Endocrine ophthalmopathy is an organ-specific progressive lesion of the soft tissues of the orbit and eye, developing against the background of autoimmune pathology of the thyroid gland. The course of endocrine ophthalmopathy is characterized by exophthalmos, diplopia, swelling and inflammation of the eye tissues, limited mobility of the eyeballs, changes in the cornea, intraocular hypertension. Diagnosis requires an ophthalmological examination (exophthalmometry, biomicroscopy, CT of the orbit); studies of the state of the immune system (determination of the level of Ig, At to TG, At to TPO, anti-nuclear antibodies, etc.), endocrinological examination (T4 sv., T3 sv., ultrasound of the thyroid gland, puncture biopsy). Treatment of endocrine ophthalmopathy is aimed at achieving an euthyroid state; it may include drug therapy or removal of the thyroid gland.
ICD 10
H57.9 E05.0
Meaning
Endocrine ophthalmopathy (thyroid ophthalmopathy, Graves’ ophthalmopathy, autoimmune ophthalmopathy) is an autoimmune process that occurs with a specific lesion of retrobulbar tissues and is accompanied by exophthalmos and ophthalmoplegia of varying severity. The disease was first described in detail by K. Graves in 1776 .
Endocrine ophthalmopathy is a problem of clinical interest for endocrinology and ophthalmology. Approximately 2% of the total population suffers from endocrine ophthalmopathy, while the disease develops 5-8 times more often among women than among men. The age dynamics is characterized by two peaks of manifestation of Graves’ ophthalmopathy – in 40-45 years and 60-65 years. Endocrine ophthalmopathy can also develop in childhood, more often in girls of the first and second decades of life.
Causes
Endocrine ophthalmopathy occurs against the background of primary autoimmune processes in the thyroid gland. Ocular symptoms may appear simultaneously with the thyroid gland lesion clinic, precede it or develop in the long term (on average after 3-8 years). Endocrine ophthalmopathy may accompany hyperthyroidism (60-90%), hypothyroidism (0.8-15%), autoimmune thyroiditis (3.3%), euthyroid status (5.8-25%).
The factors initiating endocrine ophthalmopathy have not yet been definitively elucidated. The role of triggers can be:
- respiratory infections,
- small doses of radiation,
- insolation,
- smoking,
- heavy metal salts,
- stress,
- autoimmune diseases (diabetes mellitus, etc.) that cause a specific immune response.
The association of endocrine ophthalmopathy with some antigens of the HLA system was noted: HLA-DR3, HLA-DR4, HLA-B8. Mild forms of endocrine ophthalmopathy are more common among young people, severe forms of the disease are characteristic of the elderly.
Pathogenesis
It is assumed that due to spontaneous mutation, T-lymphocytes begin to interact with the receptors of the membranes of the eye muscle cells and cause specific changes in them. The autoimmune reaction of T-lymphocytes and target cells is accompanied by the release of cytokines (interleukin, tumor necrosis factor, gamma interferon, transforming growth factor b, platelet growth factor, insulin-like growth factor 1), which induce fibroblast proliferation, collagen formation and glycosaminoglycan production. The latter, in turn, contribute to the binding of water, the development of edema and an increase in the volume of retrobulbar fiber. Edema and infiltration of orbital tissues eventually give way to fibrosis, as a result of which exophthalmos becomes irreversible.
Classification
In the development of endocrine ophthalmopathy, there is a phase of inflammatory exudation, a phase of infiltration, which is replaced by a phase of proliferation and fibrosis. Taking into account the severity of ocular symptoms, there are three forms of endocrine ophthalmopathy:
- Thyrotoxic zkzophthalmos. It is characterized by insignificant true or false protrusion of the eyeballs, retraction of the upper eyelid, eyelid lag when lowering the eyes, tremor of closed eyelids, eye gloss, insufficient convergence.
- Edematous exophthalmos. Edematous exophthalmos is spoken of when the eyeballs stand at 25-30 mm, pronounced bilateral edema of the periorbital tissues, diplopia, and severe limited mobility of the eyeballs. Further progression of endocrine ophthalmopathy is accompanied by complete ophthalmoplegia, non-closure of the eye slits, conjunctival chemosis, corneal ulcers, congestion on the fundus, pain in the orbit, venous stasis. In the clinical course of edematous exophthalmos, there are phases of compensation, subcompensation and decompensation.
- Endocrine myopathy. With endocrine myopathy, there is weakness more often of the direct oculomotor muscles, leading to diplopia, the inability to divert the eyes outward and upward, strabismus, deviation of the eyeball downwards. Due to hypertrophy of the oculomotor muscles, their collagen degeneration is progressively increasing.
Symptoms
The early clinical manifestations of endocrine ophthalmopathy include transient sensations of “sand” and pressure in the eyes, lacrimation or dry eyes, photophobia, swelling of the periorbital region. In the future, exophthalmos develops, which initially has an asymmetric or unilateral character.
At the stage of expanded clinical manifestations, these symptoms of endocrine ophthalmopathy become permanent; a noticeable increase in the retention of eyeballs, injection of conjunctiva and sclera, swelling of the eyelids, diplopia, headaches are added to them. The inability to completely close the eyelids leads to the formation of corneal ulcers, the development of conjunctivitis and iridocyclitis. Inflammatory infiltration of the lacrimal gland is aggravated by dry eye syndrome.
Complications
With pronounced exophthalmos, compression of the optic nerve may occur, leading to its subsequent atrophy. Mechanical limitation of the mobility of the eyeballs leads to an increase in intraocular pressure and the development of so-called pseudoglaucoma; in some cases, retinal vein occlusion develops. Involvement of the eye muscles is often accompanied by the development of strabismus.
Diagnostics
The diagnostic algorithm for endocrine ophthalmopathy involves examination of the patient by an endocrinologist and an ophthalmologist with the implementation of a complex of instrumental and laboratory procedures.
1. Endocrinological examination is aimed at clarifying the function of the thyroid gland and includes the study of thyroid hormones (free T4 and T3), antibodies to thyroid tissue (At to thyroglobulin and At to thyroperoxidase), thyroid ultrasound. If thyroid nodules with a diameter of more than 1 cm are detected, a puncture biopsy is indicated.
2. Functional ophthalmological examination in endocrine ophthalmopathy aims to clarify the visual function. The functional block includes:
- visometry
- perimetry
- convergence research
- electrophysiological studies
- biometric studies of the eye (exophthalmometry, measurement of the angle of strabismus) – allow you to determine the height of standing and the degree of deviation of the eyeballs
3. Visualization methods are aimed at morphological assessment of eye structures. Include the following studies:
- examination of the fundus (ophthalmoscopy) is performed to exclude the development of optic neuropathy
- biomicroscopy – to assess the condition of eye structures
- tonometry – performed to detect intraocular hypertension
- Ultrasound, MRI, CT orbits) make it possible to differentiate endocrine ophthalmopathy from tumors of retrobulbar tissue.
4. Immunological examination. In endocrine ophthalmopathy, it is extremely important to examine the patient’s immune system. Changes in cellular and humoral immunity in endocrine ophthalmopathy are characterized by a decrease in the number of CD3+ T-lymphocytes, a change in the ratio of CD3+ and lymphocytes, a decrease in the number of CD8+T-suppressors; an increase in the level of IgG, anti-nuclear antibodies; an increase in the titer of At to TG, TPO, AMAb (ocular muscles), the second colloidal antigen. According to the indications, a biopsy of the affected oculomotor muscles is performed.
Exophthalmos in endocrine ophthalmopathy should be differentiated from pseudoexophthalmos observed with a high degree of myopia, orbital cellulitis (orbital phlegmon), tumors (hemangiomas and sarcomas of the orbit, meningioma, etc.).
Treatment
Pathogenetic therapy
Therapeutic tactics are determined by the stage of endocrine ophthalmopathy, the degree of thyroid dysfunction and the reversibility of pathological changes. All treatment options are aimed at achieving an euthyroid state.
- Immunosuppressive therapy. It includes the appointment of glucocorticoids (prednisolone), which have anti-edematous, anti-inflammatory and immunosuppressive effects. Corticosteroids are used orally and in the form of retrobulbar injections. If there is a threat of vision loss, pulse therapy with methylprednisolone and orbit X-ray therapy are performed. The use of glucocorticoids is contraindicated in gastric or duodenal ulcer, pancreatitis, thrombophlebitis, hypertension, blood clotting disorders, mental and oncological diseases.
- Extracorporeal hemocorrection. Methods that complement immunosuppressive therapy are plasmapheresis, hemosorption, immunosorption, cryoaferesis.
- Correction of the thyroid function. In the presence of thyroid dysfunction, its correction is carried out with thyrostatics (with thyrotoxicosis) or thyroid hormones (with hypothyroidism).
- Surgical tactics. If it is impossible to stabilize the function of the thyroid gland, it may be necessary to perform a thyroidectomy followed by HRT.
Ophthalmological treatment
Symptomatic therapy for endocrine ophthalmopathy is aimed at normalizing metabolic processes in tissues and neuromuscular transmission. For these purposes, injections of actovegin, proserin, instillation of drops, laying ointments and gels, taking vitamins A and E. Among the methods of physiotherapy for endocrine ophthalmopathy, electrophoresis with lidase or aloe is used, magnetic therapy for the orbits.
Possible surgical treatment of endocrine ophthalmopathy includes three types of ophthalmological operations:
- Decompression of the orbit. It is aimed at increasing the volume of the eye socket and is indicated for progressive neuropathy of the optic nerve, pronounced exophthalmos, corneal ulceration, subluxation of the eyeball, etc. situations. Decompression of the orbit (orbitotomy) is achieved by resection of one or more of its walls, removal of retrobulbar fiber.
- Operations on oculomotor muscles. They are indicated with the development of persistent painful diplopia, paralytic strabismus, if it cannot be corrected with prismatic glasses.
- Eyelid surgery. They represent a large group of various plastic and functional interventions, the choice of which is dictated by the developed disorder (retraction, spastic inversion, lagophthalmos, lacrimal gland prolapse, hernia with loss of orbital fiber, etc.).
Forecast
In 1-2% of cases, a particularly severe course of endocrine ophthalmopathy is observed, leading to severe visual complications or residual phenomena. Timely medical intervention makes it possible to achieve induced remission and avoid severe consequences of the disease. The result of therapy in 30% of patients is clinical improvement, in 60% – stabilization of the course of endocrine ophthalmopathy, in 10% – further progression of the disease.
