Advertisement

International Ophthalmology

, Volume 39, Issue 4, pp 821–828 | Cite as

Vitreous IL-8 and VEGF levels in diabetic macular edema with or without subretinal fluid

  • Fatih YenihayatEmail author
  • Berna Özkan
  • Murat Kasap
  • V. Levent Karabaş
  • Nil Güzel
  • Gürler Akpınar
  • Dilara Pirhan
Original Paper

Abstract

Purpose

To determine the cytokine levels in vitreous samples of diabetic macular edema (DME) patients in comparison with nondiabetic patients, and to evaluate the effect of subretinal fluid on the cytokine levels of vitreous samples.

Methods

In this prospective case–control study, 11 eyes of 11 patients with DME and subretinal fluid, 11 eyes of 11 patients with DME without subretinal fluid, and 14 eyes of 14 patients who had undergone vitreoretinal surgery for the epiretinal membrane or a macular hole (control group) were evaluated. The blood glycated hemoglobin (HbA1c) level, vitreous vascular endothelial growth factor (VEGF), and interleukin-8 (IL-8) levels were determined.

Results

The vitreous VEGF level of patients in DME groups was significantly higher than the control group (p < 0.001) without significant difference between DME patients with and without subretinal fluid (p = 0.796). The vitreous IL-8 level of DME patients with subretinal fluid was significantly higher than both control (p = 0.002) and DME without subretinal fluid groups (p = 0.019). The blood HbA1c level was significantly higher in DME group with subretinal fluid than those without subretinal fluid (8.7 ± 1.32 and 7.1 ± 1.13%, respectively, p = 0.010). The only significant correlation was between vitreous VEGF level and blood HbA1c level in DME patients without subretinal fluid (r = 0.813, p = 0.002).

Conclusions

IL-8 level in vitreous samples was higher in DME patients with subretinal fluid than those without subretinal fluid, suggesting that inflammation is an important factor in the progression of DME leading to the subretinal fluid formation in diabetic patients.

Keywords

Cystoid macular edema Intraocular cytokines Subretinal fluid Diabetes Interleukin-8 

Notes

Acknowledgements

This study was supported by Kocaeli University Scientific Research Project Coordination Unit (KOU-BAP: Project Number: 2014/83-84HD, 2015/49-50HD). Institutional Review Board Approval Number: KOÜ KAEK 2014/155.

Funding

This study was supported by Kocaeli University Scientific Research Project Coordination Unit (KOU-BAP: Project Number: 2014/83-84HD, 2015/49-50HD).

Compliance with ethical standards

Conflict of interest

All the authors declared that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional ethical committee with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Institutional Review Board Approval Number: KOÜ KAEK 2014/155.

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    Klein R, Klein BE, Moss SE, Davis MD, DeMets DL (1984) The Wisconsin epidemiologic study of diabetic retinopathy IV: diabetic macular edema. Ophthalmology 91:1464–1474CrossRefGoogle Scholar
  2. 2.
    Antcliff RJ, Marshall J (1999) The pathogenesis of edema in diabetic maculopathy. Semin Ophthalmol 14:223–232CrossRefGoogle Scholar
  3. 3.
    Frank RN (2004) Diabetic retinopathy. N Engl J Med 350:48–58CrossRefGoogle Scholar
  4. 4.
    Bhagat N, Grigorian RA, Tutela A, Zarbin MA (2008) Diabetic macular edema: pathogenesis and treatment. Surv Ophthalmol 54:1–32.  https://doi.org/10.1016/j.survophthal.2008.10.001 CrossRefGoogle Scholar
  5. 5.
    Adamis AP, Berman AJ (2008) Immunological mechanisms in the pathogenesis of diabetic retinopathy. Semin Immunopathol 30:65–84.  https://doi.org/10.1007/s00281-008-0111-x CrossRefGoogle Scholar
  6. 6.
    Roh MI, Kim HS, Song JH, Lim JB, Kwon OW (2009) Effect of intravitreal bevacizumab injection on aqueous humor cytokine levels in clinically significant macular edema. Ophthalmology 116:80–86.  https://doi.org/10.1016/j.ophtha.2008.09.036 CrossRefGoogle Scholar
  7. 7.
    Funatsu HD, Noma H, Tatsuya M, Shuichiro E, Hori S (2009) Association of vitreous inflammatory factors with diabetic macular edema. Ophthalmology 116:73–79.  https://doi.org/10.1016/j.ophtha.2008.09.037 CrossRefGoogle Scholar
  8. 8.
    Otani T, Kishi S, Maruyama Y (1999) Patterns of diabetic macular edema with optical coherence tomography. Am J Ophthalmol 127:688–693CrossRefGoogle Scholar
  9. 9.
    Özdemir H, Karaçorlu M, Karaçorlu SA (2005) Regression of serous macular detachment after intravitreal triamcinolone acetonide in patients with diabetic macular edema. Am J Ophthalmol 140:251–255CrossRefGoogle Scholar
  10. 10.
    Sohn HJ, Han DH, Kim IT et al (2011) Changes in aqueous concentrations of various cytokines after intravitreal triamcinolone versus bevacizumab for diabetic macular edema. Am J Ophthalmol 152:686–694.  https://doi.org/10.1016/j.ajo.2011.03.033 CrossRefGoogle Scholar
  11. 11.
    Jonas JB, Jonas RA, Neumaier M, Findeisen P (2012) Cytokine concentration in aqueous humor of eyes with diabetic macular edema. Retina 32:2150–2157.  https://doi.org/10.1097/IAE.0b013e3182576d07 CrossRefGoogle Scholar
  12. 12.
    Gaucher D, Sebah C, Erginay A et al (2008) Optical Coherence tomography features during the evolution of serous retinal detachment in patients with diabetic macular edema. Am J Ophthalmol 145:289–296CrossRefGoogle Scholar
  13. 13.
    Antonetti DA, Barber AJ, Khin S, Lieth E, Tarbell JM, Gardner TW (1998) Vascular permeability in experimental diabetes is associated with reduced endothelial occludin content: vascular endothelial growth factor decreases occludin in retinal endothelial cells. Penn State Retina Research Group. Diabetes 47:1953–1959CrossRefGoogle Scholar
  14. 14.
    Marmor MF (1999) Mechanisms of fluid accumulation in retinal edema. Doc Ophthalmol 97:239–249CrossRefGoogle Scholar
  15. 15.
    Kang SW, Park CY, Ham DI (2004) The correlation between fluorescein angiographic and optical coherence tomographic features in clinically significant diabetic macular edema. Am J Ophthalmol 137:313–322CrossRefGoogle Scholar
  16. 16.
    Nishikiori N, Osanai M, Chiba H et al (2007) Glial cell-derived cytokines attenuate the breakdown of vascular integrity in diabetic retinopathy. Diabetes 56:1333–1340CrossRefGoogle Scholar
  17. 17.
    Aiello LP, Avery RL, Arrigg PG et al (1994) Vascular endothelial growth factor in ocular fluids of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 331:1480–1487CrossRefGoogle Scholar
  18. 18.
    Murata T, Ishibashi T, Khalil A, Hata Y, Yoshikawa H, Inomata H (1995) Vascular endothelial factor plays a role in hyperpermeability of diabetic retinal vessels. Ophthalmic Res 27:48–52CrossRefGoogle Scholar
  19. 19.
    Murata T, Nakagawa K, Khalil A, Ishibashi T, Inomata H, Sueishi K (1996) The relation between expression of vascular endothelial growth factor and breakdown of the blood-retinal barrier in diabetic rat retinal retinas. Lab Invest 74:819–825Google Scholar
  20. 20.
    Antonetti DA, Barber AJ, Hollinger LA, Wolpert EB, Gardner TW (1999) Vascular endothelial growth factor induces rapid phosphorylation of tight junction proteins occludin and zonula occludens 1. J Biol Chem 274:23463–23467CrossRefGoogle Scholar
  21. 21.
    Kaji Y, Usui T, Ishida S et al (2007) Inhibition of diabetic leukostasis and blood-retinal barrier breakdown with a soluble form of a receptor for advanced glycation end products. Invest Ophthalmol Vis Sci 48:858–865CrossRefGoogle Scholar
  22. 22.
    Cohen T, Nahari D, Cerem LW, Neufeld G, Levi BZ (1996) Interleukin 6 induces the expression of vascular endothelial growth factor. J Biol Chem 271:736–741CrossRefGoogle Scholar
  23. 23.
    Pfeiffer A, Spranger J, Meyer-Schwickerath R, Schatz H (1997) Growth factor alterations in advanced diabetic retinopathy: a possible role of blood-retina barrier breakdown. Diabetes 46(Suppl 2):S26–S30CrossRefGoogle Scholar
  24. 24.
    Ozdemir H, Karacorlu M, Karacorlu SA (2005) Regression of serous macular detachment after intravitreal triamcinolone acetonide in patients with diabetic macular edema. Am J Ophthalmol 140:251–255CrossRefGoogle Scholar
  25. 25.
    Lee YS, Choi I, Ning Y et al (2012) Interleukin 8 and its receptor CXCR2 in the tumour microenvironment promote colon cancer growth, progression and metastasis. Br J Cancer 106:1833–1841.  https://doi.org/10.1038/bjc.2012.177 CrossRefGoogle Scholar
  26. 26.
    Aksunger A, Or M, Okur H, Hasanreisoğlu B, Akbatur H (1997) Role of interleukin 8 in the pathogenesis of proliferative vitreoretinopathy. Ophthalmologica 211:223–225CrossRefGoogle Scholar
  27. 27.
    Petrovič MG, Korošec P, Košnik M, Hawlina M (2007) Vitreous levels of interleukin-8 in patients with proliferative diabetic retinopathy. Am J Ophthalmol 143:175–176CrossRefGoogle Scholar
  28. 28.
    Kim M, Kim Y, Lee SJ (2015) Comparison of aqueous concentrations of angiogenic and inflammatory cytokines based on optical coherence tomography patterns of diabetic macular edema. Indian J Ophthalmol 63:312–317.  https://doi.org/10.4103/0301-4738.158069 CrossRefGoogle Scholar
  29. 29.
    American Diabetes Association (1998) Standards of medical care for patients with diabetes mellitus. Diabetes Care 21:23–31.  https://doi.org/10.2337/diacare.21.1.S23 CrossRefGoogle Scholar
  30. 30.
    Klein R, Klein BE, Boss SE, Cruickshanks KJ (1995) Wisconsin-epidemiologic study of diabetic retinopathy. XV. The long-term incidence of macular edema. Ophthalmology 102:7–16CrossRefGoogle Scholar
  31. 31.
    Turgut B, Gul FC, Ilhan N, Demir T, Celiker U (2010) Comparison of serum glycosylated hemoglobin levels in patients with diabetic cystoid macular edema with and without serous macular detachment. Indian J Ophthalmol 58:381–384.  https://doi.org/10.4103/0301-4738.67044 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of OphthalmologyKocaeli State HospitalKocaeliTurkey
  2. 2.Department of OphthalmologyAcıbadem Mehmet Ali Aydınlar University Medical SchoolIstanbulTurkey
  3. 3.DEKART Proteomics LaboratoryKocaeli University Medical SchoolKocaeliTurkey
  4. 4.Department of OphthalmologyKocaeli University Medical SchoolKocaeliTurkey

Personalised recommendations