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Biomedical subjects

A C Bird

Publications and source records attributed to A C Bird.

At least 91 records · Page 5Linked to original sources
PubMed1999

Long-term drusen study.

PURPOSE: To determine the yearly incidence of visual loss in the fellow eyes of patients with unilateral neovascular age-related macular degeneration (ARMD) and to assess the drusen characteristics portending the greatest risk for this outcome. METHODS: A total of 101 patients with unilateral exudative ARMD and drusen only in the fellow eye were entered into the study and prospectively followed up to 9 years. Visual acuity, color fundus photography, fluorescein angiography, and grading of drusen characteristics were obtained for each patient on entry into the study. Patients were followed at annual intervals with color fundus photography. The study endpoint was the development of choroidal neovascularization (CNV) or geographic atrophy (GA) in the fellow eye. RESULTS: Yearly incidence rates for the development of an endpoint lesion were between 5 and 14%. The risk of CNV peaked at 4 years and dissipated thereafter. Longer follow-up was associated with a slightly increased incidence of GA. Greater drusen number was most highly associated with the development of an endpoint lesion. Drusen size and confluence were also significant. CONCLUSIONS: The risk of CNV in patients with ARMD is heralded by an increase in the number, size, and confluence of drusen. This risk eventually declines and is followed by later increased risk of GA.

Aged↗
PubMed1999

Difference between RP2 and RP3 phenotypes in X linked retinitis pigmentosa.

AIM: X linked retinitis pigmentosa (XLRP) has two genetic loci known as "RP2" and "RP3". Clinical features reported to differentiate RP2 from RP3 include a higher prevalence of myopia and primary cone dysfunction in RP2, and late onset night blindness and tapetal reflex in RP3. Members from 14 XLRP families were examined in an attempt to verify these differences. METHODS: 16 affected males and 37 females from 14 XLRP families assigned as either RP2 or RP3 by haplotype analysis and/or by heterogeneity analysis were examined. Members of all 14 families who were willing to participate but unavailable for examination were contacted and detailed interviews carried out. RESULTS: No clear phenotypic differences were found that could be used to reliably differentiate RP2 from RP3 with respect to myopia and onset of night blindness. The tapetal reflex was also found to be present in carriers of both RP2 and RP3. CONCLUSIONS: XLRP is a heterogeneous class of rod degenerative disorders with no clear phenotypic differentiation between the two genetic loci RP2 and RP3. There is a continuum of clinical presentations which can be seen in both RP2 and RP3, but the features within a given family tend to be consistent. However, interfamilial variability is prevalent leading to a wide range of clinical presentations and more than one abnormal allele at each gene locus cannot be excluded.

Adult↗
PubMed1999

Reproducibility of fundus autofluorescence measurements obtained using a confocal scanning laser ophthalmoscope.

AIM: To evaluate the reproducibility of the background fundus autofluorescence measurements obtained using a confocal scanning laser ophthalmoscope. METHODS: 10 normal volunteers and 10 patients with retinal disease were included in the study. One eye per subject was chosen randomly. Five images of the same eye of each individual were obtained, after pupillary dilatation, by two investigators using a confocal scanning laser ophthalmoscope. Background fundus autofluorescence was measured at 7 degrees temporal to the fovea in normal volunteers and between 7 and 15 degrees temporal to the fovea in patients. Within session reproducibility of the measurements obtained by each investigator and interobserver reproducibility were evaluated. RESULTS: For investigator 1 the median values of fundus autofluorescence obtained were 31.9 units for normal volunteers and 27.3 units for patients. The median largest differences in readings in normal volunteers was 5.7 units (range 1.4-13.5 units) and in patients 4.2 units (1.5-15.1 units). For investigator 2 the median values of fundus autofluorescence obtained were 28.9 units for normal volunteers and 27.4 units for patients. The median largest difference in readings in normal volunteers was 3.6 units (2.7-11.7 units), and in patients 4.1 units (1.5-9.3 units). The median interobserver difference in readings in normal volunteers was 3.3 units and for patients 6.6 units. The median greatest interobserver difference in measurements obtained for normal volunteers was 8.8 units (8.4-23.0 units) and for patients 11.1 units (7.1-40.8 units). CONCLUSION: Within session reproducibility of the measurements of background fundus autofluorescence was satisfactory. Although interobserver reproducibility was moderate, the variability of the measurements of fundus autofluorescence between observers appears to be small when compared with variation in fundus autofluorescence with age and disease.

Adolescent↗
PubMed1999

Repeated injections of a ciliary neurotrophic factor analogue leading to long-term photoreceptor survival in hereditary retinal degeneration.

PURPOSE: To determine whether ciliary neurotrophic factor (CNTF) or brain-derived neurotrophic factor (BDNF) treatment leads to long-term photoreceptor survival in hereditary retinal degeneration. METHODS: An autosomal dominant feline model of rod-cone dystrophy was used throughout the study with two normal animals. In the first experiment, intravitreal injections of a human CNTF analogue (Axokine; Regeneron Pharmaceuticals, Tarrytown, NY) were administered to one eye of each animal (n = 10) beginning on postnatal day 10 and were repeated every 4 weeks. Clinical and histopathologic examinations were performed at 5.5, 9.5, and 13.5 weeks. In the second experiment, animals (n = 17) were randomly assigned to receive intravitreal injections of either Axokine (at half the initial dose), human BDNF, or the vehicle for Axokine to one eye at 5.5 weeks. The same therapy was repeated every 4 weeks in each group. Clinical and histopathologic examinations were performed at 9.5, 13.5, and 17.5 weeks. Photoreceptor survival was assessed by cell counting. Apoptotic cells were identified by morphology and a modified TdT-dUTP terminal nick-end labeling (TUNEL) technique. In the third experiment, two normal animals were treated with Axokine as in the first experiment. Glial fibrillary acidic protein ((GFAP) immunohistochemistry was performed to assess glial cell reaction. RESULTS: In the first two experiments, Axokine significantly prolonged photoreceptor survival (P < 0.01) and reduced the presence of apoptotic cells (P < 0.05) and TUNEL-positive cells (P < 0.05). In the second experiment, results in the the BDNF- and sham-injected eyes were not significantly different from those in the untreated eyes. Minimal posterior subcapsular cataract and mild retinal folds were found in all Axokine-treated eyes in both dystrophic and normal animals. These complications were milder in the second experiment when injections were started later and at a reduced dose. GFAP immunolabeling was also increased in all Axokine-treated eyes. CONCLUSIONS: Axokine, but not BDNF, delays photoreceptor loss in this hereditary retinal degeneration. Repeated injections maintain the protective effect.

Animals↗
PubMed1999

Genetic analysis of the guanylate cyclase activator 1B (GUCA1B) gene in patients with autosomal dominant retinal dystrophies.

The guanylate cyclase activator proteins (GCAP1 and GCAP2) are calcium binding proteins which by activating Ret-GC1 play a key role in the recovery phase of phototransduction. Recently a mutation in the GUCA1A gene (coding for GCAP1) mapping to the 6p21.1 region was described as causing cone dystrophy in a British family. In addition mutations in Ret-GC1 have been shown to cause Leber congenital amaurosis and cone-rod dystrophy. To determine whether GCAP2 is involved in dominant retinal degenerative diseases, the GCAP2 gene was screened in 400 unrelated subjects with autosomal dominant central and peripheral retinal dystrophies. A number of changes involving the intronic as well as the coding sequence were observed. In exon 1 a T to C nucleotide change was observed leaving the tyrosine residue 57 unchanged. In exon 3 a 1 bp intronic insertion, a single nucleotide substitution G to A in the intron 3' of this exon, and a GAG to GAT change at codon 155 were observed. This latter change results in a conservative change of glutamic acid to aspartic acid. In exon 4 a 7 bp intronic insertion, a single nucleotide A to G substitution in the intron 5' of this exon, and a single base pair change C to G in the intron 3' of exon 4 were seen. None of these changes would be expected to affect correct splicing of this gene. All these changes were observed in controls. The results of this study do not show any evidence so far that GCAP2 is involved in the pathogenesis of autosomal dominant retinal degeneration in this group of patients. All the changes detected were found to be sequence variations or polymorphisms and not disease causing.

Calcium-Binding Proteins↗
PubMed1999

Intrafamilial variation of phenotype in Stargardt macular dystrophy-Fundus flavimaculatus.

PURPOSE: To evaluate the intrafamilial phenotypic variation in Stargardt macular dystrophy-Fundus flavimaculatus (SMD-FFM). METHODS: Thirty-one siblings from 15 families with SMD-FFM were examined. Age of onset, visual acuity, and clinical features on fundus examination and fundus autofluorescence images, including presence or absence of central and peripheral atrophy and distribution of flecks, were recorded. In addition, electrophysiological studies were undertaken. RESULTS: Large differences between siblings in age of onset (median, 12 years; range, 5-23 years) were observed in six of the 15 families studied, whereas in 9 families differences in age of onset between siblings were small (median, 1 year; range, 0-3 years). Visual acuity varied two or more lines among siblings in nine families. In 10 families (67%) siblings were found to have different clinical appearance on fundus examination and fundus autofluorescence images, whereas in 5 families (33%), affected siblings had similar clinical features. Electrodiagnostic tests were performed on affected members of 12 families and disclosed similar qualitative findings among siblings. In nine families there was loss of central function only; in two, global loss of cone function; and in one, global loss of cone and rod function. CONCLUSIONS: In this series, although differences in age of onset, visual acuity, and fundus appearance were observed between siblings, electrophysiological studies demonstrated intrafamilial homogeneity in retinal function. The findings are difficult to reconcile with expression studies showing ABCR transcripts in rod photoreceptors but not in cones.

Adolescent↗
PubMed1999

The relationships of age changes in retinal pigment epithelium and Bruch's membrane.

PURPOSE: To study the correlations between age, Bruch's membrane (BM) thickness, retinal pigment epithelial (RPE) autofluorescence, and RPE residual body content. METHODS: Eight-millimeter-diameter macular discs from 88 unpaired human eye bank eyes were obtained within 72 hours of death, fixed in 10% neutral buffered formalin, and hemisected horizontally. One portion of the macular disc was embedded in paraffin and stained with periodic acid-Schiff for the measurement of BM thickness. RPE autofluorescence measurements were performed on unstained, deparaffinized sections. A second portion of the macular disc was prepared for electron microscopy to evaluate RPE residual body content. Linear and polynomial regression techniques were used to investigate the correlations between age, BM thickness, RPE autofluorescence, and RPE residual body content. RESULTS: Bruch's membrane thickness increased with age according to the linear model. RPE autofluorescence and RPE residual body content also increased with age, but the correlations were best approximated by a quadratic model. The correlations between RPE autofluorescence and residual body content and between BM thickness and RPE autofluorescence were best approximated by a linear regression model. There was considerable variation in these correlations between specimens and within the same age group. CONCLUSIONS: Although the changes in RPE and Bruch's membrane increased with age and there was a direct correlation between changes in the two tissues, there was considerable variation within each age group and between specimens. This probably reflects the multifactorial nature of the process.

Adolescent↗
PubMed1998

[Studies of the distribution of lipofuscin in the retinal pigment epithelium using high-resolution TV laser scanning ophthalmoscopy].

BACKGROUND: The fundus autofluorescence imaging technique has been modified allowing improved image resolution (768 x 572 pixel). We present results of fundus autofluorescence studies using this technique. MATERIALS AND METHODS: Fundus autofluorescence was studied in 286 eyes of 143 patients with retinitis pigmentosa, macular dystrophies and age-related macular degeneration using a confocal laser scanning ophthalmoscope prototype (Zeiss, Oberkochen; excitation wavelength: 488 nm, cut-off filter at 521 nm). RESULTS: The spatial distribution of autofluorescence was different in all diseased eyes investigated compared to the normal pattern of fundus autofluorescence. Each disorder showed a specific fundus autofluorescence appearance. CONCLUSIONS: The advanced technique of imaging fundus autofluorescence allows detailed studies of the lipofuscin distribution. In vivo analysis of the dynamics of accumulation and degradation of lipofuscin in eyes with tapeto-retinal dystrophies and age-related macular disease may contribute to elucidation of the pathogenesis of these disorders.

Adolescent↗
PubMed1998

Prophylactic laser treatment to fellow eyes of unilateral retinal pigment epithelial tears.

PURPOSE: To evaluate prophylactic laser treatment of the macula in reducing the risk of visual loss in the fellow eye of patients with a retinal pigment epithelial tear caused by age-related macular degeneration in the first eye. METHODS: In a prospective study, 12 patients with a retinal pigment epithelial tear in one eye caused by age-related macular degeneration and drusen in the fellow eye received prophylactic laser treatment of the retina in their fellow eyes and were followed up for 2 years or more after prophylactic treatment. RESULTS: In 12 fellow eyes that received prophylactic laser treatment, a reduction in best-corrected visual acuity to 20/80 or worse occurred in one (8%) of 12 eyes in the first year and two (18%) of the remaining 11 eyes in the second year after treatment. The cumulative risk of visual loss in the treated fellow eye was 25% in 2 years. CONCLUSIONS: In historical control subjects in a natural history study of patients with retinal pigment epithelial tear in one eye, central visual loss occurred in 16 (37%) of 43 eyes in the first year and in seven (30%) of 23 eyes in the second year for a cumulative loss of 59% in the first 2 years. Compared with these historical control subjects, our findings suggest that visual loss in the fellow eyes of patients with a retinal pigment epithelial tear in the first eye is reduced by prophylactic low intensity laser photocoagulation of the macula.

Aged↗
PubMed1998

Disturbance of sleep in blindness.

PURPOSE: To determine the prevalence and severity of sleep disturbance in blind subjects and its relation to the form and duration of visual loss. METHODS: Of 403 blind subjects (visual acuity of less than 20/200 or a visual field of less than 5 degrees) recruited for the study, 15 were excluded because of affective disorder as identified by Montgomery Asberg Depression Scale. The remaining 388 subjects and a comparison group of 44 normally sighted individuals underwent an interview, and the Pittsburgh Sleep Quality Index questionnaire was administered. Sleep disturbance was classified as mild, moderate, or severe. RESULTS: Disturbance of sleep was recorded in 189 (48.7%) of the blind subjects. The prevalence was higher and the sleep disturbance was more severe in those with no perception of light than in those with light perception or better visual acuity. In the comparison group, four (9.1%) had mild sleep disturbance only. The differences between blind subjects and normally sighted individuals were highly significant (P < .001). The most common sleep-related problem among the blind subjects was interrupted sleep, followed by increased sleep latency, short sleep duration, and daytime naps. Among the blind subjects, no correlation was found between the extent of sleep disturbance and the duration and pattern of visual loss. CONCLUSIONS: Blind subjects who retain light perception, as well as those with total loss of vision, have a high frequency of sleep disturbance, although disorder is more common and more severe in subjects with no light perception. Management of the sleep disturbance may improve the quality of life in the visually handicapped.

Adult↗
PubMed1998

[Fundus autofluorescence in patients with hereditary macular dystrophies, malattia leventinese, familial dominant and aged-related drusen].

PURPOSE: The lack of histopathological material has placed limitation on our knowledge on the composition of focal deposits in eyes with macular dystrophies, malattia leventinese, dominant drusen and age related macular degeneration. This study was designed to study the composition of focal deposits in these eyes by documenting fundus autofluorescence in vivo. METHODS: Fundus autofluorescence was documented in 343 eyes of 199 subjects with macular dystrophies, malattia leventinese, dominant drusen and age-related macular degeneration using a laser scanning ophthalmoscope (Zeiss, Oberkochen; excitation wavelength: 488 nm, barrier filter at 521 nm). RESULTS: Autofluorescence of focal deposits was increased in eyes with macular dystrophies. In eyes with malattia leventinese and dominant drusen autofluorescence intensity of focal deposits showed a wide spectrum. In contrast, autofluorescence of age-related drusen was within normal limits. Background autofluorescence intensity was increased in eyes with macular dystrophies and within normal limits in eyes with malattia leventinese, dominant drusen and age-related drusen. CONCLUSION: The technique of in-vivo recording of fundus autofluorescence allows the differential diagnosis between macular dystrophies/malattia leventinese, dominant drusen/age related drusen when otherwise not possible.

Adult↗
PubMed1998

A mutation in guanylate cyclase activator 1A (GUCA1A) in an autosomal dominant cone dystrophy pedigree mapping to a new locus on chromosome 6p21.1.

We report a mutation (Y99C) in guanylate cyclase activator 1A (GUCA1A), the gene for guanylate cyclase activating protein (GCAP1), in a family with autosomal dominant cone dystrophy. Linkage analysis excluded all the known cone and cone-rod dystrophy loci, except the chromosome 6p21.1 region. This is known to contain the RDS gene, which is associated with dominant cone-rod dystrophy. Screening of the RDS gene by heteroduplex analysis and direct sequencing failed to demonstrate sequence changes in the coding region of this gene. The gene for GCAP1, a calcium binding protein which is highly expressed in photoreceptor outer segments, is also located in 6p21.1. It was screened for mutations, and all affected individuals showed a single base pair missense mutation (A-->G) at codon 99 in exon 2 of this gene generating a tyrosine-to-cysteine change in the GCAP1 protein. This change was absent from 206 unrelated normal controls. We propose that this change would at least disrupt the EF3handof GCAP1 thereby preventing calcium binding and consequently interfere with activation. The resulting effect on cGMP production would predictably modify the number of open cGMP gated cation channels, and could explain the ultimate demise of cone photoreceptor cells.

Amino Acid Sequence↗
PubMed1998

Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy.

The dominant cone-rod dystrophy gene CORD6 has previously been mapped to within an 8 cM interval on chromosome 17p12-p13. The retinal-specific guanylate cyclase gene (RETGC-1), which maps to within this genetic interval and previously was implicated in Leber's congenital amaurosis, was screened for mutations within this family and in a panel of small families and individuals with various cone and cone- rod dystrophy phenotypes. A missense mutation (E837D) was identified in affected members of the CORD6 family, as well as a second missense mutation (R838C) in three other families with dominant cone-rod dystrophy. RETGC-1 is only the fourth gene to be implicated in cone-rod dystrophy and this is the first report of dominant mutations in this gene.

Adolescent↗