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Biomedical subjects

A T Moore

Publications and source records attributed to A T Moore.

At least 19 recordsLinked to original sources
PubMed2006

Is optic nerve fibre mis-routing a feature of congenital stationary night blindness?

PURPOSE: To determine whether patients with congenital stationary night blindness (CSNB) have electrophysiological evidence of optic nerve fibre mis-routing similar to that found in patients with ocular albinism (OA). METHOD: We recorded the Pattern Onset VEP using a protocol optimised to detect mis-routing of optic nerve fibres in older children and adults. We tested 20 patients (age 15-69 yrs) with X-linked or autosomal recessive CSNB, 14 patients (age 9-56 yrs) with OA and 13 normally pigmented volunteers (age 21-66 yrs). We measured the amplitude and latency of the CI component at the occipital midline and over left and right occipital hemispheres. We also assessed the computed inter-hemispheric "difference" signal. Subjects with CSNB were classified as having the "complete" or "incomplete" phenotype on the basis of their ERG characteristics. Members of X-linked CSNB pedigrees underwent mutation screening of the NYX and CACNA1F genes. RESULTS: CI was significantly smaller over the ipsilateral hemisphere and more prominent over the contralateral hemisphere in OA patients compared with both controls and CSNB patients. In CSNB patients CI response amplitudes were not significantly different from controls but peak latency was prolonged at all three electrodes compared with controls. The inter-hemispheric "difference" signal was abnormal for the OA group but not for the CSNB group. Contralateral dominance of CI could be identified in the majority of OA patients and the "difference" signal was opposite in polarity for left compared with right eye stimulation in every patient in this group. Only 3 of 20 patients with CSNB showed significant inter-hemispheric asymmetry similar to that seen in the OA patients. All 3 CSNB patients with evidence for optic nerve fibre mis-routing had X-linked pedigrees: 2 had an identified mutation in the NYX gene but no mutation in either the NYX or CACNA1F genes was identified in the third. VEP evidence of optic nerve fibre mis-routing was present in 3 of the 11 subjects with "complete" phenotype and none of the 9 patients with "incomplete" phenotype CSNB. CONCLUSION: Mis-routing of optic nerve fibres does occur in CSNB but we found evidence of it in only 15% of our patients.

Adolescent↗
PubMed2006

Smoking and age related macular degeneration: the number of pack years of cigarette smoking is a major determinant of risk for both geographic atrophy and choroidal neovascularisation.

BACKGROUND/AIMS: There is evidence that smoking is a risk factor for age related macular degeneration (AMD). However, not all studies have demonstrated this association and several key questions about the role of smoking in AMD have still to be determined. The aim of this study was to further investigate this relation for both choroidal neovascularisation (CNV) and geographic atrophy (GA). METHODS: To investigate the relation between smoking and the risk of developing age related macular degeneration (AMD) in white people, 435 cases with end stage AMD were compared with 280 controls. All subjects had graded stereoscopic colour fundus photography and AMD was defined as the presence of GA or CNV. Smoking history was assessed using multiple parameters in a detailed questionnaire. RESULTS: Comparison of current and former smokers with non-smokers was consistent with smoking being a risk factor for AMD but did not reach statistical significance. There was a strong association between AMD and pack years of cigarette smoking (p = 0.002), the odds ratio increasing with the amount smoked; for subjects with more than 40 pack years of smoking the odds ratio was 2.75 (95% CI 1.22 to 6.20) compared with non-smokers. Both types of AMD showed a similar relation; smoking more than 40 pack years of cigarettes was associated with an odds ratio of 3.43 (95% CI 1.28 to 9.20) for GA and 2.49 (95% CI 1.06 to 5.82) for CNV. Stopping smoking was associated with reduced odds of AMD and the risk in those who had not smoked for over 20 years was comparable to non-smokers. The risk profile was similar for males and females. Passive smoking exposure was associated with an increased risk of AMD (OR 1.87; 95% CI 1.03 to 3.40) in non-smokers. CONCLUSIONS: The authors have demonstrated a strong association between the risk of both GA and CNV and pack years of cigarette smoking. This provides support for a causal relation between smoking and AMD. They also show an increased risk for AMD in non-smokers exposed to passive smoking. Stopping smoking appears to reduce the risk of developing AMD.

Aged↗
PubMed2006

Age related macular degeneration and sun exposure, iris colour, and skin sensitivity to sunlight.

BACKGROUND/AIM: It has been suggested that sun exposure may be a risk factor for age related macular degeneration (AMD) and that skin sensitivity to sunlight and iris colour could be confounding factors. The aim was to investigate this further in the white population. METHODS: 446 cases with end stage AMD were compared with 283 spouse controls. Data on sun exposure, places of residence, iris colour, subjective assessment of change in iris colour, hair colour at age 20, and skin sensitivity were obtained using a questionnaire. Iris colour was graded clinically by comparison with standard photographs. AMD was graded using stereoscopic colour fundus photographs as well as clinical examination and was defined as the presence of geographic atrophy or choroidal neovascularisation. All variables were included in a multiple logistic regression model including age, sex, and smoking. RESULTS: There was no association between AMD and sun exposure or related factors except for the suggestion of an association between sunburn prone skin type and geographic atrophy which reached borderline significance. CONCLUSIONS: No significant association between AMD and sun exposure, iris colour, change in iris colour, or hair colour was demonstrated.

Aged↗
PubMed2006

A novel GJA8 mutation is associated with autosomal dominant lamellar pulverulent cataract: further evidence for gap junction dysfunction in human cataract.

PURPOSE: To identify the gene responsible for autosomal dominant lamellar pulverulent cataract in a four-generation British family and characterise the functional and cellular consequences of the mutation. METHODS: Linkage analysis was used to identify the disease locus. The GJA8 gene was sequenced directly. Functional behaviour and cellular trafficking of connexins were examined by expression in Xenopus oocytes and HeLa cells. RESULTS: A 262C>A transition that resulted in the replacement of proline by glutamine (P88Q) in the coding region of connexin50 (Cx50) was identified. hCx50P88Q did not induce intercellular conductance and significantly inhibited gap junctional activity of co-expressed wild type hCx50 RNA in paired Xenopus oocytes. In transfected cells, immunoreactive hCx50P88Q was confined to the cytoplasm but showed a temperature sensitive localisation at gap junctional plaques. CONCLUSIONS: The pulverulent cataract described in this family is associated with a novel GJA8 mutation and has a different clinical phenotype from previously described GJA8 mutants. The cataract likely results from lack of gap junction function. The lack of function was associated with improper targeting to the plasma membrane, most probably due to protein misfolding.

Cataract↗
PubMed2005

Blue cone monochromatism: a phenotype and genotype assessment with evidence of progressive loss of cone function in older individuals.

AIM: To perform a detailed clinical and psychophysical assessment of the members of three British families affected with blue cone monochromatism (BCM), and to determine the molecular basis of disease in these families. METHODS: Affected and unaffected members of three families with BCM were examined clinically and underwent electrophysiological and detailed psychophysical testing. Blood samples were taken for DNA extraction. The strategy for molecular analysis was to amplify the coding regions of the long wavelength-sensitive (L) and middle wavelength-sensitive (M) cone opsin genes and the upstream locus control region by polymerase chain reaction, and to examine these fragments for mutations by direct sequencing. RESULTS: We have confirmed the reported finding of protan-like D-15 arrangements of patients with BCM. In addition, we have demonstrated that the Mollon-Reffin (MR) Minimal test is a useful colour-discrimination test to aid in the diagnosis of BCM. Affected males were shown to fail the protan and deutan axes, but retained good discrimination on the tritan axis of the MR test, a compelling evidence for residual colour vision in BCM. This residual tritan discrimination was also readily detected with HRR plates. In two families, psychophysical testing demonstrated evidence for progression of disease. In two pedigrees, BCM could be linked to unequal crossovers within the opsin gene array that resulted in a single 5'-L/M-3' hybrid gene, with an inactivating Cys203Arg mutation. The causative mutations were not identified in the third family. CONCLUSIONS: The MR test is a useful method of detecting BCM across a wide range of age groups; residual tritan colour discrimination is clearly demonstrated and allows BCM to be distinguished from rod monochromatism. BCM is usually classified as a stationary cone dysfunction syndrome; however, two of our families show evidence of progression. This is the first report of progression associated with a genotype consisting of a single 5'-L/M-3' hybrid gene carrying an inactivating mutation. We have confirmed that the Cys203Arg inactivating mutation is a common sequence change in blue cone monochromats.

Adolescent↗
PubMed2005

A detailed phenotypic study of "cone dystrophy with supernormal rod ERG".

AIMS: To characterise the detailed phenotype of "cone dystrophy with supernormal rod ERG" in a case series of 10 patients. METHODS: 10 affected patients were examined clinically and underwent colour fundus photography, with nine undergoing detailed electrophysiological testing. Five patients were assessed further with fundus autofluorescence (AF) imaging, automated photopic and dark adapted perimetry, and dark adaptometry. Detailed colour vision assessment was performed in six subjects. Blood samples were taken from four patients for DNA extraction and mutation screening of NR2E3 was undertaken. RESULTS: The onset of symptoms was in the first and second decades of life. Subjects presented with reduced central vision and marked photophobia. All individuals were myopic and colour vision testing revealed severely reduced colour discrimination predominantly along the red-green axes; tritan colour vision was relatively well preserved. Nyctalopia is a later feature of the disorder. Funduscopy and AF imaging revealed a range of macular appearances. There was electrophysiological evidence of marked macular dysfunction, reduced and delayed cone responses, and supernormal and delayed rod responses. Photopic and dark adapted perimetry revealed central scotomata with widespread peripheral sensitivity loss. No disease causing sequence variants in NR2E3 were identified. CONCLUSIONS: The largest case series to date has been described of the clinical, psychophysical and electrophysiological characteristics of this unusual cone dystrophy with supernormal rod responses. Electrophysiological data were consistent with a post-phototransduction, but pre-inner nuclear layer, site of dysfunction. While the definitive diagnosis can only be made with electrophysiological testing, several characteristics that may increase suspicion of this diagnosis are presented.

Adolescent↗
PubMed2005

A detailed study of the phenotype of an autosomal dominant cone-rod dystrophy (CORD7) associated with mutation in the gene for RIM1.

AIM: To characterise the phenotype of an autosomal dominant cone-rod dystrophy (CORD7) associated with the Arg844His mutation in RIM1. METHODS: Eight members of a four generation, non-consanguineous British family were examined clinically and underwent electrophysiological testing, automated dark adapted perimetry, dark adaptometry, colour vision assessment, colour fundus photography, fundus fluorescein angiography (FFA), and fundus autofluorescence (AF) imaging. RESULTS: The majority of affected individuals described a progressive deterioration of central vision, night vision, and peripheral visual field usually between the third and fourth decades. The visual acuity ranged from 6/6 to 3/60. Colour vision testing showed mild to moderate dyschromatopsia in the majority of individuals. Fundus changes comprised a range of macular appearances varying from mild retinal pigment epithelial (RPE) disturbance to extensive atrophy and pigmentation. In some individuals retinal vessels were attenuated and in two subjects peripheral areas of retinal atrophy were present. An absent or severely reduced PERG was detected in all subjects, indicative of marked macular dysfunction. Full field ERG showed abnormal rod and cone responses. AF imaging revealed decreased macular AF centrally surrounded by a ring of increased AF in the majority of individuals. "Bull's eye" lesions were present in two individuals, comprising of a ring of decreased perifoveal AF bordered peripherally and centrally by increased AF. Photopic sensitivity testing demonstrated elevated central visual field thresholds with additional superior greater than inferior peripheral field loss. There were rod and cone sensitivity reductions in the central and peripheral visual fields, with the inferior retina being more affected than the superior. CONCLUSIONS: The detailed phenotype is described of the autosomal dominant cone-rod dystrophy, CORD7, which is associated with a point mutation in RIM1, a gene encoding a photoreceptor synaptic protein. The pattern of disease progression and long term visual outcome facilitates improved genetic counselling and advice on prognosis. Such phenotypic data will be invaluable in the event of future therapy.

Adolescent↗
PubMed2005

Posterior polar cataract is the predominant consequence of a recurrent mutation in the PITX3 gene.

BACKGROUND: The authors recently identified three large genetically unrelated families with an identical 17 base pair duplication mutation in exon 4 of the PITX3 gene. Here, they report the detailed clinical phenotype. METHODS: Affected and unaffected individuals in the three families with autosomal dominant posterior polar cataract underwent full clinical examination and donated blood samples for DNA extraction and molecular genetic studies. RESULTS: In all three families, an identical 17 base pair duplication mutation in PITX3 was identified which co-segregated with disease status in the family. All affected individuals had bilateral progressive posterior polar cataracts. In one family, posterior polar cataract was the only clinical abnormality but in the other two families, one of 10 affected individuals and four of 11 affected individuals also had anterior segment mesenchymal dysgenesis (ASMD). CONCLUSION: Mutations in the PITX3 gene in humans result in posterior polar cataract and variable ASMD. The gene encodes a transcription factor which has a key role in lens and anterior segment development. The mechanism by which the mutant protein gives rise to such a regional pattern of lens opacity remains to be elucidated.

Adolescent↗
PubMed2005

X-linked retinoschisis: clinical phenotype and RS1 genotype in 86 UK patients.

BACKGROUND: Inactivating mutations of the gene RS1 lead to X-linked retinoschisis, a progressive retinal dystrophy characterised by schisis within the inner layers of the neuroretina. The mutation spectrum is large and the phenotype variable. AIM: To determine whether there is a correlation between mutation type and disease severity. METHODS: We identified the causative mutation in 86 affected patients and examined each of these patients in detail. Different categories of mutation were compared for each phenotypic characteristic. RESULTS: We found a reduction in visual acuity with increasing age and worsening macular pathology in patients over 30 years old (p < or = 0.001), but there was no correlation between mutation type and severity of disease. Furthermore, we found a wide variation in phenotype even within families. CONCLUSIONS: Identifying the causative mutation in patients with X-linked retinoschisis is helpful in confirming diagnosis and in counselling of family members but cannot be used to predict prognosis for an individual patient.

Adolescent↗
PubMed2004

Cognitive functioning in humans with mutations of the PAX6 gene.

Fourteen patients with PAX6 gene mutations and previously identified MRI abnormalities were administered tests of cognitive functioning. No deficits were found. A subgroup with agenesis of the anterior commissure performed significantly more poorly on measures of working memory than those without this abnormality, suggesting the anterior commissure may play a role in cognitive processing in addition to an earlier identified role in sensory development and processing.

Adolescent↗
PubMed2004

Characterization of the G91del CRYBA1/3-crystallin protein: a cause of human inherited cataract.

Congenital cataract is a leading cause of visual disability in children. Inherited isolated (non-syndromic) cataract represents a significant proportion of cases and the identification of genes responsible for inherited cataract will lead to a better understanding of the mechanism of cataract formation at the molecular level both in congenital and age-related cataract. Crystallins are abundantly expressed in the developing human lens and represent excellent candidate genes for inherited cataract. A genome-wide search of a five-generation family with autosomal dominant lamellar cataract demonstrated linkage to the 17p12-q11 region. Screening of the CRYBA1/3 gene showed a 3 bp deletion, which resulted in a G91del mutation within the tyrosine corner, that co-segregated with disease and was not found in 96 normal controls. In order to understand the molecular basis of cataract formation, the mutant protein was expressed in vitro and its unfolding and refolding characteristics assessed using far-UV circular dichroism spectroscopy. Defective folding and a reduction in solubility were found. As the wild-type protein did not refold into the native conformation following unfolding, a corresponding CRYBB2 mutant was genetically engineered and its refolding characteristics analysed and compared with wild-type CRYBB2. Its biophysical properties support the hypothesis that removal of the glycine residue from the tyrosine corner impairs the folding and solubility of beta-crystallin proteins. This study represents the first comprehensive description of the biophysical consequences of a mutant beta-crystallin protein that is associated with human inherited cataract.

Amino Acid Sequence↗
PubMed2004

Full-field ERG responses recorded with skin electrodes in paediatric patients with retinal dystrophy.

PURPOSE: Assess ERG responses recorded with skin electrodes in children with retinal dystrophies. METHOD: ERG responses were recorded using skin electrodes in 17 healthy children and 43 paediatric patients with retinal dystrophy. Subjects were aged 4-14 years. ERG responses were recorded to full-field stimuli similar to those recommended in the ISCEV standard. The type of retinal dystrophy was classified on the basis of standard clinical criteria and the ERG responses were compared with those of the age-matched controls. RESULTS: ERG responses were abnormal in every patient. The specific type of ERG abnormality was also consistent with the clinical findings in the majority of patients. Rod responses were abnormal in every patient with a rod-cone dystrophy and cone responses were also abnormal in the majority of patients. Those patients with cone dystrophy or rod monochromatism had normal or near normal rod responses but sub-normal or absent cone responses. Patients with CSNB or XLRS had a sub-normal b-wave but normal amplitude a-wave. CONCLUSION: ERGs can be recorded successfully with skin electrodes in paediatric patientsand responses can aid the diagnosis of the type of retinal dystrophy.

Adolescent↗
PubMed2004

Juvenile neuronal ceroid lipofuscinosis (Batten disease) CLN3 mutation (Chrom 16p11.2) with different phenotypes in a sibling pair and low intensity in vivo autofluorescence.

BACKGROUND: The neuronal ceroid lipofuscinoses (Batten disease) are a heterogeneous group of autosomal recessively inherited disorders causing progressive neurological failure, mental deterioration, seizures and visual loss secondary to retinal dystrophy. The juvenile type is of special interest to the ophthalmologist as visual loss is the earliest symptom of the disorder. HISTORY AND SIGNS: We present two siblings with severe retinal dystrophy due to juvenile Batten disease. Sibling A (age 10) presented with visual loss, photophobia and night blindness, starting at age 4. His vision was perception of light by the age of 10.5 years. Fundus examination revealed severe pigmentary retinopathy. Sibling B (age 7) presented with night vision difficulties. Fundus examination revealed a bull's eye maculopathy with minimal peripheral atrophic changes. In vivo autofluorescence level was found to be very low. Electroretinography (ERG) showed generalized retinal dysfunction involving both cone and rod systems, with an electronegative maximal response. In both siblings vacuolated lymphocytes were found on a peripheral blood film and on molecular genetic testing both were homozygous for the commonly reported 1.02-kb deletion of the CLN3 gene. THERAPY AND OUTCOME: Although there is no effective treatment, the early diagnosis allowed accurate genetic and social counseling. CONCLUSIONS: Juvenile Batten disease should be considered in children with a retinal dystrophy, especially where there is a bull's eye maculopathy and an abnormal full field ERG. The novel finding of very low in vivo autofluorescence is consistent with histopathological studies and may be secondary to photoreceptor cell loss.

Blindness↗
PubMed2004

Microbial keratitis in ITU staff: an occupational hazard?

Microbial keratitis is a potentially blinding corneal infection; the infection may progress rapidly if untreated and result in corneal perforation. The breakdown of the innate ocular defences is known to predispose to corneal infection. We present three cases of microbial keratitis in intensive therapy unit (ITU) staff each of whom had compromised corneal immunity. Anaesthetists and nurses regularly perform high-risk procedures, such as tracheal suctioning, which have been known to cause ocular infections by aerosol inoculation. We suggest that although the absolute risk of infection is low, susceptible individuals may be at increased risk of corneal infection from exposure to potentially pathogenic organisms in such environments. We stress the need for ITU staff, particularly those who wear contact lenses, to wear eye protection when performing procedures likely to cause infected aerosols.

Adult↗
PubMed2004

The cone dysfunction syndromes.

The cone dystrophies comprise a heterogeneous group of disorders characterised by visual loss, abnormalities of colour vision, central scotomata, and a variable degree of nystagmus and photophobia. They may be stationary or progressive. The stationary cone dystrophies are better described as cone dysfunction syndromes since a dystrophy often describes a progressive process. These different syndromes encompass a wide range of clinical and psychophysical findings. The aim is to review current knowledge relating to the cone dysfunction syndromes, with discussion of the various phenotypes, the currently mapped genes, and genotype-phenotype relations. The cone dysfunction syndromes that will be discussed are complete and incomplete achromatopsia, oligocone trichromacy, cone monochromatism, blue cone monochromatism, and Bornholm eye disease. Disorders with a progressive cone dystrophy phenotype will not be discussed.

Color Vision Defects↗
PubMed2004

Oligocone trichromacy: a rare and unusual cone dysfunction syndrome.

AIM: To describe the phenotype of a case series of six patients with oligocone trichromacy. METHODS: The six affected individuals underwent an ophthalmological examination, electrophysiological testing and detailed psychophysical assessment. RESULTS: All six affected patients had a history of moderately reduced visual acuity (6/12 to 6/24) from infancy, not improved by full spectacle correction. They complained of mild photophobia and they were not aware of any colour vision deficiency. They had no nystagmus and fundi were normal. Electrophysiological testing revealed either absent/profoundly reduced cone flicker responses or preserved but delayed and mildly reduced flicker responses. Colour vision was found to be within normal limits, but some patients showed mildly elevated discrimination thresholds along all axes. CONCLUSION: The largest case series to date of patients with oligocone trichromacy is presented. The electrophysiological findings suggest that there may be more than one disease mechanism. The mode of inheritance is likely to be autosomal recessive, and while previous reports have suggested that this disorder is stationary, in one of these families there is clinical evidence of progression.

Adolescent↗