Diabetes affects 5% of the world’s population and its prevalence doubles every generation. The International Diabetes Federation (IDF) estimates that in 2013 approximately 382 million people in the world had diabetes.
Every 18 seconds someone is diagnosed with Diabetes. Even more worryingly, according to the IDF, by 2035 the number of diabetics in the world is expected to rise to 592 million.
Diabetic Retinopathy is the most frequent and most serious complication of Diabetes that afflicts vision, affecting up to 80 percent of all patients who have had diabetes for 10 years or more .You can learn more about Diabetic Retinopathy here.
Brief literature review regarding the relationship between Microaneurysms and Diabetic Retinopathy Progression
Four Independent Longitudinal Studies confirm MA Turnover-based Phenotypes as predictors of Macular Edema increased progression risk.
Ribeiro, Luísa, et al. Diabetic Retinopathy Phenotypes of Progression to Macular Edema: Pooled Analysis From Independent Longitudinal Studies of up to 2 Years' Duration in Investigative ophthalmology & visual science 58.6 (2017): BIO206-BIO210, Ophthalmic research, 2017.
New study with LV Prasad Eye Institute, India, confirms that Diabetic Retinopathy progression is predicted by Microaneurysm Turnover, a measure automatically computed by RetmarkerDR from the analysis of non-invasive field 2 images.
Pappuru, Rajeev KR, et al. Microaneurysm turnover is a predictor of diabetic retinopathy progression , British Journal of Ophthalmology (2018).
Progression risk for Macular Edema in Diabetic Retinopahy is identified by three Phenotypes based in Retinal Thickness and MA Turnover (computed with RetmarkerDR). Different Ethnical groups present different Phenotypes distributions.
Ribeiro, Luísa, et al. Different Phenotypes of Mild Nonproliferative Diabetic Retinopathy with Different Risks for Development of Macular Edema (C-TRACER Study). Ophthalmic research, 2017.
Using the RetmarkerDR software, the team from the LMU in Munich was able to identify patients with higher risk to develop CSME during a follow-up period of up to 5 years. The automated analysis may help to determine the individual risk of a patient to develop sight-threatening complications related to diabetic retinopathy.
Haritoglou C, Kernt M, Neubauer A, Gerss J, Oliveira CM, Kampik A and Ulbig M Microaneurysm formation rate as a predictive marker for progression to clinically significant macular edema in nonproliferative diabetic retinopathy. Retina, vol. 34, no. 1, pp. 157–164, Jan. 2014.
Microaneurysm turnover computed automatically in digital color fundus photography images using the RetmarkerDR is a good biomarker for worsening of retinopathy and development of clinically significant macular edema.
Ribeiro L, Nunes S, and Cunha-Vaz J. Microaneurysm turnover in the macula is a biomarker for development of clinically significant macular edema in type 2 diabetes. Current Biomarker Findings, 201;3:11–15.
Low MA turnover values identify well the eyes that are less likely to develop CSME in a 2-year period.
Ribeiro ML, Nunes SG and Cunha-Vaz JG Microaneurysm turnover at the macula predicts risk of development of clinically significant macular edema in persons with mild nonproliferative diabetic retinopathy. Diabetes Care, vol. 36, no. 5, pp. 1254–9, May 2013.
Recently Sjolie et al. (2011) showed that microaneurysms counts were predictive of an increased risk of retinopathy.
Sjolie AK, Klein R, Porta M, Orchard T, Fuller J, Parving HH, Bilous R, Aldington S, Chaturvedi N (2011) Retinal microaneurysms count predicts progression and regression of diabetic retinopathy. Post-hoc results from the DIRECT Programme. Diabet Medicine 28():345-351.
Over a 10- year follow-up period, microaneurysm turnover determined in the first 2 years identifies the patients at risk of progression to CSME and vision loss.
Nunes S, Pires I, Rosa A, Duarte L, Bernardes R, Cunha-Vaz J. Microaneurysm Turnover Is a Biomarker for Diabetic Retinopathy Progression to Clinically Significant Macular Edema: Findings for Type 2 Diabetics with Nonproliferative Retinopathy. Ophthalmologica. 2009;223(5):292-7.
Retinal microaneurysm counting has been suggested as an appropriate marker of retinopathy progression.
Csaky KG, Richman EA, Ferris FL (2008) Report from the NEI/FDA Ophthalmic Clinical Trials Design and Endpoints Symposium. Invest Ophthalmol Vis Sci 49:479-489
Systemic Markers of Diabetes such as duration of the disease, poor glycemic control, increased blood pressure and lipid levels are relevant factors but they do not identify DR progression. It is fundamental to identify lesions, their number and dynamics.
Hove MN, Kristensen JK, Lauritzen T, and Bek T. The relationships between risk factors and the distribution of retinopathy lesions in type 2 diabetes. Acta Ophthalmologica Scandinavica, 8(5), 619-623
Sharp et al. found that Microaneurysm turnover values vary widely between eyes that have similar ETDRS grading value.
Sharp PF, Olson J, Strachan F, Hipwell J, Ludbrook A, O’Donnell M, Wallece S, Goatman K, Grant A, Waugh N, McHardy K, Forrester JV (2003) The value of digital imaging in diabetic retinopathy. Health Technol Assess 7:1-119
Retinal microaneurysms are important lesions of diabetic retinopathy and even one or two microaneurysms in an eye should not regarded as unimportant.
Kohner AM, Stratton IM, Aldington SJ, Turner RC, Matthews DR for the UK Prospective Study Group (1999) Microaneurysms in the development of diabetic retinopathy (UKPDS). Diaetologia 45:1780-1785
On fundus photography, microaneurysms and small hemorrhages are the initial changes detected in the diabetic retina. They may be counted, and retinal microaneurysms counting has been suggested as an appropriated marker of retinopathy progression.
Klein R, Klein B, Moss SE, Cruickshanks KJ (1995) The Wisconsin Epidemiologic Study of Diabetic Retinopathy. XV. The long-term incidence of macular edema. Ophthamology 102:7-16
Klein et al. (1989) looked at the relationship between retinal microaneurysms and the progression of diabetic retinopathy over a 4-year period. In their study the number of microaneurysms at the baseline examination was positively associated with significant progression of retinopathy.
Klein R, Meuer SM, Scot E Moss MA, Klein BEK (1989) The relationship of Retinal Microaneurysms Counts to the 4-Year Progression of Diabetic Retinopathy. Arch Ophthalmol 107: 1780-1785.
AIBILI has been presenting research related to RetmarkerDR and RetmarkerC underlying concepts at important scientific forums and publications:
- Ribeiro, Luísa, et al. Diabetic Retinopathy Phenotypes of Progression to Macular Edema: Pooled Analysis From Independent Longitudinal Studies of up to 2 Years' Durationin Investigative ophthalmology & visual science 58.6 (2017): BIO206-BIO210, Ophthalmic research, 2017
- Pappuru, Rajeev KR, et al. Microaneurysm turnover is a predictor of diabetic retinopathy progression, British Journal of Ophthalmology (2018).
- Ribeiro, Luísa, et al. "Different Phenotypes of Mild Nonproliferative Diabetic Retinopathy with Different Risks for Development of Macular Edema (C-TRACER Study)." Ophthalmic research, 2017
- Haritoglou C, Kernt M, Neubauer A, Gerss J, Oliveira C, Kampik A and Ulbig M, "Microaneurysm Formation Rate As A Predictive Marker for Progression to Clinically Significant Macular Edema in Nonproliferative Diabetic Retinopathy", RETINA, Published ahead of print, 2013
- Ribeiro L and Cunha-Vaz J, "Surrogate outcomes for progression in the initial stages of diabetic retinopathy", Immunology, Endocrine & Metabolic Agents - Medicinal Chemistry, 13(1), 25-34, 2013
- Ribeiro L, Nunes S, and Cunha-Vaz J, "Microaneurysm turnover in the macula is a biomarker for development of clinically significant macular edema in type 2 diabetes", Current Biomarker Findings, 201;3:11–15 2013
- Ribeiro M, Nunes S, and Cunha-Vaz J, "Microaneurysm Turnover at the macula predicts risk of development of clinically significant macular edema in persons with mild non-proliferative diabetic retinopathy", Diabetes Care published ahead of print November 20, 2012
- Cunha-Vaz J, Bernardes R, Santos T, Oliveira C, Lobo C, Pires I, Ribeiro L, "Computer-Aided Detection of Diabetic Retinopathy Progression", Digital Teleretinal Screening 2012
- Ribeiro L, Bernardes R, Cunha-Vaz J, "Computer-aided Analysis of Fundus Photographs", European Ophthalmic Review 2011; 5(2): 104-7
- Bernardes R, Nunes S, Pereira I, Torrent T, Rosa A, Coelho D, Cunha-Vaz J, "Computer-Assisted Microaneurysm Turnover in the Early Stages of Diabetic Retinopathy", Ophthalmologica 2009;223; 284–291
- Nunes S, Pires I, Rosa A, Duarte L, Bernardes R, Cunha-Vaz J, "Microaneurysm Turnover Is a Biomarker for Diabetic Retinopathy Progression to Clinically Significant Macular Edema: Findings for Type 2 Diabetics with Nonproliferative Retinopathy", Ophthalmologica 2009;223:292–297
- Bernardes R, Ferreira J, Baptista P, Cunha-Vaz J, "Earmarking in a Sequence of Digital Color Fundus Photographs", The 3rd European Medical and Biological Engineering Conference (EMBEC'05), November 20 – 25, 2005, Prague, Czech Republic, ISSN: 1727-1983
- Lobo C, Bernardes R, Figueira J, Abreu J, Cunha-Vaz J, "Three-Year Follow-up Study of Blood-Retinal Barrier and Retinal Thickness Alterations in Patients With Type 2 Diabetes Mellitus and Mild Nonproliferative Diabetic Retinopathy", Arch Ophthalmol, February 1, 2004; 122(2): 211 - 217
- Lobo C, Ribeiro L, Bento G, Nunes S, Simões MJ, Miranda T, Bernardes R, Faro C, Cunha-Vaz J, "Patterns of progression in Diabetic Retinopathy correlation between phenotypes and genotypes"
- Nunes S, Santos T, Ribeiro L, Lobo C, Bernardes R, Cunha-Vaz J, "Phenotypes of Diabetic Retinopathy Progression to CSME based on non-invasive examinations"
- Nunes S, Santos T, Pires I, Lobo C, Bernardes R, Cunha-Vaz J, "Cluster Analysis Identification Of Early Diabetic Retinopathy Phenotypes"
- Nunes S, Bernardes R, Pereira I, Santos T, Soares M, Pires I, Lobo C, Cunha-Vaz J, "Validation of a predictive model for diabetic retinopathy progression in type-2 diabetic patients with mild nonproliferative diabetic retinopathy"
- Pires I, Duarte L, Nunes S, Pereira I, Bernardes R, Cunha-Vaz J, "Microaneurysms Formation Rate as a Predictor of DR Progression to CSME Needing Photocoagulation in Nonproliferative Retinopathy in Diabetes Type 2"
- Bernardes R, Baptista P, Ferreira J, Duarte L, Cunha-Vaz J "Earmarking Retinal Changes on a Color Fundus Photograph Time-Sequence"