Thyroid Eye Disease , orbit Opthalmology.pptx

Thyroid eye disease, etiology , treatment and pathogenesis

1. Thyroid Eye Disease Dr Hafiz Muhammad Abdullah Roll no 166 Fourth year MBBS

2. Thyroid eye disease Thyroid eye disease (TED) is a very common orbital disorder Most common cause of both bilateral and unilateral proptosis in an adult between the ages of 25 and 50 years Thyroid eye disease (TED) also known as:- Graves ophthalmopathy Thyroid associated ophthalmopathy Thyrotoxic exophthalmos and several other terms.

3. Thyroid eye disease (TED) is an autoimmune inflammatory disorder involving the soft tissues of the orbit. It is a self-limiting process. Most of patients with TED are hyperthyroid at presentation (90%). Some cases are associated with Hashimoto’s thyroiditis (3%). Primary hypothyroidism (1%).

4. Epidemiology Female > Male TED occurs 5 times more frequently in women. incidence of 16 per 100,000 in women and 3 per 100,000 in men. The age of presentation is bimodal, with peak incidence rates occurring in the age groups of 40 to 44 years and 60 to 64 years in women.

5. Risk factors Smoking Tobacco Genetics Type of treatment for hyperthyroidism:- Eg. Radioactive iodine Drugs Advanced age Smoking is the most important modifiable risk factor.

6. Pathogenesis Pathological changes of TAO in the orbit appear to involve both the extraocular muscles and the orbital fat compartments Proptosis is due to expansion of orbital tissue The consequent increase in orbital pressure can also lead to venous outflow congestion and chronic periorbital oedema extraocular muscle enlargement is due to deposition of glycosaminoglycan (GAG), predominantly hyaluronic acid (HA). Hyaluronic acid which is hydrophilic and causes edema in extraocular muscles

7. Histology of extraocular muscles shows diffuse and focal lymphocytic in fi ltrates and fi brosis, whereas orbital fat and connective tissue contains few in fi ltrating cells. EFFECTOR CELL IN TAO:- Fibroblasts are the target cells in TAO They are extremely sensitive to stimulation by cytokines and immunoglobulins Cellular immunity T cell in fi ltrates in TAO orbital tissues are predominantly CD4+,TCELLS Th1-like cytokine pro fi le predominates in TAO retrobulbar tissue.

8. Role of cytokines:- Interferon (IFN)- γ, tumour necrosis factor (TNF)- α, IL-1 β and IL-6 has been detected mainly in TAO extraocular muscle. IL-4 and IL-10, Th2-type cytokines were detected predominantly in orbital fat

9. Increased prevalence of HLA B8, DR-3 may increase susceptibility to TAO Higher frequency of HLA-DRB1-16 allele in TRO patients with severe extra ocular muscle involvement .

10. Clinical features T ED typically proceeds through a congestive (inflammatory) stage in which the eyes are red and painful. 10% of patients develop serious long term ocular problems. A fibrotic (quiescent) stage follows in which the eyes are white, although a painless motility defect may be present.

11. Classification for the severity Classification for the severity of TED has been issued by the European Group on Graves Orbitopathy (EUGOGO):- ( i ) sight-threatening due to optic neuropathy or corneal breakdown (ii) moderate- severe, with one of moderate–severe soft tissue involvement, lid retraction of 2 mm or more, diplopia and proptosis of 3 mm or more. (iii) mild, with only a minor impact on daily life.

12. Werner classification Werner classification reflects the severity of the ophthalmopathy. Each grade is further subdivided as 0–4 and a–c. Grade 0—No signs or symptoms Grade 1—Only signs (lid retraction) Grade 2—Soft tissue involvement (chemosis, grit, etc.) Grade 3— Proptosis (minimum < 23, moderate, marked>28) Grade 4—Extraocular muscle involvement Grade 5—Corneal involvement Grade 6—Loss of sight.

13. Common Signs of Graves Disease Lid retraction Lid lag (upper and lower) Infrequent blinking Exophthalmos Diplopia Lid oedema and chemosis Conjunctival injection over insertion of the recti Increased intraocular pressure with elevation Superior limbic keratopathy

14. Soft tissue involvement Symptoms:- Grittiness red eyes Lacrimation photophobia, puffy lids retrobulbar discomfort.

15. Signs:- 1)Epibulbar hyperaemia:- This is a sensitive sign of inflammatory activity. Intense focal hyperaemia may outline the insertions of the horizontal recti. 2)Periorbital swelling: caused by oedema and infiltration behind the orbital septum, this may be associated with chemosis and prolapse of retroseptal fat into the eyelids

16. Tear insufficiency and instability is common Corneal signs are exacerbated by lid retraction and can include punctate epithelial erosions, superior limbic keratoconjunctivitis.

17. Lid retraction Retraction of upper and lower lids occurs in about 50% of patients with Graves disease. Humorally induced overaction of Müller muscle is postulated to occur as a result of sympathetic overstimulation secondary to high levels of thyroid hormones Contracture of the levator palpebrae and inferior rectus muscles another probable mechanism

18. Symptoms:- Staring or bulging eyed appearance Difficulty closing the eyes Ocular surface symptom Signs:- 1)The upper lid margin normally rests 2 mm below the l imbus scleral show 2) The lower eyelid margin normally rests at the inferior limbus

19. The Dalrymple sign is lid retraction in primary gaze. The Kocher sign describes a staring and frightened appearance of the eyes which is particularly marked on attentive fixation The von Graefe sign signifies retarded descent of the upper lid on downgaze

20. Proptosis Symptoms are similar to those of lid retraction. Signs:- Proptosis is axial, unilateral or bilateral, symmetrical or asymmetrical, and frequently permanent. Severe proptosis may compromise lid closure. Along with lid retraction and tear dysfunction can lead to exposure keratopathy, corneal ulceration and infection

21. symmetrical Asymmetrical Bacterial keratitis due to severe exposure

22. Restrictive myopathy Between 30% and 50% of patients with TED develop ophthalmoplegia and this may be permanent Symptoms:- Double vision, and often discomfort in some positions of gaze. Signs:- Elevation defect caused by fibrotic contracture of the inferior rectus.

23. Abduction defect due to fibrosis of the medial rectus, which may simulate sixth nerve palsy. Depression defect secondary to fibrosis of the superior rectus. Adduction defect caused by fibrosis of the lateral rectus.

24. Optic neuropathy A fairly common (up to 6%) serious complication caused by compression of the optic nerve or its blood supply at the orbital apex by the congested and enlarged recti and swollen orbital tissue. Symptoms:- Impairment of central vision Signs:- Visual acuity (VA) is usually reduced, but not invariably. Colour desaturation is a sensitive feature. There may be diminished light brightness appreciation. A relative afferent pupillary defect. Visual field defects can be central or paracentral and may be combined with nerve fiber bundle defects. The optic disc may be normal, swollen or, rarely, atrophic.

25. Investigation TSH Free thyroxine FT4 Free thyroxine FT3 Thyroid auto antibodies Visual fields Ct scan MRI Thyroid uptake scan or orbital biopsy are some time required.

26. Treatment Treatment can be classified into that of mild disease, moderate to severe active disease, and treatment of post inflammatory complications. Stop smoking Mild disease:- Lubricants for superior limbic keratoconjunctivitis,corneal exposure and dryness. Topical anti-inflammatory agents (steroids, non-steroidal anti-inflammatory drugs (NSAIDs), ciclosporin) are advocated by some authorities. Head elevation with three pillows during sleep to reduce periorbital oedema. Eyelid taping during sleep may alleviate mild exposure keratopathy.

27. Moderate to severe active disease:- Clinical activity score:-EUGOGO suggests calculating a ‘clinical activity score’ Determining a threshold for the use of immunosuppressive one point for each feature:- 1. Spontaneous orbital pain. 2. Gaze-evoked orbital pain. 3. Eyelid swelling considered to be due to active (inflammatory phase) TED. 4. Eyelid erythema. 5. Conjunctival redness considered to be due to active (inflammatory phase) TED. 6. Chemosis. 7. Inflammation of caruncle or plica.

28. Systemic steroids are the mainstay of treatment for moderate to severe disease. Oral prednisolone 60–80 mg/ day may be given initially. Orbital steroid injections are occasionally used in selected cases to minimize systemic side effects. Low-dose fractionated radiotherapy may be used. Combined therapy with irradiation, azathioprine and low-dose prednisolone may be more effective than steroids or radiotherapy alone. Optic neuropathy, and corneal exposure, requires aggressive treatment.

29. Several drugs targeting specific aspects of the immune response in TED are under investigation, notably monoclonal antibody treatment with rituximab. Post-inflammatory complications:- Surgery should be performed in- Proptosis Restrictive myopathy Lid retraction.