A New Scoring System for Scaling Patients With LHON: Getting Away From the Carrier/Affected Paradigm

Abstract

Purpose:: Recently, we described subclinical visual manifestations in asymptomatic Carriers with Leber’s Hereditary Optic Neuropathy (LHON) found in a giant pedigree from Brazil. What is required is a scoring system that provides a sliding scale of signs and psychophysical measures for all individuals with this type of mtDNA mutation.

Methods:: We have prospectively studied a pedigree of 332 patients with 11778 LHON (J-haplogroup) seen regularly over the last 6 years with field investigations in Brazil and quantitated several signs and psychophysical features in asymptomatic Carriers. In particular, we have characterized abnormalities regarding examinations of the fundus, visual fields (HVF), color and contrast sensitivity functions, OCT, GDx and a serological marker, neuron specific enolase (NSE).

Results:: Subclinical or occult abnormalities were found in structural and functional measures of the optic nerve and retina. We designed a 1 to 10 point scoring system to be used on LHON Carriers and Affected patients. This scale was developed by assigning points to each of seven measures (0-3 points for OCT, 0-2 for fundus changes and 0-1 for all other signs and tests). Asymptomatic LHON subjects may show minimal to nil evidence of their disease (a score of 0-1). However, most LHON Carriers demonstrated mild manifestations (2-4), or a pre-conversion accumulation of anomalies (5-7). LHON Affected patients also had a sliding scale of abnormalities (8-10).

Conclusions:: LHON patients may show subtle variable expressions of their disease that can be quantitated in contrast to the conventional description of Affected vs. Carrier states. This new paradigm allows for the use of a 0-10 sliding scale, which may prove useful as an outcome measure for both retrospective analysis and clinical trials.

Keywords: optic nerve • mitochondria • neuro-ophthalmology: optic nerve