New opportunities in endocrine ophthalmopathy diagnostics (review)
https://doi.org/10.14341/ket2017320-28
Abstract
Endocrine ophthalmopathy (EOP) is a progressive autoimmune disease that affects soft retrobulbar tissues in thyroid gland diseases. The statistical data on this disease are presented. The review presents both generally accepted and alternative approaches to the diagnosis of EOP different stages. Detailed clinical symptoms, main severity and activity score classifications of EOP, the required list of physical and instrumental examinations are given. We described the diagnostic value of computed tomography, magnetic resonance imaging, optical coherence tomography, Heidelberg Retina Tomography, radioisotope studies, triplex scanning of the major vessels of the eye, the Doppler mapping method, indocyanine-green angiography, as well as the histological examination of soft retrobulbar tissues biopsy in EOP. Generally accepted diagnostic methods of EOP have their disadvantages. Therefore, nowadays the promising direction is immunological, biochemical and genetic studies of EOP activity markers. The peculiarity of these methods in EOP diagnosis is an accuracy, possibility of multiple measurements, few side effects and a relatively low cost. Further studies of key mechanisms of the development of edema, leukocyte infiltration with subsequent formation of fibrosis of extraocular muscles and retrobulbar fiber in EOP is of significance, which may improve diagnostics of clinical complicated cases and initial stages of the disease.
About the Authors
Elizaveta S. TaskinaChita State Medical Academy
Russian Federation
MD
Svetlana V. Charinzeva
Chita State Medical Academy
Russian Federation
MD, PhD, Professor
Vladimir V. Charinzev
Chita State Medical Academy
Russian Federation
MD
Dmitriy M. Serkin
Chita State Medical Academy
Russian Federation
MD, PhD
References
1. Бровкина А.Ф. Эндокринная офтальмопатия. — М.: ГЭОТАР-Медиа; 2008. [Brovkina AF. Endokrinnaya oftal’mopatiya. Moscow: GEOTAR-Media; 2008. (In Russ.)]
2. Дедов И.И., Мельниченко Г.А., Свириденко Н.Ю., и др. Федеральные клинические рекомендации по диагностике и лечению эндокринной офтальмопатии при аутоиммунной патологии щитовидной железы. // Проблемы эндокринологии. — 2015. — Т. 61. — №1. — С. 61–74. [Dedov II, Melnichenko GA, Sviridenko NY, et al. Federal clinical recommendations on diagnostics and treatment of endocrine ophthalmopathy associated with autoimmune thyroid pathology. Problems of Endocrinology. 2015;61(1):61-74. (In Russ.)] doi: 10.14341/probl201561161-74
3. Петунина Н.А., Трухина Л.В., Мартиросян Н.С. Эндокринная офтальмопатия: современный взгляд. // Проблемы эндокринологии. — 2012. — Т. 58. — №6. — C. 24–32. [Petunina NA, Trukhina LV, Martirosyan NS. Endocrine ophthalmopathy: state-of-the-art approaches. Problems of Endocrinology. 2012;58(6):24-32. (In Russ.)] doi: 10.14341/probl201258624-32
4. Исмаилова Д.С., Подгорная Н.Н. Поражение роговицы при эндокринной офтальмопатии. // Вестник офтальмологии. — 2015. — Т. 131. — №5. — C. 98-103. [Ismailova DS, Podgornaya NN. Corneal damage in patients with thyroid eye disease. Annals of ophthalmology. 2015;131(5):98-103. (In Russ.)] doi: 10.17116/oftalma2015131598-103
5. Sahli E, Gunduz K. Thyroid-associated Ophthalmopathy. Turk J Ophthalmol. 2017;47(2):94-105. doi: 10.4274/tjo.80688
6. Salvi M, Campi I. Medical Treatment of Graves' Orbitopathy. Horm Metab Res. 2015;47(10):779-788. doi: 10.1055/s-0035-1554721
7. Bahn RS. Current Insights into the Pathogenesis of Graves' Ophthalmopathy. Horm Metab Res. 2015;47(10):773-778. doi: 10.1055/s-0035-1555762
8. Konuk O, Onaran Z, Ozhan Oktar S, et al. Intraocular pressure and superior ophthalmic vein blood flow velocity in Graves' orbitopathy: relation with the clinical features. Graefes Arch Clin Exp Ophthalmol. 2009;247(11):1555-1559. doi: 10.1007/s00417-009-1144-0
9. Lee H, Lee YH, Suh SI, et al. Characterizing Intraorbital Optic Nerve Changes on Diffusion Tensor Imaging in Thyroid Eye Disease Before Dysthyroid Optic Neuropathy. J Comput Assist Tomogr. 2017. doi: 10.1097/RCT.0000000000000680
10. Holds JB, Chang WJ, Durairaj VD, et al. Orbital inflammatory and infectious disorders: thyroid eye disease. In: American Academy of Ophthalmology. Basic and clinical science course: Orbit, eyelids, and lacrimal system. San-Francisco: American Academy of Ophthalmology. 2013:47-55.
11. Bartalena L, Baldeschi L, Boboridis K, et al. The 2016 European Thyroid Association/European Group on Graves' Orbitopathy Guidelines for the Management of Graves' Orbitopathy. Eur Thyroid J. 2016;5(1):9-26. doi: 10.1159/000443828
12. Menconi F, Marcocci C, Marino M. Diagnosis and classification of Graves' disease. Autoimmun Rev. 2014;13(4-5):398-402. doi: 10.1016/j.autrev.2014.01.013
13. Серкин Д.М., Серебрякова О.В., Просяник В.И. Клиническая характеристика эндокринной офтальмопатии в Забайкалье. // Вестник Новосибирского государственного университета. Серия: Биология, клиническая медицина. — 2011. — Т. 9. — №1. — С. 168-171. [Serkin DM, Serebryakova OV, Prosyanik VI. Clinical сharacteristic of Graves' orbitopathy in region Vestnik Novosibirskogo gosudarstvennogo universiteta. Seriia biologiia, klinicheskaia meditsina. 2011;9(1):168-171. (In Russ.)]
14. Бровкина А.Ф., Яценко О.Ю. О целесообразности выделения клинической формы липогенного варианта отечного экзофтальма. // Вестник офтальмологии. — 2013. — Т. 129. — №2. — C. 28-32. [Brovkina AF, Yatsenko OY. Rationale for distinguishing the lipogenic form of thyroid orbitopath. Annals of ophthalmology. 2013;129(2):28-32. (In Russ.)]
15. Wiersinga WM, Prummel MF, Terwee CB. Effects of Graves' ophthalmopathy on quality of life. J Endocrinol Invest. 2004;27(3):259-264. doi: 10.1007/BF03345275
16. Dagi LR, Zoumalan CI, Konrad H, et al. Correlation between extraocular muscle size and motility restriction in thyroid eye disease. Ophthal Plast Reconstr Surg. 2011;27(2):102-110. doi: 10.1097/IOP.0b013e3181e9a063
17. Cеркин Д.М., Серебрякова О.В., Просяник В.И., и др. Рентгенологическая характеристика эндокринной офтальмопатии в условиях Забайкалья. Кубанский научный медицинский вестник. — 2011. — №1. — C. 145-148. [Sherkin DM, Serebryakova OV, Prosyanik VI, et al. X-ray characteristic of Graves orbitopathy in region Zabaykalye. Kubanskii nauchnyii meditsinskii vestnik. 2011;(1):145-148. (In Russ.)]
18. Gonçalves ACP, Gebrim EM, Monteiro ML. Imaging studies for diagnosing Graves' orbitopathy and dysthyroid optic neuropathy. Clinics. 2012;67(11):1327-1334. doi: 10.6061/clinics/2012(11)18
19. Lee JY, Bae K, Park KA, et al. Correlation between Extraocular Muscle Size Measured by Computed Tomography and the Vertical Angle of Deviation in Thyroid Eye Disease. PLoS One. 2016;11(1):e0148167. doi: 10.1371/journal.pone.0148167
20. Чепурина А.А., Свириденко Н.Ю., Ремизов О.В., и др. Клинико-томографические взаимоотношения при диплопии у пациентов с эндокринной офтальмопатией и болезнью Грейвса. // Клиническая и экспериментальная тиреоидология. — 2012. — Т. 8. — №1. — С. 40-45. [Chepurina AA, Sviridenko NY, Remizov OV, et al. The clinical tomographic interconnection in diplopia of patients with Graves' orbitopathy. Clinical and experimental thyroidology. 2012;8(1):40-45. (In Russ.)] doi: 10.14341/ket20128140-45
21. Tachibana S, Murakami T, Noguchi H, et al. Orbital magnetic resonance imaging combined with clinical activity score can improve the sensitivity of detection of disease activity and prediction of response to immunosuppressive therapy for Graves’ ophthalmopathy. Endocrine J. 2010;57(10):853-861. doi: 10.1507/endocrj.K10E-156
22. Rabinowitz MP, Carrasco JR. Update on advanced imaging options for thyroid-associated orbitopathy. Saudi J Ophthalmol. 2012;26(4):385-392. doi: 10.1016/j.sjopt.2012.07.006
23. Fallon M, Valero O, Pazos M, Anton A. Diagnostic accuracy of imaging devices in glaucoma: A meta-analysis. Surv Ophthalmol. 2017;62(4):446-461. doi: 10.1016/j.survophthal.2017.01.001
24. Park KA, Kim YD, In Woo K, et al. Optical coherence tomography measurements in compressive optic neuropathy associated with dysthyroid orbitopathy. Graefes Arch Clin Exp Ophthalmol. 2016;254(8):1617-1624. doi: 10.1007/s00417-016-3335-9
25. Yang B, Ye C, Yu M, et al. Optic disc imaging with spectral-domain optical coherence tomography: variability and agreement study with Heidelberg retinal tomograph. Ophthalmology. 2012;119(9):1852-1857. doi: 10.1016/j.ophtha.2012.02.033
26. Michelessi M, Lucenteforte E, Oddone F, et al. Optic nerve head and fibre layer imaging for diagnosing glaucoma. Cochrane Database Syst Rev. 2015(11):CD008803. doi: 10.1002/14651858.CD008803.pub2
27. Харинцева С.В., Серебрякова О.В., Харинцев В.В., Cеркин Д.М. Оптическая когерентная томография в диагностике нейропатии у больных с эндокринной офтальмопатией. // Бюллетень ВСНЦ СО РАМН. — 2011. — №6. — C. 97-99. [Kharintseva SV, Serebryakova OV, Kharintsev VV, Serkin DM. Optic coherent tomography in optic neuropathy diagnostics in patients with endocrine ophthalmopathy. Bull Vost Sib Naucn Sent. 2011;(6):97-99. (In Russ.)]
28. Caliskan S, Acar M, Gurdal C. Choroidal Thickness in Patients with Graves' Ophthalmopathy. Curr Eye Res. 2017;42(3):484-490. doi: 10.1080/02713683.2016.1198488
29. Aguirre-Balsalobre F, Mengual-Verdú E, Muñoz-Acosta JM, et al. Octreotide scintigraphy in thyroid orbitopathy. Arch Soc Esp Oftalmol. 2007;82(3):133-139. doi: 10.4321/s0365-66912007000300004
30. Sun B, Zhang Z, Dong C, et al. (99)Tc(m)-octreotide scintigraphy and serum eye muscle antibodies in evaluation of active thyroid-associated ophthalmopathy. Eye (Lond). 2017;31(5):668-676. doi: 10.1038/eye.2017.42
31. Lopes FP, de Souza SA, Dos Santos Teixeira Pde F, et al. 99mTc-Anti-TNF-alpha scintigraphy: a new perspective within different methods in the diagnostic approach of active Graves ophthalmopathy. Clin Nucl Med. 2012;37(11):1097-1101. doi: 10.1097/RLU.0b013e31826c0c16
32. Жукова О.Д., Нечеснюк С.Ю. Изменение экстраокулярных мышц у больных эндокринной офтальмопатией. // Вестник офтальмологии. — 2016. — T. 132. — №2. — C. 77-79. [Zhukova OD, Nechesnyuk SY. Extraocular muscles involvement in patients with thyroid-associated ophthalmopathy. Annals of ophthalmology. 2016;132(2):77-79. (In Russ.)]
33. Лихванцева В.Г. Харлап С.И., Коростелева Е.В., и др. Гемодинамические нарушения в магистральных сосудах глаза в прогрессировании оптической нейропатии и изменении офтальмотонуса при эндокринной офтальмопатии // Вестник офтальмологии. — 2015. — Т. 131. — №4. — C. 32-37. [Likhvantseva VG, Kharlap SI, Korosteleva EV, et al. Contribution of hemodynamic disturbances in magistral vessels to optic neuropathy progression and ocular tension changes in endocrine ophthalmopathy. Annals of ophthalmology. 2015;131(4):32-37. (In Russ.)]
34. Киселева Т.Н., Пантелеева О.Г., Шамшинова А.М. Кровоток в сосудах глаза и орбиты у больных эндокринной офтальмопатией. // Вестник офтальмологии. — 2007. — T. 123. — №1. — C. 33-36. [Kiseleva TN, Panteleeva OG, Shamshinova АМ. Ocular and orbital vascular blood flow in patients with endocrine ophthalmopathy. Annals of ophthalmology. 2007;123(1):33-36. (In Russ.)]
35. Nik N, Fong A, Derdzakyan M, et al. Changes in Choroidal Perfusion after Orbital Decompression Surgery for Graves' Ophthalmopathy. J Ophthalmic Vis Res. 2017;12(2):183-186. doi: 10.4103/jovr.jovr_165_16
36. Walasik-Szemplinska D, Pauk-Domanska M, Sanocka U, Sudol-Szopinska I. Doppler imaging of orbital vessels in the assessment of the activity and severity of thyroid-associated orbitopathy. J Ultrason. 2015;15(63):388-397. doi: 10.15557/JoU.2015.0036
37. Somer D, Ozkan SB, Ozdemir H, et al. Colour Doppler imaging of superior ophthalmic vein in thyroid-associated eye disease. Jpn J Ophthalmol. 2002;46(3):341-345. doi: 10.1016/s0021-5155(02)00485-9
38. Alp MN. Colour Doppler imaging of the orbital vasculature in Graves' disease with computed tomographic correlation. Br J Ophthalmol. 2000;84(9):1027-1030. doi: 10.1136/bjo.84.9.1027
39. Krieger CC, Neumann S, Place RF, et al. Bidirectional TSH and IGF-1 receptor cross talk mediates stimulation of hyaluronan secretion by Graves' disease immunoglobins. J Clin Endocrinol Metab. 2015;100(3):1071-1077. doi: 10.1210/jc.2014-3566
40. Khong JJ, McNab AA, Ebeling PR, et al. Pathogenesis of thyroid eye disease: review and update on molecular mechanisms. Br J Ophthalmol. 2016;100(1):142-150. doi: 10.1136/bjophthalmol-2015-307399
41. Martin CS, Sirbu AE, Betivoiu MA, et al. Serum immunoglobulin G4 levels and Graves' disease phenotype. Endocrine. 2017;55(2):478-484. doi: 10.1007/s12020-016-1157-5
42. Zhao P, Deng Y, Gu P, et al. Insulin-like growth factor 1 promotes the proliferation and adipogenesis of orbital adipose-derived stromal cells in thyroid-associated ophthalmopathy. Exp Eye Res. 2013;107:65-73. doi: 10.1016/j.exer.2012.11.014
43. Minich WB, Dehina N, Welsink T, et al. Autoantibodies to the IGF1 receptor in Graves' orbitopathy. J Clin Endocrinol Metab. 2013;98(2):752-760. doi: 10.1210/jc.2012-1771
44. Nowak M, Marek B, Karpe J, et al. Serum concentration of VEGF and PDGF-AA in patients with active thyroid orbitopathy before and after immunosuppressive therapy. Exp Clin Endocrinol Diabetes. 2014;122(10):582-586. doi: 10.1055/s-0034-1383579
45. Lee JY, Yun M, Paik JS, et al. PDGF-BB Enhances the Proliferation of Cells in Human Orbital Fibroblasts by Suppressing PDCD4 Expression Via Up-Regulation of microRNA-21. Invest Ophthalmol Vis Sci. 2016;57(3):908-913. doi: 10.1167/iovs.15-18157
46. Virakul S, Dalm VA, Paridaens D, et al. Platelet-Derived Growth Factor-BB Enhances Adipogenesis in Orbital Fibroblasts. Invest Ophthalmol Vis Sci. 2015;56(9):5457-5464. doi: 10.1167/iovs.15-17001
47. Gianoukakis AG, Khadavi N, Smith TJ. Cytokines, Graves' disease, and thyroid-associated ophthalmopathy. Thyroid. 2008;18(9):953-958. doi: 10.1089/thy.2007.0405
48. Роль некоторых про- и противовоспалительных цитокинов в течении эндокринной офтальмопатии. // Забайкальский медицинский вестник. — 2016. — №2. — С. 33-40. [Kharintsev VV, Serebryakova OV, Serkin DM, et al. Rol' nekotorykh pro- i protivovospalitel'nykh tsitokinov v techenii endokrinnoy oftal'mopatii. Zabaykal'skiy meditsinskiy vestnik. 2016;(2):33-40. (In Russ.)]
49. Wong KH, Rong SS, Chong KK, et al. Genetic Associations of Interleukin-related Genes with Graves' Ophthalmopathy: a Systematic Review and Meta-analysis. Sci Rep. 2015;5:16672. doi: 10.1038/srep16672
50. Gillespie EF, Raychaudhuri N, Papageorgiou KI, et al. Interleukin-6 production in CD40-engaged fibrocytes in thyroid-associated ophthalmopathy: involvement of Akt and NF-kappaB. Invest Ophthalmol Vis Sci. 2012;53(12):7746-7753. doi: 10.1167/iovs.12-9861
51. Slowik M, Urbaniak-Kujda D, Bohdanowicz-Pawlak A, et al. CD8+CD28-lymphocytes in peripheral blood and serum concentrations of soluble interleukin 6 receptor are increased in patients with Graves' orbitopathy and correlate with disease activity. Endocr Res. 2012;37(2):89-95. doi: 10.3109/07435800.2011.635622
52. Antonelli A, Ferrari SM, Fallahi P, et al. Monokine induced by interferon gamma (IFNgamma) (CXCL9) and IFNgamma inducible T-cell alpha-chemoattractant (CXCL11) involvement in Graves' disease and ophthalmopathy: modulation by peroxisome proliferator-activated receptor-gamma agonists. J Clin Endocrinol Metab. 2009;94(5):1803-1809. doi: 10.1210/jc.2008-2450
53. Fang S, Huang Y, Wang S, et al. IL-17A Exacerbates Fibrosis by Promoting the Proinflammatory and Profibrotic Function of Orbital Fibroblasts in TAO. J Clin Endocrinol Metab. 2016;101(8):2955-2965. doi: 10.1210/jc.2016-1882
54. Wei H, Guan M, Qin Y, et al. Circulating levels of miR-146a and IL-17 are significantly correlated with the clinical activity of Graves' ophthalmopathy. Endocr J. 2014;61(11):1087-1092. doi: 10.1507/endocrj.EJ14-0246
55. Krizova L, Kuchar M, Petrokova H, et al. p19-targeted ABD-derived protein variants inhibit IL-23 binding and exert suppressive control over IL-23-stimulated expansion of primary human IL-17+ T-cells. Autoimmunity. 2017;50(2):102-113. doi: 10.1080/08916934.2016.1272598
56. Tesmer LA, Lundy SK, Sarkar S, Fox DA. Th17 cells in human disease. Immunol Rev. 2008;223:87-113. doi: 10.1111/j.1600-065X.2008.00628.x
57. Pujol-Borrell R, Gimenez-Barcons M, Marin-Sanchez A, Colobran R. Genetics of Graves' Disease: Special Focus on the Role of TSHR Gene. Horm Metab Res. 2015;47(10):753-766. doi: 10.1055/s-0035-1559646
58. Серкин Д.М., Серебрякова О.В., Харинцева С.В., и др. Значение сочетаний полиморфизмов PRO12ALA И C1431T PPARγ в формировании эндокринной офтальмопатии. // Забайкальский медицинский вестник. — 2014. — №2. — С. 38-43. [Serkin DM, Serebryakova OV, Kharintseva SV, et al. Znachenie sochetaniy polimorfizmov PRO12ALA I C1431T PPARγ v formirovanii endokrinnoy oftal'mopatii. Zabaykal'skiy meditsinskiy vestnik. 2014;(2):38-43 (In Russ.)]
59. Wong KH, Rong SS, Chong KK, et al. Genetic Associations of Interleukin-related Genes with Graves' Ophthalmopathy: a Systematic Review and Meta-analysis. Sci Rep. 2015;5:16672. doi: 10.1038/srep16672
Supplementary files
Review
For citations:
Taskina E.S., Charinzeva S.V., Charinzev V.V., Serkin D.M. New opportunities in endocrine ophthalmopathy diagnostics (review). Clinical and experimental thyroidology. 2017;13(3):20-28. (In Russ.) https://doi.org/10.14341/ket2017320-28

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