Natural History of Leber's Hereditary Optic Neuropathy: Longitudinal Analysis of the Retinal Nerve Fiber Layer by Optical Coherence Tomography
Presented in part at: Association for Research in Vision and Ophthalmology Meeting, May 2008, Fort Lauderdale, Florida.
Received 11 April 2009; received in revised form 9 July 2009; accepted 21 July 2009. published online 24 December 2009.
Purpose
To investigate by optical coherence tomography (OCT) the topographic pattern and temporal sequence of fiber loss in the peripapillary retinal nerve fiber layer (RNFL) of patients with Leber's hereditary optic neuropathy (LHON) in a longitudinal follow-up.
Design
Cohort study.
Participants
Six eyes of 4 patients with molecularly defined LHON were enrolled before the subacute period of visual loss.
Methods
Subjects were studied by StratusOCT (Carl Zeiss Meditec, Inc., Dublin, CA) during a 9-month follow-up starting from the presymptomatic stage of the disease. Examinations were carried out at 4 different time points: presymptomatic stage, time of visual loss, and 3 and 9 months later.
Main Outcome Measures
Peripapillary RNFL thickness for each quadrant of the optic nerve. Statistical comparisons were performed by ordinary analysis of variance with Dunnett's post-test.
Results
A significant increase of RNFL thickness was detected in the temporal and inferior quadrants between the presymptomatic stage and the disease onset (P<0.05). The 360-degree average and the superior and nasal quadrants showed a nonstatistically significant increase of thickness at this time. In the 360-degree average (P<0.01), superior (P<0.01), nasal (P<0.05), and inferior (P<0.01) quadrants, RNFL thickening showed statistically significant changes between the presymptomatic stage and the 3-month follow-up. At 3 months, a nonsignificant reduction of RNFL thickness was detected in the temporal quadrant. A significant reduction of RNFL was detected in all but the nasal quadrants between the presymptomatic stage and the 9-month Follow-up.
Conclusions
The RNFL thickness increase first appeared at the temporal and inferior quadrants. Conversely, at 3 months the thickening fibers were more evident in the superior and nasal quadrants. These findings are consistent with the established preferential early involvement of the papillomacular bundle in LHON. We also demonstrated the previously unrecognized simultaneous early involvement of the inferior quadrant. The late involvement of both superior and nasal quadrants suggests a dynamic evolution of the acute stage that continues for 3 months and may represent a therapeutic window of opportunity.
Financial Disclosure(s)
The authors have no proprietary or commercial interest in any materials discussed in this article.
ABSTRACT