Perimetric parameters in unaffected carriers of Leber’s Hereditary Optic Neuropathy (LHON)

Abstract

Purpose: To evaluate Humphrey Visual Fields (HVF) for subclinical changes among carriers of the 11778 mitochondrial DNA mutation of LHON in a large Brazilian cohort. Previously, we have shown a decrease in multifocal electroretinogram (mERG) signals from the central retina in carriers of LHON from this cohort (Sadun A.A. et al, Trans Am Ophthalmol Soc 2006; 104:51). We aimed to determine whether carriers had an abnormal central perimetry when compared to affected and paternally-related controls.

Methods: The HVFs from the initial assessment of each subject were obtained for both eyes, and were categorized by disease status: affected (n=19), carriers (n=59) and controls (n=147). Subjects were excluded if they had any other ophthalmological problem, such as retinal scars or glaucoma. Observations for each HVF included assessments of mean deviation (MD), foveal threshold (FT), and threshold levels at each of the four central points around the fovea. Each variable was assessed as the dependent variable against disease status and controlled for age and gender in a multivariate linear regression analysis with estimates of significance adjusted using the Bonferroni correction.

Results: Affected patients had lower MD, FT and central thresholds, as expected. Carriers of all ages were not distinguishable from paternally-related controls by any perimetric measure. This finding is in contrast to previous reported findings which showed a decrease in central responses on mERG (Sadun A.A. et al, 2006), suggesting that changes in electrical activity in the retina are not reflected by retinal ganglion cell activity. The MD calculation is based on the HVF database to correct for age-related decline in visual sensitivity. We found that neither controls, nor carriers, demonstrated an association between age and MD (or other perimetric measures), suggesting that the rate of visual decline is normal in all groups. In the affected patients, there were no changes associated with age, presumably due to a floor effect.

Conclusions: Carriers in this large cohort displayed a normal phenotype on HVF perimetry, which is a subjective test of visual loss. There were no associations between MD and age, indicating the rate of perimetric decline in carriers is equal to the widely used database of controls in the HVF, which adjusts for age.

Keywords: 613 neuro-ophthalmology: optic nerve • 642 perimetry • 600 mitochondria