Macular Retinal Sublayer Thickness Changes in Patients and Carriers in the Natural History Phase of the Leber Hereditary Optic Neuropathy G11778A Gene Therapy Clinical Trial

Abstract

Purpose: We determined macular retinal sublayer thickness changes of patients and carriers with G11778A Leber hereditary optic neuropathy (LHON) by utilizing data from the natural history phase of the gene therapy trial where subjects underwent visual examination every 6 months from 2008 to 2013.

Methods: Spectral-domain Cirrus OCT 512x128 macular cube scans were segmented for the baseline examination. Segmented retinal sublayers were the RNFL, GCL-IPL, INL-OPL, ONL-IS, and OS. Poor quality scans that cannot be segmented accurately were excluded. The thickness of the retinal sublayers of the LHON affected subjects and asymptomatic carriers were compared to a normal group.

Results: Segmented macular OCT data were available from 20 LHON affected subjects (age 31+14 years, range 10-61), 31 asymptomatic LHON carriers (age 38+18, 9-65), and 14 normal subjects (age 39+13, 23-61). In general, parameters were not significantly correlated with age in any of the groups. There were no differences between carriers and normals for any sublayers but some layers were thinner or thicker in LHON subjects. Layers showing the most striking differences between LHON and the other two groups included the RNFL, GCL-IPL, and OS (p-values from 0.046 to <0.001). LHON RNFL and GCL-IPL were thinner than carriers and normals while LHON OS was thicker than carriers and normals. Differences between groups were not significant in the INL+OPL. The ONL+IS layer of the temporal and inferior quadrants (inner and outer macular annular rings) was thicker in LHON (0.041≥p≥0.009).

Conclusions: LHON affected patients, compared to normal subjects, have thickened photoreceptor outer segment layer and some thickening of the ONL-IS in spite of having thinner RNFL and GCL-IPL layers. Asymptomatic LHON carriers have retinal sublayer thickness similar to normal subjects. The findings indicate optic nerve degeneration in LHON also has an effect on the morphology of the outer retinal layers of the macula.