Retinal abiotrophy is a heterogeneous group of hereditary diseases of a dystrophic nature caused by the gradual destruction of the retina with a decrease in visual acuity, and in some forms – complete blindness. Symptoms are variable: there may be a decrease in visual acuity, hemeralopia, color perception disorders. Diagnosis is carried out by ophthalmological and genetic methods (ophthalmoscopy, electroretinography, fluorescent angiography, family history study and detection of defective genes). In most forms of retinal abiotrophy, there is no specific treatment, symptomatic and supportive therapy can weaken some symptoms and slow the progression of the disease.
H35.5 Hereditary retinal dystrophy
Retinal abiotrophy (retinal degeneration, retinal dystrophy) is a pathology of the organ of vision, in which dystrophy of the retina of the eye develops. It can be part of the symptom complex of some hereditary diseases, act as an independent pathology, in some cases secondary degeneration after injuries and other influences is possible.
Independent hereditary forms of retinal abiotrophy have different prevalence, on average it ranges from 1-10:10000. The mechanism of inheritance of various forms can be autosomal dominant, autosomal recessive and sex-linked. For this reason, there are strong differences in the sexual distribution of the disease – from the equal incidence of persons of both sexes to the almost complete prevalence of men among the sick (with X-linked inheritance). Genetically determined retinal abiotrophy is the most common cause of hereditary vision loss.
The etiology of retinal abiotrophy varies depending on the specific type of disease. The general mechanism is a mutation of a certain gene or genes that encode specific proteins involved in the vital activity of the retina of the eye. At the same time, the pathogenesis of most forms has not been sufficiently studied.
Retinal pigmented dystrophy. The cause of the most common form of retinal abiotrophy – pigmented dystrophy – can be more than 150 variants of mutations in several dozen genes, most of which are inherited by autosomal dominant type. Almost a quarter of all cases of retinal pigment abiotrophy are caused by various mutations in the opsin protein gene. In the gene of the CRB1 photoreceptor protein, the mutation has a recessive nature of inheritance, and in the RP2 and RPGR genes it is linked to the X chromosome.
There is a rare form of retinal pigment abiotrophy with a mutation in mitochondrial DNA and, consequently, inheritance from mother to offspring. Despite the huge number of different variants of the primary disorder in retinitis pigmentosa, the pathogenesis of the disease is generally the same – there is a violation of the disposal of spent sticks, as a result of which they become a source of toxins in the retina. Due to the fact that the concentration of rods increases towards the periphery of the retina, pathological changes begin there, the formation of new photosensitive cells slows down, which leads to a decrease in photosensitivity.
White-dot retinal abiotrophy is associated with mutations of one of the four genes – RHO, PRPH2, RDH5 or RLBP1, while the most common form is due to changes in the PRPH2 gene encoding the peripheral protein. The disease is inherited in an autosomal recessive type. It is assumed that peripherin participates in the stabilization of photoreceptor membranes, mainly rods, so violations in its structure make them less stable and leads to their destruction. White-dot retinal abiotrophy has a progressive course, while the first disturbances (which are noticeable when examining the fundus in the form of white dots) are formed on the periphery of the retina.
Yellow-spotted retinal abiotrophy (Stargardt’s disease) is also caused by mutations of several genes. The most common form of yellow-spotted retinal degeneration is associated with a violation of the structure of the ABCA4 protein, which performs transport and energy functions in photoreceptor membranes. This form of the disease is inherited by an autosomal recessive type. A change in the structure of the transmembrane protein ABCA4 leads to the accumulation of toxic metabolites in the retina (in particular, lipofuscin), which causes dystrophy of the photosensitive layer.
Another variant of Stargardt’s disease with autosomal dominant inheritance is caused by a change in the structure of the ELOVL4 protein, which controls the formation of long-chain fatty acids in the tissues of the eye. In this case, the degeneration of photoreceptors is associated with a violation of the synthesis of some components of their membranes. Another type of yellow-spotted retinal abiotrophy is associated with a mutation of the PROM1 gene. The pathogenesis of disorders in this case has not been thoroughly studied.
Best’s retinal abiotrophy is caused by mutations of the BEST1 gene, the transcription product of which is the protein bestrophin, belonging to the class of anion channels. Inheritance is autosomal dominant, the pathogenesis of dystrophy is unknown.
Congenital stationary night blindness is a generalized retinal abiotrophy with a predominant lesion of the rods, it is also accompanied by other visual organ disorders – strabismus, cataract. There are complete and incomplete forms of congenital stationary night blindness, both are inherited by the X-linked mechanism.
The complete type is due to a mutation of the NYX gene encoding a protein that provides the transmission of excitation from rods to bipolar cells. As a result, the transmission of information from photoreceptors is disrupted, hemeralopia occurs with almost complete absence of vision in the dark, while acuity and color perception usually do not suffer.
The incomplete form is associated with a mutation of the CACNA1F gene, the product of which is a similar protein, but it is present in both rods and cones. At the same time, however, the transmission of the pulse is not completely blocked, so twilight vision is only weakened, but also acuity and color perception suffer.
In ophthalmology , all hereditary forms of retinal dystrophy are divided into three groups:
- Peripheral, in which disorders occur mainly at the edges of the fundus, but with some forms of abiotrophy, they can progress and capture the central areas, up to the macula. In addition, peripheral vision suffers the most from them, the adaptation of the eye to darkness is disrupted, hemeralopia often occurs. These include pigmented and white-dot retinal abiotrophy.
- Central, which are characterized by a predominant lesion of the macula and the central areas of the fundus. At the same time, color perception is disrupted, visual acuity drops significantly. It is such manifestations that accompany Stargardt’s disease and Best’s disease.
- Generalized. With some mutations or a combination of them, retinal abiotrophy can affect the entire retina of the eye, so some researchers distinguish a third group of dystrophies – generalized. Congenital stationary night blindness belongs to this type. Generalized retinal disorders accompany other hereditary diseases – for example, Leber’s amaurosis.
At the same time, due to the large number of different mutations, the above separation is somewhat conditional. Thus, some forms of pigmented dystrophy can acquire a generalized character, and with a mutation of the PROM1 gene (the fourth type of Stargardt’s disease), abiotrophy from the central regions of the retina can spread to the periphery.
The symptoms of retinal abiotrophy are quite variable due to the large number of different mutations that lead to the development of this pathology. But at the same time, there are a number of similar manifestations between different variants of dystrophy within the same group (peripheral, central or generalized abiotrophy).
Peripheral retinal abiotrophy (pigmented dystrophy, white-dot abiotrophy) begins with a predominant lesion of the rods, so one of the first symptoms of the disease will be hemeralopia. With the progression of pathology, with further destruction of the rods, a decrease in night vision can develop into its complete loss – nyctalopia. Peripheral vision is impaired, a concentric scotoma occurs, after which the field of vision narrows so much that it becomes “tubular”.
With white-dot retinal abiotrophy, more severe disorders most often do not develop, daytime vision and color perception remain unchanged. In some cases of pigmented dystrophy, cones are also involved in the pathological process, which leads to a drop in daytime vision, a decrease in its acuity and sometimes complete blindness. The course of the disease can take decades, although there are also transient and juvenile forms.
Central retinal abiotrophy is characterized by a predominant lesion of cones, the concentration of which is highest in the macular area – therefore they are also called macular degenerations. A sharp decrease in visual acuity comes to the fore, the perception of colors is disrupted, with the complete destruction of photoreceptors, a central scotoma develops in the center of the fundus.
If the pathological process does not extend to the peripheral areas of the retina, then peripheral and twilight vision is poorly affected. With forms of abiotrophy characterized by focal lesions of photoreceptors, blind spots develop in the field of vision. In particularly severe forms, atrophy of the optic nerve fibers and complete blindness may occur.
The full form of congenital stationary night blindness is characterized by pronounced nyctalopia with preservation of daytime vision and color perception. At the same time, the disease does not progress. Symptoms of an incomplete form of VSNS are moderate hemeralopia, decreased visual acuity, color vision abnormalities, difficulty adapting to low light.
Patients with retinal abiotrophy should be consulted by a geneticist and an ophthalmologist. The definition of dystrophic processes in the retina of the eye is based on the data of the fundus examination, electroretinography, visual acuity and color perception studies. An important role is played by the study of hereditary anamnesis, as well as genetic studies to identify mutations in genes associated with a particular type of retinal abiotrophy.
With pigmented dystrophy, foci of pigment deposition are detected along the periphery of the fundus, they can also be observed in the central areas with the corresponding form of the disease. There is a narrowing of the arterioles of the retina, and at the later stages there is atrophy of the capillaries of the vascular membrane of the eye. In some cases, waxy atrophy of the optic disc is detected. Electroretinography shows a significant decrease in the amplitude of all waves, which indicates a sharp decrease in the number of photoreceptors in the retina. DNA sequencing in order to detect mutations is most often performed in relation to the genes RP1, RHO, RDS, RLBP1, PRPF8 and a number of others.
White-dot retinal abiotrophy during examination of the fundus is characterized by the presence of white, sometimes with a metallic tinge, foci located on the periphery of the retina. The arterioles of the retina are narrowed, pigment deposits are represented in a single amount, paleness of the optic nerve disc is revealed. Changes in electroretinography are poorly expressed and are not a reliable diagnostic criterion. Genetic diagnosis is represented by sequencing of the PRPH2 gene.
In Stargardt and Best diseases, ophthalmoscopy reveals atrophic foci of a light shade, often surrounded by pigment deposits. The size and number of foci can vary significantly and reflects the severity of the lesion of the retina of the eye. They are mainly located in the central zones, but they can also spread to the periphery. Electroretinography reveals a sharp decrease in the amplitude of the A wave, which indicates the predominant destruction of the cones. Genetic diagnosis is reduced to the detection of mutations in the ABCA4 and CNGB3 genes and the study of hereditary history.
There is currently no specific etiotropic treatment for any form of retinal abiotrophy. As a supportive treatment that delays the progression of the disease, preparations of vitamins A, E, and riboflavin are used. Vasodilators can improve the blood supply to the retina, which also slows down dystrophic processes.
In recent years, there has been evidence of the successful use of bionic retinal implants (Argus, Argus 2), which partially restored vision to patients who completely lost it due to abiotrophy. Some developments in the use of stem cells, gene therapy also aim to find a method of treating retinal abiotrophy.
Due to the large number of mutations that cause abiotrophy, and the different clinical course of dystrophic processes in the retina, the prognosis is almost always uncertain. Some types of pigmented dystrophy may be limited to hemeralopia and peripheral vision impairment, while other forms of this pathology lead to complete blindness. By taking vitamin A preparations, in some cases it is possible to slow down the progression of retinal abiotrophy, according to some data, the use of sunglasses also allows you to achieve a similar result.