Stargardts disease. Stargardt's disease - causes of pathology, diagnostic measures, treatment methods for Stargardt, statistics of visual impairment

It’s a pleasure to talk to Mikhail: he is smart and well-read, has many hobbies, and can talk about the main thing - auto racing - for hours. An intelligent face - glasses adorn it. A calm, confident young man, 18 years old. And it’s even stranger to listen to what he says.

Stargardt's dystrophy: the road to blindness

“My vision has always been poor. I have been seeing an ophthalmologist since childhood. I took it calmly, the glasses didn’t bother me. And at the age of 16, I began to notice that in the dark I could see worse and worse. In addition, some areas of vision began to disappear, literally: I see here, I don’t see here. To be honest, I was scared.

A visit to the military registration and enlistment office put an end to it. The medical commission issued a verdict: “retinal abiotrophy.”

At home with our parents, we turned the entire Internet upside down, through friends we received consultations from several ophthalmologist professors, we found access to clinics in Israel, Germany, the USA... Everywhere we thought medicine could do anything, we were told that there was no hope for a successful outcome of treatment.

I had no options other than blindness.”

“Stargardt abiotrophy is a fairly common genetic disease. According to statistics, it occurs in one in 20,000 people. Thus, in Russia alone there are about 7,000 patients who, because of it, are losing or have already lost their sight.

Yellow-spotted fundus, another name for this syndrome, usually manifests itself in adolescence and early adolescence - from 12 to 16 years. Loss of vision usually occurs very abruptly - in Mikhail's case, the process took only six months.

Mikhail came to UnikaMed at the age of 18, that is, a year and a half after his diagnosis. By this point, he could see practically nothing in the darkness, he was observed scotomas- loss of areas of vision.

Without correction, the right eye saw 20%, the left - 15%. After optical correction, the right eye was 65%, the left eye was 55%.

The dynamics of the development of the process suggested complete loss of vision by the age of 20.”

Stargardt degeneration is not a death sentence

“We continued to search, and on the UnikaMed website we read that they treat Stargardt syndrome! It was hard to believe, but we went to Moscow.

After the first session of regenerative therapy, I began to see better in the dark, my vision improved. It felt like someone had finally washed the dirty windshield that was blocking the view. Fantastic!

I've had three sessions in total so far - I'm taking a break now. After 6 months you will need to undergo another procedure. By the way, I’ve already returned to motorsport, including night racing!”

“There are, of course, no miracles and no fantasy in the case of Mikhail.

In short, regenerative therapy is based on a unique cellular autologous transplant that stimulates retinal renewal (the prefix “auto” denotes a transplant for which cells are taken from the person himself and transplanted into him).

The use of the method shows a positive effect in almost all patients. The field of vision expands and its sharpness improves. And if the disease is not genetic or very advanced, we always see a significant improvement in visual acuity and quality.

Complex diseases, like Mikhail’s, stop progressing. The condition of the retina and its nutrition improves - accordingly, improves significantly and visual function.

In Mikhail’s case, three months after the first session of regenerative therapy, the scotomas disappeared, and his vision indicators changed as follows:

Without optics: right eye - 30%, left - 25%

With selected optics: right eye - 85%, left eye - 75%.

Now, after three treatment sessions, Mikhail does not yet need further therapy, but in 6-8 months he should come back for an examination: no matter how magical the method may seem, no one has yet learned how to reprogram genes, and to maintain the result, the treatment must be repeated periodically ."

Marina Yurievna, chief physician of the UnikaMed clinic

Mikhail’s case is far from isolated: people who have been rejected by other clinics come to us at UnikaMed. And even at the stage of blindness, many of them, thanks to regenerative therapy, restore their vision.

How does the procedure work?

Regenerative therapy does not require a hospital stay. Cellular material transplantation is performed on an outpatient basis within one day: the patient spends 10-12 hours in the clinic.

But what seems like a miracle from the outside is actually the result of painstaking work.

The production of a transplant begins with the collection of bone marrow. Then it is prepared in a special way. The cell preparation procedure is very complex. It requires special equipment, the simultaneous participation of several excellent cell biologists in the process, and the precise sequential execution of a series of operations.

The resulting material is administered to the patient using a special technology, depending on his disease and the condition of his visual organs.

In the evening, after an examination by an ophthalmologist, you are discharged home until the next procedure. The interval between procedures is determined individually, but their effect is cumulative. And if, say, three months are required between the first, second and third procedures, then six months may pass between the third and fourth. And so on.

Between procedures, treatment of Stargardt disease requires regular follow-up an ophthalmologist in order to “intercept” possible vision loss in time.

Of course, it is easier to get an effect when treating the disease at a very early stage, without waiting for loss of vision, complete or partial. If you notice that vision gets worse(especially in the dark or at dusk), if your field of vision has narrowed, if colors have begun to seem less bright to you, take the time to see an ophthalmologist.

There are fewer and fewer incurable diseases - and at the UnikaMed clinic we have every opportunity for this. Regenerative therapy shows positive results not only in patients with Stargardt disease, but also in the treatment of optic nerve atrophy, macular degeneration of various natures, and other forms.

Stargardt's disease, which is a classic example of central pigmentary degeneration, was described by K. Stargardt (1909, 1913) at the beginning of the 20th century. as a hereditary disease of the macular region, manifesting itself in childhood and young age (7-20 years). Changes in the fundus, although polymorphic, are characterized by the appearance in both eyes of pigmented round dots, areas of depigmentation and atrophy of the retinal pigment epithelium (RPE), in some cases of the “bull’s eye” type, often combined with whitish-yellowish spots in the paramacular zone. A similar clinical picture of progressive degeneration of the macular region of the retina in children was described back in the 19th century.

Changes in the form of yellowish-whitish dots and stripes with or without changes in the macular area were designated by A. Franceschetti with the term “fundus flavimaculatus”. In the literature, the terms “Stargardt disease” and “fundus flavimaculatus” are often combined (Stargardt disease/fundus flavimaculatus), thereby emphasizing the presumed unity of origin and/or transition from one form of the disease (Stargardt disease) to another (fundus flavimaculatus) as it develops .

If vision loss, caused by typical dystrophic changes in the macula, begins in the first two decades of life, then it is preferable to use the term “Stargardt disease.” If changes appear in the central and peripheral parts of the retina at a later age and the disease progresses more acutely, then it is recommended to use the term “fundus flavimaculatus”.

It has been established that this is a heterogeneous group of diseases with hereditary transmission.

Symptoms (in order of appearance):

• In the fovea - without changes or with redistribution of pigment
• Oval lesions of the "snail track" type or bronze reflex, which may be surrounded by white-yellow spots.
• "Geographic" atrophy may have a "bull's eye" appearance.

Classification

Along with the classical distinction of two types of Stadgardt's disease, including dystrophy of the macular region with and without fundus flavimaculatus, several other classifications have been proposed based on variations in the clinical picture of the fundus.

So, K.G. Noble and R.E. Carr (1971) identified four types of diseases:

• Type I - macular degeneration without spots (mottling). Visual acuity decreases early.
• II - with parafoveal mottling,
• III - macular degeneration with diffuse mottling,
• Type IV - diffuse mottling without macular degeneration. Visual acuity remains quite high, since retinal damage does not affect the foveal region.

Genetic research

Stargardt's dystrophy is most often inherited in an autosomal recessive manner, but many families have been described in which the disease is transmitted in an autosomal dominant manner. There is an opinion that the dominant type of inheritance is characteristic mainly of types III and IV of Stargardt disease.

Positional cloning identified a disease-causing gene locus for Stargardt disease expressed in photoreceptors, which was named ABCR. ABCR has been shown to be identical in sequence to the human RmP gene.

The RmP protein is an integral membrane glycoprotein with a molecular weight of 210 kDa, which is localized along the edge of the discs of the outer segments of visual cells. RmP has been shown to belong to the ABC superfamily of ATP-binding cassette transporters, which stimulate ATP hydrolysis and influence the ATP-dependent movement of specific substrates across cell membranes.

Genes for several members of the ABC transporter superfamily have been found to be involved in the development of a number of hereditary diseases of the human retina. Thus, in the autosomal dominant type of inheritance of Stargardt disease, the localization of mutated genes on chromosomes 13q and 6ql4 was shown, and the gene for a new dominant form of Stargardt-like retinal disease (possibly related to type IV) was mapped on chromosome 4p between markers D4S1582 and D4S2397.

The human RmP gene is mapped between markers D1S424 and D1S236 on the lp chromosome (Ip21-pl3). The genes for the most common autosomal recessive form of Stargardt's dystrophy and fundus flavimaculatus are also localized there, and the location of the gene for the autosomal recessive form of retinitis pigmentosa RP19 is determined between markers D1S435-D1S236 on the lp chromosome. In the study by S.M. Azarian et al. (1998) established the complete thin intron-exon structure of the ABCR gene.

Immunofluorescence microscopy and Western blot analysis have shown that ABCR is present in foveal and perifoveal cones, suggesting that the loss of central vision in Stargardt's dystrophy may be a direct consequence of foveal cone degeneration caused by mutations in the ABCR gene.

It was also revealed that ABCR mutations are present in a subpopulation of patients with non-exudative age-related macular degeneration (AMD) and cone-rod dystrophy, which suggests the presence of a genetically determined risk of developing AMD in relatives of patients with Stargardt disease. However, not all researchers support this statement, although there is no doubt that the phenotypic and genotypic manifestations of Stargardt disease and AMD are associated with mutations of the ABCR gene.

J.M. Rozet et al. (1999), examining a family that included among its members patients with both retinitis pigmentosa and Stargardt disease, showed that heterozygosity of the ABCR gene leads to the development of Stargardt dystrophy, and homozygosity leads to the development of retinitis pigmentosa.

Thus, the results of genetic studies in recent years indicate that, despite the obvious differences in the clinical picture of retinitis pigmentosa, Stargardt disease, fundus flavimaculatus and AMD, they are allelic disorders of the ABCR locus.

The wide range of phenotypic manifestations of Stargardt's dystrophy and the age of detection of clinical signs (from the first to the seventh decade of life), observed even in one family, makes differential diagnosis and prognosis of changes in visual acuity difficult. Angiography data, medical history, reduced visual function, altered cone components in the ERG, the specifics of changes in local and multifocal ERG help in making a diagnosis.

Thus, in recent years, the results of genetic studies have become increasingly important for diagnosis. So, G.A. Fishman et al. (1999), having examined a large group of patients with Stargardt's dystrophy and fundus flavimaculatus with mutations of the ABCR gene, showed that the variability of phenotypic manifestations in a certain way depends on variations in the specific amino acid sequence. Based on the results of fluorescein angiography, ophthalmoscopy, electroretinographic and perimetric studies, they identified three disease phenotypes

• One of these phenotypes is characterized, along with atrophic damage to the macula, by the appearance of perifoveal yellowish-white spots, the absence of a dark choroid and the normal amplitude of ERG waves. In this phenotype, a sequence change was identified in exon 42 of the ABCR gene, consisting of the replacement of glycine with glutamine (Gly]961Glu).
• The other phenotype was characterized by a dark choroid and yellowish-white spots more diffusely scattered across the fundus, but no Glyl961Glu substitution was detected.
• In a phenotype with pronounced atrophic changes in the RPE and reduced rod and cone ERGs, the ABCR mutation was found in only one patient out of 7.

Due to the fact that ABCR mutations are accompanied by various phenotypic manifestations, it is believed that advances in identifying correlations between specific gene mutations and clinical phenotypes will facilitate counseling of patients regarding the prognosis of visual acuity.

All these studies are aimed not only at revealing the subtle mechanisms of genetic diseases of the retina, but also at finding possible therapies for them.

Clinical picture

line of sight

With fundus flavimaculatus, the field of vision may not be changed, especially in the first two decades of life; in all patients with Stargardt disease, relative or absolute central scotomas of varying sizes are detected, depending on the distribution of the process in the macular region.

Color vision

Most patients with type I Stargardt disease have deuteranopia; in type II Stargardt disease, color vision impairments are more pronounced and cannot be classified. The type of color abnormality appears to depend on which type of cones is predominantly involved in the pathological process, therefore, with fundus flavimaculatus, color vision may not be affected or red-green dichromasia may be observed.

Dark adaptation

According to O. Gelisken, J.J. De Jaey (1985), of 43 patients with Stargardt disease and fundus flavimaculatus, 4 had an increased final threshold of light sensitivity, 10 had no cone segment of the dark adaptation curve.

Spatial contrast sensitivity

In Stargardt's dystrophy, it is changed throughout the entire frequency range with a significant decrease in the region of medium spatial frequencies and its complete absence in the region of high spatial frequencies - the pattern of cone dystrophy.

Contrast sensitivity , on- and off-activity of the cone system, assessed by the time of the sensorimotor reaction upon presentation of a stimulus darker and lighter than the background, are absent in the central region of the retina with some preservation of off-sensitivity in the zone 10° from the center.

Electroretinography and electrooculography

Of the electrophysiological methods, electroretinography and electrooculography are the most informative in the diagnosis and differential diagnosis of diseases of the macular region of the retina.
According to the literature, in the initial stages of Stargardt's dystrophy and fundus flavimaculatus, the general, or ganzfeld, ERG is normal. However, the use of various methodological techniques of electroretinography makes it possible to assess the topic of functional disorders in the retina at the level of its various layers and sections.

Thus, when recording local ERG (LERG) using an LED mounted in a suction lens, the biopotentials of the macular region are subnormal already in the initial stage of Stargardt dystrophy, in contrast to the normal ganzfeld ERG amplitudes. As the process progresses, LERH decreases until it disappears completely. Other authors also note an increase in peak latency and a decrease in the amplitudes of local foveal responses; in 64% of patients with fundus flavimaculatus with visual acuity of 20/20 - 20/30.

The use of zonal electroretinography made it possible to detect inhibition of the reaction of the outer layer of the retina (photoreceptors) not only in the macular zone, but also in the paramacular and peripheral parts in the early stages of Stargardt's disease while the proximal layers of the retina were preserved.

A decrease in the amplitudes of a- and 1a ERG waves in different zones of the retina (center, paracentre, periphery) indicates a generalized lesion of the entire photoreceptor layer of both systems (cone and rod) already in the first stage of the disease. The development of the process is accompanied by the spread of pathological changes deep into the retina, which is expressed in an increase in the frequency of detection and the severity of changes in all ERG components.

However, already in the initial (I-II) stages of Stargardt's disease, a greater degree of suppression of the cone ERG components is revealed compared to the rod components.

According to P. A. Blacharski (1988), after long-term dark adaptation (45 min) in patients with fundus flavimaculatus, a greater (29%) degree of decrease in photopic ERG components is noted than in healthy individuals. The scotopic ERG responses decrease slightly, by only 6-10%. According to J. B. M. Moloney et al. (1983), suppression of the cone ERG was detected in 100% of those examined and a decrease in the rod ERG in 50%.

R. Itabashi et al. (1993) presented the results of a study of a large group of patients with Stargardt disease, comparing the degree of inhibition of various ERG components.

According to the classification proposed by K.G. Noble and R.E. Sugg (1971), several groups of patients were identified according to the stages of the disease: 1-4. The average amplitudes of all ERG components were below normal values ​​with more pronounced changes in the cone system of the retina. The photopic b-wave was 57.4% of normal, the scotopic b-wave was 77.9%, responses to a “white” flickering stimulus of 32 Hz were 78.9%, the a-wave was 87.7%, the b-wave was 95.8% of normal. The greatest decrease in all ERG components was observed in patients of group 3.

Timing parameters have also been changed; the prolongation of the peak time is most significant for the a-wave, especially in patients of group 3. This stage is also characterized by the most frequent detection of a subnormal light-dark coefficient of the EOG (73.5%). According to the authors, the prognosis for patients in group 3 is the most unfavorable.

Observation of patients for 7-14 years made it possible to trace the dynamics of electrophysiological parameters in comparison with the clinical process. More pronounced ophthalmoscopic changes were accompanied by a decrease in both electroretinographic and electrooculographic parameters. These results are consistent with the opinion of other researchers who, based on electroretinographic and histological data, suggest an initial lesion in the RPE in fundus flavimaculatus and further damage to the retinal photoreceptors in Stargardt's dystrophy.

There are certain discrepancies in the results of electrooculography in the literature. Most often, a normal or slightly reduced EOG is noted in most patients with fundus flavimaculatus and Stargardt's dystrophy. However, a number of researchers note a high percentage of subnormal EOG based on the Arden coefficient: in 75-80% of patients with FF. It should be taken into account that most publications present the results of examination of small groups of patients: from 3 to 29.

G.A. Fishman (1976, 1979) made a correlation between fundus flavimaculatus stages and EOG results. He showed that in the disease of stages I-II in all examined patients the EOG was not changed (28/28), whereas in stages III-IV in 90% of patients it was subnormal. According to G.A. Fishman et al (1976 1977 1979), only if a significant area of ​​the retina is affected by the pathological process will the EOG be abnormal. Other researchers also note the absence of EOG changes in the vast majority of patients with fundus flavimaculatus. It is possible that research results are influenced by differences in methodological techniques, despite attempts to standardize them.

Thus, electrophysiological studies are more likely to reveal the presence and severity of changes in the cone and rod systems of the retina, as well as to assess the condition of the RPE, rather than help in the differential diagnosis of Stargardt disease and fundus flavimaculatus.

Differential diagnosis

The clinical picture of some hereditary diseases may be similar to that of Stargardt disease. Such diseases include dominant progressive foveal dystrophy, cone-rod and rod-cone (retinitis pigmentosa) dystrophy, juvenile retinoschisis. Atrophic macular degeneration has been described in various spinocerebral and cerebral spastic disorders, including oligopontocerebral atrophy. Similar morphological findings have been described in non-hereditary diseases, for example, chloroquine retinopathy or ocular manifestations of severe toxicosis of pregnancy.

Based on differences in the fundus picture, age, onset of the disease, and data from functional research methods, S. Merin (1993) identified two main types of Stargardt disease.

Stargardt disease type I

This type is most consistent with the originally described Stargardt disease. This is a juvenile hereditary macular degeneration, the clinical manifestations of which are observed in children aged 6-12 years. Boys and girls get sick with equal frequency; hereditary transmission is carried out according to an autosomal recessive type.

The disease manifests itself bilaterally and symmetrically. In advanced stages, the foveal reflex is absent. Changes at the level of the retinal pigment epithelium (RPE) appear as a central cluster of brownish pigment, surrounded by areas of hyper- and depigmentation. The clinical picture resembles a bull's eye.

Fluorescein angiography confirms the typical bull's eye phenomenon. The dark, non-fluorescein-permeable center is surrounded by a wide ring of hypofluorescent dots, usually followed by another ring of hyperpigmentation. This picture is explained by an increase in the amount of pigment in the central zone of the fundus, atrophy of adjacent RPE cells, and a combination of atrophy and hypertrophy of the pigment epithelium. The absence of fluorescein in the macular region is called “silent choroid” or dark choroid and is explained by the accumulation of acidic mucopolysaccharides in the RPE. According to D.A. Klein and A.E. Krill (1967), the bull's eye phenomenon is detected in almost all patients with type I Stargardt disease.

As the disease progresses, visual acuity decreases, resulting in the development of low vision. If in the early stages of the disease the ERG and EOG remain normal, in the advanced stages the responses of the cone system according to the ERG data decrease and the EOG indicators become moderately subnormal. Due to damage to the predominantly cone system, patients also have impaired color vision, often of the deuteranopia type.

During a histological examination of two eyes of a patient with typical Stargardt disease type I, who died as a result of a car accident, R.C. Eagl et al. (1980) found significant variability in the size of RPE cells - from 14 to 83 μm. Large RPE cells formed a granular substance, which in its ultrastructure, autofluorescent and histochemical properties corresponded to pathological (abnormal) lipofuscin. The amount of melanin was reduced and melanin granules were shifted towards the inside of the cell

In later stages of Stargardt disease, the disappearance of most of the photoreceptors and RPE cells from the macular region of the retina is revealed. At the same time, some of the RPE cells were in the stage of degeneration with the accumulation of lipofuscin; hyperplasia of RPE cells was observed at the edges of the areas of atrophy.

F. Schutt et al. (2000) showed that in retinal diseases associated with intense accumulation of lipofuscin, including Stargardt disease, AMD and retinal aging, the retinoid fluorescent component of lipofuscin A2-E (N-retinylidene-N-retinyl) plays a role in RPE dysfunction -ethanol-amine). It weakens the degradative function of lysosomes and increases the intralysosomal pH of RPE cells, leading to the loss of their membrane integrity. In addition to lysosomotropic properties, the photoreactive properties of A2-E and its phototoxicity are shown.

Stargardt disease type II

Unlike type I, in addition to typical changes in the macular region of the retina, there are multiple and widespread FF spots in the fundus, which can reach the equator. The disease begins somewhat later, although this may be due to the fact that the decrease in visual acuity in type II Stargardt disease occurs more slowly and, as a result, patients turn to the ophthalmologist later. Due to the fact that in type II Stargardt disease there are more changes beyond the boundaries of the macular region, electrophysiological data differ from those in type I.

Thus, in the ERG the responses of the rod system are significantly reduced. EOG indicators are also changed to a greater extent. The presence of yellowish spots in a high percentage of cases outside the macular area (macula) makes it difficult to clearly distinguish Stargardt disease from FF.

Fundus flavimaculatus

As a rule, fundus flavimaculatus, or yellow-spotted fundus, is combined with Stargardt disease and is not common as an isolated form of retinal disease. In typical (“pure”) cases, patients have virtually no symptoms of the disease. Visual acuity, color vision, and field of vision are within normal limits. Dark adaptation may be normal or slightly reduced. In the fundus of the eye, the macula and periphery of the retina are unchanged, only between the fovea and the equator are visible multiple grayish or yellowish spots of various shapes: round, oval, elongated, comma- or fish-tail-shaped, which can merge or be located separately from each other, be small - 200-300 microns or 3-5 times more. During dynamic observation, the color, shape, and size of these spots may change. The spots, initially yellowish and clearly defined, after a few years may become gray with unclear boundaries or disappear.

In parallel, the picture revealed by fluorescein angiography becomes different: areas with hyperfluorescence become hypofluorescent. At subsequent stages of disease development, RPE atrophy manifests itself as the disappearance of individual spots and their replacement by irregular areas of hypofluorescence.
Similar changes in spots with fundus flavimaculatus (FF) are characteristic of both types of Stargardt disease, however, with the “pure form” of FF they are less pronounced.

The onset of the disease, and most likely the time of its detection, does not depend on age. An autosomal recessive type of inheritance of FF is assumed, but in some cases it is not possible to establish the hereditary nature of this pathology.

Stargardt disease type 1 (Stargardt disease, STGD) And retinal abiotrophy Franceschetti type (fundus flavimaculatus (FFM) or yellow-spotted fundus) belong to hereditary retinal abiotrophies - a heterogeneous group of hereditary diseases of the retina, caused by degenerative changes in the photoreceptor cells of the pigment epithelium and leading to a significant decrease in visual acuity. Stargardt disease is one of the most common hereditary dystrophies of the macular region of the retina.
STGD, a classic example of central pigmentary retinal degeneration, manifests in childhood and young adulthood (7–20 years). The disease debuts with a decrease in the acuity of central vision, usually at the age of 7-9 years, then slowly progresses with the addition of gross disturbances in color perception of all colors. Changes in the fundus, although polymorphic, are characterized by the appearance in both eyes of pigmented round dots, areas of depigmentation and atrophy of the retinal pigment epithelium, often combined with whitish-yellowish spots in the paramacular zone. Changes in the form of yellowish-whitish dots and stripes with or without changes in the macular area were designated by A. Franceschetti as "fundus flavimaculatus"(retinal abiotrophy of the Franceschetti type). In the literature, the terms “Stargardt disease” and “fundus flavimaculatus” are often combined, thereby emphasizing the supposed unity of origin. Clinical manifestations STGD also include decreased visual acuity, loss of color vision, photophobia, paracentral scotoma, and poor adaptation to darkness. Histologically, the disease is characterized by excessive accumulation of lipofuscin-like substance in the retinal pigment epithelium, mainly in those areas that contain cone photoreceptors.
STGD and FFM are inherited in an autosomal recessive manner, when a child receives a gene with a mutation from both parents. The incidence of the disease is 1 case per 10,000 newborns.
One of the genetic causes leading to hereditary retinal abiotrophies is gene damage ABCA4 (АВСR).
ABCR is a specific protein of neurosensory cells of the retina, necessary for their normal functioning and vision. The ABCR gene is located in the chromosomal region 1p22.1-p21, consists of 50 exons, encodes 2273 amino acids and is ~150 kb in length.
To date, more than 400 different mutations in the ABCA4 gene are known, leading to hereditary retinal abiotrophies.

Mutations in the gene CNGB3 may lead to the development of type 1 Stargardt disease. The CNGB3 gene is located on the long arm of chromosome 8 (8q21.3) and consists of 18 exons. This gene encodes the beta 3 subunit of the G protein. G proteins are expressed in all cells of the body and play a major role in transmitting signals from a variety of receptors on the cell surface. About 40 mutations have been described. Mutations in the CNGB3 gene also lead to the development of achromatopsia type 3.

Stargardt disease type 3 (Stargardt disease 3, STGD3) (OMIM 600110) has clinical manifestations similar to Stargardt disease type 1, but is inherited in an autosomal dominant manner, where one mutation is enough to cause the disease. Stargardt disease type 3 is caused by mutations in the gene ELOVL4, which is located on the long arm of chromosome 6 (6q14). It encodes the ELOVL4 (elongation of very long chain fatty acids-like 4) protein, which is involved in the synthesis of saturated and unsaturated very long chain fatty acids. The ELOVL4 gene consists of 6 exons. Four mutations have been described, all of them localized in exon 6 of the ELOVL4 gene. The Center for Molecular Genetics is searching for mutations in “hot spots” (exon 6) of the ELOVL4 gene using direct automated sequencing.

Stargardt disease is a dangerous disease that is quite rare in medical practice. It can lead to complete loss of vision and is not always treatable. The pathology is popularly called bull's eye. It provokes the destruction of the central shell of the retina - the macula, in which light-sensitive cells are localized.

Stargardt disease develops in childhood. It is usually diagnosed in children 8-11 years old, and less often in adolescents.

Why does retinal pigmentary dystrophy occur - the cause of Stargardt disease?

Retinal degeneration in Stargardt disease is not caused by any external factors. This is a genetically determined disease that is absolutely independent of gender. At the same time, Stargardt's dystrophy is not always transmitted to the children of sick people.

Types of Stargardt disease

Depending on the location and extent of the area of ​​retinal pigmentary degeneration, Stargardt disease is classified into three forms:

• Central. During an ophthalmological examination, it turns out that the cells located in the very center of the macula of the eye are damaged. The patient loses central vision. When examining objects, he sees a darker spot in their middle.
• Pericentral. The disease affects cells that are located to the side of the central spot - above, below, to the right or left of the point of fixation. Subjectively, this manifests itself as follows: while looking at some image, a person notices that one of its sides falls out of his field of vision and looks like a black moon. Over the years, the affected area takes the form of a black circle.
• Mixed. Retinal pigment abiotrophy begins in the middle of the central visual spot and quickly shifts to one side. As a result, the eye becomes completely blind.

How does Stargardt disease manifest?

Stargardt's macular degeneration, as the disease described is also called, begins to make itself felt when the child turns 6 or 7 years old. The patient begins to complain of a black spot, which he sees when looking at any objects. It prevents him from looking at them. He sees bright objects of saturated colors better, pale, black and white objects - worse. It is also possible that the perception of the usual color scheme will change.

At first, the black spot is small in size, but as the disease progresses, its volume increases. This can lead to irreversible blindness and destruction of the optic nerve.

How quickly does Stargardt disease progress?

It is difficult to predict the course of the disease. It can progress slowly and then “freeze.” When the patient relaxes and believes that his vision will no longer deteriorate, Stargardt's disease can manifest itself with renewed vigor and in a few years cause the development of complete blindness.

According to statistics, by the age of 50, half of sick people have very poor vision - 20/200, while the norm is expressed as 20/20. As a result, it decreases to 20/400.

Since Stargardt's disease disrupts the functioning of the visual organs and causes nerve tissue to die, it is impossible to correct the situation with glasses, contact lenses, or even modern refractive surgery methods.

Diagnostic measures for Stargardt disease

Stargardt disease occurs in one in 20 thousand people, so not all ophthalmologists encounter it in their medical practice. To understand that the patient has this particular genetic disease, the doctor must conduct a comprehensive examination and competent differential diagnosis. It includes:

1. Visometry - determination of visual acuity when a person looks into the distance (usually a special ophthalmological table with letters is used).
2. Tonometry - measurement of intraocular pressure.
3. Refractometry is an assessment of the optical power of the organ of vision.
4. Study of color vision using special Rabkin ophthalmological tables.
5. Perimetry is a technique for studying a patient’s peripheral vision.
6. Electrooculography - recording the constant potential of the eye by applying special electrodes fixed directly to the lower eyelid area on both sides. The method makes it possible to identify abnormal changes in the pigmented epithelium of the retina and study photoreceptors.
7. Ophthalmoscopy - examination of the fundus, blood vessels and retina.
8. Electroretinography is an informative way to study the functional state of the retina.
9. Campimetry - determination of the central field of vision.
10. Electrophysiological study - aimed at studying the functions of the retina, optic nerve, and assessing the condition of the cerebral cortex.
11. Fluorescein angiography is a technique for studying the vessels that supply the retina.
12. OTC (optical coherence tomography) is an optical coherence tomography used to detect diseases of the retina and optic nerve.

One of the main signs of the disease is its onset at the age of 6-8 years. The child complains to his parents about a black spot that he constantly sees. During the examination, the doctor discovers a spot of reduced pigmentation with a dark center in the eye. Around it are pigmented cells. Visually, it resembles the eye of a bull (hence the above-mentioned popular name).

In the macula zone there are yellowish or whitish spots of different sizes and shapes. Over time, the clear boundaries of these formations disappear - they become blurred and acquire a grayish tint. They can completely dissolve.

One should not think that with Stargardt's disease the patient always goes blind very quickly. A child may have good visual acuity for a long time and experience difficulties only because of poor adaptation to movement in the dark.

Molecular genetic examination can finally confirm or refute the preliminary diagnosis of retinal abiotrophy.

Treatment of Stargardt disease

It is impossible to eliminate the causative factors and thus avoid the development or progression of an ophthalmological disease. Usually, to improve the condition of patients and slow down the pathological process, patients are prescribed:

• Antioxidant drugs;
• Injections of the amino acid taurine;
• Vasodilator drops;
• Hormonal solutions;
• Vitamins (especially important A, B, C, E);
• Means to improve blood circulation.

Among the physiotherapeutic procedures, the ophthalmologist can prescribe electrophoresis using a number of drugs, laser stimulation of the retina, and ultrasound.

Radical methods of treating Stargardt disease

Today, modern techniques such as:

1. Retinal revascularization;
2. Autologous tissue therapy.

In the first case, the surgeon installs a bundle consisting of muscle fibers in the area of ​​the affected macula. This preserves visual function for some time, as the atrophied nerve is replaced. But the transplant does not avoid blindness - over the years the dark spot becomes wider.

As for autologous tissue therapy, this is a more modern technique. It involves the use of stem cells obtained from the patient's own adipose tissue. The technology was developed by Russian scientist V.P. Filatov. According to his theory, Stargardt disease must be treated at the cellular level.

This therapy is safe, since destroyed eye cells are replaced with new, healthy ones.

The risk of their rejection is minimal, since during the operation not donor material is used, but material obtained from the patient himself. It quickly takes root and restores the functions of the visual organs.

It is impossible to say that autologous tissue therapy provides a 100% guarantee of vision restoration. But today this is the only technique that effectively resists the further development of the disease and helps improve visual acuity even when the patient sees the world around him very poorly.

Agreement No. 1
public offer for voluntary donation

Interregional public organization for the promotion and assistance of patients with hereditary retinal diseases “To see!” (MOO “To See!”), hereinafter referred to as the “Beneficiary” represented by President Baibarin Kirill Aleksandrovich, acting on the basis of the Charter, hereby invites individuals and legal entities or their representatives, hereinafter referred to as the “Donor”, ​​collectively referred to as the “Parties”, conclude a Voluntary Donation Agreement on the following terms:

1. General provisions on public offer

1.1. This proposal is a public offer in accordance with paragraph 2 of Article 437 of the Civil Code of the Russian Federation.
1.2. Acceptance (acceptance) of this offer is the Donor's transfer of funds to the Beneficiary's bank account as a voluntary donation for the statutory activities of the Beneficiary. Acceptance of this offer by the Donor means that the latter has read and agrees with all the terms of this Agreement on voluntary donation with the Beneficiary.
1.3..
1.4. The text of this offer may be changed by the Beneficiary without prior notice and is valid from the day following the day of its posting on the Site.
1.5. The Offer is valid until the day following the day the notice of cancellation of the Offer is posted on the Site. The Beneficiary has the right to cancel the Offer at any time without giving reasons.
1.6. The invalidity of one or more terms of the Offer does not entail the invalidity of all other terms of the Offer.
1.7. By accepting the terms of this agreement, the Donor confirms the voluntary and gratuitous nature of the donation.

2. Subject of the agreement

2.1. Under this agreement, the Donor, as a voluntary donation, transfers his own funds to the Beneficiary’s current account, and the Beneficiary accepts the donation and uses it for statutory purposes.
2.2. The Donor's performance of actions under this agreement constitutes a donation in accordance with Article 582 of the Civil Code of the Russian Federation.

3. Activities of the Beneficiary

3.1 The main purpose of the Beneficiary’s activities is:
providing comprehensive assistance and support to patients with hereditary retinal diseases, including social, psychological and labor adaptation, training;
promoting the prevention, diagnosis, treatment and research in the field of inherited retinal diseases;
attracting the attention of government agencies and the public to the problems of people with hereditary retinal diseases; representation and protection of the rights and legitimate interests of persons of this category and members of their families in government bodies; protection of the common interests of the Beneficiary's members;
development of comprehensive cooperation between public organizations and health authorities, promoting the strengthening of connections between science, education and practice;
international cooperation in the field of care for patients with hereditary retinal diseases;
establishing personal contacts, communication between members of the Beneficiary, providing mutual support and assistance;
promoting activities in the field of prevention and health protection of citizens, promoting a healthy lifestyle, improving the moral and psychological state of citizens;
promoting the implementation of humane and peace-loving initiatives of public and government organizations, projects and programs of international and national development.
The main types of activities of the Beneficiary in accordance with the current legislation of the Russian Federation are specified in the Charter of the Beneficiary.
3.2..

4. Conclusion of an agreement

4.1. Individuals and legal entities or their representatives have the right to accept the Offer and thereby conclude an Agreement with the Beneficiary.
4.2. The date of acceptance of the Offer and, accordingly, the date of conclusion of the Agreement is the date of crediting funds to the Beneficiary’s current account or, in appropriate cases, to the Beneficiary’s account in the payment system. The place of conclusion of the Agreement is the city of Moscow of the Russian Federation. In accordance with paragraph 3 of Article 434 of the Civil Code of the Russian Federation, the Agreement is considered to be concluded in writing.
4.3. The terms of the Agreement are determined by the Offer as amended (including amendments and additions) valid on the day of execution of the payment order or the day of depositing cash into the Beneficiary's cash desk.

5. Making a donation

5.1. The Donor independently determines the amount of the voluntary donation (one-time or regular) and transfers it to the Beneficiary using any payment method specified on the website under the terms of this Agreement. According to Article 582 of the Civil Code of the Russian Federation, donations are not subject to VAT.
5.2. Purpose of payment: “Donation for statutory activities. VAT is not assessed” or “Voluntary donation for statutory activities” or “Voluntary donation for statutory purposes”.
5.3. Donations received by the Beneficiary without specifying a specific purpose are directed to achieve the statutory goals of the Beneficiary
5.4. The donor has the right to choose the object of assistance at his own discretion, indicating the appropriate purpose of payment when transferring the donation.
5.5. Upon receipt of a donation indicating the last and first name of the person in need, the Beneficiary sends the donation to help this person. In the event that the amount of donations to a specific person exceeds the amount necessary to provide assistance, the Beneficiary informs the Donors about this by posting information on the website. The Beneficiary uses the positive difference between the amount of donations received and the amount necessary to help the specific person for the statutory purposes of the Beneficiary. A donor who does not agree with the change in the purpose of financing has the right to request a refund in writing within 14 calendar days after the publication of the specified information.
5.6. When transferring a Donation through an electronic payment system, the Donor may be charged a commission depending on the chosen payment method (electronic money, SMS payments, money transfers). Donations transferred by the Donor through the electronic payment system are accumulated by the payment system in the system's accounts, then the total amount of money collected over a certain period is transferred to the Fund's current account. The electronic system may deduct a commission from the amount of money transferred to the Fund’s current account. The amount of funds received by the Fund will be equal to the amount of the Donation made by the Donor, minus the fees charged by the payment system.
5.7. The donor can arrange for a regular (monthly) debit of the donation from a bank card.
The order is considered completed from the moment the donation is first successfully debited from the bank card.
The order for regular debiting is valid until the owner’s card expires or until the Donor submits a written notice of termination of the order. The notification must be sent to the email address info@site at least 10 days before the date of the next automatic debit. The notification must contain the following information: last name and first name, as indicated on the bank card; the last four digits of the card from which the payment was made; email address to which the recipient will send confirmation of the termination of regular debiting.

6. Rights and obligations of the parties

6.1. The Beneficiary undertakes to use the funds received from the Donor under this agreement strictly in accordance with the current legislation of the Russian Federation and within the framework of statutory activities.
6.2. The Donor gives permission to process and store personal data used by the Beneficiary solely for the execution of the specified agreement, as well as to inform the activities of the Beneficiary.
6.3. Consent to the processing of personal data is given to the Donor for an indefinite period. In case of withdrawal of consent, the Beneficiary undertakes to destroy or depersonalize the Donor's personal data within 5 (five) business days.
6.4. The Beneficiary undertakes not to disclose the Donor's personal and contact information to third parties without his written consent, except in cases where this information is required by government agencies that have the authority to require such information.
6.5. The donation received from the Donor, due to the closure of the need, partially or completely not spent according to the purpose of the donation specified by the Donor in the payment order, is not returned to the Donor, but is redistributed by the Beneficiary independently to other current programs and the statutory goals of the Beneficiary.
6.6. At the request of the Donor (in the form of an email or regular letter), the Beneficiary is obliged to provide the Donor with information about the donations made by the Donor.
6.7. The Beneficiary does not bear any other obligations to the Donor other than the obligations specified in this Agreement.

7. Other conditions

7.1. In the event of disputes and disagreements between the Parties under this agreement, they will, if possible, be resolved through negotiations. If it is impossible to resolve a dispute through negotiations, disputes and disagreements may be resolved in accordance with the current legislation of the Russian Federation in the courts at the location of the Beneficiary.

8. Details

BENEFICIARY:
Interregional public organization for the promotion and assistance of patients with hereditary retinal diseases “To see!”

Legal address: 127422, Moscow, Dmitrovsky proezd, building 6, building 1, apartment 122,

OGRN 1167700058283
TIN 7713416237
Gearbox 771301001