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Thyroid Orbitopathy & Glaucoma. 高雄醫學大學 眼科 張丞賢. Graves orbitopathy Thyroid associated ophthalmopathy Thyroid eye disease. Shared autoantigen? *EO Muscles 64Kd protein *Adipocyte TSH receptor glycosaminoglycan. Thyroid Orbitopathy. TO Thyroid Orbit
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Thyroid Orbitopathy& Glaucoma 高雄醫學大學 眼科 張丞賢
Graves orbitopathy Thyroid associated ophthalmopathy Thyroid eye disease Shared autoantigen? *EO Muscles 64Kd protein *Adipocyte TSH receptor glycosaminoglycan Thyroid Orbitopathy TO Thyroid Orbit Autoimmune inflammation
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? Thyroid Orbitopathy (TO)
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?
Question one • Do TO patients tend to have glaucoma? Or ocular hypertension only.
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) :24% (124/500) vs. 5% ??? • Glaucoma (Disc & VF)/Ocular HT:2% vs. 2.7%(IOP 21-25 mmHg), 12% (IOP 26-30 mmHg) 43 months follow • Cockerham, Kennerdell et al, Ophthalmology 1997
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
Measurement of IOP • Applanation • Slight upgaze • IOP increased with upgaze • Compression of episcleral vein by enlarged inferior rectus muscles
IOP change on different vertical gaze Reader A. Ophthalmology 1982
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
Time and Increased IOP (ΔIOP)Gamblin GT et al, N Eng J Med 1983)
Augmented Increase of IOP on UpgazeSpierer A, Eisenstein Z. Ophthalmolgy 1991
Augmented Increase of IOP on UpgazeSpierer A, Eisenstein Z. Ophthalmolgy 1991
Other evidence- Increased IOP at upgaze • Adhesive myopathy • Blow-out orbital fracture with inferior rectus muscle incarceration • Orbital myositis Zappia et al. AJO 1971
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?
Different subgroups of TO patients and IOPCockerham KP et al, Ophthalmology 1997
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?
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 typesof visual field abnormalities have been reported with compression of the optic nerve.
Vancouver (UBC TO data) • Ocular Hypertension Prevalence = 4/85 = 4.7%
Vancouver (UBC TO data) • Increase of IOP at upgaze > 7mmHg = 7/81 = 8.6%
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?
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
OVP æ EVP æ IOP • OVP: orbital venous pressure • EVP: episcleral vein pressure • MAP: mean arteral pressure Reitsamerand & Kiel 2002 IVOS
The initial steps of the hypothesis • Enlarged extra-ocular muscles • Accumulation of glycosaminoglycan in orbit ?? Increased orbital pressure VOP EVP IOP Orbital decompression
Intraorbital Pressure(Retrobulbar Pressure, RBP) • Normal “steady state” RBP 3-4.5 mmHg Otto JA et al, BJO1996
To-associated Ocular HypertensionDo 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
Risk of subsequent glaucomatous visual field lossSommer AJO 1989
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
To-associated Ocular HypertensionDo 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
Orbital DecompressionKalmann and Mourits BJO 1998, Dev et al. 1998 CJO 23 18 mmHg
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
How about Hypothyroidism? • TO mostly hyperthyroidism • Hypothyroidism • No proptosis • No enlargement of EOM • No restrictive myopathy
Hypothyroidism association with POAG or NTG • Controversial • Autoimmune • Deposition of mucopolysacharide in trabecualr meshwork
Conclusion • Ocular Hypertension in TO • 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
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) • 南區眼科醫師