RU2644701C1 - Method of conservative treatment of adapted penetrating wounds of the cornea - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly ophthalmology, and may be used for conservative treatment of adapted penetrating corneal wounds. For this, 2 % combined hydrogel solution of chitosan ascorbate with a deacetylation degree of 94–98 %, and molecular weight of 100–700 kDa, containing in 1 liter of the solution 200 mg of hyaluronic acid, 2 g of chondroitinsulfuric acid, 110–440 μg of cattle serum growth factor "adgelon", and 50 mg of heparin. Treatment is carried out in the form of instillations in the conjunctival cavity 4 times a day for 1 month.

EFFECT: method provides an increase in the effectiveness of treatment by accelerating the regeneration processes, reducing the processes of scarring of the damaged cornea, which clinically manifests itself in the improvement of visual functions in the long period after the injury.

1 cl, 2 ex, 4 dwg

Description

The invention relates to medicine, namely to ophthalmology, and can be used for the conservative treatment of adapted penetrating wounds of the cornea, as well as microtraumas, burns and diseases associated with lesions of the cornea.

Successful treatment of penetrating wounds of the cornea begins with ensuring a good adaptation of the edges of the wound through primary surgical treatment. There are suture and seamless techniques for primary surgical treatment of corneal wounds. In medical practice, methods of adapting the edges of the corneal wound with suturing are more often used. However, these methods are accompanied by additional trauma. With small wounds of the cornea (up to 2-3 mm), good adaptation of the edges of the wound, normal depth of the anterior chamber, primary surgical treatment is usually not performed.

Despite the successes achieved in ophthalmotraumatology, the most modern methods are not able to prevent the processes of scarring, the occurrence of post-traumatic corneal astigmatism in the long term.

In addition to creating conditions for good wound sealing, a comprehensive conservative treatment is necessary, which includes the appointment of drugs that stimulate regenerative processes in the cornea, which contribute to good wound healing and the formation of a more delicate and optically transparent scar.

A known method of conservative treatment of injuries of the cornea, keratopathies, pathological changes in the conjunctiva, xerophthalmia, which is eye drops, which include 10-30% deproteinized dialysate from the blood of calves, 0.01-1% chitosan oligosaccharide with a molecular weight of 5000, 3000, 2000, 1500, water (patent US 2012/0003323 A1). The authors recommend using drops in the clinic to accelerate healing, improve trophism and moisturize the injured cornea.

The disadvantage of this method is the presence in the composition of the drops of preservatives in different concentrations, such as phenoxyethanol, phenylethanol, benzalkonium chloride and others, which are toxic and allergenic to the tissues of the eye, especially to the cornea.

Closest to the claimed method is a method of conservative treatment of injuries, burns, trophic and dystrophic disorders of the cornea, in which an eye film containing chitosan, polyvinyl alcohol, collagenase KK and glycerin is used (RF patent No. 2232582, 2004).

However, the presence of glycerol and polyvinyl alcohol in the film can provoke allergic reactions and corneal irritation. In addition, the manufacture of film is a laborious process, and its use causes inconvenience to use in patients.

The authors propose a new effective method for the conservative treatment of adapted penetrating wounds of the cornea, which even minimizes the risk of corneal astigmatism, which significantly affects the patient’s visual acuity, even after the injury. From the sources of domestic and foreign literature, no analogue was found that has such a high biocompatibility with eye tissues, biodegradability, lack of toxicity and irritating effect, and extremely low allergenicity.

The technical result of the proposed method is to increase the effectiveness of treatment by accelerating the regeneration processes, reducing the scarring of the damaged cornea, which is clinically manifested in the improvement of visual functions in the long term after the injury.

The technical result is achieved due to the fact that using a 2% combined hydrogel solution of chitosan ascorbate with a degree of deacetylation of 94-98%, a molecular weight of 100-700 kDa, containing 200 mg of hyaluronic acid, 2 g of chondroitinsulfuric acid, 110-440 μg in 1 liter of solution Adgelon serum cattle growth factor, 50 mg heparin, in the form of installations in the conjunctival cavity 4 times a day for 1 month.

The method is as follows.

The effectiveness of the method is illustrated by figures 1, 2, 3, 4 in the form of photographs.

The figure 1 on the optical coherent tomogram shows the corneal wound of patient M. with the lack of adaptation of the inner layers on the 10th day of standard conservative treatment.

The figure 2 on the optical coherence tomogram shows a corneal wound with incomplete adaptation of the edges and the formation of a scar on 1/3 of the thickness of the cornea in patient M., treated by the standard method for 1 month.

The figure 3 on the optical coherent tomogram of the cornea shows the complete closure of the edges of the wound and the formation of a scar in patient P. on the 10th day of treatment of the claimed method.

The figure 4 on the optical coherent tomogram of the cornea shows the formation of a delicate scar of the cornea in patient P., treated by the claimed method for 1 month.

To confirm the effectiveness of the proposed method, experimental studies were conducted on animals.

The study involved 6 somatically healthy chinchilla rabbits (12 eyes) of both sexes weighing 1.5-2 kg, contained in standard vivarium conditions. Rabbits are divided into experimental and control groups, 3 rabbits (6 eyes) in each group. Typical linear penetrating corneal incisions were applied to all rabbits under operating conditions under general and local anesthesia for 11 to 19 hours of the conventional dial using 2.75 mm steel keratom Optimed. Subject to adaptation of the wound edges the day after surgery, treatment is started: rabbits of the experimental group installing 2% of the combined hydrogel solution of chitosan ascorbate with a deacetylation rate of 94-98%, molecular weight 100-700 kDa containing 200 mg of hyaluronic acid in 1 liter of solution in the conjunctival cavity acid, 2 g of chondroitin sulfuric acid, 110-440 μg of serum cattle growth factor "gelon", 50 mg of heparin 4 times a day.

The control group rabbits were installed in the conjunctival cavity with a 0.25% solution of chloramphenicol and dexpanthenol gel 4 times a day. Treatment in both groups was carried out for 1 month. Rabbits were removed from the experiment after 2 weeks, 1 month, 3 months. Eyes were fixed in neutral 10% formalin, embedded in paraffin, serial sections were prepared stained with hematoxylin-eosin, histological examination was performed.

On the 14th day after treatment by the claimed method, in the experimental group of rabbits, thickening of the epithelial layer due to the actively proliferating basal layer, numerous figures of mitosis with preservation of slight edema of the epithelium in the form of vacuolization, active proliferation and migration of stromal fibroblasts to the area of damage, random arrangement of newly formed fibers were noted stroma. Inflammatory infiltrate was absent.

On the 14th day after treatment, the control group of rabbits histologically observed moderate pronounced edema of the epithelium and its own substance: vacuolization of the epithelium, swelling and loosening of the fibers, folds of the Bowman capsule, active proliferation of young fibroplastic elements with the formation of soft fibrous granulation tissue, a sharp thickening of the epithelium consisting of 9 layers of cells lined with stratification of the layers. Inflammatory infiltrate was absent.

1 month after treatment in the experimental group of rabbits, edema of the epithelium and its own substance persisted, proliferation sites were determined in the epithelium, the number of layers was up to 5-6. Newly formed stromal fibers in a large number were located correctly, weak fibroblast activity remained.

1 month after treatment, in the control group of rabbits, there was a decrease in edema of the cornea's own substance and the formation of tender fibrous connective tissue with pronounced fibroblast activity, as well as the regeneration of the epithelium in the form of a thick layer over a considerable length consisting of 8 layers of cells.

3 months after treatment in the experimental group of rabbits, mild edema of their own substance persisted, the epithelium consisted of 5 layers of cells, regeneration and inflammatory cells in the epithelium and stroma were absent. Significant areas were identified where the corneal tissue itself had a normal structure.

3 months after treatment in the control group of rabbits, the corneal epithelium had a clearly structured structure, consisted of 8 layers of cells, edema and signs of regeneration were absent. Mild edema persisted in the stroma, for a considerable extent the structure of the stroma in the scar area was disrupted, there were isolated sites with the normal structure of the cornea’s own tissue.

During histological examination of corneal sections on preparations in the experimental and control groups of rabbits, 5 layers were determined: epithelium, Bowman's membrane, stroma, Descemet's membrane, endothelium, and the wound channel passing through all layers of the cornea was also determined.

Comparative results of histological studies in the experimental and control groups showed that in the treatment of penetrating adapted wounds of the cornea under the conditions of using the proposed method, a delicate scar is formed with minimal deformation of the stroma and epithelium, while using an alternative method of conservative treatment, a scar is formed with thickening of the epithelial layer and deformation of the stroma.

The natural polysaccharides that make up the hydrogel, such as hyaluronic acid, which is found in large quantities in the cornea and vitreous body, chondroitin sulfuric acid, along with chitosan ascorbate, form a stable protective film on the ocular surface, stimulate metabolism, proliferation and differentiation of cells, improve tissue regeneration processes cornea. Heparin, similar in chemical composition to hyaluronic acid, improves microcirculation, has an antiexudative effect. Serum cattle growth factor “gelon” promotes healing of the corneal wound and normal restoration of its tissue.

Clinical example

1. Patient M., 52 years old, was admitted with a penetrating adapted corneal wound with damage to the lens of the left eye. On admission: visual acuity: 0.9 / 0.1 n.c., an adapted linear wound 2 mm long just below the optical center was determined on the cornea, local clouding of the lens in the same projection without swelling was recorded, the fundus was without pathology. Primary surgical treatment of the wound was not performed. The patient was prescribed complex therapy, including topical use of antibacterial, glucocorticosteroid, keratoplastic drugs, systemic and parabulbar administration of antibacterial and glucocorticosteroid drugs, physiotherapy.

On the 10th day of treatment, ophthalmological studies showed the following: pneumotonometry - 15/16 mm Hg, atorefractometry: sph -0.25 cyl -0.25 ah 12 / sph -0.5 cyl -0.75 ah 78. According to optical coherence tomography, incomplete closure of the edges of the wound (Fig. 1). At discharge, visual acuity was 0.9 / 0.4 N.K.

3 months after injury and treatment, the following research results are presented: pneumotonometry - 15/15 mm Hg, atorefractometry: sph -0.5 cyl -0.25 ah 12 / sph -0.5 cyl -1.75 ah 75 , visual acuity 0.9 / 0.7 n.k. The following dynamics was determined on the optical coherent tomogram: the scar was formed at 1/3 of the cornea thickness, there was maladaptation of the wound in the inner layers (Fig. 2). During biomicroscopy, residual pericorneal injection of the eyeball was noted; a 1.5 mm long scar was formed on the cornea just below the optical center, a lens with local peripheral opacification without swelling. The underlying structures are intact.

2. Patient P., 27 years old, was admitted with a diagnosis of penetrating adapted corneal wound with damage to the lens of the right eye. On admission: an adapted linear wound on the cornea was localized immediately below the optical center at 6 hours of a conventional 1.5 mm long dial, local lens opacification was recorded in the peripheral part without swelling, the fundus without pathology. Visual acuity at admission: 0.4 n.c. / 1.0. The primary surgical treatment of a corneal wound was not performed. The patient was prescribed treatment according to the claimed method, including installations in the conjunctival cavity of a 2% combined hydrogel solution of chitosan ascorbate with a degree of deacetylation of 94-98%, a molecular weight of 100-700 kDa containing in 1 liter of a solution of 200 mg of hyaluronic acid, 2 g of chondroitin sulfuric acid, -440 mcg of serum growth factor cattle "Adgelon", 50 mg of heparin 4 times a day. On the 10th day of treatment, ophthalmologic studies were performed: pneumotonometry - 7/11 mm Hg, atorefractometry: sph -0.25 cyl -0.5 ax 180 / sph -0.25. According to optical coherence tomography, a complete closure of the wound edges was noted (Fig. 3). At discharge, visual acuity was 0.8 NK / 1.0.

3 months after the injury and treatment, the following research results were presented: pneumotonometry - 13/12 mm Hg, atorefractometry: sph -0.25 / sph -0.25, visual acuity 0.95 / 1.0. Positive dynamics was determined on the optical coherent tomogram: the formed scar is delicate, the cornea is homogeneous over a large area (Fig. 4). During biomicroscopy, the eye condition remained calm, a translucent scar was formed on the cornea, a lens with local peripheral opacification without swelling. The underlying structures are intact.

The treatment according to the claimed method is carried out for one month, as a result of which a scar is formed with minimal deformation of the epithelium and corneal stroma. A total of 10 patients were treated. The advantages of the proposed method of treatment are early regeneration of the cornea, reduced scarring, ease of use, lack of toxicity and allergenicity, good biocompatibility with the tissues of the eye.

The inventive method provides effective treatment by providing on the cornea the anti-inflammatory, antioxidant, wound healing effects of natural mucopolysaccharides contained in the solution, the good mucoadhesive properties of chitosan ascorbate, its prolonged contact with the ocular surface due to electrostatic interactions of the positively charged chitosan ascorbate molecule with a negative film and membranes of the corneal and conjunctival epithelium.

Claims (1)

A method of conservative treatment of adapted penetrating wounds of the cornea, characterized in that they use a 2% combined hydrogel solution of chitosan ascorbate with a degree of deacetylation of 94-98%, a molecular weight of 100-700 kDa containing 200 mg of hyaluronic acid, 2 g of chondroitin sulfuric acid in 1 liter of solution 110-440 mcg of serum growth factor cattle "Adgelon", 50 mg of heparin, in the form of instillations into the conjunctival cavity 4 times a day for 1 month.

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