Congenital glaucoma is more often a hereditary disease accompanied by a gradual increase in intraocular pressure and related concomitant visual disturbances. The main symptoms of this pathology include an increase in the size of the eyes (in infants), soreness, which leads to anxiety and tearfulness of the child, photophobia, myopia or astigmatism. The diagnosis of congenital glaucoma is made on the basis of ophthalmological examination data, the study of the patient’s hereditary history and the course of pregnancy, genetic studies. Treatment is only surgical, and it should be performed as early as possible before the development of irreversible secondary disorders in the organ of vision.
Congenital glaucoma is a genetic, less commonly acquired intrauterine disease, which is characterized by underdevelopment of the angle of the anterior chamber of the eye and the trabecular network, which ultimately leads to an increase in intraocular pressure. This condition is considered relatively rare in ophthalmology and occurs in about one case per 10,000 births. Some researchers believe that this statistic does not quite correctly reflect reality, because some forms of congenital glaucoma may not manifest themselves until adolescence. Despite the fact that the pathology is inherited by an autosomal recessive mechanism, boys prevail somewhat among patients – the sexual distribution is approximately 3:2. According to the age of development of the main symptoms, as well as the presence or absence of genetic defects, several clinical forms of this disease are distinguished. The importance of timely detection of congenital glaucoma is due to the fact that without treatment, a child may go blind 4-5 years after the development of the first manifestations of pathology.
The vast majority of cases of congenital glaucoma (at least 80%) are accompanied by a mutation of the CYP1B1 gene, which is localized on the 2nd chromosome. It encodes the cytochrome P4501B1 protein, the functions of which are currently insufficiently studied. It is assumed that this protein is somehow involved in the synthesis and destruction of signaling molecules that participate in the formation of the trabecular network of the anterior chamber of the eye. Defects in the structure of cytochrome P4501B1 lead to the fact that the metabolism of the above compounds becomes abnormal, which contributes to the disruption of eye formation and the development of congenital glaucoma. Now there are more than fifty varieties of mutations of the CYP1B1 gene that are reliably associated with the development of this disease, but it has not yet been possible to identify the relationship between specific gene defects and certain clinical forms.
In addition, there are indications of the role in the development of congenital glaucoma of another gene – MYOC, located on the 1st chromosome. The product of its expression, a protein called myocillin, is widely represented in the eye tissues and is also involved in the formation and functioning of the trabecular network of the eye. It was previously known that mutations of this gene are the cause of open-angle juvenile glaucoma, however, with simultaneous damage to MYOC and CYP1B1, a congenital variety of this pathology develops. Some researchers in the field of genetics believe that the detection of a mutation of the myocillin gene against the background of a CYP1B1 defect does not play a special clinical role in the development of congenital glaucoma and is just a coincidence. Mutations of these two genes are inherited by an autosomal recessive mechanism.
In addition to hereditary forms of this pathology, approximately 20% of cases are diagnosed with congenital glaucoma in the absence of both cases of the disease and pathological genes in the parents. In this case, the cause of the development of ocular disorders may be either spontaneous mutations, or damage to the tissues of the eye in the prenatal period. The latter may be due to infection of the mother during pregnancy with certain infections (for example, toxoplasmosis, rubella), intrauterine fetal injuries, retinoblastoma, exposure to teratogenic factors. Since there is no genetic defect in such a situation, such a pathology is called secondary congenital glaucoma. In addition, similar visual organ disorders can occur in some other congenital diseases (Marfan syndrome, anhidrosis, and others).
Whatever the cause of congenital glaucoma, the mechanism of development of disorders in this condition is almost the same. Due to the underdevelopment of the angle of the anterior chamber of the eye and the trabecular network, watery moisture cannot normally leave the cavity, its accumulation occurs, which is accompanied by a gradual increase in intraocular pressure. A feature of congenital glaucoma is the fact that the tissues of the sclera and cornea in children have greater elasticity than in adults, therefore, when moisture accumulates, the size of the eyeball increases (most often two at once, very rarely only one). This somewhat reduces intraocular pressure, but over time this mechanism becomes insufficient. There is a flattening of the lens and cornea, microfractures may appear on the latter, leading to turbidity; the optic nerve disc is damaged, the retina is thinned. Eventually, its detachment may occur – clouding of the cornea and detachment of the retina of the eye are the leading causes of blindness in congenital glaucoma.
In clinical practice, congenital glaucoma is primarily divided into three types – primary, secondary and combined. The primary one is caused by genetic disorders, is inherited by an autosomal recessive mechanism and accounts for about 80% of all cases of the disease. The cause of secondary congenital glaucoma is an intrauterine violation of the formation of visual organs of various non-genetic nature. The combined variety, as the name implies, is accompanied by the presence of congenital glaucoma against the background of other hereditary diseases and conditions. The primary form caused by genetic defects, in turn, is divided into three clinical forms:
- Early congenital glaucoma – in this form, signs of the disease are detected at birth, or they manifest themselves in the first three years of a child’s life.
- Infantile congenital glaucoma – develops at the age of 3-10 years, its clinical course is no longer similar to the early type and approaches that of adults with other forms of glaucoma.
- Juvenile congenital glaucoma – the first manifestations of this form of the disease are registered most often in adolescence, the symptoms are very similar to the infantile type of pathology.
Such a significant difference in the age of development of congenital glaucoma is directly related to the degree of underdevelopment of the trabecular network of the eye. The more pronounced the disturbances in these structures, the earlier the accumulation of watery moisture begins with an increase in intraocular pressure. If the underdevelopment of the angle of the anterior chamber of the eye does not reach significant values, then in the first years of the child’s life, the outflow occurs quite normally, and the disorders develop much later. Attempts to link certain clinical forms of congenital glaucoma with specific types of mutations of the CYP1B1 gene have not been successful to date, and the mechanisms of development of this or that type of disease are still unknown.
The most peculiar manifestations are characterized by the early form of primary congenital glaucoma, which is due to the anatomical features of the structure of the eye in a child under the age of 3 years. In very rare cases, glaucoma changes can be noticed already at birth, most often in the first 2-3 months of life, the disease does not manifest itself in any way. Then the child becomes restless, sleeps poorly, is very often capricious – this is due to unpleasant and painful sensations with which congenital glaucoma debuts. After a few weeks or months, a slow increase in the size of the eyeballs begins (less often – one). An increase in intraocular pressure and the elasticity of the sclera tissues can lead to a significant increase in the eyes, which outwardly creates a false impression of a beautiful “big-eyed” child. Then these symptoms are joined by edema, photophobia, lacrimation, sometimes there is a clouding of the cornea.
Infantile and juvenile forms of congenital glaucoma are very similar in many ways, only the age of development of the first manifestations of the disease differs. An increase in the size of the eyeballs, as a rule, does not occur, the pathology begins with a feeling of discomfort and soreness in the eyes, headaches. The child may complain of visual impairment (the appearance of bright halos around light sources, “midges” in front of the eyes). These types of congenital glaucoma are often accompanied by other disorders of the visual apparatus – strabismus, astigmatism, myopia. Over time, there is a narrowing of the field of vision (the ability to see objects with lateral vision is lost), a violation of dark adaptation. Photophobia, edema and vascular injection of the sclera, characteristic of the early form of the disease, are most often not observed in these forms. In the absence of treatment, any kind of congenital glaucoma eventually leads to blindness due to retinal detachment or optic nerve atrophy.
The detection of congenital glaucoma is performed by an ophthalmologist on the basis of examination data, ophthalmological studies (tonometry, gonioscopy, keratometry, biomicroscopy, ophthalmoscopy, ultrasound biometry). Also, an important role in the diagnosis of this condition is played by genetic studies, the study of hereditary anamnesis and the course of pregnancy. Upon examination, enlarged (with an early form) or normal eye sizes are found, swelling of the tissues surrounding the eyeball may also be observed. The horizontal diameter of the cornea is enlarged, microfractures and turbidity are possible on it, the sclera is thinned and has a bluish tinge, the iris is also affected with congenital glaucoma – atrophic processes occur in it, the pupil reacts sluggishly to light stimuli. The anterior chamber of the eye is deepened (1.5-2 times the age norm).
There are no pathological changes on the fundus for a long time, since due to the increase in the size of the eyeball, intraocular pressure does not initially reach significant values. But then the excavation of the optic nerve disc develops quite quickly, however, with a decrease in pressure, the severity of this phenomenon also decreases. Due to the increase in the size of the eyes with congenital glaucoma, the retina is thinning, which, if left untreated, can lead to its rupture and regmatogenic detachment. Often, against the background of such changes, myopia is detected. Tonometry shows a slight increase in intraocular pressure, but this indicator should be compared with the anterior-posterior size of the eye, since the stretching of the sclera smoothes the IOP indicators.
The study of the hereditary history can reveal similar changes in the relatives of the patient, while it is often possible to determine the autosomal recessive type of inheritance – this indicates in favor of primary congenital glaucoma. The presence of infectious diseases of the mother during pregnancy, injuries, exposure to teratogenic factors indicates the possibility of developing a secondary form of the disease. Genetic diagnosis is carried out by direct sequencing of the sequence of the CYP1B1 gene, which makes it possible to identify its mutations. Thus, only a geneticist can unequivocally prove the presence of primary congenital glaucoma. In addition, if one of the parents or their relatives has such a condition, it is possible to search for the pathological form of the gene before conception or prenatal diagnosis by amniocentesis or other techniques.
Treatment and prognosis
Treatment of congenital glaucoma is only surgical, it is possible to use modern laser technologies. Conservative therapy using traditional means (pilocarpine drops, clonidine, epinephrine, dorzolamide) is auxiliary and can be used for some time during the waiting for surgery. Surgical intervention is reduced to the formation of a pathway of outflow of watery moisture, which reduces intraocular pressure and eliminates congenital glaucoma. The method and scheme of the operation is chosen in each case strictly individually. Depending on the clinical picture and the structure of the eyeball, goniotomy, sinustrabeculectomy, drainage operations, laser cyclophotocoagulation or cyclocryocoagulation can be performed.
The prognosis of congenital glaucoma with timely diagnosis and surgery is most often favorable, but if the treatment is performed late, various visual impairments are possible. After the elimination of glaucoma, at least three months of dispensary observation by an ophthalmologist is necessary.