Retinitis pigmentosa: causes, symptoms, diagnosis, treatment

Pigment retinitis (a more precise term is "pigmentary degeneration of the retina", as there is no inflammation in this process, diffuse dystrophy of the retina with a predominant lesion of the rod system.) Pigment retinitis (retinitis pigmental degeneration, taperotinal degeneration) is a disease characterized by damage to the pigment epithelium and photoreceptors with different types of inheritance: autosomal dominant, autosomal recessive or sex-linked Prevalence - 1: 5000. Occurs as a result of the formation of d The gene of rhodopsin is the first identified gene whose mutations are the cause of the development of pigment retinitis with an autosomal dominant type of inheritance.

[1]

Type of inheritance of retinitis pigmentosa

The age of the onset, the rate of progress, the forecast of visual functions and the concomitant ophthalmological signs are often associated with the type of inheritance. Mutations in the gene of rhodopsin are most common. The electrocardiogram can occur sporadically or have an autosomal dominant, autosomal recessive or X-linked type of inheritance, and also be a part of hereditary syndromes, usually autosomal recessive.

• Isolated with unhealthy heredity is common.
• Autosomal dominant is common and has a better prognosis.
• Autosomal recessive is common and the prognosis is worse.
• Coupled with the X-chromosome is the rarest and has the heaviest prognosis. The ocular bottom in female carriers can be normal or have a metal tapetal reflex, atrophic or pigmented foci.

Symptoms of retinitis pigmentosa

Pigment retinitis manifests itself in early childhood and is characterized by a triad of symptoms: typical pigment foci on the middle periphery of the fundus and venules (called bone bodies) along the way, waxy pallor of the optic nerve disk, narrowing of the arterioles.

In patients with pigment retinitis, pigment changes in the macular area may develop with time due to degeneration of the photoreceptors, which is accompanied by a decrease in visual acuity, a posterior detachment of the vitreous body and the deposition of a gentle pigment in it. Perhaps the appearance of macular edema caused by the penetration of fluid from the choroid through the pigment epithelium, and as the process develops - preretinal macular fibrosis. In patients with pigment retinitis with a greater frequency than in the general population, there are druses of the optic nerve disk, posterior subcapsular cataract, open-angle glaucoma, keratoconus and myopia. The choroid remains for a long time intact and is involved in the process only in the late stages of the disease.

In connection with the defeat of the rod system, there is night blindness, or niktalopia. Dark adaptation has been disrupted already in the initial stage of the disease, the threshold of light sensitivity is increased both in rod and in the cone part.

Atypical forms of pigment retinitis

Other forms of pigment retinitis include pigmented inverted retinitis (central form), pigmentary retinitis without pigment, pigmentary pigment retinitis and pseudopigment retinitis. Each of these forms has a characteristic ophthalmoscopic picture and an electroretinographic symptomatology.

1. Sectoral retinitis pigmentosa is characterized by changes in the water quadrant (usually nasal) or half (more often in the lower quadrant). Progresses slowly or does not progress at all.
2. Pericentral pigmentary retinitis, in which the pigmentation spreads from the optic nerve disc and passes to the temporal arcades and nasally.
3. Retinitis pigmentosa with exudative vasculopathy is characterized by a similar to Coats disease ophthalmoscopic picture with lipid deposits in the peripheral retina and exudative retinal detachment.

[2], [3], [4]

Pigmented inverted retinitis (central form)

Unlike the typical form of retinitis pigmentosa, the disease begins in the macular area and the lesions of the cone system are more significant than the rod-shaped system. First of all, the central and color vision decreases, and photophobia (photophobia) appears. In the macular area, characteristic pigment changes are noted, which can be combined with dystrophic changes at the periphery. In such cases, one of the main symptoms is the lack of day vision. In the field of vision of the central scotoma, the ERG significantly reduced the cone components compared to rod-shaped components.

Pigment retinitis without pigment

The name is due to the absence of pigmental deposits typical for pigment retinitis in the form of bony corpuscles in the presence of symptoms similar to manifestations of retinitis pigmentosa and an unregistered ERG.

Pure retinitis pigmentosa

A characteristic ophthalmoscopic feature is multiple white spot spots throughout the eye fundus with accompanying pigment changes ("moth-eaten tissue") or without them. Functional symptoms are similar to manifestations of retinitis pigmentosa. The disease must be differentiated from a stationary congenital night blindness and a white-spot eye fundus (fundus albipunctatus).

Pseudopigment retinitis

Pseudopigment retinitis is a non-hereditary disease. The cause of its occurrence may be inflammatory processes in the retina and choroid, the side effect of medications (thioridazine, melliril, chloroquine, deferoxamine, clofazamine, etc.), the state after trauma, retinal detachment, etc. On the fundus, changes similar to those with retinitis pigmentosa. The main distinguishing symptom is a normal or slightly decreased ERG. With this form, there is never an unregistered or sharply reduced ERG.

Currently, there is no pathogenetically substantiated treatment of retinitis pigmentosa. Substitution or stimulation therapy is ineffective. Patients with pigment retinitis are recommended to wear dark goggles to prevent damage to light, select the maximum spectacle correction of visual acuity, prescribe symptomatic treatment: for macular edema, systemic and topical use of diuretics (inhibitors of carbonic anhydrase), for example, diacarb, diamox (acetazolamide); in the presence of lens opacities, surgical treatment of cataracts for improvement of visual acuity, in the presence of neovascularization for the prevention of complications, photocoagulation of vessels, prescribe vascular drugs. Patients, their relatives and children should undergo genetic counseling, research of other organs and systems to avoid syndrome lesions and other diseases.

Identification of the pathological gene and its mutations is the basis for understanding the pathogenesis of the disease, predicting the course of the process and searching for ways of rational therapy.

At present, attempts are being made in the experiment to transplant pigment epithelial cells and retinal neuronal cells from a weekly embryo. A new promising approach to the treatment of retinitis pigmentosa is associated with gene therapy based on subretinal adenovirus administration, with the contents of healthy minichromosomes within the capsule. Scientists suggest that viruses, penetrating the cells of pigment epithelium, contribute to the replacement of mutated genes.

Generalized hereditary retinal dystrophy associated with systemic diseases and metabolic disorders

There are many systemic disorders that are combined with atypical forms of retinitis pigmentosa. To date, there are about 100 diseases with various eye disorders, caused by a violation of the metabolism of lipids, carbohydrates, proteins. The lack of intracellular enzymes leads to gene mutations, which determines a different genetic pathology, including the disappearance or dystrophy of photoreceptor cells.

Specific systemic diseases, combined with retinitis pigmentosa, include metabolic disorders of carbohydrates (mucopolysaccharidosis), lipids (mucolipidosis, fucosidosis, seroid lipofuscinosis), lipoproteins and proteins, central nervous system damage, Usher syndromes, Lawrence-Muna-Barde-Biddle syndrome, etc.

Diagnosis of retinitis pigmentosa

Functional research methods allow us to identify progressive changes in photoreceptors. At perimetry on the middle periphery (30-50 °) there are annular full and incomplete scotomas that expand to the periphery and center. In the late stage of the disease, the field of vision concentrically tapers to 10 °, only central tubular vision remains.

The absence or sharp decrease in total ERG is a pathognomonic sign of pigment retinitis.

Local ERG remains normal for a long time, and changes occur when the conical system of the macular area is involved in the pathological process. In carriers of the pathological gene, a reduced ERG and an elongated latent period of the b-wave ERG are noted, despite the normal ocular fundus.

Diagnostic criterion of retinitis pigmentosa is bilateral lesion, reduction of peripheral vision and progressive deterioration of the functional state of rod-shaped photoreceptors. Classical triad of pigment retinitis: a decrease in the caliber of arterioles

• pigmentation of the retina in the form of "bony bodies"
• waxy pallor of the optic disc.

Pigment retinitis is manifested by niktalopia in the third decade of life, but it can occur earlier.

Diagnostic criteria of pigmentary retinitis

• Narrowing of arterioles, tender dust-like intra-retinal pigmentation and defects of RPE, ophthalmoscopic picture of pigment retinitis sine pigmenlo. Less common is "white-spotted" retinitis - white spots, whose density is maximum in the equator.
• On the middle periphery there are large perivasal pigment deposits in the form of "bony bodies".
• Ophthalmoscopic picture is mosaic due to atrophy of RPE and exposure of large choroidal vessels, pronounced narrowing of arterioles and waxy pallor of the optic nerve disk.
• Maculopathy can be atrophic, "cellophane" or manifest as cystoid macular edema, which is stopped by the systemic administration of acetazolamide.
• Electroretinogram scotopic (rod) and mixed reduced; later the photopic electroretinogram decreases.
• The electro-oculogram is subnormal.
• Dark adaptation is slowed down and is necessary at early stages, when the diagnosis requires specification.
• Central vision suffers.
• Perimetry reveals a ring cattle on the middle periphery, which expands to the center and periphery. The central part of the field of view remains, which can be lost with time.
• The FAG is not necessary for the diagnosis. Detects diffuse hyperfluorescence due to "final" PE defects, small areas of hypofluorescence (pigment screening).

[5], [6]

Differential diagnosis of retinitis pigmentosa

Terminal stage of chloroquine retinopathy

• Similarity: two-sided diffuse atrophy of RPE, unmasking choroidal large vessels and thinning of the arterioles.
• Differences: pigment changes differ from changes in the form of "bony bodies"; atrophy of the optic nerve disk without waxy pallor.

Terminal thioridazin retinopathy

• Similarity: two-sided diffuse atrophy of RP.
• Differences: pigmentary changes in the plaque shape, niktalopia not.

Terminal syphilitic neuroretinitis

• Similarity: marked narrowing of the visual fields, narrowing of the vessels and pigment changes.
• Differences: Nictalopia is poorly expressed, changes are asymmetric, with mild or severe choroidal unmasking.

Associated with cancer retinopathy

• Similarity: niktalopiya, narrowing of the fields of vision, narrowing of the vessels and fading Electroretinogram.
• Differences: rapid progression of minor pigment changes or their absence.

Associated systemic diseases

Pigment retinitis, especially atypical retinitis, can be accompanied by a wide range of systemic diseases. The most common combinations are:

1. Bassen-Kornzweig syndrome, autosomal dominant, is caused by a deficiency of b-lipoprotein, which leads to intestinal malabsorption.
   • symptoms: spinocerebellar ataxia and acanthocytosis of peripheral blood;
   • Retinopathy - at the end of 1 decade of life. Pigmented lumps are larger than with classical pigment retinitis, and are not confined to the equator; peripheral "white-spot" changes are characteristic;
   • other symptoms: ophthalmoplegia and ptosis;
   • taking vitamin E daily to reduce neurologic changes.
2. Refsum disease is an autosomal recessive congenital metabolic disorder: the deficiency of the enzyme 2-hydroxylase of phytic acid leads to an increase in its level in the blood and tissues.
   • Symptoms: polyneuropathy, cerebellar ataxia, deafness, aiosmia, cardiomyopathy, ichthyosis and increased protein levels in the cerebrospinal fluid in the absence of pinocytosis (cyto-albumin inversion);
   • Retinopathy is manifested in the 2nd decade of life by generalized changes such as "salt with pepper".
   • other manifestations: cataract, miosis, thickening of the nerves of the cornea;
   • treatment: first of all plasmapheresis, later - a diet without phytic acid, which can prevent the progression of systemic disorders and degeneration of the retina.
3. Usher syndrome is an autosomal recessive disease, manifested in 5% of cases in children with severe deafness and about 50% - a combination of deafness and blindness. Pigment retinitis develops in prepubertate.
4. Kearns-Sayre syndrome is a mitochondrial cytopathy associated with fission of mitochondrial DNA. Pigment retinitis is atypical and is characterized by the deposition of pigment lumps, mainly in the central parts of the retina.
5. Bardet-Biedl syndrome manifests itself as mental retardation, polydactyly, obesity and hypogonadism. Pigment retinitis has a severe course: 75% of patients become blind by the age of 20, some develop maculopathy as a "bull's eye".

[7], [8], [9]

Forecast

The long-term prognosis is unfavorable, the reason for the gradual decrease in central vision is the changes in the foveal zone. Daily intake of vitamin A in the form of nutritional supplements can slow progression.

Overall forecast

• About 25% of patients retain the visual acuity needed for reading, despite the absence of the Electroretinogram and the narrowing of the field of vision to 2-3.
• Up to 20 years of visual acuity in the majority> 6/60.
• By the age of 50, many patients had visual acuity <6/60.

Concomitant ocular pathology

Patients with retinitis pigmentosa should be observed regularly to identify other causes leading to reduced vision, including those that are removable.

• Rear subcapsular cataracts are detected with all types of pigment retinitis, surgical intervention is effective.
• Open angle glaucoma - in 3% of patients.
• Myopia occurs frequently.
• Keratoconus is rarely detected.
• Changes in the vitreous: a posterior vitreous detachment (often), peripheral uveitis (rarely).
• Druises of the optic disc are more common than in the normal population.

[10], [11], [12], [13], [14]