Vitovskaya O. P.1, Taha Salah Ahmad1, Klimenko P. P.2
1Bogomolets National Medical University, Kyiv, Ukraine 2The State Institution “Institute of Gerontology of them D. F. Chebotareva” Academy of Medical Sciences of Ukraine, Kyiv, Ukraine
Summary. In the present study, the analysis of gene activity of VEGF, TNF-alfa, Ang-1, IL-10 in mucosal biopsies of the conjunctiva of the eyes of diabetic patients – type 2, with nonproliferative diabetic retinopathy (NPDR). The study included 55 patients (110 eyes) who were divided into two groups: the first control group consisted of 20 patients (40 eyes); the second – patients with type 2 diabetes with NPDR comprised 35 patients (70 eyes). The obtained results in the biopsy of the conjunctiva of the eyes of diabetic patients – type 2, with nonproliferative diabetic retinopathy (NPDR) testify to the increase in the activity of genes of VEGF, TNF-alfa, participating in the processes involved in angiogenesis and inflammation, and the inhibition of the activity of genes Ang-1, IL-10, contribute to the stabilization of the structure and functioning of the vascular wall and inhibiting inflammatory processes.
Poveshchenko АF, Konenkov VI. [Mechanisms and Factors of Angiogenesis]. Uspyekhi fiziologichyeskikh nauk. 2010;41(2):68–89. (in Russian).
Halvorsen B, Wæhre T, Scholz H, Damås JK, Yndestad A, Aukrust P. Role of interleukin-10 in atherogenesis and plaque stabilization. Future Cardiology. 2006 Jan;2(1):75–83.
Chen JX, Stinnett A. Disruption of Ang-1/Tie-2 signaling contributes to the impaired myocardial vascular maturation and angiogenesis in type II diabetic mice. Arterioscler Thromb Vasc Biol. 2008;28(9):1606–13.
Costagliola С, Romano V, De Tollis M, Aceto F, dell’Omo R, Romano MR, Pedicino C, Semeraro F. TNF-Alpha Levels in Tears: A Novel Biomarker to Assess the Degree of Diabetic Retinopathy. Mediators of Inflammation. 2013;2013:1–6.
Graves DT, Kayal RA. Diabetic complications and dysregulated innate immunity. Front Biosci. 2008;1(13):1227–39.
Haddad JJ, Fahlman CS. Redox- and oxidant-mediated regulation of interleukin-10: an antiinflammatory, antioxidant cytokine? Biochemical and Biophysical Research Communications. 2002;297:163–76.
Maloney JP, Gao L. Proinflammatory Cytokines Increase Vascular Endothelial Growth Factor Expression in Alveolar Epithelial Cells. Mediators of Inflammation. 2015;2015:1–7.
Ohba T, Haro H, Ando T, Wako M, Suenaga F, Aso Y, Koyama K, Hamada Y, Nakao A. TNF-alpha-induced NF-kappaB signaling reverses age-related declines in VEGF induction and angiogenic activity in intervertebral disc tissues. J Orthop Res. 2009;27(2):229–35.
Osaadon P, Fagan XJ, Lifshitz T, Levy J. A review of anti-VEGF agents for proliferative diabetic retinopathy. Eye (Lond). 2014;28(5):510–20.
Thurston G, Rudge JS, Ioffe E, Zhou H, Ross L, Croll SD, Glazer N, Holash J, McDonald DM, Yancopoulos GD. Angiopoietin-1 protects the adult vasculature against plasma leakage. Nat Med. 2000;6(4):460–63.
Unwin N, Whiting D, Guariguata L, Ghyoot G, Gan D. IDF Diabetes atlas. 5th ed. International Diabetes federation; 2011. 137 р.
Wang X, Wang G, Wang Y. Intravitreous vascular endothelial growth factor and hypoxiainducible factor 1a in patients with proliferative diabetic retinopathy. Am J Ophthalmol. 2009;148(6):883–889.
Yaghini N, Mahmoodi M, Asadikaram Gh R, Hassanshahi GhH, Khoramdelazad H, Kazemi Arababadi M. Serum Levels of Interleukin 10 (IL-10) in Patients with Type 2 Diabetes. Iran Red Crescent Med J. 2011;13(10):752.
Yoshida S, Yoshida A, Ishibashi T. Induction of IL-8, MCP-1, and bFGF by TNF-alpha in retinal glial cells: implications for retinal neovascularization during post-ischemic inflammation. Graefes Arch Clin Exp Ophthalmol. 2004;242(5):409–13.
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. Meta-Analysis for Eye Disease (META-EYE) Study Group. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012;35(3):556–64.
1Kharkiv National Medical University, Kharkiv, Ukraine 2Higher State Educational Establishment of Ukraine “Bukovinian State Medical University”, Chernivtsi, Ukraine
Summary. According to the various authors, the damage of optic nerve is found in 7–30.7 % of patients with diabetes mellitus and is one of the causes of disability due to reduced or complete loss of vision. Diabetic optic neuropathy is a local manifestation of the systemic diabetic polyneuropathy, which affects the second pair of cranial nerves – optic nerve.
The aim was to define the peculiarities of the optic nerve damage in patients with diabetes mellitus depending on the duration, degree of compensation of diabetes mellitus, the form of diabetic retinopathy and the severity of diabetic polyneuropathy.
Material and methods of research. 575 patients with type II diabetes were examined. In addition to standard ophthalmologic methods included ophthalmochromoscopy, optical coherent tomography of the retina and optic nerve, electrophysiological examination.
Results. Analyzing the results of examination, scientific data on the risk factors of diabetic optical neuropathy has been defined and it has been proved that in patients with diabetes mellitus there is a direct correlation between the level of glycated hemoglobin (HbA1C) in blood, the duration of the disease, the frequency and form of the diabetic retinopathy, severity of diabetic polyneuropathy and type and stage of diabetic optical neuropathy: r = 0.62, r = 0.74, r = 0.72, r = 0.81, respectively. The highest degree of correlation is observed between the severity of diabetic polyneuropathy and the type and stage of diabetic optical neuropathy (r = 0.81), which confirms the role of diabetic polyneuropathy in the pathogenesis of optic nerve damage in patients with diabetes mellitus.
Conclusions. Peculiarities of the optic nerve damage in patients with diabetes mellitus depend on the duration, degree of compensation of diabetes mellitus, the form of diabetic retinopathy and the severity of diabetic polyneuropathy. The highest degree of correlation is observed between the severity of diabetic polyneuropathy and the type and stage of diabetic optical neuropathy.
Keywords: diabetic optical neuropathy, duration of diabetes mellitus, degree of compensation of diabetes mellitus, form of diabetic retinopathy, severity of diabetic polyneuropathy.
REFERENCES
Hohina IF, Andriyuk LV, Ohranovych OE. [Diabetic angio-, retino-, neuropathies: pathogenesis, clinics, treatment]. Lviv: Liha press; 2000. (in Ukrainian).
Zhaboedov HD. [New in diagnosis and treatment of diabetic optic neuropathy]. Mezhdunarodnyy meditsinskiy zhurnal. 2002;8(1–2):92–7. (in Russian).
Nedzvetskaya OV, Chumak SA. [Clinical and functional peculiarities of optic nerve change in juvenile diabetic retinopathy]. Vestnik oftalmologii. 2001;117(3):7–11. (in Russian).
Polyakova MA. [Pathogenetic and clinical-diagnostic aspects of early stages of diabetic optic neuropathy] [extended abstract of dissertation]. Moscow; 2016. (in Russian).
Skrypnyk RL. [Damage to the optic nerve diabetes (pathogenesis, clinical manifestations, diagnosis, treatment)] [extended abstract of dissertation]. Odesa; 2005. (in Ukrainian).
Tsyrenzhapova RB. [Damage to the peripheral nervous system in disorders of carbohydrate metabolism] [dissertation]. Tomsk; 2015. (in Russian).
Khan A, Petropoulos IN, Ponirakis G, Malik RA. Visual complications in diabetes mellitus: beyond retinopathy. Diabet Med. 2017 Apr;34(4):478–484. https://doi.org/10.1111/dme.13296.
Pop-Busui R, Boulton AJ, Feldman EL, Bril V, Freeman R, Malik RA, Sosenko JM, Ziegler D. Diabetic Neuropathy: A Position Statement by the American Diabetes Association. Diabetes Care. 2017 Jan;40(1):136–154. https://doi.org/10.2337/dc16-2042.
Vas PR, Edmonds ME. Early recognition of diabetic peripheral neuropathy and the need for one-stop microvascular assessment. Lancet Diabetes Endocrinol. 2016 Sep;4(9):723–5. https://doi.org/10.1016/S2213-8587(16)30063-8.
Kharkiv National Medical University, Kharkiv, Ukraine
Abstract
Introduction. Meibomian gland dysfunction (MGD) is a chronic, diffuse abnormality of the meibomian glands, commonly characterized by terminal duct obstruction and/or qualitative/quantitative changes in the glandular secretion. Diabetic polyneuropathy can be a cause of MGD.
Purpose. To improve the efficacy of diagnosis of MGD in patients with symptomatic A- and B-diabetic polyneuropathy.
Material and methods. Standard ophthalmological examination, the Schirmer’s test before and 2 hours after eyelid compression, the Norn’s test, the OPI test, a compression test, an IVAD test, contact meibography with green filter were performed. Symptomatic A (N2A) stage of DPN were recorded in 31 patients (62 eyes). Symptomatic B (N2B) stage of DPN were recorded in 34 patients (68 eyes). A control group consisted of 97 persons (194 eyes) without diabetes.
Results. The Shirmer test was 1.7 and 2.2 times reduced in patients with N2A (5.87 mm) and with N2B (7.34 mm) stages in comparison with that in the control group (12.82) (p < 0.001). The Norn test was 1.7 and 2.3 times lower in patients with N2A (5.54 mm) and with N2B (4.22 mm) stages than in patients without diabetes (9.48 sec) (p < 0.001). The OPI test in patients with N2A and N2B stages was 1.6 and 1.7 times lower than that in the control group (p < 0.001). The Schirmer test in patients with N2A and with N2B were 1.6 times higher after compression than before it (p < 0.05). According to mebography, in patients with N2A and N2B, loss area of the meibomian glands corresponded to stage 2 and 3.
Conclusion. The patients with N2A had MGD stage II (41.9 %) and stage III (32.3 %). Stage I of MGD was found in 16.1 %, and stage IV – in 9.7 %. The patients with N2B had MGD stage III (47.1 %). Stage I of MGD was found in 8.8 % patients, stage II – in 26.5 % and stage IV – in 17.6 %.
Mozherencov VP, Prokofyeva GL, Usova LA. [Eye manifestations of diabetes mellitus]. RMZh “Klinicheskaya Oftalmologiya”. 2002;1:31. (in Russian).
Tronko ND. [According to the materials of the 42nd Congress of the European Association for the Study of Diabetes]. Zdorovia Ukrainy. 2006;21(154):10−15. (in Russian).
Blackie CA, Korb DR. Recovery time of an optimally secreting meibomian gland. Cornea. 2009;28:293–7. https://doi.org/10.1097/ICO.0b013e31818913b4
Bron AJ, Benjamin L, Snibson GR. Meibomian gland disease. Classification and grading of lid changes. Eye (Lond). 1991;5:395–411. https://doi.org/10.1038/eye.1991.65
Dyck PJ, Kratz KM, Karnes JL, Litchy WJ, Klein R, Pach JM, Wilson DM, O’Brien PC, Melton LJ 3rd, Service FJ. Prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in population-based cohort: Rochester Diabetic Neuropathy Study. Neurology. 1993;43(4):817−24.
Foulks GN, Bron AJ. Meibomian gland dysfunction: A clinical scheme for description, diagnosis, classification and grading. Ocul Surf. 2003;1(3):107–26.
Linton RG, Curnow DH, Riley WJ. The meibomian glands: an investigation into the secretion and some aspects and some aspects of the physiology. Br J Ophthalmol. 1961 Nov; 45(11):718−23.
Pflugfelder SC, Tseng S, Sanabria O, Kell H, Garcia CG, Felix C, Feuer W, Reis BL. Evaluation of subjective assessments and objective diagnostic tests for diagnosing tear-film disorders known to cause ocular irritation. Cornea. 1998;17:38−56.
Savettieri G, Rocca WA, Salemi G, Meneghini F, Grigoletto F, Morgante L, Reggio A, Costa V, Coraci MA, Di Perri R. Prevalence of diabetic neuropathy with somatic symptoms: a door-to-door survey in two Sicilian municipalities. Neurology. 1993;43(6):1115−20.
Nichols KK, Foulks GN, Bron AJ, et al. The international workshop on meibomian gland dysfunction: executive summary. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1922−9.