Visual signs and symptoms of corticobasal degeneration

Corticobasal degeneration is a rare, progressive neurodegenerative disease and a member of the 'parkinsonian' group of disorders, which also includes Parkinson's disease, progressive supranuclear palsy, dementia with Lewy bodies and multiple system atrophy. The most common initial symptom is limb clumsiness, usually affecting one side of the body, with or without accompanying rigidity or tremor. Subsequently, the disease affects gait and there is a slow progression to influence ipsilateral arms and legs. Apraxia and dementia are the most common cortical signs. Corticobasal degeneration can be difficult to distinguish from other parkinsonian syndromes but if ocular signs and symptoms are present, they may aid clinical diagnosis. Typical ocular features include increased latency of saccadic eye movements ipsilateral to the side exhibiting apraxia, impaired smooth pursuit movements and visuo-spatial dysfunction, especially involving spatial rather than object-based tasks. Less typical features include reduction in saccadic velocity, vertical gaze palsy, visual hallucinations, sleep disturbance and an impaired electroretinogram. Aspects of primary vision such as visual acuity and colour vision are usually unaffected. Management of the condition to deal with problems of walking, movement, daily tasks and speech problems is an important aspect of the disease.

Ultrastructural and Histological Study of Oogenesis and Oocyte Degeneration in the PenshellAtrina maura(Bivalvia: Pinnidae)

The successive stages of oogenesis and the changes involved in the oocyte degeneration process in the penshell Atrina maura were examined using light and transmission electron microscopy. The ovarian maturation process is asynchronous, as oocytes at different developmental stages can be found simultaneously. Oocytes develop from oogonia and then undergo three distinct stages of oogenesis: previtellogenesis, vitellogenesis and postvitellogenesis with mature oocytes. Atrina maura displays a solitary oogenesis type, in which follicular cells become associated with oocytes from the earliest stages of development and seem to play an integral role in vitellogenesis. The cytoplasm of vitellogenic oocytes contains numerous whorls of rough endoplasmic reticulum and Golgi bodies, suggesting that auto-synthetic vitellogenesis may occur in this species. In addition, the degeneration process of postvitellogenic oocytes triggered by a seasonal increase in water temperature (> 25°C) is described.

Ultrastructural and Histological Study of Oogenesis and Oocyte Degeneration in the PenshellAtrina maura(Bivalvia: Pinnidae)

The successive stages of oogenesis and the changes involved in the oocyte degeneration process in the penshell Atrina maura were examined using light and transmission electron microscopy. The ovarian maturation process is asynchronous, as oocytes at different developmental stages can be found simultaneously. Oocytes develop from oogonia and then undergo three distinct stages of oogenesis: previtellogenesis, vitellogenesis and postvitellogenesis with mature oocytes. Atrina maura displays a solitary oogenesis type, in which follicular cells become associated with oocytes from the earliest stages of development and seem to play an integral role in vitellogenesis. The cytoplasm of vitellogenic oocytes contains numerous whorls of rough endoplasmic reticulum and Golgi bodies, suggesting that auto-synthetic vitellogenesis may occur in this species. In addition, the degeneration process of postvitellogenic oocytes triggered by a seasonal increase in water temperature (> 25°C) is described.

Risk factors and biomarkers of age-related macular degeneration

A biomarker can be a substance or structure measured in body parts, fluids or products that can affect or predict disease incidence. As age-related macular degeneration (AMD) is the leading cause of blindness in the developed world, much research and effort has been invested in the identification of different biomarkers to predict disease incidence, identify at risk individuals, elucidate causative pathophysiological etiologies, guide screening, monitoring and treatment parameters, and predict disease outcomes. To date, a host of genetic, environmental, proteomic, and cellular targets have been identified as both risk factors and potential biomarkers for AMD. Despite this, their use has been confined to research settings and has not yet crossed into the clinical arena. A greater understanding of these factors and their use as potential biomarkers for AMD can guide future research and clinical practice. This article will discuss known risk factors and novel, potential biomarkers of AMD in addition to their application in both academic and clinical settings.

Effectiveness of Community versus Hospital Eye Service follow-up for patients with neovascular age-related macular degeneration with quiescent disease (ECHoES): a virtual non-inferiority trial

OBJECTIVES: To compare the ability of ophthalmologists versus optometrists to correctly classify retinal lesions due to neovascular age-related macular degeneration (nAMD).

DESIGN: Randomised balanced incomplete block trial. Optometrists in the community and ophthalmologists in the Hospital Eye Service classified lesions from vignettes comprising clinical information, colour fundus photographs and optical coherence tomographic images. Participants' classifications were validated against experts' classifications (reference standard).

SETTING: Internet-based application.

PARTICIPANTS: Ophthalmologists with experience in the age-related macular degeneration service; fully qualified optometrists not participating in nAMD shared care.

INTERVENTIONS: The trial emulated a conventional trial comparing optometrists' and ophthalmologists' decision-making, but vignettes, not patients, were assessed. Therefore, there were no interventions and the trial was virtual. Participants received training before assessing vignettes.

MAIN OUTCOME MEASURES: Primary outcome-correct classification of the activity status of a lesion based on a vignette, compared with a reference standard. Secondary outcomes-potentially sight-threatening errors, judgements about specific lesion components and participants' confidence in their decisions.

RESULTS: In total, 155 participants registered for the trial; 96 (48 in each group) completed all assessments and formed the analysis population. Optometrists and ophthalmologists achieved 1702/2016 (84.4%) and 1722/2016 (85.4%) correct classifications, respectively (OR 0.91, 95% CI 0.66 to 1.25; p=0.543). Optometrists' decision-making was non-inferior to ophthalmologists' with respect to the prespecified limit of 10% absolute difference (0.298 on the odds scale). Optometrists and ophthalmologists made similar numbers of sight-threatening errors (57/994 (5.7%) vs 62/994 (6.2%), OR 0.93, 95% CI 0.55 to 1.57; p=0.789). Ophthalmologists assessed lesion components as present less often than optometrists and were more confident about their classifications than optometrists.

CONCLUSIONS: Optometrists' ability to make nAMD retreatment decisions from vignettes is not inferior to ophthalmologists' ability. Shared care with optometrists monitoring quiescent nAMD lesions has the potential to reduce workload in hospitals.

TRIAL REGISTRATION NUMBER: ISRCTN07479761; pre-results registration.

Molecular Mechanisms of Frontotemporal Lobar Degeneration

The aim of this thesis was to identify genetic factors involved in frontotemporal lobar degeneration (FTLD), a neurodegenerative disorder clinically characterised by a progressive change in personality, behaviour and language. FTLD is a genetically complex disorder and a positive family history is found in up to 40% of the cases. In 10-20% of the familial cases the disease can be explained by mutations in the gene encoding the microtubule associated protein tau (MAPT). In the first study we describe the clinical and neuropathological features of a Finnish family with FTLD caused by a mutation in MAPT. We also provide evidence that the pathogenic mechanism of this mutation is through altered splicing of MAPT transcripts. Recently, mutations in the gene encoding progranulin (PGRN) were identified as a major cause of FTLD. In the second study we describe a Swedish family with FTLD caused by a frameshift mutation in PGRN. We provide a clinical and neuropathological description of the family, as well as evidence that the pathogenicity of this mutation is through nonsense-mediated decay of the mutant mRNA transcripts and PGRN haploinsufficiency. In the third study we describe a novel PGRN splice site mutation and a previously described PGRN frameshift mutation, found in a mutation screen of 51 FTLD patients. We describe the clinical and neuropathological characteristics of the mutation carriers and demonstrate that haploinsufficiency is the pathogenic mechanism of the two mutations. In the fourth study we investigate the prevalence of PGRN and MAPT gene dosage alterations in 39 patients with FTLD. No gene dosage alterations were identified, indicating that variations in copy number of the PGRN and MAPT genes are not a common cause of disease, at least not in this FTLD patient collection.

The synthetic progestin norgestrel modulates Nrf2 signaling and acts as an antioxidant in a model of retinal degeneration

Retinitis pigmentosa (RP) is one of the most common retinal degenerative conditions affecting people worldwide, and is currently incurable. It is characterized by the progressive loss of photoreceptors, in which the death of rod cells leads to the secondary death of cone cells; the cause of eventual blindness. As rod cells die, retinal-oxygen metabolism becomes perturbed, leading to increased levels of reactive oxygen species (ROS) and thus oxidative stress; a key factor in the secondary death of cones. In this study, norgestrel, an FDA-approved synthetic analog of progesterone, was found to be a powerful neuroprotective antioxidant, preventing light-induced ROS in photoreceptor cells, and subsequent cell death. Norgestrel also prevented light-induced photoreceptor morphological changes that were associated with ROS production, and that are characteristic of RP. Further investigation showed that norgestrel acts via post-translational modulation of the major antioxidant transcription factor Nrf2; bringing about its phosphorylation, subsequent nuclear translocation, and increased levels of its effector protein superoxide dismutase 2 (SOD2). In summary, these results demonstrate significant protection of photoreceptor cells from oxidative stress, and underscore the potential of norgestrel as a therapeutic option for RP.

Automatic Glaucoma Detection Based on Optic Disc Segmentation and Texture Feature Extraction

The use of digital image processing techniques is prominent in medical settings for the automatic diagnosis of diseases. Glaucoma is the second leading cause of blindness in the world and it has no cure. Currently, there are treatments to prevent vision loss, but the disease must be detected in the early stages. Thus, the objective of this work is to develop an automatic detection method of Glaucoma in retinal images. The methodology used in the study were: acquisition of image database, Optic Disc segmentation, texture feature extraction in different color models and classification of images in glaucomatous or not. We obtained results of 93% accuracy

Embolisation of Vertebral Artery Damaged Following Cervical Disc Removal

Introduction: The incidence of vertebral artery (VA) injury during cervical spine surgery is rare. Even though tamponade is effective in many cases, early consultation of an endovascular team is recommended if bleeding cannot be controlled. We report a case of emergent endovascular embolisation of left VA due to iatrogenic injury during anterior cervical disc removal and fusion. Case: A 47-year-old woman was admitted to our emergency department with serious arterial bleeding from the neck only hours after undergoing anterior cervical disc removal and fusion surgery. She was intubated and mechanically ventilated, however hemorrhage could not be successfully controlled by packing with surgical hemostatic agents. Cranial computed tomography, computed tomography of the cervical spine and CT angiography confirmed the suspected diagnosis of injury to the VA. Emergent endovascular embolisation successfully stopped the bleeding. Occlusion of the vessel was achieved by vascular plugging. The patient was discharged from our hospital 14 days after the intervention, receiving a revision surgery of the cervical spine on the day of embolisation. At the date of discharge she presented without any focal neurological deficit. Conclusion: Pre-operative radiographic imaging of the cervical spine should be used routinely to identify anatomic abnormalities of the vertebral arteries. Endovascular embolisation appears to be effective in treating acute iatrogenic dissection of the vertebral arteries.

An epidemiological surveillance network of lumbar disc surgery to help prevention of and compensation for low back pain

International audience

Efecto del plasma rico en plaquetas y/o factores de crecimiento sobre la regeneración y el dolor crónico asociado a discopatía intervertebral: revisión sistemática

Objetivo: Determinar el efecto del plasma rico en plaquetas y factores de crecimiento sobre la regeneración y la reducción del dolor en discopatía degenerativa. Material y método: Revisión sistemática de la literatura. Se siguió las recomendaciones de la colaboración Cochrane expuestas en el Cochrane Hand book for Systematic Reviews of interventions. Se incluyeron ensayos clínicos aleatorizados fases preclínicas y clínicas donde evaluaban el efecto del plasma rico en plaquetas o factores de crecimiento sobre la discopatía degenerativa entre el 1 de septiembre de 2013 y el 30 de septiembre de 2014, publicados en PubMed, MEDLINE y LILACS. Resultados: En la búsqueda inicial se identificaron 11 artículos, de los cuales 3 cumplieron los criterios de selección determinados para esta revisión. Se realizó estrategia de búsqueda donde se revisaron las citas relacionadas de los tres artículos principales. De éstos, sólo 6 cumplieron los criterios de selección. Se incluyeron dos artículos más que arrojó la búsqueda en google académico, quedando un total de 10 estudios para el análisis final. En esta revisión, nosotros incluimos en la búsqueda de no sólo aquellos estudios realizados in vitro, sino además aquellos estudios en modelos murinos y estudio realizado en humanos. De estos estudios, la mayor parte de ellos fueron realizados in vitro (6), en modelos animales (2) y en humanos (2). En este estudio se seleccionaron sólo aquellos estudios donde fue evaluado el PRP y/o los factores de crecimiento sobre las células o tejidos del disco intervertebral. Para poder conocer el efecto que estas sustancias, tienen que ser evaluadas en estudios tanto preclínicos como clínicos. Todos los estudios analizados coincidieron sobre el efecto antiinflamatorio, reparador, proliferador e incluso en la mejoría del dolor de la discopatía vertebral. Conclusiones: Los resultados de los estudios muestra el efecto antiinflamatorio, reparador, proliferador e incluso en la mejoría del dolor de la discopatía vertebral. En ninguno de ellos se mencionó si este aumento de la síntesis de la matriz conllevaría a una mayor fibrosis del tejido y mayor deterioro, por lo que los estudios en animales o en humanos deberían enfocarse a evaluar un seguimiento mayor para poder evaluar los efectos tardíos de la terapia. Por lo tanto, podemos concluir que los puntos de enfoque de la investigación actual debe apuntar hacia entender más el mecanismo de la degeneración discal conjuntamente con los beneficios del PRP en tratarla.

Impaired Mesopic Visual Acuity in Eyes with Early Age-Related Macular Degeneration

Purpose.: To determine photopic and mesopic distance high-contrast visual acuity (HC-VA) and low-contrast visual acuity (LC-VA) in eyes with early age-related macular degeneration (AMD). Methods.: Measurements were made in 22 subjects with early AMD and 28 healthy control subjects. Inclusion criteria included a photopic HC-VA of 20/25 or better. Distance VA was measured using HC (96%) and LC (10%) Bailey-Lovie logMAR letter charts under photopic (85 cd/m2) and mesopic (0.1–0.2 cd/m2) luminance conditions. Results.: Mean mesopic distance HC-VA and LC-VA were significantly worse (0.1 logMAR and 0.28 logMAR, respectively) in the early AMD group than in the control group. Under mesopic conditions, the mean difference between LC-VA and HC-VA was significantly greater in the early AMD (0.45 logMAR) than the control group (0.27 logMAR). Mean differences between mesopic versus photopic HC-VA and mesopic versus photopic LC-VA were significantly greater in the early AMD than the control group (0.13 and 0.32 logMAR of difference between the means, respectively). Sensitivity and specificity were significantly greater for mesopic LC-VA than for mesopic HC-VA (Receiver Operating Characteristics, area under the curve [AUC], 0.94 ± 0.030 and 0.76 ± 0.067, respectively). AUC values for photopic HC-VA and LC-VA were below 0.70. Conclusions.: Visual acuity testing under low luminance conditions emerged as an optimal quantitative measure of retinal function in early AMD.