Vision-Related Quality of Life in Patients with Optic Neuropathy: Insights from a Portuguese Single Center Using the NEI-VFQ-25

<b>Background/Objectives</b>: Optic neuropathies (ON) are a clinically heterogeneous group of disorders that can cause profound and lasting visual disability, with wide-ranging effects on patients' quality of life. Although the NEI-VFQ-25 is an instrument for assessing vision-related quality of life (VRQoL), few studies have systematically compared patient-reported outcomes across multiple ON subtypes, especially in underrepresented populations. We aimed to delineate how etiological differences and longitudinal visual acuity trajectories shape VRQoL in a diverse Portuguese cohort with ON. <b>Methods</b>: This retrospective, cross-sectional study included 152 patients diagnosed with ON and followed at São João University Hospital, Portugal. All participants completed the validated NEI-VFQ-25. Diagnosis-specific differences in VRQoL were interrogated using ANCOVA and linear mixed-effects models, controlling for age and sex. Visual acuity changes over time were analyzed in relation to patient-reported outcomes. <b>Results</b>: Substantial heterogeneity in VRQoL was observed across ON subtypes. Patients with MS-related ON (MS-RON) and idiopathic ON reported significantly higher NEI-VFQ-25 scores in domains such as general vision, mental health, and dependency (F = 3.30, <i>p</i> = 0.013; ηp² = 0.08), while those with ischemic or other inflammatory etiologies showed persistently lower scores. Notably, both final visual acuity and diagnosis were independently associated with NEI-VFQ-25 composite scores, highlighting the correlation between objective and subjective measures of visual function. Age and diagnosis independently predicted poorer VRQoL. <b>Conclusions</b>: This study provides the first comprehensive evaluation of vision-related quality of life (VRQoL) across a diverse cohort of optic neuropathy patients in a Portuguese tertiary center, using the NEI-VFQ-25. Our results underscore the heterogeneity of functional impact across ON subtypes, emphasizing the value of integrating sensitive, multidimensional assessment tools into neuro-ophthalmic clinical care, especially in populations historically underrepresented in research.