Abstract
The changes in retinal thickness and visual function in type 2 diabetic patients without clinical evidence of diabetic retinopathy were evaluated. A total of 141 diabetic subjects without retinopathy and 158 healthy subjects were enrolled in this study. Superior macular ganglion cell complex thicknesses were significantly decreased in diabetic cases, and no significant peripapillary retinal nerve fiber layer thickness changes were observed. The contrast sensitivities at all space frequencies were significantly different between diabetic patients and controls. The mean P50 amplitude from pattern electroretinogram results was reduced significantly in the diabetic group. In the diabetic group, average superior ganglion cell complex thicknesses positively correlated with both contrast sensitivities at high spatial frequencies and P50 amplitudes. The results indicated that ganglion cell complex thickness and visual function changes could be observed in diabetic subjects before the onset of any significant diabetic retinopathy. Macular ganglion cell complex reduction occurred much earlier than peripapillary retinal nerve fiber layer thinning in diabetic patients without retinopathy.
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UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet, 1988, 352: 854–865
Barber AJ, Lieth E, Khin SA, Antonetti DA, Buchanan AG, Gardner TW. Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin. J Clin Invest, 1998, 102: 783–791
Takano M, Sango K, Horie H, Sato M, Iijima Y, Ohno S, Ihno S, Ishikawa Y. Diabetes alters neurite regeneration from mouse retinal explants in culture. Neurosci Lett, 1999, 275: 175–178
Asnaghi V, Gerhardinger C, Hoehn T, Adeboje A, Lorenzi M. A role for the polyol pathway in the early neuroretinal apoptosis and glial changes induced by diabetes in the rat. Diabetes, 2003, 52: 506–511
Martin PM, Roon P, Van Ells TK, Ganapathy V, Smith SB. Death of retinal neurons in streptozotocin-induced diabetic mice. Invest Ophthalmol Vis Sci, 2004, 45: 3330–3336
Fletcher EL, Phipps JA, Wilkinson-berka JL. Dysfunction of retinal neurons and glia during diabetes. Clin Exp Optom, 2005, 3: 132–145
Goebel W, Kretzchmar-Gross T. Retinal thickness in diabetic retinopathy: a study using optical coherence tomography (OCT). Retina, 2002, 22: 759–767
Sugimoto M, Sasohm, Ido M, Wakitani Y, Takahashi C, Uji Y. Detection of early diabetic change with optical coherence tomography in type 2 diabetes mellitus patients without retinopathy. Ophthalmologica, 2005, 219: 379–385
Lopes de Faria JM, Russ H, Costa VP. Retinal nerve fiber layer loss in patients with type 1 diabetes mellitus without retinopathy. Br J Ophthalmol, 2002, 86: 725–728
Tyberg M, Lindblad U, Melander A, Lovestam-Adrian M, Ponjavic V, Andréasson S. Electrophysiological studies in newly onset type 2 diabetes without visible vascular retinopathy. Doc Ophthalmol, 2011, 123: 193–198
Bronson-Castain KW, Bearse MA Jr, Neuville J, Jonasdottir S, King-Hooper B, Barez S, Schneck ME, Adams AJ. Adolescents with Type 2 diabetes: early indications of focal retinal neuropathy, retinal thinning, and venular dilation. Retina, 2009, 29: 618–626
Di Leo MA, Caputo S, Falsini B, Porciatti V, Minnella A, Greco AV, Ghirlanda G. Nonselective loss of contrast sensitivity in visual system testing in early type I diabetes. Diabetes Care, 1992, 15: 620–625
Várkonyi TT, Petõ T, Dégi R, Keresztes K, Lengyel C, Janáky M, Kempler P, Lonovics J. Impairment of visual evoked potentials: an early central manifestation of diabetic neuropathy? Diabetes Care, 2002, 25: 1661–1662
Abraham FA, Haimovitz J, Berezin M. The photopic and scotopic visual thresholds in diabetics without diabetic retinopathy. Metab Pediatr Syst Ophthalmol, 1988, 11: 76–77
Wilkinson CP, Ferris FL 3rd, Klein RE, Lee PP, Agardh CD, Davis M, Dills D, Kampik A, Pararajasegaram R, Verdaguer JT; Global Diabetic Retinopathy Project Group. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology, 2003, 110: 1677–1682
Bach M1, Brigell MG, Hawlina M, Holder GE, Johnson MA, McCulloch DL, Meigen T, Viswanathan S. ISCEV standard for clinical pattern electroretinography. Doc Ophthalmol, 2007, 114: 111–126
Antonetti DA, Barber AJ, Bronson SK, Freeman WM, Gardner TW, Jefferson LS, Kester M, Kimball SR, Krady JK, LaNoue KF, Norbury CC, Quinn PG, Sandirasegarane L, Simpson IA; JDRF Diabetic Retinopathy Center Group. Diabetic retinopathy: seeing beyond glucose-induced microvascular disease. Diabetes, 2006, 55: 2401–2411
Kim NR, Kim JH, Lee J, Lee ES, Seong GJ, Kim CY. Determinants of perimacular inner retinal layer thickness in normal eyes measured by fourier-domain optical coherence tomography. Invest Ophthalmol Vis Sci, 2011, 52: 3414–3418
Demirkaya N, van Dijk HW, van Schuppen SM, Abràmoff MD, Garvin MK, Sonka M, Schlingemann RO, Verbraak FD. Effect of age on individual retinal layer thickness in normal eyes as measured with spectral-domain optical coherence tomography. Invest Ophthalmol Vis Sci, 2013, 54: 4934–4940
Stela Vujosevic, Midena Edoardo. Retinal layers changes in human preclinical and early clinical diabetic retinopathy support early retinal neuronal and Müller cells alterations. J Diabetes Res, 2013, 2013: 905058
Oshitari T, Hanawa K, Adachi-Usami E. Changes of macular and RNFL thicknesses measured by Stratus OCT in patients with early stage diabetes. Eye (Lond), 2009, 23: 884–889
Park HY, Kim IT, Park CK. Early diabetic changes in the nerve fibre layer at the macula detected by spectral domain optical coherence tomography. Br J Ophthalmol, 2011, 95: 1223–1228
Peng PH, Lin HS, Lin S. Nerve fibre layer thinning in patients with preclinical retinopathy. Can J Ophthalmol, 2009, 44: 417–422
Verma A, Raman R, Vaitheeswaran K, Pal SS, Laxmi G, Gupta M, Shekar SC, Sharma T. Does neuronal damage precede vascular damage in subjects with Type 2 diabetes mellitus and having no clinical diabetic retinopathy? Ophthalmic Res, 2012, 47: 202–207
Blumenthal EZ, Williams JM, Weinreb RN, Girkin CA, Berry CC, Zangwill LM. Reproducibility of nerve fiber layer thickness measurements by use of optical coherence tomography. Ophthalmology, 2000, 107: 2278–2282
Paunescu LA, Schuman JS, Price LL, Stark PC, Beaton S, Ishikawa H, Wollstein G, Fujimoto JG. Reproducibility of nerve fiber thickness, macular thickness, and optical nerve head measurements using StratusOCT. Invest Ophthalmol Vis Sci, 2004, 45: 1716–1724
Savini G, Zanini M, Carelli V, Sadun AA, Ross-Cisneros FN, Barboni P. Correlation between retinal nerve fibre layer thickness and optic nerve head size: an optical coherence tomography study. Br J Ophthalmol, 2005, 89: 489–492
Hood DC, Fortune B, Arthur SN, Xing D, Salant JA, Ritch R, Liebmann JM. Blood vessel contributions to retinal nerve fiber layer thickness profiles measured with optical coherence tomography. J Glaucoma, 2008, 17: 519–528
Kim NR, Lee ES, Seong GJ, Kim JH, An HG, Kim CY. Structure-function relationship and diagnostic value of macular ganglion cell complex measurement using Fourier-domain OCT in glaucoma. Invest Ophthalmol Vis Sci, 2010, 51: 4646–4651
van Dijk HW, Verbraak FD, Kok PH, Garvin MK, Sonka M, Lee K, Devries JH, Michels RP, van Velthoven ME, Schlingemann RO, Abràmoff MD. Decreased retinal ganglion cell layer thickness in patients with type 1 diabetes. Invest Ophthalmol Vis Sci, 2010, 51: 3660–3665
van Dijk HW, Verbraak FD, Kok PH, Stehouwer M, Garvin MK, Sonka M, DeVries JH, Schlingemann RO, Abràmoff MD. Early neurodegeneration in the retina of type 2 diabetic patients. Invest Ophthalmol Vis Sci, 2012, 53: 2715–2719
Quigley HA, Addicks EM. Quantitative studies of retinal nerve fiber layer defects. Arch Ophthalmol, 1982, 100: 807–814
Harwerth RS, Wheat JL, Fredette MJ, Anderson DR. Linking structure and function in glaucoma. Prog Retin Eye Res, 2010, 29: 249–271
Kern TS, Engerman RL. Vascular lesions in diabetes are distributed non-uniformly within the retina. Exp Eye Res, 1995, 60: 545–549
Ewing FM, Deary IJ, Strachan MW, Frier BM. Seeing beyond retinopathy in diabetes: electrophysiological and psychophysical abnormalities and alterations in vision. Endocr Rev, 1998, 19: 462–476
North RV, Farrell U, Banford D, Jones C, Gregory JW, Butler G, Owens DR. Visual function in young IDDM patients over 8 years of age: a 4-year longitudinal study. Diabetes Care, 1997, 20: 1724–1730
Fletcher EL, Phipps JA, Ward MM, Puthussery T, Wilkinson-Berka JL. Neuronal and glial cell abnormality as predictors of progression of diabetic retinopathy. Curr Pharmaceut Design, 2007, 13: 2699–2712
Dosso AA, Yenice-Ustun F, Sommerhalder J, Golay A, Morel Y, Leuenberer PM. Contrast sensitivity in obese dyslipidemic patients with insulin resistance. Arch Ophthalmol, 1998, 116: 1316–1320
Lieth E, Gardner TW, Barber AJ, Antonetti DA; Penn State Retina Research Group. Retinal neurodegeneration: early pathology in diabetes. Clin Exp Ophthalmol, 2000, 26: 3–8
Shapley R, Perry VH. Cat and monkey retinal ganglion cells and their visual functional roles. Trends Neurosci, 1986, 9: 229–235
Maffei L, Fiorentini A. Electroretinographic responses to alternating gratings before and after section of the optic nerve. Science, 1981, 211: 953–955
Hood DC, Frishman LJ, Viswanathan S, Robson JG, Ahmed J. Evidence for a ganglion cell contribution to the primate electroretinogram (ERG): effects of TTX on the multifocal ERG in macaque. Vis Neurosci, 1999, 16: 411–416
Ventura LM, Porciatti V. Restoration of retinal ganglion cell function in early glaucoma after intraocular pressure reduction: a pilot study. Ophthalmology, 2005, 112: 20–27
Ng JS, Bearse MA Jr, Schneck ME, Barez S, Adams AJ. Local diabetic retinopathy prediction by multifocal ERG delays over 3 years. Invest Ophthalmol Vis Sci, 2008, 49: 1622–1628
Reiter CE, Gardner TW. Functions of insulin and insulin receptor signaling in retina: possible implications for diabetic retinopathy. Prog Retin Eye Res, 2003, 22: 545–562
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Zhu, T., Ma, J., Li, Y. et al. Association between retinal neuronal degeneration and visual function impairment in type 2 diabetic patients without diabetic retinopathy. Sci. China Life Sci. 58, 550–555 (2015). https://doi.org/10.1007/s11427-015-4858-8
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DOI: https://doi.org/10.1007/s11427-015-4858-8