Retinal abiotrophy is a heterogeneous group of hereditary diseases of dystrophic nature, caused by the gradual destruction of the retina with decreased visual acuity, and in some forms – complete blindness. Symptoms are variable: there may be a decrease in visual acuity, gemeralopia, impaired color perception. Diagnosis is carried out by ophthalmological and genetic methods (ophthalmoscopy, electroretinography, fluorescent angiography, family history and detection of defective genes). In most forms of retinal abiotrophy, there is no specific treatment, and symptomatic and supportive therapy can alleviate some symptoms and slow the progression of the disease.
Retinal abiotrophy
Retinal abiotrophy (retinal degeneration, retinal degeneration) is a pathology of the visual organ in which retinal degeneration develops. It can be a part of a symptom complex of some hereditary diseases, to act as 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 sex distribution of the disease – from equal involvement of persons of both sexes to almost complete prevalence of men among patients (with X-linked inheritance). Genetically determined retinal abiotrophy is the most common cause of hereditary vision loss.
Causes of retinal abiotrophy
The etiology of retinal abiotrophy varies depending on the specific type of disease. A common mechanism is a mutation in a specific gene or genes that encodes specific proteins that are involved in the activity of the retina. The pathogenesis of most forms has not been studied enough.
The cause of the most common form of retinal abiotrophy – pigment dystrophy – may 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 due to various mutations in the opsin protein gene. In the CRB1 photoreceptor protein gene, the mutation is recessive in nature, 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, therefore, inherited from mother to offspring. Despite the huge number of different variants of primary disorders in retinitis pigmentosa, the pathogenesis of the disease is generally the same – there is a violation of the utilization 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 is slowed down, which leads to a decrease in photosensitivity.
White spot abyotrophy of the retina is associated with mutations in one of four genes – RHO, PRPH2, RDH5 or RLBP1, with the most common form due to changes in the PRPH2 gene encoding the protein peripherin. The disease is inherited by autosomal recessive type. It is assumed that peripheral is involved in the stabilization of photoreceptor membranes, mainly rods, so violations in its structure make them less stable and leads to their destruction. White spot abiotrophy of the retina is progressive, with the first violations (which are visible 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 in several genes. The most common form of retinal degeneration is associated with a violation of the structure of the protein ABCA4, which performs transport and energy functions in the membranes of photoreceptors. This form of the disease is inherited by autosomal recessive type. Changing the structure of the transmembrane protein ABCA4 leads to the accumulation in the retina of toxic metabolites (including lipofuscin), which causes dystrophy of the light-sensitive layer. Another variant of Stargardt’s disease with autosomal dominant inheritance is due to changes in the structure of the ELOVL4 protein, which controls the formation of long-chain fatty acids in eye tissues. In this case, the degeneration of photoreceptors is associated with impaired synthesis of some components of their membranes. Another type of retinal abotrophy is associated with a mutation in the PROM1 gene. The pathogenesis of disorders in this case has not been thoroughly studied.
Beet retinal abiotrophy is caused by mutations in the BEST1 gene, the transcription product of which is the bestrophin protein, which belongs to the class of anion channels. Inheritance is autosomal dominant, the pathogenesis of dystrophy is unknown.
Congenital inpatient night blindness is a generalized abiotrophy of the retina with a predominant lesion of the rods, it is also accompanied by other disorders of the visual analyzer – strabismus, cataracts. There are complete and incomplete forms of congenital stationary night blindness, both are inherited by X-linked mechanism. The complete type is caused by a mutation in the NYX gene, which encodes a protein that transmits excitation from rods to bipolar cells. As a result, the transmission of information from photoreceptors is disrupted, there is gemeralopia with almost complete absence of vision in the dark, with sharpness and color perception usually do not suffer. Incomplete form is due to a mutation in the CACNA1F gene, which is a product of a similar protein, but it is present in both rods and cones. However, the transmission of the pulse is not completely blocked, so twilight vision is only weakened, but also suffers from sharpness and color perception.
Classification of retinal abiotrophy
In ophthalmology, all hereditary forms of retinal degeneration are divided into three groups:
- Peripheral, in which disorders occur mainly at the edges of the fundus, but in some forms of abiotrophy, they can progress and capture the central areas, up to the macula. In addition, they suffer the most from peripheral vision, impaired adaptation of the eye to darkness, often gemeralopia. These include pigmented and White spot abiotrophy of the retina.
- 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 broken, visual acuity strongly falls. Such manifestations accompany Stargardt’s disease and Best’s disease.
- With some mutations or their combination, retinal abiotrophy can affect the entire retina of the eye, so some researchers identify a third group of dystrophies – generalized. Congenital inpatient night blindness belongs to this type. Generalized retinal disorders accompany other inherited diseases, such as Leber’s blindness.
Due to the large number of different mutations, the above distribution is conditional. Thus, some forms of pigmentary dystrophy may become generalized, and with mutations in the PROM1 gene (the fourth type of Stargardt’s disease) abiotrophy from the central regions of the retina may spread to the periphery.
Symptoms of retinal abiotrophy
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 one group (peripheral, central or generalized abiotrophies).
Peripheral retinal abiotrophies (pigment dystrophy, white spot abiotrophy) begin with a predominant lesion of the rods, so one of the first symptoms of the disease will be gemeralopia. With the progression of the pathology, with the subsequent destruction of the rods, the decrease in night vision can turn into its complete loss – chicken blindness. Peripheral vision is disturbed, there is a concentric scotoma, after which the field of view narrows so much that it becomes “tubular”. With white-spot abyotrophy of the retina, severe disorders often do not develop, day vision and color perception remains unchanged. In some cases of pigmentary dystrophy cones are involved in the pathological process, which leads to a decrease in day vision, reducing its severity and sometimes complete blindness. The course of the disease can take decades, although there are both transient and juvenile forms.
Central abiotrophies of the retina are characterized by a predominant lesion of the bulbs, the concentration of which is highest in the macula – so they are also called macular degeneration. In the foreground is a sharp decrease in visual acuity, impaired color perception, with the complete destruction of photoreceptors in the center of the fundus develops central scotoma. If the pathological process does not extend to the peripheral areas of the retina, the peripheral and twilight vision is weakly impaired. In forms of abiotrophy characterized by focal lesions of photoreceptors, blind spots develop in the field of view. In particularly severe forms, atrophy of the optic nerve fibers and complete blindness may occur.
The full form of congenital inpatient night blindness is characterized by severe chicken blindness with preservation of day vision and color perception. The disease does not progress. Symptoms of incomplete form of VNS are moderate gemeralopia, decreased visual acuity, color vision abnormalities, difficulty adapting to low light.
Diagnosis of retinal abiotrophy
Patients with retinal abiotrophy should consult a geneticist and ophthalmologist. Determination of dystrophic processes in the retina of the eye is based on the data of the fundus examination, electroretinography, study of visual acuity and color perception. An important role is played by the study of hereditary anamnesis, as well as genetic research to detect mutations in genes associated with one or another type of retinal abiotrophy.
At a pigmentary dystrophy on periphery of an eyeground the centers of deposition of a pigment come to light, also they can be observed and in the central sites at the corresponding form of a disease. Narrowing of the retinal arterioles is noted, and in the later stages there is atrophy of the capillaries of the vascular membrane of the eye. In some cases, there is a waxy atrophy of the optic disc. 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 to detect mutations is most often performed on the genes RP1, RHO, RDS, RLBP1, PRPF8 and others.
White-spot abiotrophy of the retina on examination of the fundus is characterized by the presence of white, sometimes with a metallic tint, foci located on the periphery of the retina. The arterioles of the retina are narrowed, pigment deposits are presented in a single amount, there is a pallor of the optic disc. Changes in electroretinography are weak and are not a reliable diagnostic criterion. Genetic diagnosis is represented by sequencing of the PRPH2 gene.
In diseases of Stargardt and Best ophthalmoscopy reveals atrophic foci of light color, often surrounded by pigment deposits. The size and number of foci can vary greatly and reflects the severity of retinal damage. They are mainly located in the central areas, but may extend to the periphery. Electroretinography shows a sharp decrease in the amplitude of wave A, which indicates the predominant destruction of the bulbs. Genetic diagnosis is reduced to the detection of mutations in the genes ABCA4 and CNGB3 and the study of hereditary history.
Treatment and prognosis for retinal abiotrophy
There is currently no specific etiotropic treatment for any form of retinal abiotrophy. As a supportive treatment that delays the progression of the disease, drugs of vitamins A, E, riboflavin are used. Vasodilators can improve the blood supply to the retina, which also slows down dystrophic processes. In recent years, there have been reports of successful use of bionic retinal implants (Argus, Argus 2), which have partially restored vision in patients who have completely lost it due to abiotrophy. Some developments in the use of stem cells, gene therapy also aim to find a method of treatment of 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 pigmentary dystrophy may be limited to gemeralopia and peripheral vision disorders, while other forms of this pathology lead to complete blindness. By taking vitamin A 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.
