Retinal abiotrophy – causes, symptoms, diagnosis and treatment

Medically reviewed: 27, October 2023

Read Time:10 Minute

Retinal abiotrophy: what is it?

Retinal abiotrophy (retinal degeneration, retinal dystrophy) is an oftalmological pathology, where the dystrophy of the retina develops. It can be part of the symptom complex of some hereditary diseases, also it can be an independent pathology. In some cases, secondary degeneration after trauma and other complications are possible.

Independent hereditary forms of retinal abiotrophy have a different prevalence, on average, it ranges from 1-10: 10,000. 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 the equal affection of persons of both sexes to the almost complete prevalence of men among the sick (with X-linked inheritance).

Genetically determined abiotrophy of the retina is the most common cause of vision loss of a hereditary nature.

Causes of retinal abiotrophy

The etiology of retinal abiotrophy varies depending on the particular type of disease. A common mechanism is a mutation of a specific gene or genes that encode specific proteins involved in the vital activity of the retina. However, the pathogenesis of most forms has not been studied sufficiently.

The reason for the most common form of retinal abiotrophy – pigmentary dystrophy – can be more than 150 variants of mutations in several dozen genes, most of which are inherited in an autosomal dominant type. Almost a quarter of all cases of pigmented abiotrophy of the retina are due to various mutations in the opsin protein gene. In the CRB1 photoreceptor protein gene, the mutation has a recessive nature of inheritance, and in the genes RP2 and RPGR – linked to the X chromosome.

There is a rare form of pigmented retina abiotrophy with a mutation in mitochondrial DNA and, consequently, inheritance from the mother of offspring. Despite a huge number of different variants of the primary disorder in pigment retinitis, the pathogenesis of the disease as a whole is the same – there is a disruption in the utilization of used sticks, as a result of which they become a source of toxins in the retina. Due to the fact that the concentration of rods grows towards the periphery of the reticular membrane, pathological changes begin precisely there, the formation of new photosensitive cells slows down, which leads to a decrease in photosensitivity.

The white spot abiotrophy of the retina is associated with mutations in one of the four genes – RHO, PRPH2, RDH5 or RLBP1, with the most common form due to changes in the PRPH2 gene encoding the peripheral protein. The disease is inherited by autosomal recessive type. It is suggested that the peripheral participates in the stabilization of the membranes of photoreceptors, mainly rods, so that disturbances in its structure make them less stable and lead to their destruction. The white spot abiotrophy of the retina has a progressive course, with the first disturbances (which are visible when examining the fundus in the form of white dots) are formed on the periphery of the retina.

Yellow-spotted abiotrophy of the retina (Stargardt’s disease) is also caused by mutations of several genes. The most common form of yellow-spotted degeneration of the reticular membrane 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 an autosomal recessive type.

The change in the structure of the transmembrane protein ABCA4 leads to the accumulation of toxic metabolites (in particular, lipofuscin) in the retina, which causes the dystrophy of the photosensitive layer. Another variant of Stargardt’s disease with autosomal dominant inheritance is due to 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 certain components of their membranes.

Another type of yellow-spotted abiotrophy of the retina is associated with the mutation of the PROM1 gene. The pathogenesis of disorders in this case has not been thoroughly studied.

Abiotrophy of the Besta retina is caused by mutations of the BEST1 gene, the transcription product of which is the protein of bustrophin, belonging to the class of anion channels. Inheritance is autosomal dominant, the pathogenesis of dystrophy is unknown.

Congenital inpatient night blindness is a generalized retinal abiotrophy with a predominant lesion of the rods, it is also accompanied by other disorders of the organ of vision – strabismus, cataracts. Isolate the complete and incomplete forms of congenital stationary night blindness, both inherited by the X-linked mechanism. The full type is due to a mutation of the NYX gene, which encodes a protein, which provides transmission of excitation from the rods to bipolar cells.

As a result, the transfer of information from the photoreceptors is disrupted, there is a hemeralopia with almost no vision in the dark, and acuity and color perception usually do not suffer. The incomplete form is caused by the mutation of the CACNA1F gene, the product of which is a similar protein, but it is found in both rods and cones. At the same time, however, the transfer of the pulse is not blocked completely, so the twilight vision is only weakened, but the acuity and color perception also suffer.

Retinal abiotrophy classification

In ophthalmology, all hereditary forms of dystrophy of the retina of the eye are divided into three groups:

  1. Peripheral, in which disturbances occur mainly along the edges of the fundus, but in some forms of abiotrophy they can progress and capture the central regions, up to the yellow spot. In addition, with them, peripheral vision is most severely affected, the adaptation of the eye to darkness is disturbed, hemeralopia often occurs. These include pigmented and white-spot abiotrophy of the retina.
  2. Central, which are characterized by a predominant lesion of the macula and the central regions of the fundus. At the same time, color perception is disturbed, visual acuity is greatly reduced. It is these manifestations that accompany Stargardt’s disease and Best’s disease.
  3. With some mutations or a combination of them, retinal abiotrophy can affect the entire retina of the eye, so some researchers identify a third group of dystrophies, generalized. Congenital inpatient night blindness refers precisely to this type. Generalized retinal disorders accompany other hereditary diseases – for example, Leber’s amaurosis.

However, due to the large number of different mutations, the above-described division is somewhat arbitrary. Thus, some forms of pigmentary dystrophy can acquire a generalized character, and with mutation of the PROM1 gene (the fourth type of Stargardt disease), abiotrophy from the central regions of the retina can extend to the periphery.

Symptoms of retinal abiotrophy

Symptoms and signs of retina abiotrophy are quite variable because of 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 abiotrophies (pigmentary dystrophy, white-spot abiotrophy) begin with a predominant lesion of the rods, so one of the first symptoms of the disease will be hemorrhagia. With the progression of pathology, with the further destruction of the rods, a decrease in night vision can develop into its total loss, niktalopia.

Violated peripheral vision, there is a concentric scotoma, after which the field of view narrows so much that it becomes “tubular”. With the white point abiotrophy of the retina, the more severe disturbances do not usually develop, day vision and color perception remain unchanged. In a number of cases of pigmentary dystrophy, the cones are also involved in the pathological process, which leads to a drop in daytime vision, a decrease in its severity, and sometimes complete blindness. The course of the disease can take dozens of years, although there are also fleeting, as well as juvenile forms.

Central abiotrophy of the retina is characterized by the predominant involvement of cones, the concentration of which is highest in the area of ​​the macula – therefore they are also called macular degenerations. At the forefront is a sharp reduction in visual acuity, the perception of colors is violated, with the complete destruction of photoreceptors in the center of the fundus the central scotoma develops.

If the pathological process does not extend to the peripheral areas of the retina, then peripheral and twilight vision is affected poorly.

In the forms of abiotrophy characterized by focal lesion of photoreceptors, blind spots develop in the field of vision. In particularly severe forms, atrophy of optic nerve fibers and complete blindness can occur.

The full form of congenital stationary night blindness is characterized by pronounced niktalopiya with preservation of day vision and color perception. At the same time, there is no progression of the disease. Symptoms of the incomplete form of the VSNS are moderate hemostalopia, decreased visual acuity, color vision anomalies, the complexity of adaptation to reduced illumination.

How to diagnose retinal abiotrophy

Patients with retinal abiotrophy should be consulted by a geneticist and an ophthalmologist. Definition of dystrophic processes in the retina of the eye is made on the basis of data from the examination of the fundus, electroretinography, visual acuity studies and color perception. An important role is played by the study of the hereditary history, as well as genetic studies for the detection of mutations in the genes associated with this or that type of retinal abiotrophy.

Pigmented dystrophy along the periphery of the fundus reveals foci of pigment deposition, and 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 later stages, atrophy of the capillaries of the choroid of the eye occurs. In a number of cases wax-like atrophy of the optic nerve 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 for the detection of mutations is most often performed with respect to the genes RP1, RHO, RDS, RLBP1, PRPF8 and a number of others.

The white spot abiotrophy of the retina in the examination of the fundus is characterized by the presence of white, sometimes with a metallic hue, foci located along the periphery of the retina. The arterioles of the reticular membrane are narrowed, the pigment deposits are present in a single quantity, the blanching of the optic nerve disk is revealed.

Changes in electroretinography are poorly expressed and are not a reliable diagnostic criterion. Genetic diagnosis is represented by the sequencing of the PRPH2 gene.

In diseases of Stargardt and Best, ophthalmoscopy reveals atrophic foci of light shade, often surrounded by pigment deposits. The size and number of foci may differ significantly and reflect the severity of the damage to the retina of the eye. They are mainly located in the central zones, but they can also extend to the periphery. Electroretinography reveals a sharp decrease in the amplitude of wave A, which indicates the predominant destruction of the cones. Genetic diagnosis is reduced to the identification of mutations in the ABCA4 and CNGB3 genes and the study of a hereditary anamnesis.

Retinal abiotrophy: Treatment and prognosis

There is no specific etiotropic treatment for any form of retinal abiotrophy at the moment. As a supportive treatment, delaying the progression of the disease, preparations of vitamins A, E, riboflavin are used. The vasodilators help improve the blood supply to the retina, which also slows the dystrophic processes.

In recent years, there have been reports of the successful use of bionic retinal implants (Argus, Argus 2), which have partially restored sight 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.

Because of 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 can be limited to hemorrhagia and impaired peripheral vision, while other forms of this pathology lead to complete blindness. By taking vitamin A supplements in some cases, it is possible to slow the progression of retinal abiotrophy, according to some data the use of sunglasses also allows to achieve a similar result.

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