ANALYSIS OF RETINAL CAPILLARIES IN PATIENTS WITH TYPE 1 DIABETES AND NONPROLIFERATIVE DIABETIC RETINOPATHY USING ADAPTIVE OPTICS IMAGING

Purpose: To illustrate a noninvasive method to analyze the retinal capillary lumen caliber in patients with Type 1 diabetes. Methods: Adaptive optics imaging of the retinal capillaries were acquired in two parafoveal regions of interest in eyes with nonproliferative diabetic retinopathy and unaffected controls. Measures of the retinal capillary lumen caliber were quantified using an algorithm written in Matlab by an independent observer in a masked manner. Comparison of the adaptive optics images with red-free and color wide fundus retinography images was also assessed. Results: Eight eyes with nonproliferative diabetic retinopathy (eight patients, study group), no macular edema, and preserved visual acuity and eight control eyes (eight healthy volunteers; control group) were analyzed. The repeatability of capillary lumen caliber measurements was 0.22 &mgr;m (3.5%) with the 95% confidence interval between 0.12 and 0.31 &mgr;m in the study group. It was 0.30 &mgr;m (4.1%) with the 95% confidence interval between 0.16 and 0.43 &mgr;m in the control group. The average capillary lumen caliber was significantly narrower in eyes with nonproliferative diabetic retinopathy (6.27 ± 1.63 &mgr;m) than in the control eyes (7.31 ± 1.59 &mgr;m, P = 0.002). Conclusion: The authors demonstrated a noninvasive method to analyze, with micrometric scale of resolution, the lumen of retinal capillaries. The parafoveal capillaries were narrower in patients with Type 1 diabetes and nonproliferative diabetic retinopathy than in healthy subjects, showing the potential capability of adaptive optics imaging to detect pathologic variations of the retinal microvascular structures in vaso-occlusive diseases.

[1]  Seiyo Harino,et al.  Relationship between macular microcirculation and progression of diabetic macular edema. , 2006, Ophthalmology.

[2]  Mette Owner-Petersen,et al.  Noninvasive imaging of human foveal capillary network using dual-conjugate adaptive optics. , 2011, Investigative ophthalmology & visual science.

[3]  Amiram Grinvald,et al.  Functional imaging using the retinal function imager: Direct imaging of blood velocity, achieving fluorescein angiography-like images without any contrast agent, qualitative oximetry, and functional metabolic signals , 2009, Japanese Journal of Ophthalmology.

[4]  A. Albert,et al.  Risk of developing retinopathy in Diabetes Control and Complications Trial type 1 diabetic patients with good or poor metabolic control. , 2001, Diabetes care.

[5]  D McLeod,et al.  Three dimensional analysis of microaneurysms in the human diabetic retina , 1999, Journal of anatomy.

[6]  R. Kronmal,et al.  Measurement of retinal vascular caliber: issues and alternatives to using the arteriole to venule ratio. , 2007, Investigative ophthalmology & visual science.

[7]  Toco Y P Chui,et al.  The use of forward scatter to improve retinal vascular imaging with an adaptive optics scanning laser ophthalmoscope , 2012, Biomedical optics express.

[8]  D G Altman,et al.  Statistics Notes: Measurement error proportional to the mean , 1996, BMJ.

[9]  Marco Lombardo,et al.  Adaptive optics photoreceptor imaging. , 2012, Ophthalmology.

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

[11]  T. Wong,et al.  Retinal Vascular Changes in Pre-Diabetes and Prehypertension , 2007, Diabetes Care.

[12]  R. Leitgeb,et al.  Visualization of microvasculature by dual-beam phase-resolved Doppler optical coherence tomography. , 2011, Optics express.

[13]  G. Lutty,et al.  Relationship of polymorphonuclear leukocytes to capillary dropout in the human diabetic choroid. , 1997, The American journal of pathology.

[14]  Austin Roorda,et al.  Speed quantification and tracking of moving objects in adaptive optics scanning laser ophthalmoscopy. , 2011, Journal of biomedical optics.

[15]  S. Burns,et al.  In vivo measurement of erythrocyte velocity and retinal blood flow using adaptive optics scanning laser ophthalmoscopy. , 2008, Optics express.

[16]  I. Barchetta,et al.  High prevalence of capillary abnormalities in patients with diabetes and association with retinopathy , 2011, Diabetic medicine : a journal of the British Diabetic Association.

[17]  Shuichi Makita,et al.  Comprehensive in vivo micro-vascular imaging of the human eye by dual-beam-scan Doppler optical coherence angiography. , 2011, Optics express.

[18]  Barry Cense,et al.  Imaging retinal capillaries using ultrahigh-resolution optical coherence tomography and adaptive optics. , 2011, Investigative ophthalmology & visual science.

[19]  D M Snodderly,et al.  Comparison of fluorescein angiography with microvascular anatomy of macaque retinas. , 1995, Experimental eye research.

[20]  Nagahisa Yoshimura,et al.  Foveal cystoid spaces are associated with enlarged foveal avascular zone and microaneurysms in diabetic macular edema. , 2011, Ophthalmology.

[21]  T. Wong,et al.  Retinal vessel diameter as a clinical predictor of diabetic retinopathy progression: time to take out the measuring tape. , 2011, Archives of ophthalmology.

[22]  T. Kern,et al.  Contributions of Inflammatory Processes to the Development of the Early Stages of Diabetic Retinopathy , 2007, Experimental diabetes research.

[23]  R. Engerman,et al.  Pathogenesis of Diabetic Retinopathy , 1989, Diabetes.

[24]  Ruikang K. Wang,et al.  In vivo volumetric imaging of vascular perfusion within human retina and choroids with optical micro-angiography. , 2008, Optics express.

[25]  F Jung,et al.  Retinal microcirculation in patients with diabetes mellitus: dynamic and morphological analysis of perifoveal capillary network. , 1991, The British journal of ophthalmology.

[26]  Hiroshi Imamura,et al.  The source of moving particles in parafoveal capillaries detected by adaptive optics scanning laser ophthalmoscopy. , 2012, Investigative ophthalmology & visual science.

[27]  T. Bek,et al.  Three‐dimensional structure of human retinal vessels studied by vascular casting , 1993, Acta ophthalmologica.

[28]  Kaccie Y. Li,et al.  Intersubject variability of foveal cone photoreceptor density in relation to eye length. , 2010, Investigative ophthalmology & visual science.

[29]  Arthur Bradley,et al.  Entoptic image quality of the retinal vasculature , 1998, Vision Research.

[30]  Peter F. Sharp,et al.  Automated microaneurysm detection using local contrast normalization and local vessel detection , 2006, IEEE Transactions on Medical Imaging.

[31]  Nancy J. Coletta,et al.  Effect of myopia on visual acuity measured with laser interference fringes , 2006, Vision Research.

[32]  G T Feke,et al.  Retinal circulatory abnormalities in type 1 diabetes. , 1994, Investigative ophthalmology & visual science.

[33]  Austin Roorda,et al.  Noninvasive visualization and analysis of parafoveal capillaries in humans. , 2010, Investigative ophthalmology & visual science.

[34]  Ronald Klein,et al.  The Wisconsin Epidemiologic Study of Diabetic Retinopathy XXIII: the twenty-five-year incidence of macular edema in persons with type 1 diabetes. , 2009, Ophthalmology.

[35]  Wynne Hsu,et al.  Alterations in Retinal Microvascular Geometry in Young Type 1 Diabetes , 2010, Diabetes Care.

[36]  Dao-Yi Yu,et al.  Microstructure and network organization of the microvasculature in the human macula. , 2010, Investigative ophthalmology & visual science.

[37]  A. Bradley,et al.  Entoptic evaluation of diabetic retinopathy. , 1997, Investigative ophthalmology & visual science.

[38]  G. Jerums,et al.  Pathogenesis and intervention strategies in diabetic retinopathy. , 2001, Clinical & experimental ophthalmology.

[39]  Christian Ahlers,et al.  Imaging of the parafoveal capillary network and its integrity analysis using fractal dimension , 2011, Biomedical optics express.

[40]  Mohit Chopra,et al.  Pathophysiology of Diabetic Retinopathy , 2013, ISRN ophthalmology.

[41]  A. Hendrickson,et al.  Vascular development in primate retina: comparison of laminar plexus formation in monkey and human. , 1994, Investigative ophthalmology & visual science.

[42]  Aminoguanidine treatment inhibits the development of experimental diabetic retinopathy. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[43]  Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group. , 1985, Archives of ophthalmology.

[44]  Daniel M. Schwartz,et al.  In vivo volumetric imaging of human retinal circulation with phase-variance optical coherence tomography , 2011, Biomedical optics express.

[45]  D. Snodderly,et al.  Neural-vascular relationships in central retina of macaque monkeys (Macaca fascicularis) , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[46]  Tien Yin Wong,et al.  Relationship of Retinal Vascular Caliber With Diabetes and Retinopathy , 2008, Diabetes Care.

[47]  Daniel X Hammer,et al.  Foveal fine structure in retinopathy of prematurity: an adaptive optics Fourier domain optical coherence tomography study. , 2008, Investigative ophthalmology & visual science.

[48]  J. Cunha-Vaz,et al.  Breakdown of the inner and outer blood retinal barrier in streptozotocin-induced diabetes. , 1998, Experimental eye research.

[49]  Rachel E Witt,et al.  Comparative study of the retinal vessel anatomy of rhesus monkeys and humans , 2010, Clinical & experimental ophthalmology.

[50]  Jungtae Rha,et al.  Adaptive optics flood-illumination camera for high speed retinal imaging. , 2003, Optics express.

[51]  N Drasdo,et al.  Non-linear projection of the retinal image in a wide-angle schematic eye. , 1974, The British journal of ophthalmology.

[52]  A. Bharath,et al.  Computer algorithms for the automated measurement of retinal arteriolar diameters , 2001, The British journal of ophthalmology.

[53]  Austin Roorda,et al.  Characterization of single-file flow through human retinal parafoveal capillaries using an adaptive optics scanning laser ophthalmoscope , 2011, Biomedical optics express.

[54]  Hao Li,et al.  Measurement of oxygen saturation in small retinal vessels with adaptive optics confocal scanning laser ophthalmoscope. , 2011, Journal of biomedical optics.

[55]  David R Williams,et al.  In-vivo imaging of retinal nerve fiber layer vasculature: imaging - histology comparison , 2009, BMC ophthalmology.

[56]  Alfredo Dubra,et al.  Relationship between the foveal avascular zone and foveal pit morphology. , 2012, Investigative ophthalmology & visual science.

[57]  H. Parving,et al.  Early changes in diabetic retinopathy: Capillary loss and blood‐retina barrier permeability in relation to metabolic control , 1994, Acta ophthalmologica.

[58]  Dao-Yi Yu,et al.  Correlation of histologic and clinical images to determine the diagnostic value of fluorescein angiography for studying retinal capillary detail. , 2010, Investigative ophthalmology & visual science.

[59]  Ronald Klein,et al.  Changes in retinal vessel diameter and incidence and progression of diabetic retinopathy. , 2012, Archives of ophthalmology.

[60]  T. Kern,et al.  Vascular lesions in diabetes are distributed non-uniformly within the retina. , 1995, Experimental eye research.

[61]  D. Altman,et al.  Statistics Notes: Measurement error and correlation coefficients , 1996, BMJ.

[62]  E. Kohner,et al.  Leukocytes in diabetic retinopathy. , 2007, Current diabetes reviews.

[63]  Oddbjørn Engvold,et al.  Microphotometry of the blood column and the light streak on retinal vessels in fundus photographs , 1986 .

[64]  I. Herman,et al.  Microvascular Modifications in Diabetic Retinopathy , 2011, Current diabetes reports.

[65]  Michel Paques,et al.  Structural and hemodynamic analysis of the mouse retinal microcirculation. , 2003, Investigative ophthalmology & visual science.

[66]  Ronald Klein,et al.  The relation of retinal vessel caliber to the incidence and progression of diabetic retinopathy: XIX: the Wisconsin Epidemiologic Study of Diabetic Retinopathy. , 2004, Archives of ophthalmology.

[67]  Austin Roorda,et al.  Disruption of the retinal parafoveal capillary network in type 2 diabetes before the onset of diabetic retinopathy. , 2011, Investigative ophthalmology & visual science.

[68]  Marco Lombardo,et al.  Variations in image optical quality of the eye and the sampling limit of resolution of the cone mosaic with axial length in young adults , 2012, Journal of cataract and refractive surgery.

[69]  A. Yoshida,et al.  Retinal blood flow changes in type I diabetes. A long-term follow-up study. , 1996, Investigative ophthalmology & visual science.

[70]  Austin Roorda,et al.  Subclinical Capillary Changes in Non-Proliferative Diabetic Retinopathy , 2012, Optometry and vision science : official publication of the American Academy of Optometry.