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Published in: Acta Diabetologica 5/2019

01-05-2019 | Angiography | Original Article

Do microvascular changes occur preceding neural impairment in early-stage diabetic retinopathy? Evidence based on the optic nerve head using optical coherence tomography angiography

Authors: Zijing Li, Xin Wen, Peng Zeng, Yunru Liao, Shuxian Fan, Yichi Zhang, Yuanjun Li, Jianhui Xiao, Yuqing Lan

Published in: Acta Diabetologica | Issue 5/2019

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Abstract

Aims

To evaluate the microvascular and neural differences of the optic nerve head (ONH) between type 2 diabetes mellitus (T2DM) subjects and controls.

Methods

This was a cross-sectional observational study. One hundred and eight eyes of 108 T2DM subjects with or without diabetic retinopathy (DR) (54 preclinical DR and 54 mild-to-moderate DR) were included. Fifty-two eyes of 52 healthy subjects were included as controls. The 4.5-mm Angio Disc scan mode and the ganglion cell complex scan mode were performed with all participants using AngioVue software 2.0 of the optical coherence tomography angiography (OCTA) device.

Results

Regarding ONH radial peripapillary capillary (RPC) density, the peripapillary region was mainly significantly reduced in the No-DR (NDR) group. Moreover, the RPC density of the peripapillary region and the inside optic disc area were significantly reduced in the non-proliferative DR (NPDR) group. When compared to the controls, significantly reduced peripapillary capillary density in six sections was observed in the NPDR group. However, reduced density was observed in only two sections in the NDR group. The NPDR group had significantly increased focal loss volume (FLV) and reduced peripapillary RNFL thickness in the inferior nasal section compared to those in the controls, but similar changes were not observed in the NDR group. A regression model identified RPCs inside the optic disc as a significant parameter in early-stage DR detection. In the NPDR group, BCVA showed a significantly negative correlation with RPCs inside the optic disc and a significantly positive correlation with FLV.

Conclusions

OCTA findings of the ONH area may provide evidence that microvascular changes occur preceding neural impairment in early-stage DR. However, further researches are still needed to support the statement. Reduced ONH perfusion inside the optic disc may be one of the crucial biomarkers in early-stage DR detection and is a possible sensitive visual acuity predictor in early-stage DR subjects. With the ONH mode, OCTA may be a more promising tool in DR screening.
Literature
1.
go back to reference Wong TY, Cheung CM, Larsen M, Sharma S, Simo R (2016) Diabetic retinopathy. Nat Rev Dis Primers 2:16012PubMedCrossRef Wong TY, Cheung CM, Larsen M, Sharma S, Simo R (2016) Diabetic retinopathy. Nat Rev Dis Primers 2:16012PubMedCrossRef
2.
go back to reference Stitt AW, Curtis TM, Chen M et al (2016) The progress in understanding and treatment of diabetic retinopathy. Progr Retinal Eye Res 51:156–186CrossRef Stitt AW, Curtis TM, Chen M et al (2016) The progress in understanding and treatment of diabetic retinopathy. Progr Retinal Eye Res 51:156–186CrossRef
3.
go back to reference Lechner J, O’Leary OE, Stitt AW (2017) The pathology associated with diabetic retinopathy. Vis Res 139:7–14PubMedCrossRef Lechner J, O’Leary OE, Stitt AW (2017) The pathology associated with diabetic retinopathy. Vis Res 139:7–14PubMedCrossRef
4.
go back to reference Chua J, Lim CXY, Wong TY, Sabanayagam C (2018) Diabetic retinopathy in the Asia-Pacific. Asia Pac J Ophthalmol (Phila) 7(1):3–16 Chua J, Lim CXY, Wong TY, Sabanayagam C (2018) Diabetic retinopathy in the Asia-Pacific. Asia Pac J Ophthalmol (Phila) 7(1):3–16
5.
6.
go back to reference Klaassen I, Van Noorden CJ, Schlingemann RO (2013) Molecular basis of the inner blood-retinal barrier and its breakdown in diabetic macular edema and other pathological conditions. Prog Retin Eye Res 34:19–48PubMedCrossRef Klaassen I, Van Noorden CJ, Schlingemann RO (2013) Molecular basis of the inner blood-retinal barrier and its breakdown in diabetic macular edema and other pathological conditions. Prog Retin Eye Res 34:19–48PubMedCrossRef
7.
go back to reference Carpineto P, Toto L, Aloia R et al (2016) Neuroretinal alterations in the early stages of diabetic retinopathy in patients with type 2 diabetes mellitus. Eye (Lond) 30(5):673–679CrossRef Carpineto P, Toto L, Aloia R et al (2016) Neuroretinal alterations in the early stages of diabetic retinopathy in patients with type 2 diabetes mellitus. Eye (Lond) 30(5):673–679CrossRef
8.
go back to reference Moran EP, Wang Z, Chen J, Sapieha P, Smith LE, Ma JX (2016) Neurovascular cross talk in diabetic retinopathy: pathophysiological roles and therapeutic implications. Am J Physiol Heart Circ Physiol 311(3):H738–H749PubMedPubMedCentralCrossRef Moran EP, Wang Z, Chen J, Sapieha P, Smith LE, Ma JX (2016) Neurovascular cross talk in diabetic retinopathy: pathophysiological roles and therapeutic implications. Am J Physiol Heart Circ Physiol 311(3):H738–H749PubMedPubMedCentralCrossRef
10.
go back to reference Spaide RF, Fujimoto JG, Waheed NK, Sadda SR, Staurenghi G (2018) Optical coherence tomography angiography. Prog Retin Eye Res 64:1–55PubMedCrossRef Spaide RF, Fujimoto JG, Waheed NK, Sadda SR, Staurenghi G (2018) Optical coherence tomography angiography. Prog Retin Eye Res 64:1–55PubMedCrossRef
11.
go back to reference Ashraf M, Nesper PL, Jampol LM, Yu F, Fawzi AA (2018) Statistical model of optical coherence tomography angiography parameters that correlate with severity of diabetic retinopathy. Invest Ophthalmol Vis Sci 59(10):4292–4298PubMedPubMedCentralCrossRef Ashraf M, Nesper PL, Jampol LM, Yu F, Fawzi AA (2018) Statistical model of optical coherence tomography angiography parameters that correlate with severity of diabetic retinopathy. Invest Ophthalmol Vis Sci 59(10):4292–4298PubMedPubMedCentralCrossRef
12.
go back to reference Kim K, Kim ES, Yu SY (2018) Optical coherence tomography angiography analysis of foveal microvascular changes and inner retinal layer thinning in patients with diabetes. Br J Ophthalmol 102(9):1226–1231PubMedCrossRef Kim K, Kim ES, Yu SY (2018) Optical coherence tomography angiography analysis of foveal microvascular changes and inner retinal layer thinning in patients with diabetes. Br J Ophthalmol 102(9):1226–1231PubMedCrossRef
13.
go back to reference Kaizu Y, Nakao S, Sekiryu H et al (2018) Retinal flow density by optical coherence tomography angiography is useful for detection of nonperfused areas in diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 256(12):2275–2282PubMedCrossRef Kaizu Y, Nakao S, Sekiryu H et al (2018) Retinal flow density by optical coherence tomography angiography is useful for detection of nonperfused areas in diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 256(12):2275–2282PubMedCrossRef
14.
go back to reference Alnawaiseh M, Lahme L, Müller V, Rosentreter A, Eter N (2018) Correlation of flow density, as measured using optical coherence tomography angiography, with structural and functional parameters in glaucoma patients. Graefes Arch Clin Exp Ophthalmol 256(3):589–597PubMedCrossRef Alnawaiseh M, Lahme L, Müller V, Rosentreter A, Eter N (2018) Correlation of flow density, as measured using optical coherence tomography angiography, with structural and functional parameters in glaucoma patients. Graefes Arch Clin Exp Ophthalmol 256(3):589–597PubMedCrossRef
15.
go back to reference Li Z, Alzogool M, Xiao J, Zhang S, Zeng P, Lan Y (2018) Optical coherence tomography angiography findings of neurovascular changes in type 2 diabetes mellitus patients without clinical diabetic retinopathy. Acta Diabetol 55(10):1075–1082PubMedCrossRef Li Z, Alzogool M, Xiao J, Zhang S, Zeng P, Lan Y (2018) Optical coherence tomography angiography findings of neurovascular changes in type 2 diabetes mellitus patients without clinical diabetic retinopathy. Acta Diabetol 55(10):1075–1082PubMedCrossRef
16.
17.
go back to reference Whelton PK, Carey RM, Aronow WS et al (2018) 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension 71(6):1269–1324PubMedCrossRef Whelton PK, Carey RM, Aronow WS et al (2018) 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension 71(6):1269–1324PubMedCrossRef
18.
19.
go back to reference Carnevali A, Sacconi R, Corbelli E et al (2017) Optical coherence tomography angiography analysis of retinal vascular plexuses and choriocapillaris in patients with type 1 diabetes without diabetic retinopathy. Acta Diabetol 54(7):695–702PubMedCrossRef Carnevali A, Sacconi R, Corbelli E et al (2017) Optical coherence tomography angiography analysis of retinal vascular plexuses and choriocapillaris in patients with type 1 diabetes without diabetic retinopathy. Acta Diabetol 54(7):695–702PubMedCrossRef
20.
go back to reference Simonett JM, Scarinci F, Picconi F et al (2017) Early microvascular retinal changes in optical coherence tomography angiography in patients with type 1 diabetes mellitus. Acta Ophthalmol 95(8):e751–e755PubMedCrossRef Simonett JM, Scarinci F, Picconi F et al (2017) Early microvascular retinal changes in optical coherence tomography angiography in patients with type 1 diabetes mellitus. Acta Ophthalmol 95(8):e751–e755PubMedCrossRef
22.
go back to reference Mansoori T, Sivaswamy J, Gamalapati JS, Balakrishna N (2018) Topography and correlation of radial peripapillary capillary density network with retinal nerve fibre layer thickness. Int Ophthalmol 38(3):967–974PubMedCrossRef Mansoori T, Sivaswamy J, Gamalapati JS, Balakrishna N (2018) Topography and correlation of radial peripapillary capillary density network with retinal nerve fibre layer thickness. Int Ophthalmol 38(3):967–974PubMedCrossRef
23.
go back to reference Chan G, Balaratnasingam C, Xu J et al (2015) In vivo optical imaging of human retinal capillary networks using speckle variance optical coherence tomography with quantitative clinico-histological correlation. Microvasc Res 100:32–39PubMedCrossRef Chan G, Balaratnasingam C, Xu J et al (2015) In vivo optical imaging of human retinal capillary networks using speckle variance optical coherence tomography with quantitative clinico-histological correlation. Microvasc Res 100:32–39PubMedCrossRef
24.
25.
go back to reference van Dijk HW, Verbraak FD, Kok PH et al (2012) Early neurodegeneration in the retina of type 2 diabetic patients. Invest Ophthalmol Vis Sci 53(6):2715–2719PubMedPubMedCentralCrossRef van Dijk HW, Verbraak FD, Kok PH et al (2012) Early neurodegeneration in the retina of type 2 diabetic patients. Invest Ophthalmol Vis Sci 53(6):2715–2719PubMedPubMedCentralCrossRef
26.
go back to reference Santos AR, Ribeiro L, Bandello F et al (2017) Functional and structural findings of neurodegeneration in early stages of diabetic retinopathy: cross-sectional analyses of baseline data of the EUROCONDOR project. Diabetes 66(9):2503–2510PubMedCrossRef Santos AR, Ribeiro L, Bandello F et al (2017) Functional and structural findings of neurodegeneration in early stages of diabetic retinopathy: cross-sectional analyses of baseline data of the EUROCONDOR project. Diabetes 66(9):2503–2510PubMedCrossRef
27.
go back to reference Kusari J, Zhou S, Padillo E, Clarke KG, Gil DW (2007) Effect of memantine on neuroretinal function and retinal vascular changes of streptozotocin-induced diabetic rats. Invest Ophthalmol Vis Sci 48(11):5152–5159PubMedCrossRef Kusari J, Zhou S, Padillo E, Clarke KG, Gil DW (2007) Effect of memantine on neuroretinal function and retinal vascular changes of streptozotocin-induced diabetic rats. Invest Ophthalmol Vis Sci 48(11):5152–5159PubMedCrossRef
28.
go back to reference Ziccardi L, Parisi V, Picconi F et al (2018) Early and localized retinal dysfunction in patients with type 1 diabetes mellitus studied by multifocal electroretinogram. Acta Diabetol 55(11):1191–1200PubMedCrossRef Ziccardi L, Parisi V, Picconi F et al (2018) Early and localized retinal dysfunction in patients with type 1 diabetes mellitus studied by multifocal electroretinogram. Acta Diabetol 55(11):1191–1200PubMedCrossRef
30.
go back to reference Araszkiewicz A, Zozulinska-Ziolkiewicz D et al (2012) Neurodegeneration of the retina in type 1 diabetic patients. Pol Arch Med Wewn 122(10):464–470PubMed Araszkiewicz A, Zozulinska-Ziolkiewicz D et al (2012) Neurodegeneration of the retina in type 1 diabetic patients. Pol Arch Med Wewn 122(10):464–470PubMed
31.
go back to reference Zang P, Gao SS, Hwang TS et al (2017) Automated boundary detection of the optic disc and layer segmentation of the peripapillary retina in volumetric structural and angiographic optical coherence tomography. Biomed Opt Express 8(3):1306PubMedPubMedCentralCrossRef Zang P, Gao SS, Hwang TS et al (2017) Automated boundary detection of the optic disc and layer segmentation of the peripapillary retina in volumetric structural and angiographic optical coherence tomography. Biomed Opt Express 8(3):1306PubMedPubMedCentralCrossRef
32.
go back to reference Leite MT, Rao HL, Weinreb RN et al (2011) Agreement among spectral-domain optical coherence tomography instruments for assessing retinal nerve fiber layer thickness. Am J Ophthalmol 151(1):85–92.e81PubMedCrossRef Leite MT, Rao HL, Weinreb RN et al (2011) Agreement among spectral-domain optical coherence tomography instruments for assessing retinal nerve fiber layer thickness. Am J Ophthalmol 151(1):85–92.e81PubMedCrossRef
33.
go back to reference Jia Y, Simonett JM, Wang J et al (2017) Wide-field OCT angiography investigation of the relationship between radial peripapillary capillary plexus density and nerve fiber layer thickness. Invest Ophthalmol Vis Sci 58(12):5188–5194PubMedPubMedCentralCrossRef Jia Y, Simonett JM, Wang J et al (2017) Wide-field OCT angiography investigation of the relationship between radial peripapillary capillary plexus density and nerve fiber layer thickness. Invest Ophthalmol Vis Sci 58(12):5188–5194PubMedPubMedCentralCrossRef
34.
go back to reference Wang Q, Chan SY, Yang JY et al (2017) Density of the macular and radial peripapillary capillary network measured by optical coherence tomography angiography. Acta Ophthalmol 95(6):e511–e512PubMedCrossRef Wang Q, Chan SY, Yang JY et al (2017) Density of the macular and radial peripapillary capillary network measured by optical coherence tomography angiography. Acta Ophthalmol 95(6):e511–e512PubMedCrossRef
35.
go back to reference Triolo G, Rabiolo A, Shemonski ND et al (2017) Optical coherence tomography angiography macular and peripapillary vessel perfusion density in healthy subjects, glaucoma suspects, and glaucoma patients. Invest Ophthalmol Vis Sci 58(13):5713–5722PubMedCrossRef Triolo G, Rabiolo A, Shemonski ND et al (2017) Optical coherence tomography angiography macular and peripapillary vessel perfusion density in healthy subjects, glaucoma suspects, and glaucoma patients. Invest Ophthalmol Vis Sci 58(13):5713–5722PubMedCrossRef
37.
go back to reference Samara WA, Shahlaee A, Adam MK et al (2017) Quantification of diabetic macular ischemia using optical coherence tomography angiography and its relationship with visual acuity. Ophthalmology 124(2):235–244PubMedCrossRef Samara WA, Shahlaee A, Adam MK et al (2017) Quantification of diabetic macular ischemia using optical coherence tomography angiography and its relationship with visual acuity. Ophthalmology 124(2):235–244PubMedCrossRef
38.
go back to reference Snodderly DM, Weinhaus RS, Choi JC (1992) Neural-vascular relationships in central retina of macaque monkeys (Macaca fascicularis). J Neurosci 12(4):1169–1193PubMedPubMedCentralCrossRef Snodderly DM, Weinhaus RS, Choi JC (1992) Neural-vascular relationships in central retina of macaque monkeys (Macaca fascicularis). J Neurosci 12(4):1169–1193PubMedPubMedCentralCrossRef
39.
go back to reference Stone J, van Driel D, Valter K, Rees S, Provis J (2008) The locations of mitochondria in mammalian photoreceptors: relation to retinal vasculature. Brain Res 1189:58–69PubMedCrossRef Stone J, van Driel D, Valter K, Rees S, Provis J (2008) The locations of mitochondria in mammalian photoreceptors: relation to retinal vasculature. Brain Res 1189:58–69PubMedCrossRef
40.
go back to reference Campbell JP, Zhang M, Hwang TS et al (2017) Detailed vascular anatomy of the human retina by projection-resolved optical coherence tomography angiography. Sci Rep 7:42201PubMedPubMedCentralCrossRef Campbell JP, Zhang M, Hwang TS et al (2017) Detailed vascular anatomy of the human retina by projection-resolved optical coherence tomography angiography. Sci Rep 7:42201PubMedPubMedCentralCrossRef
Metadata
Title
Do microvascular changes occur preceding neural impairment in early-stage diabetic retinopathy? Evidence based on the optic nerve head using optical coherence tomography angiography
Authors
Zijing Li
Xin Wen
Peng Zeng
Yunru Liao
Shuxian Fan
Yichi Zhang
Yuanjun Li
Jianhui Xiao
Yuqing Lan
Publication date
01-05-2019
Publisher
Springer Milan
Published in
Acta Diabetologica / Issue 5/2019
Print ISSN: 0940-5429
Electronic ISSN: 1432-5233
DOI
https://doi.org/10.1007/s00592-019-01288-8

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