A HISTOPATHOLOGIC AND MORPHOMETRIC DIFFERENTIATION OF NERVES IN OPTIC-NERVE HYPOPLASIA AND LEBER HEREDITARY OPTIC NEUROPATHY

Objectives: To characterize and quantitate optic nerve histopathologic and morphometric differences between optic nerve hypoplasia (ONH) as an early and congenital form of intrinsic axonal loss and Leber heredi tary optic neuropathy (LHON) as a late and acquired form of intrinsic axonal loss. Materials and Methods: Optic nerves from 3 sources were e xamined: a 42-year-old healthy woman (control), a 53-year-old woman wi th ONH diagnosed postmortem, and a 74-year-old woman with LHON. The op tic nerves were processed, embedded, and stained with a 1% solution of paraphenylene diamine. Histopathologic and morphometric analyses were performed via light microscopy and a semiautomatic computer image ana lysis system. Results: The ONH showed severe axonal depletion without degenerated profiles in an inferonasal sector, with only a small super otemporal sector having a near normal appearance. The LHON revealed ge neral axonal depletion centrally, fibrocytic scarring, scattered ''deg eneration dust,'' and evidence of minimal inflammation, with residual axons limited to superior and temporal peripheral clusters. Morphometr ic analysis revealed total fiber populations of 98 000 in the ONH opti c nerve and 48 000 in the LHON optic nerve, representing 90% and 95% r eductions, respectively, compared with the control optic nerve (1.2 mi llion fibers). Conclusions: Optic nerve hypoplasia and LHON present 2 distinguishable and distinctive patterns of nerve fiber distribution a nd axonal dropout. The lack of degenerated axons in ONH indicates that any axonal death probably occurred through apoptosis during developme nt. In LHON, degenerated axons and minimal grade of inflammation were obvious, implicating a more ''active'' pathologic process. This study describes distinctions between these 2 optic neuropathies.