Thyroid-related ophthalmopathy is one of the most common orbital disorders in adults and is an autoimmune disease. Most patients may have clinical or laboratory findings of abnormal thyroid function, but orbital disease may occur even in the presence of normal thyroid function. Thyroid-associated ophthalmopathy is a common cause of monocular or bilateral proptosis.
There are various grading and classification of thyroid-related ophthalmopathy. However, there is still a completely satisfactory grading and classification. The disease is usually described according to a variety of clinical features exhibited in terms of disease activity and severity.
Patients with mild disease (especially adolescents and younger adults) may present only with delayed lid drop, lid retraction (staring), rabbit eyes and simple proptosis, or proptosis combined with varying degrees of active hyperthyroidism. By controlling hyperthyroidism, some patients can achieve partial relief of their symptoms.
Moderately active disease includes persistent eyelid recession, late lid drop, proptosis, and some soft tissue signs. Soft tissue signs manifest as soft tissue swelling and intermittent myelopathy. The myelopathy usually has an acute onset but eventually quiesces, a process that usually takes 6 months to 1 year. The final outcome of this type of disease (the so-called non-infiltrative or type I) rarely presents with severe orbital and ophthalmic disorders and stabilization is relatively rapid. Imaging may reveal mild extraocular hypertrophy and protrusion of the eye disproportionate to the degree of muscle involvement, which may reflect increased fat volume.
The more severe the disease, the more rapid the onset, and severe disease is most often seen in middle-aged and older patients. The nature of the disease depends on the degree of inflammation and the degree of soft tissue volume increase (the so-called infiltrative or type II).
In many patients, the disease resolves spontaneously, with orbital involvement predominating in about 10-15% of patients clinically, and in about 5-6% of these patients, severe orbital disease develops. Severe orbital disorders are characterized by progressive proptosis, severe soft tissue signs, increased volume, and myelopathy, all of which changes usually correlate with disease severity. Orbital tip compression can lead to orbital tip compression syndrome with optic neuropathy.
One theory of pathogenesis suggests that orbital connective tissue, adipocytes, and possibly extraocular muscle cells are target tissues for T lymphocytes, and that thyrotropin receptor (TSHR) may play a role as an autoantigen in Graves’ hyperthyroidism, thyroid-related eye disease, and anterior tibial mucinous edema. Another theory suggests that primary autoantigens are present in the extraocular muscles and that activated lymphocytes (especially T cells) infiltrate the orbital tissue, especially early in the disease, and cause the corresponding orbital lesions. Infiltration of inflammatory cells leads to the release of cytokines, causing the continued expression of a large number of circulating proteins. The local tissue response to cytokines, oxygen radicals and fibrous growth factors stimulates fibroblasts, resulting in increased glycosaminoglycan (GAG) synthesis, cell growth and the expression of immunomodulatory factors produced during the concomitant transformation of adipose precursor cells. Infiltration of orbital tissues by inflammatory cells results in an increase in orbital hydrophilic glycosaminoglycan (GAG), an increase in muscle volume and orbital fat volume, inflammatory edema, muscle damage, and scar formation, especially by fibroblasts on extraocular muscles and orbital soft tissues. These mechanisms produce tissue swelling, inflammation, muscle movement restriction, and secondary compression changes.
Clinical manifestations:
Common symptoms include photophobia, tearing, foreign body sensation, ocular swelling, incomplete lid closure, diplopia, and decreased visual acuity. Bilateral or unilateral protrusion of the eyeball, eyelid congestion and edema, and fullness of periorbital tissue. The upper or lower eyelid is receding, the upper eyelid is dropping slowly, which is called the “late drop sign”, and transients are increasing or decreasing. The conjunctiva is congested and edematous, and in severe cases, the conjunctival vessels are increased at the muscle stops, and even thickened muscle stops can be seen during internal and external rotation. Restrictive eye movement disorders occur with extraocular muscle involvement. Severe protrusion of the eyeball and exposure of the cornea can lead to exposure keratitis, with the lower edge of the cornea being most commonly involved, even forming endophthalmitis and endangering vision. Long-term elevated orbital pressure, strain on the optic nerve, and muscle hypertrophy at the orbital apex can lead to optic nerve atrophy, visual field defects, color vision impairment, and visual electrophysiological abnormalities, and even loss of vision in severe cases. Long-term intraorbital venous reflux obstruction can lead to open-angle glaucoma, with loss of visual acuity and visual field defects.
I. General treatment
1.Actively adjust the thyroid hormone level to maintain it in the normal range, and avoid sudden reduction or increase of drug dosage.
Avoid spicy and irritating foods, quit smoking, prevent eye fatigue, wear sunglasses when exposed to bright light, and avoid emotional excitement. The head is elevated during sleep, and those with incomplete lid closure need to apply eye ointment or wet room protection.
Drug treatment
1. Glucocorticoids: If the disease is in the acute progressive stage or the active score CAS≥4, glucocorticoid shock therapy is feasible, either intravenous methylprednisolone or oral high-dose prednisone. Complications of hormone use need to be closely observed during treatment: secondary hypertension, diabetes mellitus, stress ulcers, electrolyte disorders, liver and kidney damage, osteoporosis, pathological fractures, mental disorders, dryness and insomnia, hyperphagia and irritability, etc. If systemic application of glucocorticoids is contraindicated, intraorbital local injection of trimethoprim may be given.
2.Immunosuppressive therapy: Patients who are suitable for glucocorticoid therapy can also try immunosuppressive drugs, including methotrexate, cyclophosphamide and cyclosporine, which can also be used in combination with glucocorticoids. Complications include bone marrow suppression, liver and kidney damage, gastrointestinal disorders, infections, etc.
3. Local application of adrenergic blockers: Early in the course of the disease, alpha adrenergic tone is increased, causing excitation of the upper and lower lid Müller muscles and eyelid retraction. The adrenergic blocker guanethidine sulfate ophthalmic solution can produce a chemical sympathectomy effect and alleviate eyelid regression.
4. Topical application of botulinum toxin A: Botulinum toxin A is an acetylcholinergic receptor blocker that competes with acetylcholine for the cholinergic receptors that govern the movement of the extraocular muscles, causing paralysis of the extraocular muscles. It can be used for upper eyelid retraction due to levator muscle spasm and other strabismus due to extraocular muscle spasm, but the therapeutic effect only lasts for a few weeks to about six months and requires repeated injections.
III. Radiation therapy
For those who are not sensitive to medication, have a rapid loss of vision, or whose systemic condition cannot tolerate medication, local radiation therapy can be tried. Complications include radiation cataract, retinopathy and carcinogenic risk, etc. A few patients may be aggravated by radiotherapy.
IV. Surgical treatment
1. Eyelid recession correction: For patients with severe eyelid recession, oversized lid fissures, secondary exposure keratitis or impact on appearance. Surgical procedures include Müller muscle resection, levator muscle lengthening, levator muscle margin dissection, lower lid reduction and posterior migration of the capsular fascia, lid suturing and lid fissure shortening.
2. Surgical treatment of ophthalmomyopathy: Restrictive extraocular myopathy is one of the most common clinical manifestations of the disease. Inflammation, edema and fibrosis of the extraocular muscles are responsible for the loss of motor function of the muscles. The timing of surgery should be after 3-6 months of ocular myopathy stabilization. In cases of combined high protrusion of the eye, orbital decompression surgery should be performed first.
Orbital decompression: Orbital decompression is an effective treatment for severe cases, and is suitable for those with stable control of hyperthyroidism, secondary optic neuropathy requiring release of orbital apical pressure, or severe protrusion of the eye secondary to exposure keratitis. The procedure is also feasible for those whose appearance is severely disfigured by the protrusion of the eye, after the disease no longer progresses.
4.Lipectomy: In cases of mild protrusion of the eye, the intraorbital fat, especially the fat in the muscle cone, can be removed through the bulbar conjunctival incision to relieve the symptoms. It has the advantages of concealed incision and small surgical trauma. It can be used in combination with orbital decompression.
V. Disease prognosis Prognosis is related to the following factors.
1. Age, gender and race: younger patients generally have milder symptoms, and older patients are prone to serious complications. Male patients have a more severe and later onset than females. Caucasians are sicker than Asians.
2. Acuteness of onset and its severity: Patients in the acute or subacute onset of inflammation have a greater chance of evolving into severe disease than those with insidious onset and slow course. Patients with mild or moderate disease are more likely to improve naturally than those in severe disease.
3. Relationship between thyroid function and orbital disease: There is a relationship between the severity of autoimmune thyroid disease and orbital disease. There is also a relationship between the treatment modality of hyperthyroidism and the occurrence and severity of orbital disease. Patients who undergo iodine radiotherapy for hyperthyroidism have a higher probability of developing severe orbital disease and further progression of the disease. Early and complete control of hyperthyroidism is essential for the treatment of orbital disease, and similarly, early detection and control of secondary hypothyroidism is beneficial for the treatment of orbital disease. Thyroid suppressant medications may reduce the incidence and severity of orbital disease. The likelihood of orbitopathy is increased in those with anterior tibial mucinous edema, and the severity of both is closely related.
Other factors determining prognosis: Patients who smoke are more likely to have progressive and more severe orbital disease. Too much physical and mental stress can cause hyperthyroidism. Diabetes mellitus contributes to thyroid-related eye disease. Other immune diseases including pernicious anemia and vitiligo can also be combined with thyroid disease. Radiotherapy to the neck in patients with non-thyroidal conditions, such as thyroid cancer and Hodgson’s disease, may predispose to thyroid-related eye disease.
VI. Edit this paragraph Disease prevention
1. Actively adjust thyroid hormone levels to maintain them in the normal range and avoid sudden reductions or increases in medication.
2. Avoid spicy and irritating foods, quit smoking, prevent eye strain, wear sunglasses when exposed to bright light, and avoid emotional excitement. Avoid emotional excitement. Sleep with the head in a high position, and those with incomplete lid closure need to apply eye ointment or wet room protection.
VII. Care:
Avoid spicy and stimulating foods, quit smoking, exercise appropriately, and adjust the mentality.