Longitudinal Analysis of Photopic Negative Response in Carriers and Affected Members of the 11778 SOA-BR Leber’s Hereditary Optic Neuropathy Pedigree

Abstract

Purpose : An extensive Brazilian family (SOA-BR) with 11778 LHON has been studied and characterized in the last two decades. Our purpose was to investigate retinal ganglion cell function by the photopic negative response (PhNR) in members from this family in a four-year follow-up (FU) study.

Methods : Light-adapted flash full-field electroretinograms (ERGs) were recorded from both eyes in three visits: baseline, 2-year and 4-year FU. A total of 17 members was included, 15 asymptomatic carriers (20-70 years; mean 39.2±22.8; 8 males) and two affected males (a 23-year old previously treated with EPI-743 and a 55-year-old without previous treatment). Stimuli were brief 1 cd.s/m² red flashes (<5ms) on a 10 cd/m² blue background. ERG parameters of amplitude (µV) and latency (ms) were determined for PhNR (baseline-to-trough-BT). PhNR amplitude was considered normal if ≥ -21.1 µV considering previous normative values from our own laboratory. In carriers, longitudinal measurements were analyzed by Friedman test followed by Dunn multiple comparison test. Chi-square test was performed to compare frequency of abnormal PhNR amplitude for carriers along the 3 visits. P<.05 was considered for statistical significance.

Results : In carriers, a 14% reduction in PhNR amplitude was found in baseline, with 9% reduction in two-year FU and 14.0% in the 4-year FU. The frequency of subjects with subnormal PhNR amplitude among the 3 visits was comparable (P=.66) and, respectively, 80% in baseline, 73.3% in the two-year FU and in 86.7% in the four-year FU. Mean PhNR BT amplitude (µV) for the 3 visits were similar and, respectively, -19.2±4.8; -19.5±4.6 and -18.1±3.7, whereas for latency (ms) the values were also comparable and, respectively, 64.5±3.4; 64.2±3.5 and 65.5±3.8. In the two affected subjects, PhNR amplitudes were severely decreased (-8.7 and -6.7 µV) and similar among the three visits.

Conclusions : Stable retinal ganglion cell dysfunction was detected in all three visits along a four-year follow-up interval, with substantial loss of function in affected and subclinical changes in carriers from this extensive LHON pedigree.

This is a 2020 ARVO Annual Meeting abstract.