Optical coherence tomography angiography findings of neurovascular changes in type 2 diabetes mellitus patients without clinical diabetic retinopathy

Abstract

Aims

To evaluate the effect of early screening with OCTA in type 2 diabetes mellitus (T2DM) patients without clinical DR (NDR).

Methods

This was a cross-sectional case–control clinical study. Eighty-four eyes of 84 patients (44 T2DM and 40 control subjects) were included. Images were obtained using AngioVue software 2.0 of the OCTA device. Foveal avascular zone (FAZ) area, FAZ perimeter (PERIM), choriocapillary flow area (CCF), acircularity index (AI), foveal vessel density in a 300-µm-wide region around FAZ (FD), macular-associated vessel density (VD) and optic disc-associated capillary density (CD) were compared between the T2DM and control groups. In the T2DM group, the correlations between the above parameters and best-corrected visual acuity (BCVA) were assessed.

Results

Enlarged FAZ, increased PERIM, reduced CCF, reduced parafoveal VD and decreased CD inside the disc were significantly more obvious in the NDR subjects than in the control subjects (FAZ 0.43 ± 0.13 versus 0.37 ± 0.08 mm2, p = 0.02; PERIM 2.60 ± 0.45 versus 2.41 ± 0.28 mm, p = 0.04; CCF 1.94 ± 0.28 versus 2.05 ± 0.11 mm2, p = 0.02; superficial parafoveal VD 48.01 ± 3.41 versus 50.74 ± 3.67%, p = 0.003; deep parafoveal VD 51.60 ± 3.52 versus 54.45 ± 4.19%, p = 0.004; CD inside disc 49.75 ± 4.84 versus 53.19 ± 4.04%, p = 0.003). In the NDR subjects, logMAR BCVA (β = − 0.55, p < 0.01) and FAZ (r = − 0.62, p < 0.01) showed a significant negative correlation with superficial total VD, respectively.

Conclusions

Preclinical DR can be detected by OCTA. Parameters such as FAZ, PERIM, CCF, VD and CD may be useful for early detection of microvascular impairments in DM patients with NDR. Superficial VD and FAZ are possible sensitive visual acuity predictors in NDR subjects. OCTA may be a promising non-invasive tool in daily DR screening.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2

References

  1. 1.

    Solomon SD, Chew E, Duh EJ et al (2017) Diabetic retinopathy: a position statement by the American Diabetes Association. Diabetes Care 40(3):412–418

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Wong TY, Cheung CM, Larsen M, Sharma S, Simo R (2016) Diabetic retinopathy. Nat Rev Dis Primers 2:16012

    Article  PubMed  Google Scholar 

  3. 3.

    Simo R, Hernandez C (2014) Neurodegeneration in the diabetic eye: new insights and therapeutic perspectives. Trends Endocrinol Metab 25(1):23–33

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    La Mantia A, Kurt RA, Mejor S, Egan CA, Tufail A, Keane PA, Sim DA (2018) Comparing fundus fluorescein angiography and swept-source optical coherence tomography angiography in the evaluation of diabetic macular perfusion. Retina. https://doi.org/10.1097/IAE.0000000000002045

    Article  PubMed  Google Scholar 

  5. 5.

    Mo S, Krawitz B, Efstathiadis E et al (2016) Imaging foveal microvasculature: optical coherence tomography angiography versus adaptive optics scanning light ophthalmoscope fluorescein angiography. Invest Ophthalmol Vis Sci 57(9):OCT130–O140

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Kwiterovich KA, Maguire MG, Murphy RP et al (1991) Frequency of adverse systemic reactions after fluorescein angiography. Results of a prospective study. Ophthalmology 98(7):1139–1142

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Lopez-Saez MP, Ordoqui E, Tornero P et al (1998) Fluorescein-induced allergic reaction. Ann Allergy Asthma Immunol 81(5):428–430

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Zahid S, Dolz-Marco R, Freund KB et al (2016) Fractal dimensional analysis of optical coherence tomography angiography in eyes with diabetic retinopathy. Invest Ophthalmol Vis Sci 57(11):4940–4947

    Article  PubMed  Google Scholar 

  9. 9.

    Soares M, Neves C, Marques IP et al (2017) Comparison of diabetic retinopathy classification using fluorescein angiography and optical coherence tomography angiography. Br J Ophthalmol 101(1):62–68

    Article  PubMed  Google Scholar 

  10. 10.

    Kashani AH, Chen CL, Gahm JK et al (2017) Optical coherence tomography angiography: a comprehensive review of current methods and clinical applications. Prog Retina Eye Res 60:66–100

    Article  Google Scholar 

  11. 11.

    Lee J, Rosen R (2016) Optical coherence tomography angiography in diabetes. Curr Diab Rep 16(12):123

    Article  Google Scholar 

  12. 12.

    Kim K, Kim ES, Yu SY (2017) Optical coherence tomography angiography analysis of foveal microvascular changes and inner retinal layer thinning in patients with diabetes. Br J Ophthalmol. https://doi.org/10.1136/bjophthalmol-2017-311149

    Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Takase N, Nozaki M, Kato A et al (2015) Enlargement of foveal avascular zone in diabetic eyes evaluated by en face optical coherence tomography angiography. Retina 35(11):2377–2383

    Article  Google Scholar 

  14. 14.

    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–e755

    Article  PubMed  Google Scholar 

  15. 15.

    Alibhai AY, Moult EM, Shahzad R et al (2017) Quantifying microvascular changes using OCT angiography in diabetic eyes without clinical evidence of retinopathy. Ophthalmol Retina. https://doi.org/10.1016/j.oret.2017.09.011

    Article  Google Scholar 

  16. 16.

    Goudot MM, Sikorav A, Semoun O et al (2017) Parafoveal OCT angiography features in diabetic patients without clinical diabetic retinopathy: a qualitative and quantitative analysis. J Ophthalmol 2017:8676091

    Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Fong DS, Aiello L, Gardner TW et al (2003) Diabetic retinopathy. Diabetes Care 26(1):226–229

    Article  PubMed  Google Scholar 

  18. 18.

    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):1269–1324

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    KDOQI Clinical Practice Guideline for Diabetes and CKD (2012) 2012 Update. Am J Kidney Dis 60(5):850–886

    Article  Google Scholar 

  20. 20.

    Tuttle KR, Bakris GL, Bilous RW et al (2014) Diabetic kidney disease: a report from an ADA Consensus Conference. Diabetes Care 37(10):2864–2883

    Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    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 7:42201

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Lechner J, O’Leary OE, Stitt AW (2017) The pathology associated with diabetic retinopathy. Vision Res 139:7–14

    Article  PubMed  Google Scholar 

  23. 23.

    Toto L, D’Aloisio R, Di Nicola M et al (2017) Qualitative and quantitative assessment of vascular changes in diabetic macular edema after dexamethasone implant using optical coherence tomography angiography. Int J Mol Sci 18(6):1181

    Article  PubMed Central  Google Scholar 

  24. 24.

    Hollo G (2017) Optical coherence tomography angiography to better understand glaucoma. J Curr Glaucoma Pract 11(2):35–37

    Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Alnawaiseh M, Lahme L, Müller V et al (2018) Correlation of flow density, as measured using optical coherence tomography angiography, with structural and functional parameters in glaucoma patients. Graefe’s Arc Clin Exp Ophthalmol 256(3):589–597

    Article  Google Scholar 

  26. 26.

    Araszkiewicz A, Zozulinska-Ziolkiewicz D, Meller M et al (2012) Neurodegeneration of the retina in type 1 diabetic patients. Pol Arch Med Wewn 122(10):464–470

    PubMed  Google Scholar 

  27. 27.

    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):2715–2719

    Article  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Sambhav K, Abu-Amero KK, Chalam KV (2017) Deep capillary macular perfusion indices obtained with OCT angiography correlate with degree of nonproliferative diabetic retinopathy. Eur J Ophthalmol 27(6):716–729

    Article  Google Scholar 

  29. 29.

    Nesper PL, Roberts PK, Onishi AC et al (2017) Quantifying microvascular abnormalities with increasing severity of diabetic retinopathy using optical coherence tomography angiography. Invest Ophthalmol Vis Sci 58(6):BIO307–BIO315

    Article  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Kaizu Y, Nakao S, Yoshida S et al (2017) Optical coherence tomography angiography reveals spatial bias of macular capillary dropout in diabetic retinopathy. Invest Ophthalmol Vis Sci 58(11):4889–4897

    Article  PubMed  Google Scholar 

  31. 31.

    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):695–702

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Rosen RB, Krawitz B, Philips E et al (2017) Anatomical location-specific normative quantification of macular nonperfusion in diabetic retinopathy using optical coherence tomography angiography (OCTA). Invest Ophthalmol Vis Sci 58(8):1658–1658

    Google Scholar 

  33. 33.

    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–H749

    Article  PubMed  PubMed Central  Google Scholar 

  34. 34.

    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):235–244. https://doi.org/10.1016/j.ophtha.2016.10.008

    Article  PubMed  Google Scholar 

  35. 35.

    Valle A, Giamporcaro GM, Scavini M et al (2013) Reduction of circulating neutrophils precedes and accompanies type 1 diabetes. Diabetes 62(6):2072–2077

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Stitt AW, Curtis TM, Chen M et al (2016) The progress in understanding and treatment of diabetic retinopathy. Progress Retinal Eye Res 51:156–186

    Article  Google Scholar 

Download references

Acknowledgements

The research was funded by the National Natural Science Foundation of China 81570845 and the Natural Science Foundation of Guangdong Province 2015A030313019. The authors wish to acknowledge Dr. David Huang, Ph.D., Casey Eye Institute, Oregon Health and Science University, who gave an excellent speech in Portland and inspired our research.

Funding

National Natural Science Foundation of China 81570845; Natural Science Foundation of Guangdong Province 2015A030313019.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Yuqing Lan.

Ethics declarations

Conflict of interest

No conflicting relationship exists for any author.

Statement of human and animal rights

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5).

Statement of informed consent

Informed consent was obtained from all patients for being included in the study.

Additional information

Managed by Massimo Federici.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Li, Z., Alzogool, M., Xiao, J. et al. Optical coherence tomography angiography findings of neurovascular changes in type 2 diabetes mellitus patients without clinical diabetic retinopathy. Acta Diabetol 55, 1075–1082 (2018). https://doi.org/10.1007/s00592-018-1202-3

Download citation

Keywords

  • Optical coherence tomography angiography
  • Diabetic retinopathy
  • Neurovascular changes
  • Early screening