The presentation of dominant optic atrophy, known as Kjer optic neuropathy, is usually less dramatic; it presents with insidious, bilateral vision loss. The abnormality might be detected, for example, during a vision screening test in the early years of school. Vision is typically modestly reduced, but the optic discs can show significant temporal pallor, with an excavated appearance. The condition shows mendelian autosomal dominant pattern because it is caused by a nuclear genetic mutation, although the dysfunctional protein causes a mitochondrial metabolic defect. Some patients have dominant optic atrophy “plus,” in which the syndrome may include other abnormalities such as hearing loss or peripheral neuropathy.
Developmental Abnormalities of the Optic Nerve
Congenital cavitary defects of the optic disc can arise from defective closure of the optic fissure during embryogenesis. These defects, known either as an optic pit or as a larger optic coloboma, may cause impaired vision when the papillomacular bundle is affected. Usually the abnormality is unilateral and unassociated with developmental abnormalities of the brain. A hereditary form is known (Brown and Tasman).
Optic nerve hypoplasia refers to nerves with abnormally small diameter. Funduscopic examination may reveal the “double ring” sign, referring to a small optic disc within the larger opening of the scleral canal. Optic nerve hypoplasia can be part of the de Morsier syndrome, which includes cortical heterotopias and other midline patterning deficits such as absence of the septum pellucidum and hypothalamic-pituitary abnormalities.
Optic nerve and chiasmal compression and infiltration by gliomas, meningiomas, craniopharyngiomas, and metastatic tumors may cause loss of vision and optic atrophy (see Chap. 30). Pituitary tumors characteristically cause bitemporal hemianopia, but very large adenomas can cause vision loss that also extends through the nasal hemifield of one or both eyes (see “Pituitary Apoplexy” in Chap. 30). Pituitary apoplexy, referring to acute involutional hemorrhage into a pituitary adenoma, presents with an acute headache that may be accompanied by visual loss from compression of the optic nerves and chiasm, as well as ocular motility deficits.
Of particular importance is the optic nerve glioma that occurs either sporadically or in patients with type I von Recklinghausen neurofibromatosis. Usually, it develops in children, often before the fourth year, causing a mass within the orbit and progressive loss of vision. If the eye is blind, the recommended therapy is surgical removal to prevent extension into the optic chiasm and hypothalamus. If vision is retained, patients may be observed carefully, but if vision declines, radiation and chemotherapy are often recommended forms of treatment. Although most such gliomas are of low grade, malignant forms (glioblastoma) can also occur in adults.
Radiation-induced damage of the optic nerves and chiasm has been well documented. It is typically delayed, occurring at an average of 18 months after radiation exposure, and is often accompanied by enhancement of the nerve on MRI. It is more common following radiation doses in excess of 50 Gy (5,000 rad) (see Jiang et al). In a series of 219 patients at the M.D. Anderson Cancer Center who received radiotherapy for carcinomas of the nasal or paranasal region, retinopathy occurred in 7, optic neuropathy with blindness in 8, and chiasmatic damage with bilateral visual impairment in 1. Attempted treatment strategies have included corticosteroids, hyperbaric oxygen, and the VEGF-inhibitor bevacizumab, but all show very limited results. This topic is also addressed in Chap. 30.