GRAVE’S OPTHALMOPATHY THYROID EYE DISEASE GRAVE’S OPTHALMOPATHY

INTRODUCTION

INTRODUCTION--THYROID EYE DISEASE Seen in 25 – 50% of graves disease. GRAVES DISEASE also known as BASEDOW’S DISEASE is an autoimmune disorder that usually presents in 3rd to 4th decade of life, affects women more than men, characterized by a triad of features: Hyperthyroidism Diffuse thyroid enlargement Opthalmopathy =HYPERTHYROIDISM =DIFFUSE THYROID ENLARGEMENT =OPTHLMOPATHY

INTRODUCTION -- TED Thyroid eye disease (TED) may occur in the absence of clinical and biochemical evidence of thyroid dysfunction. The occurrence of signs of graves disease in a patient who is not clinically hyperthyroid is referred to as euthyroid or ophthalmic graves disease. Eye disease may be the first presenting sign of graves disease.

ETIOLOGY THYROID EYE DISEASE

-- Myasthenia gravis, addison disease. ETIOLOGY ==GENETIC FACTOR ASSOCIATION: -- HLA DR3, CTLA-4, PTPN22 ( a T- cell regulatory gene). ==RADIOACTIVE THYROID: Thyroid ablation with orally ingested radioactive iodine-131 may excerbate thyroid associated orbitopathy compared with anti-thyroid drugs and surgical ablation. ==AUTOIMMUNE DISEASE ASSOCIATION: -- Myasthenia gravis, addison disease.

STRONG ASSOCIATION OF THYROID EYE DISEASE WITH SMOKING

PATHOGENESIS

PATHOGENESIS INFLAMMATION OF EXTRAOCULAR MUSCLES This involves an organ specific autoimmune reaction in which a humoral agent (IgG antibody) produces the following changes: INFLAMMATION OF EXTRAOCULAR MUSCLES INFLAMMATORY CELLULAR INFILTRATION

PATHOGENESIS: INFLAMMATION OF EXTRAOCULAR MUSCLES Pleomorphic cellular infiltration, increased secretion of glycosaminoglycans,osmotic retention of water. Muscles become enlarge( 8 times their normal size, may compress optic nerve). Subsequent degeneration of muscle fibers eventually leads to fibrosis Restrictive myopathy and diplopia.

HISTOLOGICAL PICTURE SHOWING ROUND CELL INFILTRATION OF EXTRA OCULAR MUSCLES IN THYROID EYE DISEASE

PATHOGENESIS: INFLAMMATORY CELLULAR INFILTRATION Accumulation of glycosaminoglycans & retention of fluid. Infiltration with lymphocytes, plasma cells, macrophages & mast cells of interstitial fluid, orbital fat & lacrimal glands Increase in volume of orbital contents & secondary elevation of intraorbital pressure. Secondary elevation of intraorbital pressure.

CLINICAL MANIFESTATIONS

CLINICAL MANIFESTATION 5 main clinical manifestations of TED are: 1… SOFT TISSUE INVOLVEMENT (PERIORBITAL & LID SWELLING, CONJUCTIVAL HYPEREMIA. 2...LID RETRACTION 3…PROPTOSIS (PASSIVE OR MECHANICAL PROTRUSION OF EYE BALL) 4…OPTIC NEUROPATHY (SERIOUS COMPLICATION –COMPRESSION OF OPTIC NERVE MAY LEAD TO VISUAL IMPAIREMENT) 5…RESTRICTIVE MYOPATHY (OCULAR MOTILTY IS REDUCED INITIALLY BY INFLAMMATORY EDEMA & LATER BY FIBROSIS)

SYMPTOMS OCULAR SYMTOMS SYSTEMIC SYMPTOMS DRY EYES BULGING EYES DIPLOPIA VISUAL LOSS OCULAR PRESSURE OR PAIN PHOTOPHOBIA LACRIMATION TACHYCARDIA NERVOUSNESS HEAT INTOLERANCE INCRESE SWEATING WEIGHT LOSS IRRATIBILITY SKELETAL MUSCLE WEAKNESS

OCULAR SIGNS PROPTOSIS ( eyes protude beyond orbit…unilateral or bilateral) Exophthlmos (appearance of protuding eyes) Conjuctival edema Corneal ulceration Visual impairement Visual field defects Papilloedema Loss of colour vision Opthlmoplegia Optic disc usually normal VIGOUROUX SIGN( eyelid fullness) DALRYMPLE SIGN( lid retraction in primary gaze) von GRAEFE SIGN( retarted descent of upper lid at downward gaze STELLWAG SIGN ( incomplete & infrequent blinking) GROVE SIGN( resistance to pulling down the retracted upper lid) JOFFROY SIGN ( abscent creases in forehead on sup. gaze) MOBIUS SIGN( poor convergence) BALLET SIGN ( restriction of one or more extra ocular movements) KOCHER SIGN ( staring & frightened appearance of eyes)

SEVERE BILATERAL PROPTOSIS & LID RETRACTION IN THYROID EYE DISEASE

PERIORBITAL SWELLING IN THYROID EYE DISEASE

LEFT EYE SHOW LID RETRACTION &MILD PROPTOSIS

von GRAEFE SIGN( RIGHT EYE)

KOCHER SIGN

RESTRICTED LEFT EYE ABDUCTION

SYSTEMIC SIGNS FAST/ IRREGULAR PULSE WARM MOIST SKIN FINE TREMOR PALMER ERYTHEMA HAIR LOSS

DIFFERENTIAL DIAGNOSIS

DIFFERENTIAL DIAGNOSIS ORBITAL CELLULITIS: Onset of proptosis is earlier & patient has other evidence of infection. (fever) IDIOPATHIC ORBITAL INFLAMMATORY DISEASE: More painful than thyroid eye disease. OTHER CAUSES OF THICKENED MUSCLES: sarcoidosis, amyloid, acromegaly.

INVESTIGATIONS

INVESTIGATIONS NON- SPECIFIC SPECIFIC ROUTINE BLOOD PICTURE. HAEMOGLOBIN. WBC( total & differential count.) ESR. BLOOD SUGAR. CHOLESTROL. URINE EXAMINATION. *FOR HYPERTHYROIDISM: == SERUM T3 & T4 LEVEL ==SERUM TSH LEVEL. *FOR OCULAR MUSCLE ENLARGEMENT: ==PLAIN X-RAY CALDWELL VIEW(PA view) ==ORBITAL ULTRASOUND ==CT SCAN ORBIT ( AXIAL & CORONAL VIEW) ==MRI

Axial CT scan showing enlarged extra ocular muscles in thyroid eye disease

TREATMENT

GENERAL MANAGMENT CONTROL OF OCULAR DISCOMFORT =Artificial tears =Topical lubricants =Sunglasses ADVISE THE PATIENT TO =Avoid smoking as it worsens the prognosis =Avoid dust =Elevate head when sleeping to avoid periorbital edema

MEDICAL MANAGMENT CONTROL OF HYPERTHYROIDISM Iodine and antithyroid drugs Radioactive iodine ORBITAL DECOMPRESSION Systemic steroids: Oral prednisolone: 60-80mg/day (dose should be tappered after reduction in symptoms) I/V methylprednisolone: 0.5g in 200ml isotonic saline over 30 min(may be repeated after 48 hrs)

SURGICAL MANAGMENT Surgical treatment when there is severe sight threatening condition or for cosmetic purpose. ORBITAL DECOMPRESSION: (for advanced proptosis & optic nerve compression) STRABISMUS SURGERY: (to minimize diplopia) LID LENTHENING SURGERY

OTHER MANAGEMENT OPTIONS RADIOTHERAPY FUTURE OPTIONS ORBITAL RADIOTHERAPY CAN BE USED TO TREAT OPHTHALMOPLEGIA BUT HAS LITTLE EFFECT ON PROPTOSIS. THE RADIATION(1500-2000 Cgy fractioned over 10 days) IS USUALLY ADMINISTERED VIA LATERAL FIELDS WITH POSTERIOR ANGULATION ANTI-TNF α ANTIBODIES(eg infliximab)