Stargardt disease (juvenile macular degeneration, yellow-spotted retinal abiotrophy) is a juvenile form of central retinal degeneration, which is characterized by progressive damage to the macular area. The disease has a predominantly autosomal dominant, less often an autosomal recessive or sex-linked mechanism of inheritance. The pathology occurs with a frequency of 1:10,000 and manifests itself between the ages of 6 and 20 years.
The disease was first described by the German ophthalmologist Karl Stargardt at the beginning of the 20th century. In 1997, geneticists discovered a defect in the ABCR gene, causing a disruption in the synthesis of the protein that transfers ATP to the photoreceptors of the retina. It is energy deficiency that leads to the death of different types of cones in the macula area. It should be noted that yellow-spotted retinal abiotrophy can occur with mutations in CRB1, RP2 and about 150 other genes.
There are two main types of Stargardt disease: with and without fundus flavimaculatus.
The first is characterized by the presence of typical changes in the form of yellow-white stripes and dots, while the second is characterized by their absence.
Depending on the location, there are the following forms of the disease:
Considering the nature of changes in the fundus, the following types of pathology are distinguished:
The first manifestations of the disease usually occur at the age of 6-7 years. Juvenile macular degeneration is characterized by symmetrical damage to both eyes. All children with this pathology note the appearance of absolute or relative scotomas - black or colored spots in the field of vision. The location of the scotoma directly depends on the location of the pathological focus.
The central form of juvenile macular degeneration is characterized by loss of the visual field at the very point of fixation. With a couple central shape scotomas appear away from the point of fixation. They may look like a crescent moon or a black ring. The centroperipheral form of the disease is characterized by rapid growth of the scotoma, which is why it can cover most of the visual field.
Some patients have deuteranopia, red-green dichromasia, and other unclassifiable color vision disorders. Many children complain of photophobia and a progressive decrease in visual acuity.
In children, impaired dark adaptation and decreased contrast sensitivity are often detected.
The disease is characterized by polymorphic changes, however, patients almost always exhibit areas of depigmentation and pigmented round dots. With ophthalmoscopy, visible in the fundus characteristic changes in the form of a bull's eye, a snail's mark, beaten (forged) bronze, choroidal atrophy, geographic atrophy.
In addition to the standard ophthalmological examination persons with Stargardt disease are prescribed electrophysiological research methods. The most informative are electroretinography (ERG) and electrooculography (EOG). These methods allow you to assess the functional state of the retina of the eye.
In the video, the doctor talks about the causes, symptoms and treatment of the disease:
To date, there is no etiological treatment for the disease.
As an auxiliary therapy, the patient may be prescribed physiotherapeutic procedures, vitamins, antioxidants, taurine, vasodilators, and steroid hormones.
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. How hereditary disease macular area, manifested in childhood and at a young age(7-20 years old). 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 as “fundus flavimaculatus”. In the literature, the terms “Stargardt disease” and “fundus flavimaculatus” are often combined (Stargardt disease/fundus flavimaculatus), thereby emphasizing the supposed unity of origin and/or the 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):
Along with the classical distinction of two types of Stadgardt 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:
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.
Locus determined by positional cloning disease-causing gene 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 retinitis pigmentosa RP19 is defined between markers D1S435-D1S236 on chromosome lp. 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.
Wide range of phenotypic manifestations of Stargardt's dystrophy and age of diagnosis 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 functions, altered cone components in the ERG, the specificity of changes in the local and multifocal ERG help in making the diagnosis.
Thus, in recent years All higher value The results of genetic studies are used 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
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.
Field of view
With fundus flavimaculatus, the visual field 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 seems to depend on which type of cones is predominantly involved in the pathological process, therefore, with fundus flavimaculatus, color vision may not be changed or red-green dichromasia may be observed.
According to O. Gelisken, J.J. De Jaey (1985), of 43 patients with Stargardt's 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 initial stages Stargardt's dystrophy and fundus flavimaculatus general, or ganzfeld, ERG is normal. However, the use of various methodological techniques of electroretinography makes it possible to evaluate the topic 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 identify 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 disease with preservation of the proximal layers of the retina.
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 pathological changes deep into the retina, which is reflected in an increase in the frequency of detection and 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), patients with fundus flavimaculatus experience a greater (29%) degree of decrease in photopic ERG components than 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. Sagg (1971), several groups of patients were identified according to the stages of the disease: 1-4. The average amplitudes of all ERG components were lower normal values with more pronounced changes 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 state of the RPE, rather than help in the differential diagnosis of Stargardt disease and fundus flavimaculatus.
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 juvenile hereditary macular degeneration, clinical manifestations which is 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 cluster of brownish pigment in the center, 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 central zone 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 on early stages ERG and EOG diseases remain normal; in advanced stages, the responses of the cone system according to ERG data decrease and 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 histological examination of two eyes of a patient with typical illness Stargardt Type I, killed in a car accident, R.C. Eagl et al. (1980) found significant variability in the size of RPE cells - from 14 to 83 μm. Large cells RPE 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 atrophy areas.
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 certain role in the dysfunction of the RPE -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. Availability in high percentage cases outside the macular area (macula) of yellowish spots makes it difficult to clearly separate Stargardt disease and 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 multiple grayish or yellowish spots are visible between the fovea and the equator 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.
– a hereditary disease of the retina, which is manifested by dystrophic changes in its macular zone and leads to loss of central vision. The onset of the disease occurs in childhood or adolescence. Patients have central scotomas and color vision disturbances. Progression of Stargardt disease leads to complete blindness. Diagnosis is carried out using ophthalmoscopy, fluorescein angiography and EPI of the retina. For treatment, injection therapy (vitamins, antioxidants, angioprotectors), physiotherapy is used, revascularization operations are performed, and a method of autologous tissue therapy is being developed.
Another name for Stargardt's disease - juvenile macular degeneration - reflects the essence of the disease: it begins at a young (juvenile) age and is characterized by damage to the macula - the receptor apparatus of the visual analyzer. The disease was described by the German ophthalmologist Karl Stargardt at the beginning of the twentieth century as a congenital lesion of the macular region of the eye, which was inherited in one family. Typical ophthalmoscopic signs of Stargardt's disease are polymorphic: “choroidal atrophy”, “bull's eye”, “broken (forged) bronze”. The pathogenetic name of the pathology is “yellow-spotted retinal abiotrophy” - reflects changes in the fundus of the eye.
In 1997, geneticists discovered a mutation in the ABCR gene, disruptive the production of a protein that must transfer energy to photoreceptor cells. Inferiority of the ATP transporter leads to the death of retinal photoreceptors. Various types of hereditary macular degeneration occur in 50% of cases of eye pathology. Of these, Stargardt disease accounts for about 7%. The nosological form is diagnosed with a frequency of 1:10,000 and is characterized by a progressive course. Bilateral pathology eye disease begins at a young age (6 to 21 years) and leads to severe consequences, up to complete loss of vision. The disease has social significance, because it leads to disability at a young age.
Inheritance does not depend on the gender of the patient and parents. The pathology is transmitted predominantly in an autosomal recessive manner, that is, the inheritance of the pathology is not related to gender (autosomal - associated with non-sex chromosomes) and is not always transmitted to the future generation (recessive mode of inheritance). According to the latest data from geneticists, gene pathology can also be transmitted in a dominant manner. With a dominant type of inheritance of defects in the gene that controls the synthesis of the ATP transporter protein, the disease is milder and rarely leads to disability. Most of the receptor cells in the macula (apex) of the fundus macula are functional. In patients with a dominant type of inheritance, the disease occurs with a minimum of manifestations. Patients remain able to work and can even drive vehicles.
The main reason macular cells degenerate is that they suffer from energy deficiency. The gene defect leads to the synthesis of an defective protein that transports ATP molecules through the membrane of the cells of the macula - the center of the retina in which the graphic and color image is focused. There are no blood vessels in the macula area. Cone cells are nourished by ATP transport proteins from the nearby choroid (choroid). Proteins transport ATP molecules across the membrane into cone cells.
Under normal conditions, photoreceptor rhodopsin absorbs a photon of light, transforming into trans-retinal and opsin. Then trans-retinal, under the influence of ATP energy brought by carrier proteins, is converted into retinal, which combines with opsin. This is how rhodopsin is restored. When a gene is inherited, a defective carrier protein is formed. As a result, the restoration of rhodopsin is disrupted and trans-retinal accumulates. It is converted to lipofuscin and has a direct toxic effect to cone cells.
The types of disease depend on the extent of the affected area of the macula. In ophthalmology there are following forms Stargardt's disease: central, pericentral, centroperipheral (mixed). In the central form, cells in the center of the macula are affected. This results in loss of central vision. The patient develops a central scotoma (from the gr. “skotos” - darkness). The central zone falls out of sight. The patient sees an image with a dark spot at the point of fixation of the gaze.
The pericentral form is characterized by the appearance of a scotoma away from the point of fixation. A person is able to focus his gaze, but notices loss in one of the sides from the center of the visual field in the form of a crescent. Over time, the scotoma takes on the appearance of a dark ring. The centro-peripheral form begins from the center and rapidly spreads to the periphery. dark spot grows and completely blocks the field of view.
Manifestations of the disease begin at the age of 6-7 years. All patients, regardless of the type of inheritance, have central scotomas. At favorable course Relative scotomas: the patient sees bright objects with clear contours and does not distinguish objects with a weak color range. Many patients have a color vision disorder such as red-green dyschromasia, in which a person sees light green as dark red. At the same time, some patients do not notice changes in color perception.
In the initial phase of the disease, the boundaries of peripheral vision do not change; as it progresses, the central scotomas expand, which leads to complete blindness. Simultaneously with the appearance of loss of central vision, its acuity decreases. In the final stages of Stargardt's disease optic nerve atrophies. The person completely loses his vision. There are no changes in other organs, both in the initial and in terminal stage diseases.
The disease begins in childhood– this is one of the main signs for differential diagnosis. Ophthalmoscopy reveals a wide ring of decreased pigmentation that surrounds a dark center. Around the pallidum there is a further ring of hyperpigmented cells. The painting resembles a bull's eye or hammered bronze. The foveal reflex is negative. The macular elevation is not detected. When examining the macula, yellowish-white spots of varying sizes and configurations are noted. Over time, the boundaries of the inclusions blur, the spots acquire a gray tint or completely disappear.
During perimetry in case of Shtangardt's disease, positive or negative (the patient does not feel them) central scotomas are noted. In the central form of the disease, red-green deuteranopia develops. The peripheral form is not characterized by impaired color perception. Spatial contrast sensitivity varies over the entire range: absent in the region high frequencies(in the central region up to 6-10 degrees) and decreases in the mid-frequency region.
In the initial stage of the disease, there is a decrease in macular electrography indices in the central form of dystrophy. With further progression, electrical potentials are not recorded. When dystrophy is located in the middle peripheral zone, normal electrography and electrooculography are noted in the initial stage. Then the values of the cone and rod components of electroretinography decrease to subnormal. The disease is asymptomatic - without impairment of visual acuity and color perception. The boundaries of the visual field are within normal limits. Dark adaptation is slightly reduced.
With the help of fluorescein angiography, against the background of the “bull’s eye”, hypofluorescence zones are not detected, capillaries, “silent” or “dark” choroid are visible. In areas of atrophy, hyperfluorescent areas of retinal pigment epithelial cells are noticeable. Histological examination in the central zone of the fundus determines increased amount pigment - lipofuscin. There is a combination of hypertrophied and atrophied pigment epithelial cells.
Molecular genetic analysis makes it possible to detect a gene mutation before the onset of disease manifestations. To detect nucleotide substitutions, real-time PCR is performed using several DNA probes - “molecular beacons”. Differential diagnosis Stargardt disease is carried out with acquired drug dystrophies, Kandori retinal spots, familial drusen, juvenile retinoschisis, dominant progressive foveal, cone, cone-rod and rod-cone dystrophy.
There is no etiological treatment. As a general auxiliary treatment parabulbar injections of taurine and antioxidants, administration of vasodilators (pentoxifylline, nicotinic acid) are used. steroid drugs. Vitamin therapy is carried out to strengthen blood vessels and improve blood supply (vitamin groups B, A, C, E). Physiotherapeutic methods of treatment are indicated: medicinal electrophoresis, ultrasound, laser stimulation of the retina. A technique is used for retinal revascularization by transplanting a bundle of muscle fibers into the macula area. Pathogenetic regeneration is being developed ophthalmic technology autologous tissue therapy using stem cells from the patient's adipose tissue.
Stargardt disease begins in early age and quickly leads to visual impairment. In rare cases, with a dominant type of inheritance, vision declines slowly. Patients are recommended to be observed by an ophthalmologist, take vitamin complexes and wearing sunglasses.
DEFINITION
Stargardt disease is a degeneration of the macular region of the retina, which begins in the RPE and manifests itself with a bilateral decrease in visual acuity at the age of 10-20 years.
H35.5 Hereditary retinal dystrophies.
There are four forms of Stargardt disease depending on the location pathological process: in the macular region, in the middle periphery (fundus flavimaculatus), in the paracentral region, as well as mixed form when localized in the center and on the periphery.
Currently, with the help of genetic studies, it has been proven that Stargardt disease and yellow-spotted fundus are phenotypic manifestations of the same disease with an autosomal recessive, rarely autosomal dominant form of inheritance.
Positional cloning identified the main locus of the ABCR gene for Stargardt disease, which is expressed in photoreceptors. ABCR is a member of the ATP-binding cassette transporter superfamily. In the autosomal dominant type of inheritance of Stargardt disease, the localization of mutated genes on chromosomes 13q and 6q14 was determined; linkage analysis of locus mapping for central and peripheral forms of Stargardt disease.
Intensive accumulation of lipofuscin occurs in the RPE. It weakens the oxidative function of lysosomes, increases the pH of RPE cells, which leads to disruption of membrane integrity.
In the central form of Stargardt's dystrophy, as the process develops, the ophthalmoscopic picture of the macular area has different kind: from “broken metal” to “bull’s eye”, “wrought bronze” and choroidal atrophy.
The bull's eye phenomenon is seen ophthalmoscopically as a dark center surrounded by a wide ring of hypopigmentation, usually followed by another ring of hyperpigmentation. The retinal vessels are not changed, the optic disc is pale on the temporal side, which is associated with atrophy of nerve fibers in the papillomacular bundle. The foveal reflex and macular eminence (umbo) are absent.
The presence of yellowish-white spots in the posterior pole of the eye in the retinal pigment epithelium of various sizes, shapes and configurations - a characteristic feature of a yellow-spotted fundus (fundus flavimaculatus). Over time, the color, shape, and size of these spots may change. Initially yellowish spots with clearly defined edges, after a few years they may become gray with unclear boundaries or disappear.
The time of onset of the disease (in childhood or adolescence) can play an important role in its diagnosis.
Histologically, an increase in the amount of pigment in the central zone of the fundus, atrophy of the adjacent RPE, and a combination of atrophy and hypertrophy of the pigment epithelium are noted. The yellow spots are represented by lipofuscin-like material.
During perimetry, relative or absolute central scotomas of varying sizes are detected in all patients with Stargardt disease, depending on the timing and spread of the process from early childhood or adolescence. With a yellow-spotted fundus, no changes are noted in the macular area; the field of vision may not be changed.
The form of color anomaly in most patients with central localization of the process is of the type deuteranopia, red-green dyschromasia, or more pronounced.
With yellow-spotted fundus, color vision may not be affected. Spatial contrast sensitivity in Stargardt dystrophy is significantly altered throughout the entire range of spatial frequencies with a significant decrease in the medium range and its complete absence in the high spatial frequency range - “pattern cone dystrophy”. Contrast sensitivity (on- and off-activity of the cone system) is absent in the central region of the retina within 6-10 degrees.
ERG and EOG. Macular ERG decreases already in the initial stages of the central form of Stargardt dystrophy and is not recorded in the advanced stages.
In the initial stages of fundus flavimaculatus ganzfeld, ERG and EOG remain within normal limits: in advanced stages, the cone and rod components of ERG decrease, which becomes subnormal, and EOG indicators also change. Patients with this form have no symptoms. Visual acuity, color vision, and field of vision are within normal limits. Dark adaptation may be normal or slightly reduced.
On FA, with a typical “bull’s eye” phenomenon, zones of “absence” or gynofluorescence, with visible choriocapillaris, and a “dark” or “silent” choroid are detected against a normal background. The lack of fluorescence in the macular area is explained by the accumulation of lipofuscin, which screens fluorescein. Areas with hypofluorescence may become hyperfluorescent, which corresponds to an area of RPE atrophy.
The similarity of the clinical picture of various dystrophic diseases of the macular region makes diagnosis difficult. Differential diagnosis Stargardt disease should be considered for familial drusen, fundus albipunctatus, Kandori retinal spots, dominant progressive foveal dystrophy, cone, cone-rod and rod-cone dystrophy, juvenile retinoschisis, vitelliform macular degeneration, acquired drug-induced dystrophies (eg, chloroquine retinopathy).
Stargardt degeneration is a dysfunction of the predominantly central part of the retina (macula). This disease is characterized by damage to the macula of the retina, which in turn threatens the loss of central vision. The macula is the central point of the retina of the human eye, where rays refracted by the cornea are focused.
It is the macula that allows us to clearly see objects and people that surround us. Features of the visual process healthy person consists in the fact that the reflected rays are focused clearly in the center of the macula, such vision is called one hundred percent. When the beam of rays reflected by the cornea is located in front of the macula, this phenomenon is called myopia, and when behind it - farsightedness. The macula is a rounded plane located strictly in the center of the retina, colored yellow.
For the first time, a disease that affects the macular area retina, described at the beginning of the 20th century by an oculist from Germany Karl Stargardt. A genetic predisposition to retinal abiotrophy could only be proven at the end of the 20th century. The study revealed that the cause of Stargardt's dystrophy is a mutation of the gene that is responsible for the production of proteins vital for photoreceptor cells.
Symptoms characteristic of retinal abiotrophy appear at a fairly young age - up to 20 years. When the first symptoms appear, it is extremely important timely diagnosis and treatment of the disease, otherwise the person risks becoming disabled (completely losing the ability to see) at a young age.
Stargardt syndrome is characterized by a recessive mode of inheritance. This means that even if parents are carriers of a pathologically dangerous gene, their child will not necessarily inherit it. Moreover, the frequency of inheritance of this gene does not depend on the sex of the child. Relatively recently, it was proven that Stargardt's dystrophy can also be transmitted in a dominant manner. But in this case, the chance of developing disability is much less.
The main cause of Stargardt's dystrophy is a gene mutation, resulting in a disruption in the production of a protein that has an important function - to transmit energy to photoreceptor cells located in the macula. As a result, cells suffering from energy deficiency begin to atrophy, which can lead to complete loss vision.
Symptoms of the disease depend on the type of Stargardt syndrome, of which there are two. The first type of Stargardt macular degeneration is the most common. This is a disease that is transmitted hereditarily to both men and women. The first symptoms are already appearing at the age of six.
When examining the organs of vision, a characteristic picture called “bull’s eye” appears: an accumulation of brown pigment is visible on the retinal pigment epithelium. The manifestation of the bull's eye symptom is characteristic of almost all patients with the first type of Stargardt macular degeneration. If, as the disease progresses, appropriate treatment is not applied, the patient’s vision begins to rapidly deteriorate. Color vision is the first to fail - the patient stops seeing colors. The late stage of Stargardt degeneration is characterized by almost complete atrophy photoreceptors located in the macula.
The second type of Stargardt's degeneration is characterized by a late onset of symptoms of the disease, as a result of which patients complain of vision problems to an ophthalmologist much later. The second type of Stargardt's dystrophy affects not only the retina of the eye, but also the fundus of the eye, on which numerous spots form.
In addition to types, Stargardt syndrome is also divided into forms. There are three forms of the disease:
With the central form, central vision suffers. This phenomenon is called a central scotoma (“skotos” means “darkness” in Greek). In the pericentral form of the disease, peripheral vision is affected. Most dangerous form is mixed. It is characterized by a scotoma of central vision, which gradually passes to peripheral vision.
The sooner the patient addresses his problem to an ophthalmologist, the easier it will be to take measures that will prevent complete loss of vision. Therefore, specialist help should be sought already in childhood, when the first signs and symptoms of Stargardt syndrome are just beginning to appear.
To the complex diagnostic measures To identify Stargardt's dystrophy in a patient, the following types of studies include:
Ophthalmoscopy is an examination of the fundus of the eye. The analysis is carried out using an ophthalmoscope. With the development of retinal abiotrophy, ophthalmoscopy can detect a ring of low pigmentation, framed by another ring, which includes hyperpigmented cells. This phenomenon is called "bull's eye".
Perimetry is aimed at determining the field of vision of the patient's eye. For analysis, a special apparatus is used - the perimeter. In addition, objects may be shown to the patient for analysis. different colors and observe the reaction of his visual organs to them. If symptoms of Stargardt's degeneration occur, perimetry can diagnose central scotoma.
Fluorescein angiography can help diagnose retinal disorders. To conduct the study, the patient is injected intravenously with a special drug, fluorescein, which makes it possible to isolate vascular network eyes. The results of the study are recorded by special cameras. The first photo is taken without a filter.
Any histological study is primarily aimed at analyzing the morphology of tissues and organs. With retinal abiotrophy, histological examination can detect lipofuscin in the center of the fundus, as well as a noticeable combination of atrophied and hypertrophied pigment epithelial cells.
The use of molecular genetic analysis at an early age makes it possible to detect pathologically dangerous gene mutations even before the first signs of Stargardt's dystrophy appear.
PCR diagnostics today is the most effective research method that is used to detect the DNA of viruses and bacteria that are pathologically dangerous to the human body. In Stargardt disease, polymerase chain reaction can detect nucleotide substitutions during the use of special DNA probes.
Unfortunately, today it is impossible to completely cure a hereditary disease. Abiotrophy of the retina is no exception. Treatment of Stargardt disease can only be aimed at auxiliary effects, that is, at eliminating the symptoms of the disease and preventing complete loss of vision.
A set of measures for the treatment of Stargardt macular degeneration includes:
In addition, the following treatment methods can be used:
Drug electrophoresis allows you to introduce medications under the patient's skin using current. This method allows you to save medications, because when medicinal electrophoresis A much smaller dose of medication is required to obtain the desired treatment result. Approximately in two days after the procedure medical drug completely synthesized by the body.
Laser stimulation of the retina has a trophic and reparative effect. The retinal revascularization method allows muscle fibers to be transplanted into the macula.
To date, there is no effective method for preventing hereditary diseases.
Therapeutic measures that are used for Stargardt's disease can only stop the process of vision loss.
A patient who has been diagnosed with retinal abiotrophy should regularly visit an ophthalmologist and wear sunglasses.
