PURPOSE: Peripapillary vascular alterations have been classically described as hallmarks of Lebers Hereditary Optic Neuropathy (LHON). We recently demonstrated microvascular pathology involving the macula in patients affected with chronic LHON using optical coherence tomography angiography (OCTA). Macular vascular pathology in acute LHON has not previously been reported. METHODS: The macular superficial vasculature of an asymptomatic carrier and an affected patient with acute LHON, mitochondrial DNA mutation 3460, was assessed by OCTA. RESULTS: Similar findings of peripapillary microangiopathy and vascular telangiectasias were seen the affected patient, but in the parafoveal macula. These changes were most prominent nasally and inferiorly, corresponding to the proximal portions of the papillomacular bundle. The foveal avascular zone was markedly enlarged in the affected patient relative to the asymptomatic mother. CONCLUSIONS: These findings in acute LHON further supports the clinical utility of vascular parameters and suggest that further studies focused on macular pathology may be warranted to assess the natural history of LHON.

PURPOSE: To report an accelerated course of visual recovery in a case of Lebers hereditary optic neuropathy (LHON) following treatment with idebenone and hormone replacement therapy (HRT). We hereby demonstrate the clinical utility of estrogens protective role in LHON in vivo. METHODS: We present a case of LHON in a menopausal woman carrying the 10197 mitochondrial DNA (mtDNA) mutation, who experienced loss of vision shortly after discontinuing her estrogen replacement regimen. Functional visual outcomes are reported following treatment with idebenone and HRT. RESULTS: The patient exhibited an accelerated course of visual recovery, experiencing improvement in vision as early as one month and complete reversal of vision loss by eight months post-therapy. CONCLUSION: Idebenone treatment combined with HRT may have a synergistic effect in enhancing cellular bioenergetics and may explain the patients accelerated visual improvement.

The purpose of the present article was to evaluate the previously unreported vascular alterations in Lebers Hereditary Optic Neuropathy (LHON) 3460 mitochondrial DNA (mtDNA) mutation. Among the three primary mtDNA mutations, namely 11778, 14484, and 3460, LHON 3460 is the most rare and historically recognized as having the poorest visual prognosis. Optical coherence tomography angiography (OCTA) is a novel imaging modaility providing high-resolution microcirculation maps and enhancing visualization of the optic disc and peripapillary capillary beds. We herein exploit the advantages of OCTA, for the first time, to assess the optic nerve head and peripapillary microvasculature changes in an affected patient and compare these vascular changes with an asymptomatic carrier for LHON 3460, serving as a control. Vascular changes in LHON 11778 and 14484 have classically shown microvasculature attenuation localized specifically to the temporal peripapillary quadrant. In the present case, however, OCTA in LHON 3460, the most severe of the three mutational subtypes, illustrated significant vascular attenuation involving the nasal peripapillary region in addition to the temporal peripapillary microvascular changes classically seen in LHON. Our findings suggest that vascular measures may serve useful for objectively assessing mitochondrial disease. Further OCTA studies involving the nasal peripapillary region may be warranted to further understand vascular pathogenesis in LHON.

The current study evaluated retinal function using electroretinography (ERG) in cognitively healthy (CH) participants with preclinical Alzheimers disease (AD), as classified by cerebral spinal fluid (CSF) Aβ42/Tau ratio. Individuals with normal retinal morphology ascertained by spectral-domain optical coherence tomography were enrolled. Full-field ERG, pattern PERG, and photopic negative response (PhNR) were performed in 29 adult participants (58 eyes). Amplitude and implicit times of the ERG wave components were analyzed. Preclinical AD participants showed marked retinal ganglion cell dysfunction relative to controls. The PhNR was significantly diminished in preclinical AD relative to controls. PhNR amplitude and N95 implicit time differentiated CH individuals with CSF biomarkers of AD pathology with 87% sensitivity and 82% specificity. These quantitative electrophysiologic findings expand our understanding of early retinal functional changes that precede cognitive decline in AD. Retinal ganglion cell dysfunction, as detected by ERG, may be a clinically useful, non-invasive in vivo biomarker for early disease detection, which is necessary for ultimately pursuing early intervention.

BACKGROUND: Alzheimers disease (AD) pathology precedes symptoms and its detection can identify at-risk individuals who may benefit from early treatment. Since the retinal nerve fiber layer (RNFL) is depleted in established AD, we tested whether its thickness can predict whether cognitively healthy (CH) individuals have a normal or pathological cerebrospinal fluid (CSF) Aß42 (A) and tau (T) ratio. METHODS: As part of an ongoing longitudinal study, we enrolled CH individuals, excluding those with cognitive impairment and significant ocular pathology. We classified the CH group into two sub-groups, normal (CH-NAT, n = 16) or pathological (CH-PAT, n = 27), using a logistic regression model from the CSF AT ratio that identified >85% of patients with a clinically probable AD diagnosis. Spectral-domain optical coherence tomography (OCT) was acquired for RNFL, ganglion cell-inner plexiform layer (GC-IPL), and macular thickness. Group differences were tested using mixed model repeated measures and a classification model derived using multiple logistic regression. RESULTS: Mean age (± standard deviation) in the CH-PAT group (n = 27; 75.2 ± 8.4 years) was similar (p = 0.50) to the CH-NAT group (n = 16; 74.1 ± 7.9 years). Mean RNFL (standard error) was thinner in the CH-PAT group by 9.8 (2.7) μm; p < 0.001. RNFL thickness classified CH-NAT vs. CH-PAT with 87% sensitivity and 56.3% specificity. CONCLUSIONS: Our retinal data predict which individuals have CSF biomarkers of AD pathology before cognitive deficits are detectable with 87% sensitivity. Such results from easy-to-acquire, objective and non-invasive measurements of the RNFL merit further study of OCT technology to monitor or screen for early AD pathology.

[This corrects the article DOI: 10.1371/journal.pone.0232785.].