RU2618167C1 - Method for treatment of inflammatory eye diseases associated with autoimmune pathologies - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: patient diagnosed with an inflammatory eye disease receives one drop of "Restasis" preparation in the conjunctival sac daily, 2 times a day, for at least 14 days. Additionally, 3-5 U of "Disport" preparation is administered once, departing 4-6 mm downwards from the lower lacrimal eye point.

EFFECT: method allows to interrupt the cascade of inflammatory changes in the eye and prevent local autoimmune response.

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Description

The invention relates to medicine and can be used in ophthalmology for the treatment of inflammatory eye diseases associated with autoimmune pathologies.

Inflammatory eye diseases associated with autoimmune pathologies include keratitis, keratoconjunctivitis, uveitis, and other diseases. Corneal-conjunctival disorders can adversely affect the normal structure of the corneal epithelium and, moreover, can disrupt the architecture and function of the cornea and corneal stroma intrinsic material. Uveitis is an inflammation of the choroid of the eyeball.

There are various methods of treating inflammatory eye diseases based on the use of antibiotics, mydriatics, corticosteroids and proteolytic enzymes.

There is a method of treating inflammatory eye diseases by local administration to the patient of the drug eprosartan in the form of eye drops or ointments (patent RU 2423127 C2, publ. 10.07.2011). The invention provides the treatment of diseases such as corneal ulcer, keratitis, conjunctivitis, surface spot keratitis, dry keratoconjunctivitis, superior limbic keratoconjunctivitis, or filamentous keratitis.

A known method of treating anterior uveitis by exposure to low-intensity laser IR radiation to the tissues of the damaged eye in a continuous mode, remotely at a distance of 2-3 cm, while the power density is 1-1.5 mW / cm ² , 5-7 minutes for 5-10 days daily (patent RU 2367488 C1, publ. 09/20/2009). The method provides a pronounced anti-inflammatory and vasodilation effect.

A known method of treating anterior uveitis by instilling into the eyes a liquid pharmaceutical composition comprising cyclosporine, an aqueous liquid carrier, a first solubility promoter selected from the group of phospholipids, and a second solubility promoter selected from the group of nonionic surfactants, wherein the phospholipid is is a mixture of natural phospholipids and contains cyclosporine in liposome solubilized form (patent RU 2421209 C1, publ. 06/20/2011).

The disadvantages of this method is the lack of therapeutic activity.

Closest to the claimed method, the prototype, is a method of treating inflammatory eye diseases, more specifically anterior uveitis, including installations in the conjunctival cavity of a solution of a corticosteroid drug and additional oral administration of cyclosporin in a daily dose of 2.0-2.5 mg / kg 2 times a day for 5 days from subsequent administration of cyclosporine in a daily dose of 1.0-1.25 mg / kg 2 times a day for 5 days (patent RU 2307653 C1, publ. 10.10.2007).

The disadvantages of this method is the lack of effectiveness in the late postoperative period, as well as possible side complications associated with the nephrotoxic and hepatotoxic effects of cyclosporine with prolonged systemic use.

The objective of the invention is to increase the efficiency of the method and the elimination of side complications.

Effect: increase the efficiency of the method and the exclusion of side complications.

The technical result is achieved due to the combined treatment, including local injection of the drug "Dysport" and local administration of cyclosporine in an experimentally selected optimal mode.

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

Before treatment and 2 weeks after treatment, an eye disease is diagnosed using a Schirmer test (litmus strips) and a biomicroscopic examination (corneal assessment).

The patient, stepping down 4-6 mm from the lower lacrimal opening of the eye, with an identified inflammatory disease, is injected once with 3-5 units of the Dysport preparation using a 0.3-0.5 ml syringe with a fixed needle with a diameter of 29-30 G Every day, one drop of the Restasis drug is instilled into the conjunctival sac of the patient’s course 2 times a day for at least 14 days.

The complex use of the Dysport and Restasis preparations in experimentally selected optimal regimen and dosages allows one to interrupt the cascade of inflammatory changes in the eye and prevent a local autoimmune response in the inflamed eye.

The Dysport preparation containing botulinum toxin type A causes an irreversible blockade of the transport synaptosomal protein SNAP-25, which is necessary for the release of acetylcholine into the synaptic cleft. The process of introducing the toxin into the presynaptic end and blockade of the presynaptic membrane takes from 1 to 3 days, so the clinical effect does not begin to appear immediately, but a few days after the injection.

The drug "Restasis" contains a 0.05% solution of cyclosporine, which is a cyclic polypeptide isolated from two strains of mold fungi. Cyclosporin has a selective effect on the immune system, without having a general cytotoxic effect. The immunosuppressive effect of cyclosporine is due to inhibition of the synthesis and secretion of interleukin 2 (IL 2), a key immunoregulator of T-lymphocyte activation. By blocking the activation of T-lymphocytes, cyclosporine inhibits the implementation of the immune response in the initial stage, without disturbing hematopoiesis, phagocytosis, chemotaxis and other immune reactions (Dobritsa V.P. et al. Modern immunomodulators for clinical use. A guide for doctors. C-P ., 2001, p. 236-240).

The defining differences of the proposed method from the prototype are:

1. For treatment using the drug "Dysport" containing Botulinum toxin A, in a dose of 3-5 units, while the injection of the drug is carried out once, stepping 4-6 mm from the lower lacrimal opening of the eye, which improves the effectiveness of treatment by creating a reversible denervation and local relaxation of the smooth muscles of the lower lacrimal tubule. The resulting functional denervation (paralysis) of the smooth muscles of the lower lacrimal tubule contributes to the difficulty of the outflow of fat and mucin fractions of the lacrimal fluid, as well as the activation of the synthesis of neurotrophic factors that contribute to the improvement of corneal trophism.

2. For the local anti-inflammatory and immunomodulating effect, the drug Restasis containing cyclosporin is used in the form of drops, which allows selective inhibition of the activation of T-lymphocytes that trigger the immune response, in contrast to the corticosteroid drug, which affects all stages of the immune response and therefore has general cytotoxic effect.

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

Example 1

Patient Ch., 54 years old, was admitted to the Novosibirsk branch of the FSBI MNTK “Eye Microsurgery” with a diagnosis of Marginal keratitis, keratopathy in both eyes. Concomitant diseases: Rheumatoid polyarthritis, the diagnosis is about 20 years. Visual acuity = 1.0 / 0.8n.k.

The patient complained of blurred vision, pain, foreign body sensation, discomfort.

Schirmer test tear production: right eye 4 mm, left 3 mm.

Biomicroscopic examination - inflammation of the cornea, edema, infiltration of cellular elements.

The treatment of the claimed method. Having retreated 4 mm down from the lower lacrimal opening of the right eye, the patient was once administered 3 units of the Dysport preparation using an insulin syringe of 0.3 ml volume with a fixed needle with a diameter of 30G. Additionally, in the conjunctival sac of the right eye, the patient instilled one drop of the Restasis preparation 2 r / d for 14 days.

Similar manipulations were carried out on the left eye.

Inspection after 2 weeks - there was a positive dynamics in the state of the cornea. The patient subjectively noted improvement, increased visual acuity.

Visual acuity = 1.0 / 1.0.

Schirmer test tear production: right eye 8 mm, left 7 mm.

Example 2

Patient F., 61 years old, was admitted to the Novosibirsk branch of the FSBI MNTK “Eye Microsurgery” with a diagnosis of Marginal keratitis, chronic keratoconjunctivitis in both eyes. Concomitant diseases: Rheumatoid arthritis, the diagnosis is about 8 years. Visual acuity = 0.5 / 0.6 n.k. For the underlying disease receives the drug "Metatrexate".

The patient complained of redness, photophobia, discomfort, veil before her eyes for 2 weeks.

Schirmer test tear production: right eye 3 mm, left 3 mm.

Biomicroscopic examination - inflammation of the cornea, edema, infiltration by cellular elements, redness of the conjunctiva of both eyes.

The treatment of the claimed method. Having retreated 6 mm down from the lower lacrimal opening of the right eye, the patient was once administered 5 units of the Dysport preparation using a 0.5 ml insulin syringe with a fixed needle with a diameter of 29 G. In addition, the patient instilled one drop of Restasis in the conjunctival sac of the right eye. 2 r / d for 14 days.

Similar manipulations were carried out on the left eye.

Inspection after 2 weeks - there was a positive dynamics in the state of the cornea, conjunctiva. The patient subjectively noted improvement, increased visual acuity.

Visual acuity = 0.7 / 0.8.

Schirmer test tear production: right eye 6 mm, left eye 7 mm.

Example 3

Patient K., 24 years old, was admitted to the Novosibirsk branch of the FSBI MNTK “Eye Microsurgery” with a diagnosis of Recurrent uveitis, left eye keratopathy. Concomitant diseases: Ankylosing spondylitis (ankylosing spondylitis), diagnosed in 2007. For the underlying disease receives drugs "Sulfasalazine", "Cerebrex", "Metatrexate".

Visual acuity = 1.0 / 0.005n.k.

The patient complained of decreased vision of the left eye, pain, sensation of a foreign body.

Biomicroscopic examination - the cornea is swollen, redness of the conjunctiva of the eyeball, inflammatory effusion in the pupil zone.

Schirmer test tear production: right eye 3 mm, left 1 mm.

The patient was treated with the claimed method.

Retreating 5 mm down from the lower lacrimal opening of the left eye, the patient was injected once with 5 units of the Dysport preparation using a 0.3 ml insulin syringe with a fixed needle with a diameter of 30 G. In addition, the patient instilled one drop of Restasis in the conjunctival sac of the left eye. »2 r / d for 14 days.

Inspection after 2 weeks - there was a positive dynamics in the state of the cornea, the course of the inflammatory process. The patient subjectively noted improvement, increased visual acuity.

Visual acuity = 1.0 / 0.02 n.k.

Schirmer test tear production: right eye 6 mm, left eye 4 mm.

The method allows to increase the effectiveness of treatment, to eliminate excessive systemic effects on the patient's body of an immunosuppressive drug.

Claims (2)

1. A method of treating inflammatory eye diseases associated with autoimmune pathologies, comprising administering a cyclosporin-containing preparation, characterized in that one drop of Restasis containing cyclosporin is instilled into the patient’s conjunctival sac daily with a dose of 2 times daily. per day for at least 14 days and an additional single dose of 3-5 units of the Dysport preparation containing botulinum toxin A is administered, stepping down 4-6 mm from the lower lacrimal opening of the eye. 2. The method according to p. 1, characterized in that for injection using a syringe with a volume of 0.3-0.5 ml with a fixed needle with a diameter of 29-30 G.