Thyroid orbitopathy thyroid eye disease thyroid Eyelid surgery0 by benbenzhou


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									Shirley Fung MBBS, Raman Malhotra MBChB, FRCOphth
and Dinesh Selva MBBS (Hons), FRACS, FRANZCO

Thyroid orbitopathy
A review
      hyroid orbitopathy (thyroid eye disease, thyroid

 T    ophthalmopathy) is a self-limited, organ specific, autoimmune
      disorder with the potential to cause severe functional and
 psychosocial effects. This article reviews the clinical features with
 particular emphasis on current management.

Thyroid orbitopathy (TO) is most                  Pathophysiology
prevalent among females in the fourth and         Despite evidence for an autoimmune
fifth decades and is usually associated with      aetiology, the precise pathophysiology of
thyroid dysfunction. Clinical                     TO remains unknown. The inflammatory
manifestations include soft tissue signs, lid     response is centred on the extraocular
retraction, lid lag, proptosis, restrictive       muscles and orbital connective tissue, and
myopathy, corneal exposure and optic              is thought to arise from autoantibody
neuropathy. Thyroid function tests are            cross-reactivity between thyroid and
essential, while thyroid antibodies and           orbital antigens6. There are two distinct
imaging to demonstrate extraocular                stages – an active inflammatory stage
muscle enlargement, may also aid                  followed by a quiescent stage. The
diagnosis. Correction of thyroid                  inflammatory phase is characterised by
dysfunction and supportive measures are           lymphocytic infiltration, interstitial
necessary in all cases. Immunosuppression         oedema and mucoglycoprotein deposition
is reserved for moderate to severe active         within the extraocular muscles and orbital
orbitopathy and rehabilitative surgery is         fat2,3,7. Inactive disease is distinguished by
generally used once the disease is                fibrosis and fatty infiltration of the orbital
quiescent. A good visual and cosmetic             tissues2,3,7.
outcome requires close cooperation
between the optometrist, general                  Clinical features
practitioner, endocrinologist and                 The major signs and symptoms are
ophthalmologist.                                  outlined in Table 1. Common complaints
    TO is an organ specific autoimmune            include red, gritty, photophobic and
disorder which may result in severe               watery eyes. Patients often report a change
functional and psychosocial sequelae.             in the appearance of their eyes and perusal
Although there is an association with             of old photographs may be helpful.
Graves’ disease or Hashimoto thyroiditis          Periorbital swelling is worse in the
in 90% of cases, patients may be hyper,           mornings, and diplopia, retrobulbar
hypo or euthyroid1,2. In addition, orbital        discomfort, and pain on eye movement
disease may precede, coincide with or             are other presenting symptoms (Figure
follow the onset of thyroid dysfunction.          1a). The cardinal signs are axial proptosis,     C
An estimated 30-40% of Graves’ disease            eyelid retraction and lid lag (Figure 1b).
sufferers demonstrate clinical signs of TO,       In fact, TO is the most common cause of
while 90% have radiological evidence of           bilateral, asymmetric and unilateral
extraocular muscle involvement3,4. The            proptosis in adults3 (Figure 1c). Although
incidence of TO is approximately                  progression of signs such as muscle
16/100,000 in females and 2.9/100,000 in          restriction and the presence of soft tissue
males and although it is most prevalent in        inflammation are suggestive of activity, the
the fourth and fifth decades, a wide age          differentiation of active from inactive
range exists3,5.                                  orbitopathy can be problematic. The

                Table 1:
              Symptoms and signs of thyroid orbitopathy                                            D
               Symptoms                 Signs
                                                                                                                                             Figure 1
               Impaired lid closure       Lid retraction                                                               Signs of thyroid orbitopathy
               Protruding eyes            Lid lag
               Eye pain                   Proptosis                                                                     a. Periorbital swelling due to
               Eye grittiness             Conjunctival injection                                                     mild active thyroid orbitopathy
               Photophobia                Conjunctival oedema                                               b. Axial proptosis and eyelid retraction
               Watery eyes                Corneal exposure with corneal erosion                                          c. Right axial proptosis due
               Double vision              Lid oedema                                                                          to thyroid orbitopathy
               Blurred vision             Restricted extraocular movements                                        d. Axial computerised tomography
               Washed out colour vision   Reduced visual acuity                                                (CT) scan of orbits showing enlarged
               Blind spot                 Reduced intensity of colour perception                       extraocular muscles causing crowding of the
                                          Central or paracentral scotoma                                        optic nerve at the left orbital apex

                                                                                                                         33 | June 27 | 2003 OT
                                                          Shirley Fung MBBS, Raman Malhotra MBChB, FRCOphth
                                                          and Dinesh Selva MBBS (Hons), FRACS, FRANZCO

                                                         proptosis resulting in severe corneal          Supportive therapy
                                                         exposure and ulceration. Smoking,              Supportive therapy is applicable to all
                                                         diabetes, male gender and increasing age       patients with cessation of smoking being
                                                         are risk factors for more severe disease9.     the single most effective measure13.
                                                            With regard to differential diagnosis,      Exposure symptoms can be alleviated with
                                                         active disease may require differentiation     wrap-around sunglasses, lubricant eye
                                                         from non-specific orbital inflammatory         ointment at bedtime and artificial tears
                                                         syndrome, and unilateral proptosis may         during the day2. Cool compresses and
                                            Figure 2     need exclusion of an orbital mass.             head elevation whilst sleeping help reduce
                 Coronal CT scan of orbits showing                                                      periorbital oedema2. Diplopia can be
              enlarged rectii, in particular inferior,   Natural history                                temporarily managed with monocular
                         medial and superior rectii      As with other autoimmune disorders, TO         occlusion or prisms1. The majority of
                                                         is characterised by an active dynamic          patients can be managed with these
                                                         phase with spontaneous remissions and          supportive measures alone, however, in the
                                                         exacerbations, thought to reflect a period     presence of moderate or severe disease
                                                         of self-limited autoimmune inflammation,       activity, immunosuppression either in the
                                                         which then leads to static fibrotic            form of steroids or radiotherapy should be
                                                         changes10. The active phase of the disease     considered.
                                                         usually encompasses an average period of
                                                         18 to 36 months, but late reactivation         Immunosuppression
                                                         does occur in the occasional patient.          Steroid therapy has a 65% response rate
                                                                                                        and is most effective for soft tissue signs
                                                         Investigations                                 rather than motility problems, and least
                                                         Thyroid function tests should be               efficacious for proptosis14. The treatment
                                                         performed in all cases. Thyroid stimulating    regime is 1mg/kg of prednisolone tapered
                                            Figure 3
                                                         hormone receptor antibody and                  over a six to 12-week period. However,
                Patient receiving Linear accelerator
                                                         antithyroglobulin antibody levels may be       steroid related side effects are relatively
                     external beam radiotherapy to
                                                         useful in making the diagnosis in              common and symptoms may return with
            posterior orbit for thyroid orbitopathy
                                                         euthyroid patients2. The diagnosis can also    cessation of therapy15. Pulsed intravenous
                                                         be confirmed by computerised                   (IV) steroid (1g for three days and repeated
                                                         tomography (CT) or magnetic resonance          second weekly) is usually reserved for optic
                                                         imaging (MRI) showing enlarged                 neuropathy16. Low-dose orbital
                                                         extraocular muscle bellies with relative       radiotherapy also has a 65% response rate,
                                                         sparing of the tendons3,7 (Figure 1d).         primarily in soft tissue signs, and is given
                                                         Muscle involvement is generally bilateral      as 10 fractions of 2 Gy to the posterior
                                                         and symmetrical with the inferior,             orbit17 (Figure 3). It is better tolerated than
                                                         followed by medial, superior and lateral       steroid therapy with side effects including
                                                         recti being most often affected3 (Figure 2).   hair loss at the temples (14%) and
                                                         In the majority of cases, a strong             transient increase in soft tissue involvement
                                                         presumptive diagnosis can be made on the       (14%)8. Radiation retinopathy is extremely
                                                         clinical presentation in the context of        rare18. The combination of steroids and
                                                         thyroid dysfunction, and imaging is only       radiotherapy is commonly used and
                                                         appropriate in severe disease or if the        appears more effective than
                                                         diagnosis is doubtful.                         monotherapy19,20. Although, the efficacy of
                                                                                                        radiotherapy has been recently questioned,
                                                         Management                                     it remains widely used21.
                                                         The management of TO remains                       Cyclosporin is used in combination
                                                         controversial as much of the literature        with steroids for refractory cases and also
                                                         refers to small, uncontrolled studies.         as a steroid sparing agent22. Intravenous
                                                         Nevertheless, the treatment plan shown in      IgG, somatostatin analogues and
                                                         Algorithm 1 summarises the current             cyclophosphamide have been reported in
                                                         philosophy used by the majority of orbital     small series as having similar response
                                                         clinicians. Referral to an ophthalmologist     rates to steroids, but are not commonly
                                                         should be considered if the diagnosis is       used19,23-25.
                                                         unclear, in moderate to severe active
                                            Figure 4     inflammatory disease, especially if vision     Surgery
           Intraconal fat excision during an orbital     is threatened, and in inactive disease with    Surgery is generally reserved for quiescent
                          decompression procedure        significant functional or cosmetic             disease. The exception is urgent orbital
     distinction is of particular importance as          sequelae.                                      decompression for dysthyroid optic
     medical treatment is effective only in                                                             neuropathy. However, with the advent of
     active disease and surgery is generally             Correction of thyroid status                   aggressive immunosuppression, emergency
     reserved for stable TO8.                            The initial management in all TO patients      decompression has become rare. Surgical
         It should be noted that there is a broad        is restoration of euthyroid state, as this     intervention follows a step-wise approach,
     spectrum of clinical presentation. Mild             will often ameliorate the orbitopathy. It      with orbital decompression, if required,
     disease may present solely as prominence            should be noted that there is a risk of        being performed prior to any strabismus
     of the eyes due to lid retraction. On the           exacerbation of TO following I 131             surgery, which precedes eyelid surgery. The
     other hand, severe myopathy may cause               therapy particularly in those with pre-        reason for this is that decompression may
     crowding of the optic nerve at the orbital          existing active orbitopathy11,12.              result in ocular misalignment requiring
     apex leading to dysthyroid optic                    Simultaneous prednisolone                      strabismus surgery. Similarly, strabismus
     neuropathy (Figure 1d). Loss of vision              administration or alternative therapy          surgery may affect eyelid position and
     may also occur as a consequence of gross            should be considered in these patients6,11.    should therefore be done before any lid

     34 | June 27 | 2003 OT


                                                                                        • Establish and maintain euthyroid state
                                                                                                  • Supportive therapy

                                                                                                  Active         Inactive

                                                                                                                            Persistent functional or
                                                                                                                             cosmetic sequelae?

                                                                                                                       Non-urgent ophthalmic referral
                                        Figure 5                                                                           for rehabilitative surgery
    Endoscopic transnasal view of right orbital                                                                       Following stability for six months
medial periorbita (periosteum) after removal of                                                                            - Orbital decompression
   bony medial orbital wall. Periorbita is being                                                                        - Extraocular muscle surgery
                                                                                                                                - Eyelid surgery
   incised in order to release orbital contents
                             into ethmoid sinus                 Active moderate - severe thyroid
                                                                                                           Active mild thyroid orbitopathy?

                                                                    Early ophthalmic referral
                                                                                                               Supportive therapy only
                                                                   Immunosuppresive therapy


                                                              Evidence of optic neuropathy?        Evidence of corneal exposure?
                                                                  Reduced visual acuity
                                                                  Reduced colour vision
                                                             Relative afferent pupillary defect    Semi-urgent ophthalmic referral
                                                                                                   Possible temporary tarsorrhaphy

                                                                Urgent ophthalmic referral
                                                                 Trial of pulsed IV steroid
                                                                    Emergency orbital
                                                                decompression if steroid
                                        Figure 6                  therapy unsuccessful
                                                                                                                                              Algorithim 1
     a. Right sided proptosis and lid retraction                                                                   Thyroid orbitopathy management
         prior to orbital decompression surgery
           b. Cosmetic result after right orbital   Summary                                                  Ophthalmologist in the Oculoplastic and
    decompression surgery in the same patient       • TO is an organ specific autoimmune                     Orbital Unit, Department of
                                                      disorder, most frequent in women                       Ophthalmology, Royal Adelaide Hospital,
procedures. Currently, the most common                between 40 to 50 years old and usually                 University of Adelaide, Australia.
indication for orbital decompression is               associated with thyroid dysfunction
disfiguring proptosis. It is important to           • The clinical manifestations include                    References
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blepharoplasties to debulk excess skin and          About the authors                                           Curr. Opin. Ophthalmol. 5: 65-71.
fat prolapse from the eyelids can also help         Shirley Fung is Resident Medical Officer,                8. Wiersinga WM, Prummel MF (2000)
restore the patient’s appearance closer to          Raman Malhotra is a Clinical Fellow and                     An evidence-based approach to the
the premorbid state (Figure 6).                     Dinesh Selva is a Consultant                                treatment of Graves’ ophthalmopathy.

                                                                                                                                        35 | June 27 | 2003 OT
                                                     Shirley Fung MBBS, Raman Malhotra MBChB, FRCOphth
                                                     and Dinesh Selva MBBS (Hons), FRACS, FRANZCO

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