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, ophthalmologic examination, and genetic testing. However, imaging is being increasingly recognized by LHON specialists as a 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 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 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 and 2025.

DATA ANALYSIS: Data on patient age, imaging technique/findings, ophthalmologic examinations, and mitochondrial mutations were collected and nominalized for statistical analyses.

DATA SYNTHESIS: One hundred thirty-seven 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. Of the cases, 22.6% of case reports described the finding of T2-hyperintensity of the optic nerves and/or chiasm, 10.9% described postcontrast enhancement of the optic nerves and/or chiasm, 5.1% described optic chiasm enlargement, and 13.1% described optic chiasm atrophy. T2-hyperintensity and postcontrast enhancement of the optic nerves and/or chiasm were disproportionately reported in females, rather than males (P = .04 and P = .06, respectively). T2-hyperintensity and postcontrast enhancement of the optic nerves and/or chiasm, T2-hyperintensity of the optic nerves and/or chiasm, post-contrast enhancement of the optic nerves and/or chiasm, and optic nerve enlargement were all more co-reported than expected (P < .001 for all).

LIMITATIONS: Limitations of this study include heterogeneous data from case reports, inconsistent imaging descriptions, publication bias, and retrospective design.

CONCLUSIONS

In this IPDMA, patients of all ages, both male and female, presented with vision loss from LHON. There was a propensity for T2-hyperintensity of the optic nerves and/or chiasm, particularly in females, and associated postcontrast enhancement of the lesions. Given the profound impact early diagnosis can make on saving patients' vision, it is important for radiologists to understand neuroimaging and clinical associations of LHON.