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ABSTRACT: The aim of the present study was to test the hypothesis that adjunctive local anaesthesia decreases postoperative pain, vomiting or length of stay in children having strabismus repair
A prospective, randomized, triple-armed clinical trial involving a treatment comparison between topical amethocaine, sub-conjunctival bupivacaine and, as a placebo, topical normal saline was performed. All treatments were given at the end of surgery before emergence from the anaesthetic.
Overall, there was no statistically significant difference between outcome measures in the three trial groups. Using post hoc analysis there was a statistically significant difference between the groups receiving amethocaine and bupivacaine compared with the saline group in terms of the pain score at 120 min postoperatively. This difference has little clinical significance.
Neither topical amethocaine nor subconjunctival bupivacaine makes a clinically significant difference to postoperative pain, emesis or length of stay. Moderate dose paracetamol per rectum alone appears to be effective analgesia for strabismus surgery, although it probably masked any small adjunctive effect of the topical anaesthesia used in the present trial.
Australian and New Zealand Journal of Ophthalmology 12/1998; 26(4):289-97.
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The American Journal of Human Genetics 11/1998; 63(4):1220-4. · 10.60 Impact Factor
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W L Alward,
J H Fingert,
M A Coote,
A T Johnson,
S F Lerner,
D Junqua,
F J Durcan,
P J McCartney, D A Mackey,
V C Sheffield,
E M Stone
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ABSTRACT: A substantial proportion of cases of glaucoma have a genetic basis. Mutations causing glaucoma have been identified in the chromosome 1 open-angle glaucoma gene (GLC1A), which encodes a 57-kd protein known as myocilin. The normal role of this protein and the mechanism by which mutations cause glaucoma are not known.
We screened 716 patients with primary open-angle glaucoma and 596 control subjects for sequence changes in the GLC1A gene.
We identified 16 sequence variations that met the criteria for a probable disease-causing mutation because they altered the predicted amino acid sequence and they were found in one or more patients with glaucoma, in less than 1 percent of the control subjects. These 16 mutations were found in 33 patients (4.6 percent). Six of the mutations were found in more than 1 subject (total, 99). Clinical features associated with these six mutations included an age at diagnosis ranging from 8 to 77 years and maximal recorded intraocular pressures ranging from 12 to 77 mm Hg.
A variety of mutations in the GLC1A gene are associated with glaucoma. The spectrum of disease can range from juvenile glaucoma to typical late-onset primary open-angle glaucoma.
New England Journal of Medicine 04/1998; 338(15):1022-7. · 53.30 Impact Factor
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The American Journal of Human Genetics 02/1998; 62(1):196-202. · 10.60 Impact Factor
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E M Stone,
J H Fingert,
W L Alward,
T D Nguyen,
J R Polansky,
S L Sunden,
D Nishimura,
A F Clark,
A Nystuen,
B E Nichols, D A Mackey,
R Ritch,
J W Kalenak,
E R Craven,
V C Sheffield
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ABSTRACT: Glaucoma is a major cause of blindness and is characterized by progressive degeneration of the optic nerve and is usually associated with elevated intraocular pressure. Analyses of sequence tagged site (STS) content and haplotype sharing between families affected with chromosome 1q-linked open angle glaucoma (GLC1A) were used to prioritize candidate genes for mutation screening. A gene encoding a trabecular meshwork protein (TIGR) mapped to the narrowest disease interval by STS content and radiation hybrid mapping. Thirteen glaucoma patients were found to have one of three mutations in this gene (3.9 percent of the population studied). One of these mutations was also found in a control individual (0.2 percent). Identification of these mutations will aid in early diagnosis, which is essential for optimal application of existing therapies.
Science 02/1997; 275(5300):668-70. · 31.20 Impact Factor
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ABSTRACT: The 'GIST' score was developed to facilitate linkage analysis of adult-onset primary open angle glaucoma (POAG) pedigrees in the Glaucoma Inheritance Study of Tasmania (GIST). Previous genetic linkage studies on juvenile open angle glaucoma pedigrees have relied upon an analysis of definitely affected individuals using the 'single best diagnosis' convention. Studies of adult-onset POAG have been complicated by limited numbers of unequivocally affected members identified even in very large pedigrees due to the later onset of the disease. Many members of the pedigree may have equivocal clinical features or are too young to show signs of the disease. The 'GIST score' is a numeric value between zero and one where zero is clinical certainty of absence of the disease and one is the definitive diagnosis of POAG. The score is developed by assigning relative weighting to key clinical features which results in a 'pedigee probability' of the diagnosis being present or absent in a member of a pedigree. Ranking of borderline and unaffected glaucoma subjects allows the laboratory more flexibility in the use of the members of the pedigree for linkage analysis. The score is not intended to have clinical usefulness in management of glaucoma.
Ophthalmic Genetics 01/1997; 17(4):199-208. · 0.93 Impact Factor
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J Sack,
D L Healey,
A P de Graaf,
R M Wilkinson,
C H Wilkinson,
J M Barbour,
M A Coote,
P J McCartney,
J L Rait,
R L Cooper,
M A Ring, D A Mackey
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ABSTRACT: The Glaucoma Inheritance Study in Tasmania (GIST) is a population survey of Australia's island state, Tasmania (population 450,000). Its aim is to find families with autosomal dominant, adult-onset, primary open angle glaucoma (POAG) suitable for genetic linkage analysis. POAG is relatively common, affecting around 3% of the Australian population. By finding the large families with POAG and identifying all the descendants in a captive population, it is possible that there may be overlap of different glaucoma pedigrees. Three of the first thirteen families in the study were composed of overlapping pedigrees. In one GIST family, GTas3, there has been intermarriage with other pedigrees with glaucoma on five occasions. The possibility of multiple genotypes was also reinforced by the inability to determine a single glaucoma phenotype in this family. When finding large families of POAG for linkage analysis, researchers must be aware of the risk of affected individuals inheriting their gene from the alternate parent. Thus, the alternate parents or their families must be examined, especially if the phenotype is atypical for the rest of the family.
Ophthalmic Genetics 01/1997; 17(4):209-14. · 0.93 Impact Factor
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ABSTRACT: The results of an empirical nucleotide-sequencing approach indicate that the evolution of the human mitochondrial noncoding D-loop is both more rapid and more complex than is revealed by standard phylogenetic approaches. The nucleotide sequence of the D-loop region of the mitochondrial genome was determined for 45 members of a large matrilineal Leber hereditary optic neuropathy pedigree. Two germ-line mutations have arisen in members of one branch of the family, thereby leading to triplasmic descendants with three mitochondrial genotypes. Segregation toward the homoplasmic state can occur within a single generation in some of these descendants, a result that suggests rapid fixation of mitochondrial mutations as a result of developmental bottlenecking. However, slow segregation was observed in other offspring, and therefore no single or simple pattern of segregation can be generalized from the available data. Evidence for rare mtDNA recombination within the D-loop was obtained for one family member. In addition to these germ-line mutations, a somatic mutation was found in the D-loop of one family member. When this genealogical approach was applied to the nucleotide sequences of mitochondrial coding regions, the results again indicated a very rapid rate of evolution.
The American Journal of Human Genetics 10/1996; 59(3):501-9. · 10.60 Impact Factor
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ABSTRACT: Leber hereditary optic neuropathy (LHON) is one of the more common forms of hereditary optic neuropathy and one of the few mitochondrial neuropathies. Prior to the advent of molecular DNA testing, the diagnosis depended on the recognition of typical fundal changes, as well as a family history of maternal transmission. Sporadic cases were therefore diagnosed with a level of uncertainty. The aim of this study is to identify the proportion of patients with idiopathic bilateral optic neuropathy/atrophy who are suffering from LHON.
Requests were sent to all ophthalmologists and neurologist in Australia and New Zealand for blood or hair follicle samples of patients with diagnosis of bilateral optic neuropathy/atrophy of uncertain aetiology for DNA testing by restriction endonuclease analysis.
One hundred and forty-four samples were received, of which 96 were sporadic cases of idiopathic optic atrophy. Eleven of these sporadic patients were found to harbour pathogenetic mitochondrial point mutations associated with LHON.
Our results indicated that 11% of patients with bilateral optic neuropathy/atrophy of uncertain aetiology are suffering from LHON. Comparing this data with all the known familial cases of LHON, we report that at least 8% of all LHON cases in Australia are sporadic. We concluded that mtDNA testing for LHON in patients with idiopathic optic atrophy should be included in the initial laboratory work-up.
Australian and New Zealand Journal of Ophthalmology 03/1996; 24(1):7-14.
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D A Mackey
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ABSTRACT: Recent advances in genetics tend to center on the discoveries of molecular biology. A disease is first linked to a region on a chromosome, a gene is later cloned, or a candidate gene identified, point mutations described, phenotype-genotype correlations made, and rationales for treatment proposed. Several neuro-ophthalmological diseases have recently been studied in this way; including Leber's hereditary optic neuropathy and other mitochondrial diseases, autosomal dominant (Kjer) optic atrophy, Wolfram syndrome, or DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), Usher syndrome, neurofibromatosis types I and II, and two disorders of the paired box genes: aniridia and Waardenburg's syndrome. Apart from molecular biology there are still some new disease entities being described and new inheritance patterns identified for some syndromes, such as periodic alternating nystagmus.
Current Opinion in Ophthalmology 01/1996; 6(6):48-53. · 2.65 Impact Factor
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D A Mackey
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ABSTRACT: Variations in classic Leber hereditary optic neuropathy (LHON) include recovery of vision and association with other neurological abnormalities. Sixteen multi-generational Australian families originating from the United Kingdom with LHON were studied by the one examiner, using the same protocol. In particular, recovery of vision and other neurological abnormalities were noted. One very large family (Tas2) and one small family (Vic2) were found to have frequent recovery of vision (50% of patients). They both had the 14484 T to C mutation in their mitochondrial DNA (mtDNA). One apparently unique family (Qld1) was found to have frequent juvenile encephalopathy and peripheral neurological signs. They had the 4160 T to C and 14484 T to C mutations. The remaining 13 families rarely showed visual recovery or associated neurological abnormalities. They had the common 11778 G to A or the 3460 G to A mutations. Thus mitochondrial genotypes in LHON are associated with variable phenotypes.
Eye 02/1994; 8 ( Pt 4):431-6. · 1.85 Impact Factor
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ABSTRACT: Leber hereditary optic neuropathy (LHON) presents with sudden onset of visual loss mainly in young adult males. LHON is not uncommon in Australia, accounting for 2% of invalid blind pensions. We have identified 20 unrelated families carrying mitochondrial DNA mutations associated with LHON and 135 of 291 individuals with documented LHON are currently alive in Australia. The mean age of onset of visual loss for males was 26 years and for females 27 years, with a range from six to 65 years. The mean risk of visual loss was 20% for males and 4% for females. There are over 1750 male and female carriers living in Australia who have not yet lost vision; 600 carriers are under 24 years of age. The expected number of new cases of blindness from LHON is three to four per year.
Australian and New Zealand Journal of Ophthalmology 09/1992; 20(3):177-84.
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ABSTRACT: We studied the clinical appearance and inheritance in five families with X-linked megalocornea. Affected male subjects had corneal diameters between 13.0 and 16.5 mm. Arcus juvenilis, mosaic corneal dystrophy, and cataracts were found only in adult affected male subjects. No carrier female abnormality was identified. The gene locus for the X-linked form is in the region Xq12-q26. This is near the locus described for Aarskog (facial-digital-genital) syndrome, Xq12-13.
Archives of Ophthalmology 07/1991; 109(6):829-33. · 3.71 Impact Factor
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K P Burdon,
J.D. McKay,
M M Sale,
I M Russell-Eggitt, D A Mackey,
G. M. Wirth,
J E Elder,
A. Nicoll,
M. P. Clarke,
L. M. FitzGerald, [......],
M. A. Shaw,
S. Sharma,
S. Gajovic,
P Gruss,
S. Ross,
P Thomas,
A K Voss,
T Thomas,
J. Gecz,
J. E. Graig
The American Journal of Human Genetics, v.73, 1120-1130 (2003).
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ABSTRACT: To investigate the association between maternal smoking in pregnancy, early-life environment and childhood vision.
Twin and triplet children enrolled in the Twins Eye Study in Tasmania underwent a comprehensive ophthalmic examination and their parents/guardians retrospectively answered a questionnaire regarding crawling, walking and other measures. A subset of these twins was also in the Tasmanian Infant Health Survey, which prospectively collected data on antenatal smoking, gestation, birth weight and other factors.
The mean age of the 346 individuals (172 multiple birth sets) at the time of examination was 9.25+/-2.4 years. Mean unaided visual acuity was 0.0 (6/6). The mean spherical equivalent was +0.87D, and decreased with increasing child age (p<0.01). A prospective analysis, accounting for birth set clustering and relevant confounders, showed increasing levels of maternal smoking in the third trimester was associated with poor stereoacuity on the Titmus test (worse (>) than 100'', p=0.05) and Lang test (p=0.001) and also with the presence of esotropia (p=0.02). These associations persisted after adjustment for infant postnatal smoke exposure at one month of age. Poor stereoacuity on Titmus stereo test circles was associated with late age of first crawling (RR=1.23 (1.06, 1.42) p=0.005 per month) and late age of first walking (RR 1.18 (1.05, 1.22) p=0.001 per month).
Antenatal smoking was independently associated with poor stereovision and the presence of esotropia. Poor stereoacuity may be associated with delayed age at first crawling or walking.
Ophthalmic Epidemiology 14(6):351-9. · 1.45 Impact Factor
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G Zhu,
A W Hewitt,
J B Ruddle,
L S Kearns,
S A Brown,
J R MacKinnon,
C. Y. Chen,
C J Hammond,
J E Craig,
G W Montgomery,
N G Martin, D A Mackey
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ABSTRACT: PURPOSE: To estimate heritability and locate quantitative trait loci influencing axial length. DESIGN: Classic twin study of monozygotic and dizygotic twins reared together. PARTICIPANTS: Eight hundred ninety-three individuals from 460 families were recruited through the Twin Eye Study in Tasmania and Brisbane Adolescent Twin Study (BATS) and had ocular axial length measured. METHODS: Structural equation modeling on the entire sample was used to estimate genetic and environmental components of variation in axial length. Analysis of existing microsatellite marker genomewide linkage scan data was performed on 318 individuals from 142 BATS families. MAIN OUTCOME MEASURE: Ocular axial length. RESULTS: The heritability estimate for axial length, adjusted for age and sex, in the full sample was 0.81. The highest multipoint logarithm of the odds (LOD) score observed was 3.40 (genomewide P = 0.0004), on chromosome 5q (at 98 centimorgans [cM]). Additional regions with suggestive multipoint LOD scores were also identified on chromosome 6 (LOD scores, 2.13 at 76 cM and 2.05 at 83 cM), chromosome 10 (LOD score, 2.03 at 131 cM), and chromosome 14 (LOD score, 2.84 at 97 cM). CONCLUSION: Axial length, a major endophenotype for refractive error, is highly heritable and is likely to be influenced by one or more genes on the long arm of chromosome 5.
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ABSTRACT: PAX6 is a key regulator of eye development and there are many well recognized ophthalmic sequelae of mutations at this locus. The 14 exon PAX6 gene is well conserved across species and phyla. Coding region mutations manifest in a variety of phenotypes. Predicted premature protein truncations are generally associated with classical aniridia. Missense mutations are often found in cases with variant phenotypes such as ectopia pupillae; isolated foveal hypoplasia; nystagmus and hyaloid vessel proliferation. The locus has also been implicated, through a genome-wide sib-pair scan, to be important in the normal variation of myopia. We investigated the association between identified PAX6 mutations and refractive error in Australian patients from four pedigrees. Two of eight subjects with a 1410delC PAX6 mutation had a mean spherical equivalence < -9D, whilst a mean spherical equivalence < or = -5D was recorded in two from four subjects with an Arg240Stop PAX6 mutation and one of two subjects with a Glu93Stop mutation. One individual identified with a Pro346Ala PAX6 mutation had a mean spherical equivalence of +2.8 D. Thus, our observations generally support other incidental findings, that PAX6 mutation, particularly predicted haploinsufficiency, may be associated with extreme refractive error, although the mechanism by which this occurs is not clear
Ophthalmic Genet. 28(3).
