Skip to main content

Advertisement

SpringerLink
Log in

The Role of Retinal Venous Congestion in Diabetic Retinopathy

  • Medicine
  • Published:
SN Comprehensive Clinical Medicine Aims and scope Submit manuscript

Abstract

Diabetic retinopathy (DR) is among the leading global causes of blindness and a major cause of vision loss in the working population of developed countries. The lack of understanding of the pathophysiology of DR hinders the development of efficient disease prevention and treatment. In DR, breakdown of the blood-retinal barrier occurs that causes leakage of blood and blood constituents into the retinal tissue. Several factors have been suggested as causes for the blood-retinal barrier breakdown, including metabolic, inflammatory, and hydrostatic. The purpose of this manuscript is to analyze available scientific reports concerning involvement of increased retinal venous hydrostatic pressure in DR. Data are presented from studies that investigated ocular blood flow and ocular morphology that suggest involvement of retinal vein congestion in the pathogenesis of DR. The results from fundus photography indicated that retinal venous dilation is associated with incidence and progression of DR. Fluorescein angiography studies found increased arterio-venous passage time and increased retinal venous filling time in patients with DR than in control subjects. Increased resistivity index was detected using Color Doppler imaging of the retrobulbar central retinal vein in patients with progression of DR that also suggests increased resistance to venous outflow. Retinal venous pressure measured by ophthalmodynamometry was higher in patients with DR, than in control subjects and in diabetic patients without DR. This evidence suggests an involvement of retinal venous congestion in DR. Future studies should focus on the effect of increased hydrostatic pressure in the retinal veins in the pathogenesis of DR.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data Availability

Not applicable

Code Availability

Not applicable

References

  1. Flaxman SR, Bourne RAR, Resnikoff S, Ackland P, Braithwaite T, Cicinelli MV, et al. Global causes of blindness and distance vision impairment 1990–2020: a systematic review and meta-analysis. Lancet Glob Health. 2017;5:e1221–34.

    PubMed  Google Scholar 

  2. Centers for Disease Control and Prevention. National Diabetes Statistics Report. Atlanta: Centers for Disease Control and Prevention, US Department of Health and Human Services; 2020. https://www.cdc.gov/diabetes/data/statistics/statistics-report.html. Accessed 1 Sept 2020.

  3. Li JQ, Welchowski T, Schmid M, Letow J, Wolpers AC, Holz FG, et al. Retinal Diseases in Europe: Prevalence, incidence and healthcare needs. University Hospital Bonn EURETINA. 2017. https://www.euretina.org/downloads/EURETINA_Retinal_Diseases.pdf. Accessed 1 Sept 2020.

  4. Bharadwaj AS, Appukuttan B, Wilmarth PA, Pan Y, Stempel AJ, Chipps TJ, et al. Role of the retinal vascular endothelial cell in ocular disease. Prog Retin Eye Res. 2013;32:102–80. https://doi.org/10.1016/j.preteyeres.2012.08.004.

    Article  PubMed  Google Scholar 

  5. Ehrlich R, Harris A, Ciulla TA, Kheradiya N, Winston DM, Wirostko B. Diabetic macular edema: physical, physiological and molecular factors contribute to this pathological process. Acta Ophthalmol. 2010;88:279–91.

    Article  CAS  PubMed  Google Scholar 

  6. Cunha-Vaz J. The blood-retinal barrier in the management of retinal disease: EURETINA award lecture. Ophthalmologica. 2017;237:1–10. https://doi.org/10.1159/000455809.

    Article  CAS  PubMed  Google Scholar 

  7. Kristinsson JK, Gottfredsdóttir MS, Stefánsson E. Retinal vessel dilatation and elongation precedes diabetic macular oedema. Br J Ophthalmol. 1997;81:274–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kulandavelu S, Balkan W, Hare JM. Regulation of oxygen delivery to the body via hypoxic vasodilation. Proc Natl Acad Sci U S A. 2015;112(20):6254–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Klein R, Myers CE, Lee KE, Gangnon R, Klein BEK. Changes in retinal vessel diameter and incidence and progression of diabetic retinopathy. Arch Ophthalmol. 2012;130:749–55.

    PubMed  PubMed Central  Google Scholar 

  10. Dimitrova G, Kato S, Yamashita H, Tamaki Y, Nagahara M, Fukushima H, et al. Relation between retrobulbar circulation and progression of diabetic retinopathy. Br J Ophthalmol. 2003;87(5):622–5. https://doi.org/10.1136/bjo.87.5.622.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Larsen M. Unilateral macular oedema secondary to retinal venous congestion without occlusion in patients with diabetes mellitus. Acta Ophthalmol. 2005;83:428–35.

    Article  Google Scholar 

  12. Cybulska-Heinrich AK, Baertschi M, Loesche CC, Schoetzau A, Konieczka K, Josifova T, et al. Patients with diabetic retinopathy have high retinal venous pressure. EPMA J. 2015;6:5. https://doi.org/10.1186/s13167-015-0027-1.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Bek T. Histopathology and pathophysiology of diabetic retinopathy. In: van Bijsterveld OP, editor. Diabetic Retinopathy. London: Martin Dunitz; 2000. p. 169–87.

    Google Scholar 

  14. Whitehead M, Wickremasinghe S, Osborne A, Van Wijngaarden P, Martin KR. Diabetic retinopathy: a complex pathophysiology requiring novel therapeutic strategies. Expert Opin Biol Ther. 2018;18(12):1257–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Browning DJ, Stewart MW, Lee C. Diabetic macular edema: evidence-based management. Indian J Ophthalmol. 2018;66:1736–50.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kador PF, Randazzo J, Blessing K, Makita J, Zhang P, Yu K, et al. Polyol formation in cell lines of rat retinal capillary pericytes and endothelial cells (TR-rPCT and TR-iBRB). J Ocul Pharmacol Ther. 2009;25(4):299–308. https://doi.org/10.1089/jop.2008.0070.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Peppa M, Vlassara H. Advanced glycation end products and diabetic complications: a general overview. Hormones. 2005;4(1):28–37.

    Article  PubMed  Google Scholar 

  18. Koya D, King GL. Protein kinase C activation and the development of diabetic complications. Diabetes. 1998;47(6):859–66. https://doi.org/10.2337/diabetes.47.6.859.

    Article  CAS  PubMed  Google Scholar 

  19. Peti-Peterdi J, Kang JJ, Toma I. Activation of the renal renin–angiotensin system in diabetes—new concepts. Nephrol Dial Transplant. 2008;23:3047–9. https://doi.org/10.1093/ndt/gfn377.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Verma A, Shan Z, Lei B, Yuan L, Liu X, Nakagawa T, et al. ACE2 and Ang-(1-7) Confer protection against development of diabetic retinopathy. Mol Ther. 2012;20(1):28–36.

    Article  CAS  PubMed  Google Scholar 

  21. Ibrahim AS, Saleh H, El-Shafey M, Hussein KA, El-Masry K, Baban B, et al. Targeting of 12/15-lipoxygenase in retinal endothelial cells, but not in monocytes/macrophages, attenuates high glucoseinduced retinal leukostasis. Biochim Biophys Acta. 2017;1862(6):636–45. https://doi.org/10.1016/j.bbalip.2017.03.010.

    Article  CAS  PubMed Central  Google Scholar 

  22. Lutty GA. Effects of diabetes on the eye. Invest Ophthalmol Vis Sci. 2013;54:81–7. https://doi.org/10.1167/iovs.13-12979.

    Article  Google Scholar 

  23. Bertram B, Wolf S, Fiehöfer S, Schulte K, Arend O, Reim M. Retinal circulation times in diabetes mellitus type 1. Br J Ophthalmol. 1991;75(8):462–5. https://doi.org/10.1136/bjo.75.8.462.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kang HR, Yang YS. Comparison of venous filling times and SLO findings at each quadrant region in diabetic retinopathy. Korean J Ophthalmol. 2003;17(2):133–9. https://doi.org/10.3341/kjo.2003.17.2.133.

    Article  PubMed  Google Scholar 

  25. Kim YW, Kim SJ, Yang YS. The clinical significance of venous filling time through panretinal photocoagulation in proliferative diabetic retinopathy. Korean J Ophthalmol. 2005;19:179–82.

    Article  PubMed  Google Scholar 

  26. Kang G, Lee J. Retinal circulation times in branch retinal vein occlusion. Korean J Ophthalmol. 1995;9(2):107–10. https://doi.org/10.3341/kjo.1995.9.2.107.

    Article  CAS  PubMed  Google Scholar 

  27. Dimitrova G, Kato S. Color Doppler imaging of retinal diseases. Surv Ophthalmol. 2010;55(3):193–214. https://doi.org/10.1016/j.survophthal.2009.06.010.

    Article  PubMed  Google Scholar 

  28. Tranquart F, Bergès O, Koskas P, Arsene S, Rossazza C, Pisella PJ, et al. Color Doppler imaging of orbital vessels: personal experience and literature review. J Clin Ultrasound. 2003;31(5):258–73. https://doi.org/10.1002/jcu.10169.

    Article  PubMed  Google Scholar 

  29. Pourcelot L. Applications cliniques de l’examen Doppler transcutané. INSERM. 1974;34:213–40.

    Google Scholar 

  30. Tamaki Y, Nagahara M, Yamashita H, Kikuchi M. Blood velocity in the ophthalmic artery determined by color Doppler imaging in normal subjects and diabetics. Jpn J Ophthalmol. 1993;37:385–92.

    CAS  PubMed  Google Scholar 

  31. Michelson G, Harazny J. Relationship between ocular pulse pressures and retinal vessel velocities. Ophthalmology. 1997;104:664–71.

    Article  CAS  PubMed  Google Scholar 

  32. Dimitrova G, Kato S, Tamaki Y, Yamashita H, Nagahara M, Sakurai M, et al. Choroidal circulation in diabetic patients. Eye. 2001;15(5):602–7. https://doi.org/10.1038/eye.2001.193.

    Article  CAS  PubMed  Google Scholar 

  33. Karami M, Janghorbani M, Dehghani A, Khaksar K, Kaviani A. Orbital Doppler evaluation of blood flow velocities in patients with diabetic retinopathy. Rev Diabet Stud. 2012;9:104–11.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Jonas JB, Harder B. Ophthalmodynamometric differences between ischemic vs nonischemic retinal vein occlusion. Am J Ophthalmol. 2007;143(1):112–6. https://doi.org/10.1016/j.ajo.2006.09.019.

    Article  PubMed  Google Scholar 

  35. Polito A, Polini G, GortanaChiodini R, Isola M, Soldano F, Bandello F. Effect of posture on the diurnal variation in clinically significant diabetic macular edema. Invest Ophthalmol Vis Sci. 2007;48:3318–23. https://doi.org/10.1167/iovs.06-1526.

    Article  PubMed  Google Scholar 

  36. Dimitrova G, Chihara E. Implication of deep-vascular-layer alteration detected by optical coherence tomography angiography for the pathogenesis of diabetic retinopathy. Ophthalmologica. 2019;241(4):179–82. https://doi.org/10.1159/000495624.

    Article  PubMed  Google Scholar 

  37. Lee J, Moon BG, Cho AR, Yoon YH. Optical coherence tomography angiography of DME and its association with anti-VEGF treatment response. Ophthalmology. 2016;123(11):2368–75. https://doi.org/10.1016/j.ophtha.2016.07.010.

    Article  PubMed  Google Scholar 

  38. Nesper PL, Fawzi AA. Human parafoveal capillary vascular anatomy and connectivity revealed by optical coherence tomography angiography. Invest Ophthalmol Vis Sci. 2018;59:3858–67. https://doi.org/10.1167/iovs.18-24710.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Hasegawa N, Nozaki M, Takase N, Yoshida M, Ogura Y. New insights into microaneurysms in the deep capillary plexus detected by optical coherence tomography angiography in diabetic macular edema. Invest Ophthalmol Vis Sci. 2016;57(9):348–55. https://doi.org/10.1167/iovs.15-18782.

    Article  Google Scholar 

  40. Cunha-Vaz J. The blood-retinal barrier in diabetes. In: van Bijsterveld OP, editor. Diabetic retinopathy. London: Martin Dunitz; 2000. p. 155–68.

    Google Scholar 

  41. Tsai G, Banaee T, Conti FF, Singh RP. Optical coherence tomography angiography in eyes with retinal vein occlusion. J Ophthalmic Vis Res. 2018;13(3):315–32.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Yu DY, Yu PK, Cringle SJ, Kang MH, Su EN. Functional and morphological characteristics of the retinal and choroidal vasculature. Prog Retin Eye Res. 2014;40:53–93.

    Article  PubMed  Google Scholar 

  43. Kang MH, Balaratnasingam C, Yu PK, Morgan WH, McAllister IL, Cringle SJ, et al. Morphometric characteristics of central retinal artery and vein endothelium in the normal human optic nerve head. Invest Ophthalmol Vis Sci. 2011;52(3):1359–67.

    Article  PubMed  Google Scholar 

  44. Dimitrova G, Kato S. Association of systemic cardio - vasculature status with retinal vascular endothelium in diabetes. Int Eye Sci. 2017;17(1):21–5.

    Google Scholar 

  45. McLeod DS, Lefer DG, Merges C, Lutty GA. Enhanced expression of intracellular adhesion molecule-1 and P-selectin in the diabetic human retina and choroid. Am J Pathol. 1995;147:642–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Klein BEK, Moss SE, Klein R, Magli Y, Hoyer CH. Neuroretinal rim area in diabetes mellitus. Invest Ophthalmol Vis Sci. 1990;31:805–9.

    CAS  PubMed  Google Scholar 

  47. Jonas JB, Wang N, Xu J, Wang YX, You QS, Yang D, et al. Diabetic retinopathy and estimated cerebrospinal fluid pressure. The Beijing Eye Study 2011. PLoS One. 2011;9(5):e96273. https://doi.org/10.1371/journal.pone.0096273.

    Article  CAS  Google Scholar 

  48. Stransky TJ. Diabetic papillopathy and proliferative retinopathy. Graefes Arch Clin Exp Ophthalmol. 1986;224(1):46–50.

    Article  CAS  PubMed  Google Scholar 

  49. Regillo CD, Brown GC, Savino PJ, Byrnes GA, Benson WE, Tasman WS, et al. Diabetic papillopathy - patient characteristics and fundus findings. Arch Ophthalmol. 1995;113(7):889–95.

    Article  CAS  PubMed  Google Scholar 

  50. Wang Q, Wang YX, Wu SL, Chen SH, Yan YN, Yang MC, et al. Ocular axial length and diabetic retinopathy: the Kailuan eye study. Invest Ophthalmol Vis Sci. 2019;60:3689–95.

    Article  CAS  PubMed  Google Scholar 

  51. Lin Z, Li D, Zhai G, Wang Y, Wen L, Ding XX, et al. High myopia is protective against diabetic retinopathy via thinning retinal vein: a report from Fushun Diabetic Retinopathy Cohort Study (FS-DIRECT). Diab Vasc Dis Res. 2020;17(4):1479164120940988. https://doi.org/10.1177/1479164120940988.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Akkaya S, Küçük B, Karaköse Doğan H, Can E. Evaluation of the lamina cribrosa in patients with diabetes mellitus using enhanced depth imaging spectral-domain optical coherence tomography. Diab Vasc Dis Res. 2018;15(5):442–8.

    Article  PubMed  Google Scholar 

  53. Amano S, Kaji Y, Oshika T, Oka T, Machinami R, Nagai R, et al. Advanced glycation end products in human optic nerve head. Br J Ophthalmol. 2001;85:52–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Christoffersen N, Larsen M. Unilateral diabetic macular oedema secondary to central retinal vein congestion. Acta Ophthalmol. 2004;82:591–5.

    Article  Google Scholar 

  55. Chen S, Chen Y, Xu L, Matei N, Tang J, Feng H, et al. Venous system in acute brain injury: mechanisms of pathophysiological change and function. Exp Neurol. 2015;272:4–10. https://doi.org/10.1016/j.expneurol.2015.03.007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Sleiman K, Zimny A, Kowalczyk E, Sąsiadek M. Acute cerebrovascular incident in a young woman: venous or arterial stroke? - comparative analysis based on two case reports. Pol J Radiol. 2013;78(4):70–8. https://doi.org/10.12659/PJR.889616.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Candelario-Jalil E, Taheri S, Rosenberg GA. Brain edema in neurological diseases. In: Blass JP, editor. Neurochemical mechanisms in disease. New York: Springer; 2011. p. 125–68. https://doi.org/10.1007/978-1-4419-7104-3_5.

    Chapter  Google Scholar 

  58. Bek T. Transretinalhistopathological changes in capillary-free areas of diabetic retinopathy. Acta Ophthalmol. 1994;72:409–15.

    Article  CAS  Google Scholar 

  59. Bek T. Capillary closure secondary to retinal vein occlusion. Acta Ophthalmol. 1998;76:643–8.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors wish to thank Mr. Igor Sekovski for the graphic design of the figures.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, City General Hospital “8th September”, Pariska bb, Skopje, 1000, North Macedonia

    Galina Dimitrova

  2. Department of Ophthalmology, Wilmer Ophthalmological Institute, Johns Hopkins University School of Medicine, Baltimore, USA

    Gerard Anthony Lutty

Authors
  1. Galina Dimitrova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gerard Anthony Lutty
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Galina Dimitrova: acquisition, analysis, interpretation of data for the work, and writing of manuscript.

Gerard A Lutty: analysis, interpretation of data for the work, and revised it critically for important intellectual content.

Both authors read and approved the final manuscript.

Corresponding author

Correspondence to Galina Dimitrova.

Ethics declarations

Ethics Approval

Not applicable

Consent to Participate

Not applicable

Consent for Publication

Not applicable

Competing Interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Medicine

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dimitrova, G., Lutty, G.A. The Role of Retinal Venous Congestion in Diabetic Retinopathy. SN Compr. Clin. Med. 3, 964–970 (2021). https://doi.org/10.1007/s42399-021-00809-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s42399-021-00809-3

Keywords

Search

Navigation