RU2219943C1 - Method for treatment of diabetic retinopathy - Google Patents

Abstract

FIELD: medicine, ophthalmology, endocrinology. SUBSTANCE: catheter is fitted into orbit cavity and medicinal agents are administrated through this catheter into lymphatic region of orbit. Firstly, lymphostimulating agents are administrated, mainly lidocaine and lydazum. Then curative mixture containing 10-30 mg of glutoxim, 30 000-90 000 cells/ml of autolymphocytes in 6-8 ml of physiological solution is administrated. Administration of mixture is carried out 2-3 times with interval for 48-72 h. Prepared autolymphocytes can be activated by incubation of cells with 10-20 mg of glutoxim for 40-60 min at temperature 24-26 C. Method provides the enhancement of visual functions due to acceleration of reparative and metabolic processes and enhancement of immunologic reactivity of body. Invention can be used for treatment of patients with diabetic retinopathy. EFFECT: enhanced effectiveness of treatment. 4 cl, 2 ex

Description

 The invention relates to medicine, namely to ophthalmology and efferent therapy, and is intended for the treatment of patients suffering from diabetic retinopathy before ophthalmic surgery (refractive, keratoplasty, antiglaucomatous, cataract extraction operations).

 Diabetic retinopathy (hereinafter referred to as DR) is one of the earliest and most frequent complications of diabetes. DR is based on microangiopathy, which is one of the characteristic manifestations of DR and is of a generalized nature. Among the various causes of the development of DR, there are immunological, metabolic, hormonal, hypotoxic, genetic and other factors that lead to damage to the walls of the capillary walls of the retina and impaired vascular permeability.

 After conducting ophthalmic surgeries, such patients often develop complications, and therefore the development of new methods of treatment for this group of patients remains relevant.

 There is a method of treating diabetic retinopathy by parabulbar and parenteral administration of autoplasma supernatant, with the simultaneous administration of ATP in an amount of 0.3-0.4 mg / ml and thrombin in an amount of 0.1-0.3 U / ml (RF Patent 2161020, cl. A 61 F 9/00, publ. 12/27/2000).

 The method allows you to effectively treat hemorrhages in the internal environment and the shell of the eye, but does not affect the pathogenetic mechanisms of DR.

 A known method of surgical treatment of patients with retinal detachment in the macular region (by vitrectomy through the flat part of the ciliary body) with the simultaneous introduction of autothrombocytes into the fossa of the optic disc, which allows to obtain good anatomical and functional results by enhancing the regeneration of this region (Clin. Exp. Ophthalmol ., 1998, v. 236, p. 151-153).

 However, this method is not effective for the treatment and prevention of postoperative complications in diabetic retinopathy.

 The closest to the claimed method - the prototype - is a method of pre- and postoperative treatment of patients with cataracts, including the introduction of stimulated blood autolymphocytes to the patient in the form of instillations before and after surgery for 7 days, 1 ml daily (RF Patent 2085158, class A 61 F 9/00, published July 27, 1997).

 The method allows to improve visual functions and accelerate reparative processes in the tissues of the eye after surgery, however, it is not effective enough for patients with diabetic retinopathy.

 An object of the invention is to increase the effectiveness of treatment and reduce the frequency of postoperative complications in patients with diabetic retinopathy.

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

Under aseptic conditions, after local infiltration anesthesia is performed, a puncture is performed through the pterygopalatine fossa and the lower orbital fissure of the orbit cavity with a 1 mm diameter and 80 mm long needle. After puncture, through a needle, a catheter is inserted into the cavity of the orbit, which is fixed to the skin with an adhesive plaster. Then, a therapeutic mixture containing 10-30 mg of glutoxim, 30-90 thousand cells / ml of autolymphocytes and 6-8 ml of saline solution is introduced into the lymphatic region of the orbit through a fixed catheter. The introduction of the drug mixture is carried out two to three times with an interval of 48-72 hours. In order to improve lymphocycle circulation, 1 ml of 2% lidocaine and 32 units are introduced through the catheter before the drug mixture is administered. Act. lidases. Autolymphocytes are obtained by lymphocytopheresis on a blood cell separator AS-TEC 204 from Fresenius. The resulting autolymphocytes at a concentration of 30-90 thousand cells / ml are incubated for 40-60 minutes with 10-30 mg of glutoxim at a temperature of 24-26 ^o C. The treatment is mainly carried out before the upcoming operation.

 The method allows to increase the effectiveness of treatment, to avoid postoperative complications, to achieve a significant improvement in visual functions: visual acuity, total fields of view, electrophysiology data.

 The drug glutoxim is a representative of a new class of drugs - thiopoietins, which have a modulating effect on intracellular processes of thiol metabolism, which plays an important role in the regulation of genetic and metabolic processes in cells and tissues.

 Autolymphocytes contain immunopeptides that provide mediator interactions in the immune system. They, in particular, regulate the production of proteins in the acute phase of inflammation, are responsible for the activation of T cells, stimulate proliferation and accelerate the healing processes in injured tissues.

 The technical result is achieved through targeted delivery to the lymphatic region of the posterior pole of the eye of the immunomodulator glutoxim using activated autolymphocytes as vectors in experimentally selected, optimal concentration, administration modes and topography of administration. The activation of lymphocytes is carried out by cytapheresis followed by incubation with glutoxim, which leads to saturation of the autolymphocytes with the drug due to the formation of pores in the cell membranes and sorption of the transported drug on them. When glutoxim with autolymphocytes is introduced into the lymphatic region, its pharmacokinetics changes significantly, which is expressed in the selective accumulation of glutoxim in the focus of inflammation and long-term maintenance of a high therapeutic concentration of the latter.

The defining differences of the proposed method from the prototype are:
- carry out directed transport of the drug mixture to the lymphatic region of the orbit, to the pterygopalatine fossa through a fixed catheter, which allows you to create a depot of the drug mixture, which helps to activate immunological, metabolic and reparative processes in the posterior pole of the eye;
- before the introduction of the drug mixture, the introduction through the catheter of lymphostimulants, mainly lidocaine and the enzyme lidase, which improves lymphocyte circulation in the orbit region;
- as a medicinal mixture use a mixture containing: glutoxim - 10-30 mg, autolymphocytes - 30-90 thousand cells / ml, saline solution - 6-8 ml, which allows to increase the effectiveness of treatment and reduce postoperative complications in patients with diabetic retinopathy due to the wider spectrum of anti-inflammatory, reparative and metabolic effects of the proposed mixture in comparison with the prototype;
- before administration, autolymphocytes are activated by incubation with glutoxim for 40-60 minutes at a temperature of 24-26 ^o C, which allows to stimulate the functional activity of immunocompetent cells and enhance the development of the immune response.

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

 Example 1

 Patient S., 78 years old, was admitted to the NF GU MNTK "MG" with a diagnosis of mature cataract of the right eye, left eye artifact. Diabetic non-proliferative left eye retinopathy. VIS od = proectio lutic certa (pr.lut.cer). Concomitant diagnosis: type II diabetes mellitus, moderate, compensated, coronary heart disease, CH2, FC1. Hypertension of 2-3 severity. Ophthalmoscopy of the left eye: multiple retinal hemorrhages, mild exudates. The preoperative treatment of the patient by the proposed method.

 Under aseptic conditions, after local infiltration anesthesia was performed, a puncture was performed through the pterygopalatine fossa and lower orbital fissure of the orbit cavity with a 1 mm diameter and 80 mm long needle, after puncture, a catheter was inserted through the needle into the orbit cavity, which was fixed to the skin with adhesive tape. Then, 1 ml of 2% lidocaine and 32 units were introduced into the lymphatic region of the orbit through a fixed catheter. Act. lidases. Then, a treatment mixture was introduced containing 10 mg of glutoxim, 30 thousand cells / ml of autolymphocytes and 6 ml of saline. The introduction of the drug mixture was carried out three times with an interval of 48 hours

 Operation - extracapsular extraction of cataract of the right eye with simultaneous implantation of an intraocular lens without features. The postoperative period was uneventful, the patient was discharged on the seventh day for outpatient aftercare. VIS od = 0.2, with ophthalmoscopy, resorption of multiple retinal hemorrhages was observed. At follow-up 6 months after surgery, VIS od = 0.65, at the same time, an expansion of the visual fields was observed, with both eyes: od by 57%, a os by 17%. According to the EFI, an improvement in the function of the optic nerve (papillomacular bundle) was noted due to an increase in the CSFM.

 Example 2

 Patient R-va, born in 1936. Diagnosis at admission: immature age-related cataract od, initial cataract os. VIS od = 0.05, VIS os = 0.5. Concomitant diagnosis: type II diabetes mellitus, moderate severity, subcompensation, angiopathy, coronary heart disease, CH2, FC2, hypertension of 2 severity.

 Under aseptic conditions, after local infiltration anesthesia was performed, a puncture was performed through the pterygopalatine fossa and lower orbital fissure of the orbit cavity with a 1 mm diameter and 80 mm long needle, after puncture, a catheter was inserted through the needle into the orbit cavity, which was fixed to the skin with adhesive tape. Then, 1 ml of 2% lidocaine and 32 units were introduced into the lymphatic region of the orbit through a fixed catheter. Act. lidases. Then, a treatment mixture was introduced containing 30 mg of glutoxim, 90 thousand cells / ml of autolymphocytes and 8 ml of saline. The introduction of the drug mixture was carried out twice with an interval of 72 hours

 Operation - extracapsular extraction of cataract of the right eye with simultaneous implantation of an intraocular lens without features. The postoperative period was uneventful, the patient was discharged on the sixth day for outpatient aftercare. VIS od = 0.6. At follow-up 6 months after surgery, VIS od = l, 0, with an improvement in the paired, non-operated eye, VIS os = 0.65 (15% improvement). The total expansion of the visual fields, with both eyes: od by 38%, a os by 18%. According to EFI, there was an improvement in the function of the optic nerve (axial bundles due to an increase in lability), as well as an improvement in the papillomacular bundle due to an increase in CSFM.

The advantages of the proposed technical solution, compared with the prototype, are to increase the effectiveness of treatment and reduce the frequency of postoperative complications due to:
- allocation of the exact number of autolymphocytes - cells that occupy one of the central places in the body's immune system, performing a protective, immunoregulatory and trophic function;
- targeted exposure by an immunomodulator to autolymphocytes in extracorporeal conditions;
- summing up autolymphocytes treated with an immunomodulator through a catheter directly into the lymphatic region of the eye;
- experimentally established optimal dosage regimen.

Claims (4)

1. A method of treating diabetic retinopathy, comprising administering a drug mixture containing autolymphocytes, characterized in that the introduction is carried out in the lymphatic region of the orbit of the affected eye into the pterygopalatine fossa via a fixed catheter, and as a drug mixture using a mixture containing 10-30 mg of glutoxim, 30-90 thousand cells / ml of autolymphocytes and 6-8 ml of saline; the introduction of the drug mixture is carried out two to three times with an interval of 48-72 hours, and before the introduction of the treatment mixture into the same area, lymphostimulants are introduced through the catheter. 2. The method according to claim 1, characterized in that prior to administration, autolymphocytes are incubated for 40-60 minutes with 10-20 mg of glutoxim at 24-26 ° C. 3. The method according to claim 1, characterized in that lidocaine and the lidase enzyme are used as lymphostimulants. 4. The method according to claim 3, characterized in that 1 ml of 2% lidocaine and 32 units are administered. lidase activity.