Early neurodegeneration in the retina of type 2 diabetic patients.

PURPOSE The purpose of this study was to determine whether diabetes type 2 causes thinning of retinal layers as a sign of neurodegeneration and to investigate the possible relationship between this thinning and duration of diabetes mellitus, diabetic retinopathy (DR) status, age, sex, and glycemic control (HbA1c). METHODS Mean layer thickness was calculated for retinal layers following automated segmentation of spectral domain optical coherence tomography images of diabetic patients with no or minimal DR and compared with controls. To determine the relationship between layer thickness and diabetes duration, DR status, age, sex, and HbA1c, a multiple linear regression analysis was used. RESULTS In the pericentral area of the macula, the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) were thinner in patients with minimal DR compared to controls (respective difference 1.9 μm, 95% confidence interval [CI] 0.3-3.5 μm; 5.2 μm, 95% CI 1.0-9.3 μm; 4.5 μm, 95% CI 2.2-6.7 μm). In the peripheral area of the macula, the RNFL and IPL were thinner in patients with minimal DR compared to controls (respective difference 3.2 μm, 95% CI 0.1-6.4 μm; 3.3 μm, 95% CI 1.2-5.4 μm). Multiple linear regression analysis showed DR status to be the only significant explanatory variable (R = 0.31, P = 0.03) for this retinal thinning. CONCLUSIONS This study demonstrated thinner inner retinal layers in the macula of type 2 diabetic patients with minimal DR than in controls. These results support the concept that early DR includes a neurodegenerative component.

[1]  Xiaodong Wu,et al.  Intraretinal Layer Segmentation of Macular Optical Coherence Tomography Images Using Optimal 3-D Graph Search , 2008, IEEE Transactions on Medical Imaging.

[2]  G. R. Jackson,et al.  Visual Dysfunction Associated with Diabetic Retinopathy , 2010, Current diabetes reports.

[3]  A. Cavallerano,et al.  Macular thickness and systemic markers for diabetes in individuals with no or mild diabetic retinopathy , 2008, Clinical & experimental ophthalmology.

[4]  T. Gardner,et al.  The significance of vascular and neural apoptosis to the pathology of diabetic retinopathy. , 2011, Investigative ophthalmology & visual science.

[5]  F. Verbraak,et al.  Decreased optical coherence tomography-measured pericentral retinal thickness in patients with diabetes mellitus type 1 with minimal diabetic retinopathy , 2007, British Journal of Ophthalmology.

[6]  M. Schneck,et al.  ADOLESCENTS WITH TYPE 2 DIABETES: Early Indications of Focal Retinal Neuropathy, Retinal Thinning, and Venular Dilation , 2009, Retina.

[7]  E.E. Pissaloux,et al.  Image Processing , 1994, Proceedings. Second Euromicro Workshop on Parallel and Distributed Processing.

[8]  A. Greco,et al.  From functional to microvascular abnormalities in early diabetic retinopathy. , 1997, Diabetes/metabolism reviews.

[9]  Mark Kester,et al.  Diabetic Retinopathy , 2006, Diabetes.

[10]  P. O S I T I O N S T A T E M E N T,et al.  Diagnosis and Classification of Diabetes Mellitus , 2011, Diabetes Care.

[11]  Gábor Márk Somfai,et al.  Early detection of retinal thickness changes in diabetes using Optical Coherence Tomography. , 2010, Medical science monitor : international medical journal of experimental and clinical research.

[12]  M. Sonka,et al.  Association of visual function and ganglion cell layer thickness in patients with diabetes mellitus type 1 and no or minimal diabetic retinopathy , 2011, Vision Research.

[13]  M. Nilsson,et al.  Early detection of macular changes in patients with diabetes using Rarebit Fovea Test and optical coherence tomography , 2007, British Journal of Ophthalmology.

[14]  V. Basevi Diagnosis and Classification of Diabetes Mellitus , 2011, Diabetes Care.

[15]  Xiaodong Wu,et al.  Automated 3-D Intraretinal Layer Segmentation of Macular Spectral-Domain Optical Coherence Tomography Images , 2009, IEEE Transactions on Medical Imaging.

[16]  G. R. Jackson,et al.  An integrated approach to diabetic retinopathy research. , 2011, Archives of ophthalmology.

[17]  Matthew D. Davis,et al.  Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. , 2003, Ophthalmology.

[18]  Michael D. Abràmoff,et al.  Image processing with ImageJ , 2004 .

[19]  Grading diabetic retinopathy from stereoscopic color fundus photographs--an extension of the modified Airlie House classification. ETDRS report number 10. Early Treatment Diabetic Retinopathy Study Research Group. , 1991, Ophthalmology.

[20]  M. Foerster,et al.  6 Diabetic Retinopathy , 2006 .

[21]  T. Gardner,et al.  Functions of insulin and insulin receptor signaling in retina: possible implications for diabetic retinopathy , 2003, Progress in Retinal and Eye Research.

[22]  Milan Sonka,et al.  Decreased retinal ganglion cell layer thickness in patients with type 1 diabetes. , 2010, Investigative ophthalmology & visual science.

[23]  Milan Sonka,et al.  Automated segmentation of intraretinal layers from spectral-domain macular OCT: reproducibility of layer thickness measurements , 2011, Medical Imaging.

[24]  M. Sonka,et al.  Decreased retinal ganglion cell layer thickness in type 1 diabetic patients , 2014 .

[25]  T. Gardner,et al.  Insulin Rescues Retinal Neurons from Apoptosis by a Phosphatidylinositol 3-Kinase/Akt-mediated Mechanism That Reduces the Activation of Caspase-3* , 2001, The Journal of Biological Chemistry.

[26]  R. Simó,et al.  MICROVASCULAR COMPLICATIONS — RETINOPATHY ( JK SUN , SECTION EDITOR ) Neuroprotection in Diabetic Retinopathy , 2012 .

[27]  A. Barber,et al.  A new view of diabetic retinopathy: a neurodegenerative disease of the eye , 2003, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[28]  Milan Sonka,et al.  Selective loss of inner retinal layer thickness in type 1 diabetic patients with minimal diabetic retinopathy. , 2009, Investigative ophthalmology & visual science.

[29]  T. Oshitari,et al.  Changes of macular and RNFL thicknesses measured by Stratus OCT in patients with early stage diabetes , 2009, Eye.