Evaluation of thickness of retinal nerve fiber layer and ganglion cell layer with inner plexiform layer in patients without diabetic retinopathy and mild diabetic retinopathy in type 2 diabetes mellitus patients using spectral-domain optical coherence tomography

Mitali Borooah, Y. Jennifer Nane, Jayant Ekka


Background: A widely accepted pathogenesis of DR consists of microvascular abnormalities. However recent investigations have demonstrated neurodegenerative alterations before the appearance of microvascular changes in patients with DM. Aim of the study was to evaluate thickness of retinal nerve fiber layer and ganglion cell layer with inner plexiform layer in patent without diabetic retinopathy and mild diabetic retinopathy in type 2 diabetic patients using spectral domain optical coherence tomography.

Methods: Thirty patients with type 2 diabetes mellitus without diabetic retinopathy, 30 with mild diabetic retinopathy and 30 healthy controls are taken considering inclusion and exclusion criteria. GCL-ILM and RNFL thickness was measured in each individual and measurements were compared using one way ANOVA test and Pearson’s correlation was performed to evaluate the linear correlation between variables and calculated p value <0.05 was regarded as significant.

Results: The average RNFL thickness was 86.18±8.44μm and 91.79±4.77μm in diabetic patients and controls respectively (p=0.002). Furthermore, for two different groups of diabetic patients, the average RNFL thickness was 86.74±11.18μm in the no DR group and 85.62±11.10μm in the mild DR group (p=0.697). The average GCL-IPL thickness was 79.95±4.32μm and 84.66±3.26μm in diabetic patients and controls, respectively (p=<0.001). Furthermore, for two different groups of diabetic patients, the average GCL-IPL thickness was 80.15±5.78μm in the no DR group and 79.75±5.70μm in the mild DR group (p=0.788).

Conclusions: There was a statistically significant reduction of the mean GCL-IPL and RNFL thickness in type 2 diabetic patients with no or mild DR compared with a homogenous control group indicating neuroretinal changes occur before vascular changes of diabetic retinopathy. But the correlation of average RNFL thickness and GCL-IPL thickness was not statistically significant with the duration of diabetes and HbA1c value.


Diabetic retinopathy, Diabetes mellitus, GCL-ILM thickness, RNFL thickness

Full Text:



Girach A, Manner D, Porta M. Diabetic microvascular complications: can patients at risk be identified? A review. Inter J Clin Pra. 2006 Nov 1;60(11):1471-83.

Engerman RL. Pathogenesis of diabetic retinopathy. Diabetes. 1989;38(10):1203-6.

Hammes HP, Lin J, Renner O, Shani M, Lundqvist A, Betsholtz C, et al. Pericytes and the pathogenesis of diabetic retinopathy. Diabetes. 2002;51(10):3107.

Early Treatment Diabetic Retinopathy Study Research Group. Grading diabetic retinopathy from stereoscopic color fundus photographs-an extension of the modified Airlie House classification. ETDRS report number 10. Ophthalmology. 1991;98(5 Suppl):786-806.

Fong DS, Aiello L, Gardner TW, King GL, Blankenship G, Cavallerano JD, et al. Diabetic Retinopathy. Diabetes Care. 2003;26(1):226-9.

Antonetti DA, Klein R, Gardner TW. Mechanisms of Disease Diabetic Retinopathy. N Engl J Med. 2012;366(13):1227-39.

Usui Y, Westenskow PD, Kurihara T, Aguilar E, Sakimoto S, Paris LP, et al. Neurovascular crosstalk between interneurons and capillaries is required for vision. J Clin Invest. 2015;125(6):2335-46.

Stem MS, Gardner TW. Neurodegeneration in the pathogenesis of diabetic retinopathy: molecular mechanisms and therapeutic implications. Curr Med Chem. 2012;20(26):3241-50.

Yang JH, Kwak HW, Kim TG, Han J, Moon SW, Yu SY. Retinal Neurodegeneration in Type II Diabetic Otsuka Long-Evans Tokushima Fatty Rats. Invest Ophthalmol Vis Sci. 2013;54(6):3844-51.

Barber AJ, Lieth E, Khin SA, Antonetti DA, Buchanan AG, Gardner TW. Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin. J Clin Invest. 1998;102(4):783-91.

Abcouwer SF, Gardner TW. Diabetic retinopathy: loss of neuroretinal adaptation to the diabetic metabolic environment. Ann N Y Acad Sci. 2014;1311(1):174-90.

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.

van Dijk HW, Verbraak FD, Kok PH, Garvin MK, Sonka M, Lee K, et al. Decreased retinal ganglion cell layer thickness in patients with type 1 diabetes. Invest Ophthalmol Vis Sci. 2010;51(7):3660-5.

van Dijk HW, Verbraak FD, Kok PH, Stehouwer M, Garvin MK, Sonka M, et al. Early neurodegeneration in the retina of type 2 diabetic patients. Invest Ophthalmol Vis Sci. 2012;53(6):2715-9.

Chen Y, Li J, Yan Y, Shen X. Diabetic macular morphology changes may occur in the early stage of diabetes. BMC Ophthalmol. 2016;16:12.

Ng DS, Chiang PP, Tan G, Cheung CG, Cheng CY, Cheung CY, et al. Retinal ganglion cell neuronal damage in diabetes and diabetic retinopathy. Clin Exp Ophthalmol. 2016;44(4):243-50.

Sato S, Hirooka K, Baba T, Tenkumo K, Nitta E, Shiraga F. Correlation between the ganglion cell-inner plexiform layer thickness measured with cirrus HD-OCT and macular visual field sensitivity measured with microperimetry. Invest Ophthalmol Vis Sci. 2013;54(4):3046-51.

Cabrera DD, Somfai GM. Early detection of retinal thickness changes in diabetes using optical coherence tomography. Med Sci M. 2010;16:15-21.

Garvin MK, Abramoff MD, Wu X, Russell SR, Burns TL, Sonka M. Automated 3-D intraretinal layer segmentation of macular spectral-domain optical coherence tomography images. IEEE transactions on medical imaging. 2009 Sep;28(9):1436-47.

Leite MT, Rao HL, Weinreb RN, Zangwill LM, Bowd C, Sample PA, et al. Agreement among spectral-domain optical coherence tomography instruments for assessing retinal nerve fiber layer thickness. American J Ophthalmol. 2011 Jan 1;151(1):85-92.

Aref AA, Budenz DL. Spectral domain optical coherence tomography in the diagnosis and management of glaucoma. Ophthalmic Surg Laser Imaging. 2010:41:S15.

Harwerth RS, Carter-Dawson L, Shen F, Smith EL, Crawford ML. Ganglion cell losses underlying visual field defects from experimental glaucoma. Investigative ophthalmology & visual science. 1999 Sep 1;40(10):2242-50.

Lopes de Faria JM, Russ H, Costa VP. Retinal nerve fibre layer loss in patients with type 1 diabetes mellitus without retinopathy. Br J Ophthalmol. 2002;86:725-8.

Takahashi H, Goto T, Shoji T, Tanito M, Park M, Chihara E. Diabetes-associated retinal nerve fiber damage evaluated with scanning laser polarimetry. Am J Ophthalmol. 2006 Jul 1;142(1):88-94.

Kern TS, Engerman RL. Vascular lesions in diabetes are distributed non-uniformly within the retina. Experimental eye research. 1995 May 1;60(5):545-9.

Nor-Sharina Y, Zunaina E, Shatriah I, Win-Mar K, Azriani AR. Correlation of retinal nerve fibre layer thickness with HbA1c and oxidised LDL in non-proliferative diabetic retinopathy. J Diabetes Metab. 2013;4(298):2.

Rodrigues EB, Urias MG, Penha FM, Badaró E, Novais E, Meirelles R, Farah ME. Diabetes induces changes in neuroretina before retinal vessels: a spectral-domain optical coherence tomography study. Inter J Retina Vitreous. 2015 Dec;1(1):4.

Carpineto P, Toto L, Aloia R, Ciciarelli V, Borrelli E, Vitacolonna E, et al. Neuroretinal alterations in the early stages of diabetic retinopathy in patients with type 2 diabetes mellitus. Eye. 2016 May;30(5):673.

Chihara E, Matsuoka T, Ogura Y, Matsumura M. Retinal nerve fiber layer defect as an early manifestation of diabetic retinopathy. Ophthalmol. 1993 Aug 1;100(8):1147-51.