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Augenzentrum AG
Fährweg 10
CH-4600 Olten
beim Kantonsspital
Haus M/Eingang West/1.OG
Tel. +41 62 206 87 37
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info@basedow.ch

EUGOGO (EUropean Group On Graves' Orbitopathy)

Introduction
Systemic Graves' Disease (GD) is the most common autoimmune disorder in the European Union and the world. The overall age-adjusted incidence rate for women is 16 cases per 100,000 population per year. The rate for men is 2.9 cases per 100,000 population per year (about 225'000 patients in Switzerland).

Graves' Disease also can affect the eyes in a condition known as Graves' Orbitopathy (GO). Moderate to severe GO is clinically apparent in up to 50% of patients with GD and in about 75-100% in patients with mild disease. It is caused by a positive feedback cycle of mechanical, immunologic, and cellular processes that induce proptosis (forward protrusion of the globe) and other changes within the orbital tissues which can seriously disturb or damage vision. Severe Graves' Orbitopathy is relatively rare (5% of patients with Graves' Disease), but may require aggressive and prolonged treatment. Patients with milder forms of the disease have impaired quality of life. A few patients develop visual disturbances with significant disfigurement. The management of Graves' Orbitopathy is rather difficult and the results of treatment are often disappointing.

Complications of GO
When intraorbital inflammation develops, fat and muscle tissues expand within the orbit. This may result in proptosis or forward protrusion of the globe. In addition, involvement of muscle structures within the eyelid may lead to eyelid retraction and widening of the palpebral aperture. Proptosis and eyelid retraction may, in turn, result in drying of the cornea with ocular irritation and with potential ulceration and loss of vision. The most common symptom of GO is ocular irritation. Involvement of the extraocular muscles may also cause double vision. The most worrisome complication of GO is compression or stretching of the optic nerve due to extraocular muscle or fatty tissue swelling behind the eyeball. This puts the patient at risk of permanent loss of vision. Also important from the patient's perspective are the psychosocial and quality-of-life concerns associated with the significant appearance changes, which may be associated with this chronic disorder.

Treatment
Medical approaches are the standard first-line treatment for mild cases. They include artificial tears and ointments to address ocular surface disease with dry eyes. Patients may also be fitted with glasses that provide lateral shielding of the eyes to protect the vulnerable cornea or prisms/occlusion of one eye to prevent double vision. More advanced approaches have traditionally included the use of immunosuppressive therapies, including oral or intravenous corticosteroids and cyclosporine and/or orbital irradiation. More severe cases of GO require surgical intervention to relieve elevated intraorbital pressure (orbital decompression surgery), address diplopia (eye muscle surgery), and improve ocular surface exposure (eyelid retraction repair with eyelid lengthening procedures).
In terms of medical approaches to GO, about 65% of patients only respond to immunosuppressive or radiation regimens. Recent research at the EUGOGO centres and elsewhere has raised questions regarding the effectiveness and potential complications of immunosuppressive treatment and orbital radiotherapy. The side effects of systemic immunosuppressive therapy may be significant and may limit therapy on a long-term basis. Orbital radiotherapy was shown to be most effective in patients with motility disorders of the extraocular muscles, but does not reduce proptosis.
In terms of traditional surgical approaches, decompression surgery can reduce pressure on the optic nerve and allow the eye to settle into a more normal position. Because a number of surgical approaches are possible (each with advantages and disadvantages) it is generally most helpful for surgeons to customize their approach to each patient. basedow.ch offers all available approaches, with surgery performed by a multidisciplinary team of ophthalmology, cranio-maxillo-facial, otorhinolaryngology, and neurosurgery specialists.

New Approach to Medical Treatment
In our experience, the optimal care of GO patients is based on an integrated, multidisciplinary team approach that crosses specialty lines. EUGOGO researchers work closely with clinicians to develop new medical treatments based on staging the disease and assessing its activity and severity at a given stage. Investigators at different EUGOGO centres and basedow.ch are continuously recruiting patients to participate in studies of the effectiveness of different immunosuppressive agents in the treatment of active GO.

Indications for Treatment
Medical treatment is the first line of treatment unless vision is acutely threatened. Decompression surgery is indicated when there is optic neuropathy, severe ocular surface exposure, globe subluxation, or in some cases for cosmetic considerations. Double vision may be corrected by repositioning the extraocular muscles so the patient can regain single vision. Strabismus surgery is indicated when the patient experiences functionally significant double vision. Upper and lower eyelid surgery may be performed to correct eyelid retraction associated with ocular surface exposure and/or cosmetic change. In general, orbital decompression surgery is performed initially, when required, followed by strabismus surgery and eyelid surgery sequentially.

The EUGOGO perspective
Many centres in Europe and elsewhere, have conducted clinical studies on Graves' Orbitopathy. However, difficulties in recruiting large numbers of patients have frustrated attempts to determine the role of several available treatments reported anecdotally to be of benefit.

To overcome these limitations, nine European Centres joined forces in 1999 and founded EUGOGO (EUropean Group On Graves' Orbitopathy; www.eugogo.org. These Centres share a commitment to improve the management of Graves' orbitopathy, have a good track record in clinical research in this field, are regional or national referral centres for the treatment of this disease and manage patients in a multidisciplinary setting with input from endocrinologists and ophthalmologists. To date 12 European academic centres are members of EUGOGO to share its objectives and goals.


Summary
  • Graves' Disease is the most common autoimmune disorder worldwide, with a prevalence of about 1,200 cases per 100,000 population.
  • Graves' orbitopathy is a progressive condition associated with Graves' disease that can seriously disturb or damage vision.
  • Graves' orbitopathy is caused by a positive feedback cycle of mechanical, immunologic, and cellular processes that results in proptosis, ocular motility disturbances with diplopia, and eyelid retraction with ocular exposure.
  • Multidisciplinary teams at the EUGOGO centres and basedow.ch are developing new surgical techniques and researching novel clinical treatments for Graves' orbitopathy.