Diagnostic and Imaging Features of Leber Hereditary Optic Neuropathy: An Individual Participant Data Meta-Analysis

BACKGROUND: Leber Hereditary Optic Neuropathy (LHON) is a cause of vision loss that is presently most often diagnosed from clinical evaluation, ophthalmological examination, and genetic testing. However, imaging is being increasingly recognized by LHON specialists as tool for earlier diagnosis. Given that there is an effective treatment for LHON when implemented promptly after symptom onset, it is important for radiologists to be able to recognize and suggest LHON in the appropriate clinical context. PURPOSE: In this individual participant data meta-analysis (IPDMA) study, trends in radiologic findings, additional diagnostic considerations, and treatment approaches are described in the largest cohort published to date of patients with LHON. DATA SOURCES & STUDY SELECTION: The 2020 PRISMA guidelines were followed to identify all literature-based case descriptions of LHON. Inclusion criteria were the presence of neuroimaging descriptions, full-text article format, English-language, and a publication date between 2000-2025. DATA ANALYSIS: Data on patient age, imaging modality/findings, ophthalmological exams, and mitochondrial mutations were collected and nominalized for statistical analyses. DATA SYNTHESIS: 137 cases from 120 publications across 54 journals were identified. All cases involved LHON diagnoses, confirmed through genetic testing. The patient age range was 2-81 years. 22.6% of case reports described the finding of T2-hyperintensity of the optic nerves and/or chiasm. 10.9% described post-contrast enhancement of the optic nerves and/or chiasm, 5.1% described optic chiasm enlargement, and 13.1% described optic chiasm atrophy (OCA). T2-hyperintensity and post-contrast enhancement of the optic nerves and/or chiasm were disproportionately reported in females, rather than males (p=0.04 and p=0.06, respectively). T2-hyperintensity and post-contrast enhancement of the optic nerves and/or chiasm, T2-hyperintensity of the optic nerves and/or chiasm and optic chiasm enlargement, and T2-hyperintensity of the optic nerves and/or chiasm and optic chiasm enlargement were all more co-reported than expected (p