Skip to main content

Advertisement

Log in

Systemic and vitreous biomarkers — new insights in diabetic retinopathy

  • Retinal Disorders
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

Diabetic retinopathy (DR) is a microvascular inflammatory and neurodegenerative disease. The purpose of this study was to analyze the relationship between DR severity and the levels of potential biomarkers in the serum and/or vitreous.

Methods

A prospective, consecutive, controlled, observational study was performed between June 2018 and January 2020. Blood and vitreous samples were collected on the day of vitrectomy in patients without diabetes and in patients with diabetes with epiretinal membrane, macular edema, and indication for vitrectomy.

Results

Transthyretin (TTR) was the only blood biomarker with levels statistically higher in patients with diabetes (p = 0.037). However, no correlation with DR severity was observed. Erythropoietin (EPO) was the only blood biomarker whose levels were associated with DR severity (p = 0.036). In vitreous samples, levels of EPO (p = 0.011), interleukin (IL)-6 (p < 0.001), IL-8 (p < 0.001), IL-17 (p = 0.022), monokine induced by interferon-γ (MIG) (p < 0.001), and interferon gamma–induced protein 10 (IP-10) (p = 0.005) were significantly higher in patients with diabetes. Additionally, in vitreous, IL-6, IL-8, MIG, and IPL-10 levels were also higher in more severe DR cases (p < 0.05).

Conclusions

Among the studied biomarkers, vitreous IL-6, IL-8, MIG, and IP-10 were the ones whose levels had the strongest coherent relationship with DR severity prediction and, thus, have the best potential post-vitrectomy prognostic value.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

The raw data on which this manuscript is based is available from the authors upon reasonable request.

Code availability

Not applicable.

References

  1. Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, Colagiuri S, Guariguata L, Motala AA, Ogurtsova K, Shaw JE, Bright D, Williams R (2019) Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation Diabetes Atlas, 9(th) edition. Diabetes Res Clin Pract 157:107843. https://doi.org/10.1016/j.diabres.2019.107843

    Article  PubMed  Google Scholar 

  2. Yau JW, Rogers SL, Kawasaki R, Lamoureux EL, Kowalski JW, Bek T, Chen SJ, Dekker JM, Fletcher A, Grauslund J, Haffner S, Hamman RF, Ikram MK, Kayama T, Klein BE, Klein R, Krishnaiah S, Mayurasakorn K, O’Hare JP, Orchard TJ, Porta M, Rema M, Roy MS, Sharma T, Shaw J, Taylor H, Tielsch JM, Varma R, Wang JJ, Wang N, West S, Xu L, Yasuda M, Zhang X, Mitchell P, Wong TY (2012) Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care 35:556–564. https://doi.org/10.2337/dc11-1909

    Article  PubMed  PubMed Central  Google Scholar 

  3. Simó R, Stitt AW, Gardner TW (2018) Neurodegeneration in diabetic retinopathy: does it really matter? Diabetologia 61:1902–1912. https://doi.org/10.1007/s00125-018-4692-1

    Article  PubMed  PubMed Central  Google Scholar 

  4. Sohn EH, van Dijk HW, Jiao C, Kok PH, Jeong W, Demirkaya N, Garmager A, Wit F, Kucukevcilioglu M, van Velthoven ME, DeVries JH, Mullins RF, Kuehn MH, Schlingemann RO, Sonka M, Verbraak FD, Abràmoff MD (2016) Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus. Proc Natl Acad Sci U S A 113:E2655-2664. https://doi.org/10.1073/pnas.1522014113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Sinclair SH, Schwartz SS (2019) Diabetic retinopathy-an underdiagnosed and undertreated inflammatory, neuro-vascular complication of diabetes. Front Endocrinol (Lausanne) 10:843. https://doi.org/10.3389/fendo.2019.00843

    Article  Google Scholar 

  6. Jumper JM, Embabi SN, Toth CA, McCuen BW II, Hatchell DL (2000) Electron immunocytochemical analysis of posterior hyaloid associated with diabetic macular edema. Retina 20:63–68. https://doi.org/10.1097/00006982-200001000-00012

    Article  CAS  PubMed  Google Scholar 

  7. Boss JD, Singh PK, Pandya HK, Tosi J, Kim C, Tewari A, Juzych MS, Abrams GW, Kumar A (2017) Assessment of neurotrophins and inflammatory mediators in vitreous of patients with diabetic retinopathy. Invest Ophthalmol Vis Sci 58:5594–5603. https://doi.org/10.1167/iovs.17-21973

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Luo BA, Gao F, Qin LL (2017) The association between vitamin D deficiency and diabetic retinopathy in type 2 diabetes: a meta-analysis of observational studies. Nutrients 9.https://doi.org/10.3390/nu9030307

  9. Lopes M, Laiginhas R, Madeira C, Neves JS, Barbosa M, Rosas V, Carvalho D, Falcão-Reis F, Falcão M (2020) Association between serum vitamin D and diabetic retinopathy in Portuguese patients with type 1 diabetes. Acta Med Port 33:459–465. https://doi.org/10.20344/amp.12890

    Article  CAS  PubMed  Google Scholar 

  10. Almoosa A, Ayachit S, Doms P-H, Aldoseri A, Wagih W (2019) Incidence of vitamin D deficiency in patients with type II diabetes mellitus and its relation to the severity of retinopathy. Bahrain Med Bull 41:238–240

    Google Scholar 

  11. Inomata Y, Hirata A, Takahashi E, Kawaji T, Fukushima M, Tanihara H (2004) Elevated erythropoietin in vitreous with ischemic retinal diseases. NeuroReport 15:877–879. https://doi.org/10.1097/00001756-200404090-00029

    Article  CAS  PubMed  Google Scholar 

  12. García-Arumí J, Fonollosa A, Macià C, Hernandez C, Martinez-Castillo V, Boixadera A, Zapata MA, Simo R (2009) Vitreous levels of erythropoietin in patients with macular oedema secondary to retinal vein occlusions: a comparative study with diabetic macular oedema. Eye (Lond) 23:1066–1071. https://doi.org/10.1038/eye.2008.230

    Article  CAS  Google Scholar 

  13. Hernández C, Fonollosa A, García-Ramírez M, Higuera M, Catalán R, Miralles A, García-Arumí J, Simó R (2006) Erythropoietin is expressed in the human retina and it is highly elevated in the vitreous fluid of patients with diabetic macular edema. Diabetes Care 29:2028–2033. https://doi.org/10.2337/dc06-0556

    Article  PubMed  Google Scholar 

  14. Shao J, Yao Y (2016) Transthyretin represses neovascularization in diabetic retinopathy. Mol Vis 22:1188–1197

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Chen YH, Chen HS, Tarng DC (2012) More impact of microalbuminuria on retinopathy than moderately reduced GFR among type 2 diabetic patients. Diabetes Care 35:803–808. https://doi.org/10.2337/dc11-1955

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wilkinson CP, Ferris FL 3rd, Klein RE, Lee PP, Agardh CD, Davis M, Dills D, Kampik A, Pararajasegaram R, Verdaguer JT (2003) Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology 110:1677–1682. https://doi.org/10.1016/s0161-6420(03)00475-5

    Article  CAS  PubMed  Google Scholar 

  17. Merchant ML, Klein JB (2009) Proteomics and diabetic retinopathy. Clin Lab Med 29:139–149. https://doi.org/10.1016/j.cll.2009.01.008

    Article  PubMed  Google Scholar 

  18. Zhang H, Liang L, Huang R, Wu P, He L (2020) Comparison of inflammatory cytokines levels in the aqueous humor with diabetic retinopathy. Int Ophthalmol 40:2763–2769. https://doi.org/10.1007/s10792-020-01463-9

    Article  PubMed  Google Scholar 

  19. Takeuchi M, Sato T, Tanaka A, Muraoka T, Taguchi M, Sakurai Y, Karasawa Y, Ito M (2015) Elevated levels of cytokines associated with Th2 and Th17 cells in vitreous fluid of proliferative diabetic retinopathy patients. PLoS One 10:e0137358. https://doi.org/10.1371/journal.pone.0137358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Song S, Yu X, Zhang P, Dai H (2020) Increased levels of cytokines in the aqueous humor correlate with the severity of diabetic retinopathy. J Diabetes Complications 34:107641. https://doi.org/10.1016/j.jdiacomp.2020.107641

    Article  PubMed  Google Scholar 

  21. Yoshida S, Kubo Y, Kobayashi Y, Zhou Y, Nakama T, Yamaguchi M, Tachibana T, Ishikawa K, Arita R, Nakao S, Sassa Y, Oshima Y, Kono T, Ishibashi T (2015) Increased vitreous concentrations of MCP-1 and IL-6 after vitrectomy in patients with proliferative diabetic retinopathy: possible association with postoperative macular oedema. Br J Ophthalmol 99:960–966. https://doi.org/10.1136/bjophthalmol-2014-306366

    Article  PubMed  Google Scholar 

  22. Loporchio DF, Tam EK, Cho J, Chung J, Jun GR, Xia W, Fiorello MG, Siegel NH, Ness S, Stein TD, Subramanian ML (2021) Cytokine levels in human vitreous in proliferative diabetic retinopathy. Cells 10.https://doi.org/10.3390/cells10051069

  23. Yenihayat F, Özkan B, Kasap M, Karabaş VL, Güzel N, Akpınar G, Pirhan D (2019) Vitreous IL-8 and VEGF levels in diabetic macular edema with or without subretinal fluid. Int Ophthalmol 39:821–828. https://doi.org/10.1007/s10792-018-0874-6

    Article  PubMed  Google Scholar 

  24. Deuchler S, Schubert R, Singh P, Chedid A, Brui N, Kenikstul N, Kohnen T, Ackermann H, Koch F (2021) Vitreous expression of cytokines and growth factors in patients with diabetic retinopathy-an investigation of their expression based on clinical diabetic retinopathy grade. PLoS One 16:e0248439. https://doi.org/10.1371/journal.pone.0248439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Sassa Y, Yoshida S, Ishikawa K, Asato R, Ishibashi T, Kono T (2016) The kinetics of VEGF and MCP-1 in the second vitrectomy cases with proliferative diabetic retinopathy. Eye (Lond) 30:746–753. https://doi.org/10.1038/eye.2016.20

    Article  CAS  Google Scholar 

  26. Loukovaara S, Nurkkala H, Tamene F, Gucciardo E, Liu X, Repo P, Lehti K, Varjosalo M (2015) Quantitative proteomics analysis of vitreous humor from diabetic retinopathy patients. J Proteome Res 14:5131–5143. https://doi.org/10.1021/acs.jproteome.5b00900

    Article  CAS  PubMed  Google Scholar 

  27. Takeuchi M, Sato T, Sakurai Y, Taguchi M, Harimoto K, Karasawa Y, Ito M (2017) Association between aqueous humor and vitreous fluid levels of Th17 cell-related cytokines in patients with proliferative diabetic retinopathy. PLoS One 12:e0178230. https://doi.org/10.1371/journal.pone.0178230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Gouliopoulos NS, Kalogeropoulos C, Lavaris A, Rouvas A, Asproudis I, Garmpi A, Damaskos C, Garmpis N, Kostakis A, Moschos MM (2018) Association of serum inflammatory markers and diabetic retinopathy: a review of literature. Eur Rev Med Pharmacol Sci 22:7113–7128. https://doi.org/10.26355/eurrev_201811_16243

    Article  CAS  PubMed  Google Scholar 

  29. Wang JGH, Liang L (2017) Correlation analysis of new inflammatory factor interleukin-17 with diabetic retinopathy. Chin J Optom Ophthalmol Vis Sci 19:428–431

    Google Scholar 

  30. Simó-Servat O, Hernández C, Simó R (2012) Usefulness of the vitreous fluid analysis in the translational research of diabetic retinopathy. Mediators Inflamm 2012:872978. https://doi.org/10.1155/2012/872978

    Article  PubMed  PubMed Central  Google Scholar 

  31. Nawaz MI, Van Raemdonck K, Mohammad G, Kangave D, Van Damme J, Abu El-Asrar AM, Struyf S (2013) Autocrine CCL2, CXCL4, CXCL9 and CXCL10 signal in retinal endothelial cells and are enhanced in diabetic retinopathy. Exp Eye Res 109:67–76. https://doi.org/10.1016/j.exer.2013.01.008

    Article  CAS  PubMed  Google Scholar 

  32. Davidović S, Babić N, Jovanović S, Barišić S, Grković D, Miljković A (2019) Serum erythropoietin concentration and its correlation with stage of diabetic retinopathy. BMC Ophthalmol 19:227. https://doi.org/10.1186/s12886-019-1240-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Owen LA, Hartnett ME (2013) Soluble mediators of diabetic macular edema: the diagnostic role of aqueous VEGF and cytokine levels in diabetic macular edema. Curr Diab Rep 13:476–480. https://doi.org/10.1007/s11892-013-0382-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Lee WJ, Kang MH, Seong M, Cho HY (2012) Comparison of aqueous concentrations of angiogenic and inflammatory cytokines in diabetic macular oedema and macular oedema due to branch retinal vein occlusion. Br J Ophthalmol 96:1426–1430. https://doi.org/10.1136/bjophthalmol-2012-301913

    Article  PubMed  Google Scholar 

  35. Vandercappellen J, Van Damme J, Struyf S (2008) The role of CXC chemokines and their receptors in cancer. Cancer Lett 267:226–244. https://doi.org/10.1016/j.canlet.2008.04.050

    Article  CAS  PubMed  Google Scholar 

  36. Keeley EC, Mehrad B, Strieter RM (2011) Chemokines as mediators of tumor angiogenesis and neovascularization. Exp Cell Res 317:685–690. https://doi.org/10.1016/j.yexcr.2010.10.020

    Article  CAS  PubMed  Google Scholar 

  37. Angiolillo AL, Sgadari C, Taub DD, Liao F, Farber JM, Maheshwari S, Kleinman HK, Reaman GH, Tosato G (1995) Human interferon-inducible protein 10 is a potent inhibitor of angiogenesis in vivo. J Exp Med 182:155–162. https://doi.org/10.1084/jem.182.1.155

    Article  CAS  PubMed  Google Scholar 

  38. Strieter RM, Kunkel SL, Arenberg DA, Burdick MD, Polverini PJ (1995) Interferon gamma-inducible protein 10 (IP-10), a member of the C-X-C chemokine family, is an inhibitor of angiogenesis. Biochem Biophys Res Commun 210:51–57. https://doi.org/10.1006/bbrc.1995.1626

    Article  CAS  PubMed  Google Scholar 

  39. Zhang J, Wu Y, Jin Y, Ji F, Sinclair SH, Luo Y, Xu G, Lu L, Dai W, Yanoff M, Li W, Xu GT (2008) Intravitreal injection of erythropoietin protects both retinal vascular and neuronal cells in early diabetes. Invest Ophthalmol Vis Sci 49:732–742. https://doi.org/10.1167/iovs.07-0721

    Article  PubMed  Google Scholar 

  40. Xu H, Zhang L, Gu L, Lu L, Gao G, Li W, Xu G, Wang J, Gao F, Xu JY, Yao J, Wang F, Zhang J, Xu GT (2014) Subretinal delivery of AAV2-mediated human erythropoietin gene is protective and safe in experimental diabetic retinopathy. Invest Ophthalmol Vis Sci 55:1519–1530. https://doi.org/10.1167/iovs.13-13155

    Article  CAS  PubMed  Google Scholar 

  41. Hu LM, Lei X, Ma B, Zhang Y, Yan Y, Wu YL, Xu GZ, Ye W, Wang L, Xu GX, Xu GT, Wei-Ye L (2011) Erythropoietin receptor positive circulating progenitor cells and endothelial progenitor cells in patients with different stages of diabetic retinopathy. Chin Med Sci J 26:69–76. https://doi.org/10.1016/s1001-9294(11)60023-0

    Article  CAS  PubMed  Google Scholar 

  42. Samson FP, He W, Sripathi SR, Patrick AT, Madu J, Chung H, Frost MC, Jee D, Gutsaeva DR, Jahng WJ (2020) Dual switch mechanism of erythropoietin as an antiapoptotic and pro-angiogenic determinant in the retina. ACS Omega 5:21113–21126. https://doi.org/10.1021/acsomega.0c02763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Semeraro F, Cancarini A, Morescalchi F, Romano MR, dell’Omo R, Ruggeri G, Agnifili L, Costagliola C (2014) Serum and intraocular concentrations of erythropoietin and vascular endothelial growth factor in patients with type 2 diabetes and proliferative retinopathy. Diabetes Metab 40:445–451. https://doi.org/10.1016/j.diabet.2014.04.005

    Article  CAS  PubMed  Google Scholar 

  44. Reid G, Lois N (2017) Erythropoietin in diabetic retinopathy. Vision Res 139:237–242. https://doi.org/10.1016/j.visres.2017.05.010

    Article  PubMed  Google Scholar 

  45. Tian M, Liu S, Liu L, Zhang EK, Wang HW, Deng Y, Yue YK (2019) Correlations of the severity of diabetic retinopathy with EPO, Caspase-3 expression and oxidative stress. Eur Rev Med Pharmacol Sci 23:9707–9713. https://doi.org/10.26355/eurrev_201911_19532

    Article  CAS  PubMed  Google Scholar 

  46. Bosman DR, Winkler AS, Marsden JT, Macdougall IC, Watkins PJ (2001) Anemia with erythropoietin deficiency occurs early in diabetic nephropathy. Diabetes Care 24:495–499. https://doi.org/10.2337/diacare.24.3.495

    Article  CAS  PubMed  Google Scholar 

  47. Beirão I, Moreira L, Barandela T, Lobato L, Silva P, Gouveia CM, Carneiro F, Fonseca I, Porto G, Pinho ECP (2010) Erythropoietin production by distal nephron in normal and familial amyloidotic adult human kidneys. Clin Nephrol 74:327–335. https://doi.org/10.5414/cnp74327

    Article  PubMed  Google Scholar 

  48. García-Ramírez M, Hernández C, Simó R (2008) Expression of erythropoietin and its receptor in the human retina: a comparative study of diabetic and nondiabetic subjects. Diabetes Care 31:1189–1194. https://doi.org/10.2337/dc07-2075

    Article  PubMed  Google Scholar 

  49. Kase S, Saito W, Ohgami K, Yoshida K, Furudate N, Saito A, Yokoi M, Kase M, Ohno S (2007) Expression of erythropoietin receptor in human epiretinal membrane of proliferative diabetic retinopathy. Br J Ophthalmol 91:1376–1378. https://doi.org/10.1136/bjo.2007.119404

    Article  PubMed  PubMed Central  Google Scholar 

  50. Katsura Y, Okano T, Matsuno K, Osako M, Kure M, Watanabe T, Iwaki Y, Noritake M, Kosano H, Nishigori H, Matsuoka T (2005) Erythropoietin is highly elevated in vitreous fluid of patients with proliferative diabetic retinopathy. Diabetes Care 28:2252–2254. https://doi.org/10.2337/diacare.28.9.2252

    Article  CAS  PubMed  Google Scholar 

  51. Hitchings RA, Tripathi RC (1976) Vitreous opacities in primary amyloid disease. A clinical, histochemical, and ultrastructural report. Br J Ophthalmol 60:41–54. https://doi.org/10.1136/bjo.60.1.41

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Nelson GA, Edward DP, Wilensky JT (1999) Ocular amyloidosis and secondary glaucoma. Ophthalmology 106:1363–1366. https://doi.org/10.1016/s0161-6420(99)00726-5

    Article  CAS  PubMed  Google Scholar 

  53. Monteiro JG, Martins AF, Figueira A, Saraiva MJ, Costa PP (1991) Ocular changes in familial amyloidotic polyneuropathy with dense vitreous opacities. Eye (Lond) 5(Pt 1):99–105. https://doi.org/10.1038/eye.1991.19

    Article  Google Scholar 

  54. Tsukahara S, Matsuo T (1977) Secondary glaucoma accompanied with primary familial amyloidosis. Ophthalmologica 175:250–262. https://doi.org/10.1159/000308666

    Article  CAS  PubMed  Google Scholar 

  55. Coutinho P, Martins da Silva A, Lopes Lima J, Resende Barbosa A (1980) Forty years of experience with type I amyloid neuropathy. Review of 483 cases. In: Glenner G, Costa P, de Freitas A (eds) Amyloid and Amyloidosis. Amsterdam: Execerpta Medica pp 88–98

  56. Shao J, Yao Y (2016) Repression of retinal microvascular endothelial cells by transthyretin under simulated diabetic retinopathy conditions. Int J Ophthalmol 9:809–815. https://doi.org/10.18240/ijo.2016.06.03

    Article  PubMed  PubMed Central  Google Scholar 

  57. Manaviat MR, Afkhami M, Shoja MR (2004) Retinopathy and microalbuminuria in type II diabetic patients. BMC Ophthalmol 4:9. https://doi.org/10.1186/1471-2415-4-9

    Article  PubMed  PubMed Central  Google Scholar 

  58. Tecilazich F, Formenti AM, Giustina A (2020) Role of vitamin D in diabetic retinopathy: pathophysiological and clinical aspects. Rev Endocr Metab Disord. https://doi.org/10.1007/s11154-020-09575-4

    Article  PubMed Central  Google Scholar 

  59. Patrick PA, Visintainer PF, Shi Q, Weiss IA, Brand DA (2012) Vitamin D and retinopathy in adults with diabetes mellitus. Arch Ophthalmol 130:756–760. https://doi.org/10.1001/archophthalmol.2011.2749

    Article  PubMed  Google Scholar 

  60. Kaiser PK, Riemann CD, Sears JE, Lewis H (2001) Macular traction detachment and diabetic macular edema associated with posterior hyaloidal traction. Am J Ophthalmol 131:44–49. https://doi.org/10.1016/s0002-9394(00)00872-2

    Article  CAS  PubMed  Google Scholar 

  61. Haller JA, Qin H, Apte RS, Beck RR, Bressler NM, Browning DJ, Danis RP, Glassman AR, Googe JM, Kollman C, Lauer AK, Peters MA, Stockman ME (2010) Vitrectomy outcomes in eyes with diabetic macular edema and vitreomacular traction. Ophthalmology 117:1087-1093.e1083. https://doi.org/10.1016/j.ophtha.2009.10.040

    Article  PubMed  Google Scholar 

  62. Lewis H, Abrams GW, Blumenkranz MS, Campo RV (1992) Vitrectomy for diabetic macular traction and edema associated with posterior hyaloidal traction. Ophthalmology 99:753–759. https://doi.org/10.1016/s0161-6420(92)31901-3

    Article  CAS  PubMed  Google Scholar 

  63. Harbour JW, Smiddy WE, Flynn HW Jr, Rubsamen PE (1996) Vitrectomy for diabetic macular edema associated with a thickened and taut posterior hyaloid membrane. Am J Ophthalmol 121:405–413. https://doi.org/10.1016/s0002-9394(14)70437-4

    Article  CAS  PubMed  Google Scholar 

  64. Gandorfer A, Messmer EM, Ulbig MW, Kampik A (2000) Resolution of diabetic macular edema after surgical removal of the posterior hyaloid and the inner limiting membrane. Retina 20:126–133

    Article  CAS  Google Scholar 

  65. Pendergast SD, Hassan TS, Williams GA, Cox MS, Margherio RR, Ferrone PJ, Garretson BR, Trese MT (2000) Vitrectomy for diffuse diabetic macular edema associated with a taut premacular posterior hyaloid. Am J Ophthalmol 130:178–186. https://doi.org/10.1016/s0002-9394(00)00472-4

    Article  CAS  PubMed  Google Scholar 

  66. Yamamoto T, Hitani K, Tsukahara I, Yamamoto S, Kawasaki R, Yamashita H, Takeuchi S (2003) Early postoperative retinal thickness changes and complications after vitrectomy for diabetic macular edema. Am J Ophthalmol 135:14–19. https://doi.org/10.1016/s0002-9394(02)01819-6

    Article  PubMed  Google Scholar 

  67. van Dijk HW, Kok PH, Garvin M, Sonka M, Devries JH, Michels RP, van Velthoven ME, Schlingemann RO, Verbraak FD, Abràmoff MD (2009) Selective loss of inner retinal layer thickness in type 1 diabetic patients with minimal diabetic retinopathy. Invest Ophthalmol Vis Sci 50:3404–3409. https://doi.org/10.1167/iovs.08-3143

    Article  PubMed  Google Scholar 

  68. van Dijk HW, Verbraak FD, Kok PH, Garvin MK, Sonka M, Lee K, Devries JH, Michels RP, van Velthoven ME, Schlingemann RO, Abràmoff MD (2010) Decreased retinal ganglion cell layer thickness in patients with type 1 diabetes. Invest Ophthalmol Vis Sci 51:3660–3665. https://doi.org/10.1167/iovs.09-5041

    Article  PubMed  PubMed Central  Google Scholar 

  69. Smiddy WE, Feuer W (2004) Incidence of cataract extraction after diabetic vitrectomy. Retina 24:574–581. https://doi.org/10.1097/00006982-200408000-00011

    Article  PubMed  Google Scholar 

  70. Romano V, Angi M, Scotti F, del Grosso R, Romano D, Semeraro F, Vinciguerra P, Costagliola C, Romano MR (2013) Inflammation and macular oedema after pars plana vitrectomy. Mediators Inflamm 2013:971758. https://doi.org/10.1155/2013/971758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Pessoa B, Dias DA, Baptista P, Coelho C, Beirão JNM, Meireles A (2019) Vitrectomy outcomes in eyes with tractional diabetic macular edema. Ophthalmic Res 61:94–99. https://doi.org/10.1159/000489459

    Article  PubMed  Google Scholar 

  72. Antoszyk AN, Glassman AR, Beaulieu WT, Jampol LM, Jhaveri CD, Punjabi OS, Salehi-Had H, Wells JA 3rd, Maguire MG, Stockdale CR, Martin DF, Sun JK (2020) Effect of intravitreous aflibercept vs vitrectomy with panretinal photocoagulation on visual acuity in patients with vitreous hemorrhage from proliferative diabetic retinopathy: a randomized clinical trial. JAMA 324:2383–2395. https://doi.org/10.1001/jama.2020.23027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. de Nie KF, Crama N, Tilanus MA, Klevering BJ, Boon CJ (2013) Pars plana vitrectomy for disturbing primary vitreous floaters: clinical outcome and patient satisfaction. Graefes Arch Clin Exp Ophthalmol 251:1373–1382. https://doi.org/10.1007/s00417-012-2205-3

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge Diana José and João Poças, the two highly trained technicians who performed the SD-OCT scans; Dr. José Oliveira, Chief of the Clinical Chemistry Laboratory from CHUPorto; and Carla Fontes, the nurse who conducted all the blood sample collection.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bernardete Pessoa.

Ethics declarations

Ethics approval

This study was conducted according to the tenets of the Declaration of Helsinki in its latest amendment (Brazil, 2013), and was approved by the Research Coordination Office and the Ethics Committee of the CHUPorto, and authorized by the Administration Board of the Hospital (study number: 2017.093 (084-DEFI/082-CES)).

Consent to participate

All patients signed an informed consent form.

Consent for publication

All listed authors have provided consent for publication of this article.

Conflict of interest

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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pessoa, B., Heitor, J., Coelho, C. et al. Systemic and vitreous biomarkers — new insights in diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 260, 2449–2460 (2022). https://doi.org/10.1007/s00417-022-05624-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-022-05624-7

Keywords

Navigation