Optical Coherence Tomography of the Retinal Ganglion Cell Complex in Leber’s Hereditary Optic Neuropathy and Dominant Optic Atrophy

Asanad, Samuel; Tian, Jun-Ru; Frousiakis, Starleen Elizabeth; Jiang, Jerry; Kogachi, Kaitlin; Felix, Carol; Darvizeh, Fatemeh; Irvine, Anne G.; Ter‐Zakarian, Anna; Falavarjani, Khalil Ghasemi; Barboni, Piero; Karanjia, Rustum; Sadun, Alfredo A.

doi:10.1080/02713683.2019.1567792

Cited by 38 publications

(27 citation statements)

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“…RNFL thinning, consistent with histological evidence, was seen in the superior and inferior quadrants with a relative sparing of the temporal quadrant [7]. This pattern differs from studies in patients with mitochondrial optic neuropathies and other neurodegenerative diseases, like Parkinson’s and Huntington’s Diseases, where there is a preferential involvement of the temporal quadrants due to loss of the smaller RCGs [7, 12].…”

Section: Introductionmentioning

confidence: 87%

Pupillometry evaluation of melanopsin retinal ganglion cell function and sleep-wake activity in pre-symptomatic Alzheimer’s disease

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Sultan

et al. 2019

PLoS ONE

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BackgroundMelanopsin-expressing retinal ganglion cells (mRGCs), intrinsically photosensitive RGCs, mediate the light-based pupil response and the light entrainment of the body’s circadian rhythms through their connection to the pretectal nucleus and hypothalamus, respectively. Increased awareness of circadian rhythm dysfunction in neurological conditions including Alzheimer’s disease (AD), has led to a wave of research focusing on the role of mRGCs in these diseases. Postmortem retinal analyses in AD patients demonstrated a significant loss of mRGCs, and in vivo measurements of mRGC function with chromatic pupillometry may be a potential biomarker for early diagnosis and progression of AD.MethodsWe performed a prospective case-control study in 20 cognitively healthy study participants: 10 individuals with pre-symptomatic AD pathology (pre-AD), identified by the presence of abnormal levels of amyloid β42 and total Tau proteins in the cerebrospinal fluid, and 10 age-matched controls with normal CSF amyloid β42 and Tau levels. To evaluate mRGC function, we used a standardized protocol of chromatic pupillometry on a Ganzfeld system using red (640 nm) and blue (450 nm) light stimuli and measured the pupillary light response (PLR). Non-invasive wrist actigraphy and standardized sleep questionnaires were also completed to evaluate rest-activity circadian rhythm.ResultsOur results did not demonstrate a significant difference of the PLR between pre-AD and controls but showed a variability of the PLR in the pre-AD group compared with controls on chromatic pupillometry. Wrist actigraphy showed variable sleep-wake patterns and irregular circadian rhythms in the pre-AD group compared with controls.ConclusionsThe variability seen in measurements of mRGC function and sleep-wake cycle in the pre-AD group suggests that mRGC dysfunction occurs in the pre-symptomatic AD stages, preceding cognitive decline. Future longitudinal studies following progression of these participants can help in elucidating the relationship between mRGCs and circadian rhythm dysfunction in AD.

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Section: Introductionmentioning

confidence: 87%

Pupillometry evaluation of melanopsin retinal ganglion cell function and sleep-wake activity in pre-symptomatic Alzheimer’s disease

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Sultan

et al. 2019

PLoS ONE

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“…Investigating the changes in the retinal structure and vessels in different stages of LHON can help us to understand the mechanism of the diseases and to determine the therapeutic time window. However, previous studies mainly focused on structural changes [26]. And studies of the vascular changes that occur in the different stages of LHON are limited.…”

Section: Discussionmentioning

confidence: 99%

Changes in Retinal Perfusion in Leber’s Hereditary Optic Neuropathy: An Optical Coherence Tomography-Angiography Study

Huang

et al. 2021

Ophthalmic Res

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Introduction: We aimed to study the change in the retinal perfusion in Leber’s hereditary optic neuropathy (LHON). Methods: Fourteen patients (28 eyes) diagnosed with LHON and 14 healthy controls (28 eyes) were enrolled. The retinal vessel densities in the parafoveal and peripapillary areas were measured with optical coherence tomography-angiography. Results: In the subacute LHON patients, the parafoveal superficial capillary plexus (SCP) and inner retinal thickness (IRT) were significantly reduced in all sectors compared with the controls (all p < 0.05), and the radial peripapillary capillary (RPC) network was significantly reduced in the temporal and inferior temporal sectors compared with the controls (p < 0.05). In the chronic LHON patients, the SCP and IRT were significantly lower in all sectors than in the controls (all p < 0.05), the RPC vessel density and thickness were significantly lower in all sectors than in the controls and lower in the temporal, superior temporal, inferior temporal, and nasal sectors than in the subacute-stage patients (all p < 0.05). Conclusion: The retinal structure and the perfusion of the macular and peripapillary areas are reduced in subacute LHON, and the retinal structure and the perfusion of the peripapillary area are further reduced in chronic LHON.

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“…The involvement of RGCs on the LHON pathophysiology has been confirmed by fundoscopy, optical coherence tomography (OCT) and histopathological studies (23,(33)(34)(35). Recently, it was discovered that RGCs also generate a slow negative wave response observable on the full-field electroretinogram (ff-ERG) immediately following the b-wave of the cone response.…”

Section: Introductionmentioning

confidence: 90%

Impaired Ganglion Cell Function Objectively Assessed by the Photopic Negative Response in Affected and Asymptomatic Members From Brazilian Families With Leber's Hereditary Optic Neuropathy

et al. 2021

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Purpose: The photopic negative response (PhNR) is an electrophysiological method that provides retinal ganglion cell function assessment using full-field stimulation that does not require clear optics or refractive correction. The purpose of this study was to assess ganglion cell function by PhNR in affected and asymptomatic carriers from Brazilian families with LHON.Methods: Individuals either under suspicion or previously diagnosed with LHON and their family members were invited to participate in this cross-sectional study. Screening for the most frequent LHON mtDNA mutations was performed. Visual acuity, color discrimination, visual fields, pattern-reversal visual evoked potentials (PRVEP), full-field electroretinography and PhNR were tested. 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). Optical coherence tomography scans of both the retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) were measured. PhNR amplitudes among affected, carriers and controls were compared by Kruskal-Wallis test followed by post-hoc Dunn test. The associations between PhNR amplitude and OCT parameters were analyzed by Spearman rank correlation.Results: Participants were 24 LHON affected patients (23 males, mean age=30.5 ± 11.4 yrs) from 19 families with the following genotype: m.11778G>A [N = 15 (62%), 14 males]; m.14484T>C [N = 5 (21%), all males] and m.3460G>A [N = 4 (17%), all males] and 14 carriers [13 females, mean age: 43.2 ± 13.3 yrs; m.11778G>A (N = 11); m.3460G>A (N = 2) and m.14484T>C (N = 1)]. Controls were eight females and seven males (mean age: 32.6 ± 11.5 yrs). PhNR amplitudes were significantly reduced (p = 0.0001) in LHON affected (−5.96 ± 3.37 μV) compared to carriers (−16.53 ± 3.40 μV) and controls (−23.91 ± 4.83; p < 0.0001) and in carriers compared to controls (p = 0.01). A significant negative correlation was found between PhNR amplitude and total macular ganglion cell thickness (r = −0.62, p < 0.05). Severe abnormalities in color discrimination, visual fields and PRVEPs were found in affected and subclinical abnormalities in carriers.Conclusions: In this cohort of Brazilian families with LHON the photopic negative response was severely reduced in affected patients and mildly reduced in asymptomatic carriers suggesting possible subclinical abnormalities in the latter. These findings were similar among pathogenic mutations.

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Optical Coherence Tomography of the Retinal Ganglion Cell Complex in Leber’s Hereditary Optic Neuropathy and Dominant Optic Atrophy

Cited by 38 publications

References 27 publications

Pupillometry evaluation of melanopsin retinal ganglion cell function and sleep-wake activity in pre-symptomatic Alzheimer’s disease

Pupillometry evaluation of melanopsin retinal ganglion cell function and sleep-wake activity in pre-symptomatic Alzheimer’s disease

Changes in Retinal Perfusion in Leber’s Hereditary Optic Neuropathy: An Optical Coherence Tomography-Angiography Study

Impaired Ganglion Cell Function Objectively Assessed by the Photopic Negative Response in Affected and Asymptomatic Members From Brazilian Families With Leber's Hereditary Optic Neuropathy

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