Photopic Negative Response and Retinal Nerve Fiber Layer Measured by OCT in Brazilian Families with Leber’s Hereditary Optic Neuropathy

Abstract

Purpose : To assess photopic negative response (PhNR) and retinal nerve fiber layer (RNFL) by OCT in carriers and affected members of Brazilian families with Leber’s Hereditary Optic Neuropathy (LHON).

Methods : Patients with LHON genotyped for one of the three mitochondrial DNA mutations (m.11778G>A; m.14484T>C; m.3460G>A) and carriers were examined. A control group of healthy subjects was included. Full-field ERG PhNR were recorded using red (640 nm) flashes at 1 cd.s/m2, on blue (470 nm) rod saturating background. PhNR amplitude (µV) was measured using baseline-to-trough (BT). The amplitude of PhNR was compared to average and quadrant values from optical coherence tomography scans of both the retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC). PhNR amplitudes among affected, carriers and controls were analyzed by Kruskal-Wallis test followed by post-hoc Dunn. PhNR amplitude was compared to OCT parameters by Spearman correlation. P<.05 was considered for statistical significance.

Results : A sample of 20 LHON affected patients (19 males, mean age=30.4 ±9.4 yrs) with the following genotype: m.11778G>A [N=10 (50%), 9 males, age at onset from 4.8 to 27.2 years – mean:17.9±7.1; mean disease duration: 8.9±9.4 yrs ]; m.14484T>C [N=6 (30%) males, age at onset from 12.1 to 30.3 years – mean:19.2±9.8; mean disease duration: 19.6±7.0] and m.3460G>A [4 (20%) males, age at onset from 14.9 to 29.8; disease duration: 4.2±2.3 yrs]. Carriers (mean age: 41.8±13.7 yrs) were 11 females and 1 male [11778 (N=10) and 3460 (N=2)]. Controls were 8 females and 8 males (mean age: 33.6±12.0 yrs). PhNR amplitudes were significantly reduced (p<.001) in LHON affected (-5.87±2.46 µV; n=20) compared to carriers (-16.77±3.65 µV; n=12) and controls (-22.60±5.85 µV; n=16) and in carriers compared to controls (p<.004). In affected patients PhNR amplitude (p=.37) and OCT parameters (p=.85) were comparable among the 3 mtDNA mutations. A significant negative correlation was found between PhNR amplitude and total RNFL thickness (r=-.79, p<.0001) and for superior (r=-.71; p=.0005), inferior (r=-.71; p=.0004) and nasal (r=-.60; p=.005) quadrants.

Conclusions : There was a significant decrease in the PhNR LHON affected patients and carriers. The reduction in PhNR amplitude was smaller in carriers when compared to affected patients. Similar findings were found in all three primary mutations.

This is a 2020 ARVO Annual Meeting abstract.