Selective loss of inner retinal layer thickness in type 1 diabetic patients with minimal diabetic retinopathy.

PURPOSE To determine whether type 1 diabetes preferentially affects the inner retinal layers by comparing the thickness of six retinal layers in type 1 diabetic patients who have no or minimal diabetic retinopathy (DR) with those of age- and sex-matched healthy controls. METHODS Fifty-seven patients with type 1 diabetes with no (n = 32) or minimal (n = 25) DR underwent full ophthalmic examination, stereoscopic fundus photography, and optical coherence tomography (OCT). After automated segmentation of intraretinal layers of the OCT images, mean thickness was calculated for six layers of the retina in the fovea, the pericentral area, and the peripheral area of the central macula and were compared with those of an age- and sex-matched control group. RESULTS In patients with minimal DR, the mean ganglion cell/inner plexiform layer was 2.7 microm thinner (95% confidence interval [CI], 2.1-4.3 microm) and the mean inner nuclear layer was 1.1 microm thinner (95% CI, 0.1-2.1 microm) in the pericentral area of the central macula compared to those of age-matched controls. In the peripheral area, the mean ganglion cell/inner plexiform layer remained significantly thinner. No other layers showed a significant difference. CONCLUSIONS Thinning of the total retina in type 1 diabetic patients with minimal retinopathy compared with healthy controls is attributed to a selective thinning of inner retinal layers and supports 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]  M. Schneck,et al.  Multifocal electroretinogram and short-wavelength automated perimetry measures in diabetic eyes with little or no retinopathy. , 2004, Archives of ophthalmology.

[3]  T. Gardner,et al.  Retinal neurodegeneration: early pathology in diabetes , 2000, Clinical & experimental ophthalmology.

[4]  T. Gardner,et al.  Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin. , 1998, The Journal of clinical investigation.

[5]  A. Barber,et al.  Loss of cholinergic and dopaminergic amacrine cells in streptozotocin-diabetic rat and Ins2Akita-diabetic mouse retinas. , 2006, Investigative ophthalmology & visual science.

[6]  M. Chun,et al.  Apoptotic death of photoreceptors in the streptozotocin-induced diabetic rat retina , 2003, Diabetologia.

[7]  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.

[8]  Carmen A Puliafito,et al.  Automated detection of retinal layer structures on optical coherence tomography images. , 2005, Optics express.

[9]  D. Foster,et al.  Detection of colour vision abnormalities in uncomplicated type 1 diabetic patients with angiographically normal retinas. , 1992, The British journal of ophthalmology.

[10]  E. Ling,et al.  Neuronal and microglial response in the retina of streptozotocin-induced diabetic rats , 2000, Visual Neuroscience.

[11]  T. Realini,et al.  Impact of diabetes on glaucoma screening using frequency-doubling perimetry. , 2004, Ophthalmology.

[12]  D. Puro,et al.  Diabetes-induced dysfunction of the glutamate transporter in retinal Müller cells. , 2002, Investigative ophthalmology & visual science.

[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]  A. Barber,et al.  Glial reactivity and impaired glutamate metabolism in short-term experimental diabetic retinopathy. Penn State Retina Research Group. , 1998, Diabetes.

[15]  M. Brownlee Biochemistry and molecular cell biology of diabetic complications , 2001, Nature.

[16]  Allen R Kunselman,et al.  Dendrite remodeling and other abnormalities in the retinal ganglion cells of Ins2 Akita diabetic mice. , 2008, Investigative ophthalmology & visual science.

[17]  A. Kurtenbach,et al.  Anomaloscope matches in patients with diabetes mellitus , 2002, Graefe's Archive for Clinical and Experimental Ophthalmology.

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

[19]  Luc Missotten,et al.  Expression of apoptosis markers in the retinas of human subjects with diabetes. , 2004, Investigative ophthalmology & visual science.

[20]  P. Leuenberger,et al.  Glial reactivity, an early feature of diabetic retinopathy. , 2000, Investigative ophthalmology & visual science.

[21]  M. Schneck,et al.  Local multifocal oscillatory potential abnormalities in diabetes and early diabetic retinopathy. , 2004, Investigative ophthalmology & visual science.

[22]  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.

[23]  D. Browning,et al.  The relationship of macular thickness to clinically graded diabetic retinopathy severity in eyes without clinically detected diabetic macular edema. , 2008, Ophthalmology.

[24]  Xiaodong Wu,et al.  Automated segmentation of intraretinal layers from macular optical coherence tomography images , 2007, SPIE Medical Imaging.

[25]  A J Adams,et al.  Multifocal electroretinogram delays reveal local retinal dysfunction in early diabetic retinopathy. , 1999, Investigative ophthalmology & visual science.

[26]  G. King,et al.  The cellular and molecular mechanisms of diabetic complications. , 1996, Endocrinology and metabolism clinics of North America.

[27]  T. Gardner,et al.  The Ins2Akita mouse as a model of early retinal complications in diabetes. , 2005, Investigative ophthalmology & visual science.

[28]  C. Gerhardinger,et al.  Müller cell changes in human diabetic retinopathy. , 1998, Diabetes.

[29]  V. Greenstein,et al.  Psychophysical evidence for post-receptoral sensitivity loss in diabetics. , 1992, Investigative ophthalmology & visual science.

[30]  Hiroshi Ishikawa,et al.  Macular segmentation with optical coherence tomography. , 2005, Investigative ophthalmology & visual science.

[31]  Xiaodong Wu,et al.  Incorporation of Regional Information in Optimal 3-D Graph Search with Application for Intraretinal Layer Segmentation of Optical Coherence Tomography Images , 2007, IPMI.

[32]  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.

[33]  T. Sano,et al.  [Diabetic retinopathy]. , 2001, Nihon rinsho. Japanese journal of clinical medicine.

[34]  T. Gardner,et al.  Excessive Hexosamines Block the Neuroprotective Effect of Insulin and Induce Apoptosis in Retinal Neurons* , 2001, The Journal of Biological Chemistry.

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

[36]  V. Ganapathy,et al.  Death of retinal neurons in streptozotocin-induced diabetic mice. , 2004, Investigative ophthalmology & visual science.

[37]  Xiaodong Wu,et al.  Use of Varying Constraints in Optimal 3-D Graph Search for Segmentation of Macular Optical Coherence Tomography Images , 2007, MICCAI.

[38]  M A Bearse,et al.  Assessment of early retinal changes in diabetes using a new multifocal ERG protocol. , 2001, The British journal of ophthalmology.

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