Relative preservation of central retinal layers in LHON in comparison to other optic neuropathies

Abstract

Purpose : The purpose of this study was to evaluate thickness of retinal layers in Leber hereditary optic neuropathy(LHON) compared to non-mitochondrial optic neuropathies in atrophic stage with the aim to see if in LHON any specific patterns can be found.

Methods : 14 patients(24 eyes),10 males/4 females,mean age 37.5 years, with confirmed LHON (LHON group) were compared to 13 patients(23 eyes )with optic neuropathy, mean age 46 years, 7 males/6 females, with LHON-negative genetic testing(mtDNA+WES) and without identified aetiology of the bilateral optic atrophy (nonLHON group). Seven eyes were excluded due to confounding factors. Peripapillary RNFL (pRNFL) measurement and segmentation analysis of macular region retinal layers was performed using the Heidelberg Engineering Spectralis SD-OCT. Published normal segmentation data were used for controls.

Results : In LHON group RNFL, GCL and IPL layers were thinner in all ETDRS fields compared to nonLHON group, except for the central circle where LHON group had significantly better preservation of these layers (p=0.012,p=0.006 and p=0.011). The LHON group RNFL was significantly thinner in the pericentral middle ring (p=0.005), whilst IPL was significantly thinner in both middle and outer ring (p=0.019 and p=0.04). LHON group had thicker INL even compared to controls in the central circle (p=0.008) and the outer ring (p= 0.024), whilst the INL layer in nonLHON group was not significantly thicker than in controls. The LHON group also had thicker INL in the central circle (p=0.004) compared to nonLHON group. The ratio between the middle ETDRS ring and the central circle for RNFL (0.83–2.62), GCL (0.76-2.88) and INL (0.84-3.16) thicknesses were lower in LHON group compared to non LHON group (1.45-3.46, 1.72-3.57 and 1.14–3.30). Interestingly, in 3 LHON patients with VA improvement, the ratios were similar to results of nonLHON group. This may represent a new LHON biomarker. The two groups also significantly differed in temporal (p=0.045) and temporal superior region (p=0.001) pRNFL thickness.

Conclusions : The retinal ganglion cell complex thickness (RNFL-GCL-IPL) is relatively preserved in central ETDRS circle in LHON compared to non-mitochondrial optic nerve atrophies. LHON patients also showed thickening of INL layer compared to healthy controls. Our findings might represent novel biomarkers and the structural basis for possible recovery in some LHON patients.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.