Method of treating corneal keratoconus

FIELD: medicine.

SUBSTANCE: method involves corneal impregnation with 0.1% riboflavin and ultraviolet exposure at a wave length of 365-375 nm for 30 min. Before impregnation, the cornea is coated with 40% glucose kept on the corneal surface for 9-11 min; residual glucose is removed, and the glucose-treated corneal surface is coated with 0.1% riboflavin for 30 min.

EFFECT: eliminating postoperative complications, reducing the length of the patients' rehabilitation, and achieving the high functional results of the operation.

5 ex

 

The invention relates to medicine, more specifically to ophthalmology, and can be used for the treatment of keratoconus cornea. Keratoconus or ectasia of the cornea is a degenerative disease, which weakens the strength of the collagen fibrils of the cornea, which leads to the formation of the conical shape of the cornea and the displacement of its center and astigmatism. The etiology of keratoconus hitherto unknown. In the literature lead endocrine, genetic, metabolic, immunological and immunogenetic, allergic, environmental, and even viral theory of occurrence of keratoconus, and most researchers are inclined to multifactor theory, taking into account all listed. It may be primary, genetically determined, or secondary, which is one of the most serious complications of refractive surgery

For treatment of this pathology applied soft contact lenses, hard contact lenses, surgical methods of treatment, including end-to-end and layer-by-layer keratoplasty, implantation intrastromal corneal rings, epikeratophakia, asymmetric radial keratotomy, corneal collagen cross-linking.

In recent years, for stabilization of the pathological process keratoconus was proposed cross-linking (cross-linking) is a method of treatment, based on "Platania or increasing the strength of the cornea, which comes under the influence of low-intensity ultraviolet light to the tissue stroma of the cornea in the presence of a photosensitive substance - Riboflavin (vitamin B2). Compaction due to increased production of short-lived free radicals of oxygen that is liberated, causing the formation of relationships - bridges between isolated until the collagen fibrils of the stroma, combining them into a single strong network, increasing the strength of the cornea from 3 to 6 times. The method developed by T. Seller, G. Wollensak in 2003 [Wollensak g, Spoerl e, Seiler T. Stress - strain measurements of human and porcine corneas after riboflavin Ultravoilet-A-induced collagen cross-linking // J Cataract Refract Surg. - 2003. - Vol.29. - P.-1780-1785]. There are many options for implementing this method, which is described including in the patent literature. Thus, in the patent of the Russian Federation 2434616 described a method for the treatment of keratoconus, including the formation of intrastromal pocket using a femtosecond laser with subsequent introduction into the formed pocket of 0.1% Riboflavin solution, and soaking up the last of the cornea and corneal exposure with ultraviolet light with a wavelength of 365-375 nm within 30 min, while first using the femtosecond laser in accordance with the programmed parameters of the cuts performed by two arcuate corneal incisions with the following topographic parameters: depth of incisions 120-140 µm diameter application corneal incisions - 9.0 mm, the cuts are symmetrical 90° and 270°, and then form intrastromal pocket. Thus, known methods include the step of decapitalization of the cornea, which is quite traumatic procedure for the cornea, accompanied by a strong reduction of vision sometimes up to 3 months or more. In addition, there is a risk of complications in the early post - inflammation of the anterior segment of the eye as keratoconjunctivitis (known cases of severe keratitis with the melting of the cornea) in Addition, the first 3-5 days, while the period of complete epithelization the patient feels a strong sense of discomfort until pain, pain, tearing and is disabled. When the proposed method of linking the patient is already working on the next day.

The disadvantages of these methods is conducting decapitalization cornea for delivery of the photosensitizer in the stroma of the cornea, which leads to a very long period of swelling of the cornea, as well as the possibility of the progression of keratoconus due to insufficient strength of "sutures". To correct the phase of decapitalization proposed electrophoretic saturation of the cornea with Riboflavin (see RF patent №2345956, 2005). However, this known method requires a preliminary medicamentosas in the cornea to form Misa.

Most b is erisim to the claimed method - the prototype is a method of treatment of keratoconus, which are as follows (patent RU 2434616, priority 31.03.2010). The method includes removing the epithelial layer of the cornea by the method of excimer laser ablation at a depth of not more than 2/3 of its thickness. Then saturate the cornea of 0.1% Riboflavin solution by repeated instillation. Next, perform ultraviolet irradiation of the cornea with a wavelength of 365 nm for 30 minutes

The disadvantage of this method is to conduct decapitalization cornea for delivery of the photosensitizer in the stroma of the cornea, which leads to a very long period of swelling of the cornea, heavy recovery, long term rehabilitation of the patient, and the risks attaching infection. In this regard, the researchers had the task of finding a non-invasive, safe and at the same time, an effective method for the treatment of keratoconus.

Anatomopathological and physiological characteristics of the cornea show that it is the outer part of the optical system of the eye and at the same time protective of "points" that protects the internal environment and the tissue of the eyeball. These are the main two functions of the cornea is achieved through a number of morphological features.

As you know, the cornea consists of five layers: front neoregelia is its epithelium, the Bowman's membrane, connective tissue stroma, descemets membrane and the posterior epithelium (endothelium). All these structures have high mechanical strength. Thus, the tensile strength of the cornea is 4×107Dyne/cm2in that time, bones 9×106Dyne/ cm2.

Morphofunctional features of all layers intact corneal prevent the infiltration of alien and harmful substances and microorganisms. Of particular importance in this belongs to the epithelium of Bowman's membrane and stroma of the cornea.

Front epithelium is about 10% of the total corneal thickness and presents a cylindrical cells of the basal layer, pterygoid cells of the spinous layer and flat-imbricate cells of the outer layer. All cells have tight contacts and firmly connected to each other by desmosomes and polydesmida. This structure of the epithelium prevents the release of substances from the outer surface of the cornea inside.

Barrier function for the penetration of substances and microorganisms also perform Romanova membrane and stroma. Contained in these structures glycosaminoglycans have the ability to bind large amounts of water and salts and thereby determine the required level of hydration of the tissues. The water content of the cornea reaches 80%.

Certain difficulties for p is animowane substances outside also has movement and other water-soluble compounds from the posterior layers of the cornea to the outer. All these circumstances led us to the conclusion that the arrival rate from the outer surface of the cornea into a wide range of substances, including medicines, can be significantly increased, if the conditions under which the intercellular space between epithelial cells will be increased and deeper layers of the cornea to be subjected to dehydration.

We hypothesized that this can be achieved when applied to the front surface of the cornea hypertonic substances. These substances due to osmosis will result in dehydration and temporary shrinkage of cells and partial dehydration of the deeper layers of the cornea. As such biocompatible substance can be used glucose. The above research results fully confirmed our assumptions.

The technical result of the claimed method is the elimination of postoperative complications, shorter rehabilitation patients and achieving high functional results of operations.

This technical result is achieved by the fact that in the known method of treatment of keratoconus cornea, including propityvanie cornea 0.1% Riboflavin solution and subsequent irradiation of the cornea with ultraviolet light with a wavelength of 365-375 nm within 30 min, whereas the om before impregnation of the cornea with Riboflavin at her pre-applied 40% glucose solution, keep it on the surface of the cornea for 9-11 minutes, after which the remains of the glucose solution was removed and processed glucose the surface of the cornea for 30 minutes to cause a 0.1% solution of Riboflavin

Example 1

Tests in vitro

The tests were carried out on a dedicated eyes of rabbits of the Chinchilla breed with modeling applications using the drug Riboflavin.

Brief description of the method of the experiment

On a dedicated (cadaveric) eye inflicted glucose solution directly on the cornea and kept for 10 minutes and then made the instillation of 0.1% Riboflavin solution. Cornea, washed in saline solution, fastened to the wall of the quartz cuvette inside.

Filmed transmission spectrum from 190 to 360 nm, relative to the empty cell.

Summarize the results, draw conclusions about the effect of glucose and the concentration of Riboflavin in the transmittance of the cornea.

Test results

445 nm - wavelength of a transmission spectrum of the solution of Riboflavin, which is able to penetrate the layers of the cornea without mechanical damage. The amount of the drug in the cornea linearly dependent on the exposure time. The time keeping his eyes in the solution of Riboflavin 5, 15 and 30 minutes, respectively, the amount of the drug in the cornea 0,06; 0,14; 0,25%

Pre-treatment of the cornea 40% solution is lukosi significantly increases the penetration of Riboflavin into the corneal layers. The spectrum clearly shows the difference between the optical density of the cornea treated only with the solution of Riboflavin from the cornea with pretreatment glucose. The figures have almost doubled.

Conclusions

Thus, the results of in vitro studies showed that the treatment of corneal glucose before applying Riboflavin significantly increases its penetrating ability.

Example 2

Tests in vivo

The tests were carried out on the eyes of live rabbits of the Chinchilla breed in terms of the preparation of the Riboflavin in the background of the Glucose 40%.

The eye of the rabbit is one of the experimental groups was applied glucose directly on the cornea and kept for 10 minutes, then made the instillation of Riboflavin. Another group of Riboflavin was applied without pre-treatment with glucose. In the course of the experiment conducted monitoring of the animals ' eyes on the subject of irritating effects of drugs on the eye tissue. After the experiment produced the euthanasia of animals followed by enucleation of the eye. Selected cornea, washed in saline solution, fastened to the wall of the quartz cuvette inside. Filmed transmission spectrum from 190 to 360 nm is relatively empty cell.

Summarize the results, draw conclusions about the effect of glucose and the concentration of Riboflavin is and the transmittance of the cornea, and irritant effects of drugs on the eye tissue.

Test results

In vivo studies confirmed the preliminary in vitro studies that pre-treatment of the cornea glucose increases the degree of penetration of the Riboflavin almost two times. It should be noted that in the course of the experiment is not marked irritation caused by the use of drugs.

Example 3

The patient Shogenov M. H., 25 years old, came to the clinic "Center eye surgery 28.05.13 with complaints of decreased vision in both eyes. A full eye examination. The diagnosis of Keratoconus stage 1 right eye, keratoconus stage 2 left eye.

Visual acuity

VOD = 0.6

VOS = 0.1 C/o cyl 3.5 - 4.5 ax 170=0.4

Refractometry

OD sph cyl 0 - 5.5 ax 175

OS sph - cyl 3.5 - 4.25 ax 178

Keratometry

OD 47.10 axis 90 43.28 ax 0

OS 45.90 axis 83 at 43.01 ax 173

Pachymetry OD 500 MCR OS 490 MCR

The patient has completed the treatment of the claimed method.

Visual acuity after surgery the next day right = 0.7. After 2 months = 0.7, three months 0.7. Left eye after carrying out the linking of the claimed method 0.4 not corrects, after 2 and 3 months sight to 0.5.

Example 4

The patient Kalyuzhny D. E., 24, came to the clinic "Center eye surgery 26.04.13 with complaints of decreased vision in both eyes. A full ophthalmological discuss adowanie. The diagnosis of Keratoconus 2-3 stage right eye, keratoconus 1 stage left eye.

Visual acuity

VOD = 0.01 C/o 4.75 cyl - 8.5 ax 70=0.1

VOS = 0.8 c/o - 0.75=1.0

Refractometry

OD sph - 5.0 cyl - 8.5 ax 70

OS sph - cyl 1.5 0.0

Keratometry

OD 57.94 axis 162 48.72 ax 172

OS at 43.14 axis l7243.72 ax 82

Pachymetry OD 394 MCR OS 495 MCR

The patient has completed the treatment of the claimed method.

Visual acuity after surgery the next day, left eye = C/o - 0.75=1.0. After 2 months = 1.0, three months 1.0. Right eye after carrying out the linking of the claimed method - 0.4 not corrects, after 2 and 3 months sight to 0.5.

Example 5

The patient Kobelev P. O., 20 years old, came to the clinic "Center eye surgery 25.04.13 with complaints of decreased vision in both eyes. A full eye examination. The diagnosis of Keratoconus 2-3 stage left eye, keratoconus stage 1 right eye.

Visual acuity

VOD = 0.7

VOS = 0.2

Refractometry

OD sph - cyl 2.0 - 3.5 ax 36

OS sph - cyl 6.5 0.0

Keratometry

OD 45.42 axis 123 42.96 ax 33

OS 53.22 axis 8345.13 ax 173

Pachymetry OD 474 MCR OS 440 MCR

The patient completed the treatment claimed by the way - the right eye. Left eye - implantation of corneal segments and 3 months carrying out the linking of the claimed method. Visual acuity after surgery the next day the eye - 0.8. After 2 months = 0.9, three months 0.9. The left eye of the trigge who I am 3 months after the holding of linking the claimed method 0.7, after 2 and 3 months sight - 0.7.

Thus, the claimed method allows for efficient non-traumatic treatment of keratoconus and get good consistent results.

A method of treatment of keratoconus cornea, including the impregnation of the cornea 0.1% Riboflavin solution and subsequent irradiation of the cornea with ultraviolet light with a wavelength of 365-375 nm for 30 min, characterized in that before impregnation of the cornea with Riboflavin at her pre-applied a 40% solution of glucose, maintain it on the surface of the cornea for 9-11 minutes, after which the remains of the glucose solution was removed and processed glucose the surface of the cornea for 30 minutes the solution is applied Riboflavin.



 

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1 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: composition of 5,10,15,20-tetrakis(N-methyl-3'-pyridyl)chlorine and 5,10,15,20-tetrakis(N-methyl-3'-pyridyl)bacteriochlorine is administered into a tumour tissue as a photosensitiser in an amount of 0.5-10mg per 1g of tumour tissue depending on a degree of tumour differentiation. The laser exposure starts 20-40 minutes later at wave length 760-762 nm. The cytological examination follows 6-7 days later, and if observing signs of persistent tumour growth, the presented therapeutic session is repeated.

EFFECT: gradual depression of the malignant tumour tissue up to the complete elimination of its cell and structural abnormalities, lower rate of metastasis or progression prevention that makes it possible to avoid surgical intervention in some cases.

4 cl, 3 dwg, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, namely to a photosensitiser for photodynamic therapy. What is declared is methyl ester 13,17-bis(N-methyl-N,N-diethylammonioethylamide) chlorine e6 ditosylate as a photosensitiser having formula: .

EFFECT: compound is stable, possesses high photobactericidal activity in vitro and high photodynamic effectiveness.

4 dwg, 2 tbl, 9 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to surgery, and can be used for treating sternomediastinitis. That is ensured by introducing a therapeutic mixture prepared ex tempore containing a broad-spectrum antibiotic tropic to bone tissue in a half a compendially recommended average therapeutic daily dose, 1 ml of lidase 32 thousand units, 1 ml of a lincomycine solution in a dose of 0.3 g, 1 ml of ketorolac tromethamine in a dose of 0.03 g, 1 ml of dexamethasone solution in a dose of 0.004 g, 1 ml of a 10% lidocaine solution and 5 ml of a 40% glucose solution. The therapeutic mixture is administered into interspinous ligaments of the spinal column at Th2-Th3, Th3-Th4, Th4-Th5, at a depth of 1.5-2 cm in a dose of 3 ml into each injection point into a patient lying on his/her side with bringing the knees to the stomach and bending the head as forward as possible. The length of treatment makes 12-14 days with the first 3 injections performed daily; the residual injections - every second day, 8-9 injections in total.

EFFECT: invention provides reducing a dose of the administered preparations and a rate of administration as compared to the systemic antibacterial therapy by an ability of the administered mixture to be accumulated in the inflammation centre, providing the therapeutic concentration with the total dose of the administered preparations reduced as compared to the systemic antibiotic therapy.

2 ex

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