Scientific Online Resource System

Bulgarian Review of Ophthalmology

Microstructural changes of the macula in diabetic patients with and without mild diabetic retinopathy

Darina Koseva, Zornitsa Zlatarova


Introduction: Diabetes mellitus (DM) is a group of diseases characterized by hyperglycemia due to an absolute or relative lack of insulin production or action.  Extreme organ dysfunction, caused by chronically elevated blood glucose levels, affects the heart, kidneys, nervous system and retina.


The aim of this article is to compare the macular retinal thicknesses and volume in patients with DM with and without mild diabetic retinopathy (DR) and healthy eyes.

Materials and Methods:

The people studied, 212 in total, were divided into three groups—healthy controls, diabetics without DR, and diabetics with a mild DR. In our study the ZEISS CIRRUS HD-OCT device was used as well as the Macular Cube 512x128, Macular Thickness Analysis, and Ganglion Cell Analysis protocols were used.  We analyzed the thickness of the retina from the inner limiting membrane to the retinal pigment epithelium, as well as the thickness of the ganglion cell layer, and the inner plexiform layer in the macula.


A statistically significant difference between the groups was found for the mean and the minimum thickness of the ganglion cell + inner plexiform layer. No significant difference in mean values between patient groups for mean macular cube retinal thickness, foveal retinal thickness, and macular cube volume was found.


There is no loss of ganglion cells and a decrease in the thickness of the inner layers of the retina in the macula that precedes the appearance of retinal microvascular damage, and the two processes occur simultaneously.


diabetes; diabetic retinopathy; neurodegeneration; optical coherence tomography

Full Text


Alam U, Asghar O, Azmi S, Malik RA. Chapter 15. General aspects of diabetes mellitus. In: Zochodne DW, Malik RA, editors. Handbook of Clinical Neurology [Internet]. Elsevier; 2014 [cited 09 January 2019]. pp. 211–22. (Diabetes and the Nervous System; vol. 126). Available at:

Papatheodorou K, Banach M, Bekiari E, Rizzo M, Edmonds M. Complications of Diabetes 2017. J Diabetes Res. 2018;2018:3086167. doi: 10.1155/2018/3086167.

Sivaprasad S, Pearce E. The unmet need for better risk stratification of non‐proliferative diabetic retinopathy. Diabet Med. 2019;36(4):424–33. doi: 10.1111/dme.13868.

Villarroel M, Ciudin A, Hernández C, Simó R. Neurodegeneration: An early event of diabetic retinopathy. World J Diabetes. 2010;1(2):57–64. doi: 10.4239/wjd.v1.i2.57.

Barber AJ, Gardner TW, Abcouwer SF. The significance of vascular and neural apoptosis to the pathology of diabetic retinopathy. Invest Ophthalmol Vis Sci. 2011;52(2):1156–63. doi: 10.1167/iovs.10-6293.

Apple DJ. Anatomy and histopathology of the macular region. Int Ophthalmol Clin. 1981;21(3):1–9. doi: 10.1097/00004397-198102130-00003.

Aguilar E. Endothelial proliferation in diabetic retinal microaneurysms. Arch Ophthalmol. 2003;121(5):740-1. doi: 10.1001/archopht.121.5.740.

Otani T, Kishi S, Maruyama Y. Patterns of diabetic macular edema with optical coherence tomography. Am J Ophthalmol. 1999;127(6):688–93. doi: 10.1016/s0002-9394(99)00033-1.

Yang CS, Cheng CY, Lee FL, Hsu WM, Liu JH. Quantitative assessment of retinal thickness in diabetic patients with and without clinically significant macular edema using optical coherence tomography. Acta Ophthalmol Scand. 2001;79(3):266–70. doi: 10.1034/j.1600-0420.2001.790311.x.

Asefzadeh B, Fisch BM, Parenteau CE, Cavallerano AA. Macular thickness and systemic markers for diabetes in individuals with no or mild diabetic retinopathy. Clin Experiment Ophthalmol. 2008;36(5):455–63. doi: 10.1111/j.1442-9071.2008.01769.x.

Massin P, Erginay A, Haouchine B, Mehidi AB, Paques M, Gaudric A. Retinal thickness in healthy and diabetic subjects measured using optical coherence tomography mapping software. Eur J Ophthalmol. 2002;12(2):102–8. doi: 10.1177/112067210201200205.

Rodrigues EB, Urias MG, Penha FM, Badaró E, Novais E, Meirelles R, et al. Diabetes induces changes in neuroretina before retinal vessels: a spectral-domain optical coherence tomography study. Int J Retina Vitr. 2015;1(1):4. doi: 10.1186/s40942-015-0001-z.

Srinivasan S, Pritchard N, Sampson GP, Edwards K, Vagenas D, Russell AW, et al. Retinal thickness profile of individuals with diabetes. Ophthalmic Physiol Opt J Br Coll Ophthalmic Opt Optom. 2016;36(2):158–66. doi: 10.1111/opo.12263.

Bressler NM, Edwards AR, Antoszyk AN, Beck RW, Browning DJ, Ciardella AP, et al. Retinal thickness on stratus optical coherence tomography in people with diabetes and minimal or no diabetic retinopathy. Am J Ophthalmol. 2008;145(5):894-901. doi: 10.1016/j.ajo.2007.12.025.

Verma A, Rani PK, Raman R, Pal SS, Laxmi G, Gupta M, et al. Is neuronal dysfunction an early sign of diabetic retinopathy? Microperimetry and spectral domain optical coherence tomography (SD-OCT) study in individuals with diabetes, but no diabetic retinopathy. Eye Lond Engl. 2009;23(9):1824–30. doi: 10.1038/eye.2009.184.

Dumitrescu AG, Istrate SL, Iancu RC, Guta OM, Ciuluvica R, Voinea L. Retinal changes in diabetic patients without diabetic retinopathy. Romanian J Ophthalmol. 2017;61(4):249–55.

Jiang J, Liu Y, Chen Y, Ma B, Qian Y, Zhang Z, et al. Analysis of changes in retinal thickness in type 2 diabetes without diabetic retinopathy. J Diabetes Res. 2018; 2018:3082893. doi: 10.1155/2018/3082893.

Peng XD, Shen J, Shen W, Zhu LN, Liu L. Macular thickness and macular volume in diabetic patients without apparent visual loss. Int Eye Sci. 2015;15:95–7.

Demir M, Oba E, Sensoz H, Ozdal E. Retinal nerve fiber layer and ganglion cell complex thickness in patients with type 2 diabetes mellitus. Indian J Ophthalmol. 2014;62(6):719–20. doi: 10.4103/0301-4738.136234.

Carbonell M, Alonso N, Castelblanco E, Real J, Ramírez-Morros A, Simó R, et al. Assessment of inner retinal layers and choroidal thickness in type 1 diabetes mellitus: a cross-sectional study. J Clin Med. 2019;8(9) ):1412. doi: 10.3390/jcm8091412..

Araszkiewicz A, Zozulinska-Ziolkiewicz D. Retinal neurodegeneration in the course of diabetes-pathogenesis and clinical perspective. Curr Neuropharmacol. 2016;14(8):805–9. doi: 10.2174/1570159x14666160225154536.

Chhablani J, Sharma A, Goud A, Peguda HK, Rao HL, Begum VU, et al. Neurodegeneration in type 2 diabetes: evidence from spectral-domain optical coherence tomography. Invest Ophthalmol Vis Sci. 2015;56(11):6333–8. doi: 10.1167/iovs.15-17334.

van Dijk HW, Kok PHB, Garvin M, Sonka M, DeVries JH, Michels RPJ, et al. Selective loss of inner retinal layer thickness in type 1 diabetic patients with minimal diabetic retinopathy. Invest Ophthalmol Vis Sci. 2009;50(7):3404–9. doi: 10.1167/iovs.08-3143.

Cabrera DeBuc D, Somfai GM. Early detection of retinal thickness changes in diabetes using optical coherence tomography. Med Sci Monit Int Med J Exp Clin Res. 2010;16(3):MT15-21.

Gerendas BS, Hatz K, Kaider A, Zulewski H, Lehmann R, Montuoro A, et al. Ganglion cell layer thickening in well-controlled patients with type 1 diabetes: an early sign for diabetic retinopathy? Acta Ophthalmol (Copenh). 2020;98(3):e292–300. doi: 10.1111/aos.14273.

Toprak I, Fenkci SM, Fidan Yaylali G, Martin C, Yaylali V. Early retinal neurodegeneration in preclinical diabetic retinopathy: a multifactorial investigation. Eye (Lond). 2020;34(6):1100-1107. doi: 10.1038/s41433-019-0646-1.

Tavares Ferreira J, Alves M, Dias-Santos A, Costa L, Santos BO, Cunha JP, et al. Retinal neurodegeneration in diabetic patients without diabetic retinopathy. Invest Ophthalmol Vis Sci. 2016;57(14):6455–60. doi: 10.1167/iovs.16-20215.

Kołodziej M, Waszczykowska A, Korzeniewska-Dyl I, Pyziak-Skupien A, Walczak K, Moczulski D, et al. The HD-OCT study may be useful in searching for markers of preclinical stage of diabetic retinopathy in patients with type 1 diabetes. Diagn Basel Switz. 2019;9(3):105. doi: 10.3390/diagnostics9030105.



Font Size

About The Authors

Darina Koseva
Medical University of Varna

Department of Ophthalmology and Visual Sciences, Faculty of Medicine

Zornitsa Zlatarova
Medical University of Varna

Department of Ophthalmology and Visual Sciences, Faculty of Medicine