1. GRAVE’S OPTHALMOPATHY
THYROID EYE DISEASE
GRAVE’S OPTHALMOPATHY

2. INTRODUCTION

3. 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

4. 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.

5. ETIOLOGY
THYROID EYE DISEASE

6. -- 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.

7. STRONG ASSOCIATION OF THYROID EYE DISEASE WITH SMOKING

8. PATHOGENESIS

9. 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

10. 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.

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

12. 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.

13. CLINICAL MANIFESTATIONS

14. 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)

15. 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

16. 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)

17. SEVERE BILATERAL PROPTOSIS & LID RETRACTION IN THYROID EYE DISEASE

18. PERIORBITAL SWELLING IN THYROID EYE DISEASE

19. LEFT EYE SHOW LID RETRACTION &MILD PROPTOSIS

20. von GRAEFE SIGN( RIGHT EYE)

21. KOCHER SIGN

22. RESTRICTED LEFT EYE ABDUCTION

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

24. DIFFERENTIAL DIAGNOSIS

25. 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.

26. INVESTIGATIONS

27. 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

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

29. TREATMENT

30. 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

31. 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)

32. 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

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