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Sample records for amaurosis fugax

  1. Amaurosis Fugax and Migraine

    OpenAIRE

    J Gordon Millichap

    1988-01-01

    Amaurosis fugax, a sudden, transient monocular loss of vision resolving in 5 to 10 minutes, is reported in five teenagers from the British Columbia’s Children’s Hospital, Vancouver, BC, and The Hospital for Sick Children, Toronto, Canada.

  2. Epicrania Fugax.

    Science.gov (United States)

    Cuadrado, María Luz; Guerrero, Angel L; Pareja, Juan A

    2016-04-01

    Epicrania fugax (EF) is a primary headache of recent description. EF essentially consists of brief paroxysms of pain describing a linear or zigzag trajectory across the surface of one hemicranium, commencing and terminating in the territories of different nerves. The pain of forward EF originates in a particular area of the occipital, parietal or temporal regions and moves anteriorly, whereas the pain of backward EF originates in the frontal area, the eye or the nose and moves posteriorly. Some patients have ocular or nasal autonomic accompaniments, and some have triggers. Between attacks, many patients have continuous or intermittent pain and/or tenderness at the stemming area. Pain frequency is extremely variable and some patients have spontaneous remissions. Preventive therapy is required when the paroxysms are frequent and non-remitting. Neuromodulators, indomethacin, amitryptiline, nerve anesthetic blockades, and trochlear steroid injections have been used in different cases, with partial or complete response.

  3. Linear interictal pain in Epicrania Fugax.

    Science.gov (United States)

    Pareja, Juan A; Bandrés, Pablo

    2015-01-01

    Epicrania Fugax is a paroxysmal, short-lasting, head pain moving across one hemicranium, describing a linear or zag trajectory, starting and ending in territories of different nerves. Between attacks, patients are usually free of symptoms. We describe an Epicrania Fugax patient complaining of interictal pain. The interictal pain was line-shaped and extended across the usual starting and ending points of the typical Epicrania Fugax paroxysms. Although rarely encountered, persistent linear pain may be a feature of Epicrania Fugax.

  4. A fatal case of primary cardiac chondrosarcoma presenting with amaurosis fugax

    DEFF Research Database (Denmark)

    Sundbøll, Jens; Hansson, Nils Henrik Stubkjær; Baerentzen, Steen

    2015-01-01

    discomfort, the patient was admitted to the department of neurology for further investigations. CT of the brain was normal; however, during admission, the patient developed rapid atrial fibrillation and was transferred to the department of cardiology. Transthoracic echocardiography revealed a massive tumour...

  5. Epicrania fugax: 19 cases of an emerging headache.

    Science.gov (United States)

    Cuadrado, María Luz; Ordás, Carlos M; Sánchez-Lizcano, María; Casas-Limón, Javier; Matías-Guiu, Jordi A; García-García, María Eugenia; Fernández-Matarrubia, Marta; Barahona-Hernando, Raúl; Porta-Etessam, Jesús

    2013-05-01

    Epicrania fugax (EF) is a primary headache of recent description. We aimed to report 19 new cases of EF, and thus contribute to the characterization of this emerging headache. EF is characterized by painful paroxysms starting in a particular area of the head, and rapidly radiating forwards or backwards through the territories of different nerves. The pain is felt in quick motion along a lineal or zigzag trajectory. To date, 47 cases have been published, 34 with forward EF and 13 with backward EF. We performed a descriptive study of all EF cases attending our Headache Unit from April 2010 to December 2012. Demographic and clinical data were recorded with a structured questionnaire. Overall, there were 12 women and 7 men. Mean age at onset was 51.7 ± 16.2. Fourteen patients had forward EF, while 5 patients had backward EF. Painful paroxysms lasted 1-4 seconds. Pain intensity was usually moderate or severe, and pain quality was mostly electric. Four patients had ocular autonomic accompaniments. Pain frequency was extremely variable, and 7 patients identified some triggers. Between attacks, 13 patients had some pain or tenderness in the stemming area. Thirteen patients required therapy for their pain. Neuromodulators, indomethacin, anesthetic blockades, and steroid injections were used in different cases, with partial or complete response. EF appears as a distinct headache syndrome and could be eventually included in future editions of the International Classification of Headache Disorders. © 2013 American Headache Society.

  6. Lebers Amaurosis in Three Siblings: A case report | Samaila ...

    African Journals Online (AJOL)

    This case report appears to be first reported incident of Lebers congenital amaurosis in three siblings in Kaduna State. Genetic issues, clinical presentation, counselling, treatment and future progression of this irreversible blinding condition are discussed. Keywords: Lebers amaurosis, retinitis pigmentosa, Kaduna, Nigeria

  7. [Leber congenital amaurosis: diagnosis, follow-up and differential diagnosis].

    Science.gov (United States)

    Grieshaber, M C; Niemeyer, G

    1998-05-01

    Leber's congenital amaurosis (LCA) had been diagnosed on/in 42 children between 1968 and 1996 at the Deptm. of Ophthalmology, University Hospital Zurich. We reexamined critically this rare diagnosis in retrospect and with new examinations where possible. Clinical and electroretinographic (ERG) results, often obtained in general anesthesia, were re-evaluated and when possible repeated in new examinations. Thirty-three of the total 42 patients presented with an extinguished, 35 with markedly reduced, and 6 with minimal ERGs. A profound visual loss (from no light perception to 20/200), nystagmus and strabismus were the principal symptoms. The heterogeneity of retinal findings ranged from normal to salt and pepper or bone spicules pigmentation and pronounced chorioretinal atrophy. Vascular attenuation and rarification were frequent. Patients with nonocular findings such as mental retardation (n = 12), renal (n = 3) and skeletal (n = 4) abnormalities revealed no differing ERG- or retinal findings. The oculodigital sign (eye-poking) was found in 25%, and parental consanguinity was evident in 10% of the cases. In 16 patients that were reexamined, the progression of the disease was characterized by an increase in retinal pigmentary changes, attenuation of retinal vessel, and further diminuation of the visual acuity (n = 6). Upon review, the diagnosis had to be revised in 8 patients as juvenile retinitis pigmentosa and in one as infantile Refsum syndrome. Bilateral visual impairement in infants should be assessed clinically and electroretinographically within the first year. Neuropediatric and metabolic examinations meaningfully complement the diagnostic procedures.

  8. Characterization of Leber Congenital Amaurosis-associated NMNAT1 Mutants.

    Science.gov (United States)

    Sasaki, Yo; Margolin, Zachary; Borgo, Benjamin; Havranek, James J; Milbrandt, Jeffrey

    2015-07-10

    Leber congenital amaurosis 9 (LCA9) is an autosomal recessive retinal degeneration condition caused by mutations in the NAD(+) biosynthetic enzyme NMNAT1. This condition leads to early blindness but no other consistent deficits have been reported in patients with NMNAT1 mutations despite its central role in metabolism and ubiquitous expression. To study how these mutations affect NMNAT1 function and ultimately lead to the retinal degeneration phenotype, we performed detailed analysis of LCA-associated NMNAT1 mutants, including the expression, nuclear localization, enzymatic activity, secondary structure, oligomerization, and promotion of axonal and cellular integrity in response to injury. In many assays, most mutants produced results similar to wild type NMNAT1. Indeed, NAD(+) synthetic activity is unlikely to be a primary mechanism underlying retinal degeneration as most LCA-associated NMNAT1 mutants had normal enzymatic activity. In contrast, the secondary structure of many NMNAT1 mutants was relatively less stable as they lost enzymatic activity after heat shock, whereas wild type NMNAT1 retains significant activity after this stress. These results suggest that LCA-associated NMNAT1 mutants are more vulnerable to stressful conditions that lead to protein unfolding, a potential contributor to the retinal degeneration observed in this syndrome. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Characterization of Leber Congenital Amaurosis-associated NMNAT1 Mutants*

    Science.gov (United States)

    Sasaki, Yo; Margolin, Zachary; Borgo, Benjamin; Havranek, James J.; Milbrandt, Jeffrey

    2015-01-01

    Leber congenital amaurosis 9 (LCA9) is an autosomal recessive retinal degeneration condition caused by mutations in the NAD+ biosynthetic enzyme NMNAT1. This condition leads to early blindness but no other consistent deficits have been reported in patients with NMNAT1 mutations despite its central role in metabolism and ubiquitous expression. To study how these mutations affect NMNAT1 function and ultimately lead to the retinal degeneration phenotype, we performed detailed analysis of LCA-associated NMNAT1 mutants, including the expression, nuclear localization, enzymatic activity, secondary structure, oligomerization, and promotion of axonal and cellular integrity in response to injury. In many assays, most mutants produced results similar to wild type NMNAT1. Indeed, NAD+ synthetic activity is unlikely to be a primary mechanism underlying retinal degeneration as most LCA-associated NMNAT1 mutants had normal enzymatic activity. In contrast, the secondary structure of many NMNAT1 mutants was relatively less stable as they lost enzymatic activity after heat shock, whereas wild type NMNAT1 retains significant activity after this stress. These results suggest that LCA-associated NMNAT1 mutants are more vulnerable to stressful conditions that lead to protein unfolding, a potential contributor to the retinal degeneration observed in this syndrome. PMID:26018082

  10. Involvement of LCA5 in Leber congenital amaurosis and retinitis pigmentosa in the Spanish population

    NARCIS (Netherlands)

    Corton, M.; Avila-Fernandez, A.; Vallespin, E.; Lopez-Molina, M.I.; Almoguera, B.; Martin-Garrido, E.; Tatu, S.D.; Khan, M.I.; Blanco-Kelly, F.; Riveiro-Alvarez, R.; Brion, M.; Garcia-Sandoval, B.; Cremers, F.P.M.; Carracedo, A.; Ayuso, C.

    2014-01-01

    OBJECTIVE: We aimed to identify novel genetic defects in the LCA5 gene underlying Leber congenital amaurosis (LCA) in the Spanish population and to describe the associated phenotype. DESIGN: Case series. PARTICIPANTS: A cohort of 217 unrelated Spanish families affected by autosomal recessive or

  11. Disruption of intraflagellar protein transport in photoreceptor cilia causes Leber congenital amaurosis in humans and mice

    NARCIS (Netherlands)

    Boldt, K.; Mans, D.A.; Won, J.; Reeuwijk, J. van; Vogt, A.; Kinkl, N.; Letteboer, S.J.F.; Hicks, W.L.; Hurd, R.E.; Naggert, J.K.; Texier, Y.; Hollander, A.I. den; Koenekoop, R.K.; Bennett, J.; Cremers, F.P.M.; Gloeckner, C.J.; Nishina, P.M.; Roepman, R.; Ueffing, M.

    2011-01-01

    The mutations that cause Leber congenital amaurosis (LCA) lead to photoreceptor cell death at an early age, causing childhood blindness. To unravel the molecular basis of LCA, we analyzed how mutations in LCA5 affect the connectivity of the encoded protein lebercilin at the interactome level. In

  12. Genotyping microarray (disease chip) for Leber congenital amaurosis: detection of modifier alleles.

    NARCIS (Netherlands)

    Zernant, J.; Kulm, M.; Dharmaraj, S.; Hollander, A.I. den; Perrault, I.; Preising, M.N.; Lorenz, B.; Kaplan, J.; Cremers, F.P.M.; Maumenee, I.H.; Koenekoop, R.K.; Allikmets, R.

    2005-01-01

    PURPOSE: Leber congenital amaurosis (LCA) is an early-onset inherited disorder of childhood blindness characterized by visual impairment noted soon after birth. Variants in at least six genes (AIPL1, CRB1, CRX, GUCY2D, RPE65, and RPGRIP1) have been associated with a diagnosis consistent with LCA or

  13. Mutations in LCA5, encoding the ciliary protein lebercilin, cause Leber congenital amaurosis.

    NARCIS (Netherlands)

    Hollander, A.I. den; Koenekoop, R.K.; Mohamed, M.D.; Arts, H.H.; Boldt, K.; Towns, K.V.; Sedmak, T.; Beer, M. de; Nagel-Wolfrum, K.; McKibbin, M.; Dharmaraj, S.; Lopez, I.; Ivings, L.; Williams, G.A.; Springell, K.; Woods, C.G.; Jafri, H.; Rashid, Y.; Strom, T.M.; Zwaag, B. van der; Gosens, I.; Kersten, F.F.J.; Wijk, E. van; Veltman, J.A.; Zonneveld, M.N.; Beersum, S.E.C. van; Maumenee, I.H.; Wolfrum, U.; Cheetham, M.E.; Ueffing, M.; Cremers, F.P.M.; Inglehearn, C.F.; Roepman, R.

    2007-01-01

    Leber congenital amaurosis (LCA) causes blindness or severe visual impairment at or within a few months of birth. Here we show, using homozygosity mapping, that the LCA5 gene on chromosome 6q14, which encodes the previously unknown ciliary protein lebercilin, is associated with this disease. We

  14. Leber congenital amaurosis associated with optic disk neovascularization and vitreous hemorrhage.

    Science.gov (United States)

    Kurz, Daryl; Ciulla, Thomas A

    2003-05-01

    To report an unusual case of optic disk neovascularization and vitreous hemorrhage associated with Leber congenital amaurosis (LCA). Interventional case report. A 16-year-old Caucasian girl with a history of LCA presented with decreased vision in her left eye, diffuse retinal pigmentary abnormalities characteristic of LCA, and hemorrhage over the left optic disk and macula. Six months of follow-up revealed optic disk neovascularization. A small amount of neovascularization was noted in the right eye at 6 months. An extensive systemic evaluation indicated no other cause for the neovascularization. Panretinal photocoagulation was performed in both eyes, and subsequently the neovascularization regressed. Leber congenital amaurosis like retinitis pigmentosa, can rarely be associated with neovascularization of the disk, which is amenable to treatment with peripheral photocoagulation if it does not spontaneously regress.

  15. Leber congenital amaurosis, from darkness to light: An ode to Irene Maumenee

    OpenAIRE

    Coussa, Razek Georges; Solache, Irma Lopez; Koenekoop, Robert K.

    2017-01-01

    This article is dedicated to Irene Hussels-Maumenee, Professor of Human Genetics and Ophthalmology, Johns Hopkins’ Wilmer Eye Institute, Ocular Genetics Fellowship director in 1994–1995. Leber congenital amaurosis (LCA) has almost come full circle, from a profound and molecularly uncharacterized form of congenital retinal blindness to one in which a large number of causative genes and disease pathways are known; and the world’s first human retinal disease to be treated by gene therapy. Dr. Ma...

  16. Comprehensive genotyping reveals RPE65 as the most frequently mutated gene in Leber congenital amaurosis in Denmark

    NARCIS (Netherlands)

    Astuti, G.D.N; Bertelsen, M.; Preising, M.N.; Ajmal, M.; Lorenz, B.; Faradz, S.M.H.; Qamar, R.; Collin, R.W.J.; Rosenberg, T.; Cremers, F.P.M.

    2016-01-01

    Leber congenital amaurosis (LCA) represents the most severe form of inherited retinal dystrophies with an onset during the first year of life. Currently, 21 genes are known to be associated with LCA and recurrent mutations have been observed in AIPL1, CEP290, CRB1 and GUCY2D. In addition, sequence

  17. Antisense Oligonucleotide (AON)-based Therapy for Leber Congenital Amaurosis Caused by a Frequent Mutation in CEP290

    NARCIS (Netherlands)

    Collin, R.W.J.; Hollander, A.I. den; Velde-Visser, S.D. van der; Bennicelli, J.; Bennett, J.; Cremers, F.P.M.

    2012-01-01

    Leber congenital amaurosis (LCA) is the most severe form of inherited retinal degeneration, with an onset in the first year of life. The most frequent mutation that causes LCA, present in at least 10% of individuals with LCA from North-American and Northern-European descent, is an intronic mutation

  18. Abnormalities of the five serum ions in patients with Leber congenital amaurosis

    Directory of Open Access Journals (Sweden)

    Zhi-Zhong Wu

    2017-03-01

    Full Text Available AIM:To study the concentration changes of the serum magnesium, calcium, potassium, sodium and chloride ions of the patients of Leber congenital amaurosis(LCA.METHODS:Based on the retrospective study and the simple size in the statistics, 50 cases of LCA patients and 99 cases of normal people were tested the serum ions by professionals in hospital according to the single blind study. Data were analyzed statistically between LCA and normal groups. RESULTS: In the clinical serum ions test of LCA group, the concentration of calcium and potassium were 2.338±0.090mmol/L and 4.164±0.356mmol/L respectively, which were significantly higher than those of the normal group(all PPP>0.05. CONCLUSION: In the patients with LCA, abnormal concentration changes of magnesium, calcium and potassium will be needed to concern of the ophthalmologist, which is probably related with the occurrence of LCA.

  19. Leber congenital amaurosis, from darkness to light: An ode to Irene Maumenee

    Science.gov (United States)

    Coussa, Razek Georges; Solache, Irma Lopez; Koenekoop, Robert K.

    2017-01-01

    This article is dedicated to Irene Hussels-Maumenee, Professor of Human Genetics and Ophthalmology, Johns Hopkins’ Wilmer Eye Institute, Ocular Genetics Fellowship director in 1994–1995. Leber congenital amaurosis (LCA) has almost come full circle, from a profound and molecularly uncharacterized form of congenital retinal blindness to one in which a large number of causative genes and disease pathways are known; and the world’s first human retinal disease to be treated by gene therapy. Dr. Maumenee’s insights, efforts and leadership have contributed significantly to this remarkable scientific journey. In this manuscript, we present a short summary of the known LCA genes, LCA disease subtypes and emerging treatment options. Our manuscript consolidates previous knowledge with current findings in an attempt to provide a more comprehensive understanding of LCA. PMID:28095138

  20. Mutations in the CEP290 (NPHP6) Gene Are a Frequent Cause of Leber Congenital Amaurosis

    Science.gov (United States)

    den Hollander, Anneke I.; Koenekoop, Robert K.; Yzer, Suzanne; Lopez, Irma; Arends, Maarten L.; Voesenek, Krysta E. J.; Zonneveld, Marijke N.; Strom, Tim M.; Meitinger, Thomas; Brunner, Han G.; Hoyng, Carel B.; van den Born, L. Ingeborgh; Rohrschneider, Klaus; Cremers, Frans P. M.

    2006-01-01

    Leber congenital amaurosis (LCA) is one of the main causes of childhood blindness. To date, mutations in eight genes have been described, which together account for ∼45% of LCA cases. We localized the genetic defect in a consanguineous LCA-affected family from Quebec and identified a splice defect in a gene encoding a centrosomal protein (CEP290). The defect is caused by an intronic mutation (c.2991+1655A→G) that creates a strong splice-donor site and inserts a cryptic exon in the CEP290 messenger RNA. This mutation was detected in 16 (21%) of 76 unrelated patients with LCA, either homozygously or in combination with a second deleterious mutation on the other allele. CEP290 mutations therefore represent one of the most frequent causes of LCA identified so far. PMID:16909394

  1. [Amaurosis and contralateral cranial nerve pairs III and VI paralysis after peribulbar block - Case report].

    Science.gov (United States)

    Leme, Fábio Caetano Oliveira; Moro, Eduardo Toshiyuki; Ferraz, Alexandre Alberto Fontana

    2016-08-20

    Peribulbar anesthesia (PBA) has emerged as a safer option compared with intraconal retrobulbar block. Still, PBA may not be considered without risk. Numerous complications have been described when performing this technique. This report aims to describe a rare case of amaurosis and contralateral paralysis while attempting to perform a PBA. Male patient, 75-year old, physical status ASA II, undergoing cataract surgery by phacoemulsification with intraocular lens implantation. Sedated with fentanyl and midazolam and subjected to PBA. There were no complications during surgery. After finishing the procedure, the patient reported lack of vision in the contralateral eye. Akinesia of the muscles innervated by the cranial nerve pairs III and VI, ptosis, and medium-sized pupils unresponsive to light stimulus were observed. Four hours after anesthesia, complete recovery of vision and eyelid and eyeball movements was seen in the non-operated eye. During PBA, structures located in the intraconal space can be accidentally hit leading to complications such as described in the above report. Following the technical guidelines and using appropriate size needles may reduce the risk of such complication, but not completely. Copyright © 2016. Publicado por Elsevier Editora Ltda.

  2. Leber’s congenital amaurosis and the role of gene therapy in congenital retinal disorders

    Directory of Open Access Journals (Sweden)

    Walid Sharif

    2017-03-01

    Full Text Available Leber’s congenital amaurosis (LCA and recent gene therapy advancement for treating inherited retinopathies were extensive literature reviewed using MEDLINE, PubMed and EMBASE. Adeno-associated viral vectors were the most utilised vectors for ocular gene therapy. Cone photoreceptor cells might use an alternate pathway which was not reliant of the retinal pigment epithelium (RPE derived retinoid isomerohydrolase (RPE65 to access the 11-cis retinal dehydechromophore. Research efforts dedicated on the progression of a gene-based therapy for the treatment of LCA2. Such gene therapy approaches were extremely successful in canine, porcine and rodent LCA2 models. The recombinant AAV2.hRPE65v2 adeno-associated vector contained the RPE65 cDNA and was replication deficient. Its in vitro injection in target cells induced RPE65 protein production. The gene therapy trials that were so far conducted for inherited retinopathies have generated promising results. Phase I clinical trials to cure LCA and choroideremia demonstrated that adeno-associated viral vectors containing RPE genes and photoreceptors respectively, could be successfully administered to inherited retinopathy patients. A phase III trial is presently ongoing and if successful, it will lead the way to additional gene therapy attempts to cure monogenic, inherited retinopathies.

  3. Leber congenital amaurosis/early-onset severe retinal dystrophy: clinical features, molecular genetics and therapeutic interventions.

    Science.gov (United States)

    Kumaran, Neruban; Moore, Anthony T; Weleber, Richard G; Michaelides, Michel

    2017-09-01

    Leber congenital amaurosis (LCA) and early-onset severe retinal dystrophy (EOSRD) are both genetically and phenotypically heterogeneous, and characterised clinically by severe congenital/early infancy visual loss, nystagmus, amaurotic pupils and markedly reduced/absent full-field electroretinograms. The vast genetic heterogeneity of inherited retinal disease has been established over the last 10 - 20 years, with disease-causing variants identified in 25 genes to date associated with LCA/EOSRD, accounting for 70-80% of cases, with thereby more genes yet to be identified. There is now far greater understanding of the structural and functional associations seen in the various LCA/EOSRD genotypes. Subsequent development/characterisation of LCA/EOSRD animal models has shed light on the underlying pathogenesis and allowed the demonstration of successful rescue with gene replacement therapy and pharmacological intervention in multiple models. These advancements have culminated in more than 12 completed, ongoing and anticipated phase I/II and phase III gene therapy and pharmacological human clinical trials. This review describes the clinical and genetic characteristics of LCA/EOSRD and the differential diagnoses to be considered. We discuss in further detail the diagnostic clinical features, pathophysiology, animal models and human treatment studies and trials, in the more common genetic subtypes and/or those closest to intervention. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. Differential proteomics and functional research following gene therapy in a mouse model of Leber congenital amaurosis.

    Directory of Open Access Journals (Sweden)

    Qinxiang Zheng

    Full Text Available Leber congenital amaurosis (LCA is one of the most severe forms of inherited retinal degeneration and can be caused by mutations in at least 15 different genes. To clarify the proteomic differences in LCA eyes, a cohort of retinal degeneration 12 (rd12 mice, an LCA2 model caused by a mutation in the RPE65 gene, were injected subretinally with an AAV vector (scAAV5-smCBA-hRPE65 in one eye, while the contralateral eye served as a control. Proteomics were compared between untreated rd12 and normal control retinas on P14 and P21, and among treated and untreated rd12 retinas and control retinas on P42. Gene therapy in rd12 mice restored retinal function in treated eyes, which was demonstrated by electroretinography (ERG. Proteomic analysis successfully identified 39 proteins expressed differently among the 3 groups. The expression of 3 proteins involved in regulation of apoptosis and neuroptotection (alpha A crystallin, heat shock protein 70 and peroxiredoxin 6 were investigated further. Immunofluorescence, Western blot and real-time PCR confirmed the quantitative changes in their expression. Furthermore, cell culture studies suggested that peroxiredoxin 6 could act in an antioxidant role in rd12 mice. Our findings support the feasibility of gene therapy in LCA2 patients and support a role for alpha A crystallin, heat shock protein 70 and peroxiredoxin 6 in the pathogenetic mechanisms involved in LCA2 disease process.

  5. Bax-induced apoptosis in Leber's congenital amaurosis: a dual role in rod and cone degeneration.

    Directory of Open Access Journals (Sweden)

    Séverine Hamann

    2009-08-01

    Full Text Available Pathogenesis in the Rpe65(-/- mouse model of Leber's congenital amaurosis (LCA is characterized by a slow and progressive degeneration of the rod photoreceptors. On the opposite, cones degenerate rapidly at early ages. Retinal degeneration in Rpe65(-/- mice, showing a null mutation in the gene encoding the retinal pigment epithelium 65-kDa protein (Rpe65, was previously reported to depend on continuous activation of a residual transduction cascade by unliganded opsin. However, the mechanisms of apoptotic signals triggered by abnormal phototransduction remain elusive. We previously reported that activation of a Bcl-2-dependent pathway was associated with apoptosis of rod photoreceptors in Rpe65(-/- mice during the course of the disease. In this study we first assessed whether activation of Bcl-2-mediated apoptotic pathway was dependent on constitutive activation of the visual cascade through opsin apoprotein. We then challenged the direct role of pro-apoptotic Bax protein in triggering apoptosis of rod and cone photoreceptors.Quantitative PCR analysis showed that increased expression of pro-apoptotic Bax and decreased level of anti-apoptotic Bcl-2 were restored in Rpe65(-/-/Gnat1(-/- mice lacking the Gnat1 gene encoding rod transducin. Moreover, photoreceptor apoptosis was prevented as assessed by TUNEL assay. These data indicate that abnormal activity of opsin apoprotein induces retinal cell apoptosis through the Bcl-2-mediated pathway. Following immunohistological and real-time PCR analyses, we further observed that decreased expression of rod genes in Rpe65-deficient mice was rescued in Rpe65(-/-/Bax(-/- mice. Histological and TUNEL studies confirmed that rod cell demise and apoptosis in diseased Rpe65(-/- mice were dependent on Bax-induced pathway. Surprisingly, early loss of cones was not prevented in Rpe65(-/-/Bax(-/- mice, indicating that pro-apoptotic Bax was not involved in the pathogenesis of cone cell death in Rpe65-deficient mice

  6. Comprehensive genotyping reveals RPE65 as the most frequently mutated gene in Leber congenital amaurosis in Denmark

    DEFF Research Database (Denmark)

    Astuti, Galuh D N; Bertelsen, Mette; Preising, Markus N

    2016-01-01

    Leber congenital amaurosis (LCA) represents the most severe form of inherited retinal dystrophies with an onset during the first year of life. Currently, 21 genes are known to be associated with LCA and recurrent mutations have been observed in AIPL1, CEP290, CRB1 and GUCY2D. In addition, sequence...... analysis of LRAT and RPE65 may be important in view of treatments that are emerging for patients carrying variants in these genes. Screening of the aforementioned variants and genes was performed in 64 Danish LCA probands. Upon the identification of heterozygous variants, Sanger sequencing was performed...... of the relevant genes to identify the second allele. In combination with prior arrayed primer extension analysis, this led to the identification of two variants in 42 of 86 cases (49%). Remarkably, biallelic RPE65 variants were identified in 16% of the cases, and one novel variant, p.(D110G), was found in seven...

  7. Reversal of blindness in animal models of leber congenital amaurosis using optimized AAV2-mediated gene transfer.

    Science.gov (United States)

    Bennicelli, Jeannette; Wright, John Fraser; Komaromy, Andras; Jacobs, Jonathan B; Hauck, Bernd; Zelenaia, Olga; Mingozzi, Federico; Hui, Daniel; Chung, Daniel; Rex, Tonia S; Wei, Zhangyong; Qu, Guang; Zhou, Shangzhen; Zeiss, Caroline; Arruda, Valder R; Acland, Gregory M; Dell'Osso, Lou F; High, Katherine A; Maguire, Albert M; Bennett, Jean

    2008-03-01

    We evaluated the safety and efficacy of an optimized adeno-associated virus (AAV; AAV2.RPE65) in animal models of the RPE65 form of Leber congenital amaurosis (LCA). Protein expression was optimized by addition of a modified Kozak sequence at the translational start site of hRPE65. Modifications in AAV production and delivery included use of a long stuffer sequence to prevent reverse packaging from the AAV inverted-terminal repeats, and co-injection with a surfactant. The latter allows consistent and predictable delivery of a given dose of vector. We observed improved electroretinograms (ERGs) and visual acuity in Rpe65 mutant mice. This has not been reported previously using AAV2 vectors. Subretinal delivery of 8.25 x 10(10) vector genomes in affected dogs was well tolerated both locally and systemically, and treated animals showed improved visual behavior and pupillary responses, and reduced nystagmus within 2 weeks of injection. ERG responses confirmed the reversal of visual deficit. Immunohistochemistry confirmed transduction of retinal pigment epithelium cells and there was minimal toxicity to the retina as judged by histopathologic analysis. The data demonstrate that AAV2.RPE65 delivers the RPE65 transgene efficiently and quickly to the appropriate target cells in vivo in animal models. This vector holds great promise for treatment of LCA due to RPE65 mutations.

  8. Insights into the role of RD3 in guanylate cyclase trafficking, photoreceptor degeneration and Leber Congenital Amaurosis

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    Robert S. Molday

    2014-05-01

    Full Text Available RD3 is an evolutionarily conserved 23 kDa protein expressed in rod and cone photoreceptor cells. Mutations in the gene encoding RD3 resulting in unstable non-functional C-terminal truncated proteins are responsible for early onset photoreceptor degeneration in Leber Congenital Amaurosis 12 (LCA12 patients, the rd3 mice, and the rcd2 collies. Recent studies have shown that RD3 interacts with guanylate cyclases GC1 and GC2 in retinal cell extracts and HEK293 cells co-expressing GC and RD3. This interaction inhibits GC catalytic activity and promotes the exit of GC1 and GC2 from the endoplasmic reticulum and their trafficking to photoreceptor outer segments. Adeno-associated viral vector delivery of the normal RD3 gene to photoreceptors of the Rd3 mouse restores GC1 and GC2 expression and outer segment localization and leads to the long-term recovery of visual function and photoreceptor cell survival. This review focuses on the genetic and biochemical studies that have provided insight into the role of RD3 in photoreceptor function and survival.

  9. Targeted Multifunctional Lipid ECO Plasmid DNA Nanoparticles as Efficient Non-viral Gene Therapy for Leber's Congenital Amaurosis.

    Science.gov (United States)

    Sun, Da; Sahu, Bhubanananda; Gao, Songqi; Schur, Rebecca M; Vaidya, Amita M; Maeda, Akiko; Palczewski, Krzysztof; Lu, Zheng-Rong

    2017-06-16

    Development of a gene delivery system with high efficiency and a good safety profile is essential for successful gene therapy. Here we developed a targeted non-viral delivery system using a multifunctional lipid ECO for treating Leber's congenital amaurosis type 2 (LCA2) and tested this in a mouse model. ECO formed stable nanoparticles with plasmid DNA (pDNA) at a low amine to phosphate (N/P) ratio and mediated high gene transfection efficiency in ARPE-19 cells because of their intrinsic properties of pH-sensitive amphiphilic endosomal escape and reductive cytosolic release (PERC). All-trans-retinylamine, which binds to interphotoreceptor retinoid-binding protein (IRBP), was incorporated into the nanoparticles via a polyethylene glycol (PEG) spacer for targeted delivery of pDNA into the retinal pigmented epithelium. The targeted ECO/pDNA nanoparticles provided high GFP expression in the RPE of 1-month-old Rpe65 -/- mice after subretinal injection. Such mice also exhibited a significant increase in electroretinographic activity, and this therapeutic effect continued for at least 120 days. A safety study in wild-type BALB/c mice indicated no irreversible retinal damage following subretinal injection of these targeted nanoparticles. All-trans-retinylamine-modified ECO/pDNA nanoparticles provide a promising non-viral platform for safe and effective treatment of RPE-specific monogenic eye diseases such as LCA2. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  10. Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration.

    Science.gov (United States)

    Koenekoop, Robert K; Wang, Hui; Majewski, Jacek; Wang, Xia; Lopez, Irma; Ren, Huanan; Chen, Yiyun; Li, Yumei; Fishman, Gerald A; Genead, Mohammed; Schwartzentruber, Jeremy; Solanki, Naimesh; Traboulsi, Elias I; Cheng, Jingliang; Logan, Clare V; McKibbin, Martin; Hayward, Bruce E; Parry, David A; Johnson, Colin A; Nageeb, Mohammed; Poulter, James A; Mohamed, Moin D; Jafri, Hussain; Rashid, Yasmin; Taylor, Graham R; Keser, Vafa; Mardon, Graeme; Xu, Huidan; Inglehearn, Chris F; Fu, Qing; Toomes, Carmel; Chen, Rui

    2012-09-01

    Leber congenital amaurosis (LCA) is a blinding retinal disease that presents within the first year after birth. Using exome sequencing, we identified mutations in the nicotinamide adenine dinucleotide (NAD) synthase gene NMNAT1 encoding nicotinamide mononucleotide adenylyltransferase 1 in eight families with LCA, including the family in which LCA was originally linked to the LCA9 locus. Notably, all individuals with NMNAT1 mutations also have macular colobomas, which are severe degenerative entities of the central retina (fovea) devoid of tissue and photoreceptors. Functional assays of the proteins encoded by the mutant alleles identified in our study showed that the mutations reduce the enzymatic activity of NMNAT1 in NAD biosynthesis and affect protein folding. Of note, recent characterization of the slow Wallerian degeneration (Wld(s)) mouse model, in which prolonged axonal survival after injury is observed, identified NMNAT1 as a neuroprotective protein when ectopically expressed. Our findings identify a new disease mechanism underlying LCA and provide the first link between endogenous NMNAT1 dysfunction and a human nervous system disorder.

  11. Antisense Oligonucleotide (AON-based Therapy for Leber Congenital Amaurosis Caused by a Frequent Mutation in CEP290

    Directory of Open Access Journals (Sweden)

    Rob WJ Collin

    2012-01-01

    Full Text Available Leber congenital amaurosis (LCA is the most severe form of inherited retinal degeneration, with an onset in the first year of life. The most frequent mutation that causes LCA, present in at least 10% of individuals with LCA from North-American and Northern-European descent, is an intronic mutation in CEP290 that results in the inclusion of an aberrant exon in the CEP290 mRNA. Here, we describe a genetic therapy approach that is based on antisense oligonucleotides (AONs, small RNA molecules that are able to redirect normal splicing of aberrantly processed pre-mRNA. Immortalized lymphoblastoid cells of individuals with LCA homozygously carrying the intronic CEP290 mutation were transfected with several AONs that target the aberrant exon that is incorporated in the mutant CEP290 mRNA. Subsequent RNA isolation and reverse transcription-PCR analysis revealed that a number of AONs were capable of almost fully redirecting normal CEP290 splicing, in a dose-dependent manner. Other AONs however, displayed no effect on CEP290 splicing at all, indicating that the rescue of aberrant CEP290 splicing shows a high degree of sequence specificity. Together, our data show that AON-based therapy is a promising therapeutic approach for CEP290-associated LCA that warrants future research in animal models to develop a cure for this blinding disease.

  12. Omics in Ophthalmology: Advances in Genomics and Precision Medicine for Leber Congenital Amaurosis and Age-Related Macular Degeneration.

    Science.gov (United States)

    den Hollander, Anneke I

    2016-03-01

    The genomic revolution has had a huge impact on our understanding of the genetic defects and disease mechanisms underlying ophthalmic diseases. Two examples are discussed here. The first is Leber congenital amaurosis (LCA), a severe inherited retinal dystrophy leading to severe vision loss in children, and the second is age-related macular degeneration (AMD), the most common cause of vision loss in the elderly. Twenty years ago, the genetic causes of these diseases were unknown. Currently, more than 20 LCA genes have been identified, and genetic testing can now successfully identify the genetic defects in at least 75% of all LCA cases. Gene-specific treatments have entered the clinical trial phase for three LCA genes, and for seven LCA genes gene-specific therapies have been tested in model systems. Age-related macular degeneration is a multifactorial disease caused by a combination of genetic and environmental factors. Currently, more than 40 loci have been identified for AMD, accounting for 15%-65% of the total genetic contribution to AMD. Despite the progress that has been made so far, genetic testing is not yet recommended for AMD, but this may change if we move to clinical trials or treatments that are dependent on an individual's genotype. The identification of serum or plasma biomarkers using other "-omics" technologies may further improve predictive tests and our understanding of the disease mechanisms of AMD. Ultimately, it is anticipated that predictive tests will help to stratify patients for the most suitable therapy, which will enable the development of precision medicine, tailored to individual needs.

  13. Leber congenital amaurosis associated with AIPL1: challenges in ascribing disease causation, clinical findings, and implications for gene therapy.

    Directory of Open Access Journals (Sweden)

    Mei Hong Tan

    Full Text Available Leber Congenital Amaurosis (LCA and Early Childhood Onset Severe Retinal Dystrophy are clinically and genetically heterogeneous retinal disorders characterised by visual impairment and nystagmus from birth or early infancy. We investigated the prevalence of sequence variants in AIPL1 in a large cohort of such patients (n = 392 and probed the likelihood of disease-causation of the identified variants, subsequently undertaking a detailed assessment of the phenotype of patients with disease-causing mutations. Genomic DNA samples were screened for known variants in the AIPL1 gene using a microarray LCA chip, with 153 of these cases then being directly sequenced. The assessment of disease-causation of identified AIPL1 variants included segregation testing, assessing evolutionary conservation and in silico predictions of pathogenicity. The chip identified AIPL1 variants in 12 patients. Sequencing of AIPL1 in 153 patients and 96 controls found a total of 46 variants, with 29 being novel. In silico analysis suggested that only 6 of these variants are likely to be disease-causing, indicating a previously unrecognized high degree of polymorphism. Seven patients were identified with biallelic changes in AIPL1 likely to be disease-causing. In the youngest subject, electroretinography revealed reduced cone photoreceptor function, but rod responses were within normal limits, with no measurable ERG in other patients. An increasing degree and extent of peripheral retinal pigmentation and degree of maculopathy was noted with increasing age in our series. AIPL1 is significantly polymorphic in both controls and patients, thereby complicating the establishment of disease-causation of identified variants. Despite the associated phenotype being characterised by early-onset severe visual loss in our patient series, there was some evidence of a degree of retinal structural and functional preservation, which was most marked in the youngest patient in our cohort

  14. Leber Congenital Amaurosis

    Science.gov (United States)

    ... caused by other genetic variations. Some individuals with LCA, who have remaining vision, may also benefit from the use of low-vision aids, including electronic, computer-based and optical aids. Orientation and mobility ...

  15. Thrombophilia testing in young patients with ischemic stroke.

    Science.gov (United States)

    Pahus, Sidse Høst; Hansen, Anette Tarp; Hvas, Anne-Mette

    2016-01-01

    The possible significance of thrombophilia in ischemic stroke remains controversial. We aimed to study inherited and acquired thrombophilias as risk factors for ischemic stroke, transient ischemic attack (TIA) and amaurosis fugax in young patients. We included patients aged 18 to 50 years with ischemic stroke, TIA or amaurosis fugax referred to thrombophilia investigation at Aarhus University Hospital, Denmark from 1 January 2004 to 31 December 2012 (N=685). Clinical information was obtained from the Danish Stroke Registry and medical records. Thrombophilia investigation results were obtained from the laboratory information system. Absolute thrombophilia prevalences and associated odds ratios (OR) with 95% confidence intervals (95% CI) were reported for ischemic stroke (N=377) and TIA or amaurosis fugax (N=308). Thrombophilia prevalences for the general population were obtained from published data. No strong associations were found between thrombophilia and ischemic stroke, but patients with persistent presence of lupus anticoagulant (3%) had an OR at 2.66 (95% CI 0.84-9.15) for ischemic stroke. A significantly higher risk of TIA/amaurosis fugax was found for factor V Leiden heterozygote (12%) (OR: 1.99 (95% CI 1.14-3.28)). No other inherited or acquired thrombophilia was associated with ischemic stroke, TIA or amaurosis fugax. In young patients, thrombophilia did not infer an increased risk of ischemic stroke. Only factor V Leiden heterozygote patients had an increased risk of TIA/amaurosis fugax, and persistent presence of lupus anticoagulant was likely associated with ischemic stroke. We suggest the testing restricted to investigation of persistent presence of lupus anticoagulant. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Akut glaukom efter endarterektomi af arteria carotis interna

    DEFF Research Database (Denmark)

    Lindholt, Jes Sanddal; Klaerke, A

    2000-01-01

    A 71 year-old woman had 85% and 60% stenoses of the right and left internal carotid arteries, respectively. Right-sided endarterectomy was performed because of amaurosis fugax. Two days postoperatively, she developed classical symptoms and signs of acute glaucoma. Right-sided acute angle closure ...

  17. Embolic and Nonembolic Transient Monocular Visual Field Loss: A Clinicopathologic Review

    NARCIS (Netherlands)

    Petzold, A.; Islam, N.; Hu, H.H.; Plant, G.T.

    2013-01-01

    Transient monocular blindness and amaurosis fugax are umbrella terms describing a range of patterns of transient monocular visual field loss (TMVL). The incidence rises from ≈1.5/100,000 in the third decade of life to ≈32/100,000 in the seventh decade of life. We review the vascular supply of the

  18. Results at 2 Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood-Onset Retinal Dystrophy.

    Science.gov (United States)

    Weleber, Richard G; Pennesi, Mark E; Wilson, David J; Kaushal, Shalesh; Erker, Laura R; Jensen, Lauren; McBride, Maureen T; Flotte, Terence R; Humphries, Margaret; Calcedo, Roberto; Hauswirth, William W; Chulay, Jeffrey D; Stout, J Timothy

    2016-07-01

    To provide an initial assessment of the safety of a recombinant adeno-associated virus vector expressing RPE65 (rAAV2-CB-hRPE65) in adults and children with retinal degeneration caused by RPE65 mutations. Nonrandomized, multicenter clinical trial. Eight adults and 4 children, 6 to 39 years of age, with Leber congenital amaurosis (LCA) or severe early-childhood-onset retinal degeneration (SECORD). Patients received a subretinal injection of rAAV2-CB-hRPE65 in the poorer-seeing eye, at either of 2 dose levels, and were followed up for 2 years after treatment. The primary safety measures were ocular and nonocular adverse events. Exploratory efficacy measures included changes in best-corrected visual acuity (BCVA), static perimetry central 30° visual field hill of vision (V30) and total visual field hill of vision (VTOT), kinetic perimetry visual field area, and responses to a quality-of-life questionnaire. All patients tolerated subretinal injections and there were no treatment-related serious adverse events. Common adverse events were those associated with the surgical procedure and included subconjunctival hemorrhage in 8 patients and ocular hyperemia in 5 patients. In the treated eye, BCVA increased in 5 patients, V30 increased in 6 patients, VTOT increased in 5 patients, and kinetic visual field area improved in 3 patients. One subject showed a decrease in BCVA and 2 patients showed a decrease in kinetic visual field area. Treatment with rAAV2-CB-hRPE65 was not associated with serious adverse events, and improvement in 1 or more measures of visual function was observed in 9 of 12 patients. The greatest improvements in visual acuity were observed in younger patients with better baseline visual acuity. Evaluation of more patients and a longer duration of follow-up will be needed to determine the rate of uncommon or rare side effects or safety concerns. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  19. Genetics Home Reference: Leber congenital amaurosis

    Science.gov (United States)

    ... types of cells. Cilia are necessary for the perception of several types of sensory input, including vision. ... for Links Data Files & API Site Map Subscribe Customer Support USA.gov Copyright Privacy Accessibility FOIA Viewers & ...

  20. Correlation of Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ) and Retinoid X Receptor-α (RXR-α) expression with clinical risk factors in patients with advanced carotid atherosclerosis

    Science.gov (United States)

    Giaginis, Constantinos; Klonaris, Christos; Katsargyris, Athanasios; Kouraklis, Gregorios; Spiliopoulou, Chara; Theocharis, Stamatios

    2011-01-01

    Summary Background Peroxisome proliferator-activated Receptor-γ (PPAR-γ) and its nuclear partners, the Retinoid X Receptors (RXRs), have been recognized as crucial players in the pathogenesis of atherosclerosis. The present study aimed to assess the clinical significance of PPAR-γ and RXR-α expression in different cellular populations localized within advanced carotid atherosclerosis lesions. Material/Methods PPAR-γ and RXR-α expression was assessed by immunohistochemistry ïn 134 carotid atherosclerotic plaques obtained from an equal number of patients that underwent endarterectomy procedure for vascular repair, and was correlated with patients’ medical history, risk factors and medication intake. Results Increased incidence of low PPAR-γ expression in both macrophages and smooth muscle cells was noted in patients presenting coronary artery disease (p=0.032 and p=0.046, respectively). PPAR-γ expression in smooth muscle cells was borderline down-regulated in symptomatic compared to asymptomatic patients (p=0.061), reaching statistical significance when analyzing groups of patients with specific cerebrovascular events; amaurosis fugax (p=0.008), amaurosis fugax/stroke (p=0.020) or amaurosis fugax/transient ischemic attack patients (p=0.028) compared to asymptomatic patients. Low RXR-α expression in macrophages was more frequently observed in hypertensive (p=0.048) and hyperlipidemic patients (p=0.049). Increased incidence of low RXR-α expression in smooth muscle cells was also noted in patients presenting advanced carotid stenosis grade (p=0.015). Conclusions PPAR-γ and RXR-α expression down-regulation in macrophages and smooth muscle cells was associated with a more pronounced disease progression in patients with advanced carotid atherosclerotic lesions. PMID:21709632

  1. Correlation of Peroxisome Proliferator-Activated Receptor-gamma (PPAR-gamma) and Retinoid X Receptor-alpha (RXR-alpha) expression with clinical risk factors in patients with advanced carotid atherosclerosis.

    Science.gov (United States)

    Giaginis, Constantinos; Klonaris, Christos; Katsargyris, Athanassios; Kouraklis, Gregorios; Spiliopoulou, Chara; Theocharis, Stamatios

    2011-07-01

    Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and its nuclear partners, the Retinoid X Receptors (RXRs), have been recognized as crucial players in the pathogenesis of atherosclerosis. The present study aimed to assess the clinical significance of PPAR-gamma and RXR-alpha expression in different cellular populations localized within advanced carotid atherosclerosis lesions. PPAR-gamma and RXR-alpha expression was assessed by immunohistochemistry in 134 carotid atherosclerotic plaques obtained from an equal number of patients that underwent endarterectomy procedure for vascular repair, and was correlated with patients' medical history, risk factors and medication intake. Increased incidence of low PPAR-gamma expression in both macrophages and smooth muscle cells was noted in patients presenting coronary artery disease (p=0.032 and p=0.046, respectively). PPAR-gamma expression in smooth muscle cells was borderline down-regulated in symptomatic compared to asymptomatic patients (p=0.061), reaching statistical significance when analyzing groups of patients with specific cerebrovascular events; amaurosis fugax (p=0.008), amaurosis fugax/stroke (p=0.020) or amaurosis fugax/transient ischemic attack patients (p=0.028) compared to asymptomatic patients. Low RXR-alpha expression in macrophages was more frequently observed in hypertensive (p=0.048) and hyperlipidemic patients (p=0.049). Increased incidence of low RXR-alpha expression in smooth muscle cells was also noted in patients presenting advanced carotid stenosis grade (p=0.015). PPAR-gamma and RXR-alpha expression down-regulation in macrophages and smooth muscle cells was associated with a more pronounced disease progression in patients with advanced carotid atherosclerotic lesions.

  2. Akut glaukom efter endarterektomi af arteria carotis interna

    DEFF Research Database (Denmark)

    Lindholt, Jes Sanddal; Klaerke, A

    2000-01-01

    A 71 year-old woman had 85% and 60% stenoses of the right and left internal carotid arteries, respectively. Right-sided endarterectomy was performed because of amaurosis fugax. Two days postoperatively, she developed classical symptoms and signs of acute glaucoma. Right-sided acute angle closure...... glaucoma was diagnosed by tonometry and gonioscopy, and treated with laser-iridectomy. The patient was discharged two days later without neurological or ophthalmological deficits. Manifest acute glaucoma postoperatively seems never to have been reported. However, the choroid is not autoregulated...

  3. Lebers Amaurosis in Three Siblings: A case report

    African Journals Online (AJOL)

    excluding a disease which might benefit from optical interventions. Second, the parents must be educated on the prognosis and natural history of the disorder. ... (ERG), flourescein angiography (FA), or fundus photography. When MH presented at the clinic in 2004, she had five younger siblings, two of which were also blind.

  4. Rhino-orbital Mucormycosis Treated Successfully with Posaconazole without Exenteration.

    Science.gov (United States)

    Zhang, Jason; Kim, James D; Beaver, Hilary A; Takashima, Masayoshi; Lee, Andrew G

    2013-01-01

    Mucormycosis is a rare and often fatal opportunistic angioinvasive infection seen mostly in immunocompromised patients, such as those with diabetes mellitus, cancer, or renal failure. Ophthalmic manifestations of orbital mucormycosis include ocular pain, periocular oedema, visual loss, ophthalmoplegia, proptosis, and ptosis. Although therapy for orbital mucormycosis consists of maximally tolerated doses of antifungal agents (e.g., amphotericin B) and extensive surgical debridement, treatment remains ineffective in up to 20% of cases. We describe two patients with rhino-orbitalmucormycosis who were successfully treated with posaconazole in conjunction with intravenous (IV) amphotericin B and sinus surgical debridement. These cases highlight several unusual early manifestations of orbital mucormycosis, including disc oedema and amaurosis fugax, as well as the applicability of a new extended-spectrum antifungal agent in management of orbital zygomycosis.

  5. Soluble urokinase-type plasminogen activator receptor forms in plasma as markers of atherosclerotic plaque vulnerability

    DEFF Research Database (Denmark)

    Olson, Fredrik J; Thurison, Tine; Ryndel, Mikael

    2009-01-01

    OBJECTIVES:: To test if circulating forms of the soluble urokinase-type plasminogen activator receptor (suPAR) are potential biomarkers of plaque vulnerability. DESIGN AND METHODS:: Plasma concentrations of suPAR(I-III), suPAR(II-III) and uPAR(I) were measured by time-resolved fluorescence...... immunoassays in Caucasian patients operated for symptomatic carotid atherosclerosis (n=255). Local suPAR release from plaques into the circulation was assessed in plasma passing retrogradely over the plaque in the carotid artery, collected during surgery (n=7). RESULTS:: The suPAR(I-III) (P=0.03) and su......PAR(II-III) (P=0.006) concentrations were higher after ischemic strokes and transient ischemic attacks, i.e., clinical subgroups associated with poorer prognosis and a less stable plaque phenotype, than after amaurosis fugax. Slightly elevated suPAR(I-III) levels were found in plasma from the carotid lesion...

  6. Subcutaneous hematoma associated with manual cervical massage during carotid artery stenting. A case report.

    Science.gov (United States)

    Tsurumi, A; Tsurumi, Y; Negoro, M; Yokoyama, K; Oheda, M; Susaki, N; Tsugane, T; Takahashi, T; Miyachi, S

    2011-09-01

    We describe a patient with subcutaneous hematoma associated with manual cervical massage during carotid artery stenting.A 73-year-old man with left cervical carotid artery stenosis presented with left amaurosis fugax. We performed carotid artery stenting using distal embolic protection with balloon occlusion. Dual antiplatelet therapy was maintained in the periprocedural period and an anticoagulant agent was administered during the procedure. Because the aspiration catheter became entrapped by the stent, it did not reach the distal side of the stenotic lesion, and manual compression of the cervical region was therefore performed. Immediately afterwards, a subcutaneous hemorrhage occurred in the cervical region. There was no postoperative dyspnea due to enlargement of the hematoma, which was absorbed spontaneously.Cervical subcutaneous hematoma can occur in the cervical region due to cervical massage in patients who are receiving adjuvant antiplatelet therapy and anticoagulation therapy.

  7. fMRI of retina-originated phosphenes experienced by patients with Leber congenital amaurosis.

    Directory of Open Access Journals (Sweden)

    Manzar Ashtari

    Full Text Available A phenomenon characterized by the experience of seeing light without any light actually entering the eye is called phosphenes or photopsias. Phosphenes can occur spontaneously or via induction by external stimuli. Previous reports regarding phosphenes have primarily focused on externally induced phosphenes such as by applying alternating or direct current to the cortex. A few of these reports used functional magnetic resonance (fMRI to study activations induced by cortical phosphenes. However, there are no fMRI reports on spontaneous phosphenes originating from the retina and the resulting pattern of cortical activations. We performed fMRI during a reversing checkerboard paradigm in three LCA patients who underwent unilateral gene therapy and reported experiencing frequent phosphene on a daily basis. We observed bilateral cortical activation covering the entire visual cortices when patients reported experiencing phosphenes. In contrast, in the absence of phosphenes, activation was regulated by patient's visual ability and demonstrated improved cortical activation due to gene therapy. These fMRI results illustrate the potential impact of phosphene perception on visual function and they may explain some of the variability that clinicians find in visual function testing in retinal degeneration. Although we did not perform correlations between visual function and phosphenes, we hope data presented here raises awareness of this phenomenon and its potential effect on visual function and the implications for clinical testing. We recommend a thorough history for phosphene experiences be taken in patients with retinal disease who are candidates for gene or molecular therapy. Lastly, these data illustrate the potential power of fMRI as an outcome measure of gene therapy and the negative impact phosphenes may have on vision testing. fMRI has proven to be a sensitive, non-invasive, and reproducible test paradigm for these purposes and can complement standard visual function testing.

  8. Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement

    OpenAIRE

    Cideciyan, Artur V.; Jacobson, Samuel G.; Beltran, William A.; Sumaroka, Alexander; Swider, Malgorzata; Iwabe, Simone; Roman, Alejandro J.; Olivares, Melani B.; Schwartz, Sharon B.; Komáromy, András M.; Hauswirth, William W.; Aguirre, Gustavo D.

    2013-01-01

    The first retinal gene therapy in human blindness from RPE65 mutations has focused on safety and efficacy, as defined by improved vision. The disease component not studied, however, has been the fate of photoreceptors in this progressive retinal degeneration. We show that gene therapy improves vision for at least 3 y, but photoreceptor degeneration progresses unabated in humans. In the canine model, the same result occurs when treatment is at the disease stage equivalent to humans. The study ...

  9. Outpatient primary stent-PTA in a symptomatic internal carotid artery stenosis under protection; Ambulante primaere Stent-PTA einer symptomatischen Arteria-carotis-interna-Stenose unter Protektion

    Energy Technology Data Exchange (ETDEWEB)

    Andresen, R. [Abt. fuer Bildgebende Diagnostik und Interventionelle Radiologie, Guestrower Krankenhaus (Germany); Roth, M. [Abt. Neurologie, Guestrower Krankenhaus (Germany); Brinckmann, W. [Gefaesschirurgie, Guestrower Krankenhaus (Germany)

    2003-07-01

    In a 69 year old patient, with a symptomatic ICA stenosis a stent implantation was performed under outpatient conditions. An interdisciplinary consensus was reached that the patient was suitable for outpatient therapy. In accordance with the NASCET criteria, the patient was to be classified to the high-risk group. Within 120 days before the intervention, the following clinical symptoms had occurred: 1 TIA, 2 amaurosis fugax. In the diagnostic angiography a right postbulbar ICA stenosis of 97% was verified. The stent application and subsequent PTA were performed under protection using a filter system. The transfemoral route was always fitted with an endovascular closure system. The neck vessels were followed-up by means of colour coded duplex sonography (CCDS) on days 1, 30, 180 and 360. A contrast-medium intensified MRI was performed on the 5{sup th} day post-intervention. The implantation of the stent and PTA were done without any complications. Atheromatous plaque fragments were found in the protection system. A plaque embolism was excluded clinically and in the contrast-medium intensified MRI 5 days after the intervention. After 360 days, no restenosis was found in the CCDS, the ECA was perfused. The method presented is low in complications and shows a high success rate. If patient recruitment is adequate, this intervention can be performed on an outpatient basis. (orig.) [German] Bei einem 69-jaehrigen Patienten mit symptomatischer Arteria-carotis-interna- (ACI-) Stenose erfolgte unter ambulanten Bedingungen eine primaere Stentimplantation. In einem interdisziplinaeren Konsens, bestehend aus interventionellem Radiologen, Neurologen und Gefaesschirurgen, wurde festgelegt, ob der Patient sich fuer eine ambulante Therapie eignet. Gemaess den NASCET-Kriterien war der Patient der High-Risk-Gruppe zuzuordnen. Innerhalb der letzten 120 Tage vor der Intervention traten folgende Symptome auf: 1 TIA, 2 Amaurosis fugax. In der diagnostischen selektiven 4-Gefaess

  10. Left subclavian-carotid bypass in a 38-year old female with brain ischemic symptoms secondary to Takayasu's arteritis: A case report.

    Science.gov (United States)

    Hinojosa, Carlos A; Lizola, Rene; Anaya-Ayala, Javier E; Torres-Machorro, Adriana; Laparra-Escareno, Hugo

    2016-01-01

    Takayasu's arteritis (TA) is a rare form of vasculitis that affects the aorta, its branches and pulmonary arteries. TA is primarily treated by pharmacologic therapy; however revascularization procedures may be required to treat organ ischemia. Evidence-based consensus regarding the indications for surgical or endovascular therapy for patients with supra-aortic vessels lesions remains unclear. We herein present a female patient with known TA since 2000, who experienced progressive and frequent episodes of amaurosis fugax in the left eye for 4 months. Computed tomography angiography (CTA) revealed focal stenotic segments in the right common carotid artery (CCA) and internal carotid artery (ICA) and near occlusion of the proximal left CCA. We opted to treat the left side first with open revascularization, and a subclavian-carotid bypass was performed using a 6 millimeters (mm) externally supported ePTFE graft. Patient recovered well from the surgery, her neurological exam was normal and she was discharged home in stable condition in postoperative day three. At three months she remains symptoms-free and her bypass is patent. This case illustrates the clinical presentation of TA affecting both carotid arteries; open revascularization via carotid subclavian bypass grafting was successfully performed with minimal morbidity, complete resolution of symptoms and improvement of the patient's quality of life. Revascularization procedures when indicated should be performed while the disease is inactive and close surveillance is mandatory. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  11. The Protective Effects of Lycium Barbarum Polysaccharides on Transient Retinal Ischemia

    Directory of Open Access Journals (Sweden)

    Di Yang

    2011-05-01

    Full Text Available Retinal ischemia/reperfusion (I/R injury leads to irreversible neuronal death, glial activation, retinal swelling and oxidative stress. It is a common feature in various ocular diseases, such as glaucoma, diabetic retinopathy and amaurosis fugax. In the present study, we aimed to evaluate the effects of Lycium Barbarum Polysaccharides (LBP in a murine retinal I/R model. Mice were orally treated with either vehicle (PBS or LBP (1mg/kg daily for 1 week before induction of retinal ischemia. Retinae were collected after 2 hours ischemia and 22 hours reperfusion. Paraffin-embedded sections were prepared for immunohistochemical analyses. Significantly fewer viable cells were found in vehicle-treated retinae comparing to LBP group. This finding was further confirmed by TUNEL assay where significantly fewer apoptotic cells were identified in LBP-treated retinae. Additionally, retinal swelling induced by retinal I/R injury in the vehicle-treated group was not observed in LBP-treated group. Moreover, intense GFAP immunoreactivity and IgG extravasation were observed in vehicle-treated group but not in LBP treated group. The results showed that pre-treatment with LBP was protective in retinal I/R injury via reducing neuronal death, apoptosis, retinal swelling, GFAP activation and blood vessel leakage. LBP may be used as a preventive agent for retinal ischemia diseases.

  12. Venous Thromboembolism and Cerebrovascular Events in Patients with Giant Cell Arteritis: A Population-Based Retrospective Cohort Study.

    Directory of Open Access Journals (Sweden)

    Alberto Lo Gullo

    Full Text Available To investigate the incidence of venous thromboembolism (VTE and cerebrovascular events in a community-based incidence cohort of patients with giant cell arteritis (GCA compared to the general population.A population-based inception cohort of patients with incident GCA between January 1, 1950 and December 31, 2009 in Olmsted County, Minnesota and a cohort of non-GCA subjects from the same population were assembled and followed until December 31, 2013. Confirmed VTE and cerebrovascular events were identified through direct medical record review.The study population included 244 patients with GCA with a mean ± SD age at diagnosis of 76.2 ± 8.2 years (79% women and an average length of follow-up of 10.2 ± 6.8 years. Compared to non-GCA subjects of similar age and sex, patients diagnosed with GCA had a higher incidence (% of amaurosis fugax (cumulative incidence ± SE: 2.1 ± 0.9 versus 0, respectively; p = 0.014 but similar rates of stroke, transient ischemic attack (TIA, and VTE. Among patients with GCA, neither baseline characteristics nor laboratory parameters at diagnosis reliably predicted risk of VTE or cerebrovascular events.In this population-based study, the incidence of VTE, stroke and TIA was similar in patients with GCA compared to non-GCA subjects.

  13. Varied presentations of moyamoya disease in a tertiary care hospital of north-east India

    Directory of Open Access Journals (Sweden)

    Papori Borah

    2014-01-01

    Full Text Available Introduction: Moyamoya disease is a chronic progressive cerebrovascular disorder, characterized by stenosis or occlusion of bilateral internal carotid arteries (ICAs, anterior cerebral arteries (ACAs and middle cerebral arteries (MCAs, accompanied by a collateral network of vessels formed at the base of the brain. Ischemia and intracranial hemorrhage are the common typical manifestations. However moyamoya disease has been associated with atypical presentations like headache, seizures and involuntary movements. Although frequently reported from Asian countries like Japan, China and Korea, only few studies reported on clinical manifestations of moyamoya disease from India. Objectives: To study the varied presentations of moyamoya disease in a tertiary care hospital of north-east India. Material and Methods: Relevant investigations were done to rule out other causes of moyamoya syndrome. Results: We report 6 cases of moyamoya disease with varied presentations from a tertiary care referral government hospital. Case 1, 2 and 6 presented with alternating hemiparesis. Case 3 had amaurosis fugax. Case 4 had history suggestive of ischemic stroke and presented with hemichorea. Case 4 had focal seizure as the only manifestation. Cases 4 and 5 notably had stenosis of posterior cerebral artery (PCA in addition to stenosis of bilateral ICAs, ACAs and MCAs. Conclusion: Owing to its low incidence in India, moyamoya disease is easily overlooked as a possible diagnosis. However, because of its progressive nature, it is imperative to diagnose this disease early and offer surgical treatment to the patients.

  14. [Hypercoagulable workup in ophthalmology. When and what].

    Science.gov (United States)

    Muñoz-Negrete, F J; Casas-Lleras, P; Pérez-López, M; Rebolleda, G

    2009-07-01

    Most ophthalmologic disorders secondary to hypercoagulabe state are due to the confluence of congenital and adquired factors. A systematic workup is mandatory. Most of congenital coagulation disorders cause venous trombosis and are inherited autosomal dominantly. In order of frequency these are factor V Leiden mutation (activated protein C resistance), G20210A mutation of the prothrombin gen and protein C, protein S, and antithrombin III deficiencies. Sickle cell anemia can determine arerial and venous thrombosis. In relation with arterial occlusion, the markers most frequently involved are homcysteine fasting levels and the markers of antiphospholipid antibody syndrome. Both of them can also determine venous thrombosis. Several acquired factors can lead to hypoercoagulable state, especially hyperhomocysteinemia, antiphospholipid antibody syndrome, hepatic disease, alcohol and tobacco intake, oral contraceptives, immobilization, surgeries and malignancies. In central venous occlusion is only necessary to rule out hyperhomocysteinemia and antiphospholipid antibody syndrome in young patients without known risk factors. In central artery occlusion, hypercoagulable workup is only recommended for patients less than 50 years-old with unknown emboli source. In this cases protein C, protein S, and antithrombin III deficiencies, homocystein, sickle cell disease and antiphospholipid antibody syndrome will ruled out. In non arteritic ischemic optic neuropathy hypercoagulable work up is not necessary. In amaurosis fugax without known emboli source, it is recommended to rule out etiologies of arterial occlusion, especially antithrombin III deficiencies, homocystein, sickle cell disease and antiphospholipid antibody syndrome.

  15. Amaurose bilateral por menigoencefalite criptocócica: relato de caso Bilateral amaurosis due to cryptococcus meningoencephalitis: case report

    Directory of Open Access Journals (Sweden)

    Ricardo Evangelista Marrocos de Aragão

    2008-02-01

    Full Text Available Meningoencefalite criptocócica é infecção causada por um fungo denominado Cryptococcus neoformans. Duas formas são conhecidas: variação gattii e neoformans. A infecção antes da puberdade é rara. Cerca de metade dos pacientes apresentam algum estado imunossupressivo. O papiledema está presente em um terço dos pacientes por ocasião do diagnóstico. Relatamos um caso de meningoencefalite por criptococose em paciente de oito anos de idade, sem relato de doenças prévias, que evoluiu com amaurose bilateral. O diagnóstico foi confirmado por detecção do C. neoformans, var. gattii. O paciente foi tratado com anfotericina B e dexametasona. Na literatura existem poucos relatos de perda visual permanente após meningite por criptococose. A existência de um protocolo para tratamento de pacientes com papiledema é um fator determinante para evitar a perda visual.Cryptococcal meningitis is caused by the yeast Cryptococcus neoformans. Two varieties are recognized: var. gattii and var. neoformans. It is usually associated with immunosuppressive states, particularly HIV infection. Cryptococcal infection of the central nervous system is uncommon in immunocompetent children and difficult to diagnose. Ocular complications are common. Optic disc swelling was found in 33%. The following report describes a case of meningitis caused by C. neoformans var. gattii in an 8 year-old immunocompetent child who developed optic atrophy. The patient was treated with amphotericin B associated with corticosteroids. Possible therapeutic strategies aimed at reducing visual loss in cryptococcal meningitis have great importance to avoid this important morbidity.

  16. Carotid ultrasonographic and brain computerized tomographic findings in patients with vascular ocular syndromes

    Energy Technology Data Exchange (ETDEWEB)

    Iwamoto, Toshihiko; Matsushima, Chikage; Shimizu, Souichirou; Takasaki, Masaru; Iwasaki, Takuya; Usui, Masahiko [Tokyo Medical Coll. (Japan)

    2002-02-01

    To clarify the characteristics of cerebrovascular lesions in subtypes of vascular ocular syndrome, including amaurosis fugax (AF), retinal artery occlusion (RAO), and retinal vein occlusion (RVO), 93 patients with vascular ocular syndrome were studied by means of carotid ultrasonography (US) and brain computerized tomography (CT). The subjects comprised 21 patients with AF, 37 with RAO, and 35 with RVO who were sequentially given these diagnoses by the department of ophthalmology. On the basis of US findings, carotid lesions were defined as the presence of plaque or stenotic changes. CT findings were assessed for the presence and distribution of low-density areas (LDAs). Mean age was similar in each group, ranging from 64.5 to 67.4 years. The RAO group had high rates of men, hypertension, and smokers. US showed that the prevalence of carotid lesions ipsilateral to the affected eye was high in the RAO group and that severe stenosis and ulcerated plaque were present in 28.6% of the AF group and 45.9% of the RAO group. On CT examination, cerebral infarctions appeared as LDAs in about 10% of the patients in each group, and the incidence and distribution of LDAs were similar. Of 13 patients with cerebral infarction, only 2 were presumably due to carotid lesions; the others had a variety of causes. The discrepancy between US and CT findings was attributed to the small number of patients with cerebral infarction, since most patients had visual defects as an initial symptom. Our results suggest that extracranial carotid lesions, considered to be a major risk factor for stroke, should be carefully assessed in patients with AF or RAO to prevent further stroke. (author)

  17. Symptomatic carotid stenosis and stroke risk in patients with transient ischemic attack according to the tissue-based definition.

    Science.gov (United States)

    Al-Khaled, Mohamed; Scheef, Björn

    2016-10-01

    Symptomatic carotid stenosis (sCS), a common cause of transient ischemic attack (TIA), is correlated with higher stroke risk. We investigated the frequency and associated factors of sCS in patients with TIA and the association between sCS and stroke risk following TIA. Over a three-year period (2011-2013), 861 consecutive patients with TIA, who were admitted to the Department of Neurology at the University of Lübeck, Germany, were included in a monocenter study and prospectively evaluated. Diagnosis of TIA was in accordance with the tissue-based definition (transient neurological symptoms without evidence of infarction by brain imaging). Of 827 patients (mean age, 70 ± 13.2 years; 49.7% women), 64 patients (7.7%; 95% confidence interval [CI], 5.9%-9.7%) exhibited sCS and 3 patients (0.3%) showed an occlusion of the corresponding internal carotid artery. Logistic regression revealed that sCS was associated with male sex (odds ratio [OR], 2.7; 95% CI, 1.2-3.6; p = 0.012), amaurosis fugax (OR, 8.1; 95% CI, 3.4-19-4; p risk was higher in patients with sCS than in those without sCS (6.3% vs. 0.1%; p risk (2.6%) did not differ between the groups (4.7% vs. 2.5%; p = 0.29). SCS appears to be associated with a higher risk of stroke in patients with TIA defined according to the tissue-based definition.

  18. Alternative Splicing of FOXP3 Controls Regulatory T Cell Effector Functions and Is Associated with Human Atherosclerotic Plaque Stability.

    Science.gov (United States)

    Joly, Anne-Laure; Seitz, Christina; Liu, Sang; Kouznetsov, Nikolai V; Gertow, Karl; Westerberg, Lisa S; Paulsson-Berne, Gabrielle; Hansson, Göran K; Andersson, John

    2018-04-04

    Rationale: Regulatory T (Treg) cells suppress immune responses and have been shown to attenuate atherosclerosis. The Treg cell lineage specification factor FOXP3 is essential for Treg cells' ability to uphold immunological tolerance. In humans, FOXP3 exists in several different isoforms, however, their specific role is poorly understood. Objective: To define the regulation and functions of the two major FOXP3 isoforms, FOXP3fl and FOXP3Δ2, as well as to establish whether their expression is associated with ischemic atherosclerotic disease. Methods and Results: Human primary T-cells were transduced with lentiviruses encoding distinct FOXP3 isoforms. The phenotype and function of these cells were analyzed by flow cytometry, in vitro suppression assays and RNA-sequencing. We also assessed the effect of activation on Treg cells isolated from healthy volunteers. Treg cell activation resulted in increased FOXP3 expression that predominantly was made up of FOXP3Δ2. FOXP3Δ2 induced specific transcription of GARP, which functions by tethering the immunosuppressive cytokine TGF-β to the cell membrane of activated Treg cells. RT-PCR was used to determine the impact of alternative splicing of FOXP3 in relation with atherosclerotic plaque stability in a cohort of over 150 patients that underwent carotid endarterectomy. Plaque instability was associated with a lower FOXP3Δ2 transcript usage, when comparing plaques from patients without symptoms and patients with occurrence of recent (<1 month) vascular symptoms including minor stoke, transient ischemic attack or amaurosis fugax. No difference was detected in total levels of FOXP3 mRNA between these two groups. Conclusions: These results suggest that activated Treg cells suppress the atherosclerotic disease process and that FOXP3Δ2 controls a transcriptional program that acts protectively in human atherosclerotic plaques.

  19. Advantage of whole exome sequencing over allele-specific and targeted segment sequencing in detection of novel TULP1 mutation in leber congenital amaurosis

    DEFF Research Database (Denmark)

    Guo, Yiran; Prokudin, Ivan; Yu, Cong

    2015-01-01

    by targeted segment sequencing of 61 regions in 14 causative genes was performed. Subsequently, exome sequencing was undertaken in the proband, unaffected consanguineous parents and two unaffected siblings. Bioinformatic analysis used two independent pipelines, BWA-GATK and SOAP, followed by Annovar and Snp...

  20. Stroke syndromes in young people.

    Science.gov (United States)

    Chambers, B R; Bladin, P F; McGrath, K; Goble, A J

    1981-01-01

    All contributory factors to the unusual occurrence of stroke in young people were evaluated in patients under age 40 admitted to the Stroke Unit of the Austin Hospital in Melbourne, Australia. Over the August 1977 to December 1980 period there were 700 admissions. Of these 14 patients were under the age of 40. There were 7 males and 7 females whose ages ranged from 17-38 years. Each patient was screened for factors which might contribute to premature vascular disease including hypertension, diabetes, smoking, obesity, and hyperlipidemia. In addition, the following tests were performed to exclude an arteritic process: full blood examination; ESR; protein electrophoresis; syphilis serology; and the presence of antinuclear factor. Each of the 14 patients suffered cerebral infarction. A summary of each case is presented in a table. In 9 patients, infarction occurred in the carotid territory of supply. Large cortical infarcts with or without subcortical involvement occurred in cases 1-8, of whom 5 had major vessel occlusion demonstrated angiographically and another had stenosing and ulcerative atheromatous disease at the extracranial carotid bifurcation. In a further 4 patients, infarction occurred within the vertebrobasilar territory and was either confined to the brain stem, the occiptal cortex, or involved both. Angiograms were performed in 2 of these patients and showed irregular narrowing of the vertebral artery which was interpreted as spasm and segmentally narrowing of the basilar artery. The final patient had several ischemic events which included right sided amaurosis fugax, and left frontal, right parieto-occipital and left occipital infarctions. Angiography was normal. All patients survived the stroke and were able to go home. There may be an interrelationship between the pathological findings of Irey et al. (1978) and the effect oral contraceptives (OCs) has on migraine. This is relevant to Case 13. Sustained exposure to OCs may produce the pathological

  1. Non-traumatic neurological emergencies: imaging of cerebral ischemia

    International Nuclear Information System (INIS)

    Grunwald, Iris; Reith, Wolfgang

    2002-01-01

    Cardiovascular disease is the leading cause of death worldwide with almost one-third of all cardiovascular deaths ascribed to stroke. Imaging modalities, such as CT, MRI, positron emission tomography (PET), and single photon emission CT (SPECT) provide tremendous insight into the pathophysiology of acute stroke. Computed tomography is considered the most important initial diagnostic study in patients with acute stroke, because underlying structural lesions, such as tumor, vascular malformation, or subdural hematoma, can mimic stroke clinically. Diffusion-weighted imaging (DWI) has the ability to visualize changes in diffusion within minutes after the onset of ischemia and has become a powerful tool in the evaluation of patients with stroke syndrome. Territories with diffusion and perfusion mismatch may define tissues at risk, but with potential recovery. An alternative strategy with CT technology uses rapid CT for dynamic perfusion imaging, with similar goals in mind. Angiography can be performed in the hyperacute stage if thrombolytic therapy is being considered. Indications for diagnostic angiography include transient ischemic attacks in a carotid distribution, amaurosis fugax, prior stroke in a carotid distribution, a high-grade stenotic lesion in a carotid artery, acquiring an angiographic correlation of magnetic resonance angiography (MRA) or computed tomographic angiography (CTA) concerning stenotic findings. In 50% of all angiograms performed in the hyperacute stage, occlusion of a vessel is observed; however, the need for angiography has been made less necessary due to the improvements of MRA, duplex ultrasound, and CTA. Numerous etiologies can lead to infarction. In children, pediatric stroke is very uncommon. The most common cause is an embolus from congenital heart disease with right-to-left shunts. Also a dissection of large extracranial vessels may result in cerebral infarction, and although the brain is equipped with numerous venous drainage routes

  2. Non-traumatic neurological emergencies: imaging of cerebral ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Grunwald, Iris; Reith, Wolfgang [Department of Neuroradiology, Saarland University Clinic, Homburg/Saar (Germany)

    2002-07-01

    Cardiovascular disease is the leading cause of death worldwide with almost one-third of all cardiovascular deaths ascribed to stroke. Imaging modalities, such as CT, MRI, positron emission tomography (PET), and single photon emission CT (SPECT) provide tremendous insight into the pathophysiology of acute stroke. Computed tomography is considered the most important initial diagnostic study in patients with acute stroke, because underlying structural lesions, such as tumor, vascular malformation, or subdural hematoma, can mimic stroke clinically. Diffusion-weighted imaging (DWI) has the ability to visualize changes in diffusion within minutes after the onset of ischemia and has become a powerful tool in the evaluation of patients with stroke syndrome. Territories with diffusion and perfusion mismatch may define tissues at risk, but with potential recovery. An alternative strategy with CT technology uses rapid CT for dynamic perfusion imaging, with similar goals in mind. Angiography can be performed in the hyperacute stage if thrombolytic therapy is being considered. Indications for diagnostic angiography include transient ischemic attacks in a carotid distribution, amaurosis fugax, prior stroke in a carotid distribution, a high-grade stenotic lesion in a carotid artery, acquiring an angiographic correlation of magnetic resonance angiography (MRA) or computed tomographic angiography (CTA) concerning stenotic findings. In 50% of all angiograms performed in the hyperacute stage, occlusion of a vessel is observed; however, the need for angiography has been made less necessary due to the improvements of MRA, duplex ultrasound, and CTA. Numerous etiologies can lead to infarction. In children, pediatric stroke is very uncommon. The most common cause is an embolus from congenital heart disease with right-to-left shunts. Also a dissection of large extracranial vessels may result in cerebral infarction, and although the brain is equipped with numerous venous drainage routes

  3. Extended Daily Eye Patching Effective at Treating Stubborn Amblyopia in Children

    Science.gov (United States)

    ... Related Macular Degeneration (AMD) AIDS-related eye disease (cytomegalovirus [CMV] retinitis) Amblyopia Anophthalmia and ... Congenital Amaurosis (LCA) Low Vision Macular Degeneration Macular Edema ...

  4. A synopsis of the Malesian species of Kibara (Monimiaceae)

    NARCIS (Netherlands)

    Philipson, W.R.

    1985-01-01

    Thirty-nine species are recognized of which twenty-four are described as new ( K. bullata, K. carrii, K. chimbuensis, K. ferox, K. flagelliformis, K. fragrans, K. fugax, K. hartleyi, K. karengana, K. katikii, K. kostermansii, K. latifolia, K. leachii, K. macrantha, K. nitens, K. novobritanica, K.

  5. NEI You Tube Videos: Amblyopia

    Medline Plus

    Full Text Available ... Education Program (NEHEP) Diabetic Eye Disease Education Program Glaucoma Education Program Low Vision Education Program Hispanic/Latino ... Disease Dilated Eye Exam Dry Eye For Kids Glaucoma Healthy Vision Tips Leber Congenital Amaurosis Low Vision ...

  6. NEI You Tube Videos: Amblyopia

    Medline Plus

    Full Text Available ... Information Frequently asked questions Clinical Studies Publications Catalog Photos and Images Spanish Language Information Grants and Funding ... Eye Disease Dilated Eye Exam Dry Eye For Kids Glaucoma Healthy Vision Tips Leber Congenital Amaurosis Low ...

  7. Glaucoma

    Medline Plus

    Full Text Available ... Information Frequently asked questions Clinical Studies Publications Catalog Photos and Images Spanish Language Information Grants and Funding ... Eye Disease Dilated Eye Exam Dry Eye For Kids Glaucoma Healthy Vision Tips Leber Congenital Amaurosis Low ...

  8. Glaucoma

    Medline Plus

    Full Text Available ... Amaurosis Low Vision Refractive Errors Retinopathy of Prematurity Science Spanish ... Site Map NEI on Social Media Information in Spanish (Información en español) Website, ...

  9. RPE65 gene: multiplex PCR and mutation screening in patients from ...

    Indian Academy of Sciences (India)

    We used multiplex PCR followed by sequencing to screen for mutations in the 14 exons of the RPE65 gene in early-childhood-onset autosomal recessive retinitis pigmentosa (arRP) and Leber's congenital amaurosis (LCA) patients. The RPE65 protein is believed to play an important role in the metabolism of vitamin A in ...

  10. Simultaneous Mutation Detection in 90 Retinal Disease Genes in Multiple Patients Using a Custom-designed 300-kb Retinal Resequencing Chip

    NARCIS (Netherlands)

    Booij, Judith C.; Bakker, Arne 1; Kulumbetova, Jamilia; Moutaoukil, Youssef; Smeets, Bert; Verheij, Joke; Kroes, Hester Y.; Klaver, Caroline C. W.; van Schooneveld, Mary; Bergen, Arthur A. B.; Florijn, Ralph J.

    Purpose: To develop a high-throughput, cost-effective diagnostic strategy for the identification of known and new mutations in 90 retinal disease genes. Design: Evidence-based study. Participants: Sixty patients with a variety of retinal disorders, including Leber's congenital amaurosis, ocular

  11. Glaucoma

    Medline Plus

    Full Text Available ... Jobs Fellowships NEI Summer Intern Program Diversity In Vision Research & Ophthalmology (DIVRO) Student Training Programs To search for ... Glaucoma Healthy Vision Tips Leber Congenital Amaurosis Low Vision Refractive ... NEI Home Contact Us A-Z Site Map NEI on Social Media Information ...

  12. NEI You Tube Videos: Amblyopia

    Medline Plus

    Full Text Available ... Jobs Fellowships NEI Summer Intern Program Diversity In Vision Research & Ophthalmology (DIVRO) Student Training Programs To search for ... Glaucoma Healthy Vision Tips Leber Congenital Amaurosis Low Vision Refractive ... NEI Home Contact Us A-Z Site Map NEI on Social Media Information ...

  13. NEI You Tube Videos: Amblyopia

    Medline Plus

    Full Text Available ... Amaurosis Low Vision Refractive Errors Retinopathy of Prematurity Science Spanish Videos Webinars NEI YouTube Videos: Amblyopia Embedded video for NEI YouTube Videos: Amblyopia NEI Home Contact Us A-Z Site Map NEI on Social Media Information in Spanish (Información en español) Website, ...

  14. Genetic analysis of a consanguineous Pakistani family with Leber ...

    Indian Academy of Sciences (India)

    2014-08-01

    Aug 1, 2014 ... Genetic analysis of a consanguineous Pakistani family with Leber congenital amaurosis identifies a novel mutation in GUCY2D gene. MUZAMMIL AHMAD KHAN1, VERENA RUPP2, MUHAMMAD AYAZ KHAN1, MUHAMMAD PERVAIZ KHAN3,. MUHAMMAD ANSAR4 and CHRISTIAN WINDPASSINGER2 ...

  15. NEI You Tube Videos: Amblyopia

    Science.gov (United States)

    ... NEI YouTube Videos: Amblyopia Listen NEI YouTube Videos YouTube Videos Home Age-Related Macular Degeneration Amblyopia Animations Blindness Cataract Convergence Insufficiency Diabetic Eye Disease Dilated Eye Exam Dry Eye For Kids Glaucoma Healthy Vision Tips Leber Congenital Amaurosis Low ...

  16. Glaucoma

    Science.gov (United States)

    ... NEI YouTube Videos: Glaucoma Listen NEI YouTube Videos YouTube Videos Home Age-Related Macular Degeneration Amblyopia Animations Blindness Cataract Convergence Insufficiency Diabetic Eye Disease Dilated Eye Exam Dry Eye For Kids Glaucoma Healthy Vision Tips Leber Congenital Amaurosis Low ...

  17. Glaucoma

    Medline Plus

    Full Text Available ... NEI YouTube Videos: Glaucoma Listen NEI YouTube Videos YouTube Videos Home Age-Related Macular Degeneration Amblyopia Animations Blindness Cataract Convergence Insufficiency Diabetic Eye Disease Dilated Eye Exam Dry Eye For Kids Glaucoma Healthy Vision Tips Leber Congenital Amaurosis Low ...

  18. NEI You Tube Videos: Amblyopia

    Medline Plus

    Full Text Available ... NEI YouTube Videos: Amblyopia Listen NEI YouTube Videos YouTube Videos Home Age-Related Macular Degeneration Amblyopia Animations Blindness Cataract Convergence Insufficiency Diabetic Eye Disease Dilated Eye Exam Dry Eye For Kids Glaucoma Healthy Vision Tips Leber Congenital Amaurosis Low ...

  19. multiplex PCR and mutation screening in patients from India with ...

    Indian Academy of Sciences (India)

    We used multiplex PCR followed by sequencing to screen for mutations in the 14 exons of the RPE65 gene in early-childhood-onset autosomal recessive retinitis pigmentosa (arRP) and Leber's congenital amaurosis (LCA) patients. The RPE65 protein is believed to play an important role in the metabolism of vitamin A in ...

  20. Journal of Genetics | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    Genetic analysis of a consanguineous Pakistani family with Leber congenital amaurosis identifies a novel mutation in GUCY2D gene. Muzammil Ahmad Khan Verena Rupp Muhammad Ayaz Khan Muhammad Pervaiz Khan Muhammad Ansar Christian Windpassinger. Research Note Volume 93 Issue 2 August 2014 pp ...

  1. NEI You Tube Videos: Amblyopia

    Medline Plus

    Full Text Available ... Macular Degeneration Amblyopia Animations Blindness Cataract Convergence Insufficiency Diabetic Eye Disease Dilated Eye Exam Dry Eye For Kids Glaucoma Healthy Vision Tips Leber Congenital Amaurosis Low Vision Refractive Errors Retinopathy of Prematurity Science Spanish Videos Webinars NEI YouTube ...

  2. Glaucoma

    Medline Plus

    Full Text Available ... Macular Degeneration Amblyopia Animations Blindness Cataract Convergence Insufficiency Diabetic Eye Disease Dilated Eye Exam Dry Eye For Kids Glaucoma Healthy Vision Tips Leber Congenital Amaurosis Low Vision Refractive Errors Retinopathy of Prematurity Science Spanish Videos Webinars NEI YouTube ...

  3. RPE65 gene: multiplex PCR and mutation screening in patients from ...

    Indian Academy of Sciences (India)

    Unknown

    Abstract. We used multiplex PCR followed by sequencing to screen for mutations in the 14 exons of the RPE65 gene in early- childhood-onset autosomal recessive retinitis pigmentosa (arRP) and Leber's congenital amaurosis (LCA) patients. The RPE65 protein is believed to play an important role in the metabolism of ...

  4. Genetic analysis of a consanguineous Pakistani family with Leber ...

    Indian Academy of Sciences (India)

    2014-08-01

    Aug 1, 2014 ... Leber congenital amaurosis (LCA) is an eye condition which ultimately leads to complete blindness. It is a rare hereditary disease with an early onset characterized by severe retinal degeneration, cataract, nystagmus, null pupillary response to light, photophobia and keratoconus (Chung and Traboulsi.

  5. New concept of functional anorectal disorders. In relation to newly published ROME III

    International Nuclear Information System (INIS)

    Takano, Masahiro

    2007-01-01

    In newly published Rome III, Functional anorectal disorders are divided into 7 disorders. F1 Functional fecal incontinence is divided into staining, soiling, seepage and leakage in the degree and urge and passive incontinences in the dynamics, of which the former is dysfunction of the rectum and the latter of the anus. For the treatment, the most effective is biofeedback therapy (BF). F2 Functional anorectal pain is divided into F2a Chronic proctalgia, F2a1 Levator ani syndrome, F2a2 Unspecified functional anorectal pain and F2b Proctalgia fugax. F2a1 Levator ani syndrome is defined as a pain caused by traction of the levator ani, but in my experience, only 4 (3.5%) among 116 cases accorded to the criteria making us dubious of the definition. As for F2b Proctalgia fugax, the cause has not yet been found. In these two F2a, various treatments are tried without significant effectiveness due perhaps to the unknown pathogenesis which I assume to be the neuralgia of pudendal nerve. F3 Functional defecation disorders consist of F3a Dyssynergic defecation and F3b Inadequate defecatory propulsion of which, the former is caused by paradoxical contraction or inadequate relaxation of the pelvic floor muscles and the latter caused by inadequate propulsive force in defecation. Their treatments are BF and defecatory enforcement. (author)

  6. Inherited Retinal Degenerative Disease Registry

    Science.gov (United States)

    2017-09-13

    Eye Diseases Hereditary; Retinal Disease; Achromatopsia; Bardet-Biedl Syndrome; Bassen-Kornzweig Syndrome; Batten Disease; Best Disease; Choroidal Dystrophy; Choroideremia; Cone Dystrophy; Cone-Rod Dystrophy; Congenital Stationary Night Blindness; Enhanced S-Cone Syndrome; Fundus Albipunctatus; Goldmann-Favre Syndrome; Gyrate Atrophy; Juvenile Macular Degeneration; Kearns-Sayre Syndrome; Leber Congenital Amaurosis; Refsum Syndrome; Retinitis Pigmentosa; Retinitis Punctata Albescens; Retinoschisis; Rod-Cone Dystrophy; Rod Dystrophy; Rod Monochromacy; Stargardt Disease; Usher Syndrome

  7. Artery Agenesis: Ipsilateral Common Carotid Artery Hypoplasia

    Directory of Open Access Journals (Sweden)

    Omer Kaya

    2014-01-01

    Full Text Available A 42-year-old female patient, who had been diagnosed with an occlusion of her left internal carotid artery (ICA following Doppler ultrasonographic (US and digitally-subtracted angiographic (DSA examinations performed in an outer healthcare center in order to eliminate the underlying cause of her complaint of amorosis fugax, later applied to our hospital with the same complaint. At Doppler US performed in our hospital’s radiology department, her right common carotid artery (CCA was normal, but her left CCA was hypoplastic. The right internal artery (ICA was validated as normal. At the left side, however, the ICA was apparent only as a stump and it did not demonstrate a continuity. The diagnosis of ICA agenesis was confirmed by the utilization of Doppler US, CT, and DSA imaging, and it was concluded also that ipsilateral CCA hypoplasia could be evaluated as an important clue to the diagnosis of ICA agenesis.

  8. Pain Management in Functional Gastrointestinal Disorders

    Directory of Open Access Journals (Sweden)

    Antonio Vigano

    1995-01-01

    Full Text Available Pain is a common feature in functional gastrointestinal disorders (FGID. An abnormally low visceral sensory threshold, as well as a number of central, spinal and peripheral pain-modulating abnormalities, have been proposed for this syndrome. Clinical aspects of pain associated with irritable esophagus, functional dyspepsia, biliary dysmotility, inflammatory bowel syndrome and proctalgia fugax are reviewed. Because of its unclear pathophysiology, pain expression is the main target for the successful assessment and management of symptomatic FGID. The sensory, cognitive and affective components of pain intensity expression need to be addressed in the context of a good physician-patient rapport. A multidisciplinary team approach is ideal for the smaller subset of patients with severe and disabling symptoms. Although pharmacotherapy may target specific functional disorders, the role of behavioural techniques and psychotherapy appears much more important for pain management in FGID. Functional performance and quality of life improvement, rather than pain intensity, are the main therapeutic goals in these patients.

  9. Moraea intermedia and M. vuvuzela (Iridaceae-Iridoideae, two new species from western South Africa, and some nomenclatural changes and range extensions in the genus

    Directory of Open Access Journals (Sweden)

    P. Goldblatt

    2010-07-01

    Full Text Available We describe two new species in the largely sub-Saharan genus Moraea Mill. (± 205 spp. from its centre of diversity in the winter rainfall region of southern Africa. Moraea intermedia, from north-central Namaqualand near Springbok, is a member of the small section Tubiflorae (now eight species, remarkable in its growth habit with a long basal intemode. leaves clustered at the first aerial node, and Moraea-type stamens and style branches but subequal tepals with very short claws that clasp only the base of the filament column. Moraea vuvuzela. a member of series Galaxia of the Galaxia group of the genus (now 17 species, has deeply fringed stigma lobes, filaments free in the upper 1 mm, ± prostrate, lanceolate leaves and. remarkable for the series, dark brown to purple markings near the base of the tepal limbs. In the unusually variable M.fugax, currently with two subspecies, new collections of subsp. fugax co-occurring but on different soils with subsp.  filicaulis, cast doubt on their current treatment as members of the same species. We now favour recognition of the diminutive subsp.filicaulis as a separate species, M. filicaulis. In the M iripetala group we recommend recognition of the early blooming M. punctata, described in 1892 and later subsumed in M. iripetala but readily distinguished by the long inner  tepals broader in the midline and short, relatively broad, plane rather than channelled leaves. We also report small but significant range extensions for M. barkerae, M. macrocarpa and M. tricolor.

  10. [The migraine of Immanual Kant].

    Science.gov (United States)

    Podoll, K; Hoff, P; Sass, H

    2000-07-01

    The German philosopher Immanuel Kant (1724-1804) suffered, since his forties, from a migraine with aura which showed a significant exacerbation in his seventies, coinciding with the onset of symptoms of a senile dementia of Alzheimer's type. Recorded symptoms of Kant's migraine include recurrent scintillating scotomas, one episode of diplopia, two episodes of complete amaurosis and frequent headaches described as oppressions of the head. The said symptoms of Kant's migraine can be traced not only in his letters and in accounts of his contemporary biographers, but also in the philosopher's published work.

  11. [Progress in research on pathogenic genes and gene therapy for inherited retinal diseases].

    Science.gov (United States)

    Zhu, Ling; Cao, Cong; Sun, Jiji; Gao, Tao; Liang, Xiaoyang; Nie, Zhipeng; Ji, Yanchun; Jiang, Pingping; Guan, Minxin

    2017-02-10

    Inherited retinal diseases (IRDs), including retinitis pigmentosa, Usher syndrome, Cone-Rod degenerations, inherited macular dystrophy, Leber's congenital amaurosis, Leber's hereditary optic neuropathy are the most common and severe types of hereditary ocular diseases. So far more than 200 pathogenic genes have been identified. With the growing knowledge of the genetics and mechanisms of IRDs, a number of gene therapeutic strategies have been developed in the laboratory or even entered clinical trials. Here the progress of IRD research on the pathogenic genes and therapeutic strategies, particularly gene therapy, are reviewed.

  12. Young patient with arterial thrombosis and skin changes as the onset manifestations: POEMS syndrome.

    Science.gov (United States)

    Han, Ting-Ting; Zheng, Shuang; Chen, Zeng-Ai; Liu, Wei; Hu, Yao-Min

    2016-11-08

    POEMS syndrome is a rare multi-systemic disease characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes. Arterial thrombosis is a distinctively unusual feature in patients with POEMS syndrome. We report a 33-year-old man with intermittent amaurosis of left eye and skin changes as the onset manifestations, who was finally confirmed as having POEMS syndrome. Most notably, this was a young man without high risk factors of arterial thrombosis and no monoclonal protein was detected until the repeated measurement later. This case evokes the need to consider the diagnosis of POEMS syndrome for young patients with symptoms of arterial thrombosis but no high risk factors of thrombosis.

  13. Manejo de recaída en enfermedad de Devic. Primer tratamiento exitoso, reportado con plasmaféresis en Ecuador; revisión bibliográfica, actualidad y reporte de caso

    OpenAIRE

    Alemán-Iñiguez, Juan Miguel; Alemán-Iñiguez, Verónica Alexandra; Díaz-Heredia, Fabián

    2015-01-01

    La enfermedad de Devic es una rara patología desmielinizante que afecta al nervio óptico y que se acompaña de sintomatología medular. A continuación se presenta el éxito terapéutico de la plasmaféresis en este caso, como el primero en Ecuador; asimismo caracterizamos el cuadro y analizamos el beneficio del tratamiento en la historia natural de la enfermedad. Se trata de un paciente masculino, adulto, con antecedente de amaurosis súbita, y que comienza con una mielopatía aguda. En ausencia de ...

  14. What was Glaucoma Called Before the 20th Century?

    Science.gov (United States)

    Leffler, Christopher T.; Schwartz, Stephen G.; Giliberti, Francesca M.; Young, Matthew T.; Bermudez, Dennis

    2015-01-01

    Glaucoma involves a characteristic optic neuropathy, often with elevated intraocular pressure. Before 1850, poor vision with a normal eye appearance, as occurs in primary open-angle glaucoma, was termed amaurosis, gutta serena, or black cataract. Few observers noted palpable hardness of the eye in amaurosis. On the other hand, angle-closure glaucoma can produce a green or gray pupil, and therefore was called, variously, glaucoma (derived from the Greek for glaucous, a nonspecific term connoting blue, green, or light gray) and viriditate oculi. Angle closure, with palpable hardness of the eye, mydriasis, and anterior prominence of the lens, was described in greater detail in the 18th and 19th centuries. The introduction of the ophthalmoscope in 1850 permitted the visualization of the excavated optic neuropathy in eyes with a normal or with a dilated greenish-gray pupil. Physicians developed a better appreciation of the role of intraocular pressure in both conditions, which became subsumed under the rubric “glaucoma”. PMID:26483611

  15. Article Commentary: What was Glaucoma Called before the 20th Century?

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    Christopher T. Leffler

    2015-01-01

    Full Text Available Glaucoma involves a characteristic optic neuropathy, often with elevated intraocular pressure. Before 1850, poor vision with a normal eye appearance, as occurs in primary open-angle glaucoma, was termed amaurosis, gutta serena , or black cataract. Few observers noted palpable hardness of the eye in amaurosis. On the other hand, angle-closure glaucoma can produce a green or gray pupil, and therefore was called, variously, glaucoma (derived from the Greek for glaucous, a nonspecific term connoting blue, green, or light gray and viriditate oculi. Angle closure, with palpable hardness of the eye, mydriasis, and anterior prominence of the lens, was described in greater detail in the 18th and 19th centuries. The introduction of the ophthalmoscope in 1850 permitted the visualization of the excavated optic neuropathy in eyes with a normal or with a dilated greenish-gray pupil. Physicians developed a better appreciation of the role of intraocular pressure in both conditions, which became subsumed under the rubric “glaucoma”.

  16. Progress toward the maintenance and repair of degenerating retinal circuitry.

    Science.gov (United States)

    Vugler, Anthony A

    2010-01-01

    Retinal diseases such as age-related macular degeneration and retinitis pigmentosa remain major causes of severe vision loss in humans. Clinical trials for treatment of retinal degenerations are underway and advancements in our understanding of retinal biology in health/disease have implications for novel therapies. A review of retinal biology is used to inform a discussion of current strategies to maintain/repair neural circuitry in age-related macular degeneration, retinitis pigmentosa, and Type 2 Leber congenital amaurosis. In age-related macular degeneration/retinitis pigmentosa, a progressive loss of rods/cones results in corruption of bipolar cell circuitry, although retinal output neurons/photoreceptive melanopsin cells survive. Visual function can be stabilized/enhanced after treatment in age-related macular degeneration, but in advanced degenerations, reorganization of retinal circuitry may preclude attempts to restore cone function. In Type 2 Leber congenital amaurosis, useful vision can be restored by gene therapy where central cones survive. Remarkable progress has been made in restoring vision to rodents using light-responsive ion channels inserted into bipolar cells/retinal ganglion cells. Advances in genetic, cellular, and prosthetic therapies show varying degrees of promise for treating retinal degenerations. While functional benefits can be obtained after early therapeutic interventions, efforts should be made to minimize circuitry changes as soon as possible after rod/cone loss. Advances in retinal anatomy/physiology and genetic technologies should allow refinement of future reparative strategies.

  17. Reversão de amaurose por neuropatia óptica em orbitopatia de Graves após descompressão orbitária: relato de caso Reversal of blindness due to Graves' optic neuropathy after orbital decompression: case report

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    Valmor Rios Leme

    2003-12-01

    Full Text Available OBJETIVO: Descrever o caso de uma paciente portadora de orbitopatia de Graves com baixa visual no olho esquerdo há 9 meses e amaurose no direito há 20 dias secundária à neuropatia óptica. MÉTODOS: Foi realizada descompressão orbitária bilateral ínfero-medial por via transconjuntival. RESULTADOS: Após a cirurgia a paciente evoluiu lentamente com melhora progressiva da acuidade visual, obtendo 20/20 em ambos os olhos ao cabo de 10 meses. CONCLUSÕES: A descompressão orbitária é eficaz em restabelecer a visão em casos de amaurose por neuropatia óptica da orbitopatia de Graves com até 20 dias de instalação.PURPOSE: To describe a patient with Graves' orbitopathy who presented with loss of vision of the left eye for 9 months and amaurosis of the right eye for 20 days. METHODS: Bilateral inferomedial transnconjunctival orbital decompression was performed. RESULTS: After orbital decompression, vision slowly improved and ten months after the surgery the vision was normal in both eyes. CONCLUSIONS: Orbital decompression can reestablish optic nerve function at least 20 days after amaurosis.

  18. Anorectal and Pelvic Pain

    Science.gov (United States)

    Bharucha, Adil E.; Lee, Tae Hee

    2016-01-01

    Although pelvic pain is a symptom of several structural anorectal and pelvic disorders (eg, anal fissure, endometriosis, and pelvic inflammatory disease), this comprehensive review will focus on the three most common nonstructural, or functional, disorders associated with pelvic pain: functional anorectal pain (ie, levator ani syndrome, unspecified anorectal pain, and proctalgia fugax), interstitial cystitis/bladder pain syndrome, and chronic prostatitis/chronic pelvic pain syndrome. The first two conditions occur in both sexes, while the latter occurs only in men. They are defined by symptoms, supplemented with levator tenderness (levator ani syndrome) and bladder mucosal inflammation (interstitial cystitis). Although distinct, these conditions share several similarities, including associations with dysfunctional voiding or defecation, comorbid conditions (eg, fibromyalgia, depression), impaired quality of life, and increased health care utilization. Several factors, including pelvic floor muscle tension, peripheral inflammation, peripheral and central sensitization, and psychosocial factors, have been implicated in the pathogenesis. The management is tailored to symptoms, is partly supported by clinical trials, and includes multidisciplinary approaches such as lifestyle modifications and pharmacologic, behavioral, and physical therapy. Opioids should not be avoided, and surgery has a limited role, primarily in refractory interstitial cystitis. PMID:27712641

  19. Clinical features of unspecified functional bowel disorder in servicemen from a Chinese army unit

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    Xin YAO

    2017-02-01

    Full Text Available Objective To investigate clinical manifestation of unspecified functional bowel disorder (UFBD, the features of coexistence with functional gastrointestinal disorder (FGID and its relationship with psychological factors and sleep disturbance in the Chinese Army servicemen. Methods cFGIDs were diagnosed based on the Rome Ⅲ Modular Questionnaire. The subjects were 189 servicemen with UFBD (UFBD group and 372 without FGID (control group. All subjects completed symptom checklist 90 (SCL-90 and Pittsburgh Sleep Quality Index (PSQI questionnaire. Results 'Have to rush to the toilet when having a desire to defecate' was the most frequent symptom of UFBD (93.7%. More than one half of UFBD patients had the symptom 'a feeling of incomplete emptying as bowel movements' or 'straining during bowel movements'. Twenty-eight percent of UFBD subjects had combined FGID (namely cFGID. Among them, the most frequent was proctalgia fugax (7.9%, followed by cyclic vomiting syndrome (6.3%, functional fecal incontinence (6.3%, functional dyspepsia (4.8% and belching (4.8%. The UFBD group scored significantly higher than the control group in the global severity index (GSI and in all SCL-90 subscales (P0.05. Conclusion Pathogenesis of UFBD may be closely correlated with psychiatric and psychological factors and sleep disturbance. cFGID are associated with an increased severity of psychopathological features. DOI: 10.11855/j.issn.0577-7402.2017.01.15

  20. Chronic idiopathic anal pain. Results of a diagnostic-therapeutic protocol in a colorectal referral unit.

    Science.gov (United States)

    Armañanzas, Laura; Arroyo, Antonio; Ruiz-Tovar, Jaime; López, Alberto; Santos, Jair; Moya, Pedro; Gómez, María Amparo; Candela, Fernando; Calpena, Rafael

    2015-01-01

    Chronic idiopathic anal pain (CIAP) remains a diagnosis of exclusion. Its study and management still lack a standardized protocol. The aim of this study is to evaluate the results obtained with the diagnostic-therapeutic protocol established in our service. We performed a retrospective study of patients diagnosed with CIAP at the Colorectal Unit of the General University Hospital of Elche, between 2005 and 2011. We evaluated 57 patients with a diagnosis of chronic anal pain for functional anorectal disease (FAD). After the application of our diagnostic protocol, final diagnosis of chronic anal pain (CAP) was achieved in 43 cases (75%), including 22 cases of descending perineum syndrome, 12 of proctalgia fugax, 2 of pudendal neuritis and 7 of coccydynia. In 14 patients exclusion diagnosis of CIAP was established. Among the therapies used on patients with CIAP, biofeedback combined with conservative measures improved symptoms in 43% of the cases. Sacral nerve stimulation was assessed in patients who did not respond to other treatments. Through proper anamnesis, physical examination and complementary tests, a specific diagnosis of the cause of CAP by FAD can be achieved, reducing exclusion diagnosis of CIAP to 25% of cases. Conservative measures combined with biofeedback achieved an improvement in pain in more than 40% of the cases of CIAP in our study. Sacral nerve stimulation can be considered as a treatment option in refractory cases. Copyright © 2013 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. [Changes introduced into the recent International Classification of Headache Disorders: ICHD-III beta classification].

    Science.gov (United States)

    Belvis, Robert; Mas, Natàlia; Roig, Carles

    2015-01-16

    The International Headache Society (IHS) has published the third edition of the International Classification of Headache Disorders (ICHD-III beta), the most commonly used guide to diagnosing headaches in the world. To review the recent additions to the guide, to explain the new entities that appear in it and to compare the conditions that have had their criteria further clarified against the criteria in the previous edition. We have recorded a large number of clarifications in the criteria in practically all the headaches and neuralgias in the classification, but the conditions that have undergone the most significant clarifications are chronic migraine, primary headache associated with sexual activity, short-lasting unilateral neuralgiform headache attacks, new daily persistent headache, medication-overuse headache, syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis. The most notable new entities that have been incorporated are external-compression headache, cold-stimulus headache, nummular headache, headache attributed to aeroplane travel and headache attributed to autonomic dysreflexia. Another point to be highlighted is the case of the new headaches (still not considered entities in their own right) included in the appendix, some of the most noteworthy being epicrania fugax, vestibular migraine and infantile colic. The IHS recommends no longer using the previous classification and changing over to the new classification (ICHD-III beta) in healthcare, teaching and research, in addition to making this new guide as widely known as possible.

  2. Revisión bibliográfica sobre la influencia de la baja visión en el estado socioemocional y la calidad de vida de los pacientes mayores

    OpenAIRE

    García Manjarrés, Marta

    2014-01-01

    En esta revisión bibliográfica se objetiva la dificultad de establecer una definición universal para la baja visión a lo largo de la historia. Se puede apreciar cómo los conceptos y definiciones han ido modificándose y evolucionando con el tiempo. Sólo la ceguera total o amaurosis implica ausencia de visión. Pero la mayoría de las personas a las que llamamos comúnmente “ciegas” conservan restos visuales que pueden ser útiles en su vida diaria. Así, entre la ceguera y la visión ...

  3. Rathke's cleft cyst associated with pituitary granulomatosis with polyangiitis: An unusual combination of hypothalamus-pituitary region pathologies

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    Riccardo Draghi, MD

    2018-02-01

    Full Text Available The authors present an unusual case of a patient suffering from visual deficit due to pituitary granulomatosis with polyangiitis (GPA associated with Rathke's cleft cyst (RCC. The patient was referred to our Neurosurgery Department presenting right eye amaurosis, third cranial nerve palsy, and left temporal hemianopsia. Magnetic resonance imaging documented a sellar or suprasellar lesion with solid and cystic components. The dura mater of the skull base was also strongly enhanced. The patient underwent surgery. Histologic examination revealed RCC associated with pituitary GPA. To our knowledge, this is the first reported case of concomitant pituitary GPA and RCC. Pituitary involvement in GPA is rare, usually diagnosed in hormonal dysfunctions. The patient in case first presented optic chiasm compression, probably due to inflammation of both the pituitary gland and the previously asymptomatic RCC. We focus on the symptoms that led us to diagnose GPA pituitary involvement and on the peculiar and unusual Magnetic resonance imaging of the case presented.

  4. An unusual case of a serious blunt injury of the eye

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    Jovanović Miloš

    2009-01-01

    Full Text Available Introduction. Optic nerve avulsion is a serious injury of the eye. The objective of the paper was to present the peculiarity of the eye injury caused by a penetrating orbital wound with foreign body being retained in the orbit. Case report. A 15-year-old boy who sustained injury by chain link is presented. While he was turning the chain round in his hand, the last link broke off, piercing the lower lid, penetrated the left orbital cavity and remained behind the eyeball at the top of orbit. While passing towards the top of the orbit, the foreign body caused a blunt injury of the eyeball and avulsion of the ocular nerve. The accurate localization of the foreign body was verified by X-ray and CT imaging. The foreign body was removed through the entry wound. The eye injury resulted in amaurosis. Conclusion. This injury was one of those that could have been prevented.

  5. [Extrapontine osmotic myelinolysis].

    Science.gov (United States)

    Silva, Federico A; Rueda-Clausen, Christian F; Ramírez, Fabián

    2005-06-01

    Extrapontine osmotic myelinolysis is a rare nervous system complication. Symptoms of this malady were presented during the clinical examination of a 49-year-old alcoholic male, who arrived at the hospital emergency room in a state of cardiorespiratory arrest. After resuscitation methods were applied, the patient was found in metabolic acidosis (pH 7.014) and was treated with sodium bicarbonate. Forty-eight hours later, sodium levels in the patient had risen from 142 to 174 mEq/l. During the period of clinical observation, the patient showed signs of cognitive impairment, disartria, bilateral amaurosis, hyporeflexia and right-half body hemiparesias. After 72 hours, computer tomography was applied; this showed a bilateral lenticular hypodensity with internal and external capsule compromise. One month later, when the patient was referred to another institution for rehabilitation, the patient showed cognitive impairment, bilateral optic atrophy, residual disartria, bradikynesia and double hemiparesia.

  6. Surgical Management of a Patient with Anterior Megalophthalmos, Lens Subluxation, and a High Risk of Retinal Detachment

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    María Carmen Guixeres Esteve

    2017-01-01

    Full Text Available The early development of lens opacities and lens subluxation are the most common causes of vision loss in patients with anterior megalophthalmos (AM. Cataract surgery in such patients is challenging, however, because of anatomical abnormalities. Intraocular lens dislocation is the most common postoperative complication. Patients with AM also seem to be affected by a type of vitreoretinopathy that predisposes them to retinal detachment. We here present the case of a 36-year-old man with bilateral AM misdiagnosed as simple megalocornea. He had a history of amaurosis in the right eye due to retinal detachment. He presented with vision loss in the left eye due to lens subluxation. Following the removal of the subluxated lens, it was deemed necessary to perform a vitrectomy in order to prevent retinal detachment. Seven months after surgery, an Artisan® Aphakia iris-claw lens was implanted in the anterior chamber. Fifteen months of follow-up data are provided.

  7. Central retinal artery occlusion after phacoemulsification under peribulbar anaesthesia: Pathogenic hypothesis.

    Science.gov (United States)

    Rodríguez Villa, S; Salazar Méndez, R; Cubillas Martín, M; Cuesta García, M

    2016-01-01

    A 77-year-old patient had uneventful cataract surgery in the right eye under peribulbar anaesthesia. The next day, a severe and progressive eyelid swelling was noted, caused by an unknown allergic reaction to povidone-iodine. The allergic signs dissapeared by the fifth day, but amaurosis and a cherry-red spot were detected. Doppler ultrasound and CT angiography confirmed an 80% ipsilateral internal carotid artery stenosis. Retinal vascular occlusion after orbital loco-regional anaesthesia is rare. When this complication occurs, carotid disease, and local or systemic factors, should be evaluated. Copyright © 2015 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  8. In Vitro Modeling Using Ciliopathy-Patient-Derived Cells Reveals Distinct Cilia Dysfunctions Caused by CEP290 Mutations

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    Hiroko Shimada

    2017-07-01

    Full Text Available Mutations in CEP290, a transition zone protein in primary cilia, cause diverse ciliopathies, including Leber congenital amaurosis (LCA and Joubert-syndrome and related disorders (JSRD. We examined cilia biogenesis and function in cells derived from CEP290-LCA and CEP290-JSRD patients. CEP290 protein was reduced in LCA fibroblasts with no detectable impact on cilia; however, optic cups derived from induced pluripotent stem cells (iPSCs of CEP290-LCA patients displayed less developed photoreceptor cilia. Lack of CEP290 in JSRD fibroblasts resulted in abnormal cilia and decreased ciliogenesis. We observed selectively reduced localization of ADCY3 and ARL13B. Notably, Hedgehog signaling was augmented in CEP290-JSRD because of enhanced ciliary transport of Smoothened and GPR161. These results demonstrate a direct correlation between the extent of ciliogenesis defects in fibroblasts and photoreceptors with phenotypic severity in JSRD and LCA, respectively, and strengthen the role of CEP290 as a selective ciliary gatekeeper for transport of signaling molecules in and out of the cilium.

  9. RE-EDUCATIVE METHOD IN THE PROCESS OF MINIMIZING OF AUTOAGRESIVE WAYS OF BEHAVIOR

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    Nenad GLUMBIC

    1999-05-01

    Full Text Available Autoagressive behavior is a relatively frequent symptom of mental disturbances and behavior disturbances which are the subject of professional engagement of clinically oriented defectologists. In the process of rehabilitation numerous methods are used, from behavioral to psychopharmacological ones by which the above mentioned problems are eliminated of softened.The paper deals with four children with different diagnosis (autism, disintegrative psychosis, Patau syndrome and amaurosis that have the same common denominator-mental retardation and autoagression.We have tried to point out-by the description of a study case as well as the ways od work with these children-an application possibly of the particular methods of general and special re-education of psychomotorics in the process of autoagressive ways of behavior minimizing.The paper gives the autor’s notion of indications for re-educative method application with in the multihandicapped children population. Defectological treatment discovers new forms of existence in the existential field, not only to the retarded child but also to the very therapist. Epistemological consequences of the mentioned transfer are given in details in the paper.

  10. C2 Domains as Protein-Protein Interaction Modules in the Ciliary Transition Zone

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    Kim Remans

    2014-07-01

    Full Text Available RPGR-interacting protein 1 (RPGRIP1 is mutated in the eye disease Leber congenital amaurosis (LCA and its structural homolog, RPGRIP1-like (RPGRIP1L, is mutated in many different ciliopathies. Both are multidomain proteins that are predicted to interact with retinitis pigmentosa G-protein regulator (RPGR. RPGR is mutated in X-linked retinitis pigmentosa and is located in photoreceptors and primary cilia. We solved the crystal structure of the complex between the RPGR-interacting domain (RID of RPGRIP1 and RPGR and demonstrate that RPGRIP1L binds to RPGR similarly. RPGRIP1 binding to RPGR affects the interaction with PDEδ, the cargo shuttling factor for prenylated ciliary proteins. RPGRIP1-RID is a C2 domain with a canonical β sandwich structure that does not bind Ca2+ and/or phospholipids and thus constitutes a unique type of protein-protein interaction module. Judging from the large number of C2 domains in most of the ciliary transition zone proteins identified thus far, the structure presented here seems to constitute a cilia-specific module that is present in multiprotein transition zone complexes.

  11. The human visual cortex responds to gene therapy–mediated recovery of retinal function

    Science.gov (United States)

    Ashtari, Manzar; Cyckowski, Laura L.; Monroe, Justin F.; Marshall, Kathleen A.; Chung, Daniel C.; Auricchio, Alberto; Simonelli, Francesca; Leroy, Bart P.; Maguire, Albert M.; Shindler, Kenneth S.; Bennett, Jean

    2011-01-01

    Leber congenital amaurosis (LCA) is a rare degenerative eye disease, linked to mutations in at least 14 genes. A recent gene therapy trial in patients with LCA2, who have mutations in RPE65, demonstrated that subretinal injection of an adeno-associated virus (AAV) carrying the normal cDNA of that gene (AAV2-hRPE65v2) could markedly improve vision. However, it remains unclear how the visual cortex responds to recovery of retinal function after prolonged sensory deprivation. Here, 3 of the gene therapy trial subjects, treated at ages 8, 9, and 35 years, underwent functional MRI within 2 years of unilateral injection of AAV2-hRPE65v2. All subjects showed increased cortical activation in response to high- and medium-contrast stimuli after exposure to the treated compared with the untreated eye. Furthermore, we observed a correlation between the visual field maps and the distribution of cortical activations for the treated eyes. These data suggest that despite severe and long-term visual impairment, treated LCA2 patients have intact and responsive visual pathways. In addition, these data suggest that gene therapy resulted in not only sustained and improved visual ability, but also enhanced contrast sensitivity. PMID:21606598

  12. Assessment of Hereditary Retinal Degeneration in the English Springer Spaniel Dog and Disease Relationship to an RPGRIP1 Mutation

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    Kristina Narfström

    2012-01-01

    Full Text Available Intensive breeding and selection on desired traits have produced high rates of inherited diseases in dogs. Hereditary retinal degeneration, often called progressive retinal atrophy (PRA, is prevalent in dogs with disease entities comparable to human retinitis pigmentosa (RP and Leber’s congenital amaurosis (LCA. Recent molecular studies in the English Springer Spaniel (ESS dog have shown that PRA cases are often homozygous for a mutation in the RPGRIP1 gene, the defect also causing human RP, LCA, and cone rod dystrophies. The present study characterizes the disease in a group of affected ESS in USA, using clinical, functional, and morphological studies. An objective evaluation of retinal function using electroretinography (ERG is further performed in a masked fashion in a group of American ESS dogs, with the examiner masked to the genetic status of the dogs. Only 4 of 6 homozygous animals showed clinical signs of disease, emphasizing the need and importance for more precise studies on the clinical expression of molecular defects before utilizing animal models for translational research, such as when using stem cells for therapeutic intervention.

  13. HHV-6 encephalitis in pediatric pazient: case report

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    Agata Calvario

    2009-12-01

    Full Text Available We report the case of a seventeen-month-old child, with a monocular amaurosis, hospitalized for inconsolable crying followed by a deep sleepiness.At neurological examination, and in the absence of clearly focal neurological signs, the child seemed drowsy and could wake only by moderately intense stimuli.A modest metabolic acidosis and an occasional delay of brain electrical activity at EEG, especially on posterior regions of the right hemisphere, were reported. Cranial CT scan, encephalic NMR and ECG were negative. Standard analysis and isofocusing of cerebro-spinal fluid (CSF were normal, while the virological analysis by Real Time PCR, performed on CSF and whole blood, revealed the presence of HHV-6 DNA. Guthrie Card, tested in triplicate, was positive for HHV-6 and negative for CMV. An antiviral, antibiotic and glucorticoid therapy was started. Following clinical improvement, the little patient was dismissed with a diagnosis of HHV-6 encephalitis. Neurological damages linked to HHV-6 are documented in pediatric patients. But while the infection is suspected of possible vertical viral transmission, HHV-6 remains a little known and misdiagnosed virus.

  14. [Balloon occlusion test of the internal carotid artery for evaluating resectability of blood vessel infiltrating cervical metastasis of advanced head and neck cancers--Heidelberg experience].

    Science.gov (United States)

    Dietz, A; von Kummer, R; Adams, H P; Kneip, M; Galito, P; Maier, H

    1993-11-01

    During the last two years 17 patients of the ENT-Department of the University of Heidelberg suffering from squamous-cell carcinomas of the head and neck underwent a balloon occlusion test of the internal carotid artery (ICA). The investigation was performed because of tumorous infiltration of the large cervical vessels. The balloon occlusion of the ICA was accomplished at the Department of Neuroradiology of the University of Heidelberg. While stopping bloodflow in the ICA of one side for 15-20 min, clinical, electrophysiological and Doppler sonographic monitoring was performed, to detect severe cerebral complications. The specific electrophysiological monitoring contained the detection of MSSEP's (median nerve stimulated somatosensorial evoked potentials) and TCMEP's (transcortical motor evoked potentials) during test occlusion. Balloon occlusion was not possible in three patients because of severe arteriosclerosis. Test occlusion had to be discontinued in three patients because of clinical complications (temporary amaurosis, orthostatic complications). Finally, seven patients showed contraindications during test occlusion for permanent occlusion of the ICA. Four patients had a permanent occlusion of the ICA after tumour resection. In two patients the ICA was removed without problems in test occlusion. The third patient underwent a permanent carotid occlusion because of bleeding complications (in spite of poor clinical tolerance of the test occlusion). In the fourth patient, only intraoperative neuromonitoring with MSSEP's was conducted before permanent carotid occlusion. All four patients did not show any neurological deficits after resection of the ICA. Neurophysiological monitoring played an important role in predicting cerebral complications after permanent occlusion of the ICA.

  15. Present-day conservative treatment retinopathy of prematurity.

    Science.gov (United States)

    Monika, Modrzejewska; Katarzyna, Kubasik-Kładna; Leszek, Kuprjanowicz

    2013-01-01

    Retinopathy of prematurity occurs in prematurely born babies. Etiology of disease is multifactorial and frequency of retinopathy of prematurity diagnosis increases. Retinopathy is one of causes for major loss of vision and amaurosis in newborns around the world. Low efficacy of treatment leads to necessity for looking for new solutions and modern therapy use in treatment of this disease. So far, therapies used are: laser and cryotherapy and cases of retina detachment, the course is combined with surgical procedures of sclera and vitrectomy. The aim of the paper was detailed observation of available literature concerning new methods of management in retinopathy of prematurity. Newest reviews on role of vascular endothelial growth factor secreted under the influence of hypoxia indicate that it takes part in angiogenesis and neovascularization. Thus, in retinopathy of prematurity management vitreous application of vascular endothelial growth factor inhibitors such as ranibizumab, bevacizumab are used as supplement or treatment combined with laser therapy or surgical procedures, however there are many controversies on this form of treatment. Recently there has been an interest in vitreous application of Triamcinolon and other experimental substances inhibiting fibro-vascular proliferations in mouse models of retinopathy of prematurity. Hopes connected with high efficacy of retinopathy of prematurity treatment are also related to use of gene therapy, beta-blockers, supplementation with Omega-3 acids, matrix metalloproteinase-2 inhibitors, gold nanoparticles-GNP and anthrax lethal toxin.

  16. Clinical features of paralytic strabismus

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    Xin-Ling Wang

    2013-09-01

    Full Text Available AIM: To observe the clinical features of paralytic strabismus and analyze its etiology.METHODS: Eighty-nine cases(97 eyeswere diagnosed with paralytic strabismus and recruited in this study in the Department of Ophthalmology, the Fourth Affiliated Hospital, China Medical University between July 2008 and February 2013. The clinical data were recorded including the general and ophthalmic history, symptom, visual acuity, fundus, pupil, eyelid, visual field, eye movement, synoptophore, acting countervail head, ultrasound of eyeball and ocular muscle, color Doppler ultrasonography of the carotid artery, orbital computed tomography(CT, brain magnetic resonance imaging(MRI, blood biochemistry and immunologic tests.RESULTS: The medical history disclosed that among these cases, hypertension in 36 cases, diabetic mellitus in 28 cases, hyperlipidemia in 19 cases, heart diseases in 17 cases, ischemic cerebrovascular disease in 12 cases and hyperthyroidism in 3 cases. Symptoms included vertigo in 47 cases and binocular temporal amaurosis in 36 cases. The horizontal restriction was manifested in 38 cases 45 eyes, vertical restriction in 42 cases with 42 eyes, and horizontal-and-vertical restriction in 9 cases with 10 eyes. CONCLUSION: Brain vascular ischemic disease is one of the top reasons causing paralytic strabismus. Systemic disease history was found in a high proportion of the cases. It is of great essence to detect the life-threatening ischemia of vertebrobasilar artery system and take priority for treatment.

  17. Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of childhood blindness.

    Science.gov (United States)

    Acland, Gregory M; Aguirre, Gustavo D; Bennett, Jean; Aleman, Tomas S; Cideciyan, Artur V; Bennicelli, Jeannette; Dejneka, Nadine S; Pearce-Kelling, Susan E; Maguire, Albert M; Palczewski, Krzysztof; Hauswirth, William W; Jacobson, Samuel G

    2005-12-01

    The short- and long-term effects of gene therapy using AAV-mediated RPE65 transfer to canine retinal pigment epithelium were investigated in dogs affected with disease caused by RPE65 deficiency. Results with AAV 2/2, 2/1, and 2/5 vector pseudotypes, human or canine RPE65 cDNA, and constitutive or tissue-specific promoters were similar. Subretinally administered vectors restored retinal function in 23 of 26 eyes, but intravitreal injections consistently did not. Photoreceptoral and postreceptoral function in both rod and cone systems improved with therapy. In dogs followed electroretinographically for 3 years, responses remained stable. Biochemical analysis of retinal retinoids indicates that mutant dogs have no detectable 11-cis-retinal, but markedly elevated retinyl esters. Subretinal AAV-RPE65 treatment resulted in detectable 11-cis-retinal expression, limited to treated areas. RPE65 protein expression was limited to retinal pigment epithelium of treated areas. Subretinal AAV-RPE65 vector is well tolerated and does not elicit high antibody levels to the vector or the protein in ocular fluids or serum. In long-term studies, wild-type cDNA is expressed only in target cells. Successful, stable restoration of rod and cone photoreceptor function in these dogs has important implications for treatment of human patients affected with Leber congenital amaurosis caused by RPE65 mutations.

  18. Genetic Testing in Pediatric Ophthalmology.

    Science.gov (United States)

    Verma, Ishwar Chander; Paliwal, Preeti; Singh, Kanika

    2018-03-01

    The authors review the utility of genetic testing in ophthalmic disorders - precise diagnosis, accurate prognosis, genetic counseling, prenatal diagnosis, and entry into gene-specific therapeutic trials. The prerequisites for a successful outcome of a genetic test are an accurate clinical diagnosis, a careful family history that guides which genes to study, and genetic counseling (both pre-test and post-test). The common eye disorders for which genetic testing is commonly requested are briefly discussed - anophthalmia, microphthalmia, coloboma, anterior segment dysgenesis, corneal dystrophies, cataracts, optic atrophy, congenital glaucoma, congenital amaurosis, retinitis pigmentosa, color blindness, juvenile retinoshisis, retinoblastoma etc. A protocol for genetic testing is presented. If specific mutations in a gene are common, they should form the first tier test, as the mutations in Leber hereditary optic neuropathy. If mutations in one gene are likely, sequencing of that gene should be carried out, e.g. GALT gene in galactosemia, RS1 gene in retinoshisis. Disorders with genetic heterogeneity require multi-gene panel tests, and if these show no abnormality, then deletion / duplication or microarray studies are recommended, followed in sequence by clinical exome (5000 to 6000 genes), full exome (about 20,000 genes or whole genome studies (includes all introns). It is fortunate that most genetic tests in ophthalmology are available in India, including gene panel and whole exome/genome sequencing tests.

  19. Control of the Nucleotide Cycle in Photoreceptor Cell Extracts by Retinal Degeneration Protein 3

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    Hanna Wimberg

    2018-02-01

    Full Text Available Retinal degeneration protein 3 (RD3 is crucial for photoreceptor cell survival and linked to Leber Congenital Amaurosis type 12 (LCA12, a hereditary retinal disease in humans. RD3 inhibits photoreceptor guanylate cyclases GC-E and GC-F and is involved in transport of GCs from the inner to the outer segments. Otherwise, its role in photoreceptor physiology is poorly understood. Here, we describe a new function of RD3. Purified RD3 evoked an increase in guanylate kinase activity, an enzyme that is involved in the nucleotide cycle in photoreceptors. We demonstrate a direct interaction between guanylate kinase and RD3 using back-scattering interferometry and show by immunohistochemistry of mouse retina sections that RD3 and guanylate kinase co-localize in photoreceptor inner segments and to a lesser extent in the outer plexiform layer. Our findings point toward a more complex function of RD3 in photoreceptors. The RD3 – guanylate kinase interaction may also play a role in other cellular systems, while the GC – RD3 interaction is exclusive to photoreceptors.

  20. Synaptogenesis and outer segment formation are perturbed in the neural retina of Crx mutant mice

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    Raviola Elio

    2005-01-01

    Full Text Available Abstract Background In Leber's congenital amaurosis (LCA, affected individuals are blind, or nearly so, from birth. This early onset suggests abnormal development of the neural retina. Mutations in genes that affect the development and/or function of photoreceptor cells have been found to be responsible in some families. These examples include mutations in the photoreceptor transcription factor, Crx. Results A Crx mutant strain of mice was created to serve as a model for LCA and to provide more insight into Crx's function. In this study, an ultrastructural analysis of the developing retina in Crx mutant mice was performed. Outer segment morphogenesis was found to be blocked at the elongation stage, leading to a failure in production of the phototransduction apparatus. Further, Crx-/- photoreceptors demonstrated severely abnormal synaptic endings in the outer plexiform layer. Conclusions This is the first report of a synaptogenesis defect in an animal model for LCA. These data confirm the essential role this gene plays in multiple aspects of photoreceptor development and extend our understanding of the basic pathology of LCA.

  1. The ADAMTS18 gene is responsible for autosomal recessive early onset severe retinal dystrophy

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    Peluso Ivana

    2013-01-01

    Full Text Available Abstract Background Inherited retinal dystrophies, including Retinitis Pigmentosa and Leber Congenital Amaurosis among others, are a group of genetically heterogeneous disorders that lead to variable degrees of visual deficits. They can be caused by mutations in over 100 genes and there is evidence for the presence of as yet unidentified genes in a significant proportion of patients. We aimed at identifying a novel gene for an autosomal recessive form of early onset severe retinal dystrophy in a patient carrying no previously described mutations in known genes. Methods An integrated strategy including homozygosity mapping and whole exome sequencing was used to identify the responsible mutation. Functional tests were performed in the medaka fish (Oryzias latipes model organism to gain further insight into the pathogenic role of the ADAMTS18 gene in eye and central nervous system (CNS dysfunction. Results This study identified, in the analyzed patient, a homozygous missense mutation in the ADAMTS18 gene, which was recently linked to Knobloch syndrome, a rare developmental disorder that affects the eye and the occipital skull. In vivo gene knockdown performed in medaka fish confirmed both that the mutation has a pathogenic role and that the inactivation of this gene has a deleterious effect on photoreceptor cell function. Conclusion This study reveals that mutations in the ADAMTS18 gene can cause a broad phenotypic spectrum of eye disorders and contribute to shed further light on the complexity of retinal diseases.

  2. Greek mythology: the eye, ophthalmology, eye disease, and blindness.

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    Trompoukis, Constantinos; Kourkoutas, Dimitrios

    2007-06-01

    In distant eras, mythology was a form of expression used by many peoples. A study of the Greek myths reveals concealed medical knowledge, in many cases relating to the eye. An analysis was made of the ancient Greek texts for mythological references relating to an understanding of vision, visual abilities, the eye, its congenital and acquired abnormalities, blindness, and eye injuries and their treatment. The Homeric epics contain anatomical descriptions of the eyes and the orbits, and an elementary knowledge of physiology is also apparent. The concept of the visual field can be seen in the myth of Argos Panoptes. Many myths describe external eye disease ("knyzosis"), visual disorders (amaurosis), and cases of blinding that, depending on the story, are ascribed to various causes. In addition, ocular motility abnormalities, congenital anomalies (cyclopia), injuries, and special treatments, such as the "licking" method, are mentioned. The study of mythological references to the eye reveals reliable medical observations of the ancient Greeks, which are concealed within the myths.

  3. [Metastasis of a pleomorphic adenoma].

    Science.gov (United States)

    Eladioui, K; Ntima, A; Noublanche, P; Cucherousset, N; Attar, A

    2008-06-01

    A 53-year-old man underwent a right parotidectomy in 1993 for a pleomorphic adenoma. The tumor relapsed locally, three years later, imposing a reoperation. The histology was unchanged. Two years later, the excision of a new local recurrence revealed a histological evolution with intravascular emboli, some cellular atypia and some mitoses. One year later, in a context of cephalgia and amaurosis, metastases were discovered on the calvarial skull. These were treated by radiotherapy. The patient died of a cerebral hemorrhage related to a history of familial autoimmune thrombocytopenia. Regional and systemic metastases of pleomorphic adenomas are exceptional. The local recurrence is characteristic of metastatic forms of pleomorphic adenomas; it occurs in 90% of the cases. No clinical or histological criterion allows distinguishing between recurrent metastatic forms and non-recurrent metastatic pleomorphic adenomas. The metastatic mechanism is not clearly elucidated yet. The best treatment for metastases of a pleomorphic adenoma is surgical excision. The recurrence after a complete surgical excision is rare and the prognosis excellent.

  4. Visual electrophysiology in children

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    Jelka Brecelj

    2005-10-01

    Full Text Available Background: Electrophysiological assessment of vision in children helps to recognise abnormal development of the visual system when it is still susceptible to medication and eventual correction. Visual electrophysiology provides information about the function of the retina (retinal pigment epithelium, cone and rod receptors, bipolar, amacrine, and ganglion cells, optic nerve, chiasmal and postchiasmal visual pathway, and visual cortex.Methods: Electroretinograms (ERG and visual evoked potentials (VEP are recorded non-invasively; in infants are recorded simultaneously ERG with skin electrodes, while in older children separately ERG with HK loop electrode in accordance with ISCEV (International Society for Clinical Electrophysiology of Vision recommendations.Results: Clinical and electrophysiological changes in children with nystagmus, Leber’s congenital amaurosis, achromatopsia, congenital stationary night blindness, progressive retinal dystrophies, optic nerve hypoplasia, albinism, achiasmia, optic neuritis and visual pathway tumours are presented.Conclusions: Electrophysiological tests can help to indicate the nature and the location of dysfunction in unclear ophthalmological and/or neurological cases.

  5. Homozygosity mapping and targeted sanger sequencing reveal genetic defects underlying inherited retinal disease in families from pakistan.

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    Maleeha Maria

    Full Text Available Homozygosity mapping has facilitated the identification of the genetic causes underlying inherited diseases, particularly in consanguineous families with multiple affected individuals. This knowledge has also resulted in a mutation dataset that can be used in a cost and time effective manner to screen frequent population-specific genetic variations associated with diseases such as inherited retinal disease (IRD.We genetically screened 13 families from a cohort of 81 Pakistani IRD families diagnosed with Leber congenital amaurosis (LCA, retinitis pigmentosa (RP, congenital stationary night blindness (CSNB, or cone dystrophy (CD. We employed genome-wide single nucleotide polymorphism (SNP array analysis to identify homozygous regions shared by affected individuals and performed Sanger sequencing of IRD-associated genes located in the sizeable homozygous regions. In addition, based on population specific mutation data we performed targeted Sanger sequencing (TSS of frequent variants in AIPL1, CEP290, CRB1, GUCY2D, LCA5, RPGRIP1 and TULP1, in probands from 28 LCA families.Homozygosity mapping and Sanger sequencing of IRD-associated genes revealed the underlying mutations in 10 families. TSS revealed causative variants in three families. In these 13 families four novel mutations were identified in CNGA1, CNGB1, GUCY2D, and RPGRIP1.Homozygosity mapping and TSS revealed the underlying genetic cause in 13 IRD families, which is useful for genetic counseling as well as therapeutic interventions that are likely to become available in the near future.

  6. Skin ERGs: their effectiveness in paediatric visual assessment, confounding factors, and comparison with ERGs recorded using various types of corneal electrode.

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    Kriss, A

    1994-05-01

    Comparison of scotopic and photopic ERGs recorded using a variety of ERG electrodes show that contact lens electrodes produce the largest ERGs, and these are about 30-50% larger compared with those recorded with foil or thread electrodes, which contact a smaller part of the cornea. Flash ERGs recorded from infra-orbital skin electrodes are about one eighth the size of those recorded with contact lens electrodes, and around one quarter the size of those recorded with foil or fibre corneal electrodes. Reliable ERGs can be obtained in young children from infra-orbital electrodes sited centrally, within 1 cm of the rim of the eyelid, when signal averaging is used. Stimulation under fully darkened laboratory conditions with red and dim blue flashes permit assessment of cone and rod function, respectively. Factors such the recording electrode position, electrode derivation, upward rotation of the eye, eyelid closure and markedly constricted pupils can degrade the skin ERG. There are strong diagnostic advantages in recording the VEP concurrently with the skin ERG, particularly in young children. Examples of recordings in Leber's amaurosis, delayed visual maturation, albinism, optic nerve hypoplasia, achromatopsia add X-linked congenital stationary nightblindness are shown to demonstrate how ERG/VEP recordings can help in distinguishing between these conditions.

  7. Unravelling the Complexity of Inherited Retinal Dystrophies Molecular Testing: Added Value of Targeted Next-Generation Sequencing

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    Isabella Bernardis

    2016-01-01

    Full Text Available To assess the clinical utility of targeted Next-Generation Sequencing (NGS for the diagnosis of Inherited Retinal Dystrophies (IRDs, a total of 109 subjects were enrolled in the study, including 88 IRD affected probands and 21 healthy relatives. Clinical diagnoses included Retinitis Pigmentosa (RP, Leber Congenital Amaurosis (LCA, Stargardt Disease (STGD, Best Macular Dystrophy (BMD, Usher Syndrome (USH, and other IRDs with undefined clinical diagnosis. Participants underwent a complete ophthalmologic examination followed by genetic counseling. A custom AmpliSeq™ panel of 72 IRD-related genes was designed for the analysis and tested using Ion semiconductor Next-Generation Sequencing (NGS. Potential disease-causing mutations were identified in 59.1% of probands, comprising mutations in 16 genes. The highest diagnostic yields were achieved for BMD, LCA, USH, and STGD patients, whereas RP confirmed its high genetic heterogeneity. Causative mutations were identified in 17.6% of probands with undefined diagnosis. Revision of the initial diagnosis was performed for 9.6% of genetically diagnosed patients. This study demonstrates that NGS represents a comprehensive cost-effective approach for IRDs molecular diagnosis. The identification of the genetic alterations underlying the phenotype enabled the clinicians to achieve a more accurate diagnosis. The results emphasize the importance of molecular diagnosis coupled with clinic information to unravel the extensive phenotypic heterogeneity of these diseases.

  8. Mielinólisis osmótica extrapóntica.

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    Federico A. Silva

    2005-06-01

    Full Text Available La mielinólisis osmótica extrapóntica es una complicación rara del sistema nervioso central. Se presentan los hallazgos clínicos de un paciente de 49 años, alcohólico, que ingresó al servicio de urgencias en paro cardiorrespiratorio. Después de las maniobras de reanimación, el paciente se encontró en acidosis metabólica (pH 7,014 y fue tratado con bicarbonato de sodio. Cuarenta y ocho horas después, el sodio aumentó de 142 a 174 mEq/l. Durante el curso clínico, el paciente presentó signos de compromiso cognitivo, disartria, amaurosis bilateral, hiporreflexia y hemiparesia doble de predominio en el hemicuerpo derecho. La tomografía computarizada, tomada a las 72 horas de inicio del cuadro, evidenció hipodensidad lenticular bilateral con compromiso de las cápsulas internas y externas. Un mes después el paciente continuó con compromiso cognoscitivo, atrofia óptica bilateral, disartria residual, bradicinesia y hemiparesia doble.

  9. Retinal Diseases Caused by Mutations in Genes Not Specifically Associated with the Clinical Diagnosis.

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    Xia Wang

    Full Text Available When seeking a confirmed molecular diagnosis in the research setting, patients with one descriptive diagnosis of retinal disease could carry pathogenic variants in genes not specifically associated with that description. However, this event has not been evaluated systematically in clinical diagnostic laboratories that validate fully all target genes to minimize false negatives/positives.We performed targeted next-generation sequencing analysis on 207 ocular disease-related genes for 42 patients whose DNA had been tested negative for disease-specific panels of genes known to be associated with retinitis pigmentosa, Leber congenital amaurosis, or exudative vitreoretinopathy.Pathogenic variants, including single nucleotide variations and copy number variations, were identified in 9 patients, including 6 with variants in syndromic retinal disease genes and 3 whose molecular diagnosis could not be distinguished easily from their submitted clinical diagnosis, accounting for 21% (9/42 of the unsolved cases.Our study underscores the clinical and genetic heterogeneity of retinal disorders and provides valuable reference to estimate the fraction of clinical samples whose retinal disorders could be explained by genes not specifically associated with the corresponding clinical diagnosis. Our data suggest that sequencing a larger set of retinal disorder related genes can increase the molecular diagnostic yield, especially for clinically hard-to-distinguish cases.

  10. Prior surgical intervention and tumor size impact clinical outcome after precision radiotherapy for the treatment of optic nerve sheath meningiomas (ONSM)

    International Nuclear Information System (INIS)

    Adeberg, Sebastian; Welzel, Thomas; Rieken, Stefan; Debus, Jürgen; Combs, Stephanie E

    2011-01-01

    We analyzed our long-term experience with fractionated stereotactic radiotherapy (FSRT) in patients with meningioma of the optic nerve sheath (ONSM). Between January 1991 and January 2010, 40 patients with ONSM were treated using FSRT. Of these, 19 patients received radiotherapy as primary treatment, and 21 patients were treated after surgical resection. The median target volume was 9.2 ml, median total dose was 54 Gy in median single fractions of 1,8 Gy. Local progression-free survival was 100%. Median survival after FSRT was 60 months (range 4-228 months). In all patients overall toleration of FSRT was very good. Acute toxicity was mild. Prior to RT, 29 patients complained about any kind of visual impairment including visual field deficits, diplopia or amaurosis. Prior surgical resection was identified as a negative prognostic factor for visual outcome, whereas patients with larger tumor volumes demonstrated a higher number of patients with improvement of pre-existing visual deficits. Long-term outcome after FSRT for ONSM shows improved vision in patients not treated surgically prior to RT; moreover, the best improvement of visual deficits are observed in patients with larger target volumes. The absence of tumor recurrences supports that FSRT is a strong alternative to surgical resection especially in small tumors without extensive compression of normal tissue structures

  11. Inguinal hernia vs. arthritis of the hip in sporting adolescents--case report and review of the literature.

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    Holzheimer, R G; Gresser, U

    2007-07-26

    Chronic pain in the hip, groin or thigh can be caused by a wide spectrum of diseases posing extended diagnostic problems. We describe the case of a 10-years old child with chronic pain in the groin with gait restriction for more than six months without successful classification and treatment. The girl suffered from heavy pain in the groin after a sporting contest which forced her to walk with walking sticks and to avoid climbing stairs. Within six months she was examined by pediatric, orthopedic, pediatric surgery, pediatric orthopedic, radiology, pediatric rheumatology specialists. Working diagnoses were transient synovitis (coxitis fugax), arthritis, streptococcal arthritis, Morbus Perthes, rheumatic fever, rheumatoid arthritis. She was treated with antibiotics and ibuprofen in high dosage. Repeated laboratory tests and imaging studies (ultrasound, x-rays, magnetic resonance imaging) of the hip and pelvis did not support any of these diagnoses. Six months after beginning of the complaints the girl was presented by her mother to our institution. The physical examination showed a sharp localized pain in the groin, just in the region of the inguinal ligament with otherwise free hip movement. There was no visible inguinal hernia. The family history for hernia was positive. After infiltration of the ilioinguinal nerve the girl had a complete long-lasting disappearance of pain and gait disturbance. This led to the diagnosis of inguinal hernia with nerve entrapment. After hernia repair and neurolysis/neurectomy there was a continuous state of disappearance of pain and gait disturbances. To avoid such a diagnostic dilemma one should always discuss all possible causes. Non-visible inguinal hernia may be more common in females than previously thought. Nerve entrapment as a cause of groin pain has been well described. The relationship of the start of complaints with sporting activity, a positive family history for inguinal hernia, a lack of signs of inflammation and bone

  12. Radiologic diagnosis of Legg-Calve-Perthes disease; Radiologische Diagnostik des Morbus Perthes

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    Ranner, G. [Graz Univ. (Austria). Universitaetsklinik fuer Radiologie und Gemeinsame Einrichtung von Kliniken und Instituten ``Magnet Resonanz``; Fotter, R. [Graz Univ. (Austria). Universitaetsklinik fuer Radiologie und Gemeinsame Einrichtung von Kliniken und Instituten ``Magnet Resonanz``; Linhart, W. [Graz Univ. (Austria). Universitaetsklinik fuer Radiologie und Gemeinsame Einrichtung von Kliniken und Instituten ``Magnet Resonanz``; Ebner, F. [Graz Univ. (Austria). Universitaetsklinik fuer Radiologie und Gemeinsame Einrichtung von Kliniken und Instituten ``Magnet Resonanz``

    1994-01-01

    In Legg-Calve-Perthes disease (LCPD), magnetic resonance imaging (MRI) and conventional radiography in two planes are considered the most important methods of investigation for early diagnosis and for assessment of the course of the disease. MRI can reveal the early marrow oedema, thus allowing early differential diagnosis against diseases that are similar in clinical appearance (coxitis fugax, epiphyseal dysplasia). The extent of the necrotica area within the epiphysis, the most important indicator of the prognosis of the disease and thus for the therapeutic management, can be assessed earlier and more reliably with MRI than with other techniques. The loss of containment can be visualized by MRI, because depiction of the cartilaginous structures is possible earlier than with conventional radiography. Staging of LCPD is also possible with MRI, especially in stages I and II. Radiography shows the reossification and the osseous remodelling of the epiphysis better. A disadvantage of MRI seems to be the occasional need for sedation or anaesthesia of the child to avoid motion artefacts. (orig.) [Deutsch] In der radiologischen Fruehdiagnostik und Verlaufsbeurteilung des Morbus Legg-Calve-Perthes stehen als aussagekraeftigste Methoden das konventionelle Roengten in 2 Ebenen, die MRT und die Knochenszintigraphie im Vordergrund. In der Fruehdiagnostik bewaehrt sich die Magnetresonanztomographie als empfindliche Methode. Mit aehnlicher Sensitivitaet kann die Knochenszintigraphie die umschriebene Durchblutungsstoerung nachweisen. Daraus ergeben sich Moeglichkeiten zur bereits fruehzeitigen Differentialdiagnose gegenueber Krankheitsbildern mit aehnlicher klinischer Symptomatik. Die Groesse des Nekroseareals als prognostisch bedeutsamster und somit fuer die einzuschlagende Therapie richtungsweisender Faktor kann ebenfalls mittels MR-Tomographie am fruehesten und verlaesslichsten bestimmt werden. Kommt es im Verlauf der Erkrankung durch Subluxation des Caput femoris zum Verlust

  13. Metastasis of hepatocellular carcinoma presented as a tumor of the maxillary sinus and retrobulbar tumor

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    Kolarević Daniela

    2011-01-01

    Full Text Available Introduction. Hepatocellular carcinoma (HCC is the most frequent primary malignant tumor of the liver. It is usually seen in the 6th and 7th decades of life and chronic hepatitis B is the most frequent cause. Extrahepatic metastasis of HCC is an indicator of a poor prognosis and the most common sites are lungs, bones, lymph nodes, kidneys and adrenal glands. We reported a case of isolated metastasis in the right maxilla, which had been found initially, before the tumor in the liver was diagnosed. Case report. A 70-year-old man underwent dental surgery of the upper right molar. Prolonged bleeding control was difficult for up to two weeks, so the biopsy was performed. Histopathological analysis revealed a metastatic hepatocellular carcinoma. Computerized tomography (CT of the abdomen revealed a diffusely heterogeneous liver parenchyma with irregular borders and two foci of mass lesions. There were metastasis in the spleen and also two pathological retroperitoneal lymph nodes were detected, but no ascit, liver cirrhosis, cholestasis or portal vein thrombosis were seen. CT of the orbital and maxillary regions revealed a tumor mass in the right maxillary sinus, spreading to the alveolar sinus, nasal cavity and partially infratemporal space. A tumor mass was in the right orbit as well, infiltrating the surrounding bones and muscles. Clinically, there was proptosis of the right eye accompanied by amaurosis. The treatment started with chemotherapy based on 5-fluorouracil (sorafenib was not available. After three cycles, control CTs showed a stable disease in the liver, but progression in the right maxillary sinus and orbit. Enucleation of the right eye was performed and postoperative radiotherapy was planed. The patient deteriorated rapidly and died, about 6 months after the disease had been diagnosed. Conclusion. Extrahepatic metastasis of HCC represents a progressive phase of the disease with poor prognosis, so the main aim of the treatment should be

  14. Poly(β-Amino Ester)-Nanoparticle Mediated Transfection of Retinal Pigment Epithelial Cells In Vitro and In Vivo

    Science.gov (United States)

    Bhutto, Imran; Handa, James T.; Green, Jordan J.

    2012-01-01

    A variety of genetic diseases in the retina, including retinitis pigmentosa and leber congenital amaurosis, might be excellent targets for gene delivery as treatment. A major challenge in non-viral gene delivery remains finding a safe and effective delivery system. Poly(beta-amino ester)s (PBAEs) have shown great potential as gene delivery reagents because they are easily synthesized and they transfect a wide variety of cell types with high efficacy in vitro. We synthesized a combinatorial library of PBAEs and evaluated them for transfection efficacy and toxicity in retinal pigment epithelial (ARPE-19) cells to identify lead polymer structures and transfection formulations. Our optimal polymer (B5-S5-E7 at 60 w/w polymer∶DNA ratio) transfected ARPE-19 cells with 44±5% transfection efficacy, significantly higher than with optimized formulations of leading commercially available reagents Lipofectamine 2000 (26±7%) and X-tremeGENE HP DNA (22±6%); (ptransfection efficacy. This high non-viral efficacy was achieved with comparable cytotoxicity (23±6%) to controls; optimized formulations of Lipofectamine 2000 and X-tremeGENE HP DNA showed 15±3% and 32±9% toxicity respectively (p>0.05 for both). Our optimal polymer was also significantly better than a gold standard polymeric transfection reagent, branched 25 kDa polyethyleneimine (PEI), which achieved only 8±1% transfection efficacy with 25±6% cytotoxicity. Subretinal injections using lyophilized GFP-PBAE nanoparticles resulted in 1.1±1×103-fold and 1.5±0.7×103-fold increased GFP expression in the retinal pigment epithelium (RPE)/choroid and neural retina respectively, compared to injection of DNA alone (p = 0.003 for RPE/choroid, ptransfection of the RPE in vivo suggests that these nanoparticles could be used to study a number of genetic diseases in the laboratory with the potential to treat debilitating eye diseases. PMID:22629417

  15. Systemic air embolism during percutaneous core needle biopsy of the lung: frequency and risk factors

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    Freund Martin C

    2012-02-01

    Full Text Available Abstract Background Detection of risk factors for an air embolism in the left atrium, left ventricle, or systemic circulation (systemic air embolism, SAE during a percutaneous core needle biopsy (PCNB of the thorax. Methods In a retrospective observational study, all PCNBs of the thorax in 610 patients between 2007 and 2009 were analyzed. The SmartStep™ technique (General Electric was used for the biopsy, with which the examiner can prepare a batch of three 1.25-mm or 2.5-mm collimated slices within a second using a foot switch in the CT room to check the needle position. The image data thus generated and the control CT scans that followed were examined retrospectively for the presence of intravascular air. Intravascular air was defined as two or more adjacent voxels with absorption values of Results The radiological incidence of an SAE during a PCNB was 3.8% (23/610 patients, whereas the clinically apparent incidence was 0.49%. Two patients developed clinical symptoms consisting of transient hemiplegia or transient amaurosis; one died due to a fatal SAE of the coronary arteries. The mortality was thus 0.16%. The depth of the needle in the lesion (Wald: 6.859, endotracheal anesthesia (Wald: 5.721, location of the lesion above the level of the left atrium (Wald: 5.159, and prone position of the patients (Wald: 4.317 were independent risk factors for the incidence of an SAE (p Conclusion If possible, the PCNB should be performed under local anesthesia. We recommend avoiding endotracheal anesthesia and prone position. Whenever possible, patients should be positioned on the back in such a way that the tumor is lower than the left atrium. The tip of the needle should be within the tumor during the biopsy procedure.

  16. Distilling a Visual Network of Retinitis Pigmentosa Gene-Protein Interactions to Uncover New Disease Candidates.

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    Daniel Boloc

    Full Text Available Retinitis pigmentosa (RP is a highly heterogeneous genetic visual disorder with more than 70 known causative genes, some of them shared with other non-syndromic retinal dystrophies (e.g. Leber congenital amaurosis, LCA. The identification of RP genes has increased steadily during the last decade, and the 30% of the cases that still remain unassigned will soon decrease after the advent of exome/genome sequencing. A considerable amount of genetic and functional data on single RD genes and mutations has been gathered, but a comprehensive view of the RP genes and their interacting partners is still very fragmentary. This is the main gap that needs to be filled in order to understand how mutations relate to progressive blinding disorders and devise effective therapies.We have built an RP-specific network (RPGeNet by merging data from different sources: high-throughput data from BioGRID and STRING databases, manually curated data for interactions retrieved from iHOP, as well as interactions filtered out by syntactical parsing from up-to-date abstracts and full-text papers related to the RP research field. The paths emerging when known RP genes were used as baits over the whole interactome have been analysed, and the minimal number of connections among the RP genes and their close neighbors were distilled in order to simplify the search space.In contrast to the analysis of single isolated genes, finding the networks linking disease genes renders powerful etiopathological insights. We here provide an interactive interface, RPGeNet, for the molecular biologist to explore the network centered on the non-syndromic and syndromic RP and LCA causative genes. By integrating tissue-specific expression levels and phenotypic data on top of that network, a more comprehensive biological view will highlight key molecular players of retinal degeneration and unveil new RP disease candidates.

  17. The susceptibility of the retina to photochemical damage from visible light

    Science.gov (United States)

    Hunter, Jennifer J; Morgan, Jessica I W; Merigan, William H; Sliney, David H; Sparrow, Janet R; Williams, David R

    2011-01-01

    The photoreceptor/RPE complex must maintain a delicate balance between maximizing the absorption of photons for vision and retinal image quality while simultaneously minimizing the risk of photodamage when exposed to bright light. We review the recent discovery of two new effects of light exposure on the photoreceptor/RPE complex in the context of current thinking about the causes of retinal phototoxicity. These effects are autofluorescence photobleaching in which exposure to bright light reduces lipofuscin autofluorescence and, at higher light levels, RPE disruption in which the pattern of autofluorescence is permanently altered following light exposure. Both effects occur following exposure to visible light at irradiances that were previously thought to be safe. Photopigment, retinoids involved in the visual cycle, and bisretinoids in lipofuscin have been implicated as possible photosensitizers for photochemical damage. The mechanism of RPE disruption may follow either of these paths. On the other hand, autofluorescence photobleaching is likely an indicator of photooxidation of lipofuscin. The permanent changes inherent in RPE disruption might require modification of the light safety standards. AF photobleaching recovers after several hours although the mechanisms by which this occurs are not yet clear. Understanding the mechanisms of phototoxicity is all the more important given the potential for increased susceptibility in the presence of ocular diseases that affect either the visual cycle and/or lipofuscin accumulation. In addition, knowledge of photochemical mechanisms can improve our understanding of some disease processes that may be influenced by light exposure, such as some forms of Leber’s congenital amaurosis, and aid in the development of new therapies. Such treatment prior to intentional light exposures, as in ophthalmic examinations or surgeries, could provide an effective preventative strategy. PMID:22085795

  18. AJO Centennial: AJO contributions to Ophthalmic Genetics.

    Science.gov (United States)

    MacDonald, Ian M; Sieving, Pamela C

    2018-03-09

    To review the contributions to ophthalmic genetics through the American Journal of OphthalmologyDesign: Perspective. A literature search to retrieve original articles, letters, editorials, and published lectures from 1966 to 2017, providing a 50 year review. Titles were excluded that gave no reference to genetics or presented findings related to a non-genetic ocular condition. From a search of the Scopus database, 719 articles were ascertained. Of these 115 were excluded as the title did not reference a genetic condition or have a focus on genetic factors. Of these, four were excluded describing animal phenotypes (1966-7) and four were excluded having received no citations up to and including 2015. The highest number of citations was 283 times for a single article on familial aggregation in age-related macular degeneration. The Web of Science database yielded 771 articles; of these, 118 were excluded as not reporting human genetic studies; 55 received no citations. The highest number of citations was 307 for a single article, a 1991 paper on Leber hereditary optic neuropathy. The Journal's contributions to our understanding of the heritability of human ocular traits have been broad and deep, with international reach. The development of new techniques fostered new concepts and new approaches to rapidly expand the number of known single gene disorders with a defined molecular genetic cause. Reports on Mendelian and complex traits in the Journal abound along with six Edward Jackson Memorial Lectures on retinal dystrophies, Leber congenital amaurosis, age-related macular degeneration and glaucoma. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. THE NUMERICAL REPRESENTATION OF CHILDREN WITH DAMAGED EYESIGHT ON THE TERRITORY OF SKOPJE AND WORK ORGANIZATION WITH THIS POPULATION AT PRESCHOOL PERIOD

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    Snezana TALEVSKA

    1997-09-01

    Full Text Available The binocular function of the eyesight as a process develops as early as the first years of life.Taking into consideration the great number of inherent factors, which disturb the normal development of the eye-sight function, and the great number of causes of damages in the prenatal and natal period, the question of early detection of the reasons, diagnostics and treatment are of utmost importance.That’s possible, only if there is a cooperation among persons that are in the closest contacts with the child:· the mother;· the pediatrician;· the nurse;· the ophthalmologist;· the educator and· the physician.It’s not so necessary to talk about the importance of the sight in the human life, i.e. the importance of the binocular function of the children sight, from the early age when their psycho-physical development is the most flourishing.The importance of the early detection, diagnostics and treatment of the damaged eyesight is great. Especially, this is of great importance for ambliopia, which can be hardly detected at this early period, but it can be easily and successfully treated. We say it is hard to detect because of the delusion and inertness of parents, just during early years from birth to the 3 year, that the child is small and it’s too early to start a treatment.On the contrary, practice has shown that this time is lost and hardly can be compensate, either in means of cure of ambliopia and treatment or rehabilitation of amaurosis.The numerical data of children with damaged eyesight on the territory of Skopje and the need of organized work with this population of children at preschool age will be confirmed and enclosed.

  20. The main clinical symptoms of multiple sclerosis at the children in the debut. Own observation

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    Stetsenko T.I.

    2016-05-01

    Full Text Available Objective: evaluate first clinical signs of MS for early diagnosis and prevention of disability. Patients and methods. There are results of examination of 9 patients (5 boys, 4 girls aged 15 to 17 years, who sought a neurological department NDSL «OKHMATDYT» during 2014 for further diagnosis & treatment. Researches included a general clinical examination, immunological parameters, visual evoked potentials, CT, MRI with contrast of brain and spinal cord. Data analysis was performed according to McDonald criteria. Results. The complaints are presented in all cases of violation of the sensitivity of the limbs (numbness of limbs mainly in the left part of a body as a result of stress, during the studies at school, after physical exercises, against a background of full health. Later, they were accompanied by paresis of facial muscles in the central-type, by the central amaurosis of both eyes, by the periodic urinary incontinence in the last 7 years, lower spastic paraparesis and left-side hemiparesis. Clinically: nistahmoyid in extreme abduction of the eyeballs, asymmetry of reflexes, abnormal volatility of iambic signs, violation of statics and coordination. In the first case there were detected 7 exacerbations. In MRI of the brain was detected multiple hiperintense foci of periventricular and subcortical mostly (8 cases, spread to the spinal cord (2 cases. At the previous stages was diagnosed herpes infection, subacute encephalitis, brain volumetric process, ADEM, acute myelitis, tuberous sclerosis, CVA. After the examination in conditions of highly specialized branch was established in RS for appropriate treatment. Conclusions. 1. The manifestation of MS among children 15–17 year old mostly presented monosymptomatic and sensitivity violation almost in all cases. 2. Characteristic remitting and relapsing-remitting-relapsing course of MS, cerebral form (in 2 cases cerebrovascular spinal. 3. A clearly shown dissemination in space and time

  1. Noninvasive, in vivo assessment of mouse retinal structure using optical coherence tomography.

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    M Dominik Fischer

    Full Text Available BACKGROUND: Optical coherence tomography (OCT is a novel method of retinal in vivo imaging. In this study, we assessed the potential of OCT to yield histology-analogue sections in mouse models of retinal degeneration. METHODOLOGY/PRINCIPAL FINDINGS: We achieved to adapt a commercial 3(rd generation OCT system to obtain and quantify high-resolution morphological sections of the mouse retina which so far required in vitro histology. OCT and histology were compared in models with developmental defects, light damage, and inherited retinal degenerations. In conditional knockout mice deficient in retinal retinoblastoma protein Rb, the gradient of Cre expression from center to periphery, leading to a gradual reduction of retinal thickness, was clearly visible and well topographically quantifiable. In Nrl knockout mice, the layer involvement in the formation of rosette-like structures was similarly clear as in histology. OCT examination of focal light damage, well demarcated by the autofluorescence pattern, revealed a practically complete loss of photoreceptors with preservation of inner retinal layers, but also more subtle changes like edema formation. In Crb1 knockout mice (a model for Leber's congenital amaurosis, retinal vessels slipping through the outer nuclear layer towards the retinal pigment epithelium (RPE due to the lack of adhesion in the subapical region of the photoreceptor inner segments could be well identified. CONCLUSIONS/SIGNIFICANCE: We found that with the OCT we were able to detect and analyze a wide range of mouse retinal pathology, and the results compared well to histological sections. In addition, the technique allows to follow individual animals over time, thereby reducing the numbers of study animals needed, and to assess dynamic processes like edema formation. The results clearly indicate that OCT has the potential to revolutionize the future design of respective short- and long-term studies, as well as the preclinical

  2. Linkage mapping of canine rod cone dysplasia type 2 (rcd2) to CFA7, the canine orthologue of human 1q32.

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    Kukekova, Anna V; Nelson, Jacquelyn; Kuchtey, Rachel W; Lowe, Jennifer K; Johnson, Jennifer L; Ostrander, Elaine A; Aguirre, Gustavo D; Acland, Gregory M

    2006-03-01

    To map the canine rcd2 retinal degeneration locus. Rod-cone dysplasia type 2 (rcd2), an early-onset autosomal recessive form of progressive retinal atrophy (PRA), is phenotypically similar to early-onset forms of retinitis pigmentosa collectively termed Leber congenital amaurosis and segregates naturally in the collie breed of dog. Multiple genes have previously been evaluated as candidates for rcd2, but all have been excluded. A set of informative experimental pedigrees segregating the rcd2 phenotype was produced. A genome-wide scan of these pedigrees using a set of 241 markers was undertaken. To refine the localized homology between canine and human maps, an RH map of the identified rcd2 region was built using a 3000 cR panel. A positional candidate gene strategy was then undertaken to begin to evaluate potentially causative genes. A locus responsible for the rcd2 phenotype was mapped to CFA7 in a region corresponding to human chromosome 1, region q32.1-q32.2. Maximum linkage was observed between rcd2 and marker FH3972 (theta = 0.02; lod = 25.53), and the critical region was flanked by markers FH2226 and FH3972. As CRB1 is the closest gene on human chromosome 1q known to cause retinal degeneration, canine gene-specific markers for CRB1 were developed, and this gene was excluded as a positional candidate for rcd2. The rcd2 locus represents a novel retinal degeneration gene. It is anticipated that when identified, this gene will offer new insights into retinal developmental and degenerative processes, and new opportunities for exploring experimental therapies.

  3. Atypical clinical presentation and long-term survival in a patient with optic nerve medulloepithelioma: a case report

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    Pastora-Salvador Natalia

    2012-05-01

    Full Text Available Abstract Introduction Medulloepithelioma is a rare congenital tumor of the primitive medullary neuroepithelium. A significant proportion of patients with medulloepithelioma arising from the optic nerve die from intracranial spread or cerebral metastasis. Because it has no known distinct clinical features and because of its low frequency, this tumor presents within the first two to six years of life and is usually misdiagnosed clinically as a different type of optic nerve tumor. Here, we describe a new and atypical case of medulloepithelioma of the optic nerve in a 12-year-old boy. To the best of our knowledge, he is the oldest reported patient to present with this disease and, now as an adult, has the longest documented period of disease-free survival. Case presentation A 12-year-old Caucasian boy with headache and unilateral amaurosis was referred for a presumed optic nerve glioma to our hospital. A computed tomography scan showed optic nerve enlargement, and fundoscopy showed a whitish mass at the optic disc. Our patient had been followed at his local hospital for four years for an 'optic disc cyst' with no change or progression. He experienced mild progressive visual impairment during that period. He was admitted for resection, and a histopathological analysis revealed a medulloepithelioma of the optic nerve. Supplemental orbital radiotherapy was performed. He remained disease-free for 25 years. Conclusions Medulloepithelioma of the optic nerve can clinically mimic more common pediatric tumors, such as optic glioma, meningioma, or retinoblastoma. Thus, medulloepithelioma should be included in the differential diagnoses of pediatric optic nerve lesions. Fundoscopy in these patients may provide relevant information for diagnosis. Anterior optic nerve medulloepitheliomas may behave differently from and have a better prognosis than medulloepitheliomas that have a more posterior location. Our case report illustrates that long-term survival can be

  4. The Pathway From Genes to Gene Therapy in Glaucoma: A Review of Possibilities for Using Genes as Glaucoma Drugs.

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    Borrás, Teresa

    2017-01-01

    Treatment of diseases with gene therapy is advancing rapidly. The use of gene therapy has expanded from the original concept of re-placing the mutated gene causing the disease to the use of genes to con-trol nonphysiological levels of expression or to modify pathways known to affect the disease. Genes offer numerous advantages over conventional drugs. They have longer duration of action and are more specific. Genes can be delivered to the target site by naked DNA, cells, nonviral, and viral vectors. The enormous progress of the past decade in molecular bi-ology and delivery systems has provided ways for targeting genes to the intended cell/tissue and safe, long-term vectors. The eye is an ideal organ for gene therapy. It is easily accessible and it is an immune-privileged site. Currently, there are clinical trials for diseases affecting practically every tissue of the eye, including those to restore vision in patients with Leber congenital amaurosis. However, the number of eye trials compared with those for systemic diseases is quite low (1.8%). Nevertheless, judg-ing by the vast amount of ongoing preclinical studies, it is expected that such number will increase considerably in the near future. One area of great need for eye gene therapy is glaucoma, where a long-term gene drug would eliminate daily applications and compliance issues. Here, we review the current state of gene therapy for glaucoma and the possibilities for treating the trabecular meshwork to lower intraocular pressure and the retinal ganglion cells to protect them from neurodegeneration. Copyright© 2017 Asia-Pacific Academy of Ophthalmology.

  5. Bicistronic lentiviruses containing a viral 2A cleavage sequence reliably co-express two proteins and restore vision to an animal model of LCA1.

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    Jonathan D Verrier

    Full Text Available The disease processes underlying inherited retinal disease are complex and are not completely understood. Many of the corrective gene therapies designed to treat diseases linked to mutations in genes specifically expressed in photoreceptor cells restore function to these cells but fail to stop progression of the disease. There is growing consensus that effective treatments for these diseases will require delivery of multiple therapeutic proteins that will be selected to treat specific aspects of the disease process. The purpose of this study was to design a lentiviral transgene that reliably expresses all of the proteins it encodes and does so in a consistent manner among infected cells. We show, using both in vitro and in vivo analyses, that bicistronic lentiviral transgenes encoding two fluorescent proteins fused to a viral 2A-like cleavage peptide meet these expression criteria. To determine if this transgene design is suitable for therapeutic applications, we replaced one of the fluorescent protein genes with the gene encoding guanylate cyclase-1 (GC1 and delivered lentivirus carrying this transgene to the retinas of the GUCY1*B avian model of Leber congenital amaurosis-1 (LCA1. GUCY1*B chickens carry a null mutation in the GC1 gene that disrupts photoreceptor function and causes blindness at hatching, a phenotype that closely matches that observed in humans with LCA1. We found that treatment of these animals with the 2A lentivector encoding GC1 restored vision to these animals as evidenced by the presence of optokinetic reflexes. We conclude that 2A-like peptides, with proper optimization, can be successfully incorporated into therapeutic vectors designed to deliver multiple proteins to neural retinal. These results highlight the potential of this vector design to serve as a platform for the development of combination therapies designed to enhance or prolong the benefits of corrective gene therapies.

  6. Paraneoplastic retinopathies

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    Marko Hawlina

    2005-10-01

    Full Text Available Background: Two types of retinopathy are known to be associated with patients with malignancies: cancer associated retinopathy-CAR and cutaneus melanoma associated retinopathy-MAR. Autoantibodies against recoverin or against α -enolase have been described in CAR, and autoatibodies against ON-bipolar cells are formed in MAR. An outline of the pathogenetic mechanisms and an example of each cases disorder are presented.Case reports: In both patients, the following were performed: complete clinical examination, visual acuity, visual fields, fluorescein angiography and electroretinography. The first patient was a 78 year-old man with epidermoid carcinoma of the the lung and metastases of liver and kidney suffered rapidly progressive bilateral visual loss. He suffered complete loss of vision (amaurosis with Anton’s syndrome. Retinal examination showed severe arterial narrowing with lipid plaques and age-related pigmentary changes. The ERG was nondetectable, and the diagnosis was CAR. The second patient was a 62 years old man who presented with acute onset of bilateral night blindness, photopsia and shimmering four years after excision of a cutaneus malignant melanoma. Visual acuity was 0.5 in the right eye and 0.8 in the left eye. The visual fields showed constriction to 15° in both eyes on Goldmann perimetry. The retinal examination was normal. ERG maximal response was electronegative, with normal a-wave amplitude and reduced b-wave. ON-OFF ERG showed loss of ON-response b-wave and normal OFF-response d-wave, typical for MAR.Conclusions: CAR and MAR are rare paraneoplastic sindromes, that are characterised by rapid onset of acquired bilateral visual loss and night blindness. There are usually shimmering photopsias in MAR and fundus examination is normal. The fundus is initially normal in CAR, but becomes abnormal as the disorder progresses. Typical changes in ERG may precede the presentation of malignancy and therefore awareness of this

  7. Targeting iodothyronine deiodinases locally in the retina is a therapeutic strategy for retinal degeneration.

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    Yang, Fan; Ma, Hongwei; Belcher, Joshua; Butler, Michael R; Redmond, T Michael; Boye, Sanford L; Hauswirth, William W; Ding, Xi-Qin

    2016-12-01

    Recent studies have implicated thyroid hormone (TH) signaling in cone photoreceptor viability. Using mouse models of retinal degeneration, we found that antithyroid treatment preserves cones. This work investigates the significance of targeting intracellular TH components locally in the retina. The cellular TH level is mainly regulated by deiodinase iodothyronine (DIO)-2 and -3. DIO2 converts thyroxine (T4) to triiodothyronine (T3), which binds to the TH receptor, whereas DIO3 degrades T3 and T4. We examined cone survival after overexpression of DIO3 and inhibition of DIO2 and demonstrated the benefits of these manipulations. Subretinal delivery of AAV5-IRBP/GNAT2-DIO3, which directs expression of human DIO3 specifically in cones, increased cone density by 30-40% in a Rpe65 -/- mouse model of Lebers congenital amaurosis (LCA) and in a Cpfl1 mouse with Pde6c defect model of achromatopsia, compared with their respective untreated controls. Intravitreal and topical delivery of the DIO2 inhibitor iopanoic acid also significantly improved cone survival in the LCA model mice. Moreover, the expression levels of DIO2 and Slc16a2 were significantly higher in the diseased retinas, suggesting locally elevated TH signaling. We show that targeting DIOs protects cones, and intracellular inhibition of TH components locally in the retina may represent a novel strategy for retinal degeneration management.-Yang, F., Ma, H., Belcher, J., Butler, M. R., Redmond, T. M., Boye, S. L., Hauswirth, W. W., Ding, X.-Q. Targeting iodothyronine deiodinases locally in the retina is a therapeutic strategy for retinal degeneration. © FASEB.

  8. Inhibition of thyroid hormone receptor locally in the retina is a therapeutic strategy for retinal degeneration.

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    Ma, Hongwei; Yang, Fan; Butler, Michael R; Belcher, Joshua; Redmond, T Michael; Placzek, Andrew T; Scanlan, Thomas S; Ding, Xi-Qin

    2017-08-01

    Thyroid hormone (TH) signaling regulates cell proliferation, differentiation, and metabolism. Recent studies have implicated TH signaling in cone photoreceptor viability. Using mouse models of retinal degeneration, we demonstrated that antithyroid drug treatment and targeting iodothyronine deiodinases (DIOs) to suppress cellular tri-iodothyronine (T3) production or increase T3 degradation preserves cones. In this work, we investigated the effectiveness of inhibition of the TH receptor (TR). Two genes, THRA and THRB , encode TRs; THRB 2 has been associated with cone viability. Using TR antagonists and Thrb2 deletion, we examined the effects of TR inhibition. Systemic and ocular treatment with the TR antagonists NH-3 and 1-850 increased cone density by 30-40% in the Rpe65 -/- mouse model of Leber congenital amaurosis and reduced the number of TUNEL + cells. Cone survival was significantly improved in Rpe65 -/- and Cpfl1 (a model of achromatopsia with Pde6c defect) mice with Thrb2 deletion. Ventral cone density in Cpfl1/Thrb2 -/- and Rpe65 -/- / Thrb2 -/- mice was increased by 1- to 4-fold, compared with age-matched controls. Moreover, the expression levels of TR were significantly higher in the cone-degeneration retinas, suggesting locally elevated TR signaling. This work shows that the effects of antithyroid treatment or targeting DIOs were likely mediated by TRs and that suppressing TR protects cones. Our findings support the view that inhibition of TR locally in the retina is a therapeutic strategy for retinal degeneration management.-Ma, H., Yang, F., Butler, M. R., Belcher, J., Redmond, T. M., Placzek, A. T., Scanlan, T. S., Ding, X.-Q. Inhibition of thyroid hormone receptor locally in the retina is a therapeutic strategy for retinal degeneration. © FASEB.

  9. Electroretinographic assessment and diagnostic reappraisal of children with visual dysfunction: A prospective study

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    Vedantham Vasumathy

    2007-01-01

    Full Text Available Purpose: To assess the presence or absence of a retinal cause of visual impairment using electroretinography (ERG in children with no obvious discernable cause on ocular examination. Design: Prospective observational case series. Materials and Methods: A prospective study was carried out involving 120 children with the mean age 4.4±3.2 years with visual dysfunction. All children underwent ERG under general anesthesia using a special handheld mini-Ganzfeld (Kurbisfeld dome. Results: Fifty-two (43.3% children were male and 68 (56.7% were female. The clinical diagnosis was as follows: Leber′s congenital amaurosis (LCA (n=47, achromatopsia (n=25, congenital stationary night blindness (CSNB (n=9 and others (unclassifiable, n=39. The visual acuity ranged from perception of light (PL to PL with projection in children with LCA. In the rest (n=73, some sort of visually guided behavior was discernable. Following ERG, a diagnostic reappraisal resulted as follows: LCA (n=49, achromatopsia (n=28, CSNB (n=4, cone-rod dystrophy (n=22, rod-cone degeneration (n=7, normal (n=8 and others (unclassifiable, n=2. Except for the two unclassifiable cases, ERG was successful in the diagnosis or exclusion of retinal dysfunction in the rest. By Pearson Chi-square test, there was a statistically significant association between the clinical and ERG diagnosis ( P < 0.001. Conclusion: LCA was the commonest cause of visual dysfunction in our series. A statistically significant correlation between clinical and electrophysiological diagnosis was seen. ERG helped in firmly establishing the presence or absence of global retinal dysfunction in the majority (118/120 of pediatric patients with visual dysfunction.

  10. Exome sequencing of index patients with retinal dystrophies as a tool for molecular diagnosis.

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    Marta Corton

    Full Text Available Retinal dystrophies (RD are a group of hereditary diseases that lead to debilitating visual impairment and are usually transmitted as a Mendelian trait. Pathogenic mutations can occur in any of the 100 or more disease genes identified so far, making molecular diagnosis a rather laborious process. In this work we explored the use of whole exome sequencing (WES as a tool for identification of RD mutations, with the aim of assessing its applicability in a diagnostic context.We ascertained 12 Spanish families with seemingly recessive RD. All of the index patients underwent mutational pre-screening by chip-based sequence hybridization and resulted to be negative for known RD mutations. With the exception of one pedigree, to simulate a standard diagnostic scenario we processed by WES only the DNA from the index patient of each family, followed by in silico data analysis. We successfully identified causative mutations in patients from 10 different families, which were later verified by Sanger sequencing and co-segregation analyses. Specifically, we detected pathogenic DNA variants (∼50% novel mutations in the genes RP1, USH2A, CNGB3, NMNAT1, CHM, and ABCA4, responsible for retinitis pigmentosa, Usher syndrome, achromatopsia, Leber congenital amaurosis, choroideremia, or recessive Stargardt/cone-rod dystrophy cases.Despite the absence of genetic information from other family members that could help excluding nonpathogenic DNA variants, we could detect causative mutations in a variety of genes known to represent a wide spectrum of clinical phenotypes in 83% of the patients analyzed. Considering the constant drop in costs for human exome sequencing and the relative simplicity of the analyses made, this technique could represent a valuable tool for molecular diagnostics or genetic research, even in cases for which no genotypes from family members are available.

  11. Dawn of ocular gene therapy: implications for molecular diagnosis in retinal disease

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    Jacques, ZANEVELD; Feng, WANG; Xia, WANG; Rui, CHEN

    2013-01-01

    Personalized medicine aims to utilize genomic information about patients to tailor treatment. Gene replacement therapy for rare genetic disorders is perhaps the most extreme form of personalized medicine, in that the patients’ genome wholly determines their treatment regimen. Gene therapy for retinal disorders is poised to become a clinical reality. The eye is an optimal site for gene therapy due to the relative ease of precise vector delivery, immune system isolation, and availability for monitoring of any potential damage or side effects. Due to these advantages, clinical trials for gene therapy of retinal diseases are currently underway. A necessary precursor to such gene therapies is accurate molecular diagnosis of the mutation(s) underlying disease. In this review, we discuss the application of Next Generation Sequencing (NGS) to obtain such a diagnosis and identify disease causing genes, using retinal disorders as a case study. After reviewing ocular gene therapy, we discuss the application of NGS to the identification of novel Mendelian disease genes. We then compare current, array based mutation detection methods against next NGS-based methods in three retinal diseases: Leber’s Congenital Amaurosis, Retinitis Pigmentosa, and Stargardt’s disease. We conclude that next-generation sequencing based diagnosis offers several advantages over array based methods, including a higher rate of successful diagnosis and the ability to more deeply and efficiently assay a broad spectrum of mutations. However, the relative difficulty of interpreting sequence results and the development of standardized, reliable bioinformatic tools remain outstanding concerns. In this review, recent advances NGS based molecular diagnoses are discussed, as well as their implications for the development of personalized medicine. PMID:23393028

  12. Lentiviral expression of retinal guanylate cyclase-1 (RetGC1 restores vision in an avian model of childhood blindness.

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    Melissa L Williams

    2006-06-01

    Full Text Available Leber congenital amaurosis (LCA is a genetically heterogeneous group of retinal diseases that cause congenital blindness in infants and children. Mutations in the GUCY2D gene that encodes retinal guanylate cyclase-1 (retGC1 were the first to be linked to this disease group (LCA type 1 [LCA1] and account for 10%-20% of LCA cases. These mutations disrupt synthesis of cGMP in photoreceptor cells, a key second messenger required for function of these cells. The GUCY1*B chicken, which carries a null mutation in the retGC1 gene, is blind at hatching and serves as an animal model for the study of LCA1 pathology and potential treatments in humans.A lentivirus-based gene transfer vector carrying the GUCY2D gene was developed and injected into early-stage GUCY1*B embryos to determine if photoreceptor function and sight could be restored to these animals. Like human LCA1, the avian disease shows early-onset blindness, but there is a window of opportunity for intervention. In both diseases there is a period of photoreceptor cell dysfunction that precedes retinal degeneration. Of seven treated animals, six exhibited sight as evidenced by robust optokinetic and volitional visual behaviors. Electroretinographic responses, absent in untreated animals, were partially restored in treated animals. Morphological analyses indicated there was slowing of the retinal degeneration.Blindness associated with loss of function of retGC1 in the GUCY1*B avian model of LCA1 can be reversed using viral vector-mediated gene transfer. Furthermore, this reversal can be achieved by restoring function to a relatively low percentage of retinal photoreceptors. These results represent a first step toward development of gene therapies for one of the more common forms of childhood blindness.

  13. Children with blindness - major causes, developmental outcomes and implications for habilitation and educational support: a two-decade, Swedish population-based study.

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    de Verdier, Kim; Ulla, Ek; Löfgren, Stefan; Fernell, Elisabeth

    2017-11-23

    The aim was to describe the population of children with congenital or early infancy blindness in Sweden, with regard to causes of blindness and prevalence of neurodevelopmental impairments. Medical, psychological and pedagogical records of Swedish children with congenital or early infancy blindness (total blindness or light perception at the most) born in 1988-2008 were analysed regarding year of birth, gender, cause of blindness, gestational age, associated neurological disorders/syndromes, associated neurodevelopmental impairments, cognitive level and type of school placement. A total of 150 individuals, 80 girls and 70 boys, were identified, corresponding to a prevalence of 7/100 000. Five causes of blindness dominated, constituting 76% of all represented aetiologies: retinopathy of prematurity (ROP), optic nerve hypoplasia (ONH), Leber congenital amaurosis (LCA), optic nerve atrophy (ONA) and microphthalmia/anophthalmia. Nearly three of four children in the study population had at least one additional disability besides blindness; the most common being intellectual disability (ID) and autism spectrum disorder (ASD). More than half of the population had more than one additional disability. Autism spectrum disorder (ASD) was most common in children with ONH, ROP, LCA and microphthalmia/anophthalmia. In children born within the last decades, isolated blindness is uncommon and the rate of multidisabilities is high. Autism spectrum disorder (ASD) seems to be more strongly associated with specific aetiological subgroups. Further development of the support to families and schools should be based on knowledge about the considerable heterogeneity of the population of children with blindness, and the common occurrence of coexisting neurodevelopmental disorders, especially ID and ASD. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  14. Progress and challenges in viral vector manufacturing.

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    van der Loo, Johannes C M; Wright, J Fraser

    2016-04-15

    Promising results in several clinical studies have emphasized the potential of gene therapy to address important medical needs and initiated a surge of investments in drug development and commercialization. This enthusiasm is driven by positive data in clinical trials including gene replacement for Hemophilia B, X-linked Severe Combined Immunodeficiency, Leber's Congenital Amaurosis Type 2 and in cancer immunotherapy trials for hematological malignancies using chimeric antigen receptor T cells. These results build on the recent licensure of the European gene therapy product Glybera for the treatment of lipoprotein lipase deficiency. The progress from clinical development towards product licensure of several programs presents challenges to gene therapy product manufacturing. These include challenges in viral vector-manufacturing capacity, where an estimated 1-2 orders of magnitude increase will likely be needed to support eventual commercial supply requirements for many of the promising disease indications. In addition, the expanding potential commercial product pipeline and the continuously advancing development of recombinant viral vectors for gene therapy require that products are well characterized and consistently manufactured to rigorous tolerances of purity, potency and safety. Finally, there is an increase in regulatory scrutiny that affects manufacturers of investigational drugs for early-phase clinical trials engaged in industry partnerships. Along with the recent increase in biopharmaceutical funding in gene therapy, industry partners are requiring their academic counterparts to meet higher levels of GMP compliance at earlier stages of clinical development. This chapter provides a brief overview of current progress in the field and discusses challenges in vector manufacturing. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Classificação diagnóstica dos portadores de doenças degenerativas de retina, integrantes dos grupos Retina São Paulo e Retina Vale do Paraíba Diagnostic classification of retinal degenerative diseases São Paulo and Vale Retina groups

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    Nichard Unonius

    2003-08-01

    ,5% eram casos isolados. CONCLUSÃO: Destaca-se assim a importância desta classificação como a primeira referência nacional dos padrões de hereditariedade das distrofias retinianas do país. Este é o primeiro passo para se proceder em seguida a classificação genético-molecular baseada no seqüenciamento de cada gene responsável por cada um dos padrões de herança. A freqüência de cada tipo específico é semelhante à encontrada em outros trabalhos epidemiológicos de outros países.PURPOSE: To organize a regional data bank of all individuals that have retinal degenerative diseases, with the aim to classify each patient according to the type of distrophy and pattern of inheritance. METHODS: During the meeting of the São Paulo Retina Group on May 5th, 2001, two hundred and forty-three persons were registered, part of whom provided information concerning ocular, personal and family history and family tree. Ninety-three patients were asked about age, origin, type of dystrophy, family history and family tree information, type of inheritance, other systemic abnormalities and complementary examination. They were classified according to the diagnosis and pattern of inhe-ritance. RESULTS: The distrophies found in the registered two hundred and forty-three patients, were: retinitis pigmentosa, Stargardt disease, Usher syndrome, Leber congenital amaurosis and choroideremia. Of the ninety-three patients examined on the same day, sixty-two had retinitis pigmentosa, thirteen had Stargardt disease, thirteen had Usher syndrome, three had Leber congenital amaurosis and two had choroideremia. The inheritance pattern of the patients with retinitis pigmentosa was autosomal dominant in 4 cases (7%, autosomal recessive in twenty cases (32%, X-linked recessive in 7 cases (11%. Twenty-nine cases were isolated (47% and two had an indeterminate pattern of inheritance (3%. Of the Stargardt disease patients, three (23% were autosomal recessive and ten (77% were isolated cases. Of the

  16. Impact of set-aside management on soil mesofauna

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    Landi, Silvia; d'Errico, Giada; Mazza, Giuseppe; Mocali, Stefano; Bazzoffi, Paolo; Roversi, Pio Federico

    2014-05-01

    (MI) resulted significantly higher in set-aside managements than in conventional crops in Fagna and Metaponto sites. In contrast, Caorle was characterized by a significant soil degradation (prevalence of extreme colonizers) and any increase of MI values in the set-aside have been not detected. About microarthropods, the taxa richness was significantly higher in set-aside managements than conventional crops in all the sites sampled. QBS index showed the same trend, but the differences were not significant. Caorle site was characterized by a lack of balance in the relative abundance among soil microarthropods taxa. In particular, set-aside managements showed a strong prevalence of an aggressive ants Solenopsis fugax (Hymenoptera: Formicidae). In conclusion, the best results were observed in Fagna and Metaponto sites, where MI and QBS values increased under set-aside management as compared to the conventional. Further analyses will be carried out over a long period to better understand the possible correlation between the enhancement of the organic matter observed in the soils less degraded and the biological quality improvement.

  17. Recombinant adeno-associated virus-mediated gene transfer for the potential therapy of adenosine deaminase-deficient severe combined immune deficiency.

    Science.gov (United States)

    Silver, Jared N; Elder, Melissa; Conlon, Thomas; Cruz, Pedro; Wright, Amy J; Srivastava, Arun; Flotte, Terence R

    2011-08-01

    ). Currently, rAAV vectors are being utilized in phase I/II clinical trials for cystic fibrosis, α-1 antitrypsin deficiency, Canavan's disease, Parkinson's disease, hemophilia, limb-girdle muscular dystrophy, arthritis, Batten's disease, and Leber's congenital amaurosis (Flotte et al., 1996 , 2004 ; Kay et al., 2000 ; Aitken et al., 2001 ; Wagner et al., 2002 ; Manno et al., 2003 ; Snyder and Francis, 2005 ; Maguire et al., 2008 ; Cideciyan et al., 2009 ). In this study, we present preclinical data to support the viability of an rAAV-based gene transfer strategy for cure of ADA-SCID. We report efficient transduction of a variety of postmitotic target tissues in vivo, subsequent human ADA (hADA) expression, and enhanced hADA secretion in tissues and blood, with increasing peripheral lymphocyte populations over time.

  18. RETINOBASE: a web database, data mining and analysis platform for gene expression data on retina

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    Léveillard Thierry

    2008-05-01

    Full Text Available Abstract Background The retina is a multi-layered sensory tissue that lines the back of the eye and acts at the interface of input light and visual perception. Its main function is to capture photons and convert them into electrical impulses that travel along the optic nerve to the brain where they are turned into images. It consists of neurons, nourishing blood vessels and different cell types, of which neural cells predominate. Defects in any of these cells can lead to a variety of retinal diseases, including age-related macular degeneration, retinitis pigmentosa, Leber congenital amaurosis and glaucoma. Recent progress in genomics and microarray technology provides extensive opportunities to examine alterations in retinal gene expression profiles during development and diseases. However, there is no specific database that deals with retinal gene expression profiling. In this context we have built RETINOBASE, a dedicated microarray database for retina. Description RETINOBASE is a microarray relational database, analysis and visualization system that allows simple yet powerful queries to retrieve information about gene expression in retina. It provides access to gene expression meta-data and offers significant insights into gene networks in retina, resulting in better hypothesis framing for biological problems that can subsequently be tested in the laboratory. Public and proprietary data are automatically analyzed with 3 distinct methods, RMA, dChip and MAS5, then clustered using 2 different K-means and 1 mixture models method. Thus, RETINOBASE provides a framework to compare these methods and to optimize the retinal data analysis. RETINOBASE has three different modules, "Gene Information", "Raw Data System Analysis" and "Fold change system Analysis" that are interconnected in a relational schema, allowing efficient retrieval and cross comparison of data. Currently, RETINOBASE contains datasets from 28 different microarray experiments performed

  19. Using the NAFX to measure the effectiveness over time of gene therapy in canine LCA.

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    Jacobs, Jonathan B; Dell'Osso, Louis F; Wang, Zhong I; Acland, Gregory M; Bennett, Jean

    2009-10-01

    To use ocular motility recordings to determine the changes over time of infantile nystagmus syndrome (INS) in RPE65-deficient canines with Leber Congenital Amaurosis (LCA) and assess the time course of the recalibration of the ocular motor system (OMS). Nine dogs were treated bilaterally with AAV-RPE65. A second cohort of four dogs was treated with AAV2.RPE65, an optimized vector. Their fixation eye movements were recorded before treatment and at 4-week intervals for 3 months, by using high-speed (500 Hz) digital videography. The dogs were suspended in a sling and encouraged to fixate on distant (57 inches) targets at gaze angles varying between +/-15 degrees horizontally and +/-10 degrees vertically. The records for each eye were examined for qualitative changes in waveform and for quantitative changes in centralisation with the expanded nystagmus acuity function (NAFX) and compared with ERG results for restoration of receptor function. First group: Before treatment, five of the dogs had clinically apparent INS with jerk, pendular, or both waveforms and with peak-to-peak amplitudes as great as 15 degrees . One dog had intermittent nystagmus. At the 1- and 2-month examinations, no change in nystagmus waveform or NAFX was observed in any of the initial dogs, while at 10 weeks, one dog treated bilaterally with the standard dosage showed reduced nystagmus in only one eye. The other eye did not respond to treatment, as confirmed by ERG. This result was unexpected since it was previously documented that unilateral treatment leads to bilateral reduction of INS. The other dog treated with the standard dosage showed no reduction of its small-amplitude, high-frequency pendular nystagmus despite positive ERG responses. Second group: Only one dog of the four had clinically detectable INS, similar in characteristics to that seen in the affected dogs of the first group. Unlike any previous dog studied, this one showed a damping of the nystagmus within the first 4 weeks after

  20. [Anorexia with sinus bradycardia: a case report].

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    Wang, Fang-fang; Xu, Ling; Chen, Bao-xia; Cui, Ming; Zhang, Yuan

    2016-02-18

    As anorexia patients always go to the psychiatric clinic, little is concerned about the occurrence of sinus bradycardia in these patients for cardiologists and psychiatrists. The aim of this paper is to discuss the relationship between anorexia and sinus bradycardia, and the feature analysis, differential diagnosis and therapeutic principles of this type of sinus bradycardia. We report a case of sinus bradycardia in an anorexia patient with the clinical manifestations, laboratory exams, auxiliary exams, therapeutic methods, and her prognosis, who was admitted to Peking University Third Hospital recently. The patient was a 19-year-old female, who had the manifestation of anorexia. She lost obvious weight in a short time (about 15 kg in 6 months), and her body mass index was 14.8 kg/m(2). The patient felt apparent palpitation, chest depression and short breath, without dizziness, amaurosis or unconsciousness. Vitals on presentation were notable for hypotension, and bradycardia. The initial exam was significant for emaciation, but without lethargy or lower extremity edema. The electrocardiogram showed sinus bradycardia with her heart rate being 32 beats per minute. The laboratory work -up revealed her normal blood routine, electrolytes and liver function. But in her thyroid function test, the free thyroid (FT) hormones 3 was 0.91 ng/L (2.3-4.2 ng/L),and FT4 was 8.2 ng/L (8.9-18.0 ng/L), which were all lower; yet the thyroid stimulating hormone (TSH) was normal 1.48 IU/mL (0.55-4.78 IU/mL). Ultrasound revealed her normal thyroid. Anorexia is an eating disorder characterized by extremely low body weight, fear of gaining weight or distorted perception of body image, and amenorrhea. Anorexia patients who lose weight apparently in short time enhance the excitability of the parasympathetic nerve, and inhibit the sympathetic nerve which lead to the appearance of sinus bradycardia, and functional abnormalities of multiple systems such as hypothyroidism. But this kind of sinus

  1. Two novel mutations in the EYS gene are possible major causes of autosomal recessive retinitis pigmentosa in the Japanese population.

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    Katsuhiro Hosono

    Full Text Available Retinitis pigmentosa (RP is a highly heterogeneous genetic disease including autosomal recessive (ar, autosomal dominant (ad, and X-linked inheritance. Recently, arRP has been associated with mutations in EYS (Eyes shut homolog, which is a major causative gene for this disease. This study was conducted to determine the spectrum and frequency of EYS mutations in 100 Japanese arRP patients. To determine the prevalence of EYS mutations, all EYS exons were screened for mutations by polymerase chain reaction amplification, and sequence analysis was performed. We detected 67 sequence alterations in EYS, of which 21 were novel. Of these, 7 were very likely pathogenic mutations, 6 were possible pathogenic mutations, and 54 were predicted non-pathogenic sequence alterations. The minimum observed prevalence of distinct EYS mutations in our study was 18% (18/100, comprising 9 patients with 2 very likely pathogenic mutations and the remaining 9 with only one such mutation. Among these mutations, 2 novel truncating mutations, c.4957_4958insA (p.S1653KfsX2 and c.8868C>A (p.Y2956X, were identified in 16 patients and accounted for 57.1% (20/35 alleles of the mutated alleles. Although these 2 truncating mutations were not detected in Japanese patients with adRP or Leber's congenital amaurosis, we detected them in Korean arRP patients. Similar to Japanese arRP results, the c.4957_4958insA mutation was more frequently detected than the c.8868C>A mutation. The 18% estimated prevalence of very likely pathogenic mutations in our study suggests a major involvement of EYS in the pathogenesis of arRP in the Japanese population. Mutation spectrum of EYS in 100 Japanese patients, including 13 distinct very likely and possible pathogenic mutations, was largely different from the previously reported spectrum in patients from non-Asian populations. Screening for c.4957_4958insA and c.8868C>A mutations in the EYS gene may therefore be very effective for the genetic testing

  2. Neurossífilis atípica: Relato de caso Atypical neurosyphilis: case report

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    Fábio Leite Gastal

    1995-09-01

    Full Text Available O presente estudo é baseado na observação de um caso de neurossífilis no serviço de internação da Clínica Olivé Leite em agosto-1992. A paciente, do sexo feminino e com 31 anos de idade, foi admitida por apresentar quadro de psicose orgânica no qual predominavam sintomas de tipo deterioração cognitiva (síndrome demencial, associados a elementos paranoides (alucinações e delírios. A investigação diagnóstica evidenciou testes imunológicos positivos para sífilis no sangue e no LCR. Destaca-se este caso pelos seguintes aspectos peculiares: forma da apresentação clínica, gravidade dos sintomas (amaurose e severo déficit cognitivo, sexo, idade e por ser este o primeiro caso diagnosticado no serviço desde 1968 (data do último registro de caso de neurossífilis no seu Banco de Dados. Após penicilinoterapia e seguimento de 9 meses, a paciente apresenta algumas melhoras, caracterizadas por: diminuição da sintomatologia produtiva de tipo alucinatória e delirante, diminuição do déficit cognitivo em termos de orientação e maior produtividade nas atividades sociais e comportamentais.The present study is based on the observation of a case at the inpatient service of Clinica Olivé Leite in August 1992. A 31 years old female patient, showing cognitive deterioration and demential syndrome associated with paranoid elements (hallucination and delirium, was admitted as a case of organic psychosis. Diagnostic investigation evidenced positive tests for syphilis in serum and cerebrospinal fluid. The following peculiar aspects are emphasized in this case: severe clinical presentation, severe presentation symptoms (amaurosis and a severe cognitive deficit, sex, age, and for being the first case diagnosed in the service since 1968 (occasion in wich the last neurosyphilis case was registered in its data bank. In the following nine months, after penicillin therapy, the patient showed some improvement characterized by a reduction of

  3. Canine and human visual cortex intact and responsive despite early retinal blindness from RPE65 mutation.

    Science.gov (United States)

    Aguirre, Geoffrey K; Komáromy, András M; Cideciyan, Artur V; Brainard, David H; Aleman, Tomas S; Roman, Alejandro J; Avants, Brian B; Gee, James C; Korczykowski, Marc; Hauswirth, William W; Acland, Gregory M; Aguirre, Gustavo D; Jacobson, Samuel G

    2007-06-01

    RPE65 is an essential molecule in the retinoid-visual cycle, and RPE65 gene mutations cause the congenital human blindness known as Leber congenital amaurosis (LCA). Somatic gene therapy delivered to the retina of blind dogs with an RPE65 mutation dramatically restores retinal physiology and has sparked international interest in human treatment trials for this incurable disease. An unanswered question is how the visual cortex responds after prolonged sensory deprivation from retinal dysfunction. We therefore studied the cortex of RPE65-mutant dogs before and after retinal gene therapy. Then, we inquired whether there is visual pathway integrity and responsivity in adult humans with LCA due to RPE65 mutations (RPE65-LCA). RPE65-mutant dogs were studied with fMRI. Prior to therapy, retinal and subcortical responses to light were markedly diminished, and there were minimal cortical responses within the primary visual areas of the lateral gyrus (activation amplitude mean +/- standard deviation [SD] = 0.07% +/- 0.06% and volume = 1.3 +/- 0.6 cm(3)). Following therapy, retinal and subcortical response restoration was accompanied by increased amplitude (0.18% +/- 0.06%) and volume (8.2 +/- 0.8 cm(3)) of activation within the lateral gyrus (p < 0.005 for both). Cortical recovery occurred rapidly (within a month of treatment) and was persistent (as long as 2.5 y after treatment). Recovery was present even when treatment was provided as late as 1-4 y of age. Human RPE65-LCA patients (ages 18-23 y) were studied with structural magnetic resonance imaging. Optic nerve diameter (3.2 +/- 0.5 mm) was within the normal range (3.2 +/- 0.3 mm), and occipital cortical white matter density as judged by voxel-based morphometry was slightly but significantly altered (1.3 SD below control average, p = 0.005). Functional magnetic resonance imaging in human RPE65-LCA patients revealed cortical responses with a markedly diminished activation volume (8.8 +/- 1.2 cm(3)) compared to controls

  4. Mechanical injuries of the eyeball: Frequency, structure, and possibility of the prevention

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    Jovanović Miloš

    2006-01-01

    , etc. According to months in a year and days in a week, the injuries were almost evenly distributed. Considering the period of a day, even 77.4% of the injuries occurred during daytime, from 10 a.m. to 10 p.m. The highest percentage - 43.5% - of the injuries occurred while working something out of working place, while 24.5% of injuries were inflicted at working places. On admission, the majority of patients - 32.9% had visual acuity L+P+, but this visual acuity ranged from amaurosis to 1.0. There were 746 (45.4% contusion injuries and 870 (53.0% penetrating injuries. The rest were the injuries of other ocular adnexa. The majority of primary wound managements were performed in the first 24 hours of the injury - 67.1%. Conclusion. It may be concluded that working population and students are most commonly injured, and that men are five times more frequently injured than women; then, a piece of wood, sharp objects and glass are the most often causes of injury; the number of contusion and penetrating injuries is equal, and that required primary surgical wound management is most often performed in the first 24 hours from the injury. Further analysis of these factors suggests that many of these injuries could have been prevented, and consequently long-term treatment and treatment costs could have been evaded. Most important is that permanent disability due to visual impairment or even blindness of the injured eye could have been avoided.

  5. Canine and human visual cortex intact and responsive despite early retinal blindness from RPE65 mutation.

    Directory of Open Access Journals (Sweden)

    Geoffrey K Aguirre

    2007-06-01

    Full Text Available RPE65 is an essential molecule in the retinoid-visual cycle, and RPE65 gene mutations cause the congenital human blindness known as Leber congenital amaurosis (LCA. Somatic gene therapy delivered to the retina of blind dogs with an RPE65 mutation dramatically restores retinal physiology and has sparked international interest in human treatment trials for this incurable disease. An unanswered question is how the visual cortex responds after prolonged sensory deprivation from retinal dysfunction. We therefore studied the cortex of RPE65-mutant dogs before and after retinal gene therapy. Then, we inquired whether there is visual pathway integrity and responsivity in adult humans with LCA due to RPE65 mutations (RPE65-LCA.RPE65-mutant dogs were studied with fMRI. Prior to therapy, retinal and subcortical responses to light were markedly diminished, and there were minimal cortical responses within the primary visual areas of the lateral gyrus (activation amplitude mean +/- standard deviation [SD] = 0.07% +/- 0.06% and volume = 1.3 +/- 0.6 cm(3. Following therapy, retinal and subcortical response restoration was accompanied by increased amplitude (0.18% +/- 0.06% and volume (8.2 +/- 0.8 cm(3 of activation within the lateral gyrus (p < 0.005 for both. Cortical recovery occurred rapidly (within a month of treatment and was persistent (as long as 2.5 y after treatment. Recovery was present even when treatment was provided as late as 1-4 y of age. Human RPE65-LCA patients (ages 18-23 y were studied with structural magnetic resonance imaging. Optic nerve diameter (3.2 +/- 0.5 mm was within the normal range (3.2 +/- 0.3 mm, and occipital cortical white matter density as judged by voxel-based morphometry was slightly but significantly altered (1.3 SD below control average, p = 0.005. Functional magnetic resonance imaging in human RPE65-LCA patients revealed cortical responses with a markedly diminished activation volume (8.8 +/- 1.2 cm(3 compared to controls

  6. Distrofias retinianas da infância: análise retrospectiva Retinal dystrophies in childhood: retrospective analysis

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    Heloisa Andrade Maestrini

    2004-12-01

    distrofias retinianas da infância são um grupo heterogêneo de doenças que se manifestam por meio de sintomas inespecíficos. Uma análise cuidadosa dos sintomas, o exame oftalmológico completo e os exames complementares, principalmente ERG, testes de visão de cores e campo visual, podem ser úteis em seu diagnóstico.PURPOSE: To describe the clinical features and the results of diagnostic methods in all patients with diagnosis of one of the following retinal dystrophies: Leber congenital amaurosis (LCA, achromatopsia, cone distrophy or cone-rod distrophy, examined at the Low Vision Department of the Federal University of Minas Gerais, in the period of 1992 to 2003. METHODS: Retrospective analysis of charts of 40 patients. Ten had LCA, 17 had achromatopsia, 6 had cone distrophy and 7 had cone-rod distrophy. RESULTS: Visual acuity was extremely low in patients with LCA, ranging from 20/710 to light perception. The mean value for achromatopsia was 20/200, 20/280 for cone distrophy and 20/260 for cone-rod distrophy. High hyperopia was the most common refractional error in LCA patients. Hyperopia was more frequent in cases of achromatopsia and cone distrophy, while in cone-rod distrophy myopia predominated. Fundoscopy was altered in most cases of LCA, cone distrophy and rod-cone distrophy, and normal in most cases of achromatopsia. Oculodigital sign and enophtalmus were found only in LCA patients while photofobia and color vision defects prevailed in other groups. Nistagmus and strabismus were frequent findings in all groups. There was a high incidence of delayed neuro-psycho-motor development in LCA patients. Two of them had also associated genetic syndromes. Patients presented symptoms very early in life in LCA and achromatopsia, while in cone and cone-rod distrophies symptoms appeared later, but never after the age of 10. Consanguinity and positive familial history were strongly associated in all groups. The ERG was extinct in LCA, showed reduced photopic response in