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Biomedical subjects

A C Bird

Publications and source records attributed to A C Bird.

At least 37 records · Page 2Linked to original sources
PubMed2003

Prophylactic laser treatment appears to promote choroidal neovascularisation in high-risk ARM: results of an interim analysis.

PURPOSE: The Drusen Laser Study (DLS) of high-risk age-related maculopathy (ARM) is a randomised, controlled clinical trial designed to answer two questions: (1). Do drusen resolve after macular laser photocoagulation (2). Does macular laser photocoagulation prevent choroidal neovascularisation (CNV) in high-risk eyes? In this report, we present the results of the interim, pooled analysis of CNV prophylaxis for patients in the Unilateral Group of the DLS. METHODS: The DLS is a randomised controlled clinical trial of prophylactic macular photocoagulation for high-risk ARM. Patients in the Unilateral Group had a neovascular complication in the first eye; their fellow eye (Study Eye) had visual acuity of 6/12 or better and drusen. Following informed consent, patients were randomised to the Treatment Group or the No Treatment Group. Patients randomised to treatment received 12 light spots of argon laser photocoagulation to their Study Eye: four burns were placed 750 microm from the centre of the fovea at 12, 3, 6, and 9 o'clock, and the eight remaining burns were placed 1500 microm from the centre of the fovea at 12, 1:30, 3, 4:30, 6, 7:30, 9, and 10:30 o'clock. Drusen were treated directly only if they were present at the protocol treatment locations. All patients were followed in an identical fashion at regular intervals. Best-corrected visual acuity was measured and recorded by a masked observer. Fluorescein angiography was performed at baseline and yearly review, as well as nonprotocol visits if symptoms suggested CNV. Five clinical centres utilised and conformed to a common DLS protocol. Patient care and data collection methodologies were deemed sufficiently similar to permit a pooled data analysis. RESULTS: There were 156 patients included in the interim analysis, and timed information was available on 153. CNV occurred in 21 of 81 (26%) patients in the Treatment Group and in 13 of 75 (17%) patients in the No Treatment Group (P=0.19). Kaplan-Meier survival analysis showed earlier onset of CNV in the Treatment Group compared to patients in the No Treatment Group (statistical significance not calculated). Visual acuity loss at 2 years occurred in nine of 54 (17%) patients in the Treatment Group compared to the two of 48 (4%) patients in the No Treatment Group (P=0.056). CONCLUSIONS: We are only the second group to identify possible laser-induced CNV despite other similar studies in progress. Equipoise of the DLS investigators was lost, and recruitment was halted. We feel ethically bound to notify the ophthalmic community of this finding.

Choroidal Neovascularization↗
PubMed2003

Fundus autofluorescence imaging compared with different confocal scanning laser ophthalmoscopes.

BACKGROUND: With the advent of confocal scanning laser ophthalmoscopes (cSLO), fundus autofluorescence (FAF) resulting mainly from lipofuscin accumulation on the level of the retinal pigment epithelium can be visualised in vivo. Various cSLOs are available to document FAF. The authors analysed and compared results of FAF using three different instruments. METHODS: Eight eyes of eight normal volunteers and 18 eyes of 12 patients with different retinal diseases (age related macular degeneration, macular dystrophy, central serous retinopathy) were examined. FAF images were recorded from each subject with the Heidelberg retina angiograph (HRA), the Rodenstock cSLO (RcSLO) and the Zeiss Prototype SM 30-4024 (ZcSLO). For excitation an argon laser (488 nm) was used (barrier filter: HRA 500 nm; RcSLO 515 nm; ZcSLO 521 nm). 32 FAF images were aligned and averaged using the same software for all cSLOs. FAF distribution was measured and grey scale values as well as root mean square (RMS) contrast were compared. RESULTS: Mean age of all subjects was 55.5 (SD 21.4) years. The maximum grey scale value averaged across all eyes was 76.19 (39.34) for the HRA, 61.44 (22.12) for the ZcSLO and 37.0 (9.97) for the RcSLO. The RMS contrast was 0.46 (0.20) for the ZcSLO, 0.40 (0.12) for the HRA, and 0.13 (0.05) for the RcSLO. The differences between the cSLOs were statistically significant with higher grey scale levels and more contrast for the HRA and ZcSLO than the RcSLO (repeated measures ANOVA; p<0.0001). The differences between the HRA and the ZcSLO were not significant (post hoc comparisons; p<0.05). CONCLUSIONS: All cSLOs allow clinically useful FAF imaging in retinal diseases. However, grey scale levels and contrast were much lower on the RcSLO. Therefore, RcSLO images appear much darker than HRA or ZcSLO images. Furthermore, not all cSLOs have a fixed photodetector gain and a standardised value for the argon laser amplification, which is mandatory for an absolute comparison of FAF imaging results.

Aged↗
PubMed2003

Genotype-phenotype correlation in British families with X linked congenital stationary night blindness.

AIM: To correlate the phenotype of X linked congenital stationary night blindness (CSNBX) with genotype. METHODS: 11 CSNB families were diagnosed with the X linked form of the disease by clinical evaluation and mutation detection in either the NYX or CACNA1F gene. Phenotype of the CSNBX patients was defined by clinical examination, psychophysical, and standardised electrophysiological testing. RESULTS: Comprehensive mutation screening identified NYX gene mutations in eight families and CACNA1F gene mutations in three families. Electrophysiological and psychophysical evidence of a functioning but impaired rod system was present in subjects from each genotype group, although the responses tended to be more severely affected in subjects with NYX gene mutations. Scotopic oscillatory potentials were absent in all subjects with NYX gene mutations while subnormal OFF responses were specific to subjects with CACNA1F gene mutations. CONCLUSIONS: NYX gene mutations were a more frequent cause of CSNBX than CACNA1F gene mutations in the 11 British families studied. As evidence of a functioning rod system was identified in the majority of subjects tested, the clinical phenotypes "complete" and "incomplete" do not correlate with genotype. Instead, electrophysiological indicators of inner retinal function, specifically the characteristics of scotopic oscillatory potentials, 30 Hz flicker and the OFF response, may prove more discriminatory.

Base Sequence↗
PubMed2002

Pigment epithelial detachment in the elderly. Clinical differentiation, natural course and pathogenetic implications.

BACKGROUND: A prospective analysis was performed to characterize the angiographic appearance, natural course and prognosis of serous pigment epithelial detachments (PEDs) in elderly patients. The aim was to differentiate PEDs according to their angiographic characteristics and to analyze the specific clinical, visual and morphologic course of the different PEDs. METHODS: Fluorescein and indocyanine green angiography were performed in 101 consecutive patients (53-87 years; 63 female, 38 male) with clinical signs of serous PED and drusen. RESULTS: Different types of serous PED were identified: polypoidal choroidal vasculopathy (PCV)-associated PED in 14 patients (13.9%), vascular PED in 72 (71.2%), and avascular PED in 15 (14.9%). All PEDs resulted initially in similar visual loss. Avascular PEDs were smaller than vascular PEDs, and the latter were smaller than PCV-PEDs. During follow-up these differences were always present, but all PEDs enlarged initially followed by regression. This course was associated in all PEDs with progressive visual loss, accompanied by the development of RPE atrophy in avascular PEDs or disciform scars or RPE tears in the two other types. CONCLUSION: Despite different associations, all PEDs have a similar clinical course with respect to visual loss and enlargement or regression. This is compatible with the proposed common pathogenetic background with a hydrophobic barrier in Bruch's membrane causing fluid resulting from RPE pumping activity to accumulate between the pigment epithelium and Bruch's membrane.

Aged↗
PubMed2002

Visual outcomes in the subfoveal radiotherapy study: a randomized controlled trial of teletherapy for age-related macular degeneration.

OBJECTIVE: To determine whether teletherapy with 6-mV photons can reduce visual loss in patients with subfoveal choroidal neovascularization in age-related macular degeneration. DESIGN: A multicenter, single-masked, randomized controlled trial of 12 Gy of external beam radiation therapy delivered to the macula of an affected eye vs observation only. SETTING: Three United Kingdom-based hospital units. PARTICIPANTS: Patients with age-related macular degeneration, aged 60 years and older, who had subfoveal choroidal neovascularization and a visual acuity of 20/200 (logMAR 1.0) or better. METHODS: Two hundred three patients were randomly assigned to radiotherapy or observation. Treatment was undertaken at designated radiotherapy centers, and patients assigned to the treatment group received a total dosage of 12 Gy of 6-mV photons in 6 fractions. Follow-up was scheduled at 3, 6, 12, and 24 months. After excluding protocol violators, the data from 199 patients were analyzed. MAIN OUTCOME MEASURES: The primary outcome measure was mean loss of distance visual acuity in the study eye at 12 and 24 months. Other outcome variables analyzed were near visual acuity and contrast sensitivity. The proportions of patients losing 3 or more or 6 or more lines of distance and near acuity and 0.3 or more or 0.6 or more log units of contrast sensitivity at each follow-up were also analyzed. RESULTS: At all time points, mean distance visual acuity was better in the radiotherapy-treated group than in the control group, but the differences did not reach statistical significance. At 24 months, analysis of the proportions of patients with loss of 3 or more (moderate) (P =.08) or 6 or more (severe) (P =.29) lines of distance vision showed that fewer treated patients had severe losses, but there was no statistically significant difference between groups. For near visual acuity, although there was no evidence of treatment benefit at 12 and 24 months, a significant difference in favor of treatment was present at 6 months (P =.048). When analyzed by the proportions of patients losing 3 lines of contrast sensitivity, there was a significant difference in favor of treatment at 24 months (P =.02). No adverse retinal effects were observed during the study, but transient disturbance of the precorneal tear film was noted in treated patients. CONCLUSION: The results of the present trial do not support the routine clinical use of external beam radiation therapy in subjects with subfoveal choroidal neovascularization in age-related macular degeneration.

Aged↗
PubMed2002

Symptomatic abnormalities of dark adaptation in patients with EFEMP1 retinal dystrophy (Malattia Leventinese/Doyne honeycomb retinal dystrophy).

PURPOSE: To investigate the nature of symptomatic visual disturbance in patients with EFEMP1 retinal dystrophy in the absence of geographic atrophy or choroidal neovascularization. METHODS: Patients presenting to a tertiary referral centre underwent clinical evaluation, fluorescein angiography, colour contrast sensitivity, focal, pattern, and standard electroretinography, electrooculography, scotopic threshold perimetry and dark adaptometry. RESULTS: Clinical features included reduced central vision, difficulty passing from light to dark, and diffuse submacular and peripapillary deposits, which were hyperfluorescent by fluorescein angiography. Colour contrast thresholds were abnormal in all six patients studied and both pattern and focal electroretinograms were abnormal in five of six patients. The scotopic and mixed rod-cone single flash ERG was normal but two patients demonstrated reduced oscillatory potentials and one had borderline delayed 30 Hz responses. Scotopic thresholds were elevated and rod-mediated dark adaptation kinetics were markedly prolonged in all six patients when measured over the central visible confluent deposits. CONCLUSIONS: In patients with EFEMP1 retinal dystrophy with confluent macular deposits, scotopic sensitivity is reduced and dark adaptation kinetics are prolonged over the macular deposits but are normal elsewhere. These results emphasize the localised nature of functional deficits in some patients with EFEMP1 retinal dystrophy and correlate well with the patient's visual symptoms. Symptomatic visual dysfunction may precede the development of clinically evident geographic atrophy or choroidal neovascularization in this disorder.

Color Vision Defects↗
PubMed2002

Low vision services for vision rehabilitation in the United Kingdom.

AIM: Little is known about the distribution and methods of delivery of low vision services across the United Kingdom. The purpose of this study was to determine the type and location of low vision services within the UK. METHODS: Survey by means of a 29 point postal questionnaire, followed when necessary by a five point telephone questionnaire. All known potential providers of low vision services (n = 2539) including hospitals (n = 277), optician/optometry practices (n = 1683), social services (n = 177), voluntary groups (n = 190), specialist teachers (n = 205), and universities (n = 6) were surveyed. For each service provider, the type, magnitude, and geographical location were determined. The distribution of services across the United Kingdom and the ratio of providers to population density of people with a visual impairment were mapped using the Geographic Information System (GIS). RESULTS: Data were obtained on 1945 (77%) service providers: 1679 (66%) responded to the postal questionnaire and 266 (11%) to the telephone questionnaire. Of all respondents, 59% (n = 1135) offer some form of help to people with a visual disability, of which 26% (n = 497) only sell magnifiers and 33% (n = 638) provide low vision services. It is estimated that in total just under 155,000 low vision consultations are offered annually, the bulk of which are provided by hospital eye departments. The distribution was geographically uneven and there appears to be scarcity in some areas. CONCLUSION: When compared to the probable number of people with a visual impairment in the UK there are apparent inadequacies in service provision in terms of distribution, magnitude, and coordination. The results highlight a need to review current services.

Health Care Surveys↗
PubMed2001

Mutations in the pre-mRNA splicing factor gene PRPC8 in autosomal dominant retinitis pigmentosa (RP13).

Retinitis pigmentosa (RP) is a genetically heterogeneous disorder characterized by progressive degeneration of the peripheral retina leading to night blindness and loss of visual fields. With an incidence of approximately 1 in 4000, RP can be inherited in X-linked, autosomal dominant or autosomal recessive modes. The RP13 locus for autosomal dominant RP (adRP) was placed on chromosome 17p13.3 by linkage mapping in a large South African adRP family. Using a positional cloning and candidate gene strategy, we have identified seven different missense mutations in the splicing factor gene PRPC8 in adRP families. Three of the mutations cosegregate within three RP13 linked families including the original large South African pedigree, and four additional mutations have been identified in other unrelated adRP families. The seven mutations are clustered within a 14 codon stretch within the last exon of this large 7 kb transcript. The altered amino acid residues at the C-terminus exhibit a high degree of conservation across species as diverse as humans, Arabidopsis and trypanosome, suggesting that some functional significance is associated with this part of the protein. These mutations in this ubiquitous and highly conserved splicing factor offer compelling evidence for a novel pathway to retinal degeneration.

Animals↗
PubMed2001

Autosomal dominant cone-rod dystrophy with mutations in the guanylate cyclase 2D gene encoding retinal guanylate cyclase-1.

OBJECTIVE: To describe the phenotype in 4 families with dominantly inherited cone-rod dystrophy, 1 with an R838C mutation and 1 with an R838H mutation in the guanylate cyclase 2D (GUCY2D) gene encoding retinal guanylate cyclase-1. METHODS: Psychophysical and electrophysiological evaluation and confocal laser scanning ophthalmoscopic imaging was performed on 10 affected members of 4 British families. RESULTS: Although subjects had lifelong poor vision in bright light, a major reduction in visual acuity did not occur in most of them until after their late teens. Fundus abnormalities were confined to the central macula, and increasing central atrophy was noted with age. Increased background autofluorescence was observed surrounding the central atrophic area. Electrophysiological testing revealed a marked loss of cone function with only minimal rod involvement, even in older subjects. Photopic and scotopic static perimetry demonstrated central and peripheral cone-mediated threshold elevations with midperipheral sparing. CONCLUSION: The phenotype associated with autosomal dominant cone-rod dystrophy with either an R838C or R838H mutation in GUCY2D is distinctive, with predominantly cone system involvement. There is some variation in severity within the 3 families with the R838C mutation. CLINICAL RELEVANCE: Families with the R838C or R838H mutation have a much milder phenotype than the family previously described that had 2 sequence changes, E837D and R838S, in GUCY2D.

Adolescent↗
PubMed2001

Phenotypic subtypes of Stargardt macular dystrophy-fundus flavimaculatus.

OBJECTIVE: To determine if phenotypic subtypes exist in Stargardt macular dystrophy-fundus flavimaculatus (SMD-FFM). METHODS: A cross-sectional study of 63 patients with autosomal recessive SMD-FFM was undertaken. The age of onset, duration of symptoms, visual acuity, and clinical features on fundus examination, color fundus photographs, and fundus autofluorescence images were recorded. Electrophysiological tests, including pattern, focal, and full-field electroretinogram (ERG), electro-oculogram, and color-contrast sensitivity measurement, were also performed. RESULTS: Based on electrophysiological attributes (ERG), patients with SMD-FFM could be classified into 3 groups. In group 1, there was severe pattern ERG abnormality with normal scotopic and full-field ERGs. In group 2, there was additional loss of photopic function, and in group 3, there was loss of both photopic and scotopic function. Differences in scotopic or photopic function among groups were not explained on the basis of differences in age of onset or duration of disease. CONCLUSIONS: Patients with SMD-FFM can be classified into 3 groups based on the absence or presence of generalized loss of either photopic or photopic and scotopic function. It appears that these 3 groups may represent distinct phenotypic subtypes in SMD-FFM.

Adult↗
PubMed2001

Spectrum of mutations in USH2A in British patients with Usher syndrome type II.

Usher syndrome (USH) is a combination of a progressive pigmentary retinopathy, indistinguishable from retinitis pigmentosa, and some degree of sensorineural hearing loss. USH can be subdivided in Usher type I (USHI), type II (USHII) and type III (USHIII), all of which are inherited as autosomal recessive traits. The three subtypes are genetically heterogeneous, with six loci so far identified for USHI, three for USHII and only one for USHIII. Mutations in a novel gene, USH2A, encoding the protein usherin, have recently been shown to be associated with USHII. The gene encodes a protein with partial sequence homology to both laminin epidermal growth factor and fibronectin motifs. We analysed 35 British and one Pakistani Usher type II families with at least one affected member, for sequence changes in the 20 translated exons of the USH2A gene, using heteroduplex analysis and sequencing. Probable disease-causing mutations in USH2A were identified in 15 of 36 (41.7%) Usher II families. The most frequently encountered mutation (11/15 families or 11/18 mutated alleles) was del2299G in exon 13, resulting in a frameshift and premature stop codon. Other mutations include insertions and point mutations, of which two are previously unreported. Five different polymorphisms were also detected. Our results indicate that mutations in this gene are responsible for disease in a large proportion of British Usher type II patients. Moreover, if screening for mutations in USH2A is considered, it is sensible to screen for the del2299G mutation first.

Chromosome Deletion↗
PubMed2001

[Macular pigment and age-related macular degeneration].

The present concepts of the pathogenesis of AMD include cumulative light damage by oxidative processes in the macular photoreceptors as environmental co-factor for the development of AMD. The direct causative connection of this hypothesis has still to be established but wide circumstantial evidence from epidemiological and basic scientific investigations are strongly supportive. Macular pigment consisting of lutein and zeaxanthin through there ability to filter light and by direct antioxidative properties, has been proposed as the most effective protective factor in the central retina ("natural sun glasses") and could be important to reduce light induced oxidative retinal damage. The observation, that with age and especially in eyes with AMD lower concentrations of macular pigment could be found, can be interpreted that low macular pigment concentrations may be associated with higher risk for AMD. Through dietary intake and eventually with supplementation the concentration of macular pigment can be increased, and analysis of the correlation between macular pigment and AMD may be important to characterise a possible influenceable AMD risk factor.

Aged↗
PubMed2001

A human homolog of yeast pre-mRNA splicing gene, PRP31, underlies autosomal dominant retinitis pigmentosa on chromosome 19q13.4 (RP11).

We report mutations in a gene (PRPF31) homologous to Saccharomyces cerevisiae pre-mRNA splicing gene PRP31 in families with autosomal dominant retinitis pigmentosa linked to chromosome 19q13.4 (RP11; MIM 600138). A positional cloning approach supported by bioinformatics identified PRPF31 comprising 14 exons and encoding a protein of 499 amino acids. The level of sequence identity to the yeast PRP31 gene indicates that PRPF31 is also likely to be involved in pre-mRNA splicing. Mutations that include missense substitutions, deletions, and insertions have been identified in four RP11-linked families and three sporadic RP cases. The identification of mutations in a pre-mRNA splicing gene implicates defects in the splicing process as a novel mechanism of photoreceptor degeneration.

Alleles↗