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Biomedical subjects

A C Bird

Publications and source records attributed to A C Bird.

At least 19 recordsLinked to original sources
PubMed2006

Does smoking influence the type of age related macular degeneration causing visual impairment?

AIMS: To assess the influence of smoking on the type of age related macular degeneration (AMD) lesion causing visual impairment in a large cohort of patients with AMD at a tertiary referral UK centre. METHODS: Prospective, observational, cross sectional study to analyse smoking data on 711 subjects, of western European origin, in relation to the type of AMD lesion present. Colour fundus photographs were graded according to a modified version of the international classification. Multiple logistic regression analysis was performed, adjusting for age and sex using the statistical package SPSS ver 9.0 for Windows. chi(2) tests were also used to assess pack year and ex-smoker data. RESULTS: 578 subjects were graded with neovascular AMD and 133 with non-neovascular AMD. There was no statistically significant association found between smoking status or increasing number of pack years and type of AMD lesion. The odds of "current smokers" compared to "non-smokers" developing neovascular rather than non-neovascular AMD when adjusted for age and sex was 1.88 (95% CI: 0.91 to 3.89; p = 0.09). CONCLUSIONS: Smoking is known to be a risk factor for AMD and this study suggests that smokers are at no more risk of developing neovascular than atrophic lesions.

Age Distribution↗
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

Functional characterisation and serial imaging of abnormal fundus autofluorescence in patients with retinitis pigmentosa and normal visual acuity.

AIM: To characterise and monitor abnormal fundus autofluorescence (AF) in patients with retinitis pigmentosa (RP) who have good visual acuity. METHODS: 21 patients with a clinical diagnosis of RP were examined. All had rod-cone dystrophy (ISCEV standard electroretinograms (ERGs)), visual acuity of 6/9 or better, and manifested a parafoveal ring of high density fundus AF. Repeat AF imaging was performed after periods of between 2 years and 5 years in 12 patients. Pattern ERG (PERG) and multifocal ERG (mfERG) were performed in 20 cases. Visual fields (VF), photopic and scotopic fine matrix mapping and small field PERGs were performed in representative cases. RESULTS: The rings of high density AF varied in size between patients (from 4 degrees -16 degrees diameter). MfERGs showed relative preservation over the central macular area, correlating with the size of AF ring and with PERG and psychophysical data. Progressive constriction of the AF ring was demonstrated at follow up in three patients. Serial PERG, mfERG, and VFs, performed in one of these cases, showed evidence of deterioration concordant with ring constriction. CONCLUSIONS: High density rings of AF, seen in some patients with RP with good visual acuity, demarcate areas of preserved central photopic function. MfERGs correlate with the area encircled by high density AF and the PERG data. The size of the ring of AF can show progressive constriction accompanied by increasing macular dysfunction.

Adolescent↗
PubMed2006

Clinical characterisation of a family with retinal dystrophy caused by mutation in the Mertk gene.

BACKGROUND/AIM: MERTK, a tyrosine kinase receptor protein expressed by the retinal pigment epithelium (RPE), is mutated in both rodent models and humans affected by retinal disease. This study reports a survey of families for Mertk mutations and describes the phenotype exhibited by one family. METHODS: 96 probands with retinal dystrophy, consistent with autosomal recessive segregation, were screened by direct sequencing. A family homozygous for a likely null allele was investigated clinically. RESULTS: A novel frame shifting deletion was identified in one of 96 probands. Other polymorphisms were detected. The deletion allele occurred on both chromosomes of four affected family members. Electrophysiology demonstrated early loss of scotopic and macular function with later loss of photopic function. Visual acuities and visual fields were preserved into the second decade. Perception of light vision was present in a patient in the fourth decade. A "bull's eye" appearance and a hyperautofluorescent lesion at the central macula were consistent clinical findings. CONCLUSIONS: Mutations in Mertk are a rare cause of ARRP in humans. The study extends the phenotypic characteristics of this retinal dystrophy and shows distinctive clinical signs that may improve its clinical identification. The moderate severity and presence of autofluorescence implies that outer segment phagocytosis is not entirely absent.

Adult↗
PubMed2005

Functional observations in vitamin A deficiency: diagnosis and time course of recovery.

AIMS: To describe the effects of vitamin A deficiency (VAD) on retinal function and the subsequent recovery following treatment in three patients with systemic conditions (two with Crohn disease; one secondary to IgE syndrome). METHODS: Electrophysiological testing (including pattern electroretinogram, PERG; electroretinogram, ERG; visual-evoked potential) established the diagnosis of VAD. Repeat testing was carried out in two patients to monitor the time course of recovery following intramuscular vitamin A injection. The third patient had repeat recordings following 13 months of oral supplementation. RESULTS: All three patients initially displayed a characteristic absence of rod function associated with VAD. In addition, delayed and reduced amplitude cone ERGs, loss of short wavelength cone (S-cone) function and subnormal macular function were observed in two patients. Restoration of rod and generalised cone function was rapid in the two patients who received intramuscular injection, with normalisation of some electrophysiological responses after only 3 days. Normal S-cone amplitudes and cone latencies were reached within 12 days of vitamin A injection. Macular function returned to within normal limits by 12 days postinjection in one patient, but remained mildly subnormal in the second patient. Full recovery was present after 13 months oral supplementation in the third patient. CONCLUSIONS: Novel observations regarding dark-adapted cone function, S-cone function, and PERG are presented. The differences between the effects of VAD on rod and cone function, and their rate of recovery, may reflect differences in the visual cycle between the two photoreceptor classes. The importance of rapidly and accurately diagnosing VAD, a treatable condition, is noted.

Administration, Oral↗
PubMed2005

[Pathogenesis of lesions in late age-related macular disease].

To summarize the evidence that exists concerning the pathogenesis of lesions in late age-related macular disease (AMD), we reviewed both experimental evidence and clinical observations that address these problems. There is good evidence that choroidal neovascularization is due to a change in the balance of growth factors derived from the retinal pigment epithelial basolateral plasma membrane domain (RPE). Retinal angiomatous proliferation may also have a similar pathogenesis involving the apical domain. Detachment of the RPE is likely to be a consequence of increased resistance of Bruch's membrane to water flow due to deposition of lipids. Geographic atrophy is preceded by accumulation of autofluorescent material in the RPE and possible causal relationships between the two have been demonstrated. There is increasing understanding concerning the sequence of events that lead to those lesions causing loss of central vision in AMD. Therapeutic approaches that address the underlying mechanisms are more likely to succeed than current treatment options. Such an approach has already been initiated in the management of choroidal neovascularization.

Humans↗
PubMed2005

Visual functioning and quality of life in the SubFoveal Radiotherapy Study (SFRADS): SFRADS report 2.

AIMS: To determine whether or not self reported visual functioning and quality of life in patients with choroidal neovascularisation caused by age related macular degeneration (AMD) is better in those treated with 12 Gy external beam radiotherapy in comparison with untreated subjects. METHODS: A multicentre single masked randomised controlled trial of 12 Gy of external beam radiation therapy (EBRT) delivered as 6 x 2 Gy fractions to the macula of an affected eye versus observation. Patients with AMD, aged 60 years or over, in three UK hospital units, who had subfoveal CNV and a visual acuity equal to or better than 6/60 (logMAR 1.0). METHODS: Data from 199 eligible participants who were randomly assigned to 12 Gy teletherapy or observation were available for analysis. Visual function assessment, ophthalmic examination, and fundus fluorescein angiography were undertaken at baseline and at 3, 6, 12, and 24 months after study entry. To assess patient centred outcomes, subjects were asked to complete the Daily Living Tasks Dependent on Vision (DLTV) and the SF-36 questionnaires at baseline, 6, 12, and 24 months after enrolment to the study. Cross sectional and longitudinal analyses were conducted using arm of study as grouping variable. Regression analysis was employed to adjust for the effect of baseline co-variates on outcome at 12 months and 24 months. RESULTS: Both control and treated subjects had significant losses in visual functioning as seen by a progressive decline in mean scores in the four dimensions of the DLTV. There were no statistically significant differences between treatment and control subjects in any of dimensions of the DLTV at 12 months or 24 months after study entry. Regression analysis confirmed that treatment status had no effect on the change in DLTV dimensional scores. CONCLUSIONS: The small benefits noted in clinical measures of vision in treated eyes did not translate into better self reported visual functioning in patients who received treatment when compared with the control arm. These findings have implications for the design of future clinical trials and studies.

Activities of Daily Living↗
PubMed2005

Acute zonal occult outer retinopathy: towards a set of diagnostic criteria.

BACKGROUND: Individuals with acute zonal occult outer retinopathy (AZOOR) present with initially progressive scotomata and photopsia. Characteristically, the extent of the visual field defect is unexplained by fundal examination, but there is marked retinal dysfunction evident electrophysiologically. It is the authors' experience that a group of patients exhibit characteristic clinical and electrophysiological abnormalities, which serve as criteria for a working diagnosis. METHODS: A retrospective observational case series of 28 patients were identified with the clinical diagnosis of AZOOR who shared similar abnormal electrophysiology. Details of the history and ophthalmic findings were obtained from the case notes. RESULTS: Electrophysiology demonstrated a consistent pattern of dysfunction both at the photoreceptor/retinal pigment epithelial complex but also at inner retinal levels, essentially comprising a delayed 30 Hz flicker ERG and a reduction in the EOG light rise. CONCLUSION: This study determines diagnostic criteria applicable to a group of patients with AZOOR, typically those with classic symptomatology. Electrophysiological testing can help avoid lengthy, costly, and potentially invasive investigations, and the unnecessary use of immunosuppressive therapy.

Acute Disease↗
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↗
PubMed2004

Congenital stationary night blindness and a "Schubert-Bornschein" type electrophysiology in a family with dominant inheritance.

BACKGROUND/AIMS: To present the clinical, psychophysical, and electrophysiological characteristics of a family with dominantly inherited congenital stationary night blindness (CSNB). METHODS: Five affected family members from three generations were ascertained. Four affected individuals underwent ophthalmic examination and electrodiagnostic investigations. Three affected individuals also underwent scanning laser ophthalmoscopy and psychophysical testing. RESULTS: Affected individuals reported night blindness from an early age. Visual acuities were normal. Fundal appearances were normal apart from one older patient showing areas of peripheral chorioretinal atrophy. Autofluorescence images showed no gross abnormality. International Society for Clinical Electrophysiology of Vision (ISCEV) standard electroretinography (ERG) showed undetectable rod specific responses and electronegative maximal responses, but normal ISCEV cone responses. Additional S-cone specific ERG recordings were of reduced amplitude in all patients studied. There was no apparent rod component to the dark adaptation curve. Central 30 degrees thresholds were normal under photopic conditions but showed increased thresholds under scotopic conditions for both red and blue stimuli. CONCLUSION: Results from investigation of this family are consistent with an impairment of rod photoreceptor signalling. The ERG findings suggest an abnormality occurring after phototransduction with rod and S-cone pathway involvement. These findings differ from those rare families reported previously with dominant CSNB.

Adolescent↗
PubMed2003

Macular pigment: quantitative analysis on autofluorescence images.

BACKGROUND: Macular pigment (MP) reduces oxidative damage in the central retina and can be quantified by flicker-photometric analysis (HFP) of MP optical density. These analyses demonstrate a very good correlation with central absorption by MP on autofluorescence (AF) images. With these techniques different types of MP-distribution have been described. In the present study a quantification analysis of MP in AF images was developed to verify these MP types and to compare MP distribution patterns between healthy individuals and those with age-related macular degeneration (AMD). METHODS: AF images (HRA) were analysed with respect to the area of central and paracentral absorption in 400 eyes with a computerised analysis program of MP optical density. The patients were between 41 and 90 years old (mean 67.2 years); 168 were male and 232 female, and 253 had early AMD and 147 showed no AMD characteristics. The central MP concentrations (peak) were measured, the amount of MP values within the first 8-pixel radius ("C"), the total amount of MP within a 120-pixel radius ("T") were calculated as the volume of the MP values over the regarded radius and the C/T ratio was registered. RESULTS: Four types of MP distribution (type 1, intense central and paracentral MP; type 2, less intense central and paracentral MP; type 3, only central MP; type 4, only paracentral MP) were identified. The differences in MP distribution were confirmed and clearly characterised by quantitative analyses of peak, total MP ("T"), central MP ("C") and C/T ratio: mean peak in type 1, 0.65; type 2, 0.42; type 3, 0.42; type 4, 0.29; mean total amount of MP in 120-pixel radius ("T") in type 1, 5829.0; type 2, 4412.5; type 3, 2709; type 4, 4302.8. MP types with lower levels of MP were significantly more often observed in the AMD group (AMD: type 1, 120=47.4%; types 2-4, 133=52.6%; healthy eyes: type 1, 112=76.2%; types 2-4, 35=23.8%) ( P<0.0001) CONCLUSIONS: Analysis of MP on AF images is a quantitative method for investigation of MP. With this method a wide variation in concentration and distribution of MP could be seen in the population. Four different types of MP distribution could be characterised and quantitatively distinguished. Reduced levels of MP seem to be associated with a higher risk of development of AMD as they were significantly more often observed in the AMD group. This strategy of quantitative MP analysis on AF images is easily practicable and may be used in further studies to investigate the role of MP as a potential risk factor for AMD.

Adult↗
PubMed2003

The contribution of USH1C mutations to syndromic and non-syndromic deafness in the UK.

Denaturing high-performance liquid chromatography (DHPLC) was used to screen 14 UK patients with Usher syndrome type 1, in order to assess the contribution of mutations in USH1C to type 1 Usher. In addition, 16 Caucasian sib pairs and two small consanguineous families with non-syndromic deafness, who were concordant for haplotypes around DFNB18, were also screened for mutations in the USH1C gene. Two Usher type 1 patients were found to have the 238-239insC mutation reported previously; one of Greek Cypriot origin was homozygous for the mutation and another Caucasian was heterozygous. This indicates that mutations in the USH1C gene make a greater contribution to Usher syndrome type 1 than originally thought, which has implications for the genetic testing of families with Usher syndrome in the UK. Analysis using intragenic single nucleotide polymorphisms (SNPs) revealed that the haplotypic background bearing this common mutation was not consistent across the gene in two families, and that there are either two haplotypes on which the mutation has arisen or that there has been a recombination on a single haplotype. We found no evidence of mutations in USH1C in the patients with non-syndromic deafness, suggesting that the gene is not a major contributor to autosomal-recessive non-syndromic deafness in the UK.

Adaptor Proteins, Signal Transducing↗