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A.A. Sadun, F.N. Ross–Cisneros, M.N. Moraes, M.N. Moraes–Filho, R. Belfort, Jr., A. Berezovsky, S.R. Salomao, V. Carelli; Subclinical Injury in an Asymptomatic Carrier of 11778 Leber's Hereditary Optic Neuropathy: Histopathological Evidence for Fascicular Patterns of Axonal Loss in the Optic Nerve . Invest. Ophthalmol. Vis. Sci. 2006;47(13):751.
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Recent studies have demonstrated subtle psychophysical abnormalities in asymptomatic carriers of Leber's Hereditary Optic Neuropathy (LHON) in a prospective study of a large Brazilian pedigree. This investigation seeks to identify the anatomical basis of these ophthalmic abnormalities through histopathologic studies of the eye and optic nerve of a well–studied carrier who has come to autopsy.
This subject was an 83 year old woman when she first entered our prospective study in 2001. We verified that she had LHON with the homoplasmic 11778 mt DNA mutation, J–haplogroup. At presentation she had no visual symptomatology. Her examination was normal except for mild decreased visual acuities that corresponded to her refractive error, mild cataracts and early RPE macular changes. She did not have changes in her visual fields or evidence of optic disc atrophy. About 4 years later, she died and gave permission for post–mortem studies that included retina and optic nerve histopathology and axonal morphometry.
Optic nerve cross sections showed mild degeneration and moderate amounts of axonal drop out most predominant in the temporal and central areas that correspond to the papillo–macular bundle. In one optic nerve, the degeneration followed a peculiar bundle–by–bundle effect suggesting an all–or–nothing threshold for each fascicle. Yet, each involved fascicle was isolated from other such involved fascicles.
We show pathological evidence of axonal loss in the optic nerve that suggests a double threshold effect, which occurs within each fascicle as well as between fascicles. This also establishes the basis of subclinical injury in asymptomatic carriers of LHON.
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