Practical dry goods: Diagnosis and treatment of "thyroid related ophthalmopathy", all in one article

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Introduction: Diagnosis and treatment of thyroid-related ophthalmopathy, all in one article
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 Thyroid-associated ophthalmopathy (TAO) is an organ-specific autoimmune disease characterized by infiltrating lesions in the posterior and periorbital ocular tissues.
It is one of the most common extrathyroid manifestations of thyroid diseases
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TAO is more common in patients with Graves disease (GD), also known as Graves ophthalmopathy (GO), and can also be seen in a small number of patients with Hashimoto's thyroiditis and normal thyroid function
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The content of this article is selected from the medical book "Systemic Endocrinology" (China Science and Technology Press), edited by Academician Ning Guang, and edited by Professor Zhao Jiajun and Professor Peng Yongde.
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Incidence and clinical manifestations of TAO 1.
Epidemiological investigation TAO is the adult orbital disease with the highest incidence
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The incidence in the population is about 42/100 million, and the incidence in GD patients is about 25%.
It can occur at any age, especially in women aged 40-60
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TAO lesions mainly involve orbital fat and extraocular muscles, which can lead to a series of clinical manifestations such as exophthalmos, eye-face recession, eyelid edema, delayed upper eyelid, restricted eye movement, exposure keratitis, and oppressive optic neuropathy.
It affects the facial appearance of patients, and about 5% of patients have visual impairment.
Therefore, the treatment of TAO needs to take into account both mental health and physical health
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 2.
Clinical manifestations of TAO patients TAO can be divided into simple (non-invasive) exophthalmos and invasive exophthalmos based on ocular manifestations
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Simple exophthalmos are mainly manifested as mild eyeball protrusion, widening of eye clefts, and decreased blinking
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Infiltrating exophthalmos is manifested as prominent eyeballs.
Patients often have eyeball pain, foreign body sensation, photophobia, tearing, diplopia, strabismus, and decreased visual acuity.
On physical examination, eyelid swelling, conjunctival congestion and edema, and restricted eye movement are often seen.
And stare
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In severe cases, incomplete closure of the eyelids and corneal exposure can cause corneal ulcers and even blindness
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 The presence or absence of optic neuropathy in TAO patients has nothing to do with exophthalmos.
The involvement of the optic nerve can be manifested as decreased vision, color vision disorders, and visual field defects.
Fundus examination shows optic disc edema, optic disc pallor, and choroidal folds
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TAO can present a single eye disease, both eyes can be onset one after another, or both eyes can be affected at the same time
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 The diagnosis and severity of TAO 1.
Bartley diagnostic criteria The Bartley diagnostic criteria are the most commonly used in the diagnosis of TAO
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If the patient has eyelid retraction, the diagnosis of TAO can be made as long as one of the following signs or examination evidence is combined: ➤ Thyroid function is abnormal, the patient's serum TT3, TT4, FT3, and FT levels increase, and the TSH level decreases; ➤Protrusion of the eyeballs, eyeball protrusion ≥20mm, and the difference between the convexity of the eyes ＞2mm; ➤Extraocular muscles are affected, eyeball movement is restricted, and CT shows that the extraocular muscles are enlarged; ➤Optical nerve dysfunction, including visual acuity, pupil reflex, color vision , The visual field is abnormal, which cannot be explained by other lesions
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 Patients without eyelid retraction If there is no eyelid retraction, in addition to abnormal thyroid function, the patient should also have one of the following signs to make the diagnosis of TAO, such as exophthalmos, involvement of extraocular muscles or optic nerve dysfunction, and exclude other eye diseases.
Of similar signs
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At the same time, laboratory and imaging auxiliary examinations are of great value to the diagnosis of TAO
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  2.
Judgment of severity and type There are currently two methods for judging the severity of TAO, one is the NOSPECS classification, and the other is the EUGOGO evaluation standard.
The evaluation of severity is of great significance to the treatment and emergency referral of TAO
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➤NOSPECS classification: see Table 8-4
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➤EUGOGO evaluation criteria: see Table 8-5
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➤CAS score: CAS score (Clinical ActivityScore) can judge the activity of TAO, and has an important guiding role in the clinical diagnosis and treatment of TAO (Table 8-6)
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CAS score greater than 3 is divided into TAO activities, the more points, the higher the activity
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 Table 8-4 NOSPECS classification table 8-5 EUGOGO evaluation criteria Table 8-6 CAS score TAO treatment of "mild TAO" treatment Most of the mild or inactive TAO does not require treatment, as the thyroid function stabilizes, TAO Can get better on its own
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According to the severity, TAO treatment methods can be divided into general measures, drug treatment, retrobulbar irradiation and surgical treatment
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 General measures are often used in the treatment of mild TAO and regular follow-ups, including: quit smoking; maintain normal thyroid function; other measures, including artificial tears, wearing sunglasses, and lying on the pillow; some mild TAO patients can be supplemented Selenium improves symptoms
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 If the quality of life of patients with mild TAO is significantly affected, they should be treated as moderate-to-severe TAO.
If they are in an inactive period, they can be treated with surgery
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 The use of selenium: Patients with mild TAO can achieve good therapeutic effects by controlling risk factors, maintaining normal thyroid function, local treatment and the use of selenium
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A large, multicenter, randomized, double-blind, placebo-controlled study evaluated the effect of supplementation of selenium on patients with mild TAO
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The patients were randomly assigned to receive sodium selenite (2 times a day, 100 ug each time, equivalent to 93.
6 ug elemental selenium per day) or placebo for 6 months
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The main outcome was the change in quality of life (QoL) and overall eye involvement at 6 months of treatment
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Compared with the placebo group, the selenium preparation group can significantly improve the quality of life (P <0.
001), reduce eye involvement (P=0.
01), and maintain improvement within 12 months after stopping the selenium preparation
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In addition, the incidence of TAO deterioration in the selenium preparation group was lower (P<0.
001).
The above results suggest that patients with mild TAO receiving selenium treatment can significantly improve the quality of life, reduce eye involvement, and slow the progression of the disease
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 Treatment of "moderate and severe TAO" in TAO treatment 1.
Glucocorticoid therapy Glucocorticoid is the first choice for the treatment of moderate to severe active TAO.
It has anti-inflammatory and immunomodulatory effects.
It is fast and effective in the treatment of TAO, with a curative effect of 63.
%～77%, it can also prevent TAO induced by radioactive iodine treatment of GD
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The routes of administration of glucocorticoids include oral, intravenous, retrobulbar and subconjunctival administration, but the adverse reactions and poor efficacy of retrobulbar and subconjunctival administration are relatively rare
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The glucocorticoid treatment program recommended by the EUGOGO guidelines in 2016 can be used by most patients: ➤Methylprednisolone 0.
5g, once a week × 6 weeks + 0.
25g, once a week × 6 weeks (cumulative dose 4.
5g), condition In severe cases, the dose can be increased appropriately: Methylprednisolone 0.
75g, once a week × 6 weeks + 0.
5g, once a week × 6 weeks (cumulative dose 7.
5g), the cumulative dose of intravenous corticosteroid therapy should not exceed 8.
0 g
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➤During the treatment period, the patient's liver enzymes, blood sugar and blood pressure levels will be tested to prevent adverse effects of hormone use, such as peptic ulcers and osteoporosis
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➤Glucocorticoid therapy is prohibited for TAO patients with viral hepatitis, severe liver dysfunction, severe cardiovascular disease or mental illness
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 2.
Post-bulb irradiation therapy For TAO patients who are ineffective in hormone therapy and have progressive exophthalmos, eye movement disorders and early signs of optic nerve compression, post-bulb irradiation may be considered
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Post-bulb irradiation has a non-specific anti-inflammatory effect, which can reduce GAG ​​production and lymphocyte infiltration, and improve eye movement
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The 2016 EUGOGO guidelines recommend 10 radiotherapy for one eye, 2 Gy each time, for 2 consecutive weeks, or 1 radiotherapy once a week for 20 consecutive weeks, 1 Gy each time
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The adverse reactions of retrobulbar irradiation mainly include early-onset cataracts, radiation retinopathy and radiation optic neuropathy, and diabetic retinopathy and patients with potential disease risk do not consider the treatment of retrobulbar radiation
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 3.
Immunotherapy drugs For more severe TAO patients, conventional therapy cannot reverse the occurrence and development of the disease.
In addition to glucocorticoids, immunotherapy is a better choice
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Sometimes immunotherapy drugs are effective when used alone, and sometimes immunotherapy drugs need to be combined with orbital radiation or thyroidectomy to achieve better results.
Here are several relatively mature immunotherapy drugs
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 ➤Cyclosporine: It is a commonly used immunosuppressive drug that can improve TAO eye discomfort and congestion.
It can be combined with hormone drugs and reduce the dosage of hormones, but it has the effect of restoring extraocular muscle function and improving exophthalmos Not obvious
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➤Rituximab (rituximab): is a humanized chimeric monoclonal antibody that specifically binds to CD20 on the membrane of B lymphocytes and inhibits the function of B lymphocytes
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CD20 induces the transition from B lymphocyte precursors to mature B lymphocytes, which is an essential membrane protein in the maturation process of B cells
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Rituximab can inhibit the antibody production of B cells and reduce the antigen presentation and secretion of pro-inflammatory factors of B cells
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Rituximab has been clinically used in the treatment of non-Hodgkin's B-cell lymphoma, rheumatoid arthritis and vasculitis, and has an active anti-inflammatory effect
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Although rituximab can effectively inhibit inflammatory diseases, its use in the treatment of TAO is still controversial, and its adverse reactions and adverse reactions cannot be ignored
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Therefore, more studies are still needed to confirm the effect of rituximab on TAO to determine its status in TAO treatment
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➤Tocilizumab: It is a recombinant humanized monoclonal antibody against IL-6 receptor, which is used to treat rheumatoid arthritis
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Active TAO has Th1 cell infiltration and increased IL-6 expression, leading to the production of GAG and the increase of adipose tissue
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Studies have found that tocilizumab can relieve the CAS score of TAO and reduce the severity of TAO
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➤Adalimumab: It is a recombinant humanized monoclonal antibody of TNFα, which can significantly reduce the production of IL-6 and TNFα, and inhibit the stimulating effect of these inflammatory factors on fibroblasts
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➤Teprotumumab: It is an IGF-1R monoclonal antibody that can be used for TAO treatment, and it can inhibit the interaction with TSHR signal by blocking the activation of IGF-1R
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In the field of TAO treatment, it has been found that teprozumab can reduce the patient's CAS score, and the adverse reactions and adverse reactions are less than rituximab
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4.
Surgical treatment should be performed immediately for patients whose general measures and medications are not effective or whose visual function deteriorates rapidly
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Surgical methods include orbital decompression surgery, strabismus correction surgery and eyelid surgery
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➤The main purpose of orbital decompression surgery is to enlarge the bony orbit and remove fat to reduce eyeball protrusion, intraorbital pressure, and improve periorbital edema and eyelid contracture
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Common complications of orbital decompression surgery are diplopia and ocular deviation
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➤Strabismus correction surgery can restore the fusion of the first eye position and avoid diplopia when looking down.
At the same time, conjunctival retraction surgery can maintain the muscle contact arc and avoid weakening the effect of muscle retraction surgery
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➤Eyelid surgery includes upper eyelid surgery and lower eyelid surgery.
Upper eyelid surgery corrects ptosis by injection of botulinum toxin or upper eyelid lengthening.
Lower eyelid surgery usually requires suitable gaskets and materials are difficult to obtain
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The surgical treatment of TAO can not only relieve symptoms, but also have a positive impact on the patient's appearance and mental health
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