Purpose: To assess the reliability of microaneurysm turnover, computed from color fundus photographs, in evaluating diabetic retinopathy in patients with type 2 diabetes and nonproliferative retinopathy. Methods: A new method (MA-Tracker) was developed to count microaneurysms by mapping their locations through image co-registration. To compute the reliability of microaneurysm turnover, 3 different graders were asked to earmark microaneurysms on the same set of color fundus photographs. Results: The total numbers of microaneurysms earmarked in each of 5 visits suggest that microaneurysms remain stable over time (p ≥ 0.138). However, an analysis of each microaneurysm showed that only 29.4% remained at the same location. By computing the formation and disappearance rates of microaneurysms (2.3 and 1.7 microaneurysms/year, respectively), a significant turnover of microaneurysms was found. Conclusions: The formation and disappearance rates of microaneurysms obtained from color fundus photographs using MA-Tracker show very good agreement between different graders, and can be used as indicators of microaneurysm turnover in the initial stages of diabetic retinopathy.

Keywords:
Microaneurysm count, Microaneurysm turnover, Microaneurysm formation rate, Microaneurysm disappearance rate, Diabetic retinopathy, Image co-registration, Color fundus photography
1.
Cunha-Vaz J: Characterization and relevance of different diabetic retinopathy phenotypes. Dev Ophthalmol 2007;39:13–30.
2.
Kohner EM, Stratton IM, Aldington SJ, Turner RC, Matthews DR: Microaneurysms in the development of diabetic retinopathy (UKPDS 42). UK Prospective Diabetes Study Group. Diabetologia 1999;42:1107–1112.
3.
Hove MN, Kristensen JK, Lauritzen T, Bek T: The relationships between risk factors and the distribution of retinopathy lesions in type 2 diabetes. Acta Ophthalmol Scand 2006;84:619–623.
4.
Klein R, Klein B, Moss SE, Cruickshanks KJ: The Wisconsin epidemiologic study of diabetic retinopathy. XV. The long-term incidence of macular edema. Ophthalmology 1995;102:7–16.
5.
Hellstedt T, Immonen I: Disappearance and formation rates of microaneurysms in early diabetic retinopathy. Br J Ophthalmol 1996;80:135–139.
6.
Kohner EM: Microvascular disease: what does the UKPDS tell us about diabetic retinopathy? Diabet Med 2008;25(suppl 2):20–24.
7.
Frame AJ, Undrill PE, Cree MJ, Olson JA, McHardy KC, Sharp PF, Forrester JV: A comparison of computer based classification methods applied to the detection of microaneurysms in ophthalmic fluorescein angiograms. Comput Biol Med 1998;28:225–238.
8.
Ege BM, Hejlesen OK, Larsen OV, Møller K, Jennings B, Kerr D, Cavan DA: Screening for diabetic retinopathy using computer based image analysis and statistical classification. Comput Methods Programs Biomed 2000;62:165–175.
9.
Teng T, Lefley M, Claremont D: Progress towards automated diabetic ocular screening: a review of image analysis and intelligent systems for diabetic retinopathy. Med Biol Eng Comput 2002;40:2–13.
10.
Goatman KA, Cree MJ, Olson JA, Forrester JV, Sharp PF: Automated measurement of microaneurysm turnover. Invest Ophthalmol Vis Sci 2003;44:5335–5341.
11.
Quellec G, Lamard M, Josselin PM, Cazuguel G, Cochener B, Roux C: Optimal wavelet transform for the detection of microaneurysms in retina photographs. IEEE Trans Med Imaging 2008;27:1230–1241.
12.
Ferreira J, Bernardes R, Baptista P, Cunha-Vaz J: Earmarking retinal changes in a sequence of digital color fundus photographs. 3rd Eur Med Biol Eng Conf, Prague, IFMBE Proc 2005, vol 11.
13.
Petrou M, Bosdogianni P: Image Processing: The Fundamentals. Chichester, John Wiley & Sons, 1999.
14.
Foracchia M, Grisan E, Ruggeri A: Luminosity and contrast normalization in retinal images. Med Image Anal 2005;9:179–190.
15.
Sinthanayothin C, Boyce J, Cook H, Williamson T: Automated localisation of the optic disc, fovea, and retinal blood vessels from digital colour fundus images. Br J Ophthalmol 1999;83:902–910.
16.
Tek H, Comaniciu D, Williams J: Vessel detection by mean shift based ray propagation. IEEE Workshop Math Methods Biomed Image Analysis, 2001, pp 228–235.
17.
Matsopoulos G, Asvestas P, Mouravliansky N, Delibasis K: Multimodal registration of retinal images using self organizing maps. IEEE Trans Med Imaging 2004;23:1557–1563.
18.
Bernardes R, Baptista P, Dias J, Cunha-Vaz J: Multimodal functional and morphological nonrigid image registration. IEEE International Conference on Image Processing 2005;1:1133–1136.
19.
Pearson J, Hines D, Golosman S, Kuglin C: Video-rate image correlation processor. Proceedings of SPIE, 1977, vol 119, pp 197–205.
20.
Rangarajan L, Chui H, Bookstein F: The softassign procrustes matching algorithm; in Duncan J, Gindi G (eds): Information Processing in Medical Imaging. Heidelberg, Springer, 1997, pp 29–42.
21.
Fleiss JL: Design and Analysis of Clinical Experiments. New York, John Wiley & Sons, 1986.
22.
Landis JR, Koch GG: The measurement of observer agreement for categorical data. Biometrics 1977;33:159–174.
23.
Lobo C, Bernardes R, Figueira JP, de Abreu JR, Cunha-Vaz JG: Three-year follow-up of blood-retinal barrier and retinal thickness alterations in patients with type 2 diabetes mellitus and mild nonproliferative diabetic retinopathy. Arch Ophthalmol 2004;122:211–217.
24.
Csaky KG, Richman EA, Ferris FL: Report from the NEI/FDA Ophthalmic Clinical Trial Design and Endpoints Symposium. Invest Ophthalmol Vis Sci 2008;49:479–489.
© 2009 S. Karger AG, Basel
2009
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.