Retinitis pigmentosa: causes, symptoms, diagnosis, treatment

Pigmentary retinitis (a more accurate term is "pigmentary retinal dystrophy", since there is no inflammation in this process, diffuse retinal dystrophy with predominant damage to the rod system. Pigmentary retinitis (pigmentary degeneration of the retina, tapetoretinal 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 is 1: 5000. It occurs as a result of the formation of defects in the genetic code, which results in an abnormal composition of specific proteins. The course of the disease with different types of inheritance has some features. The rhodopsin gene is the first identified gene, mutations of which cause the development of pigmentary retinitis with an autosomal dominant type of inheritance.

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Pattern of inheritance of retinitis pigmentosa

Age of onset, rate of progression, prognosis of visual functions and associated ophthalmologic features are often related to the mode of inheritance. Mutations in the rhodopsin gene are the most common. Electrocupogram may occur sporadically or have an autosomal dominant, autosomal recessive or X-linked mode of inheritance, and may also be part of hereditary syndromes, usually autosomal recessive.

• Isolated, without a hereditary burden, is common.
• Autosomal dominant is common and has a better prognosis.
• Autosomal recessive is common and has a worse prognosis.
• X-linked - the rarest and has the most severe prognosis. The fundus of female carriers may be normal or have a metallic tapetal reflex, atrophic or pigmented foci.

Symptoms of retinitis pigmentosa

Pigmentary retinitis manifests itself in early childhood and is characterized by a triad of symptoms: typical pigmented foci on the middle periphery of the fundus and along the venules (they are called bone bodies), waxy pallor of the optic disc, and narrowing of the arterioles.

Patients with retinitis pigmentosa may eventually develop pigmentary changes in the macular region due to degeneration of photoreceptors, which is accompanied by a decrease in visual acuity, posterior vitreous detachment, and deposition of delicate pigment in it. Macular edema may occur due to the penetration of fluid from the choroid through the pigment epithelium, and as the process progresses, preretinal macular fibrosis. Patients with retinitis pigmentosa are more likely than the general population to have optic disc drusen, posterior subcapsular cataracts, open-angle glaucoma, keratoconus, and myopia. The choroid remains intact for a long time and is involved in the process only in the late stages of the disease.

Night blindness, or nyctalopia, occurs due to damage to the rod system. Dark adaptation is impaired already at the initial stage of the disease, the threshold of light sensitivity is increased in both the rod and cone parts.

Atypical forms of retinitis pigmentosa

Other forms of retinitis pigmentosa include inverted retinitis pigmentosa (central form), non-pigmented retinitis pigmentosa, punctate retinitis pigmentosa, and pseudo-pigmented retinitis. Each of these forms has a characteristic ophthalmoscopic picture and electroretinographic symptoms.

1. Sectoral retinitis pigmentosa is characterized by changes in one quadrant (usually the nasal one) or half (usually the lower one). It progresses slowly or does not progress at all.
2. Pericentral retinitis pigmentosa, in which pigmentation extends from the optic disc to the temporal arcades and nasally.
3. Retinitis pigmentosa with exudative vasculopathy is characterized by an ophthalmoscopic picture similar to Coats disease with lipid deposits in the peripheral retina and exudative retinal detachment.

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Retinitis pigmentosa inverta (central form)

Unlike the typical form of pigment retinitis, the disease begins in the macular area and the damage to the cone system is more significant than to the rod system. First of all, central and color vision decreases, photophobia (photophobia) appears. Characteristic pigment changes are noted in the macular area, which can be combined with dystrophic changes in the periphery. In such cases, one of the main symptoms is the absence of daytime vision. In the visual field, there is a central scotoma, on the ERG, the cone components are significantly reduced compared to the rod components.

Retinitis pigmentosa without pigment

The name is associated with the absence of pigment deposits in the form of bone bodies, which are characteristic of retinitis pigmentosa, in the presence of symptoms similar to the manifestations of retinitis pigmentosa, and an unrecorded ERG.

Retinitis pigmentosa albicans

The characteristic ophthalmoscopic sign is multiple white punctate spots throughout the fundus with or without associated pigment changes ("moth-eaten tissue"). Functional symptoms are similar to those of retinitis pigmentosa. The disease must be differentiated from stationary congenital night blindness and fundus albipunctatus.

Pseudo pigment retinitis

Pseudo pigment retinitis is a non-hereditary disease. It can be caused by inflammatory processes in the retina and choroid, side effects of medications (thioridazine, melliril, chloroquine, deferoxamine, clofazamine, etc.), conditions after trauma, retinal detachment, etc. The fundus shows changes similar to those in pigment retinitis. The main distinguishing symptom is normal or slightly reduced ERG. In this form, there is never an unrecorded or sharply reduced ERG.

Currently, there is no pathogenetically substantiated treatment for retinitis pigmentosa. Replacement or stimulating therapy is ineffective. Patients with retinitis pigmentosa are recommended to wear dark protective glasses to prevent the damaging effects of light, select the maximum spectacle correction of visual acuity, and prescribe symptomatic treatment: in case of macular edema - systemic and local use of diuretics (carbonic anhydrase inhibitors), such as diacarb, diamox (acetazolamide); in the presence of lens opacities, surgical treatment of cataracts to improve visual acuity, in the presence of neovascularization, photocoagulation of vessels is performed to prevent complications, vascular drugs are prescribed. Patients, their relatives and children should undergo genetic counseling, examination of other organs and systems to exclude syndromic 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 finding ways of rational therapy.

Currently, attempts are being made to transplant pigment epithelial cells and neuronal retinal cells from a week-old embryo. A promising new approach to treating retinitis pigmentosa involves gene therapy based on subretinal administration of an adenovirus containing healthy minichromosomes inside its capsule. Scientists believe that the viruses, penetrating the pigment epithelial cells, help replace 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 pigment retinitis. To date, about 100 diseases with various eye disorders are known, caused by a violation of the metabolism of lipids, carbohydrates, proteins. Insufficiency of intracellular enzymes leads to gene mutations, which determines various genetic pathologies, including the disappearance or dystrophy of photoreceptor cells.

Specific systemic diseases associated with retinitis pigmentosa include disorders of carbohydrate metabolism (mucopolysaccharidoses), lipids (mucolipidoses, fucosidosis, serous lipofuscinoses), lipoproteins and proteins, lesions of the central nervous system, Usher syndrome, Lawrence-Moon-Bardet-Biedl syndrome, etc.

Diagnosis of retinitis pigmentosa

Functional methods of examination allow to detect progressive changes in photoreceptors. During perimetry on the middle periphery (30-50°) annular complete and incomplete scotomas are found, which expand to the periphery and center. In the late stage of the disease the visual field concentrically narrows to 10°, only central tubular vision is preserved.

The absence or sharp decrease of the total ERG is a pathognomonic sign of retinitis pigmentosa.

Local ERG remains normal for a long time, and changes occur when the cone system of the macular region is involved in the pathological process. Carriers of the pathological gene have reduced ERG and an extended latent period of the ERG b-wave, despite a normal fundus.

The diagnostic criterion for retinitis pigmentosa is bilateral lesions, decreased peripheral vision, and progressive deterioration of the functional state of rod photoreceptors. The classic triad of retinitis pigmentosa: decreased arteriolar caliber

• retinal pigmentation in the form of "bone bodies"
• waxy pallor of the optic disc.

Pigmentary retinitis manifests itself as nyctalopia in the 3rd decade of life, but can occur earlier.

Diagnostic criteria for retinitis pigmentosa

• Narrowing of the arterioles, delicate dust-like intraretinal pigmentation and RPE defects, ophthalmoscopic picture of pigment retinitis sine pigmenlo. Less common is "white-spot" retinitis - white spots, the density of which is maximum in the equatorial region.
• On the middle periphery there are large perivascular pigment deposits in the form of “bone bodies”.
• The ophthalmoscopic picture is mosaic due to atrophy of the RPE and exposure of large choroidal vessels, marked narrowing of the arterioles and waxy pallor of the optic disc.
• Maculopathy can be atrophic, “cellophane,” or manifest as cystic macular edema, which is relieved by systemic administration of acetazolamide.
• The scotopic (rod) and mixed electroretinograms are reduced; later, the photopic electroretinogram is reduced.
• The electrooculogram is subnormal.
• Dark adaptation is slow and is necessary in the early stages when the diagnosis requires clarification.
• Central vision is impaired.
• Perimetry reveals a ring-shaped scotoma at the midperiphery, which expands toward the center and periphery. The central part of the visual field remains intact, but may be lost over time.
• FAG is not necessary for diagnosis. It reveals diffuse hyperfluorescence due to "final" defects of the PE, small zones of hypofluorescence (shielding by pigment).

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Differential diagnosis of retinitis pigmentosa

Terminal stage chloroquine retinopathy

• Similarity: bilateral diffuse RPE atrophy unmasking choroidal large vessels and arteriole thinning.
• Differences: Pigmentary changes differ from "bone body" changes; optic disc atrophy without waxy pallor.

Terminal thioridazine retinopathy

• Similarity: bilateral diffuse RPE atrophy.
• Differences: plaque-shaped pigment changes, no nyctalopia.

Terminal syphilitic neuroretinitis

• Similarities: marked narrowing of the visual fields, narrowing of blood vessels and pigmentary changes.
• Differences: nyctalopia is weakly expressed, changes are asymmetrical, with slight or pronounced choroidal unmasking.

Cancer-associated retinopathy

• Similarities: nyctalopia, visual field constriction, vasoconstriction and fading electroretinogram.
• Differences: rapid progression, minor or no pigmentary changes.

Associated systemic diseases

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

1. Bassen-Kornzweig syndrome, an autosomal dominant disorder, is caused by a deficiency of b-lipoprotein, resulting in intestinal malabsorption.
   • symptoms: spinocerebellar ataxia and acanthocytosis of peripheral blood;
   • retinopathy - at the end of the first decade of life. Pigment lumps are larger than in classical retinitis pigmentosa and are not limited to the equator; peripheral "white-dot" changes are characteristic;
   • other symptoms: ophthalmoplegia and ptosis;
   • Taking vitamin E daily to reduce neurological changes.
2. Refsum disease is an autosomal recessive inborn error of metabolism: deficiency of the enzyme phytanic acid 2-hydroxylase leads to increased levels of phytanic acid 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 (cytoalbumin inversion);
   • Retinopathy manifests itself in the 2nd decade of life with generalized changes of the “salt and pepper” type.
   • other manifestations: cataract, miosis, thickening of the corneal nerves;
   • Treatment: first of all, plasmapheresis, later - a diet without phytanic acid, which can prevent the progression of systemic disorders and retinal dystrophy.
3. Usher syndrome is an autosomal recessive disorder that manifests itself in 5% of children as severe deafness and in about 50% of cases as a combination of deafness and blindness. Retinitis pigmentosa develops in prepuberty.
4. Kearns-Sayre syndrome is a mitochondrial cytopathy associated with mitochondrial DNA deletions. Retinitis pigmentosa is atypical and is characterized by the deposition of pigment lumps, predominantly in the central retina.
5. Bardet-Biedl syndrome is characterized by mental retardation, polydactyly, obesity, and hypogonadism. Retinitis pigmentosa is severe: 75% of patients become blind by age 20, and some develop bull's-eye maculopathy.

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Treatment of retinitis pigmentosa

There is currently no cure for retinitis pigmentosa, but there are treatments and management options available to slow the progression of the disease and improve patients' quality of life.

Conservative treatment

• Vitamin therapy: Studies have shown that taking vitamin A can slow the progression of the disease in some cases. However, vitamin A should only be taken under the supervision of a doctor due to the risk of hypervitaminosis.
• Omega-3 fatty acids: There is preliminary evidence that omega-3 fatty acid supplements may help slow vision loss.

Sun protection products

Using sunglasses to protect your eyes from ultraviolet and blue light may help slow the progression of the disease.

Progressive treatment methods

• Gene therapy: Recent research is aimed at correcting the genetic defects that cause retinitis pigmentosa. For example, in 2017, the FDA approved the world's first gene therapy to treat an inherited retinal disorder caused by mutations in a specific gene called RPE65.
• Implantation of microelectronic devices: Various types of retinal implants are being researched and developed that can restore vision to some level in patients with retinitis pigmentosa.
• Stem Cells: Research into stem cell therapy aims to repair damaged retinas.

Supporting technologies

• The use of special visual devices such as telescopic glasses, electronic magnifying devices, and screen reading software can help patients better navigate their surroundings and maintain independence.

Lifestyle and Diet

• Maintaining a healthy lifestyle, including regular exercise and a balanced diet rich in antioxidants, can support overall health and slow the progression of the disease.

Treatment of retinitis pigmentosa should be comprehensive and individualized, taking into account the stage of the disease, genetic characteristics and general health of the patient. Regular observation by an ophthalmologist is important to monitor the disease and adjust the treatment strategy.

Forecast

The long-term prognosis is poor, with changes in the foveal zone causing a gradual decline in central vision. Daily supplementation with vitamin A may slow the progression.

General forecast

• About 25% of patients retain the visual acuity necessary for reading throughout their working age, despite the absence of an electroretinogram and a narrowing of the visual field to 2-3.
• Up to 20 years of age, visual acuity in most people is >6/60.
• By age 50, many patients have visual acuity <6/60.

Associated ocular pathology

Patients with retinitis pigmentosa should be monitored regularly to identify other causes of vision loss, including treatable ones.

• Posterior subcapsular cataracts are detected in all types of retinitis pigmentosa, and surgical intervention is effective.
• Open-angle glaucoma - in 3% of patients.
• Myopia is common.
• Keratoconus is rarely diagnosed.
• Vitreous changes: posterior vitreous detachment (common), peripheral uveitis (rare).
• Optic disc drusen are more common than in the normal population.

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