J Korean Ophthalmol Soc.  2018 Jul;59(7):599-605. 10.3341/jkos.2018.59.7.599.

Risk Factors for Structural Changes in Meibomian Gland in Thyroid Eye Disease

• Kim M
• Yang S
• Park J
• Lee H
• Baek S

• KMID: 2416261
• DOI: http://doi.org/10.3341/jkos.2018.59.7.599

Abstract

PURPOSE
To investigate the effect of clinical activity score (CAS) and thyroid stimulating hormone receptor autoantibody (TSHR autoantibody) on structural changes in Meibomian gland in patients with thyroid eye disease (TED).
METHODS
From March 2015 to February 2016, retrospective and cross-sectional studies were performed on patients diagnosed with TED. We investigated thyroid function, TSHR autoantibody (thyrotopin-binding inhibitor immunoglobulin [TBII] assay) status, duration of TED, CAS, and analyzed the Meibomian gland structure using a Lipiview inferometer® (TearScience Inc., Morrisville, NC, USA). We evaluated the degree of meibum expression (ME) and the tear film breakdown time by slit lamp microscopy.
RESULTS
A total of 37 patients (13 males and 24 females) with TED were included in the study, and the mean age was 43.8 ± 13.3 years. At the time of the study, 24 patients (64.9%) had hyperthyroidism, five patients (13.5%) had hypothyroidism, and eight patients (21.6%) had normal functioning. The mean CAS was 1.86 ± 1.74 (0-7), nine patients (24.3%) were in the active group with ≥3 points of CAS, and 28 patients (75.7%) were in the inactive group with < 3 points of CAS. The meiboscore was 1.05 ± 0.82 in the upper eyelid, and 0.76 ± 0.76 in the lower eyelid, with a significantly higher upper eyelid (p = 0.001). The mean value of the TBII was 6.11 ± 11.35 IU/L. Sixteen patients (43.2%) had TBII above the normal 1.5 value, and 21 patients (56.8%) had a normal TBII. The meiboscore of the upper eyelid was significantly higher when the TBII was higher than normal (p = 0.045). CAS (r = 0.356, p = 0.030), ME (r = 0.379, p = 0.021), and TBII (r = 0.334, p = 0.044) were significantly associated with the meiboscore in the upper eyelid. Using multiple regression analyses, CAS (p = 0.010) and TBII (p = 0.011) were factors affecting the upper eyelid meiboscore, and CAS (p = 0.015) and TBII (p = 0.038) were factors affecting the lower eyelid meiboscore.
CONCLUSIONS
The structural loss of Meibomian glands in patients with TED was greater in the upper eyelid than lower eyelid, and CAS and TSHR autoantibody had an effect on the structural loss of the Meibomian gland.

Keyword

Clinical activity score; Meibomian gland dysfunction; Meiboscore; Thyroid eye disease; Thyroid stimulating hormone receptor autoantibody

MeSH Terms

Cross-Sectional Studies
Eye Diseases*
Eyelids
Humans
Hyperthyroidism
Hypothyroidism
Immunoglobulins
Male
Meibomian Glands*
Microscopy
Receptors, Thyrotropin
Retrospective Studies
Risk Factors*
Slit Lamp
Tears
Thyroid Gland*
Immunoglobulins
Receptors, Thyrotropin

Figure

• 

  Figure 1 Representative cases of each grade of the meibomian gland changes. Changes in meibomian glands were scored using the following grades in each eyelid (meiboscore): (A) Grade 0, no loss of meibomian glands; (B) Grade 1, area loss was less than one third of the total meibomian gland area; (C) Grade 2, area loss was between one third and two thirds; (D) Grade 3, area loss was more than two thirds.

Reference

1. Prabhakar BS, Bahn RS, Smith TJ. Current perspective on the pathogenesis of Graves' disease and ophthalmopathy. Endocr Rev. 2003; 24:802–835.

2. Bahn RS, Heufelder AE. Pathogenesis of Graves' ophthalmopathy. N Engl J Med. 1993; 329:1468–1475.

3. Char DH. Thyroid eye disease. Br J Ophthalmol. 1996; 80:922–926.

4. Gürdal C, Saraç O, Genç İ, et al. Ocular surface and dry eye in Graves' disease. Curr Eye Res. 2011; 36:8–13.

5. Bartley GB, Fatourechi V, Kadrmas EF, et al. Long-term follow-up of Graves ophthalmopathy in an incidence cohort. Ophthalmology. 1996; 103:958–962.

6. Brasil MV, Brasil OF, Vieira RP, et al. Tear film analysis and its relation with palpebral fissure height and exophthalmos in Graves' ophthalmopathy. Arq Bras Oftalmol. 2005; 68:615–618.

7. Rocha EM, Mantelli F, Nominato LF, Bonini S. Hormones and dry eye syndrome: an update on what we do and don't know. Curr Opin Ophthalmol. 2013; 24:348–355.

8. Kim YS, Kwak AY, Lee SY, et al. Meibomian gland dysfunction in Graves' orbitopathy. Can J Ophthalmol. 2015; 50:278–282.

9. Park J, Kim J, Lee H, et al. Functional and structural evaluation of the meibomian gland using a LipiView interferometer in thyroid eye disease. Can J Ophthalmol. 2017; [Article In Press]. DOI: 10.1016/j.jcjo.2017.11.006.

10. Bartley GB, Gorman CA. Diagnostic criteria for Graves' ophthalmopathy. Am J Ophthalmol. 1995; 119:792–795.

11. Bartalena L, Baldeschi L, Dickinson AJ, et al. Consensus statement of the European group on Graves' orbitopathy (EUGOGO) on management of Graves' orbitopathy. Thyroid. 2008; 18:333–346.

12. Jung HH, Kang YS, Sung MS, Yoon KC. Clinical efficacy of topical 3% diquafosol tetrasodium in short tear film break-up time dry eye. J Korean Ophthalmol Soc. 2015; 56:339–344.

13. Shimazaki J, Goto E, Ono M, et al. Meibomian gland dysfunction in 6 patients with Sjögren syndrome. Ophthalmology. 1998; 105:1485–1488.

14. Arita R, Itoh K, Inoue K, Amano S. Noncontact Infrared meibography to document age-related changes of the meibomian glands in a normal population. Ophthalmology. 2008; 115:911–915.

15. Schott M, Feldkamp J, Bathan C, et al. Detecting TSH-receptor antibodies with the recombinant TBII assay: technical and clinical evaluation. Horm Metab Res. 2000; 32:429–435.

16. Den S, Shimizu K, Ikeda T, et al. Association between meibomian gland changes and aging, sex, or tear function. Cornea. 2006; 25:651–655.

17. Kim JH, Ro JW, Yi K, et al. Changes of the meibomian gland according to age in the normal Korean population. J Korean Ophthalmol Soc. 2015; 56:13–18.

18. Miz.oguchi S, Iwanishi H, Arita R, et al. Ocular surface inflammation impairs structure and function of meibomian gland. Exp Eye Res. 2017; 163:78–84.

19. Eckstein AK, Plicht M, Lax H, et al. Thyrotropin receptor autoantibodies are independent risk factors for Graves' ophthalmopathy and help to predict severity and outcome of the disease. J Clin Endocrinol Metab. 2006; 91:3464–3470.

20. Kohn LD, Harii N. Thyrotropin receptor autoantibodies (TSHRAbs): epitopes, origins and clinical significance. Autoimmunity. 2003; 36:331–337.

21. Kim WB, Chung HK, Park YJ, et al. Clinical significance of classification of Graves' disease according to the characteristics of TSH receptor antibodies. Korean J Intern Med. 2001; 16:187–200.

22. Eckstein AK, Finkenrath A, Heiligenhaus A, et al. Dry eye syndrome in thyroid-associated ophthalmopathy: lacrimal expression of TSH receptor suggests involvement of TSHR-specific autoantibodies. Acta Ophthalmol Scand. 2004; 82(3 Pt 1):291–297.

23. Ponto KA, Kanitz M, Olivo PD, et al. Clinical relevance of thyroid-stimulating immunoglobulins in graves' ophthalmopathy. Ophthalmology. 2011; 118:2279–2285.

24. McCann LC, Tomlinson A, Pearce EI, Diaper C. Tear and meibomian gland function in blepharitis and normals. Eye Contact Lens. 2009; 35:203–208.

25. Eom Y, Choi KE, Kang SY, et al. Comparison of meibomian gland loss and expressed meibum grade between the upper and lower eyelids in patients with obstructive meibomian gland dysfunction. Cornea. 2014; 33:448–452.

26. Andrews JS. The Meibomian secretion. Int Ophthalmol Clin. 1973; 13:23–28.

27. Jang SY, Shin DY, Lee EJ, et al. Correlation between TSH receptor antibody assays and clinical manifestations of Graves' orbitopathy. Yonsei Med J. 2013; 54:1033–1039.