THYROID RELATED OPHTALMOPATHY Dr. RANJAKUMAR M.S, DO, MBA ranjakumar@hotmail.com Professor of Ophthalmology, Kannur Medical College, Anjarakandy PO, Kannur – India - 670612

Thyroid Related Ophthalmopathy Thyroid Ophthalmopathy is a disease wherein eye manifestations march on relentlessly & often independently of the systemic disease Ophthalmologist assesses, monitors, evaluates and intervenes in an ailing or cured dysthyroid to safeguard sight

Definition Ocular and orbital pathology occuring as a part of an autoimmune process affecting thyroid gland -‘Graves ophthalmopathy’

Thyroid disorders Hyperthyroidism - 70% graves disease toxic multi nodular goitre toxic adenoma thyrotoxicosis factitia Hypothyroidism - 10% primary hypothyroidism hashimotos disease Euthyroidism – 20%

In graves disease eye signs may precede, coincide with or follow hyperthyrodism Eye signs seen without detectable thyroid abnormality

Epidemiology 4th to 5th decade female:male - 4:1 to 8:1 males prone to severe disease severe disease in older age group strong family history

Immunology Autoimmune disease Both humoral & cellular mediated Target tissue-orbital connective tissue particularly fibroblasts & extra ocular muscles Antibody to 64-kd eye muscle membrane antigen-60% Antibody to 23-kd fibroblast antigen-50% Most of cellular infiltrations are T-lymphocytes

Pathophysiology Active phase of inflammation Quiescent fibrotic phase –scarring of orbital tissue stable phase (5-6mnths) burnt out phase(> 5-6mnths)

Changes in the orbit Increased secretory activity of orbital fibroblast which secrete collagen & glycosaminoglycans –causes the muscle to swell EOM tendons & ON sheath uninvolved

Extra Ocular Muscles Swelling due to inflmmn & GAG accumuln Involves endomysium,perimysium & interstitial connective tissue A/c phase-lymphocyitc infiltrn,progressive fibrosis & fatty infiltrn C/c phase – restrictive myopathy

Proptosis 30% pts with TRO have proptosis Axial proptosis 4ml change in orbital content – 6mm proptosis EOM enlargement Venous stasis Orbital fat hypertrophy (?)

Eye lid changes lid swelling hypertrophy, alopecia upper lid retraction lower lid retraction lid lag

Upper eye lid retraction SR/LPS over action to counter IR tethering Increase sympathetic stimulation – mullers muscle overaction Protruding globe pushing up the upper lid Levator infiltration,tethering & scarring

Conjunctiva Congestion & Chemosis over insertion of horizontal recti muscles

Cornea Exposure ,Sup.limbic keratoconjunctivitis Inadequate lid closure from proptosis & lid retraction Compromised bell’s reflex Dry eye from infiltrn of lacrimal gland

Optic nerve Nerve compression in the crowded orbital apex If EOM volume >11%of total orbital volume optic neuropathy occur No inflammatory process

Lacrimal system Enlargement of lacrimal gland Tearing inflmmn of lacrimal gland reflex tearing lower lid retraction interference with lacrimal pump blockage of puncta

Intra Ocular Pressure Increase in 30% of TRO Restrictive myopathy Proptosis & increase in orbital volume Increase in episcleral venous pressure Steroid induced

Clinical features Non infiltrative ophthalmopathy

Non infiltrative ophthalmopathy Minimal ocular inflmmn & myopathy Any combination of lid lag,stare & lid retrn With/without exophthalmos No threat to cornea or optic nerve

Infiltrative ophthalmopathy Soft tissue changes Myopathy Orbital apex syndrome

Soft tissue changes Aching behind eyes,eye strain, burning, redness,gritty feeling,excess mucus & intermittent blurring Lid edema,retraction & lid lag Conj.congestion & chemosis Corneal dryness,dellen,epithelial breakdown Choroidal folds

Myopathy Fatigue,discomfort on reading,vertical diplopia IR>MR>SR-LPS>LR Obliques rare- pseudo 4thnerve palsy 30-50% pts with TRO have myopathy

Dysthyroid optic neuropathy 5% of pts-potentially blinding Disc oedema / atrophy Usually bilateral (70%) Older males prone Impairment of central vision Defective red green color appreciation Field defects-central, centrocecal, paracentral scotoma, gneralised constriction

Classification-Werner-NOSPECS No signs,symptoms Only signs Soft tissue changes Proptosis EOM involvement Corneal involvement Sight loss Pt falls into many class,progression not in order, no prognostic value,used in many endocrine studies

Classification -Vandyk Resistance to retropulsion Edema of conjunctiva Lacrimal gland enlargement Inflammation of conjunctiva Edema of lids Fullness of lids

Thyroid eye signs Darlymples -35-60% lid retraction Von Graffe’s-40-50%- lid lag on down gaze Enroth’s- lower lid edema Joffroy’s- abscent forehead creases Kocher’s- spasmodic retraction of upperlid Mobius-defective convergence Stellawag’s-infrequent blinking

Systemic features Increase appetite, loss of weight Tremor,palpitation,heat intolerance Diarrhoea , amenorrhoea Warm moist hands Diffuse thyroid swelling Skin changes in hand & feet- thyroid acropatchy

Differential diagnosis Pseudotumour Orbital cellulitis C/c orbital myositis Cysts Systemic disorders-lymphoma,sarcoidosis,amyloidosis Vascular malformations

Lab investigations Endocrine evaluation Imaging studies Electro diagnostic tests

Endocrine evaluation Biochemical tests for serum T4,T3,TSH Immunological tests for antithyroglobulin & antimicrosomal antibodies

Ultrasonography Enlargement of EOM with high internal reflectivity Reduplication of ON sheath due to expansion of subarachnoid space Irregular post: outline of RB fat pattern

CT Scan Thick muscles with tendon sparing Proptosis Lacrimal gland enlargement Nasal bowing of medial orbital walls-coca cola sign Thinning of optic nerve Tenting of posterior globe

MRI Better delineation of compressive optic neuropathy Greater soft tissue spatial resolution

Natural history Spontaneous remission in 3-36mths Eye lid retraction resolves Proptosis remain stationary Diplopia resolves in majority Optic neuropathy does not improve spontaneously Euthyroid has more benign course

Response to therapy Acute active inflammatory phase responds to treatment with steroids, immunosuppressants & local irradiation Chronic stable cases need surgical options

Management Local measures Medical therapy Radiation Surgical options

Local measures Sun glasses, moist chamber goggles Sleep in supine position with head elevated Taping of lids at night Prisms in diplopia

Medical therapy Topical tear substitutes Topical adrenergic blockers Systemic diuretics-minimal role Corticosteroids Immunomodulators, cytotoxic agents

Corticosteroids Indications A/c inflammatory phase Compressive optic neuropathy Prior to orbital decompression Non responsiveness to irradiation / surgery Effect may be temporary Rebounds can occur

Corticosteroids -regimen 60-100mg orally prednisolone in divided doses for several days followed by slow taper Pulse intravenous therapy of methyl prednisolone 1gm every other day for 3-5 cycles

Immunosuppressives Cyclosporin – 7.5 to 10mg/kg for 4-12 months Methotrexate / azathioprim / cyclophosphamide Bromocryptine – decreases TSH & has anti lymphocyte activity Somatostatin analogue- octreotide Anti tumour necrosis factor drugs-infiximab / daclizumab Plasmapheresis Pentoxiphylline & nicotinamide Botulinum toxin s/c inj for lid retraction

Radiation therapy Substitute or adjunct to steroids & surgery Less dramatic,more prolonged effect Donaldson’s protocol- 2000 rads in 10 fractions over 2 weeks- mainly to posterior orbit

Surgical management Orbital decompression Starbismus surgery Eye lid surgery

Orbital decompression Done in c/c stable cases Severe exophthalmos Globe luxation Exposure keratopathy Optic nerve compression Cosmetic purpose

Surgical approaches Lateral orbitotomy Coronal approach- all 4 walls Floor & medial walls Trans frontal( nafzigers) Ethmoidal / maxillary Conjunctival / Skin approach

Strabismus surgery Done in stable inactive TRO To minimise diplopia in primary & reading position To under correct hypo & exo tropia To over correct hyper & eso tropias Muscle recession with marginal myotomy Adjustable suture surgery

Eye lid surgeries Lateral tarsorrhaphy Muller’s & LPS lenghthening Blepharoplasty with orbital fat excision Lower eyelid elevation / lenghthening Spacer materials / grafts

to conclude… TRO is a common ocular entity Rarely sight threatening complications can occur Ophthalmologist has a key role in diagnosing & directing the patient for proper evaluation and treatment In monitoring the patient to prevent complications

Major issues remaining unresolved What is the relationship between autoimmune thyroid disease and eye sign Why do some patient with hyperthyroidism develop eye signs while others do not What is the relationship between the cause of treated thyroid disease & thyroid oph’pathy What is the role of thyroid in the development of euthyoroid ophthalmopathy

thank You