Current Diabetes Reports

, 17:83 | Cite as

Intraocular Inflammation in Diabetic Populations

  • Wajiha J. Kheir
  • Huda A. Sheheitli
  • Rola N. Hamam
Microvascular Complications—Retinopathy (JK Sun and PS Silva, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Microvascular Complications—Retinopathy


Purpose of review

The purpose of this review is to determine the prevalence of uveitis in the diabetic population, the clinical features of the uveitis and diabetes when coexisting and pathophysiology of a possible correlation. We also aim to review the cases of diabetes and uveitis in the literature.

Recent findings

The basis of an association between uveitis and diabetes mellitus (DM) is the common pathophysiology of inflammation. There are several reports on a DM-related uveitis, defined as idiopathic anterior uveitis in the presence of poorly controlled DM, but causation has not been established.


There are conflicting results in the literature regarding an association between uveitis and DM. More studies are needed to determine if an association truly exists.


Uveitis Diabetes mellitus Blood-retinal barrier Blood-aqueous barrier Panretinal photocoagulation Intraocular inflammation 


Compliance with Ethical Standards

Conflict of Interest

Wajiha J. Kheir, Huda A. Sheheitli, and Rola N. Hamam declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: •Of importance•• Of major importance

  1. 1.
    Castagna I, Fama F, Salmeri G. Anterior uveitis and diabetes mellitus: immunological study. Ophthalmologica. 1995;209(2):53–5.CrossRefPubMedGoogle Scholar
  2. 2.
    Herranz M, et al. Increased prevalence of NIDDM in anterior uveitis. Diabetes Care. 1997;20(11):1797.CrossRefPubMedGoogle Scholar
  3. 3.
    Oswal KS, et al. Clinical features of patients with diabetes mellitus presenting with their first episode of uveitis. Ocul Immunol Inflamm. 2009;17(6):390–3.CrossRefPubMedGoogle Scholar
  4. 4.
    Al-Halafi A, et al. The association of systemic disorders with Vogt-Koyanagi-Harada and sympathetic ophthalmia. Graefes Arch Clin Exp Ophthalmol. 2011;249(8):1229–33.CrossRefPubMedGoogle Scholar
  5. 5.
    Waite JH, Beetham WP. The visual mechanism in diabetes mellitus: a comparative study of 2002 diabetics, and 457 non-diabetics for control. N Engl J Med. 1935;212(9):367–79.CrossRefGoogle Scholar
  6. 6.
    Rothova A, et al. Uveitis and systemic disease. Br J Ophthalmol. 1992;76(3):137–41.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Noyes HD. Retinitis in glycosuria. Trans Am Ophthalmol Soc. 1868;1(4–5):71.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Ojaimi E, et al. Vogt-Koyanagi-Harada disease, diabetes mellitus, and psoriasis in a child. Ocul Immunol Inflamm. 2012;20(1):56–8.CrossRefPubMedGoogle Scholar
  9. 9.
    Rottgers E, Holdeman NR. An unusual case of chorioretinitis in a diabetic patient. Clin Exp Optom. 2009;92(2):142–5.CrossRefPubMedGoogle Scholar
  10. 10.
    Sinha MK, Narayanan R, Chhablani JK. Hypopyon uveitis following panretinal photocoagulation in a diabetic patient. Semin Ophthalmol. 2014;29(3):166–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Takahashi Y, et al. Severe anterior uveitis associated with idiopathic dacryoadenitis in diabetes mellitus patient. Clin Ophthalmol. 2011;5:619–21.PubMedPubMedCentralGoogle Scholar
  12. 12.
    • Tyagi M, Ambiya V, Rani PK. Hypopyon uveitis following panretinal photocoagulation. BMJ Case Rep. 2016; This case report is of a patient with DM and uveitis who develops recurrent ocular inflammation after panretinal photoagulation Google Scholar
  13. 13.
    Stanga P, Boyd S, Hamilton A. Ocular manifestations of diabetes mellitus. Curr Opin Ophthalmol. 1999;10(6):483–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Liberman P, et al. Causes of uveitis in a tertiary center in Chile: a cross-sectional retrospective review. Ocul Immunol Inflamm. 2014:1–7.Google Scholar
  15. 15.
    Rothova A, et al. Uveitis and diabetes mellitus. Am J Ophthalmol. 1988;106(1):17–20.CrossRefPubMedGoogle Scholar
  16. 16.
    •• Oswal KS, et al. Clinical course and visual outcome in patients with diabetes mellitus and uveitis. BMC research notes. 2013;6(1):167. This retrospective study reported a greater complication rate, reduced vision and poor glycemic control in patients with DM who develop uveitis CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Chatzistefanou K, et al. Characteristics of uveitis presenting for the first time in the elderly. Ophthalmology. 1998;105(2):347–52.CrossRefPubMedGoogle Scholar
  18. 18.
    Yawata N, et al. High incidence of glucose intolerance in Vogt–Koyanagi–Harada disease. Br J Ophthalmol. 1999;83(1):39–42.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Barton K, et al. Uveitis presenting de novo in the elderly. Eye (Lond). 1994;8(Pt 3):288–91.CrossRefGoogle Scholar
  20. 20.
    Nalcacioglu-Yuksekkaya P, et al. Clinical and demographic characteristics of patients with uveitis starting later in life. Ocul Immunol Inflamm. 2014:1–7.Google Scholar
  21. 21.
    Martyn C, Young R, Ewing D. Is there a link between iritis and diabetic autonomic neuropathy? Br Med J (Clin Res Ed). 1986;292(6525):934.CrossRefGoogle Scholar
  22. 22.
    Gregoire MA, et al. Characteristics of uveitis presenting for the first time in the elderly: analysis of 91 patients in a tertiary center. Ocul Immunol Inflamm. 2011;19(4):219–26.CrossRefPubMedGoogle Scholar
  23. 23.
    Hemidan A, Tabbara K, Althomali T. Vogt-Koyanagi-Harada associated with diabetes mellitus and celiac disease in a 3-year-old girl. Eur J Ophthalmol. 2006;16(1):173.PubMedGoogle Scholar
  24. 24.
    Jaggarao N, Voth D, Jacobsen J. The Vogt-Koyanagi-Harada syndrome: association with hypothyroidism and diabetes mellitus. Postgrad Med J. 1989;65(766):587–8.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Maruyama Y, et al. A case of insulin dependent diabetes mellitus following systemic treatment with corticosteroids for Vogt-Koyanagi-Harada syndrome. Ophthalmic Surgery, Lasers and Imaging Retina. 2000;31(6):487–90.Google Scholar
  26. 26.
    Murray D, Sung V, Headon M. Asymmetric diabetic retinopathy associated with Fuchs’ heterochromic cyclitis. Br J Ophthalmol. 1999;83(8):987-987.CrossRefGoogle Scholar
  27. 27.
    Al Shehri FS. Uveitis in diabetic woman. International Journal of Diabetes Mellitus. 2009;1(1):59–60.CrossRefGoogle Scholar
  28. 28.
    Guy R, et al. Diabetic autonomic neuropathy and iritis: an association suggesting an immunological cause. Br Med J (Clin Res Ed). 1984;289(6441):343–5.CrossRefGoogle Scholar
  29. 29.
    Patel AK, et al. Risk of retinal neovascularization in cases of uveitis. Ophthalmology. 2016;123(3):646–54.CrossRefPubMedGoogle Scholar
  30. 30.
    Joussen AM, et al. A central role for inflammation in the pathogenesis of diabetic retinopathy. FASEB J. 2004;18(12):1450–2.PubMedGoogle Scholar
  31. 31.
    Joussen AM, et al. Leukocyte-mediated endothelial cell injury and death in the diabetic retina. Am J Pathol. 2001;158(1):147–52.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Fujikawa LS, et al. Retinal vascular endothelium expresses fibronectin and class II histocompatibility complex antigens in experimental autoimmune uveitis. Cell Immunol. 1987;106(1):139–50.CrossRefPubMedGoogle Scholar
  33. 33.
    Tang J, Kern TS. Inflammation in diabetic retinopathy. Prog Retin Eye Res. 2011;30(5):343–58.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Ongkosuwito JV, et al. Analysis of immunoregulatory cytokines in ocular fluid samples from patients with uveitis. Invest Ophthalmol Vis Sci. 1998;39(13):2659–65.PubMedGoogle Scholar
  35. 35.
    Nussenblatt RB, et al. The immunological basis of degenerative diseases of the eye. Int Rev Immunol. 2013;32(1):97–112.CrossRefPubMedGoogle Scholar
  36. 36.
    Adamis AP, Berman AJ. Immunological mechanisms in the pathogenesis of diabetic retinopathy. Semin Immunopathol. 2008;30(2):65–84.CrossRefPubMedGoogle Scholar
  37. 37.
    Cantón A, et al. CD4-CD8 and CD28 expression in t cells infiltrating the vitreous fluidin patients with proliferative diabetic retinopathy: a flow cytometric analysis. Arch Ophthalmol. 2004;122(5):743–9.CrossRefPubMedGoogle Scholar
  38. 38.
    Demircan N, et al. Determination of vitreous interleukin-1 (IL-1) and tumour necrosis factor (TNF) levels in proliferative diabetic retinopathy. Eye (Lond). 2006;20(12):1366–9.CrossRefGoogle Scholar
  39. 39.
    Elner SG, et al. Interferon-induced protein 10 and interleukin 8: CXC chemokines present in proliferative diabetic retinopathy. Arch Ophthalmol. 1998;116(12):1597–601.CrossRefPubMedGoogle Scholar
  40. 40.
    Adamiec-Mroczek J, Oficjalska-Mlynczak J, Misiuk-Hojlo M. Roles of endothelin-1 and selected proinflammatory cytokines in the pathogenesis of proliferative diabetic retinopathy: Analysis of vitreous samples. Cytokine. 2010;49(3):269–74.CrossRefPubMedGoogle Scholar
  41. 41.
    Murugeswari P, et al. Proinflammatory cytokines and angiogenic and anti-angiogenic factors in vitreous of patients with proliferative diabetic retinopathy and Eales’ disease. Retina. 2008;28(6):817–24.CrossRefPubMedGoogle Scholar
  42. 42.
    Zhou J, Wang S, Xia X. Role of intravitreal inflammatory cytokines and angiogenic factors in proliferative diabetic retinopathy. Curr Eye Res. 2012;37(5):416–20.CrossRefPubMedGoogle Scholar
  43. 43.
    Bromberg-White JL, et al. Identification of VEGF-independent cytokines in proliferative diabetic retinopathy vitreous. Invest Ophthalmol Vis Sci. 2013;54(10):6472–80.CrossRefPubMedGoogle Scholar
  44. 44.
    Takeuchi M, et al. Elevated levels of cytokines associated with Th2 and Th17 cells in vitreous fluid of proliferative diabetic retinopathy patients. PLoS One. 2015;10(9):e0137358.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Doganay S, et al. Comparison of serum NO, TNF-α, IL-1β, sIL-2R, IL-6 and IL-8 levels with grades of retinopathy in patients with diabetes mellitus. Eye. 2002;16(2):163–70.CrossRefPubMedGoogle Scholar
  46. 46.
    Funatsu H, et al. Aqueous humor levels of cytokines are related to vitreous levels and progression of diabetic retinopathy in diabetic patients. Graefes Arch Clin Exp Ophthalmol. 2005;243(1):3–8.CrossRefPubMedGoogle Scholar
  47. 47.
    Gerl VB, et al. Extensive deposits of complement C3d and C5b-9 in the choriocapillaris of eyes of patients with diabetic retinopathy. Invest Ophthalmol Vis Sci. 2002;43(4):1104–8.PubMedGoogle Scholar
  48. 48.
    Cunha-Vaz J, De Abreu JF, Campos A. Early breakdown of the blood-retinal barrier in diabetes. Br J Ophthalmol. 1975;59(11):649–56.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Jandrasits K, Krepler K, Wedrich A. Aqueous flare and macular edema in eyes with diabetic retinopathy. Ophthalmologica. 2003;217(1):49–52.CrossRefPubMedGoogle Scholar
  50. 50.
    Ino-ue M, et al. Laser flare intensity in diabetics: correlation with retinopathy and aqueous protein concentration. Br J Ophthalmol. 1994;78(9):694–7.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Moriarty A, et al. Studies of the blood-aqueous barrier in diabetes mellitus. Am J Ophthalmol. 1994;117(6):768–71.CrossRefPubMedGoogle Scholar
  52. 52.
    Nguyen N, Schönherr U, Küchle M. Aqueous flare and retinal capillary changes in eyes with diabetic retinopathy. Ophthalmologica. 1995;209(3):145–8.CrossRefPubMedGoogle Scholar
  53. 53.
    Moriarty AP, et al. Breakdown of the blood-aqueous barrier after argon laser panretinal photocoagulation for proliferative diabetic retinopathy. Ophthalmology. 1996;103(5):833–8.CrossRefPubMedGoogle Scholar
  54. 54.
    Baudouin C, et al. MHC class II antigen expression by ocular cells in proliferative diabetic retinopathy. Fundamental & clinical pharmacology. 1993;7(9):523–30.CrossRefGoogle Scholar
  55. 55.
    Udoetuk JD, et al. Risk of corticosteroid-induced hyperglycemia requiring medical therapy among patients with inflammatory eye diseases. Ophthalmology. 2012;119(8):1569–74.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Savin J. Diabetes mellitus, sarcoidosis,? necrobiosis lipoidica. Proceedings of the Royal Society of Medicine. 1969;62(4):350.PubMedPubMedCentralGoogle Scholar
  57. 57.
    Gordon D, Browne B. Macular oedema with associated uveitis and cataract following presentation of type 1 diabetes mellitus in severe ketoacidosis. Diabet Med. 2000;17(4):326–8.CrossRefPubMedGoogle Scholar
  58. 58.
    Yamamoto J, et al. Severe bilateral necrotising retinitis caused by toxoplasma gondii in a patient with systemic lupus erythematosus and diabetes mellitus. Br J Ophthalmol. 2003;87(5):651–2.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Knol JA, et al. Rapid progression of diabetic retinopathy in eyes with posterior uveitis. Am J Ophthalmol. 2006;141(2):409–12.CrossRefPubMedGoogle Scholar
  60. 60.
    Suzuki H, Isaka M, Suzuki S. Type 1 diabetes mellitus associated with Graves’ disease and Vogt-Koyanagi-Harada syndrome. Intern Med. 2008;47(13):1241–4.CrossRefPubMedGoogle Scholar
  61. 61.
    Krifa F, et al. Uveitis responding on gluten free diet in a girl with celiac disease and diabetes mellitus type 1. Gastroenterol Clin Biol. 2010;34(4–5):319–20.CrossRefPubMedGoogle Scholar
  62. 62.
    Talat L, et al. The influence of diabetes mellitus on the management and visual outcome of patients with uveitis. Acta Ophthalmol. 2014;92(4):e329–30.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Wajiha J. Kheir
    • 1
  • Huda A. Sheheitli
    • 1
  • Rola N. Hamam
    • 1
  1. 1.Department of Ophthalmology, Ocular Immunology and Uveitis ServiceAmerican University of BeirutBeirutLebanon

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