Best disease is one of the forms of bilateral central (macular) retinal pigment abiotrophy, leading to macular photoreceptor dystrophy and significant visual impairment. It is characterized by an initially asymptomatic course, visual acuity decreases over time, and a central scotoma occurs. Diagnosis is made on the basis of examination of the fundus, electrooculography and fluorescence angiography of retinal vessels, genetic studies. There is no specific treatment for Best disease, supportive treatment is used to slow the progression of manifestations of pathology.
Best disease (central pigmented abiotrophy, Best vitelliform dystrophy) is a genetic disease characterized by the development of cystic dystrophic changes in the macular area. It was first described in 1905 by F. Best, who studied identical visual impairments in eight relatives and suggested the hereditary nature of the pathology. Best disease affects both men and women with the same frequency, the incidence is approximately 3-4:100,000. Unlike many other forms of retinal abiotrophy, Best disease rarely leads to complete blindness, in addition, it is characterized by a long multi-stage course. At the initial stages of pathology, visual disturbances do not develop, and there are practically no symptoms, changes in the retina are often an accidental finding during a medical examination by an ophthalmologist. Timely prescribed maintenance therapy can significantly slow down the development of Best disease.
The cause of retinal dystrophy, which occurs in Best disease, is a mutation of the BEST1 gene localized on the 11th chromosome. It encodes the protein bestrophin, which belongs to the class of anion channels of the pigment epithelium of the retina of the eye. The pathogenesis of disorders in Best disease has not been thoroughly studied – it was found out that with this pathology there is a slow destruction of the pigment epithelium in the macular area, and the properties of the Bruch membrane change. As a result, capillaries germinate into the subretinal space, granules of a substance similar in its biochemical properties to lipofuscin accumulate in the retina. Macroscopically, with Best disease, pigment disorders slowly increase in the macular area, then a cyst appears, which blocks the flow of light to most of the photoreceptors of the macular area. Then there is a rupture of the cyst, its contents are resorbed, a scar forms in its place, which is the cause of persistent visual impairment.
The mechanism of inheritance of mutations of the BEST1 gene is autosomal dominant with a sufficiently high penetrance. In addition to Best disease, disorders of the structure of this gene can cause some other forms of retinal pigment degeneration, bestrophinopathy, and adult vitelliform dystrophy. The latter is very similar in its course to Best disease, but unlike it develops not in childhood, but in adulthood. This suggests that adult vitelliform dystrophy is a type of Best syndrome – modern genetics has not yet found other mutations that would lead to this condition.
The first changes in the fundus of Best disease occur at the age of 2-5 years, but there are no subjective symptoms. Therefore, the disease is diagnosed either based on the results of a random medical examination, or at a later age, after the development of the first visual impairments. In general, Best disease is characterized by a certain stage.
The zero stage of Best disease is very rarely diagnosed, since there are not even minor changes in the macular area. There is only a decrease in the foveal reflex and changes in electrooculography. When studying the latter, a decrease in the Arden coefficient is revealed. Sometimes such manifestations are registered in adults without further development of the clinical picture of Best disease – this is considered a sign of carrying a mutation of the BEST1 gene.
During the first stage, subjective symptoms are still not expressed, only in some cases there is a slight decrease in visual acuity. On the fundus, several yellowish dots are revealed in the macular region of the retina. During the second stage, the dots grow to a size comparable to the diameter of the optic disc, and look similar to an egg yolk. Visual acuity disorders at this stage of Best disease do not correspond to the ophthalmological picture and are insignificant – it remains at the level of 0.6-0.9. At the third stage of Best disease, a rupture of vitelliform cysts occurs, which leads to a sharp decrease in visual acuity. Also common complaints at this stage are blurred vision, difficulty reading small text. The fourth stage is characterized by the resorption of cystic rupture products and the formation of a scar in their place. Visual acuity in different patients at this stage ranges from 0.02 to 0.7, in addition, there is a relative central scotoma and pseudohypopion. The boundaries of the field of view, as a rule, do not change, the normal perception of colors remains.
The duration of each stage in different patients can vary widely. In addition, in some cases, Best disease can develop more quickly, so some stages are not diagnosed. Changes in the fundus of both eyes are most often asymmetric in nature. As a rule, complete blindness does not occur, one of the complications of Best disease may be the formation of a subretinal neovascular membrane, which significantly reduces visual acuity. In addition, with age, choriodal sclerosis may develop at the site of scars after vitelliform cysts.
Diagnosis of Best disease is performed using methods of modern ophthalmology – examination of the fundus, electrooculography, fluorescent angiography of retinal vessels. Upon examination, depending on the stage of the disease, either yellow dots or formed vitelliform cysts are detected, concentrated in the center. After their rupture (the third stage of Best disease), the picture of the fundus resembles a “scrambled egg”. In addition, retinal hemorrhages may occur at any stage of the disease, also noticeable during examination. At the last stage of Best disease, a pseudohypopion is formed, pigment deposits in the macular area are noticeable.
One of the very first manifestations of the disease is an abnormal picture of electrooculography, which is recorded even before the appearance of the first changes in the fundus. The pathognomonic sign of Best disease is a decrease in the Arden coefficient or the ratio of the light peak to the light decline, which at the final stages of the pathology does not exceed 1.5. With fluorescence angiography in the first stages of the disease (before the formation of vitelliform cysts), areas of local hyperfluorescence corresponding to the sites of pigment epithelium atrophy are observed. After the formation of cysts (the second stage of Best disease), a complete absence of fluorescence is detected in the places of their localization, and when they rupture (the third stage), hyperfluorescence in the upper parts of the cysts and its absence in the lower ones.
A geneticist can also make a genetic diagnosis of Best disease, which boils down to sequencing the sequence of the BEST1 gene in order to search for mutations. This study is quite complex, since a huge number of genes are located in this area of the 11th chromosome, mutations of many of them can also lead to hereditary ophthalmological diseases. Differential diagnosis of Best disease is carried out with Coats syndrome and detachment of the pigment epithelium. In contrast, the central pigment abiotrophy always has a bilateral character and is characterized by abnormal electrooculography.
Treatment and prognosis
There is no specific treatment for Best disease, and therefore supportive therapy is used, which can significantly slow the progression of pathology. It includes the appointment of vitamins A and E, vasodilating and improving retinal trophism – meldonium, methylethylpyridinol, ethylmethylhydroxypyridine succinate. This inhibits the development and subsequent rupture of vitelliform cysts, allowing you to maintain satisfactory visual acuity for a long time. In cases where Best disease was complicated by the formation of a subretinal neovascular membrane, laser correction is indicated.
The prognosis of Best disease is usually conditionally favorable. Complete loss of vision occurs in very rare cases, usually everything is limited to a decrease in visual acuity and relative central scotoma. Peripheral and twilight vision does not suffer, patients in the future only find it difficult when working with small font and small details. With adult vitelliform dystrophy, visual impairments are even less pronounced, in some cases patients have no complaints at all, and the presence of the disease is determined only by ophthalmological and genetic studies.