RU2472475C2 - Method of combined treatment of glaucomatous optic neuropathy - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to ophthalmology, and can be used for treatment of glaucomatous optic neuropathy. Method includes carrying out sinus trabeculectomy and introduction of medication citicoline (ceraxon). Citicoline is introduced in dependence on structural and functional eye disorders after sinus trabeculectomy in differentiated manner, combining intravenous introduction of citicoline with its intake. To patients with I-II stage of glaucoma citiciline is introduced intravenously fy drop infusion in dose 500 mg daily during 5 days with further transition to intake in dose 200 mg 3 times per day during 10 days. Patients with III stage of glaucoma citicoline is introduced intravenously by drop infusion in dose 1000 mg daily during 5 days with further transition to intake in dose 200 mg 3 times per day during 15 days.

EFFECT: method ensures efficient treatment of disease, making it possible to avoid "excessive" drug load and reduce probability of development of side effects, especially in elderly patients.

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Description

The invention relates to medicine, namely to ophthalmology and is intended for the treatment of uncompensated unstabilized primary open-angle glaucoma.

Combined therapy for glaucoma optic neuropathy (GON) includes surgical treatment (sinusotrabeculectomy (STE)) and neuroprotective therapy (intravenous injection of citicoline solution (Ceraxon), followed by oral administration). Differentiated treatment consists in the use of different doses and the duration of the drug, depending on the structural and functional disorders of the eye with glaucoma. The method provides compensation for intraocular pressure, preservation and improvement of visual functions and stabilization of the glaucomatous process.

The direct cause of blindness in glaucoma is glaucoma optic neuropathy with apoptosis of retinal ganglion cells. The main pathogenic factors in glaucoma include intraocular pressure that exceeds individual tolerant, ischemia and hypoxia of the optic head [1]. Secondary pathogenic factors include impaired transport of cerebral trophic factors to the ganglion cells of the retina and their death by apoptosis. In conditions of chronic hypoxia, lipid peroxidation products and excitatory amino acids (glutamate and aspartate) accumulate, a glutamate-calcium cascade of reactions occurs, leading to the formation of dangerous neurotoxins and death of nerve cells. Cerebral changes (age-related decrease in brain mass and the number of neurons) lead to a decrease in the production of cerebral trophic factors and their entry into the ganglion cells of the retina, as well as in the subcortical visual centers and in the neurons of the visual cortex. This induces the death of neurons of the visual analyzer not only in the retina, but also in other cerebral structures [2, 3].

A known method for the surgical treatment of glaucoma is sinusotrabeculectomy, proposed by Cairns J. in 1968 [4]. The operation is performed as follows: conjunctiva 6 mm long is separated in the upper quadrant 8 mm from the limb. A square flap of sclera with sides of 5 mm, in 2/3 of its thickness, is outlined, separated anteriorly to the limbus. At the base, a sclera with trabecular tissue and a sinus of 4 × 1 mm is cut and excised. The fibrous membrane is fixed with 2-4 seams in place. Suture the conjunctiva. This method allows you to create an outflow of intraocular fluid from the anterior chamber into the area between the stratified sclera, which leads to compensation of intraocular pressure (IOP).

The disadvantage of this method is that not in all cases the normalization of intraocular pressure (IOP) leads to stabilization of visual functions in patients with glaucoma, progression (GON) is noted with pseudo-normal pressure [5]. Primary glaucoma has a complex pathogenesis, chronic hypoxia in glaucoma leads to the death of neurons in the retina and other cerebral structures of the visual analyzer. In this regard, the surgical method of treatment does not completely solve the problem of the treatment of glaucoma optical neuropathy.

A known method of improving the visual functions of the eye by retrobulbar exposure to the neuroreceptor apparatus of the retina with the drug retilin [6].

The disadvantage of this method is its local effect on the metabolism of the retina, which limits the effectiveness of the treatment of glaucoma optical neuropathy.

There is a method of treating glaucoma optical neuropathy, including the introduction of complexes of peptide drugs, first patients receive dibicor, which normalizes intracellular metabolism, then cortexin and retinalamine are administered according to the proposed scheme [7]. Multicomponent peptide preparations are used to increase visual functions in the pathology of a visual analyzer of various origins.

The disadvantage of this method is its low efficiency in the treatment of patients with increased ophthalmotonus, the method does not eliminate the primary damage of axons as a result of direct compression in the microtubules of the ethmoid plate with the subsequent development of descending and ascending atrophy.

The closest in technical essence and the achieved result is a method of treating glaucomatous neuropathy [8]. The essence of the method consists in a complex solution, in which a sinusotrabeculectomy is performed, a trepanation hole in the sclera is cut out in the lower external quadrant of the eyeball in the region of the flat part of the ciliary body, a hemostatic sponge is placed on the area of the trepanation hole, in the postoperative period, the subconjunctival opening of the trepanation hole is performed for 10 days drug Cortexin and percutaneous magnetolaserostimulation in the temporal region of the orbit.

The disadvantage of this method is the low efficiency as a result of the local effect of the drug on retinal metabolism, which limits its use in the treatment of glaucoma optical neuropathy, and the trauma due to additional surgery in the lower outer quadrant of the eyeball.

The objective of the invention is to increase the effectiveness of the treatment of glaucoma optical neuropathy, which consists in maintaining and improving visual functions, stabilizing structural parameters in patients with glaucoma and reducing trauma.

The problem is achieved due to the fact that in the method of combined treatment of glaucoma optical neuropathy, including sinusotrabeculectomy and administration of the drug citicoline (ceraxon), which is administered to patients depending on structural and functional disorders of the eye after sinusotrabeclectomy differentially, combining intravenous administration of citicoline with administration at the same time, patients with stage I-II glaucoma are prescribed citicoline intravenously in a dose of 500 mg daily for 5 days, followed by a transition 200 mg oral home 3 times a day for 10 days, patients of III tbsp. glaucoma is prescribed citicoline intravenously in a dose of 1000 mg daily for 5 days, followed by switching to oral administration of 200 mg 3 times a day for 15 days.

The essence of the proposed solution is a comprehensive neuroprotection - performing sinusotrabeculectomy and conducting a differentiated course of treatment with citicoline, depending on the structural and functional disorders of the eye with glaucoma.

The method is as follows.

Under local anesthesia, a conjunctiva and tenon capsule incision is performed in the meridian for 11 hours at an angle of 110 ° towards the cornea and further along the limbus from 11 to 13 hours. A square surface scleral flap with a base of 5 × 5 mm is cut out on 1 / 3-1 / 2 of its thickness. Under it, a deep scleral flap is outlined and removed with the base to the limbus. In the distal section, the deep layers of the fibrous membrane are excised with the formation of a sclerectomy hole 1 × 1 mm in size. At the base of the flap, a strip of sclera with trabecular tissue and a schlemm canal 4 × 1 mm in size is excised. Perform basal iridectomy. The surface sclera flap is fixed with 4 sutures in place. A continuous suture is applied to the conjunctiva and tenon shell. The operation is completed by the administration of a dexazone solution and an antibiotic under the conjunctiva.

In the postoperative period, intravenous drip infusions of citicoline are prescribed with a subsequent transition to taking the drug inside. A differentiated approach consists in the use of various doses and duration of administration; in the postoperative period, intravenous drip infusions of citicoline are prescribed depending on the stage of the disease.

Patients I-II Art. glaucoma (a moderate decrease in visual function and a decrease in the thickness of the layer of nerve fibers in the peripapillary region of the retina) in the postoperative period, intravenous drip infusions of citicoline are administered intravenously in a dose of 500 mg (4 ml) daily for 5 days, followed by 200 mg 3 times per day. per day for 10 days.

Patients III Art. glaucoma (a significant loss of visual function, pronounced changes in the parameters of the optic disc and the peripapillary retina) in the postoperative period, intravenous drip infusions of citicoline are administered intravenously in drops of 1000 mg (4 ml) daily for 5 days, followed by 200 mg 3 times per day for 15 days. Re-examination of patients is carried out after the end of the drug, 1 and 6 months after treatment.

Citicoline (cytidine 5'-diphoffocholine, citicoline or CDP-choline), being the precursor of key ultrastructural components of the cell membrane (mainly phospholipids), has a wide spectrum of action - it helps restore damaged cell membranes, inhibits the action of phospholipases, preventing the excessive formation of free radicals, as well as prevents cell death by acting on the mechanisms of apoptosis [9]. Citicoline is a new generation neuroprotective agent, the effectiveness and safety of which has been proven in various diseases, has a variety of effects, including neurotransmitter and neurometabolic [10, 11]. Citicoline is involved in the biosynthesis of membrane phospholipids of neurons, primarily phosphatidylcholine, as well as the neurotransmitter acetylcholine. The preservation of phospholipids of neuroreceptor membranes and ion transport provide retinal functional activity, reception and processing of visual information [12].

The diverse effects of citicoline justify the feasibility of including the drug in complex treatment according to the proposed method.

In this way, 26 patients (52 eyes) aged 45-79 years with primary open-angle glaucoma were treated. In all 26 patients, the drug acted on the brain; the results of the combined treatment were monitored in 30 operated eyes. All eyes had high intraocular pressure (average true IOP (Po) was 37.4 ± 3.1 mm Hg) and disease progression was noted. Comprehensive treatment included sinusotrabeculectomy and a differentiated course of treatment with citicoline, depending on the severity of the glaucomatous lesion. Before the study, the parameters of the central and peripheral visual fields, the thickness of the peripapillary layer of the nerve fibers of the retina, and the head of the optic nerve were evaluated. Automatic static perimetry was performed on a Carl-Zeiss Meditec, Humphrey Field Analyzer apparatus, the Central 30-2 Threshold Test and Peripheral 60-4 Threshold Test programs, the optic nerve head and the thickness of the nerve fiber layer of the peripapillary region were evaluated using an instrument "Stratus OST 3000" (Carl-Zeiss Meditec). We used the Fast Optic Disc and Fast RNFL Thickness 3.4 scanning protocols, followed by analysis of the data obtained using the Optic Nerve Head and RNFL Thickness Average programs.

After the complex treatment, the average true intraocular pressure (Po) was 15.5 ± 2.1 mm Hg, the maximum level of intraocular pressure did not exceed 21 mm Hg. Visual acuity increased slightly, but the statistical difference was unreliable. According to perimetry, immediately after taking the drug, an improvement in visual fields was observed in 20 eyes, 6 eyes showed a slight deterioration, and visual fields in 4 eyes did not change. The average thickness of the peripapillary layer of the retinal nerve fibers increased from 68.77 ± 12.46 μm to 70.32 ± 13.24 μm (M ± σ, P> 0.05).

1 month after taking the drug, intraocular pressure and visual acuity remained stable. The total average photosensitivity of the central field of view increased from the initial 1453 ± 98.24 dB to 1578 ± 102.35 dB (M ± σ), the difference was statistically significant (P <0.05). The number of absolute and relative cattle in the central field of vision decreased. The MD index improved from -13.04 ± 0.99 dB to -10.09 ± 0.64 dB (P> 0.05). In 4 eyes out of 6, where deterioration was noted, a month after taking the drug, the field of view (PZ) improved and the indicators exceeded the initial ones. In those eyes where there was an improvement in the visual fields immediately after taking the drug, their improvement continued: the number of absolute and relative cattle decreased. The average thickness of the peripapillary layer of the nerve fibers of the retina maximally increased a month after treatment (from 68.77 ± 12.46 μm to 72.07 ± 12.78 μm (M ± σ, P> 0.05).

After 6 months of observation, visual acuity and intraocular pressure remained unchanged in all patients. The fields of vision in 10 eyes were at a higher level compared to the initial ones, in 14 eyes the fields of vision were at the initial level, and in 6 eyes the state of PZ slightly worsened. The average thickness of the peripapillary layer of nerve fibers remained stable in 23 eyes, decreased in 7 eyes, and morphometric parameters of the optic nerve head stabilized.

The invention is illustrated by clinical examples.

Example 1. Patient B., 1952. Diagnosis: primary unstabilized open-angle II art. glaucoma OD.

Before treatment: Po 29.4 mm Hg, visual acuity 0.2 s - 2.5 = 0.5. Automatic static perimetry in the central field of view: 1735 dB, MD - 5.43 dB, surface and deep relative defects in the upper half of the field of view.

Optical coherence tomography: the thickness of the peripapillary layer of nerve fibers is 55.75 μm, the ratio of excavation area to disk area (Cup / Disc Area Ratio) is 0.744, Vert Integrated Rim Area (Vol.) Is 0.067 mm ³ , Cup Volume is 0.484 mm ³ .

The patient underwent a sinusotrabeculectomy, 5 intravenous drip injections of citicoline a were administered at 500 mg (4 ml) daily for 5 days, followed by oral administration of 200 mg 3 times a day for 10 days.

After the treatment, the following changes were noted: Po 11 mm Hg, visual acuity 0.3 s - 2.5 = 0.6.

Automatic static perimetry in the central field of view: 1926 dB, MD - 3.63 dB, the number of defects in the upper half of the field of view decreased.

Optical coherence tomography: the thickness of the peripapillary layer of nerve fibers increased, is 66.36 microns, morphometric indicators in the optic head improved - the ratio of excavation area to disk area (Cup / Disc Area Ratio) - 0.577, Vert Integrated Rim Area (Vol.) - 0.115 mm ³ , Cup Volume - 0.313 mm ³ .

1 month after taking the drug, intraocular pressure, visual acuity, total photosensitivity of the retina and the thickness of the peripapillary layer of nerve fibers remained stable.

After 6 months of observation, visual acuity, IOP, and the thickness of the peripapillary layer of nerve fibers remained stable. Indicators of the visual field were at a higher level compared to the original.

Example 2. Patient P., 1939. Diagnosis: primary unstabilized open-angle III art. glaucoma OS.

Before treatment: Po 37.2 mm Hg, visual acuity 0.3 s -1.0 = 0.5.

Automatic static perimetry in the central field of view: 1200 dB, MD - 14.49 dB, in the upper nasal and lower nasal fields of view there are deep relative and absolute scotomas along the horizontal meridian, an arched scotoma in the Bierrum zone in the lower temporal field of view.

Optical coherence tomography: the thickness of the peripapillary layer of nerve fibers is 39.84 μm, the ratio of the excavation area to the disk area (Cup / Disc Area Ratio) is 0.767, the excavation volume (Cup volume) is 0.36 mm ³ , Vert Integrated Rim Area (Vol .) - 0.059 mm ³ .

The patient underwent sinusotrabeculectomy, 5 intravenous drops of citicoline 1000 mg (4 ml) were administered daily for 5 days, followed by oral administration of 200 mg 3 times a day for 15 days.

After the treatment, the following changes were noted: Po 11.2 mm Hg, visual acuity 0.4 s -1.0 = 0.5.

Automatic static perimetry in the central field of view: 1396 dB, MD - 10.3 dB, the depth and area of defects in the central field of view decreased.

Optical coherence tomography: the thickness of the peripapillary layer of nerve fibers increased, is 44.87 microns, morphometric indices in the optic head were stabilized.

1 month after taking the drug, intraocular pressure, visual acuity, total photosensitivity of the retina and the thickness of the peripapillary layer of nerve fibers remained stable.

After 6 months of observation, visual acuity was at the same level. Intraocular pressure increased to 15 mmHg. (Ro). Indicators of the visual field were at a higher level compared to the original. The morphometric parameters of GBV and peripapillary retina remained stable.

Thus, the obtained positive treatment results for the proposed method confirm its pathogenetic orientation and effectiveness. The proposed method for the differential treatment of glaucoma optical neuropathy, along with the hypotensive effect, has a pronounced effect on ischemic processes in the optic nerve and retina. A positive result of treatment is expressed in improving visual functions and stabilizing the glaucomatous process. Improvement and stabilization of visual functions is observed in 80% of patients with primary open-angle glaucoma. The proposed method allows to reliably (P <0.05) increase the overall average photosensitivity of the retina in the central field of view, reduce the number of absolute and relative cattle, and improve the MD index. The proposed method allows to stabilize the morphometric parameters of the optic disc and peripapillary retina in most patients.

Information sources

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7. RF patent for the invention No. 2335283 "Method for the treatment of glaucoma optical neuropathy", IPC A61K 31/195, publ. 10/10/2008.

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Claims (1)

A method for the combined treatment of glaucoma optic neuropathy, including sinusotrabeclectomy and administration of a citicoline drug (ceraxone), characterized in that citicoline is administered differentially depending on the structural and functional disorders of the eye after sinusotrabeclectomy, by combining intravenous administration of citicoline with oral administration, while patient I-II the stage of glaucoma is prescribed citicoline intravenously in a dose of 500 mg daily for 5 days, followed by a transition to oral administration of 200 mg 3 times a day for 10 days, patients with stage III glaucoma are prescribed citicoline intravenously in a dose of 1000 mg daily for 5 days, followed by an oral dose of 200 mg 3 times a day for 15 days.