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1.
Wien Med Wochenschr ; 174(5-6): 123-125, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37079176

RESUMO

Acute bilateral vision loss (ABVL) is a rare and challenging diagnostic issue that is most often caused by a neurological disorder. Since it can be the presenting symptom of potentially life-threatening diseases, priority should be given to excluding such diagnoses. Special caution is required if ABVL symptoms result after an intracranial intervention. This article reports on a diagnostic approach for a patient suffering from ABVL due to vitreous hemorrhage related to a subarachnoid hemorrhage (SAH) after endovascular intracranial aneurysm treatment. This case study highlights the importance of imaging interpretation and its consequences.


Assuntos
Aneurisma Intracraniano , Hemorragia Subaracnóidea , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/etiologia , Hemorragia Subaracnóidea/cirurgia , Hemorragia Vítrea/complicações , Hemorragia Vítrea/diagnóstico
2.
Exp Eye Res ; 215: 108904, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34954205

RESUMO

PAX6 haploinsufficiency related aniridia is characterized by disorder of limbal epithelial cells (LECs) and aniridia related keratopathy. In the limbal epithelial cells of aniridia patients, deregulated retinoic acid (RA) signaling components were identified. We aimed to visualize differentiation marker and RA signaling component expression in LECs, combining a differentiation triggering growth condition with a small interfering RNA (siRNA) based aniridia cell model (PAX6 knock down). Primary LECs were isolated from corneoscleral rims of healthy donors and cultured in serum free low Ca2+ medium (KSFM) and in KSFM supplemented with 0.9 mmol/L Ca2+. In addition, LECs were treated with siRNA against PAX6. DSG1, PAX6, KRT12, KRT 3, ADH7, RDH10, ALDH1A1, ALDH3A1, STRA6, CYP1B1, RBP1, CRABP2, FABP5, PPARG, VEGFA and ELOVL7 expression was determined using qPCR and western blot. DSG1, FABP5, ADH7, ALDH1A1, RBP1, CRABP2 and PAX6 mRNA and FABP5 protein expression increased (p ≤ 0.03), PPARG, CYP1B1 mRNA expression decreased (p ≤ 0.0003) and DSG1 protein expression was only visible after Ca2+ supplementation. After PAX6 knock down and Ca2+ supplementation, ADH7 and ALDH1A1 mRNA and DSG1 and FABP5 protein expression decreased (p ≤ 0.04), compared to Ca2+ supplementation alone. Using our cell model, with Ca2+ supplementation and PAX6 knockdown with siRNA treatment against PAX6, we provide evidence that haploinsufficiency of the master regulatory gene PAX6 contributes to differentiation defect in the corneal epithelium through alterations of RA signalling. Upon PAX6 knockdown, DSG1 differentiation marker and FABP5 RA signaling component mRNA expression decreases. A similar effect becomes apparent at protein level though differentiation triggering Ca2+ supplementation in the siRNA-based aniridia cell model. Expression data from this cell model and from our siRNA aniridia cell model strongly indicate that FABP5 expression is PAX6 dependent. These new findings may lead to a better understanding of differentiation processes in LECs and are able to explain the insufficient cell function in AAK.


Assuntos
Aniridia , Desmogleína 1 , Proteínas de Ligação a Ácido Graxo , Fator de Transcrição PAX6 , Aniridia/genética , Antígenos de Diferenciação , Desmogleína 1/biossíntese , Desmogleína 1/genética , Células Epiteliais/metabolismo , Proteínas de Ligação a Ácido Graxo/biossíntese , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Humanos , Fator de Transcrição PAX6/genética , Fator de Transcrição PAX6/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Tretinoína/metabolismo
3.
Exp Eye Res ; 179: 8-17, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30292490

RESUMO

PAX6-related Aniridia is a sight-threatening disease involving progression of secondary glaucoma and aniridia related keratopathy (ARK). Change or loss of limbal epithelial progenitors causes epithelial surface defects. We analyzed the effect of PAX6 on mRNA expression changes with a two-step approach, as follows. First, we sequenced mRNA from limbal epithelial cells isolated from controls and aniridia patients. Second, we confirmed the bioinformatics and literature-based result list for a small interfering RNA (siRNA)-based primary aniridia cell model (PAX6 knockdown). With this approach, we expected that the genes directly influenced by PAX6 would be distinguishable from those affected secondarily by the ARK disease state. Therefore, epithelial cells were isolated from the limbus region of two patients with aniridia and cultured in keratinocyte serum-free medium. Normal control cells were obtained from the limbus region of corneal donors. For the siRNA-based aniridia cell model, cells were transfected with Lipofectamine and 5 nM siRNA against PAX6 or control treatment. All cells were lysed to yield DNA, RNA, and protein. Reduction of PAX6 protein was assessed by western blot. Aniridia and control Poly-A-enriched RNA libraries were subjected to next-generation sequencing. The differential analysis was a combination of quantification with RSEM and differential tests with edgeR. Gene lists were filtered by comparison to NCBI GEO datasets, annotated with DAVID, and manually annotated using a literature search. Based on the resulting filtered gene list, qPCR primers were purchased, and candidate genes (TP63, ABCG2, ADH7, ALDH1A1, PITX1, DKK1, DSG1, KRT12, KRT3, KRT13, SPINK6, SPINK7, CTSV, SERPINB1) were verified by qPCR on the siRNA-based aniridia cell model. We identified genes that might be regulated by PAX6 and showed that SPINK7 mRNA, which codes for a protease inhibitor, is downregulated in patients as well as in our primary aniridia cell model. ALDH1A1 and AHD7 mRNA levels were reduced in limbal epithelial cells of aniridia patients, and both transcripts were downregulated by PAX6 knockdown in our cell model. This siRNA-based aniridia cell model is a valuable tool for confirming identified PAX6-affected genes that might promote ARK pathogenesis. The model recapitulated expression changes for SPINK7, ADH7, and ALDH1A1 that were also observed in patient samples. These results provide evidence that PAX6 might drive corneal epithelial differentiation by direct or indirect control of retinoic acid signaling processes through ADH7 and ALDH1A1.


Assuntos
Álcool Desidrogenase/genética , Aldeído Desidrogenase/genética , Aniridia/genética , Epitélio Corneano/metabolismo , Limbo da Córnea/metabolismo , Transdução de Sinais/fisiologia , Tretinoína/metabolismo , Família Aldeído Desidrogenase 1 , Western Blotting , Diferenciação Celular , Células Cultivadas , Doenças da Córnea/genética , Doenças da Córnea/metabolismo , Regulação da Expressão Gênica/fisiologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Modelos Biológicos , Fator de Transcrição PAX6/fisiologia , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Retinal Desidrogenase , Inibidores de Serinopeptidase do Tipo Kazal/genética , Transfecção
4.
Clin Anat ; 31(3): 398-403, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28857277

RESUMO

The endoscope is thought to provide an improved exposure of the internal acoustic meatus after retrosigmoid craniotomy for microsurgical resection of intrameatal tumors. The aim of this study is to quantify the differences in internal acoustic meatus (IAM) exposure comparing microscopic and endoscopic visualization. A retrosigmoid approach was performed on 5 cadaver heads. A millimeter gauge was introduced into the internal acoustic meatus, and examinations with a surgical microscope and 0°, 30° and 70° rigid endoscopes were performed. The extent of IAM depth visualized with the microscope and the different angled endoscopes were analyzed. The microscopic view allowed an average IAM depth visualization of 2.8 mm. The endoscope allowed an improved exposure of IAM in all cases. The 0°, 30° and 70° endoscopes permitted an exposure that was respectively 96% (5.5 mm), 139% (6.7 mm) and 200% (8.4 mm) more lateral than the microscopic view. Angled optics, however, provided an image distortion, specifically the 70° endoscope. The endoscope provides a superior visualization of the IAM compared to the microscope when using a retrosigmoid approach. The 30° endoscope represented an ideal compromise of superior visualization with marginal image distortion. Additional implementation of the endoscope into microsurgery of intrameatal tumors likely facilitates complete tumor removal and might spare facial and vestibulocochlear function. Clin. Anat. 31:398-403, 2018. © 2017 Wiley Periodicals, Inc.


Assuntos
Orelha/cirurgia , Orelha/anatomia & histologia , Endoscopia , Feminino , Humanos , Masculino , Microscopia
5.
Clin Anat ; 31(3): 392-397, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28906020

RESUMO

PAX6 is a master gene of ocular development and postnatal ocular equilibrium. Congenital aniridia is the hallmark of PAX6 gene haploinsufficiency (Chr. 11 p. 13), but PAX6-associated aniridia is a profound, progressive pan-ocular developmental disorder often leading to blindness. There is congenital visual impairment with advancing loss of vision mainly due to secondary glaucoma and to corneal blindness caused by limbal stem cell insufficiency (LSCI). LSCI leads to ARK (aniridia-related keratopathy), which typically develops in four stages. Incipient LSCI with vessels starting to grow into the cornea can be imaged by fluorescein anterior segment angiography, which enables fine vessels to be more easily detected than by routine slit lamp examination, especially in patients with nystagmus. Thus, clinical stage 1 ARK is often diagnosed at stage 2 by angiography. Corneal neovascularizations often start at the 12 and 6 positions and subsequently progress circumferentially, not at the 3 and 9 positions as previously believed. Anterior segment angiography can provide an easily standardizable tool for monitoring progress, treatment-induced regress or stabilization of ARK. Especially in children, angiography could be used to monitor new treatment regimens for reducing LSCI. Angiography could enable treatment to begin earlier to preserve corneal hemostasis. In addition, the fact that vascularization often starts at the subpalpebral 6 and 12 positions as opposed to the 3 and 9 positions raises more questions concerning factors that promote LSCI and related corneal injuries. Clin. Anat. 31:392-397, 2018. © 2018 Wiley Periodicals, Inc.


Assuntos
Aniridia/diagnóstico por imagem , Angiografia , Aniridia/genética , Progressão da Doença , Humanos , Fator de Transcrição PAX6/genética , Nicho de Células-Tronco
6.
Clin Anat ; 31(1): 72-76, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28612422

RESUMO

To provide insight into the clinical anatomy of Tenon's capsule and to describe a technique to manage sclerocorneal defects using autologous Tenon's tissue. A thin layer of Tenon's capsule harvested from the patient's own eye is used to seal the defect and act as a scaffold. The Tenon's flap is spread over the defect and held in place by Vicryl sutures. A bandage contact lens is then placed on the eye. Tenon's capsule is composed of thick fibrous tissue with smooth muscle fibers and a thin posterior capsule of orbital fat. It is rich in fibroblasts, which can accelerate wound healing and eventually lead to robust scarring without risk of immunogenicity and without cost. Tenonplasty uses easily-available autologous Tenon's tissue in patients with sclerocorneal defects to preserve globe morphology. The technique is a feasible alternative not limited by the availability of graft tissue. Clin. Anat. 31:72-76, 2018. © 2017 Wiley Periodicals, Inc.


Assuntos
Perfuração da Córnea/cirurgia , Cirurgia Filtrante , Procedimentos Cirúrgicos Oftalmológicos/métodos , Procedimentos de Cirurgia Plástica/métodos , Pterígio/cirurgia , Doenças da Esclera/cirurgia , Cápsula de Tenon/transplante , Córnea/cirurgia , Humanos , Esclera/cirurgia , Técnicas de Sutura , Trabeculectomia/métodos , Cicatrização
7.
Clin Anat ; 31(1): 60-63, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28556202

RESUMO

Acanthameoba keratitis is a serious ophthalmological condition with a potentially vision-threatening prognosis. Early diagnosis and recognition of relapse, and the detection of persistent Acanthamoeba cysts, are essential for informing the prognosis and managing the condition. We suggest the use of in vivo confocal microscopy not only to identify the early signs of relapse after keratoplasty in patients with Acanthamoeba keratitis, but also as an additional follow-up tool after antimicrobial crosslinking. This study shows that in vivo confocal microscopy is, in experienced hands, a quick and reliable diagnostic tool. Clin. Anat. 31:60-63, 2018. © 2017 Wiley Periodicals, Inc.


Assuntos
Ceratite por Acanthamoeba/patologia , Microscopia Intravital/métodos , Microscopia Confocal/métodos , Ceratite por Acanthamoeba/diagnóstico , Ceratite por Acanthamoeba/cirurgia , Adulto , Criocirurgia/métodos , Diagnóstico Precoce , Feminino , Humanos , Ceratoplastia Penetrante/métodos , Pessoa de Meia-Idade , Recidiva
8.
Childs Nerv Syst ; 33(5): 825-827, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28342117

RESUMO

INTRODUCTION: Although Hans Chiari made significant and meaningful contributions to our understanding and classification of hindbrain herniations, others have also contributed to this knowledge. One figure who has been lost to history is Otto Mennicke. Herein, we discuss his role in our understanding of tonsillar ectopia and his life and connection to Hans Chiari. CONCLUSIONS: Our knowledge of what is now known as the Chiari malformations has been shaped by several clinicians including Otto Mennicke.


Assuntos
Malformação de Arnold-Chiari/história , Cerebelo/anormalidades , Médicos/história , Base do Crânio/anormalidades , Malformação de Arnold-Chiari/diagnóstico , História do Século XIX , História do Século XX , Humanos
9.
Br J Neurosurg ; 31(1): 113-115, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27216244

RESUMO

INTRODUCTION: The anatomy of the accessory nerve has been well described but continued new clinical and anatomical findings exemplify our lack of a full understanding of the course of this nerve. Therefore, this study aimed to expand on our knowledge of the course of the 11th cranial nerve via anatomical dissections. METHODS: Fifty-six cadavers (112 sides) underwent dissection of the accessory nerve from its cranial and spinal origins to its emergence into the posterior cervical triangle. Immunohistochemistry was performed when appropriate. RESULTS: Our findings included two cases (1.8%) where the nerve was duplicated, one intracranially and one extracranially. One accessory nerve (0.9%) was found to enter its own dural compartment within the jugular foramen. The majority of sides (80%) were found to have a cranial root of the accessory nerve. Thirty-one sides (28%) had connections to cervical dorsal roots medially and three sides (2.7%) laterally. Medial connections were most common with the C1 nerve. Medial components of these dorsal root connections were all sensory in nature. However, lateral components were motor on two sides (1.8%). Nerves traveled anterior to the internal jugular vein on 88% of sides. One (0.9%) left side nerve joined an interneural anastomosis between the dorsal rootlets. Macroganglia were found on the spinal part of the intracranial nerve on 13% of sides. The lesser occipital nerve arose directly from the accessory nerve on two sides (1.8%) and communicated with the accessory nerve on 5.4% of sides. One side (0.9%) was found to communicate with the facial nerve with both nerves innervating the sternocleidomastoid muscle. CONCLUSIONS: Additional anatomical knowledge of the variants of the accessory nerve may benefit patient care when this nerve is pathologically involved.


Assuntos
Nervo Acessório/anatomia & histologia , Idoso , Encéfalo/anatomia & histologia , Cadáver , Nervos Cranianos/anatomia & histologia , Dissecação , Músculos Faciais/inervação , Feminino , Gânglios Espinais/anatomia & histologia , Humanos , Imuno-Histoquímica , Masculino , Medula Espinal/anatomia & histologia , Raízes Nervosas Espinhais/anatomia & histologia
10.
Childs Nerv Syst ; 32(6): 1093-100, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27003576

RESUMO

INTRODUCTION: Neurosurgical approaches often involve the atlas. Therefore, the arterial relationships and anatomical variations are of paramount importance to the neurosurgeon. METHODS: Using standard search engines, a literature review of arterial variants near the first cervical vertebra was performed. CONCLUSIONS: Arterial variations around the atlas are surgically significant. Awareness of their existence and course may provide better pre-operative planning and surgical intervention, potentially leading to better clinical outcomes. Three-dimensional computed tomography angiography (3D CTA) is an important tool for identifying and diagnosing such abnormalities and should be used when such vascular anomalies are suspected.


Assuntos
Atlas Cervical/cirurgia , Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Atlas Cervical/diagnóstico por imagem , Humanos , Imageamento Tridimensional , Tomografia Computadorizada por Raios X , Artéria Vertebral/diagnóstico por imagem , Artéria Vertebral/cirurgia
11.
Childs Nerv Syst ; 32(7): 1245-8, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27184559

RESUMO

BACKGROUND: We hypothesized that by using coronal MRI, Chiari I malformation could be more precisely diagnosed, would provide simple anatomic landmarks, would provide information regarding asymmetry of hindbrain herniation, and would be a better method for analyzing the tonsillar herniation postoperatively when the opisthion has been removed. METHODS: Fifty consecutive pediatric patients diagnosed with Chiari I malformation had comparison between the measurements of their caudally descended cerebellar tonsils on midsagittal and coronal MRI images. RESULTS: On MRI coronal imaging, tonsillar asymmetry was found in 48 patients. Maximal left tonsillar descent was 20.9 mm, and maximal right tonsillar descent was 17.4 mm. On MRI sagittal imaging, tonsillar descent ranged from 5 to 27.4 mm. Fifty-eight % of patients had syringomyelia. Five patients (10 %) on coronal MRI were found to have both cerebellar tonsils that were less than 3 mm below the foramen magnum. However, all of these patients had greater than 3 mm of tonsillar ectopia on sagittal imaging. Nineteen patients (38 %) on coronal MRI were found to have one of the cerebellar tonsils that were less than 3 mm below the foramen magnum. Similarly, each of these had greater than 3 mm of tonsillar ecotpia as measured on midsagittal MRI. Also, based on these findings, Chiari I malformation is almost always an asymmetrical tonsillar ectopia. CONCLUSIONS: Sagittal MRI overestimates the degree of tonsillar ectopia in patients with Chiari I malformation. Misdiagnosis may occur if sagittal imaging alone is used. The cerebellar tonsils are paramedian structures, and this should be kept in mind when interpreting midline sagittal MRI.


Assuntos
Malformação de Arnold-Chiari/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Forame Magno/diagnóstico por imagem , Imageamento por Ressonância Magnética , Adolescente , Cerebelo/patologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Adulto Jovem
12.
Clin Anat ; 29(4): 430-8, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26990112

RESUMO

The presence of a human tail is a rare and intriguing phenomenon. While cases have been reported in the literature, confusion remains with respect to the proper classification, definition, and treatment methods. We review the literature concerning this anatomical derailment. We also consider the importance of excluding underlying congenital anomalies in these patients to prevent neurological deficits and other abnormal manifestations.


Assuntos
Cóccix/anormalidades , Região Sacrococcígea/anormalidades , Cauda , Anormalidades Múltiplas , Anatomia/classificação , Anatomia/história , Animais , Cóccix/embriologia , Hirsutismo , História do Século XV , História do Século XVI , História do Século XVII , História do Século XX , História Antiga , História Medieval , Humanos , Região Sacrococcígea/embriologia , Cauda/embriologia
13.
Orbit ; 35(6): 305-308, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27599797

RESUMO

We compare, on left and right side of human skulls, the length of Whitnall's tubercle as a relevant landmark and anchor point for the lateral retinaculum. Twenty human skulls were used in this study. A caliper was used to measure the length of Whitnall's tubercle, the distance from Whitnall's tubercle to the frontozygomatic suture and the height of the orbit. An overall mean for these three parameters was calculated using the data obtained. There were no significant differences between left and the right sides. The combined mean length of Whitnall's tubercle was 4.9 mm ± 23%. The combined mean distance from the frontozygomatic suture was 7.8 mm ± 25%. The orbital height was found to be the measurement with the highest congruence between the two sides having a combined mean of 32.3 mm ± 7%. Although 6 out of 20 skulls were found to have no tubercle, five out of twenty skulls had a tubercle only on one side. Even though human skulls develop from bilateral symmetric osteogenesis, surgeons should always be aware of possible asymmetry and possible absence of Whitnall's tubercle between sides or among individuals. The frontozygomatic suture was found to be a useful landmark in identifying the position of Whitnall's tubercle in the majority of specimens. Such information will be useful in realigning the lateral retinaculum following surgery.


Assuntos
Pontos de Referência Anatômicos/anatomia & histologia , Osso Frontal/anatomia & histologia , Órbita/anatomia & histologia , Órbita/cirurgia , Zigoma/anatomia & histologia , Suturas Cranianas , Humanos , Ligamentos/anatomia & histologia , Músculos Oculomotores/anatomia & histologia
14.
Cornea ; 43(5): 627-634, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38147570

RESUMO

PURPOSE: Aniridia is a rare corneal disease that is often associated with aniridia-associated keratopathy (AAK). In AAK, the conjunctival tissue crosses the limbal border, forming a corneal pannus that extends into the corneal center. With increasing AAK severity, corneal pannus formation, vascularization, and ocular surface inflammation increase. The purpose of this study was to investigate inflammation-related mRNA expression in conjunctival epithelial cells in AAK and its relationship with AAK severity. METHODS: Using impression cytology, bulbar conjunctival cells were sampled from 20 subjects with congenital aniridia and 20 age-matched and sex-matched healthy control subjects. RNA was extracted, and mRNA analyses were performed using microarray, which was evaluated for inflammatory markers. RESULTS: In the analyzed aniridia subjects, 70 deregulated mRNAs encoding proinflammatory or antiinflammatory cytokines or factors associated with chronic inflammation, including increased IL-1, IL-8, and MIP3A/CCL20 mRNA. The most downregulated mRNA was TIMP3, and the most upregulated mRNA was Protein c-Fos.Of the 70 mRNAs, 14 inflammation-related genes were altered only in the mild AAK forms, whereas only 2 mRNAs were altered only in the severe AAK forms (TLR4 and PPARG). CONCLUSIONS: The expression of numerous proinflammatory and antiinflammatory cytokines is deregulated at the ocular surface of aniridia subjects with mild AAK. Thus, early antiinflammatory treatment may prevent or slow down corneal scarring and pannus formation in aniridia subjects.


Assuntos
Aniridia , Doenças da Córnea , Neovascularização da Córnea , Humanos , RNA Mensageiro/genética , Análise de Dados Secundários , Citologia , Doenças da Córnea/complicações , Aniridia/genética , Aniridia/complicações , Neovascularização da Córnea/complicações , Inflamação/genética , Transtornos da Visão , Citocinas/genética
15.
Acta Ophthalmol ; 102(4): e635-e645, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38130099

RESUMO

PURPOSE: Congenital aniridia is a rare disease, which is in most cases related to PAX6 haploinsufficiency. Aniridia associated keratopathy (AAK) also belongs to ocular signs of congenital aniridia. In AAK, there is corneal epithelial thinning, corneal inflammation, vascularization and scarring. In advanced stage AAK, typically, conjunctival epithelial cells slowly replace the corneal epithelium. Based on previous results we hypothesize that alterations of the conjunctival cells in congenital aniridia may also support the corneal conjunctivalization process. The aim of this study was to identify deregulated proteins in conjunctival impression cytology samples of congenital aniridia subjects. METHODS: Conjunctival impression cytology samples of eight patients with congenital aniridia [age 34.5 ± 9.9 (17-51) years, 50% female] and eight healthy subjects [age 34.1 ± 11.9 (15-54) years, 50% female] were collected and analysed using mass spectrometry. Proteomic profiles were analysed in terms of molecular functions, biological processes, cellular components and pathway enrichment using the protein annotation of the evolutionary relationship (PANTHER) classification system. RESULTS: In total, 3323 proteins could be verified and there were 127 deregulated proteins (p < 0.01) in congenital aniridia. From the 127 deregulated proteins (DEPs), 82 altered biological processes, 63 deregulated cellular components, 27 significantly altered molecular functions and 31 enriched signalling pathways were identified. Pathological alteration of the biological processes and molecular functions of retinol binding and retinoic acid biosynthesis, as well as lipid metabolism and apoptosis related pathways could be demonstrated. CONCLUSIONS: Protein profile of conjunctival impression cytology samples of aniridia subjects identifies alterations of retinol binding, retinoic acid biosynthesis, lipid metabolism and apoptosis related pathways. Whether these changes are directly related to PAX6 haploinsufficiency, must be investigated in further studies. These new findings offer the possibility to identify potential new drug targets.


Assuntos
Aniridia , Túnica Conjuntiva , Humanos , Feminino , Aniridia/genética , Aniridia/metabolismo , Aniridia/diagnóstico , Adulto , Masculino , Adolescente , Adulto Jovem , Túnica Conjuntiva/metabolismo , Túnica Conjuntiva/patologia , Pessoa de Meia-Idade , Proteômica/métodos , Espectrometria de Massas , Proteínas do Olho/metabolismo , Proteínas do Olho/genética , Citologia
16.
Int J Stroke ; : 17474930241248516, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38591748

RESUMO

RATIONALE: Meta-analyses of case series of non-arteritic central retinal artery occlusion (CRAO) indicate beneficial effects of intravenous thrombolysis when initiated early after symptom onset. Randomized data are lacking to address this question. AIMS: The REperfusion therapy with intravenous alteplase for recovery of VISION in acute central retinal artery occlusion (REVISION) investigates intravenous alteplase within 4.5 h of monocular vision loss due to acute CRAO. METHODS: This study is the randomized (1:1), double-blind, placebo-controlled, multicenter adaptive phase III trial. STUDY OUTCOMES: Primary outcome is functional recovery to normal or mildly impaired vision in the affected eye defined as best-corrected visual acuity of the Logarithm of the Minimum Angle of Resolution of 0.5 or less at 30 days (intention-to-treat analysis). Secondary efficacy outcomes include modified Rankin Score at 90 days and quality of life. Safety outcomes include symptomatic intracranial hemorrhage, major bleeding (International Society on Thrombosis and Haemostasis definition) and mortality. Exploratory analyses of optical coherence tomography/angiography, ultrasound and magnetic resonance imaging (MRI) biomarkers will be conducted. SAMPLE SIZE: Using an adaptive design with interim analysis at 120 patients, up to 422 participants (211 per arm) would be needed for 80% power (one-sided alpha = 0.025) to detect a difference of 15%, assuming functional recovery rates of 10% in the placebo arm and 25% in the alteplase arm. DISCUSSION: By enrolling patients within 4.5 h of CRAO onset, REVISION uses insights from meta-analyses of CRAO case series and randomized thrombolysis trials in acute ischemic stroke. Increased rates of early reperfusion and good neurological outcomes in stroke may translate to CRAO with its similar pathophysiology. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04965038; EU Trial Number: 2023-507388-21-00.

17.
Front Physiol ; 14: 1281327, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37929210

RESUMO

Long-duration spaceflight can have adverse effects on human health. One of the most common ocular conditions experienced by astronauts is dry eye disease (DED). Symptoms of DED include feelings of eye irritation, eye strain, foreign body sensation and blurred vision. Over 30% of International Space Station expedition crew members reported irritation and foreign body sensation. We reviewed the current literature on the prevalence and mechanisms of DED in astronauts and its potential implications for long-duration spaceflight, including the influence of environmental factors, such as microgravity and fluid shift on tear film physiology in space. DED has negative effects on astronaut performance, which is why there is a need for further research into the pathophysiology and countermeasures. As an in-flight countermeasure, neurostimulation seems to be among the most promising options.

18.
Br J Ophthalmol ; 2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36517210

RESUMO

AIM: To evaluate changes in the ocular surface and tear film with age and mutational status in congenital aniridia. METHODS: 45 participants with congenital aniridia (89 eyes) in a prospective, cross-sectional study. Whole-exome sequencing identified the causative mutation. Examinations included slit-lamp biomicroscopy, in vivo confocal microscopy, Ocular Surface Disease Index (OSDI) score, blink rate, Schirmer I test, Oxford Staining Score (OSS), tear film break-up time (TFBUT) and Ocular Protection Index (OPI). RESULTS: There were age-dependent increases in OSDI (ß=0.34, 95% CI 0.03 to 0.66; p=0.030), blink rate (ß=0.18, 95% CI 0.08 to 0.27; p<0.001) and OSS (ß=0.05, 95% CI 0.03 to 0.07; p<0.001) and age-dependent reductions in tear production (ß=-0.23, 95% CI -0.43 to 0.02; p=0.029) and TFBUT (ß=-0.10, 95% CI -0.17 to -0.04; p<0.001). Perturbed OSDI, OSS, blink rate, tear production and TFBUT were noted after the age of ten and OSDI, OSS, blink rate and TFBUT correlated with deficient corneal nerves and limbal stem cell function. OSDI, blink rate, Schirmer, OSS, TFBUT and OPI were not associated with type of PAX6 mutation, but OSDI, OSS and blink rate associated with grade of aniridia-associated keratopathy. CONCLUSIONS: Ocular surface damage and dry eye signs appear in congenital aniridia regardless of mutation, appearing after 10 years of age and progressing thereafter. An early treatment window may exist for therapies to protect the ocular surface homoeostasis and limbal function, to possibly delay keratopathy development and progression.

19.
Ophthalmologe ; 119(5): 471-480, 2022 May.
Artigo em Alemão | MEDLINE | ID: mdl-34705089

RESUMO

AIM: This study compared Saarland University Eye Hospital employees' satisfaction with the FIDUS electronic patient record between December 2016 and September 2020, after its introduction in January 2016. METHODS: For the retrospective study, the FIDUS team at the Saarland University Eye Hospital created a questionnaire which was distributed to all participants (physicians, nursing staff, and administrative staff) in December 2016 and September 2020. The questionnaire contained 19 questions, each scored from 0 to 10 (0: disagree; 5: partly agree; 10: completely agree). RESULTS: The number of participants increased significantly from 60/136 (47%) to 89/140 (64%) between 2016 and 2020. Of these participants, 23 (25.8%) were physicians, 27 (30.3%) were nurses, 12 (13.4%) were in administration, 16 (17.9%) were in other employment, and 11 (12.3%) did not disclose their employment. In 2020, 75.6% of employees agreed with a score of 10 that implementation of electronic medical records was the right step, compared to only 36.7% in 2016 (p < 0.001). The highest rating for "record entries are faster to write with a computer than handwritten" was obtained in 38% in 2020 vs. 25% in 2016 (p < 0.001). CONCLUSION: Satisfaction with the FIDUS electronic patient record has improved significantly in 2020 compared to 2016, particularly concerning file clarity and faster workflows. The proportion of respondents who see their initial expectations of electronic patient files as 100% fulfilled has tripled. However, there is still a need for optimization of details.


Assuntos
Registros Eletrônicos de Saúde , Eletrônica , Hospitais Universitários , Humanos , Estudos Retrospectivos , Inquéritos e Questionários , Universidades
20.
Ophthalmologe ; 118(1): 53-55, 2021 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-32211921

RESUMO

A Wessely immune ring can be found in various corneal infections as well as in non-infectious processes. Its appearance can aid in the differential diagnosis but can also be misleading. A definitive diagnosis can only be reached when all clinical and microbiological findings are taken into consideration. This article discusses and critically reflects on the differential diagnostic considerations and treatment strategies in the context of a case report on a 31-year-old patient with contact lenses and diffuse endothelial decompensation with a focal, mid-peripheral infiltrate and a Wessely immune ring.


Assuntos
Ceratite por Acanthamoeba , Lentes de Contato , Ceratite , Ceratite por Acanthamoeba/diagnóstico , Adulto , Diagnóstico Diferencial , Humanos , Ceratite/diagnóstico , Ceratite/terapia
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