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Ophthalmology

Surgical advances and research insights in Graves’-related eye disorders

12/01/2007

Graves’ disease, an autoimmune disorder that affects the entire body, has particular impact on the thyroid and the eyes, including the eye muscles and the fat cushions behind the eyes. Eye damage from Graves’ disease can lead to double vision and even loss of vision.

Disease stages

During an initial inflammatory phase, typically lasting from 12 to 18 months, inflammatory cells invade the orbit and extra-cellular matrix materials are deposited between the muscle fibers causing the muscles and fat to expand. This inflammatory and fibrotic response causes the proptosis (bulging) of the eyes often associated with Graves’ disease. The same disease processes in the eyelid muscles can cause the eyelids to retract, compounding the proptotic effect.

Following this inflammatory stage, the disease progresses into a stable phase where eye condition remains unchanged with only a 4 percent chance of further inflammatory damage.

Treating Graves’ disease eye disorders

Treating orbital disorders of Graves’ disease traditionally divides between the inflammatory and stable phases. Anti-inflammatory therapy – including steroids and orbital radiation – is most often used during the inflammatory phase. Recent studies, however, have not shown that anti-inflammatory therapy produces good outcomes in terms of resolving proptosis and decreasing visual defects.

After the inflammatory stage of Graves’ disease, eye proptosis can be treated surgically with a decompression procedure that removes tissue from behind the eye and bone from the orbit to allow the eye to recess back to its normal position. Advances in minimally invasive decompression surgery with an incision hidden in the eyelid crease pioneered at UCLA are providing improved cosmetic results with fewer complications.

Conventional decompression surgery requires the removal of the sinus walls and is associated with postoperative double-vision rates of 30 percent to 50 percent. The minimally invasive technique uses a high-speed drill to remove bone from the orbit without removing the sinus walls and is producing double vision in only about 4 percent of patients. If needed following decompression surgery, patients can have an operation to correct double vision or to repair eyelids that have become retracted due to the inflammatory and fibrotic damage of Graves’ disease.

Graves’ disease ocular research

Research at UCLA has sought to identify the causes of the inflammatory and fibrotic process affecting the eyes of Graves’ disease patients. These patients, along with rheumatoid arthritis patients, have been found to possess an antibody to insulin-like growth factor (IGF-1) receptor that is found in few other people. When this antibody binds to orbital fibroblasts, it creates a number of inflammatory mediators along with a great quantity of hyaluronic acid. Hyaluronic acid is the primary extra-cellular matrix material that impairs muscle function by depositing between muscle fibers, causing them to expand to up to 10 times their normal size.

UCLA researchers have made recent discoveries that clarify the role of the immune system in the inflammatory process. They found that in Graves’ disease patients, a preponderance of T-cells over express the IGF-1 receptor, leading to excessive survival and propagation of these cells. Over expression of this receptor may play a role in how the immune system develops and responds in patients with Graves’ and other autoimmune diseases.

Working with Graves’ fibroblast cells both in culture and in situ, UCLA researchers have gained insight into the molecular mechanism behind the production of extra-cellular matrix proteins, especially in response to inflammatory mediators. They are currently working to develop a mouse model to test research findings and to develop a targeted inhibitor of the IGF-1 receptor to potentially block the inflammatory effects of Graves’ disease.

The development of molecular markers can also have clinical application in disease diagnosis and in tracking disease activity to help identify which treatments would be appropriate for a patient and when.

Physicians

Raymond S. Douglas, M.D., Ph. D.
Assistant Professor of Ophthalmology

Robert Goldberg, M.D.
Professor of Ophthalmology

Patient referral

For more information, or to refer a patient, please call the UCLA Orbital and Ophthalmic Plastic Surgery Division at (310) 206-8250.





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