2026 American Academy of Neurology Abstract Website

Objective:

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.

Background:

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.

Design/Methods:

A cross-sectional study was conducted for a convenience sample of patients with chronic optic neuropathies who underwent genetic testing following nondiagnostic neuro-ophthalmologic evaluation. Clinical characteristics, including color vision (Ishihara plates), high-contrast visual acuity, low-contrast letter acuity, visual field mean deviation (VFMD), and peripapillary retinal nerve fiber layer (pRNFL) thickness by optical coherence tomography (OCT), were compared between eyes of patients with vs. without a confirmed genetic diagnosis. Generalized estimating equation models (GEE) were used to examine whether having a confirmed genetic diagnosis was associated with worse scores/measurements. Only clinically affected eyes were included, with most patients contributing data for both eyes.

Results:

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.

Conclusions:

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.