RU2281775C1 - Method for treatment of central atherosclerotic chorioretinopathy - Google Patents

Abstract

FIELD: medicine, ophthalmology.

SUBSTANCE: method involves a single administration of 1.0 ml of 2% combined hydrogel solution of chitosan ascorbate with deacetylation degree 94-98% and molecular mass 100-700 kDa into Tenon's space wherein this solution comprises 200 mg of hyaluronic acid, 2 g of chondroitinsulfuric acid, 110-440 mcg of cattle serum factor and 50 mg of heparin in 1 l of the solution. Method provides revascularization of the eye posterior pole based on resorption and substitution of hydrogen by the own connective tissue enriched with newly formed vessels of capillary type and activation of perivasal chorioepiscleral anastomosis. Invention can be used in treatment of the central atherosclerotic chorioretinopathy.

EFFECT: improved method of treatment.

1 tbl, 1 ex

Description

The invention relates to medicine, namely to ophthalmology, and can be used to treat central atherosclerotic chorioretinopathy.

Various auto-, allo-, xenoplastic, synthetic materials in the form of implants, suspensions and suspensions introduced into the tenon space of the eye are used to stabilize hemodynamics, improve metabolic processes in the posterior part of the eye and improve visual functions.

B.C. Belyaev (1983) introduced pieces of the donor sclera into the tenon space with simultaneous microdermatocoagulation of the sclera of the recipient, which subsequently contributed to the thinning of the sclera and the appearance of newly formed vessels. The authors explain the increase in visual acuity by the increased vascularization and blood supply to the posterior pole of the eye, which was confirmed by experimental histological studies [1].

The disadvantage of this method is the use of donor tissues, for the use of which it is necessary to conduct a series of laboratory studies to exclude viral (HIV, HBV, HCV, etc.) infection of the material, as well as to prepare and store tissues in accordance with the method proposed by the authors, which may cause certain difficulties in the absence of a bank of canned donor tissue.

Closest to the proposed method for the treatment of central atherosclerotic chorioretinopathy is a method where a suspension of Alloplant biomaterial is used, which is introduced after diluting alloplant powder in a volume of 1.5 ml of physiological saline and 2 mg of dexamethasone into the tenon space retrobulbarly. According to experimental studies, a loose regenerate with a well-developed vasculature is formed on the surface of the episclera, perivasal choroidoepiscleral anastomoses (vasa vasorum arteriarum ciliarium longarum et brevium atque venarum vorticosarum) are activated [2]. However, the biomaterial used is a dispersed substrate, consisting of collagen fibers and a complex of proteoglycans of the extracellular matrix of the dense connective tissue of donor organs, contains foreign proteins and antigens, which can cause a pronounced immunological reaction to the graft, followed by severe scarring.

The objective of the invention is the revascularization of the posterior pole of the eyeball in patients with central atherosclerotic chorioretinopathy.

The problem is solved due to the fact that 1.0 ml of a 2% combined hydrogel solution of chitosan ascorbate with a degree of deacetylation of 94-98%, molecular weight of 100-700 kDa, containing 200 mg of hyaluronic acid in 1 liter g of chondroitin sulfuric acid, 110-440 μg of serum cattle growth factor, 50 mg of heparin.

The method is as follows. Patients are introduced via cannula through a small puncture of the conjunctiva into the tenon space retrobulbarly, in the lower external quadrant, 1.0 ml of a water-soluble 2% hydrogel solution of chitosan ascorbate with a degree of deacetylation of 94-98%, with a molecular weight of 100-700 kDa, containing in 1 liter a solution of 200 mg of hyaluronic acid, 2 g of chondroitin sulfuric acid, 220 μg of serum cattle growth factor, 50 mg of heparin. The seam on the puncture wound of the conjunctiva is not superimposed. In the postoperative period, patients receive drops: Sol. Dexamethasoni 0.1%, Sol. Cipromedi 0.3%, parabulbar injection: Sol. Dexamethasoni 2 mg, Sol. Gentamycini sulfatis 4% - 0.5 ml, as standard anti-inflammatory therapy, 7 days.

7 patients (3 men and 4 women) between the ages of 64 and 75 were treated. Patients were determined visual acuity, the critical frequency of flicker fusion, optic nerve lability, biomicroscopy, ophthalmoscopy, biometry, refractometry, electroretinography, tonography, tonometry, perimetry, a study of the central field of vision, rheophthalmography with a cold breakdown, before surgery, after surgery (during surgery) were determined ), after 1 and 6 months.

Preliminary histological studies of serial sections of the rabbit's eyeball in the area of chitosan hydrogel implantation in the tenon space result in an aseptic inflammatory cell reaction, which leads to gradual lysis, resorption and replacement of the hydrogel with its own connective tissue, rich in newly formed vessels of the capillary type, activating perivasal anterior chorioidrioid eryloid eryoidereiosis the poles of the eye.

Immediate and long-term results showed the effectiveness of the proposed treatment. The table below shows the positive dynamics of the average electrophysiological parameters and visual functions of the eye.

Table
The results of studies of patients with central atherosclerotic chorioretinopathy at various times. Average electrophysiological indicators Norm Before surgery 7 days after surgery 1 month after surgery 6 months after surgery Visual acuity without correction 1,0 0.12 ± 0.02 0.14 ± 0.04 0.19 ± 0.07 0.31 ± 0.22 Refraction, diopters 0 1.0 ± 0.48 0.75 ± 0.5 1.0 ± 0.37 1.44 ± 0.5 Visual acuity with correction 1,0 0.26 ± 0.06 0.37 ± 0.06 0.43 ± 0.13 0.59 ± 0.27 Biometry, mm 24.27 23.1 ± 1.37 23.1 ± 1.34 23.3 ± 1.8 23.21 ± 1.35 The sum of the degrees of peripheral fields of view, degrees 485 350 ± 61 427 ± 12 441 ± 7 458 ± 4 Sensitivity threshold of the optic nerve, mA 100-160 271 ± 31 270 ± 36 288 ± 72 300 ± 23 Lability, Hz 40 40 40 40 40 Critical flicker fusion frequency, Hz 40 39 ± 0.85 40 39 ± 0.9 40 Electroretinography wave a, mA 50-75 54 ± 15 60 ± 12 50 ± 19 55 ± 24 Electroretinography wave b, mA 150-250 150 ± 33 150 ± 27 161 ± 12 155 ± 46 True intraocular pressure, mmHg 9-15 14.7 ± 1.4 14.2 ± 2.3 14.5 ± 0.8 15 ± 1.3 Ease of outflow 0.15-0.55 0.17 ± 0.04 0.18 ± 0.04 0.2 ± 0.03 0.15 ± 0.11 Intraocular fluid production 1.7-4.0 1.01 ± 0.37 1.11 ± 0.46 0.83 ± 0.13 0.73 ± 0.26 Geographic coefficient, ppm 1,5-3 1.26 ± 0.49 2.47 ± 0.27 2.24 ± 0.73 2.38 ± 0.18 Pulse volume according to Kedrov, cu 8-10 8.8 ± 3.59 17.87 ± 1.97 16.3 ± 5.28 17.2 ± 1.72

The table shows that visual acuity without correction increases from 0.12 ± 0.02 (before surgery) to 0.31 ± 0.22 (after 6 months), and with correction - from 0.26 ± 0.06 to 0.59 ± 0.27. The increase in visual acuity begins on the 7th day after the operation and lasts throughout the entire observation period, reaching a maximum of 6 months after the operation. In this case, the refraction of the eye practically does not change, fluctuating within the measurement error. Peripheral visual fields expand from 350 ± 61 degrees (before surgery), to 458 ± 4 degrees (by 6 months after surgery), approaching almost the norm. These indicators indicate an increase in the visual function of the eye after surgery.

The reographic coefficient, which amounted to 1.26 ± 0.49 ppm before the operation, which is less than the lower limit of the norm, reached the average maximum value of 2.47 ± 0.27 ppm 7 days after the operation and slightly decreased by the 6th month of observation to 2.38 ± 0.18 ppm, which corresponds to the age norm. The Kedrov pulse volume indicator before the operation averaged 8.8 ± 3.59 cu, after the operation its value increased significantly and changed slightly within the measurement error, and amounted to 17.2 ± 1.72 cu by 6 months after surgery. These parameters show an increase in intraocular blood flow in the operated eyes, which lasts all 6 months of observation of patients. The increased blood supply to the membranes of the posterior pole of the eye provides an increase in visual functions.

The sensitivity threshold of the optic nerve practically does not change, remaining within the measurement error, and amounted to, on average, 280 mA. The lability of the optic nerve and the critical frequency of flicker fusion also do not change during the entire observation period of patients, averaging 40 Hz. The values of waves a and b of electroretinography practically do not change during 6 months of observation of patients, amounting, on average, to 55 and 153 mA, respectively. True intraocular pressure, ease of outflow also vary within the measurement error, amounting to, on average, 14.5 mm Hg and 0.17, respectively. There is a slight decrease in the production of intraocular fluid from 1.0 before surgery to 0.73 by 6 months after surgery. Eye biometry did not change over the entire observation period and amounted to 23.2 mm on average. All of the above indicators remain within the age norm and almost do not change after the operation, therefore, the proposed operation in patients with central atherosclerotic chorioretinopathy does not affect the functional state of the optic nerve, the state of hydrodynamics of the eye, and the size of the eyeball.

Clinical example: Patient S., 65 years old. The diagnosis is central atherosclerotic chorioretinopathy, the initial age-related cataract of both eyes, based on complaints, medical history, biomicroscopy, ophthalmoscopy, electrophysiological studies. Before treatment, the visual acuity of the left eye without correction is 0.1, visual acuity with correction (sphere (+) 1.0 diopters) is 0.3, the sum of the degrees of peripheral fields of view is 426, the threshold of sensitivity of the optic nerve is 280 mA, the lability of the optic nerve is 40 Hz , the critical flicker fusion frequency is 40 Hz, the electroretinography wave a is 50 mA, the electroretinography wave b is 100 mA, the eye biometry is 23.1 mm, the true intraocular pressure is 15 mm Hg, the ease of the outflow of intraocular fluid is 0.14, the production of intraocular fluid is 0, 6, reographic coefficient 1.75, pulse volume m according to Kedrov 8.3.

The patient was introduced into the tenon space, in the lower-outer quadrant, retrobulbarly, using a cannula with a 1.0 ml water-soluble 2% hydrogel solution of chitosan ascorbate with a degree of deacetylation of 98%, a molecular weight of 700 kDa, containing 200 mg of hyaluronic acid in 1 liter of solution, 2 g of chondroitinsulfuric acid, 220 μg of serum cattle growth factor, 50 mg of heparin. In the postoperative period, for 7 days, the patient received standard anti-inflammatory therapy - drops: Sol. Dexamethasoni 0.1%, Sol. Cipromedi 0.3%, parabulbar injection: Sol. Dexamethasoni 2 mg, Sol. Gentamycini sulfatis 4% - 0.5 ml. In the postoperative period, an almost reactive course is observed, a minor injection of the conjunctival vessels, stopped on the 2nd day after the operation.

On the 7th day after the operation, at discharge from the patient, the following electrophysiological indicators of the left eye were recorded: visual acuity without correction 0.1, visual acuity with correction (sphere (+) 1.0 diopters) equal to 0.4, the sum of degrees of peripheral fields of view 435 degrees , optic nerve sensitivity threshold 270 mA, optic nerve lability 40 Hz, flickering critical fusion frequency 40 Hz, electroretinography wave a 50 mA, electroretinography wave b 155 mA, eye biometry 23.1 mm, true intraocular pressure 14.6 mmHg ., ease of outflow 0.14 triglaznoy fluid, intraocular fluid products 0.73, 2.74 rheographic ratio, pulse volume of Kedrov 19.4.

These changes in indicators indicate an increase in visual functions, a significant increase in intraocular circulation on the 7th day after the operation.

1 month after surgery, the patient showed the following electrophysiological parameters of the left eye: visual acuity without correction of 0.2, visual acuity with correction (sphere (+) 1.0 diopters) is 0.5, the sum of the degrees of peripheral fields of view is 448 degrees, the threshold the sensitivity of the optic nerve 260 mA, the lability of the optic nerve 40 Hz, the critical fusion flicker frequency of 40 Hz, the wave a of electroretinography 55 mA, wave b of electroretinography 150 mA, eye biometry 23.1 mm, true intraocular pressure 14.6 mm Hg, ease of outflow of intraocular dots 0.17, intraocular fluid production 0.73, reographic coefficient 2.58, pulse volume according to Kedrov 21.1.

These changes in indicators indicate a continued improvement in visual functions, the preservation of enhanced intraocular circulation by 1 month after surgery.

6 months after surgery, the patient recorded the following electrophysiological parameters of the left eye: visual acuity without correction of 0.3, visual acuity with correction (sphere (+) 1.0 diopters) is 0.6, the sum of the degrees of peripheral fields of view is 452 degrees, the threshold the sensitivity of the optic nerve 270 mA, the lability of the optic nerve 40 Hz, the critical fusion flicker frequency 40 Hz, wave a electroretinography 45 mA, wave b electroretinography 155 mA, eye biometry 23.1 mm, true intraocular pressure 13.7 mm Hg, ease of outflow inside 0.26 Lazne fluid, intraocular fluid products 0.81 rheographic coefficient of 2.68, the pulse volume of Kedrov 18.9.

These values indicate the preservation of the achieved indicators of visual functions, the level of intraocular circulation and intraocular hydrodynamics by 6 months after the operation, and confirm the small effect of the operation on the functional state of the optic nerve, the state of hydrodynamics of the eye, and the size of the eyeball.

Thus, after the operation, an increase in visual acuity without correction and with correction, an expansion of the field of view, an increase in the rheographic coefficient, and pulse volume are noted. The result remains stable for 6 months after surgery.

The advantages of the proposed method - the combined hydrogel does not have allergenic properties [3, 4], biodegradable, low trauma during implantation, the formation of its own connective tissue, replacing the combined hydrogel, rich in newly formed vessels of the capillary type, activating perivasal choroidoepiscleral anastomoses, causing the eyes to increase the backlightness increase in visual function after surgery and preservation of the achieved effect for 6 months.

Bibliography

1. Belyaev B.C., Gossen J.Kh. On the possibility of surgical treatment and prevention of dystrophy of the retina and optic nerve. - Bulletin of Ophthalmology, No. 6, 1983, p. 18-21.

2. Rodionov OV, Sultanov RZ, Larin A.I., Bulatov R.T. Dispersed Alloplant biomaterial in the treatment of diabetic retinopathy. - Materials of the 1st Euro-Asian Conference on Ophthalmic Surgery, Ekaterinburg, 1998

3. Bolshakov I.N., Nasibov S.M. The use of chitosan in the treatment of hypercholesterolemia. - Siberian Medical Review, 2001, No. 1, pp. 9-15.

4. Tanaka Y., Tanioka S., Tanaka M., Tanigawa T., Kitamura Y., Minami S., Okamoto Y., Miyashita M., Nanno M. Effects of chitin and chitosan particles on BALB / c mice by oral and parenteral administration. Biomaterials. 1997 .-- Vol. 18. - No 8. - P.591-595.

Claims (1)

A method of treating central atherosclerotic chorioretinopathy, comprising administering biomaterial through a cannula into the tenon space to the posterior pole of the eye, followed by standard anti-inflammatory therapy, characterized in that 1.0 ml of a 2% chitosan ascorbate hydrogel solution with a degree of deacetylation of 94-98 is used as biomaterial %, molecular weight 100-700 kDa, containing in 1 l of a solution of 200 mg of hyaluronic acid, 2 g of chondroitin sulfuric acid, 110-440 μg of serum cattle growth factor, 50 mg of heparin, while the specified biomaterial is administered once.