Stargardt’s disease is 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 disorders. The progression of Stargardt’s disease leads to complete blindness. Diagnosis is carried out using ophthalmoscopy, fluorescent angiography and retinal ultrasound. Injection therapy (vitamins, antioxidants, angioprotectors), physiotherapy are used for treatment, revascularization operations are carried out, a technique 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 area of the eye, which was inherited in one family. Typical ophthalmoscopic signs of Stargardt’s disease are polymorphic: “choroid atrophy”, “bull’s eye”, “broken (forged) bronze”. The pathogenetic name of the pathology – “yellow-spotted retinal abiotrophy” – reflects changes in the fundus area.
In 1997, geneticists discovered a mutation of the ABCR gene that causes a disruption in the production of a protein that should transfer energy to photoreceptor cells. The inferiority of the ATP transporter leads to the death of retinal photoreceptors. Various types of hereditary macular dystrophy occur in 50% of cases of eye pathology. Of these, Stargardt’s disease is about 7%. The nosological form is diagnosed with a frequency of 1:10000 and is characterized by a progressive course. Bilateral eye pathology begins at a young age (from 6 to 21 years) and leads to severe consequences, up to complete loss of vision. The disease has a social significance because it leads to disability at a young age.
Inheritance does not depend on the gender of the patient and the parents. Pathology is transmitted mainly by autosomal recessive type, that is, the inheritance of pathology is not related to gender (autosomal – associated with non–sex chromosomes) and is not always transmitted to the future generation (recessive inheritance pathway). According to the latest data from geneticists, gene pathology can also be transmitted by the dominant type. With the dominant type of inheritance of defects in the gene – the controller of protein synthesis-the ATP transporter – the disease proceeds more easily and infrequently leads to disability. Most of the receptor cells of the macula (apex) of the fundus macula are functioning. In patients with a dominant type of inheritance, the disease proceeds with a minimum of manifestations. Patients remain functional and can even drive vehicles.
The main reason for the degeneration of macular cells is that they suffer from a lack of energy. A gene defect leads to the synthesis of an inferior protein that transports ATP molecules through the membrane of the cells of the macula – the center of the retina of the eye, in which the graphic and color image is focused. There are no blood vessels in the macular area. Nutrition of cone cells is carried out due to proteins-carriers of ATP from the nearby vascular membrane (choroid). Proteins transfer ATP molecules through the membrane into the cone cells.
Under normal conditions, photoreceptor rhodopsin absorbs a photon of light, transforming into trans-retinal and opsin. Then, the trans-retinal, under the action of ATP energy, which is brought by carrier proteins, turns into a retinal, which combines with opsin. This is how rhodopsin is restored. With a hereditary mutation of the gene, an incomplete carrier protein is formed. As a result, the restoration of rhodopsin is disrupted and trans-retinal accumulates. It turns into lipofuscin and has a direct toxic effect on cone cells.
The types of the disease depend on the prevalence of the affected area of the macula. In ophthalmology, the following forms of Stargardt’s disease are distinguished: central, pericentral, centroperiferal (mixed). In the central form, the cells in the center of the macula are affected. This is expressed in the loss of central vision. The patient has a central scotoma (from 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 fixation point. A person is able to focus his eyes, but notes a dropout in one of the sides from the center of the field of view in the form of a crescent. Over time, the scotoma takes on the appearance of a dark ring. The centroperiferical form starts from the center and rapidly spreads to the periphery. The dark spot grows and completely covers the field of view.
Manifestations of the disease begin at the age of 6-7 years. Central scotomas are observed in all patients, regardless of the type of inheritance. With a favorable course, scotomas are relative: the patient sees bright objects with clear contours and does not distinguish objects with a weak color scheme. Many patients have a violation of color vision by the type of red-green dyschromasia, in which a person sees a light green color as dark red. At the same time, some patients do not notice changes in the perception of the color gamut.
In the initial phase of the disease, the boundaries of peripheral vision do not change, with progression, the central scotomas expand, which leads to complete blindness. Simultaneously with the appearance of central vision loss, its acuity decreases. In the final stage of Stargardt’s disease, the optic nerve atrophies. A person completely loses his sight. There are no changes in other organs, both in the initial and terminal stages of the disease.
The disease begins in childhood – this is one of the main signs for differential diagnosis. Ophthalmoscopy reveals a wide ring of reduced pigmentation that surrounds the dark center. The following ring of hyperpigmented cells is marked around the pale ring. The painting resembles a “bull’s eye” or “forged bronze”. The foveolar reflex is negative. Macular elevation is not determined. When examining the yellow spot, yellowish-white spots of different sizes and configurations are noted. Over time, the boundaries of inclusions are blurred, the spots become gray or completely disappear.
During perimetry in Stangardt’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 a violation of color perception. Spatial contrast sensitivity varies over the entire range: it is absent in the high frequency region (in the central region up to 6-10 degrees) and decreases in the middle frequency region.
In the initial stage of the disease, there is a decrease in macular electrography in the central form of dystrophy. With further progression, electrical potentials are not recorded. When the dystrophy is located in the middle peripheral zone in the initial stage, normal electrography and electrooculography are noted. Then the values of the cone and rod components of eletroretinography decrease to subnormal. The disease is asymptomatic – without impaired visual acuity and color perception. The boundaries of the visual field are within the normal range. Slightly reduced dark adaptation.
With the help of fluorescent angiography, hypofluorescence zones are not detected against the background of the “bull’s eye”, capillaries, “silent” or “dark” vascular membrane are viewed. Hyperfluorescent areas of retinal pigment epithelium cells are noticeable in areas of atrophy. Histological examination in the central area of the fundus determines an increased amount of pigment – lipofuscin. A combination of hypertrophied and atrophied pigment epithelial cells is noted.
Molecular genetic analysis allows you to notice a gene mutation before the onset of the disease. To detect the replacement of nucleotides, real-time PCR is performed using several DNA probes – “molecular beacons”. Differential diagnosis of Stargardt’s disease is carried out with acquired drug dystrophies, retinal Candori spots, familial druses, juvenile retinoschisis, dominant progressive foveal, cone, cone-rod and rod-cone dystrophy.
Treatment and prognosis
There is no etiological treatment. As a general auxiliary treatment, parabulbar injections of taurine and antioxidants, the introduction of vasodilators (pentoxifylline, nicotinic acid), steroid preparations are used. Vitamin therapy is carried out to strengthen blood vessels and improve blood supply (vit. groups B, A, C, E). Physiotherapeutic methods of treatment are shown: medicinal electrophoresis, ultrasound, laser stimulation of the retina. The technique of retinal revascularization is used by transplantation of a bundle of muscle fibers into the macular area. Pathogenetic regenerative ophthalmological technology of autologous tissue therapy with the help of adipose tissue stem cells of the patient is being developed.
Stargardt’s disease begins at an early age and quickly leads to visual disability. In rare cases, with the dominant type of inheritance, vision drops slowly. Patients are recommended to follow an ophthalmologist, take vitamin complexes and wear sunglasses.