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Background: To investigate the repeatability in vessel caliber measurements by optical coherence tomography angiography (OCTA). Methods: In this prospective study, 28 patients (47 eyes) underwent sequential OCTA imaging of the optic nerve head and macula. Two independent masked graders measured vessel caliber for sequential images of the optic nerve head and macula. The average vessel width was determined and variability between graders and images. Results: A total of 8400 measurements of 420 vessels from 84 OCTA images were included in the analysis. Overall, inter-grader agreement was excellent (ICC 0.90). The coefficient of variation (CoV) for all repeated OCTA images was 0.10. Greater glaucoma severity, older age, macular location, and diagnosis of diabetes were associated with thinner vessels (p < 0.05). CoV was higher in the peripapillary region (0.07) as compared to the macula (0.15). ICC was high for all subgroups except for the macula (ICC = 0.72). Conclusions: Overall, the repeatability of vessel caliber measurements by OCTA was high and variability low. There was greater variability in the measurement of macular vessels, possibly due to technical limitations in acquiring accurate vessel widths for smaller macular vessels.

Background: Long-term disability after stroke is standardly assessed 3m post-onset, using the modified Rankin Scale (mRS), but clinical trial patients lost to follow-up require imputation of likely outcome. An early post-onset, e.g. day 4, mRS is often available but its utility to forecast outcome in ischemic and in hemorrhagic stroke patients has not been delineated. Methods: We analyzed all patients with acute cerebral ischemia (ACI) and with intracranial hemorrhage (ICH) enrolled in the NIH Field Administration of Stroke Therapy- Magnesium (FAST-MAG) Phase 3 trial. The performance of ordinal day 4 mRS, alone and as part of multivariate models, in predicting ordinal day 90 mRS was assessed using Spearman correlation coefficients (r s ) and kappa (chance corrected agreement) statistics. Results: Among the 1206 acute cerebral ischemic patients, age was 70.9, 45.5 % were female, and initial NIHSS was 9.28 ± 8.28. In univariate analysis, day 4 mRS and day 90 mRS correlated strongly, r s = 0.76, weighted kappa = 0.71 increasing in multivariate analysis to r s = 0.78 and weighted kappa = 0.76 (Figure 1A). Among the 367 intracranial hemorrhage patients, age was 65.4, 32.7% were female, and initial NIHSS was 18.3 ± 11. In univariate analysis, day 4 mRS and day 90 mRS also correlated moderately r s = 0.64, weighted kappa = 0.63, increasing in multivariate analysis to r s = 0.81 and weighted kappa = 0.78 (Figure 1B). In the multivariate predictive models, day 4 mRS was the most determinative variable along with age and initial NIHSS for both ICH and ACI. Conclusion: For both acute cerebral ischemia and intracranial hemorrhage patients, long-term, 3m mRS disability outcomes can be predicted well using mRS assessment on day 4, alone and even more accurately in combination with baseline prognostic variables. Age and baseline NIHSS exert more additional influence on 3m mRS outcome in ICH than ACI, likely reflecting the better functional recovery among ICH than ACI stroke survivors.

The purpose of this study was to compare autoregulation of retinal arteriolar and venular blood flow in patients with glaucoma, glaucoma suspect participants, and control participants using erythrocyte mediated velocimetry.This prospective cohort pilot study included 7 eyes of 5 participants with glaucoma, 15 eyes of 8 glaucoma suspect participants, and 11 eyes of 6 control participants. Mean erythrocyte velocity in retinal arterioles and venules was measured using erythrocyte mediated velocimetry at room air and after oxygen supplementation. Change in erythrocyte velocity was compared among all groups using generalized estimating equations.In total, 64 vessels (18 with glaucoma, 31 that were glaucoma suspect, and 15 controls) of 33 eyes of 19 participants were analyzed. There was no significant difference in baseline velocities in arterioles or venules among the three groups. With induction of hyperoxia, mean arterial erythrocyte velocity decreased in glaucoma (-7.2 ± 13.7%), which differed from controls and glaucoma suspects where erythrocyte velocity increased with hyperoxia by 4.6 ± 13.3% (P = 0.002) and 7.2 ± 21.7% (P = 0.03), respectively. A higher baseline arteriolar velocity (β = -3.9% per mm/s, P = 0.002), glaucoma diagnosis (β = -21.1%, P = 0.03), and White race (β = -20.0%, P = 0.01) were associated with decreased velocity in response to arterial hyperoxia.Hyperoxia increased erythrocyte velocity in control and glaucoma suspect participants, but decreased erythrocyte velocity in glaucoma participants, possibly due to impaired autoregulation. Baseline velocity, glaucoma diagnosis, and White race were associated with a decrease in velocity with induction of hyperoxia.The European Medicines Agency (EMA) permits precision measurements of blood flow which may aid in the development of biomarkers of glaucoma-related dysregulation of blood flow.

BACKGROUND: Cabin pressurization is the process by which aircraft maintain a comfortable and safe environment for passengers flying at high altitudes. At high altitudes, most patients can tolerate changes in pressurization; however, passengers at high risk of hypoxia may experience ischemic events. The purpose of this study was to evaluate variations in pressurization of commercial aircraft at cruising altitude and describe its relevance in relation to patients with non-arteritic anterior ischemic optic neuropathy (NAION).METHODS: Altimeters were used to measure altitude and cabin altitude at cruising altitude aboard 113 commercial flights, including 53 narrow-body and 60 wide-body aircraft.RESULTS: Cabin altitude ranged from 4232 ft to 7956 ft at cruising altitudes ranging from 30,000 ft to 41,000 ft. The mean cabin altitude for all flights was 6309 876 ft. Narrow-body aircraft had a significantly higher mean cabin altitude (6739 829 ft) compared to wide-body aircraft (5929 733 ft). For all flights, the mean cruising altitude was 35,369 2881 ft with narrow-body aircraft cruising at a lower altitude of 34,238 2389 ft compared to wide-body aircraft at 36,369 2925 ft. Newer generation aircraft had a mean cabin altitude of 6066 837 ft, which was lower than the mean cabin altitude of older aircraft (6616 835 ft).DISCUSSION: Innovation in flight design has offered the ability for aircraft to fly at greater altitudes while maintaining lower cabin altitude. Those at high risk of hypoxia-induced complications may consider aircraft type when air travel is required.Nazarali S, Liu H, Syed M, Wood T, Asanad S, Sadun AA, Karanjia R. Aircraft cabin pressurization and concern for non-arteritic anterior ischemic optic neuropathy. Aerosp Med Hum Perform. 2020; 91(9):715719.

Objective To assess the repeatability of blood flow velocity index (BFVi) metrics obtained with a recently FDA-cleared laser speckle contrast imaging device, the XyCAM RI, and characterize differences in these metrics between control, glaucoma suspect, and glaucoma subjects. Design Prospective observational study Participants 46 subjects (20 control, 16 glaucoma suspect, and 10 glaucoma; one eye per subject) Methods Key dynamic BFVi metrics–mean, peak, dip, volumetric rise index (VRI), volumetric fall index (VFI), time to rise (TtR), time to fall (TtF), blow out time (BOT), skew, acceleration time index (ATI)–were measured in the optic disc, optic disc vessels, optic disc perfusion region, and macula in four imaging sessions on the same day. Intrasession and intersession variability were calculated using the coefficient of variation (CV) for each metric in each region of interest (ROI). Values for each dynamic BFVi variable were compared between glaucoma subjects, glaucoma suspects, and controls using bivariate and multivariable analysis. Pearson correlation coefficients were used to correlate each variable in each ROI with age, intraocular pressure, cup to disc ratio, mean deviation, pattern standard deviation, retinal nerve fiber layer thickness, and minimum rim width. Main outcome measures CV for the intrasession and intersession variability for each dynamic BFVi metric in each ROI, and differences in each metric in each ROI between each diagnostic group. Results The intersession CV for mean, peak, dip, as well as VRI, VFI, TtR, and TtF ranged from 3.2 ± 2.5% to 11.0 ± 3.8%. Age, cup-to-disc ratio, optical coherence tomography metrics, and visual field metrics showed significant correlations with dynamic BFVi variables. Peak, mean, dip, VRI, and VFI, were significantly lower in glaucoma subjects than in control subjects in all ROI except the fovea. These metrics were also significantly lower in glaucoma subjects than suspects in the disc vessels. Conclusions Dynamic blood flow metrics measured with the XyCAM RI are reliable, associated with structural and functional glaucoma metrics, and significantly different between glaucoma subjects, glaucoma suspects, and controls. The XyCAM RI may serve as an important tool in glaucoma management in the future.

Purpose We evaluated the patient-control differences and predictive value of the retina as potential biomarkers for schizophrenia. Methods The institutional study included both eyes of 58 schizophrenia spectrum disorder (SSD) patients (age 37.2 ± 12.3 years) and 35 controls (age 41.1 ± 15.2 years). Retinal nerve fiber layer (RNFL), ganglion cell-inner plexiform layer, outer retinal photoreceptor complex, and total macula thicknesses were measured by optical coherence tomography (OCT). Anterior segment parameters including central corneal thickness, anterior chamber depth, and axial length were measured to rule out confounds on the retinal measures. Results The peripapillary RNFL was overall significantly thinner in SSD relative to controls (F = 3.97, P = 0.049), most pronounced in the temporal (5.2 µm difference, F = 6.95, P = 0.010) and inferior quadrants (12.1 µm difference, F = 7.32, P = 0.009). There were no significant group differences in thickness for the macular RNFL, ganglion, or photoreceptor cell related measures (P > 0.05). Peripapillary RNFL, central macula, and outer photoreceptor complex thicknesses were together able to classify SSD patients with 80% sensitivity and 71% specificity; area under the curve = 0.82 (95% confidence interval, 0.75-0.88). Conclusions SSD patients exhibited significant RNFL thinning relative to controls. Notably, retinal thickness measures including both peripapillary and macular data exhibited improved diagnostic accuracy for SSD as compared to these regions alone. Translational relevance This is the first study to evaluate the predictive value of both the inner and outer retina in SSD. OCT retinal thickness measures including peripapillary data in conjunction with macular data may provide an informative, noninvasive in vivo ocular biomarker for schizophrenia.

Background The intermediate cleft tip rhinoplasty is performed in childhood to address residual tip asymmetries during the most critical period of psychosocial development. The authors describe and evaluate long-term outcomes of that approach for the unilateral cleft lip and palate patient based on the concept of individual restoration of each abnormal anatomical component. Methods Photomorphometric analyses of unilateral cleft lip and palate patients (n = 50) who underwent intermediate cleft tip rhinoplasty using the component restoration technique were evaluated preoperatively (time 0) and postoperatively at less than 1 year (time 1), 1 to 3 years (time 2), and more than 3 years (time 3) and compared to age-matched unilateral cleft lip and palate control patients. Nasal relationships (alar symmetry, nasal tip protrusion-to-alar base width ratio, and height-to-width dimensions for the cleft and noncleft nostrils) were compared over time using a linear mixed-effect model. Results At time 0, both groups demonstrated similar nasal relationships, with the exception of a wider cleft-side nostril in relationship to height in the rhinoplasty group. The component restoration technique improved all four nasal relationships at all postoperative time points compared with time 0 in a statistically significant manner, whereas control patients did not demonstrate significant changes at the corresponding ages. Long-term differences at time 3 revealed a trend toward improved alar symmetry and cleft-side and non-cleft-side nostril dimensions, and a significant improvement in the nasal tip protrusion-to-alar base width ratio in intermediate cleft tip rhinoplasty-treated versus control patients (p = 0.002). Conclusion The component restoration technique for the unilateral intermediate cleft tip rhinoplasty improves nasal relationships toward normal immediately and in a sustained manner for at least 3 years. Clinical question/level of evidence Therapeutic, III.

Purpose: This study aimed to demonstrate the value of the chief compliant and patient history to accurately diagnose patient pathology without requiring ocular examination or imaging in an outpatient neuro-ophthalmology clinic. Methods: We prospectively evaluated 115 consecutive patients at our institution from January to April 2009. The attending neuro-ophthalmologist committed to a single most likely diagnosis while solely being exposed to patient demographic information (age, gender, race) and chief complaint, but was otherwise blinded to ocular examination or imaging. The validity of the initial diagnosis was assessed by further acquiring subjective and objective findings and the percentage of correct diagnoses was determined. Results: Patient cases were categorized based on the neuro-ophthalmologic localization of the final diagnoses: afferent nervous system, central nervous system (CNS), efferent nervous system, orbital system, and pupillary system. Correct diagnoses by chief complaint and patient history were 84%, 100%, 86%, 80%, 50% and 100% for afferent, central, efferent, orbit, pupil, and other neuro-ophthalmic diseases, respectively. Over half the cases were correctly diagnosed by chief complaint alone, which improved to 88% when combined with the patient history. Conclusions: A simple combination of patient history and chief complaint predicts an overall diagnostic accuracy in approximately 90% of cases. Our study demonstrates the remarkable diagnostic value of patient history in neuro-ophthalmologic clinic practice. Keywords: Diagnostic accuracy, Patient history, Neuro-ophthalmology

Purpose: To report an accelerated course of visual recovery in a case of Leber's hereditary optic neuropathy (LHON) following treatment with idebenone and hormone replacement therapy (HRT). We hereby demonstrate the clinical utility of estrogen's 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 patient's accelerated visual improvement. Keywords: Leber's hereditary optic neuropathy, Mitochondrial disease, Hormone replacement therapy, Accelerated visual improvement

Transient stoppage of erythrocytes through different vascular beds has important implications for local tissue metabolism. By combining adaptive optics retinal imaging with erythrocyte-mediated angiography (AO-EMA), erythrocyte stasis events can be readily observed in the microvasculature of living human eyes. Localization of erythrocyte stasis using EMA alongside AO-based indocyanine green (ICG) angiography illustrate the notion that there is a previously uncharacterized population of erythrocytes in stasis residing in the smallest choroidal vessels. These observations are an important step towards elucidating the hemodynamic properties of the choroidal microcirculation and demonstrate a novel application of ICG imaging.

The current study evaluated retinal function using electroretinography (ERG) in cognitively healthy (CH) participants with preclinical Alzheimer’s 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.

Optical coherence tomography angiography (OCTA) is an emerging technique for non-invasively imaging the ocular vasculature, enabling quantitative measurements of retinal vascular anatomy. As extensions of the central nervous system, the optic nerve and the retina share many vascular characteristics with the brain. Measuring the structural and functional changes within the ocular vasculature may be useful as an objective approach for non-invasively evaluating the cerebrovascular architecture. The current article reviews the most recent applications of OCTA imaging at the eye-brain interface and highlights the emerging vascular biomarkers for neurodegenerative optic neuropathies, as reported in Alzheimer’s disease, Parkinson’s disease, schizophrenia, and mitochondrial optic neuropathies. These ophthalmologic findings offer objective measures of a more accessible clinical marker and may improve our understanding of neurodegenerative disease.

Endotheliitis is the inflammation of the corneal endothelium resulting in edema and subsequent loss of vision. Bacterial causes of corneal inflammation primarily of the epithelium with subsequent, secondary involvement of the endothelium have previously been described. Notably, however, there are no reports of isolated endotheliitis related to a bacterial pathogen. We report, for the first time, a case of corneal endotheliitis associated with a pyogenic liver abscess caused by methicillin resistant Staphylococcus aureus (MRSA). Treatment targeting the underlying source of infection led to visual recovery in our patient.

BackgroundAlzheimer's 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.MethodsAs 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.ResultsMean 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.ConclusionsOur 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.

Background Melanopsin-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. Methods We 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. Results Our 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. Conclusions The 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.

Entero-endocrine cells involved in the regulation of digestive function form a large and diverse cell population within the intestinal epithelium of all animals. Together with absorptive enterocytes and secretory gland cells, entero-endocrine cells are generated by the embryonic endoderm and, in the mature animal, from a pool of endoderm derived, self-renewing stem cells. Entero-endocrine cells share many structural/functional and developmental properties with sensory neurons, which hints at the possibility of an ancient evolutionary relationship between these two cell types. We will survey in this article recent findings that emphasize the similarities between entero-endocrine cells and sensory neurons in vertebrates and insects, for which a substantial volume of data pertaining to the entero-endocrine system has been compiled. We will then report new findings that shed light on the specification and morphogenesis of entero-endocrine cells in Drosophila. In this system, presumptive intestinal stem cells (pISCs), generated during early metamorphosis, undergo several rounds of mitosis that produce the endocrine cells and stem cells (ISCs) with which the fly is born. Clonal analysis demonstrated that individual pISCs can give rise to endocrine cells expressing different types of peptides. Immature endocrine cells start out as unpolarized cells located basally of the gut epithelium; they each extend an apical process into the epithelium which establishes a junctional complex and apical membrane specializations contacting the lumen of the gut. Finally, we show that the Drosophila homolog of ngn3, a bHLH gene that defines the entero-endocrine lineage in mammals, is expressed and required for the differentiation of this cell type in the fly gut.

Retinal imaging technology is rapidly advancing and can provide ever-increasing amounts of information about the structure, function and molecular composition of retinal tissue in humans in vivo. Most importantly, this information can be obtained rapidly, non-invasively and in many cases using Food and Drug Administration-approved devices that are commercially available. Technologies such as optical coherence tomography have dramatically changed our understanding of retinal disease and in many cases have significantly improved their clinical management. Since the retina is an extension of the brain and shares a common embryological origin with the central nervous system, there has also been intense interest in leveraging the expanding armamentarium of retinal imaging technology to understand, diagnose and monitor neurological diseases. This is particularly appealing because of the high spatial resolution, relatively low-cost and wide availability of retinal imaging modalities such as fundus photography or OCT compared to brain imaging modalities such as magnetic resonance imaging or positron emission tomography. The purpose of this article is to review and synthesize current research about retinal imaging in neurodegenerative disease by providing examples from the literature and elaborating on limitations, challenges and future directions. We begin by providing a general background of the most relevant retinal imaging modalities to ensure that the reader has a foundation on which to understand the clinical studies that are subsequently discussed. We then review the application and results of retinal imaging methodologies to several prevalent neurodegenerative diseases where extensive work has been done including sporadic late onset Alzheimer's Disease, Parkinson's Disease and Huntington's Disease. We also discuss Autosomal Dominant Alzheimer's Disease and cerebrovascular small vessel disease, where the application of retinal imaging holds promise but data is currently scarce. Although cerebrovascular disease is not generally considered a neurodegenerative process, it is both a confounder and contributor to neurodegenerative disease processes that requires more attention. Finally, we discuss ongoing efforts to overcome the limitations in the field and unmet clinical and scientific needs.

Purpose To provide a histopathologic, morphometric analysis of the retina in Alzheimer's disease (AD). Methods Human postmortem retinas from eight patients with AD (mean age: 80 ± 12.7 years) and from 11 age-matched controls (mean age: 78 ± 16.57 years) were analyzed. The retinas were sampled from the superior quadrant on both the temporal and nasal sides with respect to the optic nerve. Thickness of the inner and outer layers involving the retinal nerve fiber layer (RNFL), retinal ganglion cell layer (RGCL), inner plexiform layer (IPL), inner nuclear layer (INL), and outer nuclear layer (ONL) were measured and compared between controls and AD. A total of 16 measurements of retinal thickness were acquired for each layer. Results RNFL thinning supero-temporally was significant closest to the optic nerve (∼35% thickness reduction; P < 0.001). Supero-nasally, RNFL was thinner throughout all points (∼40% reduction; P < 0.001). Supero-temporally, RGCL thinning was pronounced toward the macula (∼35% thickness reduction; P < 0.001). Supero-nasally, RGCL showed uniform thinning throughout (∼35% reduction; P < 0.001). IPL thinning supero-temporally was statistically significant in the macula (∼15% reduction; P < 0.01). Supero-nasal IPL featured uniform thinning throughout (∼25% reduction; P < 0.001). Supero-temporally, INL and ONL thinning were pronounced toward the macula (∼25% reduction; P < 0.01). Supero-nasally, INL and ONL were thinner throughout (∼25% reduction; P < 0.01). Conclusions Our study revealed marked thinning in both the inner and outer layers of the retina. These quantified histopathologic findings provide a more comprehensive understanding of the retina in AD than previously reported.

The purpose of the present article was to evaluate the previously unreported vascular alterations in Leber's 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.

Background: Mitochondrial optic neuropathies such as Leber's Hereditary Optic Neuropathy (LHON) and Dominant Optic Atrophy (DOA) have been shown to produce an optic neuropathy secondary to retinal ganglion cell loss with thinning of the retinal ganglion cell complex (RGCC). Methods: We performed a retrospective analysis assessing the thicknesses of the peripapillary retinal nerve fiber layer (pRNFL) along with the macular retinal ganglion cell-inner plexiform layer (RGC-IPL) using optical coherence tomography (OCT). We compared these changes among acute and chronic LHON, DOA, and normal healthy control patients. Results: Patients with chronic LHON exhibited statistically significant thinning of the RNFL in the superior, nasal, and inferior quadrants of the retina. In acute LHON, the RNFL was relatively thicker in all but the temporal quadrant when compared with respective quadrants in normal eyes; however, statistical significance was not achieved. In DOA, the RNFL was thinnest in the superior and inferior quadrants of the retina, measuring between acute and chronic LHON thickness values. In chronic LHON and DOA, both the pRNFL and RGC-IPL were significantly thinner in all four retinal quadrants relative to controls. Conclusions: This article represents the first comparative study of the RGCC between LHON and DOA. Our findings demonstrated significant thickness reductions in pRNFL and macular RGC-IPL in patients with LHON and DOA, with different specific patterns consistent with the general patterns of thinning classically observed. This study suggests the usefulness of the RGCC as a potential in vivo biomarker for assessing disease in patients with LHON and DOA.

Gilles de la Tourette syndrome (GTS) is a complex disorder characterized by the presence of motor and vocal tics, as well as neuropsychiatric pathological features. Visual field defects have also been described in GTS patients by Enoch et al. in the 1980s. In the current paper, the authors discuss Enoch et al. studies showing visual field defects in patients with GTS, presenting a similar case evaluated in the context of newer structural and functional examination modalities.