New risk factors for post-surgical recurrent diabetic maculopathy in type 2 diabetes mellitus
DOI:
https://doi.org/10.31288/oftalmolzh20195917Keywords:
diabetic maculopathy, surgical treatment, recurrences, PDGF, TNF?, Endothelin-1, type 2 diabetes mellitusAbstract
Background: Some pathogenetic risk factors (platelet-derived growth factor (PDGF); tumor necrosis factor alpha (TNF?); and Endothelin-1 (ET1)) are involved in the development of diabetic maculopathy (DMP) in type 2 diabetes mellitus. We hypothesized that the same factors are involved in the formation of postsurgical recurrent DMP.
Purpose: To investigate new risk factors of postsurgical recurrent DMP in patients with DM2.
Materials and Methods: The study included 313 patients with DM2 (313 eyes) and diabetic maculopathy. These included patients with mild nonproliferative diabetic retinopathy (NPDR; Group 1; n=40), moderate or severe NPDR (Group 2; n=92), and proliferative diabetic retinopathy (PDR; Group 3; n=181). Patients received one of the four types of surgical treatment: only three-port closed subtotal vitrectomy (CSTV; n=78); CSTV combined with internal limiting membrane (ILM) peeling (n=85); CSTV combined with ILM peeling and panretinal laser coagulation (PRLC) (n=81); and CSTV combined with ILM peeling, PRLC and cataract phacoemulsification (phaco) (n=69). Enzyme-linked immunosorbent assay was used to determine presurgical levels of DMP risk factors in blood. Statistical analyses were conducted using Statistica 10.0 (StatSoft, Tulsa, OK, USA) software.
Results: Presurgical levels of DMP risk factors in blood substantially increased with an increase in severity of diabetic retinopathy (from Group 1 to Group 3), with the maximum values achieved in patients with PDR. For each group, PDGF blood levels in patients with recurrent DMP were 1.3- to 1.4-fold (and statistically significantly, p < 0.001) higher than in those without recurrent DMP. TNF? blood levels in Group 1 and Group 2 patients with recurrent DMP were 1.2- to 1.4-fold (and statistically significantly) higher than in those without recurrent DMP. Only for Group 1, median ET1 blood level in patients with recurrent DMP was significantly (1.4-fold; p < 0.001) higher than in those without recurrent DMP. All patients exhibiting recurrent DMP after any of the used surgical treatment technologies had statistically significantly increased baseline PDGF levels (p < 0.001). The pre-surgery cut-off PDGF blood level for which the development of recurrent DMP becomes probable was > 51.8 ng/mL. Associations of TNF? and ЕТ1 blood levels with recurrent DMP were most prominent in NPDR, and depended on recurrence time points: presurgical TNF? blood levels were associated with early recurrent DMP, whereas presurgical ЕТ1 blood levels were associated with late recurrent DMP.
Conclusion: New risk factors for post-surgical recurrent DMP in DM2 were established. The PDGF blood level was found to influence the development of both early and late recurrent DMP, whereas the TNF? blood level, only early SMP recurrence, and the ET1 blood level, only late recurrent DMP.
References
1.Kamoi K, Takeda K, Hashimoto K, Tanaka R, Okuyama S. Identifying risk factors for clinically significant diabetic macula edema in patients with type 2 diabetes mellitus. Curr Diabetes Rev. 2013 May;9(3):209-17. https://doi.org/10.2174/1573399811309030002
2.Sivaprasad S, Gupta B, Crosby-Nwaobi R, Evans J. Prevalence of diabetic retinopathy in various ethnic groups: a worldwide perspective. Surv Ophthalmol. 2012;57(4):347-70. https://doi.org/10.1016/j.survophthal.2012.01.004
3.Pasyechnikiva NV, Suk SA, Kuznetsova TA, Parkhomenko OG. [Diabetic maculopathy. Current aspects of the pathogenesis, clinical picture, diagnosis and treatment]. Kyiv: Karbon LTD;2010. Russian.
4.Diep TM, Tsui I. Risk factors associated with diabetic macular edema. Diabetes Res Clin Practice. 2013 Jun;100(3):298-305. https://doi.org/10.1016/j.diabres.2013.01.011
5.Jenkins AJ, Joglekar MV, Hardikar AA, Keech AC, O'Neal DN, Januszewski AS. Biomarkers in Diabetic Retinopathy. Rev Diabet Stud. 2015 Spring-Summer;12(1-2):159-95.https://doi.org/10.1900/RDS.2015.12.159
6.Eshaq RS, Aldalati AMZ, Alexander JS, Harris NR. Diabetic retinopathy: Breaking the barrier. Pathophysiology. 2017;24(4):229-41.https://doi.org/10.1016/j.pathophys.2017.07.001
7.Mogilevskyy SIu, Panchenko YuO, Ziablitsev SV, Ziablytsev DS. Influence of local and systemic factors of type 2 diabetes mellitus on the functional status of platelets in patients with diabetic and maculopathy. Journal of Ophthalmology (Ukraine). 2018;6(485):23-9.
8.Mogilevskyy SIu, Panchenko IuO, Ziablytsev SV. Predicting the risk of diabetic retinopathy-assosiated macular edema in patients with type 2 diabetes mellitus. Journal of Ophthalmology (Ukraine). 2019;3(488):3-8.https://doi.org/10.31288/oftalmolzh2019338
9.Zhang J, Cao R, Zhang Y, Jia T, Cao Y, Wahlberg E. Differential roles of PDGFR-alpha and PDGFR-beta in angiogenesis and vessel stability. FASEB J. 2009 Jan;23(1):153-63.https://doi.org/10.1096/fj.08-113860
10.Rodriguez A, Friman T, Kowanetz M, van Wieringen T, Gustafsson R, Sundberg C. Phenotypical differences in connective tissue cells emerging from microvascular pericytes in response to overexpression of PDGF-B and TGF-?1 in normal skin in vivo. Am J Pathol. 2013 Jun;182(6):2132-46.https://doi.org/10.1016/j.ajpath.2013.01.054
11.Mori K, Gehlbach P, Ando A, Dyer G, Lipinsky E, Chaudhry AG, Hackett SF, Campochiaro PA. Retina-specific expression of PDGF-B versus PDGF-A: vascular versus nonvascular proliferative retinopathy. Invest Ophthalmol Vis Sci. 2002;43:2001-6.
12.McAuley AK, Sanfilippo PG, Hewitt AW, Liang H, Lamoureux E, Wang JJ, Connell PP. Vitreous biomarkers in diabetic retinopathy: a systematic review and meta-analysis. J Diabetes Complications. 2014 May-Jun;28(3):419-25.https://doi.org/10.1016/j.jdiacomp.2013.09.010
13.IRS1 - Insulin receptor substrate 1 - Homo sapiens (Human) - IRS1 gene & protein". www.uniprot.org. Retrieved 2016-04-21.
14.Takaguri A. [Elucidation of a new mechanism of onset of insulin resistance: effects of statins and tumor necrosis factor-? on insulin signal transduction]. Yakugaku Zasshi. 2018;138(11):1329-1334.https://doi.org/10.1248/yakushi.18-00116
15.Copps KD, White MF. Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2. Diabetologia. 2012;55(10):2565-82.https://doi.org/10.1007/s00125-012-2644-8
16.Loukovaara S, Piippo N, Kinnunen K, Hytti M, Kaarniranta K, Kauppinen A. NLRP3 inflammasome activation is associated with proliferative diabetic retinopathy. Acta Ophthalmol. 2017 Dec;95(8):803-808.https://doi.org/10.1111/aos.13427
17.Babik B, Pet?k F, Ag?cs S, Blaskovics I, Al?cs E, Bod? K, S?dy R. [Diabetes mellitus: endothelial dysfunction and changes in hemostasis]. OrvHetil. 2018; 159(33):1335-1345.https://doi.org/10.1556/650.2018.31130
18.Raminderjit Kaur, Manpreet Kaur, Jatinder Singhcorresponding. Endothelial dysfunction and platelet hyperactivity in type 2 diabetes mellitus: molecular insights and therapeutic strategies. Cardiovasc Diabetol. 2018; 17: 121.https://doi.org/10.1186/s12933-018-0763-3
19.Pi X, Xie L, Patterson C. Emerging roles of vascular endothelium in metabolic homeostasis. Circ Res. 2018; 123 (4): 477-494.https://doi.org/10.1161/CIRCRESAHA.118.313237
20.Polovina MM, Potpara TS. Endothelial dysfunction in metabolic and vascular disorders. Postgrad Med. 2014; 126(2): 38-53.https://doi.org/10.3810/pgm.2014.03.2739
21.Balashevich LI, Izmailov AS. [Diabetic ophthalmopathy]. St. Petersburg: Chelovek; 2012. Russian.
22.Xiao K, Dong YC, Xiao XG, Liang SZ, Wang J, Qian C, Wan GM. Effect of pars plana vitrectomy with or without cataract surgery in patients with diabetes: a systematic review and meta-analysis. Diabetes Ther. 2019 Jul 25.https://doi.org/10.1007/s13300-019-0672-9
23.Praidou A, Klangas I, Papakonstantinou E, Androudi S, Georgiadis N, Karakiulakis G, Dimitrakos S. Vitreous and serum levels of platelet-derived growth factor and their correlation in patients with proliferative diabetic retinopathy. Curr Eye Res. 2009 Feb; 34 (2): 152-61.https://doi.org/10.1080/02713680802585920
24.Raczy?ska D, Lisowska KA, Pietruczuk K, Borucka J, ?lizie? M, Raczy?ska K, Glasner L, Witkowski JM. The level of cytokines in the vitreous body of severe proliferative diabetic retinopathy patients undergoing posterior vitrectomy. Curr Pharm Des. 2018;24(27):3276-3281.https://doi.org/10.2174/1381612824666180926110704
25.Boss JD, Singh PK, Pandya HK, Tosi J, Kim C, Tewari A, Juzych MS, Abrams GW, Kumar A. Assessment of neurotrophins and inflammatory mediators in vitreous of patients with diabetic retinopathy. Invest Ophthalmol Vis Sci. 2017 Oct 1;58(12):5594-5603.https://doi.org/10.1167/iovs.17-21973
26.Kovacs K, Marra KV, Yu G, Wagley S, Ma J, Teague GC, Nandakumar N, Lashkari K, Arroyo JG. Angiogenic and inflammatory vitreous biomarkers associated with increasing levels of retinal ischemia. Invest Ophthalmol Vis Sci. 2015 Oct;56(11):6523-30.https://doi.org/10.1167/iovs.15-16793
27.Blum A, Socea D, Sirchan R. Vascular responsiveness in type 2 diabetes mellitus (T2DM). QJM. 2016; 109(12): 791-796.https://doi.org/10.1093/qjmed/hcw081
28.Chang W, Lajko M, Fawzi AA. Endothelin-1 is associated with fibrosis in proliferative diabetic retinopathy membranes. PLoS One. 2018 Jan 19;13(1):e0191285.https://doi.org/10.1371/journal.pone.0191285
29.Zhou J, Wang S, Xia X. Role of intravitreal inflammatory cytokines and angiogenic factors in proliferative diabetic retinopathy. Curr Eye Res. 2012 May;37(5):416-20.https://doi.org/10.3109/02713683.2012.661114
30.Adamiec-Mroczek J, Oficjalska-M?y?czak J, Misiuk-Hoj?o M. Roles of endothelin-1 and selected proinflammatory cytokines in the pathogenesis of proliferative diabetic retinopathy: Analysis of vitreous samples. Cytokine. 2010 Mar;49(3):269-74. https://doi.org/10.1016/j.cyto.2009.11.004
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