Multifocal electroretinogram delays reveal local retinal dysfunction in early diabetic retinopathy.

PURPOSE To identify local retinal abnormalities in diabetic patients with and without retinopathy, by using the multifocal electroretinogram (M-ERG). METHODS Electroretinograms were recorded at 103 discrete retinal locations in each eye of eight persons with nonproliferative diabetic retinopathy (NPDR) and eight diabetic persons without retinopathy, using VERIS (EDI, San Mateo, CA). The amplitude and implicit time of each local (first-order) retinal response were derived and compared with normal values obtained from 16 age-matched, nondiabetic subjects. Maps of local response amplitude and implicit time were compared with fundus photographs taken at the time of testing. RESULTS In eyes with NPDR, the implicit times of responses from retinal sites manifesting clinical pathologic fundus lesions (e.g., microaneurysms and focal edema), were markedly delayed (e.g., up to 7 msec from normal). Responses from adjacent retinal sites that were more normal in clinical appearance were also delayed, but to a lesser extent (e.g., 2-5 msec). Smaller, yet significant local response delays were also found in eyes without retinopathy. By contrast, local response amplitudes bore no consistent relationship to fundus abnormalities in eyes with retinopathy, and amplitudes were typically normal in eyes without retinopathy. CONCLUSIONS The M-ERG reveals local retinal dysfunction in diabetic eyes even before retinopathy. The magnitude of delay of local ERG implicit time reflects the degree of local clinical abnormality in eyes with retinopathy. Local response delays found in some eyes without retinopathy suggest that the M-ERG detects subclinical local retinal dysfunction in diabetes. Analysis of M-ERG implicit time, independent of amplitude, improves the sensitivity of detection of local retinal dysfunction in diabetes.

[1]  K. Nakagawa,et al.  The relation between expression of vascular endothelial growth factor and breakdown of the blood-retinal barrier in diabetic rat retinas. , 1996, Laboratory investigation; a journal of technical methods and pathology.

[2]  G. Lutty,et al.  Choriocapillaris degeneration and related pathologic changes in human diabetic eyes. , 1998, Archives of ophthalmology.

[3]  S. Smith Nonproliferative diabetic retinopathy and macular edema. , 1999, Insight.

[4]  Joan W. Miller,et al.  Cloning and mRNA expression of vascular endothelial growth factor in ischemic retinas of Macaca fascicularis. , 1996, Investigative ophthalmology & visual science.

[5]  S E Simonsen,et al.  THE VALUE OF THE OSCILLATORY POTENTIAL IN SELECTING JUVENILE DIABETICS AT RISK OF DEVELOPING PROLIFERATIVE RETINOPATHY , 1980, Metabolic and pediatric ophthalmology.

[6]  Michael Bach,et al.  Principles and practice of clinical electrophysiology of vision , 1991 .

[7]  E Zrenner,et al.  Implicit time topography of multifocal electroretinograms. , 1998, Investigative ophthalmology & visual science.

[8]  B. Brown,et al.  Contrast and luminance as parameters defining the output of the VERIS topographical ERG. , 1996, Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians.

[9]  W Seiple,et al.  A comparison of the components of the multifocal and full-field ERGs , 1997, Visual Neuroscience.

[10]  H. Suzuki,et al.  Ocular vascular endothelial growth factor levels in diabetic rats are elevated before observable retinal proliferative changes , 1997, Diabetologia.

[11]  C. Karwoski,et al.  Current source density analysis of retinal field potentials. II. Pharmacological analysis of the b-wave and M-wave. , 1994, Journal of neurophysiology.

[12]  L. Lanting,et al.  Effects of high glucose on vascular endothelial growth factor expression in vascular smooth muscle cells. , 1997, The American journal of physiology.

[13]  M Palta,et al.  Predicting progression to severe proliferative diabetic retinopathy. , 1987, Archives of ophthalmology.

[14]  R. Carr,et al.  Evidence for photoreceptor changes in patients with diabetic retinopathy. , 1997, Investigative Ophthalmology and Visual Science.

[15]  H Iijima,et al.  Photopic electroretinogram implicit time in diabetic retinopathy. , 1994, Japanese journal of ophthalmology.

[16]  D. Hood,et al.  Human cone receptor activity: The leading edge of the a–wave and models of receptor activity , 1993, Visual Neuroscience.

[17]  S. Kondo,et al.  Vascular endothelial growth factor is induced by long-term high glucose concentration and up-regulated by acute glucose deprivation in cultured bovine retinal pigmented epithelial cells. , 1996, Biochemical and biophysical research communications.

[18]  Y. Hata,et al.  Vascular endothelial growth factor plays a role in hyperpermeability of diabetic retinal vessels. , 1995, Ophthalmic research.

[19]  H. Hammes,et al.  Upregulation of the vascular endothelial growth factor/vascular endothelial growth factor receptor system in experimental background diabetic retinopathy of the rat. , 1998, Diabetes.

[20]  B. Gallacher,et al.  Glucose-Induced Protein Kinase C Activation Regulates Vascular Permeability Factor mRNA Expression and Peptide Production by Human Vascular Smooth Muscle Cells In Vitro , 1997, Diabetes.

[21]  R. Linsenmeier,et al.  Retinal hypoxia in long-term diabetic cats. , 1998, Investigative ophthalmology & visual science.

[22]  M A Bearse,et al.  Imaging localized retinal dysfunction with the multifocal electroretinogram. , 1996, Journal of the Optical Society of America. A, Optics, image science, and vision.

[23]  L. Aiello,et al.  Hypoxic regulation of vascular endothelial growth factor in retinal cells. , 1995, Archives of ophthalmology.

[24]  D. Eliott,et al.  Vascular endothelial growth factor is present in glial cells of the retina and optic nerve of human subjects with nonproliferative diabetic retinopathy. , 1997, Investigative ophthalmology & visual science.

[25]  P. Sieving,et al.  Push–pull model of the primate photopic electroretinogram: A role for hyperpolarizing neurons in shaping the b-wave , 1994, Visual Neuroscience.

[26]  C. Karwoski,et al.  Current source density analysis of the electroretinographic d wave of frog retina. , 1995, Journal of neurophysiology.

[27]  W Seiple,et al.  A comparison of photopic and scotopic electroretinographic changes in early diabetic retinopathy. , 1992, Investigative ophthalmology & visual science.

[28]  D. Hood,et al.  Beta wave of the scotopic (rod) electroretinogram as a measure of the activity of human on-bipolar cells. , 1996, Journal of the Optical Society of America. A, Optics, image science, and vision.

[29]  M A Bearse,et al.  Mapping of retinal function in diabetic retinopathy using the multifocal electroretinogram. , 1997, Investigative ophthalmology & visual science.

[30]  G. Lutty,et al.  Vascular endothelial growth factor and vascular permeability changes in human diabetic retinopathy. , 1997, Investigative ophthalmology & visual science.

[31]  M. Palta,et al.  Oscillatory potential amplitudes. Relation to severity of diabetic retinopathy. , 1987, Archives of ophthalmology.

[32]  Erich E. Sutter,et al.  The field topography of ERG components in man—I. The photopic luminance response , 1992, Vision Research.

[33]  P. Sieving,et al.  A proximal retinal component in the primate photopic ERG a-wave. , 1994, Investigative ophthalmology & visual science.

[34]  Joan W. Miller,et al.  Intravitreous injections of vascular endothelial growth factor produce retinal ischemia and microangiopathy in an adult primate. , 1996, Ophthalmology.

[35]  P. Sieving,et al.  Inner retinal contributions to the primate photopic fast flicker electroretinogram. , 1996, Journal of the Optical Society of America. A, Optics, image science, and vision.

[36]  E S Gragoudas,et al.  Intravitreous injections of vascular endothelial growth factor produce retinal ischemia and microangiopathy in an adult primate. , 1996, Ophthalmology.

[37]  Kazuo Kawasaki,et al.  Electrical responses from diabetic retina , 1998, Progress in Retinal and Eye Research.

[38]  M Palta,et al.  Temporal aspects of the electroretinogram in diabetic retinopathy. , 1987, Archives of ophthalmology.

[39]  E Zrenner,et al.  Multifocal electroretinography in retinitis pigmentosa. , 1998, American journal of ophthalmology.

[40]  Fundus photographic risk factors for progression of diabetic retinopathy. ETDRS report number 12. Early Treatment Diabetic Retinopathy Study Research Group. , 1991, Ophthalmology.

[41]  K. Tsuzuki,et al.  Electroretinogram in diabetic retinopathy. , 1962, Archives of ophthalmology.