Neurofibromatosis and eye lesions

Neurofibromatosis is divided into two autosomal dominant forms, characterized by different clinical courses:

1. neurofibromatosis type I (NF1) - Recklinghausen syndrome;
2. neurofibromatosis type II - bilateral acoustic neurofibromatosis.

Additional forms of neurofibromatosis have been described, including segmental neurofibromatosis, cutaneous mixed neurofibromatosis type III, a variant of neurofibromatosis type IV, and late-onset neurofibromatosis type VII. It is unclear whether all of these forms are distinct diseases.

[ 1 ], [ 2 ], [ 3 ]

Prevalence of neurofibromatosis type I

It has been established that the prevalence of neurofibromatosis corresponds to 1:3000-1:5000, thus this disease is one of the most common autosomal dominant disorders. Penetrance is almost complete, as a result of the high level of spontaneous mutations in 50% of patients with neurofibromatosis, new mutations are determined. The affected gene is localized on the proximal long arm of chromosome 17 (17qll.2).

Symptoms of Neurofibromatosis Type I

• Pigmented spots on the body the color of coffee with milk. However, these changes are not a pathognomonic sign of neurofibromatosis and can occur in healthy people.
• Small spots are localized mainly in the folds of the skin - in the armpits, in the groin area and under the breasts in women.

Peripheral neurofibromas

Almost all patients with neurofibromatosis type I develop peripheral neurofibromas of the skin by the age of 16 and, in rarer cases, neurofibromas of the subcutaneous tissue, palpable along the course of the peripheral nerves.

Plexiform neurofibromas

Peculiar neoplasms of soft consistency. Pathognomonic symptom for neurofibromatosis type I. Characteristic signs are hypertrophy of surrounding tissues, local tissue proliferation and hypertrichosis in the affected area. When the process is localized in the orbit, significant vision loss is possible due to direct compression of the optic nerve or amblyopia developing due to ptosis and/or strabismus caused by the tumor.

Reduced learning ability

Although intellectual disability is rare in neurofibromatosis type I, mild visual impairment may occur.

Ophthalmological manifestations

An ophthalmologist's examination of a patient with suspected neurofibromatosis is important not only to confirm the diagnosis, but also to identify complications in the visual organ and, if possible, to prescribe treatment early. Pathological changes in the visual organ can be localized in the orbit and include:

1. optic nerve glioma;
2. meningeal meningioma of the optic nerve;
3. orbital neurofibroma;
4. orbital bone defects.

Exophthalmos may be associated with a change in the position of the eyeball, subsequently accompanied by strabismus and amblyopia. Orbital tumors often cause changes in the optic nerve, manifested by congestion of the papilla, atrophy and, less frequently, hypoplasia of the optic nerve. Additional changes include:

1. optociliary shunts (especially in case of optic nerve meningioma);
2. choroidal membrane folding;
3. amaurosis determined by the direction of gaze.

Neurologic studies are indicated to differentiate various causes of exophthalmos in neurofibromatosis type I.

Eyelids

1. The most common eyelid lesions are plexiform neurofibroma, which has a characteristic S-shaped deformity of the upper eyelid margin. Strabismus and/or ptosis resulting from these changes can lead to amblyopia.
2. Congenital ptosis occurs even in the absence of an orbital tumor.

Iris

Lisch nodules (melanocytic hamartomas of the iris) are pathognomonic for neurofibromatosis type I. They are rare in neurofibromatosis type II. Their prevalence in neurofibromatosis type I increases with age. Lisch nodules are not common in early childhood, but by the age of 20 they are found in almost 100% of patients.

Optic nerve

Involvement of the optic nerve in the pathological process is manifested by optic nerve gliomas (astrogliomas). 70% of all optic nerve gliomas occur in patients with neurofibromatosis type I. The true frequency of their prevalence in neurofibromatosis type I is difficult to determine due to the absence of symptoms and, therefore, the subclinical course. Approximately 15% of patients with neurofibromatosis type I and normal visual acuity have optic nerve gliomas radiographically detected. These neoplasms are divided into two categories.

Anterior (orbital gliomas)

These gliomas present with exophthalmos, loss of vision and, occasionally, a change in the position of the eyeball. Involvement of the optic nerve in the process is expressed in its atrophy, dysplasia, direct tumor damage and congestive papilla. Sometimes, optociliary vascular shunts are formed on the side of the tumor. As a result of these changes, strabismus often occurs.

Posterior (chiasmal gliomas)

Symptoms of these gliomas include hydrocephalus, endocrine pathology, and decreased vision combined with nystagmus. Nystagmus may be vertical, rotary, or asymmetrical (rarely mimicking nutans spasms). Dissociated vertical nystagmus often occurs.

Conjunctiva

Conjunctival neurofibromas are rare and are usually located in the limbal zone.

Cornea

In neurofibromatosis type I, thickening of the corneal nerves is observed, but this symptom is not pathognomonic. Much more often, this disorder occurs in multiple endocrine neoplasia syndrome.

Uveal tract

Pigmented choroidal hamartomas occur in 35% of patients. Diffuse neurofibromas cause thickening of the entire uveal tract, leading to glaucoma.

Retina

In neurofibromatosis type I, the retina is rarely involved in the pathological process. There are isolated reports of cases of astrocytic hamartomas of the retina and its pigment epithelium.

Research

1. Computed tomography (CT) or magnetic resonance imaging (MRI) of the brain and orbit can detect bone pathology, meningiomas, and optic nerve gliomas.
2. Visual evoked potentials (VEP) help in assessing the state of the chiasm, as well as in monitoring the dynamics of chiasmal gliomas.

Symptoms of Neurofibromatosis Type II

• Coffee-with-milk colored spots on the body occur in approximately 60% of patients.
• Neurofibromas of the skin are observed in approximately 30% of cases. Plexiform fibromas are rare.

Manifestations from the central nervous system

The hallmark of neurofibromatosis is bilateral acoustic neuromas. Other cranial nerves may also become involved as the tumor grows, especially the V, VI, and VII pairs. Gliomas, meningiomas, and schwannomas are common.

Manifestations from the organ of vision

• Lisch nodules, if they occur, are rare.
• Posterior subcapsular cataracts occur frequently but have little effect on visual acuity.
• Combined hamartomas of the pigment epithelium and retina.
• Epiretinal membranes with mild visual impairment.

In most cases of ocular manifestations of neurofibromatosis type II, treatment is not required. The need for treatment arises when a bilateral meningioma of the VIII pair of cranial nerves appears, especially if the tumor is small.

Neurofibromatosis type I

Neurofibromatosis type II (bilateral acoustic)

This form of the disease is less common than neurofibromatosis type I. The gene responsible for the disorder is located near the center of the long arm of chromosome 22 (22qll.l-ql3.1).

Diagnostic criteria for neurofibromatosis type I

The following features have been defined as criteria for establishing the diagnosis of neurofibromatosis type I. At least two of these features must be present to establish the diagnosis.

1. Five or more café-au-lait pigmented macules, greater than 5 mm in diameter, in a prepubertal child and six or more café-au-lait pigmented macules, greater than 15 mm in diameter, in a postpubertal patient.
2. Two or more neurofibromas of any type or one plexiform neurofibroma.
3. Armpit or groin spots.
4. Optic nerve glioma.
5. Two or more Lisch nodules.
6. Characteristic bone defects (pseudoarthrosis of the tibia or dysplasia of the wing of the sphenoid bone).
7. Close relatives with neurofibromatosis type I.

[ 4 ]

Treatment of neurofibromatosis type I

The tactics of managing patients with neurofibromatosis type I remain controversial to this day. Treatment is usually complex. An integral component in the overall set of appointments is genetic counseling of all family members of the patient. Treatment of complications of neurofibromatosis from the organ of vision is complex and includes:

Plexiform neuroma

Chemotherapy and radiation therapy are ineffective. Surgical removal is technically difficult and has a high complication rate. If amblyopia is suspected, occlusion is recommended.

Gliomas of the optic nerve and chiasm

Treatment issues remain relevant to this day. Conservative treatment is indicated for small tumors and preserved visual functions. In older patients, radiation therapy is sometimes recommended (in younger children, radiation therapy may be complicated by mental retardation). Surgery is advisable on the blind eye with severe exophthalmos. Surgical removal of chiasmal gliomas is technically impossible. In some cases, only associated cysts are removed. Chemotherapy is becoming increasingly popular in the treatment of chiasmal gliomas when they are combined with hypothalamic dysfunction. Some patients with chiasmal gliomas with increased intracranial pressure are indicated for bypass. Endocrinological examination of all patients with chiasmal gliomas is advisable.

Glaucoma

Usually requires surgical intervention and has an unfavorable prognosis.