Different Patterns of Optic Disc Excavation in Leber’s Hereditary Optic Neuropathy, Dominant Optic Atrophy and High Tension Glaucoma

Abstract

Purpose:: To investigate by OCT the excavation pattern in patients with different causes of optic nerve atrophy. We compared patients with confirmed diagnosis of Leber’s hereditary optic neuropathy (LHON), dominant optic atrophy (DOA) and high-tension glaucoma (HTG).

Methods:: We evaluated 16 LHON affected patients belonging to the same very large Brazilian maternal lineage (SOA-BR family) carrying the homoplasmic 11778/ND4 mtDNA mutation, 26 LHON affected probands from 26 unrelated Italian pedigrees carrying a primary mtDNA mutation (11778/ND4, 3460/ND1, 14484/ND6 and 3733/ND1), 30 DOA patients from 15 molecularly defined OPA1 Italian pedigrees and 50 HTG patients in an advanced stage. Stratus OCT was used to analyze the ONH (fast optic disc acquisition protocol). One randomly selected eye was considered for each patient. Groups were compared by one-way ANOVA analysis of variance.

Results:: LHON patients revealed a significantly increased cup disc volume (p=0.048), cup area (p=0.001) and cup disc vertical ratio (p=0.02) compared to DOA patients. LHON patients showed a significantly reduced cup disc volume (p<0.0001) and no differences in cup area and cup disc vertical ratio compared to HTG patients. No differences were found between Brazilian and Italian LHON patients. However, stratification of the data by LHON primary mutation indicated that the most prominent excavation was recurrent in 3460/ND1 and 14484/ND6 mutations.

Conclusions:: Our study revealed different patterns of excavation in LHON, DOA and HTG patients, according to OCT evaluation. This may be helpful in distinguishing these optic neuropathies. Furthermore, our results also suggest that different pathogenic mechanisms are possibly responsible for the observed patterns of disc excavation, which may have primary or secondary mitochondrial involvement in all these forms of optic neuropathies. The different level of excavation associated with the LHON mutations further indicates that even within the same pathology there may be differences in the pathogenic mechanisms.

Keywords: neuro-ophthalmology: optic nerve • optic nerve • mitochondria