Ophthalmologica. 2026 Jun 23:1-18. doi: 10.1159/000553194. Online ahead of print.
ABSTRACT
PURPOSE: To clarify how relative afferent pupillary defect (RAPD) relates to interocular visual acuity asymmetry in Leber hereditary optic neuropathy (LHON), and to derive clinically interpretable thresholds of absolute interocular best-corrected visual acuity difference (|ΔBCVA|) for RAPD interpretation.
MATERIALS AND METHODS: This retrospective study included patients with genetically confirmed LHON (one of the three primary mitochondrial DNA mutations: m.11778G>A, m.14484T>C, or m.3460G>A) who presented within 6 months of symptom onset and underwent RAPD assessment at the initial visit. The absolute interocular difference in best-corrected visual acuity (|ΔBCVA|, logMAR) was analyzed using multivariable logistic regression. Discrimination was assessed by receiver operating characteristic (ROC) analysis. In unilateral-onset cases, time to fellow-eye involvement was compared by Kaplan-Meier analysis.
RESULTS: Ninety-two patients were included; 23 (25%) were RAPD-positive. In multivariable logistic regression, |ΔBCVA| was independently associated with RAPD (adjusted odds ratio 1.20 per 0.1 logMAR, 95% confidence interval 1.08-1.35; p<0.001). ROC analysis showed good discrimination (AUC 0.791, 95%CI 0.672-0.910). The Youden-optimal cutoff was 0.88 logMAR (sensitivity 56.5%, specificity 92.8%); additional thresholds were 0.47 logMAR for higher sensitivity (87.0%, 58.0%) and 1.14 logMAR for higher specificity (52.2%, 97.1%). In Kaplan-Meier analysis, fellow-eye involvement occurred earlier in RAPD-negative than RAPD-positive cases (log-rank p=0.020), with an estimated median time to involvement of 2 months and 4 months, respectively.
CONCLUSIONS: In LHON, RAPD is largely driven by interocular acuity asymmetry. Quantitative |ΔBCVA| thresholds can support interpretation of RAPD without prematurely excluding LHON and may help plan diagnostic work-up and follow-up while confirmatory testing is pending.
PMID:42334989 | DOI:10.1159/000553194