Graves disease, originally called Graves-Basedow disease, was first described as the triad of hyperthyroidism, goiter, and exophthalmos in 1835. It is relatively common; it may occur in people of any age but is most common during the third to fifth decades of life. The female-to-male ratio varies from 4:1
to 8:1. The distribution is bimodal, with the peak incidence in the fifth and seventh decades of life.
Men tend to develop more severe orbitopathy.
Severe ophthalmopathy is an uncommon but problematic manifestation of Graves disease. Only 5–6% of patients with Graves disease develop problems severe enough to warrant surgical decompression on a functional basis. This does not include patients who seek cosmetic decompression.
Approximately half of all patients with Graves hyperthyroidism develop ophthalmopathy. In its most involved forms, the ophthalmopathy can result in severe corneal problems that necessitate decompression. Optic neuropathy due to compression of the optic nerve is another indication for decompression.
Orbitopathy associated with Graves disease may severely compromise a patient’s vision. The condition may cause diplopia, decreased ocular motility, exposure keratitis, optic neuropathy, and poor cosmesis. Surgical management is both an alternative and adjunctive treatment to medical therapy, which most often involves corticosteroids, external beam radiotherapy, or both.
Various approaches have been described since surgical decompression of the orbit for thyroid ophthalmopathy was initially advocated in 1911.
Orbital decompression most often involves the removal of the bones that comprise the orbit. Decompression of a lesser nature can be accomplished with the removal of extraconal and intraconal fat. This fat decompression can be combined with bone removal for more extensive decompression.
The advent of advanced endoscopic techniques has enabled surgeons to decompress the orbit endoscopically, allowing effective decompression with less morbidity. This is primarily a result of circumventing a gingival incision and a low incidence of cranial nerve V2 hypesthesia. Although an endoscopic approach to the medial and inferior walls can be performed in isolation, a balanced approach, incorporating a lateral decompression with repositioning of the lower lid, can be required.
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Pathophysiology and etiology of Graves ophthalmopathy
Orbital findings result from an increase in the volume of orbital tissues secondary to inflammation, edema, and congestion. Most notable is the enlargement of the extraocular muscles secondary to infiltration with inflammatory cells, deposition of immune complexes, and an increase in glycosaminoglycans, particularly hyaluronic acid, which is hydrophilic. In some cases, this is ultimately followed by fibrosis. These alterations are modulated by circulating antibodies. Smoking has been shown to increase venous congestion in the orbit via reduction of flow in the superior ophthalmic vein separate from extraocular muscle involvment, which were comparable between smokers and non smokers.
These autoimmune dysfunctions are considered to be mediated by both humoral and cellular dysfunctions; however, this is debated. Regardless, the processes show a predilection for the orbital tissues, the extraocular muscles, and periorbital structures. Both orbitopathy and thyroid dysfunction are more common in family members of patients who have thyroid-related orbitopathy.
Severe cases of ophthalmopathy may be associated with lid edema, chemosis (edema of the conjunctiva), and diminished ocular motility. Eventual sequelae may include corneal exposure with subsequent ulceration, diplopia due to extraocular muscle restriction, or fibrosis and optic nerve compression with resulting visual field deficits, including blindness.
Patients with Graves orbitopathy usually have hyperthyroidism but can have euthyroidism or hypothyroidism. A patient may present with signs of orbitopathy before being diagnosed with a thyroid disorder. At some point, 90% of patients with orbitopathy have hyperthyroidism. More than 50% of patients develop orbitopathy after they have had hyperthyroidism. The degree of control of the thyroid disorder does not exactly correlate with the extent of the orbitopathy.
The orbit’s inflammatory response to the thyroid dysfunction consists of an increase in both B and T lymphocytes, accompanied by edema. These processes can cause scarring. In addition, fibroblastic activity with the resultant production of collagen and glycosaminoglycans also increases. Increased edema and increases in the thickness of the extraocular muscles and fat cells are also found. Some early fibroblasts convert into fat cells.
If a patient has hyperthyroidism, cigarette smoking increases the incidence and severity of thyroid-related orbitopathy. The antigens that specifically cause this are unclear.
Clinical presentation of Graves ophthalmopathy
Graves-related exophthalmos usually occurs in adult life. The condition most commonly affects middle-aged women. It is more severe in older men, usually with greater exophthalmos. Graves orbitopathy is the most common cause of unilateral and bilateral proptosis. Most commonly it occurs in patients who are hyperthyroid, but also occurs in patients with hypothyroidism, euthyroidism, and Hashimoto’s thyroiditis.
Ethnic variations in the anatomy of the orbits can be found; therefore, the degree of proptosis with its concomitant problems can vary greatly, regardless of race or gender. A person with a tighter orbit is more at risk for compressive optic neuropathy from the disease process and may not show as much proptosis as a person with a much less tight orbit who is more proptotic but does not as readily experience compressive optic neuropathy.
Retraction of the upper or lower lid (Dalrymple sign) may develop. This is due to hyperstimulation of the sympathetically innervated Mueller muscle in the upper lid and its analog, the inferior tarsal muscle, in the lower lid. When the patient tries to look downward, the upper lid can hold back and lag behind the movement of the globe (von Graefe sign; also termed lid lag).
Unilateral or bilateral proptosis (34–93% of patients), tearing (epiphora), chemosis (edema of the conjunctiva), and hyperemia or injection of the conjunctiva (an increase in the size of the blood vessels) may develop.
A prominence of the blood vessels that overlie the insertion of the rectus muscles may develop. Edema of the lids and of the malar pad areas may develop. Corneal problems may vary from dryness to perforation when a full-thickness opening in the cornea is present.
Patients can present in various stages. Patients with very mild cases may have low-grade orbital inflammation with some orbital discomfort, tearing, and chemosis. Other patients may have mild proptosis with or without lid retraction. Still other patients present with marked inflammation, tremendous discomfort, corneal problems, or optic nerve compression. Patients may have diplopia.
In burnt-out Graves orbitopathy, many of the same signs persist, except that the inflammation is gone and the eyes and orbits appear quiet. However, the proptosis, lid retraction, and diplopia still remain.
Patients with hyperthyroidism can present with symptoms and signs of hyperstimulation of their sympathetic nervous system. These symptoms and signs include the following: weight loss, sweating, tremulousness, edginess, heart palpitations, an increase in appetite, feeling warm, and feeling “revved up.”
Nonsurgical treatment of Graves ophthalmopathy
Severe orbital manifestations of Graves disease early in the disease course often respond to high-dose corticosteroid therapy. If this is unsuccessful, external beam radiation therapy at a dose of 20 Gy may be considered.
When orbital findings have been present for a long time, they are less likely to respond to medical management because of fibrosis of the involved tissues.
Steroid treatment combined with radiation treatment has also proven effective.
In patients for whom nonsurgical modalities are unsuccessful or those who are not considered candidates, surgical decompression may be considered. Medical treatment can also be used in conjunction with surgical decompression.
Newer treatment modalities include the use of biologics. In one trial, rituximab showed benefits compared to steroids, and in another trial, it showed no benefit against placebo.
One trial reported increased adverse events with the use of rituximab compared to saline.
Compared to adalimumab, tocilizumab, and etanercept, rituximab reduced B cells that are CD20 positive.
However, rituximab may have a role in steroid-resistant cases.
Teprotumumab, a monoclonal antibody that is an IGF-1 inhibitor, is showing promise in offsetting inflammation in Graves orbitopathy and decreasing proptosis.
Various surgical approaches can be used for decompression. Otolaryngologists commonly perform decompression via a transantral approach to the medial and inferior orbital walls. An endoscopic approach to the medial and inferior walls is currently used. Oculoplastic specialists often use a transcutaneous or transconjunctival lower-lid approach. Often, the lower lid must be separated from its periosteal attachment and subsequently repaired. Transcaruncular approaches can also be used to access the medial orbital wall.
The lateral wall can be surgically approached in different ways. A team approach that involves the services of an otolaryngologist and an oculoplastic specialist is common. If the decompression requires the removal of the frontal bone, the services of a neurosurgeon may be required.
Ultimately, the approach or approaches used are tailored to the severity of the problem and therefore the degree of decompression desired and the anatomy of the patient. These decisions can be influenced by the cosmesis achieved, especially in patients who are undergoing decompressions to improve their appearance. A balanced approach in which the inferior wall and medial wall decompression are combined with lateral decompression may be used.
Medial wall decompression with preservation of the medial strut between the ethmoid cavity and the inferior wall, balanced with lateral wall decompression and with or without inferior wall decompression, may provide effective reduction of exophthalmos without a high risk for new-onset postoperative diplopia, especially in patients who are having surgery for cosmetic indications.
In the authors’ view, this combined approach to surgery for patients with Graves ophthalmopathy, incorporating both an otolaryngologist with endoscopic experience and an oculoplastic surgeon, provides for ideal surgical management.
The orbit, which protects, supports, and maximizes the function of the eye, is shaped like a quadrilateral pyramid, with its base in plane with the orbital rim. Seven bones conjoin to form the orbital structure, as shown in the image below.
This image of the right orbit shows the 7 bones that contribute to its structure.
The orbital process of the frontal bone and the lesser wing of the sphenoid form the orbital roof. The orbital plate of the maxilla joins the orbital plate of the zygoma and the orbital plate of the palatine bones to form the floor. Medially, the orbital wall consists of the frontal process of the maxilla, the lacrimal bone, the sphenoid, and the thin lamina papyracea of the ethmoid. The lateral wall is formed by the lesser and greater wings of the sphenoid and the zygoma.
For the transcutaneous or transconjunctival lower-lid approach, the inferior oblique muscle must be avoided. In fact, with either approach, during a bony decompression, the orbital space is not entered until the bone has been removed. Opening the periorbita earlier can allow the fat to prolapse, interfering with the dissection. The infraorbital nerve is to be avoided during any dissection to avoid postoperative paresthesia.
Medially, the dissection and bone removal is accomplished but stays below the ethmoidal arteries to avoid compromising the anterior or posterior ethmoidal arteries (and thereby causing hemorrhages) and to avoid disrupting the cribriform plate.
Posteromedially, care must be exercised when the sphenoid sinus is entered. If the carotid artery is violated, the result can be catastrophic.
Additionally, in more posterior dissections, damaging or resecting the optic nerve must be avoided during the dissection.
The relevant anatomy for endoscopic orbital decompression is similar to that for endoscopic ethmoidectomy and maxillary antrostomy. Specifically, the middle turbinate insertion at the skull base represents the medial limit of dissection, the fovea ethmoidalis is the superior limit, and the lamina papyracea is the lateral limit. The lamina extends from the nasolacrimal system anteriorly to the annulus of Zinn posteriorly. Cranial nerve V2 runs in the maxillary roof and can be dehiscent. For more information about the relevant anatomy, see Orbit Anatomy.
In all cases, the globe must not be unduly pressed on. The amount and duration of pressure must be monitored to prevent inadvertently compression of the ophthalmic artery.
Historically, the indications for surgical decompression of the orbit have included exophthalmos accompanied by corneal exposure and disfigurement and increased orbital pressure produced by swelling of extraocular muscles, which can lead to compressive optic neuropathy and visual loss. Recent advances in the techniques for orbital decompression have decreased the morbidity of the procedure, and a need for cosmetic decompressions is also an indication.
Emergency decompression can be warranted in the most severe cases of compression and visual loss. However, this situation is usually concomitantly treated with immunosuppressive agents, most commonly systemic steroids. Radiation therapy can be used in the acute setting in addition to immunosuppressives; it may also be used for patients who are not surgical candidates.
Patients who are unable to undergo a surgical procedure or who are unwilling to accept the potential complications of surgery are not candidates for orbital decompression. Other relative contraindications include a history of chronic sinusitis, immunocompromise, bleeding disorders, and atretic sinuses.