Curcio CA (2007) The length of Henle fibers in the human retina and a model of ganglion receptive field density in the visual field. Vis Res 47(22):2901–2911CrossRefPubMedCentralPubMedGoogle Scholar
  39. 39.
    Sjöstrand J, Popovic Z, Conradi N, Marshall J (1999) Morphometric study of the displacement of retinal ganglion cells subserving cones within the human fovea. Graefes Arch Clin Exp Ophthalmol 237(12):1014–1023CrossRefPubMedGoogle Scholar
  40. 40.
    Raza AS, Cho J, de Moraes CG, Wang M, Zhang X, Kardon RH, Liebmann JM, Ritch R, Hood DC (2011) Retinal ganglion cell layer thickness and local visual field sensitivity in glaucoma. Arch Ophthalmol 129(12):1529–1536CrossRefPubMedCentralPubMedGoogle Scholar
  41. 41.
    Pinto LM, Costa EF, Gross PB, Kavay MM, Fogaça L, Melo LAS Jr, Paranhos A Jr (2010) Evaluation of macular structure and function in glaucoma. Invest Ophthalmol Vis Sci 51:E-Abstract 4913Google Scholar
  42. 42.
    Zhang X, Bregman CJ, Raza AS, De Moraes G, Hood DC (2011) Deriving visual field loss based upon OCT of inner retinal thicknesses of the macula. Biomed Opt Express 2(6):1734–1742CrossRefPubMedCentralPubMedGoogle Scholar
  43. 43.
    Hood DC, Raza AS (2011) Method for comparing visual field defects to local RNFL and RGC damage seen on frequency domain OCT in patients with glaucoma. Biomed Opt Express 5(2):1097–1105CrossRefGoogle Scholar
  44. 44.
    Leite M, Zangwill L, Weinreb R, Rao H, Alencar L, Medeiros F (2012) Structure–function relationships using the Cirrus spectral domain optical coherence tomograph and standard automated perimetry. J Glaucoma 21(1):49–54CrossRefPubMedCentralPubMedGoogle Scholar
  45. 45.
    Sihota R, Sony P, Gupta V, Dada T, Singh R (2006) Diagnostic capability of optical coherence tomography in evaluating the degree of glaucomatous retinal nerve fiber damage. Invest Ophthalmol Vis Sci 47(5):2006–2010CrossRefPubMedGoogle Scholar
  46. 46.
    Falsini B, Marangoni D, Salgarello T, Stifano G, Montrone L, Campagna F, Aliberti S, Balestrazzi E, Colotto A (2008) Structure–function relationship in ocular hypertension and glaucoma: interindividual and interocular analysis by OCT and pattern ERG. Graefes Arch Clin Exp Ophthalmol 246(8):1153–1162CrossRefPubMedGoogle Scholar
  47. 47.
    Bowd C, Tafreshi A, Zangwill LM, Medeiros FA, Sample PA, Weinreb RN (2011) Pattern electroretinogram association with spectral domain-OCT structural measurements in glaucoma. Eye (Lond) 25(2):224–232CrossRefGoogle Scholar
  48. 48.
    Ventura L, Sorokac N, De Los Santos R, Feuer W, Porciatti V (2006) The relationship between retinal ganglion cell function and retinal nerve fiber thickness in early glaucoma. Invest Ophthalmol Vis Sci 47(9):3904–3911CrossRefPubMedCentralPubMedGoogle Scholar
  49. 49.
    Bach M, Birkner-Binder D, Pfeiffer N (1990) Das Musterelektroretinogramm bei fruhem Glaukom und bei okularer Hypertension. Fortschr-Ophthalmol 87(6):591–593PubMedGoogle Scholar
  50. 50.
    Fortune B, Burgoyne CF, Cull GA, Reynaud J, Wang L (2012) Structural and functional abnormalities of retinal ganglion cells measured in vivo at the onset of optic nerve head surface change in experimental glaucoma. Invest Ophthalmol Vis Sci. 53(7):3939–3950CrossRefPubMedCentralPubMedGoogle Scholar
  51. 51.
    Quigley HA, Dunkelberger GR, Green WR (1989) Retinal ganglion cell atrophy correlated with automated perimetry in human eyes with glaucoma. Am J Ophthalmol 107:453–464CrossRefPubMedGoogle Scholar
  52. 52.
    Drasdo N, Mortlock KE, North RV (2008) Ganglion cell loss and dysfunction: relationship to perimetric sensitivity. Optom Vis Sci 85(11):1036–1042CrossRefPubMedGoogle Scholar
  53. 53.
    Harwerth RS, Wheat JL, Fredette MJ, Anderson DR (2010) Linking structure and function in glaucoma. Prog Retin Eye Res 29(4):249–271CrossRefPubMedCentralPubMedGoogle Scholar
  54. 54.
    Chen E, Gedda U, Landau I (2001) Thinning of the papillomacular bundle in the glaucomatous eye and its influence on the reference plane of the Heidelberg retinal tomography. J Glaucoma 10(5):386–389CrossRefPubMedGoogle Scholar
  55. 55.
    Kita Y, Kita R, Nitta A, Nishimura C, Tomita G (2011) Glaucomatous eye macular ganglion cell complex thickness and its relation to temporal circumpapillary retinal nerve fiber layer thickness. Jpn J Ophthalmol 55(3):228–234CrossRefPubMedGoogle Scholar
  56. 56.
    Marín-Franch I, Malik R, Crabb DP, Swanson WH (2013) Choice of statistical method influences apparent association between structure and function in glaucoma. Invest Ophthalmol Vis Sci 54(6):4189–4196CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Anna A. Ledolter
    • 1
    • 2
  • Matthias Monhart
    • 3
  • Andreas Schoetzau
    • 1
  • Margarita G. Todorova
    • 1
  • Anja M. Palmowski-Wolfe
    • 1
  1. 1.Department of OphthalmologyUniversity of BaselBaselSwitzerland
  2. 2.Department of OphthalmologyMedical University of ViennaViennaAustria
  3. 3.Carl Zeiss AGFeldbachSwitzerland

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