Pseudoexfoliative syndrome is a uveopathy characterized by the deposition of an amyloid–like substance on the structures of the anterior segment of the eyeball. The clinical picture is represented by visual dysfunction, the appearance of “opacities” and “rainbow circles” in front of the eyes, blurred vision. Diagnostics is based on ultrasound biomicroscopy, classical biomicroscopy using a slit lamp, scopolamine test, ultrasound, visometry, tonometry, perimetry, gonioscopy. Conservative therapy is based on the use of antioxidants, antihypoxants, antihypertensive agents, vitamins B, A, E.
Pseudoexfoliative syndrome was first described by the Finnish scientist J. Lindberg in 1917. There is a relationship between the development of the disease and the age of the patient. In 50-59 years, the probability of pathology is 1-2.5%, in 60-69 years – 30%, after 70 years – 42%. According to statistics, the disease is diagnosed in 30% of Americans over the age of 50. The risk of glaucoma in patients with pseudoexfoliative syndrome is 64.6%. Pathology is more common among women, but it is more severe in men. The prevalence is highest in server regions.
The etiology of the disease is not fully understood. For a long time, scientists associated the development of pathology with changes in the structure of the lens epithelium, but the diagnosis of pseudoexfoliative syndrome after intracapsular cataract extraction allowed to refute this theory. To date, the leading role in the development of the disease is assigned to the action of the following factors:
- Ultraviolet radiation. Exposure to ultraviolet light induces free radical oxidation and destruction of the cell membrane. This entails atrophy with typical signs of exfoliation.
- Traumatic injury. Injuries to the eyeball lead to local changes, which in genetically compromised individuals are the trigger factor of pigment dispersion.
- Intraorbital infections. Many authors believe that eye damage is caused by increased permeability of the hematophthalmic barrier (HOB). The ability to penetrate through HOB is endowed with toxoplasma, herpes zoster virus and rubella.
- Violations of the immune status. This etiological theory of pseudoexfoliative syndrome is supported by the detection of increased concentrations of interleukins 6, 10, class A immunoglobulin and lactoferrin in the lacrimal fluid.
- Genetic predisposition. In some patients, it is possible to establish a violation of gene expression in the nucleus and mitochondria. The occurrence of PEX among relatives is much higher than in the population. There is an autosomal dominant type of inheritance.
Scientists believe that smoking and autoimmune pathologies contribute to the development of the disease. It is possible to trace the relationship between the occurrence of PEX and arterial hypertension, atherosclerosis, aortic aneurysm in the anamnesis. Some researchers believe that these changes are a consequence of systemic vasculopathy, so patients with PEX often suffer from cardiovascular diseases.
A key role in the mechanism of disease development is assigned to the formation and deposition of abnormal extracellular microfibrillary protein on the surface of the anterior capsule of the lens and iris, ciliary body, zinc ligaments, along the edge of the pupillary opening. Pathological deposits in the anterior chamber are less often visualized. It has been established that the protein belongs to an amyloid-like substance, the pigment epithelium and melanocytes of the iris are responsible for its synthesis. According to modern concepts, the pathogenesis of PEX is associated with a violation of epithelial-mesenchymal relationships in the structures of the eyeball. The penetration of protein structures into the thickness of its shells leads to their dystrophic degeneration.
Pseudoexfoliative syndrome is considered to be a systemic disorder of connective tissue metabolism. Confirmation of this theory is the detection of specific deposits in parenchymal organs (liver, kidneys, heart, brain) and skin. Scientists have discovered 14 antigens of the main histocompatibility complex (HLA) in the inherited form of pathology. The progression of the disease leads to atrophy of the pigment border, which is manifested by a pronounced dispersion of the pigment. Pigmentocytes can be detected in the FCA and on the iris. Due to damage to the drainage network, the outflow of watery moisture is disrupted, followed by an increase in intraocular pressure.
In ophthalmology, a genetically determined and immuno-mediated variant of development is distinguished. Regardless of the pathogenesis, the disease always occurs in old age. According to the severity of dystrophic changes , the following degrees of pseudoexfoliative syndrome are distinguished:
- I – is manifested by a slight atrophy of the iris. The pathological process does not extend beyond the root of the shell. The rim of the pupil has an uneven structure. In the area of the lens, a poorly expressed layering of amyloid is determined.
- II – moderate atrophy of the iris stroma. Pronounced pseudoexfoliative and pigmented deposits are detected on the surface of the iris and in the FCA zone.
- III – atrophic changes are pronounced. The pigment border has the appearance of a “cellophane film”, which is due to the dispersion of the pigment. The lesion of the ligamentous apparatus causes subluxation, less often – dislocation of the lens.
The clinical classification is based on the results of ultrasound biomicroscopy. The following stages of the pathological process are distinguished:
- I – signs of the lesion correspond to the pseudoexfoliative syndrome. It is possible to visualize point inclusions in the anterior parts of the eyes.
- II – the above changes are joined by the initial signs of damage to the zinc ligament in the form of alternating zones of thinning with thickening. The length of the fibers is different.
- III – abnormal inclusions become more dense, provoke the destruction of the ligamentous apparatus.
- IV inclusions are combined into large conglomerates, which lead to an increase in the longitudinal axis of the eyeball due to the elongation of the anterior segment.
The disease is characterized by a long asymptomatic course. Initially, one eye is affected (often the left). Involvement of the second eyeball is usually observed 5-10 years after the development of the first symptoms. Complaints usually occur after massive deposition of amyloid. Patients note the appearance of “opacities” in front of their eyes. When looking at the light source, specific “rainbow circles” appear. The decrease in visual acuity is caused by damage to the lens, increased IOP and atrophy of the iris sphincter. The accommodative ability is impaired, in the future, accommodation disorders are accompanied by blurred vision, impaired refraction. Pain syndrome appears only when the ligamentous apparatus is damaged.
The disease progresses very slowly. Patients often ignore clinical manifestations. In addition to complaints from the eyes, when protein is deposited in the internal organs, symptoms of their defeat occur. When amyloid is deposited in the liver, there is a feeling of heaviness in the right hypochondrium, less often – jaundice of the skin. Lower back pain by the type of renal colic, urination disorders are typical signs of accumulation of protein masses in the parenchyma of the kidneys. When the pathological process spreads into the thickness of the myocardium, there is a feeling of compression behind the sternum, tingling in the heart area. It has been proven that PEX is widespread among patients with senile dementia, cognitive disorders, chronic cerebral ischemia, Alzheimer’s disease.
The deposition of protein in the thickness of the lens masses provokes the development of a secondary nuclear-type cataract, which is often accompanied by weakness of the ligamentous apparatus. This leads to the fact that more than half of cataract patients have subluxation, less often – lens luxation. In most cases, the pathology is complicated by ophthalmohypertension. Damage to the trabecular network leads to the appearance of pseudoexfoliative open–angle glaucoma, and with the progression of the disease – to glaucoma optic neuropathy or blindness. The defeat of the meibomian glands causes xerophthalmia.
Diagnosis at the preclinical stage is difficult. It is possible to identify the first signs only with the help of ultrasound biomicroscopy. Specific diagnostic methods include:
- Biomicroscopy of the eye. Allows you to visualize clusters of white or grayish hue, resembling flakes on the surface of the shells of the anterior part of the organ of vision. Chaotic clusters of pigment can form a Krukenberg spindle. Pseudoexfoliation is structurally similar to inflammatory precipitates.
- Gonioscopy. Multiple inclusions are detected in the anterior chamber, which form large conglomerates in the later stages. If the permeability of the hematophthalmic barrier is violated, a blood suspension is detected in the watery moisture. The volume of the camera is not changed.
- Non-contact tonometry. It is characterized by an increase in intraocular pressure, which in secondary glaucoma is difficult to reduce by medication. In case of damage to the drainage system, electronic tonography is additionally performed.
- Ultrasound of the eyes. When using ultrasound diagnostics, it is possible to detect a rupture of the zinc ligament with the appearance of spherophakia. Due to massive protein deposits, the ratio of the sizes of the anterior and posterior segments is violated. The technique is also used to examine the posterior segment of the eyes with a decrease in the transparency of optical media.
- Ultrasound biomicroscopy. It makes it possible to identify small-point inclusions of weak acoustic density on the membranes of the eye, the difference in length and lysis of individual fibers of the zinc ligament.
- Scopalamine test. At 1 degree, during the test, the pupillary opening expands to 5 mm, at 2 – to 3.5-4 mm. At the 3rd degree of pathology, there is no pupil reaction.
- Visometry. Visual dysfunction is observed with clouding of optical media or secondary glaucoma. In severe cases, visual acuity decreases down to light perception.
- Perimetry. The concentric narrowing of the visual field is determined. In some cases, it is possible to diagnose the loss of individual areas from the visual fields, scotomas.
Patients with this pathology have a history of consultation with a neurologist, rheumatologist, cardiologist, gastroenterologist, otolaryngologist. The need for a comprehensive examination is caused by a systemic lesion of fibrous tissue. Often, the identification of the first symptoms of an eye lesion makes it possible to diagnose amyloid deposits in other parenchymal organs.
Etiotropic therapy of pseudoexfoliative syndrome has not been developed. The goal of conservative treatment is to prevent the development of severe complications. In the early stages, the use of:
- Antioxidants. Medicines are used, which include superoxide dismutase. SOD belongs to the class of metalloproteins. Antioxidants cause the destruction of reactive oxygen species, which have a damaging effect on the tissues of the eye.
- Antihypoxants. In order to improve metabolism and stimulate the process of tissue respiration, cytochrome C. Instillations of the drug help accelerate epithelialization and repair damage to the structures of the anterior segments of the eyes.
- Antihypertensive drugs. They are indicated with increased intraocular pressure, signs of ophthalmohypertension and the initial stages of development of pseudoexfoliative glaucoma.
- Vitamin therapy. The effectiveness of the use of methylethylpyridinol (a structural analogue of vitamin B6), which has a fibrinolytic and antioxidant effect, has been proven. Vitamin A (retinol acetate) is also involved in redox processes and E (tocopherol acetate).
With a long course of pathology, the goal of treatment is to eliminate or reduce the severity of secondary complications. Drug therapy of pseudoexfoliative glaucoma often does not have the desired effect. There is a need for laser or surgical intervention. It is most advisable to perform early laser trabeculoplasty, but after 3-4 years there are relapses of increased IOP. When choosing a method for removing the subluxated lens, phacoemulsification should be preferred. Extracapsular extraction remains the reserve technique.
Prognosis and prevention
The outcome of the disease depends on the severity, the nature of damage to the structures of the anterior eye and the type of complications. With timely diagnosis and treatment of complications, the prognosis for visual functions is favorable. The occurrence of secondary glaucoma is associated with resistance to conservative therapy and the risk of irreversible vision loss. Specific prevention has not been developed. Even with early symptoms of pseudoexfoliative syndrome, registration with an ophthalmologist is necessary due to the high probability of glaucoma development. Regular monitoring of intraocular pressure is indicated. Patients should undergo a comprehensive ophthalmological examination at least twice a year.