Clinical features In most patients, the visual loss begins between 18 and 25 years of age, but the range of age of onset is much broader. Usually the visual loss has a fairly rapid onset and a subacute evolution suggesting a retrobulbar neuritis; moreover, in these instances, aching in the eye or brow may accompany the visual loss, just as it does in the demyelinative variety. Subjective visual phenomena are reported by some. Usually both eyes are affected simultaneously, although in many, one eye is affected first, followed by the other after an interval of several weeks or months. In practically all cases, the second eye is affected within a year of the first. In the unimpaired eye, abnormalities of visual evoked potentials may antedate impairment of visual acuity (Carroll and Mastaglia).
Once started, the visual loss progresses over a period of weeks to months. Characteristically, central vision is lost before peripheral, and there is a stage at which bilateral central scotomata are readily demonstrated. Early on, perception of blue-yellow is deficient, while that of red and green is relatively preserved. In the more advanced stages, however, the patients are totally color-blind. Constriction of the fields may be added later. At first there may be swelling and hyperemia of the discs, but soon they become atrophic. Peripapillary vasculopathy, consisting of tortuosity and arteriovenous shunting, is the primary structural change; this has been present also in asymptomatic offspring of carrier females.
As visual symptoms develop, fluorescein angiography shows shunting in the abnormal vascular bed, with reduced filling of the capillaries of the papillomacular bundle. Although patients are left with dense central scotomata, it is of some importance that the visual impairment is seldom complete; in some patients, relative stabilization of visual function occurs. In a few, there may be a surprising improvement.
Examination of the optic nerve lesion shows the central parts of the nerves to be degenerated from papillae to the lateral geniculate bodies, that is, the papillomacular bundles are particularly affected. Presumably axis cylinders and myelin degenerate together, as would be expected from the loss of nerve cells in the superficial layer of the retina. Both astrocytic glial and endoneurial fibroblastic connective tissue are increased. Tests for the 3 main mitochondrial mutations that give rise to the disorder are available.
Congenital optic atrophy (of which recessive and dominant forms are known), retrobulbar neuritis, and nutritional optic neuropathy are the main considerations in differential diagnosis.
Retinitis Pigmentosa (See Also Chap. 12)
This remarkable retinal abiotrophy, known to Helmholtz in 1851, soon after he invented the ophthalmoscope, usually begins in childhood and adolescence. Unlike the optic atrophy of Leber, which affects only the third neuron of the visual neuronal chain, retinitis pigmentosa affects all the retinal layers, both the neuroepithelium and pigment epithelium (see Fig. 12-2). The incidence of this disorder is 2 or 3 times greater in males than in females. Inheritance is more often autosomal recessive than dominant; in the former, consanguinity plays an important part, increasing the likelihood of the disease by approximately 20 times. Sex-linked types are also known. It is estimated that 100,000 Americans are afflicted with this disease. Mutations in approximately 60 genes have been associated with the disorder but the most commonly affected in autosomal dominant cases is RHO; in recessive cases, USH2A, and in X-linked cases, RPGR and RP2.