The eye and thyroid disease

Current Opinion in Ophthalmology

Volumn 19, Issue 6, 2008, Pages 499-506

  Kuriyan, Ajay E ^a   Phipps, Richard P ^a,b   Feldon, Steven E ^b  

^a UNIVERSITY OF ROCHESTER SCHOOL OF MEDICINE AND DENTISTRY   (United States)

^b UNIVERSITY OF ROCHESTER   (United States)

Author keywords

Graves' disease; Graves' ophthalmopathy; Graves' orbitopathy; Thyroid eye disease; Thyroid associated ophthalmopathy

Indexed keywords

CORTICOSTEROID; ETANERCEPT; GLUCOCORTICOID; IMMUNOMODULATING AGENT; RAPAMYCIN; RITUXIMAB; THIAMAZOLE;

AUTOIMMUNE DISEASE; BONE MARROW SUPPRESSION; CORTICOSTEROID THERAPY; ENDOCRINE OPHTHALMOPATHY; EYE DISEASE; HUMAN; HYPERLIPIDEMIA; INFECTION; INFLAMMATION; MALIGNANT NEOPLASTIC DISEASE; NERVE COMPRESSION; OPTIC NERVE INJURY; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REVIEW; SERUM SICKNESS; THROMBOCYTOPENIA; THYROID DISEASE; UNSPECIFIED SIDE EFFECT;

AUTOIMMUNITY; COMBINED MODALITY THERAPY; GLUCOCORTICOIDS; GRAVES OPHTHALMOPATHY; HUMANS; OCULOMOTOR MUSCLES; OPHTHALMOLOGIC SURGICAL PROCEDURES; RADIOTHERAPY; RISK FACTORS;

EID: 56249113832     PISSN: 10408738     EISSN: None     Source Type: Journal    
DOI: 10.1097/ICU.0b013e3283131557     Document Type: Review

References (48)

1. Garrity JA, Bahn RS. Pathogenesis of Graves ophthalmopathy: implications for prediction, prevention, and treatment. Am J Ophthalmol 2006; 142:147-153.
2. Prummel M, Bakker A, Wiersinga W, et al. Multicenter study on the characteristics and treatment strategies of patients with Graves' orbitopathy: the first European Group on Graves' Orbitopathy experience. Eur J Endocrinol 2003; 148:491-495.
3. Schotthoefer EO, Wallace DK. Strabismus associated with thyroid eye disease. Curr Opin Ophthalmol 2007; 18:361-365. This article reviews methods for the treatment and evaluation of strabismus associated with TED, with a focus on the developments in 2006.
4. Eckstein AK, Lax H, Losch C, et al. Patients with severe Graves' ophthalmopathy have a higher risk of relapsing hyperthyroidism and are unlikely to remain in remission. Clin Endocrinol 2007; 67:607-612. This retrospective observational study of 158 TED patients reports that patients with more severe TED and with higher levels of TSH-R autoantibodies were less likely to go into remission.
5. Lehmann GM, Garcia-Bates TM, Smith TJ, et al. Regulation of lymphocyte function by PPARgamma: relevance to thyroid eye disease-related inflammation. PPAR Res 2008; 2008:895-901. This article reviews TED pathophysiology, with an emphasis on PPARγ's potential dual anti-inflammatory and proadipogenic roles.
6. Entingh-Pearsall A, Kahn CR. Differential roles of the insulin and insulin-like growth factor-I (IGF-I) receptors in response to insulin and IGF-I. J Biol Chem 2004; 279:38016-38024.
7. Vondrichova T, de Capretz A, Parikh H, et al. COX-2 and SCD, markers of inflammation and adipogenesis, are related to disease activity in Graves' ophthalmopathy. Thyroid 2007; 17:511-517. A study of the difference in levels of COX-2 and SCD gene expression in orbital adipose/connective tissue between acute and chronic phase TED patients demonstrated increased levels of COX-2 and SCD gene expression among acute phase patients. Diclofenac, a COX-2 inhibitor and PPARγ antagonist, reduced adipogenesis in vitro and requires further study.
8. Feldon SE, Park DJ, O'Loughlin CW, et al. Autologous T-lymphocytes stimulate proliferation of orbital fibroblasts derived from patients with Graves' ophthalmopathy. Invest Ophthalmol Vis Sci 2005; 46:3913-3921.
9. Chen M, Chen M, Liao S, et al. Role of macrophage infiltration in the orbital fat of patients with Graves' ophthalmopathy. Clin Endocrinol 2008; 69-322-327. Using orbital adipose tissue of 15 TED and six controls patients, this study demonstrated increased expression of MCP-1 and macrophage infiltration within adipose tissue but not connective tissue. The authors conclude that macrophages may play an important role in the adipogenic process of TED.
10. Cawood TJ, Moriarty P, O'Farrelly C, et al. Smoking and thyroid-associated ophthalmopathy: a novel explanation of the biological link. J Clin Endocrinol Metab 2007; 92:59-64. A study of the effects of CSE ± IL-1 on ICAM-1, GAG production, and adipogenesis in orbital tissue from 10 TED patients and nine controls. The authors found a dose-dependent relationship between CSE and both GAG production and adipogenesis but no effect on ICAM-1 expression. Furthermore, IL-1 and CSE had a synergistic effect on adipogenesis, which was reduced by 81 % with an anti-IL-1 antibody. The authors suggest IL-1 as a possible therapeutic target.
11. Bednarczuk T, Gopinath B, Ploski R, et al. Susceptibility genes in Graves' ophthalmopathy: searching for a needle in a haystack? Clin Endocrinol (Oxf) 2007; 67:3-19. This review article examines several potential loci in candidate genes, which may increase susceptibility to TED. The studies were considered to be inconclusive. Suggestions were made for the design of future genetic studies.
12. Syed AA, Simmonds MJ, Brand OJ, et al. Preliminary evidence for interaction of PTPN12 polymorphism with TSHR genotype and association with Graves' ophthalmopathy. Clin Endocrinol (Oxf) 2007; 67:663-667. A study of the relationship between seven SNPs of the PTPN12 gene and the development of Graves' disease in 1058 Graves' disease patients and 864 controls demonstrated no association between the SNPs and the development of Graves' disease. However, three SNPs were associated with the development of TED, and four SNPs revealed evidence of interaction with the TSH-R. Larger studies are required to confirm these preliminary findings.
13. Huber AK, Jacobson EM, Jazdzewski K, et al. Interleukin (IL)-23 receptor is a major susceptibility gene for Graves' ophthalmopathy: the IL-23/T-helper 17 axis extends to thyroid autoimmunity. J Clin Endocrinol Metab 2008; 93:1077-1081. The association between four SNPs of the IL-23R gene and development of TED and Graves' disease was studied in 216 TED patients and 368 controls. Two SNPs were associated with development of TED and Graves' disease, and one SNP was associated with Graves' disease development alone. These were considered as potentially proinflammatory SNPs, contributing to the development of TED.
14. Kurylowicz A, Hiromatsu Y, Jurecka-Lubieniecka B, et al. Association of NFKB1-94ins/del ATTG promoter polymorphism with susceptibility to and phenotype of Graves' disease. Genes Immun 2007; 8:532-538. The association between the NF-κB1-94ins/del ATTG promoter polymorphism and Graves' disease was studied in 586 Graves' disease and 882 control Polish patients and 424 Graves' disease and 222 control Japanese patients. There was a correlation between the polymorphism and both the development and age of onset of TED within the Japanese cohort. This polymorphism was associated with other chronic inflammatory diseases, possibly contributing to TED's comorbidity with other autoimmune disorders.
15. Chong KK, Chiang SW, Wong GW, et al. Association of CTLA-4, IL-13 Gene polymorphism with Graves' disease and ophthalmopathy in Chinese children. Invest Ophthalmol Vis Sci 2008; 49:2409-2415. A study examining the relationship between polymorphisms of CTLA-4 and IL-13 genes and the development of Graves' disease and TED in 177 GD and 151 control Chinese children did not find a significant association but did find a trend between the IL-13 SNP, 2044G/A (R130Q), and proptosis.
16. Boyle B, Koranyi K, Patocs A, et al. Polymorphisms of the glucocorticoid receptor gene in Graves ophthalmopathy. Br J Ophthalmol 2008; 92:131-134. No association between polymorphisms of the glucocorticoid receptor gene and the development and clinical phenotype of TED was established in a study of 95 TED and 160 control Hungarian patients. However, the BcII polymorphism was significantly more frequent in patients with milder TED, which the authors attributed to increased glucocorticoid receptor signaling. This polymorphism may contribute to variable responses to corticosteroid therapy.
17. Akaishi PM, Cruz AA, Silva FL, et al. The role of major histocompatibility complex alleles in the susceptibility of Brazilian patients to develop the myogenic type of Graves' orbitopathy. Thyroid 2008; 18:443-447. A study of 81 TED and 161 control Brazilian patients found that patients with muscle involvement had a higher frequency of HLA-DRB1 *16, whereas patients with minimal muscle involvement had a higher frequency of HLA-DRB1 *03. There may be a genetic predisposition for extraocular muscle involvement in TED.
18. Majos A, Pajak M, Grzelak P, et al. Magnetic resonance evaluation of disease activity in Graves' ophthalmopathy: T2-time and signal intensity of extraocular muscles. Med Sci Monit 2007; 13 (Suppl 1):44-48. A study of MRIs of 40 orbits demonstrated a correlation between both signal intensity and T2-time and the muscle volume of the superior, inferior, and medial recti. The T2-time generally had a stronger correlation. Further testing directly correlating MRI findings with patient symptoms is needed to establish signal intensity and T2-time as measures of disease activity.
19. Chang TC, Hsiao YL, Liao SL. Application of digital infrared thermal imaging in determining inflammatory state and follow-up effect of methylprednisolone pulse therapy in patients with Graves' ophthalmopathy. Graefes Arch Clin Exp Ophthalmol 2008; 246:45-49. A study of the ability of thermography to assess TED inflammatory activity and response to treatment found a positive correlation between disease severity and temperature and a significant decrease in temperatures after pulse methylprednisone therapy.
20. 99mTc(V)-DMSA scintigraphy to assess TED activity was studied in eight clinically active patients and 20 clinically inactive patients. The authors found that uptake of the agent was significantly correlated with clinical activity.
21. 99mTc-HYNIC- octreotide are needed to establish it as a tool in assessing TED severity and response to treatment.
22. Mourits MP, Koornneef L, Wiersinga WM, et al. Clinical criteria for the assessment of disease activity in Graves' ophthalmopathy: a novel approach. Br J Ophthalmol 1989; 73:639-644.
23. Wiersinga WM, Prummel MF, Mourits MP, et al. Classification of the eye changes of Graves' disease. Thyroid 1991; 1:357-360.
24. Dolman PJ, Rootman J. VISA classification for Graves orbitopathy. Ophthal Plast Reconstr Surg 2006; 22:319-324.
25. Bradley EA, Sloan JA, Novotny PJ, et al. Evaluation of the National Eye Institute visual function questionnaire in Graves' ophthalmopathy. Ophthalmology 2006; 113:1450-1454.
26. Estcourt S, Vaidya B, Quinn A, et al. The impact of thyroid eye disease upon patients' wellbeing: a qualitative analysis. Clin Endocrinol (Oxf) 2008; 68:635-639. Taped, semistructured interviews of 25 TED patients revealed that the physical manifestations of TED led to patients developing an altered sense of identity, which impacted other domains of life.
27. Rajendram R, Lee RW, Potts MJ, et al. Protocol for the combined immune-suppression & radiotherapy in thyroid eye disease (CIRTED) trial: a multi-centre, double-masked, factorial randomised controlled trial. Trials 2008; 9:6.
28. Zoumalan CI, Cockerham KP, Turbin RE, et al. Efficacy of corticosteroids and external beam radiation in the management of moderate to severe thyroid eye disease. J Neuroophthalmol 2007; 27:205-214. This article reviewed studies on the use of corticosteroids and orbital radiation for TED management. The authors found combined corticosteroid and orbital radiation therapy was more effective than oral corticosteroid monotherapy. Weekly pulse i.v. doses of corticosteroids were found to be more effective and had fewer side effects than oral corticosteroids.
29. Gursoy A, Cesur M, Erdogan MF, et al. New-onset acute heart failure after intravenous glucocorticoid pulse therapy in a patient with Graves' ophthalmopathy. Endocrine 2006; 29:513-516.
30. Weissel M, Hauff W. Fatal liver failure after high-dose glucocorticoid pulse therapy in a patient with severe thyroid eye disease. Thyroid 2000; 10:521.
31. Le Moli R, Baldeschi L, Saeed P, et al. Determinants of liver damage associated with intravenous methylprednisolone pulse therapy in Graves' ophthalmopathy. Thyroid 2007; 17:357-362. A prospective observational study comparing the hepatotoxic effects of high-dose i.v. methylprednisone and low-dose IV methylprednisone in 27 TED patients found dose-dependent liver damage caused by the toxic effects of glucocorticoids on hepatocytes. The authors concluded that i.v. methylprednisone could be safely administered if the cumulative dose is less than 8 g and liver function is monitored.
32. Bradley EA, Gower EW, Bradley DJ, et al. Orbital radiation for Graves ophthalmopathy: a report by the American Academy of Ophthalmology. Ophthalmology 2008; 115:398-409. Five observational studies and nine randomized controlled trials were reviewed to assess orbital radiation treatment for TED. Although three of five observational studies found favorable outcomes for 40-97% of patients, there was no level I evidence demonstrating that orbital radiation led to an improvement in proptosis, eyelid retraction, or soft tissue changes. The heterogeneity of the studies reviewed limited the authors' ability to assess the effect of orbital radiation.
33. Wei RL, Cheng JW, Cai JP. The use of orbital radiotherapy for Graves' ophthalmopathy: quantitative review of the evidence. Ophthalmologica 2008; 222:27-31. A metaanalysis that established orbital radiation and corticosteroid combination therapy was more effective than orbital radiation alone. Orbital radiation was found to be as effective as oral corticosteroids and significantly more effective than a vehicle control. Corticosteroids were more effective when administered intravenously than orally.
34. Paridaens D, van den Bosch WA, van der Loos TL, et al. The effect of etanercept on Graves' ophthalmopathy: a pilot study. Eye 2005; 19:1286-1289.
35. El Fassi D, Nielsen CH, Bonnema SJ, et al. B lymphocyte depletion with the monoclonal antibody rituximab in Graves' disease: a controlled pilot study. J Clin Endocrinol Metab 2007; 92:1769-1772. A prospective, controlled, nonrandomized study demonstrated higher rate of remission of Graves' disease among patients treated with rituximab. However, no significant difference in levels of autoantibodies was observed in rituximab-treated patients. The authors concluded that the high cost, low efficacy, and potential side effects were barriers to the use of rituximab in uncomplicated Graves' disease.
36. Salvi M, Vannucchi G, Campi I, et al. Efficacy of rituximab treatment for thyroid-associated ophthalmopathy as a result of intraorbital B-cell depletion in one patient unresponsive to steroid immunosuppression. Eur J Endocrinol 2006; 154:511-517.
37. Chang S, Perry JD, Kosmorsky GS, et al. Rapamycin for treatment of refractory dysthyroid compressive optic neuropathy. Ophthal Plast Reconstr Surg 2007; 23:225-226. The authors report the use of rapamycin in a patient with dysthyroid optic neuropathy refractory to steroids, and orbital decompression improvements in visual acuity, color vision, and visual fields were noted.
38. Jernfors M, Valimaki MJ, Setala K, et al. Efficacy and safety of orbital decompression in treatment of thyroid-associated ophthalmopathy: long-term follow-up of 78 patients. Clin Endocrinol (Oxf) 2007; 67:101-107. Orbital decompression surgery in 78 TED patients demonstrated decompression surgery could produce long-term improvement in measurements of proptosis and visual acuity in many patients but did not improve measurements to the level of matched controls.
39. Richter DF, Stoff A, Olivari N. Transpalpebral decompression of endocrine ophthalmopathy by intraorbital fat removal (Olivari technique): experience and progression after more than 3000 operations over 20 years. Plast Reconstr Surg 2007; 120:109-123. In a retrospective study of transpalpebral fat removal decompression surgery on 1374 TED patients, TED symptoms improved and no cases of postoperative diplopia were reported. The authors recommended this technique as a viable surgical option for TED soft tissue complications.
40. Wu CH, Chang TC, Liao SL Results and predictability of fat-removal orbital decompression for disfiguring Graves exophthalmos in an Asian patient population. Am J Ophthalmol 2008; 145:755-759. A cross-sectional study of fat-removal orbital decompression surgery in 222 TED orbits demonstrated reduction of proptosis and improvement of diplopia in 20% of patients, with a 2.8% rate of postsurgical diplopia. On the basis of volume of fat removed during surgeries and the resulting changes in Hertel measurement,, using multivariate analysis, a formula was developed to predict the change in proptosis, which may be helpful for surgical decision making.
41. Thomas SM, Cruz OA. Comparison of two different surgical techniques for the treatment of strabismus in dysthyroid ophthalmopathy. J AAPOS 2007; 11:258-261. A retrospective study of extraocular muscle surgery for strabismus-associated TED demonstrated no difference in outcomes with correction of the restricted duction or correction for degree of deviation in 52 patients. These findings contradicted the findings of previous studies that demonstrated improved outcomes with correction for the restricted duction.
42. Nguyen VT, Park DJ, Levin L, et al. Correction of restricted extraocular muscle motility in surgical management of strabismus in Graves' ophthalmopathy. Ophthalmology 2002; 109:384-388.
43. Dal Canto AJ, Crowe S, Perry JD, et al. Intraoperative relaxed muscle positioning technique for strabismus repair in thyroid eye disease. Ophthalmology 2006; 113:2324-2330.
44. Yan J, Zhang H. The surgical management of strabismus with large angle in patients with Graves' ophthalmopathy. Int Ophthalmol 2008; 28:75-82. A retrospective study of surgical management of large deviation (≥25) in 27 patients with strabismus associated with TED found favorable outcomes and low reoperation rates. The authors found that surgery involving one rectus muscle was adequate in the majority of cases.
45. Bartalena L, Baldeschi L, Dickinson A, et al. Consensus statement of the European Group on Graves' orbitopathy (EUGOGO) on management of GO. Eur J Endocrinol 2008; 158:273-285. This is a consensus statement, based on current research, on the management of TED by the European Group on Graves' Orbitopathy. The recommendations are graded following the guidelines of the Agency for Healthcare Research and Quality. They are defined for different levels of severity and complications of TED.
46. Mysliwiec J, Adamczyk M, Pawlowski P, et al. Serum gelatinases (MMP-2 and MMP-9) and VCAM-1 as a guideline in a therapeutic approach in Graves' ophthalmopathy. Endokrynologia Polska 2007; 58:105-109. This study demonstrated higher matrix metallopeptidase-9 (MMP-9) levels in TED patients and higher vascular cell adhesion molecule 1 (VCAM-1) levels among corticosteroid responders than nonresponders.
47. Tsai CC, Kao SC, Cheng CY, et al. Oxidative stress change by systemic corticosteroid treatment among patients having active Graves ophthalmopathy. Arch Ophthalmol 2007; 125:1652-1656. Levels of the oxidative stress marker, 8-hydroxy-2′-deoxyguanosine (8-OHdG), were elevated in patients with active TED and decreased after corticosteroid treatment.
48. Mysliwiec J, Waligorski D, Nikolajuk A, et al. Soluble CD40 and its ligand CD154 in patients with Graves' ophthalmopathy during combined therapy with corticosteroids and teleradiotherapy. Adv Med Sci 2007; 52:104-108. A study of soluble CD40 and CD154 measurements as markers of TED in 51 TED patients and 10 controls demonstrated that serum CD40 and CD154 were elevated in TED patients. Nonresponders to i.v. methylprednisone were found to have significantly elevated CD40/CD154 ratios after treatment and at the end of the study.