Search

Leber hereditary optic neuropathy (LHON) is a mitochondrial disease leading to rapid and severe bilateral vision loss. Idebenone has been shown to be effective in stabilizing and restoring vision in patients treated within 1 year of onset of vision loss. The open-label, international, multicenter, natural history-controlled LEROS study (ClinicalTrials.gov NCT02774005) assesses the efficacy and safety of idebenone treatment (900 mg/day) in patients with LHON up to 5 years after symptom onset (N = 199) and over a treatment period of 24 months, compared to an external natural history control cohort (N = 372), matched by time since symptom onset. LEROS meets its primary endpoint and confirms the long-term efficacy of idebenone in the subacute/dynamic and chronic phases; the treatment effect varies depending on disease phase and the causative mtDNA mutation. The findings of the LEROS study will help guide the clinical management of patients with LHON., SCOPUS: ar.j, info:eu-repo/semantics/published

[Resumen]: Las enfermedades neurodegenerativas constituyen un reto global significativo, afectando a millones de personas y deteriorando su calidad de vida, con el riesgo de desencadenar consecuencias fatales. Además de impactar en el cerebro, estos trastornos también afectan a la retina y al nervio óptico, alteraciones que pueden ser tempranamente detectadas mediante la tomografía de coherencia óptica (OCT). La identificación precoz de estas enfermedades a través del OCT es crucial para un diagnóstico temprano y efectivo. En nuestra investigación, hemos desarrollado una metodología innovadora que integra imágenes OCT con técnicas avanzadas de aprendizaje automático, en particular, el uso de redes neuronales convolucionales. Hemos enriquecido nuestro enfoque con la implementación de modelos tridimensionales, proporcionando una representación más exhaustiva y detallada de la retina. Esta combinación no solo mejora la resolución de las imágenes sino que también facilita un análisis más completo, marcando un hito en el campo. Gracias a este enfoque innovador, nuestro sistema puede clasificar de manera totalmente automática y precisa los pacientes en cinco categorías de relevancia clínica: Control, Alzheimer, Parkinson, Esclerosis Múltiple y Temblor Esencial. El sistema se distingue por su rapidez y objetividad en la clasificación, elevando notablemente la precisión y eficiencia del diagnóstico de enfermedades neurodegenerativas mediante técnicas no invasivas. La incorporación de modelos tridimensionales brinda una visión más detallada y profunda para identificar características patológicas, facilitando diagnósticos más tempranos, seguros y precisos. Este avance representa un significativo paso adelante hacia el desarrollo de tratamientos más efectivos, contribuyendo a mejorar de manera sustancial la calidad de vida de los pacientes., [Abstract]: Neurodegenerative diseases pose a significant global challenge, affecting millions and significantly deteriorating their quality of life, with the potential to lead to fatal consequences. These disorders impact not only the brain but also the retina and optic nerve, alterations that can be detected early on through Optical Coherence Tomography (OCT). Early identification of these diseases via OCT is crucial for timely and effective diagnosis. In our research, we have developed an innovative methodology that combines OCT images with advanced machine learning techniques, specifically the use of convolutional neural networks. We have enhanced our approach by incorporating three-dimensional models, providing a more comprehensive and detailed representation of the retina. This combination not only improves the resolution of the images but also facilitates a more thorough analysis, marking a milestone in the field. Thanks to this innovative approach, our system is capable of accurately and automatically classifying patients into five clinically relevant categories: Control, Alzheimer’s, Parkinson’s, Multiple Sclerosis, and Essential Tremor. Our system stands out for its speed and objectivity in classification, significantly enhancing the precision and efficiency of diagnosing neurodegenerative diseases through noninvasive methods. The inclusion of three-dimensional models offers a more detailed and indepth view for identifying pathological characteristics, leading to earlier, more reliable, and precise diagnoses. This advancement represents a significant leap forward towards developing more effective treatments, contributing substantially to improving the quality of life for patients.

Background and purpose: Serum levels of neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) are promising neuro-axonal damage and astrocytic activation biomarkers. Susac syndrome (SS) is an increasingly recognized neurological condition and biomarkers that can help assess and monitor disease evolution are highly needed for the adequate management of these patients. sNfL and sGFAP levels were evaluated in patients with SS and their clinical relevance in the relapse and remission phase of the disease was assessed. Methods: As part of a multicentre study that enrolled patients diagnosed with SS from six international centres, sNfL and sGFAP levels were assessed in 22 SS patients (nine during a relapse and 13 in remission) and 59 age-and sex-matched healthy controls using SimoaTM assay Neurology 2-Plex B Kit. Results: Serum NfL levels were higher than those of healthy controls (p < 0.001) in SS patients and in both subgroups of patients in relapse and in remission (p < 0.001 for both), with significantly higher levels in relapse than in remission (p = 0.008). sNfL levels showed a negative correlation with time from the last relapse (r = -0.663; p = 0.001). sGFAP levels were slightly higher in the whole group of patients than in healthy controls (p = 0.046) and were more pronounced in relapse than in remission (p = 0.013). Conclusion: In SS patients, both sNFL and sGFAP levels increased compared with healthy controls. Both biomarkers had higher levels during clinical relapse and much lower levels in remission. sNFL was shown to be time sensitive to clinical changes and can be useful to monitor neuro-axonal damage in SS.

[Resumen]: La enfermedad de Alzheimer representa uno de los desafíos más apremiantes en el ámbito médico y farmacológico actual. Identificar biomarcadores efectivos y desarrollar técnicas de diagnóstico temprano son elementos clave para combatir esta epidemia silenciosa. En este entorno, el presente Trabajo de Fin de Grado (TFG) explora un enfoque novedoso: el uso de imágenes de tomografía de coherencia óptica (OCT) retinianas obtenidas de ratones transgénicos PS19 tau. Estos ratones se caracterizan por su susceptibilidad a desarrollar sintomatología similar a la del alzhéimer en humanos, lo que los convierte en modelos preclínicos ideales para esta investigación. Nuestro enfoque innovador emplea técnicas de aprendizaje profundo para construir un sistema de segmentación automática tridimensional. Este sistema es capaz de extraer biomarcadores retinianos críticos que pueden correlacionarse con el desarrollo de la enfermedad de Alzheimer. Este conjunto de algoritmos forma parte de un pipeline de diagnóstico automatizado, complementado por un modelo de clasificación específico para estos biomarcadores. Los resultados iniciales son alentadores, mostrando un alto grado de precisión y validando la aplicabilidad de nuestra metodología en entornos preclínicos y farmacológicos. Este enfoque no solo mejora la velocidad y la eficacia del diagnóstico, sino que también reduce la subjetividad y la variabilidad asociadas a la interpretación humana. El proyecto se desglosa en dos fases fundamentales: la primera enfocada en la segmentación automática de imágenes OCT para la identificación de biomarcadores relevantes, y la segunda en la clasificación robusta de dichos biomarcadores para un diagnóstico preciso de la enfermedad de Alzheimer., [Abstract]: The Alzheimer’s disease represents one of the most pressing challenges in today’s medical and pharmacological fields. Identifying effective biomarkers and developing early diagnosis techniques are key elements in combating this silent epidemic. Within this context, the present Thesis explores a novel approach: the use of Optical Coherence Tomography (OCT) retinal images obtained from PS19 tau transgenic mice. These mice are characterized by their susceptibility to develop symptoms similar to Alzheimer’s in humans, making them ideal preclinical models for this research. Our innovative approach employs deep learning techniques to build a three-dimensional automatic segmentation system. This system is capable of extracting critical retinal biomarkers that can be correlated with the development of Alzheimer’s disease. This set of algorithms forms part of an automated diagnostic pipeline, complemented by a specific classification model for these biomarkers. The initial results are encouraging, showing a high degree of accuracy and validating the applicability of our methodology in preclinical and pharmacological settings. This approach not only improves the speed and efficacy of the diagnosis but also reduces the subjectivity and variability associated with human interpretation. The project is broken down into two fundamental phases: the first focuses on the automatic segmentation of OCT images for the identification of relevant biomarkers, and the second on the robust classification of these biomarkers for an accurate diagnosis of Alzheimer’s disease.

[Resumen]: Las enfermedades neurodegenerativas afectan a millones de personas en todo el mundo y pueden disminuir significativamente la calidad de vida y en algunos casos llevar a la muerte. Recientes estudios han demostrado que las enfermedades neurodegenerativas no solo afectan el cerebro, sino que también pueden tener un impacto en la retina y el nervio óptico. Segmentar e identificar estas enfermedades a partir de tomografía de coherencia óptica (OCT) es un paso crítico para un diagnóstico temprano. No obstante, el desafío radica en que los efectos de estas enfermedades en la retina suelen ser sutiles y difíciles de distinguir. En este trabajo, presentamos una metodología robusta basada en técnicas de Geometric Deep Learning para proporcionar un apoyo objetivo y mejorar el diagnóstico. La metodología se compone de dos fases. En la primera, se realiza una segmentación automática de las capas de la retina en imágenes OCT empleando nnU-Net, una arquitectura de aprendizaje profundo clásico. En la segunda, utilizamos los resultados de la segmentación en diferentes arquitecturas de Geometric Deep Learning como PointNet++ y DGCNN, aprovechando la información geométrica de todo el volumen OCT. Una de las mayores ventajas de utilizar Geometric Deep Learning en este contexto es su eficiencia en el uso de datos. Estas arquitecturas son especialmente aptas para trabajar con datos estructurados de manera irregular, como son las nubes de puntos en imágenes tridimensionales. Esto nos permite hacer un uso más eficiente de los datos disponibles, extrayendo patrones y relaciones complejas que serían difíciles de capturar con métodos convencionales. Además, la capacidad de estas arquitecturas para trabajar con diferentes números de puntos en una nube ofrece un equilibrio eficaz entre precisión y eficiencia computacional. El potencial de este estudio es considerable. Mejorar la precisión del diagnóstico de enfermedades neurodegenerativas a través de técnicas no invasivas implica un, [Abstract]: Neurodegenerative diseases affect millions of people worldwide, significantly diminishing their quality of life and, in some cases, leading to death. Recent studies have shown that neurodegenerative diseases not only impact the brain but can also affect the retina and optic nerve. Segmenting and identifying these diseases through Optical Coherence Tomography (OCT) is a critical step for early diagnosis. However, the challenge lies in the fact that the effects of these diseases on the retina are often subtle and difficult to distinguish. In this work, we present a robust methodology based on Geometric Deep Learning techniques to provide objective support and improve diagnosis. The methodology consists of two phases. In the first phase, we perform automatic segmentation of the retinal layers in OCT images using nnU-Net, a classic deep learning architecture. In the second phase, we employ the segmentation results in different Geometric Deep Learning architectures like PointNet++ and DGCNN, leveraging the geometric information across the entire OCT volume. One of the significant advantages of using Geometric Deep Learning in this context is its data efficiency. These architectures are particularly suited for working with irregularly structured data, such as point clouds in three-dimensional images. This allows us to make more efficient use of available data, extracting complex patterns and relationships that would be difficult to capture with conventional methods. Additionally, the capability of these architectures to work with different numbers of points in a cloud offers an effective balance between accuracy and computational efficiency. The potential of this study is considerable. Improving the accuracy of diagnosing neurodegenerative diseases through non-invasive techniques implies a safer, earlier, and more accurate diagnosis, which can lead to more effective treatments and an improved quality of life for the patient.

Background and purpose: Serum levels of neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) are promising neuro-axonal damage and astrocytic activation biomarkers. Susac syndrome (SS) is an increasingly recognized neurological condition and biomarkers that can help assess and monitor disease evolution are highly needed for the adequate management of these patients. sNfL and sGFAP levels were evaluated in patients with SS and their clinical relevance in the relapse and remission phase of the disease was assessed.Methods: As part of a multicentre study that enrolled patients diagnosed with SS from six international centres, sNfL and sGFAP levels were assessed in 22 SS patients (nine during a relapse and 13 in remission) and 59 age-and sex-matched healthy controls using SimoaTM assay Neurology 2-Plex B Kit.Results: Serum NfL levels were higher than those of healthy controls (p < 0.001) in SS patients and in both subgroups of patients in relapse and in remission (p < 0.001 for both), with significantly higher levels in relapse than in remission (p = 0.008). sNfL levels showed a negative correlation with time from the last relapse (r = -0.663; p = 0.001). sGFAP levels were slightly higher in the whole group of patients than in healthy controls (p = 0.046) and were more pronounced in relapse than in remission (p = 0.013).Conclusion: In SS patients, both sNFL and sGFAP levels increased compared with healthy controls. Both biomarkers had higher levels during clinical relapse and much lower levels in remission. sNFL was shown to be time sensitive to clinical changes and can be useful to monitor neuro-axonal damage in SS.

PurposePolymorphous low-grade adenocarcinoma is a tumor of the salivary glands that typically localizes within the oral cavity. We present a case of isolated third cranial nerve palsy as the initial presentation of polymorphous low-grade adenocarcinoma involving the left cavernous sinus in a patient status post glaucoma surgery.ObservationsA 68-year-old woman status post glaucoma drainage device implantation in her left eye presented with an isolated left third nerve palsy ten weeks postoperatively. Differential diagnoses included microvascular ischemic neuropathy, postoperative ptosis, and compressive mass. MRI revealed a left cavernous sinus mass, and subsequent excisional biopsy revealed a diagnosis of polymorphous low-grade adenocarcinoma.ConclusionsThere are few cases reporting polymorphous low-grade adenocarcinoma originating from and extending beyond the nasopharynx. This report emphasizes an unexpected neuro-ophthalmic manifestation of this salivary gland tumor.

PurposePolymorphous low-grade adenocarcinoma is a tumor of the salivary glands that typically localizes within the oral cavity. We present a case of isolated third cranial nerve palsy as the initial presentation of polymorphous low-grade adenocarcinoma involving the left cavernous sinus in a patient status post glaucoma surgery.ObservationsA 68-year-old woman status post glaucoma drainage device implantation in her left eye presented with an isolated left third nerve palsy ten weeks postoperatively. Differential diagnoses included microvascular ischemic neuropathy, postoperative ptosis, and compressive mass. MRI revealed a left cavernous sinus mass, and subsequent excisional biopsy revealed a diagnosis of polymorphous low-grade adenocarcinoma.ConclusionsThere are few cases reporting polymorphous low-grade adenocarcinoma originating from and extending beyond the nasopharynx. This report emphasizes an unexpected neuro-ophthalmic manifestation of this salivary gland tumor.

Lebers Hereditary Optic Neuropathy (LHON) is the most common primary mitochondrial DNA disorder. It is characterized by bilateral severe central subacute vision loss due to specific loss of Retinal Ganglion Cells and their axons. Historically, treatment options have been quite limited, but ongoing clinical trials show promise, with significant advances being made in the testing of free radical scavengers and gene therapy. In this review, we summarize management strategies and rational of treatment based on current insights from molecular research. This includes preventative recommendations for unaffected genetic carriers, current medical and supportive treatments for those affected, and emerging evidence for future potential therapeutics.

Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) affecting more than two million people worldwide. The disease is characterised by inflammation in the CNS (leading to episodes of focal neurological dysfunction, i.e. relapses) and neurodegeneration (leading to progressive and permanent disability). Depending on the localisation of the CNS damage, patients exhibit a wide range of symptoms including muscle weakness, sensory disturbances, problems with coordination, fatigue and cognitive impairment. Visual symptoms are common as well, with more dan 50% of MS patients experiencing one or more episodes of optic neuritis (ON) during the course of the disease. The disease course in MS is highly variable and difficult to predict. However, predicting the disease course is crucial for determining the proper treatment. This thesis focuses on how optical coherence tomography (OCT) can aid in monitoring and predicting the disease course in patients with MS. OCT is an imaging technique that generates high resolution images of the retina and all its layers. The inner two retinal layers consist of the retinal ganglion cells and their axons that will eventually form the optic nerve. Thereby, these two layers are directly connected to the brain. Previous research has demonstrated that previous episodes of ON result in atrophy (thinning) of these two layers. Sometimes, it can be challenging to establish whether a patient has ever experienced an episode of optic neuritis clinically. The absolute thickness of the retinal layers is not a good indicator for this. Our research shows that the difference in retinal layer thickness between the eyes of a single patient can, with high accuracy, discriminate ON patients from non-ON patients. Being able to establish the presence of a previous episode of ON in this way, might lead to an earlier diagnosis of MS and earlier treatment. In another study described in this thesis, we found that atrophy of the inner retinal

Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) affecting more than two million people worldwide. The disease is characterised by inflammation in the CNS (leading to episodes of focal neurological dysfunction, i.e. relapses) and neurodegeneration (leading to progressive and permanent disability). Depending on the localisation of the CNS damage, patients exhibit a wide range of symptoms including muscle weakness, sensory disturbances, problems with coordination, fatigue and cognitive impairment. Visual symptoms are common as well, with more dan 50% of MS patients experiencing one or more episodes of optic neuritis (ON) during the course of the disease. The disease course in MS is highly variable and difficult to predict. However, predicting the disease course is crucial for determining the proper treatment. This thesis focuses on how optical coherence tomography (OCT) can aid in monitoring and predicting the disease course in patients with MS. OCT is an imaging technique that generates high resolution images of the retina and all its layers. The inner two retinal layers consist of the retinal ganglion cells and their axons that will eventually form the optic nerve. Thereby, these two layers are directly connected to the brain. Previous research has demonstrated that previous episodes of ON result in atrophy (thinning) of these two layers. Sometimes, it can be challenging to establish whether a patient has ever experienced an episode of optic neuritis clinically. The absolute thickness of the retinal layers is not a good indicator for this. Our research shows that the difference in retinal layer thickness between the eyes of a single patient can, with high accuracy, discriminate ON patients from non-ON patients. Being able to establish the presence of a previous episode of ON in this way, might lead to an earlier diagnosis of MS and earlier treatment. In another study described in this thesis, we found that atrophy of the inner retinal

Background: Diagnosis of multiple sclerosis (MS) may sometimes be ascertained at the time of optic neuritis (ON) but other times require the advent of new disease activity. Objectives: The aim of this study was to examine the predictive value of optical coherence tomography (OCT) and visual evoked potential (VEP) measurements of the non-symptomatic, fellow eye of ON patients, for conversion to MS. Methods: This is a prospective cohort study in patients with acute ON. OCT thickness measurements of peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell layer–inner plexiform layer (GCLIPL), and multifocal (mf) VEP and full-field (ff) VEP, were performed. Univariate and multivariate Cox regression examined the value of predictors for the conversion to MS. Results: A total of 79 unilateral, acute ON patients, with no MS diagnosis or prior demyelination, were included. Of which, 28 patients developed MS during follow-up. Inferonasal GCLIPL, mean GCLIPL, and pRNFL thickness significantly predicted MS development in multivariate analysis (hazard ratio (HR) = 0.922–0.939, p = 0.0172–0.021). MfVEP mean latency (HR = 1.052, p = 0.006) only predicted MS conversion in univariate analysis. No significant predictive value was shown for the other parameters (p > 0.2). Conclusion: While both mfVEP and OCT are useful tools in the evaluation of acute ON patients, only OCT measurements of fellow eyes may serve as an independent predictor of MS development.

PurposeOptical coherence tomography (OCT) captures retinal damage in neuromyelitis optica spectrum disorders (NMOSD). Previous studies investigating OCT in NMOSD have been limited by the rareness and heterogeneity of the disease. The goal of this study was to establish an image repository platform, which will facilitate neuroimaging studies in NMOSD. Here we summarise the profile of the Collaborative OCT in NMOSD repository as the initial effort in establishing this platform. This repository should prove invaluable for studies using OCT to investigate NMOSD.ParticipantsThe current cohort includes data from 539 patients with NMOSD and 114 healthy controls. These were collected at 22 participating centres from North and South America, Asia and Europe. The dataset consists of demographic details, diagnosis, antibody status, clinical disability, visual function, history of optic neuritis and other NMOSD defining attacks, and OCT source data from three different OCT devices.Findings to dateThe cohort informs similar demographic and clinical characteristics as those of previously published NMOSD cohorts. The image repository platform and centre network continue to be available for future prospective neuroimaging studies in NMOSD. For the conduct of the study, we have refined OCT image quality criteria and developed a cross-device intraretinal segmentation pipeline.Future plansWe are pursuing several scientific projects based on the repository, such as analysing retinal layer thickness measurements, in this cohort in an attempt to identify differences between distinct disease phenotypes, demographics and ethnicities. The dataset will be available for further projects to interested, qualified parties, such as those using specialised image analysis or artificial intelligence applications.

PurposeOptical coherence tomography (OCT) captures retinal damage in neuromyelitis optica spectrum disorders (NMOSD). Previous studies investigating OCT in NMOSD have been limited by the rareness and heterogeneity of the disease. The goal of this study was to establish an image repository platform, which will facilitate neuroimaging studies in NMOSD. Here we summarise the profile of the Collaborative OCT in NMOSD repository as the initial effort in establishing this platform. This repository should prove invaluable for studies using OCT to investigate NMOSD.ParticipantsThe current cohort includes data from 539 patients with NMOSD and 114 healthy controls. These were collected at 22 participating centres from North and South America, Asia and Europe. The dataset consists of demographic details, diagnosis, antibody status, clinical disability, visual function, history of optic neuritis and other NMOSD defining attacks, and OCT source data from three different OCT devices.Findings to dateThe cohort informs similar demographic and clinical characteristics as those of previously published NMOSD cohorts. The image repository platform and centre network continue to be available for future prospective neuroimaging studies in NMOSD. For the conduct of the study, we have refined OCT image quality criteria and developed a cross-device intraretinal segmentation pipeline.Future plansWe are pursuing several scientific projects based on the repository, such as analysing retinal layer thickness measurements, in this cohort in an attempt to identify differences between distinct disease phenotypes, demographics and ethnicities. The dataset will be available for further projects to interested, qualified parties, such as those using specialised image analysis or artificial intelligence applications.

Purpose: To report a case of eight-and-a-half syndrome presenting with a conjugate horizontal gaze palsy, an ipsilateral internuclear ophthalmoplegia, and an ipsilateral lower motor neuron-like facial palsy. Methods: A 56-year-old male who came in for limitation of extraocular muscle motion - wherein the only remaining movement is abduction of the left eye - and right-sided facial weakness. Magnetic resonance imaging revealed a well-defined lesion resembling a cavernoma, at the level of the ponto-medullary junction.Results: Eight-and-a-half syndrome results from a lesion affecting the paramedian pontine reticular formation, the median longitudinal fasciculus, and the facial nerve fascicle on one side. In this case, a cavernoma at the level of the ponto-medullary junction was compressing the important pontine structures. Conclusion: Although eight-and-a-half syndrome is most commonly caused by an infarction or demyelination, in rare instances, a space-occupying lesion at the level of the pons can be the etiology. It is of utmost importance to recognize the features of this disease entity to be able to exhaust the proper diagnostic exams, localize the lesion and determine the proper treatment regimen catered to each patient.

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.

PurposeMigraine, particularly with aura, has been associated with ocular and systemic ischemic complications, but there are limited data on the ocular vasculature in migraine. We used optical coherence tomography angiography (OCTA) to assess perfusion of the macula and optic nerve in migraine patients, with (MA) and without (MO) aura, compared to healthy controls (HC).MethodsWe recruited 15 MA (mean age 42 years), 12 MO (mean age 46 years), and 22 HC (mean age 39 years) participants from neurology and neuro-ophthalmology clinics. Participants underwent optical coherence tomography and 3 × 3 mm OCTA of the macula and optic nerve. Foveal avascular zone area was automatically measured using AngioVue software, and vessel density was calculated as blood vessel length divided by scan area (mm-1) after skeletonization of OCTA images.ResultsOn macular OCTA, MA participants had an enlarged foveal avascular zone area when compared with HC (0.300 ± 0.019 vs. 0.220 ± 0.066 mm2, P = 0.006). In addition, superficial foveal vessel density was decreased in MA participants when compared with MO participants (7.8 ± 0.31 vs. 9.3 ± 0.44, P = 0.04) and HC (7.8 ± 0.31 vs. 9.4 ± 0.21 mm-1, P = 0.002). On optic nerve OCTA, the MA participants had reduced superior peripapillary vessel density when compared with the MO participants (12.0 ± 0.45 vs. 14.0 ± 0.38 mm-1, P = 0.031) and HC (12.0 ± 0.45 vs. 14.1 ± 0.53 mm-1, P = 0.035). There were no significant differences between the MO and HC groups.ConclusionsMigraine with, but not without, aura was associated with foveal and peripapillary vascular decrements, which may possibly mediate increased risk of ocular and systemic vascular complications in these patients. OCTA could potentially be useful as a biomarker for migraine with aura.

PurposeMigraine, particularly with aura, has been associated with ocular and systemic ischemic complications, but there are limited data on the ocular vasculature in migraine. We used optical coherence tomography angiography (OCTA) to assess perfusion of the macula and optic nerve in migraine patients, with (MA) and without (MO) aura, compared to healthy controls (HC).MethodsWe recruited 15 MA (mean age 42 years), 12 MO (mean age 46 years), and 22 HC (mean age 39 years) participants from neurology and neuro-ophthalmology clinics. Participants underwent optical coherence tomography and 3 × 3 mm OCTA of the macula and optic nerve. Foveal avascular zone area was automatically measured using AngioVue software, and vessel density was calculated as blood vessel length divided by scan area (mm-1) after skeletonization of OCTA images.ResultsOn macular OCTA, MA participants had an enlarged foveal avascular zone area when compared with HC (0.300 ± 0.019 vs. 0.220 ± 0.066 mm2, P = 0.006). In addition, superficial foveal vessel density was decreased in MA participants when compared with MO participants (7.8 ± 0.31 vs. 9.3 ± 0.44, P = 0.04) and HC (7.8 ± 0.31 vs. 9.4 ± 0.21 mm-1, P = 0.002). On optic nerve OCTA, the MA participants had reduced superior peripapillary vessel density when compared with the MO participants (12.0 ± 0.45 vs. 14.0 ± 0.38 mm-1, P = 0.031) and HC (12.0 ± 0.45 vs. 14.1 ± 0.53 mm-1, P = 0.035). There were no significant differences between the MO and HC groups.ConclusionsMigraine with, but not without, aura was associated with foveal and peripapillary vascular decrements, which may possibly mediate increased risk of ocular and systemic vascular complications in these patients. OCTA could potentially be useful as a biomarker for migraine with aura.

Dural arteriovenous fistulas (dAVFs) may present in a variety of ways, including as carotid-cavernous sinus fistulas. The ophthalmologic sequelae of carotid-cavernous sinus fistulas are known and recognizable, but less commonly seen is the rare clival fistula. Clival dAVFs may have a variety of potential anatomical configurations but are defined by the involvement of the venous plexus just overlying the bony clivus. Here we present two cases of clival dAVFs that most likely evolved from carotid-cavernous sinus fistulas.

Dural arteriovenous fistulas (dAVFs) may present in a variety of ways, including as carotid-cavernous sinus fistulas. The ophthalmologic sequelae of carotid-cavernous sinus fistulas are known and recognizable, but less commonly seen is the rare clival fistula. Clival dAVFs may have a variety of potential anatomical configurations but are defined by the involvement of the venous plexus just overlying the bony clivus. Here we present two cases of clival dAVFs that most likely evolved from carotid-cavernous sinus fistulas.

We present the case of a 19-year-old female with a history of Down syndrome (DS) who was referred to our neuro-ophthalmology clinic for evaluation of Leber's hereditary optic neuropathy (LHON). The patient's family history was significant for a known G11778A mutation in a maternal relative, consistent with LHON. The patient was also positive for the G11778A mutation; however, the genotype demonstrated low penetrance in the pedigree, with only 1 out of 10 adult male offspring showing signs or symptoms of the disease. Mitochondrial mutations implicated in LHON have been shown to impair complex I of the electron transport chain and thereby reducing the effective generation of adenosine triphosphate and increasing the production of toxic reactive oxygen species. Although the partial or complete triplicate of chromosome 21 constitutes the etiology of DS, some of the pleiotropic phenotypes of the syndrome have been attributed to oxidative stress and mitochondrial dysfunction. Given the low penetrance of the mutation and the patient's sex, this case illustrates the possibility that the mitochondrial mutation demonstrated increased penetrance due to pre-existing mitochondrial dysfunction related to DS.

We present the case of a 19-year-old female with a history of Down syndrome (DS) who was referred to our neuro-ophthalmology clinic for evaluation of Leber's hereditary optic neuropathy (LHON). The patient's family history was significant for a known G11778A mutation in a maternal relative, consistent with LHON. The patient was also positive for the G11778A mutation; however, the genotype demonstrated low penetrance in the pedigree, with only 1 out of 10 adult male offspring showing signs or symptoms of the disease. Mitochondrial mutations implicated in LHON have been shown to impair complex I of the electron transport chain and thereby reducing the effective generation of adenosine triphosphate and increasing the production of toxic reactive oxygen species. Although the partial or complete triplicate of chromosome 21 constitutes the etiology of DS, some of the pleiotropic phenotypes of the syndrome have been attributed to oxidative stress and mitochondrial dysfunction. Given the low penetrance of the mutation and the patient's sex, this case illustrates the possibility that the mitochondrial mutation demonstrated increased penetrance due to pre-existing mitochondrial dysfunction related to DS.

The University of California (UC) Davis Reading Center evaluated 19,961 scans from 981 subjects in two multiple sclerosis therapeutic trials with the aim of determining the influence of optical coherence tomography quality control procedures on error rates. There was no optical coherence tomography technician certification in Trial 1, and technicians had very limited monitoring and feedback during the trial in view of the fact that data were received retrospectively. However, technicians were certified in Trial 2 and submitted data in accordance with the protocol. Trial 2 scans had higher signal strengths, fewer errors, and more useable data than the scans in Trial 1. Thus, certified technicians and prompt transmission of data for ongoing quality control monitoring provided higher quality data in multiple sclerosis trials.

The University of California (UC) Davis Reading Center evaluated 19,961 scans from 981 subjects in two multiple sclerosis therapeutic trials with the aim of determining the influence of optical coherence tomography quality control procedures on error rates. There was no optical coherence tomography technician certification in Trial 1, and technicians had very limited monitoring and feedback during the trial in view of the fact that data were received retrospectively. However, technicians were certified in Trial 2 and submitted data in accordance with the protocol. Trial 2 scans had higher signal strengths, fewer errors, and more useable data than the scans in Trial 1. Thus, certified technicians and prompt transmission of data for ongoing quality control monitoring provided higher quality data in multiple sclerosis trials.

Purpose: To compare the eye and head movements and lane-keeping of drivers with hemianopia and quadrantanopia with that of age-matched controls when driving under real world conditions. Methods: Participants included 22 hemianopes and 8 quadrantanopes (M age 53 yrs) and 30 persons with normal visual fields (M age 52 yrs) who were ≥ 6 months from the brain injury date and either a current driver or aiming to resume driving. All participants drove an instrumented dual-brake vehicle along a 14-mile route in traffic that included non-interstate city driving and interstate driving. Driving performance was scored using a standardised assessment system by two “backseat” raters and the Vigil Vanguard system which provides objective measures of speed, braking and acceleration, cornering, and video-based footage from which eye and head movements and lane-keeping can be derived. Results: As compared to drivers with normal visual fields, drivers with hemianopia or quadrantanopia on average were significantly more likely to drive slower, to exhibit less excessive cornering forces or acceleration, and to execute more shoulder movements off the seat. Those hemianopic and quadrantanopic drivers rated as safe to drive by the backseat evaluator made significantly more excursive eye movements, exhibited more stable lane positioning, less sudden braking events and drove at higher speeds than those rated as unsafe, while there was no difference between safe and unsafe drivers in head movements. Conclusions: Persons with hemianopic and quadrantanopic field defects rated as safe to drive have different driving characteristics compared to those rated as unsafe when assessed using objective measures of driving performance.

The incidence of eye injuries during United States armed conflicts has ranged from 0.5% during the United States Civil War to 13% during Operation Desert Storm (Table 1). Although improvements in body armor have allowed soldiers to survive explosions that would have resulted in fatal chest or abdominal wounds in the past, there has been an increasing incidence of injuries to the relatively unprotected extremities, face, neck, and eyes. From October 2001 through September 2006, the total number of American casualties in Operations Iraqi and Enduring Freedom (OIF/OEF) included 21,695 wounded in action and 2335 killed in action. From 2002 through 2007, the number of U.S. military OIF/OEF soldiers with significant battle ocular injuries requiring evacuation was 13%. However, analysis of visual outcomes of all combat ocular trauma (COT) patients during OIF/OEF has not yet been published. This study was designed to report the visual and anatomic outcomes of COT seen at Walter Reed Army Medical Center (WRAMC) and to predict the visual prognosis after the initial injury., Published in Ophthalmology, v115 n12 p2235-2245, December 2008.

Lesions involving the visual system due to the remote effect of cancer are uncommon. Their clinical manifestations are protean. The main symptoms are visual loss, caused by retinopathy or optic neuritis, and abnormal eye movements. Cancer-related retinopathy (CAR) has been primarily described in patients with small-cell lung carcinoma, and it is distinct from melanoma associated retinopathy (MAR), and the retinopathy caused by bilateral diffuse uveal melanocytic proliferation (BDUMP) observed in patients with various neoplasias. The main underlying tumours in patients with paraneoplastic optic neuritis are lung and breast carcinomas. Eye movement disorders consist of opsoclonus, associated with neuroblastoma in infants and children and various tumours in adults, and ophtalmoplegia caused by paraneoplastic myasthenia gravis or paraneoplastic brainstem encephalitis. The differential diagnosis of the neuroophthalmological paraneoplastic syndromes includes primarily metastatic and treatment-related lesions. In some patients the paraneoplastic nature of the ophthalmological disorder my by proven by specific serum antibodies. These antibodies are also markers of the underlying and often non-diagnosed cancer, but their pathogenic role remains unproven., SCOPUS: re.j, info:eu-repo/semantics/published

Purpose. Although amblyopia is diagnosed in terms of a monocular letter acuity loss, individuals typically present with deficits on a wide range of spatial tasks. Many of these deficits can be collapsed along two basic visual dimensions (visual acuity and contrast sensitivity) that together account for most of the variability in performance of the amblyopic visual system. In this study, this space was exploited, to target the main deficits and fully characterize the pattern of learned visual improvements in adult amblyopic subjects. Methods. Twenty-six amblyopic subjects (mean age, 39 ±12 years) were trained on one of four tasks, categorized as either visual acuity (letter or grating acuity) or contrast sensitivity (letter or grating contrast) tasks. Performance was measured on all tasks before and after training, to quantify learning along each dimension and generalization to the other dimension. Performance in 35 visually normal subjects (mean, age 24 ± 5 years) was used to establish normal variation in visual performance along each dimension, against which the learned improvements in amblyopic subjects was compared. Results. Training on the contrast sensitivity tasks produced substantial within-task learning and generalization to measures of visual acuity. The learned improvements in performance after training on the letter acuity task were also substantial, but did not generalize to contrast sensitivity. Conclusions. Mapping the pattern of learning onto the known deficit space for amblyopia enabled the identification of tasks and stimulus configurations that optimized learning, guiding further development of learning-based interventions in this clinical group.

Purpose. Although amblyopia is diagnosed in terms of a monocular letter acuity loss, individuals typically present with deficits on a wide range of spatial tasks. Many of these deficits can be collapsed along two basic visual dimensions (visual acuity and contrast sensitivity) that together account for most of the variability in performance of the amblyopic visual system. In this study, this space was exploited, to target the main deficits and fully characterize the pattern of learned visual improvements in adult amblyopic subjects. Methods. Twenty-six amblyopic subjects (mean age, 39 ±12 years) were trained on one of four tasks, categorized as either visual acuity (letter or grating acuity) or contrast sensitivity (letter or grating contrast) tasks. Performance was measured on all tasks before and after training, to quantify learning along each dimension and generalization to the other dimension. Performance in 35 visually normal subjects (mean, age 24 ± 5 years) was used to establish normal variation in visual performance along each dimension, against which the learned improvements in amblyopic subjects was compared. Results. Training on the contrast sensitivity tasks produced substantial within-task learning and generalization to measures of visual acuity. The learned improvements in performance after training on the letter acuity task were also substantial, but did not generalize to contrast sensitivity. Conclusions. Mapping the pattern of learning onto the known deficit space for amblyopia enabled the identification of tasks and stimulus configurations that optimized learning, guiding further development of learning-based interventions in this clinical group.