1. Thyroid Orbitopathy & Glaucoma
高雄醫學大學 眼科
張丞賢

4. Autoimmune inflammation
Thyroid Orbitopathy
Graves orbitopathy
Thyroid associated ophthalmopathy
Thyroid eye disease
Shared autoantigen?
*EO Muscles
64Kd protein
*Adipocyte
TSH receptor
glycosaminoglycan TO
Thyroid Orbit
Autoimmune inflammation

5. Thyroid Orbitopathy (TO)
No sign
Only sign: lid retraction, lid lag, staring
Soft tissue sign: chemosis, congested conj.
Proptosis
Extraocular myopathy
Corneal epithelial defects (Corneal Ulcer)
Sight (Optic neuropathy)
American Thyroid Association 1977
IOP?
Glaucoma?

6. Questions
Do TO patients tend to have glaucoma? or ocular hypertension only.
TO-associated ocular hypertension, how does it happen? What is the mechanism?
TO-associated ocular hypertension, do we have to treat? How should we treat?

7. Question one Do TO patients tend to have glaucoma?
Or ocular hypertension only.

8. Do TO patients tend to have ocular hypertension or glaucoma?
The prevalence of ocular hypertension and glaucoma in TO patients
TO patients vs. Normal
Ocular HT (22-30 mmHg) : % (124/500) vs. 5% ???
Glaucoma (Disc & VF)/Ocular HT : % vs. 2.7%(IOP mmHg), 12% (IOP mmHg) 43 months follow
Cockerham, Kennerdell et al, Ophthalmology 1997

9. Is the above finding consistent?
Prevalence of ocular H/T and glaucoma in a Dutch TO study
Ocular H/T: 4.8% (23/482)
Glaucoma (POAG): 0.8% (4/482) vs 1.1% Dutch general population
Kalmann & Mourits BJO 1998
Why???? American vs. European

10. Measurement of IOP Applanation Slight upgaze IOP increased with upgaze
Compression of episcleral vein by enlarged inferior rectus muscles

12. IOP change on different vertical gaze
Reader A. Ophthalmology 1982

14. TO: Augmented Δ IOP in upgaze
Normal: 0.6 ± 0.2 mmHg
Graves’ patients without exophthalmos: 4.8 ± 0.4 mmHg
Graves’ patients with exophthalmos: 9.2 ± 1 mmHg
81 patients
Gamblin et al. NEJM 1983

15. Δ IOP increased with exophthalmos

16. Time and Increased IOP (ΔIOP) Gamblin GT et al, N Eng J Med 1983)

17. Augmented Increase of IOP on Upgaze Spierer A, Eisenstein Z
Augmented Increase of IOP on Upgaze Spierer A, Eisenstein Z. Ophthalmolgy 1991

18. Augmented Increase of IOP on Upgaze Spierer A, Eisenstein Z
Augmented Increase of IOP on Upgaze Spierer A, Eisenstein Z. Ophthalmolgy 1991

19. Other evidence- Increased IOP at upgaze
Adhesive myopathy
Blow-out orbital fracture with inferior rectus muscle incarceration
Orbital myositis
Zappia et al. AJO 1971

20. Back to the Question of Different Prevalence of Ocular Hypertension in TO
American vs. European Studies
Ethnic?
Black, Hispanic and Indian (First Nations) in American Study?

21. Different subgroups of TO patients and IOP Cockerham KP et al, Ophthalmology 1997

22. Caucasian vs. Oriental Japanese study
13% (14/104): (7 POAG + 7 NTG) / TO
Ohtsuka & Nakamura Am J Ophthalmol 2000
Question?
NTG or compressive optic neuropathy
Difference of VF/optic disc change?
/104

23. V.F. of compressive optic neuropathy
The most common defects found with compression of the optic nerve anterior to the chiasma include enlarged blind spot, relative central scotoma, and constriction.
Nearly all types of visual field abnormalities have been reported with compression of the optic nerve.

24. Vancouver (UBC TO data)
Ocular Hypertension Prevalence = 4/ = 4.7%

25. Vancouver (UBC TO data)
Increase of IOP at upgaze > 7mmHg = 7/ = 8.6%

26. TO-associated ocular hypertension, how does it happen
TO-associated ocular hypertension, how does it happen? What is the mechanism?
Angle closure?
Trabecular meshwork, resistance?
Ciliary body, overproduction of aqueous?
Orbit, congested?
Hypothesis?

27. Hypothesis of ocular H/T in TO
Enlarged extraocular muscles
Accumulation of glycosaminoglycan in orbit
 Increased orbital pressure
 Increased orbital venous pressure (OVP)
 Increased episcleral vein pressure (EVP)
Increased IOP
OVP æ EVP æ IOP

28. OVP æ EVP æ IOP OVP: orbital venous pressure
EVP: episcleral vein pressure
MAP: mean arteral pressure
Reitsamerand & Kiel 2002 IVOS

29. The initial steps of the hypothesis
Enlarged extra-ocular muscles
Accumulation of glycosaminoglycan in orbit
??  Increased orbital pressure
 VOP
 EVP
 IOP Orbital decompression

30. Intraorbital Pressure (Retrobulbar Pressure, RBP)
Normal “steady state” RBP mmHg
Otto JA et al, BJO1996

31. To-associated Ocular Hypertension Do we have to treat
To-associated Ocular Hypertension Do we have to treat? How should we treat?
What is the indication to treat?
IOP?
Will treat patients with IOP between 22 and 26 mmHg? Or between 26 and 30?
Other parameters
Optic disc
Visual field

32. Risk of subsequent glaucomatous visual field loss Sommer AJO 1989
Armaly et al.
1-13 year follow
David et al.
Mean follow 43 months
IOP (mmHg)
Risk (%)
Risk (%)
<16
0.8
16-19
1.4
21-25
2.7
20-23
3.1
26-30
12.0
≧24
8.4
>30
41.2

33. Risk factors for developing Glaucoma in TO, Ocular hypertension
Degree of Propotosis
Degree of Myopathy
Exposure to corticosteroid
Prior anti-glaucoma therapy
Family history of glaucoma
Duration of active orbitopathy
Cockerham et al, Ophthalmology 1997

34. To-associated Ocular Hypertension Do we have to treat
To-associated Ocular Hypertension Do we have to treat? How should we treat?
Reduce the aqueous production –
b blocker, CAI, a2 agonist
Facilitate aqueous outflow –
Miotics, a agonist
Prostaglandin
Hyperosmotic agent
Sugar-based medication, Manitol
Others?
Surgery, TRBC

35. Orbital Decompression Kalmann and Mourits BJO 1998, Dev et al. 1998 CJO
23  18 mmHg

36. IOP decreased after Tx in TO
Inferior rectus muscle recession
Kalmann and Mouritiz BJO1998
Botulinum toxin injection for myopathic strabismus
Kikkawa et al. AJO 2003

37. How about Hypothyroidism?
TO mostly hyperthyroidism
Hypothyroidism
No proptosis
No enlargement of EOM
No restrictive myopathy

38. Hypothyroidism association with POAG or NTG
Controversial
Autoimmune
Deposition of mucopolysacharide in trabecualr meshwork

39. Conclusion Ocular Hypertension in TO D.D. compressive optic neuropathy
Subgroup of enlarged / restrictive EOM
D.D. compressive optic neuropathy
Treatment
Medical : inhibition of aqueous production, b-blocker, CAI
Orbital decompression, muscle recession, botulinum injection

40. Appreciation 吳國揚 會長 蔡榮坤 主任 高醫眼科 所有住院醫師 林玫琪 小姐 (MSD) 林斐嬋 小姐 (南區眼科醫師會秘書)