AUTHOR=La Morgia Chiara , Cascavilla Maria Lucia , De Negri Anna Maria , Romano Marcello , Canalini Fabrizio , Rossi Silvia , Centonze Diego , Filippi Massimo 

TITLE=Recognizing Leber’s Hereditary Optic Neuropathy to avoid delayed diagnosis and misdiagnosis

JOURNAL=Frontiers in Neurology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1466275

DOI=10.3389/fneur.2024.1466275

ISSN=1664-2295

ABSTRACT=Leber's Hereditary Optic Neuropathy (LHON) is a maternally inherited optic nerve disease primarily caused by mutations in mitochondrial DNA (mtDNA). The peak of onset is typically between 15-30 years, but variability exists. Misdiagnosis, often as inflammatory optic neuritis, delays treatment, compounded by challenges in timely genetic diagnosis. Given the availability of a specific treatment for LHON, its early diagnosis is imperative to ensure therapeutic appropriateness. This work gives an updated guidance about LHON differential diagnosis to clinicians dealing also with multiple sclerosis and neuromyelitis optica spectrum disorders. LHON diagnosis relies on clinical signs and paraclinical evaluations. Differential diagnosis in the acute phase primarily involves distinguishing inflammatory optic neuropathies, considering clinical clues such as ocular pain, fundus appearance and visual recovery. Imaging analysis obtained with Optical Coherence Tomography (OCT) assists clinicians in early recognition of LHON and help avoiding misdiagnosis. Genetic testing for the three  most common LHON mutations is recommended initially, followed by comprehensive mtDNA sequencing if suspicion persists despite negative results. We present and discuss crucial strategies for accurate diagnosis and management of LHON cases.A combination of clinical signs and paraclinical examinations is necessary to reach a diagnosis of LHON. To establish the severity and the stage of the disease, the following evaluations are recommended: 1) Measurement of best-corrected visual acuity and color vision 2) Assessment of visual fields (VF) with static or kinetic perimetry 3) Measurement of retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness with Optical Coherence Tomography (OCT) imaging.