Complex treatment of diseases of the cornea of ​​xerotic origin. Xerophthalmia - what is it, causes and treatment Xerosis of the conjunctiva

Xerophthalmia (xerosis) is a drying of the mucous membrane of the eye, which can lead to its softening and decay.

As a rule, xerophthalmia is caused by general diseases or prolonged local damaging effects on the eye.

The first group of causative factors includes cicatricial changes in the conjunctiva, which are caused by: trachoma, pemphigoid, burns, diphtheria, etc. They begin with small delimited areas, gradually involving the entire conjunctiva and cornea in the pathological process. In addition, ectropion and lagophthalmos contribute to the development of pathology, as a result of which there is insufficient covering of the eye with eyelids.

Causes of xerosis

The second group of causative factors of xerosis is a dietary deficiency of a fat-soluble vitamin.

Violations of the functions of the lacrimal apparatus, with xerophthalmia does not occur. It does not occur during the extirpation of the lacrimal gland, because the conjunctiva is able to be very effectively wetted with its own secret. However, when the secretory activity of the conjunctiva is reduced, then xerosis can occur even with normal or high secretion of tear fluid.

Symptoms

Changes during the development of the disease occur mainly in the epithelium, which over time becomes similar to the epidermis of the skin. The formation of granulation and stratum corneum occurs, the secretion of mucus stops. Because of this, there is a compensatory activation of the meibomian glands, due to which their fatty secret covers the dry surface of the conjunctiva. But as a result, the lacrimal fluid loses its ability to wet and moisturize the mucous membrane. This gives impetus to the increased growth of xerosis bacillus (non-pathogenic microorganism of the conjunctival cavity), although this saprophyte has no causal relationship with the disease.

Do not self-medicate - this can lead to serious complications, up to loss of vision. If you have noticed the first signs of corneal xerosis, please contact our ophthalmological center: this will help prescribe effective treatment and avoid the development of unwanted complications.

The disease caused by deficiency of fat-soluble vitamins has a mild form and is usually observed in children (boys), accompanied by night blindness. The conjunctiva, while becoming less transparent, dry. On the mucous membrane, from the inner and outer sides of the cornea, small, rough triangular-shaped spots (Iskersky-Bito spots) appear, covered with a foamy discharge, which are not wetted by tears. Their appearance is due to excess secretion of the meibomian glands, which, when blinking, are whipped into foam and mixed with the lowered epithelium of the cornea, in the process of settling on the affected areas of the conjunctiva.

Ocular xerosis occurs as a result of prolonged irritation, trauma or burns of the membrane. Pathology is manifested by severe dryness, burning and photophobia. With ophthalmoscopy, areas with ulcers and corneal erosions are determined, which, without the necessary treatment, can provoke the formation of a large number of scars and clouding of the eye. This provokes loss of vision and disability of the patient.

The disease is caused by insufficient production of tear fluid.

Reasons for development

Provoke xerosis of the conjunctiva and cornea can be influenced by the following factors on the human body:

• lack of vitamin A in the body;
• burn;
• injury;
• trachoma;
• surgical removal of the lacrimal gland;
• autoimmune diseases;
• autonomic dysfunction of the nervous system;
• chronic radiation sickness;
• irritation;
• hormonal imbalance;
• long-term inflammation;
• traumatic brain injury;
• exposure to bacterial or viral infections;
• poor tolerance to contact lenses;
• age-related neuroendocrine involution;
• changes in the anterior segment of the eye;
• smoking and exposure to cigarette smoke on the eyeball;
• taking medications.

Pathology is the result of poor production of tear fluid.

Xerosis is a severe dryness of the eye and occurs as a result of impaired tear production. This is due to a decrease in the stability of the precorneal tear film. The process occurs as a result of a violation of the volume, composition and production of tears, as well as the damaging effect of various factors on the eye. All this causes excessive dryness and malnutrition of the body.

Types of pathology

Xerophthalmia has the following clinical forms:

• Recurrent microerosion, which is characterized by periods of exacerbation and subsidence of manifestations and minor changes in the eyeball.
• Recurrent macroerosion with severe violations of the structure of the cornea.
• Dry, in which the pathology also extends to the conjunctiva.
• Filamentous with pronounced growths of connective tissue.

Main symptoms

Often, a disease of the organs of vision manifests itself in a person with a headache.

Xerophthalmia causes the patient to develop such clinical manifestations of the disease:

• burning eyes;
• lacrimation;
• photophobia;
• headache;
• dizziness;
• violation of the general condition;
• bad feeling;
• decreased sensitivity of the eye to irritants;
• nausea;
• redness of the mucous membrane;
• sensation of a foreign body in the eye;
• puffiness;
• incomplete occlusion of the eye.

With the help of ophthalmoscopy, a decrease in the transparency of the conjunctiva is determined, it becomes dry and matte-white spots with a rough surface are determined on it. The injection of the eye is well defined, and single erosive foci are determined on the cornea. With a long course of the disease and the absence of the necessary treatment, the patient may lose vision as a result of severe scarring of the membranes of the eye.

How is the diagnosis carried out?

An ophthalmoscopy will help identify the problem.

It is possible to suspect xerosis by the presence of symptoms characteristic of this pathology in a patient. To confirm the diagnosis, it is necessary to carry out ophthalmoscopy, with the help of which areas with erosions and ulcers of the cornea and conjunctiva are determined. You also need to pass a general and biochemical blood test to identify possible comorbidities. An ultrasound of the eyeball is performed, as well as a measurement of visual acuity. When wearing contact lenses, you need to identify the tear meniscus, which is a thickening of the tear film along the edge of the lower eyelid.

Violations of the mechanism of the functioning of the tear film can relate to any of its links: tear production, the distribution of SP on the surface of the eyeball, the structure of each of its layers, the rate of evaporation of the fluid, the intensity of the processes of cleavage of dying cells of the corneal epithelium, and even the outflow of tears from the conjunctival cavity.

In this case, great importance is attached to the intensity of evaporation of the joint venture. The consequence of these processes is the accelerated formation of areas of the corneal epithelium that are not wetted by the tear film, that is, a violation of the stability of the precorneal SP. Naturally, remaining unstable for a long time, the joint venture does not fully perform its functions and this causes the development of a number of pathological changes characteristic of the "dry eye" syndrome.

Thus, DES can be defined as a complex of signs of pronounced or latent corneal or corneal-conjunctival xerosis, which occurs on the basis of a long-term violation of the stability of the precorneal SP. The clinical classification of dry eye syndrome developed by us is presented in Table 1. In it, all cases of dry eye syndrome are assigned, depending on the etiology of the xerotic process, to one of two clinical groups: syndromic or

symptomatic. Syndromic means xerosis, caused by a decrease in the secretory function of the lacrimal and mucous glands on the basis of any systemic disease. Symptomatic DES develops as a result of "drying" of the tissues of the anterior part of the eye due to local causes or severe avitaminosis A.

Table 1

Clinical classification of corneal-conjunctival xerosis type of dry eye syndrome

____________________ Distinguishing signs ____________________
By etiology		By pathogenesis	According to clinical manifestations and severity
syndromic	Symptomatic
Caused by a decrease in the excretory function of the lacrimal and mucous glands on the basis of certain immune, endocrine diseases and collagenoses	It is associated with drying of the tissues of the anterior part of the eye due to incomplete closure of the eyelids, destructive and trophic corneal disorders, beriberi A.	Conditional: Deficiency in the production of SP components (tears, mucus or lipids); Decreased stability of the precorneal joint venture; The combined effect of two main pathogenetic factors	With macro-signs of xerosis (severe); With microsigns of xerosis (moderate); With microsigns of xerosis against the background of hyperlacrimia (mild).

From the above definitions, it follows that the first group should include patients with manifestations of female and male menopause, autoimmune diseases of the external secretion glands and collagenosis (Sjogren's syndrome, Stevens-Johnson syndrome, etc.), hereditary complex dysfunction of the autonomic nervous system (Riley- Day), some diencephalic disorders and other similar conditions (see.

Annex 1). According to R.I. Fox (1994), a number of systemic diseases are also associated with DES: infiltrative processes (lymphoma, amyloidosis, hemochromatosis, sarcoidosis), infectious diseases (diffuse infiltrative lymphadenopathy syndrome caused by human immunodeficiency virus, hepatitis B and C, syphilis, tuberculosis), as well as the autoimmune process of bone marrow transplant rejection. Should

It should be noted that Sjögren's syndrome, traditionally identified by most doctors in our country with DES, occupies a very modest share in the overall structure of the pathology under consideration. One of the reasons for the decrease in the secretion of the lacrimal glands and goblet cells of the conjunctiva, which has become relevant in recent years, is chronic radiation sickness (Gamus D., et al., 1994). It is partly associated with thyrotoxic and autoimmune ophthalmopathy, which we often observe in patients with DES referred from regions with radioactive contamination of the area. However, the specific mechanism of occurrence of the considered disorders in such patients is still not entirely clear.

In the etiology of symptomatic dry eye syndrome, the leading role is played by pronounced anatomical disorders of ocular localization: incomplete closure and (or) excessive opening of the palpebral fissure due to cicatricial or paralytic lagophthalmos, exophthalmos of various origins, endocrine (thyrotoxic and autoimmune) ophthalmopathy, as well as buphthalmos. The group under consideration also includes cases of dry eye syndrome caused by corneal trophism, deformation of the surface of the eyeball of a congenital or acquired nature (keratoconus, pterygium, symblepharon) and scarring of the lacrimal and mucous glands of the conjunctiva (stage IV trachoma, stage IV burn disease of the eye, conjunctival pemphigus). Xerosis may also develop as a result of functional failure of the lacrimal gland after dacryoadenitis, its extirpation due to a malignant tumor, congenital alacrymia, or inhibition of tear secretion as a result of prolonged use of certain pharmacological drugs or instillation of some of them into the conjunctival cavity (see Appendix 2).

A sharp decrease in the production of lacrimal fluid and mucins also occurs when the innervation of the lacrimal gland is disturbed (with lesions of the facial nerve, multiple sclerosis, etc.) and due to a lack of vitamin A in the body. Severe dysfunction of the meibomian glands is also of some importance.

(for example, with meibomian blepharitis). Finally, the group of patients under consideration should also include patients in whom the so-called transient DES is stimulated by permanent or temporary damage to the spinal joint by external artificial factors. These include smoke, smog, air-conditioned air (the so-called "office eye syndrome" - "office-eye syndrome": Sommer HJ. et al., 1994). electromagnetic radiation from monitors of computer or television systems, ultraviolet radiation (according to Michalos P., et al.; 1994), rays with X, = 100-280 nm are even partially absorbed by the tear film), cosmetics and, in particular, contact lenses .

The above list of reasons underlying the development of DES indicates that the problem under consideration is of great practical importance. So according to R.MarquardtuF.N.Wenz, referring to 1980, DES occurs in every third patient who first turned to an ophthalmologist. Our studies (1988-1996) revealed the presence of functional and clinical signs of this disease in all patients with a violation of the integrity of the corneal epithelium (acute inflammation, trauma, dystrophy), in 65.2% -91.7% - with chronic conjunctivitis and blepharoconjunctivitis of various etiologies, 90.0% with chronic dacryocystitis and 65.7% with the so-called reflex lacrimation. Figure 7 graphically shows the spectrum and frequency of occurrence of the main nosological forms related to DES in 486 such patients examined by us. It can be seen from the graph that the largest share in the structure of the considered pathology is occupied by dysfunction of the Becher glands of climacteric genesis (in women), burn eye disease, lagophthalmos of various etiologies, as well as transient disturbances in the stability of the joint venture due to its damage by environmental factors.

According to modern data, the pathogenesis of DES is not homogeneous. It usually presents with three main clinical types. The first of them is due to a decrease in the production of various components of the joint venture, with all the ensuing consequences. In particular,

a drop in total tear production leads to a decrease in the thickness of the aqueous layer of the joint venture, and a decrease in the secretion of mucins or lipids leads to a thinning of these layers. Various combinations of the violations discussed above are also possible. As a result, the joint venture in one way or another loses its strength properties.

Rice. 7. Quantitative structure of nosological forms of DES, diagnosed) 500 examined patients.

1 - Sjogren's syndrome; "2- dysfunction of Becher's glands on the basis of climacteric syndrome; 3- burn eye pain; 4- lagophthalmos of various etiologies; 5- endocrine ophthalmopathy; 6- absence of the lacrimal gland after extirpation; -7 - impaired innervation of the lacrimal gland; 8- pemphigus of the conjunctiva; 9 - transient DES caused by instillations of beta-blockers; 10 - transient DES caused by prolonged instillations of corticosteroids; 11-transient DES, stimulated by adverse environmental factors; 12 - transient DES, caused by wearing contact lenses.13 - transient "narcotic" lagophthalmos 14- DES of undifferentiated autoimmune etiology.

Let us dwell in more detail on the essence of the violations mentioned above. They boil down to the following: 1 - thinning of the aqueous layer of the SP will inevitably lead to "sticking" of lipids with mucins in the most "vulnerable" areas of the cornea (more often - in places

cleavage of dying epithelial cells) and to the formation of non-wetted areas of its surface (see Fig. 6); 2 - local deficiency of mucins impairs the wettability of the corneal epithelium. In this place, the joint venture, "smoothed out" by the previous blinking movements of the eyelids, immediately breaks, exposing the hydrophobic epithelial membrane; 3 - a decrease in the thickness of the lipid film results in an intensification of the evaporation of the aqueous layer of the joint venture.

The problem of tear evaporation from the conjunctival cavity in DES has received increasing attention in foreign literature in recent years. According to A. Heiligenhaus und and. (1995), in 78% of patients with DES, corneal-conjunctival xerosis was predominantly associated with an increase in SP volatility, and only in 8% with an isolated deficiency of tear production. At the same time, the value of the indicator under consideration, even in the norm, depends on the direction of gaze (Table 2).

table 2

Dependence of tear fluid evaporation on the area of ​​the open surface of the eyeball

(according to Tsubota K.., 1994; with clarifications).

However, the problem under consideration acquires the greatest significance in patients with a deficiency in the secretion of lacrimal fluid. So, with a decrease in tear production from 12 µl / min to 0.12 µl / min, only due to the normal evaporation of moisture (0.094 µl / min), up to 78% of its volume is lost. But even if the volatility of the liquid components of the tear decreases compensatory (usually due to

increase in lipid secretion) up to 0.057 µl/min, then in this case up to 47.5% of the moisture in the conjunctival cavity is lost (Fig. 8). Normally, this figure does not exceed 10% (Tsubota K.. 1994). In order to increase the stability of SP in such patients, K.Tsubotan K.N akamori (1995) even suggest recommending that patients slightly squint the palpebral fissure and, if possible, normalize the frequency of blinking movements.

Rice. Fig. 8. The ratio of indicators of production and evaporation of the lacrimal fluid in the norm (a) and in patients with the "dry eye" syndrome (b) (according to Tsubota K., 1994; with clarifications).

A decrease in the secretion of one of the components of the joint venture stimulates a compensatory increase in the production of its other structural elements. As a result, this leads to the development of reflex lacrimation or mucus secretion in the form of threads, painfully tolerated by patients. Hyperproduction of lipids is manifested by the formation on the eyelids (more often near the outer adhesion of the eyelids) of a characteristic white "foam", which is rather a cosmetic defect.

Below is a list of nosological forms of eye pathology (in descending order of frequency) related to the first pathogenetic type of DES, ecib, with deficiency

products of the main components of the joint venture. This circumstance causes the possibility of manifestation of the disease in four clinical variants:

1. With a predominant decrease in tear production due to one of the following reasons:

Absence or underdevelopment of the lacrimal gland (after extirpation in the development of a tumor, congenital aplasia or hypoplasia of the gland (congenital alacrimia, Bonnevie-Ulrich syndrome), senile or idiopathic atrophy of the lacrimal gland);

Violations of the innervation of the lacrimal glands (damage to the secretory "tear" fibers during surgical interventions on the temporal bone, pterygopalatine fossa, orbit, compression of the lacrimal fibers by a tumor, impaired blood supply, congenital aplasia of the secretory nucleus);

Dysfunction of the lacrimal gland after suffering dacryoadenitis;

Pharmacological inhibition of tear separation.

Hereditary complex dysfunction of the autonomic nervous system (Riley-Day syndrome);

2. With a predominant decrease in the secretion of mucins on the basis of dysfunction of Becher's conjunctival glands of climacteric genesis, vitamin A deficiency in food or exudative erythema multiforme (Stevens-Johnson syndrome).

3. With a violation of lipid production (meibomian blepharitis with a decrease in lipid production).

4. Combined forms (Sjogren's syndrome).

The second pathogenetic type of DES development is due to a decrease in the stability of the precorneal SP already due to secondary causes - lagophthalmos or pathology of the epithelial membrane, on which the "full-layer" SP either easily breaks or does not form at all. It is possible that the decrease in the secretion of mucins by epithelial cells of the conjunctiva and cornea is also important in this case. A similar situation, in particular, occurs in patients with squamous metaplasia of the conjunctival epithelium (for example, vitamin A deficiency, already mentioned above). Smoothing the villi

the anterior membrane of the epithelium, a decrease in the production of mucopolysaccharides by epithelial cells results in a thinning of the mucin layer of the SP and a violation of the interaction of mucins with the aqueous layer of the SP, the thickness of which decreases (Fig. 9).

Fig.9. Scheme of tear film structure disorders in patients with scaly metaplasia of the conjunctival epithelium (according to TsengS.C.G., 1987). a-norm; b- squamous metaplasia of the conjunctival epithelium.

1,2 and 3 - lipid, watery and mucin layers of the joint venture;

4- epithelial cell glycoprotein membrane coated with glycoconjugates that retain water-soluble mucins.

In addition, with corneal scars and symblepharon, the congruence of the contacting surfaces of the eyeball and eyelids is disturbed, as a result of which, with blinking movements of the eyelids, the normal “smoothing” of the tear film no longer occurs.

Clinical variants of pathological disorders typical for DES of the considered genesis are given (in descending order of frequency) below:

1. Lagophthalmos of various origins (cicatricial shortening of the eyelids; paresis or paralysis of the facial nerve; autoimmune ophthalmopathy

(1-2 (infiltrative and transition to fibrosis) stages); thyrotoxic ophthalmopathy; exophthalmos

post-traumatic and other nature; "Night" and "narcotic" incomplete closure of the eyelids.

2. Pathological changes in the surfaces of the cornea and conjunctiva (scars of various origins; symblepharon; true and false pterygium; epitheliopathy of various origins).

Xerophthalmia or xerosis is the name given to the drying of the mucous membrane of the eye. The appearance of xerophthalmia can cause a number of reasons.

This is usually caused by the following reasons:

• Prolonged local damaging effect.
• General diseases.

The first group of factors includes cicatricial changes in the conjunctiva due to:

• Trachoma, burns, diphtheria, pemphigoid, etc. They begin in the form of limited small areas, gradually involving all tissues of the conjunctiva and cornea in the pathological process.
• Ectropion and lagophthalmos, which cause incomplete covering of the surface of the eyeball with the eyelids.

Pathological changes in the development of xerophthalmia mainly occur in the epithelium, which gradually begins to resemble the epidermis of the skin. The secretion of mucus stops, new layers appear - granulation and horny. For this reason, there is a compensatory increase in the work of the meibomian glands, and therefore, the dry surface of the conjunctiva is completely covered with a greasy secret and the tear loses its ability to moisten the mucous membrane through wetting. With the development of the process, there is a high growth of xerosis bacilli (non-pathogenic microflora of the conjunctival cavity), although the named saprophyte has no causal relationship with this disease.

It should be noted that with xerophthalmia, there are no disturbances in the work of the lacrimal apparatus. The disease does not occur even as a result of extirpation (removal) of the lacrimal gland, since the conjunctiva is able to effectively wet itself with its own secret. But, when the secretory function of the conjunctiva itself decreases, xerophthalmia can occur, including with normal or even high production of lacrimal fluid in the eyes.

The second group of xerophthalmia factors includes a deficiency in the diet of a fat-soluble vitamin. The pathological process, while having a rather mild form, is accompanied by twilight blindness and is usually observed in children, often in boys. The conjunctiva with the development of xerophthalmia loses its transparency, becomes dry. Small triangular, rough spots appear on the surface of the mucous membrane, on the outer and inner sides of the cornea. The spots are covered with foamy discharge, which is not washed off with a tear (the so-called Iskersky-Bito spots). These spots are formed due to excess secretory fluid of the meibomian glands, which, when blinking, whips into foam, and then mixes with the deflated corneal epithelium and settles on the altered areas of the dry, rough conjunctiva. Such changes in children are typical for the summer months, and are not necessarily associated with poor nutrition. Similar mild forms of xerophthalmia, accompanied by night blindness, are also often detected in children with mental retardation and are often combined with keratomalacia or corneal necrosis.

Turning to the Moscow Eye Clinic, each patient can be sure that one of the best Russian specialists will be responsible for the results of treatment. Confidence in the right choice, of course, will be added by the high reputation of the clinic and thousands of grateful patients. The most modern equipment for the diagnosis and treatment of eye diseases and an individual approach to the problems of each patient are a guarantee of high treatment results at the Moscow Eye Clinic. We diagnose and treat children over 4 years of age and adults.

3
1 St. Petersburg State Pediatric Medical University of the Ministry of Health of Russia, St. Petersburg
2 SBEE HPE "St. Petersburg State Pediatric Medical University" of the Ministry of Health of Russia; GBUZ "Mariinsky Hospital", St. Petersburg
3 St. Petersburg State Medical University of the Ministry of Health of Russia, St. Petersburg, Russia

Drug therapy today occupies a leading place in the treatment of patients with dry eye syndrome. It is aimed at replenishing the moisture deficit in the conjunctival cavity, stopping the inflammatory process, tear film hyperosmolarity, normalizing local immunity, etc.
In many ways, these tasks are solved by tear substitutes of various composition. An effective direction in the treatment of such patients is metabolic therapy, the possibilities of which have expanded today due to the development of the “artificial tear” Stillavit® containing 0.05% sodium chondroitin sulfate, 0.16% sodium hyaluronate and 1% dexpanthenol. The effect of the drug is manifested due to its high moisturizing, anti-inflammatory properties, as well as stimulation of reparative processes in the tissues of the ocular surface.
Keywords:"dry eye" syndrome, xerosis of the ocular surface, "artificial tears" preparations, Stillavit.
For citation: Brzhesky V.V., Kalinina I.V., Popov V.Yu. New opportunities for drug therapy in patients with corneal-conjunctival xerosis // BC. Clinical ophthalmology. 2016. No. 1. P. -46.

For citation: Brzhesky V.V., Kalinina I.V., Popov V.Yu. New opportunities for drug therapy in patients with corneal-conjunctival xerosis // BC. Clinical ophthalmology. 2016. No. 1. pp. 39-46

New possibilities of drug-based therapy in patients with corneoconjunctival xerosis

Brzhesky V.V. 1, Kalinina I.V. 2 , Popov V.Yu. 1

1 Saint Petersburg State Medical Pediatric University, Russia
2 Mariinsky Hospital, St. Petersburg, Russia

Today drug-based therapy is the most convenient treatment in patients with dry eye syndrome (DES). It makes up tear deficiency in the conjunctival cavity, decreases inflammation, hyperosmolarity of the tear film and normalizes the local immunity.
The artificial tears can solve some of these problems. Metabolic therapy is effective in patients with DES. Eye drops Stillavit® contains 0.05% - sodium chondroitin sulfate, 0.16% - sodium hyaluronate and 1% - dexpanthenol, which provides a comprehensive pharmacological effect, e.g. moisturizing (due to acid hyaluronic and chondroitin sulfate), stimulation of reparative processes in ocular surface tissue (due to all 3 components), and anti-inflammatory activity (due to chondroitin sulfate).
The paper addresses main directions of drug-based therapy in patients with DES (anti-inflammatory, immunomodulating, metabolic therapy and osmoprotection of ocular surface epithelium).
keywords: dry eye syndrome, xerosis of the ocular surface, artificial tears, Stillavit.
For citation: Brzhesky V.V., Kalinina I.V., Popov V.Yu. New possibilities of drug-based therapy in patients with corneoconjunctival xerosis // RMJ. clinical ophthalmology. 2016. No. 1. P. 39–46.

The article is devoted to new possibilities of drug therapy in patients with corneal-conjunctival xerosis

For a number of years, the dry eye syndrome (DES) has not lost its significance in the structure of ophthalmic pathology. On the one hand, this is due to the wide prevalence of the disease in question, on the other hand, to the severity of the clinical course and outcomes of some of its clinical forms. In particular, according to a number of researchers, in recent years DES has been observed in 4–8% of adolescents, 12–22% of people over 40 years old, and 30–34% over 65 years old.
At the same time, the clinical manifestations of DES, which consist in the development of the so-called corneal-conjunctival xerosis (RCC), are often accompanied by irreversible morphological changes in the conjunctiva and, mainly, the cornea. At the same time, as practice shows, they can be found in a wide range: from minimal degenerative changes in the epithelium to a deep destructive process: a progressive corneal ulcer or even keratomalacia.
As is known, the central link in the pathogenesis of DES is a violation of the stability of the precorneal tear film (PSP) with an increase in its volatility and an increase in osmolarity. This is accompanied by dehydration of the epithelial cells of the ocular surface (due to the transfer of moisture from them into the hypertonic tear film), the development of an inflammatory reaction of the cornea and conjunctiva. Together, these conditions aggravate each other, leading to metabolic disorders in the epithelium of the ocular surface, clinically manifested by its degenerative changes. As a result of these processes, the stability of the tear film is disturbed, its volatility and osmolarity increase even more, and a vicious circle closes.
Accordingly, the treatment of such patients should also include a set of measures aimed at stopping pathogenic factors that are links in this vicious circle (Fig. 1). It includes tear replacement, metabolic, anti-inflammatory (if necessary, immunosuppressive) therapy, correction of the osmolarity of the tear film and / or corneal and conjunctival epithelial cells, and others, including surgical therapeutic measures.

Of course, the treatment of patients in this category traditionally begins with drug therapy, the basis of which for many years has been the use of "artificial tears" preparations. They are designed to compensate for the lack of moisture in the conjunctival cavity and increase the stability of the PSP. In addition, they "dilute" the moisture of the conjunctival cavity, reducing its osmolarity and, accordingly, prevent dehydration of the ocular surface epithelium.
Table 1 shows the drugs currently registered in Russia. They differ mainly in viscosity and chemical composition, which ultimately determines their clinical effect.

The pharmacological effect of these drugs is due to their substituting effect mainly on the mucinous and aqueous layers of the PSP. The hydrophilic polymers of artificial origin included in their composition (derivatives of methylcellulose, polyacrylic acid, polyvinyl alcohol, polyvinylpyrrolidone, etc.), as well as natural mucopolysaccharides, trehalose disaccharide and many others, mix with the remnants of native tears and stabilize PSP.
"Artificial tear" is instilled into the conjunctival cavity of the diseased eye, like any other eye drops, with a frequency of 3-4 rubles / day. In the future, the frequency of instillations of the drug is regulated by the patient himself, focusing on the resumption of subjective discomfort after the previous instillation.
The preparations under consideration are divided into 3 groups: low and high viscosity, as well as eye gels (Table 1).
Gel preparations are usually instilled less often than low viscosity tear substitutes. As practice shows, in most cases, it is advisable for patients with RCC to combine ophthalmic gels with low-viscosity preparations. At the same time, a gel preparation is instilled as a base drug in patients with moderate and severe xerosis (“artificial tears” of low viscosity only supplement therapy), and with mild and, conversely, extremely severe DES, low-viscosity tear substitutes are instilled. The gel preparation is prescribed to such patients once, at night. The last "point" in the choice of the drug "artificial tears" is still its individual tolerance to specific patients.
Many of the “artificial tears” preparations listed in Table 1, along with the ability to stabilize the tear film, also have additional properties that allow them to implement some of the above directions in the complex treatment of patients with DES.
In particular, a number of tear substitutes, in addition to the qualities discussed above, also have the properties to stimulate metabolic processes in the tissues of the cornea and conjunctiva. Such preparations contain substances that stimulate the reparative regeneration of the cornea.
In particular, such additional ingredients of tear substitutes that stimulate metabolic processes are dexpanthenol, sodium heparin, vitamin B12 (cyanocobalamin), vitamin A, mitochondria-targeted antioxidant SkQ1, etc. .
Some polymer bases of "artificial tears" preparations, which combine the functions of stabilizing PSP and stimulating metabolic processes in the epithelium of the ocular surface, also possess no less significant metabolic activity.
Among the considered polymer bases of tear substitutes, natural mucopolysaccharides have a similar effect: hyaluronic acid (HA) (in the range of 0.1–0.3%), hydroxypropyl guar, chondroitin sulfate (0.05%), trehalose (3%) and tamarind seed polysaccharide ( TS-polysaccharide).
Of the "artificial tears" based on natural polysaccharides, HA preparations are the most widely used. As is known, along with high metabolic activity (stimulation of corneal epithelial cell migration and reparative capabilities of the corneal and bulbar conjunctiva stroma, antioxidant properties, etc.), HA has a number of characteristics that determine its moisturizing properties. The main ones are the concentration of HA in an aqueous solution of a tear substitute and its molecular weight, which is directly proportional to the length of the molecular chain of the polysaccharide. Both concentration and molecular weight determine the rheological properties of such solutions.
Molecules of HA twist in an aqueous solution with the formation of a spatial structure of a "coil". At a concentration of ≥1 mg/ml (≥0.1%), these molecules begin to contact each other, and at higher concentrations, their "coils" mutually penetrate each other and form a flexible three-dimensional molecular network - the so-called "molecular sponge" that binds water .
The results of a number of studies have found that HA solutions with a concentration of 0.1–0.3% have therapeutic efficacy in RCC. At the same time, the lower limit of viscosity is determined by the minimum pharmacological effect of the drug, and the upper limit is determined by the individual sensitivity of a patient with dry eye to it, since with a further increase in the concentration of HA, the tolerability of such solutions deteriorates due to a significant increase in their viscosity.
Another natural polymeric compound is chondroitin sulfate. This glycosaminoglycan is associated with a number of clinical effects, the main of which are anti-inflammatory action and stimulation of reparative regeneration. In particular, chondroitin sulfate is able to bind to damaged collagen structures of the cornea, reduce the chemoattraction of cytokines and other inflammatory mediators in the lesion. It also tends to modulate reparative processes without excessive scarring, by binding protofibrils into fibrils and organizing fibrils into collagen fibers. And finally, chondroitin sulfate stimulates the production of the cornea's own glycosaminoglycans, which regulate healing processes and prevent excessive scarring and clouding of the cornea.
As part of one "artificial tear" preparation, Stillavit® managed to combine 0.05% sodium chondroitin sulfate, 0.16% sodium hyaluronate and 1% dexpanthenol, thus providing a complex pharmacological effect. The latter is manifested by a pronounced moisturizing effect of the drug (the effect of hyaluronic acid and chondroitin sulfate), stimulation of reparative processes in the tissues of the ocular surface (all three components of the drug), as well as an anti-inflammatory effect (chondroitin sulfate).
The indication for the appointment of the drug Stillavit® is the presence of DES in a patient, accompanied by xerotic changes in the epithelium of the ocular surface. However, taking into account the fact that Stillavit® is a low-viscosity "artificial tear" preparation, the area of ​​its application can naturally be expanded.
Of course, the therapy of patients with DES is not limited to the use of tear substitutes of the considered direction. It is supplemented by metabolic agents (dexpanthenol, deproteinized dialysate from the blood of healthy dairy calves, sulfated glycosaminoglycans, retinol palmitate (vitamin A), etc.).
Along with metabolic therapy, therapeutic measures aimed at preventing and relieving the inflammatory process associated with DES are gaining increasing clinical acceptance (Fig. 1).
In particular, patients in whom DES is associated with increased volatility and hyperosmolarity of the tear film are shown tear substitutes containing osmoprotectors: levocarnitine and erythritol or glycerin. Osmoprotectors, penetrating into the cells of the epithelium of the ocular surface, increase their osmolarity, preventing dehydration due to the loss of intracellular fluid into the "hyperosmolar" tear film along the osmotic gradient.
An important direction in the treatment of patients with DES is anti-inflammatory therapy. Traditionally, it is based on instillations of glucocorticosteroid drugs. However, in the treatment of patients with RCC, their effect is ambiguous.
On the one hand, the drugs in question are the most effective anti-inflammatory drugs, moreover, they have an antiproliferative effect that prevents excessive scarring of the tissues of the eye surface and corneal conjunctivization. On the other hand, their long-term use is often accompanied by thinning of the xerotically altered cornea, progression of the ulcerative process with the development of appropriate complications.
Taking into account these circumstances, it is necessary to prescribe official preparations of glucocorticosteroids to patients with corneal xerosis, accompanied by clinical signs of inflammation, only when it is completely epithelized. Strict control of corneal thickness is required during treatment. In other situations (with the exception of cases of extensive de-epithelialization of the cornea or its ulceration), it is advisable to confine ourselves to instillations of a low concentration of dexamethasone solution (0.01%) into the conjunctival cavity. Moreover, the tolerance of this drug is significantly improved when using a 6% solution of polyvinylpyrrolidone as a solvent for the medicinal substance. Possessing a fairly pronounced anti-inflammatory effect, the drug has the properties of an "artificial tear" (6% polyvinylpyrrolidone), providing a complex therapeutic effect.
Instillations of glucocorticosteroid drugs into the conjunctival cavity are contraindicated in patients with severe destructive changes in the cornea of ​​a xerotic nature, including extensive erosions, ulcers, etc. In such cases, non-steroidal anti-inflammatory drugs come to the fore. Of these, 0.09% bromfenac is used for these purposes. It is enough to bury it 1 rub./day.
Systemic use of tetracycline (doxycycline, minocycline) serves as an adjunct to local anti-inflammatory therapy. In recent years, it has been established that, along with a dubious antibacterial effect, the antibiotics in question have a rather tangible anti-inflammatory effect. In particular, it is known that these drugs are able to inhibit the activity and synthesis of matrix metalloproteases, the synthesis of nitric oxide and interleukin-1, as well as tumor necrosis factor alpha in various tissues, including the epithelium of the ocular surface. Tetracycline is administered orally in tablets at a dose of 50-100 mg / day, doxycycline - from 40 to 200 mg / day for 2-3 months, minocycline - 100 mg / day for 3 months. .
And yet, taking into account the need for prevention in patients with this category of secondary infection, it was quite timely to prescribe instillations into the conjunctival cavity of 1% azithromycin, which, along with pronounced antibacterial activity, also has a proven anti-inflammatory effect.
A very effective direction in the treatment of patients with severe and extremely severe course of RCC is immunosuppressive therapy. The basis of this therapeutic area today is the systematic instillation of 0.05% cyclosporine into the conjunctival cavity. An ophthalmic solution of 0.05% cyclosporine, registered in our country, is instilled into the conjunctival cavity of the diseased eye at a frequency of 2 times a day for 6 months. . It should be noted that the instillations of this drug are not without side effects, which are mainly in its irritating effect.
This circumstance was a stimulus for the modification of cyclosporine preparations in order to improve their tolerability, but without reducing the effectiveness. In particular, a cationic cyclosporine emulsion with improved drug tolerance and increased duration of its stay in the conjunctival cavity was developed, which made it possible, on the one hand, to increase the dose of cyclosporine in eye drops and dispense with its single instillation during the day, on the other.
In some cases of corneal ulcer progression in patients with an extremely severe form of RCC, it is advisable to supplement the ongoing therapy with 4-6-fold instillations of anti-enzymatic drugs into the conjunctival cavity: aprotinin or its analogues. The main directions of therapeutic measures carried out in patients with various features of the clinical course of RCC are presented in Table 2.
Significantly less practical use was received by stimulants for the production of PSP components (Table 3). These include the pentoxifylline used in our country, which has a vasodilating effect, improves microcirculation, blood rheology and oxygen supply to tissues.

At the suggestion of A.I. Eremenko and S.V. Yanchenko (2010), pentoxifylline is administered both parabulbarno, at a dose of 0.5 ml of a 2% solution (10 mg), and lymphotropically (mixed with an anesthetic), in courses of 8 injections. E.E. Lutsevich et al. (2005), E.A. Matevosova (2009) and others.
An important aspect of the treatment of patients with syndromic forms of RCC is the therapy of a systemic disease associated with DES, which is prescribed and controlled by a specialist of the appropriate profile (rheumatologist, endocrinologist, hematologist, etc.).
In general, medical treatment of corneal diseases of xerotic etiology is not an easy task. At the same time, a rational choice of "artificial tears" preparations, which include metabolically active ingredients, anti-inflammatory, immunosuppressive and other drugs, creates optimal conditions for both the prevention of these diseases and their timely treatment. These circumstances stimulate the active prescription of the drugs discussed above, registered in our country, to patients with DES, and the further development of domestic drugs of the appropriate direction.

Literature

1. Tsubota K., Kawashima M., Inaba T. et al. The antiaging approach for the treatment of dry eye // Cornea. 2012. Vol. 31(1). P. 3–8.
2. Versura P., Profazio V., Giannaccare G. et al. Discomfort symptoms reduction and ocular surface parameters recovery with Artelac Rebalance treatment in mild–moderate dry eye // Europ. J. Ophthalmol. 2013. Vol. 23(4). P. 488–495.
3. Brzhesky V.V., Somov E.E. Corneal-conjunctival xerosis (diagnosis, clinic, treatment). 2nd ed., revised. and additional St. Petersburg: Levsha, 2003.
4. Brzhesky V.V., Kalinina I.V. The main directions of drug therapy in patients with corneal-conjunctival xerosis // Medical Council. 2015. No. 11. C. 120–125.
5. Brzheskiy V.V., Efimova E.L., Vorontsova T.N. et al. Results of a multicenter, randomized, double-masked, placebo-controlled clinical study of the efficacy and safety of visomitin eye drops in patients with dry eye syndrome // Advances in Therapy. 2015. Vol. 32 (12). P. 1263–1279.
6. Skulachev M.V., Antonenko Y.N., Anisimov V.N. et al. Mitochondrial-targeted plastoquinone derivatives. Effect on senescenceandacuteage-related pathologies // Curr. drug targets. 2011 Vol. 12. P. 800–826.
7. Li J., Roubeix Ch., Wang Y. et al. Therapeutic efficacy of trehalose eye drops for treatment of murine dry eye induced by an intelligently controlled environmental system // Molec. Vis. 2012. Vol. 18. P. 317–329.
8. Müller-Lierheim W.G.K. Trunenersatzlösungen. Neues über Hyaluronsäure // Aktuelle Kontaktologie. 2015. Vol. 11 (24). P. 17–19.
9. Ridder W.H., Karsolia A. New drugs for the treatment of dry eye disease // Clinical Optometry. 2015. Vol. 7. P. 91–102.
10. Hamano T., Horimoto K., Lee M., Komemushi S. Sodium hyaluronate eye drops enhance tear film stability // Jap. J. Ophthalmol. 1996 Vol. 40(1). P. 62–65.
11. Takhchidi E.Kh., Gorbunova K.S. The use of sulfated glycosaminoglycans in ophthalmology // Vestnik OGU. 2012. No. 148 (12). pp. 201–204.
12. Guillon M., Maissa C., Ho S. Evaluation of the effects on conjunctival tissues of Optive eye drops over one month usage // Contact Lens Ant. eye. 2010 Vol. 33(2). P. 93–99.
13. De Paiva C.S., Corrales R.M., Villarreal A.L. et al. Apical corneal barrier disruption in experimental murine dry eye is abrogated by methylprednisolone and doxycycline // Invest. Ophthalmol. Vis. sci. 2006 Vol. 47. P. 2847–2856.
14. Fujishima H., Fuseya M., Ogata M., Murat D. Efficacy of bromfenac sodium ophthalmic solution for treatment of dry eye disease // Asia Pac. J. Ophthalmol. 2015. Vol. 4(1). P. 9–13.
15. Li D.Q., Luo L., Chen Z. et al. JNK and ERK MAP kinases mediate induction of IL-1beta, TNF-alpha and IL-8 following hyperosmolar stress in human limbal epithelial cells // Exp. Eye Res. 2006 Vol. 82. P. 588–596.
16. Aronowicz J.D., Shine W.E., Oral D. et al. Short term oral minocycline treatment of meibomianitis // Brit. J. Ophthalmol. 2006 Vol. 90. P. 856–860.
17. Foulks G.N., Borchman D., Yappert M., Kakar S. Topical azithromycin and oral doxycycline therapy of meibomian gland dysfunction: a comparative clinical and spectroscopic pilot study // Cornea. 2013. Vol. 32(1). P. 44–53.
18. Perry H.D., Solomon R., Donnenfeld E.D. et al. Evaluation of topical cyclosporine for the treatment of dry eye disease // Arch. Ophthalmol. 2008 Vol. 126(8). P. 1046–1050.
19. Zhurova S.G., Brzhesky V.V., Kalinina I.V., Efimova E.L. Treatment of corneal ulcer of xerotic etiology // BC. Clinical ophthalmology. 2010. No. 11 (2). pp. 49–52.
20. Rocha E.M., Сotrim A.P., Marques D.L. et al. Secretagogues, mucolytics and anticollagenolytics for dry eye diseases treatment // Ocular surface disorders / Ed by: J.M. Benitez del Castillo, M.A. Lemp. London etc.: JP Medical LTD, 2013, pp. 263–266.
21. Eremenko A.I., Yanchenko S.V. Optimization of therapy for the age-related form of the "dry eye" syndrome. Ophthalmologicheskie Vedomosti. 2010. No. 3 (2). pp. 73–80.
22. Lutsevich E.E., Safonova T.N., Labidi A. et al. Possibilities of stimulation of tear production // Modern methods of diagnosis and treatment of diseases of the lacrimal organs. M. 2005. S. 201–204.
23. Matevosova E.A. Possibilities of stimulation of tear secretion in patients with hypolacrimia in the syndrome of "dry" eye: Abstract of the thesis. dis. … cand. honey. Sciences. M., 2009 .