1. THYROID RELATED OPHTALMOPATHY
Dr. RANJAKUMAR
M.S, DO, MBA
Professor of Ophthalmology, Kannur Medical College, Anjarakandy PO, Kannur – India

2. 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

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

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

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

6. 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

7. 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

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

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

10. 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

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

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

13. 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

14. Conjunctiva
Congestion & Chemosis over insertion of horizontal recti muscles

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

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

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

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

19. Clinical features Non infiltrative ophthalmopathy

20. 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

21. Infiltrative ophthalmopathy
Soft tissue changes
Myopathy
Orbital apex syndrome

22. 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

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

24. 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

25. 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

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

27. 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

28. 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

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

30. Lab investigations Endocrine evaluation Imaging studies
Electro diagnostic tests

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

32. 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

33. 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

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

35. 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

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

37. Management
Local measures
Medical therapy
Radiation
Surgical options

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

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

40. 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

41. 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

42. 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

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

44. Surgical management Orbital decompression Starbismus surgery
Eye lid surgery

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

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

47. 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

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

49. 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

50. 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

51. thank You