The Case Record Survey-2 (CRS-2; NCT02796274) was conducted to establish the natural history of LHON in idebenone-naïve patients. Here, we report 12-month clinical outcomes by sex and age at symptom onset. 

LHON is a rare mitochondrial disorder resulting in severe bilateral vision loss. Estrogen levels and age at symptom onset are thought to influence disease progression. 

Retrospective clinical data were extracted from case records of LHON patients. Eligibility criteria were LHON patients aged ≥12y, with m.11778G>A, m.3460G>A, or m.14484T>C mitochondrial DNA mutation, symptom onset after 1999, and ≥2 visual acuity (VA) assessments within 5 years of symptom onset. Patients were grouped by sex and age at symptom onset. Spontaneous clinically relevant benefit (sCRB), recovery (sCRR), stabilization (sCRS), and worsening (sCRW) at 12±3 months from baseline (first VA assessment after symptom onset) were calculated in subacute/dynamic eyes (≤1y since symptom onset).

Overall, eyes had similar rates of sCRB (male: 21.0% [17/81]; female: 20.0% [3/15]) and sCRW (male: 65.1% [41/63]; female: 69.2% [9/13]), regardless of sex. Male eyes had a lower rate of sCRR (male: 11.1% [9/81]; female: 20.0% [3/15]) and higher rate of sCRS (male: 32.4% [11/34]; female: 0.0% [0/8]).

In females, there were no eyes <15y at symptom onset. Eyes 15–50y at onset had a higher rate of sCRR (15–50y: 33.3% [3/9] vs >50y: 0.0% [0/6]) and lower rate of sCRW (15–50y: 50.0% [4/8] vs >50y: 100.0% [5/5]) compared to eyes >50y.

In males, eyes 15–50y at onset had the lowest rate of sCRR (<15y: 19.0% [4/21]; 15–50y: 6.0% [3/50]; >50y: 20.0% [2/10]) and the highest rate of sCRW (<15y: 47.4% [9/19]; 15–50y: 77.1% [27/35]; >50y: 55.6% [5/9]) compared to eyes <15y and >50y. 

The clinical course of LHON may differ based on sex and age at symptom onset.