Combined Occurrence of Autosomal Dominant Aniridia and Autosomal Recessive Albinism in Several Members of a Family.

PubMed

Yahalom, Claudia; Sharon, Dror; Dalia, Eli; Simhon, Shiran Ben; Shemesh, Efrat; Blumenfeld, Anat

2015-06-01

To characterize clinical and genetic aspects of a family with a unique combination of two hereditary blinding eye diseases. Comprehensive eye examination of proband and family members. Molecular analyses of the TYR and PAX6 genes. A young couple, both legally blind, requested genetic counselling regarding their ocular condition. The female was previously diagnosed with oculocutaneous albinism (OCA1A) and her spouse was diagnosed with Peters anomaly. A comprehensive clinical examination revealed that the female had OCA1A combined with signs of another ocular disease, showing some similarity to aniridia. A complete ocular examination of her family members revealed that her brother also suffered from the same combined phenotype, her father had typical OCA1A signs, and her mother and sister had aniridia-like phenotype, without clinical diagnosis until the time of presentation. Molecular analysis identified two compound heterozygous TYR mutations known to cause OCAIA and cosegregate with oculocutaneous albinism. In addition, we identified a novel heterozygous PAX6 mutation confirming the atypical aniridia phenotype. We report here a unique and rare clinical phenotype that is explained by the segregation of two severe inherited eye diseases. The clinical and genetic analysis in this family allowed them to receive accurate genetic counseling.

Apparent digenic inheritance of Waardenburg syndrome type 2 (WS2) and autosomal recessive ocular albinism (AROA).

PubMed

Morell, R; Spritz, R A; Ho, L; Pierpont, J; Guo, W; Friedman, T B; Asher, J H

1997-05-01

Waardenburg syndrome (WS) is a clinically and genetically heterogeneous disease accounting for >2% of the congenitally deaf population. It is characterized by deafness in association with pigmentary anomalies and various defects of neural crest-derived tissues. At least four types are recognized (WS1, WS2, WS3 and WS4) on the basis of clinical and genetic criteria. Two previously described families seemed to delineate a new subtype characterized by WS2 in conjunction with ocular albinism (OA). Since mutations in the MITF gene are responsible for some instances of WS2, we screened for mutations in one of the WS2-OA families and discovered a 1 bp deletion in exon 8 of MITF. OA previously has been associated with compound heterozygosity for a mutant TYR allele and the TYR(R402Q) allele, a functionally significant polymorphism that is associated with moderately reduced tyrosinase catalytic activity. In this family, all of the individuals with the OA phenotype are either homozygous or heterozygous for TYR(R402Q), and heterozyous for the 1 bp deletion in MITF This suggests that the WS2-OA phenotype may result from digenic interaction between a gene for a transcription factor (MITF) and a gene that it regulates (TYR).

Albinism

MedlinePlus

... teen years, resulting in slight changes in pigmentation. Hair Hair color can range from very white to brown. ... or Asian descent who have albinism may have hair color that's yellow, reddish or brown. Hair color ...

Albinism

MedlinePlus

... normal skin and hair Patches of missing skin color Many forms of albinism are associated with the following symptoms: Crossed eyes Light sensitivity Rapid eye movements Vision problems, or functional blindness Exams and Tests Genetic testing offers the most ...

Transcription map of Xq27: candidates for several X-linked diseases.

PubMed

Zucchi, I; Jones, J; Affer, M; Montagna, C; Redolfi, E; Susani, L; Vezzoni, P; Parvari, R; Schlessinger, D; Whyte, M P; Mumm, S

1999-04-15

Human Xq27 contains candidate regions for several disorders, yet is predicted to be a gene-poor cytogenetic band. We have developed a transcription map for the entire cytogenetic band to facilitate the identification of the relatively small number of expected candidate genes. Two approaches were taken to identify genes: (1) a group of 64 unique STSs that were generated during the physical mapping of the region were used in RT-PCR with RNA from human adult and fetal brain and (2) ESTs that have been broadly mapped to this region of the chromosome were finely mapped using a high-resolution yeast artificial chromosome contig. This combined approach identified four distinct regions of transcriptional activity within the Xq27 band. Among them is a region at the centromeric boundary that contains candidate regions for several rare developmental disorders (X-linked recessive hypoparathyroidism, thoracoabdominal syndrome, albinism-deafness syndrome, and Borjeson-Forssman-Lehman syndrome). Two transcriptionally active regions were identified in the center of Xq27 and include candidate regions for X-linked mental retardation syndrome 6, X-linked progressive cone dystrophy, X-linked retinitis pigmentosa 24, and a prostate cancer susceptibility locus. The fourth region of transcriptional activity encompasses the FMR1 (FRAXA) and FMR2 (FRAXE) genes. The analysis thus suggests clustered transcription in Xq27 and provides candidates for several heritable disorders for which the causative genes have not yet been found. Copyright 1999 Academic Press.

Homozygosity mapping in albinism patients using a novel panel of 13 STR markers inside the nonsyndromic OCA genes: introducing 5 novel mutations.

PubMed

Khordadpoor-Deilamani, Faravareh; Akbari, Mohammad Taghi; Karimipoor, Morteza; Javadi, Gholam Reza

2016-05-01

Albinism is a heterogeneous genetic disorder of melanin synthesis that results in hypopigmented hair, skin and eyes. It is associated with decreased visual acuity, nystagmus, strabismus and photophobia. Six genes are known to be involved in nonsyndromic oculocutaneous albinism (OCA). In this study, we aimed to find the disease causing mutations in albinism patients using homozygosity mapping. Twenty three unrelated patients with nonsyndromic OCA or autosomal recessive ocular albinism were recruited in this study. All of the patients' parents had consanguineous marriage and all were screened for TYR mutations previously. At first, we performed homozygosity mapping using fluorescently labeled primers to amplify a novel panel of 13 STR markers inside the OCA genes and then the screened loci in each family were studied using PCR and cycle sequencing methods. We found five mutations including three mutations in OCA2, one mutation in SLC45A2 and one mutation in C10ORF11 genes, all of which were novel. In cases where the disease causing mutations are identical by descent due to a common ancestor, these STR markers can enable us to screen for the responsible genes.

Subnormal visual acuity (SVAS) and albinism in Mexican 12-13-year-old children.

PubMed

Sjöström, A; Kraemer, M; Ohlsson, J; Garay-Cerro, G; Abrahamsson, M; Villarreal, G

2004-01-01

In a previous study the vision of 1046 12-13-year-olds in Sweden was examined. Of those 67 had some kind of visual disturbances and in 20 no obvious cause was found. In this group, defined as children with subnormal visual acuity syndromes (SVAS), albinism was shown to be a major cause to the visual dysfunction giving a prevalence of about 1%. This is about 100 times higher than previous figures. Albinism can therefore be the cause in many cases of unexplained low visual acuity, at least in Sweden. Subnormal visual acuity is usually found in 2-4% in a pediatric population and is often called 'amblyopia'. The Swedish study showed that in many cases 'amblyopia' should be replaced by 'SVAS' and further investigation. The present Mexican study was designed identically to the Swedish study. The objective was to describe the distribution of visual acuity and the prevalence of ocular disorders, including incidence of subnormal visual acuity (SVAS) and the occurrence of albinism in a Mexican population of 12-13-year-olds. Altogether 1035 children, 12-13 years of age, were examined. A total number of 344 children were referred to the university pediatric eye clinic for further examination. 272 of these had simple refractive errors, 59 were diagnosed with an ophthalmological disorder and 13 children could not be pathologically classified. These were referred to a second ophthalmological examination, including VEP (Visual Evoked Potential) recordings. VEP reveals an asymmetric (right vs. left) cortical response after monocular stimulation in albinism. No child showed iris translucency or any other typical albinoic sign. VEP was recorded from 11 children. Three children showed an asymmetric VEP and were classified as albinos. The VEP response was normal in 8 of the children. The results indicate that albinism is common in Mexico, although not as common as in a similar Swedish population. A prevalence of albinism of approximately 0.3% was found in the Mexican population

Clinical, laboratory and molecular signs of immunodeficiency in patients with partial oculo-cutaneous albinism

PubMed Central

2013-01-01

Hypopigmentation disorders that are associated with immunodeficiency feature both partial albinism of hair, skin and eyes together with leukocyte defects. These disorders include Chediak Higashi (CHS), Griscelli (GS), Hermansky-Pudlak (HPS) and MAPBP-interacting protein deficiency syndromes. These are heterogeneous autosomal recessive conditions in which the causal genes encode proteins with specific roles in the biogenesis, function and trafficking of secretory lysosomes. In certain specialized cells, these organelles serve as a storage compartment. Impaired secretion of specific effector proteins from that intracellular compartment affects biological activities. In particular, these intracellular granules are essential constituents of melanocytes, platelets, granulocytes, cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Thus, abnormalities affect pigmentation, primary hemostasis, blood cell counts and lymphocyte cytotoxic activity against microbial pathogens. Among eight genetically distinct types of HPS, only type 2 is characterized by immunodeficiency. Recently, a new subtype, HPS9, was defined in patients presenting with immunodeficiency and oculocutaneous albinism, associated with mutations in the pallidin-encoding gene, PLDN. Hypopigmentation together with recurrent childhood bacterial or viral infections suggests syndromic albinism. T and NK cell cytotoxicity are generally impaired in patients with these disorders. Specific clinical and biochemical phenotypes can allow differential diagnoses among these disorders before molecular testing. Ocular symptoms, including nystagmus, that are usually evident at birth, are common in patients with HPS2 or CHS. Albinism with short stature is unique to MAPBP-interacting protein (MAPBPIP) deficiency, while hemophagocytic lymphohistiocytosis (HLH) mainly suggests a diagnosis of CHS or GS type 2 (GS2). Neurological disease is a long-term complication of CHS, but is uncommon in other syndromic albinism

Albinism, stigma, subjectivity and global-local discourses in Tanzania.

PubMed

Brocco, Giorgio

2016-12-01

Societal ideas and explanations of albinism at the local level in Tanzania are conceived in terms of family history, social relations, economic status, moral-religious positions, global-local flows of information and humanitarian actions on behalf of people with the congenital condition. This paper aims to show how the subjectivities of people with albinism in Tanzania are shaped and re-shaped through local moral conceptions as well as globalizing (bio)medical explanations of albinism. An exemplary case study of a 28-year-old woman, plus episodes from the lives of seven other informants with the condition, are analyzed in order to understand, on the one hand, local social relationships between people with albinism and other individuals in family and community settings, and on the other hand, the interconnections between persons with albinism and global humanitarian actors and the broadcast media. When stigma and marginalizing behaviors are perceived by individuals with albinism in Tanzania as impeding their social lives, they employ different coping strategies and discourses to enhance social acceptance.

Children with albinism in African regions: their rights to 'being' and 'doing'.

PubMed

Franklin, Anita; Lund, Patricia; Bradbury-Jones, Caroline; Taylor, Julie

2018-01-12

Albinism is an inherited condition with a relatively high prevalence in populations throughout sub-Saharan Africa. People with oculocutaneous albinism have little or no pigment in their hair, skin and eyes; thus they are visually impaired and extremely sensitive to the damaging effect of the sun on their skin. Aside from the health implications of oculocutaneous albinism, there are also significant sociocultural risks. The impacts of albinism are particularly serious in areas that associate albinism with legend and folklore, leading to stigmatisation and discrimination. In regions of Africa those with albinism may be assaulted and sometimes killed for their body parts for use in witchcraft-related rites or to make 'lucky' charms. There is a dearth of research on the psychosocial aspects of albinism and particularly on how albinism impacts on the everyday lives of people with albinism. There is a growing recognition and acceptance in Africa that people with albinism should be considered disabled. Thomas's social-relational model of disability proposes it is essential to understand both the socio-structural barriers and restrictions that exclude disabled people (barriers to doing); and the social processes and practices which can negatively affect their psycho-emotional wellbeing (barriers to being). In this article, we combine a social model of disability with discussion on human rights to address the lacuna surrounding the psychosocial and daily experiences of people with albinism. Through using this combined framework we conclude that the rights of people with albinism in some regions of Africa are not being enacted. Our debate highlights the need to develop a holistic concept of rights for children and young people with albinism which sees human rights as indivisible. We illuminate some of the specific ways in which the lives of children with albinism could be improved by addressing 'barriers to being' and 'barriers to doing', at the heart of which requires a

A Partial Gene Deletion of SLC45A2 Causes Oculocutaneous Albinism in Doberman Pinscher Dogs

PubMed Central

Winkler, Paige A.; Gornik, Kara R.; Ramsey, David T.; Dubielzig, Richard R.; Venta, Patrick J.; Petersen-Jones, Simon M.; Bartoe, Joshua T.

2014-01-01

The first white Doberman pinscher (WDP) dog was registered by the American Kennel Club in 1976. The novelty of the white coat color resulted in extensive line breeding of this dog and her offspring. The WDP phenotype closely resembles human oculocutaneous albinism (OCA) and clinicians noticed a seemingly high prevalence of pigmented masses on these dogs. This study had three specific aims: (1) produce a detailed description of the ocular phenotype of WDPs, (2) objectively determine if an increased prevalence of ocular and cutaneous melanocytic tumors was present in WDPs, and (3) determine if a genetic mutation in any of the genes known to cause human OCA is causal for the WDP phenotype. WDPs have a consistent ocular phenotype of photophobia, hypopigmented adnexal structures, blue irides with a tan periphery and hypopigmented retinal pigment epithelium and choroid. WDPs have a higher prevalence of cutaneous melanocytic neoplasms compared with control standard color Doberman pinschers (SDPs); cutaneous tumors were noted in 12/20 WDP (<5 years of age: 4/12; >5 years of age: 8/8) and 1/20 SDPs (p<0.00001). Using exclusion analysis, four OCA causative genes were investigated for their association with WDP phenotype; TYR, OCA2, TYRP1 and SLC45A2. SLC45A2 was found to be linked to the phenotype and gene sequencing revealed a 4,081 base pair deletion resulting in loss of the terminus of exon seven of SLC45A2 (chr4∶77,062,968–77,067,051). This mutation is highly likely to be the cause of the WDP phenotype and is supported by a lack of detectable SLC45A2 transcript levels by reverse transcriptase PCR. The WDP provides a valuable model for studying OCA4 visual disturbances and melanocytic neoplasms in a large animal model. PMID:24647637

TYPES OF ALBINISM IN THE BLACK SOUTHERN AFRICA POPULATION.

PubMed

Kromberg, J G R; Bothwell, J; Kidson, S H; Manga, P; Kerr, R; Jenkins, T

2012-01-01

Oculocutaneous albinism (OCA) is the most common inherited disorder in Southern African blacks and several types have been described. Molecular techniques, where available, can be used to confirm a clinical diagnosis and the type of OCA, if necessary, and for prenatal diagnosis. To investigate and classify the different types of albinism commonly found and to determine the clinical implications for each type. A descriptive survey. Gauteng province, South Africa, and Lesotho. Three groups of subjects with OCA (96 from a genetics clinic, 62 from a dermatology clinic, and 31 from community surveys) from the black African population participated. Subjects underwent clinical and/or dermatological examinations and were then classified according to type of OCA. Four forms of OCA were identified: most (82%) subjects had OCA2 (a tyrosinase- positive type) with three sub-types: those without large freckles (ephelides) on exposed areas (named OCA 2a in this study), those with such freckles (named OCA 2b), and those with brown albinism (BOCA); the remainder had red/rufous albinism, ROCA (OCA 3). The four forms could be distinguished from each other clinically without using molecular genetic testing. The most common types of albinism found in the black population of Southern Africa are OCA2 and OCA3. Given the high prevalence of the disorder, together with the high risk of skin cancer, and the recent persecution of affected individuals in certain East African countries, these findings and their clinical implications have significance in terms of both education and awareness for health professionals and lay people caring for those with albinism.

A family with X-linked anophthalmia: exclusion of SOX3 as a candidate gene.

PubMed

Slavotinek, Anne; Lee, Stephen S; Hamilton, Steven P

2005-10-01

We report on a four-generation family with X-linked anophthalmia in four affected males and show that this family has LOD scores consistent with linkage to Xq27, the third family reported to be linked to the ANOP1 locus. We sequenced the SOX3 gene at Xq27 as a candidate gene for the X-linked anophthalmia based on the high homology of this gene to SOX2, a gene previously mutated in bilateral anophthlamia. However, no amino acid sequence alterations were identified in SOX3. We have improved the definition of the phenotype in males with anophthalmia linked to the ANOP1 locus, as microcephaly, ocular colobomas, and severe renal malformations have not been described in families linked to ANOP1. (c) 2005 Wiley-Liss, Inc.

Relationship Between Foveal Cone Specialization and Pit Morphology in Albinism

PubMed Central

Wilk, Melissa A.; McAllister, John T.; Cooper, Robert F.; Dubis, Adam M.; Patitucci, Teresa N.; Summerfelt, Phyllis; Anderson, Jennifer L.; Stepien, Kimberly E.; Costakos, Deborah M.; Connor, Thomas B.; Wirostko, William J.; Chiang, Pei-Wen; Dubra, Alfredo; Curcio, Christine A.; Brilliant, Murray H.; Summers, C. Gail; Carroll, Joseph

2014-01-01

Purpose. Albinism is associated with disrupted foveal development, though intersubject variability is becoming appreciated. We sought to quantify this variability, and examine the relationship between foveal cone specialization and pit morphology in patients with a clinical diagnosis of albinism. Methods. We recruited 32 subjects with a clinical diagnosis of albinism. DNA was obtained from 25 subjects, and known albinism genes were analyzed for mutations. Relative inner and outer segment (IS and OS) lengthening (fovea-to-perifovea ratio) was determined from manually segmented spectral domain-optical coherence tomography (SD-OCT) B-scans. Foveal pit morphology was quantified for eight subjects from macular SD-OCT volumes. Ten subjects underwent imaging with adaptive optics scanning light ophthalmoscopy (AOSLO), and cone density was measured. Results. We found mutations in 22 of 25 subjects, including five novel mutations. All subjects lacked complete excavation of inner retinal layers at the fovea, though four subjects had foveal pits with normal diameter and/or volume. Peak cone density and OS lengthening were variable and overlapped with that observed in normal controls. A fifth hyper-reflective band was observed in the outer retina on SD-OCT in the majority of the subjects with albinism. Conclusions. Foveal cone specialization and pit morphology vary greatly in albinism. Normal cone packing was observed in the absence of a foveal pit, suggesting a pit is not required for packing to occur. The degree to which retinal anatomy correlates with genotype or visual function remains unclear, and future examination of larger patient groups will provide important insight on this issue. PMID:24845642

Mutations in X-linked PORCN, a putative regulator of Wnt signaling, cause focal dermal hypoplasia

USDA-ARS?s Scientific Manuscript database

Focal dermal hypoplasia is an X-linked dominant disorder characterized by patchy hypoplastic skin and digital, ocular, and dental malformations. We used array comparative genomic hybridization to identify a 219-kb deletion in Xp11.23 in two affected females. We sequenced genes in this region and fou...

Being black in a white skin: Beliefs and stereotypes around albinism at a South African university.

PubMed

Phatoli, Relebohile; Bila, Nontembeko; Ross, Eleanor

2015-01-01

Background: Partly because of the legacy of apartheid, and despite being a constitutional democracy, South Africa continues to be a deeply divided society, particularly along racial lines. In this context many people with albinism do not fit neatly into black and white categories and are likely to experience social discrimination and marginalisation. Objectives: The study endeavoured to explore the beliefs and practices regarding albinism within a South African university, and the availability of support services. Method: The research was located within an interpretive qualitative paradigm and was framed within the theories of stigma, discrimination and 'othering'. Interviews were conducted with five students with albinism and 10 students without albinism. Results: Findings confirmed the existence of myths and stereotypes regarding albinism. Students with albinism tended to exclude themselves from the rest of the student community to avoid discrimination and stereotypes around their condition. Conclusion: People with albinism can teach us about social constructions of race, colour and relations between minority groups and the majority culture. Results have implications for schools, disability units at universities, and albinism societies in terms of opening up channels of communication between people with albinism and the general public and fostering knowledge and awareness thereof.

Being black in a white skin: Beliefs and stereotypes around albinism at a South African university

PubMed Central

Phatoli, Relebohile; Bila, Nontembeko

2015-01-01

Background: Partly because of the legacy of apartheid, and despite being a constitutional democracy, South Africa continues to be a deeply divided society, particularly along racial lines. In this context many people with albinism do not fit neatly into black and white categories and are likely to experience social discrimination and marginalisation. Objectives: The study endeavoured to explore the beliefs and practices regarding albinism within a South African university, and the availability of support services. Method: The research was located within an interpretive qualitative paradigm and was framed within the theories of stigma, discrimination and ‘othering’. Interviews were conducted with five students with albinism and 10 students without albinism. Results: Findings confirmed the existence of myths and stereotypes regarding albinism. Students with albinism tended to exclude themselves from the rest of the student community to avoid discrimination and stereotypes around their condition. Conclusion: People with albinism can teach us about social constructions of race, colour and relations between minority groups and the majority culture. Results have implications for schools, disability units at universities, and albinism societies in terms of opening up channels of communication between people with albinism and the general public and fostering knowledge and awareness thereof. PMID:28730019

David S. Albin | NREL

Science.gov Websites

Optics+Photonics Meeting-Reliability of Photovoltaic Cells, Modules, Components and Systems (2008). R.L Photovoltaic Cells, Modules, Components and Systems (2011). D.S. Albin, "Growth temperature and of governing factors for photovoltaic loss mechanism of n-CdS/p-CdTe heterojunction via multiway data

Ocular Features in Alport Syndrome: Pathogenesis and Clinical Significance

PubMed Central

Sheth, Shivanand; Leys, Anita; Nicholson, Anjali; Mack, Heather G.; Colville, Deb

2015-01-01

Alport syndrome is an inherited disease characterized by progressive renal failure, hearing loss, and ocular abnormalities. Mutations in the COL4A5 (X-linked), or COL4A3 and COL4A4 (autosomal recessive) genes result in absence of the collagen IV α3α4α5 network from the basement membranes of the cornea, lens capsule, and retina and are associated with corneal opacities, anterior lenticonus, fleck retinopathy, and temporal retinal thinning. Typically, these features do not affect vision or, in the case of lenticonus, are correctable. In contrast, the rarer ophthalmic complications of posterior polymorphous corneal dystrophy, giant macular hole, and maculopathy all produce visual loss. Many of the ocular features of Alport syndrome are common, easily recognizable, and thus, helpful diagnostically, and in identifying the likelihood of early-onset renal failure. Lenticonus and central fleck retinopathy strongly suggest the diagnosis of Alport syndrome and are associated with renal failure before the age of 30 years, in males with X-linked disease. Sometimes, ophthalmic features suggest the mode of inheritance. A peripheral retinopathy in the mother of a male with hematuria suggests X-linked inheritance, and central retinopathy or lenticonus in a female means that recessive disease is likely. Ocular examination, retinal photography, and optical coherence tomography are widely available, safe, fast, inexpensive, and acceptable to patients. Ocular examination is particularly helpful in the diagnosis of Alport syndrome when genetic testing is not readily available or the results are inconclusive. It also detects complications, such as macular hole, for which new treatments are emerging. PMID:25649157

Ocular features in Alport syndrome: pathogenesis and clinical significance.

PubMed

Savige, Judy; Sheth, Shivanand; Leys, Anita; Nicholson, Anjali; Mack, Heather G; Colville, Deb

2015-04-07

Alport syndrome is an inherited disease characterized by progressive renal failure, hearing loss, and ocular abnormalities. Mutations in the COL4A5 (X-linked), or COL4A3 and COL4A4 (autosomal recessive) genes result in absence of the collagen IV α3α4α5 network from the basement membranes of the cornea, lens capsule, and retina and are associated with corneal opacities, anterior lenticonus, fleck retinopathy, and temporal retinal thinning. Typically, these features do not affect vision or, in the case of lenticonus, are correctable. In contrast, the rarer ophthalmic complications of posterior polymorphous corneal dystrophy, giant macular hole, and maculopathy all produce visual loss. Many of the ocular features of Alport syndrome are common, easily recognizable, and thus, helpful diagnostically, and in identifying the likelihood of early-onset renal failure. Lenticonus and central fleck retinopathy strongly suggest the diagnosis of Alport syndrome and are associated with renal failure before the age of 30 years, in males with X-linked disease. Sometimes, ophthalmic features suggest the mode of inheritance. A peripheral retinopathy in the mother of a male with hematuria suggests X-linked inheritance, and central retinopathy or lenticonus in a female means that recessive disease is likely. Ocular examination, retinal photography, and optical coherence tomography are widely available, safe, fast, inexpensive, and acceptable to patients. Ocular examination is particularly helpful in the diagnosis of Alport syndrome when genetic testing is not readily available or the results are inconclusive. It also detects complications, such as macular hole, for which new treatments are emerging. Copyright © 2015 by the American Society of Nephrology.

Albinism in the Great Gray Owl (Strix nebulosa) and other owls

Treesearch

Pentti Alaja; Heimo Mikkola

1997-01-01

An incomplete albino Great Gray Owl (Strix nebulosa) was observed in Vesanto and Kajaani, Finland, 1994-1995. The literature pertaining to albinism in owls indicates that total and incomplete albinism has only been reported in 13 different owl species, the Great Gray Owl being the only species with more than five records. Thus six to seven incomplete...

Ocular Motor Indicators of Executive Dysfunction in Fragile X and Turner Syndromes

ERIC Educational Resources Information Center

Lasker, Adrian G.; Mazzocco, Michele M. M.; Zee, David S.

2007-01-01

Fragile X and Turner syndromes are two X-chromosome-related disorders associated with executive function and visual spatial deficits. In the present study, we used ocular motor paradigms to examine evidence that disruption to different neurological pathways underlies these deficits. We tested 17 females with fragile X, 19 females with Turner…

Changes in brain morphology in albinism reflect reduced visual acuity.

PubMed

Bridge, Holly; von dem Hagen, Elisabeth A H; Davies, George; Chambers, Claire; Gouws, Andre; Hoffmann, Michael; Morland, Antony B

2014-07-01

Albinism, in humans and many animal species, has a major impact on the visual system, leading to reduced acuity, lack of binocular function and nystagmus. In addition to the lack of a foveal pit, there is a disruption to the routing of the nerve fibers crossing at the optic chiasm, resulting in excessive crossing of fibers to the contralateral hemisphere. However, very little is known about the effect of this misrouting on the structure of the post-chiasmatic visual pathway, and the occipital lobes in particular. Whole-brain analyses of cortical thickness in a large cohort of subjects with albinism showed an increase in cortical thickness, relative to control subjects, particularly in posterior V1, corresponding to the foveal representation. Furthermore, mean cortical thickness across entire V1 was significantly greater in these subjects compared to controls and negatively correlated with visual acuity in albinism. Additionally, the group with albinism showed decreased gyrification in the left ventral occipital lobe. While the increase in cortical thickness in V1, also found in congenitally blind subjects, has been interpreted to reflect a lack of pruning, the decreased gyrification in the ventral extrastriate cortex may reflect the reduced input to the foveal regions of the ventral visual stream. Copyright © 2012 Elsevier Ltd. All rights reserved.

Myths, Stereotypes and Self-Perception: The Impact of Albinism on Self-Esteem

ERIC Educational Resources Information Center

Palmer, Carolyn

2007-01-01

Albinism has the potential to affect young people both emotionally and psychologically. Their condition is unique and is surrounded by myths and stereotypes. The unusual appearance of children with oculocutaneous albinism draws attention to them and their vision impairment can impact on their development of social skills and peer relationships. In…

Genotype-phenotype variations in five Spanish families with Norrie disease or X-linked FEVR.

PubMed

Riveiro-Alvarez, Rosa; Trujillo-Tiebas, Maria José; Gimenez-Pardo, Ascension; Garcia-Hoyos, Maria; Cantalapiedra, Diego; Lorda-Sanchez, Isabel; Rodriguez de Alba, Marta; Ramos, Carmen; Ayuso, Carmen

2005-09-02

Norrie disease (OMIM 310600) is a rare X-linked disorder characterized by congenital blindness in males. Approximately 40 to 50% of the cases develop deafness and mental retardation. X-linked familial exudative vitreoretinopathy (XL-FEVR) is a hereditary ocular disorder characterized by a failure of peripheral retinal vascularization. Both X-linked disorders are due to mutations in the NDP gene, which encodes a 133 amino acid protein called Norrin, but autosomal recessive (AR) and autosomal dominant (AD) forms of FEVR have also been described. In this study, we report the molecular findings and the related phenotype in five Spanish families affected with Norrie disease or XL-FEVR due to mutations of the NDP gene. The study was conducted in 45 subjects from five Spanish families. These families were clinically diagnosed with Norrie disease or similar conditions. The three exons of the NDP gene were analyzed by automatic DNA sequencing. Haplotype analyses were also performed. Two new nonsense mutations, apart from other mutations previously described in the NDP gene, were found in those patients affected with ND or X-linked FEVR. An important genotype-phenotype variation was found in relation to the different mutations of the NDP gene. In fact, the same mutation may be responsible for different phenotypes. We speculate that there might be other molecular factors that interact in the retina with Norrin, which contribute to the resultant phenotypes.

Convergence of Human Genetics and Animal Studies: Gene Therapy for X-Linked Retinoschisis

PubMed Central

Bush, Ronald A.; Wei, Lisa L.; Sieving, Paul A.

2015-01-01

Retinoschisis is an X-linked recessive genetic disease that leads to vision loss in males. X-linked retinoschisis (XLRS) typically affects young males; however, progressive vision loss continues throughout life. Although discovered in 1898 by Haas in two brothers, the underlying biology leading to blindness has become apparent only in the last 15 years with the advancement of human genetic analyses, generation of XLRS animal models, and the development of ocular monitoring methods such as the electroretinogram and optical coherence tomography. It is now recognized that retinoschisis results from cyst formations within the retinal layers that interrupt normal visual neurosignaling and compromise structural integrity. Mutations in the human retinoschisin gene have been correlated with disease severity of the human XLRS phenotype. Introduction of a normal human retinoschisin cDNA into retinoschisin knockout mice restores retinal structure and improves neural function, providing proof-of-concept that gene replacement therapy is a plausible treatment for XLRS. PMID:26101206

Oral medicine case book 51: actinic cheilitis in a patient with oculocutaneous albinism.

PubMed

Wood, N H; Moodley, A

2013-07-01

Patients with oculocutaneous albinism are more prone to sun-induced damage due to the lack of melanin. Actinic cheilitis is a potentially malignant disorder that occurs due to chronic UV-B radiation to the vermillion region of the lip, a region that is already at risk due to its morphology. A case of actinic cheilitis in a patient with oculocutaneous albinism is presented with a literature review.

Foveal hemorrhage in an eye with foveal hypoplasia associated with albinism.

PubMed

Masuda, Naonori; Hasegawa, Taiji; Yamashita, Mariko; Ogata, Nahoko

2014-01-01

Oculocutaneous albinism is a group of congenital disorders caused by alterations of melanin biosynthesis. We report our findings in a patient with oculocutaneous albinism who presented with foveal hypoplasia and a foveal hemorrhage. A 48-year-old man noted a dark spot in the middle of the visual field of his right eye. He had depigmented skin, white hair, white eyebrows, and white cilia. He also had horizontal nystagmus and depigmented irides. His best-corrected visual acuity was 2/100 with -14.0 diopters in the right eye and 3/100 with -5.0 diopters in the left eye. Ophthalmoscopy showed diffuse depigmentation in both eyes and a foveal hemorrhage in the right eye. Optical coherence tomography showed the absence of a foveal pit in both eyes and a subretinal hyperreflective lesion corresponding to the foveal hemorrhage in the right eye. Fluorescein angiography showed that the retinal and choroidal vessels were relatively hypofluorescent because of the lack of a blocking effect of the pigments in the retinal pigment epithelium. Fluorescein angiography and indocyanine green angiography did not show any evidence of choroidal neovascularization in either eye. The foveal hemorrhage in the right eye spontaneously regressed and finally resolved at 3 months after onset. At the final examination, the patient reported that his vision had recovered. A foveal hemorrhage is a rare condition in an eye with foveal hypoplasia associated with albinism. The hemorrhage may be related to high myopia and also to the hypoplasia of the fovea associated with albinism.

[Preimplantation genetic diagnosis and monogenic inherited eye diseases].

PubMed

Hlavatá, L; Ďuďáková, Ľ; Trková, M; Soldátová, I; Skalická, P; Kousal, B; Lišková, P

Preimplantation genetic diagnosis (PGD) is an established application of genetic testing in the context of in vitro fertilization. PGD is an alternative method to prenatal diagnosis which aims to prevent the transmission of an inherited disorder to the progeny by implanting only embryos that do not carry genetic predisposition for a particular disease. The aim of this study is to provide an overview of eye disorders for which PGD has been carried out. The European literature search focused on best practices, ethical issues, risks and results of PGD for inherited eye disorders. PGD is performed for a number of ocular disorders; a prerequisite for its application is however, the knowledge of a disease-causing mutation(s). The main advantage of this method is that the couple is not exposed to a decision of whether or not to undergo an abortion. Qualified counselling must be provided prior to the PGD in order to completely understand the risk of disability in any child conceived, consequences of disease manifestation, and advantages as well as limitations of this method. In the group of non-syndromic eye diseases and diseases in which ocular findings dominate, PGD has been performed in European countries for aniridia, choroideremia, congenital fibrosis of extraocular muscles, Leber congenital amaurosis, ocular albinism, retinitis pigmentosa, X-linked retinoschisis, Stargardt disease, blepharophimosis-ptosis-inverse epicanthus syndrome and retinoblastoma. Sexing for X-linked or mitochondrial diseases has been carried out for blue cone monochromatism, choroideremia, familial exudative vitreoretinopathy, Leber hereditary optic neuropathy, macular dystrophy (not further specified), Norrie disease, X-linked congenital stationary night blindness, X-linked retinoschisis and nystagmus (not further specified). In recent years, there has been an increase in potential to use PGD. The spectrum of diseases for this method has widened to include severe inherited eye diseases

Design and evaluation of moxifloxacin hydrochloride ocular inserts.

PubMed

Pawar, Pravin K; Katara, Rajesh; Majumdar, Dipak K

2012-03-01

The objective of the present investigation was to prepare and evaluate ocular inserts of moxifloxacin. An ocular insert was made from an aqueous dispersion of moxifloxacin, sodium alginate, polyvinyl alcohol, and dibutyl phthalate by the film casting method. The ocular insert (5.5 mm diameter) was cross-linked by CaCl2 and was coated with Eudragit S-100, RL-100, RS-100, E-100 or L-100. The in vitro drug drainage/permeation studies were carried out using an all-glass modified Franz diffusion cell. The drug concentration and mucoadhesion time of the ocular insert were found satisfactory. Cross-linking and coating with polymers extended the drainage from inserts. The cross-linked ocular insert coated with Eudragit RL-100 showed maximum drug permeation compared to other formulations.

Genetics Home Reference: X-linked thrombocytopenia

MedlinePlus

... Facebook Twitter Home Health Conditions X-linked thrombocytopenia X-linked thrombocytopenia Printable PDF Open All Close All ... Javascript to view the expand/collapse boxes. Description X-linked thrombocytopenia is a bleeding disorder that primarily ...

Prenatal molecular diagnosis of oculocutaneous albinism (OCA) in a large cohort of Israeli families.

PubMed

Rosenmann, Ada; Bejarano-Achache, Idit; Eli, Dalia; Maftsir, Genia; Mizrahi-Meissonnier, Liliana; Blumenfeld, Anat

2009-10-01

To present our accumulated data on prenatal molecular diagnosis of oculocutaneous albinism (OCA) in a large cohort of Israeli albino families. Albinism consists of variable phenotypes, but only families with predicted severely handicapped albino offspring, who declared their wish to terminate a pregnancy of such a fetus, are eligible for prenatal testing. Prenatal testing is not offered otherwise. Following detailed genetic investigation and counseling, molecular prenatal testing was performed using the combination of mutation screening, direct sequencing, and haplotype analysis. A total of 55 prenatal tests were performed in 37 families; in 26 families the propositus was the child, and in 11, a parent or a close relative. In 32 families tyrosinase (TYR) mutations were diagnosed. In 5 families a P gene mutation was detected. Twelve albino fetuses were diagnosed. Following further genetic counseling, all couples elected to terminate the pregnancy. Three additional pregnancies were terminated for other reasons. Families with increased risk for an albino child with severe visual handicap, seek premarital and prenatal genetic counseling and testing, for the prevention of affected offspring. Our combined methods of molecular genetic testing enable a nationwide approach for prevention of albinism. The same paradigm can be applied to other populations affected with albinism.

Partial Oculocutaneous Albinism: Two Siblings with Features of both Hermansky Pudlak and Waardenburg's Syndrome.

PubMed

Ishaq, Mazhar; Niazi, Muhammad Khizar; Khan, Muhammad Saim; Nadeem, Yasser

2015-04-01

Albinism is an inherited abnormality of melanin synthesis with incidence of one per 20,000 births. Its clinical manifestations are related to the reduction or absence of pigmentation in the visual system and/or the skin and teguments. The clinical spectrum of Oculocutaneous Albinism (OCA) has four types ranging from OCA 1 - 4, of which OCA 1, A-1 is the most severe form. Partial cutaneous albinism which is a subtype of OCA is associated with systemic immunodeficiency disorders like Chediak Higashi (CHS), Griscelli (GS) and Hermansky-Pudlak (HPS) syndromes. A7 years boy was labeled initially as a case of Hermansky Pudlak syndrome at the age of 01 year. He as well as his 4 years old younger brother when examined in detail along with audiological investigations were diagnosed as a rare presentation of both Hermansky Pudlak and Waardenburg's syndrome.

Glycerogelatin-based ocular inserts of aceclofenac: physicochemical, drug release studies and efficacy against prostaglandin E₂-induced ocular inflammation.

PubMed

Mathurm, Manish; Gilhotra, Ritu Mehra

2011-01-01

An attempt has been made in the present study to formulate soluble ocular inserts of aceclofenac to facilitate the bioavailability of the drug into the eye, as no eye drop solution could be formulated. Glycero-gelatin ocular inserts/films were prepared and physicochemical parameters and drug release profiles of glycerol-gelatin films of aceclofenac were compared with surface cross-linked films of similar compositions. Ocular irritation of the developed formulation was also checked by HET-CAM test and efficacy of the developed formulation against prostaglandin-induced ocular inflammation in rabbit eye was determined. The non-cross-linked films showed poor mechanical, physicochemical properties, and very little potential of sustaining drug release, however cross-linking the films enhanced tensile strength by 70%, but elasticity decreased by 95%. The cross-linked ocular inserts showed less swelling than non-cross-linked. Formulation AF8 (20% gelatin and 70% glycerin, treated by cross-linker for 1 h) demonstrated the longest drug release for 24 h. As per the kinetic models all films showed a constant drug release with Higuchi diffusion mechanism. Formulation was found to be practically non-irritant. The optimized formulation was tested and compared with eye drops of aceclofenac for anti-inflammatory activity in rabbits against PGE₂-induced inflammation. In vivo studies with developed formulation indicated a significant inhibition of PGE₂-induced PMN migration as compared to eye drops. In conclusion, ocular inserts of aceclofenac was found promising as it achieved sustained drug release and better pharmacodynamic activity.

Diagnosis of X-Linked Hypohidrotic Ectodermal Dysplasia by Meibography and Infrared Thermography of the Eye.

PubMed

Kaercher, Thomas; Dietz, Jasna; Jacobi, Christina; Berz, Reinhold; Schneider, Holm

2015-09-01

X-linked hypohidrotic ectodermal dysplasia (XLHED) is the most common form of ectodermal dysplasia. Clinical characteristics include meibomian gland disorder and the resulting hyperevaporative dry eye. In this study, we evaluated meibography and ocular infrared thermography as novel methods to diagnose XLHED. Eight infants, 12 boys and 14 male adults with XLHED and 12 healthy control subjects were subjected to a panel of tests including the ocular surface disease index (OSDI), meibography and infrared thermography, non-invasive measurement of tear film break-up time (NIBUT) and osmolarity, Schirmer's test, lissamine green staining and fluorescein staining. Sensitivity and specificity were determined for single tests and selected test combinations. Meibography had 100% sensitivity and specificity for identifying XLHED. Infrared thermography, a completely non-invasive procedure, revealed a typical pattern for male subjects with XLHED. It was, however, less sensitive (86% for adults and 67% for children) than meibography or a combination of established routine tests. In adults, OSDI and NIBUT were the best single routine tests (sensitivity of 86% and 71%, respectively), whereas increased tear osmolarity appeared as a rather unspecific ophthalmic symptom. In children, NIBUT was the most convincing routine test (sensitivity of 91%). Meibography is the most reliable ophthalmic examination to establish a clinical diagnosis in individuals with suspected hypohidrotic ectodermal dysplasia, even before genetic test results are available. Tear film tests and ocular surface staining are less sensitive in children, but very helpful for estimating the severity of ocular surface disease in individuals with known XLHED.

Multifocal visual evoked potentials reveal normal optic nerve projections in human carriers of oculocutaneous albinism type 1a.

PubMed

Hoffmann, Michael B; Wolynski, Barbara; Meltendorf, Synke; Behrens-Baumann, Wolfgang; Käsmann-Kellner, Barbara

2008-06-01

In albinism, part of the temporal retina projects abnormally to the contralateral hemisphere. A residual misprojection is also evident in feline carriers that are heterozygous for tyrosinase-related albinism. This study was conducted to test whether such residual abnormalities can also be identified in human carriers of oculocutaneous tyrosinase-related albinism (OCA1a). In eight carriers heterozygous for OCA1a and in eight age- and sex-matched control subjects, monocular pattern-reversal and -onset multifocal visual evoked potentials (mfVEPs) were recorded at 60 locations comprising a visual field of 44 degrees diameter (VERIS 5.01; EDI, San Mateo, CA). For each eye and each stimulus location, interhemispheric difference potentials were calculated and correlated with each other, to assess the lateralization of the responses: positive and negative correlations indicate lateralizations on the same or opposite hemispheres, respectively. Misrouted optic nerves are expected to yield negative interocular correlations. The analysis also allowed for the assessment of the sensitivity and specificity of the detection of projection abnormalities. No significant differences were obtained for the distributions of the interocular correlation coefficients of controls and carriers. Consequently, no local representation abnormalities were observed in the group of OCA1a carriers. For pattern-reversal and -onset stimulation, an assessment of the control data yielded similar specificity (97.9% and 94.6%) and sensitivity (74.4% and 74.8%) estimates for the detection of projection abnormalities. The absence of evidence for projection abnormalities in human OCA1a carriers contrasts with the previously reported evidence for abnormalities in cat-carriers of tyrosinase-related albinism. This discrepancy suggests that animal models of albinism may not provide a match to human albinism.

Refractive errors, visual impairment, and the use of low-vision devices in albinism in Malawi.

PubMed

Schulze Schwering, M; Kumar, N; Bohrmann, D; Msukwa, G; Kalua, K; Kayange, P; Spitzer, M S

2015-04-01

This study focuses on the refractive implications of albinism in Malawi, which is mostly associated with the burden of visual impairment. The main goal was to describe the refractive errors and to analyze whether patients with albinism in Malawi, Sub-Saharan Africa, benefit from refraction. Age, sex, refractive data, uncorrected and best-corrected visual acuity (UCVA, BCVA), colour vision, contrast sensitivity, and the prescription of sunglasses and low vision devices were collected for a group of 120 albino individuals with oculocutaneous albinism (OCA). Refractive errors were evaluated objectively and subjectively by retinoscopy, and followed by cycloplegic refraction to reconfirm the results. Best-corrected visual acuity (BCVA) was also assessed binocularly. One hundred and twenty albino subjects were examined, ranging in age from 4 to 25 years (median 12 years), 71 (59 %) boys and 49 (41 %) girls. All exhibited horizontal pendular nystagmus. Mean visual acuity improved from 0.98 (0.33) logMAR to 0.77 (0.15) logMAR after refraction (p < 0.001). The best improvement of VA was achieved in patients with mild to moderate myopia. Patients with albinism who were hyperopic more than +1.5 D hardly improved from refraction. With the rule (WTR) astigmatism was more present (37.5 %) than against the rule (ATR) astigmatism (3.8 %). Patients with astigmatism less than 1.5 D improved in 15/32 of cases (47 %) by 2 lines or more. Patients with astigmatism equal to or more than 1.5 D in any axis improved in 26/54 of cases (48 %) by 2 lines or more. Refraction improves visual acuity of children with oculocutaneous albinism in a Sub-Saharan African population in Malawi. The mean improvement was 2 logMAR units.

Genetics Home Reference: X-linked dilated cardiomyopathy

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... Twitter Home Health Conditions X-linked dilated cardiomyopathy X-linked dilated cardiomyopathy Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description X-linked dilated cardiomyopathy is a form of heart ...

Genetics Home Reference: X-linked myotubular myopathy

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... Twitter Home Health Conditions X-linked myotubular myopathy X-linked myotubular myopathy Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description X-linked myotubular myopathy is a condition that primarily ...

Genetics Home Reference: X-linked sideroblastic anemia

MedlinePlus

... Twitter Home Health Conditions X-linked sideroblastic anemia X-linked sideroblastic anemia Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description X-linked sideroblastic anemia is an inherited disorder that ...

Golden tapetal reflex in male patients with X-linked retinitis pigmentosa. Case report and practical implications.

PubMed

van Osch, L; van Schooneveld, M; Bleekerwagemakers, E M

1990-12-01

The golden tapetal reflex in the ocular fundus is considered pathognomonic of the carrier state in some families with X-linked retinitis pigmentosa (XRP). Reports concerning affected males with this characteristic reflex are scarce. A six-year-old boy with XRP having a tapetal reflex is described. Recently the tapetal reflex has drawn attention in linkage studies. XRP is probably genetically heterogeneous and has at least two genetic forms. The finding of a tapetal reflex in one or more female carriers in a family with XRP may be helpful in differentiating between these two genetic forms.

Mapping the x-linked lymphoproliferative syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Skare, J.C.; Milunsky, A.; Byron, K.S.

1987-04-01

The X-linked lymphoproliferative syndrome is triggered by Epstein-Barr virus infection and results in fatal mononucleosis, immunodeficiency, and lymphoproliferative disorders. This study shows that the mutation responsible for X-linked lymphoproliferative syndrome is genetically linked to a restriction fragment length polymorphism detected with the DXS42 probe (from Xq24-q27). The most likely recombination frequency between the loci is 4%, and the associated logarithm of the odds is 5.26. Haplotype analysis using flanking restriction fragment length polymorphism markers indicates that the locus for X-linked lymphoproliferative syndrome is distal to probe DXS42 but proximal to probe DXS99 (from Xq26-q27). It is now possible to predictmore » which members of a family with X-linked lymphoproliferative syndrome are carrier females and to diagnose the syndrome prenatally.« less

BCOR analysis in patients with OFCD and Lenz microphthalmia syndromes, mental retardation with ocular anomalies, and cardiac laterality defects

PubMed Central

Hilton, Emma; Johnston, Jennifer; Whalen, Sandra; Okamoto, Nobuhiko; Hatsukawa, Yoshikazu; Nishio, Juntaro; Kohara, Hiroshi; Hirano, Yoshiko; Mizuno, Seiji; Torii, Chiharu; Kosaki, Kenjiro; Manouvrier, Sylvie; Boute, Odile; Perveen, Rahat; Law, Caroline; Moore, Anthony; Fitzpatrick, David; Lemke, Johannes; Fellmann, Florence; Debray, François-Guillaume; Dastot-Le-Moal, Florence; Gerard, Marion; Martin, Josiane; Bitoun, Pierre; Goossens, Michel; Verloes, Alain; Schinzel, Albert; Bartholdi, Deborah; Bardakjian, Tanya; Hay, Beverly; Jenny, Kim; Johnston, Kathreen; Lyons, Michael; Belmont, John W; Biesecker, Leslie G; Giurgea, Irina; Black, Graeme

2009-01-01

Oculofaciocardiodental (OFCD) and Lenz microphthalmia syndromes form part of a spectrum of X-linked microphthalmia disorders characterized by ocular, dental, cardiac and skeletal anomalies and mental retardation. The two syndromes are allelic, caused by mutations in the BCL-6 corepressor gene (BCOR). To extend the series of phenotypes associated with pathogenic mutations in BCOR, we sequenced the BCOR gene in patients with (1) OFCD syndrome, (2) putative X-linked (‘Lenz') microphthalmia syndrome, (3) isolated ocular defects and (4) laterality phenotypes. We present a new cohort of females with OFCD syndrome and null mutations in BCOR, supporting the hypothesis that BCOR is the sole molecular cause of this syndrome. We identify for the first time mosaic BCOR mutations in two females with OFCD syndrome and one apparently asymptomatic female. We present a female diagnosed with isolated ocular defects and identify minor features of OFCD syndrome, suggesting that OFCD syndrome may be mild and underdiagnosed. We have sequenced a cohort of males diagnosed with putative X-linked microphthalmia and found a mutation, p.P85L, in a single case, suggesting that BCOR mutations are not a major cause of X-linked microphthalmia in males. The absence of BCOR mutations in a panel of patients with non-specific laterality defects suggests that mutations in BCOR are not a major cause of isolated heart and laterality defects. Phenotypic analysis of OFCD and Lenz microphthalmia syndromes shows that in addition to the standard diagnostic criteria of congenital cataract, microphthalmia and radiculomegaly, patients should be examined for skeletal defects, particularly radioulnar synostosis, and cardiac/laterality defects. PMID:19367324

Ocular radioimmunoscintigraphy: sensitivity and practical considerations.

PubMed

Bomanji, J; Nimmon, C C; Hungerford, J L; Solanki, K; Granowska, M; Britton, K E

1988-06-01

Ocular radioimmunoscintigraphy was performed in 20 patients using 99mTc-labeled monoclonal antibody 225.28S, F(ab')2 fragments. Radioimmunoscintigraphy was positive in 13 patients and the diagnosis of ocular melanoma was confirmed by enucleation of the eye or clinical follow-up. Scintigraphy was positive in one patient with lymph node metastasis from an ocular melanoma. In six patients immunoscintigraphy was negative. Using this technique a sensitivity of 92.8% was achieved for detecting ocular melanomas. Single photon emission tomography helped to separate the lesions situated in the nasal quadrant of the eye from the adjacent nasopharyngeal activity. With appropriate imaging techniques small tumors of the order of 3 x 5 x 3 mm could be detected clearly.

Caspase-9 Mediates Photoreceptor Death After Blunt Ocular Trauma

PubMed Central

Blanch, Richard J.; Ahmed, Zubair; Thompson, Adam R.; Akpan, Nsikan; Snead, David R. J.; Berry, Martin; Troy, Carol M.; Scott, Robert A. H.; Logan, Ann

2014-01-01

Purpose. Ocular trauma is common in civilian and military populations. Commotio retinae involves acute disruption of photoreceptor outer segments after blunt ocular trauma, with subsequent photoreceptor apoptosis causing permanent visual impairment. The mechanisms of photoreceptor death in commotio retinae have not previously been described, although caspase-dependent death is important in other nontraumatic retinal degenerations. We assessed the role of caspase-9 as a mediator of photoreceptor death in a rat model of ballistic ocular trauma causing commotio retinae. Methods. Bilateral commotio retinae was induced in rats by ballistic ocular trauma. Caspase-9 activity was assessed by immunohistochemistry, Western blotting, and bVAD-fmk active caspase capture. Caspase-9 was inhibited by unilateral intravitreal injection of highly specific X-linked inhibitor of apoptosis (IAP) baculoviral IAP repeat 3 (XBIR3) domain linked to the cell transduction peptide penetratin 1 (Pen-1) after ballistic injury, and the affected eyes were compared with control eyes treated with Pen-1 injection alone, and retinal function was assessed by electroretinogram a-wave amplitude and photoreceptor survival by outer nuclear layer thickness. Results. Increased levels of cleaved caspase-9 were shown in photoreceptors 5 hours after injury, and catalytically active full-length caspase-9 was isolated from retinas. Photoreceptor death after commotio retinae was reduced by caspase-9 inhibition by using Pen-1–XBIR3, and electroretinographic measurements of photoreceptor function was preserved, providing structural and functional neuroprotection. Conclusions. The time course of caspase-9 activation and the neuroprotective effects of inhibition suggest that caspase-9 initiates cell death in a proportion of photoreceptors after blunt ocular trauma and that an intravitreally delivered biologic inhibitor may be an effective translational treatment strategy. PMID:25190658

Molecular links among the causative genes for ocular malformation: Otx2 and Sox2 coregulate Rax expression

PubMed Central

Danno, Hiroki; Michiue, Tatsuo; Hitachi, Keisuke; Yukita, Akira; Ishiura, Shoichi; Asashima, Makoto

2008-01-01

The neural-related genes Sox2, Pax6, Otx2, and Rax have been associated with severe ocular malformations such as anophthalmia and microphthalmia, but it remains unclear as to how these genes are linked functionally. We analyzed the upstream signaling of Xenopus Rax (also known as Rx1) and identified the Otx2 and Sox2 proteins as direct upstream regulators of Rax. We revealed that endogenous Otx2 and Sox2 proteins bound to the conserved noncoding sequence (CNS1) located ≈2 kb upstream of the Rax promoter. This sequence is conserved among vertebrates and is required for potent transcriptional activity. Reporter assays showed that Otx2 and Sox2 synergistically activated transcription via CNS1. Furthermore, the Otx2 and Sox2 proteins physically interacted with each other, and this interaction was affected by the Sox2-missense mutations identified in these ocular disorders. These results demonstrate that the direct interaction and interdependence between the Otx2 and Sox2 proteins coordinate Rax expression in eye development, providing molecular linkages among the genes responsible for ocular malformation. PMID:18385377

Molecular links among the causative genes for ocular malformation: Otx2 and Sox2 coregulate Rax expression.

PubMed

Danno, Hiroki; Michiue, Tatsuo; Hitachi, Keisuke; Yukita, Akira; Ishiura, Shoichi; Asashima, Makoto

2008-04-08

The neural-related genes Sox2, Pax6, Otx2, and Rax have been associated with severe ocular malformations such as anophthalmia and microphthalmia, but it remains unclear as to how these genes are linked functionally. We analyzed the upstream signaling of Xenopus Rax (also known as Rx1) and identified the Otx2 and Sox2 proteins as direct upstream regulators of Rax. We revealed that endogenous Otx2 and Sox2 proteins bound to the conserved noncoding sequence (CNS1) located approximately 2 kb upstream of the Rax promoter. This sequence is conserved among vertebrates and is required for potent transcriptional activity. Reporter assays showed that Otx2 and Sox2 synergistically activated transcription via CNS1. Furthermore, the Otx2 and Sox2 proteins physically interacted with each other, and this interaction was affected by the Sox2-missense mutations identified in these ocular disorders. These results demonstrate that the direct interaction and interdependence between the Otx2 and Sox2 proteins coordinate Rax expression in eye development, providing molecular linkages among the genes responsible for ocular malformation.

Genetics Home Reference: X-linked severe combined immunodeficiency

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... Facebook Twitter Home Health Conditions X-linked SCID X-linked severe combined immunodeficiency Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description X-linked severe combined immunodeficiency (SCID) is an inherited ...

Genetics Home Reference: X-linked adrenal hypoplasia congenita

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... Home Health Conditions X-linked adrenal hypoplasia congenita X-linked adrenal hypoplasia congenita Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description X-linked adrenal hypoplasia congenita is a disorder that ...

Genetics Home Reference: X-linked chondrodysplasia punctata 1

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... Home Health Conditions X-linked chondrodysplasia punctata 1 X-linked chondrodysplasia punctata 1 Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description X-linked chondrodysplasia punctata 1 is a disorder of ...

In Southern Africa, Brown Oculocutaneous Albinism (BOCA) Maps to the OCA2 Locus on Chromosome 15q: P-Gene Mutations Identified

PubMed Central

Manga, Prashiela; Kromberg, Jennifer G. R.; Turner, Angela; Jenkins, Trefor; Ramsay, Michele

2001-01-01

In southern Africa, brown oculocutaneous albinism (BOCA) is a distinct pigmentation phenotype. In at least two cases, it has occurred in the same families as tyrosinase-positive oculocutaneous albinism (OCA2), suggesting that it may be allelic, despite the fact that this phenotype was attributed to mutations in the TYRP1 gene in an American individual of mixed ancestry. Linkage analysis in five families mapped the BOCA locus to the same region as the OCA2 locus (maximum LOD 3.07; θ=0 using a six-marker haplotype). Mutation analysis of the human homologue of the mouse pink-eyed dilution gene (P), in 10 unrelated individuals with BOCA revealed that 9 had one copy of the 2.7-kb deletion. No other mutations were identified. Additional haplotype studies, based on closely linked markers (telomere to centromere: D15S1048, D15S1019, D15S1533, P-gene 2.7-kb deletion, D15S219, and D15S156) revealed several BOCA-associated P haplotypes. These could be divided into two core haplotypes, suggesting that a limited number of P-gene mutations give rise to this phenotype. PMID:11179026

Albinism in Botswana Junior Secondary Schools: A Double Case Study

ERIC Educational Resources Information Center

Dart, Gareth; Nkanotsang, Tiroyaone; Chizwe, Ose; Kowa, Lily

2010-01-01

Pupils with albinism potentially face a number of challenges in accessing quality education in schools in Botswana. Physical issues such as poor eyesight related to the condition and the problems of sensitive skin in such a dry and warm climate are both contributing factors to making learning problematic for some pupils. This study by Gareth Dart…

Ocular toxocariasis.

PubMed

Arevalo, J Fernando; Espinoza, Juan V; Arevalo, Fernando A

2013-01-01

Ocular toxocariasis is an uncommon worldwide parasitic infection that affects mostly children and is found in both rural and metropolitan areas. In many parts of the world, parasitic infections of the eye are a major cause of blindness. The diagnosis of toxocariasis is essentially clinical, based on the lesion morphology and supportive laboratory data such as serum enzyme-linked immunosorbent assay (ELISA) titers and ELISA Toxocara titers on aqueous humor; other diagnostic methods are imaging studies including optical coherence tomography, fluorescein angiography, computed tomography, and ocular ultrasound. Treatment is directed at complications arising from intraocular inflammation and vitreous membrane traction. Early vitrectomy may be of value both diagnostically and therapeutically. Copyright 2013, SLACK Incorporated.

Multifocal ERG findings in carriers of X-linked retinoschisis

PubMed Central

Kim, Linda S.; Seiple, William; Szlyk, Janet P.

2006-01-01

Purpose To determine whether retinal dysfunction in obligate carriers of X-linked retinoschisis (XLRS) could be observed in local electroretinographic responses obtained with the multifocal electroretinogram (mfERG). Methods Nine obligate carriers of XLRS (mean age, 46.2 years) were examined for the study. Examination of each carrier included an ocular examination and mfERG testing. For the mfERG, we used a 103-scaled hexagonal stimulus array that subtended a retinal area of approximately 40° in diameter. The amplitudes and implicit times in each location for the mfERG were compared with the corresponding values determined for a group of 34 normally-sighted, age-similar control subjects. Results Mapping of 103 local electroretinographic response amplitudes and implicit times within a central 40° area with the mfERG showed regions of reduced mfERG amplitudes and delayed implicit times in two of nine carriers. Conclusions The mfERG demonstrated areas of retinal dysfunction in two carriers of XLRS. When present, retinal dysfunction was evident in the presence of a normal-appearing fundus. Multifocal ERG testing can be useful for identifying some carriers of XLRS. PMID:17180613

Genetics Home Reference: X-linked congenital stationary night blindness

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... Health Conditions X-linked congenital stationary night blindness X-linked congenital stationary night blindness Printable PDF Open ... Javascript to view the expand/collapse boxes. Description X-linked congenital stationary night blindness is a disorder ...

Genetics Home Reference: X-linked lissencephaly with abnormal genitalia

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... Health Conditions X-linked lissencephaly with abnormal genitalia X-linked lissencephaly with abnormal genitalia Printable PDF Open ... Javascript to view the expand/collapse boxes. Description X-linked lissencephaly with abnormal genitalia (XLAG) is a ...

Genetics Home Reference: X-linked sideroblastic anemia and ataxia

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... Health Conditions X-linked sideroblastic anemia and ataxia X-linked sideroblastic anemia and ataxia Printable PDF Open ... Javascript to view the expand/collapse boxes. Description X-linked sideroblastic anemia and ataxia is a rare ...

Genetics Home Reference: X-linked intellectual disability, Siderius type

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... Health Conditions X-linked intellectual disability, Siderius type X-linked intellectual disability, Siderius type Printable PDF Open ... Javascript to view the expand/collapse boxes. Description X-linked intellectual disability, Siderius type is a condition ...

Genetics Home Reference: X-linked hyper IgM syndrome

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Psychological aspects of albinism: an exploratory study with Nigerian (Igbo) albino subjects.

PubMed

Ezeilo, B N

1989-01-01

This paper reviews some studies done on the psychological aspects of albinism. Studies on the intellectual ability of albinos produce equivocal results. Results from personality studies seem more consistent and show albinos to be more emotionally unstable than non-albinos. This paper also reports a study by the author which examines the phenomenon of albinism from the albino's viewpoint. It examined the responses of three undergraduate albino subjects--one female and two males--to the author's request for each to write an essay on the merits and demerits of being an albino based on personal experiences. All consider being an albino to be more of a demerit than a merit. The demerits include conspicuous colour, delicate skin which blisters under the sun, defective sight, interpersonal, especially heterosexual, problems and society's unkind attitude. The paper ends with a discussion of possible future research in the area and a recommendation of the need for psychological rehabilitation as part of the management programme for albinos.

Genetics Home Reference: X-linked dystonia-parkinsonism

MedlinePlus

... X-linked dystonia-parkinsonism syndrome (XDP): clinical and molecular genetic analysis. Brain Pathol. 1992 Oct;2(4):287-95. Review. Citation on PubMed Kaji R, Goto S, Tamiya G, Ando S, Makino S, Lee LV. Molecular dissection and anatomical basis of dystonia: X-linked ...

X-Linked Glomerulopathy Due to COL4A5 Founder Variant.

PubMed

Barua, Moumita; John, Rohan; Stella, Lorenzo; Li, Weili; Roslin, Nicole M; Sharif, Bedra; Hack, Saidah; Lajoie-Starkell, Ginette; Schwaderer, Andrew L; Becknell, Brian; Wuttke, Matthias; Köttgen, Anna; Cattran, Daniel; Paterson, Andrew D; Pei, York

2018-03-01

Alport syndrome is a rare hereditary disorder caused by rare variants in 1 of 3 genes encoding for type IV collagen. Rare variants in COL4A5 on chromosome Xq22 cause X-linked Alport syndrome, which accounts for ∼80% of the cases. Alport syndrome has a variable clinical presentation, including progressive kidney failure, hearing loss, and ocular defects. Exome sequencing performed in 2 affected related males with an undefined X-linked glomerulopathy characterized by global and segmental glomerulosclerosis, mesangial hypercellularity, and vague basement membrane immune complex deposition revealed a COL4A5 sequence variant, a substitution of a thymine by a guanine at nucleotide 665 (c.T665G; rs281874761) of the coding DNA predicted to lead to a cysteine to phenylalanine substitution at amino acid 222, which was not seen in databases cataloguing natural human genetic variation, including dbSNP138, 1000 Genomes Project release version 01-11-2004, Exome Sequencing Project 21-06-2014, or ExAC 01-11-2014. Review of the literature identified 2 additional families with the same COL4A5 variant leading to similar atypical histopathologic features, suggesting a unique pathologic mechanism initiated by this specific rare variant. Homology modeling suggests that the substitution alters the structural and dynamic properties of the type IV collagen trimer. Genetic analysis comparing members of the 3 families indicated a distant relationship with a shared haplotype, implying a founder effect. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

A novel missense mutation of NDP in a Chinese family with X-linked familial exudative vitreoretinopathy.

PubMed

Liu, Hong Yan; Huang, Jia; Wang, Rui Li; Wang, Yue; Guo, Liang Jie; Li, Tao; Wu, Dong; Wang, Hong Dan; Guo, Qian Nan; Dong, Dao Quan

2016-11-01

Familial exudative vitreoretinopathy (FEVR) is a hereditary ocular disorder characterized by a failure of peripheral retinal vascularization. In this report, we describe a novel missense mutation of the Norrie disease gene (NDP) in a Chinese family with X-linked FEVR. Ophthalmologic evaluation was performed on four male patients and seven unaffected individuals after informed consent was obtained. Venous blood was collected from the 11 members of this family, and genomic DNA was extracted using standard methods. The coding exons 2 and 3 and their corresponding exon-intron junctions of NDP were amplified by polymerase chain reaction and then subjected to direct DNA sequencing. A novel missense mutation (c.310A>C) in exon 3, leading to a lysine-to-glutamine substitution at position 104 (p.Lys104Gln), was identified in all four patients with X-linked FEVR. Three unaffected female individuals (III2, IV3, and IV11) were found to be carriers of the mutation. This mutation was not detected in other unaffected individuals. The mutation c.310A>C (p.Lys104Gln) in exon 3 of NDP is associated with FEVR in the studied family. This result further enriches the mutation spectrum of FEVR. Copyright © 2016. Published by Elsevier Taiwan LLC.

Genetics Home Reference: alpha thalassemia X-linked intellectual disability syndrome

MedlinePlus

... thalassemia X-linked intellectual disability syndrome Alpha thalassemia X-linked intellectual disability syndrome Printable PDF Open All ... view the expand/collapse boxes. Description Alpha thalassemia X-linked intellectual disability syndrome is an inherited disorder ...

Dextran and protamine-based solid lipid nanoparticles as potential vectors for the treatment of X-linked juvenile retinoschisis.

PubMed

Delgado, Diego; del Pozo-Rodríguez, Ana; Solinís, Maria Ángeles; Avilés-Triqueros, Marcelino; Weber, Bernhard H F; Fernández, Eduardo; Gascón, Alicia R

2012-04-01

The goal of the present study was to analyze the potential application of nonviral vectors based on solid lipid nanoparticles (SLN) for the treatment of ocular diseases by gene therapy, specifically X-linked juvenile retinoschisis (XLRS). Vectors were prepared with SLN, dextran, protamine, and a plasmid (pCMS-EGFP or pCEP4-RS1). Formulations were characterized and the in vitro transfection capacity as well as the cellular uptake and the intracellular trafficking were studied in ARPE-19 cells. Formulations were also tested in vivo in Wistar rat eyes, and the efficacy was studied by monitoring the expression of enhanced green fluorescent protein (EGFP) after intravitreal, subretinal, and topical administration. The presence of dextran and protamine in the SLN improved greatly the expression of retinoschisin and EGFP in ARPE-19 cells. The nuclear localization signals of protamine, its ability to protect the DNA, and a shift in the entry mechanism from caveola-mediated to clathrin-mediated endocytosis promoted by the dextran, justify the increase in transfection. After ocular administration of the dextran-protamine-DNA-SLN complex to rat eyes, we detected the expression of EGFP in various types of cells depending on the administration route. Our vectors were also able to transfect corneal cells after topical application. We have demonstrated the potential usefulness of our nonviral vectors loaded with XLRS1 plasmid and provided evidence for their potential application for the management or treatment of degenerative retinal disorders as well as ocular surface diseases.

[Tapeto-retinal degeneration combined with incomplete general albinism (author's transl)].

PubMed

Ivandić, T

1975-05-01

Report on a family, which presented the rare autosomal dominant transmitted, incomplete general albinism associated with autosomal recessive inherited, diffuse tapeto-retinal degeneration "sine pigmento". hypopigmentation of skin, eyebrows and hair, blue iris and fundus albinoticus with hypoplasia of the macula. In 3 cases additionally appeared: waxy pallor of optic disc, vascular narrowing, reflexless hypoplastic macula, pigmentless periphery, acquired blue-yellow blindness, concentric limitation of the visual field, reduced darkadaptation, abolished electroretinogram and myopic astigmatism.

FARVATX: Family-Based Rare Variant Association Test for X-Linked Genes.

PubMed

Choi, Sungkyoung; Lee, Sungyoung; Qiao, Dandi; Hardin, Megan; Cho, Michael H; Silverman, Edwin K; Park, Taesung; Won, Sungho

2016-09-01

Although the X chromosome has many genes that are functionally related to human diseases, the complicated biological properties of the X chromosome have prevented efficient genetic association analyses, and only a few significantly associated X-linked variants have been reported for complex traits. For instance, dosage compensation of X-linked genes is often achieved via the inactivation of one allele in each X-linked variant in females; however, some X-linked variants can escape this X chromosome inactivation. Efficient genetic analyses cannot be conducted without prior knowledge about the gene expression process of X-linked variants, and misspecified information can lead to power loss. In this report, we propose new statistical methods for rare X-linked variant genetic association analysis of dichotomous phenotypes with family-based samples. The proposed methods are computationally efficient and can complete X-linked analyses within a few hours. Simulation studies demonstrate the statistical efficiency of the proposed methods, which were then applied to rare-variant association analysis of the X chromosome in chronic obstructive pulmonary disease. Some promising significant X-linked genes were identified, illustrating the practical importance of the proposed methods. © 2016 WILEY PERIODICALS, INC.

FARVATX: FAmily-based Rare Variant Association Test for X-linked genes

PubMed Central

Choi, Sungkyoung; Lee, Sungyoung; Qiao, Dandi; Hardin, Megan; Cho, Michael H.; Silverman, Edwin K; Park, Taesung; Won, Sungho

2016-01-01

Although the X chromosome has many genes that are functionally related to human diseases, the complicated biological properties of the X chromosome have prevented efficient genetic association analyses, and only a few significantly associated X-linked variants have been reported for complex traits. For instance, dosage compensation of X-linked genes is often achieved via the inactivation of one allele in each X-linked variant in females; however, some X-linked variants can escape this X chromosome inactivation. Efficient genetic analyses cannot be conducted without prior knowledge about the gene expression process of X-linked variants, and misspecified information can lead to power loss. In this report, we propose new statistical methods for rare X-linked variant genetic association analysis of dichotomous phenotypes with family-based samples. The proposed methods are computationally efficient and can complete X-linked analyses within a few hours. Simulation studies demonstrate the statistical efficiency of the proposed methods, which were then applied to rare-variant association analysis of the X chromosome in chronic obstructive pulmonary disease (COPD). Some promising significant X-linked genes were identified, illustrating the practical importance of the proposed methods. PMID:27325607

X-linked congenital panhypopituitarism.

PubMed

Schimke, R N; Spaulding, J J; Hollowell, J G

1971-05-01

Two half brothers with panhypopituitary dwarfism are reported who have the same mother and different, unrelated fathers. The subject of hereditary panhypopituitarism is reviewed briefly. It is concluded that there are at least two forms of hereditary panhypopituitary dwarfism, one of which may be X-linked.

Ocular flutter following Zika virus infection.

PubMed

Karam, Emely; Giraldo, Jose; Rodriguez, Flor; Hernandez-Pereira, Carlos E; Rodriguez-Morales, Alfonso J; Blohm, Gabriela M; Paniz-Mondolfi, Alberto E

2017-12-01

Zika virus (ZIKV) is an emerging flavivirus which has been linked to a number of neurologic manifestations such as Guillain-Barré syndrome (GBS), transverse myelitis, and meningo-encephalitis. Ophthalmologic manifestations are increasingly being reported; however, ocular dyskinesias have not been described in this context to date. Herein, we report a case of a 22-year-old female who presented with ocular flutter and associated Guillain-Barré syndrome following acute ZIKV infection. We speculate that although such symptoms may have originated from a direct viral insult, a post-infectious autoimmune mechanism may not be excluded. Physicians should include ZIKV as well as other flaviviruses in their diagnostic workup for all patients with ocular flutter/opsoclonus, after excluding other non-infectious causes of central nervous system pathology. To the best of our knowledge, this is the first report on the association of ocular flutter, GBS, and ZIKV infection.

Cataract formation associated with ocular toxocariasis.

PubMed

Ahn, Seong Joon; Woo, Se Joon; Hyon, Joon Young; Park, Kyu Hyung

2013-06-01

To report the clinical features of cataracts in eyes with ocular toxocariasis. Department of Ophthalmology, Seoul National University Bundang Hosptal, Seongnam, South Korea. Retrospective observational case series. The clinical diagnosis of ocular toxocariasis was based on the following characteristic features: retinal granuloma with or without ocular inflammation and positive results in serum antibody enzyme-linked immunosorbent assay. Patients younger than 60 years who presented with a unilateral cataract and were diagnosed with ocular toxocariasis between January 2009 and January 2012 were included. Demographic and ocular examination data for all patients showing atypical cataract features were collected. All cataracts were documented with anterior segment photography. Seven of 83 patients (8.4%) presented with an atypical cataract in the eye with ocular toxocariasis only. The mean patient age was 49.7 years ± 8.3 (SD) (range 38 to 59 years). All patients had small, round, white lens opacities resembling retinal granulomas. The granuloma-like opacities were located primarily in the lens midperiphery and in the subcapsular level. The lens opacity migrated in 1 patient. Ocular toxocariasis can cause a cataract with distinctive clinical features. These cataracts show a granuloma-like opacity primarily in the posterior subcapsular level; the opacity can migrate. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2013 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Phenotype-genotype correlations in X linked retinitis pigmentosa.

PubMed Central

Kaplan, J; Pelet, A; Martin, C; Delrieu, O; Aymé, S; Bonneau, D; Briard, M L; Hanauer, A; Larget-Piet, L; Lefrançois, P

1992-01-01

Retinitis pigmentosa (RP) represents a group of clinically heterogeneous retinal degenerations in which all modes of inheritance have been described. We have previously found two different clinical profiles in X linked RP as a function of age and mode of onset. The first clinical form has very early onset with severe myopia. The second form starts later with night blindness with mild myopia or none. At least two genes have been identified in X linked forms, namely RP2 (linked to DXS7, DXS255, and DXS14) and RP3 (linked to DXS84 and OTC) on the short arm of the X chromosome. In order to contribute to phenotype-genotype correlations in X linked RP, we tested the hypothesis that the two clinical profiles could be accounted for by the two different gene loci. The present study provides evidence for linkage of the clinical form with early myopia as the onset symptom with the RP2 gene (pairwise linkage to DXS255: Z = 3.13 at theta = 0), while the clinical form with later night blindness as the onset symptom is linked to the RP3 gene (pairwise linkage to OTC: Z = 4.16 at theta = 0). Images PMID:1357178

Sex-specific silencing of X-linked genes by Xist RNA

PubMed Central

Gayen, Srimonta; Maclary, Emily; Hinten, Michael; Kalantry, Sundeep

2016-01-01

X-inactive specific transcript (Xist) long noncoding RNA (lncRNA) is thought to catalyze silencing of X-linked genes in cis during X-chromosome inactivation, which equalizes X-linked gene dosage between male and female mammals. To test the impact of Xist RNA on X-linked gene silencing, we ectopically induced endogenous Xist by ablating the antisense repressor Tsix in mice. We find that ectopic Xist RNA induction and subsequent X-linked gene silencing is sex specific in embryos and in differentiating embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs). A higher frequency of XΔTsixY male cells displayed ectopic Xist RNA coating compared with XΔTsixX female cells. This increase reflected the inability of XΔTsixY cells to efficiently silence X-linked genes compared with XΔTsixX cells, despite equivalent Xist RNA induction and coating. Silencing of genes on both Xs resulted in significantly reduced proliferation and increased cell death in XΔTsixX female cells relative to XΔTsixY male cells. Thus, whereas Xist RNA can inactivate the X chromosome in females it may not do so in males. We further found comparable silencing in differentiating XΔTsixY and 39,XΔTsix (XΔTsixO) ESCs, excluding the Y chromosome and instead implicating the X-chromosome dose as the source of the sex-specific differences. Because XΔTsixX female embryonic epiblast cells and EpiSCs harbor an inactivated X chromosome prior to ectopic inactivation of the active XΔTsix X chromosome, we propose that the increased expression of one or more X-inactivation escapees activates Xist and, separately, helps trigger X-linked gene silencing. PMID:26739568

Mutations of the tyrosinase gene in patients with oculocutaneous albinism from various ethnic groups in Israel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gershoni-Baruch, R.; Rosenmann, A.; Droetto, S.

1994-04-01

The authors have analyzed the tyrosinase (TYR) gene in 38 unrelated patients with oculocutaneous albinism (OCA), derived from several different ethnic groups of the diverse population of Israel. They detected TYR gene mutations in 23 of the 34 patients with apparent type I (i.e., tyrosinase-deficient) OCA and in none of the patients with other clinical forms of albinism. Among Moroccan Jews with type IA (i.e., tyrosinase-negative) OCA, they detected a highly predominant mutant allele containing a missense substitution, Gly47Asp (G47D). This mutation occurs on the same haplotype as in patients from the Canary Islands and Puerto Rico, suggesting that themore » G47D mutation in these ethnically distinct populations may stem from a common origin. 28 refs., 1 fig., 2 tabs.« less

BOL-303242-X, a novel selective glucocorticoid receptor agonist, with full anti-inflammatory properties in human ocular cells

PubMed Central

Cavet, Megan E.; VanDerMeid, Karl R.; Salvador-Silva, Mercedes; López, Francisco J.; Ward, Keith W.

2009-01-01

Purpose BOL-303242-X is a novel selective glucocorticoid receptor agonist under clinical evaluation for the treatment of inflammatory skin and eye diseases. Data from in vitro and in vivo studies suggest an improved side-effect profile of this compound compared to classical glucocorticoids. The aim of this study was to determine the anti-inflammatory effect of BOL-303242-X in ocular cells. Methods Four primary human ocular cell cultures, including human conjunctival fibroblasts (HConFs), human corneal epithelial cells (HCEpiCs), human optic nerve astrocytes (HONAs), and human retinal endothelial cells (HRECs), as well as a human monocytic cell line, THP-1, were challenged with either lipopolysacharide (LPS) or interleukin-1ß (IL-1ß). Luminex technology was used to determine the effect of BOL-303242-X on LPS- or IL-1ß-induced cytokine release and intercellular adhesion molecule-1 (ICAM-1) levels. Effects of BOL-303242-X on nuclear factor kappa B (NFκB) and mitogen-activated protein kinase (MAPK) in HCEpiCs were also assessed by measuring inhibitory kappa B protein-α (IκB-α), phosphorylated p65 NFκB, and MAPK levels by western blotting. Dexamethasone (DEX) or triamcinolone acetonide (TA) was used as the control. Results LPS or IL-1ß induced multiple cytokine release in all cell types studied. BOL-303242-X significantly reduced LPS- or IL-1ß-induced inflammatory cytokine release in a dose-dependent manner, including granulocyte colony-stimulating factor (G-CSF), IL-1ß, IL-6, IL-8, IL-12p40, monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α). BOL-303242-X showed activity and potency comparable to that observed for DEX or TA. A statistically significant inhibitory effect of BOL-303242-X was observed at doses ranging from 1 to 100 nM in HConFs, HCEpiCs, HONAs, and THP-1. The IC50 values for these effects were in the low nM range. BOL-303242-X also significantly reduced LPS-induced IL-1ß release and ICAM-1 levels in HRECs

BOL-303242-X, a novel selective glucocorticoid receptor agonist, with full anti-inflammatory properties in human ocular cells.

PubMed

Zhang, Jin-Zhong; Cavet, Megan E; VanderMeid, Karl R; Salvador-Silva, Mercedes; López, Francisco J; Ward, Keith W

2009-12-08

BOL-303242-X is a novel selective glucocorticoid receptor agonist under clinical evaluation for the treatment of inflammatory skin and eye diseases. Data from in vitro and in vivo studies suggest an improved side-effect profile of this compound compared to classical glucocorticoids. The aim of this study was to determine the anti-inflammatory effect of BOL-303242-X in ocular cells. Four primary human ocular cell cultures, including human conjunctival fibroblasts (HConFs), human corneal epithelial cells (HCEpiCs), human optic nerve astrocytes (HONAs), and human retinal endothelial cells (HRECs), as well as a human monocytic cell line, THP-1, were challenged with either lipopolysacharide (LPS) or interleukin-1ss (IL-1ss). Luminex technology was used to determine the effect of BOL-303242-X on LPS- or IL-1ss-induced cytokine release and intercellular adhesion molecule-1 (ICAM-1) levels. Effects of BOL-303242-X on nuclear factor kappa B (NFkappaB) and mitogen-activated protein kinase (MAPK) in HCEpiCs were also assessed by measuring inhibitory kappa B protein-alpha (IkappaB-alpha), phosphorylated p65 NFkappaB, and MAPK levels by western blotting. Dexamethasone (DEX) or triamcinolone acetonide (TA) was used as the control. LPS or IL-1ss induced multiple cytokine release in all cell types studied. BOL-303242-X significantly reduced LPS- or IL-1ss-induced inflammatory cytokine release in a dose-dependent manner, including granulocyte colony-stimulating factor (G-CSF), IL-1ss, IL-6, IL-8, IL-12p40, monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor-alpha (TNF-alpha). BOL-303242-X showed activity and potency comparable to that observed for DEX or TA. A statistically significant inhibitory effect of BOL-303242-X was observed at doses ranging from 1 to 100 nM in HConFs, HCEpiCs, HONAs, and THP-1. The IC(50) values for these effects were in the low nM range. BOL-303242-X also significantly reduced LPS-induced IL-1ss release and ICAM-1 levels in HRECs. Furthermore

A Comparison of Selective Pressures in Plant X-Linked and Autosomal Genes

PubMed Central

Krasovec, Marc; Filatov, Dmitry A.

2018-01-01

Selection is expected to work differently in autosomal and X-linked genes because of their ploidy difference and the exposure of recessive X-linked mutations to haploid selection in males. However, it is not clear whether these expectations apply to recently evolved sex chromosomes, where many genes retain functional X- and Y-linked gametologs. We took advantage of the recently evolved sex chromosomes in the plant Silene latifolia and its closely related species to compare the selective pressures between hemizygous and non-hemizygous X-linked genes as well as between X-linked genes and autosomal genes. Our analysis, based on over 1000 genes, demonstrated that, similar to animals, X-linked genes in Silene evolve significantly faster than autosomal genes—the so-called faster-X effect. Contrary to expectations, faster-X divergence was detectable only for non-hemizygous X-linked genes. Our phylogeny-based analyses of selection revealed no evidence for faster adaptation in X-linked genes compared to autosomal genes. On the other hand, partial relaxation of purifying selection was apparent on the X-chromosome compared to the autosomes, consistent with a smaller genetic diversity in S. latifolia X-linked genes (πx = 0.016; πaut = 0.023). Thus, the faster-X divergence in S. latifolia appears to be a consequence of the smaller effective population size rather than of a faster adaptive evolution on the X-chromosome. We argue that this may be a general feature of “young” sex chromosomes, where the majority of X-linked genes are not hemizygous, preventing haploid selection in heterogametic sex. PMID:29751495

A Comparison of Selective Pressures in Plant X-Linked and Autosomal Genes.

PubMed

Krasovec, Marc; Nevado, Bruno; Filatov, Dmitry A

2018-05-03

Selection is expected to work differently in autosomal and X-linked genes because of their ploidy difference and the exposure of recessive X-linked mutations to haploid selection in males. However, it is not clear whether these expectations apply to recently evolved sex chromosomes, where many genes retain functional X- and Y-linked gametologs. We took advantage of the recently evolved sex chromosomes in the plant Silene latifolia and its closely related species to compare the selective pressures between hemizygous and non-hemizygous X-linked genes as well as between X-linked genes and autosomal genes. Our analysis, based on over 1000 genes, demonstrated that, similar to animals, X-linked genes in Silene evolve significantly faster than autosomal genes—the so-called faster-X effect. Contrary to expectations, faster-X divergence was detectable only for non-hemizygous X-linked genes. Our phylogeny-based analyses of selection revealed no evidence for faster adaptation in X-linked genes compared to autosomal genes. On the other hand, partial relaxation of purifying selection was apparent on the X-chromosome compared to the autosomes, consistent with a smaller genetic diversity in S. latifolia X-linked genes (π x = 0.016; π aut = 0.023). Thus, the faster-X divergence in S. latifolia appears to be a consequence of the smaller effective population size rather than of a faster adaptive evolution on the X-chromosome. We argue that this may be a general feature of “young” sex chromosomes, where the majority of X-linked genes are not hemizygous, preventing haploid selection in heterogametic sex.

Albinism and lung fibrosis in a young man - the first case of adult Hermansky-Pudlak Syndrome reported in Malaysia.

PubMed

Liza, A F; Aziah, A M

2012-12-01

A young gentleman of Indian descent with oculacutaneous albinism (OCA) was found to have severe pulmonary fibrosis at first presentation. Following investigations, he was diagnosed with Hermansky-Pudlak Syndrome (HPS). It is a genetic condition characterised by albinism, bleeding diathesis and multisystem disorder observed in individuals of particular descents. Although there is no curative treatment apart from lung transplantation, preventive measures to minimise pulmonary insult may change the natural history of the disease. Therefore HPS should be actively sought, monitored and risk factors addressed in individuals with OCA and bleeding diathesis particularly those of Indian descent as they may develop serious complications such as pulmonary fibrosis in the future.

Macular hole in juvenile X-linked retinoschisis.

PubMed

Al-Swaina, Nayef; Nowilaty, Sawsan R

2013-10-01

An 18 year-old male with no antecedent of trauma, systemic syndrome or myopia was referred for surgical treatment of a full thickness macular hole in the left eye. A more careful inspection revealed discrete foveal cystic changes in the fellow eye and subtle peripheral depigmented retinal pigment epithelial changes in both eyes. A spectral-domain optical coherence tomography (SD-OCT) scan confirmed, in addition to the full thickness macular hole in the left eye, microcystic spaces in the nuclear layers of both retinae. The diagnosis of X-linked retinoschisis was confirmed with a full field electroretinogram displaying the typical negative ERG. Macular holes are uncommon in the young and those complicating X-linked retinoschisis are rare. This report highlights the importance of investigating the presence of a macular hole in a young patient and illustrates the clinical and SD-OCT clues beyond the foveal center which led to the correct diagnosis of X-linked juvenile retinoschisis.

X-linked dominant retinitis pigmentosa in an American family

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGuire, R.E.; Daiger, S.P.; Blanton, S.H.

1994-09-01

Retinitis pigmentosa is a genetically heterogeneous disease with autosomal dominant (adRP), autosomal recessive and X-linked forms. At least 3 forms of X-linked retinitis pigmentosa have been reported: RP2 which maps to Xp11.4-p 11.23, RP3 which maps to Xp21.1 and RP6, which maps to Xp21.3-p21.1. The X-linked forms of retinitis pigmentosa are generally considered to be recessive as female carriers are not affected or are much less affected than males. Here we report a five generation American family with X-linked retinitis pigmentosa in which both males and females are significantly affected. The disease locus in this family appears to be distinctmore » from RP2 and RP3. The American family (UTAD054) presents with early-onset retinitis pigmentosa. The family appeared to fit an autosomal dominant pattern; however, linkage testing excluded all known adRP loci. Absence of male-to-male transmission in the pedigree suggested the possibility of X-linked dominant inheritance. Thus we tested six microsatellite markers that map to Xp (DXS987, DXS989, DXS993, DXS999, DXS1003 and DXS1110). Of these, DXS989 showed tight linkage with one allele (199) showing a 100% concordance with disease status. The odds favoring an X-linked dominant mode of inheritance in this family, versus autosomal dominant, are 10{sup 5}:1. In addition, recombinations for DXS999, and dXS1110, the two markers flanking DXS989, were observed in affected individuals. These data map the disease locus in this family to a 9 mb region on the X chromosome between Xp22.11 and Xp21.41. In addition, the recombinant individuals exclude close linkage to RP2 and RP3. The observance of high penetrance in females indicates that this family has X-linked dominant retinitis pigmentosa. We suggest that this mode of inheritance should be considered in other families with dominant retinitis pigmentosa but an absence of male-to-male transmission.« less

Ocular cytokinome is linked to clinical characteristics in ocular toxoplasmosis

PubMed Central

de-la-Torre, Alejandra; Pfaff, Alexander W.; Grigg, Michael E.; Villard, Odile; Candolfi, Ermanno; Gomez-Marin, Jorge E.

2016-01-01

Purpose To determine the cytokine levels in aqueous humor (AH) of Colombian patients with active ocular toxoplasmosis (OT), and to correlate them with their clinical characteristics. Methods 27 Cytokines/chemokines were assayed in 15 AH samples (nine patients with diagnosis of OT biologically-confirmed and six controls that underwent cataract surgery). Correlations were assessed between cytokine/chemokine levels, type of inflammatory response (Th1, Th2, Th17, Treg), and clinical characteristics. Results Th2 predominant response was related to more severe clinical features. The presence of VEGF and IL-5 was related to higher number of recurrences. Growth factors (VEGF, FGF, PDGF-β), were related to higher number of lesions. Patients infected by type-I/III strains had a particular intraocular cytokine-pattern. Conclusions Th2 response was related to more severe clinical characteristics in patients infected by Type I/III strains. IL-5 and VEGF were associated with recurrences. We correlate for the first time, specific cytokine-patterns with clinical characteristics and with the infecting Toxoplasma strain. PMID:24787053

Role of prostaglandins in the pathogenesis of X-linked hypophosphatemia.

PubMed

Baum, Michel; Syal, Ashu; Quigley, Raymond; Seikaly, Mouin

2006-08-01

X-linked hypophosphatemia is an X-linked dominant disorder resulting from a mutation in the PHEX gene. PHEX stands for phosphate-regulating gene with endopeptidase activity, which is located on the X chromosome. Patients with X-linked hypophosphatemia have hypophosphatemia due to renal phosphate wasting and low or inappropriately normal levels of 1,25-dihydroxyvitamin D. The renal phosphate wasting is not intrinsic to the kidney but likely due to an increase in serum levels of fibroblast growth factor-23 (FGF-23), and perhaps other phosphate-wasting peptides previously known as phosphatonins. Patients with X-linked hypophosphatemia have short stature, rickets, bone pain and dental abscesses. Current therapy is oral phosphate and vitamin D which effectively treats the rickets and bone pain but does not adequately improve short stature. In this review, we describe recent observations using Hyp mice; mice with the same mutation as patients with X-linked hypophosphatemia. We have recently found that Hyp mice have abnormal renal prostaglandin production, which may be an important factor in the pathogenesis of this disorder. Administration of FGF-23 in vivo results in phosphaturia and an increase in prostaglandin excretion, and FGF-23 increases proximal tubule prostaglandin production in vitro. In Hyp mice, indomethacin improves the phosphate transport defect in vitro and in vivo. Whether indomethacin has the same effect in patients with X-linked hypophosphatemia is unknown.

Macular pigment optical density spatial distribution measured in a subject with oculocutaneous albinism.

PubMed

Putnam, Christopher M; Bland, Pauline J

2014-01-01

Previous studies of macular pigment optical density (MPOD) distribution in individuals with oculocutaneous albinism (OCA) have primarily used objective measurement techniques including fundus reflectometry and autofluorescence. We report here on a subject with OCA and their corresponding MPOD distribution assessed through heterochromatic flicker photometry (HFP). A subject with a history of OCA presented with an ocular history including strabismus surgery of the LE with persistent amblyopia and mild, latent nystagmus. Best corrected visual acuity was 20/25- RE and 20/40- LE. Spectral domain optical coherence tomography (SD-OCT) and fundus photography were also obtained. Evaluation of MPOD spatial distribution up to 8 degrees eccentricity from the fovea was performed using HFP. SD-OCT indicated a persistence of multiple inner retinal layers within the foveal region in the RE and LE including symmetric foveal thickening consistent with foveal hypoplasia. Fundus photography showed mild retinal pigmented epithelial (RPE) hypopigmentation and a poorly demarcated macula. OriginPro 9 was used to plot MPOD spatial distribution of the subject and a 33-subject sample. The OCA subject demonstrated a foveal MPOD of 0.10 with undetectable levels at 6 degrees eccentricity. The study sample showed a mean foveal MPOD of 0.34 and mean 6 degree eccentricity values of 0.03. Consistent with previous macular pigment (MP) studies of OCA, overall MPOD is reduced in our subject. Mild phenotypic expression of OCA with high functional visual acuity may represent a Henle fiber layer amenable to additional MP deposition. Further study of MP supplementation in OCA patients is warranted. Copyright © 2014 Spanish General Council of Optometry. Published by Elsevier Espana. All rights reserved.

Renal, auricular, and ocular outcomes of Alport syndrome and their current management.

PubMed

Zhang, Yanqin; Ding, Jie

2017-09-01

Alport syndrome is a hereditary glomerular basement membrane disease caused by mutations in the COL4A3/4/5 genes encoding the type IV collagen alpha 3-5 chains. Most cases of Alport syndrome are inherited as X-linked dominant, and some as autosomal recessive or autosomal dominant. The primary manifestations are hematuria, proteinuria, and progressive renal failure, whereas some patients present with sensorineural hearing loss and ocular abnormalities. Renin-angiotensin-aldosterone system blockade is proven to delay the onset of renal failure by reducing proteinuria. Renal transplantation is a curative treatment for patients who have progressed to end-stage renal disease. However, only supportive measures can be used to improve hearing loss and visual loss. Although both stem cell therapy and gene therapy aim to repair the basement membrane defects, technical difficulties require more research in Alport mice before clinical studies. Here, we review the renal, auricular, and ocular manifestations and outcomes of Alport syndrome and their current management.

Contemporary Medical and Surgical Management of X-linked Hypophosphatemic Rickets.

PubMed

Sharkey, Melinda S; Grunseich, Karl; Carpenter, Thomas O

2015-07-01

X-linked hypophosphatemia is an inheritable disorder of renal phosphate wasting that clinically manifests with rachitic bone pathology. X-linked hypophosphatemia is frequently misdiagnosed and mismanaged. Optimized medical therapy is the cornerstone of treatment. Even with ideal medical management, progressive bony deformity may develop in some children and adults. Medical treatment is paramount to the success of orthopaedic surgical procedures in both children and adults with X-linked hypophosphatemia. Successful correction of complex, multiapical bone deformities found in patients with X-linked hypophosphatemia is possible with careful surgical planning and exacting surgical technique. Multiple methods of deformity correction are used, including acute and gradual correction. Treatment of some pediatric bony deformity with guided growth techniques may be possible. Copyright 2015 by the American Academy of Orthopaedic Surgeons.

Sequence-Based Mapping and Genome Editing Reveal Mutations in Stickleback Hps5 Cause Oculocutaneous Albinism and the casper Phenotype.

PubMed

Hart, James C; Miller, Craig T

2017-09-07

Here, we present and characterize the spontaneous X-linked recessive mutation casper , which causes oculocutaneous albinism in threespine sticklebacks ( Gasterosteus aculeatus ). In humans, Hermansky-Pudlak syndrome results in pigmentation defects due to disrupted formation of the melanin-containing lysosomal-related organelle (LRO), the melanosome. casper mutants display not only reduced pigmentation of melanosomes in melanophores, but also reductions in the iridescent silver color from iridophores, while the yellow pigmentation from xanthophores appears unaffected. We mapped casper using high-throughput sequencing of genomic DNA from bulked casper mutants to a region of the stickleback X chromosome (chromosome 19) near the stickleback ortholog of Hermansky-Pudlak syndrome 5 ( Hps5 ). casper mutants have an insertion of a single nucleotide in the sixth exon of Hps5 , predicted to generate an early frameshift. Genome editing using CRISPR/Cas9 induced lesions in Hps5 and phenocopied the casper mutation. Injecting single or paired Hps5 guide RNAs revealed higher incidences of genomic deletions from paired guide RNAs compared to single gRNAs. Stickleback Hps5 provides a genetic system where a hemizygous locus in XY males and a diploid locus in XX females can be used to generate an easily scored visible phenotype, facilitating quantitative studies of different genome editing approaches. Lastly, we show the ability to better visualize patterns of fluorescent transgenic reporters in Hps5 mutant fish. Thus, Hps5 mutations present an opportunity to study pigmented LROs in the emerging stickleback model system, as well as a tool to aid in assaying genome editing and visualizing enhancer activity in transgenic fish. Copyright © 2017 Hart and Milller.

Postnatal ocular expression of tyrosinase and related proteins: disruption by the pink-eyed unstable (p(un)) mutation.

PubMed

Chiu, E; Lamoreux, M L; Orlow, S J

1993-09-01

Ocular pigmentation in the mouse occurs primarily postnatally as a result of the melanization of neural crest-derived melanocytes. Using immunologic and biochemical techniques, we demonstrate that in normal mice the expression of tyrosinase and the related proteins TRP-1 and TRP-2, rises during the first week of life, remains elevated for a week, and then steadily declines to low levels by adulthood. Sucrose gradient density centrifugation demonstrates that tyrosinase, TRP-1 and TRP-2 are present in high molecular weight forms in the eyes of wild-type mice. The normal time course is disrupted in mice carrying the pink-eyed unstable (p(un)) mutation at the P-locus, a model for tyrosinase-positive albinism in man. Tyrosinase and TRP-2 are present at wild-type levels in the eyes of p(un)/p(un) mice at birth, but, rather than rising, their levels rapidly decline over the first week of life. TRP-1 is almost undetectable, even at birth. High molecular weight complexes could not be detected in eyes of p(un)/p(un) mice. Our results suggest that postnatal ocular melanogenesis in the mouse presents an attractive model for the study of the orderly expression and action of the proteins involved in eumelanin synthesis, and that the p(un) mutation disrupts this temporally controlled process.

Genetics Home Reference: immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome

MedlinePlus

... Health Conditions IPEX syndrome Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome Printable PDF Open All Close All ... expand/collapse boxes. Description Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome primarily affects males and is ...

Thiolated nanostructured lipid carriers as a potential ocular drug delivery system for cyclosporine A: Improving in vivo ocular distribution.

PubMed

Shen, Jie; Deng, Yanping; Jin, Xuefeng; Ping, Qineng; Su, Zhigui; Li, Lejun

2010-12-15

Ophthalmic drug delivery with long pre-corneal retention time and high penetration into aqueous humor and intraocular tissues is the key-limiting factor for the treatment of ocular diseases and disorders. Within this study, the conjugate of cysteine-polyethylene glycol monostearate (Cys-PEG-SA) was synthesized and was used to compose the thiolated nanostructured lipid carrier (Cys-NLC) as a potential nanocarrier for the topical ocular administration of cyclosporine A (CyA). The rapid cross-linking process of Cys-PEG-SA in vitro was found in simulated physiological environment. The in vitro CyA release from Cys-NLC was slower than that of non-thiolated nanostructured lipid carriers (NLC) due to the cross-linking of thiomers on the surface of nanocarriers. After topical ocular administration in rabbits, the in vivo ocular distribution of CyA was investigated in comparison of Cys-NLC with non-thiolated NLCs and oil solution. The results showed that CyA concentration in systemic blood was very low and close to the detection limit. The area-under-the-curve (AUC(0-24h)) and mean retention time (MRT(0-24h)) of Cys-NLC group in aqueous humor, tear and eye tissues were significantly higher than that of oil solution, non-thiolated NLCs (p<0.05). These results demonstrated that the thiolated NLC could deliver high level of CyA into intraocular tissues due to its bioadhesive property and sustained release characteristics. Copyright © 2010 Elsevier B.V. All rights reserved.

X-linked hypophosphatemia attributable to pseudoexons of the PHEX gene.

PubMed

Christie, P T; Harding, B; Nesbit, M A; Whyte, M P; Thakker, R V

2001-08-01

X-linked hypophosphatemia is commonly caused by mutations of the coding region of PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome). However, such PHEX mutations are not detected in approximately one third of X-linked hypophosphatemia patients who may harbor defects in the noncoding or intronic regions. We have therefore investigated 11 unrelated X-linked hypophosphatemia patients in whom coding region mutations had been excluded, for intronic mutations that may lead to mRNA splicing abnormalities, by the use of lymphoblastoid RNA and RT-PCRs. One X-linked hypophosphatemia patient was found to have 3 abnormally large transcripts, resulting from 51-bp, 100-bp, and 170-bp insertions, all of which would lead to missense peptides and premature termination codons. The origin of these transcripts was a mutation (g to t) at position +1268 of intron 7, which resulted in the occurrence of a high quality novel donor splice site (ggaagg to gtaagg). Splicing between this novel donor splice site and 3 preexisting, but normally silent, acceptor splice sites within intron 7 resulted in the occurrences of the 3 pseudoexons. This represents the first report of PHEX pseudoexons and reveals further the diversity of genetic abnormalities causing X-linked hypophosphatemia.

Impaired plasticity of macrophages in X-linked adrenoleukodystrophy.

PubMed

Weinhofer, Isabelle; Zierfuss, Bettina; Hametner, Simon; Wagner, Magdalena; Popitsch, Niko; Machacek, Christian; Bartolini, Barbara; Zlabinger, Gerhard; Ohradanova-Repic, Anna; Stockinger, Hannes; Köhler, Wolfgang; Höftberger, Romana; Regelsberger, Günther; Forss-Petter, Sonja; Lassmann, Hans; Berger, Johannes

2018-05-30

X-linked adrenoleukodystrophy is caused by ATP-binding cassette transporter D1 (ABCD1) mutations and manifests by default as slowly progressive spinal cord axonopathy with associated demyelination (adrenomyloneuropathy). In 60% of male cases, however, X-linked adrenoleukodystrophy converts to devastating cerebral inflammation and demyelination (cerebral adrenoleukodystrophy) with infiltrating blood-derived monocytes and macrophages and cytotoxic T cells that can only be stopped by allogeneic haematopoietic stem cell transplantation or gene therapy at an early stage of the disease. Recently, we identified monocytes/macrophages but not T cells to be severely affected metabolically by ABCD1 deficiency. Here we found by whole transcriptome analysis that, although monocytes of patients with X-linked adrenoleukodystrophy have normal capacity for macrophage differentiation and phagocytosis, they are pro-inflammatory skewed also in patients with adrenomyloneuropathy in the absence of cerebral inflammation. Following lipopolysaccharide activation, the ingestion of myelin debris, normally triggering anti-inflammatory polarization, did not fully reverse the pro-inflammatory status of X-linked adrenoleukodystrophy macrophages. Immunohistochemistry on post-mortem cerebral adrenoleukodystrophy lesions reflected the activation pattern by prominent presence of enlarged lipid-laden macrophages strongly positive for the pro-inflammatory marker co-stimulatory molecule CD86. Comparative analyses of lesions with matching macrophage density in cases of cerebral adrenoleukodystrophy and acute multiple sclerosis showed a similar extent of pro-inflammatory activation but a striking reduction of anti-inflammatory mannose receptor (CD206) and haemoglobin-haptoglobin receptor (CD163) expression on cerebral adrenoleukodystrophy macrophages. Accordingly, ABCD1-deficiency leads to an impaired plasticity of macrophages that is reflected in incomplete establishment of anti-inflammatory responses

Nontuberculous Mycobacterial Ocular Infections: A Systematic Review of the Literature

PubMed Central

Kheir, Wajiha J.; Sheheitli, Huda; Abdul Fattah, Maamoun; Hamam, Rola N.

2015-01-01

Nontuberculous or atypical mycobacterial ocular infections have been increasing in prevalence over the past few decades. They are known to cause periocular, adnexal, ocular surface and intraocular infections and are often recalcitrant to medical therapy. These infections can potentially cause detrimental outcomes, in part due to a delay in diagnosis. We review 174 case reports and series on nontuberculous mycobacterial (NTM) ocular infections and discuss etiology, microbiology, risk factors, diagnosis, clinical presentation, and treatment of these infections. History of interventions, trauma, foreign bodies, implants, contact lenses, and steroids are linked to NTM ocular infections. Steroid use may prolong the duration of the infection and cause poorer visual outcomes. Early diagnosis and initiation of treatment with multiple antibiotics are necessary to achieve the best visual outcome. PMID:26106601

Genetics Home Reference: X-linked spondyloepiphyseal dysplasia tarda

MedlinePlus

... Educational Resources (6 links) Cincinnati Children's Hospital: Coxa Vera Disease InfoSearch: Spondyloepiphyseal dysplasia tarda X-linked Johns ... Free article on PubMed Central Savarirayan R, Thompson E, Gécz J. Spondyloepiphyseal dysplasia tarda (SEDL, MIM #313400). ...

siRNAs from an X-linked satellite repeat promote X-chromosome recognition in Drosophila melanogaster.

PubMed

Menon, Debashish U; Coarfa, Cristian; Xiao, Weimin; Gunaratne, Preethi H; Meller, Victoria H

2014-11-18

Highly differentiated sex chromosomes create a lethal imbalance in gene expression in one sex. To accommodate hemizygosity of the X chromosome in male fruit flies, expression of X-linked genes increases twofold. This is achieved by the male- specific lethal (MSL) complex, which modifies chromatin to increase expression. Mutations that disrupt the X localization of this complex decrease the expression of X-linked genes and reduce male survival. The mechanism that restricts the MSL complex to X chromatin is not understood. We recently reported that the siRNA pathway contributes to localization of the MSL complex, raising questions about the source of the siRNAs involved. The X-linked 1.688 g/cm(3) satellite related repeats (1.688(X) repeats) are restricted to the X chromosome and produce small RNA, making them an attractive candidate. We tested RNA from these repeats for a role in dosage compensation and found that ectopic expression of single-stranded RNAs from 1.688(X) repeats enhanced the male lethality of mutants with defective X recognition. In contrast, expression of double-stranded hairpin RNA from a 1.688(X) repeat generated abundant siRNA and dramatically increased male survival. Consistent with improved survival, X localization of the MSL complex was largely restored in these males. The striking distribution of 1.688(X) repeats, which are nearly exclusive to the X chromosome, suggests that these are cis-acting elements contributing to identification of X chromatin.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ion, A.; Telvi, L.; Galacteros, F.

We describe a pedigree presenting X-linked severe mental retardation associated with multiple congenital abnormalities and 46,XY gonadal dysgenesis, leading in one family member to female gender assignment. Female carriers are unaffected. The dysmorphic features are similar to those described in the {alpha}-thalassemia and mental retardation (ATR-X) syndrome, although there is no clinical evidence of {alpha}-thalassemia in this family. In addition, the family had other clinical features not previously observed in the ATR-X syndrome, including partial optic-nerve atrophy and partial ocular albinism. Mutations in a putative DNA helicase, termed XH2, have been reported to give rise to the ATR-X syndrome. Wemore » screened the YCH2 gene for mutations in affected members of the family and identified a 4-bp deletion at an intron/exon boundary that removes an invariant 3{prime} splice-acceptor site. The mutation cosegregates with the syndrome. The genomic deletion causes missplicing of the pre-mRNA, which results in the loss of 8 bp of coding sequence, thereby generating a frameshift and a downstream premature stop codon. Our finding increases the range of clinical features associated with mutations in the XH2 gene. 17 refs., 4 figs., 2 tabs.« less

Genetics Home Reference: X-linked agammaglobulinemia

MedlinePlus

... Sep;104(3):221-30. Citation on PubMed Smith CIE, Berglöf A. X-Linked Agammaglobulinemia. 2001 Apr ... Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): ...

Severe manifestations in carrier females in X linked retinitis pigmentosa.

PubMed Central

Souied, E; Segues, B; Ghazi, I; Rozet, J M; Chatelin, S; Gerber, S; Perrault, I; Michel-Awad, A; Briard, M L; Plessis, G; Dufier, J L; Munnich, A; Kaplan, J

1997-01-01

Retinitis pigmentosa (RP) is a group of progressive hereditary disorders of the retina in which various modes of inheritance have been described. Here, we report on X linked RP in nine families with constant and severe expression in carrier females. In our series, however, the phenotype was milder and delayed in carrier females compared to hemizygous males. This form of X linked RP could be regarded therefore as partially dominant. The disease gene maps to chromosome Xp2.1 in the genetic interval encompassing the RP3 locus (Zmax=13.71 at the DXS1100 locus). Single strand conformation polymorphism and direct sequence analysis of the retinitis pigmentosa GTPase regulator (RPGR) gene, which accounts for RP3, failed to detect any mutation in our families. Future advances in the identification of X linked RP genes will hopefully help to elucidate the molecular basis of this X linked dominant RP. Images PMID:9350809

Dry eye disease: an immune-mediated ocular surface disorder

PubMed Central

Stevenson, William; Chauhan, Sunil K.; Dana, Reza

2013-01-01

Dry eye disease is a multifactorial disorder of the tears and ocular surface characterized by symptoms of dryness and irritation. Although the pathogenesis of dry eye disease is not fully understood, it is recognized that inflammation has a prominent role in the development and propagation of this debilitating condition. Factors that adversely affect tear film stability and osmolarity can induce ocular surface damage and initiate an inflammatory cascade that generates innate and adaptive immune responses. These immunoinflammatory responses lead to further ocular surface damage and the development of a self-perpetuating inflammatory cycle. Herein, we review the fundamental links between inflammation and dry eye disease and discuss the clinical implications of inflammation in disease management. PMID:22232476

Molecular and clinical studies of X-linked deafness among Pakistani families.

PubMed

Waryah, Ali M; Ahmed, Zubair M; Bhinder, Munir A; Binder, Munir A; Choo, Daniel I; Sisk, Robert A; Shahzad, Mohsin; Khan, Shaheen N; Friedman, Thomas B; Riazuddin, Sheikh; Riazuddin, Saima

2011-07-01

There are 68 sex-linked syndromes that include hearing loss as one feature and five sex-linked nonsyndromic deafness loci listed in the OMIM database. The possibility of additional such sex-linked loci was explored by ascertaining three unrelated Pakistani families (PKDF536, PKDF1132 and PKDF740) segregating X-linked recessive deafness. Sequence analysis of POU3F4 (DFN3) in affected members of families PKDF536 and PKDF1132 revealed two novel nonsense mutations, p.Q136X and p.W114X, respectively. Family PKDF740 is segregating congenital blindness, mild-to-profound progressive hearing loss that is characteristic of Norrie disease (MIM#310600). Sequence analysis of NDP among affected members of this family revealed a novel single nucleotide deletion c.49delG causing a frameshift and premature truncation (p.V17fsX1) of the encoded protein. These mutations were not found in 150 normal DNA samples. Identification of pathogenic alleles causing X-linked recessive deafness will improve molecular diagnosis, genetic counseling and molecular epidemiology of hearing loss among Pakistanis.

Molecular and Clinical Studies of X-linked Deafness Among Pakistani Families

PubMed Central

Waryah, Ali M.; Ahmed, Zubair M.; Choo, Daniel I.; Sisk, Robert A.; Binder, Munir A.; Shahzad, Mohsin; Khan, Shaheen N.; Friedman, Thomas B.; Riazuddin, Sheikh; Riazuddin, Saima

2011-01-01

There are 68 sex-linked syndromes that include hearing loss as one feature and five sex-linked nonsyndromic deafness loci listed in the OMIM database. The possibility of additional such sex-linked loci was explored by ascertaining three unrelated Pakistani families (PKDF536, PKDF1132, PKDF740) segregating X-linked recessive deafness. Sequence analysis of POU3F4 (DFN3) in affected members of families PKDF536 and PKDF1132 revealed two novel nonsense mutations, p.Q136X and p.W114X, respectively. Family PKDF740 is segregating congenital blindness, mild to profound progressive hearing loss that is characteristic of Norrie disease (MIM#310600). Sequence analysis of NDP among affected members of this family revealed a novel single nucleotide deletion c.49delG causing a frameshift and premature truncation (p.V17fsX1) of the encoded protein. These mutations were not found in 150 normal DNA samples. Identification of pathogenic alleles causing X-linked recessive deafness will improve molecular diagnosis, genetic counseling, and molecular epidemiology of hearing loss among Pakistanis. PMID:21633365

Ocular presentation of sarcoidosis in children.

PubMed

Kataria, S; Trevathan, G E; Holland, J E; Kataria, Y P

1983-12-01

Ocular manifestations of sarcoidosis in children are the second most common occurrence after hilar adenopathy and pulmonary abnormalities. We present the case history of a 14-year-old black boy who presented with redness of the left eye, blurred vision, and decreased visual acuity. He was subsequently diagnosed as having sarcoidosis. All patients with uveitis or ocular findings suggestive of sarcoidosis should have a through medical examination and a chest x-ray. Those suspected of or proven to have sarcoidosis should have a complete ophthalmological examination. Sarcoidosis in children appears to be more frequent than previously estimated.

X linked mental retardation: a clinical guide.

PubMed

Raymond, F L

2006-03-01

Mental retardation is more common in males than females in the population, assumed to be due to mutations on the X chromosome. The prevalence of the 24 genes identified to date is low and less common than expansions in FMR1, which cause Fragile X syndrome. Systematic screening of all other X linked genes in X linked families with mental retardation is currently not feasible in a clinical setting. The phenotypes of genes causing syndromic and non-syndromic mental retardation (NLGN3, NLGN4, RPS6KA3(RSK2), OPHN1, ATRX, SLC6A8, ARX, SYN1, AGTR2, MECP2, PQBP1, SMCX, and SLC16A2) are first discussed, as these may be the focus of more targeted mutation analysis. Secondly, the relative prevalence of genes causing only non-syndromic mental retardation (IL1RAPL1, TM4SF2, ZNF41, FTSJ1, DLG3, FACL4, PAK3, ARHGEF6, FMR2, and GDI) is summarised. Thirdly, the problem of recurrence risk where a molecular genetics diagnosis has not been made and what proportion of the male excess of mental retardation is due to monogenic disorders of the X chromosome are discussed.

A Simulation of X-Linked Inheritance.

ERIC Educational Resources Information Center

Harrell, Pamela Esprivalo

1997-01-01

Describes how to lead students through a classroom-based simulation to teach a variety of concepts such as X-linked traits, sex determination, and sex anomalies. The simulation utilizes inexpensive materials such as plastic eggs that twist apart to represent human eggs and sperm. (AIM)

Escape of X-linked miRNA genes from meiotic sex chromosome inactivation

PubMed Central

Sosa, Enrique; Flores, Luis; Yan, Wei; McCarrey, John R.

2015-01-01

Past studies have indicated that transcription of all X-linked genes is repressed by meiotic sex chromosome inactivation (MSCI) during the meiotic phase of spermatogenesis in mammals. However, more recent studies have shown an increase in steady-state levels of certain X-linked miRNAs in pachytene spermatocytes, suggesting that either synthesis of these miRNAs increases or that degradation of these miRNAs decreases dramatically in these cells. To distinguish between these possibilities, we performed RNA-FISH to detect nascent transcripts from multiple miRNA genes in various spermatogenic cell types. Our results show definitively that Type I X-linked miRNA genes are subject to MSCI, as are all or most X-linked mRNA genes, whereas Type II and III X-linked miRNA genes escape MSCI by continuing ongoing, active transcription in primary spermatocytes. We corroborated these results by co-localization of RNA-FISH signals with both a corresponding DNA-FISH signal and an immunofluorescence signal for RNA polymerase II. We also found that X-linked miRNA genes that escape MSCI locate non-randomly to the periphery of the XY body, whereas genes that are subject to MSCI remain located within the XY body in pachytene spermatocytes, suggesting that the mechanism of escape of X-linked miRNA genes from MSCI involves their relocation to a position outside of the repressive chromatin domain associated with the XY body. The fact that Type II and III X-linked miRNA genes escape MSCI suggests an immediacy of function of the encoded miRNAs specifically required during the meiotic stages of spermatogenesis. PMID:26395485

Ocular sarcoidosis masked by positive IgM for toxoplasmosis.

PubMed

Peres, Murilo Bertazzo; Sousa, Jacqueline Martins de; Nascimento, Heloisa

2017-01-01

We report a case of ocular sarcoidosis with positive immunoglobulin (Ig) M and IgG serology for toxoplasmosis. The patient was a young female with red painful eyes, bilateral eyelid edema, and panuveitis with periphlebitis. In laboratory testing, she was IgM and IgG positive for toxoplasmosis and anergic in the tuberculin test. Topical treatment for anterior uveitis and oral antibiotics for toxoplasmosis were started, without improvement. Orbit tomography showed increased lacrimal glands bilaterally, and chest X-ray radiographic findings were consistent with pulmonary sarcoidosis, which supported the presumed ocular sarcoidosis diagnosis. The patient was treated with oral prednisone and methotrexate without antibiotics. She showed clinical and vision improvement without recurrences during the 1-year follow-up. Ocular sarcoidosis is an important differential diagnosis requiring careful anamnesis and ophthalmological examinations. Ancillary tests, such as X-ray radiography, tomography, and clinical and laboratory evaluations may help rule out other causes. Treatment mainly consists of corticosteroids and immunosuppression.

The relationship between demodex and ocular discomfort.

PubMed

Lee, Seok Hyun; Chun, Yeoun Sook; Kim, Jae Hoon; Kim, Eung Suk; Kim, Jae Chan

2010-06-01

To determine the correlative relationship between the prevalence of Demodex in eyelashes and the severity of ocular discomfort, by investigating the demographic epidemiology associated with Demodex. One hundred seventy patients underwent epilation of four eyelashes of each eye, and the number of Demodex was counted. The patients answered questionnaires about ocular surface discomfort and underwent ophthalmic examinations, including slit lamp, tear film breakup time (BUT), Schirmer test, and microbial culturing. The correlative relationship between the number of Demodex and these variable data was analyzed. Demodex was found in 120 (70%) of the 170 tested patients. Of 1360 eyelashes, 740 (54%) had Demodex. There was no significant difference in the prevalence of Demodex between males and females (P = 0.35). The number of Demodex showed significant positive correlations with increased age, ocular discomfort, and 1/BUT (P < 0.001), but not with the Schirmer scores. The number of Demodex was significantly higher in patients with conjunctival papillary hypertrophy than in those without (P = 0.003). The presence or distribution of bacteria on eyelashes was similar between eyelids with and without Demodex. However, methicillin-resistant Staphylococcus aureus (MRSA) was detected more often on eyelids with Demodex, but this difference was not statistically significant. There is a strong correlation between the number of Demodex and the severity of ocular discomfort, suggesting that Demodex plays a pathogenic role in the ocular discomfort linked with aging.

DNA Variations in Oculocutaneous Albinism: An Updated Mutation List and Current Outstanding Issues in Molecular Diagnostics

PubMed Central

Simeonov, Dimitre R.; Wang, Xinjing; Wang, Chen; Sergeev, Yuri; Dolinska, Monika; Bower, Matthew; Fischer, Roxanne; Winer, David; Dubrovsky, Genia; Balog, Joan Z.; Huizing, Marjan; Hart, Rachel; Zein, Wadih M.; Gahl, William A.; Brooks, Brian P.; Adams, David R.

2014-01-01

Oculocutaneous albinism (OCA) is a rare genetic disorder of melanin synthesis that results in hypopigmented hair, skin, and eyes. There are four types of OCA, caused by mutations in TYR (OCA-1), OCA2 (OCA-2), TYRP1 (OCA-3), or SLC45A2 (OCA-4). Here we report 22 novel mutations; 14 from a cohort of 61 patients seen as part of the NIH OCA Natural History Study and 8 from a prior study at the University of Minnesota. We also include a comprehensive list of almost 600 previously reported OCA mutations, along with ethnicity information, carrier frequencies, and in silico pathogenicity predictions. In addition to discussing the clinical and molecular features of OCA, we address the cases of apparent missing heritability. In our cohort, 25% of patients did not have two mutations in a single OCA gene. We demonstrate the utility of multiple detection methods to reveal mutations missed by Sanger sequencing. Finally, we review the TYR p.R402Q temperature sensitive variant and confirm its association with cases of albinism with only one identifiable TYR mutation. PMID:23504663

PEDIATRIC OCULAR TOXOCARIASIS IN JIANGSU PROVINCE, EASTERN CHINA.

PubMed

Zhang, Hai-Fang; Hua, Hai-Yong; Wang, Wei

2015-01-01

Ocular toxocariasis is caused by migration of a Toxocara larva through the posterior eye. We report the first case of pediatric ocular toxocariasis caused by T. canis in Jiangsu Province, eastern China. A 6-year-old girl presented to Suzhou Municipal Children's Hospital with a complaint of right eye redness, minimal white discharge, no photophobia, eye pain, visual impairment, fever or arthralgia. She was initially diagnosed as having conjunctivitis; however, a 2-month treatment with lomefloxacin 0.3% eye drops gave no improvements. The diagnosis was made based on medical history (contact with dogs), clinical features and detection of T. canis IgG antibodies with an enzyme-linked immunosorbent assay (ELISA). Anthelmintic therapy with albendazole in combination with prednisolone resulted in improvement of the ocular symptoms. Ocular toxocariasis is rarely reported in China. However, the rapid economic development in China, could mean an increase in pet dogs with the potential increased risk of contracting toxocariasis if no control measures are taken. Disposal of pet litter, deworming of infected pets, complete cooking of meats, thorough rinsing of fruits and vegetables, and good hand-washing may help prevent human infections. Ocular toxocariasis should be considered in the differential diagnosis of patients with conjunctivitis that does not resolve with treatment.

Screening for X-linked adrenoleukodystrophy among adult men with Addison's disease.

PubMed

Horn, Morten A; Erichsen, Martina M; Wolff, Anette S B; Månsson, Jan-Eric; Husebye, Eystein S; Tallaksen, Chantal M E; Skjeldal, Ola H

2013-09-01

X-linked adrenoleukodystrophy is an important cause of Addison's disease in boys, but less is known about its contribution to Addison's disease in adult men. After surveying all known cases of X-linked adrenoleukodystrophy in Norway in a separate study, we aimed to look for any missed cases among the population of adult men with nonautoimmune Addison's disease. Among 153 adult men identified in a National Registry for Addison's Disease (75% of identified male cases of Addison's disease in Norway), those with negative indices for 21-hydroxylase autoantibodies were selected. Additionally, cases with low autoantibody indices (48-200) were selected. Sera from subjects included were analysed for levels of very long-chain fatty acids, which are diagnostic for X-linked adrenoleukodystrophy in men. Eighteen subjects had negative indices and 17 had low indices for 21-hydroxylase autoantibodies. None of those with low indices and only one of those with negative indices were found to have X-linked adrenoleukodystrophy; this subject had already been diagnosed because of the neurological symptoms. Cases of Addison's disease proved to be caused by X-linked adrenoleukodystrophy constitute 1·5% of all adult male cases in Norway; the proportion among nonautoimmune cases was 15%. We found X-linked adrenoleukodystrophy to be an uncommon cause of Addison's disease in adult men. However, this aetiological diagnosis has far-reaching consequences both for the patient and for his extended family. We therefore recommend that all adult men with nonautoimmune Addison's disease be analysed for levels of very long-chain fatty acids. © 2013 John Wiley & Sons Ltd.

Ocular toxocariasis in Korea.

PubMed

Kwon, Soon Il; Lee, Jung Pil; Park, Sung Pyo; Lee, Eun Kyung; Huh, Sun; Park, In Won

2011-03-01

To analyze the characteristics and clinical manifestations of clinically diagnosed and serologically confirmed ocular toxocariasis in patients. Thirty-three eyes of 33 patients diagnosed as having ocular toxocariasis at the Hallym University Medical Center between January 1999 and December 2008 were included in the study. The diagnosis of ocular toxocariasis was based on clinical features and confirmed serologically by enzyme-linked immunosorbent assay and immunoblotting. All patients were interviewed by using a structured questionnaire that included risk factors that might account for the introduction of Toxocara larvae. Demographics, social characteristics determined from the questionnaire, and clinical features were evaluated. A total of 33 eyes of 33 patients were enrolled in this study: 24 (73%) patients were men, and mean patient age was 41.6 ± 11.0 years. Ten of 28 patients (36%) who responded to the questionnaire had a history of contact with pets, and 23 (82%) had a history of consuming raw food. The most common symptoms were blurred vision in 22 eyes (67%) and floaters in six eyes (18%). The toxocariasis was unilateral in all patients, and the inflammation was acute in two-thirds of the patients. In 17 eyes (52%), Toxocara granuloma was found in the peripheral retina. Nineteen eyes (58%) had visual acuity of 20/40 or better at presentation and improved significantly after treatment. Final visual acuity was 20/40 or better in 26 eyes (79%). Ocular toxocariasis in Korea usually affects young adults to middle-aged men. The clinical manifestation is unilateral and presents as acute inflammation with a peripheral inflammatory mass. Visual prognosis with appropriate treatment is good.

A Potential Benefit of Albinism in Astyanax Cavefish: Downregulation of the oca2 Gene Increases Tyrosine and Catecholamine Levels as an Alternative to Melanin Synthesis

PubMed Central

Parkhurst, Amy; Jeffery, William R.

2013-01-01

Albinism, the loss of melanin pigmentation, has evolved in a diverse variety of cave animals but the responsible evolutionary mechanisms are unknown. In Astyanax mexicanus, which has a pigmented surface dwelling form (surface fish) and several albino cave-dwelling forms (cavefish), albinism is caused by loss of function mutations in the oca2 gene, which operates during the first step of the melanin synthesis pathway. In addition to albinism, cavefish have evolved differences in behavior, including feeding and sleep, which are under the control of the catecholamine system. The catecholamine and melanin synthesis pathways diverge after beginning with the same substrate, L-tyrosine. Here we describe a novel relationship between the catecholamine and melanin synthesis pathways in Astyanax. Our results show significant increases in L-tyrosine, dopamine, and norepinephrine in pre-feeding larvae and adult brains of Pachón cavefish relative to surface fish. In addition, norepinephrine is elevated in cavefish adult kidneys, which contain the teleost homologs of catecholamine synthesizing adrenal cells. We further show that the oca2 gene is expressed during surface fish development but is downregulated in cavefish embryos. A key finding is that knockdown of oca2 expression in surface fish embryos delays the development of pigmented melanophores and simultaneously increases L-tyrosine and dopamine. We conclude that a potential evolutionary benefit of albinism in Astyanax cavefish may be to provide surplus L-tyrosine as a precursor for the elevated catecholamine synthesis pathway, which could be important for adaptation to the challenging cave environment. PMID:24282555

Genetics Home Reference: X-linked lymphoproliferative disease

MedlinePlus

... infects most humans. In some people it causes infectious mononucleosis (commonly known as "mono"). Normally, after initial infection, ... severe susceptibility to EBV infection severe susceptibility to infectious mononucleosis X-linked lymphoproliferative syndrome XLP Related Information How ...

Informed reasoning: repositioning of nitisinone to treat oculocutaneous albinism.

PubMed

Manga, Prashiela; Orlow, Seth J

2011-10-01

Oculocutaneous albinism (OCA) is a group of genetic disorders characterized by hypopigmentation of the skin, hair, and eyes. Affected individuals experience reduced visual acuity and substantially increased skin cancer risk. There are four major types of OCA (OCA1-OCA4) that result from disruption in production of melanin from tyrosine. Current treatment options for individuals with OCA are limited to attempts to correct visual problems and counseling to promote use of sun protective measures. However, Onojafe et al., reporting in this issue of the JCI, provide hope for a new treatment approach for OCA, as they demonstrate that treating mice that model OCA-1b with nitisinone, which is FDA approved for treating hereditary tyrosinemia type 1, elevates plasma tyrosine levels, and increases eye and hair pigmentation.

Oculocutaneous albinism: identifying and overcoming barriers to vision care in a Nigerian population.

PubMed

Udeh, N N; Eze, B I; Onwubiko, S N; Arinze, O C; Onwasigwe, E N; Umeh, R E

2014-06-01

To assess eye care service utilization, and identify access barriers in a south-eastern Nigerian albino population. The study was a population-based, cross-sectional survey conducted in Enugu state between August, 2011 and January, 2012. Using the data base of the state's Albino Foundation and tailored awareness creation, persons living with albinism were identified and recruited at two study centres. Data on participants' socio-demographics, perception of vision, visual needs, previous eye examination and or low vision assessment, use of glasses or low vision devices were collected. Reasons for non-utilisation of available vision care services were also obtained. Descriptive and comparative statistics were performed. A p < 0.05 was considered statistically significant. The participants (n = 153; males 70; females 83; sex ratio: 1:1.1) were aged 23.46 + 10.44 SD years (range 6-60 years). Most--95.4 % of the participants had no previous low vision assessment and none--0.0% had used low vision device. Of the participants, 82.4% reported previous eye examination, 33.3% had not used spectacles previously, despite the existing need. Ignorance--88.9% and poor access--8.5% were the main barriers to uptake of vision care services. In Enugu, Nigeria, there is poor awareness and low utilization of vision care services among people with albinism. The identified barriers to vision care access are amenable to awareness creation and logistic change in the provision of appropriate vision care services.

X-chromosomal inactivation directly influences the phenotypic manifestation of X-linked protoporphyria

PubMed Central

Brancaleoni, V.; Balwani, M.; Granata, F.; Graziadei, G.; Missineo, P.; Fiorentino, V.; Fustinoni, S.; Cappellini, M.D.; Naik, H.; Desnick, R.J.; Di Pierro, E.

2015-01-01

X-linked protoporphyria (XLP), a rare erythropoietic porphyria, results from terminal exon gain-of-function mutations in the ALAS2 gene causing increased ALAS2 activity and markedly increased erythrocyte protoporphyrin levels. Patients present with severe cutaneous photosensitivity and may develop liver dysfunction. XLP was originally reported as X-linked dominant with 100% penetrance in males and females. We characterized 11 heterozygous females from six unrelated XLP families and show markedly varying phenotypic and biochemical heterogeneity, reflecting the degree of X-chromsomal inactivation of the mutant gene. ALAS2 sequencing identified the specific mutation and confirmed heterozygosity among the females. Clinical history, plasma and erythrocyte protoporphyrin levels were determined. Methylation assays of the androgen receptor and zinc-finger MYM type 3 short tandem repeat polymorphisms estimated each heterozygotes X-chromosomal inactivation pattern. Heterozygotes with equal or increased skewing, favoring expression of the wild-type allele had no clinical symptoms and only slightly increased erythrocyte protoporphyrin concentrations and/or frequency of protoporphyrin-containing peripheral blood fluorocytes. When the wild-type allele was preferentially inactivated, heterozygous females manifested the disease phenotype and had both higher erythrocyte protoporphyrin levels and circulating fluorocytes. These findings confirm that the previous dominant classification of XLP is inappropriate and genetically misleading, as the disorder is more appropriately designated XLP. PMID:25615817

Linkage localization of X-linked Charcot-Marie-Tooth disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bergoffen, J.; Trofatter, J.; Haines, J.L.

1993-02-01

Charcot-Marie-Tooth disease (CMT), also known as hereditary motor and sensory neuropathy, is a heterogeneous group of slowly progressive, degenerative disorders of peripheral nerve. X-linked CMT (CMTX) (McKusick 302800), a subdivision of type I, or demyelinating, CMT is an X-linked dominant condition with variable penetrance. Previous linkage analysis using RFLPs demonstrated linkage to markers on the proximal long and short arms of the X chromosome, with the more likely localization on the proximal long arm of the X chromosome. Available variable simple-sequence repeats (VSSRs) broaden the possibilities for linkage analysis. This paper presents new linkage data and recombination analysis derived frommore » work with four VSSR markers - AR, PGKP1, DXS453, and DXYS1X - in addition to analysis using RFLP markers described elsewhere. These studies localize the CMTX gene to the proximal Xq segment between PGKP1 (Xq11.2-12) and DXS72 (Xq21.1), with a combined maximum multipoint lod score of 15.3 at DXS453 ([theta] = 0). 32 refs., 3 figs., 2 tabs.« less

Profile of ocular trauma in industries-related hospital.

PubMed

Shashikala, P; Sadiqulla, Mohammed; Shivakumar, D; Prakash, K H

2013-05-01

Ocular trauma is a worldwide cause of visual morbidity, a significant proportion of which occurs in the industrial workplace and includes a spectrum of simple ocular surface foreign bodies, abrasions to devastating perforating injuries causing blindness. Being preventable is of social and medical concern. A prospective case series study, to know the profile of ocular trauma at a hospital caters exclusively to factory employees and their families, to co-relate their demographic and clinical profile and to identify the risk factors. Patients with ocular trauma who presented at ESIC Model hospital, Rajajinagar, Bangalore, from June 2010 to May 2011 were taken a detailed demographic data, nature and cause of injury, time interval between the time of injury and presentation along with any treatment received. Ocular evaluation including visual acuity, anterior and posterior segment findings, intra-ocular pressure and gonio-scopy in closed globe injuries, X-rays for intraocular foreign body, B-scan and CT scan were done. Data analyzed as per the ocular trauma classification group. The rehabilitation undertaken medically or surgically was analyzed. At follow-up, the final best corrected visual acuity was noted. A total of 306 cases of ocular trauma were reported; predominantly in 20-40 year age group (72.2%) and in men (75%). The work place related cases were 50.7%and of these, fall of foreign bodies led the list. Visual prognosis was poorer in road traffic accidents rather than work place injuries owing to higher occurrence of open globe injuries and optic neuropathy. Finally, 11% of injured cases ended up with poor vision. Targeting groups most at risk, providing effective eye protection, and developing workplace safety cultures may together reduce occupational eye injuries.

X-inactivation patterns in female Leber`s hereditary optic neuropathy patients do not support a strong X-linked determinant

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pegoraro, E.; Hoffman, E.P.; Carelli, V.

1996-02-02

Leber`s hereditary optic neuropathy (LHON) accounts for about 3% of the cases of blindness in young adult males. The underlying mitochondrial pathogenesis of LHON has been well studied, with specific mitochondrial DNA (mtDNA) mutations of structural genes described and well characterized. However, enigmatic aspects of the disease are not explained by mutation data, such as the higher proportion of affected males, the later onset of the disease in females, and the presence of unaffected individuals with a high proportion of mutant mtDNA. A hypothesis which has been put forward to explain the unusual disease expression is a dual model ofmore » mtDNA and X-linked nuclear gene inheritance. If a nuclear X-linked modifier gene influences the expression of the mitochondrial-linked mutant gene then the affected females should be either homozygous for the nuclear determinant, or if heterozygous, lyonization should favor the mutant X. In order to determine if an X-linked gene predisposes to LHON phenotype we studied X-inactivation patterns in 35 females with known mtDNA mutations from 10 LHON pedigrees. Our results do not support a strong X-linked determinant in LHON cause: 2 of the 10 (20%) manifesting carriers showed skewing of X-inactivation, as did 3 of the 25 (12%) nonmanifesting carriers. 39 refs., 2 figs., 1 tab.« less

Genome-wide misexpression of X-linked versus autosomal genes associated with hybrid male sterility.

PubMed

Lu, Xuemei; Shapiro, Joshua A; Ting, Chau-Ti; Li, Yan; Li, Chunyan; Xu, Jin; Huang, Huanwei; Cheng, Ya-Jen; Greenberg, Anthony J; Li, Shou-Hsien; Wu, Mao-Lien; Shen, Yang; Wu, Chung-I

2010-08-01

Postmating reproductive isolation is often manifested as hybrid male sterility, for which X-linked genes are overrepresented (the so-called large X effect). In contrast, X-linked genes are significantly under-represented among testis-expressing genes. This seeming contradiction may be germane to the X:autosome imbalance hypothesis on hybrid sterility, in which the X-linked effect is mediated mainly through the misexpression of autosomal genes. In this study, we compared gene expression in fertile and sterile males in the hybrids between two Drosophila species. These hybrid males differ only in a small region of the X chromosome containing the Ods-site homeobox (OdsH) (also known as Odysseus) locus of hybrid sterility. Of genes expressed in the testis, autosomal genes were, indeed, more likely to be misexpressed than X-linked genes under the sterilizing action of OdsH. Since this mechanism of X:autosome interaction is only associated with spermatogenesis, a connection between X:autosome imbalance and the high rate of hybrid male sterility seems plausible.

[No X-chromosome linked juvenile foveal retinoschisis].

PubMed

Pérez Alvarez, M J; Clement Fernández, F

2002-08-01

To describe the clinical characteristics of two cases of juvenile foveal retinoschisis in women with an atypical hereditary pattern, no X-chromosome linked. An autosomal recessive inheritance is proposed. Two generations of a family (5 members) in which only two sisters were evaluated. The complete examination of these two cases includes retinography, fluorescein angiography, automated perimetry, color vision testing, electroretinogram, electrooculogram and visually evoked potentials. Comparing our cases with the classic form of X-linked juvenile retinoschisis, they are less severely affected. The best visual acuity and the less disturbed or even normal electroretinogram confirm this fact. We emphasise the existence of isolated plaques of retinal pigment epithelium atrophy with perivascular pigment clumps without foveal schisis in one patient, which could represent an evolved form of this entity. The hereditary foveal juvenile retinoschisis in women suggests an autosomal inheritance (autosomal recessive in our cases) and presents less severe involvement (Arch Soc Esp Oftalmol 2002; 77: 443-448).

OCA2 splice site variant in German Spitz dogs with oculocutaneous albinism.

PubMed

Caduff, Madleina; Bauer, Anina; Jagannathan, Vidhya; Leeb, Tosso

2017-01-01

We investigated a German Spitz family where the mating of a black male to a white female had yielded three puppies with an unexpected light brown coat color, lightly pigmented lips and noses, and blue eyes. Combined linkage and homozygosity analysis based on a fully penetrant monogenic autosomal recessive mode of inheritance identified a critical interval of 15 Mb on chromosome 3. We obtained whole genome sequence data from one affected dog, three wolves, and 188 control dogs. Filtering for private variants revealed a single variant with predicted high impact in the critical interval in LOC100855460 (XM_005618224.1:c.377+2T>G LT844587.1:c.-45+2T>G). The variant perfectly co-segregated with the phenotype in the family. We genotyped 181 control dogs with normal pigmentation from diverse breeds including 22 unrelated German Spitz dogs, which were all homozygous wildtype. Comparative sequence analyses revealed that LOC100855460 actually represents the 5'-end of the canine OCA2 gene. The CanFam 3.1 reference genome assembly is incorrect and separates the first two exons from the remaining exons of the OCA2 gene. We amplified a canine OCA2 cDNA fragment by RT-PCR and determined the correct full-length mRNA sequence (LT844587.1). Variants in the OCA2 gene cause oculocutaneous albinism type 2 (OCA2) in humans, pink-eyed dilution in mice, and similar phenotypes in corn snakes, medaka and Mexican cave tetra fish. We therefore conclude that the observed oculocutaneous albinism in German Spitz is most likely caused by the identified variant in the 5'-splice site of the first intron of the canine OCA2 gene.

Observation of a unique case of metastatic basal cell carcinoma found by radiographic evaluation in a patient with oculocutaneous albinism

PubMed Central

Johnston, Mickaila

2014-01-01

Background: Basal cell carcinoma is one of the more common cancers worldwide; 2.8 million are diagnosed annually in the USA.  However, the rate at which it metastasizes is considered very low, between 0.0028 and 0.5%.  For those rare cases in which metastases occur, approximately one third metastasize to the lung.  Case: Presented is a 62-year-old Caucasian male with oculocutaneous albinism and a history of basal cell carcinomas occurring in multiple anatomic sites, most recently at the bilateral forearm and back.  Surveillance PET/CT imaging led to the discovery of no less than 30 lung nodules which were consistent with basal cell carcinoma on biopsy.  Histological features were remarkably similar in both the primary tumor and in the metastases. Conclusion:  An unusual case of a non-head and neck primary basal cell carcinoma metastatic to the lung was discovered on surveillance PET/CT imaging, in a patient with oculocutaneous albinism. PMID:24555117

Genome-wide misexpression of X-linked versus autosomal genes associated with hybrid male sterility

PubMed Central

Lu, Xuemei; Shapiro, Joshua A.; Ting, Chau-Ti; Li, Yan; Li, Chunyan; Xu, Jin; Huang, Huanwei; Cheng, Ya-Jen; Greenberg, Anthony J.; Li, Shou-Hsien; Wu, Mao-Lien; Shen, Yang; Wu, Chung-I

2010-01-01

Postmating reproductive isolation is often manifested as hybrid male sterility, for which X-linked genes are overrepresented (the so-called large X effect). In contrast, X-linked genes are significantly under-represented among testis-expressing genes. This seeming contradiction may be germane to the X:autosome imbalance hypothesis on hybrid sterility, in which the X-linked effect is mediated mainly through the misexpression of autosomal genes. In this study, we compared gene expression in fertile and sterile males in the hybrids between two Drosophila species. These hybrid males differ only in a small region of the X chromosome containing the Ods-site homeobox (OdsH) (also known as Odysseus) locus of hybrid sterility. Of genes expressed in the testis, autosomal genes were, indeed, more likely to be misexpressed than X-linked genes under the sterilizing action of OdsH. Since this mechanism of X:autosome interaction is only associated with spermatogenesis, a connection between X:autosome imbalance and the high rate of hybrid male sterility seems plausible. PMID:20511493

Genetics Home Reference: X-linked cardiac valvular dysplasia

MedlinePlus

... inflammation of the inner lining of the heart (endocarditis), abnormal blood clots, or sudden death. X-linked ... Johns Hopkins Medicine: Mitral Valve Prolapse MedlinePlus Encyclopedia: Endocarditis MedlinePlus Encyclopedia: Mitral Valve Prolapse General Information from ...

Defensins and Other Antimicrobial Peptides at the Ocular Surface

PubMed Central

McDermott, Alison M.

2006-01-01

Although constantly exposed to the environment and “foreign bodies” such as contact lenses and unwashed fingertips, the ocular surface succumbs to infection relatively infrequently. This is, in large part, due to a very active and robust innate immune response mounted at the ocular surface. Studies over the past 20 years have revealed that small peptides with antimicrobial activity are a major component of the human innate immune response system. The ocular surface is no exception, with peptides of the defensin and cathelicidin families being detected in the tear film and secreted by corneal and conjunctival epithelial cells. There is also much evidence to suggest that the role of some antimicrobial peptides is not restricted to direct killing of pathogens, but, rather, that they function in various aspects of the immune response, including recruitment of immune cells, and through actions on dendritic cells provide a link to adaptive immunity. A role in wound healing is also supported. In this article, the properties, mechanisms of actions and functional roles of antimicrobial peptides are reviewed, with particular emphasis on the potential multifunctional roles of defensins and LL-37 (the only known human cathelicidin) at the ocular surface. PMID:17216098

Clinical and genetic features in autosomal recessive and X-linked Alport syndrome.

PubMed

Wang, Yanyan; Sivakumar, Vanessa; Mohammad, Mardhiah; Colville, Deb; Storey, Helen; Flinter, Frances; Dagher, Hayat; Savige, Judy

2014-03-01

This study determined the family history and clinical features that suggested autosomal recessive rather than X-linked Alport syndrome. All patients had the diagnosis of Alport syndrome and the mode of inheritance confirmed by genetic testing, and underwent examination at a single centre. Patients comprised 9 males and 6 females with autosomal recessive Alport syndrome, and 18 males and 22 females with X-linked disease. Fourteen (93 %) individuals with autosomal recessive Alport syndrome developed early end-stage renal failure, all 15 had hearing loss, and most had lenticonus (12, 80 %), and a central (13, 87 %) or peripheral (13, 87 %) retinopathy. These features occurred as often as in males with X-linked disease. Females with autosomal recessive inheritance were less likely to have an affected family member in another generation (p = 0.01) than females with X-linked disease. They were more likely to have renal failure (p = 0.003), hearing loss (p = 0.02) and lenticonus (p < 0.001). Fifty percent had a central retinopathy compared with 18 % with X-linked disease (p = 0.14), but peripheral retinopathy prevalence was not different (p = 0.64). Nonsense mutations accounted for 67 % (8/12) of these disease-causing mutations. Autosomal recessive inheritance is increased in females with Alport syndrome and early onset renal failure, hearing loss, lenticonus, and, possibly, central retinopathy.

Ocular dominance stability and reading skill: a controversial relationship.

PubMed

Zeri, Fabrizio; De Luca, Maria; Spinelli, Donatella; Zoccolotti, Pierluigi

2011-11-01

Evidence is mixed concerning the relationship between stability of ocular dominance and reading deficits. Contrasting results may be due to the use of different tests of dominance, different samples of readers, and different scoring methods. The aim of this study was to investigate the relationship among ocular dominance, general visual abilities, and reading performance, and to evaluate the consistency and reliability of different tests of ocular dominance and the effects of different types of eye dominance scoring. In a group of young adults, we measured: (a) main optometric parameters; (b) reading time and accuracy; and (c) ocular dominance in two sighting and four motor tests. Dominance was determined using different scoring methods (relative, absolute, and binary scores). All dominance tests showed good levels of internal reliability. Sighting tests were consistent regardless of the scoring method, and all participants had stable dominance. Three of four motor tests were moderately consistent when dominance was measured with relative scores but not when it was measured with absolute or binary scores. No relationship was found between stability of dominance and reading performance, regardless of the type of test or scoring method. No systematic pattern of correlation was found between binocular vision variables and dominance measures. Choosing the type of motor test to measure ocular dominance is crucial, because the level of consistency among tests is low to moderate. Furthermore, motor tests were not correlated with reading performances. Present results suggest caution when trying to link reading difficulties with specific profiles of ocular dominance.

Custom-made ocular prosthesis.

PubMed

Gunaseelaraj, Rajkumar; Karthikeyan, Suma; Kumar, Mohan N; Balamurugan, T; Jagadeeshwaran, A R

2012-08-01

An ocular defect may affect a patient psychologically. An ocular prosthesis is given to uplift the patient psychologically and improve the confidence. Ocular prosthesis can be custom made or a stock shell. To improve the comfort and matching of the prosthesis with that of the adjacent natural eye an custom made ocular prosthesis is preferred. Different techniques are available to fabricate a custom ocular prosthesis, here we have used paper iris disk technique.

X-linked mental retardation associated with macro-orchidism.

PubMed Central

Turner, G; Eastman, C; Casey, J; McLeay, A; Procopis, P; Turner, B

1975-01-01

Two families are described with an X-linked form of mental retardation in whom the affected males were found to have bilateral enlargement of the testes. No conclusive evidence of any endocrinological disturbance was found. Images PMID:1240971

In vivo ocular efficacy profile of mapracorat, a novel selective glucocorticoid receptor agonist, in rabbit models of ocular disease.

PubMed

Shafiee, Afshin; Bucolo, Claudio; Budzynski, Ewa; Ward, Keith W; López, Francisco J

2011-03-14

To compare the efficacy of mapracorat (formerly ZK-245186, and subsequently BOL-303242-X), a novel selective glucocorticoid receptor agonist (SEGRA), with that of dexamethasone (DEX) in rabbit models of ocular disease. The effects of topical BOL-303242-X and DEX on intraocular pressure (IOP) and body weight changes were also evaluated. Dry eye was induced by atropine sulfate administration and was treated with saline, BOL-303242-X (0.1%-1.0%), DEX (0.1%), Restasis 0.05% (Allergan, Inc., Irvine, CA), or Refresh Endura (Allergan, Inc.) three times per day for 7 to 8 days. For paracentesis studies, vehicle, BOL-303242-X (0.1%, 0.5%, and 1.0%), or DEX (0.1%) were repeatedly administered topically 3 hours before paracentesis and continued for 90 minutes afterward. For IOP and body weight measurements, right eyes of rabbits were topically treated with vehicle, BOL-303242-X (1.0% or 0.1%), or DEX (0.1%) four times per day for 6 weeks. In the dry eye model, BOL-303242-X and DEX were fully efficacious, maintaining tear volume and tear breakup time (TBUT) at baseline levels. Although Restasis improved tear volume compared with vehicle, no changes were observed in TBUT. In the paracentesis study, BOL-303242-X and DEX improved ocular inflammation. BOL-303242-X reduced protein and PGE(2) levels. Finally, BOL-303242-X showed no effects on integrated IOP or body weight, whereas DEX significantly increased integrated IOP and prevented the increase of body weight observed in the vehicle-treated animals. BOL-303242-X shows full anti-inflammatory efficacy (similar to DEX) in experimental models of dry eye and postoperative inflammation while demonstrating reduced effects in IOP and body weight. These data indicate that mapracorat, a SEGRA, shows efficacy similar to that of traditional steroids while exhibiting an improved side effect profile in IOP and muscle wasting.

Cluster bomb ocular injuries.

PubMed

Mansour, Ahmad M; Hamade, Haya; Ghaddar, Ayman; Mokadem, Ahmad Samih; El Hajj Ali, Mohamad; Awwad, Shady

2012-01-01

To present the visual outcomes and ocular sequelae of victims of cluster bombs. This retrospective, multicenter case series of ocular injury due to cluster bombs was conducted for 3 years after the war in South Lebanon (July 2006). Data were gathered from the reports to the Information Management System for Mine Action. There were 308 victims of clusters bombs; 36 individuals were killed, of which 2 received ocular lacerations and; 272 individuals were injured with 18 receiving ocular injury. These 18 surviving individuals were assessed by the authors. Ocular injury occurred in 6.5% (20/308) of cluster bomb victims. Trauma to multiple organs occurred in 12 of 18 cases (67%) with ocular injury. Ocular findings included corneal or scleral lacerations (16 eyes), corneal foreign bodies (9 eyes), corneal decompensation (2 eyes), ruptured cataract (6 eyes), and intravitreal foreign bodies (10 eyes). The corneas of one patient had extreme attenuation of the endothelium. Ocular injury occurred in 6.5% of cluster bomb victims and 67% of the patients with ocular injury sustained trauma to multiple organs. Visual morbidity in civilians is an additional reason for a global ban on the use of cluster bombs.

Editorial: X-chromosome-linked Kallmann's syndrome: Pathology at the molecular level

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prager, D.; Braunstein, G.D.

Kallmann's syndrome or olfactogenital dysplasia refers to a disorder characterized by hypogonadotropic hypogonadism and anosmia or hyposmia which can occur sporadically or in a familial setting. Originally described in 1856, the first familial cases were reported by Kallmann et al., in 1944. Based on segregation analysis of multiple families, three modes of transmission have been documented: X-linked, autosomal dominant with variable penetrance, and autosomal recessive. Kallmann's syndrome occurs in less than 1 in 10,000 male births, with a 5-fold excess of affected males to females, suggesting that the X-linked form is the most frequent. By genetic linkage analysis the X-linkedmore » form of Kallmann's syndrome was localized to Xp22.3. This was confirmed by the description of patients with contiguous gene syndromes due to deletions of various portions of the distal short arm of the X-chromosome. Such patients present with complex phenotypes characterized by a combination of Kallmann's syndrome with X-linked icthyosis due to steroid sulfatase deficiency, chondrodysplasia punctata, short stature, and mental retardation. DNA analysis has identified and mapped the genes responsible for these disorders. 10 refs., 1 fig., 1 tab.« less

Aberrant ocular architecture and function in patients with Klinefelter syndrome.

PubMed

Brand, Cristin; Zitzmann, Michael; Eter, Nicole; Kliesch, Sabine; Wistuba, Joachim; Alnawaiseh, Maged; Heiduschka, Peter

2017-10-13

Klinefelter Syndrome (KS), the most common chromosomal disorder in men (47,XXY), is associated with numerous comorbidities. Based on a number of isolated case reports, we performed the first systematic and comprehensive evaluation of eye health in KS patients with a focus on ocular structure and vascularization. Twenty-one KS patients and 26 male and 38 female controls underwent a variety of non-invasive examinations investigating ocular morphology (examination of retinal thickness, optic nerve head, and cornea) and function (visual field testing and quantification of ocular vessel density by optical coherence tomography angiography). In comparison to healthy controls, KS patients exhibited a smaller foveal avascular zone and a decreased retinal thickness due to a drastically thinner outer nuclear layer. The cornea of KS patients showed a decreased peripheral thickness and volume. In perimetry evaluation, KS patients required brighter stimuli and gave more irregular values. KS patients show an ocular phenotype including morphological and functional features, which is very likely caused by the supernumerary X chromosome. Thus, KS should not be limited to infertility, endocrine dysfunction, neurocognitive and psychosocial comorbidities. Defining an aberrant ocular morphology and function, awareness for possible eye problems should be raised.

Ocular Rosacea

MedlinePlus

... Signs and symptoms of ocular rosacea may include: Dry eyes Burning or stinging in the eyes Itchy eyes ... signs and symptoms of ocular rosacea, such as dry eyes, burning or itchy eyes, redness, or blurred vision. ...

Ocular TRUST: nationwide antimicrobial susceptibility patterns in ocular isolates.

PubMed

Asbell, Penny A; Colby, Kathryn A; Deng, Sophie; McDonnell, Peter; Meisler, David M; Raizman, Michael B; Sheppard, John D; Sahm, Daniel F

2008-06-01

Ocular Tracking Resistance in U.S. Today (TRUST) annually evaluates in vitro antimicrobial susceptibility of Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae to ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, penicillin, azithromycin, tobramycin, trimethoprim, and polymyxin B in national samples of ocular isolates. Laboratory investigation. Prospectively collected ocular isolates (197 S. aureus, 49 S. pneumoniae, and 32 H. influenzae) from 35 institutions and archived ocular isolates (760 S. pneumoniae and 356 H. influenzae) from 34 institutions were tested by an independent, central laboratory. Mean minimum inhibitory concentrations that would inhibit growth of 90% of the tested isolates (MIC(90)) were interpreted as susceptible, intermediate, or resistant according to standardized breakpoints for systemic treatment. S. aureus isolates were classified as methicillin susceptible (MSSA) or methicillin resistant (MRSA). MSSA or MRSA susceptibility patterns were virtually identical for the fluoroquinolones, that is, MSSA susceptibility was 79.9% to 81.1% and MRSA susceptibility was 15.2%. Trimethoprim was the only agent tested with high activity against MRSA. All S. pneumoniae isolates were susceptible to gatifloxacin, levofloxacin, and moxifloxacin; 89.8% were susceptible to ciprofloxacin. H. influenzae isolates were 100% susceptible to all tested agents but trimethoprim. Ocular TRUST 1 data were consistent with the eight-year longitudinal sample of archived ocular isolates. The fluoroquinolones were consistently active in MSSA, S. pneumoniae, and H. influenzae. After more than a decade of intensive ciprofloxacin and levofloxacin use as systemic therapy, 100% of ocular S. pneumoniae isolates were susceptible to gatifloxacin, levofloxacin, and moxifloxacin; nonsusceptibility to ciprofloxacin was less than 15%. High-level in vitro MRSA resistance suggests the need to consider alternative therapy to fluoroquinolones when MRSA is a

Cluster Bomb Ocular Injuries

PubMed Central

Mansour, Ahmad M.; Hamade, Haya; Ghaddar, Ayman; Mokadem, Ahmad Samih; El Hajj Ali, Mohamad; Awwad, Shady

2012-01-01

Purpose: To present the visual outcomes and ocular sequelae of victims of cluster bombs. Materials and Methods: This retrospective, multicenter case series of ocular injury due to cluster bombs was conducted for 3 years after the war in South Lebanon (July 2006). Data were gathered from the reports to the Information Management System for Mine Action. Results: There were 308 victims of clusters bombs; 36 individuals were killed, of which 2 received ocular lacerations and; 272 individuals were injured with 18 receiving ocular injury. These 18 surviving individuals were assessed by the authors. Ocular injury occurred in 6.5% (20/308) of cluster bomb victims. Trauma to multiple organs occurred in 12 of 18 cases (67%) with ocular injury. Ocular findings included corneal or scleral lacerations (16 eyes), corneal foreign bodies (9 eyes), corneal decompensation (2 eyes), ruptured cataract (6 eyes), and intravitreal foreign bodies (10 eyes). The corneas of one patient had extreme attenuation of the endothelium. Conclusions: Ocular injury occurred in 6.5% of cluster bomb victims and 67% of the patients with ocular injury sustained trauma to multiple organs. Visual morbidity in civilians is an additional reason for a global ban on the use of cluster bombs. PMID:22346132

[Ocular sarcoidosis].

PubMed

Springer-Wanner, C; Brauns, T

2017-06-01

Ocular manifestation of sarcoidosis occurs in up to 60% of patients with confirmed systemic sarcoidosis and represents one of the most common forms of noninfectious uveitis. In known pulmonary sarcoidosis, ocular involvement can occur in up to 80% of cases. Sarcoidosis can also present only in the eye, without a systemic manifestation (ocular sarcoidosis). Typically, ocular sarcoidosis shows bilateral granulomatous uveitis and can involve all parts of the eye. Apart from an acute anterior uveitis, chronic intermediate or posterior uveitis can be found. In order to prevent a severe reduction of visual acuity leading to blindness, early diagnosis and treatment is essential. For diagnosis, specific clinical signs involving the eye (bilateral granulomatous changes in all parts of the eye) and typical laboratory investigations (angiotensin-converting enzyme, ACE; lysozyme; soluble interleukin 2 receptor, sIL2R; chest X‑ray; chest CT) have to be taken into account, since biopsy to prove noncaseating granulomas is not performed with changes restricted to the eye due to the high risk of vision loss. Ocular sarcoidosis mostly responds well to local or systemic steroid treatment. If the therapeutic effect is insufficient, immunosuppressive agents and biologics can be applied.

The albinism of the feral Asinara white donkeys (Equus asinus) is determined by a missense mutation in a highly conserved position of the tyrosinase (TYR) gene deduced protein.

PubMed

Utzeri, V J; Bertolini, F; Ribani, A; Schiavo, G; Dall'Olio, S; Fontanesi, L

2016-02-01

A feral donkey population (Equus asinus), living in the Asinara National Park (an island north-west of Sardinia, Italy), includes a unique white albino donkey subpopulation or colour morph that is a major attraction of this park. Disrupting mutations in the tyrosinase (TYR) gene are known to cause recessive albinisms in humans (oculocutaneous albinism Type 1; OCA1) and other species. In this study, we analysed the donkey TYR gene as a strong candidate to identify the causative mutation of the albinism of these donkeys. The TYR gene was sequenced from 13 donkeys (seven Asinara white albino and six coloured animals). Seven single nucleotide polymorphisms were identified. A missense mutation (c.604C>G; p.His202Asp) in a highly conserved amino acid position (even across kingdoms), which disrupts the first copper-binding site (CuA) of functional protein, was identified in the homozygous condition (G/G or D/D) in all Asinara white albino donkeys and in the albino son of a trio (the grey parents had genotype C/G or H/D), supporting the recessive mode of inheritance of this mutation. Genotyping 82 donkeys confirmed that Asinara albino donkeys had genotype G/G whereas all other coloured donkeys had genotype C/C or C/G. Across-population association between the c.604C>G genotypes and the albino coat colour was highly significant (P = 6.17E-18). The identification of the causative mutation of the albinism in the Asinara white donkeys might open new perspectives to study the dynamics of this putative deleterious allele in a feral population and to manage this interesting animal genetic resource. © 2015 Stichting International Foundation for Animal Genetics.

The multifocal electroretinogram in X-linked juvenile retinoschisis.

PubMed

Huang, Shizhou; Wu, Dezheng; Jiang, Futian; Luo, Guangwei; Liang, Jiongji; Wen, Feng; Yu, Minzhong; Long, Shixian; Wu, Lezheng

2003-05-01

To measure and compare the multifocal electroretinography in normal control and X-linked juvenile retinoschisis, 13 cases (13 right eyes) of normal control and nine cases (17 eyes) of X-linked juvenile retinoschisis were measured with VERIS Science 4.0. Four cases (eight eyes) out of the nine retinoschisis cases were tested with Ganzfeld ERG at the same day. The results showed statistically significant difference of average response densities and latencies in six ring retinal regions between the normal control and retinoschisis. The trace array and 3-D topography of multifocal ERG showed multi-area amplitude decrease with absence or reduction of central peak amplitude in patients with retinoschisis. The P1/N1 ratio of multifocal ERG average response densities in six ring retinal regions was different from the b/a ratio of Ganzfeld ERG. The multifocal ERG and Ganzfeld ERG each had its advantage in the diagnosis of retinoschisis.

Proteomics Analysis of Molecular Risk Factors in the Ocular Hypertensive Human Retina

PubMed Central

Yang, Xiangjun; Hondur, Gözde; Li, Ming; Cai, Jian; Klein, Jon B.; Kuehn, Markus H.; Tezel, Gülgün

2015-01-01

Purpose To better understand ocular hypertension–induced early molecular alterations that may determine the initiation of neurodegeneration in human glaucoma, this study analyzed retinal proteomic alterations in the ocular hypertensive human retina. Methods Retina samples were obtained from six human donors with ocular hypertension (without glaucomatous injury) and six age- and sex-matched normotensive controls. Retinal proteins were analyzed by two-dimensional LC-MS/MS (liquid chromatography and linear ion trap mass spectrometry) using oxygen isotope labeling for relative quantification of protein expression. Proteomics data were validated by Western blot and immunohistochemical analyses of selected proteins. Results Out of over 2000 retinal proteins quantified, hundreds exhibited over 2-fold increased or decreased expression in ocular hypertensive samples relative to normotensive controls. Bioinformatics linked the proteomics datasets to various pathways important for maintenance of cellular homeostasis in the ocular hypertensive retina. Upregulated proteins included various heat shock proteins, ubiquitin proteasome pathway components, antioxidants, and DNA repair enzymes, while many proteins involved in mitochondrial oxidative phosphorylation exhibited downregulation in the ocular hypertensive retina. Despite the altered protein expression reflecting intrinsic adaptive/protective responses against mitochondrial energy failure, oxidative stress, and unfolded proteins, no alterations suggestive of an ongoing cell death process or neuroinflammation were detectable. Conclusions This study provides information about ocular hypertension–related molecular risk factors for glaucoma development. Molecular alterations detected in the ocular hypertensive human retina as opposed to previously detected alterations in human donor retinas with clinically manifest glaucoma suggest that proteome alterations determine the individual threshold to tolerate the ocular

X-Linked Retinoschisis: Phenotypic Variability in a Chinese Family

PubMed Central

Xiao, Yangyan; Liu, Xiao; Tang, Luosheng; Wang, Xia; Coursy, Terry; Guo, Xiaojian; Li, Zhuo

2016-01-01

X-linked juvenile retinoschisis (XLRS), a leading cause of juvenile macular degeneration, is characterized by a spoke-wheel pattern in the macular region of the retina and splitting of the neurosensory retina. Our study is to describe the clinical characteristics of a four generations of this family (a total of 18 members)with X-linked retinoschisis (XLRS) and detected a novel mutations of c.3G > A (p.M1?) in the initiation codon of the RS1 gene. by direct sequencing.Identification of this mutation in this family provides evidence about potential genetic or environmental factors on its phenotypic variance, as patients presented with different phenotypes regardless of having the same mutation. Importantly, OCT has proven vital for XLRS diagnosis in children. PMID:26823236

X-Linked Retinoschisis: Phenotypic Variability in a Chinese Family.

PubMed

Xiao, Yangyan; Liu, Xiao; Tang, Luosheng; Wang, Xia; Coursey, Terry G; Coursy, Terry; Guo, Xiaojian; Li, Zhuo

2016-01-29

X-linked juvenile retinoschisis (XLRS), a leading cause of juvenile macular degeneration, is characterized by a spoke-wheel pattern in the macular region of the retina and splitting of the neurosensory retina. Our study is to describe the clinical characteristics of a four generations of this family (a total of 18 members)with X-linked retinoschisis (XLRS) and detected a novel mutations of c.3G > A (p.M1?) in the initiation codon of the RS1 gene. by direct sequencing.Identification of this mutation in this family provides evidence about potential genetic or environmental factors on its phenotypic variance, as patients presented with different phenotypes regardless of having the same mutation. Importantly, OCT has proven vital for XLRS diagnosis in children.

X-linked adrenoleukodystrophy in heterozygous female patients: women are not just carriers.

PubMed

Lourenço, Charles Marques; Simão, Gustavo Novelino; Santos, Antonio Carlos; Marques, Wilson

2012-07-01

X-linked adrenoleukodystrophy (X-ALD) is a recessive X-linked disorder associated with marked phenotypic variability. Female carriers are commonly thought to be normal or only mildly affected, but their disease still needs to be better described and systematized. To review and systematize the clinical features of heterozygous women followed in a Neurogenetics Clinic. We reviewed the clinical, biochemical, and neuroradiological data of all women known to have X-ADL. The nine women identified were classified into three groups: with severe and aggressive diseases; with slowly progressive, spastic paraplegia; and with mildly decreased vibratory sensation, brisk reflexes, and no complaints. Many of these women did not have a known family history of X-ALD. Heterozygous women with X-ADL have a wide spectrum of clinical manifestations, ranging from mild to severe phenotypes.

Mutations in the XLRS1 gene in Thai families with X-linked juvenile retinoschisis.

PubMed

Atchaneeyasakul, La-ongsri; Trinavarat, Adisak; Pituksung, Auengporn; Jinda, Worapoj; Thongnoppakhun, Wanna; Limwongse, Chanin

2010-01-01

To identify genetic mutations of the XLRS1 gene and to describe the ocular phenotypes in two unrelated Thai patients with X-linked juvenile retinoschisis. Ophthalmic examination, including best-corrected visual acuity and fundus examination and photography, was performed in all participants. Electroretinography (ERG) and optical coherence tomography were performed when possible. All six exons of the XLRS1 gene were amplified, and mutation screening was determined by denaturing high-performance liquid chromatography and DNA sequencing. Two point mutations were identified, a novel missense mutation c.378A > G (p.D126G) in exon 5 and a reported mutation c.637C > T (p.R213W) in exon 6. The first proband with the p.D126G mutation developed vitreous hemorrhage in both eyes at age 7 months. Foveal and peripheral schisis with several inner layer holes were detected in both eyes. The second proband with the p.R213W mutation developed slightly blurred vision at age 10 years. Fundus examination showed numerous fine white dots at the macula without foveal or peripheral schisis. Electronegative ERG results were documented in both probands. A novel p.D126G mutation appeared to be associated with a severe phenotype with vitreous hemorrhage developing in infancy. Both intra- and interfamilial clinical variabilities were recognized in our patients.

SIGNALING PATHWAYS IN MELANOSOME BIOGENESIS AND PATHOLOGY

PubMed Central

Schiaffino, Maria Vittoria

2010-01-01

Melanosomes are the specialized intracellular organelles of pigment cells devoted to the synthesis, storage and transport of melanin pigments, which are responsible for most visible pigmentation in mammals and other vertebrates. As a direct consequence, any genetic mutation resulting in alteration of melanosomal function, either because affecting pigment cell survival, migration and differentiation, or because interfering with melanosome biogenesis, transport and transfer to keratinocytes, is immediately translated into color variations of skin, fur, hair or eyes. Thus, over one hundred genes and proteins have been identified as pigmentary determinants in mammals, providing us with a deep understanding of this biological system, which functions by using mechanisms and processes that have parallels in other tissues and organs. In particular, many genes implicated in melanosome biogenesis have been characterized, so that melanosomes represent an incredible source of information and a model for organelles belonging to the secretory pathway. Furthermore, the function of melanosomes can be associated with common physiological phenotypes, such as variation of pigmentation among individuals, and with rare pathological conditions, such as albinism, characterized by severe visual defects. Among the most relevant mechanisms operating in melanosome biogenesis are the signal transduction pathways mediated by two peculiar G protein-coupled receptors: the melanocortin-1 receptor (MC1R), involved in the fair skin/red hair phenotype and skin cancer; and OA1 (GPR143), whose loss-of-function results in X-linked ocular albinism. This review will focus on the most recent novelties regarding the functioning of these two receptors, by highlighting emerging signaling mechanisms and general implications for cell biology and pathology. PMID:20381640

The Relationship Between Ocular Itch, Ocular Pain, and Dry Eye Symptoms (An American Ophthalmological Society Thesis).

PubMed

Galor, Anat; Small, Leslie; Feuer, William; Levitt, Roy C; Sarantopoulos, Konstantinos D; Yosipovitch, Gil

2017-08-01

To evaluate associations between sensations of ocular itch and dry eye (DE) symptoms, including ocular pain, and DE signs. A cross-sectional study of 324 patients seen in the Miami Veterans Affairs eye clinic was performed. The evaluation consisted of questionnaires regarding ocular itch, DE symptoms, descriptors of neuropathic-like ocular pain (NOP), and evoked pain sensitivity testing on the forehead and forearm, followed by a comprehensive ocular surface examination including corneal mechanical sensitivity testing. Analyses were performed to examine for differences between those with and without subjective complaints of ocular itch. The mean age was 62 years with 92% being male. Symptoms of DE and NOP were more frequent in patients with moderate-severe ocular itch compared to those with no or mild ocular itch symptoms. With the exception of ocular surface inflammation (abnormal matrix metalloproteinase 9 testing) which was less common in those with moderate-severe ocular itch symptoms, DE signs were not related to ocular itch. Individuals with moderate-severe ocular itch also demonstrated greater sensitivity to evoked pain on the forearm and had higher non-ocular pain, depression, and post-traumatic stress disorders scores, compared to those with no or mild itch symptoms. Subjects with moderate-severe ocular itch symptoms have more severe symptoms of DE, NOP, non-ocular pain and demonstrate abnormal somatosensory testing in the form of increased sensitivity to evoked pain at a site remote from the eye, consistent with generalized hypersensitivity.

The Relationship Between Ocular Itch, Ocular Pain, and Dry Eye Symptoms (An American Ophthalmological Society Thesis)

PubMed Central

Galor, Anat; Small, Leslie; Feuer, William; Levitt, Roy C.; Sarantopoulos, Konstantinos D.; Yosipovitch, Gil

2017-01-01

Purpose To evaluate associations between sensations of ocular itch and dry eye (DE) symptoms, including ocular pain, and DE signs. Methods A cross-sectional study of 324 patients seen in the Miami Veterans Affairs eye clinic was performed. The evaluation consisted of questionnaires regarding ocular itch, DE symptoms, descriptors of neuropathic-like ocular pain (NOP), and evoked pain sensitivity testing on the forehead and forearm, followed by a comprehensive ocular surface examination including corneal mechanical sensitivity testing. Analyses were performed to examine for differences between those with and without subjective complaints of ocular itch. Results The mean age was 62 years with 92% being male. Symptoms of DE and NOP were more frequent in patients with moderate-severe ocular itch compared to those with no or mild ocular itch symptoms. With the exception of ocular surface inflammation (abnormal matrix metalloproteinase 9 testing) which was less common in those with moderate-severe ocular itch symptoms, DE signs were not related to ocular itch. Individuals with moderate-severe ocular itch also demonstrated greater sensitivity to evoked pain on the forearm and had higher non-ocular pain, depression, and post-traumatic stress disorders scores, compared to those with no or mild itch symptoms. Conclusions Subjects with moderate-severe ocular itch symptoms have more severe symptoms of DE, NOP, non-ocular pain and demonstrate abnormal somatosensory testing in the form of increased sensitivity to evoked pain at a site remote from the eye, consistent with generalized hypersensitivity. PMID:29391860

Ocular Sarcoidosis

PubMed Central

Pasadhika, Sirichai; Rosenbaum, James T

2015-01-01

Sarcoidosis is one of the leading causes of inflammatory eye disease. Ocular sarcoidosis can involve any part of the eye and its adnexal tissues, and may cause uveitis, episcleritis/scleritis, eyelid abnormalities, conjunctival granuloma, optic neuropathy, lacrimal gland enlargement and orbital inflammation. Glaucoma and cataract can be complications from inflammation itself or adverse effects from therapy. Ophthalmic manifestations can be isolated, or associated with other organ involvement. Patients with ocular sarcoidosis can present with a wide range of clinical presentations and severity. Multi-disciplinary approaches are required to achieve the best treatment outcomes for both ocular and systemic manifestations. PMID:26593141

Paternal inheritance of classic X-linked bilateral periventricular nodular heterotopia.

PubMed

Kasper, Burkhard S; Kurzbuch, Katrin; Chang, Bernard S; Pauli, Elisabeth; Hamer, Hajo M; Winkler, Jürgen; Hehr, Ute

2013-06-01

Periventricular nodular heterotopia (PNH) is a developmental disorder of the central nervous system, characterized by heterotopic nodules of gray matter resulting from disturbed neuronal migration. The most common form of bilateral PNH is X-linked dominant inherited, caused by mutations in the Filamin A gene (FLNA) and associated with a wide variety of other clinical findings including congenital heart disease. The typical patient with FLNA-associated PNH is female and presents with difficult to treat seizures. In contrast, hemizygous FLNA loss of function mutations in males are reported to be perinatally lethal. In X-linked dominant traits like FLNA-associated PNH the causal mutation is commonly inherited from the mother. Here, we present an exceptional family with paternal transmission of classic bilateral FLNA-associated PNH from a mildly affected father with somatic and germline mosaicism for a c.5686G>A FLNA splice mutation to both daughters with strikingly variable clinical manifestation and PNH extent in cerebral MR imaging. Our observations emphasize the importance to consider in genetic counseling and risk assessment the rare genetic constellation of paternal transmission for families with X-linked dominant inherited FLNA-associated PNH. Copyright © 2013 Wiley Periodicals, Inc.

Proposal for management and dermoscopy follow-up of nevi in patients affected by oculocutaneous albinism type Ia.

PubMed

Peralta, Rosario; Sabban, Emilia Cohen; Friedman, Paula; Marcucci, Carolina; Bollea Garlatti, Luis A; Galimberti, Gastón; Cabo, Horacio

2017-01-01

Albino patients are at great risk for developing cutaneous neoplasms, including melanomas. In this paper we describe the dermatoscopic findings of nevi in two patients with oculocutaneous albinism type Ia (OCA-Ia) highlighting that they manifest a vascular pattern similar to that described for amelanotic melanoma. We propose managing these patients with dermoscopy, using the comparative approach, digital follow up (DFU), and reflectance confocal microscopy as a complementary tool for difficult cases.

Neovascular glaucoma in a patient with X-linked juvenile retinoschisis.

PubMed

Zuo, Chengguo; Chen, Changzheng; Xing, Yiqiao; Du, Lei

2005-09-01

To report the rubeosis iridis and neovascular glaucoma findings in one patient of X-linked juvenile retinoschisis(XLRS). Color fundus photography, fluorescein angiography (FFA), OCT and B-scan were performed in a patient with X-linked juvenile retinoschisis complicated with neovascular glaucoma. Color fundus photography, fluorescein angiography (FFA), OCT and B-scan unveiled a rare condition of XLRS complicated with neovascular glaucoma. XLRS may complicate with neovascular glaucoma. It is necessary to test OCT, FFA, ERG and carefully examine the fundus of the follow eye when it comes to uncertain neovascular glaucoma of youth and child. And only in this way, can we exclude XLRS.

Genotypic analysis of X-linked retinoschisis in Western Australia.

PubMed

Lamey, Tina; Laurin, Sarina; Chelva, Enid; De Roach, John

2010-01-01

X-linked Retinoschisis is a leading cause of juvenile macular degeneration. Four Western Australian families affected by X-Linked Retinoschisis were analysed using DNA and clinical information from the Australian Inherited Retinal Disease (IRD) Register and DNA Bank. By direct sequencing of the RS1 gene, three genetic variants were identified; 52+1G > T, 289T > G and 416delA. 289T > G has not been previously reported and is likely to cause a substitution of a membrane binding residue (W92G) in the functional discoidin domain. All clinically diagnosed individuals showed typical electronegative ERGs. The 52+1G > T obligate carrier also recorded a bilaterally abnormal rod ERG and mildly abnormal photopic responses. mfERG trace arrays showed reduced response densities in the paramacular region extending futher temporally for each eye.

Cornea and ocular lens visualized with three-dimensional confocal microscopy

NASA Astrophysics Data System (ADS)

Masters, Barry R.

1992-08-01

This paper demonstrates the advantages of three-dimensional reconstruction of the cornea and the ocular crystalline lens by confocal microscopy and volume rendering computer techniques. The advantages of noninvasive observation of ocular structures in living, unstained, unfixed tissue include the following: the tissue is in a natural living state without the artifacts of fixation, mechanical sectioning, and staining; the three-dimensional structure can be observed from any view point and quantitatively analyzed; the dynamics of morphological changes can be studied; and the use of confocal microscopic observation results in a reduction of the number of animals required for ocular morphometric studies. The main advantage is that the dynamic morphology of ocular structures can be investigated in living ocular tissue. A laser scanning confocal microscope was used in the reflected light mode to obtain the two- dimensional images from the cornea and the ocular lens of a freshly enucleated rabbit eye. The light source was an argon ion laser with 488 nm wavelength. The microscope objective was a Leitz 25X, NA 0.6 water immersion lens. The 400 micron thick cornea was optically sectioned into 133, three micron sections. The semi-transparent cornea and the in-situ ocular lens was visualized as high resolution, high contrast two-dimensional images. The under sampling resulted in a three-dimensional visualization rendering in which the corneal thickness (z-axis) is compressed. The structures observed in the cornea include: superficial epithelial cells and their nuclei, basal epithelial cells and their `beaded' cell borders, basal lamina, nerve plexus, nerve fibers, free nerve endings in the basal epithelial cells, nuclei of stromal keratocytes, and endothelial cells. The structures observed in the in-situ ocular lens include: lens capsule, lens epithelial cells, and individual lens fibers.

Pyoderma Gangrenosum–Like Ulcer in a Patient With X-Linked Agammaglobulinemia

PubMed Central

Murray, Patrick R.; Jain, Ashish; Uzel, Gulbu; Ranken, Raymond; Ivy, Cristina; Blyn, Lawrence B.; Ecker, David J.; Sampath, Rangarajan; Lee, Chyi-Chia Richard; Turner, Maria L.

2011-01-01

Background Pyoderma gangrenosum–like ulcers and cellulitis of the lower extremities associated with recurrent fevers in patients with X-linked (Bruton) agammaglobulinemia have been reported to be caused by Helicobacter bilis (formerly classified as Flexispira rappini and then Helicobacter strain flexispira taxon 8). Consistent themes in these reports are the difficulty in recovering this organism in blood and wound cultures and in maintaining isolates in vitro. We confirmed the presence of this organism in a patient’s culture by using a novel application of gene amplification polymerase chain reaction and electrospray ionization time-of-flight mass spectrometry. Observation An adolescent boy with X-linked agammaglobulinemia presented with indurated plaques and a chronic leg ulcer whose origin was strongly suspected to be an H bilis organism. Histologic analysis demonstrated positive Warthin-Starry staining of curvilinear rods, which grew in culture but failed to grow when sub-cultured. They could not be identified by conventional techniques. A combination of gene amplification by polymerase chain reaction and electrospray ionization time-of-flight mass spectrometry confirmed the identity of this organism. Conclusions This novel technology was useful in the identification of a difficult-to-grow Helicobacter organism, the cause of pyoderma gangrenosum–like leg ulcers in patients with X-linked agammaglobulinemia. Correct identification of this organism as the cause of pyoderma gangrenosum–like ulcers in patients with X-linked agammaglobulinemia is of great importance for the early initiation of appropriate and curative antibiotic therapy. PMID:20479300

Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia.

PubMed

Jonsson, Kenneth B; Zahradnik, Richard; Larsson, Tobias; White, Kenneth E; Sugimoto, Toshitsugu; Imanishi, Yasuo; Yamamoto, Takehisa; Hampson, Geeta; Koshiyama, Hiroyuki; Ljunggren, Osten; Oba, Koichi; Yang, In Myung; Miyauchi, Akimitsu; Econs, Michael J; Lavigne, Jeffrey; Jüppner, Harald

2003-04-24

Mutations in fibroblast growth factor 23 (FGF-23) cause autosomal dominant hypophosphatemic rickets. Clinical and laboratory findings in this disorder are similar to those in oncogenic osteomalacia, in which tumors abundantly express FGF-23 messenger RNA, and to those in X-linked hypophosphatemia, which is caused by inactivating mutations in a phosphate-regulating endopeptidase called PHEX. Recombinant FGF-23 induces phosphaturia and hypophosphatemia in vivo, suggesting that it has a role in phosphate regulation. To determine whether FGF-23 circulates in healthy persons and whether it is elevated in those with oncogenic osteomalacia or X-linked hypophosphatemia, an immunometric assay was developed to measure it. Using affinity-purified, polyclonal antibodies against [Tyr223]FGF-23(206-222)amide and [Tyr224]FGF-23(225-244)amide, we developed a two-site enzyme-linked immunosorbent assay that detects equivalently recombinant human FGF-23, the mutant form in which glutamine is substituted for arginine at position 179 (R179Q), and synthetic human FGF-23(207-244)amide. Plasma or serum samples from 147 healthy adults (mean [+/-SD] age, 48.4+/-19.6 years) and 26 healthy children (mean age, 10.9+/-5.5 years) and from 17 patients with oncogenic osteomalacia (mean age, 43.0+/-13.3 years) and 21 patients with X-linked hypophosphatemia (mean age, 34.9+/-17.2 years) were studied. Mean FGF-23 concentrations in the healthy adults and children were 55+/-50 and 69+/-36 reference units (RU) per milliliter, respectively. Four patients with oncogenic osteomalacia had concentrations ranging from 426 to 7970 RU per milliliter, which normalized after tumor resection. FGF-23 concentrations were 481+/-528 RU per milliliter in those with suspected oncogenic osteomalacia and 353+/-510 RU per milliliter (range, 31 to 2335) in those with X-linked hypophosphatemia. FGF-23 is readily detectable in the plasma or serum of healthy persons and can be markedly elevated in those with oncogenic

Unusual phenotypic expression of an XLRS1 mutation in X-linked juvenile retinoschisis.

PubMed

Dodds, Jodi A; Srivastava, Anand K; Holden, Kenton R

2006-04-01

X-linked juvenile retinoschisis is a rare progressive vitreoretinal degenerative process that appears in early childhood, results in decreased visual acuity and blindness (if severe), and is caused by various mutations within the XLRS1 gene at Xp22.2. We report an affected family of Western European ancestry with X-linked juvenile retinoschisis. The family was found to carry a 304C-->T substitution in exon 4 of the XLRS1 gene, resulting in an Arg102Trp amino acid substitution. Two of the four available clinical cases in this family were found to carry the mutation. All available mothers of affected males were found to be unaffected carriers of the mutation, a typical feature of X-linked diseases. Two new female carriers, sisters of affected males, were identified and counseled accordingly. Questionnaires on visual functioning were given to the affected family members to examine the psychologic and sociologic impact of X-linked juvenile retinoschisis, which documented an associated stigma even when affected with a "mild" phenotype.

Expression pattern of X-linked genes in sex chromosome aneuploid bovine cells.

PubMed

Basrur, Parvathi K; Farazmand, Ali; Stranzinger, Gerald; Graphodatskaya, Daria; Reyes, Ed R; King, W Allan

2004-01-01

Expression of the X-inactive specific transcript (XIST) gene is a prerequisite step for dosage compensation in mammals, accomplished by silencing one of the two X chromosomes in normal female diploid cells or all X chromosomes in excess of one in sex chromosome aneuploids. Our previous studies showing that XIST expression does not eventuate the inactivation of X-linked genes in fetal bovine testis had suggested that XIST expression may not be an indicator of X inactivation in this species. In this study, we used a semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) approach on cultures of bovine cells with varying sex chromosome constitution (XY, XX, XXY and XXX) to test whether the levels of XIST expressed conform to the number of late replicating (inactive) X chromosomes displayed by proliferating cells in these cultures. Expression patterns of four X-linked genes, including hypoxanthine phosphorybosyl transferase (HPRT), glucose-6-phosphate dehydrogenase (G6PD), zinc finger protein locus on the X (ZFX). and 'selected mouse cDNA on the X' (SMCX), in all these cells were also tested. Results showed that XIST expression was significantly higher (p < 0.05) in XXX cells compared to XX and XXY cells and that G6PD. HPRT, and SMCX loci are subject to X inactivation. The significantly higher levels of ZFX expressed in XXX cells compared to XX and XXY cells (p < 0.05) confirmed that this bovine locus, as human ZFX, escapes X inactivation. However, the levels of XIST and ZFX expressed were not proportional to the X chromosome load in these cells suggesting that X-linked loci escaping inactivation may be regulated at transcription (or post-transcription) level by mechanisms that prevent gene-specific product accumulation beyond certain levels in sex chromosome aneuploids.

[Rare ocular manifestation with suspect alport syndrome].

PubMed

Krejčířová, I; Varadyová, B; Doležel, Z; Autrata, R; Matúšová, J; Gregorová, E

2014-06-01

The authors mention a case report of a 13 year old girl with renal disease, who visited the outpatient Department of Pediatric Ophthalmology, University Hospital Brno with subjective complaints on decreased vision of both eyes. Ophthalmologic examination showed physiological foveolar reflex on fundus and very discrete changes of the retinal pigment epithelium in macula, the fundus periphery was without pathology. OCT images showed bilateral atrophy of central macula and changes at the level of the photoreceptors. The authors describe a rare ocular manifestation of macular atrophy with suspect Alport syndrome, which strengthened the suspicion of this disease. The authors also mention other possible ocular manifestations of Alport syndrome and compare the findings with the up to date international references. Key words: Alport syndrome, X heterozygot Alport syndrome, macular atrophy, lentikonus.

X-linked cardiomyopathy is heterogeneous

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilson, M.J.; Sillence, D.O.; Mulley, J.C.

Two major loci of X-linked cardiomyopathy have been mapped by linkage analysis. The gene for X-linked dilated cardiomyopathy (XLCM) is mapped to the dystrophin locus at Xp21, while Barth syndrome has been localised to distal Xq28. XLCM usually presents in juvenile males with no skeletal disease but decreased dystrophin in cardiac muscle. Barth syndrome most often presents in infants and is characterized by skeletal myopathy, short stature and neutropenia in association with cardiomyopathy of variable severity. Prior to carrier or prenatal diagnosis in a family, delineation of the cardiomyopathy locus involved is essential. We report the linkage mapping of amore » large kindred in which several male infants have died with hypertrophic cardiomyopathy. There is a family history of unexplained death of infant males less than 6 months old over 4 generations. Features of Barth syndrome such as short stature, skeletal myopathy and neutropenia have not been observed. Genotyping at 10 marker loci in Xq28 has revealed significant pairwise lod scores with the cardiomyopathy phenotype at DXS52 (Z=2.21 at {theta}=0.0), at markers p26 and p39 near DXS15 (Z=2.30 at {theta}=0.0) and at F8C (Z=2.24 at {theta}=0.0). A recombinant detected with DXS296 defines the proximal limit to the localization. No recombinants were detected at any of the loci distal to DXS296. The most distal marker in Xq28, DXS1108, is within 500 kb of the telomere. As the gene in this family is localized to Xq28, it is possible that this disorder is an allelic variant at the Barth syndrome locus.« less

X-Linked Intellectual Disability: Unique Vulnerability of the Male Genome

ERIC Educational Resources Information Center

Stevenson, Roger E.; Schwartz, Charles E.

2009-01-01

X-linked intellectual disability (XLID) accounts for approximately 16% of males with intellectual disability (ID). This is, in part, related to the fact that males have a single X chromosome. Progress in the clinical and molecular characterization of XLID has outpaced progress in the delineation of ID due to genes on the other 22 chromosomes.…

Silencing of X-Linked MicroRNAs by Meiotic Sex Chromosome Inactivation

PubMed Central

Royo, Hélène; Seitz, Hervé; ElInati, Elias; Peters, Antoine H. F. M.; Stadler, Michael B.; Turner, James M. A.

2015-01-01

During the pachytene stage of meiosis in male mammals, the X and Y chromosomes are transcriptionally silenced by Meiotic Sex Chromosome Inactivation (MSCI). MSCI is conserved in therian mammals and is essential for normal male fertility. Transcriptomics approaches have demonstrated that in mice, most or all protein-coding genes on the X chromosome are subject to MSCI. However, it is unclear whether X-linked non-coding RNAs behave in a similar manner. The X chromosome is enriched in microRNA (miRNA) genes, with many exhibiting testis-biased expression. Importantly, high expression levels of X-linked miRNAs (X-miRNAs) have been reported in pachytene spermatocytes, indicating that these genes may escape MSCI, and perhaps play a role in the XY-silencing process. Here we use RNA FISH to examine X-miRNA expression in the male germ line. We find that, like protein-coding X-genes, X-miRNAs are expressed prior to prophase I and are thereafter silenced during pachynema. X-miRNA silencing does not occur in mouse models with defective MSCI. Furthermore, X-miRNAs are expressed at pachynema when present as autosomally integrated transgenes. Thus, we conclude that silencing of X-miRNAs during pachynema in wild type males is MSCI-dependent. Importantly, misexpression of X-miRNAs during pachynema causes spermatogenic defects. We propose that MSCI represents a chromosomal mechanism by which X-miRNAs, and other potential X-encoded repressors, can be silenced, thereby regulating genes with critical late spermatogenic functions. PMID:26509798

Ocular disease and driving.

PubMed

Wood, Joanne M; Black, Alex A

2016-09-01

As the driving population ages, the number of drivers with visual impairment resulting from ocular disease will increase given the age-related prevalence of ocular disease. The increase in visual impairment in the driving population has a number of implications for driving outcomes. This review summarises current research regarding the impact of common ocular diseases on driving ability and safety, with particular focus on cataract, glaucoma, age-related macular degeneration, hemianopia and diabetic retinopathy. The evidence considered includes self-reported driving outcomes, driving performance (on-road and simulator-based) and various motor vehicle crash indices. Collectively, this review demonstrates that driving ability and safety are negatively affected by ocular disease; however, further research is needed in this area. Older drivers with ocular disease need to be aware of the negative consequences of their ocular condition and in the case where treatment options are available, encouraged to seek these earlier for optimum driving safety and quality of life benefits. © 2016 Optometry Australia.

Ocular manifestations of rheumatoid arthritis and their correlation with anti-cyclic citrullinated peptide antibodies.

PubMed

Vignesh, Ammapati Paul Pandian; Srinivasan, Renuka

2015-01-01

To study the ocular manifestations of rheumatoid arthritis and to correlate the role of anti-cyclic citrullinated peptide antibody (anti-CCP antibody) with the ocular manifestations. Three-hundred and ninety-two eyes of the 196 rheumatoid arthritis patients who attended the ophthalmology outpatient department underwent a detailed ocular examination using slit lamp biomicroscopy and ophthalmoscopy. The tear function of all the patients was assessed using Schirmer's test, tear film break-up time and ocular surface staining. The anti-CCP antibody titers for all the rheumatoid arthritis patients were estimated using enzyme-linked immunosorbent assay tests. Seventy-seven patients (135 eyes, 39%) out of the 196 patients studied had ocular manifestations typical of rheumatoid arthritis. Dry eye was the most common manifestation (28%, 54 patients). Of the patients, 78% was females (60 patients). The mean duration of rheumatoid arthritis in patients with ocular manifestations was 5.4±2.7 years and without ocular manifestations was 2.1±1.6years. Three percent of the patients had episcleritis (six patients). Scleritis was present in 2% of the patients (four patients). Peripheral ulcerative keratitis and sclerosing keratitis was present in 1% of the population each (two patients each). Eighty-five percent (66 patients) had bilateral manifestations 15% (eleven patients) had unilateral manifestations. There was a strong association between the presence of anti-CCP antibodies and ocular manifestations of rheumatoid arthritis which was shown by the statistically significant P-value of <0.0001. Ocular manifestations are a significant part of the extra-articular manifestation of rheumatoid arthritis. Dry eye was the most common ocular manifestation. There was a statistically significant association between the presence of anti-CCP antibodies specific to rheumatoid arthritis and the ocular manifestations.

Mutational studies in X-linked Charcot-Marie-Tooth disease (CMTX)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cherryson, A.K.; Yeung, L.; Kennerson, M.L.

1994-09-01

Charcot-Marie-Tooth disease, also known as hereditary motor and sensory neuropathy (HMSN), is a heterogeneous group of slowly progressive disorders of the peripheral nerve. X-linked CMT (CMTX) is characterized by slow motor nerve conduction velocities in affected males and the presence of mildly affected or normal carrier females with intermediate or normal nerve conduction velocities. CMTX, which has an incidence of 3.1 per 100,000 and accounts for approximately 10% of CMT cases, has been mapped to Xq13. One of the genes lying in this region, connexin 32, has been found to contain alterations in individuals affected with X-linked CMT. We havemore » identified our X-linked families from dominant type 1 CMT families using the clinical criteria given above. These families were screened for point mutations in connexin 32. We have identified three missense mutations, a G{r_arrow}A transition at amino acid 35 (valine to methionine), a C{r_arrow}G transition at amino acid 158 (proline to alanine) and a T{r_arrow}A transition at amino acid 182 (serine to threonine). Another family showed a 18 bp deletion, which removed the amino acid 111 to 116 inclusive (histidine, glycine, aspartic acid, proline, leucine, histidine).« less

Severe X-linked chondrodysplasia punctata in nine new female fetuses.

PubMed

Lefebvre, Mathilde; Dufernez, Fabienne; Bruel, Ange-Line; Gonzales, Marie; Aral, Bernard; Saint-Onge, Judith; Gigot, Nadège; Desir, Julie; Daelemans, Caroline; Jossic, Frédérique; Schmitt, Sébastien; Mangione, Raphaele; Pelluard, Fanny; Vincent-Delorme, Catherine; Labaune, Jean-Marc; Bigi, Nicole; D'Olne, Dominique; Delezoide, Anne-Lise; Toutain, Annick; Blesson, Sophie; Cormier-Daire, Valérie; Thevenon, Julien; El Chehadeh, Salima; Masurel-Paulet, Alice; Joyé, Nicole; Vibert-Guigue, Claude; Rigonnot, Luc; Rousseau, Thierry; Vabres, Pierre; Hervé, Philippe; Lamazière, Antonin; Rivière, Jean-Baptiste; Faivre, Laurence; Laurent, Nicole; Thauvin-Robinet, Christel

2015-07-01

Conradi-Hünermann-Happle [X-linked dominant chondrodysplasia punctata 2 (CDPX2)] syndrome is a rare X-linked dominant skeletal dysplasia usually lethal in men while affected women show wide clinical heterogeneity. Different EBP mutations have been reported. Severe female cases have rarely been reported, with only six antenatal presentations. To better characterize the phenotype in female fetuses, we included nine antenatally diagnosed cases of women with EBP mutations. All cases were de novo except for two fetuses with an affected mother and one case of germinal mosaicism. The mean age at diagnosis was 22 weeks of gestation. The ultrasound features mainly included bone abnormalities: shortening (8/9 cases) and bowing of the long bones (5/9), punctuate epiphysis (7/9) and an irregular aspect of the spine (5/9). Postnatal X-rays and examination showed ichthyosis (8/9) and epiphyseal stippling (9/9), with frequent asymmetric short and bowed long bones. The X-inactivation pattern of the familial case revealed skewed X-inactivation in the mildly symptomatic mother and random X-inactivation in the severe fetal case. Differently affected skin samples of the same fetus revealed different patterns of X-inactivation. Prenatal detection of asymmetric shortening and bowing of the long bones and cartilage stippling should raise the possibility of CPDX2 in female fetuses, especially because the majority of such cases involve de novo mutations. © 2015 John Wiley & Sons, Ltd.

Albinism due to transposable element insertion in fish.

PubMed

Koga, A; Hori, H

1997-12-01

The i locus of the medaka fish, Oryzias latipes, is responsible for tyrosinase expression, and several mutant alleles have been identified. The genotype i1/i1 exhibits a complete albino phenotype, having pale orange-red skin and red eyes. This mutant lacks in vivo tyrosinase activity. The genotype i4/i4, on the other hand, shows a quasi-albino phenotype with skin as bright as that of i1/i1 but with red-wine-colored eyes. At the light microscope level, reduced pigmentation is observed both in the skin and eyes of this mutant. The tyrosinase genes for the i1 and the i4 alleles were cloned and sequenced, and compared with that of the wild-type tyrosinase gene. The i1 allele was found to contain a 1.9-kb transposable element in the 1st exon, and the i4 allele was found to contain a 4.7-kb transposable element in the 5th exon. Both i1 and i4 are alleles that were found in a commercial breeding population. The insertion of a transposable element thus appears to constitute a natural cause of mutations that cause albinism in this organism.

MRI in ocular drug delivery

PubMed Central

Li, S. Kevin; Lizak, Martin J.; Jeong, Eun-Kee

2008-01-01

Conventional pharmacokinetic methods for studying ocular drug delivery are invasive and cannot be conveniently applied to humans. The advancement of MRI technology has provided new opportunities in ocular drug-delivery research. MRI provides a means to non-invasively and continuously monitor ocular drug-delivery systems with a contrast agent or compound labeled with a contrast agent. It is a useful technique in pharmacokinetic studies, evaluation of drug-delivery methods, and drug-delivery device testing. Although the current status of the technology presents some major challenges to pharmaceutical research using MRI, it has a lot of potential. In the past decade, MRI has been used to examine ocular drug delivery via the subconjunctival route, intravitreal injection, intrascleral injection to the suprachoroidal space, episcleral and intravitreal implants, periocular injections, and ocular iontophoresis. In this review, the advantages and limitations of MRI in the study of ocular drug delivery are discussed. Different MR contrast agents and MRI techniques for ocular drug-delivery research are compared. Ocular drug-delivery studies using MRI are reviewed. PMID:18186077

Genetics Home Reference: X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia

MedlinePlus

... Share: Email Facebook Twitter Home Health Conditions XMEN X-linked immunodeficiency with magnesium defect, Epstein-Barr virus ... Javascript to view the expand/collapse boxes. Description X-linked immunodeficiency with magnesium defect, Epstein-Barr virus ...

Ocular Fundus Photography as a Tool to Study Stroke and Dementia.

PubMed

Cheung, Carol Y; Chen, Christopher; Wong, Tien Y

2015-10-01

Although cerebral small vessel disease has been linked to stroke and dementia, due to limitations of current neuroimaging technology, direct in vivo visualization of changes in the cerebral small vessels (e.g., cerebral arteriolar narrowing, tortuous microvessels, blood-brain barrier damage, capillary microaneurysms) is difficult to achieve. As the retina and the brain share similar embryological origin, anatomical features, and physiologic properties with the cerebral small vessels, the retinal vessels offer a unique and easily accessible "window" to study the correlates and consequences of cerebral small vessel diseases in vivo. The retinal microvasculature can be visualized, quantified and monitored noninvasively using ocular fundus photography. Recent clinic- and population-based studies have demonstrated a close link between retinal vascular changes seen on fundus photography and stroke and dementia, suggesting that ocular fundus photography may provide insights to the contribution of microvascular disease to stroke and dementia. In this review, we summarize current knowledge on retinal vascular changes, such as retinopathy and changes in retinal vascular measures with stroke and dementia as well as subclinical makers of cerebral small vessel disease, and discuss the possible clinical implications of these findings in neurology. Studying pathologic changes of retinal blood vessels may be useful for understanding the etiology of various cerebrovascular conditions; hence, ocular fundus photography can be potentially translated into clinical practice. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Molecular genetic analysis of patients with sporadic and X-linked infantile nystagmus

PubMed Central

Zhao, Hui; Huang, Xiu-Feng; Zheng, Zhi-Li; Deng, Wen-Li; Lei, Xin-Lan; Xing, Dong-Jun; Ye, Liang; Xu, Su-Zhong; Chen, Jie; Zhang, Fang; Yu, Xin-Ping; Jin, Zi-Bing

2016-01-01

Objectives Infantile nystagmus (IN) is a genetically heterogeneous condition characterised by involuntary rhythmic oscillations of the eyes accompanied by different degrees of vision impairment. Two genes have been identified as mainly causing IN: FRMD7 and GPR143. The aim of our study was to identify the genetic basis of both sporadic IN and X-linked IN. Design Prospective analysis. Patients Twenty Chinese patients, including 15 sporadic IN cases and 5 from X-linked IN families, were recruited and underwent molecular genetic analysis. We first performed PCR-based DNA sequencing of the entire coding region and the splice junctions of the FRMD7 and GPR143 genes in participants. Mutational analysis and co-segregation confirmation were then performed. Setting All clinical examinations and genetic experiments were performed in the Eye Hospital of Wenzhou Medical University. Results Two mutations in the FRMD7 gene, including one novel nonsense mutation (c.1090C>T, p.Q364X) and one reported missense mutation (c.781C>G, p.R261G), were identified in two of the five (40%) X-linked IN families. However, none of putative mutations were identified in FRMD7 or GPR143 in any of the sporadic cases. Conclusions The results suggest that mutations in FRMD7 appeared to be the major genetic cause of X-linked IN, but not of sporadic IN. Our findings provide further insights into FRMD7 mutations, which could be helpful for future genetic diagnosis and genetic counselling of Chinese patients with nystagmus. PMID:27036142

X-linked intellectual disability update 2017.

PubMed

Neri, Giovanni; Schwartz, Charles E; Lubs, Herbert A; Stevenson, Roger E

2018-04-25

The X-chromosome comprises only about 5% of the human genome but accounts for about 15% of the genes currently known to be associated with intellectual disability. The early progress in identifying the X-linked intellectual disability (XLID)-associated genes through linkage analysis and candidate gene sequencing has been accelerated with the use of high-throughput technologies. In the 10 years since the last update, the number of genes associated with XLID has increased by 96% from 72 to 141 and duplications of all 141 XLID genes have been described, primarily through the application of high-resolution microarrays and next generation sequencing. The progress in identifying genetic and genomic alterations associated with XLID has not been matched with insights that improve the clinician's ability to form differential diagnoses, that bring into view the possibility of curative therapies for patients, or that inform scientists of the impact of the genetic alterations on cell organization and function. © 2018 Wiley Periodicals, Inc.

A family study of congenital X linked sideroblastic anaemia.

PubMed Central

Holmes, J; May, A; Geddes, D; Jacobs, A

1990-01-01

We report on the cytogenetic findings in a family study of pyridoxine responsive, X linked sideroblastic anaemia. An increase in the number of X chromosomes was observed in a small proportion of metaphases prepared from five female members, but these findings did not strictly correlate with the carrier status of the condition. No consistent cytogenetic abnormality could be identified or associated with this rare familial condition. The diagnosis and counselling of carriers of this condition is discussed. Images PMID:2308152

Use of topical dorzolamide for patients with X-linked juvenile retinoschisis: case report.

PubMed

Bastos, André Luís Carvalho de Moura; Freitas, Bruno de Paula; Villas Boas, Oscar; Ramiro, Alexandre Campelo

2008-01-01

X-linked juvenile retinoschisis (XLRS) is a recessively inherited vitreoretinal degeneration characterized by macular pathology and splitting of the neuroretinal layers that is associated with alterations in the XLRS1 gene. There have been no therapeutic interventions known to be effective for patients with X-linked juvenile retinoschisis, but some studies are trying to determine the importance of dorzolamide for the treatment of foveal lesions in this disease. The authors, using optical coherence tomography, describe findings in a patient with X-linked juvenile retinoschisis, before and after a topical use of dorzolamide. Besides the improvement in his visual acuity, further studies are required to elucidate the real prevalence of nonresponse to dorzolamide and the frequency with which there may be a recurrence of foveal cystic changes during continued treatment.

Ocular changes with oxaliplatin.

PubMed

O'Dea, Denise; Handy, Catherine M; Wexler, Ann

2006-04-01

Ocular toxicity, although uncommon, can occur with many chemotherapeutic agents. Platinum compounds have been documented to produce a variety of ocular side effects, and reports have been made of ocular toxicity with oxaliplatin. This article reports on four patients who experienced ocular symptoms while receiving oxaliplatin. The symptoms included tunnel vision and visual loss with postural changes. One patient had objective findings that included papilledema. All of the changes were reversible. Oxaliplatin will continue to be used widely, so clinicians treating patients with it must be alert for unusual toxicities such as those described in this article.

Lamellar macular hole in X linked retinoschisis

PubMed Central

Kumar, Vinod; Goel, Neha

2016-01-01

X linked retinoschisis (XLRS) is the most common juvenile onset retinal degeneration. The disorder leads to poor vision in old age. Complications, however, can lead to earlier loss of vision in this condition. This report describes two patients of XLRS, who had presented with poor vision because of having had a lamellar macular hole at a young age. Lamellar macular holes are rare and have never been reported to cause early onset poor vision in XLRS. PMID:27170611

Optical coherence tomography in the diagnosis of juvenile X-linked retinoschisis.

PubMed

Eriksson, Urban; Larsson, Eva; Holmström, Gerd

2004-04-01

To describe the value of optical coherence tomography (OCT) as a diagnostic tool in the diagnosis of X-linked retinoschisis. We report three boys aged between 8 and 17 years, diagnosed with X-linked retinoschisis. During investigations they were examined with OCT (Zeiss Humphrey OCT 1, upgraded version). Single scans of the central posterior pole and the region around the vascular arcades were obtained. Two of the boys underwent full-field ERG according to ISCEV standards. Genetic analysis was performed in all three boys, with sequencing of the XLRS gene. The OCT results revealed a pattern with a cleavage of the retina in two distinct planes, one deep (outer retina) and one superficial. This was very obvious in one patient and a similar but not as pronounced pattern was seen in the other two cases. The two layers were superficially connected with thin-walled, vertical palisades, separated by low reflective, cystoid spaces, confluent and most prominent in the foveal region. Full-field ERG and/or DNA analysis are well known methods used for diagnosis of X-linked juvenile retinoschisis. In this paper, we suggest that OCT can also be a helpful diagnostic tool.

X-linked cataract and Nance-Horan syndrome are allelic disorders.

PubMed

Coccia, Margherita; Brooks, Simon P; Webb, Tom R; Christodoulou, Katja; Wozniak, Izabella O; Murday, Victoria; Balicki, Martha; Yee, Harris A; Wangensteen, Teresia; Riise, Ruth; Saggar, Anand K; Park, Soo-Mi; Kanuga, Naheed; Francis, Peter J; Maher, Eamonn R; Moore, Anthony T; Russell-Eggitt, Isabelle M; Hardcastle, Alison J

2009-07-15

Nance-Horan syndrome (NHS) is an X-linked developmental disorder characterized by congenital cataract, dental anomalies, facial dysmorphism and, in some cases, mental retardation. Protein truncation mutations in a novel gene (NHS) have been identified in patients with this syndrome. We previously mapped X-linked congenital cataract (CXN) in one family to an interval on chromosome Xp22.13 which encompasses the NHS locus; however, no mutations were identified in the NHS gene. In this study, we show that NHS and X-linked cataract are allelic diseases. Two CXN families, which were negative for mutations in the NHS gene, were further analysed using array comparative genomic hybridization. CXN was found to be caused by novel copy number variations: a complex duplication-triplication re-arrangement and an intragenic deletion, predicted to result in altered transcriptional regulation of the NHS gene. Furthermore, we also describe the clinical and molecular analysis of seven families diagnosed with NHS, identifying four novel protein truncation mutations and a novel large deletion encompassing the majority of the NHS gene, all leading to no functional protein. We therefore show that different mechanisms, aberrant transcription of the NHS gene or no functional NHS protein, lead to different diseases. Our data highlight the importance of copy number variation and non-recurrent re-arrangements leading to different severity of disease and describe the potential mechanisms involved.

X-linked cataract and Nance-Horan syndrome are allelic disorders

PubMed Central

Coccia, Margherita; Brooks, Simon P.; Webb, Tom R.; Christodoulou, Katja; Wozniak, Izabella O.; Murday, Victoria; Balicki, Martha; Yee, Harris A.; Wangensteen, Teresia; Riise, Ruth; Saggar, Anand K.; Park, Soo-Mi; Kanuga, Naheed; Francis, Peter J.; Maher, Eamonn R.; Moore, Anthony T.; Russell-Eggitt, Isabelle M.; Hardcastle, Alison J.

2009-01-01

Nance-Horan syndrome (NHS) is an X-linked developmental disorder characterized by congenital cataract, dental anomalies, facial dysmorphism and, in some cases, mental retardation. Protein truncation mutations in a novel gene (NHS) have been identified in patients with this syndrome. We previously mapped X-linked congenital cataract (CXN) in one family to an interval on chromosome Xp22.13 which encompasses the NHS locus; however, no mutations were identified in the NHS gene. In this study, we show that NHS and X-linked cataract are allelic diseases. Two CXN families, which were negative for mutations in the NHS gene, were further analysed using array comparative genomic hybridization. CXN was found to be caused by novel copy number variations: a complex duplication–triplication re-arrangement and an intragenic deletion, predicted to result in altered transcriptional regulation of the NHS gene. Furthermore, we also describe the clinical and molecular analysis of seven families diagnosed with NHS, identifying four novel protein truncation mutations and a novel large deletion encompassing the majority of the NHS gene, all leading to no functional protein. We therefore show that different mechanisms, aberrant transcription of the NHS gene or no functional NHS protein, lead to different diseases. Our data highlight the importance of copy number variation and non-recurrent re-arrangements leading to different severity of disease and describe the potential mechanisms involved. PMID:19414485

Genetic localization and phenotypic expression of X-linked cataract (Xcat) in Mus musculus.

PubMed

Favor, J; Pretsch, W

1990-01-01

Linkage data relative to the markers tabby and glucose-6-phosphate dehydrogenase are presented to locate X-linked cataract (Xcat) in the distal portion of the mouse X-chromosome between jimpy and hypophosphatemia. The human X-linked cataract-dental syndrome, Nance-Horan Syndrome, also maps closely to human hypophosphatemia and would suggest homology between mouse Xcat and human Nance-Horan Syndrome genes. In hemizygous males and homozygous females penetrance is complete with only slight variation in the degree of expression. Phenotypic expression in Xcat heterozygous females ranges from totally clear to totally opaque lenses. The phenotypic expression between the two lenses of a heterozygous individual could also vary between totally clear and totally opaque lenses. However, a correlation in the degree of expression between the eyes of an individual was observed. A variegated pattern of lens opacity was evident in female heterozygotes. Based on these observations, the site of gene action for the Xcat locus is suggested to be endogenous to the lens cells and the precursor cell population of the lens is concluded to be small. The identification of an X-linked cataract locus is an important contribution to the estimate of the number of mutable loci resulting in cataract, an estimate required so that dominant cataract mutagenesis results may be expressed on a per locus basis. The Xcat mutation may be a useful marker for a distal region of the mouse X-chromosome which is relatively sparsely marked and the X-linked cataract mutation may be employed in gene expression and lens development studies.

Human X-Linked genes regionally mapped utilizing X-autosome translocations and somatic cell hybrids.

PubMed Central

Shows, T B; Brown, J A

1975-01-01

Human genes coding for hypoxanthine phosphoribosyltransferase (HPRT, EC 2.4.2.8; IMP:pyrophosphate phosphoribosyltransferase), glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49; D-glucose-6-phosphate:NADP+ 1-oxidoreductase), and phosphoglycerate kinase (PGK, EC 2.7.2.3; ATP:3-phospho-D-glycerate 1-phosphotransferase) have been assigned to specific regions on the long arm of the X chromosome by somatic cell gentic techniques. Gene assignment and linear order were determined by employing human somatic cells possessing an X/9 translocation or an X/22 translocation in man-mouse cell hybridization studies. The X/9 translocation involved the majority of the X long arm translocated to chromosome 9 and the X/22 translocation involved the distal half of the X long arm translocated to 22. In each case these rearrangements appeared to be reciprocal. Concordant segregation of X-linked enzymes and segments of the X chromosome generated by the translocations indicated assignment of the PGK gene to a proximal long arm region (q12-q22) and the HPRT and G6PD genes to the distal half (q22-qter) of the X long arm. Further evidence suggests a gene order on the X long arm of centromere-PGK-HPRT-G6PD. Images PMID:1056018

ELISA-Confirmed Bilateral Ocular Toxocariasis with Different Features.

PubMed

Lee, Tae Hee; Ji, Yong Sok; Lee, Seung Hyun

2015-08-01

To report a rare case of bilateral ocular toxocariasis with a different clinical presentation in each eye. A 56-year-old man presented with severe ocular pain and acute visual loss in the right eye (RE). His best-corrected visual acuity was hand motion in the RE and 20/30 in the left eye (LE). Slit-lamp examination showed a severe anterior chamber reaction in the RE and a moderate anterior chamber reaction in the LE. The fundus of the LE showed a posterior hemorrhagic granuloma with vascular sheathing whereas the fundus of the RE was not visible because of severe vitreous opacification. Blood laboratory testing disclosed hyperproduction of IgE but no eosinophilia. Serum enzyme-linked immunosorbent assay testing was positive for Toxocara canis IgG (1:38). Toxocara antibody was also detected in the aqueous humor from both eyes (RE, 1:321; LE, 1:254). The patient was treated with topical and oral steroids along with oral albendazole. Additionally, phacoemulsification, a therapeutic vitrectomy, and vitreous cultures were performed in the RE. During the vitrectomy, the fundus of the RE showed diffuse retinal vascular obstruction with sheathing. Toxocara antibodies were detected in the vitreous fluid from the RE (1:679). A laser barrier was placed around the granuloma in the LE. After 1 month of steroid therapy, a tapering schedule was started. At 6 months postoperatively, the fundi of both eyes were stable. The final best-corrected visual acuity was 8/20 in the RE and 20/20 in the LE. A rare case of bilateral ocular toxocariasis is reported with a different clinical presentation in each eye that was diagnosed using enzyme-linked immunosorbent assay analysis of intraocular fluids. Both eyes were successfully treated medically with a vitrectomy eventually being required in the RE.

Coal dust contiguity-induced changes in the concentration of TNF- and NF- B p65 on the ocular surface

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Z.Y.; Hong, J.; Liu, Z.Y.

2009-07-01

To observe the influence of coal dust on ocular surface of coal miners and rabbits with coal dust contiguity on expression TNF- and NF- Bp65 and dry eye occurrence. Expression TNF- and NF- Bp65 in ocular surface were determined. Results showed tear production, BUT and lysozyme decreased for coal miners and rabbits with coal dust contiguity. Coal dust exposure was linked to development of xerophthalmia, and induced a higher expression of NF- B p65 and TNF- perhaps as a mechanism to resist coal dust ocular surface injury.

Epidemiology of Ocular Toxoplasmosis in Three Community Surveys in the Central Region of Ghana, West Africa.

PubMed

Abu, Emmanuel Kwasi; Boampong, Johnson Nyarko; Amoabeng, Joseph Kwame; Ilechie, Alex A; Kyei, Samuel; Owusu-Ansah, Andrew; Boadi-Kusi, Samuel Bert; Amoani, Benjamin; Ayi, Irene

2016-01-01

To conduct the first ever population-based survey on ocular toxoplasmosis in the Central Region of Ghana. A cross-sectional population-based study was conducted in three randomly selected communities in the Central Region, Ghana. Visual acuity (VA) measurement, dilated fundus examination by indirect ophthalmoscopy and serology testing were performed on all participants. Ocular toxoplasmosis was diagnosed based on characteristic retinal lesions and supported by positive serologic testing using commercial enzyme-linked immunosorbent assay (ELISA) kits. A total of 390 subjects aged 10-100 years (mean age 47 years) were examined; 118 (30.3%) were male and 272 (69.7%) female. Ten subjects (6 females and 4 males) had toxoplasmic ocular lesions (prevalence 2.6%). Of these, two had bilateral lesions and eight had unilateral lesions. Subjects with toxoplasmic ocular lesions were older than those without lesions (p = 0.028). The development of ocular toxoplasmosis was not associated with rural dwelling, sex, keeping cats, or consumption of meat. The prevalence of ocular toxoplasmosis in our Ghanaian study population was lower than findings from Southern Brazil, where there is a similar prevalence of infection in the general population.

Lamellar macular hole in X linked retinoschisis.

PubMed

Kumar, Vinod; Goel, Neha

2016-05-11

X linked retinoschisis (XLRS) is the most common juvenile onset retinal degeneration. The disorder leads to poor vision in old age. Complications, however, can lead to earlier loss of vision in this condition. This report describes two patients of XLRS, who had presented with poor vision because of having had a lamellar macular hole at a young age. Lamellar macular holes are rare and have never been reported to cause early onset poor vision in XLRS. 2016 BMJ Publishing Group Ltd.

Ocular inflammatory effects of intravitreally-injected tumor necrosis factor.

PubMed Central

Rosenbaum, J. T.; Howes, E. L.; Rubin, R. M.; Samples, J. R.

1988-01-01

Many of the pathophysiologic effects of bacterial endotoxin have recently been attributed to a monokine, tumor necrosis factor (TNF). The rabbit eye is extremely sensitive to locally injected endotoxin. The authors have investigated the possible contribution of TNF to ocular inflammation in a rabbit model. The intravitreal injection of 10(5) to 5 X 10(5) units of recombinant human TNF produced a sustained disruption of the blood-aqueous barrier as manifested by elevated aqueous humor protein levels. In addition, 83% of rabbits receiving this dose of TNF developed hyperemia of limbal vessels and early neovascularization of the cornea. Many developed posterior synechiae (fibrous adhesions between the iris and the lens). TNF induced only a slight cellular response in the anterior chamber. Histologic studies confirmed the presence of new vessels and demonstrated a marked mononuclear infiltrate within and beneath the epithelium of the iris and ciliary body. Lower doses of TNF produced inconsistent results. Heating TNF completely destroyed its inflammatory effects. The time course of the ocular response to TNF and the quantity of recombinant protein needed to produce consistent effects were vastly different from effects observed with interleukin-1. For example, 24 hours after an intravitreal injection, 2.2 X 10(4) ng of TNF (5 X 10(5) units) produced significantly less protein extravasation and polymorphonuclear leukocyte infiltration than 4 ng of recombinant interleukin-1. Similarly, 24 hours after intravitreal injection, 1 ng of Escherichia coli endotoxin tended to be a more potent inflammatory stimulus than this quantity of TNF. These observations indicate that the ocular pathophysiologic effects of TNF can be readily distinguished from changes induced by either endotoxin or another endotoxin induced monokine, interleukin-1. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:3263050

A major X-linked locus affects kidney function in mice

PubMed Central

Leduc, Magalie S.; Savage, Holly S.; Stearns, Timothy M.; Cario, Clinton L.; Walsh, Kenneth A.; Paigen, Beverly; Berndt, Annerose

2012-01-01

Chronic kidney disease is a common disease with increasing prevalence in the western population. One common reason for chronic kidney failure is diabetic nephropathy. Diabetic nephropathy and hyperglycemia are characteristics of the mouse inbred strain KK/HlJ, which is predominantly used as a model for metabolic syndrome due to its inherited glucose intolerance and insulin resistance. We used KK/HlJ, an albuminuria-sensitive strain, and C57BL/6J, an albuminuria-resistant strain, to perform a quantitative trait locus (QTL) cross to identify the genetic basis for chronic kidney failure. Albumin-creatinine-ratio (ACR) was measured in 130 F2 male offspring. One significant QTL was identified on chromosome (Chr) X and four suggestive QTLs were found on Chrs 6, 7, 12, and 13. Narrowing of the QTL region was focused on the X-linked QTL and performed by incorporating genotype and expression analyses for genes located in the region. From the 485 genes identified in the X-linked QTL region, a few candidate genes were identified using a combination of bioinformatic evidence based on genomic comparison of the parental strains and known function in urine homeostasis. Finally, this study demonstrates the significance of the X chromosome in the genetic determination of albuminuria. PMID:23011808

The tear film and ocular mucins.

PubMed

Davidson, Harriet J; Kuonen, Vanessa J

2004-01-01

Abstract The trilaminar tear film, composed of the lipid, aqueous and mucin layers, has many functions including defending the ocular surface. The aqueous layer has several soluble antimicrobial factors that protect the ocular surface. Ocular mucins have recently been studied with regard to their role in the defense of the eye as well as in dry eye syndromes. To date, 15 mucin genes have been identified, and six of these mucin genes are localized to or secreted by ocular glands or epithelia. Understanding the production, secretion and function of ocular mucins will aid in the treatment of dry eye syndromes and ocular surface microbial infections.

Refined genetic mapping of X-linked Charcot-Marie-Tooth neuropathy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fain, P.R.; Barker, D.F.; Chance, P.F.

1994-02-01

Genetic linkage studies were conducted in four multigenerational families with X-linked Charcot-Marie-Tooth disease (CMTX), using 12 highly polymorphic short-tandem-repeat markers for the pericentromeric region of the X Chromosome. Pairwise linkage analysis with individual markers confirmed tight linkage of CMTX to the pericentromeric region in each family. Multipoint analyses strongly support the order DXS337-CMTX-DXS441-(DXS56, PGK1). 38 refs., 2 figs., 1 tab.

X-linked Alport syndrome caused by splicing mutations in COL4A5.

PubMed

Nozu, Kandai; Vorechovsky, Igor; Kaito, Hiroshi; Fu, Xue Jun; Nakanishi, Koichi; Hashimura, Yuya; Hashimoto, Fusako; Kamei, Koichi; Ito, Shuichi; Kaku, Yoshitsugu; Imasawa, Toshiyuki; Ushijima, Katsumi; Shimizu, Junya; Makita, Yoshio; Konomoto, Takao; Yoshikawa, Norishige; Iijima, Kazumoto

2014-11-07

X-linked Alport syndrome is caused by mutations in the COL4A5 gene. Although many COL4A5 mutations have been detected, the mutation detection rate has been unsatisfactory. Some men with X-linked Alport syndrome show a relatively mild phenotype, but molecular basis investigations have rarely been conducted to clarify the underlying mechanism. In total, 152 patients with X-linked Alport syndrome who were suspected of having Alport syndrome through clinical and pathologic investigations and referred to the hospital for mutational analysis between January of 2006 and January of 2013 were genetically diagnosed. Among those patients, 22 patients had suspected splice site mutations. Transcripts are routinely examined when suspected splice site mutations for abnormal transcripts are detected; 11 of them showed expected exon skipping, but others showed aberrant splicing patterns. The mutation detection strategy had two steps: (1) genomic DNA analysis using PCR and direct sequencing and (2) mRNA analysis using RT-PCR to detect RNA processing abnormalities. Six splicing consensus site mutations resulting in aberrant splicing patterns, one exonic mutation leading to exon skipping, and four deep intronic mutations producing cryptic splice site activation were identified. Interestingly, one case produced a cryptic splice site with a single nucleotide substitution in the deep intron that led to intronic exonization containing a stop codon; however, the patient showed a clearly milder phenotype for X-linked Alport syndrome in men with a truncating mutation. mRNA extracted from the kidney showed both normal and abnormal transcripts, with the normal transcript resulting in the milder phenotype. This novel mechanism leads to mild clinical characteristics. This report highlights the importance of analyzing transcripts to enhance the mutation detection rate and provides insight into genotype-phenotype correlations. This approach can clarify the cause of atypically mild phenotypes in X-linked

Three-dimensional confocal microscopy of the living cornea and ocular lens

NASA Astrophysics Data System (ADS)

Masters, Barry R.

1991-07-01

The three-dimensional reconstruction of the optic zone of the cornea and the ocular crystalline lens has been accomplished using confocal microscopy and volume rendering computer techniques. A laser scanning confocal microscope was used in the reflected light mode to obtain the two-dimensional images from the cornea and the ocular lens of a freshly enucleated rabbit eye. The light source was an argon ion laser with a 488 nm wavelength. The microscope objective was a Leitz X25, NA 0.6 water immersion lens. The 400 micron thick cornea was optically sectioned into 133 three micron sections. The semi-transparent cornea and the in-situ ocular lens was visualized as high resolution, high contrast two-dimensional images. The structures observed in the cornea include: superficial epithelial cells and their nuclei, basal epithelial cells and their 'beaded' cell borders, basal lamina, nerve plexus, nerve fibers, nuclei of stromal keratocytes, and endothelial cells. The structures observed in the in- situ ocular lens include: lens capsule, lens epithelial cells, and individual lens fibers. The three-dimensional data sets of the cornea and the ocular lens were reconstructed in the computer using volume rendering techniques. Stereo pairs were also created of the two- dimensional ocular images for visualization. The stack of two-dimensional images was reconstructed into a three-dimensional object using volume rendering techniques. This demonstration of the three-dimensional visualization of the intact, enucleated eye provides an important step toward quantitative three-dimensional morphometry of the eye. The important aspects of three-dimensional reconstruction are discussed.

X linked exudative vitreoretinopathy: clinical features and genetic linkage analysis.

PubMed

Fullwood, P; Jones, J; Bundey, S; Dudgeon, J; Fielder, A R; Kilpatrick, M W

1993-03-01

A four generation family in which familial exudative vitreoretinopathy is inherited as an X linked condition is described. Essentially the condition is one of abnormal vascularisation and signs at birth are those of a retinopathy superficially resembling retinopathy of prematurity, retinal folds, or, in advanced cases, enophthalmos or even phthisis. Prognosis depends on the progression of the retinal changes. The family members, including seven affected males and five obligate carrier females, have been types for 20 DNA markers, and linkage analysis suggests a gene locus either at Xq21.3 or at Xp11. As the latter region includes the locus for the gene for Norrie disease, it is possible that this and X linked vitreoretinopathy are allelic. We can further speculate that the differences in severity of the clinical manifestations are dependent only upon the timing of the insult.

CAPILLARY NETWORK ALTERATIONS IN X-LINKED RETINOSCHISIS IMAGED ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PubMed

Romano, Francesco; Arrigo, Alessandro; Chʼng, Soon Wai; Battaglia Parodi, Maurizio; Manitto, Maria Pia; Martina, Elisabetta; Bandello, Francesco; Stanga, Paulo E

2018-06-05

To assess foveal and parafoveal vasculature at the superficial capillary plexus, deep capillary plexus, and choriocapillaris of patients with X-linked retinoschisis by means of optical coherence tomography angiography. Six patients with X-linked retinoschisis (12 eyes) and seven healthy controls (14 eyes) were recruited and underwent complete ophthalmologic examination, including best-corrected visual acuity, dilated fundoscopy, and 3 × 3-mm optical coherence tomography angiography macular scans (DRI OCT Triton; Topcon Corp). After segmentation and quality review, optical coherence tomography angiography slabs were imported into ImageJ 1.50 (NIH; Bethesda) and digitally binarized. Quantification of vessel density was performed after foveal avascular zone area measurement and exclusion. Patients were additionally divided into "responders" and "nonresponders" to dorzolamide therapy. Foveal avascular zone area resulted markedly enlarged at the deep capillary plexus (P < 0.001), particularly in nonresponders. Moreover, patients disclosed a significant deep capillary plexus rarefaction, when compared with controls (P: 0.04); however, a subanalysis revealed that this damage was limited to the fovea (P: 0.006). Finally, the enlargement of foveal avascular zone area positively correlated with a decline in best-corrected visual acuity (P: 0.01). Prominent foveal vascular impairment is detectable in the deep capillary plexus of patients with X-linked retinoschisis. Our results correlate with functional outcomes, suggesting a possible vascular role in X-linked retinoschisis clinical manifestations.

A COMPREHENSIVE INSIGHT ON OCULAR PHARMACOKINETICS

PubMed Central

Agrahari, Vibhuti; Mandal, Abhirup; Agrahari, Vivek; Trinh, Hoang My; Joseph, Mary; Ray, Animikh; Hadji, Hicheme; Mitra, Ranjana; Pal, Dhananjay; Mitra, Ashim K.

2017-01-01

Eye is a distinctive organ with protective anatomy and physiology. Several pharmacokinetics compartment model of ocular drug delivery has been developed for describing the absorption, distribution and elimination of ocular drugs in the eye. Determining pharmacokinetics parameters in ocular tissues is a major challenge because of the complex anatomy and dynamic physiological barrier of the eye. In this review, pharmacokinetics of these compartments exploring different drugs, delivery systems and routes of administration are discussed including factors affecting intraocular bioavailability. Factors such as pre-corneal fluid drainage, drug binding to tear proteins, systemic drug absorption, corneal factors, melanin binding, drug metabolism renders ocular delivery challenging and elaborated in this manuscript. Several compartment models are discussed those are developed in ocular drug delivery to study the pharmacokinetics parameters. There are several transporters present in both anterior and posterior segments of the eye which play a significant role in ocular pharmacokinetics and summarized briefly. Moreover, several ocular pharmacokinetics animal models and relevant studies are reviewed and discussed in addition to the pharmacokinetics of various ocular formulations. PMID:27798766

Clinical Characteristics of Pediatric Patients with Ocular Toxocariasis in China.

PubMed

Liu, Yalu; Zhang, Qi; Li, Jing; Ji, Xunda; Xu, Yu; Zhao, Peiquan

2016-01-01

The aim of the study was to analyze the clinical characteristics of pediatric patients with ocular toxocariasis. Ocular toxocariasis was diagnosed and treated in 46 children from Shanghai and surrounding provinces. The diagnosis of ocular toxocariasis was confirmed immunologically by performing an enzyme-linked immunosorbent assay on serum and/or intraocular fluid. All pediatric patients and their guardians completed a questionnaire concerning their cases and living habits. The mean age of onset was 6 ± 3 years. Most children (85%) resided in rural areas, and 91% of the children had contact with adult dogs or puppies. At the first visit, visual acuity (VA) was <20/200 in 36 cases, and we detected peripheral granuloma in 36 patients. In our study, the most common signs were vitritis, vitreous strands, and tractional retinal detachment. The Optomap 200Tx device detected granuloma with an 85% sensitivity, which is much higher than that of other techniques. We treated 40 cases (87%) with topical corticosteroids, while 28 patients (61%) were treated with systemic corticosteroids. Only 18 children (39%) required surgical intervention. All patients were examined and treated by the same ophthalmologists. Preschool children in China are more often affected by toxocariasis compared with other age groups. The most common signs included unilateral granuloma and ocular inflammation. In our study, clinical manifestations were severe and complicated. At the first visit, VA was <20/200 in most patients. Ocular toxocariasis was diagnosed on the basis of clinical signs and symptoms; the diagnosis was confirmed by immunological testing. Techniques using the Optomap 200Tx device can facilitate the early detection and lead to better visual prognosis. © 2016 S. Karger AG, Basel.

Functional anatomy and immunological interactions of ocular surface and adnexa.

PubMed

Paulsen, Friedrich

2008-01-01

This chapter gives an overview about the structures and physiology of the ocular surface and its adnexa and focuses in a second part on the possible meaning of eye-associated lymphoid tissue (EALT) in a context with the development of dry eye. Sections deal with (1) anatomy of the ocular surface, lacrimal gland, eyelid and nasolacrimal ducts. (2) The meaning and importance of the lacrimal functional unit and the function of the mucosal innate immune system are briefly summarized. (3) Finally, the occurrence and the possible function of EALT is discussed with regard to tolerance induction and dry eye. The epithelial surface of the eye and its specialized glandular infoldings produce the components of the tear film, which include water, protective antimicrobials, cytokines, lipids as well as mucins and trefoil factor family (TFF) peptides. Antimicrobials, mucins and TFF peptides perform a number of essential functions which, collectively, provide protection of the ocular surface. Their production changes in cases of dry eye. The development of EALT is a common feature frequently occurring in symptomatically normal conjunctiva and nasolacrimal ducts. The production of antimicrobials, mucins and TFF peptides can be linked with cell signaling, tear film rheology, and antimicrobial defense at the ocular surface. Changes in the production of such peptides and proteins in cases of dry eye support the assumption that these peptides and proteins are involved in the pathophysiological events that occur at the ocular surface and lacrimal apparatus. Whether special types of bacteria, viruses, or other factors, e.g., immune deviation, are responsible for the development of EALT in humans requires further investigation in prospective and experimental studies.

X-linked Acrogigantism (X-LAG) Syndrome: Clinical Profile and Therapeutic Responses

PubMed Central

Beckers, Albert; Lodish, Maya Beth; Trivellin, Giampaolo; Rostomyan, Liliya; Lee, Misu; Faucz, Fabio R; Yuan, Bo; Choong, Catherine S; Caberg, Jean-Hubert; Verrua, Elisa; Naves, Luciana Ansaneli; Cheetham, Tim D; Young, Jacques; Lysy, Philippe A; Petrossians, Patrick; Cotterill, Andrew; Shah, Nalini Samir; Metzger, Daniel; Castermans, Emilie; Ambrosio, Maria Rosaria; Villa, Chiara; Strebkova, Natalia; Mazerkina, Nadia; Gaillard, Stéphan; Barra, Gustavo Barcelos; Casulari, Luis Augusto; Neggers, Sebastian J.; Salvatori, Roberto; Jaffrain-Rea, Marie-Lise; Zacharin, Margaret; Santamaria, Beatriz Lecumberri; Zacharieva, Sabina; Lim, Ee Mun; Mantovani, Giovanna; Zatelli, Maria Chaira; Collins, Michael T; Bonneville, Jean-François; Quezado, Martha; Chittiboina, Prashant; Oldfield, Edward H.; Bours, Vincent; Liu, Pengfei; De Herder, Wouter; Pellegata, Natalia; Lupski, James R.; Daly, Adrian F.; Stratakis, Constantine A.

2015-01-01

X-linked acro-gigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplications on chromosome Xq26.3, encompassing the gene GPR101, which is highly upregulated in pituitary tumors. We conducted this study to explore the clinical, radiological and hormonal phenotype and responses to therapy in patients with X-LAG syndrome. The study included 18 patients (13 sporadic) with X-LAG and a microduplication in chromosome Xq26.3. All sporadic cases had unique duplications and the inheritance pattern in 2 families was dominant with all Xq26.3 duplication carriers being affected. Patients began to grow rapidly as early as 2–3 months of age (median 12 months). At diagnosis (median delay 27 months), patients had a median height and weight SDS score of >+3.9 SDS. Apart from the increased overall body size, the children had acromegalic symptoms including acral enlargement and facial coarsening. More than a third of cases had increased appetite. Patients had marked hypersecretion of GH/IGF-1 and prolactin, usually due to a pituitary macroadenoma or hyperplasia. Primary neurosurgical control was achieved with extensive anterior pituitary resection but postoperative hypopituitarism was frequent. Control with somatostatin analogs was not readily achieved despite moderate to high somatostatin receptor subtype-2 expression in tumor tissue. Postoperative adjuvant pegvisomant achieved control of IGF-1 all 5 cases in which it was employed. X-LAG is a new infant-onset gigantism syndrome that has a severe clinical phenotype leading to challenging disease management. PMID:25712922

Gene therapy for ocular diseases.

PubMed

Liu, Melissa M; Tuo, Jingsheng; Chan, Chi-Chao

2011-05-01

The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. After nearly two decades of ocular gene therapy research, preliminary successes are now being reported in phase 1 clinical trials for the treatment of Leber congenital amaurosis. This review describes current developments and future prospects for ocular gene therapy. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus- and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma. These methodological advancements are critical for the implementation of additional gene-based therapies for human ocular diseases in the near future.

Genetic Analysis of a Kindred With X-linked Mental Handicap and Retinitis Pigmentosa

PubMed Central

Aldred, M. A.; Dry, K. L.; Knight-Jones, E. B.; Hardwick, L. J.; Teague, P. W.; Lester, D. H.; Brown, J.; Spowart, G.; Carothers, A. D.; Raeburn, J. A.; Bird, A. C.; Fielder, A. R.; Wright, A. F.

1994-01-01

A kindred is described in which X-linked nonspecific mental handicap segregates together with retinitis pigmentosa. Carrier females are mentally normal but may show signs of the X-linked retinitis pigmentosa carrier state and become symptomatic in their later years. Analysis of polymorphic DNA markers at nine loci on the short arm of the X chromosome shows that no crossing-over occurs between the disease and Xp11 markers DXS255, TIMP, DXS426, MAOA, and DXS228. The 90% confidence limits show that the locus is in the Xp21-q21 region. Haplotype analysis is consistent with the causal gene being located proximal to the Xp21 loci DXS538 and 5'-dystrophin on the short arm of the X chromosome. The posterior probability of linkage to the RP2 region of the X chromosome short arm (Xp11.4-p11.23) is .727, suggesting the possibility of a contiguous-gene-deletion syndrome. No cytogenetic abnormality has been identified. PMID:7977353

A heterozygous mutation in RPGR associated with X-linked retinitis pigmentosa in a patient with Turner syndrome mosaicism (45,X/46,XX).

PubMed

Zhou, Qi; Yao, Fengxia; Wang, Feng; Li, Hui; Chen, Rui; Sui, Ruifang

2018-01-01

Turner syndrome with retinitis pigmentosa (RP) is rare, with only three cases reported based on clinical examination alone. We summarized the 4-year follow-up and molecular findings in a 28-year-old patient with Turner syndrome and the typical features of short stature and neck webbing, who also had X-linked RP. Her main complaints were night blindness and progressive loss of vision since the age of 9 years. Ophthalmologic examination, optical coherent tomographic imaging, and visual electrophysiology tests showed classic manifestations of RP. The karyotype of peripheral blood showed mosaicism (45,X [72%]/46,XX[28%]). A novel heterozygous frameshift mutation (c.2403_2406delAGAG, p.T801fsX812) in the RP GTPase regulator (RPGR) gene was detected using next generation sequencing and validated by Sanger sequencing. We believe that this is the first report of X-linked RP in a patient with Turner syndrome associated with mosaicism, and an RPGR heterozygous mutation. We hypothesize that X-linked RP in this woman is not related to Turner syndrome, but may be a manifestation of the lack of a normal paternal X chromosome with intact but mutated RPGR. © 2017 Wiley Periodicals, Inc.

Foveomacular schisis in juvenile X-linked retinoschisis: an optical coherence tomography study.

PubMed

Yu, Jia; Ni, Yingqin; Keane, Pearse A; Jiang, Chunhui; Wang, Wenji; Xu, Gezhi

2010-06-01

To explore the structural features of juvenile X-linked retinoschisis using spectral-domain optical coherence tomography (OCT). Retrospective, observational cross-sectional study. Eighteen male patients (34 eyes) who were diagnosed with juvenile X-linked retinoschisis at the Eye & ENT Hospital of Fudan University over an 18-month period were included. Their OCT images, which were obtained using spectral-domain OCT (Cirrus HD-OCT; Carl Zeiss Meditec), were analyzed. The anatomic location of the schisis cavity in juvenile X-linked retinoschisis was characterized by direct inspection of OCT images. On OCT, the schisis cavity was visible at the fovea in all 34 eyes, and it was associated with increased retinal thickness. Schisis was present at the retinal nerve fiber layer in 4 eyes, at the inner nuclear layer in 29 eyes, and at the outer nuclear layer/outer plexiform layer in 22 eyes. In most cases, widespread foveomacular schisis was detected using OCT; however, in 9 eyes (6 patients), the schisis was confined to the fovea. Schisis of the inner nuclear layer and outer nuclear layer/outer plexiform layer almost always involved the foveal center, but retinal nerve fiber layer schisis was seen only in the parafoveal area. Despite conventional wisdom, in patients with X-linked retinoschisis, the schisis cavity can occur in a number of different layers of the neurosensory retina (retinal nerve fiber layer, inner nuclear layer, and outer nuclear layer/outer plexiform layer). In addition, different forms of schisis may affect different locations in the macula (foveal vs parafoveal), and, in most eyes, the schisis involves the entire foveomacular region. Copyright 2010 Elsevier Inc. All rights reserved.

Cicatricial changes in ocular pemphigus

PubMed Central

Chirinos-Saldaña, P; Zuñiga-Gonzalez, I; Hernandez-Camarena, J C; Navas, A; Ramirez-Luquin, T; Robles-Contreras, A; Jimenez-Martinez, M C; Ramirez-Miranda, A; Bautista-de Lucio, V M; Graue-Hernandez, E O

2014-01-01

Purpose To describe the clinical characteristics of ocular involvement in patients with pemphigus at an ophthalmological referral center. Methods A retrospective review was conducted on patients with the immunopathological diagnosis of pemphigus examined between 1 January 2000 and 1 April 2010. Uncorrected distance visual acuity (UDVA), best corrected distance visual acuity (BCVA), ocular symptoms, and ocular surface inflammatory and scarring changes were assessed. Results A total of 15 patients were identified, with a mean age of 68.27±14.35 years, and 80% (n=12) were female. Extraocular involvement was reported in one patient. All of the eyes showed cicatricial changes in the conjunctiva. In all, 6 eyes (20%) were classified as stage I; 12 eyes (40%) as stage II; 10 eyes (33%) as stage III; and 2 eyes (7%) as stage IV. A statistically significant association was found between BCVA and the severity of ocular involvement. The mean BCVA logMAR was 1.66 (20/914), with a range from logMAR 0 (20/20) to logMAR 4 (NLP). Other ocular diseases were found in 8 (53.3%), systemic diseases in 10 (66.7%), and the use of pemphigus-inducing drugs in 10 patients (66.7%). Conclusions The present report represents the largest series of ocular involvement in pemphigus confirmed by immunopathology. The clinical manifestations varied from conjunctival hyperemia to corneal scarring and perforation. There was a strong association between scarring changes and low BCVA. Ocular and systemic diseases as well as the use of pemphigus-inducing drugs may predispose to ocular cicatricial changes observed in this series. PMID:24480839

Ocular drug delivery systems: An overview

PubMed Central

Patel, Ashaben; Cholkar, Kishore; Agrahari, Vibhuti; Mitra, Ashim K

2014-01-01

The major challenge faced by today’s pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration, especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal, dynamic and static ocular barriers. Also, therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades, ocular drug delivery research acceleratedly advanced towards developing a novel, safe and patient compliant formulation and drug delivery devices/techniques, which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also, it includes development of conventional topical formulations such as suspensions, emulsions and ointments. Various nanoformulations have also been introduced for anterior segment ocular drug delivery. On the other hand, for posterior ocular delivery, research has been immensely focused towards development of drug releasing devices and nanoformulations for treating chronic vitreoretinal diseases. These novel devices and/or formulations may help to surpass ocular barriers and associated side effects with conventional topical drops. Also, these novel devices and/or formulations are easy to formulate, no/negligibly irritating, possess high precorneal residence time, sustain the drug release, and enhance ocular bioavailability of therapeutics. An update of current research advancement in ocular drug delivery necessitates and helps drug delivery scientists to modulate their think process and develop novel and safe drug delivery strategies. Current review intends to summarize the existing conventional formulations for ocular delivery and their advancements followed by current nanotechnology based formulation developments

Ocular drug delivery systems: An overview.

PubMed

Patel, Ashaben; Cholkar, Kishore; Agrahari, Vibhuti; Mitra, Ashim K

The major challenge faced by today's pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration, especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal, dynamic and static ocular barriers. Also, therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades, ocular drug delivery research acceleratedly advanced towards developing a novel, safe and patient compliant formulation and drug delivery devices/techniques, which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also, it includes development of conventional topical formulations such as suspensions, emulsions and ointments. Various nanoformulations have also been introduced for anterior segment ocular drug delivery. On the other hand, for posterior ocular delivery, research has been immensely focused towards development of drug releasing devices and nanoformulations for treating chronic vitreoretinal diseases. These novel devices and/or formulations may help to surpass ocular barriers and associated side effects with conventional topical drops. Also, these novel devices and/or formulations are easy to formulate, no/negligibly irritating, possess high precorneal residence time, sustain the drug release, and enhance ocular bioavailability of therapeutics. An update of current research advancement in ocular drug delivery necessitates and helps drug delivery scientists to modulate their think process and develop novel and safe drug delivery strategies. Current review intends to summarize the existing conventional formulations for ocular delivery and their advancements followed by current nanotechnology based formulation developments

A Novel Mutation in the XLRS1 Gene in a Korean Family with X-linked Retinoschisis

PubMed Central

Jwa, Nam Soo; Kim, Sung Soo; Lee, Sung Chul; Kwon, Oh Woong

2006-01-01

Purpose To report a novel missense mutation in the XLRS1 gene in a Korean family with X-linked retinoschisis. Methods Observation case report of a family with a proband with X-linked retinoschisis underwent complete ophthalmologic examination. Genomic DNA was excluded from the family's blood and all exons of the XLRS1 gene were amplified by polymerase chain reaction and analyzed using a direct sequencing method. Results A novel Leu103Phe missense mutation was identified. Conclusions A novel Leu103Phe mutation is an additional missense mutation which is responsible for the pathogenesis of X-linked retinoschisis. PMID:16768192

Ocular emergencies presenting to Menelik II Hospital.

PubMed

Negussie, Dereje; Bejiga, Abebe

2011-01-01

Ocular conditions such as trauma, painful red eye of any cause, painless sudden visual loss and others are commonly seen as ocular emergencies, and can lead to ocular morbidity and visual loss. To determine types and causes of ocular emergencies seen at Menelik II hospital. A cross-sectional study was conducted from April to October, 2007. Consecutive patients who presented with ocular emergencies at any time of the day were prospectively evaluated and registered on a formatted questionnaire. Evaluation of the patients included history of presenting illness, visual acuity testing intraocular pressure measurement on non-perforated and non-infected eyes, and complete eye examination in order to arrive at the diagnosis. A total of 26,400 patients attended Menelik II hospital during the study period. Of these, 758 (3%) were persons with an ocular emergency. The majority of patients (n=551; 72.7%) were male, with a male to female ratio of 2.7:1. The age group of 16 to 30 years was the most affected (47.9%), followed by those aged 15 years or younger (27.3%). Ocular trauma and ocular infections accounted for 75.6% and 13.1% of cases, respectively. Of the total ocular emergencies, open globe injuries constituted 171 (22.6%), corneal foreign bodies and abrasion 125 (16.5%), and open adnexal injuries 119 (15.7%). Metal and wood were the commonest work-related causes of ocular injuries in adults, with both together accounting for 60% of all ocular injuries. Children, on the other hand, sustained ocular injury while playing with others in 128 (22.3%) of cases. This study was able to provide a more complete picture to improve understanding of the nature and circumstances of ocular emergencies in Ethiopia. Ocular emergencies were dominated by ocular trauma, particularly affecting males and working-age adults. Public education and use of protective safety measures are recommended to alleviate the problem.

[Application of Ocular Trauma Score in Mechanical Ocular Injury in Forensic Medicine].

PubMed

Xiang, Jian; Guo, Zhao-ming; Wang, Xu; Yu, Li-li; Liu, Hui

2015-10-01

To evaluate the application value for the prognosis of mechanical ocular injury cases using ocular trauma score (OTS). Four hundred and eleven cases of mechanical ocular trauma were retrospectively reviewed. Of the 449 eyes, there were 317 closed globe injury and 132 open globe injury. OTS variables included numerical values as initial visual acuity, rupture, endophthalmitis, perforat- ing or penetrating injury, retinal detachment and relative afferent pupillary block. The differences be- tween the distribution of the final visual acuity and the probability of standard final visual acuity were compared to analyze the correlation between OTS category and final visual acuity. The different types of ocular trauma were compared. Compared with the distribution of final visual acuity in standard OTS score, the ratio in OTS-3 category was statistically different in present study, and no differences were found in other categories. Final visual acuity showed a great linear correlation with OTS category (r = 0.71) and total score (r = 0.73). Compared with closed globe injury, open globe injury was generally associated with lower total score and poorer prognosis. Rupture injury had poorer prognosis compared with penetrating injury. The use of OTS for the patients with ocular trauma can provide re- liable information for the evaluation of prognosis in forensic medicine.

X-linked nephrogenic diabetes insipidus mutations in North America and the Hopewell hypothesis.

PubMed Central

Bichet, D G; Arthus, M F; Lonergan, M; Hendy, G N; Paradis, A J; Fujiwara, T M; Morgan, K; Gregory, M C; Rosenthal, W; Didwania, A

1993-01-01

In X-linked nephrogenic diabetes insipidus (NDI) the urine of male patients is not concentrated after the administration of the antidiuretic hormone arginine-vasopressin. This disease is due to mutations in the V2 receptor gene that maps to chromosome region Xq28. In 1969, Bode and Crawford suggested that most NDI patients in North America shared common ancestors of Ulster Scot immigrants who arrived in Halifax in 1761 on the ship Hopewell. A link between this family and a large Utah kindred was also suggested. DNA was obtained from 17 affected male patients from the "Hopewell" kindred and from four additional families from Nova Scotia and New Brunswick who shared the same Xq28 NDI haplotype. The Utah kindred and two families (Q2, Q3) from Quebec were also studied. The "Hopewell" mutation, W71X, is a single base substitution (G-->A) that changes codon 71 from TGG (tryptophan) to TGA (stop). The W71X mutation was found in affected members of the Hopewell and of the four satellite families. The W71X mutation is the cause of X-linked NDI for the largest number of related male patients living in North America. Other families (Utah, Q2 and Q3) that are historically and ethnically unrelated bear other mutations in the V2 receptor gene. Images PMID:8104196

Burosumab Therapy in Children with X-Linked Hypophosphatemia.

PubMed

Carpenter, Thomas O; Whyte, Michael P; Imel, Erik A; Boot, Annemieke M; Högler, Wolfgang; Linglart, Agnès; Padidela, Raja; Van't Hoff, William; Mao, Meng; Chen, Chao-Yin; Skrinar, Alison; Kakkis, Emil; San Martin, Javier; Portale, Anthony A

2018-05-24

X-linked hypophosphatemia is characterized by increased secretion of fibroblast growth factor 23 (FGF-23), which leads to hypophosphatemia and consequently rickets, osteomalacia, and skeletal deformities. We investigated burosumab, a monoclonal antibody that targets FGF-23, in patients with X-linked hypophosphatemia. In an open-label, phase 2 trial, we randomly assigned 52 children with X-linked hypophosphatemia, in a 1:1 ratio, to receive subcutaneous burosumab either every 2 weeks or every 4 weeks; the dose was adjusted to achieve a serum phosphorus level at the low end of the normal range. The primary end point was the change from baseline to weeks 40 and 64 in the Thacher rickets severity total score (ranging from 0 to 10, with higher scores indicating greater disease severity). In addition, the Radiographic Global Impression of Change was used to evaluate rachitic changes from baseline to week 40 and to week 64. Additional end points were changes in pharmacodynamic markers, linear growth, physical ability, and patient-reported outcomes and the incidence of adverse events. The mean Thacher rickets severity total score decreased from 1.9 at baseline to 0.8 at week 40 with every-2-week dosing and from 1.7 at baseline to 1.1 at week 40 with every-4-week dosing (P<0.001 for both comparisons); these improvements persisted at week 64. The mean serum phosphorus level increased after the first dose in both groups, and more than half the patients in both groups had levels within the normal range (3.2 to 6.1 mg per deciliter [1.0 to 2.0 mmol per liter]) by week 6. Stable serum phosphorus levels were maintained through week 64 with every-2-week dosing. Renal tubular phosphate reabsorption increased from baseline in both groups, with an overall mean increase of 0.98 mg per deciliter (0.32 mmol per liter). The mean dose of burosumab at week 40 was 0.98 mg per kilogram of body weight with every-2-week dosing and 1.50 mg per kilogram with every-4-week dosing. Across both

The forensic value of X-linked markers in mixed-male DNA analysis.

PubMed

He, HaiJun; Zha, Lagabaiyila; Cai, JinHong; Huang, Jian

2018-05-04

Autosomal genetic markers and Y chromosome markers have been widely applied in analysis of mixed stains at crime scenes by forensic scientists. However, true genotype combinations are often difficult to distinguish using autosomal markers when similar amounts of DNA are contributed by multiple donors. In addition, specific individuals cannot be determined by Y chromosomal markers because male relatives share the same Y chromosome. X-linked markers, possessing characteristics somewhere intermediate between autosomes and the Y chromosome, are less universally applied in criminal casework. In this paper, X markers are proposed to apply to male mixtures because their true genes can be more easily and accurately recognized than the decision of the genotypes of AS markers. In this study, an actual two-man mixed stain from a forensic case file and simulated male-mixed DNA were examined simultaneously with the X markers and autosomal markers. Finally, the actual mixture was separated successfully by the X markers, although it was unresolved by AS-STRs, and the separation ratio of the simulated mixture was much higher using Chr X tools than with AS methods. We believe X-linked markers provide significant advantages in individual discrimination of male mixtures that should be further applied to forensic work.

Ocular pulsation correlates with ocular tension: the choroid as piston for an aqueous pump?

PubMed

Phillips, C I; Tsukahara, S; Hosaka, O; Adams, W

1992-01-01

In 26 random out-patients, including 13 treated glaucoma patients and ocular hypertensives, the higher the ocular tension, the greater the pulse amplitude, by Alcon pneumotonometry, at a statistically significant level. In a single untreated hypertensive, when 2-hourly pneumotonometry was done for 24 h, the correlation was similar and significant. The higher the diastolic blood pressure, the higher the ocular pulsation, also significantly. Pulsation is suggested to be a pump, the choroid being the piston, contributing (1) to an increase in the outflow of aqueous humour and (2) to a homeostatic mechanism contributing to normalization of the intra-ocular pressure, wherein pulsation increases or decreases, as the intraocular pressure increases or decreases, respectively.

Variation in the X-Linked EFHC2 Gene Is Associated with Social Cognitive Abilities in Males

PubMed Central

Startin, Carla M.; Fiorentini, Chiara; de Haan, Michelle; Skuse, David H.

2015-01-01

Females outperform males on many social cognitive tasks. X-linked genes may contribute to this sex difference. Males possess one X chromosome, while females possess two X chromosomes. Functional variations in X-linked genes are therefore likely to impact more on males than females. Previous studies of X-monosomic women with Turner syndrome suggest a genetic association with facial fear recognition abilities at Xp11.3, specifically at a single nucleotide polymorphism (SNP rs7055196) within the EFHC2 gene. Based on a strong hypothesis, we investigated an association between variation at SNP rs7055196 and facial fear recognition and theory of mind abilities in males. As predicted, males possessing the G allele had significantly poorer facial fear detection accuracy and theory of mind abilities than males possessing the A allele (with SNP variant accounting for up to 4.6% of variance). Variation in the X-linked EFHC2 gene at SNP rs7055196 is therefore associated with social cognitive abilities in males. PMID:26107779

A family with X-linked optic atrophy linked to the OPA2 locus Xp11.4-Xp11.2.

PubMed

Katz, Bradley J; Zhao, Yu; Warner, Judith E A; Tong, Zongzhong; Yang, Zhenglin; Zhang, Kang

2006-10-15

Autosomal dominant optic atrophy (ADOA) is the most common inherited optic atrophy. Clinical features of ADOA include a slowly progressive bilateral loss of visual acuity, constriction of peripheral visual fields, central scotomas, and color vision abnormalities. Although ADOA is the most commonly inherited optic atrophy, autosomal recessive, X-linked, mitochondrial, and sporadic forms have also been reported. Four families with X-linked optic atrophy (XLOA) were previously described. One family was subsequently linked to Xp11.4-Xp11.2 (OPA2). This investigation studied one multi-generation family with an apparently X-linked form of optic atrophy and compared their clinical characteristics with those of the previously described families, and determined whether this family was linked to the same genetic locus. Fifteen individuals in a three-generation Idaho family underwent complete eye examination, color vision testing, automated perimetry, and fundus photography. Polymorphic markers were used to genotype each individual and to determine linkage. Visual acuities ranged from 20/30 to 20/100. All affected subjects had significant optic nerve pallor. Obligate female carriers were clinically unaffected. Preliminary linkage analysis (LOD score = 1.8) revealed that the disease gene localized to the OPA2 locus on Xp11.4-Xp11.2. Four forms of inherited optic neuropathy, ADOA, autosomal recessive optic atrophy (Costeff Syndrome), Leber hereditary optic neuropathy, and Charcot-Marie-Tooth disease with optic atrophy, are associated with mitochondrial dysfunction. Future identification of the XLOA gene will reveal whether this form of optic atrophy is also associated with a mitochondrial defect. Identification of the XLOA gene will advance our understanding of the inherited optic neuropathies and perhaps suggest treatments for these diseases. An improved understanding of inherited optic neuropathies may in turn advance our understanding of acquired optic nerve diseases, such

Application of carrier testing to genetic counseling for X-linked agammaglobulinemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Allen, R.C.; Nachtman, R.G.; Belmont, J.W.

Bruton X-linked agammaglobulinemia (XLA) is a phenotypically recessive genetic disorder of B lymphocyte development. Female carriers of XLA, although asymptomatic, have a characteristic B cell lineage-specific skewing of the pattern of X inactivation. Skewing apparently results from defective growth and maturation of B cell precursors bearing a mutant active X chromosome. In this study, carrier status was tested in 58 women from 22 families referred with a history of agammaglobulinemia. Primary carrier analysis to examine patterns of X inactivation in CD19[sup +] peripheral blood cells (B lymphocytes) was conducted using quantitative PCR at the androgen-receptor locus. Obligate carriers of XLAmore » demonstrated >95% skewing of X inactivation in peripheral blood CD19[sup +] cells but not in CD19[sup [minus

Ocular trauma.

PubMed

Cassen, J H

1997-10-01

A review of the literature was conducted to investigate recent articles about ocular trauma. Eye injuries may be divided into blunt and penetrating types. Males are more affected than females. Evaluation of eye injuries should start with visual acuity and continue with prompt referral to an ophthalmologist as indicated. Medlines search/American Academy of Ophthalmology. Ocular trauma is a frequent reason for emergency room visits. Most injuries stem from sports, recreation, military, occupational, or automotive. Patient education is highly recommended, as well as prevention by use of protective polycarbonate eyewear.

Meiotic drive impacts expression and evolution of x-linked genes in stalk-eyed flies.

PubMed

Reinhardt, Josephine A; Brand, Cara L; Paczolt, Kimberly A; Johns, Philip M; Baker, Richard H; Wilkinson, Gerald S

2014-01-01

Although sex chromosome meiotic drive has been observed in a variety of species for over 50 years, the genes causing drive are only known in a few cases, and none of these cases cause distorted sex-ratios in nature. In stalk-eyed flies (Teleopsis dalmanni), driving X chromosomes are commonly found at frequencies approaching 30% in the wild, but the genetic basis of drive has remained elusive due to reduced recombination between driving and non-driving X chromosomes. Here, we used RNAseq to identify transcripts that are differentially expressed between males carrying either a driving X (XSR) or a standard X chromosome (XST), and found hundreds of these, the majority of which are X-linked. Drive-associated transcripts show increased levels of sequence divergence (dN/dS) compared to a control set, and are predominantly expressed either in testes or in the gonads of both sexes. Finally, we confirmed that XSR and XST are highly divergent by estimating sequence differentiation between the RNAseq pools. We found that X-linked transcripts were often strongly differentiated (whereas most autosomal transcripts were not), supporting the presence of a relatively large region of recombination suppression on XSR presumably caused by one or more inversions. We have identified a group of genes that are good candidates for further study into the causes and consequences of sex-chromosome drive, and demonstrated that meiotic drive has had a profound effect on sequence evolution and gene expression of X-linked genes in this species.

Design and Validation of a New MLPA-Based Assay for the Detection of RS1 Gene Deletions and Application in a Large Family with X-Linked Juvenile Retinoschisis.

PubMed

Nicoletti, Annalisa; Ziccardi, Lucia; Maltese, Paolo Enrico; Benedetti, Sabrina; Palumbo, Orazio; Rendina, Michelina; D'Agruma, Leonardo; Falsini, Benedetto; Wang, Xinjing; Bertelli, Matteo

2017-02-01

X-linked juvenile retinoschisis (XLRS) is a severe ocular disorder that can evolve to blindness. More than 200 different disease-causing mutations have been reported in the RS1 gene and approximately 10% of these are deletions. Since transmission is X-linked, males are always affected and females are usually carriers. The identification of female carriers is always important and poses a technical challenge. Therefore, we sought to develop a multiplex ligation dependent probe amplification (MLPA)-based method to identify deletions or duplications in this gene. We then used our assay to study a large XLRS family. We designed six probes specific for each RS1 exon and then optimized and validated our method using control samples with known gene deletions. In the XLRS family, RS1 gene copy number variation was assessed by "home-made" MLPA analysis and by single nucleotide polymorphism (SNP) array analysis using the CytoScan HD Array. Direct sequencing was used for deletion breakpoint mapping. Our assay detected all deletions in control samples. All affected males of the family were positive for a deletion of exon 2 of the RS1 gene (RS1:NM_000330:c.53-?_78+?del). Carrier females were also identified. Our method is easily replicated, reliable, and inexpensive and allows female carriers to be detected. This is the first report of deep characterization of a whole exon deletion in the RS1 gene.

Design and Validation of a New MLPA-Based Assay for the Detection of RS1 Gene Deletions and Application in a Large Family with X-Linked Juvenile Retinoschisis

PubMed Central

Nicoletti, Annalisa; Ziccardi, Lucia; Benedetti, Sabrina; Palumbo, Orazio; Rendina, Michelina; D'Agruma, Leonardo; Falsini, Benedetto; Wang, Xinjing; Bertelli, Matteo

2017-01-01

Aims: X-linked juvenile retinoschisis (XLRS) is a severe ocular disorder that can evolve to blindness. More than 200 different disease-causing mutations have been reported in the RS1 gene and approximately 10% of these are deletions. Since transmission is X-linked, males are always affected and females are usually carriers. The identification of female carriers is always important and poses a technical challenge. Therefore, we sought to develop a multiplex ligation dependent probe amplification (MLPA)-based method to identify deletions or duplications in this gene. We then used our assay to study a large XLRS family. Methods: We designed six probes specific for each RS1 exon and then optimized and validated our method using control samples with known gene deletions. In the XLRS family, RS1 gene copy number variation was assessed by “home-made” MLPA analysis and by single nucleotide polymorphism (SNP) array analysis using the CytoScan HD Array. Direct sequencing was used for deletion breakpoint mapping. Results: Our assay detected all deletions in control samples. All affected males of the family were positive for a deletion of exon 2 of the RS1 gene (RS1:NM_000330:c.53-?_78+?del). Carrier females were also identified. Conclusion: Our method is easily replicated, reliable, and inexpensive and allows female carriers to be detected. This is the first report of deep characterization of a whole exon deletion in the RS1 gene. PMID:27997221

Epidemiology of ocular toxoplasmosis.

PubMed

Petersen, Eskild; Kijlstra, Aize; Stanford, Miles

2012-04-01

Retinal infection with Toxoplasma gondii is the most important cause of posterior uveitis, whereby prevalence and incidence of ocular symptoms after infection depend on socio-economic factors and the circulating parasite genotypes. Ocular toxoplasmosis is more common in South America, Central America, and the Caribbean and parts of tropical Africa as compared to Europe and Northern America, and is quite rare in China. Ocular disease in South America is more severe than in other continents due to the presence of extremely virulent genotypes of the parasite. Drinking untreated water is considered the major source of Toxoplasma infection in developing countries, whereas in the Western world the consumption of raw or undercooked meat (products) is the most important cause. Since acquired infection with T. gondii is currently a more important cause of ocular toxoplasmosis compared to congenital infection, prevention should be directed not only toward pregnant women but toward the general population.

[Descending ocular myopathy].

PubMed

de Freitas, M R; Nascimento, O J

1975-06-01

The case of a 23 years old female patient, with primary involvement of the extraocular and faringeal muscles without familiar history is reported. Electromyographic and muscular biopsy studies proved the myogenic nature of the process. A clinical comparison between the ocular myopathy and the descending ocular myopathy is made, the authors thinking that both of them would be variants of the same muscle disease.

Ocular sarcoidosis: new diagnostic modalities and treatment.

PubMed

Yang, Sung J; Salek, Sherveen; Rosenbaum, James T

2017-09-01

Ocular involvement in sarcoidosis is present in up to 80% of patients and is frequently manifested before diagnosis of the underlying systemic disease. Considering the therapeutic consequences, early diagnosis of the underlying disease is advantageous in patients presenting with ocular inflammation. There are several ocular findings suggestive of underlying sarcoidosis, such as granulomatous keratic precipitates, iris nodules, cells in the vitreous humor known as snowballs and snowbanks, and retinal periphlebitis. High suspicion is crucial for the diagnosis of sarcoidosis. This review on ocular sarcoidosis will mainly focus on new diagnostic and treatment modalities. Recent studies found possible new diagnostic indicators for the diagnosis of ocular sarcoidosis which include not only serum profiles but also vitreous sample analysis. Ophthalmologic imaging techniques have improved to investigate the ocular structure in detail. Results from recent uveitis clinical trials have included sarcoidosis as an underlying cause and have reported positive results. The diagnosis of ocular sarcoidosis can be challenging in some cases. High suspicion is important to diagnose ocular sarcoidosis with various laboratory and ophthalmic tools. There are many possible options for the treatment of ocular sarcoidosis including various biologic agents.

Ocular Manifestations of Acquired Immunodeficiency Syndrome.

PubMed

Kim, Young Shin; Sun, Hae Jung; Kim, Tae Hyong; Kang, Kui Dong; Lee, Sung Jin

2015-08-01

To investigate the patterns and risk factors of the ocular manifestations of acquired immunodeficiency syndrome (AIDS) and their correlation with CD4+ count in the era of highly active antiretroviral therapy (HAART). This retrospective study examined 127 AIDS patients who presented to Soonchunhyang University Hospital. Data were collected from patient interviews, clinical examinations, and laboratory investigations. Ophthalmologic examinations included the best-corrected visual acuity, intraocular pressure, anterior segment and adnexal examination, and dilated fundus examination. Of the 127 patients with AIDS, 118 were on HAART and 9 were not. The mean CD4+ count was 266.7 ± 209.1 cells/µL. There were ocular manifestations in 61 patients (48.0%). The incidence of anterior segment manifestations was higher than posterior segment manifestations at 28.3% and 19.7%, respectively. The mean CD4+ count was significantly (p < 0.05) lower in the patients with posterior versus anterior segment ocular manifestations. The most common ocular manifestation was retinal microvasculopathy (15.0%), followed by keratoconjunctivitis sicca (14.2%), conjunctival microvasculopathy (9.4%), cytomegalovirus retinitis (3.1%), herpes zoster ophthalmicus (2.4%), and blepharitis (1.6%). Retinal microvasculopathy and cytomegalovirus retinitis were common in patients with CD4+ counts <200 cells/µL, while keratoconjunctivitis sicca and conjunctival microvasculopathy were common in patients with CD4+ counts of 200 to 499 cells/µL. There was a significant (p < 0.05) association between ocular manifestation and CD4+ count or age. The introduction of HAART has changed the landscape of ocular presentations in patients with AIDS. In this study, anterior segment and external ocular manifestations occurred more frequently than posterior segment manifestations. Also, the mean CD4+ count was significantly lower in patients with posterior segment ocular manifestations versus anterior segment ocular

Alport syndrome, mental retardation, midface hypoplasia, and elliptocytosis: a new X linked contiguous gene deletion syndrome?

PubMed Central

Jonsson, J J; Renieri, A; Gallagher, P G; Kashtan, C E; Cherniske, E M; Bruttini, M; Piccini, M; Vitelli, F; Ballabio, A; Pober, B R

1998-01-01

We describe a family with four members, a mother, two sons, and a daughter, who show clinical features consistent with X linked Alport syndrome. The two males presented with additional features including mental retardation, dysmorphic facies with marked midface hypoplasia, and elliptocytosis. The elliptocytosis was not associated with any detectable abnormalities in red cell membrane proteins; red cell membrane stability and rigidity was normal on ektacytometry. Molecular characterisation suggests a submicroscopic X chromosome deletion encompassing the entire COL4A5 gene. We propose that the additional abnormalities found in the affected males of this family are attributable to deletion or disruption of X linked recessive genes adjacent to the COL4A5 gene and that this constellation of findings may represent a new X linked contiguous gene deletion syndrome. Images PMID:9598718

Non-syndromic posterior lenticonus a cause of childhood cataract: evidence for X-linked inheritance.

PubMed

Russell-Eggitt, I M

2000-12-01

When an X-linked pedigree of posterior lenticonus with cataract was identified further evidence for X-linked inheritance of this condition was sought. Forty-three cases of posterior lenticonus were identified from a database of 354 children with cataract. Two children with the X-linked syndromes of Lowe and Nance-Horan and 3 children with Fanconi syndrome have been excluded from further analysis. None of the children was deaf. None of the non-syndromic cases had microcornea. There were 38 cases of non-syndromic posterior lenticonus (approximately 11%). There were 15 children from 13 pedigrees and 23 apparently sporadic cases. Of the 106 cases on the database with unilateral cataract 15 had posterior lenticonus (approximately 14%). Eleven of 13 pedigrees were compatible with X-linked inheritance or autosomal dominant inheritance with variable expression. However, in 2 pedigrees there was father to son transmission. Posterior lenticonus is a common cause of unilateral infantile cataract, but is thought to be a rare cause of bilateral cataracts. This study suggests that posterior lenticonus is responsible for a significant proportion of childhood cataracts (approximately 14% of unilateral and approximately 9% of bilateral cases). Posterior lenticonus is generally thought to occur as a sporadic condition. This study demonstrates that there is a family history of early-onset cataract in a significant number of bilateral cases (approximately 58%).

Accommodation-based liquid crystal adaptive optics system for large ocular aberration correction.

PubMed

Mu, Quanquan; Cao, Zhaoliang; Li, Chao; Jiang, Baoguang; Hu, Lifa; Xuan, Li

2008-12-15

According to ocular aberration property and liquid crystal (LC) corrector characteristics, we calculated the minimum pixel demand of the LC corrector used for compensating large ocular aberrations. Then, an accommodation based optical configuration was introduced to reduce the demand. Based on this an adaptive optics (AO) retinal imaging system was built. Subjects with different defocus and astigmatism were tested to prove this. For myopia lower than 5D it performs well. When myopia is as large as 8D the accommodation error increased to nearly 3D, which requires the LC corrector to have 667 x 667 pixels to get a well-corrected image.

Genetic analysis of a kindred with X-linked mental handicap and retinitis pigmentosa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aldred, M.A.; Dry, K.L.; Hardwick, L.J.

1994-11-01

A kindred is described in which X-linked nonspecific mental handicap segregates together with retinitis pigmentosa. Carrier females are mentally normal but may show signs of the X-linked retinitis pigmentosa carrier state and become symptomatic in their later years. Analysis of polymorphic DNA markers at nine loci on the short arm of the X chromosome shows that no crossing-over occurs between the disease and Xp11 markers DXS255, TIMP, DXS426, MAOA, and DXS228. The 90% confidence limits show that the locus is in the Xp21-q21 region. Haplotype analysis is consistent with the causal gene being located proximal to the Xp21 loci DXS538more » and 5{prime}-dystrophin on the short arm of the X chromosome. The posterior probability of linkage to the RP2 region of the X chromosome short arm (Xp11.4-p11.23) is .727, suggesting the possibility of a contiguous-gene-deletion syndrome. No cytogenetic abnormality has been identified. 33 refs., 2 figs., 2 tabs.« less

Ocular findings in patients with the Hermansky-Pudlak syndrome (types 1 and 3)

PubMed Central

Jardón, Javier; Izquierdo, Natalio J.; Renta, Jessica Y; García-Rodríguez, Omar; Cadilla, Carmen L.

2014-01-01

Purpose To describe and compare ocular findings in patients with Hermansky-Pudlak syndrome (HPS) type 1 and 3. Methods This is a retrospective case series of 64 patients with HPS from 1999 to 2009 evaluated at an outpatient private ophthalmologic clinic. Patients underwent genetic analysis of selected albinism (Tyrosine and P gene) and HPS genes (HPS-1 and HPS-3) by screening for common mutations and exon sequencing with DNA screening. Descriptive and a non-parametric statistical analysis were done. Results Nearly 70% of the patients were homozygous for common Puerto Rican mutations leading to the HPS1 gene (16-BP DUP, 53.6%), while 30% had the 3904-BP DEL HPS3 gene mutation. BCVA was poorer in patients with type 1 HPS than in patients with type 3 HPS (p<0.001), esotropia was more common among type 1 HPS (p<0.018), while exotropia was more common among patients with type 3 HPS. Total iris transillumination was more common in patients with type 1 HPS and minimal iris transillumination in patients with type 3 HPS (p<0.001). The maculae were translucent in patients with type 1 HPS, while patients with type 3 HPS had opaque maculae (p<0.001). Conclusions Patients with type 1 HPS had poorer BCVA, increase incidence of esotropia, lighter iris and macular appearance. In contrast, patients with type 3 HPS 3 had more exotropia. In addition, to our knowledge this is the largest series type 3 HPS ever reported. PMID:24766090

Ocular Findings in Patients with the Hermansky-Pudlak Syndrome (Types 1 and 3).

PubMed

Jardón, Javier; Izquierdo, Natalio J; Renta, Jessica Y; García-Rodríguez, Omar; Cadilla, Carmen L

2016-01-01

To describe and compare ocular findings in patients with Hermansky-Pudlak syndrome (HPS) type 1 and 3. This is a retrospective case series of 64 patients with HPS from 1999 to 2009 evaluated at an outpatient private ophthalmologic clinic. Patients underwent genetic analysis of selected albinism (Tyrosine and P gene) and HPS genes (HPS-1 and HPS-3) by screening for common mutations and exon sequencing with DNA screening. Descriptive and non-parametric statistical analyses were carried out. Nearly 70% of the patients were homozygous for common Puerto Rican mutations leading to the HPS1 gene (16-BP DUP, 53.6%), while 30% had the 3904-BP DEL HPS3 gene mutation. Best corrected visual acuity (BCVA) was poorer in patients with type 1 HPS than in patients with type 3 HPS (p < 0.001), esotropia was more common among type 1 HPS patients (p < 0.018), while exotropia was more common among patients with type 3 HPS. Total iris transillumination was more common in patients with type 1 HPS and minimal iris transillumination in patients with type 3 HPS (p < 0.001). The maculae were translucent in patients with type 1 HPS, while patients with type 3 HPS had opaque maculae (p < 0.001). Patients with type 1 HPS had poorer BCVA, increased incidence of esotropia, lighter iris and macular appearance. In contrast, patients with type 3 HPS had more exotropia. In addition, to our knowledge this is the largest series type 3 HPS ever reported.

[Prenatal diagnosis of X-linked anhidrotic ectodermal dysplasia with X-chromosome inversion].

PubMed

Shi, Hui-juan; Fang, Qun; Wang, Lian-tang

2005-07-13

To investigate the possibility of prenatal diagnosis of the fetal suspected to be affected by anhidrotic ectodermal dysplasia (EDA) in a family with X-linked EDA so as to provide a basis for prenatal diagnosis and genetic counseling of this disorder. Pedigree analysis and genetic counseling were performed in a family after a proband was diagnosed with EDA. The peripheral blood samples were collected from the proband, a 12-year-old boy, his mother, and his 2 aunts, one being pregnant, to undergo chromosome karyotype analysis. The fetus Puncture of umbilical vein was performed to collect the blood of fetus for chromosome examination. Induced abortion was conducted due to the diagnosis of the fetus with EDA. Autopsy, immunohistochemistry of the skin tissues of face, breast, epigastrium, and thigh, and X-ray photography of the lower jawbone were made. Pericentric inversion occurring at one of the X-chromosome [inv (x) (p22q13)] was found in the proband and his nephew (the fetus), both patients, and his mother and his second aunt (the pregnant woman), both carriers. Autopsy of the fetus showed epidermis dysplasia and deficiency of hair follicle and sebaceous gland. Immunohistochemistry showed that epithelial membrane antigen and cytokeratin were negatively expressed in the fetal skin tissues. Pedigree analysis and genetic counseling for the family members of EDA patients and prenatal and postpartum examination for the fetus help diagnose EDA.

A Complex Genetic Basis to X-Linked Hybrid Male Sterility Between Two Species of House Mice

PubMed Central

Good, Jeffrey M.; Dean, Matthew D.; Nachman, Michael W.

2008-01-01

The X chromosome plays a central role in the evolution of reproductive isolation, but few studies have examined the genetic basis of X-linked incompatibilities during the early stages of speciation. We report the results of a large experiment focused on the reciprocal introgression of the X chromosome between two species of house mice, Mus musculus and M. domesticus. Introgression of the M. musculus X chromosome into a wild-derived M. domesticus genetic background produced male-limited sterility, qualitatively consistent with previous experiments using classic inbred strains to represent M. domesticus. The genetic basis of sterility involved a minimum of four X-linked factors. The phenotypic effects of major sterility QTL were largely additive and resulted in complete sterility when combined. No sterility factors were uncovered on the M. domesticus X chromosome. Overall, these results revealed a complex and asymmetric genetic basis to X-linked hybrid male sterility during the early stages of speciation in mice. Combined with data from previous studies, we identify one relatively narrow interval on the M. musculus X chromosome involved in hybrid male sterility. Only a handful of spermatogenic genes are within this region, including one of the most rapidly evolving genes on the mouse X chromosome. PMID:18689897

A complex genetic basis to X-linked hybrid male sterility between two species of house mice.

PubMed

Good, Jeffrey M; Dean, Matthew D; Nachman, Michael W

2008-08-01

The X chromosome plays a central role in the evolution of reproductive isolation, but few studies have examined the genetic basis of X-linked incompatibilities during the early stages of speciation. We report the results of a large experiment focused on the reciprocal introgression of the X chromosome between two species of house mice, Mus musculus and M. domesticus. Introgression of the M. musculus X chromosome into a wild-derived M. domesticus genetic background produced male-limited sterility, qualitatively consistent with previous experiments using classic inbred strains to represent M. domesticus. The genetic basis of sterility involved a minimum of four X-linked factors. The phenotypic effects of major sterility QTL were largely additive and resulted in complete sterility when combined. No sterility factors were uncovered on the M. domesticus X chromosome. Overall, these results revealed a complex and asymmetric genetic basis to X-linked hybrid male sterility during the early stages of speciation in mice. Combined with data from previous studies, we identify one relatively narrow interval on the M. musculus X chromosome involved in hybrid male sterility. Only a handful of spermatogenic genes are within this region, including one of the most rapidly evolving genes on the mouse X chromosome.

Localisation of the gene for X-linked reticulate pigmentary disorder with systemic manifestations (PDR), previously known as X-linked cutaneous amyloidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gedeon, A.K.; Mulley, J.C.; Kozman, H.

1994-08-01

X-linked reticulate pigmentary disorder (PDR), previously reported as X-linked cutaneous amyloidosis (MIM No. 301220), is characterized by brown pigmentation of the skin which follows the lines of Blaschko in females but appears as reticulate sheets in males. Males may suffer severe gastrointestinal disorders in infancy with failure to thrive and early death. Nowadays symptomatic treatment allows survival and other manifestations may appear such as corneal dystrophy with severe photophobia or chronic respiratory disease. Amyloid deposition in the skin may be no more than an age-dependent secondary manifestation. The PDR gene was localized by linkage analysis to Xp21-p22. The background geneticmore » map is Xpter-DXS996-22.5-DXS207-3.3-DXS999-3.3-DXS365-14.2-DXS989-4.1-3`DMD-3.5-DXS997-1.0-STR44-9.3-DYSI-2.3-DXS1068-11.0-DXS228 with distances between markers given in cM. Recombinants detected with DXS999 distally and DXS228 proximally, define the limits to the localization. Linkage was found with several markers within this interval. Peak lod scores of 3.21 at {theta} = 0.0 were obtained between PDR and DXS989 and between PDR and 5`DYSI within the dystrophin locus. 29 refs., 2 figs., 2 tabs.« less

[Ocular surface system integrity].

PubMed

Safonova, T N; Pateyuk, L S

2015-01-01

The interplay of different structures belonging to either the anterior segment of the eye or its accessory visual apparatus, which all share common embryological, anatomical, functional, and physiological features, is discussed. Explanation of such terms, as ocular surface, lacrimal functional unit, and ocular surface system, is provided.

Advances in the treatment of ocular dryness associated with Sjögren׳s syndrome.

PubMed

Ciurtin, Coziana; Ostas, Anca; Cojocaru, Viorica M; Walsh, Stephen B; Isenberg, David A

2015-12-01

Sjögren´s syndrome (SS) is an autoimmune rheumatic disease that is characterised by decreased exocrine gland function and frequent ocular symptoms associated with eye dryness. Significantly, dry eyes can lead to corneal abrasions, infection, ulceration, chronic scarring and, in severe cases, perforation. The available conventional therapies have limited efficacy and there are no biologic therapies licensed for use in SS patients. A literature search of PubMed (MEDLINE) and EMBASE electronic data bases was performed covering the period from January 1994 to September 2014. Evidence was graded in categories I-IV and a treatment algorithm, comprising first line, second line and rescue therapies for ocular dryness associated with SS was proposed. It is based on the current evidence of efficacy of different therapies and explores their link with the pathogenesis of ocular dryness associated with SS. Recent developments in the understanding of the pathogenesis of SS provided evidence that the ocular dryness is associated with pathologic infiltration and dysfunction of the lacrimal glands and changes in the tear composition, together with abnormalities involving the neurosecreting circuits. There is good evidence for the efficacy of topical artificial tears, antiinflammatories and Cyclosporine, and oral Pilocarpine and Cevimeline in controlling the symptoms of ocular dryness associated with SS. Conventional DMARDs are not particularly effective in addressing the symptoms of ocular dryness associated with SS, despite being commonly prescribed for other SS manifestations. Emerging evidence suggests that B cell and co-stimulatory targeted therapy may play a role in the future. Copyright © 2015 Elsevier Inc. All rights reserved.

MicroRNAs and intellectual disability (ID) in Down syndrome, X-linked ID, and Fragile X syndrome

PubMed Central

Siew, Wei-Hong; Tan, Kai-Leng; Babaei, Maryam Abbaspour; Cheah, Pike-See; Ling, King-Hwa

2013-01-01

Intellectual disability (ID) is one of the many features manifested in various genetic syndromes leading to deficits in cognitive function among affected individuals. ID is a feature affected by polygenes and multiple environmental factors. It leads to a broad spectrum of affected clinical and behavioral characteristics among patients. Until now, the causative mechanism of ID is unknown and the progression of the condition is poorly understood. Advancement in technology and research had identified various genetic abnormalities and defects as the potential cause of ID. However, the link between these abnormalities with ID is remained inconclusive and the roles of many newly discovered genetic components such as non-coding RNAs have not been thoroughly investigated. In this review, we aim to consolidate and assimilate the latest development and findings on a class of small non-coding RNAs known as microRNAs (miRNAs) involvement in ID development and progression with special focus on Down syndrome (DS) and X-linked ID (XLID) [including Fragile X syndrome (FXS)]. PMID:23596395

Challenging ocular image recognition

NASA Astrophysics Data System (ADS)

Pauca, V. Paúl; Forkin, Michael; Xu, Xiao; Plemmons, Robert; Ross, Arun A.

2011-06-01

Ocular recognition is a new area of biometric investigation targeted at overcoming the limitations of iris recognition performance in the presence of non-ideal data. There are several advantages for increasing the area beyond the iris, yet there are also key issues that must be addressed such as size of the ocular region, factors affecting performance, and appropriate corpora to study these factors in isolation. In this paper, we explore and identify some of these issues with the goal of better defining parameters for ocular recognition. An empirical study is performed where iris recognition methods are contrasted with texture and point operators on existing iris and face datasets. The experimental results show a dramatic recognition performance gain when additional features are considered in the presence of poor quality iris data, offering strong evidence for extending interest beyond the iris. The experiments also highlight the need for the direct collection of additional ocular imagery.

Increases in Ocular Syphilis-North Carolina, 2014-2015.

PubMed

Oliver, Sara E; Cope, Anna Barry; Rinsky, Jessica L; Williams, Charnetta; Liu, Gui; Hawks, Stephanie; Peterman, Thomas A; Markowitz, Lauri; Fleischauer, Aaron T; Samoff, Erika

2017-10-30

Ocular syphilis is an inflammatory eye disease due to Treponema pallidum infection. In the United States, syphilis rates have increased since 2000; clusters of ocular syphilis were reported in 2015. We investigated ocular syphilis in North Carolina to describe the epidemiology and clinical course of disease. We reviewed syphilis cases reported to North Carolina during 2014-2015 and abstracted information from health department interviews for cases with ocular symptoms and no other defined etiology. To assess duration and severity of ocular symptoms, we also reviewed medical records and conducted structured interviews. We compared the prevalence of ocular manifestations among reported syphilis cases by demographic and clinical characteristics. Among 4232 syphilis patients, 63 (1.5%) had ocular syphilis: 21 in 2014 and 42 in 2015, a 100% increase. Total syphilis cases increased 35% through 2015. No patient with ocular syphilis named another ocular syphilis patient as a sex partner. Patients presented in all syphilis stages; 24 (38%) were diagnosed in primary or secondary syphilis. Ocular manifestations were more prevalent among syphilis patients who were male, aged ≥40 years, white, and infected with human immunodeficiency virus. No risk behaviors were associated with ocular syphilis. Among 39 interviewed patients, 34 (87%) reported reduced vision during infection; 12 (31%) reported residual visual symptoms posttreatment. In North Carolina, ocular syphilis increased from 2014 to 2015 and may be due to increased recognition of ocular manifestations, or a true increase in ocular syphilis. Many ocular syphilis patients experienced vision loss; however, most improved posttreatment. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Ocular complications of boxing

PubMed Central

Bianco, M; Vaiano, A; Colella, F; Coccimiglio, F; Moscetti, M; Palmieri, V; Focosi, F; Zeppilli, P; Vinger, P

2005-01-01

Objectives: To investigate the prevalence of ocular injuries in a large population of boxers over a period of 16 years, in particular, the most severe lesions that may be vision threatening. Methods: Clinical records of the medical archive of the Italian Boxing Federation were analysed. A total of 1032 boxers were examined from February 1982 to October 1998. A complete ophthalmological history was available for 956, who formed the study population (a total of 10 697 examinations). The following data were collected: age when started boxing; duration of competitive boxing career (from the date of the first bout); weight category; a thorough ocular history. The following investigations were carried out: measurement of visual acuity and visual fields, anterior segment inspection, applanation tonometry, gonioscopy, and examination of ocular fundus. Eighty age matched healthy subjects, who had never boxed, formed the control group. Results: Of the 956 boxers examined, 428 were amateur (44.8%) and 528 professional (55.2%). The median age at first examination was 23.1 (4.3) years (range 15–36). The prevalence of conjunctival, corneal, lenticular, vitreal, ocular papilla, and retinal alterations in the study population was 40.9% compared with 3.1% in the control group (p⩽0.0001). The prevalence of serious ocular findings (angle, lens, macula, and peripheral retina alterations) was 5.6% in boxers and 3.1% in controls (NS). Conclusions: Boxing does not result in a higher prevalence of severe ocular lesions than in the general population. However, the prevalence of milder lesions (in particular with regard to the conjunctiva and cornea) is noteworthy, justifying the need for adequate ophthalmological surveillance. PMID:15665199

Evaluating ocular blood flow

PubMed Central

Maram, Jyotsna; Srinivas, Sowmya; Sadda, Srinivas R

2017-01-01

Studies have shown that vascular impairment plays an important role in the etiology and pathogenesis of various ocular diseases including glaucoma, age-related macular degeneration, diabetic retinopathy, and retinal venous occlusive disease. Thus, qualitative and quantitative assessment of ocular blood flow (BF) is a topic of interest for early disease detection, diagnosis, and management. Owing to the rapid improvement in technology, there are several invasive and noninvasive techniques available for evaluating ocular BF, with each of these techniques having their own limitations and advantages. This article reviews these important techniques, with a particular focus on Doppler Fourier domain optical coherence tomography (OCT) and OCT-angiography. PMID:28573987

Combat ocular trauma and systemic injury.

PubMed

Weichel, Eric D; Colyer, Marcus H

2008-11-01

To review the recent literature regarding combat ocular trauma during hostilities in Operations Iraqi Freedom and Enduring Freedom, describe the classification of combat ocular trauma, and offer strategies that may assist in the management of eye injuries. Several recent publications have highlighted features of combat ocular trauma from Operation Iraqi Freedom. The most common cause of today's combat ocular injuries is unconventional fragmentary munitions causing significant blast injuries. These explosive munitions cause high rates of concomitant nonocular injuries such as traumatic brain injury, amputation, and other organ injuries. The most frequent ocular injuries include open-globe and adnexal lacerations. The extreme severity of combat-related open-globe injuries leads to high rates of primary enucleation and retained intraocular foreign bodies. Visual outcomes of intraocular foreign body injuries are similar to other series despite delayed removal, and no cases of endophthalmitis have occurred. Despite these advances, however, significant vision loss persists in cases of perforating globe injuries as well as open and closed-globe trauma involving the posterior segment. This review summarizes the recent literature describing ocular and systemic injuries sustained during Operations Iraqi and Enduring Freedom. An emphasis on classification of ocular injuries as well as a discussion of main outcome measures and complications is discussed.

[Severe ocular burns by calcium carbide in a speleologist: a case report].

PubMed

Testud, F; Voegtlé, R; Nordmann, J P; Descotes, J

2002-03-01

A case of severe ocular burns in an amateur speleologist is reported. The explosion of his acetylene lamp caused the projection of calcium carbide particles, which induced burning of the cornea and conjunctiva in both eyes. He slowly recovered in several months. The pathophysiology of the burns, linked to the in situ production of lime, and their management are discussed.

Ocular Manifestations of Acquired Immunodeficiency Syndrome

PubMed Central

Kim, Young Shin; Sun, Hae Jung; Kim, Tae Hyong; Kang, Kui Dong

2015-01-01

Purpose To investigate the patterns and risk factors of the ocular manifestations of acquired immunodeficiency syndrome (AIDS) and their correlation with CD4+ count in the era of highly active antiretroviral therapy (HAART). Methods This retrospective study examined 127 AIDS patients who presented to Soonchunhyang University Hospital. Data were collected from patient interviews, clinical examinations, and laboratory investigations. Ophthalmologic examinations included the best-corrected visual acuity, intraocular pressure, anterior segment and adnexal examination, and dilated fundus examination. Results Of the 127 patients with AIDS, 118 were on HAART and 9 were not. The mean CD4+ count was 266.7 ± 209.1 cells/µL. There were ocular manifestations in 61 patients (48.0%). The incidence of anterior segment manifestations was higher than posterior segment manifestations at 28.3% and 19.7%, respectively. The mean CD4+ count was significantly (p < 0.05) lower in the patients with posterior versus anterior segment ocular manifestations. The most common ocular manifestation was retinal microvasculopathy (15.0%), followed by keratoconjunctivitis sicca (14.2%), conjunctival microvasculopathy (9.4%), cytomegalovirus retinitis (3.1%), herpes zoster ophthalmicus (2.4%), and blepharitis (1.6%). Retinal microvasculopathy and cytomegalovirus retinitis were common in patients with CD4+ counts <200 cells/µL, while keratoconjunctivitis sicca and conjunctival microvasculopathy were common in patients with CD4+ counts of 200 to 499 cells/µL. There was a significant (p < 0.05) association between ocular manifestation and CD4+ count or age. Conclusions The introduction of HAART has changed the landscape of ocular presentations in patients with AIDS. In this study, anterior segment and external ocular manifestations occurred more frequently than posterior segment manifestations. Also, the mean CD4+ count was significantly lower in patients with posterior segment ocular manifestations

Autoimmune retinopathy with RPE hypersensitivity and 'negative ERG' in X-linked hyper-IgM syndrome.

PubMed

Schuster, Andreas; Apfelstedt-Sylla, Eckart; Pusch, Carsten M; Zrenner, Eberhart; Thirkill, Charles E

2005-01-01

To report the clinical, electrophysiological, and immunological features of a patient with X-linked hyper-IgM immunodeficiency syndrome type 1 (HIGM1) accompanied by a novel type of autoimmune retinopathy, including retinal pigment epithelium (RPE) hypersensitivity. Comprehensive ophthalmological examinations, electrophysiological function testing, and inquiries into the immunological status of a 13-year-old presenting with subacute loss of vision in association with a molecularly confirmed diagnosis of HIGM1 were performed. The patient was genotyped by a PCR-based sequence tag content mapping strategy to define the genetic defect within the causative X-HIM gene TNFSF5. Since conventional allogenic bone marrow transplantation has been reported to cure HIGM1, a peripheral blood stem-cell transplantation was performed. (1) The patient's reduced visual acuity included prolonged dark adaptation and visual field constriction. Electrophysiology revealed a 'negative ERG' indicating post-receptoral dysfunction. (2) Initial immunological examination of the patient's serum identified abnormal antibody activity with components of the photoreceptors and the inner nuclear layer. The patient later developed indications of RPE hypersensitivity. A massively reduced light-peak to dark-trough ratio of the EOG slow oscillations (L/D ratio) corresponded to impaired RPE-photoreceptor complex function. (3) Molecular genetic analyses revealed the patient to be nullizygous for the tumor necrosis factor ligand member 5 gene (TNFSF5; CD40LG). A large chromosomal deletion of approximately 27.6-32.3 kb in size was identified in Xq26. (4) The transplant with its associated immunomodulation appeared to worsen rather than improve the patient's condition. The fundus appearance and electrophysiological function testing revealed indications of atypical retinal degeneration. However, the clinical course and the serological findings were consistent with those of ocular autoimmunity involving both

What We Have Learned From the Ocular Hypertension Treatment Study.

PubMed

Gordon, Mae O; Kass, Michael A

2018-05-01

To identify results from the Ocular Hypertension Study that can aid patients and clinicians to make evidence-based decisions about the management of ocular hypertension. Perspective. At 60 months, the cumulative frequency of developing primary open-angle glaucoma (POAG) was 4.4% in the medication group and 9.5% in the observation group (hazard ratio for medication, 0.40; 95% confidence interval [CI], 0.27-0.59; P < .0001). At 13 years the cumulative proportion of participants who developed POAG was 0.22 (95% CI 0.19-0.25) in the original observation group and 0.16 (95% CI 0.13-0.19) in the original medication group (complementary log-log x 2 P = .009). A 5-factor model (older age, higher IOP, thinner central corneal thickness, larger cup-to-disc ratio, and higher visual field pattern standard deviation) separated participants at high and low risk of developing POAG. Clinicians and patients can make evidence-based decisions about the management of ocular hypertension using the risk model and considering patient age, medical status, life expectancy, and personal preference. Copyright © 2018 Elsevier Inc. All rights reserved.

Ocular diseases: immunological and molecular mechanisms.

PubMed

Song, Jing; Huang, Yi-Fei; Zhang, Wen-Jing; Chen, Xiao-Fei; Guo, Yu-Mian

2016-01-01

Many factors, such as environmental, microbial and endogenous stress, antigen localization, can trigger the immunological events that affect the ending of the diverse spectrum of ocular disorders. Significant advances in understanding of immunological and molecular mechanisms have been researched to improve the diagnosis and therapy for patients with ocular inflammatory diseases. Some kinds of ocular diseases are inadequately responsive to current medications; therefore, immunotherapy may be a potential choice as an alternative or adjunctive treatment, even in the prophylactic setting. This article first provides an overview of the immunological and molecular mechanisms concerning several typical and common ocular diseases; second, the functions of immunological roles in some of systemic autoimmunity will be discussed; third, we will provide a summary of the mechanisms that dictate immune cell trafficking to ocular local microenvironment in response to inflammation.

Plasticity of the human otolith-ocular reflex

NASA Technical Reports Server (NTRS)

Wall, C. 3rd; Smith, T. R.; Furman, J. M.

1992-01-01

The eye movement response to earth vertical axis rotation in the dark, a semicircular canal stimulus, can be altered by prior exposure to combined visual-vestibular stimuli. Such plasticity of the vestibulo-ocular reflex has not been described for earth horizontal axis rotation, a dynamic otolith stimulus. Twenty normal human subjects underwent one of two types of adaptation paradigms designed either to attenuate or enhance the gain of the semicircular canal-ocular reflex prior to undergoing otolith-ocular reflex testing with horizontal axis rotation. The adaptation paradigm paired a 0.2 Hz sinusoidal rotation about a vertical axis with a 0.2 Hz optokinetic stripe pattern that was deliberately mismatched in peak velocity. Pre- and post-adaptation horizontal axis rotations were at 60 degrees/s in the dark and produced a modulation in the slow component velocity of nystagmus having a frequency of 0.17 Hz due to putative stimulation of the otolith organs. Results showed that the magnitude of this modulation component response was altered in a manner similar to the alteration in semicircular canal-ocular responses. These results suggest that physiologic alteration of the vestibulo-ocular reflex using deliberately mismatched visual and semicircular canal stimuli induces changes in both canal-ocular and otolith-ocular responses. We postulate, therefore, that central nervous system pathways responsible for controlling the gains of canal-ocular and otolith-ocular reflexes are shared.

[Clinical and molecular study in a child with X-linked hypohidrotic ectodermal dysplasia].

PubMed

Callea, Michele; Yavuz, Izzet; Clarich, Gabriella; Cammarata-Scalisi, Francisco

2015-12-01

Ectodermal dysplasia encompasses more than 200 clinically distinct entities, which affect at least two structures derived from the ectoderm, including the skin, hair, nails, teeth, sweat glands, and sebaceous glands. X-linked hypohidrotic ectodermal dysplasia is the most common type and is caused by mutation of the EDA gene that encodes Ectodysplasin-A. It occurs in less than 1 in 100 000 individuals and is clinically characterized by hypodontia, hypohidrosis, hypotrichosis, and eye dis orders. We present a child evaluated in a multidisciplinary manner with clinical and molecular diagnosis of X-linked hypohidrotic ectodermal dysplasia with type missense mutation c.1133C> T; p.T378M in EDA gene.

What Is an Ocular Migraine?

MedlinePlus

... When to seek help What is an ocular migraine? Is it a sign of something serious? Answers ... and retinal migraine, which could signal something serious. Migraine aura affecting your vision Ocular migraine sometimes describes ...

Ocular Purine Receptors as Drug Targets in the Eye

PubMed Central

Civan, Mortimer M.

2016-01-01

Abstract Agonists and antagonists of various subtypes of G protein coupled adenosine receptors (ARs), P2Y receptors (P2YRs), and ATP-gated P2X receptor ion channels (P2XRs) are under consideration as agents for the treatment of ocular diseases, including glaucoma and dry eye. Numerous nucleoside and nonnucleoside modulators of the receptors are available as research tools and potential therapeutic molecules. Three of the 4 subtypes of ARs have been exploited with clinical candidate molecules for treatment of the eye: A1, A2A, and A3. An A1AR agonist is in clinical trials for glaucoma, A2AAR reduces neuroinflammation, A3AR protects retinal ganglion cells from apoptosis, and both A3AR agonists and antagonists had been reported to lower intraocular pressure (IOP). Extracellular concentrations of endogenous nucleotides, including dinucleoside polyphosphates, are increased in pathological states, activating P2Y and P2XRs throughout the eye. P2YR agonists, including P2Y2 and P2Y6, lower IOP. Antagonists of the P2X7R prevent the ATP-induced neuronal apoptosis in the retina. Thus, modulators of the purinome in the eye might be a source of new therapies for ocular diseases. PMID:27574786

Ocular Purine Receptors as Drug Targets in the Eye.

PubMed

Jacobson, Kenneth A; Civan, Mortimer M

2016-10-01

Agonists and antagonists of various subtypes of G protein coupled adenosine receptors (ARs), P2Y receptors (P2YRs), and ATP-gated P2X receptor ion channels (P2XRs) are under consideration as agents for the treatment of ocular diseases, including glaucoma and dry eye. Numerous nucleoside and nonnucleoside modulators of the receptors are available as research tools and potential therapeutic molecules. Three of the 4 subtypes of ARs have been exploited with clinical candidate molecules for treatment of the eye: A 1 , A 2A , and A 3 . An A 1 AR agonist is in clinical trials for glaucoma, A 2A AR reduces neuroinflammation, A 3 AR protects retinal ganglion cells from apoptosis, and both A 3 AR agonists and antagonists had been reported to lower intraocular pressure (IOP). Extracellular concentrations of endogenous nucleotides, including dinucleoside polyphosphates, are increased in pathological states, activating P2Y and P2XRs throughout the eye. P2YR agonists, including P2Y 2 and P2Y 6 , lower IOP. Antagonists of the P2X7R prevent the ATP-induced neuronal apoptosis in the retina. Thus, modulators of the purinome in the eye might be a source of new therapies for ocular diseases.

A Review of Ocular Graft-Versus-Host Disease.

PubMed

Munir, Saleha Z; Aylward, James

2017-05-01

: Graft-versus-host disease (GVHD) is a major complication that occurs following allogeneic hematopoietic stem cell transplantation, which is a potential curative therapy used in a variety of malignant or benign hematological diseases. Graft-versus-host disease primarily occurs in many organs, but most notably in the skin, lungs, gastrointestinal tract, liver, eyes, mucosa, and musculoskeletal system. Ocular manifestations of GVHD may precede other systemic GVHD findings, and it may be a poor prognosis for mortality. While all parts of the eye may be affected, ocular GVHD occurs primarily in the ocular surface. Dry eye disease or keratoconjunctivitis sicca is the most common presenting manifestation of chronic ocular GVHD. Dry eye disease in ocular GVHD is a multifactorial process, which involves destruction and fibrosis of lacrimal glands and conjunctiva, leading to tear film deficiency and instability. Depending on the severity of ocular involvement and response to treatment, ocular GVHD may cause decreased quality of life. Management of GVHD begins with prevention by understanding risk factors and by implementing prophylactic treatment after allogeneic hematopoietic stem cell transplantation. A multidisciplinary approach to the prevention and treatment of GVHD is important, and there are currently no preventive therapies available for ocular GVHD. Once diagnosed, ocular GVHD treatment strategies target ocular surface lubrication and support, tear film stabilization, inflammation reduction, and surgical intervention. The goal of this review is to define ocular GVHD and its categorical manifestations, as well as to describe the importance of comprehensive assessment, diagnosis, and ophthalmologic treatment and management of ocular GVHD with a multidisciplinary approach.

Ocular diseases: immunological and molecular mechanisms

PubMed Central

Song, Jing; Huang, Yi-Fei; Zhang, Wen-Jing; Chen, Xiao-Fei; Guo, Yu-Mian

2016-01-01

Many factors, such as environmental, microbial and endogenous stress, antigen localization, can trigger the immunological events that affect the ending of the diverse spectrum of ocular disorders. Significant advances in understanding of immunological and molecular mechanisms have been researched to improve the diagnosis and therapy for patients with ocular inflammatory diseases. Some kinds of ocular diseases are inadequately responsive to current medications; therefore, immunotherapy may be a potential choice as an alternative or adjunctive treatment, even in the prophylactic setting. This article first provides an overview of the immunological and molecular mechanisms concerning several typical and common ocular diseases; second, the functions of immunological roles in some of systemic autoimmunity will be discussed; third, we will provide a summary of the mechanisms that dictate immune cell trafficking to ocular local microenvironment in response to inflammation. PMID:27275439

Mapping of the X-linked cataract (Xcat) mutation, the gene implicated in the Nance Horan syndrome, on the mouse X chromosome.

PubMed

Stambolian, D; Favor, J; Silvers, W; Avner, P; Chapman, V; Zhou, E

1994-07-15

The Xcat mutation in the mouse, an X-linked inherited disorder, is characterized by the congenital onset of cataracts. The cataracts have morphologies similar to those of cataracts found in the human Nance Horan (X-linked cataract dental) syndrome, suggesting that Xcat is an animal model for Nance Horan. The Xcat mutation provides an opportunity to investigate, at the molecular level, the pathogenesis of cataract. As a first step to cloning the Xcat gene, we report the localization of the Xcat mutation with respect to known molecular markers on the mouse X chromosome. Back-cross progeny carrying the Xcat mutation were obtained from an interspecific cross. Genomic DNA from each mouse was subjected to Southern and PCR analysis to identify restriction fragment length polymorphisms and simple sequence length polymorphisms, respectively. Our results refine the location of Xcat to a 2-cM region, eliminate several genes from consideration as the Xcat mutation, identify molecular probes tightly linked with Xcat, and suggest candidate genes responsible for the Xcat phenotype.

Assessing interethnic admixture using an X-linked insertion-deletion multiplex.

PubMed

Ribeiro-Rodrigues, Elzemar Martins; dos Santos, Ney Pereira Carneiro; dos Santos, Andrea Kely Campos Ribeiro; Pereira, Rui; Amorim, António; Gusmão, Leonor; Zago, Marco Antonio; dos Santos, Sidney Emanuel Batista

2009-01-01

In this study, a PCR multiplex was optimized, allowing the simultaneous analysis of 13 X-chromosome Insertion/deletion polymorphisms (INDELs). Genetic variation observed in Africans, Europeans, and Native Americans reveals high inter-population variability. The estimated proportions of X-chromosomes in an admixed population from the Brazilian Amazon region show a predominant Amerindian contribution (approximately 41%), followed by European (approximately 32%) and African (approximately 27%) contributions. The proportion of Amerindian contribution based on X-linked data is similar to the expected value based on mtDNA and Y-chromosome information. The accuracy for assessing interethnic admixture, and the high differentiation between African, European, and Native American populations, demonstrates the suitability of this INDEL set to measure ancestry proportions in three-hybrid populations, as it is the case of Latin American populations.

Genetic testing for oculocutaneous albinism type 1 and 2 and Hermansky-Pudlak syndrome type 1 and 3 mutations in Puerto Rico.

PubMed

Santiago Borrero, Pedro J; Rodríguez-Pérez, Yolanda; Renta, Jessicca Y; Izquierdo, Natalio J; Del Fierro, Laura; Muñoz, Daniel; Molina, Norma López; Ramírez, Sonia; Pagán-Mercado, Glorivee; Ortíz, Idith; Rivera-Caragol, Enid; Spritz, Richard A; Cadilla, Carmen L

2006-01-01

Hermansky-Pudlak syndrome (HPS) (MIM #203300) is a heterogeneous group of autosomal recessive disorders characterized by oculocutaneous albinism (OCA), bleeding tendency, and lysosomal dysfunction. HPS is very common in Puerto Rico (PR), particularly in the northwest part of the island, with a frequency of approximately 1:1,800. Two HPS genes and mutations have been identified in PR, a 16-base pair (bp) duplication in HPS1 and a 3,904-bp deletion in HPS3. In Puerto Ricans with more typical OCA, the most common mutation of the tyrosinase (TYR) (human tyrosinase (OCA1) gene) gene was G47D. We describe screening 229 Puerto Rican OCA patients for these mutations, and for mutations in the OCA2 gene. We found the HPS1 mutation in 42.8% of cases, the HPS3 deletion in 17%, the TYR G47D mutation in 3.0%, and a 2.4-kb deletion of the OCA2 gene in 1.3%. Among Puerto Rican newborns, the frequency of the HPS1 mutation is highest in northwest PR (1:21; 4.8%) and lower in central PR (1:64; 1.6%). The HPS3 gene deletion is most frequent in central PR (1:32; 3.1%). Our findings provide insights into the genetics of albinism and HPS in PR, and provide the basis for genetic screening for these disorders in this minority population.

Solid lipid nanoparticles for ocular drug delivery.

PubMed

Seyfoddin, Ali; Shaw, John; Al-Kassas, Raida

2010-01-01

Ocular drug delivery remains challenging because of the complex nature and structure of the eye. Conventional systems, such as eye drops and ointments, are inefficient, whereas systemic administration requires high doses resulting in significant toxicity. There is a need to develop novel drug delivery carriers capable of increasing ocular bioavailability and decreasing both local and systemic cytotoxicity. Nanotechnology is expected to revolutionize ocular drug delivery. Many nano-structured systems have been employed for ocular drug delivery and yielded some promising results. Solid lipid nanoparticles (SLNs) have been looked at as a potential drug carrier system since the 1990s. SLNs do not show biotoxicity as they are prepared from physiological lipids. SLNs are especially useful in ocular drug delivery as they can enhance the corneal absorption of drugs and improve the ocular bioavailability of both hydrophilic and lipophilic drugs. SLNs have another advantage of allowing autoclave sterilization, a necessary step towards formulation of ocular preparations. This review outlines in detail the various production, characterization, sterilization, and stabilization techniques for SLNs. In-vitro and in-vivo methods to study the drug release profile of SLNs have been explained. Special attention has been given to the nature of lipids and surfactants commonly used for SLN production. A summary of previous studies involving the use of SLNs in ocular drug delivery is provided, along with a critical evaluation of SLNs as a potential ocular delivery system.

The rapid evolution of X-linked male-biased gene expression and the large-X effect in Drosophila yakuba, D. santomea, and their hybrids.

PubMed

Llopart, Ana

2012-12-01

The X chromosome has a large effect on hybrid dysfunction, particularly on hybrid male sterility. Although the evidence for this so-called large-X effect is clear, its molecular causes are not yet fully understood. One possibility is that, under certain conditions, evolution proceeds faster in X-linked than in autosomal loci (i.e., faster-X effect) due to both natural selection and their hemizygosity in males, an effect that is expected to be greatest in genes with male-biased expression. Here, I study genome-wide variation in transcript abundance between Drosophila yakuba and D. santomea, within these species and in their hybrid males to evaluate both the faster-X and large-X effects at the level of expression. I find that in X-linked male-biased genes (MBGs) expression evolves faster than in their autosomal counterparts, an effect that is accompanied by a unique reduction in expression polymorphism. This suggests that Darwinian selection is driving expression differences between species, likely enhanced by the hemizygosity of the X chromosome in males. Despite the recent split of the two sister species under study, abundant changes in both cis- and trans-regulatory elements underlie expression divergence in the majority of the genes analyzed, with significant differences in allelic ratios of transcript abundance between the two reciprocal F(1) hybrid males. Cis-trans coevolution at molecular level, evolved shortly after populations become isolated, may therefore contribute to explain the breakdown of the regulation of gene expression in hybrid males. Additionally, the X chromosome plays a large role in this hybrid male misexpression, which affects not only MBG but also, to a lesser degree, nonsex-biased genes. Interestingly, hybrid male misexpression is concentrated mostly in autosomal genes, likely facilitated by the rapid evolution of sex-linked trans-acting factors. I suggest that the faster evolution of X-linked MBGs, at both protein and expression levels

[Ocular tuberculosis : A case series].

PubMed

Koubaa, M; Smaoui, F; Gargouri, S; Ben Ayed, H; Rekik, K; Abid, I; Maaloul, I; Feki, J; Marrakchi, C; Ben Jemaa, M

2018-05-01

Ocular tuberculosis is a rare form of extra pulmonary tuberculosis. It represents 1-2% of all clinical forms. The aim of this work was to focus on diagnostic and therapeutic characteristics of ocular tuberculosis. We report a case series of 14 patients with ocular tuberculosis seen in an infectious diseases department between 2006 and 2015. The diagnosis was retained on clinical data and a positive tuberculin skin test or interferon-gamma release assay. The patient's mean age was 40.7±9years. The most common clinical presentation was uveitis (11 patients and 16 eyes). An extra ocular involvement was associated in three patients. The mean duration of antitubercular therapy was 10±2.5 months. Corticosteroid therapy was associated in 11 cases. The outcome was favorable in all cases. Two patients had maintained visual sequelae. Ocular tuberculosis is a rare disease but still remains a diagnostic problem. It should be considered in case of any chronic ocular symptoms, especially in endemic countries. Early management can improve the visual prognosis. Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Ocular manifestations of systemic disease: toxoplasmosis.

PubMed

Vasconcelos-Santos, Daniel V

2012-11-01

To provide an overview of ocular toxoplasmosis, the leading cause of infectious posterior uveitis, focusing on recent trends of disease epidemiology, pathogenesis, diagnosis, therapy and prevention. Novel aspects of epidemiology, including growing importance of water transmission are discussed. The historical controversy of congenital versus postnatally acquired toxoplasmosis is revisited. Recent insights into pathogenesis of ocular toxoplasmosis are also reviewed, tipping the delicate balance between parasite virulence and host immunity. Diagnosis of ocular toxoplasmosis is also discussed in the light of serological, molecular and imaging tools. Finally, a critical analysis of current and emerging therapies for ocular toxoplasmosis is made. Preventive aspects are also commented upon. Waterborne toxoplasmosis is increasingly recognized in outbreaks and in endemic areas. The importance of postnatally acquired toxoplasmosis is now well established, but should not lead to underestimation of congenital disease. Genetic determination of parasite virulence/individual susceptibility might correlate with disease outcomes. Serological, molecular and imaging tools may improve the diagnosis and follow-up of individuals with ocular toxoplasmosis. Despite emergence of alternative therapeutic regimens, including intravitreal antibiotics, classical therapy with sulfadiazine/pyrimethamine is still standard for toxoplasmic retinochoroiditis. Adequate prophylaxis is expected to have an effect in ocular burden of toxoplasmosis.

X-linked primary immunodeficiency associated with hemizygous mutations in the moesin (MSN) gene.

PubMed

Lagresle-Peyrou, Chantal; Luce, Sonia; Ouchani, Farid; Soheili, Tayebeh Shabi; Sadek, Hanem; Chouteau, Myriam; Durand, Amandine; Pic, Isabelle; Majewski, Jacek; Brouzes, Chantal; Lambert, Nathalie; Bohineust, Armelle; Verhoeyen, Els; Cosset, François-Loïc; Magerus-Chatinet, Aude; Rieux-Laucat, Frédéric; Gandemer, Virginie; Monnier, Delphine; Heijmans, Catherine; van Gijn, Marielle; Dalm, Virgil A; Mahlaoui, Nizar; Stephan, Jean-Louis; Picard, Capucine; Durandy, Anne; Kracker, Sven; Hivroz, Claire; Jabado, Nada; de Saint Basile, Geneviève; Fischer, Alain; Cavazzana, Marina; André-Schmutz, Isabelle

2016-12-01

We investigated 7 male patients (from 5 different families) presenting with profound lymphopenia, hypogammaglobulinemia, fluctuating monocytopenia and neutropenia, a poor immune response to vaccine antigens, and increased susceptibility to bacterial and varicella zoster virus infections. We sought to characterize the genetic defect involved in a new form of X-linked immunodeficiency. We performed genetic analyses and an exhaustive phenotypic and functional characterization of the lymphocyte compartment. We observed hemizygous mutations in the moesin (MSN) gene (located on the X chromosome and coding for MSN) in all 7 patients. Six of the latter had the same missense mutation, which led to an amino acid substitution (R171W) in the MSN four-point-one, ezrin, radixin, moesin domain. The seventh patient had a nonsense mutation leading to a premature stop codon mutation (R533X). The naive T-cell counts were particularly low for age, and most CD8 + T cells expressed the senescence marker CD57. This phenotype was associated with impaired T-cell proliferation, which was rescued by expression of wild-type MSN. MSN-deficient T cells also displayed poor chemokine receptor expression, increased adhesion molecule expression, and altered migration and adhesion capacities. Our observations establish a causal link between an ezrin-radixin-moesin protein mutation and a primary immunodeficiency that could be referred to as X-linked moesin-associated immunodeficiency. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Nanostructured lipid carriers as novel ophthalmic delivery system for mangiferin: improving in vivo ocular bioavailability.

PubMed

Liu, Rui; Liu, Zhidong; Zhang, Chengui; Zhang, Boli

2012-10-01

The aim of this study was to develop a novel nanostructured lipid carriers (NLCs) system to improve ocular bioavailability of mangiferin (MGN) for the potential treatment of cataract. The physicochemical properties of MGN-loaded NLC (MGN-NLC) formulation were characterized by particle size, polydispersity index, zeta potential, entrapment efficiency, drug loading, morphological property, and crystalline state. in vitro characteristics were investigated by drug release from NLC system, physical stability, and corneal permeation through excised rabbit cornea. Moreover, in vivo ocular tolerability was assessed by a modified Draize test and histological microscopy. Preocular retention capability was evaluated by slit-lamp observation. Pharmacokinetic study in the aqueous humor was performed by microdialysis technique. Transmission electron microscopy depicted spherical and uniform morphology. Differential scanning calorimetry and X-ray diffractometry displayed imperfect crystalline lattice. The optimized MGN-NLC formulation exhibited a sustained drug release with 3 months stability and 4.31-fold increase of in vitro corneal permeation. Furthermore, in vivo studies exhibited a high tolerance in the ocular tissues and prolonged drug retention capacity on the corneal surface. Finally, pharmacokinetic study suggested a 5.69-fold increase of ocular bioavailability compared with MGN solution (MGN-SOL). Therefore, NLC system is a promising approach for ocular delivery of MGN. Copyright © 2012 Wiley Periodicals, Inc.

Serological IgG avidity test for ocular toxoplasmosis.

PubMed

Suresh, Subramaniam; Nor-Masniwati, Saidin; Nor-Idahriani, Muhd Nor; Wan-Hazabbah, Wan-Hitam; Zeehaida, Mohamed; Zunaina, Embong

2012-01-01

The purpose of this study was to evaluate the immunoglobulin (Ig) G avidity of serological toxoplasmosis testing in patients with ocular inflammation and to determine the clinical manifestations of ocular toxoplasmosis. A retrospective review of all patients presenting with ocular inflammation to the Hospital Universiti Sains Malaysia, Kelantan, Malaysia between 2005 and 2009 was undertaken. Visual acuity, clinical manifestations at presentation, toxoplasmosis antibody testing, and treatment records were analyzed. A total of 130 patients with ocular inflammation were reviewed retrospectively. The patients had a mean age of 38.41 (standard deviation 19.24, range 6-83) years. Seventy-one patients (54.6%) were found to be seropositive, of whom five (3.8%) were both IgG and IgM positive (suggestive of recently acquired ocular toxoplasmosis) while one (0.8%) showed IgG avidity ≤40% (suggestive of recently acquired ocular toxoplasmosis) and 65 patients (50.0%) showed IgG avidity >40% (suggestive of reactivation of toxoplasmosis infection). Chorioretinal scarring as an ocular manifestation was significantly more common in patients with seropositive toxoplasmosis (P = 0.036). Eighteen patients (13.8%) were diagnosed as having recent and/or active ocular toxoplasmosis based on clinical manifestations and serological testing. Ocular toxoplasmosis is a clinical diagnosis, but specific toxoplasmosis antibody testing helps to support the diagnosis and to differentiate between reactivation of infection and recently acquired ocular toxoplasmosis.

Ocular and systemic pharmacokinetics of lidocaine hydrochloride ophthalmic gel in rabbits after topical ocular administration.

PubMed

Liu, Bing; Ding, Li; Xu, Xiaowen; Lin, Hongda; Sun, Chenglong; You, Linjun

2015-12-01

Lidocaine hydrochloride ophthalmic gel is a novel ophthalmic preparation for topical ocular anesthesia. The study is aimed at evaluating the ocular and systemic pharmacokinetics of lidocaine hydrochloride 3.5 % ophthalmic gel in rabbits after ocular topical administration. Thirty-six rabbits were randomly placed in 12 groups (3 rabbits per group). The rabbits were quickly killed according to their groups at 0 (predose), 0.0833, 0.167, 0.333, 0.667, 1, 1.5, 2, 3, 4, 6, and 8 h postdose and then the ocular tissue and plasma samples were collected. All the samples were analyzed by a validated LC-MS/MS method. The test result showed that the maximum concentration (C max) of lidocaine in different ocular tissues and plasma were all achieved within 20 min after drug administration, and the data of C max were (2,987 ± 1814) μg/g, (44.67 ± 12.91) μg/g, (26.26 ± 7.19) μg/g, (11,046 ± 2,734) ng/mL, and (160.3 ± 61.0) ng/mL for tear fluid, cornea, conjunctiva, aqueous humor, and plasma, respectively. The data of the elimination half-life in these tissues were 1.5, 3.2, 3.5, 1.9, and 1.7 h for tear fluid, cornea, conjunctiva, aqueous humor, and plasma, respectively. The intraocular lidocaine levels were significantly higher than that in plasma, and the elimination half-life of lidocaine in cornea, conjunctiva, and aqueous humor was relatively longer than that in tear fluid and plasma. The high intraocular penetration, low systemic exposure, and long duration in the ocular tissues suggested lidocaine hydrochloride 3.5 % ophthalmic gel as an effective local anesthetic for ocular anesthesia during ophthalmic procedures.

Novel XLRS1 gene mutations cause X-linked juvenile retinoschisis in Chinese families.

PubMed

Ma, Xiang; Li, Xiaoxin; Wang, Lihua

2008-01-01

To investigate various XLRS1 (RS1) gene mutations in Chinese families with X-linked juvenile retinoschisis (XLRS or RS). Genomic DNA was isolated from leukocytes of 29 male patients with X-linked juvenile retinoschisis, 38 female carriers, and 100 normal controls. All 6 exons of the RS1 gene were amplified by polymerase chain reaction, and the RS1 gene mutations were determined by direct sequencing. Eleven different RS1 mutations in 12 families were identified in the 29 male patients. The mutations comprised eight missense, two frameshift, and one splice donor site mutation. Four of these mutations, one frameshift mutation (26 del T) in exon 1, one frameshift mutation (488 del G) in exon 5, Asp145His and Arg156Gly in exon 5, have not been previously described. One novel non-disease-related polymorphism, 576C to T (Pro192Pro) in exon 6, was also found. Six recurrent mutations, Ser73Pro and Arg102Gln mutations in exon 4 and Arg200Cys, Arg209His, Arg213Gln, and Cys223Arg mutations in exon 6, were also identified in this study. RS1 gene mutations caused X-linked juvenile retinoschisis in these Chinese families.

Ocular complications in patients with lung transplants.

PubMed

Tarabishy, Ahmad B; Khatib, Omar F; Nocero, John R; Budev, Marie; Kaiser, Peter K

2011-09-01

To describe infectious and non-infectious ocular complications found in patients with lung transplants. 545 patients underwent lung transplantation from January 1998 to September 2008 at the Cleveland Clinic. Patients who underwent ophthalmic examination at the Cole Eye Institute after lung transplantation were included in the study. Diagnoses, treatments, surgeries, laboratory parameters of immune status and patient survival were examined. Of the 545 patients who received a lung transplant during the study period at the Cleveland Clinic, 46 (8.4%) patients underwent ophthalmology examination after a lung transplant. The most common ocular finding was posterior subcapsular cataract, found in 13/46 (28.3%) patients. Infectious ocular complications were present in 6/46 patients (13.0%) including fungal infections (rhino-orbital mucormycosis (n=1), disseminated Pseudallescheria boydii infection (n=2)), cytomegalovirus retinitis (n=1), varicella-zoster virus keratouveitis (n=1) and herpes zoster ophthalmicus (n=1). Five of six patients with infectious ocular complications died within 6 months of evaluation. Decreased absolute lymphocyte count was associated with infectious ocular complications (p=0.014). Many ocular conditions can occur in patients with lung transplants. Ocular infectious complications were uncommon but may be associated with increased mortality.

Significance of mucin on the ocular surface.

PubMed

Watanabe, Hitoshi

2002-03-01

To review the significance of mucin in the tear film and the ocular surface epithelium. Summary of the information on how mucin derived from the corneal and conjunctival epithelia and from goblet cells plays a role in the stability of the tear film over the ocular surface. The change in mucin expression derived from the ocular surface epithelium is also discussed with reference to ocular surface disease. The corneal and conjunctival epithelia produce transmembrane mucins such as MUC1, MUC2, and MUC4. In contrast, goblet cells produce the gel-forming secretory mucin, MUC5AC. The lacrimal gland produces MUC7. On the ocular surface, cooperation between transmembrane mucin and secretory mucin is necessary for the stability of the tear film. The expression of mucin from the ocular surface epithelium is coordinated from the time of eyelid opening and is altered in conditions such as squamous metaplasia and dry eye. This alteration may result in instability of the tear film. CONCLU SION: The induction of mucin from the ocular surface may facilitate the stability of the tear film, and increased knowledge may lead to the development of a new modality for the treatment of dry eye.

Ocular sports injuries: the current picture

PubMed Central

Barr, A; Baines, P; Desai, P; MacEwen, C

2000-01-01

Objectives—To determine the recent incidence of eye injury due to sport in Scotland, identify any trend, and establish which sports are responsible for most injury? The type of injury and final visual outcome is also evaluated. Methods—A prospective observational study of ocular injuries sustained during sport was performed over a one year period. Only patients requiring hospital admission were included. Data were collected on a standardised proforma and entered into a central database. Patients were followed up for at least three months. Results—Of 416 patients admitted because of ocular injury, 52 (12.5%) resulted from playing a sport. Although all racquet sports together accounted for 47.5% of these injuries, football was the single most common sport associated with ocular trauma, being responsible for 32.5% of cases. The most common clinical finding was macroscopic hyphaema occurring in 87.5% of patients. Overall the final visual acuity was 6/6 in 92.5% of patients. Conclusions—The incidence of eye injury due to sport at 12.5% is lower than previously reported, suggesting a change in the pattern of ocular trauma. Football is the single most common cause of ocular injury from sport in Scotland, but the wearing of protective headgear would be difficult to instigate. The incidence of hyphaema in sport related ocular trauma (87.5%) is almost double that of all ocular injury (47.8%), so the potential for serious visual loss as the result of a sports injury should not be underrated. Ophthalmologists have a role in protecting this young population at risk by actively encouraging the design and use of protective eyewear. Key Words: eye injury; ocular trauma; hyphaema; protective eyewear PMID:11131235

Defining the cause of skewed X-chromosome inactivation in X-linked mental retardation by use of a mouse model.

PubMed

Muers, Mary R; Sharpe, Jacqueline A; Garrick, David; Sloane-Stanley, Jacqueline; Nolan, Patrick M; Hacker, Terry; Wood, William G; Higgs, Douglas R; Gibbons, Richard J

2007-06-01

Extreme skewing of X-chromosome inactivation (XCI) is rare in the normal female population but is observed frequently in carriers of some X-linked mutations. Recently, it has been shown that various forms of X-linked mental retardation (XLMR) have a strong association with skewed XCI in female carriers, but the mechanisms underlying this skewing are unknown. ATR-X syndrome, caused by mutations in a ubiquitously expressed, chromatin-associated protein, provides a clear example of XLMR in which phenotypically normal female carriers virtually all have highly skewed XCI biased against the X chromosome that harbors the mutant allele. Here, we have used a mouse model to understand the processes causing skewed XCI. In female mice heterozygous for a null Atrx allele, we found that XCI is balanced early in embryogenesis but becomes skewed over the course of development, because of selection favoring cells expressing the wild-type Atrx allele. Unexpectedly, selection does not appear to be the result of general cellular-viability defects in Atrx-deficient cells, since it is restricted to specific stages of development and is not ongoing throughout the life of the animal. Instead, there is evidence that selection results from independent tissue-specific effects. This illustrates an important mechanism by which skewed XCI may occur in carriers of XLMR and provides insight into the normal role of ATRX in regulating cell fate.

Ocular anatomy in medieval arabic medicine. A review.

PubMed

Laios, Konstantinos; Moschos, Marilita M; George, Androutsos

2016-01-01

In medieval Arabic medicine Ophthalmology had a central role. Ocular anatomy was described in many ophthalmological treatises of the physicians of the time. These physicians followed the doctrines of Galen according ocular anatomy, nevertheless their contribution to the history of ocular anatomy was the presentation of ocular anatomical sketches in their manuscripts for the fist time in medical history.

A challenging case of ocular melanoma.

PubMed

Costache, Mariana; Dumitru, Adrian Vasile; Pătraşcu, Oana Maria; Popa-Cherecheanu, Daniela Alina; Bădilă, Patricia; Miu, Jeni Cătălina; Procop, Alexandru; Popa, Manuela; Tampa, Mircea Ştefan; Sajin, Maria; Simionescu, Olga; Cîrstoiu, Monica Mihaela

2015-01-01

Ocular melanoma is a rare malignancy found in clinical practice. In this paper, we present a case of highly aggressive ocular melanoma, which was surgically removed at the Department of Ophthalmology and diagnosed at the Department of Pathology, Emergency University Hospital, Bucharest, Romania, using conventional histopathological techniques. Uveal melanoma, a subset of ocular melanoma, has a distinct behavior in comparison to cutaneous melanoma and has a widely divergent prognosis. Approximately half of patients with ocular melanoma will develop metastatic disease, predominantly with hepatic, pulmonary or cerebral location, over a 10 to 15 years period. No systemic therapy was associated with an evident clinical outcome for patients with advanced disease and overall survival rate remains poor.

Effect of the Age Cross-Link Breaker Alagebrium on Anterior Segment Physiology, Morphology, and Ocular Age and Rage

PubMed Central

Kiland, Julie A.; Gabelt, B’Ann T.; Tezel, Gülgün; Lütjen-Drecoll, Elke; Kaufman, Paul L.

2009-01-01

Purpose: To determine the effects of the advanced glycation end product (AGE) cross-link breaker alagebrium on intraocular pressure (IOP), accommodation (ACC), outflow facility (OF), anterior segment morphology, and ocular AGE and receptors for AGE (RAGE) in older rhesus monkeys. Methods: Six rhesus monkeys (aged 19 to 20 years) received 3 or 4 intracameral and intravitreal (final concentration, 1 mM) injections of alagebrium to one eye over 2.5 to 3 weeks and vehicle to the opposite eye. ACC and OF responses to intramuscular or intravenous pilocarpine were measured at baseline and at 1 to 2 weeks and 2, 4, and 6 months postinjection. IOP was measured prior to all injections, ACC, and OF measurements. Monkeys were euthanized 3 to 6 months after the last injection, the eyes were enucleated, and anterior and posterior segments were examined by electron microscopy or immunohistochemistry. Results: No significant differences were found in ACC or IOP at any time point after alagebrium treatment. Baseline OF was higher (37.0 ± 6.0%; P ≤ .005) in alagebrium-treated vs control eyes at 6 months postinjection. In 3 monkeys, alagebrium-treated eyes, compared to control eyes, showed greater focal plaque formation, similar to that seen in primary open-angle glaucoma, in the juxtacanalicular meshwork/inner wall of Schlemm’s canal. No changes in anterior segment AGE or RAGE were detectable. However, some areas of the retina and optic nerve head exhibited decreased AGE and increased RAGE immunostaining. Conclusions: Intraocular injection of AGE cross-link breakers is an unlikely approach for glaucoma therapy. However, it may generate a model for further study of glaucomatous-like plaque formation. Immunohistochemical changes in the posterior segment in response to alagebrium warrant further functional studies. PMID:20126491

Ocular myasthenia gravis: A review

PubMed Central

Nair, Akshay Gopinathan; Patil-Chhablani, Preeti; Venkatramani, Devendra V; Gandhi, Rashmin Anilkumar

2014-01-01

Myasthenia gravis (MG) is a disease that affects the neuro-muscular junction resulting in classical symptoms of variable muscle weakness and fatigability. It is called the great masquerader owing to its varied clinical presentations. Very often, a patient of MG may present to the ophthalmologist given that a large proportion of patients with systemic myasthenia have ocular involvement either at presentation or during the later course of the disease. The treatment of ocular MG involves both the neurologist and ophthalmologist. Thus, the aim of this review was to highlight the current diagnosis, investigations, and treatment of ocular MG. PMID:25449931

X-linked recessive primary retinal dysplasia is linked to the Norrie disease locus.

PubMed

Ravia, Y; Braier-Goldstein, O; Bat-Miriam, K M; Erlich, S; Barkai, G; Goldman, B

1993-08-01

X-linked primary retinal dysplasia (PRD) refers to an abnormal proliferation of retinal tissue causing either its neural elements or its glial tissue to form folds, giving rise to gliosis. A Jewish family of oriental origin was previously reported by Godel and Goodman, in which a total of five males suffer from different degrees of blindness. The authors postulated that the described findings are distinguished from Norrie disease, since in this case no clinical findings, other than those associated with the eyes, were noticed in the affected males. In addition, two of the carrier females exhibit minimal eye changes. We have performed linkage analysis of the family using the L1.28, p58-1 and m27 beta probes, and DXS426 and MAOB associated microsatellites. Our results map the gene responsible for the disorder between the MAOB and DXS426, m27 beta and p58-1 loci, on the short arm of the X chromosome at Xp11.3, which suggest the possibility that the same gene is responsible for both primary retinal dysplasia and Norrie disease.

Congenital cataracts and other abnormalities in a female with 46.X, del(X)(q26q28)mat: A new locus for X-linked congenital cataract?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Babul, R.; Chitayat, D.; Teshima, I.

1994-09-01

Three forms of X-linked congenital cataracts have been delineated: congenital cataract with posterior Y-sutural opacities in heterozygotes, congenital cataract and microcornea or microphthalmia and congenital cataract-dental syndrome (Nance-Horan syndrome). Of these, only the Nance-Horan syndrome has been mapped to Xp22.3-p21.1. However, Warburg has suggested that these different forms of X-linked congenital cataracts are due to deletions of varying sizes, placing them in the vicinity of the Nance-Horan syndrome region. We report on a female patient born to a 29-year-old primigravida woman who at birth was found to have hypotonia, dysmorphic facial features, hydrocephalus and dense white congenital bilateral cataracts. Othermore » ophthalmological findings included bilateral nystagmus and shallow orbits. Chromosome analysis revealed 46,X,del(X)(q26q28)mat. The mother, however, is phenotypically normal. Brain CT scan on the female infant revealed communicating hydrocephalus and a muscle biopsy showed congenital muscle fiber disproportion. An EMG and NCV were normal. At 4 years of age, her height and weight were below -3SD and her OFC was +2SD. Molecular studies using DNA markers located in Xq26-qter have revealed that the proximal breakpoint in the patient and her mother is defined by the HPRT locus while the distal breakpoint is defined by the locus DXS1108. This indicates that the deletion is not terminal but rather interstitial, retaining sequences proximal to the telomeric region. Other molecular studies are in progress to determine the X-inactivation status of the deleted chromosome in our patient and her mother as a possible explanation for the variation in the phenotype. These clinical and molecular findings suggest that another locus for X-linked congenital cataract exists at Xq26-28.« less

X-linked juvenile retinoschisis in females and response to carbonic anhydrase inhibitors: case report and review of the literature.

PubMed

Ali, Syed; Seth, Rajeev

2013-01-01

A 63 year old woman was referred to the retina clinic after her vision failed to improve in her left eye after cataract surgery. X-linked retinoschisis was diagnosed in the patient after her retina exam revealed an area of retinoschisis and a foveal cyst. The OCT confirmed the macular cyst and the ERG showed loss of B waves. The florescein angiogram showed no significant perifoveal leakage. Her foveal cyst resolved after treatment with carbonic anhydrase inhibitors. The patient's son was examined and his ophthalmologic exam, ERG and imaging findings were consistent with X-linked retinoschisis. However, his bilateral foveal cysts did not respond to treatment with carbonic anhydrase inhibitors. X-linked retinoschisis is a very rare disease in women due to its X-linked recessive inheritance and the foveal cysts associated with it can respond to carbonic anhydrase inhibitors.

[X-linked adrenoleukodystrophy: a report of three cases. The importance of early diagnosis].

PubMed

López Úbeda, Marta; de Arriba Muñoz, Antonio; Ferrer Lozano, Marta; Labarta Aizpún, José I; García Jiménez, María C

2017-10-01

X-linked adrenoleukodystrophy is the most common peroxisomal disorder. This disease is caused by a defect in the ABCD1 gen. Saturated very long chain fatty acids are accumulated in serum, adrenal cortex and central nervous system white matter. The clinical spectrum is characterized by progressive neurological dysfunction and adrenal insufficiency with a devastating prognosis. We report a first case of X-linked adrenoleukodystrophy with fatal evolution which identified two asymptomatic family members and established a preventive treatment. Although there is no definitive cure, we stress the importance of family study and evaluation of the individual in situation of risk to establish an early preventive treatment and to give in each particular situation suitable professional advice. Sociedad Argentina de Pediatría.

Patulous Subarachnoid Space of the Optic Nerve Associated with X-Linked Hypophosphatemic Rickets.

PubMed

Galvez-Ruiz, Alberto; Chaudhry, Imtiaz

2013-01-01

Although the deficiency forms are the most common manifestations of rickets, there are other forms of rickets that are resistant to vitamin D. Of these, the most common is X-linked hypophosphatemic rickets. Rickets represents a group of multiple cranial bone disorders-craniosynostosis and the presence of Chari I malformation being the most notable-that explain the increase in intracranial pressure. We present a 4-year-old patient with an unusual association of X-linked hypophosphataemic rickets, bilateral proptosis, and prominent bilateral widening of the optic nerve sheaths. Although the association between intracranial hypertension and rickets is known, to the best of our knowledge, such a prominent distention of the subarachnoid space of the optic nerve without papilloedema has not been previously described.

Ocular Tropism of Respiratory Viruses

PubMed Central

Rota, Paul A.; Tumpey, Terrence M.

2013-01-01

SUMMARY Respiratory viruses (including adenovirus, influenza virus, respiratory syncytial virus, coronavirus, and rhinovirus) cause a broad spectrum of disease in humans, ranging from mild influenza-like symptoms to acute respiratory failure. While species D adenoviruses and subtype H7 influenza viruses are known to possess an ocular tropism, documented human ocular disease has been reported following infection with all principal respiratory viruses. In this review, we describe the anatomical proximity and cellular receptor distribution between ocular and respiratory tissues. All major respiratory viruses and their association with human ocular disease are discussed. Research utilizing in vitro and in vivo models to study the ability of respiratory viruses to use the eye as a portal of entry as well as a primary site of virus replication is highlighted. Identification of shared receptor-binding preferences, host responses, and laboratory modeling protocols among these viruses provides a needed bridge between clinical and laboratory studies of virus tropism. PMID:23471620

Seasonal and diurnal variations of ocular pressure in ocular hypertensive subjects in Pakistan.

PubMed

Qureshi, I A; Xiao, R X; Yang, B H; Zhang, J; Xiang, D W; Hui, J L

1999-05-01

Studies have been shown that intraocular pressure (IOP) shows a diurnal variation in ocular hypertensive subjects, but the amount of change differs from study to study. In recent years it has been noted that intraocular pressure is a dynamic function and is subjected to many influences both acutely and over the long term. The variability in the results may be due to negligence of factors that can affect IOP. Moreover, seasonal variations in the ocular hypertensive subjects have never been described. After placing control on those factors that can affect IOP, this study investigated seasonal and diurnal variations in IOP of ocular hypertensive subjects. IOP was measured each month over the course of 12 months with the Goldmann applanation tonometer in 91 ocular hypertensive male subjects. To see the diurnal changes, subjects were asked to stay in the hospital for 24 hours. The average IOP in the winter months was higher than those in spring, summer, and autumn. The IOP difference between winter and summer was (mean +/- sem) 2.9 +/- 0.9 mmHg (p < 0.001). The peak of mean IOP in diurnal variation curve (25.7 +/- 1.2 mmHg) appeared in the morning when the subjects had just awaken. The mean diurnal variation was found to be 4.2 +/- 0.6 mmHg (p < 0.001). This study confirms that seasons influence IOP and it shows diurnal variations. As compared to other nations, diurnal variations in ocular hypertensive subjects seem to be somewhat less in Pakistan. Knowledge of the seasonal and diurnal variations in IOP may help glaucoma screeners.

Temporal dynamics of ocular position dependence of the initial human vestibulo-ocular reflex.

PubMed

Crane, Benjamin T; Tian, Junru; Demer, Joseph L

2006-04-01

While an ideal vestibulo-ocular reflex (VOR) generates ocular rotations compensatory for head motion, during visually guided movements, Listing's Law (LL) constrains the eye to rotational axes lying in Listing's Plane (LP). The present study was conducted to explore the recent proposal that the VOR's rotational axis is not collinear with the head's, but rather follows a time-dependent strategy intermediate between LL and an ideal VOR. Binocular LPs were defined during visual fixation in eight normal humans. The VOR was evoked by a highly repeatable transient whole-body yaw rotation in darkness at a peak acceleration of 2800 deg/s2. Immediately before rotation, subjects regarded targets 15 or 500 cm distant located at eye level, 20 degrees up, or 20 degrees down. Eye and head responses were compared with LL predictions in the position and velocity domains. LP orientation varied both among subjects and between individual subject's eyes, and rotated temporally with convergence by 5 +/- 5 degrees (+/-SEM). In the position domain, the eye compensated for head displacement even when the head rotated out of LP. Even within the first 20 ms from onset of head rotation, the ocular velocity axis tilted relative to the head axis by 30% +/- 8% of vertical gaze position. Saccades increased this tilt. Regardless of vertical gaze position, the ocular rotation axis tilted backward 4 degrees farther in abduction than in adduction. There was also a binocular vertical eye velocity transient and lateral tilt of the ocular axis. These disconjugate, short-latency axis perturbations appear intrinsic to the VOR and may have neural or mechanical origins.

Experimental Models of Ocular Infection with Toxoplasma Gondii

PubMed Central

Dukaczewska, Agata; Tedesco, Roberto; Liesenfeld, Oliver

2015-01-01

Ocular toxoplasmosis is a vision-threatening disease and the major cause of posterior uveitis worldwide. In spite of the continuing global burden of ocular toxoplasmosis, many critical aspects of disease including the therapeutic approach to ocular toxoplasmosis are still under debate. To assist in addressing many aspects of the disease, numerous experimental models of ocular toxoplasmosis have been established. In this article, we present an overview on in vitro, ex vivo, and in vivo models of ocular toxoplasmosis available to date. Experimental studies on ocular toxoplasmosis have recently focused on mice. However, the majority of murine models established so far are based on intraperitoneal and intraocular infection with Toxoplasma gondii. We therefore also present results obtained in an in vivo model using peroral infection of C57BL/6 and NMRI mice that reflects the natural route of infection and mimics the disease course in humans. While advances have been made in ex vivo model systems or larger animals to investigate specific aspects of ocular toxoplasmosis, laboratory mice continue to be the experimental model of choice for the investigation of ocular toxoplasmosis. PMID:26716018

Republished review: Gene therapy for ocular diseases.

PubMed

Liu, Melissa M; Tuo, Jingsheng; Chan, Chi-Chao

2011-07-01

The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. After nearly two decades of ocular gene therapy research, preliminary successes are now being reported in phase 1 clinical trials for the treatment of Leber congenital amaurosis. This review describes current developments and future prospects for ocular gene therapy. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus- and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma. These methodological advancements are critical for the implementation of additional gene-based therapies for human ocular diseases in the near future.

Retinal detachment 7 years after prophylactic schisis cavity excision in juvenile X-linked retinoschisis.

PubMed

Sobrin, Lucia; Berrocal, Audina M; Murray, Timothy G

2003-01-01

A 7-year-old boy with X-linked juvenile retinoschisis developed a retinal detachment at the site of previous prophylactic excision of a schisis cavity. The patient underwent a scleral buckle procedure, pars plana vitrectomy, membrane peel, and silicone oil injection with successful reattachment. At last follow-up, the visual acuity was 20/400 and the retina was attached. Prophylactic excision of a schisis cavity may be complicated by retinal detachment several years after the surgery. Given the favorable natural history of schisis cavities in X-linked juvenile retinoschisis, the decision to perform prophylactic excision should be undertaken cautiously after full consideration of the potential complications.

Air bags and ocular injuries.

PubMed

Stein, J D; Jaeger, E A; Jeffers, J B

1999-01-01

This investigation retrospectively examined ocular injuries associated with air bag deployment to gain a better appreciation of potential risk factors in motor vehicle accidents. National statistics regarding the efficacy of air bags were reviewed. Review of the literature from 1991 to 1998 identified 44 articles describing 97 patients with air-bag-induced ocular injuries. Variables extracted from each case were age, sex, height, position in the car, eye wear, vehicle impact speed, visual acuity, and specific ocular injuries. Corneal abrasions occurred in 49% of occupants, hyphemas in 43%, vitreous or retinal hemorrhages in 25%, and retinal tears or detachments in 15%. The globe was ruptured in 10 patients. Patients involved in higher-speed accidents (over 30 mph) sustained a greater percentage of vitreous or retinal hemorrhages and traumatic cataracts, while those at slower speeds were more prone to retinal tears or detachments. In a subset of 14 patients with serious ocular injuries, the impact speed of 11 patients was recorded at 30 mph or less. Slower speed may be a risk factor for some ocular injuries. Occupant height was not a significant factor. National statistics confirm that air bags reduce fatalities in motor vehicle accidents. However, children sitting in the front seat without a seat belt and infants in passenger-side rear-facing car seats are at risk for fatal injury. Air bags combined with seat belts are an effective means of reducing injury and death in adults during motor vehicle accidents. However, this study has documented a wide variety of ocular injuries associated with air bag deployment. It is hoped that researchers can develop modifications that continue to save lives while minimizing additional harm.

Autosomal Genes of Autosomal/X-Linked Duplicated Gene Pairs and Germ-Line Proliferation in Caenorhabditis elegans

PubMed Central

Maciejowski, John; Ahn, James Hyungsoo; Cipriani, Patricia Giselle; Killian, Darrell J.; Chaudhary, Aisha L.; Lee, Ji Inn; Voutev, Roumen; Johnsen, Robert C.; Baillie, David L.; Gunsalus, Kristin C.; Fitch, David H. A.; Hubbard, E. Jane Albert

2005-01-01

We report molecular genetic studies of three genes involved in early germ-line proliferation in Caenorhabditis elegans that lend unexpected insight into a germ-line/soma functional separation of autosomal/X-linked duplicated gene pairs. In a genetic screen for germ-line proliferation-defective mutants, we identified mutations in rpl-11.1 (L11 protein of the large ribosomal subunit), pab-1 [a poly(A)-binding protein], and glp-3/eft-3 (an elongation factor 1-α homolog). All three are members of autosome/X gene pairs. Consistent with a germ-line-restricted function of rpl-11.1 and pab-1, mutations in these genes extend life span and cause gigantism. We further examined the RNAi phenotypes of the three sets of rpl genes (rpl-11, rpl-24, and rpl-25) and found that for the two rpl genes with autosomal/X-linked pairs (rpl-11 and rpl-25), zygotic germ-line function is carried by the autosomal copy. Available RNAi results for highly conserved autosomal/X-linked gene pairs suggest that other duplicated genes may follow a similar trend. The three rpl and the pab-1/2 duplications predate the divergence between C. elegans and C. briggsae, while the eft-3/4 duplication appears to have occurred in the lineage to C. elegans after it diverged from C. briggsae. The duplicated C. briggsae orthologs of the three C. elegans autosomal/X-linked gene pairs also display functional differences between paralogs. We present hypotheses for evolutionary mechanisms that may underlie germ-line/soma subfunctionalization of duplicated genes, taking into account the role of X chromosome silencing in the germ line and analogous mammalian phenomena. PMID:15687263

Ocular complications of diabetes mellitus

PubMed Central

Sayin, Nihat; Kara, Necip; Pekel, Gökhan

2015-01-01

Diabetes mellitus (DM) is a important health problem that induces ernestful complications and it causes significant morbidity owing to specific microvascular complications such as, retinopathy, nephropathy and neuropathy, and macrovascular complications such as, ischaemic heart disease, and peripheral vasculopathy. It can affect children, young people and adults and is becoming more common. Ocular complications associated with DM are progressive and rapidly becoming the world’s most significant cause of morbidity and are preventable with early detection and timely treatment. This review provides an overview of five main ocular complications associated with DM, diabetic retinopathy and papillopathy, cataract, glaucoma, and ocular surface diseases. PMID:25685281

Genetic Testing for Oculocutaneous Albinism Type 1 and 2 and Hermansky–Pudlak Syndrome Type 1 and 3 Mutations in Puerto Rico

PubMed Central

Santiago Borrero, Pedro J.; Rodríguez-Pérez, Yolanda; Renta, Jessicca Y.; Izquierdo, Natalio J.; del Fierro, Laura; Muñoz, Daniel; Molina, Norma López; Ramírez, Sonia; Pagán-Mercado, Glorivee; Ortíz, Idith; Rivera-Caragol, Enid; Spritz, Richard A.; Cadilla, Carmen L.

2013-01-01

Hermansky–Pudlak syndrome (HPS) (MIM #203300) is a heterogeneous group of autosomal recessive disorders characterized by oculocutaneous albinism (OCA), bleeding tendency, and lysosomal dysfunction. HPS is very common in Puerto Rico (PR), particularly in the northwest part of the island, with a frequency of ~1:1,800. Two HPS genes and mutations have been identified in PR, a 16-base pair (bp) duplication in HPS1 and a 3,904-bp deletion in HPS3. In Puerto Ricans with more typical OCA, the most common mutation of the tyrosinase (TYR) (human tyrosinase (OCA1) gene) gene was G47D. We describe screening 229 Puerto Rican OCA patients for these mutations, and for mutations in the OCA2 gene. We found the HPS1 mutation in 42.8% of cases, the HPS3 deletion in 17%, the TYR G47D mutation in 3.0%, and a 2.4-kb deletion of the OCA2 gene in 1.3%. Among Puerto Rican newborns, the frequency of the HPS1 mutation is highest in northwest PR (1:21; 4.8%) and lower in central PR (1:64; 1.6%). The HPS3 gene deletion is most frequent in central PR (1:32; 3.1%). Our findings provide insights into the genetics of albinism and HPS in PR, and provide the basis for genetic screening for these disorders in this minority population. PMID:16417222

Surfing-related ocular injuries.

PubMed

Kim, J W; McDonald, H R; Rubsamen, P E; Luttrull, J K; Drouilhet, J H; Frambach, D A; Boyer, D S; Lambrou, F H; Hendrick, A; Weiss, J N; Engstrom, R E; Ing, M

1998-01-01

This report evaluates the clinical characteristics of surfing-related ocular trauma to learn the nature of such injuries and propose possible preventive measures. The authors reviewed 11 cases of surfing-related eye injuries caused by direct trauma from the surfboard, studying their mechanism of injury, the associated ocular complications, and the anatomic and visual outcomes of surgical repair. Surfing-related ocular injuries occurred exclusively in young males (mean age, 24.8 years; range, 14-37 years). The mechanism of injury most frequently responsible was impact with the sharp nose of the surfboard following a fall. Serious posterior segment complications were observed in all 11 patients, with nine patients suffering ruptured globes. Despite immediate medical attention, five patients did not recover ambulatory levels of visual acuity (>5/200). Surfing-related ocular trauma presenting to the retinal specialist typically leaves the patient with a permanent visual disability. Important factors contributing to these high-velocity injuries include the sharply pointed nose of the surfboard and the leash keeping the surfer in close proximity to the board following a fall. A simple modification in surfboard design such as blunting the sharp nose of the surfboard, or appropriate protective guards fitted over the surfboard nose, should lessen the severity of such injuries.

A case report of an unusual presentation of ocular rhinosporidiosis as a conjunctival cystic mass.

PubMed

Shah, Sangeeta; Lavaju, Poonam; Bharati, Priyanka; Joshi, Icchya

2017-02-01

Ocular involvement of rhinosporidiosis is seen in about 15% of cases and clinically appears as a freely mobile, granular, pink, fleshy sessile or pedunculated mass. The conjunctiva is the most common site of origin. A 25-year-old male presented with a painless mass in the lower part of the left eye for 6 months which was gradually progressive. Examination revealed a pedunculated mass of 15 mm x 15 mm arising from the lower palpebrae of the left eye retracting the lower lid. It appeared to be vascular with few white spots at the apex. Rest of the ocular examinations was within the normal limit. The presentations of ocular rhinosporidiosis vary. Though the conjunctival origin is very common, it may not have a classic pink fleshy appearance at all times. A vascular/cystic painless conjunctival mass should also be considered as a case of rhinosporidiosis in prone areas.

A novel mutation in FRMD7 causing X-linked idiopathic congenital nystagmus in a large family

PubMed Central

He, Xiang; Gu, Feng; Wang, Yujing; Yan, Jinting; Zhang, Meng; Huang, Shangzhi

2008-01-01

Purpose To identify the gene responsible for causing an X-linked idiopathic congenital nystagmus (XLICN) in a six-generation Chinese family. Methods Forty-nine members of an XLICN family were recruited and examined after obtaining informed consent. Affected male individuals were genotyped with microsatellite markers around the FRMD7 locus. Mutations were comprehensively screened by direct sequencing using gene specific primers. An X-inactivation pattern was investigated by X chromosome methylation analysis. Results The patients showed phenotypes consistent with XLICN. Genotype analysis showed that male affected individuals in the family shared a common haplotype with the selected markers. Sequencing FRMD7 revealed a G>T transversion (c.812G>T) in exon 9, which caused a conservative substitution of Cys to Phe at codon 271 (p.C271F). This mutation co-segregated with all affected individuals and was present in the obligate, non-penetrant female carriers. However, the mutation was not observed in unaffected familial males or 400 control males. Females with the mutant gene could be affected or carrier and they shared the same inactivated X chromosome harboring the mutation in blood cells, which showed there is no clear causal link between X-inactivation pattern and phenotype. Conclusions We identified a novel mutation in FRMD7 and confirmed the role of this mutation in the pathogenesis of X-linked congenital nystagmus. PMID:18246032

Temporal dynamics of 2D motion integration for ocular following in macaque monkeys.

PubMed

Barthélemy, Fréderic V; Fleuriet, Jérome; Masson, Guillaume S

2010-03-01

Several recent studies have shown that extracting pattern motion direction is a dynamical process where edge motion is first extracted and pattern-related information is encoded with a small time lag by MT neurons. A similar dynamics was found for human reflexive or voluntary tracking. Here, we bring an essential, but still missing, piece of information by documenting macaque ocular following responses to gratings, unikinetic plaids, and barber-poles. We found that ocular tracking was always initiated first in the grating motion direction with ultra-short latencies (approximately 55 ms). A second component was driven only 10-15 ms later, rotating tracking toward pattern motion direction. At the end the open-loop period, tracking direction was aligned with pattern motion direction (plaids) or the average of the line-ending motion directions (barber-poles). We characterized the dependency on contrast of each component. Both timing and direction of ocular following were quantitatively very consistent with the dynamics of neuronal responses reported by others. Overall, we found a remarkable consistency between neuronal dynamics and monkey behavior, advocating for a direct link between the neuronal solution of the aperture problem and primate perception and action.

Microsatellites within the feline androgen receptor are suitable for X chromosome-linked clonality testing in archival material.

PubMed

Farwick, Nadine M; Klopfleisch, Robert; Gruber, Achim D; Weiss, Alexander Th A

2017-04-01

Objectives A hallmark of neoplasms is their origin from a single cell; that is, clonality. Many techniques have been developed in human medicine to utilise this feature of tumours for diagnostic purposes. One approach is X chromosome-linked clonality testing using polymorphisms of genes encoded by genes on the X chromosome. The aim of this study was to determine if the feline androgen receptor gene was suitable for X chromosome-linked clonality testing. Methods The feline androgen receptor gene was characterised and used to test clonality of feline lymphomas by PCR and polyacrylamide gel electrophoresis, using archival formalin-fixed, paraffin-embedded material. Results Clonality of the feline lymphomas under study was confirmed and the gene locus was shown to represent a suitable target in clonality testing. Conclusions and relevance Because there are some pitfalls of using X chromosome-linked clonality testing, further studies are necessary to establish this technique in the cat.

Emerging treatment paradigms of ocular surface disease: proceedings of the Ocular Surface Workshop.

PubMed

Rolando, M; Geerling, G; Dua, H S; Benítez-del-Castillo, J M; Creuzot-Garcher, C

2010-01-01

The objective of the Ocular Surface Workshop in Rome, Italy, on 6 February 2009, was to enhance the understanding of ocular surface disease (OSD) through an exploration of the nature of its complexities and current treatment paradigms across Europe. It was hoped that the peer-to-peer discussions and updates regarding common knowledge, clinical practices and shared experiences at this workshop would subsequently shape future treatment approaches to OSD.

X-linked agammaglobulinemia in northern Thailand.

PubMed

Trakultivakorn, Muthita; Ochs, Hans D

2006-03-01

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency characterized by a failure to generate immunoglobulins of all isotypes due to the absence of mature B cells and plasma cells, secondary to mutations in the Bruton's tyrosine kinase (Btk) gene. We report six patients with XLA, confirmed by mutation analysis, from northern Thailand. The mean age of onset was 2.5 years and the mean age at diagnosis was 7.3 years. All patients had a history of otitis media, pneumonia and arthritis at the time of diagnosis, five patients had developed bronchiectasis and 3 patients septicemia. Other infections reported included sinusitis (5/6), pericarditis (1/6), meningitis (1/6) and pyoderma (1/6). Haemophilus influenzae, Streptococcus pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus were isolated on multiple occasions. One patient died of sepsis at the age of 16 years. These observations demonstrate that early diagnosis and treatment can improve prognosis and quality of life.

Interfacial Interaction between Transmembrane Ocular Mucins and Adhesive Polymers and Dendrimers Analyzed by Surface Plasmon Resonance

PubMed Central

Noiray, M.; Briand, E.; Woodward, A. M.; Argüeso, P.; Molina Martínez, I. T.; Herrero-Vanrell, R.; Ponchel, G.

2013-01-01

Purpose Development of the first in vitro method based on biosensor chip technology designed for probing the interfacial interaction phenomena between transmembrane ocular mucins and adhesive polymers and dendrimers intended for ophthalmic administration. Methods The surface plasmon resonance (SPR) technique was used. A transmembrane ocular mucin surface was prepared on the chip surface and characterized by QCM-D (Quartz Crystal Microbalance with Dissipation) and XPS (X-ray photoelectron spectroscopy). The mucoadhesive molecules tested were: hyaluronic acid (HA), carboxymethyl cellulose (CMC), hydroxypropylmethyl cellulose (HPMC), chitosan (Ch) and polyamidoamine dendrimers (PAMAM). Results While Ch originated interfacial interaction with ocular transmembrane mucins, for HA, CMC and HPMC, chain interdiffusion seemed to be mandatory for bioadherence at the concentrations used in ophthalmic clinical practise. Interestingly, PAMAM dendrimers developed permanent interfacial interactions with transmembrane ocular mucins whatever their surface chemical groups, showing a relevant importance of co-operative effect of these multivalent systems. Polymers developed interfacial interactions with ocular membrane-associated mucins in the following order: Ch(1 %) > G4PAMAM-NH2(2 %) = G4PAMAM-OH(2 %) > G3.5PAMAM-COOH(2 %)≫ CMC(0.5 %) = HA(0.2 %) = HPMC(0.3 %). Conclusions The method proposed is useful to discern between the mucin-polymer chemical interactions at molecular scale. Results reinforce the usefulness of chitosan and den-drimers as polymers able to increase the retention time of drugs on the ocular surface and hence their bioavailability. PMID:22565639

Influence of refractive correction on ocular dominance

NASA Astrophysics Data System (ADS)

Nakayama, Nanami; Kawamorita, Takushi; Uozato, Hiroshi

2010-07-01

We investigated the effects of refractive correction and refractive defocus on the assessment of sensory ocular dominance. In 25 healthy subjects (4 males and 21 females) aged between 20 and 31 years, a quantitative measurement of sensory ocular dominance was performed with refractive correction and the addition of a positive lens on the dominant eye. Sensory ocular dominance was measured with a chart using binocular rivalry targets. The reversal point changed after the addition of a +1.00 D lens on the dominant eye in all subjects. However, sighting ocular dominance and stereopsis did not change after the addition of a positive lens on the dominant eye ( P > 0:05, Wilcoxon test). These results suggest that refractive correction affects sensory ocular dominance, indicating the possible development of a new type of occlusion for amblyopia in the future.

Nanocrystal for ocular drug delivery: hope or hype.

PubMed

Sharma, Om Prakash; Patel, Viral; Mehta, Tejal

2016-08-01

The complexity of the structure and nature of the eye emanates a challenge for drug delivery to formulation scientists. Lower bioavailability concern of conventional ocular formulation provokes the interest of researchers in the development of novel drug delivery system. Nanotechnology-based formulations have been extensively investigated and found propitious in improving bioavailability of drugs by overcoming ocular barriers prevailing in the eye. The advent of nanocrystals helped in combating the problem of poorly soluble drugs specifically for oral and parenteral drug delivery and led to development of various marketed products. Nanocrystal-based formulations explored for ocular drug delivery have been found successful in achieving increase in retention time, bioavailability, and permeability of drugs across the corneal and conjunctival epithelium. In this review, we have highlighted the ocular physiology and barriers in drug delivery. A comparative analysis of various nanotechnology-based ocular formulations is done with their pros and cons. Consideration is also given to various methods of preparation of nanocrystals with their patented technology. This article highlights the success achieved in conquering various challenges of ocular delivery by the use of nanocrystals while emphasizing on its advantages and application for ocular formulation. The perspectives of nanocrystals as an emerging flipside to explore the frontiers of ocular drug delivery are discussed.

Temporal Dynamics of Ocular Position Dependence of the Initial Human Vestibulo-ocular Reflex

PubMed Central

Crane, Benjamin T.; Tian, Junru; Demer, Joseph L.

2007-01-01

Purpose While an ideal vestibulo-ocular reflex (VOR) generates ocular rotations compensatory for head motion, during visually guided movements, Listing’s Law (LL) constrains the eye to rotational axes lying in Listing’s Plane (LP). The present study was conducted to explore the recent proposal that the VOR’s rotational axis is not collinear with the head’s, but rather follows a time-dependent strategy intermediate between LL and an ideal VOR. Methods Binocular LPs were defined during visual fixation in eight normal humans. The VOR was evoked by a highly repeatable transient whole-body yaw rotation in darkness at a peak acceleration of 2800 deg/s2. Immediately before rotation, subjects regarded targets 15 or 500 cm distant located at eye level, 20° up, or 20° down. Eye and head responses were compared with LL predictions in the position and velocity domains. Results LP orientation varied both among subjects and between individual subject’s eyes, and rotated temporally with convergence by 5 ± 5° (±SEM). In the position domain, the eye compensated for head displacement even when the head rotated out of LP. Even within the first 20 ms from onset of head rotation, the ocular velocity axis tilted relative to the head axis by 30% ± 8% of vertical gaze position. Saccades increased this tilt. Regardless of vertical gaze position, the ocular rotation axis tilted backward 4° farther in abduction than in adduction. There was also a binocular vertical eye velocity transient and lateral tilt of the ocular axis. Conclusions These disconjugate, short-latency axis perturbations appear intrinsic to the VOR and may have neural or mechanical origins. PMID:16565376

Quality of life in purely ocular myasthenia in Japan

PubMed Central

2014-01-01

Background Since there has been no conclusive evidence regarding the treatment of ocular myasthenia, treatment guidelines were recently issued by the European Federation of Neurological Societies/European Neurological Society (EFNS/ENS). However, the therapeutic outcomes concerning the quality-of-life (QOL) of patients with ocular myasthenia are not yet fully understood. Methods We investigated the therapeutic outcomes of patients with purely ocular myasthenia in a multicenter cross-sectional survey in Japan. To evaluate the severity of ocular symptoms, we used the ocular-quantitative MG (QMG) score advocated by Myasthenia Gravis Foundation of America. We used the Japanese translated version of the MG-QOL15, a self-appraised scoring system. Results Of 607 myasthenia gravis (MG) patients with an observation-duration of illness ≥ 2 years, the cases of 123 patients (20%) were limited to ocular muscles (purely ocular myasthenia). During the entire clinical course, 81 patients experienced both ptosis and diplopia, 36 had ptosis alone, and six had diplopia alone. Acetyl-cholinesterase inhibitors and prednisolone were used in 98 and 52 patients, respectively. Treatment improved ocular symptoms, with the mean reduction in ocular-QMG score of 2.3 ± 1.8 points. However, 47 patients (38%) failed to gain minimal manifestation or a better status. Patients with unfavorable outcomes also self-reported severe QOL impairment. Multivariate analyses showed that the pretreatment ocular-QMG score was associated with unfavorable outcomes, but not associated with the patient’s QOL. Conclusion A treatment strategy designed in accord with a patient's ocular presentation must be considered in order to improve ocular symptoms and the patient's QOL. PMID:24996227

A CLINICIAN'S GUIDE TO X-LINKED HYPOPHOSPHATEMIA

PubMed Central

Carpenter, Thomas O.; Imel, Erik A.; Holm, Ingrid A.; Jan de Beur, Suzanne M.; Insogna, Karl L.

2011-01-01

X-linked hypophosphatemia (XLH) is the prototypic disorder of renal phosphate wasting, and the most common form of heritable rickets. Physicians, patients, and XLH support groups have all expressed concerns about the dearth of information about this disease and the lack of treatment guidelines which frequently lead to missed diagnoses or mismanagement. This perspective addresses the recommendation by conferees for the dissemination of concise and accessible treatment guidelines for clinicians arising from the “Advances in Rare Bone Diseases Scientific Conference,” held at the National Institutes of Health in October 2008. We briefly review the clinical and pathophysiologic features of the disorder, and offer this guide in response to the conference recommendation, base on our collective accumulated experience in the management of this complex disorder. PMID:21538511

[Ultrasonographic findings in ocular toxocariasis].

PubMed

Morais, Fábio Barreto; Maciel, Ana Lúcia; Arantes, Tiago Eugênio Farias e; Muccioli, Cristina; Allemann, Norma

2012-01-01

To evaluate ophthalmic ultrasound findings in the three presentation forms of ocular toxocariasis (peripheral or posterior pole granulomas and chronic endophthalmitis), in patients with confirmed diagnosis of ocular toxocariasis. 11 patients (11 eyes) with clinical and confirmed diagnosis of active ocular toxocariasis, presented positive ELISA test, were analyzed, prospectively, in the study. The patients were submitted to an ocular ultrasound examination (10-MHz transducer, contact technique). In the series of 11 patients, mean age was 7.9 years-old (range from 2 to 17 y), 73% male, referring previous contact with dogs (91%), and with the soil (50%), no referral of appetite perversion. In the analyses of compromised eyes (11 eyes), the ophthalmoscopic examination revealed the following distribution of the 3 forms of ocular toxocariasis: 7 cases (63.6%), posterior pole granuloma; 1 (9.1%), chronic endophthalmitis; 2 (18.2%), peripheral granuloma; and 1 (9.1%), posterior pole granuloma associated with chronic endophthalmitis. Visual acuity impairment: no light perception (3 eyes, 27.3%); hand motion (4 eyes, 36.4%); counting fingers at 10 cm (1 eye, 9.1%); 20/200 (1 eye, 9.1%); 20/70 (1 eye, 9.1%); undefined (1 eye, 9.1%). Serology was positive to Toxocara canis (ELISA test) in 100% of the cases. Ophthalmoscopy was difficult or impossible in 64% of the cases due to the media opacity. Ultrasound findings noted were vitreous membranes with retinal attachment (100%); parietal lesions (granulomas) with high (80%) or medium (20%) reflectivity. The most consistent ultrasound finding in the eye with toxocariasis was a high-reflectivity retinal mass, located in posterior pole or periphery, which may be calcified, and which has as main characteristic the adherence of vitreous membranes. In addition to clinical history, systemic evaluation and serology, the ultrasound can help in the diagnosis of ocular toxocariasis, especially in media opacities.

Air bags and ocular injuries.

PubMed Central

Stein, J D; Jaeger, E A; Jeffers, J B

1999-01-01

PURPOSE: This investigation retrospectively examined ocular injuries associated with air bag deployment to gain a better appreciation of potential risk factors in motor vehicle accidents. National statistics regarding the efficacy of air bags were reviewed. METHODS: Review of the literature from 1991 to 1998 identified 44 articles describing 97 patients with air-bag-induced ocular injuries. Variables extracted from each case were age, sex, height, position in the car, eye wear, vehicle impact speed, visual acuity, and specific ocular injuries. RESULTS: Corneal abrasions occurred in 49% of occupants, hyphemas in 43%, vitreous or retinal hemorrhages in 25%, and retinal tears or detachments in 15%. The globe was ruptured in 10 patients. Patients involved in higher-speed accidents (over 30 mph) sustained a greater percentage of vitreous or retinal hemorrhages and traumatic cataracts, while those at slower speeds were more prone to retinal tears or detachments. In a subset of 14 patients with serious ocular injuries, the impact speed of 11 patients was recorded at 30 mph or less. Slower speed may be a risk factor for some ocular injuries. Occupant height was not a significant factor. National statistics confirm that air bags reduce fatalities in motor vehicle accidents. However, children sitting in the front seat without a seat belt and infants in passenger-side rear-facing car seats are at risk for fatal injury. CONCLUSION: Air bags combined with seat belts are an effective means of reducing injury and death in adults during motor vehicle accidents. However, this study has documented a wide variety of ocular injuries associated with air bag deployment. It is hoped that researchers can develop modifications that continue to save lives while minimizing additional harm. Images FIGURE 1 FIGURE 2A FIGURE 2B FIGURE 2C FIGURE 2D FIGURE 3A FIGURE 3B FIGURE 4 FIGURE 5 FIGURE 7 FIGURE 8 PMID:10703118

Epidemiological patterns of ocular trauma.

PubMed

Thylefors, B

1992-05-01

Ocular trauma is the cause of blindness in approximately half a million people worldwide, and many more have suffered partial loss of sight. Trauma is often the most important cause of unilateral loss of vision, particularly in developing countries. There is a cumulative risk of ocular trauma and visual loss during life, but the true incidence of accidents involving the eyes is not known. Males tend to have more eye trauma than females, and this is already apparent from childhood; lower socioeconomic classes are also more associated with ocular trauma. The setting for the occurrence of trauma is most commonly the workplace and, increasingly, road accidents. On the other hand, domestic accidents are probably under-reported. Of particular importance in some developing countries is the occurrence of superficial corneal trauma in agricultural work, often leading to rapidly progressing corneal ulceration and visual loss. The impact of ocular trauma, in terms of need for medical care, loss of income and cost of rehabilitation services when indicated, clearly makes the strengthening of preventive measures very worthwhile.

Fatal hepatic hemorrhage by peliosis hepatis in X-linked myotubular myopathy: a case report.

PubMed

Motoki, T; Fukuda, M; Nakano, T; Matsukage, S; Fukui, A; Akiyoshi, S; Hayashi, Y K; Ishii, E; Nishino, I

2013-11-01

We report a 5-year-old boy with X-linked myotubular myopathy complicated by peliosis hepatis. At birth, he was affected with marked generalized muscle hypotonia and weakness, which required permanent ventilatory support, and was bedridden for life. He died of acute fatal hepatic hemorrhage after using a mechanical in-exsufflator. Peliosis hepatis, defined as multiple, variable-sized, cystic blood-filled spaces through the liver parenchyma, was confirmed by autopsy. To avoid fatal hepatic hemorrhage by peliosis hepatis, routine hepatic function tests and abdominal imaging tests should be performed for patients with X-linked myotubular myopathy, especially at the time of using artificial respiration. Copyright © 2013 Elsevier B.V. All rights reserved.

Development of ocular viscosity characterization method.

PubMed

Shu-Hao Lu; Guo-Zhen Chen; Leung, Stanley Y Y; Lam, David C C

2016-08-01

Glaucoma is the second leading cause for blindness. Irreversible and progressive optic nerve damage results when the intraocular pressure (IOP) exceeds 21 mmHg. The elevated IOP is attributed to blocked fluid drainage from the eye. Methods to measure the IOP are widely available, but methods to measure the viscous response to blocked drainage has yet been developed. An indentation method to characterize the ocular flow is developed in this study. Analysis of the load-relaxation data from indentation tests on drainage-controlled porcine eyes showed that the blocked drainage is correlated with increases in ocular viscosity. Successful correlation of the ocular viscosity with drainage suggests that ocular viscosity maybe further developed as a new diagnostic parameter for assessment of normal tension glaucoma where nerve damage occurs without noticeable IOP elevation; and as a diagnostic parameter complimentary to conventional IOP in conventional diagnosis.

Ocular Perfusion Pressure and Pulsatile Ocular Blood Flow in Normal and Systemic Hypertensive Patients.

PubMed

Kanadani, Fabio N; Figueiredo, Carlos R; Miranda, Rafaela Morais; Cunha, Patricia Lt; M Kanadani, Tereza Cristina; Dorairaj, Syril

2015-01-01

Glaucomatous neuropathy can be a consequence of insufficient blood supply, increase in intraocular pressure (IOP), or other risk factors that diminish the ocular blood flow. To determine the ocular perfusion pressure (OPP) in normal and systemic hypertensive patients. One hundred and twenty-one patients were enrolled in this prospective and comparative study and underwent a complete ophthalmologic examination including slit lamp examination, Goldmann applanation tonometry, stereoscopic fundus examination, and pulsatile ocular blood flow (POBF) measurements. The OPP was calculated as being the medium systemic arterial pressure (MAP) less the IOP. Only right eye values were considered for calculations using Student's t-test. The mean age of the patients was 57.5 years (36-78), and 68.5% were women. There was a statistically significant difference in the OPP of the normal and systemic hypertensive patients (p < 0.05). The difference in the OPP between these groups varied between 8.84 and 17.9 mm Hg. The results of this study suggest that although the systemic hypertensive patients have a higher OPP in comparison to normal patients, this increase does not mean that they also have a higher OBF (as measured by POBF tonograph). This may be caused by chronic changes in the vascular network and in the blood hemodynamics in patients with systemic hypertension. How to cite this article: Kanadani FN, Figueiredo CR, Miranda RM, Cunha PLT, Kanadani TCM, Dorairaj S. Ocular Perfusion Pressure and Pulsatile Ocular Blood Flow in Normal and Systemic Hypertensive Patients. J Curr Glaucoma Pract 2015;9(1):16-19.

X-linked juvenile retinoschisis in a consanguineous family: phenotypic variability and report of a homozygous female patient.

PubMed

Gliem, Martin; Holz, Frank G; Stöhr, Heidi; Weber, Bernhard H F; Charbel Issa, Peter

2014-12-01

To describe the phenotypic variability in a consanguineous family with genetically confirmed X-linked retinoschisis. Five patients, including one homozygous female, were characterized by clinical examination, optical coherence tomography, fundus autofluorescence, mapping of macular pigment optical density, electroretinography, and DNA testing. The 36-year-old male index patient showed a ring of enhanced autofluorescence and outer retinal atrophy on optical coherence tomography. Electroretinography testing revealed a reduced a/b ratio. His mother presented with a central atrophic retina with markedly reduced autofluorescence signal and a surrounding ring of enhanced autofluorescence. The 40-year-old brother of the index patient and his 2 sons showed characteristic signs for X-linked retinoschisis, including retinal schisis and a reduced a/b ratio. Genetic testing revealed a c.293C>A mutation in the RS1 gene in all affected family members while the mother of the index patient was homozygous for this mutation. X-linked retinoschisis can present with a wide phenotypic variability. Here, detailed family history and genetic testing established the diagnosis of X-linked retinoschisis despite striking differences in phenotypic presentation in affected subjects, homozygosity of one affected female, and seemingly dominant inheritance in three subsequent generations because of multiple consanguinity.

Repeat sample intraocular pressure variance in induced and naturally ocular hypertensive monkeys.

PubMed

Dawson, William W; Dawson, Judyth C; Hope, George M; Brooks, Dennis E; Percicot, Christine L

2005-12-01

To compare repeat-sample means variance of laser induced ocular hypertension (OH) in rhesus monkeys with the repeat-sample mean variance of natural OH in age-range matched monkeys of similar and dissimilar pedigrees. Multiple monocular, retrospective, intraocular pressure (IOP) measures were recorded repeatedly during a short sampling interval (SSI, 1-5 months) and a long sampling interval (LSI, 6-36 months). There were 5-13 eyes in each SSI and LSI subgroup. Each interval contained subgroups from the Florida with natural hypertension (NHT), induced hypertension (IHT1) Florida monkeys, unrelated (Strasbourg, France) induced hypertensives (IHT2), and Florida age-range matched controls (C). Repeat-sample individual variance means and related IOPs were analyzed by a parametric analysis of variance (ANOV) and results compared to non-parametric Kruskal-Wallis ANOV. As designed, all group intraocular pressure distributions were significantly different (P < or = 0.009) except for the two (Florida/Strasbourg) induced OH groups. A parametric 2 x 4 design ANOV for mean variance showed large significant effects due to treatment group and sampling interval. Similar results were produced by the nonparametric ANOV. Induced OH sample variance (LSI) was 43x the natural OH sample variance-mean. The same relationship for the SSI was 12x. Laser induced ocular hypertension in rhesus monkeys produces large IOP repeat-sample variance mean results compared to controls and natural OH.

Factors associated with childhood ocular morbidity and blindness in three ecological regions of Nepal: Nepal pediatric ocular disease study.

PubMed

Adhikari, Srijana; Shrestha, Mohan Krishna; Adhikari, Kamala; Maharjan, Nhukesh; Shrestha, Ujjowala Devi

2014-10-23

Nepal Pediatric Ocular Diseases Study is a three year longitudinal population based study. Here we present the baseline survey report which aims to investigate various risk factors associated with childhood ocular morbidity and blindness in three ecological regions of Nepal. This baseline survey is a population based cross sectional study. The investigation was conducted in a district from each of the following regions: Terai, Hill and Mountain. The Village Development Committees (VDCs) from each district were selected by random sampling. Three Community health workers were given training on vision screening and identification of abnormal ocular signs in children. They conducted a house to house survey in their respected districts examining the children and gathering a standardized set of data variables. Children with abnormal vision or ocular signs were then further examined by pediatric ophthalmologists. A total of 10950 children aged 0-10 years (5403 from Terai, 3204 from the hills, 2343 from the mountains) were enrolled in the study. However 681 (6.2%) were non responders. The male to female ratio was 1.03. The overall prevalence of ocular morbidity was 3.7% (95% CI of 3.4%-4%) and blindness was 0.07% (95% CI of 0.02%-0.12%). Ocular morbidity was more prevalent in the mountain region whereas blindness was more prevalent in the Terai region.Children from the Terai region were more likely to suffer from congenital ocular anomalies compared to the other regions. Children whose mother smoked, drank alcohol, or was illiterate were significantly afflicted with ocular diseases (p < 0.05). In addition,a higher prevalence of ocular disease was related to children with past medical history of systemic illnesses, abnormal postnatal period or missing childhood vaccinations. Blindness was more prevalent in children who suffered from a systemic illness. Females and under-nourished children were more likely to have ocular morbidity and blindness. It was found that

Gender Disparities in Ocular Inflammatory Disorders*

PubMed Central

Sen, Hatice Nida; Davis, Janet; Ucar, Didar; Fox, Austin; Chan, Chi Chao; Goldstein, Debra A.

2014-01-01

Ocular inflammatory disorders disproportionately affect women, and the majority of affected women are of childbearing age. The role of sex or reproductive hormones has been proposed in many other inflammatory or autoimmune disorders, and findings from non-ocular autoimmune diseases suggest a complex interaction between sex hormones, genetic factors and the immune system. However, despite the age and sex bias, factors that influence this disparity are complicated and unclear. This review aims to evaluate the gender disparities in prevalence, incidence and severity of the most common infectious and non-infectious ocular inflammatory disorders. PMID:24987987

ELECTRICAL SIGNALING IN CONTROL OF OCULAR CELL BEHAVIORS

PubMed Central

Zhao, Min; Chalmers, Laura; Cao, Lin; Viera, Ana C.; Mannis, Mark; Reid, Brian

2011-01-01

Epithelia of the cornea, lens and retina contain a vast array of ion channels and pumps. Together they produce a polarized flow of ions in and out of cells, as well as across the epithelia. These naturally occurring ion fluxes are essential to the hydration and metabolism of the ocular tissues, especially for the avascular cornea and lens. The directional transport of ions generates electric fields and currents in those tissues. Applied electric fields affect migration, division and proliferation of ocular cells which are important in homeostasis and healing of the ocular tissues. Abnormalities in any of those aspects may underlie many ocular diseases, for example chronic corneal ulcers, posterior capsule opacity after cataract surgery, and retinopathies. Electric field-inducing cellular responses, termed electrical signaling here, therefore may be an unexpected yet powerful mechanism in regulating ocular cell behavior. Both endogenous electric fields and applied electric fields could be exploited to regulate ocular cells. We aim to briefly describe the physiology of the naturally occurring electrical activities in the corneal, lens, and retinal epithelia, to provide experimental evidence of the effects of electric fields on ocular cell behaviors, and to suggest possible clinical implications. PMID:22020127

Ocular involvement in paediatric haemolytic uraemic syndrome.

PubMed

Sturm, Veit; Menke, Marcel N; Landau, Klara; Laube, Guido F; Neuhaus, Thomas J

2010-11-01

The aim of this study was to estimate the frequency and severity of ocular involvement in paediatric patients with haemolytic uraemic syndrome (HUS). The study was designed as an institutional, retrospective, observational case series. Charts for all 87 paediatric patients with HUS treated at the University Children's Hospital Zurich between 1995 and 2007 were reviewed. Patients with ocular involvement were identified and clinical findings presented. Three of 69 examined patients with HUS showed ocular involvement. Ophthalmic findings in two children were consistent with bilateral Purtscher retinopathy, showing multiple haemorrhages, exudations and superficial retinal whitening. The third child presented with bilateral isolated central intraretinal haemorrhages as a milder form of ocular involvement. In one of the children with Purtscher retinopathy, laser photocoagulation was required for bilateral rubeosis irides and development of disc neovascularization. Longterm outcomes in the two severely affected children showed decreased visual acuity caused by partial atrophy of the optic nerves. In the milder case visual acuity was not impaired at any time. A minority of paediatric patients with HUS developed ocular involvement. Acute ocular findings varied in severity from isolated intraretinal haemorrhages to Purtscher-like retinopathy with retinal ischaemia. Longterm complications included the development of neovascularizations and consecutive optic nerve atrophy. Although ocular involvement in HUS seems to be rare, physicians should be aware of this complication because of its possible vision-endangering consequences. © 2009 The Authors. Journal compilation © 2009 Acta Ophthalmol.

Ocular surface injury from a microwave superheated liquid.

PubMed

Gagnon, Michael R; Walter, Keith A

2004-03-01

To describe the ocular surface injury resulting from a microwave superheated liquid. Case report. A 40-year-old man sustained an ocular surface injury from a microwave superheated liquid. The injury resulted in limbal stem cell damage requiring an autograft limbal stem cell transplantation. We are unaware of previous reports of microwave superheated liquids resulting in ocular injury. Microwave superheating of liquids is a potential ocular danger that should be brought to the attention of both ophthalmologists and their patients.

PCR-based detection of Toxoplasma gondii DNA in blood and ocular samples for diagnosis of ocular toxoplasmosis.

PubMed

Bourdin, C; Busse, A; Kouamou, E; Touafek, F; Bodaghi, B; Le Hoang, P; Mazier, D; Paris, L; Fekkar, A

2014-11-01

PCR detection of Toxoplasma gondii in blood has been suggested as a possibly efficient method for the diagnosis of ocular toxoplasmosis (OT) and furthermore for genotyping the strain involved in the disease. To assess this hypothesis, we performed PCR with 121 peripheral blood samples from 104 patients showing clinical and/or biological evidence of ocular toxoplasmosis and from 284 (258 patients) controls. We tested 2 different extraction protocols, using either 200 μl (small volume) or 2 ml (large volume) of whole blood. Sensitivity was poor, i.e., 4.1% and 25% for the small- and large-volume extractions, respectively. In comparison, PCR with ocular samples yielded 35.9% sensitivity, while immunoblotting and calculation of the Goldmann-Witmer coefficient yielded 47.6% and 72.3% sensitivities, respectively. Performing these three methods together provided 89.4% sensitivity. Whatever the origin of the sample (ocular or blood), PCR provided higher sensitivity for immunocompromised patients than for their immunocompetent counterparts. Consequently, PCR detection of Toxoplasma gondii in blood samples cannot currently be considered a sufficient tool for the diagnosis of OT, and ocular sampling remains necessary for the biological diagnosis of OT. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Dry Eye Management: Targeting the Ocular Surface Microenvironment.

PubMed

Zhang, Xiaobo; M, Vimalin Jeyalatha; Qu, Yangluowa; He, Xin; Ou, Shangkun; Bu, Jinghua; Jia, Changkai; Wang, Junqi; Wu, Han; Liu, Zuguo; Li, Wei

2017-06-29

Dry eye can damage the ocular surface and result in mild corneal epithelial defect to blinding corneal pannus formation and squamous metaplasia. Significant progress in the treatment of dry eye has been made in the last two decades; progressing from lubricating and hydrating the ocular surface with artificial tear to stimulating tear secretion; anti-inflammation and immune regulation. With the increase in knowledge regarding the pathophysiology of dry eye, we propose in this review the concept of ocular surface microenvironment. Various components of the microenvironment contribute to the homeostasis of ocular surface. Compromise in one or more components can result in homeostasis disruption of ocular surface leading to dry eye disease. Complete evaluation of the microenvironment component changes in dry eye patients will not only lead to appropriate diagnosis, but also guide in timely and effective clinical management. Successful treatment of dry eye should be aimed to restore the homeostasis of the ocular surface microenvironment.

Dry Eye Management: Targeting the Ocular Surface Microenvironment

PubMed Central

Zhang, Xiaobo; Jeyalatha M, Vimalin; Qu, Yangluowa; He, Xin; Ou, Shangkun; Bu, Jinghua; Jia, Changkai; Wang, Junqi; Wu, Han; Liu, Zuguo

2017-01-01

Dry eye can damage the ocular surface and result in mild corneal epithelial defect to blinding corneal pannus formation and squamous metaplasia. Significant progress in the treatment of dry eye has been made in the last two decades; progressing from lubricating and hydrating the ocular surface with artificial tear to stimulating tear secretion; anti-inflammation and immune regulation. With the increase in knowledge regarding the pathophysiology of dry eye, we propose in this review the concept of ocular surface microenvironment. Various components of the microenvironment contribute to the homeostasis of ocular surface. Compromise in one or more components can result in homeostasis disruption of ocular surface leading to dry eye disease. Complete evaluation of the microenvironment component changes in dry eye patients will not only lead to appropriate diagnosis, but also guide in timely and effective clinical management. Successful treatment of dry eye should be aimed to restore the homeostasis of the ocular surface microenvironment. PMID:28661456

Novel Strategies for Anterior Segment Ocular Drug Delivery

PubMed Central

Cholkar, Kishore; Patel, Sulabh P.; Vadlapudi, Aswani Dutt

2013-01-01

Abstract Research advancements in pharmaceutical sciences have led to the development of new strategies in drug delivery to anterior segment. Designing a new delivery system that can efficiently target the diseased anterior ocular tissue, generate high drug levels, and maintain prolonged and effective concentrations with no or minimal side effects is the major focus of current research. Drug delivery by traditional method of administration via topical dosing is impeded by ocular static and dynamic barriers. Various products have been introduced into the market that prolong drug retention in the precorneal pocket and to improve bioavailability. However, there is a need of a delivery system that can provide controlled release to treat chronic ocular diseases with a reduced dosing frequency without causing any visual disturbances. This review provides an overview of anterior ocular barriers along with strategies to overcome these ocular barriers and deliver therapeutic agents to the affected anterior ocular tissue with a special emphasis on nanotechnology-based drug delivery approaches. PMID:23215539

Molecular design for enhancement of ocular penetration.

PubMed

Shirasaki, Yoshihisa

2008-07-01

Over the past two decades, many oral drugs have been designed in consideration of physicochemical properties to attain optimal pharmacokinetic properties. This strategy significantly reduced attrition in drug development owing to inadequate pharmacokinetics during the last decade. On the other hand, most ophthalmic drugs are generated from reformulation of other therapeutic dosage forms. Therefore, the modification of formulations has been used mainly as the approach to improve ocular pharmacokinetics. However, to maximize ocular pharmacokinetic properties, a specific molecular design for ocular drug is preferable. Passive diffusion of drugs across the cornea membranes requires appropriate lipophilicity and aqueous solubility. Improvement of such physicochemical properties has been achieved by structure optimization or prodrug approaches. This review discusses the current knowledge about ophthalmic drugs adapted from systemic drugs and molecular design for ocular drugs. I propose the approaches for molecular design to obtain the optimal ocular penetration into anterior segment based on published studies to date.

X-linked acrogigantism syndrome: clinical profile and therapeutic responses.

PubMed

Beckers, Albert; Lodish, Maya Beth; Trivellin, Giampaolo; Rostomyan, Liliya; Lee, Misu; Faucz, Fabio R; Yuan, Bo; Choong, Catherine S; Caberg, Jean-Hubert; Verrua, Elisa; Naves, Luciana Ansaneli; Cheetham, Tim D; Young, Jacques; Lysy, Philippe A; Petrossians, Patrick; Cotterill, Andrew; Shah, Nalini Samir; Metzger, Daniel; Castermans, Emilie; Ambrosio, Maria Rosaria; Villa, Chiara; Strebkova, Natalia; Mazerkina, Nadia; Gaillard, Stéphan; Barra, Gustavo Barcelos; Casulari, Luis Augusto; Neggers, Sebastian J; Salvatori, Roberto; Jaffrain-Rea, Marie-Lise; Zacharin, Margaret; Santamaria, Beatriz Lecumberri; Zacharieva, Sabina; Lim, Ee Mun; Mantovani, Giovanna; Zatelli, Maria Chaira; Collins, Michael T; Bonneville, Jean-François; Quezado, Martha; Chittiboina, Prashant; Oldfield, Edward H; Bours, Vincent; Liu, Pengfei; W de Herder, Wouter; Pellegata, Natalia; Lupski, James R; Daly, Adrian F; Stratakis, Constantine A

2015-06-01

X-linked acrogigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplications on chromosome Xq26.3, encompassing the gene GPR101, which is highly upregulated in pituitary tumors. We conducted this study to explore the clinical, radiological, and hormonal phenotype and responses to therapy in patients with X-LAG syndrome. The study included 18 patients (13 sporadic) with X-LAG and microduplication of chromosome Xq26.3. All sporadic cases had unique duplications and the inheritance pattern in two families was dominant, with all Xq26.3 duplication carriers being affected. Patients began to grow rapidly as early as 2-3 months of age (median 12 months). At diagnosis (median delay 27 months), patients had a median height and weight standard deviation scores (SDS) of >+3.9 SDS. Apart from the increased overall body size, the children had acromegalic symptoms including acral enlargement and facial coarsening. More than a third of cases had increased appetite. Patients had marked hypersecretion of GH/IGF1 and usually prolactin, due to a pituitary macroadenoma or hyperplasia. Primary neurosurgical control was achieved with extensive anterior pituitary resection, but postoperative hypopituitarism was frequent. Control with somatostatin analogs was not readily achieved despite moderate to high levels of expression of somatostatin receptor subtype-2 in tumor tissue. Postoperative use of adjuvant pegvisomant resulted in control of IGF1 in all five cases where it was employed. X-LAG is a new infant-onset gigantism syndrome that has a severe clinical phenotype leading to challenging disease management. © 2015 Society for Endocrinology.

21 CFR 886.4360 - Ocular surgery irrigation device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Ocular surgery irrigation device. 886.4360 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Surgical Devices § 886.4360 Ocular surgery irrigation device. (a) Identification. An ocular surgery irrigation device is a device intended to be suspended over the...

21 CFR 886.4360 - Ocular surgery irrigation device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Ocular surgery irrigation device. 886.4360 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Surgical Devices § 886.4360 Ocular surgery irrigation device. (a) Identification. An ocular surgery irrigation device is a device intended to be suspended over the...

21 CFR 886.4360 - Ocular surgery irrigation device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Ocular surgery irrigation device. 886.4360 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Surgical Devices § 886.4360 Ocular surgery irrigation device. (a) Identification. An ocular surgery irrigation device is a device intended to be suspended over the...

21 CFR 886.4360 - Ocular surgery irrigation device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Ocular surgery irrigation device. 886.4360 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Surgical Devices § 886.4360 Ocular surgery irrigation device. (a) Identification. An ocular surgery irrigation device is a device intended to be suspended over the...

21 CFR 886.4360 - Ocular surgery irrigation device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ocular surgery irrigation device. 886.4360 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Surgical Devices § 886.4360 Ocular surgery irrigation device. (a) Identification. An ocular surgery irrigation device is a device intended to be suspended over the...

Ocular toxoplasmosis and retinal detachment: five case reports.

PubMed

Kianersi, F; Naderi Beni, A; Ghanbari, H; Fazel, F

2012-10-01

Ocular toxoplasmosis is a potentially blinding cause of posterior uveitis. Retinal detachment is rare complication of ocular toxoplasmosis. To report the clinical course and prognosis of retinal breaks and detachments occurring in patients with ocular toxoplasmosis. This study was a retrospective, non-comparative case series of five patients with ocular toxoplasmosis who had consulted us with retinal detachment. All of the participants had retinal detachment after severe and treatment resistant toxoplasmic retinochoroiditis, leaving one of them with decreased visual acuity to light perception in spite of treatment and final visual acuity was 20/100 or better in four patients. The functional prognosis for the patients with retinal detachment was poor. Careful retinal examination in ocular toxoplasmosis is warranted, especially in patients with severe intraocular inflammation.

The Ocular Surface Chemical Burns

PubMed Central

Baradaran-Rafii, Alireza; Djalilian, Ali R.

2014-01-01

Ocular chemical burns are common and serious ocular emergencies that require immediate and intensive evaluation and care. The victims of such incidents are usually young, and therefore loss of vision and disfigurement could dramatically affect their lives. The clinical course can be divided into immediate, acute, early, and late reparative phases. The degree of limbal, corneal, and conjunctival involvement at the time of injury is critically associated with prognosis. The treatment starts with simple but vision saving steps and is continued with complicated surgical procedures later in the course of the disease. The goal of treatment is to restore the normal ocular surface anatomy and function. Limbal stem cell transplantation, amniotic membrane transplantation, and ultimately keratoprosthesis may be indicated depending on the patients' needs. PMID:25105018

Glycobiology of ocular angiogenesis

PubMed Central

Markowska, Anna I; Cao, Zhiyi; Panjwani, Noorjahan

2014-01-01

Ocular neovascularization can affect almost all the tissues of the eye: the cornea, the iris, the retina, and the choroid. Pathological neovascularization is the underlying cause of vision loss in common ocular conditions such as diabetic retinopathy, retinopathy of prematurity and age-related macular neovascularization. Glycosylation is the most common covalent posttranslational modification of proteins in mammalian cells. A growing body of evidence demonstrates that glycosylation influences the process of angiogenesis and impacts activation, proliferation, and migration of endothelial cells as well as the interaction of angiogenic endothelial cells with other cell types necessary to form blood vessels. Recent studies have provided evidence that members of the galectin class of β-galactoside-binding proteins modulate angiogenesis by novel carbohydrate-based recognition systems involving interactions between glycans of angiogenic cell surface receptors and galectins. This review discusses the significance of glycosylation and the role of galectins in the pathogenesis of ocular neovascularization. PMID:25108228

Flurbiprofen-loaded niosomes-in-gel system improves the ocular bioavailability of flurbiprofen in the aqueous humor.

PubMed

El-Sayed, Marwa M; Hussein, Amal K; Sarhan, Hatem A; Mansour, Heba F

2017-06-01

The present work aimed to prolong the contact time of flurbiprofen (FBP) in the ocular tissue to improve the drug anti-inflammatory activity. Different niosome systems were fabricated adopting thin-film hydration technique and using the nonionic surfactant Span 60. The morphology of the prepared niosomes was characterized by scanning electron microscopy (SEM). Physical characterization by differential scanning calorimetry, X-ray powder diffraction and Fourier transform infrared spectroscopy were conducted for the optimized formula (F5) that was selected on the basis of percent entrapment efficiency, vesicular size and total lipid content. F5 was formulated as 1% w/w Carpobol 934 gel. Pharmacokinetic parameters of FBP were investigated following ocular administration of F5-loaded gel system, F5 niosome dispersion or the corresponding FBP ocular drops to albino rabbits dispersion. Anti-inflamatory effect of F5-loaded carbopol gel was investigated by histopathological examination of the corneal tissue before and after the treatment of inflamed rabbit eye with the system. Results showed that cholesterol content, surfactant type. and total lipid contents had an apparent impact on the vesicle size of the formulated niosomes. Physical characterization revealed reduced drug crystallinity and incidence of interaction with other niosome contents. F5-loaded gel showed higher C max , area under the curve (AUC 0-12 ), and thus higher ocular bioavailability than those of the corresponding FBP ocular solution. F5-loaded gel showed a promising rapid anti-inflammatory effect in the inflamed rabbit eye. These findings will eradicate the necessity for frequent ocular drug instillation and thus, improve patient compliance.

Linkage and candidate gene analysis of X-linked familial exudative vitreoretinopathy.

PubMed

Shastry, B S; Hejtmancik, J F; Plager, D A; Hartzer, M K; Trese, M T

1995-05-20

Familial exudative vitreoretinopathy (FEVR) is a hereditary eye disorder characterized by avascularity of the peripheral retina, retinal exudates, tractional detachment, and retinal folds. The disorder is most commonly transmitted as an autosomal dominant trait, but X-linked transmission also occurs. To initiate the process of identifying the gene responsible for the X-linked disorder, linkage analysis has been performed with three previously unreported three- or four-generation families. Two-point analysis showed linkage to MAOA (Zmax = 2.1, theta max = 0) and DXS228 (Zmax = 0.5, theta max = 0.11), and this was further confirmed by multipoint analysis with these same markers (Zmax = 2.81 at MAOA), which both lie near the gene causing Norrie disease. Molecular genetic analysis further reveals a missense mutation (R121W) in the third exon of the Norrie's disease gene that perfectly cosegregates with the disease through three generations in one family. This mutation was not detected in the unaffected family members and six normal unrelated controls, suggesting that it is likely to be the pathogenic mutation. Additionally, a polymorphic missense mutation (H127R) was detected in a severely affected patient.

Ocular hemodynamics and glaucoma: the role of mathematical modeling.

PubMed

Harris, Alon; Guidoboni, Giovanna; Arciero, Julia C; Amireskandari, Annahita; Tobe, Leslie A; Siesky, Brent A

2013-01-01

To discuss the role of mathematical modeling in studying ocular hemodynamics, with a focus on glaucoma. We reviewed recent literature on glaucoma, ocular blood flow, autoregulation, the optic nerve head, and the use of mathematical modeling in ocular circulation. Many studies suggest that alterations in ocular hemodynamics play a significant role in the development, progression, and incidence of glaucoma. Although there is currently a limited number of studies involving mathematical modeling of ocular blood flow, regulation, and diseases (such as glaucoma), preliminary modeling work shows the potential of mathematical models to elucidate the mechanisms that contribute most significantly to glaucoma progression. Mathematical modeling is a useful tool when used synergistically with clinical and laboratory data in the study of ocular blood flow and glaucoma. The development of models to investigate the relationship between ocular hemodynamic alterations and glaucoma progression will provide a unique and useful method for studying the pathophysiology of glaucoma.

The role of microbial flora on the ocular surface.

PubMed

Miller, Darlene; Iovieno, Alfonso

2009-10-01

Presence and interplay of microbial flora at the ocular surface reveal dynamic and evolving interactions with implications for both ocular surface health and disease. Data in this area are scarce or non-existent. The purpose of this review is to provide a snapshot of new and emerging developments in this area over the last 12 months. Recent findings signal potential roles for ocular surface microbial flora in both the preservation and extension of ocular surface health and in the initiation of new or escalation of common surface disorders. Contributions range from priming surface epithelial immune cells to regulating mucin composition and production. Other findings explore the emergent role of ocular microbial flora cross talk with pattern recognition receptors to protect and strengthen local and adaptive mucosal immunity while preserving vision. Deciphering the functional role of microbial communities at the ocular surface could bring new insights into and clarify the epidemiology and pathology of ocular surface dynamics in health and disease.

[Study of ocular surface electromyography signal analysis].

PubMed

Zhu, Bei; Qi, Li-Ping

2009-11-01

Test ocular surface electromyography signal waves and characteristic parameters to provide effective data for the diagnosis and treatment of ocular myopathy. Surface electromyography signals tests were performed in 140 normal volunteers and 30 patients with ophthalmoplegia. Surface electrodes were attached to medial canthi, lateral canthi and the middle of frontal bone. Then some alternate flashing red lamps were installed on perimeter to reduce the movement of eyeball. The computer hardware, software, and A/D adapter (12 Bit) were used. Sampling frequency could be selected within 40 kHz, frequency of amplifier was 2 kHz, and input short circuit noise was less than 3 microV. For normal volunteers, the ocular surface electromyography signals were regular, and the electric waves were similar between different sex groups and age groups. While for patients with ophthalmoplegia, the wave amplitude of ocular surface electromyography signals were declined or disappeared in the dyskinesia direction. The wave amplitude was related with the degree of pathological process. The characteristic parameters of patients with ophthalmoplegia were higher than normal volunteers. The figures of ocular surface electromyogram obtained from normal volunteers were obviously different with that from patients with ophthalmoplegia. This test can provide reliable quantized data for the diagnosis and treatment of ocular myopathy.

Vitreoretinal surgery without schisis cavity excision for the management of juvenile X linked retinoschisis.

PubMed

García-Arumí, J; Corcóstegui, I A; Navarro, R; Zapata, M A; Berrocal, M H

2008-11-01

Juvenile X linked retinoschisis (XLRS) is a congenital X linked recessive retinal disorder characterised by cystic maculopathy and peripheral schisis. This study presents the case of an 8-month-old boy with a documented positive family history of XLRS, with a large retinoschisis cavity affecting the macula, first in the left eye and 1 year later in the right eye. The patient underwent pars plana vitrectomy in both eyes using 23-G instruments, posterior hyaloid dissection, a small retinotomy, fluid drainage with a 42-G cannula, infrared diode laser and silicone oil as internal tamponade. The anatomical and functional outcomes at 3 years following the first surgery are described. To the authors' knowledge, there is no previously reported experience with this technique in patients with XLRS.

Molecular characterization of a novel X-linked syndrome involving developmental delay and deafness.

PubMed

Hildebrand, Michael S; de Silva, Michelle G; Tan, Tiong Yang; Rose, Elizabeth; Nishimura, Carla; Tolmachova, Tanya; Hulett, Joanne M; White, Susan M; Silver, Jeremy; Bahlo, Melanie; Smith, Richard J H; Dahl, Hans-Henrik M

2007-11-01

X-linked syndromes associated with developmental delay and sensorineural hearing loss (SNHL) have been characterized at the molecular level, including Mohr-Tranebjaerg syndrome and Norrie disease. In this study we report on a novel X-linked recessive, congenital syndrome in a family with developmental delay and SNHL that maps to a locus associated with mental retardation (MR) for which no causative gene has been identified. The X-linked recessive inheritance and congenital nature of the syndrome was confirmed by detailed clinical investigation and the family history. Linkage mapping of the X-chromosome was conducted to ascertain the disease locus and candidate genes were screened by direct sequencing and STRP analysis. The recessive syndrome was mapped to Xp11.3-q21.32 and a deletion was identified in a regulatory region upstream of the POU3F4 gene in affected family members. Since mutations in POU3F4 cause deafness at the DFN3 locus, the deletion is the likely cause of the SNHL in this family. The choroideremia (CHM) gene was also screened and a novel missense change was identified. The alteration changes the serine residue at position 89 in the Rab escort 1 protein (REP-1) to a cysteine (S89C). Prenylation of Rab proteins was investigated in patients and the location of REP-1 expression in the brain determined. However, subsequent analysis revealed that this change in CHM was polymorphic having no effect on REP-1 function. Although the causative gene at the MR locus in this family has not been identified, there are a number of genes involved in syndromic and nonsyndromic forms of MR that are potential candidates. Copyright 2007 Wiley-Liss, Inc.

Unique Variants in OPN1LW Cause Both Syndromic and Nonsyndromic X-Linked High Myopia Mapped to MYP1.

PubMed

Li, Jiali; Gao, Bei; Guan, Liping; Xiao, Xueshan; Zhang, Jianguo; Li, Shiqiang; Jiang, Hui; Jia, Xiaoyun; Yang, Jianhua; Guo, Xiangming; Yin, Ye; Wang, Jun; Zhang, Qingjiong

2015-06-01

MYP1 is a locus for X-linked syndromic and nonsyndromic high myopia. Recently, unique haplotypes in OPN1LW were found to be responsible for X-linked syndromic high myopia mapped to MYP1. The current study is to test if such variants in OPN1LW are also responsible for X-linked nonsyndromic high myopia mapped to MYP1. The proband of the family previously mapped to MYP1 was initially analyzed using whole-exome sequencing and whole-genome sequencing. Additional probands with early-onset high myopia were analyzed using whole-exome sequencing. Variants in OPN1LW were selected and confirmed by Sanger sequencing. Long-range and second PCR were used to determine the haplotype and the first gene of the red-green gene array. Candidate variants were further validated in family members and controls. The unique LVAVA haplotype in OPN1LW was detected in the family with X-linked nonsyndromic high myopia mapped to MYP1. In addition, this haplotype and a novel frameshift mutation (c.617_620dup, p.Phe208Argfs*51) in OPN1LW were detected in two other families with X-linked high myopia. The unique haplotype cosegregated with high myopia in the two families, with a maximum LOD score of 3.34 and 2.31 at θ = 0. OPN1LW with the variants in these families was the first gene in the red-green gene array and was not present in 247 male controls. Reevaluation of the clinical data in both families with the unique haplotype suggested nonsyndromic high myopia. Our study confirms the findings that unique variants in OPN1LW are responsible for both syndromic and nonsyndromic X-linked high myopia mapped to MYP1.

X-linked juvenile retinoschisis (XLRS): a review of genotype-phenotype relationships.

PubMed

Kim, David Y; Mukai, Shizuo

2013-01-01

X-linked juvenile retinoschisis (XLRS) is one of the most common genetic causes of juvenile progressive retinal-vitreal degeneration in males. To date, more than 196 different mutations of the RS1 gene have been associated with XLRS. The mutation spectrum is large and the phenotype variable. This review will focus on the clinical features of XLRS and examine the relationship between phenotype and genotype.

Identification of a melanosomal membrane protein encoded by the pink-eyed dilution (type II oculocutaneous albinism) gene.

PubMed Central

Rosemblat, S; Durham-Pierre, D; Gardner, J M; Nakatsu, Y; Brilliant, M H; Orlow, S J

1994-01-01

The pink-eyed dilution (p) locus in the mouse is critical to melanogenesis; mutations in the homologous locus in humans, P, are a cause of type II oculocutaneous albinism. Although a cDNA encoded by the p gene has recently been identified, nothing is known about the protein product of this gene. To characterize the protein encoded by the p gene, we performed immunoblot analysis of extracts of melanocytes cultured from wild-type mice with an antiserum from rabbits immunized with a peptide corresponding to amino acids 285-298 of the predicted protein product of the murine p gene. This antiserum recognized a 110-kDa protein. The protein was absent from extracts of melanocytes cultured from mice with two mutations (pcp and p) in which transcripts of the p gene are absent or greatly reduced. Introduction of the cDNA for the p gene into pcp melanocytes by electroporation resulted in expression of the 3.3-kb mRNA and the 110-kDa protein. Upon subcellular fractionation of cultured melanocytes, the 110-kDa protein was found to be present in melanosomes but absent from the vesicular fraction; phase separation performed with the nonionic detergent Triton X-114 confirmed the predicted hydrophobic nature of the protein. These results demonstrate that the p gene encodes a 110-kDa integral melanosomal membrane protein and establish a framework by which mutations at this locus, which diminish pigmentation, can be analyzed at the cellular and biochemical levels. Images PMID:7991586

21 CFR 882.1790 - Ocular plethysmograph.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Ocular plethysmograph. 882.1790 Section 882.1790 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1790 Ocular plethysmograph. (a...

21 CFR 882.1790 - Ocular plethysmograph.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ocular plethysmograph. 882.1790 Section 882.1790 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1790 Ocular plethysmograph. (a...

Ocular biodistribution of bevasiranib following a single intravitreal injection to rabbit eyes

PubMed Central

Dejneka, Nadine S.; Wan, Shanhong; Bond, Ottrina S.; Kornbrust, Douglas J.

2008-01-01

Purpose The primary objective of these investigations was to determine the ocular biodistribution of bevasiranib, a small interfering RNA (siRNA) targeting vascular endothelial growth factor A (VEGF-A), following a single intravitreal injection to rabbit eyes. Methods A tissue distribution and pharmacokinetic study was conducted with 3H-bevasiranib prepared in balanced-salt solution (BSS). Single doses of either 0.5 mg/eye or 2.0 mg/eye of 3H-bevasiranib were given by intravitreal injection to Dutch-Belted rabbits (both eyes were treated). Subgroups of rabbits were serially-sacrificed at various times up to 7 days following dosing for collection of tissue samples. The right eye of each rabbit was collected whole, and the left eye was dissected to isolate five ocular tissues. All samples were analyzed by liquid scintillation counting to determine the concentrations of bevasiranib equivalents. An ocular disposition study was also performed with non-radiolabeled bevasiranib, which was administered to Dutch-Belted rabbit eyes via intravitreal injection at a dose of 2.0 mg/eye. Twenty-four hours post-dose, the eyes were enucleated and dissected into eight individual ocular structures that were analyzed for intact bevasiranib using a locked nuleic acid (LNA) noncompetitive hybridization-ligation enzyme-linked immunosorbent assay. Results Following intravitreal injection of 0.5 mg or 2.0 mg radiolabeled bevasiranib to Dutch-Belted rabbits, bevasiranib was detected in the vitreous, iris, retina, retinal pigment epithelium (RPE), and sclera (+choroid). As expected, the highest concentrations were found in the vitreous, and vitreous levels steadily decreased over time, while concentrations of radioactivity in the other ocular tissues increased to maximum values between 24 h and 72 h after dosing. Of these tissues, the highest concentration of radioactivity was detected in the retina. The LNA assay further confirmed the presence of intact bevasiranib in these tissues 24 h

Sclerodermatomyositis, ocular manifestations.

PubMed

Pedroza-Seres, M; Serna-Ojeda, J C; Flores-Suárez, L F

2017-07-01

Sclerodermatomyositis is an overlap syndrome of myositis and scleroderma, with dermatological, muscular and joint involvement, but may also present with ocular manifestations. A 57 year-old woman presented with ophthalmological manifestations, including scleral thinning 360°, and the presence of cells in the anterior and posterior chamber. Oriented physical examination and laboratory studies led to the diagnosis, with the need for systemic treatment. Sclerodermatomyositis is a rare disease. Its diagnosis needs thorough clinical and laboratory studies, and its management should be multidisciplinary when inflammatory ocular manifestations may be present. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Clinical Features and Treatment of Ocular Toxoplasmosis

PubMed Central

Park, Young-Hoon

2013-01-01

Ocular toxoplasmosis is a disease caused by the infection with Toxoplasma gondii through congenital or acquired routes. Once the parasite reaches the retina, it proliferates within host cells followed by rupture of the host cells and invasion into neighboring cells to make primary lesions. Sometimes the restricted parasite by the host immunity in the first scar is activated to infect another lesion nearby the scar. Blurred vision is the main complaint of ocular toxoplasmic patients and can be diagnosed by detection of antibodies or parasite DNA. Ocular toxoplasmosis needs therapy with several combinations of drugs to eliminate the parasite and accompanying inflammation; if not treated it sometimes leads to loss of vision. We describe here clinical features and currently available chemotherapy of ocular toxoplasmosis. PMID:24039281

Clinical features and treatment of ocular toxoplasmosis.

PubMed

Park, Young-Hoon; Nam, Ho-Woo

2013-08-01

Ocular toxoplasmosis is a disease caused by the infection with Toxoplasma gondii through congenital or acquired routes. Once the parasite reaches the retina, it proliferates within host cells followed by rupture of the host cells and invasion into neighboring cells to make primary lesions. Sometimes the restricted parasite by the host immunity in the first scar is activated to infect another lesion nearby the scar. Blurred vision is the main complaint of ocular toxoplasmic patients and can be diagnosed by detection of antibodies or parasite DNA. Ocular toxoplasmosis needs therapy with several combinations of drugs to eliminate the parasite and accompanying inflammation; if not treated it sometimes leads to loss of vision. We describe here clinical features and currently available chemotherapy of ocular toxoplasmosis.

Ocular Complications of Diabetes and Therapeutic Approaches

PubMed Central

Vieira-Potter, Victoria J.; Karamichos, Dimitrios; Lee, Darren J.

2016-01-01

Diabetes mellitus (DM) is a metabolic disease defined by elevated blood glucose (BG). DM is a global epidemic and the prevalence is anticipated to continue to increase. The ocular complications of DM negatively impact the quality of life and carry an extremely high economic burden. While systemic control of BG can slow the ocular complications they cannot stop them, especially if clinical symptoms are already present. With the advances in biodegradable polymers, implantable ocular devices can slowly release medication to stop, and in some cases reverse, diabetic complications in the eye. In this review we discuss the ocular complications associated with DM, the treatments available with a focus on localized treatments, and what promising treatments are on the horizon. PMID:27119078

Ocular toxicity of fludarabine

PubMed Central

Ding, Xiaoyan; Herzlich, Alexandra A; Bishop, Rachel; Tuo, Jingsheng; Chan, Chi-Chao

2008-01-01

The purine analogs, fludarabine and cladribine represent an important class of chemotherapy agents used to treat a broad spectrum of lymphoid malignancies. Their toxicity profiles include dose-limiting myelosuppression, immunosuppression, opportunistic infection and severe neurotoxicity. This review summarizes the neurotoxicity of high- and standard-dose fludarabine, focusing on the clinical and pathological manifestations in the eye. The mechanisms of ocular toxicity are probably multifactorial. With increasing clinical use, an awareness of the neurological and ocular vulnerability, particularly to fludarabine, is important owing to the potential for life- and sight-threatening consequences. PMID:18461151

Canine ocular protothecosis: A review of 14 cases.

PubMed

Shank, Alba Maria M; Dubielzig, Richard D; Teixeira, Leandro B C

2015-09-01

To examine a series of 14 cases of canine ocular protothecosis from archived cases from the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW), and compare gross and histologic findings. Archival records from COPLOW were searched for canine cases of ocular protothecosis. Fourteen cases that contained matching criteria were identified, and gross and histologic findings, and clinical records for each case were tabulated, examined, and compared (2001-2013). Of the 14 cases identified, six had evidence of systemic disease, as per clinical history. Two of the 14 cases had Prototheca identified via cytology of ocular fluid or retinal exudate; in the remainder of cases, Prototheca identified via cytology of ocular fluid or retinal exudate in the remaining 12 cases, Prototheca was identified upon histologic examination of the submitted globe(s). Presenting ocular clinical signs were variable and nonspecific. Duration of ocular clinical signs varied from days to months. Fundoscopically, white membranes or plaques were identified on or around the retina in five cases. Retinal detachment was identified in 13 of the 14 submitted globes on gross examination following fixation and sectioning. The predominant histologic finding was granulomatous chorioretinitis with retinal detachment, with variable numbers of Prototheca within the inflammatory infiltrate. Due to the nonspecific nature of the ocular signs, a diagnosis of protothecosis generally is not made until enucleation and histopathologic examination of the globe(s). Retinal detachment and blindness were common. Cytologic sampling of retinal plaques and exudate may provide a rapid way to identify Prototheca. © 2014 American College of Veterinary Ophthalmologists.

Ocular Findings in Volcanic Fog Induced Conjunctivitis

PubMed Central

Lagunzad, John Kenneth D

2011-01-01

Objective To describe the ocular signs and symptoms of patients complaining of eye irritation due to volcanic fog (vog). Methods The study utilized a non-comparative, retrospective chart review of 30 patients who had a chief complaint of eye irritation, which the subjects attributed to vog. Ocular signs and symptoms are described and related to the ambient concentration of sulfur dioxide (SO2), particulate matter sized 2.5 microns (PM2.5), and vog visibility in O‘ahu during the period of the study. Results Ocular signs noted were conjunctival injection (100%), clear mucous discharge (100%), papillary reaction (100%), punctal edema (80%), eyelid swelling (73.3%) and chemosis (63.3%). Ocular symptoms were itchiness (100%), foreign body sensation (100%), tearing (96.6%) and burning sensation (90%). All patients had concurrent respiratory symptoms. During the period of study, the highest 24-hour average concentration of particulate matter sized 2.5 microns (PM2.5) was 49.04 µg/m3 and vog was visually present. Conclusions Patients complaining of eye irritation due to vog have observable ocular signs and symptoms. PMID:22187513

A Novel Mutation in a Kazakh Family with X-Linked Alport Syndrome

PubMed Central

Rakhimova, Saule E.; Nigmatullina, Nazym B.; Momynaliev, Kuvat T.; Ramanculov, Yerlan M.

2015-01-01

Alport syndrome is a genetic condition that results in hematuria, progressive renal impairment, hearing loss, and occasionally lenticonus and retinopathy. Approximately 80% of Alport syndrome cases are caused by X-linked mutations in the COL4A5 gene encoding type IV collagen. The objective of this study was to define the SNP profiles for COL4A5 in patients with hereditary nephritis and hematuria. For this, we examined four subjects from one Kazakh family clinically affected with X-linked Alport syndrome due to COL4A5 gene mutations. All 51 exons of the COL4A5 gene were screened by linkage analysis and direct DNA sequencing, resulting in the identification of a novel mutation (G641E) in exon 25. The mutation was found only in two affected family individuals but was not present in healthy family members or 200 unrelated healthy controls. This result demonstrates that this novel mutation is pathogenic and has meaningful implications for the diagnosis of patients with Alport syndrome. PMID:26168235

A Novel Mutation in a Kazakh Family with X-Linked Alport Syndrome.

PubMed

Baikara, Barshagul T; Zholdybayeva, Elena V; Rakhimova, Saule E; Nigmatullina, Nazym B; Momynaliev, Kuvat T; Ramanculov, Yerlan M

2015-01-01

Alport syndrome is a genetic condition that results in hematuria, progressive renal impairment, hearing loss, and occasionally lenticonus and retinopathy. Approximately 80% of Alport syndrome cases are caused by X-linked mutations in the COL4A5 gene encoding type IV collagen. The objective of this study was to define the SNP profiles for COL4A5 in patients with hereditary nephritis and hematuria. For this, we examined four subjects from one Kazakh family clinically affected with X-linked Alport syndrome due to COL4A5 gene mutations. All 51 exons of the COL4A5 gene were screened by linkage analysis and direct DNA sequencing, resulting in the identification of a novel mutation (G641E) in exon 25. The mutation was found only in two affected family individuals but was not present in healthy family members or 200 unrelated healthy controls. This result demonstrates that this novel mutation is pathogenic and has meaningful implications for the diagnosis of patients with Alport syndrome.

Minimally invasive microneedles for ocular drug delivery.

PubMed

Thakur Singh, Raghu Raj; Tekko, Ismaiel; McAvoy, Kathryn; McMillan, Hannah; Jones, David; Donnelly, Ryan F

2017-04-01

Anterior and posterior segment eye diseases are highly challenging to treat, due to the barrier properties and relative inaccessibility of the ocular tissues. Topical eye drops and systemically delivered treatments result in low bioavailability. Alternatively, direct injection of medication into the ocular tissues is clinically employed to overcome the barrier properties, but injections cause significant tissue damage and are associated with a number of untoward side effects and poor patient compliance. Microneedles (MNs) has been recently introduced as a minimally invasive means for localizing drug formulation within the target ocular tissues with greater precision and accuracy than the hypodermic needles. Areas covered: This review article seeks to provide an overview of a range of challenges that are often faced to achieve efficient ocular drug levels within targeted tissue(s) of the eye. It also describes the problems encountered using conventional hypodermic needle-based ocular injections for anterior and posterior segment drug delivery. It discusses research carried out in the field of MNs, to date. Expert opinion: MNs can aid in localization of drug delivery systems within the selected ocular tissue. And, hold the potential to revolutionize the way drug formulations are administered to the eye. However, the current limitations and challenges of MNs application warrant further research in this field to enable its widespread clinical application.

Mutations in GPR143/OA1 and ABCA4 Inform Interpretations of Short-Wavelength and Near-Infrared Fundus Autofluorescence

PubMed Central

Paavo, Maarjaliis; Zhao, Jin; Kim, Hye Jin; Lee, Winston; Zernant, Jana; Cai, Carolyn; Allikmets, Rando; Tsang, Stephen H.; Sparrow, Janet R.

2018-01-01

Purpose We sought to advance interpretations and quantification of short-wavelength fundus autofluorescence (SW-AF) emitted from bisretinoid lipofuscin and near-infrared autofluoresence (NIR-AF) originating from melanin. Methods Carriers of mutations in X-linked GPR143/OA1, a common form of ocular albinism; patients with confirmed mutations in ABCA4 conferring increased SW-AF; and subjects with healthy eyes were studied. SW-AF (488 nm excitation, 500–680 nm emission) and NIR-AF (excitation 787 nm, emission >830 nm) images were acquired with a confocal scanning laser ophthalmoscope. SW-AF images were analyzed for quantitative autofluoresence (qAF). Analogous methods of image acquisition and analysis were performed in albino and pigmented Abca4−/− mice and wild-type mice. Results Quantitation of SW-AF (qAF), construction of qAF color-coded maps, and examination of NIR-AF images from GPR143/OA1 carriers revealed mosaics in which patches of fundus exhibiting NIR-AF signal had qAF levels within normal limits whereas the hypopigmented areas in the NIR-AF image corresponded to foci of elevated qAF. qAF also was increased in albino versus pigmented mice. Although melanin contributes to fundus infrared reflectance, the latter appeared to be uniform in en face reflectance images of GPR143/OA1-carriers. In patients diagnosed with ABCA4-associated disease, NIR-AF increased in tandem with increased qAF originating in bisretinoid lipofuscin. Similarly in Abca4−/− mice having increased SW-AF, NIR-AF was more pronounced than in wild-type mice. Conclusions These studies corroborate RPE melanin as the major source of NIR-AF but also indicate that bisretinoid lipofuscin, when present at sufficient concentrations, contributes to the NIR-AF signal. Ocular melanin attenuates the SW-AF signal.

[Ocular toxoplasmosis developed after liver transplantation].

PubMed

Avkan Oğuz, Vildan; Koçak, Nilüfer; Köse, Hatice; Unek, Tarkan; Ozbilgin, Mücahit; Karademir, Sedat; Kaynak, Süleyman

2012-10-01

Ocular toxoplasmosis after solid organ transplantation occurs usually within the first three months of primary infection or reactivation of latent infection. There are a few reports of ocular toxoplasmosis following liver transplantation in the literature, however, no reports were detected in the national data. In this report a 35-year-old female patient diagnosed as ocular toxoplasmosis following reactivation in the second year after liver transplantation, was presented. The case was successfully treated with trimethoprim/sulfamethoxazole and clindamycin. This case was presented to emphasize late presentation of toxoplasmosis in transplantation patients and to withdraw attention to the importance of serological investigations done before transplantation.

Ocular chemical injuries and their management.

PubMed

Singh, Parul; Tyagi, Manoj; Kumar, Yogesh; Gupta, K K; Sharma, P D

2013-05-01

Chemical burns represent potentially blinding ocular injuries and constitute a true ocular emergency requiring immediate assessment and initiation of treatment. The majority of victims are young and exposure occurs at home, work place and in association with criminal assaults. Alkali injuries occur more frequently than acid injuries. Chemical injuries of the eye produce extensive damage to the ocular surface epithelium, cornea, anterior segment and limbal stem cells resulting in permanent unilateral or bilateral visual impairment. Emergency management if appropriate may be single most important factor in determining visual outcome. This article reviews the emergency management and newer techniques to improve the prognosis of patients with chemical injuries.

Instability of ocular alignment in childhood esotropia.

PubMed

Christiansen, Stephen P; Chandler, Danielle L; Holmes, Jonathan M; Arnold, Robert W; Birch, Eileen; Dagi, Linda R; Hoover, Darren L; Klimek, Deborah L; Melia, B Michele; Paysse, Evelyn; Repka, Michael X; Suh, Donny W; Ticho, Benjamin H; Wallace, David K; Weaver, Richard Grey

2008-12-01

Instability of ocular alignment may cause surgeons to delay surgical correction of childhood esotropia. The authors investigated the stability of ocular alignment over 18 weeks in children with infantile esotropia (IET), acquired nonaccommodative esotropia (ANAET), or acquired partially accommodative esotropia (APAET). Prospective, observational study. Two hundred thirty-three children aged 2 months to less than 5 years with IET, ANAET, or APAET of less than 6 months' duration. Ocular alignment was measured at baseline and at 6-week intervals for 18 weeks. Using definitions derived from a nested test-retest study and computer simulation modeling, ocular alignment was classified as unstable if there was a change of 15 prism diopters (PD) or more between any 2 of the 4 measurements, as stable if all 4 measurements were within 5 PD or less of one another, or as uncertain if neither criteria was met. Of those who completed all 3 follow-up visits within time windows for analysis, 27 (46%) of 59 subjects with IET had ocular alignment classified as unstable (95% confidence interval [CI], 33%-59%), 20% as stable (95% CI, 11%-33%), and 34% as uncertain (95% CI, 22%-47%). Thirteen (22%) of 60 subjects with ANAET had ocular alignment classified as unstable (95% CI, 12%-34%), 37% as stable (95% CI, 25%-50%), and 42% as uncertain (95% CI, 29%-55%). Six (15%) of 41 subjects with APAET had ocular alignment classified as unstable (95% CI, 6%-29%), 39% as stable (95% CI, 24%-56%), and 46% as uncertain (95% CI, 31%-63%). For IET, subjects who were older at presentation were less likely to have unstable angles than subjects who were younger at presentation (risk ratio for unstable vs stable per additional month of age, 0.85; 99% CI, 0.74-0.99). Ocular alignment instability is common in children with IET, ANAET, and APAET. The impact of this finding on the optimal timing for strabismus surgery in childhood esotropia awaits further study. The author(s) have no proprietary or commercial

21 CFR 886.1040 - Ocular esthesiometer.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ocular esthesiometer. 886.1040 Section 886.1040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED.... An ocular esthesiometer is a device, such as a single-hair brush, intended to touch the cornea to...

Prenatal Correction of X-Linked Hypohidrotic Ectodermal Dysplasia.

PubMed

Schneider, Holm; Faschingbauer, Florian; Schuepbach-Mallepell, Sonia; Körber, Iris; Wohlfart, Sigrun; Dick, Angela; Wahlbuhl, Mandy; Kowalczyk-Quintas, Christine; Vigolo, Michele; Kirby, Neil; Tannert, Corinna; Rompel, Oliver; Rascher, Wolfgang; Beckmann, Matthias W; Schneider, Pascal

2018-04-26

Genetic deficiency of ectodysplasin A (EDA) causes X-linked hypohidrotic ectodermal dysplasia (XLHED), in which the development of sweat glands is irreversibly impaired, an condition that can lead to life-threatening hyperthermia. We observed normal development of mouse fetuses with Eda mutations after they had been exposed in utero to a recombinant protein that includes the receptor-binding domain of EDA. We administered this protein intraamniotically to two affected human twins at gestational weeks 26 and 31 and to a single affected human fetus at gestational week 26; the infants, born in week 33 (twins) and week 39 (singleton), were able to sweat normally, and XLHED-related illness had not developed by 14 to 22 months of age. (Funded by Edimer Pharmaceuticals and others.).

Biocompatibility of Genipin and Glutaraldehyde Cross-Linked Chitosan Materials in the Anterior Chamber of the Eye

PubMed Central

Lai, Jui-Yang

2012-01-01

Chitosan is a naturally occurring cationic polysaccharide and has attracted much attention in the past decade as an important ophthalmic biomaterial. We recently demonstrated that the genipin (GP) cross-linked chitosan is compatible with human retinal pigment epithelial cells. The present work aims to further investigate the in vivo biocompatibility of GP-treated chitosan (GP-chi group) by adopting the anterior chamber of a rabbit eye model. The glutaraldehyde (GTA) cross-linked samples (GTA-chi group) were used for comparison. The 7-mm-diameter membrane implants made from either non-cross-linked chitosan or chemically modified materials with a cross-linking degree of around 80% were inserted in the ocular anterior chamber for 24 weeks and characterized by slit-lamp and specular microscopic examinations, intraocular pressure measurements, and corneal thickness measurements. The interleukin-6 expressions at mRNA level were also detected by quantitative real-time reverse transcription polymerase chain reaction. Results of clinical observations showed that the overall ocular scores in the GTA-chi groups were relatively high. In contrast, the rabbits bearing GP-chi implants in the anterior chamber of the eye exhibited no signs of ocular inflammation. As compared to the non-cross-linked counterparts, the GP-chi samples improved the preservation of corneal endothelial cell density and possessed better anti-inflammatory activities, indicating the benefit action of the GP cross-linker. In summary, the intracameral tissue response to the chemically modified chitosan materials strongly depends on the selection of cross-linking agents. PMID:23109832

Hydroxyapatite ocular implant and non-integrated implants in eviscerated patients

PubMed Central

Gradinaru, S; Popescu, V; Leasu, C; Pricopie, S; Yasin, S; Ciuluvica, R; Ungureanu, E

2015-01-01

Introduction: This study compares the outcomes and complications of hydroxyapatite ocular implant and non-integrated ocular implants following evisceration. Materials and Methods: This is a retrospective study of 90 patients who underwent evisceration for different ocular affections, in the Ophthalmology Department of the University Emergency Hospital Bucharest, between January 2009 and December 2013. The outcomes measured were conjunctival dehiscence, socket infection, implant exposure and extrusion rate. Results: Forty-three patients had the hydroxyapatite implant (coralline–Integrated Ocular Implants, USA or synthetic–FCI, France) and forty-seven received non-integrated ocular implants (24 acrylic and 23 silicone). Five cases of socket infection, thirteen cases of extrusion and two cases of conjunctival dehiscence were encountered. Conclusions: There was a higher rate of conjunctival dehiscence with hydroxyapatite ocular implant, but implant extrusion and socket infection were found in non-integrated ocular implants. PMID:25914747

Oxaliplatin-Related Ocular Toxicity

PubMed Central

Mesquida, Marina; Sanchez-Dalmau, Bernardo; Ortiz-Perez, Santiago; Pelegrín, Laura; Molina-Fernandez, Juan José; Figueras-Roca, Marc; Casaroli-Marano, Ricardo; Adán, Alfredo

2010-01-01

We report the case of a 52-year-old woman with advanced colorectal cancer who was treated with oxaliplatin on a FOLFOX schedule. After 3 cycles of chemotherapy, she started to complain of visual loss, altered color vision and neurological symptoms. Due to the suspicion of ocular and neurological toxicity, antineoplastic treatment was stopped. Her visual field showed a concentric bilateral scotoma and the electrooculogram test revealed severe impairment of the retinal pigment epithelium. Visual acuity, color vision and visual field recovered completely 8 months later, although electrooculogram remained abnormal. Ocular toxicity has been reported as an infrequent adverse event of oxaliplatin. Findings in this case indicate toxicity of this chemotherapeutic agent on the retinal pigment epithelium, which has not been reported before. This damage could be permanent, and it thus differs from previously described oxaliplatin-induced ocular toxicities, which are usually transient and reversible. With increasing use of oxaliplatin as first-line treatment in advanced colorectal cancer, we have to be aware of this possible toxicity. PMID:21151636

[Do prisms according to Hans-Joachim Haase influence ocular prevalence?].

PubMed

Kromeier, Miriam; Schmitt, Christina; Bach, Michael; Kommerell, Guntram

2002-12-01

Ocular prevalence is defined as an unequal weighting of the eyes in the directional perception of stereo objects. Opinions differ as to the cause and relevance of ocular prevalence. Hans-Joachim Haase suggested that ocular prevalence is due to fixation disparity, brought about by incomplete compensation of heterophoria. He further suggested that prismatic spectacles determined by his "measuring and correcting methodology" (MKH) could restore bicentral fixation and thus establish a perceptual balance between both eyes. We examined 10 non-strabismic subjects with a visual acuity of > or = 1.0 in both eyes. It turned out that all 10 had a "fixation disparity type II", characterised according to Haase by a "disparate retinal correspondence". All subjects underwent the automatic Freiburg Ocular Prevalence Test, without and with MKH prisms. In addition we examined ocular prevalence under forced vergence and compared ocular prevalence with stereoacuity. Spontaneous ocular prevalence ranged between 1 and 69 %. Averaged over all 10 subjects, ocular prevalence without and with the MKH prisms were not significantly different. Statistical evaluation of single subjects revealed only in one of the 10 a significant difference (Bonferroni-corrected p = 0.001). In the subgroup of 5 subjects who underwent forced vergence, ocular prevalence remained unaltered between 0 and 18 Delta base out. The stereoscopic threshold of all 10 subjects ranged between 1.5 and 14.5 arcsec. There was no correlation between ocular prevalence and stereoscopic threshold (r = - 0.2, p = 0.5). Our results indicate that ocular prevalence is largely independent of phoria correction and vergence stress. The excellent stereoacuity of all subjects suggests that ocular prevalence is abandoned for the sake of optimal resolution when very small differences in depth have to be judged.

Tear clearance implications for ocular surface health.

PubMed

de Paiva, Cintia Sade; Pflugfelder, Stephen C

2004-03-01

Tear clearance/turnover provides a global assessment of the function of the lacrimal functional unit and of tear exchange on the ocular surface. It is an indirect measure of dry eye induced inflammation on the ocular surface. It shows better correlation with the severity of ocular irritation symptoms and corneal epithelial disease in dry eye than the Schirmer 1 test. Delayed tear clearance may prove to be the best measure for identifying patients with tear film disorders who may respond to anti-inflammatory therapy.

Evidence for increased SOX3 dosage as a risk factor for X-linked hypopituitarism and neural tube defects.

PubMed

Bauters, Marijke; Frints, Suzanna G; Van Esch, Hilde; Spruijt, Liesbeth; Baldewijns, Marcella M; de Die-Smulders, Christine E M; Fryns, Jean-Pierre; Marynen, Peter; Froyen, Guy

2014-08-01

Genomic duplications of varying lengths at Xq26-q27 involving SOX3 have been described in families with X-linked hypopituitarism. Using array-CGH we detected a 1.1 Mb microduplication at Xq27 in a large family with three males suffering from X-linked hypopituitarism. The duplication was mapped from 138.7 to 139.8 Mb, harboring only two annotated genes, SOX3 and ATP11C, and was shown to be a direct tandem copy number gain. Unexpectedly, the microduplication did not fully segregate with the disease in this family suggesting that SOX3 duplications have variable penetrance for X-linked hypopituitarism. In the same family, a female fetus presenting with a neural tube defect was also shown to carry the SOX3 copy number gain. Since we also demonstrated increased SOX3 mRNA levels in amnion cells derived from an unrelated t(X;22)(q27;q11) female fetus with spina bifida, we propose that increased levels of SOX3 could be a risk factor for neural tube defects. © 2014 Wiley Periodicals, Inc.

Age-Dependent Ocular Dominance Plasticity in Adult Mice

PubMed Central

Lehmann, Konrad; Löwel, Siegrid

2008-01-01

Background Short monocular deprivation (4 days) induces a shift in the ocular dominance of binocular neurons in the juvenile mouse visual cortex but is ineffective in adults. Recently, it has been shown that an ocular dominance shift can still be elicited in young adults (around 90 days of age) by longer periods of deprivation (7 days). Whether the same is true also for fully mature animals is not yet known. Methodology/Principal Findings We therefore studied the effects of different periods of monocular deprivation (4, 7, 14 days) on ocular dominance in C57Bl/6 mice of different ages (25 days, 90–100 days, 109–158 days, 208–230 days) using optical imaging of intrinsic signals. In addition, we used a virtual optomotor system to monitor visual acuity of the open eye in the same animals during deprivation. We observed that ocular dominance plasticity after 7 days of monocular deprivation was pronounced in young adult mice (90–100 days) but significantly weaker already in the next age group (109–158 days). In animals older than 208 days, ocular dominance plasticity was absent even after 14 days of monocular deprivation. Visual acuity of the open eye increased in all age groups, but this interocular plasticity also declined with age, although to a much lesser degree than the optically detected ocular dominance shift. Conclusions/Significance These data indicate that there is an age-dependence of both ocular dominance plasticity and the enhancement of vision after monocular deprivation in mice: ocular dominance plasticity in binocular visual cortex is most pronounced in young animals, reduced but present in adolescence and absent in fully mature animals older than 110 days of age. Mice are thus not basically different in ocular dominance plasticity from cats and monkeys which is an absolutely essential prerequisite for their use as valid model systems of human visual disorders. PMID:18769674

Risk factors for ocular toxoplasmosis in Brazil.

PubMed

Ferreira, A I C; De Mattos, C C Brandão; Frederico, F B; Meira, C S; Almeida, G C; Nakashima, F; Bernardo, C R; Pereira-Chioccola, V L; De Mattos, L C

2014-01-01

The aim of this study was to investigate risk factors for ocular toxoplasmosis (OT) in patients who received medical attention at a public health service. Three hundred and forty-nine consecutive patients, treated in the Outpatient Eye Clinic of Hospital de Base, São José do Rio Preto, São Paulo state, Brazil, were enrolled in this study. After an eye examination, enzyme-linked immunosorbent assay (ELISA) was used to determine anti-Toxoplasma gondii antibodies. The results showed that 25.5% of the patients were seronegative and 74.5% were seropositive for IgG anti-T. gondii antibodies; of these 27.3% had OT and 72.7% had other ocular diseases (OOD). The presence of cats or dogs [odds ratio (OR) 2.22, 95% confidence interval (CI) 1.24-3.98, P = 0.009] and consumption of raw or undercooked meat (OR 1.77, 95% CI 1.05-2.98, P = 0.03) were associated with infection but not with the development of OT. Age (OT 48.2 ± 21.2 years vs. OOD: 69.5 ± 14.7 years, P < 0.0001) and the low level of schooling/literacy (OT vs. OOD: OR 0.414, 95% CI 0.2231-0.7692, P = 0.007) were associated with OT. The presence of dogs and cats as well as eating raw/undercooked meat increases the risk of infection, but is not associated with the development of OT.

Ocular dermoid in Pai Syndrome: A review.

PubMed

Tormey, Peter; Bilic Cace, Iva; Boyle, Michael A

2017-04-01

Pai Syndrome is a rare congenital malformation syndrome of unknown cause with hypertelorism, midline cleft lip, nasal and facial polyps, ocular anomalies and the presence of distinctive lipomas adjacent to the corpus callosum. Herein, we present an infant girl with Pai Syndrome diagnosed in the first week of life with typical facial findings and associated pericallosal lipoma identified on cranial ultrasound and brain MRI. These typical features identified included median cleft of the upper lip (in her case as a forme fruste) with a cleft alveolus and a mid-anterior alveolar process congenital polyp. In addition to these findings there was mild hypertelorism and an ocular abnormality on the right eye. An ophthalmology assessment on day 5 identified the ocular lesion as a limbal dermoid. Several ocular anomalies have been reported in association with Pai Syndrome, however, dermoids have not been frequently described in this Syndrome and not before in a limbal location. Increasing identification of previously unreported ocular abnormalities in Pai Syndrome may improve diagnosis and may prove useful in future work attempting to elucidate the aetiology of this rare syndrome. Copyright © 2017. Published by Elsevier Masson SAS.

Colloidal drug delivery system: amplify the ocular delivery.

PubMed

Ali, Javed; Fazil, Mohd; Qumbar, Mohd; Khan, Nazia; Ali, Asgar

2016-01-01

The ocular perceivers are the most voluntarily accessible organs in terms of location in the body, yet drug distribution to these tissues is one of the most intriguing and challenging endeavors and problematic to the pharmaceutical scientist. The most of ocular diseases are treated with topical application of conventional formulation, i.e. solutions, suspensions and ointment. Typically on installation of these conventional formulations, only <5% of the applied dose penetrates the cornea and reaches intraocular tissues, while a major fraction of the instilled dose is wastage due to the presence of many ocular barriers like external barriers, rapid loss of the instilled solution from the precorneal area and nasolacrimal drainage system. Systemic absorption caused systemic side effects varying from mild to life-threatening events. The main objective of this review is to explore the role of colloidal delivery of drug to minimize the drawbacks associated with them. This review provides an insight into the various constraints associated with ocular drug delivery, summarizes recent findings and applications of colloidal delivery systems, i.e. nanoparticles, nanosuspensions, liposomes, niosomes, dendrimers and contact lenses containing nanoparticles have the capacity to distribute ocular drugs to categorical target sites and hold promise to revolutionize the therapy of many ocular perceiver diseases and minimized the circumscription of conventional delivery. Form the basis of literature review, it has been found that the novel delivery system have greater impact to maximize ocular drug absorption, and minimize systemic absorption and side effects.

Petroleum Jelly: A Novel Medium for Ocular Ultrasound.

PubMed

Engelbert, Patrick R; Palma, James K

2015-08-01

Ocular ultrasound is a useful emergency department imaging modality for evaluation of many conditions, such as retinal detachment, vitreous detachment, vitreous hemorrhage, and elevated intracranial pressure. Obtaining satisfactory ocular ultrasound images requires the use of a medium that eliminates the air interface between the patient's eye and the transducer. Ultrasound gel is most commonly used; however, the use of a transparent dressing applied to the closed eye prior to the application of gel has also been described as a suitable technique. Ocular ultrasound is performed with the high-frequency linear array transducer using a medium to eliminate the air interface between the eye and the transducer. Although ultrasound gel is most frequently used, it can cause minor eye irritation. Placing a transparent dressing over a closed eye prior to application of gel can eliminate the eye irritation. However, our experience in training >500 students in ocular ultrasound has shown that air is frequently introduced underneath the dressing, which leads to poor-quality images. This article introduces petroleum jelly as a medium for ocular ultrasound. By applying a layer of petroleum jelly over the closed eye and allowing it to warm via body heat for 30 to 45 s, this medium can both minimize patient discomfort and provide easily obtainable, high-quality ocular ultrasound images. This article introduces petroleum jelly as a safe, comfortable, and effective medium for ocular ultrasound examination. Published by Elsevier Inc.

Ocular manifestations of drug and alcohol abuse

PubMed Central

Peragallo, Jason; Biousse, Valérie; Newman, Nancy J.

2015-01-01

Purpose of review To review commonly encountered adverse ocular effects of illicit drug use. Recent findings Drug and alcohol abuse can produce a variety of ocular and neuro-ophthalmic side effects. Novel, so-called “designer,” drugs of abuse can lead to unusual ocular disorders. Legal substances, when used in manners for which they have not been prescribed, can also have devastating ophthalmic consequences. Summary In this review we will systematically evaluate each part of the visual pathways and discuss how individual drugs may affect them. PMID:24100364

Ocular hemodynamic effects of nitrovasodilators in healthy subjects.

PubMed

Schmidl, D; Polska, E; Kiss, B; Sacu, S; Garhofer, G; Schmetterer, L

2010-01-01

Nitric oxide (NO) plays a key role in the regulation of ocular blood flow and may be an interesting therapeutic target in ocular ischemic disease. In the present study, we hypothesized that NO-releasing drugs may increase blood flow to the head of the optic nerve and also in the choroid. The study employed a randomized, placebo-controlled, double blind, four-way crossover design. On separate study days, 12 healthy subjects received infusions of nitroglycerin, isosorbide dinitrate, sodium nitroprusside, or placebo. All three study drugs reduced the mean arterial pressure (MAP) and ocular perfusion pressure (OPP) (P < 0.001). None of the administered drugs increased the ocular hemodynamic variables. By contrast, vascular resistance decreased dose dependently during administration of the study drugs (P < 0.001). These results indicate that systemic administration of NO-donor drugs is associated with a decrease in vascular resistance in the ocular vasculature. However, because these drugs also reduce blood pressure, they do not improve perfusion to the posterior eye pole.

Use of Lumbar Punctures in the Management of Ocular Syphilis.

PubMed

Reekie, Ian; Reddy, Yaviche

2018-01-01

Ocular syphilis has become rare in the developed world, but is a common presentation to ophthalmology departments in South Africa. We investigated the proportion of patients diagnosed with ocular syphilis who went on to receive lumbar punctures, and determined the fraction of these who had cerebrospinal fluid findings suggestive of neurosyphilis. We aimed to determine whether the use of lumbar punctures in ocular syphilis patients was beneficial in picking up cases of neurosyphilis. Retrospective study of case notes of patients admitted to two district hospitals in Durban, South Africa, with ocular syphilis over a 20-month period. A total of 31 of 68 ocular syphilis patients underwent lumbar puncture, and of these, eight (25.8%) had findings suggestive of neurosyphilis. Lumbar puncture in ocular syphilis patients should continue to be a routine part of the investigation of these patients; a large proportion of ocular syphilis patients show cerebrospinal fluid findings suggestive of neurosyphilis, are at risk of the complications of neurosyphilis, and should be managed accordingly.

Gastrointestinal Manifestations in X-linked Agammaglobulinemia

PubMed Central

Barmettler, Sara; Otani, Iris M.; Minhas, Jasmit; Abraham, Roshini S.; Chang, Yenhui; Dorsey, Morna J.; Ballas, Zuhair K.; Bonilla, Francisco A.; Ochs, Hans D.; Walter, Jolan E.

2017-01-01

Purpose X-linked agammaglobulinemia is a primary humoral immunodeficiency characterized by hypogammaglobulinemia and increased susceptibility to infection. Although there is increased awareness of autoimmune and inflammatory complications in XLA, the spectrum of gastrointestinal manifestations has not previously been fully explored. Methods We present a case report of a family with two affected patients with XLA. Given the gastrointestinal involvement of the grandfather in this family, we performed a retrospective descriptive analysis of XLA patients with reported diagnoses of GI manifestations and inflammatory bowel disease (IBD) or enteritis registered at the USIDNet, a national registry of primary immunodeficiencies. Results In this cohort of patients with XLA, we found that up to 35% had concurrent gastrointestinal manifestations, and 10% had reported diagnoses of IBD or enteritis. The most commonly reported mutations were missense, which have been associated with a less severe XLA phenotype in the literature. The severity of symptoms were wide-ranging, and management strategies were diverse and mainly experimental. Conclusions Patients with XLA may require close monitoring with particular attention for GI manifestations including IBD and infectious enteritis. Further studies are needed to improve diagnosis and management of GI conditions in XLA patients. PMID:28236219

Cerebellum and Ocular Motor Control

PubMed Central

Kheradmand, Amir; Zee, David S.

2011-01-01

An intact cerebellum is a prerequisite for optimal ocular motor performance. The cerebellum fine-tunes each of the subtypes of eye movements so they work together to bring and maintain images of objects of interest on the fovea. Here we review the major aspects of the contribution of the cerebellum to ocular motor control. The approach will be based on structural–functional correlation, combining the effects of lesions and the results from physiologic studies, with the emphasis on the cerebellar regions known to be most closely related to ocular motor function: (1) the flocculus/paraflocculus for high-frequency (brief) vestibular responses, sustained pursuit eye movements, and gaze holding, (2) the nodulus/ventral uvula for low-frequency (sustained) vestibular responses, and (3) the dorsal oculomotor vermis and its target in the posterior portion of the fastigial nucleus (the fastigial oculomotor region) for saccades and pursuit initiation. PMID:21909334

Ocular manifestations of gravity inversion.

PubMed

Friberg, T R; Weinreb, R N

To determine the ocular manifestations of inverting the human body into a head-down vertical position, we evaluated normal volunteers with applanation tonometry, fundus photography, fluorescein angiography, and ophthalmodynamometry. Compared with data obtained in the sitting position, the intraocular pressure more than doubled on inversion (35.6 +/- 4 v 14.1 +/- 2.8 mm Hg, n = 16), increasing to levels well within the glaucomatous range. Pressures in the central retinal artery underwent similar increases, while the caliber of the retinal arterioles decreased substantially. External ocular findings associated with gravity inversion included orbital congestion, conjunctival hyperemia, petechiae of the eyelids, excessive tearing (epiphora), and subconjunctival hemorrhage. We suggest that patients with retinal vascular abnormalities, macular degeneration, ocular hypertension, glaucoma, and similar disorders refrain from inversion altogether. Whether normal individuals will suffer irreversible damage from inversion is uncertain, but it seems prudent to recommend that prolonged periods of inverted posturing be avoided.

A case of recurrence of congenital ocular toxoplasmosis with frosted branch angiitis (ocular toxoplasmosis with frosted branch angiitis).

PubMed

Suzuki, Takahiro; Onouchi, Hiromi; Nakagawa, Yoshihiro; Oohashi, Hideki; Kaiken, Han; Kawai, Kenji

2010-12-20

To describe a case of recurrence of congenital ocular toxoplasmosis with frosted branch angiitis. A 24-year-old woman presented with hyperemia in her right eye. Medical history included epilepsy at age 14 and mild mental retardation. Iridocyclitis and vitreous opacity were observed in the right eye, and furthermore widespread retinal vessel sheathing due to frosted branch angiitis was seen. Acyclovir was initiated for acute retinal necrosis with frosted branch angiitis. One week later, serologic tests showed elevated toxoplasma antibody level and toxoplasma antibody IgG level, and a white retinal exudative lesion with unclear margins was noted. Therefore, acetylspiramycin and prednisolone were initiated for a recurrence of congenital ocular toxoplasmosis. After treatment, inflammation subsided, the exudative lesion shrank, and the frosted branch angiitis improved. We encountered a case of ocular toxoplasmosis due to recurrence of congenital toxoplasmosis with frosted branch angiitis. The clinical symptoms of ocular toxoplasmosis can be varied and the diagnosis should be kept in mind.

The prevalence of ocular diseases in polish Arabian horses.

PubMed

Paschalis-Trela, Katarzyna; Cywińska, Anna; Trela, Jan; Czopowicz, Michał; Kita, Jerzy; Witkowski, Lucjan

2017-11-07

Equine ocular diseases pose a medical challenge due to long-lasting and cost-consuming therapies as well as economic issues associated with potential decrease in value of affected horses. The scale of the problem is significant but difficult to precisely define because epidemiological data is limited and lacks consistency in presentation. To date, no retrospective studies specifically investigating Arabian horses have been published. The aim of this cross-sectional study was to investigate the prevalence of ocular lesions and define the ocular diseases present in Arabian horses from breeding farms in Poland. Clinical and ophthalmic examination of 615 Arabian horses at Polish breeding farms (15% of Arabian population in Poland) were performed and medical history from the previous 5 years was analyzed. Data was obtained from review of veterinary archives and epidemiological interview of the resident veterinarian at each farm. The prevalence of ocular diseases was 9.75%. The following pathologies were diagnosed (with their respective prevalence): equine recurrent uveitis (ERU; 5.5%); cataract not related to ERU (3.3%); non-visual eyes (1.13%); posttraumatic lesions (0.8%); glaucoma (0.16%). In this study, ERU was the most common ocular disease identified in Arabian horses in Poland. Its prevalence was lower than usually reported in Europe and the United States. There was no sex or farm predisposition but ocular disease prevalence increased with age. Other severe ocular pathologies were also observed, confirming that ocular diseases remain an important clinical problem.

Improved Ocular Delivery of Nepafenac by Cyclodextrin Complexation.

PubMed

Shelley, Haley; Grant, Makenzie; Smith, Forrest T; Abarca, Eva M; Jayachandra Babu, R

2018-06-13

Nepafenac is a nonsteroidal anti-inflammatory drug (NSAID), currently only available as 0.1% ophthalmic suspension (Nevanac®). This study utilized hydroxypropyl-β-cyclodextrin (HPBCD) to increase the water solubility and trans-corneal permeation of nepafenac. The nepafenac-HPBCD complexation in the liquid and solid states were confirmed by phase solubility, differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and nuclear magnetic resonance spectroscopy (NMR) analyses. Nepafenac 0.1% ophthalmic solution was formulated using HPBCD (same pH and osmolality as that of Nevanac®) and pig eye trans-corneal permeation was studied versus Nevanac®. Furthermore, nepafenac content in cornea, sclera, iris, lens, aqueous humor, choroid, ciliary body, retina, and vitreous humor was studied in a continuous isolated pig eye perfusion model in comparison to the suspension and Nevanac®. Permeation studies using porcine corneas revealed that the solution formulation had a permeation rate 18 times higher than Nevanac®. Furthermore, the solution had 11 times higher corneal retention than Nevanac®. Drug distribution studies using porcine eyes revealed that the solution formulation enables detectable levels in various ocular tissues while the drug was undetectable by Nevanac®. The ocular solution formulation had a significantly higher drug concentration in the cornea compared to the suspension or Nevanac®.

Association between Exposure to Smartphones and Ocular Health in Adolescents.

PubMed

Kim, Joowon; Hwang, Yunji; Kang, Seungheon; Kim, Minhye; Kim, Tae-Shin; Kim, Jay; Seo, Jeongmin; Ahn, Hyojeong; Yoon, Sungjoon; Yun, Jun Pil; Lee, Yae Lim; Ham, Hyunsoo; Yu, Hyeong Gon; Park, Sue K

2016-08-01

Smartphone use has dramatically increased in recent years. Smartphones may have adverse health effects, particularly on the eyes, because users stare at the screen for a much longer time than they do with ordinary mobile phones. The objective of this study was to elucidate the relationship between smartphone use and ocular symptoms among adolescents. Information on smartphone use and ocular symptoms (blurring, redness, visual disturbance, secretion, inflammation, lacrimation and dryness) related to eye fatigue and strain from 715 adolescent subjects from three cities in Korea was obtained using a structured questionnaire. Ocular health was scored using number of ocular symptoms. Odds ratios (ORs), 95% confidence intervals (95% CIs) and p-values for ocular symptoms were calculated with binomial and multinomial logistic regression models. Higher prevalence rates for ocular symptoms were observed in groups with greater exposure to smartphones (p < 0.05). Longer daily smartphone use was associated with a higher likelihood of having multiple ocular symptoms (5-7 symptoms out of 7 symptoms; p = 0.005). Excessive/intermittent use (>2 hours daily and ≤2 hours continuously) and excessive/persistent use (>2 hours daily and >2 hours continuously) compared to shorter use (<2 hours daily) were associated with multiple ocular symptoms (OR 2.18, 95% CI 1.09-4.39; OR 2.26, 95% CI 1.11-4.57, respectively). A higher lifetime exposure to smartphones was associated with a higher likelihood of having multiple ocular symptoms (OR 3.05, 95% CI 1.51-6.19; p = 0.001). Increasing exposure to smartphones can have a negative impact on ocular health in adolescents.

Determinants of ocular deviation in esotropic subjects under general anesthesia.

PubMed

Daien, Vincent; Turpin, Chloé; Lignereux, François; Belghobsi, Riadh; Le Meur, Guylene; Lebranchu, Pierre; Pechereau, Alain

2013-01-01

The authors attempted to identify the determinants of ocular deviation in a population of patients with esotropia under general anesthesia. Forty-one patients with esotropia were included. Horizontal ocular deviation was evaluated by the photographic Hirschberg test both in the awakened state and under general anesthesia before surgery. Changes in ocular deviation were measured and a multivariate analysis was used to assess its clinical determinants. The mean age (± standard deviation [SD]) of study subjects was 13 ± 11 years and 51% were females. The mean spherical equivalent refraction of the right eye was 2.44 ± 2.50 diopters (D), with no significant difference between eyes (P = .26). The mean ocular deviation changed significantly, from 33.5 ± 12.5 prism diopters (PD) at preoperative examination to 8.8 ± 11.4 PD under general anesthesia (P = .0001). The changes in ocular deviation positively correlated with the pre-operative ocular deviation (correlation coefficient r = 0.59, P = .0001) and negatively correlated with patient age (correlation coefficient r = -0.53, P = .0001). These two determinants remained significant after multivariate adjustment of the following variables: preoperative ocular deviation; age; gender; spherical equivalent refraction; and number of previous strabismus surgeries (model r(2) = 0.49, P = .0001). The ocular position under general anesthesia was reported as a key factor in the surgical treatment of subjects with esotropia; therefore, its clinical determinants were assessed. The authors observed that preoperative ocular deviation and patient age were the main factors that influenced the ocular position under general anesthesia. Copyright 2013, SLACK Incorporated.

Identification of Four Novel Synonymous Substitutions in the X-Linked Genes Neuroligin 3 and Neuroligin 4X in Japanese Patients with Autistic Spectrum Disorder.

PubMed

Yanagi, Kumiko; Kaname, Tadashi; Wakui, Keiko; Hashimoto, Ohiko; Fukushima, Yoshimitsu; Naritomi, Kenji

2012-01-01

Mutations in the X-linked genes neuroligin 3 (NLGN3) and neuroligin 4X (NLGN4X) were first implicated in the pathogenesis of X-linked autism in Swedish families. However, reports of mutations in these genes in autism spectrum disorder (ASD) patients from various ethnic backgrounds present conflicting results regarding the etiology of ASD, possibly because of genetic heterogeneity and/or differences in their ethnic background. Additional mutation screening study on another ethnic background could help to clarify the relevance of the genes to ASD. We scanned the entire coding regions of NLGN3 and NLGN4X in 62 Japanese patients with ASD by polymerase chain reaction-high-resolution melting curve and direct sequencing analyses. Four synonymous substitutions, one in NLGN3 and three in NLGN4X, were identified in four of the 62 patients. These substitutions were not present in 278 control X-chromosomes from unrelated Japanese individuals and were not registered in the database of Single Nucleotide Polymorphisms build 132 or in the Japanese Single Nucleotide Polymorphisms database, indicating that they were novel and specific to ASD. Though further analysis is necessary to determine the physiological and clinical importance of such substitutions, the possibility of the relevance of both synonymous and nonsynonymous substitutions with the etiology of ASD should be considered.

Identification of Four Novel Synonymous Substitutions in the X-Linked Genes Neuroligin 3 and Neuroligin 4X in Japanese Patients with Autistic Spectrum Disorder

PubMed Central

Yanagi, Kumiko; Kaname, Tadashi; Wakui, Keiko; Hashimoto, Ohiko; Fukushima, Yoshimitsu; Naritomi, Kenji

2012-01-01

Mutations in the X-linked genes neuroligin 3 (NLGN3) and neuroligin 4X (NLGN4X) were first implicated in the pathogenesis of X-linked autism in Swedish families. However, reports of mutations in these genes in autism spectrum disorder (ASD) patients from various ethnic backgrounds present conflicting results regarding the etiology of ASD, possibly because of genetic heterogeneity and/or differences in their ethnic background. Additional mutation screening study on another ethnic background could help to clarify the relevance of the genes to ASD. We scanned the entire coding regions of NLGN3 and NLGN4X in 62 Japanese patients with ASD by polymerase chain reaction-high-resolution melting curve and direct sequencing analyses. Four synonymous substitutions, one in NLGN3 and three in NLGN4X, were identified in four of the 62 patients. These substitutions were not present in 278 control X-chromosomes from unrelated Japanese individuals and were not registered in the database of Single Nucleotide Polymorphisms build 132 or in the Japanese Single Nucleotide Polymorphisms database, indicating that they were novel and specific to ASD. Though further analysis is necessary to determine the physiological and clinical importance of such substitutions, the possibility of the relevance of both synonymous and nonsynonymous substitutions with the etiology of ASD should be considered. PMID:22934180

Fundus autofluorescence imaging in an ocular screening program.

PubMed

Kolomeyer, A M; Nayak, N V; Szirth, B C; Khouri, A S

2012-01-01

Purpose. To describe integration of fundus autofluorescence (FAF) imaging into an ocular screening program. Methods. Fifty consecutive screening participants were included in this prospective pilot imaging study. Color and FAF (530/640 nm exciter/barrier filters) images were obtained with a 15.1MP Canon nonmydriatic hybrid camera. A clinician evaluated the images on site to determine need for referral. Visual acuity (VA), intraocular pressure (IOP), and ocular pathology detected by color fundus and FAF imaging modalities were recorded. Results. Mean ± SD age was 47.4 ± 17.3 years. Fifty-two percent were female and 58% African American. Twenty-seven percent had a comprehensive ocular examination within the past year. Mean VA was 20/39 in the right eye and 20/40 in the left eye. Mean IOP was 15 mmHg bilaterally. Positive color and/or FAF findings were identified in nine (18%) individuals with diabetic retinopathy or macular edema (n = 4), focal RPE defects (n = 2), age-related macular degeneration (n = 1), central serous retinopathy (n = 1), and ocular trauma (n = 1). Conclusions. FAF was successfully integrated in our ocular screening program and aided in the identification of ocular pathology. Larger studies examining the utility of this technology in screening programs may be warranted.

Fundus Autofluorescence Imaging in an Ocular Screening Program

PubMed Central

Kolomeyer, A. M.; Nayak, N. V.; Szirth, B. C.; Khouri, A. S.

2012-01-01

Purpose. To describe integration of fundus autofluorescence (FAF) imaging into an ocular screening program. Methods. Fifty consecutive screening participants were included in this prospective pilot imaging study. Color and FAF (530/640 nm exciter/barrier filters) images were obtained with a 15.1MP Canon nonmydriatic hybrid camera. A clinician evaluated the images on site to determine need for referral. Visual acuity (VA), intraocular pressure (IOP), and ocular pathology detected by color fundus and FAF imaging modalities were recorded. Results. Mean ± SD age was 47.4 ± 17.3 years. Fifty-two percent were female and 58% African American. Twenty-seven percent had a comprehensive ocular examination within the past year. Mean VA was 20/39 in the right eye and 20/40 in the left eye. Mean IOP was 15 mmHg bilaterally. Positive color and/or FAF findings were identified in nine (18%) individuals with diabetic retinopathy or macular edema (n = 4), focal RPE defects (n = 2), age-related macular degeneration (n = 1), central serous retinopathy (n = 1), and ocular trauma (n = 1). Conclusions. FAF was successfully integrated in our ocular screening program and aided in the identification of ocular pathology. Larger studies examining the utility of this technology in screening programs may be warranted. PMID:23316224

Nanotherapies for the treatment of ocular diseases.

PubMed

Reimondez-Troitiño, S; Csaba, N; Alonso, M J; de la Fuente, M

2015-09-01

The topical route is the most frequent and preferred way to deliver drugs to the eye. Unfortunately, the very low ocular drug bioavailability (less than 5%) associated with this modality of administration, makes the efficient treatment of several ocular diseases a significant challenge. In the last decades, it has been shown that specific nanocarriers can interact with the ocular mucosa, thereby increasing the retention time of the associated drug onto the eye, as well as its permeability across the corneal and conjunctival epithelium. In this review, we comparatively analyze the mechanism of action and specific potential of the most studied nano-drug delivery carriers. In addition, we present the success achieved until now using a number of nanotherapies for the treatment of the most prevalent ocular pathologies, such as infections, inflammation, dry eye, glaucoma, and retinopathies. Copyright © 2015 Elsevier B.V. All rights reserved.

Ocular and periocular hemangiosarcoma in six horses.

PubMed

Scherrer, Nicole M; Lassaline, Mary; Engiles, Julie

2017-11-07

To determine the characteristics of and prognosis for ocular and periocular hemangiosarcoma in horses. Six horses treated for ocular or periocular hemangiosarcoma. A retrospective review of medical records from 2007 to 2015 was performed to identify horses with a histologic diagnosis of ocular or periocular hemangiosarcoma. Signalment (age, sex, breed), duration of clinical signs, prior treatment, tumor size and location, medical and surgical treatment including postoperative chemotherapy, follow-up time, and outcome were obtained from medical records. Histopathology was reviewed by a board-certified pathologist. In six horses diagnosed with ocular or periocular hemangiosarcoma, no breed, age, or sex was overrepresented. Sites included the temporal limbus (3), third eyelid (2), and uvea (1). With the exception of one horse with uveal hemangiosarcoma, 5/6 horses had lightly pigmented periocular haircoat. Histologic features of ocular hemangiosarcoma in 6/6 cases included high cellularity, nuclear pleomorphism, and inflammation with a mitotic index ranging from 0 to 8 mitoses per 10 consecutive 400× fields. Five of six tumors displayed solar elastosis, indicating ultraviolet light-induced damage to sub-epithelial collagen. Treatment included surgical excision in all cases and was not associated with recurrence in 4/6. Three cases that received ancillary treatment with topical mitomycin C had no postoperative recurrence. Two cases with postexcisional recurrence had histologic evidence of incomplete excision. Complete surgical excision may be associated with resolution of periocular and ocular hemangiosarcoma in horses. Etiopathogenesis may include exposure to ultraviolet light. © 2017 American College of Veterinary Ophthalmologists.

Evaluation of the Goldmann-Witmer coefficient in the immunological diagnosis of ocular toxocariasis.

PubMed

Wang, Zhu Jian; Zhou, Min; Cao, Wen Jun; Ji, Jian; Bi, Ying Wen; Huang, Xin; Xu, Ge Zhi

2016-06-01

Ocular toxocariasis (OT) is a zoonotic parasitic infection mainly caused by the intraocular tissue invasion of second-stage Toxocara canis or Toxocara cati larva. Measuring specific anti-T. canis antibodies in the intraocular fluid (IF) can increase OT diagnosis accuracy using Goldmann-Witmer coefficient (GWC). However, there is no systemic evaluation of GWC application in the immunological diagnosis of OT. To assess GWC for the immunodiagnosis of ocular toxocariasis, paired IF and serum samples from 72 patients diagnosed with OT were retrospectively analyzed for specific anti-T. canis IgG by enzyme linked immunosorbent assay (ELISA). GWC values were calculated to determine intraocular specific IgG production. Clinical features and other laboratory data were recorded, and their correlations with GWC evaluated. Of the 72 OT patients, 60 (83.33%) showed intraocular specific IgG production confirmed by GWC, while intraocular nonspecific IgE production was found in 64/69 (92.75%) cases. No significant correlation was found among clinical features and IF specific IgG production. Values for peripheral blood samples were lower than those of intraocular fluid regarding OT screening, and vitreous humor samples showed increased local specific IgG and nonspecific IgE production compared with aqueous humor samples. Overall, our results indicate that GWC and intraocular IgE production have referential values in diagnosing ocular toxocariasis. Copyright © 2016 Elsevier B.V. All rights reserved.

Ocular Chromatic Aberrations and Their Effects on Polychromatic Retinal Image Quality

NASA Astrophysics Data System (ADS)

Zhang, Xiaoxiao

Previous studies of ocular chromatic aberrations have concentrated on chromatic difference of focus (CDF). Less is known about the chromatic difference of image position (CDP) in the peripheral retina and no experimental attempt has been made to measure the ocular chromatic difference of magnification (CDM). Consequently, theoretical modelling of human eyes is incomplete. The insufficient knowledge of ocular chromatic aberrations is partially responsible for two unsolved applied vision problems: (1) how to improve vision by correcting ocular chromatic aberration? (2) what is the impact of ocular chromatic aberration on the use of isoluminance gratings as a tool in spatial-color vision?. Using optical ray tracing methods, MTF analysis methods of image quality, and psychophysical methods, I have developed a more complete model of ocular chromatic aberrations and their effects on vision. The ocular CDM was determined psychophysically by measuring the tilt in the apparent frontal parallel plane (AFPP) induced by interocular difference in image wavelength. This experimental result was then used to verify a theoretical relationship between the ocular CDM, the ocular CDF and the entrance pupil of the eye. In the retinal image after correcting the ocular CDF with existing achromatizing methods, two forms of chromatic aberration (CDM and chromatic parallax) were examined. The CDM was predicted by theoretical ray tracing and measured with the same method used to determine ocular CDM. The chromatic parallax was predicted with a nodal ray model and measured with the two-color vernier alignment method. The influence of these two aberrations on polychromatic MTF were calculated. Using this improved model of ocular chromatic aberration, luminance artifacts in the images of isoluminance gratings were calculated. The predicted luminance artifacts were then compared with experimental data from previous investigators. The results show that: (1) A simple relationship exists between

OCULAR SYPHILIS IN A KIDNEY TRANSPLANT RECIPIENT

PubMed Central

ROMAO, Elen A.; BOLELLA, Valdes R.; NARDIN, Maria Estela P.; HABIB-SIMAO, Maria Lucia; FURTADO, João Marcelo; MOYSES-NETO, Miguel

2016-01-01

We present a case of ocular syphilis after a renal transplantation involving progressive vision loss without clinically identifiable ocular disease. Electroretinography showed signs of ischemia, especially in the internal retina. A serological test was positive for syphilis. Lumbar puncture revealed lymphocytic meningitis and a positive serologic test for syphilis in the cerebrospinal fluid. The patient was treated with penicillin, and had a quick vision improvement. In the case of transplant recipients, clinicians should always consider the diagnosis of ocular syphilis in cases with unexplained visual acuity decrement, as this condition may cause serious complications if not treated. PMID:27253748

Influenza Virus Respiratory Infection and Transmission Following Ocular Inoculation in Ferrets

PubMed Central

Belser, Jessica A.; Gustin, Kortney M.; Maines, Taronna R.; Pantin-Jackwood, Mary J.; Katz, Jacqueline M.; Tumpey, Terrence M.

2012-01-01

While influenza viruses are a common respiratory pathogen, sporadic reports of conjunctivitis following human infection demonstrates the ability of this virus to cause disease outside of the respiratory tract. The ocular surface represents both a potential site of virus replication and a portal of entry for establishment of a respiratory infection. However, the properties which govern ocular tropism of influenza viruses, the mechanisms of virus spread from ocular to respiratory tissue, and the potential differences in respiratory disease initiated from different exposure routes are poorly understood. Here, we established a ferret model of ocular inoculation to explore the development of virus pathogenicity and transmissibility following influenza virus exposure by the ocular route. We found that multiple subtypes of human and avian influenza viruses mounted a productive virus infection in the upper respiratory tract of ferrets following ocular inoculation, and were additionally detected in ocular tissue during the acute phase of infection. H5N1 viruses maintained their ability for systemic spread and lethal infection following inoculation by the ocular route. Replication-independent deposition of virus inoculum from ocular to respiratory tissue was limited to the nares and upper trachea, unlike traditional intranasal inoculation which results in virus deposition in both upper and lower respiratory tract tissues. Despite high titers of replicating transmissible seasonal viruses in the upper respiratory tract of ferrets inoculated by the ocular route, virus transmissibility to naïve contacts by respiratory droplets was reduced following ocular inoculation. These data improve our understanding of the mechanisms of virus spread following ocular exposure and highlight differences in the establishment of respiratory disease and virus transmissibility following use of different inoculation volumes and routes. PMID:22396651

Ocular fishhook injuries.

PubMed

Ang, C S

2001-06-01

Ocular fishhook injuries are rare, yet potentially vision threatening as complications such as corneal scarring, retinal detachment and endophthalmitis may result. The surgical management of these cases is challenging due to the construction of barbed fishhooks.

MHC class 2 deficiency and X-linked agammaglobulinaemia in a consanguineous extended family.

PubMed

Broides, A; Shubinsky, G; Parvari, R; Grimbacher, B; Somech, R; Garty, B Z; Levy, J

2009-08-01

Manifestations of immunodeficiency within the same family are presumed to be the same disease. We report a consanguineous extended family where four patients have immunodeficiency, three have X-linked agammaglobulinaemia and one has major histocompatibility complex class 2 deficiency. Within one family, two rare genetic diseases with similar clinical manifestations can occur.

Dysregulation of X-linked gene expression in Klinefelter's syndrome and association with verbal cognition.

PubMed

Vawter, Marquis P; Harvey, Philip D; DeLisi, Lynn E

2007-09-05

Klinefelter's Syndrome (KS) is a chromosomal karyotype with one or more extra X chromosomes. KS individuals often show language impairment and the phenotype might be due to overexpression of genes on the extra X chromosome(s). We profiled mRNA derived from lymphoblastoid cell lines from males with documented KS and control males using the Affymetrix U133P microarray platform. There were 129 differentially expressed genes (DEGs) in KS group compared with controls after Benjamini-Hochberg false discovery adjustment. The DEGs included 14 X chromosome genes which were significantly over-represented. The Y chromosome had zero DEGs. In exploratory analysis of gene expression-cognition relationships, 12 DEGs showed significant correlation of expression with measures of verbal cognition in KS. Overexpression of one pseudoautosomal gene, GTPBP6 (GTP binding protein 6, putative) was inversely correlated with verbal IQ (r = -0.86, P < 0.001) and four other measures of verbal ability. Overexpression of XIST was found in KS compared to XY controls suggesting that silencing of many genes on the X chromosome might occur in KS similar to XX females. The microarray findings for eight DEGs were validated by quantitative PCR. The 14 X chromosome DEGs were not differentially expressed in prior studies comparing female and male brains suggesting a dysregulation profile unique to KS. Examination of X-linked DEGs, such as GTPBP6, TAF9L, and CXORF21, that show verbal cognition-gene expression correlations may establish a causal link between these genes, neurodevelopment, and language function. A screen of candidate genes may serve as biomarkers of KS for early diagnosis. Copyright 2007 Wiley-Liss, Inc.

Aquaporins in the eye: Expression, function, and roles in ocular disease☆

PubMed Central

Schey, Kevin L.; Wang, Zhen; Wenke, Jamie L.; Qi, Ying

2015-01-01

Background All thirteen known mammalian aquaporins have been detected in the eye. Moreover, aquaporins have been identified as playing essential roles in ocular functions ranging from maintenance of lens and corneal transparency to production of aqueous humor to maintenance of cellular homeostasis and regulation of signal transduction in the retina. Scope of review This review summarizes the expression and known functions of ocular aquaporins and discusses their known and potential roles in ocular diseases. Major conclusions Aquaporins play essential roles in all ocular tissues. Remarkably, not all aquaporin function as a water permeable channel and the functions of many aquaporins in ocular tissues remain unknown. Given their vital roles in maintaining ocular function and their roles in disease, aquaporins represent potential targets for future therapeutic development. General significance Since aquaporins play key roles in ocular physiology, an understanding of these functions is important to improving ocular health and treating diseases of the eye. It is likely that future therapies for ocular diseases will rely on modulation of aquaporin expression and/or function. This article is part of a Special Issue entitled Aquaporins. PMID:24184915

Ocular complications of oral contraceptives.

PubMed

Wood, J R

1977-01-01

The systemic side effects of oral contraceptives are mentioned, and the incidence and variety of ocular complications are discussed. Experimental studies on the ocular effects of oral contraceptives in laboratory animals have shown only increased permeability of the lens and possibly vascular dilatation. Numerous case reports, however, have been published which describe neuroophthalamic, vascular, retinal and macular, aqueous humor dynamic, cornea and contact lense, lens, color vision, and other miscellaneous effects. These reports are reviewed as are the 6 reported prospective studies. These prospective studies reveal only changes in kerotometry readings. Thus the large number of case reports may represent a low overall incidence or may be normal findings in the population as a whole or may be caused by other systemic factors. Until multicenter prospective studies provide definitive guidelines, the risk associated with oral contraceptive use must be kept in its proper perpsective and ocular histories should contain information on oral contraceptive use.

An Ethyl-Nitrosourea-Induced Point Mutation in Phex Causes Exon Skipping, X-Linked Hypophosphatemia, and Rickets

PubMed Central

Carpinelli, Marina R.; Wicks, Ian P.; Sims, Natalie A.; O’Donnell, Kristy; Hanzinikolas, Katherine; Burt, Rachel; Foote, Simon J.; Bahlo, Melanie; Alexander, Warren S.; Hilton, Douglas J.

2002-01-01

We describe the clinical, genetic, biochemical, and molecular characterization of a mouse that arose in the first generation (G1) of a random mutagenesis screen with the chemical mutagen ethyl-nitrosourea. The mouse was observed to have skeletal abnormalities inherited with an X-linked dominant pattern of inheritance. The causative mutation, named Skeletal abnormality 1 (Ska1), was shown to be a single base pair mutation in a splice donor site immediately following exon 8 of the Phex (phosphate-regulating gene with homologies to endopeptidases located on the X-chromosome) gene. This point mutation caused skipping of exon 8 from Phex mRNA, hypophosphatemia, and features of rickets. This experimentally induced phenotype mirrors the human condition X-linked hypophosphatemia; directly confirms the role of Phex in phosphate homeostasis, normal skeletal development, and rickets; and illustrates the power of mutagenesis in exploring animal models of human disease. PMID:12414538

An ethyl-nitrosourea-induced point mutation in phex causes exon skipping, x-linked hypophosphatemia, and rickets.

PubMed

Carpinelli, Marina R; Wicks, Ian P; Sims, Natalie A; O'Donnell, Kristy; Hanzinikolas, Katherine; Burt, Rachel; Foote, Simon J; Bahlo, Melanie; Alexander, Warren S; Hilton, Douglas J

2002-11-01

We describe the clinical, genetic, biochemical, and molecular characterization of a mouse that arose in the first generation (G(1)) of a random mutagenesis screen with the chemical mutagen ethyl-nitrosourea. The mouse was observed to have skeletal abnormalities inherited with an X-linked dominant pattern of inheritance. The causative mutation, named Skeletal abnormality 1 (Ska1), was shown to be a single base pair mutation in a splice donor site immediately following exon 8 of the Phex (phosphate-regulating gene with homologies to endopeptidases located on the X-chromosome) gene. This point mutation caused skipping of exon 8 from Phex mRNA, hypophosphatemia, and features of rickets. This experimentally induced phenotype mirrors the human condition X-linked hypophosphatemia; directly confirms the role of Phex in phosphate homeostasis, normal skeletal development, and rickets; and illustrates the power of mutagenesis in exploring animal models of human disease.

Screening athletes with Down syndrome for ocular disease.

PubMed

Gutstein, Walter; Sinclair, Stephen H; North, Rachel V; Bekiroglu, N

2010-02-01

Persons with Down syndrome are well known to have a high prevalence of vision and eye health problems, many of which are undetected or untreated primarily because of infrequent ocular examinations. Public screening programs, directed toward the pediatric population, have become more popular and commonly use letter or symbol charts. This study compares 2 vision screening methods, the Lea Symbol chart and a newly developed interactive computer program, the Vimetrics Central Vision Analyzer (CVA), in their ability to identify ocular disease in the Down syndrome population. Athletes with Down syndrome participating in the European Special Olympics underwent an ocular screening including history, auto-refraction, colour vision assessment, stereopsis assessment, motility assessment, pupil reactivity, and tonometry testing, as well as anterior segment and fundus examinations to evaluate for ocular disease. Visual acuity was tested with the Lea chart and CVA to evaluate these as screening tests for detecting ocular disease as well as significant, uncorrected refractive errors. Among the 91 athletes that presented to the screening, 79 (158 eyes) were sufficiently cooperative for the examination to be completed. Mean age was 26 years +/-10.8 SD. Significant, uncorrected refractive errors (>/=1.00 spherical equivalent) were detected in 28 (18%) eyes and ocular pathology in 51 (32%) eyes. The Lea chart sensitivity and specificity were 43% and 74%, respectively, for detecting ocular pathology and 58% and 100% for detecting uncorrected refractive errors. The CVA sensitivity and specificity were 70% and 86% for detecting pathology and 71% and 100% for detecting uncorrected refractive errors. This study confirmed the findings of prior studies in identifying a significant presence of uncorrected refractive errors and ocular pathology in the Down syndrome population. Screening with the Lea symbol chart found borderline sufficient sensitivity and specificity for the test to be used

Ocular delivery systems for topical application of anti-infective agents.

PubMed

Duxfield, Linda; Sultana, Rubab; Wang, Ruokai; Englebretsen, Vanessa; Deo, Samantha; Rupenthal, Ilva D; Al-Kassas, Raida

2016-01-01

For the treatment of anterior eye segment infections using anti-infective agents, topical ocular application is the most convenient route of administration. However, topical delivery of anti-infective agents is associated with a number of problems and challenges owing to the unique structure of the eye and the physicochemical properties of these compounds. Topical ocular drug delivery systems can be classified into two forms: conventional and non-conventional. The efficacy of conventional ocular formulations is limited by poor corneal retention and permeation resulting in low ocular bioavailability. Recently, attention has been focused on improving topical ocular delivery of anti-infective agents using advanced drug delivery systems. This review will focus on the challenges of efficient topical ocular delivery of anti-infective agents and will discuss the various types of delivery systems used to improve the treatment anterior segment infections.

Hospital-based ocular emergencies: epidemiology, treatment, and visual outcomes.

PubMed

Cheung, Cindy A; Rogers-Martel, Melanie; Golas, Liliya; Chepurny, Anna; Martel, James B; Martel, Joseph R

2014-03-01

Ocular trauma is recognized as the leading cause of unilateral blindness. However, few studies to date have focused on the clinical features of hospital-based ocular emergencies. Effectiveness of trauma centers in treating ocular emergencies was compared with treatment in traditional community hospital emergency departments. Demographics, causes, and nature of ocular emergencies, as well as visual outcome in community hospitals emergency departments and trauma centers, were also examined. Records of 1027 patients with ocular emergencies seen between July 2007 and November 2010 at 3 community hospitals emergency departments and 2 hospitals with level II trauma centers were retrospectively examined. Unpaired t test and Pearson χ(2) test were used to determine statistical significance. The incidence of patients requiring ophthalmic intervention was 77.2 per 100 000 in the community hospitals and 208.9 per 100 000 in the trauma centers. Rates of ocular emergencies were higher in middle-aged, white men. Orbital fractures were found in 86% of all orbital contusion cases in trauma centers, whereas 66.7% of patients with fall injuries and open globe diagnoses resulted in legal blindness. The middle-aged, white men are more vulnerable to ocular injuries caused mainly by motor vehicle accidents. The ability of trauma centers to provide comparable increases in vision outcomes, despite treating more severe ocular emergencies, demonstrates the effectiveness of trauma centers. Patients diagnosed as having orbital contusions or who have fall injuries deserve careful evaluation because they are more likely to have more severe sight-threatening injuries. Copyright © 2014 Elsevier Inc. All rights reserved.

Craniofacial morphometric analysis of individuals with X-linked hypohidrotic ectodermal dysplasia.

PubMed

Goodwin, Alice F; Larson, Jacinda R; Jones, Kyle B; Liberton, Denise K; Landan, Maya; Wang, Zhifeng; Boekelheide, Anne; Langham, Margaret; Mushegyan, Vagan; Oberoi, Snehlata; Brao, Rosalie; Wen, Timothy; Johnson, Ramsey; Huttner, Kenneth; Grange, Dorothy K; Spritz, Richard A; Hallgrímsson, Benedikt; Jheon, Andrew H; Klein, Ophir D

2014-09-01

Hypohidrotic ectodermal dysplasia (HED) is the most prevalent type of ectodermal dysplasia (ED). ED is an umbrella term for a group of syndromes characterized by missing or malformed ectodermal structures, including skin, hair, sweat glands, and teeth. The X-linked recessive (XL), autosomal recessive (AR), and autosomal dominant (AD) types of HED are caused by mutations in the genes encoding ectodysplasin (EDA1), EDA receptor (EDAR), or EDAR-associated death domain (EDARADD). Patients with HED have a distinctive facial appearance, yet a quantitative analysis of the HED craniofacial phenotype using advanced three-dimensional (3D) technologies has not been reported. In this study, we characterized craniofacial morphology in subjects with X-linked hypohidrotic ectodermal dysplasia (XLHED) by use of 3D imaging and geometric morphometrics (GM), a technique that uses defined landmarks to quantify size and shape in complex craniofacial morphologies. We found that the XLHED craniofacial phenotype differed significantly from controls. Patients had a smaller and shorter face with a proportionally longer chin and midface, prominent midfacial hypoplasia, a more protrusive chin and mandible, a narrower and more pointed nose, shorter philtrum, a narrower mouth, and a fuller and more rounded lower lip. Our findings refine the phenotype of XLHED and may be useful both for clinical diagnosis of XLHED and to extend understanding of the role of EDA in craniofacial development.

X-linked recessive nephrogenic diabetes insipidus: a clinico-genetic study.

PubMed

Hong, Che Ry; Kang, Hee Gyung; Choi, Hyun Jin; Cho, Min Hyun; Lee, Jung Won; Kang, Ju Hyung; Park, Hye Won; Koo, Ja Wook; Ha, Tae-Sun; Kim, Su-Yung; Il Cheong, Hae

2014-01-01

A retrospective genotype and phenotype analysis of X-linked congenital nephrogenic diabetes insipidus (NDI) was conducted on a nationwide cohort of 25 (24 male, 1 female) Korean children with AVPR2 gene mutations, comparing non-truncating and truncating mutations. In an analysis of male patients, the median age at diagnosis was 0.9 years old. At a median follow-up of 5.4 years, urinary tract dilatations were evident in 62% of patients and their median glomerular filtration rate was 72 mL/min/1.73 m2. Weights and heights were under the 3rd percentile in 22% and 33% of patients, respectively. One patient had low intelligence quotient and another developed end-stage renal disease. No statistically significant genotype-phenotype correlation was found between non-truncating and truncating mutations. One patient was female; she was analyzed separately because inactivation and mosaicism of the X chromosome may influence clinical manifestations in female patients. Current unsatisfactory long-term outcome of congenital NDI necessitates a novel therapeutic strategy.

Four-Year Placebo-Controlled Trial of Docosahexaenoic Acid in X-Linked Retinitis Pigmentosa (DHAX Trial)

PubMed Central

Hoffman, Dennis R.; Hughbanks-Wheaton, Dianna K.; Pearson, N. Shirlene; Fish, Gary E.; Spencer, Rand; Takacs, Alison; Klein, Martin; Locke, Kirsten G.; Birch, David G.

2016-01-01

IMPORTANCE X-linked retinitis pigmentosa is a severe inherited retinal degenerative disease with a frequency of 1 in 100 000 persons. Because no cure is available for this orphan disease and treatment options are limited, slowing of disease progression would be a meaningful outcome. OBJECTIVE To determine whether high-dose docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid, slows progression of X-linked retinitis pigmentosa measured by cone electroretinography (ERG). DESIGN, SETTING, AND PARTICIPANTS A 4-year, single-site, randomized, placebo-controlled, double-masked phase 2 clinical trial at a research center specializing in medical retina. Seventy-eight male patients diagnosed as having X-linked retinitis pigmentosa were randomized to DHA or placebo. Data were omitted for 2 patients with non–X-linked retinitis pigmentosa and 16 patients who were unable to follow protocol during the first year. The remaining participants were tested annually and composed a modified intent-to-treat cohort (DHA group, n = 33; placebo group, n = 27). INTERVENTIONS All participants received a multivitamin and were randomly assigned to oral DHA (30 mg/kg/d) or placebo. MAIN OUTCOMES AND MEASURES The primary outcome was the rate of loss of cone ERG function. Secondary outcomes were rod and maximal ERG amplitudes and cone ERG implicit times. Capsule counts and red blood cell DHA levels were assessed to monitor adherence. RESULTS Average (6-month to 4-year) red blood cell DHA levels were 4-fold higher in the DHA group than in the placebo group (P < .001). There was no difference between the DHA and placebo groups in the rate of cone ERG functional loss (0.028 vs 0.022 log µV/y, respectively; P = .30). No group differences were evident for change in rod ERG (P = .27), maximal ERG (P = .65), or cone implicit time (no change over 4 years). The rate of cone loss (ie, event rate) was markedly reduced compared with rates in previous studies. No severe treatment-emergent adverse

Placental sulfatase deficiency: maternal and fetal expression of steroid sulfatase deficiency and X-linked ichthyosis.

PubMed

Bradshaw, K D; Carr, B R

1986-07-01

PSD-X-linked ichthyosis are manifestations of a similar disorder of an inborn error of metabolism characterized by a deficiency of steroid sulfatase. The decreased enzyme activity is due to the absence of the expression of enzyme (steroid sulfatase) protein. Affected individuals with this disorder are males (X-linked inheritance) with a frequency of 1/2000 to 1/6000 births. Homozygous females from cosanguineous marriages have been reported with this disorder. The diagnosis is suspected and confirmed by: Low estriol excretion; Negative DHEAS loading test Increased DHEAS in amnionic fluid; Normal DHEAS in cord plasma; Possible delayed or abnormal labor patterns; Decreased sulfatase activity in the placenta, fibroblast, erythrocytes, lymphocytes or leukocytes of affected individuals; Development of ichthyosis in male infants at 2 to 3 months of age.

A recoding scheme for X-linked and pseudoautosomal loci to be used with computer programs for autosomal LOD-score analysis.

PubMed

Strauch, Konstantin; Baur, Max P; Wienker, Thomas F

2004-01-01

We present a recoding scheme that allows for a parametric multipoint X-chromosomal linkage analysis of dichotomous traits in the context of a computer program for autosomes that can use trait models with imprinting. Furthermore, with this scheme, it is possible to perform a joint multipoint analysis of X-linked and pseudoautosomal loci. It is required that (1) the marker genotypes of all female nonfounders are available and that (2) there are no male nonfounders who have daughters in the pedigree. The second requirement does not apply if the trait locus is pseudoautosomal. The X-linked marker loci are recorded by adding a dummy allele to the males' hemizygous genotypes. For modelling an X-linked trait locus, five different liability classes are defined, in conjunction with a paternal imprinting model for male nonfounders. The formulation aims at the mapping of a diallelic trait locus relative to an arbitrary number of codominant markers with known genetic distances, in cases where a program for a genuine X-chromosomal analysis is not available. 2004 S. Karger AG, Basel.

[Mutant prevention concentrations of antibacterial agents to ocular pathogenic bacteria].

PubMed

Liang, Qing-Feng; Wang, Zhi-Qun; Li, Ran; Luo, Shi-Yun; Deng, Shi-Jing; Sun, Xu-Guang

2009-01-01

To establish a method to measure mutant prevention concentration (MPC) in vitro, and to measure MPC of antibacterial agents for ocular bacteria caused keratitis. It was an experimental study. Forty strains of ocular bacteria were separated from cornea in Beijing Institute of Ophthalmology, which included 8 strains of Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Pseudomonas aeruginosa and Klebsiella pneumoniae respectively. The minimal inhibitory concentration (MIC) of the levofloxacin (LVF), ofloxacin (OFL), ciprofloxacin (CIP), norfloxacin (NFL), tobramycin (TOB) and chloromycetin (CHL) were determined by agar dilution method from National Committee of Clinical Laboratory Standard (NCCLS). The MPC were measured by accumulate-bacterial methods with bacterial population inoculated more than 1.2 x 10(10) colony forming units per milliliter with Mueller-Hinton broth and tryptic soy agar plate. With the software of SPSS 11.0, the datum such as the range of MIC, MPC, MIC90 and MPC90 were calculated, and the selection index (MPC90/ MI90) and mutant selection window (MSW) were obtained. The MI90 of LVF and TOB (4 mg/L) to Staphylococcus aureus strains were the lowest. CIP showed the lowest MIC90 (0.25 mg/L) to Pseudomonas aeruginosa among six kinds of antibacterial agents. The MIC90 of LVF to Staphylococcus epidermidis (256 mg/L), Streptococcus pneumoniae (1 mg/L) and Klebsiella pneumoniae (0.25 mg/L) were lower than other antibacterial agents. The MPC90, MSW and the MPC90/MIC90 of levofloxacin showed lower values compared with other antibacterial medicines. From all the datum, the MIC90 of CHL was the highest and the activity was the weakest. Although the activity of LVF was higher to every kind of bacteria, CIP had the highest activity antibacterial to Pseudomonas aeruginosa. The capacity of CHL and TOB was weaker than Quinolones for restricting resistant mutants on ocular bacteria. LVF had the strongest capacity for restricting resistant

Ocular health assessment of cocoa farmers in a rural community in Ghana.

PubMed

Boadi-Kusi, Samuel Bert; Hansraj, Rekha; Kumi-Kyereme, Akwasi; Mashige, Khathutshelo Percy; Awusabo-Asare, Kofi; Ocansey, Stephen; Kyei, Samuel

2014-01-01

Cocoa farming provides employment for over 800,000 households in rural Ghana, with the country currently touted as the second largest producer of cocoa worldwide. Agriculture is one of the riskiest occupations for the eyes due to the numerous ocular hazards on farms. The authors conducted an ocular health assessment among cocoa farmers at Mfuom, a rural community in the Central Region of Ghana, to examine the ocular health status and the ocular safety measures used by cocoa farmers. A structured questionnaire was used to evaluate demographic characteristics, ocular injuries, and utilization of eye care services and ocular protection, and a clinical examination was used to evaluate their ocular status. Cocoa farmers were at high risk for ocular injuries and farm-related vision disorders and utilized eye care services and ocular protection poorly. Ocular condition identified were mainly refractive error (28.6%), cataract (20.0%), glaucoma (11.7%), conjunctivitis (13%), pterygium (2.7%), and cornea opacity (2.2%). There is a need for the introduction of an interventional eye care program to help address the ocular health challenges identified among the farmers. This can be done through collaborative efforts by educational institutions, government, and other role players in the agricultural industry to improve the quality of life of the vulnerable cocoa farmers in rural Ghana.

Indocyanine green angiography of juvenile X-linked retinoschisis.

PubMed

Souied, Eric H; Goritsa, Anna; Querques, Giuseppe; Coscas, Gabriel; Soubrane, Gisele

2005-09-01

In juvenile X-linked retinoschisis (XLRS), fluorescein angiography is usually unremarkable and contributes poorly to the diagnosis. However, indocyanine green (ICG) angiography features in eyes that are affected with XLRS were not yet described. Retrospective observational case series. A complete ophthalmologic examination that included ICG angiography was performed on three unrelated male patients (six eyes) who were 15, 22, and 48 years old. A distinct hyperfluorescent stellate pattern in the macular area that was associated with radial lines of hypofluorescence that were centered on the foveola was observed on the early phase of ICG examination (six of six eyes). This feature disappeared on the late phase of ICG examination. On these six XLRS eyes, early phases of ICG examination revealed an unusual radial aspect on the macula. This finding suggests that ICG angiography may be useful for the diagnosis of XLRS.

Biochemical and molecular analysis of an X-linked case of Leigh syndrome associated with thiamin-responsive pyruvate dehydrogenase deficiency.

PubMed

Naito, E; Ito, M; Yokota, I; Saijo, T; Matsuda, J; Osaka, H; Kimura, S; Kuroda, Y

1997-08-01

We report molecular analysis of thiamin-responsive pyruvate dehydrogenase complex (PDHC) deficiency in a patient with an X-linked form of Leigh syndrome. PDHC activity in cultured lymphoblastoid cells of this patient and his asymptomatic mother were normal in the presence of a high thiamin pyrophosphate (TPP) concentration (0.4 mmol/L). However, in the presence of a low concentration (1 x 10(-4) mmol/L) of TPP, the activity was significantly decreased, indicating that PDHC deficiency in this patient was due to decreased affinity of PDHC for TPP. The patient's older brother also was diagnosed as PDHC deficiency with Leigh syndrome, suggesting that PDHC deficiency in these two brothers was not a de novo mutation. Sequencing of the X-linked PDHC E1 alpha subunit revealed a C-->G point mutation at nucleotide 787, resulting in a substitution of glycine for arginine 263. Restriction enzyme analysis of the E1 alpha gene revealed that the mother was a heterozygote, indicating that thiamin-responsive PDHC deficiency associated with Leigh syndrome due to this mutation is transmitted by X-linked inheritance.

Combination of a Haploidentical Stem Cell Transplant With Umbilical Cord Blood for Cerebral X-Linked Adrenoleukodystrophy.

PubMed

Jiang, Hua; Jiang, Min-Yan; Liu, Sha; Cai, Yan-Na; Liang, Cui-Li; Liu, Li

2015-08-01

Childhood cerebral X-linked adrenoleukodystrophy is a rapidly progressive neurodegenerative disorder that affects central nervous system myelin and the adrenal cortex. Hematopoietic stem cell transplantation is the best available curative therapy if performed during the early stages of disease. Only 30% of patients who might benefit from a hematopoietic stem cell transplant will have a full human leukocyte antigen-matched donor, which is considered to be the best choice. We present a 5-year-old boy with cerebral X-linked adrenoleukodystrophy whose brain magnetic resonance imaging severity score was 7 and who needed an immediate transplantation without an available full human leukocyte antigen-matched donor. We combined haploidentical and umbilical cord blood sources for transplantation and saw encouraging results. After transplantation, the patient showed neurological stability for 6 months and the level of very long chain fatty acids had decreased. By 1 year, the patient appeared to gradually develop cognition, motor, and visual disturbances resulting from possible mix chimerism. Transplantation of haploidentical stem cells combined with the infusion of umbilical cord blood is a novel approach for treating cerebral X-linked adrenoleukodystrophy. It is critical to monitor posttransplant chimerism and carry out antirejection therapy timely for a beneficial clinical outcome. Copyright © 2015 Elsevier Inc. All rights reserved.

Ocular Manifestations of Mosquito-Transmitted Diseases.

PubMed

Karesh, James W; Mazzoli, Robert A; Heintz, Shannon K

2018-03-01

Of the 3,548 known mosquito species, about 100 transmit human diseases. Mosquitoes are distributed globally throughout tropical and temperate regions where standing water sources are available for egg laying and the maturation of larva. Female mosquitoes require blood meals for egg production. This is the main pathway for disease transmission. Mosquitoes carry several pathogenic organisms responsible for significant ocular pathology and vision loss including West Nile, Rift Valley, chikungunya, dengue viruses, various encephalitis viruses, malarial parasites, Francisella tularensis, microfilarial parasites, including Dirofilaria, Wuchereria, and Brugia spp., and human botfly larvae. Health care providers may not be familiar with many of these mosquito-transmitted diseases or their associated ocular findings delaying diagnosis, treatment, and recovery of visual function. This article aims to provide an overview of the ocular manifestations associated with mosquito-transmitted diseases.

Inherent X-Linked Genetic Variability and Cellular Mosaicism Unique to Females Contribute to Sex-Related Differences in the Innate Immune Response.

PubMed

Spolarics, Zoltan; Peña, Geber; Qin, Yong; Donnelly, Robert J; Livingston, David H

2017-01-01

Females have a longer lifespan and better general health than males. Considerable number of studies also demonstrated that, after trauma and sepsis, females present better outcomes as compared to males indicating sex-related differences in the innate immune response. The current notion is that differences in the immuno-modulatory effects of sex hormones are the underlying causative mechanism. However, the field remains controversial and the exclusive role of sex hormones has been challenged. Here, we propose that polymorphic X-linked immune competent genes, which are abundant in the population are important players in sex-based immuno-modulation and play a key role in causing sex-related outcome differences following trauma or sepsis. We describe the differences in X chromosome (ChrX) regulation between males and females and its consequences in the context of common X-linked polymorphisms at the individual as well as population level. We also discuss the potential pathophysiological and immune-modulatory aspects of ChrX cellular mosaicism, which is unique to females and how this may contribute to sex-biased immune-modulation. The potential confounding effects of ChrX skewing of cell progenitors at the bone marrow is also presented together with aspects of acute trauma-induced de novo ChrX skewing at the periphery. In support of the hypothesis, novel observations indicating ChrX skewing in a female trauma cohort as well as case studies depicting the temporal relationship between trauma-induced cellular skewing and the clinical course are also described. Finally, we list and discuss a selected set of polymorphic X-linked genes, which are frequent in the population and have key regulatory or metabolic functions in the innate immune response and, therefore, are primary candidates for mediating sex-biased immune responses. We conclude that sex-related differences in a variety of disease processes including the innate inflammatory response to injury and infection may be

Ocular Manifestations of Oblique Facial Clefts

PubMed Central

Ortube, Maria Carolina; Dipple, Katrina; Setoguchi, Yoshio; Kawamoto, Henry K.; Demer, Joseph L.

2014-01-01

Introduction In the Tessier classification, craniofacial clefts are numbered from 0 to 14 and extend along constant axes through the eyebrows, eyelids, maxilla, nostrils, and the lips. We studied a patient with bilateral cleft 10 associated with ocular abnormalities. Method Clinical report with orbital and cranial computed tomography. Results After pregnancy complicated by oligohydramnios, digoxin, and lisinopril exposure, a boy was born with facial and ocular dysmorphism. Examination at age 26 months showed bilateral epibulbar dermoids, covering half the corneal surface, and unilateral morning glory anomaly of the optic nerve. Ductions of the right eye were normal, but the left eye had severely impaired ductions in all directions, left hypotropia, and esotropia. Under anesthesia, the left eye could not be rotated freely in any direction. Bilateral Tessier cleft number 10 was implicated by the presence of colobomata of the middle third of the upper eyelids and eyebrows. As the cleft continued into the hairline, there was marked anterior scalp alopecia. Computed x-ray tomography showed a left middle cranial fossa arachnoid cyst and calcification of the reflected tendon of the superior oblique muscle, trochlea, and underlying sclera, with downward and lateral globe displacement. Discussion Tessier 10 clefts are very rare and usually associated with encephalocele. Bilateral 10 clefts have not been reported previously. In this case, there was coexisting unilateral morning glory anomaly and arachnoid cyst of the left middle cranial fossa but no encephalocele. Conclusions Bilateral Tessier facial cleft 10 may be associated with alopecia, morning glory anomaly, epibulbar dermoids, arachnoid cyst, and restrictive strabismus. PMID:20856062

Eye cosmetic usage and associated ocular comfort.

PubMed

Ng, Alison; Evans, Katharine; North, Rachel; Purslow, Christine

2012-11-01

Eye cosmetics usage is commonplace and whilst some products such as eyeliner are applied with close proximity to the ocular surface, there is little knowledge of the short- and long-term ocular effects of eye cosmetic formulations. This study aimed to investigate the use of eye cosmetics and identify any relationships between ocular comfort and cosmetic usage. Results were collated from an online survey comprising 23 questions that recorded demographics, Ocular Surface Disease Index (OSDI) score, extent and range of eye cosmetic use and perceived comfort differences with and without eye cosmetics. The 1360 female respondents (median age 25, interquartile range 20-34 years) completed the survey; 83% reported using eye cosmetics regularly (≥ 3 times per week) with mascara being most commonly used. Fifty three per cent used at least three different eye cosmetics products regularly. OSDI scores of cosmetics users were similar to non-users (p = 0.083), but perceived comfort was greater when cosmetics were not used (p < 0.001). In occasional cosmetics users (use of products < 3 times per week), 65% reported a reduction in comfort when cosmetics were used. Median OSDI scores suggested a trend towards reduced comfort amongst eyeliner users (p = 0.07) although frequency and type of cosmetic products used did not appear to influence OSDI scores. This study shows the use of multiple eye cosmetics is extensive and associated with the perception of ocular discomfort. With such widespread use of these products, more research is required to assess the effect on the ocular surface and tear film, which may be underestimated. Ophthalmic & Physiological Optics © 2012 The College of Optometrists.

The temperature-sensitive mutants of Toxoplasma gondii and ocular toxoplasmosis.

PubMed

Lu, Fangli; Huang, Shiguang; Kasper, Lloyd H

2009-01-22

The risk of blindness caused by ocular toxoplasmosis supports efforts to improve our understanding for control of this disease. In this study, the involvement of CD8(+), CD4(+), B cell, and IL-10 gene in the immune response of primary ocular infection with the temperature-sensitive mutant (ts-4) of the RH Toxoplasma gondii strain, and in the protective immunity of ocular ts-4 vaccination and challenge with RH strain was investigated in murine models utilizing inbred C57BL/6 mice-deficient in CD4(+), CD8(+), B cells (microMT), or IL-10 gene. Compared to naive mice, all WT and mutant mice had different degree of ocular pathological changes after ts-4 ocular infection, in which both CD8 KO and IL-10 KO mice showed the most severe ocular lesions. Immunized by ts-4 intracameral (i.c.) inoculation, all mutant mice had partially decreased vaccine-induced resistance associated with increased ocular parasite burdens after RH strain challenge. A significant increase of the percentages of B cells and CD8(+) T cells in the draining lymph nodes were observed in WT and IL-10 KO mice after either infection or challenge. The levels of specific anti-toxoplasma IgG in both eye fluid and serum from all the mice were significantly increased after ts-4 i.c. immunization, except microMT mice. These results suggest that the avirulent ts-4 of T. gondii inoculated intracamerally can induce both ocular pathology and ocular protective immunity; CD4(+), CD8(+), B cell, and IL-10 gene are all necessary to the vaccine-induced resistance to ocular challenge by virulent RH strain, in which CD8(+) T cells are the most important component.

In silico analysis of miRNA-mediated gene regulation in OCA and OA genes.

PubMed

Kamaraj, Balu; Gopalakrishnan, Chandrasekhar; Purohit, Rituraj

2014-12-01

Albinism is an autosomal recessive genetic disorder due to low secretion of melanin. The oculocutaneous albinism (OCA) and ocular albinism (OA) genes are responsible for melanin production and also act as a potential targets for miRNAs. The role of miRNA is to inhibit the protein synthesis partially or completely by binding with the 3'UTR of the mRNA thus regulating gene expression. In this analysis, we predicted the genetic variation that occurred in 3'UTR of the transcript which can be a reason for low melanin production thus causing albinism. The single nucleotide polymorphisms (SNPs) in 3'UTR cause more new binding sites for miRNA which binds with mRNA which leads to inhibit the translation process either partially or completely. The SNPs in the mRNA of OCA and OA genes can create new binding sites for miRNA which may control the gene expression and lead to hypopigmentation. We have developed a computational procedure to determine the SNPs in the 3'UTR region of mRNA of OCA (TYR, OCA2, TYRP1 and SLC45A2) and OA (GPR143) genes which will be a potential cause for albinism. We identified 37 SNPs in five genes that are predicted to create 87 new binding sites on mRNA, which may lead to abrogation of the translation process. Expression analysis confirms that these genes are highly expressed in skin and eye regions. It is well supported by enrichment analysis that these genes are mainly involved in eye pigmentation and melanin biosynthesis process. The network analysis also shows how the genes are interacting and expressing in a complex network. This insight provides clue to wet-lab researches to understand the expression pattern of OCA and OA genes and binding phenomenon of mRNA and miRNA upon mutation, which is responsible for inhibition of translation process at genomic levels.

The ocular complications of boxing.

PubMed

Giovinazzo, V J; Yannuzzi, L A; Sorenson, J A; Delrowe, D J; Cambell, E A

1987-06-01

In cooperation with the New York State Athletic Commission, 74 boxers applying for a new or yearly renewal license were sequentially referred over a 2-year period for a complete dilated ocular examination at the Sports Vision Institute of the Manhattan Eye, Ear and Throat Hospital. At least one ocular injury was found in 66% of boxers. Vision-threatening injuries, defined as significant damage to the angle, lens, macula, or peripheral retina occurred in 58% of boxers. Nineteen percent of boxers had angle abnormalities. Nineteen percent of boxers had pathologic cataracts, over 70% of these were posterior subcapsular. Six boxers had macular lesions. A total of 24% of boxers had retinal tears. Standardized photographs were used to distinguish pathologic cataracts from congenital opacities and pathologic retinal tears from atrophic holes. Attempts were made to identify risk factors in boxing that might be predictive for ocular injury. Variables included age, weight division, left- or right-handedness, total number of losses, and total number of bouts. Significant correlations were found between the total number of bouts and the total number of losses, and the presence of retinal tears. College varsity athletes were selected as controls. Significant differences were found between boxers and controls for the total number of injuries, total vision-threatening injuries, and the number of retinal tears. A series of recommendations are proposed to aide in the early detection and prevention of serious ocular injuries.

Systemic therapy of ocular and cutaneous rosacea in children.

PubMed

Gonser, L I; Gonser, C E; Deuter, C; Heister, M; Zierhut, M; Schaller, M

2017-10-01

In paediatric rosacea, ocular symptoms are often predominant. Literature about systemic therapy of paediatric ocular rosacea is sparse, though. Analysis of children with ocular rosacea treated systemically, particularly addressing remission and recurrence rates. Retrospective study reviewing the medical records of children with ocular rosacea treated with systemic antibiotic therapy. Nine of 19 patients were chosen for detailed analysis. To our knowledge, this is the first study in paediatric ocular rosacea requiring systemic therapy with a larger patient group and a longer follow-up (mean follow-up = 30.2 months). 17 patients (89.5%) suffered from blepharitis, 15 patients (78.9%) from conjunctivitis, twelve patients (63.2%) from chalazia/styes and nine female patients (47.4%) from corneal involvement. We used erythromycin (n = 9) or roxithromycin (n = 1) in patients younger than 8 years and doxycycline (n = 8) or minocycline (n = 1) in patients older than 8 years. Seven of nine patients treated with erythromycin, one of eight patients treated with doxycycline and the patient treated with minocycline achieved a complete remission of ocular and cutaneous symptoms. Two of nine patients treated with erythromycin, seven of eight patients treated with doxycycline and the patient treated with roxithromycin achieved a partial remission. Relapses occurred in the patient treated with minocycline (cutaneous), two of eight patients treated with doxycycline (ocular and cutaneous) and one of nine patients treated with erythromycin (cutaneous). To achieve a complete remission of cutaneous and ocular rosacea, a long-term anti-inflammatory treatment of at least 6 months is necessary. The relapse rates seem to be lower than in adults especially in the patients treated with erythromycin. © 2017 European Academy of Dermatology and Venereology.

Nonpolymeric nanoassemblies for ocular administration of acyclovir: pharmacokinetic evaluation in rabbits.

PubMed

Stella, Barbara; Arpicco, Silvia; Rocco, Flavio; Burgalassi, Susi; Nicosia, Nadia; Tampucci, Silvia; Chetoni, Patrizia; Cattel, Luigi

2012-01-01

The aim of this study was to increase bioavailability of the antiviral drug acyclovir (ACV) when administered by the ocular route. For this purpose, a new lipophilic derivative of acyclovir was synthesized, both possessing greater lipophilicity and providing the formation of a homogeneous water dispersion with higher amount of ACV than the aqueous solution of the parent drug. This was done by chemically linking acyclovir to the isoprenoid chain of squalene, obtaining 4'-trisnorsqualenoylacyclovir (SQACV), in which squalene is covalently coupled to the 4'-hydroxy group of acyclovir. This new prodrug was then formulated as nonpolymeric nanoassemblies through nanoprecipitation; the resulting particles were characterized in terms of mean diameter, zeta potential, and stability. The pharmacokinetic profile of the prodrug in the tear fluid and in the aqueous humor of rabbits was evaluated and compared to that of the parent drug. Data showed that SQACV nanoassemblies increased the amount of ACV in the aqueous humor of rabbits compared to free ACV solution. This new amphiphilic prodrug of acyclovir is a very promising tool to increase the ocular bioavailability of the parent drug. Copyright © 2011 Elsevier B.V. All rights reserved.

Ocular Jellyfish Stings: Report of 2 Cases and Literature Review.

PubMed

Mao, Chen; Hsu, Chien-Chin; Chen, Kuo-Tai

2016-09-01

An ocular jellyfish sting is an ophthalmic emergency and is rarely reported in the medical literature. With the evolution of aquatic activities and entertainment in recent decades, we anticipate that more patients with ocular jellyfish stings may be taken to the emergency department. However, most physicians are unaware of the typical presentations, suitable treatments, prognosis, and possible complications of ocular jellyfish stings. We reported 2 cases with ocular jellyfish stings and collected cases series from literature review. The most common clinical features of ocular jellyfish stings were pain, conjunctival injection, corneal lesion, and photophobia. All patients who sustained ocular stings did so during aquatic activities, and the best management at the scene was proper analgesics and copious irrigation of affected eyes with seawater or saline. The ocular lesions were treated with topical cycloplegics, topical steroids, topical antibiotics, topical antihistamines, and removal of nematocysts. The prognosis was good, and all patients recovered without any permanent sequelae. However, symptoms in some patients may last longer than 1 week. Reported complications included iritis, increased intraocular pressures, mydriasis, decreased accommodation, and peripheral anterior synechiae. Copyright © 2016 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

Evidence for Phex haploinsufficiency in murine X-linked hypophosphatemia.

PubMed

Wang, L; Du, L; Ecarot, B

1999-04-01

Mutations in the PHEX gene (phosphate-regulating gene with homology to endopeptidases on the X-chromosome) are responsible for X-linked hypophosphatemia (HYP). We previously reported the full-length coding sequence of murine Phex cDNA and provided evidence of Phex expression in bone and tooth. Here, we report the cloning of the entire 3.5-kb 3'UTR of the Phex gene, yielding a total of 6248 bp for the Phex transcript. Southern blot and RT-PCR analyses revealed that the 3' end of the coding sequence and the 3'UTR of the Phex gene, spanning exons 16 to 22, are deleted in Hyp, the mouse model for HYP. Northern blot analysis of bone revealed lack of expression of stable Phex mRNA from the mutant allele and expression of Phex transcripts from the wild-type allele in Hyp heterozygous females. Expression of the Phex protein in heterozygotes was confirmed by Western analysis with antibodies raised against a COOH-terminal peptide of the mouse Phex protein. Taken together, these results indicate that the dominant pattern of Hyp inheritance in mice is due to Phex haploinsufficiency.

Inflammatory profile in X-linked adrenoleukodystrophy patients: Understanding disease progression.

PubMed

Marchetti, Desirèe Padilha; Donida, Bruna; Jacques, Carlos Eduardo; Deon, Marion; Hauschild, Tatiane Cristina; Koehler-Santos, Patricia; de Moura Coelho, Daniella; Coitinho, Adriana Simon; Jardim, Laura Bannach; Vargas, Carmen Regla

2018-01-01

X-linked adrenoleukodystrophy (X-ALD) is an inherited disease characterized by progressive inflammatory demyelization in the brain, adrenal insufficiency, and an abnormal accumulation of very long chain fatty acids (VLCFA) in tissue and body fluids. Considering that inflammation might be involved in pathophysiology of X-ALD, we aimed to investigate pro- and anti-inflammatory cytokines in plasma from three different male phenotypes (CCER, AMN, and asymptomatic individuals). Our results showed that asymptomatic patients presented increased levels of pro-inflammatory cytokines IL-1β, IL-2, IL-8, and TNF-α and the last one was also higher in AMN phenotype. Besides, asymptomatic patients presented higher levels of anti-inflammatory cytokines IL-4 and IL-10. AMN patients presented higher levels of IL-2, IL-5, and IL-4. We might hypothesize that inflammation in X-ALD is related to plasmatic VLCFA concentration, since there were positive correlations between C26:0 plasmatic levels and pro-inflammatory cytokines in asymptomatic and AMN patients and negative correlation between anti-inflammatory cytokine and C24:0/C22:0 ratio in AMN patients. The present work yields experimental evidence that there is an inflammatory imbalance associated Th1, (IL-2, IL-6, and IFN-γ), Th2 (IL-4 and IL-10), and macrophages response (TNF-α and IL-1β) in the periphery of asymptomatic and AMN patients, and there is correlation between VLCFA plasmatic levels and inflammatory mediators in X-ALD. Furthermore, we might also speculate that the increase of plasmatic cytokines in asymptomatic patients could be considered an early biomarker of brain damage and maybe also a predictor of disease progression. © 2017 Wiley Periodicals, Inc.

Imprinted and X-linked non-coding RNAs as potential regulators of human placental function

PubMed Central

Buckberry, Sam; Bianco-Miotto, Tina; Roberts, Claire T

2014-01-01

Pregnancy outcome is inextricably linked to placental development, which is strictly controlled temporally and spatially through mechanisms that are only partially understood. However, increasing evidence suggests non-coding RNAs (ncRNAs) direct and regulate a considerable number of biological processes and therefore may constitute a previously hidden layer of regulatory information in the placenta. Many ncRNAs, including both microRNAs and long non-coding transcripts, show almost exclusive or predominant expression in the placenta compared with other somatic tissues and display altered expression patterns in placentas from complicated pregnancies. In this review, we explore the results of recent genome-scale and single gene expression studies using human placental tissue, but include studies in the mouse where human data are lacking. Our review focuses on the ncRNAs epigenetically regulated through genomic imprinting or X-chromosome inactivation and includes recent evidence surrounding the H19 lincRNA, the imprinted C19MC cluster microRNAs, and X-linked miRNAs associated with pregnancy complications. PMID:24081302

Autosomal-recessive and X-linked forms of hereditary motor and sensory neuropathy in childhood.

PubMed

Ouvrier, Robert; Geevasingha, Nimeshan; Ryan, Monique M

2007-08-01

The hereditary motor and sensory neuropathies (HMSNs, Charcot-Marie-Tooth neuropathies) are the most common degenerative disorders of the peripheral nervous system. In recent years a dramatic expansion has occurred in our understanding of the molecular basis and cell biology of the recessively inherited demyelinating and axonal neuropathies, with delineation of a number of new neuropathies. Mutations in some genes cause a wide variety of clinical, neurophysiologic, and pathologic phenotypes, rendering diagnosis difficult. The X-linked forms of HMSN represent at least 10%-15% of all HMSNs and have an expanded disease spectrum including demyelinating, intermediate, and axonal neuropathies, transient central nervous system (CNS) dysfunction, mental retardation, and hearing loss. This review presents an overview of the recessive and X-linked forms of HMSN observed in childhood, with particular reference to disease phenotype and neurophysiologic and pathologic abnormalities suggestive of specific diagnoses. These findings can be used by the clinician to formulate a differential diagnosis and guide targeted genetic testing.

Treatment of Chronic Enterovirus Encephalitis With Fluoxetine in a Patient With X-Linked Agammaglobulinemia.

PubMed

Gofshteyn, Jacqueline; Cárdenas, Ana María; Bearden, David

2016-11-01

Enterovirus may result in a devastating chronic encephalitis in immunocompromised patients, particularly in patients with X-linked agammaglobulinemia. Prognosis for patients with chronic enterovirus encephalitis is poor, almost invariably resulting in mortality without specific treatment. There are currently no approved antiviral agents for enterovirus, but the antidepressant drug fluoxetine has been identified through library-based compound screening as a potential anti-enteroviral agent in vitro. However, use of fluoxetine has not previously been studied in humans with enteroviral disease. A five year old boy with X-linked agammaglobulinemia presented with progressive neurological deterioration and was found to have chronic enterovirus encephalitis by brain biopsy. He failed to respond to standard treatment with high dose intravenous immunoglobulin, but showed stabilization and improvement following treatment with fluoxetine. This is the first report to describe the use of fluoxetine as a potential therapy for chronic enterovirus infection. Further investigation of fluoxetine as a treatment option for chronic enterovirus encephalitis is necessary. Copyright © 2016 Elsevier Inc. All rights reserved.

The zebrafish eye—a paradigm for investigating human ocular genetics

PubMed Central

Richardson, R; Tracey-White, D; Webster, A; Moosajee, M

2017-01-01

Although human epidemiological and genetic studies are essential to elucidate the aetiology of normal and aberrant ocular development, animal models have provided us with an understanding of the pathogenesis of multiple developmental ocular malformations. Zebrafish eye development displays in depth molecular complexity and stringent spatiotemporal regulation that incorporates developmental contributions of the surface ectoderm, neuroectoderm and head mesenchyme, similar to that seen in humans. For this reason, and due to its genetic tractability, external fertilisation, and early optical clarity, the zebrafish has become an invaluable vertebrate system to investigate human ocular development and disease. Recently, zebrafish have been at the leading edge of preclinical therapy development, with their amenability to genetic manipulation facilitating the generation of robust ocular disease models required for large-scale genetic and drug screening programmes. This review presents an overview of human and zebrafish ocular development, genetic methodologies employed for zebrafish mutagenesis, relevant models of ocular disease, and finally therapeutic approaches, which may have translational leads in the future. PMID:27612182

The mucosal surfaces of both eyes are immunologically linked by a neurogenic inflammatory reflex involving TRPV1 and substance P.

PubMed

Guzmán, Mauricio; Miglio, Maximiliano S; Zgajnar, Nadia R; Colado, Ana; Almejún, María B; Keitelman, Irene A; Sabbione, Florencia; Fuentes, Federico; Trevani, Analía S; Giordano, Mirta N; Galletti, Jeremías G

2018-06-04

Immunological interdependence between the two eyes has been reported for the cornea and the retina but not for the ocular mucosal surface. Intriguingly, patients frequently report ocular surface-related symptoms in the other eye after unilateral ocular surgery. Here we show how unilateral eye injuries in mice affect the mucosal immune response of the opposite ocular surface. We report that, despite the lack of lymphatic cross-drainage, a neurogenic inflammatory reflex in the contralateral conjunctiva is sufficient to increase, first, epithelial nuclear factor kappa B signaling, then, dendritic cell maturation, and finally, expansion of effector, instead of regulatory, T cells in the draining lymph node, leading to disrupted ocular mucosal tolerance. We also show that damage to ocular surface nerves is required. Using pharmacological inhibitors and agonists, we identified transient receptor potential vanilloid 1 (TRPV1) channel as the receptor sensing tissue damage in the injured eye and substance P released in the opposite ocular surface as the effector of the sympathetic response. Finally, blocking either step prevented subsequent ocular allergic reactions in the opposite eye in a unilateral corneal alkali burn model. This study demonstrates that both ocular surfaces are immunologically linked and suggests potential therapeutic targets for intervention.

Lentiviral hematopoietic cell gene therapy for X-linked adrenoleukodystrophy.

PubMed

Cartier, Nathalie; Hacein-Bey-Abina, Salima; Bartholomae, Cynthia C; Bougnères, Pierre; Schmidt, Manfred; Kalle, Christof Von; Fischer, Alain; Cavazzana-Calvo, Marina; Aubourg, Patrick

2012-01-01

X-linked adrenoleukodystrophy (X-ALD) is a severe genetic demyelinating disease caused by a deficiency in ALD protein, an adenosine triphosphate-binding cassette transporter encoded by the ABCD1 gene. When performed at an early stage of the disease, allogeneic hematopoietic stem cell transplantation (HCT) can arrest the progression of cerebral demyelinating lesions. To overcome the limitations of allogeneic HCT, hematopoietic stem cell (HSC) gene therapy strategy aiming to perform autologous transplantation of lentivirally corrected cells was developed. We demonstrated the preclinical feasibility of HSC gene therapy for ALD based on the correction of CD34+ cells from X-ALD patients using an HIV1-derived lentiviral vector. These results prompted us to initiate an HSC gene therapy trial in two X-ALD patients who had developed progressive cerebral demyelination, were candidates for allogeneic HCT, but had no HLA-matched donors or cord blood. Autologous CD34+ cells were purified from the peripheral blood after G-CSF stimulation, genetically corrected ex vivo with a lentiviral vector encoding wild-type ABCD1 cDNA, and then reinfused into the patients after they had received full myeloablative conditioning. Over 3 years of follow-up, the hematopoiesis remained polyclonal in the two patients treated with 7-14% of granulocytes, monocytes, and T and B lymphocytes expressing the lentivirally encoded ALD protein. There was no evidence of clonal dominance or skewing based on the retrieval of lentiviral insertion repertoire in different hematopoietic lineages by deep sequencing. Cerebral demyelination was arrested 14 and 16months, respectively, in the two treated patients, without further progression up to the last follow-up, a clinical outcome that is comparable to that observed after allogeneic HCT. Longer follow-up of these two treated patients and HSC gene therapy performed in additional ALD patients are however needed to evaluate the safety and efficacy of lentiviral HSC

Homozygosity Mapping and Whole Exome Sequencing to Detect SLC45A2 and G6PC3 Mutations in a Single Patient with Oculocutaneous Albinism and Neutropenia

PubMed Central

Cullinane, Andrew R.; Vilboux, Thierry; O’Brien, Kevin; Curry, James A.; Maynard, Dawn M.; Carlson-Donohoe, Hannah; Ciccone, Carla; Markello, Thomas C.; Gunay-Aygun, Meral; Huizing, Marjan; Gahl, William A.

2011-01-01

We evaluated a 32 year-old woman whose oculocutaneous albinism, bleeding diathesis, neutropenia, and history of recurrent infections prompted consideration of the diagnosis of Hermansky-Pudlak syndrome type 2 (HPS-2). This was ruled out due to the presence of platelet delta granules and absence of AP3B1 mutations. Since parental consanguinity suggested an autosomal recessive mode of inheritance, we employed homozygosity mapping, followed by whole exome sequencing, to identify two candidate disease-causing genes, SLC45A2 and G6PC3. Conventional di-deoxy sequencing confirmed pathogenic mutations in SLC45A2, associated with oculocutaneous albinism type 4 (OCA-4), and G6PC3, associated with neutropenia. The substantial reduction of SLC45A2 protein in the patient’s melanocytes caused the mis-localization of tyrosinase from melanosomes to the plasma membrane and also led to the incorporation of tyrosinase into exosomes and secretion into the culture medium, explaining the hypopigmentation in OCA-4. Our patient’s G6PC3 mRNA expression level was also reduced, leading to increased apoptosis of her fibroblasts under ER stress. This report describes the first North American patient with OCA-4, the first culture of human OCA-4 melanocytes, and the use of homozygosity mapping followed by whole exome sequencing to identify disease-causing mutations in multiple genes in a single affected individual. PMID:21677667

Recent Perspectives in Ocular Drug Delivery

PubMed Central

Gaudana, Ripal; Jwala, J.; Boddu, Sai H. S.; Mitra, Ashim K.

2015-01-01

Anatomy and physiology of the eye makes it a highly protected organ. Designing an effective therapy for ocular diseases, especially for the posterior segment, has been considered as a formidable task. Limitations of topical and intravitreal route of administration have challenged scientists to find alternative mode of administration like periocular routes. Transporter targeted drug delivery has generated a great deal of interest in the field because of its potential to overcome many barriers associated with current therapy. Application of nanotechnology has been very promising in the treatment of a gamut of diseases. In this review, we have briefly discussed several ocular drug delivery systems such as microemulsions, nanosuspensions, nanoparticles, liposomes, niosomes, dendrimers, implants, and hydrogels. Potential for ocular gene therapy has also been described in this article. In near future, a great deal of attention will be paid to develop non-invasive sustained drug release for both anterior and posterior segment eye disorders. A better understanding of nature of ocular diseases, barriers and factors affecting in vivo performance, would greatly drive the development of new delivery systems. Current momentum in the invention of new drug delivery systems hold a promise towards much improved therapies for the treatment of vision threatening disorders. PMID:18758924

Evolution of the vestibulo-ocular system

NASA Technical Reports Server (NTRS)

Fritzsch, B.

1998-01-01

The evolutionary and developmental changes in the eye muscle innervation, the inner ear, and the vestibulo-ocular reflex are examined. Three eye muscle patterns, based on the innervation by distinct ocular motoneurons populations, can be identified: a lamprey, an elasmobranch, and a bony fish/tetrapod pattern. Four distinct patterns of variation in the vestibular system are described: a hagfish pattern, a lamprey pattern, an elasmobranch pattern, and a bony fish/tetrapod pattern. Developmental data suggest an influence of the hindbrain on ear pattern formation, thus potentially allowing a concomitant change of eye muscle innervation and ear variation. The connections between the ear and the vestibular nuclei and between the vestibular nuclei and ocular motoneurons are reviewed, and the role of neurotrophins for pattern specification is discussed. Three patterns are recognized in central projections: a hagfish pattern, a lamprey pattern, and a pattern for jawed vertebrates. Second-order connections show both similarities and differences between distantly related species such as lampreys and mammals. For example, elasmobranchs lack an internuclear system, which is at best poorly developed in lampreys. It is suggested that the vestibulo-ocular system shows only a limited degree of variation because of the pronounced functional constraints imposed on it.

X-chromosome tiling path array detection of copy number variants in patients with chromosome X-linked mental retardation

PubMed Central

Madrigal, I; Rodríguez-Revenga, L; Armengol, L; González, E; Rodriguez, B; Badenas, C; Sánchez, A; Martínez, F; Guitart, M; Fernández, I; Arranz, JA; Tejada, MI; Pérez-Jurado, LA; Estivill, X; Milà, M

2007-01-01

Background Aproximately 5–10% of cases of mental retardation in males are due to copy number variations (CNV) on the X chromosome. Novel technologies, such as array comparative genomic hybridization (aCGH), may help to uncover cryptic rearrangements in X-linked mental retardation (XLMR) patients. We have constructed an X-chromosome tiling path array using bacterial artificial chromosomes (BACs) and validated it using samples with cytogenetically defined copy number changes. We have studied 54 patients with idiopathic mental retardation and 20 controls subjects. Results Known genomic aberrations were reliably detected on the array and eight novel submicroscopic imbalances, likely causative for the mental retardation (MR) phenotype, were detected. Putatively pathogenic rearrangements included three deletions and five duplications (ranging between 82 kb to one Mb), all but two affecting genes previously known to be responsible for XLMR. Additionally, we describe different CNV regions with significant different frequencies in XLMR and control subjects (44% vs. 20%). Conclusion This tiling path array of the human X chromosome has proven successful for the detection and characterization of known rearrangements and novel CNVs in XLMR patients. PMID:18047645

Simpson-Golabi-Behmel syndrome: an X-linked encephalo-tropho-schisis syndrome. 1988.

PubMed

Neri, G; Marini, R; Cappa, M; Borrelli, P; Opitz, J M

2013-11-01

The following paper by Professor GiovanniNeri and colleagues was originally published in 1988, American Journal of Medical Genetics 30:287–299. This paper represented a seminal work at the time of publication as it not only reported a new family with a disorder that had been called the “gigantism-dysplasia syndrome”, but also suggested naming the condition the Simpson-Golabi-Behmel syndrome. This eponym has clearly stood “the test of time”, and that designation is now widely accepted. This paper is graciously republished by Wiley-Blackwell in the Special Festschrift issue honoring Professor Neri. We report on another family with the so-called "gigantism-dysplasia syndrome", an X-linked condition characterized by pre-and postnatal overgrowth, characteristic face with apparent coarseness, dysplastic changes in several tissues, and mild intellectual impairment. This condition has been called the Golabi-Rosen syndrome; however, we agree that is the same entity as that described, in a milder form, by Simpson et al. in 1975 and by Behmel et al. in 1984. Therefore, we suggest that this entity be designated the Simpson-Golabi-Behmel syndrome. The manifestations in affected individuals suggest that this condition represents an X-linked encephalo-tropho-schisis syndrome. © 2013 Wiley Periodicals, Inc.

Lymphocyte transformation in presumed ocular histoplasmosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ganley, J.P.; Nemo, G.J.; Comstock, G.W.

Lymphocytes from individuals with inactive macular disciform lesions of presumed ocular histoplasmosis challenged with three histoplasmin antigens incorporated tritiated thymidine at a significantly higher rate than histoplasmin-stimulated lymphocytes of matched control and peripheral scar groups. This finding is consistent with the etiologic association of the disciform ocular syndrome and previous systemic infection with Histoplasma capsulatum. The disciform group had a higher mean response than the other two groups to pokeweed mitogen but not to phytohemagglutinin and had higher mean counts per minute to the specific antigens Toxoplasma gondii, Blastomyces dermatitidis, Cryptococcus neoformans, Mycobacterium tuberculosis, M battery, and M gaus, butmore » not to Candida albicans. These data would suggest that individuals with the disciform lesion of presumed ocular histoplasmosis have a hyperreactive cellular immune response; this response may play an important role in the development of the disciform.« less

Ocular side-effects associated with imatinib mesylate (Gleevec).

PubMed

Fraunfelder, Frederick W; Solomon, Jonathan; Druker, Brian J; Esmaeli, Bita; Kuyl, Jennifer

2003-08-01

This retrospective case series describes ocular side-effects associated with imatinib mesylate (Gleevec) and the clinical characteristics of these adverse reactions. A chart review of 104 patients on imatinib mesylate therapy from Oregon Health & Science University's Cancer Center were studied with regard to ocular side-effects. In addition, spontaneous reports from the Food and Drug Administration, the World Health Organization, and the National Registry of Drug-Induced Ocular Side-Effects databases were reviewed, including a Medline literature search. Seventy-three (70%) of the patients at OHSU developed periorbital edema and 19 patients (18%) developed epiphora after receiving imatinib mesylate. Average dose was 407.5+/-60 mg. Periorbital edema occurred an average of 68+/-48 days after initiation of therapy. WHO classification of side-effects is as follows: certain: periorbital edema; probable: epiphora; possible: extraocular muscle palsy, ptosis, blepharoconjunctivitis; unlikely: glaucoma, papilledema, retinal hemorrhage, photosensitivity, abnormal vision, and increased intraocular pressure. Periorbital edema and epiphora are the two most common ocular side-effects related to imatinib mesylate therapy. Clinical characteristics of imatinib mesylate induced periorbital edema are described. Management of ocular side-effects is conservative except in very rare cases of visually significant periorbital edema.

Meibomian gland dysfunction and ocular discomfort in video display terminal workers.

PubMed

Fenga, C; Aragona, P; Cacciola, A; Spinella, R; Di Nola, C; Ferreri, F; Rania, L

2008-01-01

Meibomian gland dysfunction (MGD) is one of the most common ocular disorders encountered in clinical practice. The clinical manifestations of MGD are related to the changes in the tear film and ocular surface with symptoms of ocular discomfort. In recent years, many surveys have evaluated symptoms associated with the use of Video Display Terminals (VDT), and VDT use is recognized as a risk factor for eye discomfort. The aim of the present study was to determine if the presence of MGD contributes to the signs and symptoms of ocular discomfort during the use of VDT. In course of a routine health surveillance programme, a group of 70 subjects fulfilled the inclusion criteria and responded to a questionnaire about symptoms of ocular discomfort. The following ocular tests were performed: tear break-up time, fluorescein corneal stain, and basal tear secretion test. A total of 52 subjects out of 70 (74.3%) had MGD. A statistically significant correlation between the symptoms of ocular discomfort and hours spent on VDT work was observed in the total population (r=0.358; P=0.002; 95% CI 0.13-0.54) and in the group of subjects with MGD (r=0.365; P=0.009; 95% CI 0.103-0.58). Such correlation was not shown in subjects without MGD. The high prevalence of MGD among the subjects with symptoms of ocular discomfort suggests that this diagnosis should be considered when occupational health practitioners encounter ocular complaints among VDT operators. It appears that MGD can contribute to the development of ocular discomfort in VDT operators.

Connexin mutations in X-linked Charcot-Marie-Tooth disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bergoffen, J.; Scherer, S.S.; Wang, S.

1993-12-24

X-linked Charcot-Marie-Tooth disease (CMTX) is a form of hereditary neuropathy with demyelination. Recently, this disorder was mapped to chromosome Xq13.1. The gene for the gap junction protein connexin32 is located in the same chromosomal segment, which led to its consideration as a candidate gene for CMTX. With the use of Northern (RNA) blot and immunohistochemistry techniques, it was found that connexin32 is normally expressed in myelinated peripheral nerve. Direct sequencing of the connexin32 gene showed seven different mutations in affected persons from eight CMTX families. These findings, a demonstration of inherited defects in a gap junction protein, suggest that connexin32more » plays an important role in peripheral nerve.« less

A Case of Severe Airbag Related Ocular Alkali Injury

PubMed Central

Wong, William; Affeldt, John C

2012-01-01

While airbags have saved many lives and are clearly beneficial overall, sodium hydroxide (NaOH) powder produced by the inflation reaction can cause significant alkali ocular injury if not irrigated promptly. Here we report a case of severe airbag related ocular alkali injury as a way to bring attention to the need for prompt ocular irrigation following motor vehicle accidents (MVA) with airbag deployment. A 47-year-old man was involved in a MVA with airbag deployment in a rural setting. Attention was paid to several other life-threatening traumatic injuries, however, ocular irrigation was not performed until some 6–7 hours after the MVA. Over the course of 6 months, airbag related alkali injury caused severe limbal ischemia, conjunctivalization of the cornea, corneal epithelial defects, cicatricial scarring, haze, and corneal/limbal vascularization despite amniotic membrane graft. Awareness of the importance of ocular irrigation following airbag deployment must be raised both in the ophthalmology and emergency medicine communities. PMID:22900239

[Ocular complications following surgery of chronic suppurative otitis media].

PubMed

Sun, Raoxi; Zhao, Yu

2014-04-01

To investigate the rarely reported ocular complications following surgery of chronic suppurative otitis media (CSOM) and explore the possible mechanisms. The clinical data of 4,012 cases of CSOM treated with surgery were analyzed retrospectively, including age, sex, operation time, surgical approach, time of ocular symptoms presentation, duration of ocular symptoms, treatment and prognosis. Among the 4,012 cases, 109 patients (2.72%) developed ocular complication, of which 68.81% (75/109) suffered from blurred vision, 24.77% (27/109) presented only erythema on eyelids or mild periorbital edema, 4.59% (5/109) had erythema on eyelids with periorbital edema, and 1.83% (2/109) complained of periorbital ecchymosis and edema. All of these complications recovered themselves without any sequela. Ocular complications following surgery of CSOM are rarely reported. Pre-auricular incision and fascia harvesting, turbulence of venous and lymphatic drainage and preseptal cellulitis might be the risk factors. Blurred vision might be associated with eye injury during surgery and the use of anticholinergic agent.

Should patients with ocular genetic disorders have genetic testing?

PubMed

Zanolli, Mario T; Khetan, Vikas; Dotan, Gad; Pizzi, Laura; Levin, Alex V

2014-09-01

To discuss the risks, benefits and value of genetic testing for ocular genetic disease. Testing for ocular genetics diseases is becoming more available and successful gene therapy is being reported. Clinicians must prepare for this trend by considering diagnostic genetic testing for their patients. As advances continually occur in genetic testing for ocular genetic disorders, clinicians must develop an understanding of the potential risks and benefits for their patients.

Ocular phenotypes associated with two mutations (R121W, C126X) in the Norrie disease gene.

PubMed

Kellner, U; Fuchs, S; Bornfeld, N; Foerster, M H; Gal, A

1996-06-01

To describe the ocular phenotypes associated with 2 mutations in the Norrie disease gene including a manifesting carrier. Ophthalmological examinations were performed in 2 affected males and one manifesting carrier. Genomic DNA was analyzed by direct sequencing of the Norrie disease gene. Family I: A 29-year-old male had the right eye enucleated at the age of 3 years. His left eye showed severe temporal dragging of the retina and central scars. Visual acuity was 20/300. DNA analysis revealed a C-to-T transition of the first nucleotide in codon 121 predicting the replacement of arginine-121 by tryptophan (R121W). Both the mother and maternal grandmother carry the same mutation in heterozygous form. Family 2: A 3-month-old boy presented with severe temporal dragging of the retina on both eyes and subsequently developed retinal detachment. Visual acuity was limited to light perception. His mother's left eye was amaurotic and phthitic. Her right eye showed severe retinal dragging, visual acuity was reduced to 20/60. DNA analysis revealed a T-to-A transversion of the third nucleotide in codon 126 creating a stop codon (C126X). The mother and maternal grandmother were carriers. Mutations in the Norrie disease gene can lead to retinal malformations of variable severity both in hemizygous males and manifesting carriers.

Molecular population genetics of X-linked genes in Drosophila pseudoobscura.

PubMed Central

Kovacevic, M; Schaeffer, S W

2000-01-01

This article presents a nucleotide sequence analysis of 500 bp determined in each of five X-linked genes, runt, sisterlessA, period, esterase 5, and Heat-shock protein 83, in 40 Drosophila pseudoobscura strains collected from two populations. Estimates of the neutral migration parameter for the five loci show that gene flow among D. pseudoobscura populations is sufficient to homogenize inversion frequencies across the range of the species. Nucleotide diversity at each locus fails to reject a neutral model of molecular evolution. The sample of 40 chromosomes included six Sex-ratio inversions, a series of three nonoverlapping inversions that are associated with a strong meiotic drive phenotype. The selection driven by the Sex-ratio meiotic drive element has not fixed variation across the X chromosome of D. pseudoobscura because, while significant linkage disequilibrium was observed within the sisterlessA, period, and esterase 5 genes, we did not find evidence for nonrandom association among loci. The Sex-ratio chromosome was estimated to be 25,000 years old based on the decomposition of linkage disequilibrium between esterase 5 and Heat-shock protein 83 or 1 million years old based on the net divergence of esterase 5 between Standard and Sex-ratio chromosomes. Genetic diversity was depressed within esterase 5 within Sex-ratio chromosomes, while the four other genes failed to show a reduction in heterozygosity in the Sex-ratio background. The reduced heterogeneity in esterase 5 is due either to its location near one of the Sex-ratio inversion breakpoints or that it is closely linked to a gene or genes responsible for the Sex-ratio meiotic drive system. PMID:10978282

The evaluation of eye pain with a normal ocular exam.

PubMed

Lee, Andrew G; Brazis, Paul W

2003-12-01

Eye pain with or without associated head or face pain is a common complaint to the ophthalmologist. The ocular exam may reveal the etiology (e.g., corneal disease, angle closure glaucoma) but typically the exam is normal. This paper reviews the evaluation and management of eye pain with a "normal" ocular exam, including: 1) subtle findings on ocular exam; 2) transient findings on exam, and 3) no abnormal ocular findings. Ophthalmologists should be aware of the various etiologies for eye pain and the specific and distinctive features that make the diagnosis.

1 Tb/s x km multimode fiber link combining WDM transmission and low-linewidth lasers.

PubMed

Gasulla, I; Capmany, J

2008-05-26

We have successfully demonstrated an error-free transmission of 10 x 20 Gb/s 200 GHz-spaced ITU channels through a 5 km link of 62.5-microm core-diameter graded-index multimode silica fiber. The overall figure corresponds to an aggregate bit rate per length product of 1 Tb/s x km, the highest value ever reported to our knowledge. Successful transmission is achieved by a combination of low-linewidth DFB lasers and the central launch technique.

Improvement of chronic corneal opacity in ocular surface disease with prosthetic replacement of the ocular surface ecosystem (PROSE) treatment.

PubMed

Cressey, Anna; Jacobs, Deborah S; Remington, Crystal; Carrasquillo, Karen G

2018-06-01

To demonstrate clearing of chronic corneal opacities and improvement of visual acuity with the use of BostonSight prosthetic replacement of the ocular surface ecosystem (PROSE) treatment in ocular surface disease. We undertook retrospective analysis of the medical records of a series of patients who underwent PROSE treatment from August 2006 to December 2014. Patients were referred for ocular surface disease of various etiologies. Primary inclusion criterion was corneal opacity that improved with PROSE treatment. Patients were excluded if topical steroids or adjuvant therapy used once PROSE treatment was initiated. Underlying disease, prior treatment, clinical presentation, and clinical course were extracted from the medical record. Four patients are included in this series. There were three females and one male; median age at time of treatment initiation was 30 years (range = 0.5-58 years). Median duration of PROSE treatment at time of retrospective analysis was 3.5 years (range = 1-8 years). Two cases had corneal opacification in the context of neurotrophic keratopathy: a unilateral case due to presumed herpes simplex keratitis and a bilateral case due to congenital corneal anesthesia associated with familial dysautonomia. One case had corneal opacity from exposure related to seventh nerve palsy, and one had corneal opacification associated with recurrent surface breakdown, neurotrophic keratopathy, and limbal stem deficiency of uncertain etiology. After consistent wear of prosthetic devices used in PROSE treatment for support of the ocular surface, visual acuity improved and clearing of the opacities was observed, without use of topical steroids or adjuvant therapy. These cases demonstrate clearing of chronic corneal opacity with PROSE treatment for ocular surface disease. This clearing can occur with no adjuvant therapy, suggesting that restoration of ocular surface function and integrity allows for corneal remodeling.

New nanomicelle curcumin formulation for ocular delivery: improved stability, solubility, and ocular anti-inflammatory treatment.

PubMed

Li, Mengshuang; Xin, Meng; Guo, Chuanlong; Lin, Guiming; Wu, Xianggen

2017-11-01

A stable topical ophthalmic curcumin formulation with high solubility, stability, and efficacy is needed for pharmaceutical use in clinics. The objective of this article was to describe a novel curcumin containing a nanomicelle formulation using a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (PVCL-PVA-PEG) graft copolymer. Nanomicelle curcumin was formulated and optimized and then further evaluated for in vitro cytotoxicity/in vivo ocular irritation, in vitro cellular uptake/in vivo corneal permeation, and in vitro antioxidant activity/in vivo anti-inflammatory efficacy. The solubility, chemical stability, and antioxidant activity were greatly improved after the encapsulation of the PVCL-PVA-PEG nanomicelles. The nanomicelle curcumin ophthalmic solution was simple to prepare and the nanomicelles are stable to the storage conditions, and it had good cellular tolerance. Nanomicelle curcumin also had excellent ocular tolerance in rabbits. The use of nanomicelles significantly improved in vitro cellular uptake and in vivo corneal permeation as well as improved anti-inflammatory efficacy when compared with a free curcumin solution. These findings indicate that nanomicelles could be promising topical delivery systems for the ocular administration of curcumin.

Sex-linked dominant

MedlinePlus

Inheritance - sex-linked dominant; Genetics - sex-linked dominant; X-linked dominant; Y-linked dominant ... can be either an autosomal chromosome or a sex chromosome. It also depends on whether the trait ...

[Adverse ocular effects of vaccinations].

PubMed

Ness, T; Hengel, H

2016-07-01

Vaccinations are very effective measures for prevention of infections but are also associated with a long list of possible side effects. Adverse ocular effects following vaccination have been rarely reported or considered to be related to vaccinations. Conjunctivitis is a frequent sequel of various vaccinations. Oculorespiratory syndrome and serum sickness syndrome are considered to be related to influenza vaccinations. The risk of reactivation or initiation of autoimmune diseases (e. g. uveitis) cannot be excluded but has not yet been proven. Overall the benefit of vaccination outweighs the possible but very low risk of ocular side effects.

Seasonal Effect on Ocular Sun Exposure and Conjunctival UV Autofluorescence.

PubMed

Haworth, Kristina M; Chandler, Heather L

2017-02-01

To evaluate feasibility and repeatability of measures for ocular sun exposure and conjunctival ultraviolet autofluorescence (UVAF), and to test for relationships between the outcomes. Fifty volunteers were seen for two visits 14 ± 2 days apart. Ocular sun exposure was estimated over a 2-week time period using questionnaires that quantified time outdoors and ocular protection habits. Conjunctival UVAF was imaged using a Nikon D7000 camera system equipped with appropriate flash and filter system; image analysis was done using ImageJ software. Repeatability estimates were made using Bland-Altman plots with mean differences and 95% limits of agreement calculated. Non-normally distributed data was transformed by either log10 or square root methods. Linear regression was conducted to evaluate relationships between measures. Mean (±SD) values for ocular sun exposure and conjunctival UVAF were 8.86 (±11.97) hours and 9.15 (±9.47) mm, respectively. Repeatability was found to be acceptable for both ocular sun exposure and conjunctival UVAF. Univariate linear regression showed outdoor occupation to be a predictor of higher ocular sun exposure; outdoor occupation and winter season of collection both predicted higher total UVAF. Furthermore, increased portion of day spent outdoors while working was associated with increased total conjunctival UVAF. We demonstrate feasibility and repeatability of estimating ocular sun exposure using a previously unreported method and for conjunctival UVAF in a group of subjects residing in Ohio. Seasonal temperature variation may have influenced time outdoors and ultimately calculation of ocular sun exposure. As winter season of collection and outdoor occupation both predicted higher total UVAF, our data suggests that ocular sun exposure is associated with conjunctival UVAF and, possibly, that UVAF remains for at least several months after sun exposure.

Ocular injuries sustained by survivors of the Oklahoma City bombing.