Choroideremia is a hereditary dystrophy of the vascular membrane of the eye, which is characterized by damage to the retina, pigment epithelium and photoreceptors. The clinical picture is represented by a violation of twilight vision, a feeling of a foreign body in the eyes, headache. The progression of the disease leads to amaurosis. Diagnostics is based on ophthalmoscopy, perimetry, visometry, electroretinography, retinal angiography. Etiotropic therapy has not been developed. Symptomatic treatment is reduced to the use of antihypertensive agents, angioprotectors, enzyme preparations, vitamins C, B, A and PP.
H31.2 Hereditary dystrophy of the vascular membrane of the eye
Choroideremia (tapetochoroidal dystrophy, chorioderma) is a rare genetic pathology. The prevalence of the disease in the Salla community in northern Finland is 1:40. In other regions, the disease is much less common – 1 case per 50,000 people. Only men suffer from choroideremia, since the disease is inherited by the X-linked recessive type. In women who are carriers of the pathological gene, minor changes in the vascular membrane of the eyes may be detected. In 87% of patients, the first signs of the disease occur in early childhood and only 13% – in adolescence. In 37% of cases, by the age of 50-60, visual acuity decreases up to light perception.
The etiology of the disease is associated with a mutation of the CHM gene. The child inherits the defective gene from the carrier mother. The disease develops in all boys in the family and male representatives on the mother’s side. Since females have two X chromosomes, changes in the structures of the uveal tract are insignificant in them. The causes of mutations at the gene level have not been fully elucidated. Scientists believe that their appearance is facilitated by exposure to adverse environmental factors (ultraviolet radiation, taking medications during pregnancy). At the same time, cases of spontaneous mutations are common.
Genetic mutation plays a leading role in the mechanism of disease development. The type of inheritance of pathology is X-linked recessive. The mutated CHM gene includes 15 exons on the 15 kb section of the Xq2l chromosome.2. Scientists have established that normally the affected gene encodes the synthesis of geranyltransferase. The carriers of choroideremia are women, only men are ill. In addition to degenerative-dystrophic changes in the uveal tract, the photoreceptor apparatus is involved in the pathological process. Most often, changes in the rods are found in the peripheral part of the retina. This is caused by the progression of ischemia.
Damage to the pigment epithelium leads to the accumulation of pigment granules, which at a late stage penetrate into the thickness of the entire inner shell of the eye. The consequence of this is a change in the architectonics of the epithelial layer. Complete loss of vision develops only when two or more layers of the retina are affected. According to another pathogenetic theory, the occurrence of choroideremia is associated with impaired expression of the REP1 protein. Normally, a person has a protein REP2, which is 75% REP1 in structure. Structural similarity makes it possible to compensate for visual dysfunction. However, with a total violation of the expression of proteins of this group, the development of choroideremia is inevitable.
The first symptoms of the disease occur in boys at an early age. Patients complain of visual disturbances in the dark. There is discomfort in the eyes, manifested by a feeling of “sand” under the eyelids. Performing visual work leads to a headache that radiates into the brow arches, temporal and frontal lobes. Up to 40 years of age, the functions of central vision are not changed. In patients after reaching 50-60 years of age, in addition to progressive visual dysfunction, the functions of color perception are impaired. Tunnel vision remains intact for a long time.
The nature of the course of the disease may differ significantly among individual family members. Every year the severity of symptoms increases, which often leads to blindness. With a mild degree, visual dysfunction is minimal. In severe cases, a progressive decrease in visual acuity leads to vision loss by the age of 40-45. Clinical manifestations in women can be detected only with the use of instrumental diagnostic methods. In rare cases, female patients report deterioration of visual functions at dusk, which requires differentiation with acquired hemeralopia.
10-30 years after the appearance of the first signs of choroideremia, hemeralopia develops. The risk of attachment of pathogenic microflora with the subsequent occurrence of bacterial or viral chorioretinitis increases. The accumulation of pigmentocytes in the area of the trabecular network leads to a violation of the outflow of intraocular fluid and an increase in intraocular pressure. There is a high probability of developing ophthalmohypertension, less often secondary glaucoma. Amaurosis occurs when several layers of the inner shell of the eyeball degenerate.
The diagnosis is based on the data of anamnesis and genetic analysis, the results of specific examination methods. The development of the disease in a child is indicated by such anamnestic information as the presence of pathology in men on the maternal side. Instrumental diagnostics includes:
- Ophthalmoscopy. When examining the fundus, clusters of pigment granules are detected, which have the appearance of a “metallic reflex”. Pigment deposits are visualized in all quadrants of the retina. There are signs of atrophy of the choroid capillaries up to the appearance of a false impression of the complete absence of the vascular membrane. The macular and peripapillary zones are not changed.
- Electroretinography. A gradual transition from a normal electroretinogram to a subnormal one is determined. When studying dark adaptation, an increase in the rod threshold is noted. In the last stages, the ERG is not registered. General and local varieties of the procedure are used.
- Visometry. In daylight, visual acuity persists for a long time. When conducting a study in a darkened room, pronounced visual dysfunction is determined. Visual functions often decrease only in old age.
- Perimetry. There is a concentric narrowing of the visual fields or discrete, focal and circular lesions. The function of peripheral perception is significantly impaired when the central one is unchanged at a young age. After 50-60 years, even the islands of central vision gradually disappear.
- Fluorescence angiography of the retina. At the initial stages, there are no changes in vessels of large and medium diameter. With the progression of the disease, their sclerotic changes occur, which leads to the appearance of whitish-yellow coloration and selective foci of staining. At the terminal stages, the capillary network is not visualized. Against the background of the sclera, only single large vessels are visible.
Differential diagnosis is carried out with peripheral dystrophy of the “cobblestone pavement” type, girate atrophy, X-linked retinitis pigmentosa, circular degeneration of the choroid and retina. A distinctive feature of retinitis pigmentosa is the loss of not only peripheral, but also central vision. The cause of dystrophic disorders is the accumulation of ornithine in the blood. Changes in the fundus of the carriers of the pathological gene are represented by the redistribution of pigmentocytes in the form of a reticular pattern.
Etiotropic treatment of choroideremia has not been developed. Oxford University scientist Robert McLaren and colleagues are working on the introduction of gene therapy. The essence of the technique is based on the introduction of a copy of the REP1 protein in order to prevent further death of photoreceptors. Symptomatic treatment includes:
- Antihypertensive agents. They are prescribed with an increase in intraocular pressure (IOP) in order to stimulate the outflow of watery moisture and prevent the development of secondary glaucoma.
- Angioprotectors. The drugs improve metabolic processes, normalize the permeability of the vascular wall. Calcium dobezilate, ethamzilate has an angioprotective effect.
- Reparants. A complex of polypeptide fractions is used, which have a tissue-specific effect and contribute to the regeneration of the retina. The route of administration of the pharmacological agent is parabulbar.
- Enzyme preparations. Intramuscular injections of cytochrome C are performed. The drug improves tissue respiration and stimulates oxidative processes.
- Vitamin therapy. Oral intake of vitamins C of group B, C, PP and A. Additionally, taurine is used, which stimulates regenerative processes and a decrease in IOP.
Prognosis and prevention
The outcome of the disease depends on the severity of clinical symptoms and the rate of progression of disorders. Visual acuity does not change for a long time, but by the age of 50, manifestations of visual dysfunction are increasing, which are accompanied by a violation of color perception. Specific preventive measures have not been developed. An important role is given to genetic screening of pathology and the use of assisted reproductive technologies in pregnancy planning in persons with a burdened family history. Patients with choroideremia should be registered with an ophthalmologist at the dispensary.