To determine the diagnostic yield of genetic testing in idiopathic optic neuropathy and to compare clinical characteristics of patients with a confirmed genetic etiology of their optic neuropathy to those with negative testing.

Chronic optic neuropathy classically presents with visual acuity loss, dyschromatopsia, and optic atrophy. Identifying an underlying cause is essential for management; yet many cases remain idiopathic even after comprehensive neuro-ophthalmologic evaluation. Advances in genetic testing now allow for detection of hereditary etiologies that may mimic acquired optic neuropathies.

There were 26 patients; all had received genetic testing.  The proportion who had a genetic diagnosis was 11/26 (42% [95% CI, 23%, 61%]). The most frequent pathogenic variants involved WFS1 and MT-ND4. At initial evaluation, eyes in the genetic group demonstrated less visual field loss (average VFMD −2.2 vs. −11.8 dB; difference +9.3 dB (95% CI 2.8, 15.9; p=0.005).  No significant differences were observed for other tests.

Our results demonstrate that hereditary optic neuropathies can present with subtle or variable phenotypes, supporting the inclusion of genetic testing even in mildly affected idiopathic cases.  The visual field was a key test that separated our two groups. Genetic testing may have high yield in patients with chronic idiopathic optic neuropathy.