Functional Changes of Retinal Ganglion Cells and Visual Pathways in Patients with Chronic Leber’s Hereditary Optic Neuropathy during One Year of Follow-up

Abstract

Purpose: To assess changes of retinal ganglion cells (RGCs) and visual pathways' function in patients with Leber's hereditary optic neuropathy (LHON) during 12 months of follow-up of the chronic phase.Design: Retrospective case series. Participants: Twenty-two patients with LHON (mean age, 36.3AE9.3 years) in the "chronic phase" of the disease, providing 42 eyes (LHON group) with different pathogenic mitochondrial DNA mutations (group 11778: 21 eyes; group 3460: 4 eyes; group 14484: 13 eyes; and group 14568: 4 eyes) were enrolled. Twenty-five agesimilar healthy participants, providing 25 eyes, served as controls.Methods: Pattern electroretinogram (PERG) and visual evoked potentials (VEP), in response to 60ʹ and 15ʹ checks visual stimuli, were recorded at baseline in all subjects and after 6 and 12 months of follow-up in patients with LHON. At baseline, in all LHON eyes for each PERG and VEP parameter (amplitude and implicit time), the 95% confidence limit (CL) of testeretest variability was calculated. The PERG and VEP mean values observed in LHON eyes were compared (1-way analysis of variance [ANOVA]) with those of controls. During the follow-up, the PERG and VEP differences observed with respect to baseline were evaluated by ANOVA.Main Outcome Measures: Changes of individual and mean absolute values of 60ʹ and 15ʹ PERG amplitude and VEP amplitude and implicit time at each time point compared with baseline values in the LHON group.Results: At baseline, mean values of PERG and VEP parameters detected in the LHON group were significantly (P < 0.01) different with respect to control values. In the LHON group, at 6 and 12 months of follow-up, the majority of eyes showed unmodified (within 95% CL) PERG and VEP values, and mean absolute values of these measures were not significantly (P > 0.01) different from baseline values.Conclusions: In our untreated patients with chronic LHON, with different specific pathogenic mutations, RGCs and visual pathways function were not significantly modified during 12 months of follow-up. This should be considered in the disease natural history when attempts for treatments are proposed in chronic LHON.

Visual Evoked Potentials in Joubert Syndrome: A Suggested Useful Method for Evaluating Future Approaches Targeted to Improve Visual Pathways’ Function

“…Indeed, this hypothesis has been proposed once about a JS patient [17]. In LHON, several studies reporting VEP abnormalities [24,25,[32][33][34][35] suggest that a prevalent impairment of small axons (forming the macular-papillo bundle of the optic nerve) may happen. However, different from LHON, in our JS patients we did not detect significant differences between the impaired neural conduction along large axons (delay in 60' VEP P100IT) and along small axons (delay in 15' VEP P100IT).…”

“…It is very interesting that in both the JS-A and JS-N groups, considering each VEP parameter (VEP 100 Its and N75-P100 As), there were no significant differences between the bioelectrical responses obtained with 60' of visual stimulation and 15' checks ones. This led us to believe that in JS patients with or without optic nerve morphologic abnormalities, there is a concomitant dysfunction of small and large axons [22,25].…”

“…At the viewing distance of 114 cm, the check edges subtended 60 min (60') and 15 min (15') of the visual angle. As suggested by the ISCEV standards, VEPs were recorded in response to 60' (60' VEP) and 15' (15' VEP) checks to obtain a prevalent activation of large (with 60' checks) or small (with 15' checks) axons [22,25]. The monitor screen subtended 23°.…”

“…During a recording session, VEPs were recorded at least twice (between 2 to 5 times), and the resulting waveforms were superimposed to check the consistency of results. Based on previous studies [24,25], we know that intraindividual variability (evaluated by test-retest) is approximately ± 2 ms for VEP P100 IT and approximately ± 0.18 lV for VEP N75-P100 A. During the recording session we considered two successive waveforms ''superimposable,'' and therefore repeatable, with a difference in ms (for VEP P100 IT) and in lV (for VEP N75-P100 A) less than the above-reported values of intra-individual variability.…”

“…By using appropriate characteristics of visual stimuli, it is possible to obtain an objective evaluation of the neural conduction along ''large'' and ''small'' axons forming visual pathways [22,23]. For instance, in LHON, an optic nerve dysfunction, prevalent in the component of the small axons, but also involving the large axons, was detected by using VEP recordings with appropriate visual stimuli [24,25].…”