Structure–function relationship in ocular hypertension and glaucoma: interindividual and interocular analysis by OCT and pattern ERG

  • Benedetto FalsiniEmail author
  • Dario Marangoni
  • Tommaso Salgarello
  • Giovanna Stifano
  • Lucrezia Montrone
  • Francesca Campagna
  • Stefania Aliberti
  • Emilio Balestrazzi
  • Alberto Colotto



Pattern electroretinogram (PERG) and optical coherence tomography (OCT) represent objective probes to investigate respectively the function of retinal ganglion cells and their structure as retinal nerve fiber layer (RNFL) thickness. We examined interindividual (II) correlations of PERG amplitude and RNFL thickness, as well as correlations between interocular (IO) differences in both measures, in ocular hypertension (OHT) and early glaucoma (EG) patients.


Thirty-one OHT, 34 EG (mean deviation: −1 to −6 dB) and 16 age-matched controls were examined in both eyes. Participants had clear optical media, no or moderate refractive errors and no concomitant ocular or systemic diseases. PERGs were elicited by counterphased (16.28 reversals/second) gratings (1.6 cycles/degree spatial frequency). The Fourier isolated 2nd harmonic PERG amplitude and phase were measured. RNFL thickness was quantified by means of OCT Stratus according to a standard protocol. Average, superior and inferior RNFL thicknesses were considered.


Mean PERG amplitude was decreased (p < 0.01) in both OHT and EG patients compared to controls. Mean RNFL thicknesses were reduced (p < 0.01) in EG patients compared to both OHT and controls. In OHT patients, PERG amplitude did not correlate significantly with RNFL thickness in both II and IO analysis. In EG patients, PERG amplitude was positively correlated with RNFL thickness in both II (p < 0.005) and IO (p < 0.001) analysis. The slope of the correlation predicted that PERG losses exceeded systematically RNFL losses when the latter were between 0 and −0.25 log units.


Both II and IO analyses revealed a lack of structure–function relationship in OHT, suggesting that, at this disease stage, PERG losses appear to affect primarily retinal/optic nerve head function. In EG they reflect both dysfunction and RNFL loss.


Glaucoma Ocular hypertension Pattern electroretinography Optical coherence tomography Retinal ganglion cells Optic nerve 


Grants/financial support

Intramural Grant from Ministero della Ricerca Scientifica, Fondi di Ateneo ex 60%.

Financial Disclosure



  1. 1.
    Aldebasi YH, Drasdo N, Morgan JE, North RV (2004) S-cone, L + M-cone, and pattern, electroretinograms in ocular hypertension and glaucoma. Vis Res 44:2749–2756PubMedCrossRefGoogle Scholar
  2. 2.
    Bach M, Sulimma F, Gerling J (1998) Little correlation of the pattern-electroretinogram and visual field measures in early glaucoma. Doc Ophthalmol 94:253–263CrossRefGoogle Scholar
  3. 3.
    Bach M, Unsoeld AS, Philippin H, Staubach F, Maier P, Walter HS, Bomer TG, Funk J (2006) Pattern ERG as an early glaucoma indicator in ocular hypertension: a long-term, prospective study. Invest Ophthalmol Vis Sci 47:4881–4887PubMedCrossRefGoogle Scholar
  4. 4.
    Bowd C, Weinreb RN, Williams JM, Zangwill LM (2000) The retinal nerve fiber layer thickness in ocular hypertensive, normal, and glaucomatous eyes with optical coherence tomography. Arch Ophthalmol 118:22–26PubMedGoogle Scholar
  5. 5.
    Budenz DL, Michael A, Chang RT, McSoley, Katz J (2005) Sensitivity and specificity of the Stratus OCT for perimetric glaucoma. Ophthalmology 112:3–9PubMedCrossRefGoogle Scholar
  6. 6.
    Budenz DL, Anderson DR, Varma R, Schuman J, Cantor L, Savell J, Greenfield DS, Patella VM, Quigley HA, Tielsch J (2007) Determinants of normal retinal nerve fiber layer thickness measured by stratus OCT. Ophthalmology DOI  10.1016/2006.08.046
  7. 7.
    Colotto A, Falsini B, Salgarello T, Iarossi G, Galan ME, Scullica L (2000) Photopic negative response of the human ERG: losses associated with glaucomatous damage. Invest Ophthalmol Vis Sci 41:2205–2211PubMedGoogle Scholar
  8. 8.
    Fiorentini A, Maffei L, Pirchio M, Spinelli D, Porciatti V (1981) The ERG in response to alternating gratings in patients with diseases of the peripheral visual pathway. Invest Ophthalmol Vis Sci 21:490–493PubMedGoogle Scholar
  9. 9.
    Garway-Heath DF, Holder G, Fitzke FW, Hitchings RA (2002) Relationship between electrophysiological, psychophysical and anatomical measurements in glaucoma. Invest Ophthalmol Vis Sci 43:2213–2220PubMedGoogle Scholar
  10. 10.
    Harrison WW, Viswanathan S, Malinovsky VE (2006) Multifocal pattern electroretinogram: cellular origins and clinical implications. Optom Vis Sci 83:473–485PubMedCrossRefGoogle Scholar
  11. 11.
    Harwerth RS, Vilupuru AS, Rangaswamy NV, Smith EL 3rd (2007) The relationship between nerve fiber layer and perimetry measurements. Invest Ophthalmol Vis Sci 48:763–773PubMedCrossRefGoogle Scholar
  12. 12.
    Hernandez MR (2000) The optic nerve head in glaucoma: role of astrocytes in tissue remodeling. Prog Ret Eye Res 19:297–321CrossRefGoogle Scholar
  13. 13.
    Hood DC, Xu L, Thienprasiddhi P, Greenstein VC, Odel JG, Grippo TM, Liebmann JM, Ritch R (2005) The pattern electroretinogram in glaucoma patients with confirmed visual field deficits. Invest Ophthalmol Vis Sci 46:2411–2418PubMedCrossRefGoogle Scholar
  14. 14.
    Kerrigan-Baumrind LA, Quigley HA, Pease ME, Kerrigan DF, Mitchell RS (2000) Number of ganglion cells in glaucoma eyes compared with threshold visual field tests in the same persons. Invest Ophthalmol Vis Sci 41:741–748PubMedGoogle Scholar
  15. 15.
    Kim TW, Zangwill LM, Bowd C, 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 technology but not by standard automated perimetry. Ophthalmology DOI  10.1016/2006.09.015
  16. 16.
    Korth M, Horn F, Stork B, Jonas J (1989) The pattern evoked electroretinogram: age-related alterations and changes in glaucoma. Graefes Arch Clin Exp Ophthalmol 227:123–131PubMedCrossRefGoogle Scholar
  17. 17.
    Medeiros FA, Sample PA, Weinreb RN (2003) Corneal thickness measurements and visual function abnormalities in ocular hypertensive patients. Am J Ophthalmol 135:131–137PubMedCrossRefGoogle Scholar
  18. 18.
    Parisi V, Manni G, Gandolfi SA, Centofanti M, Colacino G, Bucci MG (1999) Visual function correlates with nerve fiber layer thickness in eyes affected by ocular hypertension. Invest Ophthalmol Vis Sci 40:1828–1833PubMedGoogle Scholar
  19. 19.
    Parisi V, Manni G, Colacino G, Bucci MG (1999) Cytidine-5′-diphosphocholine (citicoline) improves retinal and cortical responses in patients with glaucoma. Ophthalmology 106:1126–1134PubMedCrossRefGoogle Scholar
  20. 20.
    Parisi V, Manni G, Centofanti M, Gandolfi SA, Olzi D, Bucci MG (2001) Correlation between optical coherence tomography, pattern electroretinogram and visual evoked potentials in open angle glaucoma patients. Ophthalmology 108:905–912PubMedCrossRefGoogle Scholar
  21. 21.
    Porciatti V, Falsini B, Brunori S, Colotto A, Moretti G (1987) Pattern electroretinogram as a function of spatial frequency in ocular hypertension and early glaucoma. Doc Ophthalmol 65:349–355PubMedCrossRefGoogle Scholar
  22. 22.
    Quigley HA, Dunkelberger GR, Green WR (1989) Retinal ganglion cell atrophy correlated with automated perimetry in human eyes with glaucoma. Am J Ophthalmol 107:453–464PubMedGoogle Scholar
  23. 23.
    Quigley HA, Nickells RW, Kerrigan LA, Pease ME, Thibault DJ, Zack DJ (1995) Retinal ganglion cell death in experimental glaucoma and after axotomy occurs by apoptosis. Invest Ophthalmol Vis Sci 36:774–786PubMedGoogle Scholar
  24. 24.
    Salgarello T, Colotto A, Falsini B, Buzzonetti L, Cesari L, Iarossi G, Scullica L (1999) Correlation of pattern electroretinogram with optic disc cup shape in ocular hypertension. Invest Ophthalmol Vis Sci 40:1989–1997PubMedGoogle Scholar
  25. 25.
    Savini G, Zanini M, Carelli V, Sadun AA, Ross-Cisneros FN, Barboni P (2005) Correlation between retinal nerve fiber layer thickness and optic nerve head size: an optical coherence tomography study. Br J Ophthalmol 89:489–492PubMedCrossRefGoogle Scholar
  26. 26.
    Swanson WH, Felius J, Pan F (2004) Perimetric defects and ganglion cell damage: interpreting linear relations using a two-stage neural model. Invest Ophthalmol Vis Sci 45:466–472PubMedCrossRefGoogle Scholar
  27. 27.
    Ventura LM, Porciatti V, Ishida K, Feuer WJ, Parrish RK II (2005) Pattern electroretinogram abnormality and glaucoma. Ophthalmology 112:10–19PubMedCrossRefGoogle Scholar
  28. 28.
    Ventura LM, Porciatti V (2005) Restoration of retinal ganglion cell function in early glaucoma after intraocular pressure reduction. A pilot study. Ophthalmology 112:20–27PubMedCrossRefGoogle Scholar
  29. 29.
    Ventura LM, Sorokac N, De Los Santos R, Feuer WJ, Porciatti V (2006) The relationship between retinal ganglion cell function and retinal nerve fiber thickness in early glaucoma. Invest Ophthalmol Vis Sci 47:3904–3911PubMedCrossRefGoogle Scholar
  30. 30.
    Viswanathan S, Frishman LJ, Robson JG (2000) The uniform field and pattern ERG in macaques with experimental glaucoma: removal of spiking activity. Invest Ophthalmol Vis Sci 41:2797–2810PubMedGoogle Scholar
  31. 31.
    Weber AJ, Kaufman PL, Hubbard WC (1998) Morphology of single ganglion cells in the glaucomatous primate retina. Invest Ophthalmol Vis Sci 39:2304–2320PubMedGoogle Scholar
  32. 32.
    Weber AJ, Harman CD (2005) Structure-function relations of parasol cells in the normal and glaucomatous primate retina. Invest Ophthalmol Vis Sci 46:3197–3207PubMedCrossRefGoogle Scholar
  33. 33.
    Weinreb RN, Friedman DS, Fechtner RD, Cioffi GA, Coleman AL, Girkin CA, Liebmann JM, Singh K, Wilson MR, Wilson R, Kannel WB (2004) Risk assessment in the management of patients with ocular hypertension. Am J Ophthalmol 138:458–467PubMedCrossRefGoogle Scholar
  34. 34.
    Wollstein G, Schuman JS, Price LL, Aydin A, Stark PC, Hertzmark E, Lai E, Ishikawa H, Mattox C, Fujimoto JG, Paunescu LA (2005) Optical coherence tomography longitudinal evaluation of retinal nerve fiber layer thickness in glaucoma. Arch Ophthalmol 123:464–470PubMedCrossRefGoogle Scholar
  35. 35.
    Wygnanski T, Desatnik H, Quigley HA, Glovinsky Y (1995) Comparison of ganglion cell loss and cone loss in experimental glaucoma. Am J Ophthalmol 120:184–189PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Benedetto Falsini
    • 1
    Email author
  • Dario Marangoni
    • 1
  • Tommaso Salgarello
    • 1
  • Giovanna Stifano
    • 1
  • Lucrezia Montrone
    • 1
  • Francesca Campagna
    • 1
  • Stefania Aliberti
    • 1
  • Emilio Balestrazzi
    • 1
  • Alberto Colotto
    • 1
  1. 1.Institute of OphthalmologyCatholic UniversityRomeItaly

Personalised recommendations