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Biomedical subjects

A C Bird

Publications and source records attributed to A C Bird.

At least 55 records · Page 3Linked to original sources
PubMed2001

Retinal pigment epithelium translocation and central visual function in age related macular degeneration: preliminary results.

PURPOSE: To test the feasibility of a new surgical technique, and to assess visual function over the translocated retinal pigment epithelium (RPE) cells in patients operated upon for subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). MATERIALS AND METHODS: Six patients presenting previously untreated exudative AMD underwent surgical excision of the subfoveal CNV with RPE translocation and were followed from 1 to 10.5 months. The surgery consisted of a standard three port pars plana vitrectomy (TPPPV), excision of the CNV and RPE translocation. Pre and post-operative ocular examination included best-corrected visual acuity measurement, fundus color stereo photography and fundus fluorescein angiography. Optical coherence tomography (OCT) and confocal laser scanning ophthalmoscopy (cLSO) were performed post-operatively. A cross fixation target and a single-point flashing light were projected on different areas of the posterior pole using a cLSO. Photopic 10-2 perimetry, photopic fine matrix mapping, cLSO microperimetry were also performed pre and post-operatively in four patients. OCT cross-sectional scans and cLSO RPE autofluorescence were recorded to detect the presence of viable translocated RPE. Visual acuity, fixation, photopic 10-2 perimetry, photopic fine matrix mapping and cLSO microperimetry were tested for the presence of central visual function. RESULTS: RPE could be effectively translocated at the time of CNV removal from the edge of the RPE defect to a subfoveal location. OCT showed the translocated RPE as an area of increased optical reflectivity with optical shadowing external to it. cLSO showed autofluorescence of the translocated RPE. The cross fixation target was seen when projected on the translocated RPE. During eccentric fixation, the patients could see a flashing point-target projected on the translocated RPE. Photopic 10-2 perimetry, photopic fine matrix mapping and cLSO microperimetry showed presence of central visual function. CONCLUSIONS: The authors propose that translocation of RPE at the time of CNV removal, from the edge of the RPE defect to a subfoveal location, may have a role in the surgical management of AMD.

Aged↗
PubMed2001

Influence of laser photocoagulation on choroidal capillary cytoarchitecture.

AIM: To identify if laser photocoagulation induces morphological changes specifically related to the choroidal capillary endothelial processes that protrude into Bruch's membrane. METHODS: Two human eyes and one adult macaque monkey eye received retinal laser photocoagulation that was just suprathreshold, before enucleation or exenteration. They were examined by electron microscopy to determine the length of the endothelial processes emanating from the choroidal capillaries in the region around the laser burn. One human and two monkey untreated eyes were used for comparison. RESULTS: In human eyes, there was no increase in the number of processes 15 hours after laser treatment but at 5 days the processes were more numerous and longer within 400-500 microm of the burn than in the untreated half of the same eye. The processes were longer 9 days after photocoagulation in the monkey, when compared with untreated monkeys, and some breached the elastic lamina, a phenomenon not seen in the untreated eyes. Qualitative differences were also noted in the endothelial cell processes following photocoagulation. Neovascularisation was not observed. CONCLUSIONS: Protrusion of choroidal endothelial cell processes into Bruch's membrane is a normal anatomical feature but the number, length, and morphology of the processes change following mild photocoagulation. It is plausible that these processes may play a part in the clearance of debris from Bruch's membrane, and represent an early stage of angiogenesis. If the latter is true prophylactic laser photocoagulation at just suprathreshold levels may carry a risk of inducing choroidal neovascularisation.

Animals↗
PubMed2001

Outcome of cataract surgery in patients with retinitis pigmentosa.

AIM: To determine the visual benefit of cataract extraction in patients with retinitis pigmentosa and to identify risk factors for poor outcome. METHODS: A retrospective analysis was undertaken of a continuous series of 142 eyes of 89 patients with retinitis pigmentosa undergoing cataract surgery between 1985 and 1997. RESULTS: Mean age at surgery was 47.5 years (range 24-81 years). In 100 eyes there was posterior subcapsular lens opacity alone, 37 eyes also had moderate nuclear sclerosis, and five had only nuclear sclerosis. All patients had central visual fields of <10 degrees. Overall, mean visual acuity improved from 1.05 (SD 0.38) preoperatively to 0.63 (SD 0.49) postoperatively on the logMAR scale. Significant postoperative capsular opacification occurred in 88/139 eyes (63%) and 45.1% required capsulotomy. Anterior capsulotomy was undertaken in 5/52 (9.6%) eyes undergoing phacoemulsification. Postoperative macular oedema was noted in 20 (14%) eyes. Visual acuity improved in 109 eyes (77%), was unchanged in 29 eyes (20.5%), and worsened after surgery in four eyes (2.5%). 86/89 patients reported major improvement of visual function. CONCLUSIONS: Cataract surgery for relatively minor lens opacities is beneficial in patients with retinitis pigmentosa, and most report subjective improvement of visual symptoms. The incidence of capsular opacification is high and anterior capsular contraction may occur. The number of eyes with poor vision due to macular oedema was unexpectedly low.

Adult↗
PubMed2001

Molecular genetic heterogeneity in autosomal dominant drusen.

OBJECTIVE: Autosomal dominant drusen is of particular interest because of its phenotypic similarity to age related macular degeneration. Currently, mutation R345W of EFEMP1 and, in a single pedigree, linkage to chromosome 6q14 have been causally related to the disease. We proposed to investigate and quantify the roles of EFEMP1 and the 6q14 locus in dominant drusen patients from the UK and USA. DESIGN: Molecular genetic analysis. PARTICIPANTS: Ten unrelated families and 17 young drusen patients. MAIN OUTCOME MEASURES: Exons 1 and 2 of EFEMP1 were characterised by 5' rapid amplification of cDNA ends and direct sequencing. Exons 1-12 of EFEMP1 were then investigated for mutation by direct sequencing. A HpaII restriction digest test was constructed to detect the EFEMP1 R345W mutation. Marker loci spanning the two dominant drusen linked loci were used to generate haplotype data. RESULTS: Only seven of the 10 families (70%) and one of the 17 sporadic patients (6%) had the R345W mutation. The HpaII restriction digest test was found to be a reliable and quick method for detecting this. No other exonic or splice site mutation was identified. Of the three families without EFEMP1 mutation, two were linked to the 2p16 region. CONCLUSIONS: EFEMP1 R345W accounts for only a proportion of the dominant drusen phenotype. Importantly, other families linked to chromosome 2p16 raise the possibility of EFEMP1 promoter sequence mutation or a second dominant drusen gene at this locus. Preliminary haplotype data suggest that the disease gene at the 6q14 locus is responsible for only a minority of dominant drusen cases.

Adult↗
PubMed2001

Autosomal dominant cone and cone-rod dystrophy with mutations in the guanylate cyclase activator 1A gene-encoding guanylate cyclase activating protein-1.

OBJECTIVE: To describe the phenotype in 3 families with dominantly inherited cone and cone-rod dystrophy with mutations in guanylate cyclase activator 1A (GUCA1A), the gene-encoding guanylate cyclase activator protein-1 (GCAP-1). METHODS: Phenotypic characterization with psychophysical and electrophysiological evaluation and confocal laser scanning ophthalmoscopy was performed in 2 families with a Tyr99Cys mutation and 1 family with a Pro50Leu mutation. Haplotype analysis was performed in the families with Tyr99Cys mutation. RESULTS: The families with a Y99C mutation were shown to be ancestrally related. Decreased visual acuity and loss of color vision occurred after the age of 20 years, followed by progressive atrophy of the central 5 degrees to 10 degrees. Electrophysiological testing revealed generalized loss of cone function, with preservation of rod function. Abnormal rod and cone sensitivities were confined to the central 5 degrees to 10 degrees. Confocal laser scanning ophthalmoscopy imaging showed abnormalities of autofluorescence in early disease. Subjects with a Pro50Leu mutation demonstrated marked variability in expressivity from minimal abnormalities of macular function to cone-rod dystrophy. CONCLUSIONS: The phenotype associated with the Y99C mutation in GUCA1A is distinctive, with little variation in expression. By contrast, that associated with the P50L mutation demonstrates variable expressivity. CLINICAL RELEVANCE: Phenotype-genotype correlation in these 2 mutations demonstrates 2 different phenotypes.

Adolescent↗
PubMed2000

Novel mutations of the RPGR gene in RP3 families.

X-linked retinitis pigmentosa is a severe retinal degeneration characterized by night blindness and visual field constriction, leading to complete blindness within the third decade of life. Mutations in the RPGR gene (retinitis pigmentosa GTPase regulator), located on Xp21.1 in the RP3 region, have been associated with an RP phenotype. Further to our previous mutation screening of RPGR in families segregating with the RP3 locus, we have expanded this study to include other 8 RP3 pedigrees. Here we report the results of this expanded study and the identification of five mutations in RPGR, four of which are novel (IVS6+5 G>A, 950-951delAA, 963 T>C, EX8del) and one of which occurs in the donor splice site of intron 1 (IVS1+1 G>A). These findings bring the proportion of "RP3 genotypes" with a mutation in this gene to 27% (10/37). Hum Mutat 15:386, 2000.

Belgium↗
PubMed2000

Novel frameshift mutations in the RP2 gene and polymorphic variants.

Mutations in the RP2 gene located on Xp11.23 are associated with X-linked retinitis pigmentosa (XLRP), a severe form of progressive retinal degeneration which leads to complete loss of vision in affected males. To date, 14 different mutations in the RP2 gene have been reported to cause XLRP, the majority of which lead to a coding frameshift within the gene and predicted truncation of the protein product. We here report two novel frameshift mutations in RP2 identified in XLRP families by PCR-SSCP and direct sequencing, namely 723delT and 796-799del. Four single nucleotide polymorphisms (SNPs) within the coding region of RP2 are also described (105A>T, 597T>C, 844C>T, 1012G>T), the first polymorphisms to be reported within this gene of unknown function, two of which alter the amino acid sequence. The current study extends the XLRP mutation profile of RP2 and highlights non-pathogenic coding sequence variations which may facilitate both functional studies of the gene and analysis of intragenic allelic contribution to the phenotype.

Alternative Splicing↗
PubMed2000

Autosomal dominant cone-rod retinal dystrophy (CORD6) from heterozygous mutation of GUCY2D, which encodes retinal guanylate cyclase.

OBJECTIVE: To describe the clinical features of autosomal dominant cone-rod retinal dystrophy (CRD) in a British family mapping to chromosome 17p12-p13 (CORD6), with a heterozygous mutation (Glu837Asp/ Arg838Ser) of GUCY2D. DESIGN: A prospective, clinical family survey. PATIENTS: Ten affected members of a family with autosomal dominant CRD. METHODS: Full clinical examinations were undertaken. Selected affected family members underwent electrophysiologic evaluation, scotopic static perimetry, dark adaptometry, and color vision assessment. MAIN OUTCOME MEASURES: Clinical appearance and electroretinographic responses. RESULTS: Typical clinical and electroretinographic features of childhood-onset CRD were recorded. In addition, moderate myopia and pendular nystagmus were seen in affected individuals. Color vision assessment in the youngest affected individual showed no color discrimination on a tritan axis, but retention of significant red-green discrimination. Electronegative electroretinogram responses were seen on electrophysiology in the only young family member examined. CONCLUSIONS: The phenotype associated with GUCY2D CRD is clinically distinct from that associated with other dominant CRD loci. Unusual electroretinographic responses may indicate that this mutation of GUCY2D is associated with early defects in photoreceptor synaptic transmission to second-order neurons.

Adolescent↗
PubMed2000

Mutational hot spot within a new RPGR exon in X-linked retinitis pigmentosa.

The gene RPGR was previously identified in the RP3 region of Xp21.1 and shown to be mutated in 10-20% of patients with the progressive retinal degeneration X-linked retinitis pigmentosa (XLRP). The mutations predominantly affected a domain homologous to RCC1, a guanine nucleotide exchange factor for the small GTPase Ran, although they were present in fewer than the 70-75% of XLRP patients predicted from linkage studies. Mutations in the RP2 locus at Xp11.3 were found in a further 10-20% of XLRP patients, as predicted from linkage studies. Because the mutations in the remainder of the XLRP patients may reside in undiscovered exons of RPGR, we sequenced a 172-kb region containing the entire gene. Analysis of the sequence disclosed a new 3' terminal exon that was mutated in 60% of XLRP patients examined. This exon encodes 567 amino acids, with a repetitive domain rich in glutamic acid residues. The sequence is conserved in the mouse, bovine and Fugu rubripes genes. It is preferentially expressed in mouse and bovine retina, further supporting its importance for retinal function. Our results suggest that mutations in RPGR are the only cause of RP3 type XLRP and account for the disease in over 70% of XLRP patients and an estimated 11% of all retinitis pigmentosa patients.

Alternative Splicing↗
PubMed2000

NRL S50T mutation and the importance of 'founder effects' in inherited retinal dystrophies.

The aim of this work was to identify NRL mutations in a panel of 200 autosomal dominant retinitis pigmentosa (adRP) families. All samples were subjected to heteroduplex analysis of the three exons of the NRL gene, and HphI restriction digest analysis of exon 2 (to identify the S50T mutation). Families found to have the S50T mutation, and six additional larger pedigrees (which had previously been excluded from the other nine adRP loci) underwent linkage analysis using polymorphic markers located in the region of 14q11. HphI restriction analysis followed by direct sequencing of the amplified NRL exon 2 product demonstrated the presence of the NRL S50T sequence change in three adRP families. Comparison of marker haplotypes in affected individuals from these families with those of affected members of the original 14q11 linked family revealed a common disease haplotype for markers within the adRP locus. Recombination events observed in these families define an adRP critical interval of 14.9 cM between D13S72 and D14S1041. Linkage analysis enabled all six of the larger adRP pedigrees to be excluded from the 14q11 locus. The NRL S50T mutation represents another example of a 'founder effect' in a dominantly inherited retinal dystrophy. Identification of such 'founder effects' may greatly simplify diagnostic genetic screening and lead to better prognostic counselling. The exclusion of several adRP families from all ten adRP loci indicates that at least one further adRP locus remains to be found.

Basic-Leucine Zipper Transcription Factors↗
PubMed2000

[Antiretinal antibodies associated with cystoid macular edema].

AIM: Recently, anti-Enolase and anti-carbonic anhydrase antibodies have been observed in over 60% of patients with retinitis pigmentosa (RP) and cystoid macular oedema (CME). We investigated the presence of these antibodies in a series of patients with CME due to different pathologies. METHODS: In 10 patients with CME serum antibodies against Carbonic anhydrase (CA) II (30 kD) and Enolase (46 kD) were sought using Western Blots, Dot Blots as well as ELISA. RESULTS: Western and dot blotting showed anti-CA II antibodies in all and anti-Enolase antibodies in six of the 10 patients. The average titer measured with ELISA was 0.9 +/- 0.08 OD Units (0.35-1.4) with a dilution of 1:400. CONCLUSION: The presence of anti-retinal antibodies in the serum of all patients confirms the high prevalence of these antibodies in patients with CME. This may suggest that a dysfunction of CA and enolase activity in the retinal pigment epithelium may lie at the root of oedema formation, whereas other mechanisms may be responsible in the absence of these antibodies.

Adult↗
PubMed2000

[Retinal vasculopathy associated with Berger's IgA nephropathy].

AIM: Ophthalmological complications associated with Berger's IgA nephropathy comprise scleritis, episcleritis, keratoconjunctivitis as well as anterior uveitis. We present a new association of IgA nephropathy with a retinal vasculopathy. METHODS: Presentation of two clinical cases. RESULTS: Two patients presented with hematuria and epistaxis associated with a retinal vasculopathy characterised by teleangiectasies, capillary occlusion with retinal hemorrhages, neovascularisations and macular edema with decreased visual acuity. Fluorescein angiography showed zones of non-perfusion as well as vasculitic changes. A general medical exam revealed a normal arterial pressure but a slightly elevated creatinine. Immunological investigations for the presence of antibodies showed no positive results. Renal biopsy demonstrated mesangial proliferations with diffuse deposits of IgA. Over the course of a 2 year follow-up some of the retinal changes regressed under treatment with cortisone and visual acuity returned to normal. The teleangiectasies showed no progression. CONCLUSION: Berger's IgA nephropathy can be associated with a retinal vasculopathy which may be due to local deposition of IgA immune complexes in the retinal vessels.

Adult↗
PubMed2000

Polypoidal choroidal vasculopathy in exudative and haemorrhagic pigment epithelial detachments.

AIMS: To determine the prevalence of polypoidal choroidopathy in consecutive patients presenting with large haemorrhagic and exudative neurosensory retinal and retinal pigment epithelial detachments (PEDs) of over 2 mm in diameter in the absence of drusen. METHODS: 40 patients were identified over a 5 month period of which 29 had haemorrhagic detachments, and 11 had purely exudative detachments. All had indocyanine green (ICG) angiography, and the presence was sought of large blood vessels in the choroid associated with localised dilated terminals that filled slowly and leaked ICG. RESULTS: In 34 cases (85%) there was an appearance consistent with previous descriptions of idiopathic polypoidal choroidal vasculopathy. Of the six without polypoidal lesions the disorder was attributed to choroidal neovascularisation in four, chorioretinitis in one, and a fibrovascular PED in one. Of those with polypoidal lesions 20 (65%) were female, the mean age was 65.4 years (range 44-88), and 25 (74%) were white, seven (20%) black, and two (6%) east Asian. Eight had a history of hypertension. Visual acuity varied from 6/6 to counting fingers in the involved eye (mean 6/24). Bilateral polypoidal choroidal lesions were demonstrated in 16 patients (47%). The predominant location for these lesions was the macular region in 23 patients (68%). Polypoidal vasculopathy was found in 16 patients (47%) who had a previous diagnosis of age related macular disease (AMD). No patients had evidence of intraocular inflammation. CONCLUSIONS: In a largely white patient population a high proportion of patients with haemorrhagic and exudative PEDs has evidence of polypoidal lesions on ICG angiography.

Adult↗
PubMed2000

Quantitative evaluation of fundus autofluorescence imaged "in vivo" in eyes with retinal disease.

AIM: To describe a new method of evaluating the topographic distribution of fundus autofluorescence in eyes with retinal disease. METHODS: Images of fundus autofluorescence were obtained in five patients and 34 normal volunteers using a confocal scanning laser ophthalmoscope (cSLO). To evaluate the topographic distribution of fundus autofluorescence throughout the posterior pole a rectangular box, 10 x 750 pixels, was used as the area of analysis. The box was placed, horizontally, across the macular region. The intensity of fundus autofluorescence of each pixel within the rectangular box was plotted against its degree of eccentricity. Profiles of fundus autofluorescence from patients were compared with those obtained from the age matched control group and with cSLO images. RESULTS: Profiles of fundus autofluorescence appeared to represent the topographic distribution of fundus autofluorescence throughout the posterior pole appreciated in the cSLO images, and allowed rapid identification and quantification of areas of increased or decreased fundus autofluorescence. CONCLUSIONS: Fundus autofluorescence profiles appear to be useful to study the spatial distribution of fundus autofluorescence in eyes with retinal disease.

Adult↗