RU2725861C1 - Method of endocrine ophthalmopathy treatment - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: invention refers to medicine, particularly to endocrinology and ophthalmology. Method comprises administering a medicinal mixture into a lymphatic region of an orbit on the side of the involved eye by performing pterygo-palatine blockades, wherein the medicinal mixture contains: lidocaine 20–40 mg, gemase 3000–5000 units, dexazone 4–8 mg, xefocam – 4.0–8.0 mg, dalargin 1–2 mg. That is followed by 6–8 blockades alternating the right and left eye orbits every second day.EFFECT: method provides higher clinical effectiveness, reduces labor intensity and reduces the risk of collateral complications.1 cl, 2 ex

Description

The invention relates to medicine, in particular to endocrinology and ophthalmology, and can be used to treat endocrine ophthalmopathy.

Endocrine ophthalmopathy (EOP) is an independent, progressive autoimmune disease of the organ of vision associated with autoimmune pathology of the thyroid gland (thyroid gland). In 80% of cases, EOP develops with diffuse toxic goiter (DTZ), in 10% in autoimmune thyroiditis (AIT) in euthyroid / hypothyroid patients, and in 10% against the background of normal levels of thyroid hormones and thyroid stimulating hormone (TSH). The development of EOP is accompanied by pathological changes in the soft tissues of the orbit: retrobulbar fiber (RBC), extraocular muscles (EOM), involvement of the optic nerve (ZN) and the cornea, as well as the adnexa (eyelid, conjunctiva, lacrimal muscle, lacrimal gland) [Clinical recommendations . Endocrine ophthalmopathy in autoimmune thyroid pathology in adults, Ministry of Health of the Russian Federation, 2017]. EOP can occur both before the appearance of functional thyroid disorders (26.3%), and against the background of the manifestation of thyrotoxicosis (18.4%), or during the patient’s stay in euthyroidism after medical correction (Endocrine ophthalmopathy from the perspective of an ophthalmologist and endocrinologist / Brovkin A .F., Pavlova T.L. // Breast Cancer Clinical Ophthalmology, No. 1, 2000).

Treatment of endocrine ophthalmopathy is a serious problem at present. The chronic progressive course of the disease, characterized by resistance to existing methods of treatment, is noteworthy. The latter circumstance is due to the complex pathogenesis of the disease, which according to modern concepts belongs to the category of autoimmune. As a result of exposure to certain clones of T-lymphocytes and antibodies, including autoantibodies, to orbital antigens (immunoglobulins G and M), edema occurs and the volume of extraocular muscles and retrobulbar fatty tissue increases, which is clinically manifested by swelling and hyperemia of the eyelids, conjunctiva, and lacrimal muscle. Increased eye retention from the orbit (exophthalmos) is often accompanied by diplopia, with a possible decrease in visual acuity, the appearance of limited mobility of the eyeballs, impaired venous outflow, which is regarded as the active stage of the disease, which shows an immediate intervention by an ophthalmologist.

For the treatment of endocrine ophthalmopathy, various drug and non-drug methods are used: taking glucocorticoids orally, administering them parenterally and retrobulbarly, as well as taking cytostatics, non-steroidal anti-inflammatory drugs, radiation therapy of the orbit area. The most effective is glucocorticoid and radiation therapy.

However, the listed methods of treatment have numerous contraindications, can cause various side effects and complications. So, the appointment of glucocorticoids in the form of pulsotherapy, which means the intravenous administration of large doses of methylprednisolone in a decreasing manner, up to 6.0-8.0 g / course can lead to impaired liver function, provoke hypertension, gastric ulcer and 12 duodenal ulcer, diabetes mellitus, osteoporosis, urinary tract infections, glaucoma.

Retrobulbar administration of glucocorticoids can also lead to damage to the eyeball itself, fibrous changes in extraocular muscles.

Radiation therapy of the soft tissues of the orbits, in turn, is not without drawbacks due to the limited access of this technique to patients, the risk of cataracts.

A known method of treating endocrine ophthalmopathy, including immunocorrection, while Wobenzym is used as an immunocorrector, 7 tablets 3 times a day for 2 weeks, then 5 tablets 3 times a day for 1 month with the addition of 40 mg intramuscular injection of triamcinolone every other day. Also, against the background of this therapy, installation of drugs is added: 0.1% indocollyr solution 1 drop 3 times a day in combination with Vidisic eye moisturizing gel 1 drop 2 times a day (patent RU 2314101 C1, publ. 10.01.2008)

The disadvantages of this method are the use of a sufficiently large number of tablets (from 21 to 15 tablets per day for a month, or even more), which is often accompanied by skin rashes, dyspepsia.

A known method of treating endocrine ophthalmopathy, including intravenous drip of 25 ml of immunoglobulin diluted in 100 ml of 0.9% sodium chloride solution at a rate of 30-40 drops per minute daily for 5 days. Subsequently, a similar course of treatment is repeated twice with a three-week interval (patent RU 2129849 C1, publ. 05/10/1999).

The disadvantage of this method is the high percentage of allergic reactions to blood products, the limitation of the appointment of this method to patients with concomitant renal, heart failure, diabetes mellitus.

A known method of treating endocrine ophthalmopathy, in which steroid therapy is carried out, and upon its completion, treatment is continued in the form of retrobulbar administration of a 10% sterile solution of placental albumin at a dose of 1.5-3.0 ml 1-2 times a week, the course of treatment is 15-20 injection (Patent RU 2213545 C1, publ. 10.10.2003).

The disadvantage of this method is its invasiveness, since patients are provided with 15-20 retrobulbar injections, which in itself can cause additional trauma to the soft tissues of the orbit, up to retrobulbar hematoma or perforation of the eyeball.

Closest to the claimed method - the prototype, is a method of treating malignant exophthalmos with thyrotoxicosis, which consists in the fact that they inject the injection needle through the conjunctiva, draw it between the conjunctiva and sclera along each of the four rectus muscles of the eye: the upper straight, lower straight, internal direct and external direct, and a suspension of hydrocortisone acetate with lidocaine hydrochloride of 0.3 ml per muscle is introduced into their abdominal region, 1-2 procedures with an interval of 7 days. This method, according to the authors of the invention, causes a long anti-inflammatory, decongestant and sclerosing effect on each muscle (Patent RU 2294745, publ. 01.06.2007).

The disadvantages of this method are the lack of effectiveness, the complexity of the procedure itself, the risk of damage to the outer capsule of the eyeball at the time of injection, when trying to isolate the abdomen of the extraocular muscle, the absence of a direct effect on other soft tissues of the orbit involved in aseptic inflammation and edema (oblique muscles, retrobulbar tissue, lacrimal gland).

The objective of the invention is to reduce the complexity and risk of damage to the eyes and soft tissues of the orbit with local exposure to drugs and the possibility of prescribing treatment of EOP on an outpatient basis, with a more pronounced and lasting effect without sclerotherapy of EOM.

Effect: increasing the efficiency of the method, reducing its complexity and reducing the risk of side complications.

The problem is achieved by the proposed method, which consists in the following.

Patients with an active stage of EOP (edema and hyperemia of the eyelids, conjunctiva and lacrimal muscle with existing exophthalmos) are given lymphotropic therapy by performing pterygopalatine blockade (RBC) with a course of 6-8 procedures, daily, alternating right and left orbits, 3-4 injections each side, using a medicinal mixture containing, in mg: lidocaine - 20-40 mg, hemase 3000-5000 ED, dexazone - 4-8 mg, xefocam - 4-8 mg, dalargin - 1-2 mg.

In this case, as a medicinal mixture, an optimally selected composition is used, including:

dexazone, a glucocorticosteroid class that disrupts the ability of macrophages to phagocytosis and the formation of interleukin-1, helps to stabilize lysosomal membranes, thereby reducing the concentration of proteolytic enzymes in the area of inflammation, inhibits the formation of antibodies, reduces the permeability of capillaries due to the release of histamine, inhibits activity and collagen formation in the soft tissues of the orbit;

synthetic hexapeptide dalargin, inhibiting proteolysis;

lymphostimulator - lidocaine:

a hemase enzyme that prevents the fibrous degeneration of the soft tissues of the orbit;

xefocam, which has a complex mechanism of action, which is based on the suppression of prostaglandin synthesis, inhibition of the activity of cyclooxygenase isoenzymes, inhibition of oxygen free radicals from activated leukocytes. Mannitol, which is part of the xefocam drug, like an osmotic diuretic, causes the movement of excess fluid from the tissues of the eyeball and orbit, which allows to increase the effectiveness of treatment and reduce swelling of the soft tissues of the orbit in patients with EOP due to a wide range of anti-inflammatory, reparative, decongestant and metabolic effects the proposed mixture in comparison with the prototype.

Lymphotropic therapy provides a high regional exposure and concentration of drugs, minimal drug burden on the body, improved microcirculation, lymphatic circulation, lymphatic drainage and venous outflow of the orbit region, preventing possible injury to the eyeball and soft tissues of the orbit at the time of injection.

The drug mixture before use is diluted in 2-5 ml of lidocaine or saline (0.9% NaCl). Pterygopalatine blockade is carried out as follows: under aseptic conditions, directly under the zygomatic arch, in the middle of the distance between the tragus of the ear and the edge of the orbit, a needle is injected. Then, the angle of the needle is changed by 30 degrees, the needle is advanced past the pterygoid processes of the main bone to a depth of 4-4.5 cm, getting into the pterygo-pit, the drug mixture is injected into the lymphatic region of the orbit.

The method is illustrated by the following examples of specific performance.

Example 1

Patient Sh., 31 years old, complained of eyelid edema, conjunctiva, increased eye condition with transient double vision when viewed with two eyes, a feeling of fullness behind the eyeballs.

On examination, hyperemia of the eyelids, with moderate swelling of the eyelids and conjunctiva, lacrimal meat, without the presence of a discharge, is noteworthy. There is a limitation in bringing both eyes.

Discomfort appeared about 6 months ago. A year ago, he was diagnosed with diffuse toxic goiter, thyrotoxicosis and an endocrinologist was prescribed tyrosol treatment. Currently, drug euthyroidism during therapy: tyrosol 10 mg with l-thyroxine 50 mg, according to the "block-replace" scheme.

Functional data before treatment:

Visus OD / OS = 0.95 / 1.0.

IOP OD / OS = 18.0 / 19.0.

Exophthalmometry OD / OS = 21.0 mm / 21.5 mm

Ultrasound examination showed moderate thickening on both sides of the internal and lower extraocular muscles (5.0-5.1 mm, respectively), with fuzzy contours, which also corresponds to the edematous stage of endocrine ophthalmopathy, moderate edema of retrobulbar fiber.

Diagnosed with endocrine ophthalmopathy, edematous form, mixed form, active stage, moderate severity of both eyes.

A course of pterygopalatine blockade was prescribed in turn, 3 CBNs on each side (total number - 6) using a medicinal mixture containing: lidocaine - 20 mg, hemase 3000 IU, dexazone - 4 mg, xefocam - 4 mg, dalargin - 1 mg, 2 ml 0.9% NaCl.

Functional data after treatment:

Visus OD / OS = 1.0 / 1.0.

IOP OD / OS = 17.0 mmHg / 18.0 mmHg

Hertel's Exophthalmometry OD / OS = 19.0 mm / 19.0 mm

At the end of the course of therapy, the patient's condition improved, the feeling of pressure and bursting behind the eyes disappeared, swelling and hyperemia of the conjunctiva, lacrimal meat decreased significantly, visual acuity in the right eye increased, intraocular pressure (IOP) moderately decreased on both sides, and the clarity of extraocular muscles appeared (EOM) on the control ultrasound examination, with a decrease in eye stand with exophthalmometry by 2.0 / 2.5 mm, respectively.

Example 2

Patient K, 44 years old, had endocrine ophthalmopathy in both eyes, an active stage, an edematous form, moderate, amid autoimmune thyroiditis (AIT), and primary hypothyroidism. The diagnosis of AIT was made by an endocrinologist about 10 years ago, 100 mg of eutirox was prescribed, and currently TSH is normal.

Functional data before treatment:

Visus OD / OS = 1.0 / 1.0.

IOP OD / OS = 22.0 / 21.0.

Hertel's Exophthalmometry OD / OS = 22.0 mm / 23.0 mm

Ultrasound examination shows a moderate thickening on both sides of the external, upper, internal and lower extraocular muscles of the right eye (4.8 mm; 4.7 mm; 5.0 mm; 5.2 mm) and the left eye (4.7 mm; 4.5 mm; 4.9 mm; 5.0 mm ) with fuzzy contours, with moderate swelling of retrobulbar fiber, which also corresponds to the edematous stage of endocrine ophthalmopathy, a mixed form.

A course of pterygopalatine blockade was prescribed with a decongestant, lymphostimulating target, 4 CBN on each side (total number - 8), daily, alternating the right and left orbits, using a medicinal mixture containing: lidocaine - 40 mg, hemase 5000 U, dexazone - 8 mg, xefocam - 8 mg, dalargin - 2 mg, 5 ml of 0.9% NaCl.

Functional data after treatment:

Visus OD / OS = 1.0 / 1.0.

IOP O / S = 19.0 mm Hg / 19.0 mm Hg

Gertel's exophthalmometry OD / OS = 19.0 mm / 20.0 mm.

At the end of the course of therapy, the patient's edema of the eyelids decreased, as did the feeling of pressure, bursting behind the eyeballs, intraocular pressure decreased by 3.0 mm Hg / 2.0 mm Hg. The smear of the contour of the EOM on the control ultrasound changed to clear boundaries, with lower numbers of eye stand with exophthalmometry at 3.0 / 3.0 mm, respectively.

Using the proposed method for the treatment of endocrine ophthalmopathy will significantly reduce swelling of the soft tissues of the orbit, with a significant decrease in exophthalmos, confirmed by the data of the control ultrasound examination, with an improvement in venous and lymphatic drainage, and with the prevention of concomitant exophthalmos of the pathology of the optic nerve and cornea.

Claims (2)

1. A method of treating endocrine ophthalmopathy, including the introduction of drugs, characterized in that the introduction of drugs is carried out in the lymphatic region of the orbit on the side of the affected eye by performing pterygopalatine blockade with a course of 6-8 procedures, daily, alternating between the right and left orbits, 3-4 injections on each side, and as medicines use a medicinal mixture containing lidocaine 20-40 mg, haemase 3000-5000 ED, dexazone 4-8 mg, xefocam 4.0-8.0 mg, dalargin 1-2 mg. 2. The method according to p. 1, characterized in that the medicinal mixture before use is diluted in 2-5 ml of saline.