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Global flash multifocal electroretinogram: early detection of local functional changes and its correlations with optical coherence tomography and visual field tests in diabetic eyes

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Abstract

Purpose To investigate the correlations of the global flash multifocal electroretinogram (MOFO mfERG) with common clinical visual assessments—Humphrey perimetry and Stratus circumpapillary retinal nerve fiber layer (RNFL) thickness measurement in type II diabetic patients. Methods Forty-two diabetic patients participated in the study: Ten were free from diabetic retinopathy (DR), while the remainder suffered from mild to moderate nonproliferative diabetic retinopathy. Fourteen age-matched controls were recruited for comparison. MOFO mfERG measurements were made under high- and low-contrast conditions. Humphrey central 30-2 perimetry and Stratus OCT circumpapillary RNFL thickness measurements were also performed. Correlations between local values of implicit time and amplitude of the mfERG components [direct component (DC) and induced component (IC)], and perimetric sensitivity and RNFL thickness were evaluated by mapping the localized responses for the three subject groups. Results MOFO mfERG was superior to perimetry and RNFL assessments in showing differences between the diabetic groups (with and without DR) and the controls. All the MOFO mfERG amplitudes (except IC amplitude at high contrast) correlated better with perimetry findings (Pearson’s r ranged from 0.23 to 0.36, p < 0.01) than did the mfERG implicit time at both high and low contrasts across all subject groups. No consistent correlation was found between the mfERG and RNFL assessments for any group or contrast conditions. The responses of the local MOFO mfERG correlated with local perimetric sensitivity but not with RNFL thickness. Conclusion Early functional changes in the diabetic retina seem to occur before morphological changes in the RNFL.

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References

  1. Van Bijsterveld OP (2000) Diabetic retinopathy. Martin Dunitz Ltd., London, p 2

    Google Scholar 

  2. Porta M, Bandello F (2002) Diabetic retinopathy—a clinical update. Diabetologia 45(12):1617–1634

    Article  PubMed  CAS  Google Scholar 

  3. Barber AJ (2003) A new view of diabetic retinopathy: a neurodegenerative disease of the eye. Prog Neuropsychopharmacol Biol Psychiatry 27(2):283–290

    Article  PubMed  CAS  Google Scholar 

  4. Barber AJ, Gardner TW, Abcouwer SF (2011) The significance of vascular and neural apoptosis to the pathology of diabetic retinopathy. Invest Ophthalmol Vis Sci 52(2):1156–1163

    Article  PubMed  CAS  Google Scholar 

  5. Barber AJ, Lieth E, Khin SA, Antonetti DA, Buchanan AG, Gardner TW (1998) Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin. J Clin Invest 102(4):783–791

    Article  PubMed  CAS  Google Scholar 

  6. Kern TS, Barber AJ (2008) Retinal ganglion cells in diabetes. J Physiol 586(Pt 18):4401–4408

    Article  PubMed  CAS  Google Scholar 

  7. Lopes de Faria JM, Russ H, Costa VP (2002) Retinal nerve fibre layer loss in patients with type 1 diabetes mellitus without retinopathy. Br J Ophthalmol 86(7):725–728

    Article  PubMed  CAS  Google Scholar 

  8. Oshitari T, Hanawa K, Adachi-Usami E (2009) Changes of macular and RNFL thicknesses measured by Stratus OCT in patients with early stage diabetes. Eye (Lond) 23(4):884–889

    Article  CAS  Google Scholar 

  9. Ozdek S, Lonneville YH, Onol M, Yetkin I, Hasanreisoglu BB (2002) Assessment of nerve fiber layer in diabetic patients with scanning laser polarimetry. Eye (Lond) 16(6):761–765

    Article  CAS  Google Scholar 

  10. Parravano M, Oddone F, Mineo D, Centofanti M, Borboni P, Lauro R, Tanga L, Manni G (2008) The role of Humphrey Matrix testing in the early diagnosis of retinopathy in type 1 diabetes. Br J Ophthalmol 92(12):1656–1660

    Article  PubMed  CAS  Google Scholar 

  11. Takahashi H, Chihara E (2008) Impact of diabetic retinopathy on quantitative retinal nerve fiber layer measurement and glaucoma screening. Invest Ophthalmol Vis Sci 49(2):687–692

    Article  PubMed  Google Scholar 

  12. Bengtsson B, Heijl A, Agardh E (2005) Visual fields correlate better than visual acuity to severity of diabetic retinopathy. Diabetologia 48(12):2494–2500

    Article  PubMed  CAS  Google Scholar 

  13. Bresnick GH, Condit RS, Palta M, Korth K, Groo A, Syrjala S (1985) Association of hue discrimination loss and diabetic retinopathy. Arch Ophthalmol 103(9):1317–1324

    Article  PubMed  CAS  Google Scholar 

  14. Ismail GM, Whitaker D (1998) Early detection of changes in visual function in diabetes mellitus. Ophthalmic Physiol Opt 18(1):3–12

    Article  PubMed  CAS  Google Scholar 

  15. Kurtenbach A, Flogel W, Erb C (2002) Anomaloscope matches in patients with diabetes mellitus. Graefes Arch Clin Exp Ophthalmol 240(2):79–84

    Article  PubMed  Google Scholar 

  16. Bengtsson B, Hellgren KJ, Agardh E (2008) Test-retest variability for standard automated perimetry and short-wavelength automated perimetry in diabetic patients. Acta Ophthalmol 86(2):170–176

    Article  PubMed  Google Scholar 

  17. Sutter EE, Tran D (1992) The field topography of ERG components in man—I. The photopic luminance response. Vis Res 32(3):433–446

    Article  PubMed  CAS  Google Scholar 

  18. Bearse MA Jr, Han Y, Schneck ME, Barez S, Jacobsen C, Adams AJ (2004) Local multifocal oscillatory potential abnormalities in diabetes and early diabetic retinopathy. Invest Ophthalmol Vis Sci 45(9):3259–3265

    Article  PubMed  Google Scholar 

  19. Bronson-Castain KW, Bearse MA Jr, Neuville J, Jonasdottir S, King-Hooper B, Barez S, Schneck ME, Adams AJ (2009) Adolescents with type 2 diabetes early indications of focal retinal neuropathy, retinal thinning, and venular dilation. Retina 29(5):618–626

    Article  PubMed  Google Scholar 

  20. Fortune B, Schneck ME, Adams AJ (1999) Multifocal electroretinogram delays reveal local retinal dysfunction in early diabetic retinopathy. Invest Ophthalmol Vis Sci 40(11):2638–2651

    PubMed  CAS  Google Scholar 

  21. Holopigian K, Greenstein VC, Seiple W, Hood DC, Carr RE (1997) Evidence for photoreceptor changes in patients with diabetic retinopathy. Invest Ophthalmol Vis Sci 38(11):2355–2365

    PubMed  CAS  Google Scholar 

  22. Kizawa J, Machida S, Kobayashi T, Gotoh Y, Kurosaka D (2006) Changes of oscillatory potentials and photopic negative response in patients with early diabetic retinopathy. Jpn J Ophthalmol 50(4):367–373

    Article  PubMed  Google Scholar 

  23. Luu CD, Szental JA, Lee SY, Lavanya R, Wong TY (2010) Correlation between retinal oscillatory potentials and retinal vascular caliber in type 2 diabetes. Invest Ophthalmol Vis Sci 51(1):482–486

    Article  PubMed  Google Scholar 

  24. Palmowski AM, Sutter EE, Bearse MA Jr, Fung W (1997) Mapping of retinal function in diabetic retinopathy using the multifocal electroretinogram. Invest Ophthalmol Vis Sci 38(12):2586–2596

    PubMed  CAS  Google Scholar 

  25. Shimada Y, Li Y, Bearse MA Jr, Sutter EE, Fung W (2001) Assessment of early retinal changes in diabetes using a new multifocal ERG protocol. Br J Ophthalmol 85(4):414–419

    Article  PubMed  CAS  Google Scholar 

  26. Yamamoto S, Kamiyama M, Nitta K, Yamada T, Hayasaka S (1996) Selective reduction of the S cone electroretinogram in diabetes. Br J Ophthalmol 80(11):973–975

    Article  PubMed  CAS  Google Scholar 

  27. Chen H, Zhang M, Huang S, Wu D (2008) The photopic negative response of flash ERG in nonproliferative diabetic retinopathy. Doc Ophthalmol 117(2):129–135

    Article  PubMed  Google Scholar 

  28. Schneck ME, Bearse MA Jr, Han Y, Barez S, Jacobsen C, Adams AJ (2004) Comparison of mfERG waveform components and implicit time measurement techniques for detecting functional change in early diabetic eye disease. Doc Ophthalmol 108(3):223–230

    Article  PubMed  Google Scholar 

  29. Tyrberg M, Ponjavic V, Lovestam-Adrian M (2005) Multifocal electroretinography (mfERG) in insulin dependent diabetics with and without clinically apparent retinopathy. Doc Ophthalmol 110(2–3):137–143

    Article  PubMed  Google Scholar 

  30. Xu J, Hu G, Huang T, Huang H, Chen B (2006) Using multifocal ERG responses to discriminate diabetic retinopathy. Doc Ophthalmol 112(3):201–207

    Article  PubMed  Google Scholar 

  31. Yamamoto S, Takeuchi S, Kamiyama M (1997) The short wavelength-sensitive cone electroretinogram in diabetes: relationship to systemic factors. Doc Ophthalmol 94(3):193–200

    Article  PubMed  Google Scholar 

  32. Lung JCY, Tang GYB, Chu PHW, Ng YF, Chan HHL (2009) Abstracts of the XLVII international symposium of the ISCEV (International Society for Clinical Electrophysiology of Vision). Global flash mfERG in the early detection of the local functional changes of diabetic retinopathy lesions. Doc Ophthalmol 119(Suppl 1):17–92

    Google Scholar 

  33. Chu PH, Chan HH, Ng YF, Brown B, Siu AW, Beale BA, Gilger BC, Wong F (2008) Porcine global flash multifocal electroretinogram: possible mechanisms for the glaucomatous changes in contrast response function. Vision Res 48(16):1726–1734

    Article  PubMed  Google Scholar 

  34. Lung JC, Chan HH (2010) Effects of luminance combinations on the characteristics of the global flash multifocal electroretinogram (mfERG). Graefes Arch Clin Exp Ophthalmol 248(8):1117–1125

    Article  PubMed  Google Scholar 

  35. Lung JC, Swann PG, Chan HH (2012) Early local functional changes in the human diabetic retina: a global flash multifocal electroretinogram study. Graefes Arch Clin Exp Ophthalmol. E-pub ahead. [PMID: 22527315]

  36. Chu PH, Chan HH, Brown B (2006) Glaucoma detection is facilitated by luminance modulation of the global flash multifocal electroretinogram. Invest Ophthalmol Vis Sci 47(3):929–937

    Article  PubMed  Google Scholar 

  37. Shimada Y, Bearse MA Jr, Sutter EE (2005) Multifocal electroretinograms combined with periodic flashes: direct responses and induced components. Graefes Arch Clin Exp Ophthalmol 243(2):132–141

    Article  PubMed  Google Scholar 

  38. Han Y, Adams AJ, Bearse MA Jr, Schneck ME (2004) Multifocal electroretinogram and short-wavelength automated perimetry measures in diabetic eyes with little or no retinopathy. Arch Ophthalmol 122(12):1809–1815

    Article  PubMed  Google Scholar 

  39. Bearse MA Jr, Han Y, Schneck M, Adams A (2003) Enhancement and mapping of inner retinal contributions to the human multifocal electroretinogram (mfERG). Invest Ophthalmol Vis Sci 44. ARVO E-abstract 2696

  40. Sutter EE, Bearse MA Jr (1999) The optic nerve head component of the human ERG. Vision Res 39(3):419–436

    Article  PubMed  CAS  Google Scholar 

  41. Wu S, Sutter EE (1995) A topographic study of oscillatory potentials in man. Vis Neurosci 12(6):1013–1025

    Article  PubMed  CAS  Google Scholar 

  42. Dersu I, Wiggins MN (2006) Understanding visual fields, Part II; Humphrey visual fields. J Ophthalmic Med Technol 2(3):1–7

    Google Scholar 

  43. Heijl A, Patella VM (2002) Essential perimetry: the field analyzer primer, 3rd edn. Carl Zeiss Meditec AG, Germany

    Google Scholar 

  44. Garway-Heath DF, Holder GE, Fitzke FW, Hitchings RA (2002) Relationship between electrophysiological, psychophysical, and anatomical measurements in glaucoma. Invest Ophthalmol Vis Sci 43(7):2213–2220

    PubMed  Google Scholar 

  45. Garway-Heath DF, Poinoosawmy D, Fitzke FW, Hitchings RA (2000) Mapping the visual field to the optic disc in normal tension glaucoma eyes. Ophthalmology 107(10):1809–1815

    Article  PubMed  CAS  Google Scholar 

  46. Nitta K, Saito Y, Kobayashi A, Sugiyama K (2006) Influence of clinical factors on blue-on-yellow perimetry for diabetic patients without retinopathy: comparison with white-on-white perimetry. Retina 26(7):797–802

    Article  PubMed  Google Scholar 

  47. Remky A, Weber A, Hendricks S, Lichtenberg K, Arend O (2003) Short-wavelength automated perimetry in patients with diabetes mellitus without macular edema. Graefes Arch Clin Exp Ophthalmol 241(6):468–471

    Article  PubMed  Google Scholar 

  48. Bearse MA Jr, Sutter EE (1999) Contrast dependence of multifocal ERG components. Vis Sci Its Appl OSA Tech Dig Ser 1:24–27

    Google Scholar 

  49. Hood DC, Greenstein V, Frishman L, Holopigian K, Viswanathan S, Seiple W, Ahmed J, Robson JG (1999) Identifying inner retinal contributions to the human multifocal ERG. Vision Res 39(13):2285–2291

    Article  PubMed  CAS  Google Scholar 

  50. Sutter EE, Shimada Y, Li Y, Bearse MA Jr (1999) Mapping inner retinal function through enhancement of adaptation components in the M-ERG. Vis Sci Its Appl OSA Tech Dig Ser 1:52–55

    Google Scholar 

  51. Feigl B, Brown B, Lovie-Kitchin J, Swann P (2005) Adaptation responses in early age-related maculopathy. Invest Ophthalmol Vis Sci 46(12):4722–4727

    Article  PubMed  Google Scholar 

  52. 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):3792–3804

    Article  PubMed  Google Scholar 

  53. 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(1):9–19

    Article  PubMed  Google Scholar 

  54. Bearse MA Jr, Adams AJ, Han Y, Schneck ME, Ng J, Bronson-Castain K, Barez S (2006) A multifocal electroretinogram model predicting the development of diabetic retinopathy. Prog Retin Eye Res 25(5):425–448

    Article  PubMed  Google Scholar 

  55. Han Y, Bearse MA Jr, Schneck ME, Barez S, Jacobsen CH, Adams AJ (2004) Multifocal electroretinogram delays predict sites of subsequent diabetic retinopathy. Invest Ophthalmol Vis Sci 45(3):948–954

    Article  PubMed  Google Scholar 

  56. Harrison WW, Bearse MA Jr, Ng JS, Jewell NP, Barez S, Burger D, Schneck ME, Adams AJ (2011) Multifocal electroretinograms predict onset of diabetic retinopathy in adult patients with diabetes. Invest Ophthalmol Vis Sci 52(2):772–777

    Article  PubMed  Google Scholar 

  57. Ng JS, Bearse MA Jr, Schneck ME, Barez S, Adams AJ (2008) Local diabetic retinopathy prediction by multifocal ERG delays over 3 years. Invest Ophthalmol Vis Sci 49(4):1622–1628

    Article  PubMed  Google Scholar 

  58. Sugimoto M, Sasoh M, Ido M, Wakitani Y, Takahashi C, Uji Y (2005) Detection of early diabetic change with optical coherence tomography in type 2 diabetes mellitus patients without retinopathy. Ophthalmologica 219(6):379–385

    Article  PubMed  Google Scholar 

  59. Zhang L, Ino-ue M, Dong K, Yamamoto M (2000) Retrograde axonal transport impairment of large- and medium-sized retinal ganglion cells in diabetic rat. Curr Eye Res 20(2):131–136

    Article  PubMed  CAS  Google Scholar 

  60. Greenstein VC, Hood DC, Ritch R, Steinberger D, Carr RE (1989) S (blue) cone pathway vulnerability in retinitis pigmentosa, diabetes and glaucoma. Invest Ophthalmol Vis Sci 30(8):1732–1737

    PubMed  CAS  Google Scholar 

  61. Jeppesen P, Knudsen ST, Poulsen PL, Mogensen CE, Schmitz O, Bek T (2007) Response of retinal arteriole diameter to increased blood pressure during acute hyperglycaemia. Acta Ophthalmol Scand 85(3):280–286

    Article  PubMed  Google Scholar 

  62. Klemp K, Larsen M, Sander B, Vaag A, Brockhoff PB, Lund-Andersen H (2004) Effect of short-term hyperglycemia on multifocal electroretinogram in diabetic patients without retinopathy. Invest Ophthalmol Vis Sci 45(10):3812–3819

    Article  PubMed  Google Scholar 

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Acknowledgments

This study was supported by the Associated Fund (Research Postgraduate) from the Hong Kong Polytechnic University, Internal Research Grants (GU585, GU858) and the Niche Areas—Myopia Research (J-BB7P) and Glaucoma Research (J-BB76) from the Hong Kong Polytechnic University. Special thanks to Prof. Brian Brown for his valued assistance.

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None of the authors have any proprietary interest.

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Authors and Affiliations

  1. Laboratory of Experimental Optometry (Neuroscience), School of Optometry, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China

    J. C. Y. Lung, P. G. Swann & H. H. L. Chan

  2. School of Optometry, The Queensland University of Technology, Brisbane, QLD, Australia

    P. G. Swann

  3. Eye Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China

    D. S. H. Wong

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  1. J. C. Y. Lung
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  2. P. G. Swann
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  3. D. S. H. Wong
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  4. H. H. L. Chan
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Correspondence to H. H. L. Chan.

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Lung, J.C.Y., Swann, P.G., Wong, D.S.H. et al. Global flash multifocal electroretinogram: early detection of local functional changes and its correlations with optical coherence tomography and visual field tests in diabetic eyes. Doc Ophthalmol 125, 123–135 (2012). https://doi.org/10.1007/s10633-012-9343-0

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  • DOI: https://doi.org/10.1007/s10633-012-9343-0

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