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Emmanuelle Souzeau,
Kathryn P Burdon,
Andrew Dubowsky,
Scott Grist,
Bronwyn Usher,
Jude T Fitzgerald,
April Crawford,
Alex W Hewitt,
Ivan Goldberg,
Richard A Mills, Jonathan B Ruddle,
John Landers,
David A Mackey,
Jamie E Craig
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ABSTRACT: OBJECTIVES: To determine the proportion of all Myocilin coding mutations responsible for advanced primary open-angle glaucoma (POAG) in early-age-at-onset individuals and to investigate the prevalence of exon 3 Myocilin mutations in advanced POAG at any age at onset in a large Australasian cohort. DESIGN: Cross-sectional study using a national disease registry. PARTICIPANTS: One thousand sixty individuals with advanced POAG (103 with age at onset of 40 years or younger) and 320 with nonadvanced POAG all recruited by the Australian and New Zealand Registry of Advanced Glaucoma. METHODS: Participants were examined and referred by their eye practitioner, and Myocilin genetic testing was performed by direct sequencing. Cascade genetic testing was made available for relatives of participants found to carry a Myocilin mutation. MAIN OUTCOME MEASURES: Advanced glaucoma diagnosis based on strict visual field entry criteria. Prevalence and spectrum of Myocilin mutations in individuals with advanced and nonadvanced POAG. RESULTS: This is the first study to report Myocilin mutations in an advanced POAG cohort. No pathogenic Myocilin mutations were identified in exons 1 and 2 in early-age-at-onset advanced POAG cases. Exon 3 Myocilin mutations were identified in 45 advanced POAG patients (4.2%), which is significantly higher (P = 0.02) compared with nonadvanced POAG patients (1.6%). A novel mutation (Trp373X) and a new variant of uncertain pathogenicity (Ala447Thr) also were reported. The prevalence of Myocilin mutations rose from 16% to 40% in selected advanced POAG subgroups based on different thresholds of maximum recorded intraocular pressure, age at diagnosis, and the presence and strength of positive family history. Twenty-six individuals with Myocilin mutations were identified through cascade genetic testing of first-degree relatives of affected mutation carriers. CONCLUSIONS: The prevalence of Myocilin mutations in glaucoma cases with severe visual field loss is significantly greater than in nonadvanced glaucoma patients. Myocilin screening in phenotypically selected cases can have a much higher yield than in previous unselected series. Identifying individuals who have Myocilin mutations provides an opportunity to screen at-risk clinically unaffected relatives and to reduce glaucoma blindness through early management and intervention. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Ophthalmology 02/2013; · 5.45 Impact Factor
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ABSTRACT: BACKGROUND: To determine the incidence and predictors of glaucoma following surgery for congenital and infantile cataract in an Australian population DESIGN: Retrospective cohort study PARTICIPANTS: Infants (age <12 months) during lens extraction between January 1992 and May 2006, from two tertiary referral centres METHODS: Children with uveitis, anterior segment dysgenesis, aniridia, retinopathy of prematurity, and lens subluxation were excluded. Potential predictors of incident glaucoma were examined using Cox proportional hazards regression with adjustment for clustering between eyes. MAIN OUTCOME MEASURES: Incidence and predictors of secondary glaucoma RESULTS: 147 eyes of 101 patients (46 bilateral cataract; 55 unilateral cataract) were included, with median follow-up of 9.9 years (range 1.2 - 18.9 years). Cumulative incidence of glaucoma was 32.0% for eyes (N=47) and 30.7% (N=31) for subjects. Incidence was higher in children with bilateral cataract (38.9 vs. 17.1%, P=0.004). There were 3.9 cases of glaucoma per 100 person years of follow-up, and the incidence rate was highest for surgery performed in the first month of life. Children with glaucoma had longer median follow-up (11.8 vs. 9.3 years, P=0.005). Risk of glaucoma decreased with increasing months of age at operation: hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.69 - 0.91, P=0.001. Median visual acuity was worse in children with unilateral cataract (P<0.001) CONCLUSIONS: We identified an increased risk of glaucoma when cataract surgery was performed in younger infants, and in those with bilateral cataract. As glaucoma may develop over a decade following lens extraction, all patients require life-long surveillance following cataract surgery to prevent glaucoma-associated vision loss.
Clinical and Experimental Ophthalmology 01/2013; · 1.98 Impact Factor
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ABSTRACT: Retinal vessel attenuation is a key finding in the diagnosis of retinitis pigmentosa (RP), but there have been no studies to determine whether quantitative measurement of this retinal sign is useful. We aimed to investigate retinal vessel caliber and its relationship with the severity of RP.
This is a cross-sectional study based on 74 patients (145 eyes) with RP who had visual field assessment with Goldmann permeter and good-quality retinal images for vessel size measurements identified by retrospective medial chart review (1973-2007) in the electrophysiology clinic of a tertiary eye hospital in Australia. Retinal vessel calibers were measured using a computer-based program as the central retinal artery and vein equivalent (CRAE and CRVE). Goldmann visual field area for III4e white test light was measured quantitatively using ImageJ software as a clinical parameter to indicate the severity of RP. We used the generalized estimating equation models to estimate the difference in retina vessel calibers accounting for correlation between right and left eyes.
Mean CRAE and CRVE were significantly narrower in persons with smaller visual field area. For each 100 cm2 decrease in visual field area, CRAE and CRVE decreased by -15.2 μm (95% confidence interval -20.7, -9.78) and -26.8 μm (-35.1, -18.5), respectively (both P<0.001).
In RP patients, the severity of visual field loss is correlated with retinal vessel attenuation. Quantitative retinal vessel caliber measurement may be a useful additional clinical marker for monitoring progression of RP or potential treatment response.
Investigative ophthalmology & visual science 06/2012; 53(7):4306-14. · 3.43 Impact Factor
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ABSTRACT: Background: To determine whether postoperative subconjunctival bevacizumab significantly alters bleb vascularity. Design: A randomised, prospective interventional study. Participants: 43 eyes from 39 patients were recruited, with 21 eyes randomised to subconjunctival injections of 5-FU, and 22 eyes to combined 5-FU/bevacizumab. Methods: All patients who underwent uncomplicated primary anti-metabolite augmented trabeculectomy who subsequently required post-operative subconjunctival 5-Fluorouracil (5-FU) injection within 4 weeks of surgery were eligible. Patients were randomised to receive subconjunctival 5-FU only (7.5mg/0.15ml) or 5 FU plus bevacizumab (1.25mg/0.05ml). Main Outcome Measures: Primary outcome was bleb vascularity with secondary endpoints including visual acuity (VA), intraocular pressure (IOP), bleb morphology, complications and total numbers of 5-FU injections were recorded at baseline, week 12 and 18 months. Results: At week 12, there was no significant difference between groups for VA, IOP, bleb vascularity and morphology or total number of 5-FU injections. By 18 months, 47.4% of the 5-FU/bevacizumab group exhibited central bleb avascularity compared to 21.1% of the 5 FU group (Fisher exact test, p = 0.17). 2 bleb complications (1 blebitis; 1 suture abscess) recorded in the 5 FU/bevacizumab group. Conclusions: After a single combined injection a trend for increased central bleb avascularity was observed; although this effect was not sufficient to reach statistical significance. This in addition to the occurrence of two bleb related complications in the bevacizumab group suggest the need for a larger clinical trial to further evaluate the safety and efficacy of bevacizumab as a modulating agent in glaucoma filtration surgery. © 2012 The Authors. Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.
Clinical and Experimental Ophthalmology 03/2012; · 1.98 Impact Factor
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ABSTRACT: To describe the phenotype of ocular hypertension and primary open-angle glaucoma in a family with individuals compound heterozygote for Gln368STOP and Thr377Met myocilin (MYOC) mutations.
Family members of the proband underwent comprehensive ocular clinical examination and DNA sequencing for MYOC mutations.
A 34-year-old woman with marked ocular hypertension was found to carry Gln368STOP and Thr377Met MYOC mutations. Three other siblings carried both mutations, while one carried Gln368STOP alone. Three of five siblings had received treatment for ocular hypertension or early glaucoma, with the average age of diagnosis 28 years; one required trabeculectomy at age 27. The mother of the proband was found to be a carrier for Gln368STOP alone, which indicates that her offspring with both Gln368STOP and Thr377Met carry variants on opposing alleles.
This pedigree is the first report with individuals compound heterozygote for the two most common glaucoma-causing MYOC variants. The combination of mutations manifests a more severe phenotype than either alone. Identification of gene changes associated with glaucoma within the family has enabled unaffected members to stratify their risk of future disease and institute closer monitoring and early treatment.
Molecular vision 01/2012; 18:3064-9. · 2.20 Impact Factor
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Emmanuelle Souzeau,
Ivan Goldberg,
Paul R Healey,
Richard A D Mills,
John Landers,
Stuart L Graham,
John R B Grigg,
Bronwyn Usher,
Tania Straga,
April Crawford,
Robert J Casson,
William H Morgan, Jonathan B Ruddle,
Michael A Coote,
Andrew White,
James Stewart,
Alex W Hewitt,
David A Mackey,
Kathryn P Burdon,
Jamie E Craig
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ABSTRACT: Glaucoma is a sight-threatening disease affecting 3% of the population over the age of 50. Glaucoma is treatable, and severe vision loss can usually be prevented if diagnosis is made at an early stage. Genetic factors play a major role in the pathogenesis of the condition, and therefore, genetic testing to identify asymptomatic at-risk individuals is a promising strategy to reduce the prevalence of glaucoma blindness. Furthermore, unravelling genetic risk factors for glaucoma would also allow a better understanding of the pathogenesis of the condition and the development of new treatments.
The Australian and New Zealand Registry of Advanced Glaucoma is a prospective study that aims to develop a large cohort of glaucoma cases with severe visual field loss to identify novel genetic risk factors for glaucoma blindness.
Clinical information and blood are collected from participants after referral by eye practitioners. Samples are collected across Australia and New Zealand using postage kits.
Our registry has recruited just over 2000 participants with advanced glaucoma, as well as secondary and developmental glaucomas.
A positive family history of glaucoma is present in more than half of the advanced glaucoma cases and the age at diagnosis is significantly younger for participants with affected relatives, which reinforces the involvement of genetic factors in glaucoma.
With the collection of glaucoma cases recruited so far, our registry aims to identify novel glaucoma genetic risk factors to establish risk profiling of the population and protocols for genetic testing.
Clinical and Experimental Ophthalmology 12/2011; 40(6):569-75. · 1.98 Impact Factor
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Manir Ali,
Paul M Hocking,
Martin McKibbin,
Sorcha Finnegan,
Mike Shires,
James A Poulter,
Katrina Prescott,
Adam Booth,
Yasmin Raashid,
Hussain Jafri, Jonathan B Ruddle,
David A Mackey,
Samuel G Jacobson,
Carmel Toomes,
Douglas H Lester,
David W Burt,
William J Curry,
Chris F Inglehearn
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ABSTRACT: To identify the defective gene in the sex-linked, recessively inherited retinal dysplasia and degeneration (rdd) chicken and to search for the human equivalent disease.
Microsatellites from chicken chromosome Z were genotyped in 77 progeny of a carrier male (rdd/+) and an affected female (rdd/W), and candidate genes were sequenced. Retinal cross-sections from rdd and wild-type birds were analyzed by immunohistology. The human orthologous gene was screened in a panel of archival DNAs from 276 patients with retinitis pigmentosa (RP) or Leber congenital amaurosis (LCA) using melting curve analysis and DNA sequencing.
The rdd locus was refined to an approximately 3-Mb region on chromosome Z. Sequence analysis identified a C→T change in the mpdz gene that created a premature stop codon (c.1372C→T, p.R458X), which segregated with the disease phenotype. As expected, the full-length mpdz protein was absent in rdd retinas, but in wild-type birds, it localized to the retinal outer limiting membrane, where it may have a role in the interactions between photoreceptors and Müller glia cells. The screen to identify the human equivalent disease found 10 heterozygous variants in the orthologous gene in patients with RP (three missense and two null alleles) and LCA (four missense and one null allele).
These findings reveal that MPDZ is essential for normal development of the retina and may have a role in maintaining photoreceptor integrity. The identification of human mutations suggests that MPDZ plays a role in human retinal disease, but the precise nature of this role remains to be determined.
Investigative ophthalmology & visual science 08/2011; 52(10):7432-40. · 3.43 Impact Factor
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Clinical and Experimental Ophthalmology 06/2011; 40(2):212-3. · 1.98 Impact Factor
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Clinical and Experimental Ophthalmology 04/2011; 40(3):322-3. · 1.98 Impact Factor
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ABSTRACT: To compare the distributional parameters for a series of ocular biometric traits between twins and their singleton siblings, to evaluate the generalizability of twin data, as used in heritability analyses to the general population.
A series of birth, anthropometric, and 13 ocular biometric traits were selected for analysis: interpupillary distance (IPD), visual acuity (logMAR), spherical equivalent refractive error, corneal curvature, axial length, anterior chamber depth (ACD), central corneal thickness (CCT), intraocular pressure (IOP), optic disc, cup and rim areas, and measures of retinal vessel caliber; central retinal arteriolar equivalent (CRAE), and central retinal venular equivalent (CRVE). Structural equation modeling was used to test the assumption that the means and variances for each trait did not differ between twins and their siblings.
Significant differences in log-likelihood for birth weight and gestational age were observed between twins and siblings, with the latter being both heavier and closer to full-term at birth. Siblings were also found to have larger IPD and axial length, and better visual acuity compared with their twin counterparts. Refractive error, corneal curvature, ACD, CCT, optic disc parameters, and retinal vascular calibers did not differ significantly between the two groups.
Twins are representative of the general population for some but not all measures of ocular biometry. Consequently, care should be taken when extrapolating twin data for these traits in heritability and other genetic studies. Birth weight differences between twins and siblings do not appear to account for the differences in ocular biometry observed in this study.
Investigative ophthalmology & visual science 04/2011; 52(8):5565-72. · 3.43 Impact Factor
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ABSTRACT: To develop, implement and evaluate a telemedicine model to reduce glaucoma blindness through the early detection of undiagnosed glaucoma in high-risk individuals.
Prospective study, private ophthalmology practice and public outpatient clinics in Tasmania.
One hundred and thirty-three individuals with primary open-angle glaucoma were invited to enrol their first-degree relatives (FDRs) to undergo an eye examination. Within the study period, 211 FDRs were available for examination.
A registered nurse was trained to perform the required assessments. Clinical data were entered into a purpose-built database, converted to a portable document format and graded offsite by an ophthalmologist to determine the presence, absence or risk of developing glaucoma. Participants were notified of the grading result and recommendations for review.
Incidence of undiagnosed glaucoma in a high-risk population.
Previously undiagnosed glaucoma was identified in 5% of those examined. For every 19 participants screened, one new case of previously undiagnosed case of glaucoma was identified. Additionally 15% of participants showed suspicious signs of glaucoma, and 6% had ocular hypertension.
A telemedicine model is an efficient method for screening, grading and notifying participants of examination results. Nurses can be adequately trained to undertake the initial screening examinations, with grading of the results performed offsite by a suitably qualified ophthalmologist. Targeted screening for glaucoma increases the yield of identifying individuals with undiagnosed glaucoma or those at greatest risk. Cost efficiencies for this model of glaucoma screening should be further explored and implemented to prevent blindness from familial glaucoma.
Clinical and Experimental Ophthalmology 03/2011; 39(8):760-5. · 1.98 Impact Factor
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Clinical and Experimental Ophthalmology 01/2011; 39(5):473-8. · 1.98 Impact Factor
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Cong Sun,
Anne-Louise Ponsonby,
Shayne A Brown,
Lisa S Kearns,
Jane R Mackinnon,
Julie M Barbour, Jonathan B Ruddle,
Alex W Hewitt,
Margret J Wright,
Nicholas G Martin,
Terence Dwyer,
David A Mackey
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ABSTRACT: To examine the relationship of birth weight with ocular measures in a Caucasian twin population.
Cross-sectional study of 1498 twins (308 monozygotic and 441 dizygotic pairs) aged between 5 to 80 years participating in the Australian Twins Eye Study.
All participants underwent ophthalmic examination including bilateral cycloplegic autorefraction, keratometry, interpupillary distance (IPD), central corneal thickness, intraocular pressure (IOP), and retinal photography. Birth weight and gestation were obtained from a self-administered questionnaire. A subset of the twins also participated in the Tasmanian Infant Health Study (288) and the Childhood Blood Pressure Study (184), which collected data on birth parameters allowing for verification of data. Linear mixed models were used for the main analysis.
Both the within-pair (β(w) 0.27, 95% confidence interval [CI] 0.15, 0.38 mm per kg increase in birth weight, P < .001) and between-pair associations (β(B) 0.22, 95% CI 0.08, 0.35, P = .002) of birth weight with axial length were significant and of similar magnitude (difference in effect, P = .56), after adjusting for relevant confounders. In contrast, birth weight was negatively associated with corneal curvature (β(w) -0.82, 95% CI -1.09, -0.55 diopters per kg increase; β(B) -0.69, 95% CI -0.98, -0.41, both P < .001). These associations remained significant within dizygotic and monozygotic pairs. Refraction, anterior chamber depth, IPD, IOP, and optic disc parameters are unrelated to birth weight.
Consistent with previous studies in singleton children, lower birth weight is associated with shorter axial length and more curved corneas in this twin study. This also adds new insights into the emmetropization process.
American journal of ophthalmology 10/2010; 150(6):909-16. · 3.83 Impact Factor
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ABSTRACT: The morphologic appearance of the optic disc is of interest in glaucoma. In contrast to descriptive classification systems that are currently used, a quantitative approach to the analysis of optic disc morphology is required. Our goal was to determine the optimal method for quantifying optic cup shape by comparing traditional (ovality, form-factor and neuroretinal rim (NRR) width ratio) and geometric morphometric approaches. Left optic disc stereophotographs of 160 (80 normal and 80 glaucomatous (stratified by severity)) subjects were examined. The optic cup margins were stereoscopically delineated with a custom tracing system and saved as a series of discrete points. The geometric morphometric methods of elliptic Fourier analysis (EFA) and sliding semi-landmark analysis (SSLA) were used to eliminate variation unrelated to shape (e.g. size) and yield a series of shape variables. Differences in optic cup shape between normal and glaucoma groups were investigated. Discriminant functions were computed and the sensitivity and specificity of each technique determined. Receiver operator characteristic (ROC) curves were calculated for all methods and evaluated in their potential to discriminate between normal and glaucomatous eyes based on the shape variables. All geometric morphometric methods revealed differences between normal and glaucomatous eyes in optic cup shape, in addition to the traditional parameters of ovality, form-factor and NRR width ratio (p<0.0005). SSLA (minimum bending energy criterion--18 points) had the best sensitivity (83%) and area under the curve (AUC) (0.91). EFA (72 points) performed similarly well (74%, 0.89) as did the set of traditional shape-based variables (76%, 0.86). This study demonstrated that a geometric morphometric approach for discriminating between normal and glaucomatous eyes in optic cup shape is superior to that provided by traditional single parameter shape measures. Such analytical techniques could be incorporated into future automated optic disc screening modalities.
Experimental Eye Research 09/2010; 91(3):405-14. · 3.26 Impact Factor
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Clinical and Experimental Ophthalmology 07/2010; 38(5):437-8. · 1.98 Impact Factor
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Stuart Macgregor,
Alex W Hewitt,
Pirro G Hysi, Jonathan B Ruddle,
Sarah E Medland,
Anjali K Henders,
Scott D Gordon,
Toby Andrew,
Brian McEvoy,
Paul G Sanfilippo, [......],
Sonya L Bennett,
Jamie E Craig,
Grant W Montgomery,
Khanh-Nhat Tran-Viet,
Nadean L Brown,
Timothy D Spector,
Nicholas G Martin,
Terri L Young,
Christopher J Hammond,
David A Mackey
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ABSTRACT: Optic nerve assessment is important for many blinding diseases, with cup-to-disc ratio (CDR) assessments commonly used in both diagnosis and progression monitoring of glaucoma patients. Optic disc, cup, rim area and CDR measurements all show substantial variation between human populations and high heritability estimates within populations. To identify loci underlying these quantitative traits, we performed a genome-wide association study in two Australian twin cohorts and identified rs3858145, P=6.2x10(-10), near the ATOH7 gene as associated with the mean disc area. ATOH7 is known from studies in model organisms to play a key role in retinal ganglion cell formation. The association with rs3858145 was replicated in a cohort of UK twins, with a meta-analysis of the combined data yielding P=3.4x10(-10). Imputation further increased the evidence for association for several SNPs in and around ATOH7 (P=1.3x10(-10) to 4.3x10(-11), top SNP rs1900004). The meta-analysis also provided suggestive evidence for association for the cup area at rs690037, P=1.5x10(-7), in the gene RFTN1. Direct sequencing of ATOH7 in 12 patients with optic nerve hypoplasia, one of the leading causes of blindness in children, revealed two novel non-synonymous mutations (Arg65Gly, Ala47Thr) which were not found in 90 unrelated controls (combined Fisher's exact P=0.0136). Furthermore, the Arg65Gly variant was found to have very low frequency (0.00066) in an additional set of 672 controls.
Human Molecular Genetics 07/2010; 19(13):2716-24. · 7.64 Impact Factor
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ABSTRACT: Intravitreal injection of bevacizumab (Avastin) in eyes with neovascular glaucoma (NVG) has recently been shown to induce rapid regression of anterior segment neovascularization and has promise as adjunct treatment to diode laser cyclophotocoagulation (CPC) to control intraocular pressure (IOP). This study presents the outcome of concomitant treatment with CPC and intravitreal bevacizumab in painful poor visual potential eyes in a case series of consecutively diagnosed NVG.
Twelve patients (14 eyes) were treated with CPC and concurrent intravitreal bevacizumab 0.05 mL (1.25 mg) and study end-points were IOP lowering, regression of anterior segment neovascularization and resolution of pain.
The mean preoperative IOP was 42.1 11.4 and was lowered to 16.6 7.1 mmHg at 1-month postoperatively. Anterior segment neovascularization regressed dramatically within 1 week of intravitreal bevacizumab in 12 eyes. Thirteen eyes reported persistent relief of ocular pain at 6 months following treatment.
Combined intravitreal bevacizumab and CPC treatment for NVG provides rapid control of anterior segment neovascularization and may lead to improved symptomatic relief and IOP control.
Clinical and Experimental Ophthalmology 05/2010; 38(4):353-7. · 1.98 Impact Factor
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Yi Lu,
David P Dimasi,
Pirro G Hysi,
Alex W Hewitt,
Kathryn P Burdon,
Tze'Yo Toh, Jonathan B Ruddle,
Yi Ju Li,
Paul Mitchell,
Paul R Healey,
Grant W Montgomery,
Narelle Hansell,
Timothy D Spector,
Nicholas G Martin,
Terri L Young,
Christopher J Hammond,
Stuart Macgregor,
Jamie E Craig,
David A Mackey
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ABSTRACT: Central corneal thickness (CCT), one of the most highly heritable human traits (h(2) typically>0.9), is important for the diagnosis of glaucoma and a potential risk factor for glaucoma susceptibility. We conducted genome-wide association studies in five cohorts from Australia and the United Kingdom (total N = 5058). Three cohorts were based on individually genotyped twin collections, with the remaining two cohorts genotyped on pooled samples from singletons with extreme trait values. The pooled sample findings were validated by individual genotyping the pooled samples together with additional samples also within extreme quantiles. We describe methods for efficient combined analysis of the results from these different study designs. We have identified and replicated quantitative trait loci on chromosomes 13 and 16 for association with CCT. The locus on chromosome 13 (nearest gene FOXO1) had an overall meta-analysis p-value for all the individually genotyped samples of 4.6x10(-10). The locus on chromosome 16 was associated with CCT with p = 8.95x10(-11). The nearest gene to the associated chromosome 16 SNPs was ZNF469, a locus recently implicated in Brittle Cornea Syndrome (BCS), a very rare disorder characterized by abnormal thin corneas. Our findings suggest that in addition to rare variants in ZNF469 underlying CCT variation in BCS patients, more common variants near this gene may contribute to CCT variation in the general population.
PLoS Genetics 05/2010; 6(5):e1000947. · 8.69 Impact Factor
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ABSTRACT: To review visual acuity outcomes from paediatric traumatic cataract and examine the mechanisms by which they occur.
A retrospective review of paediatric patients (aged less than 18 years) who underwent lens surgery following ocular trauma, between 1992 and 2006 at the Royal Children's Hospital and Royal Victorian Eye and Ear Hospital in Melbourne. Data collected included gender, mechanism of injury, wound type, age at injury, age at surgery, refractive rehabilitation, complications and visual acuity outcome.
A total of 74 patients (75% male) were identified over the 15-year period, representing an incidence of 4.9 cases per year. The mean age at injury was 7.5 years. Sixty-five cataracts (88%) followed a penetrating eye injury, whereas only nine patients (12%) developed cataract after known blunt trauma. Fourteen patients (19%) underwent lensectomy at the time of primary wound repair and 45 patients (61%) underwent primary intraocular lens (IOL) implantation. Visual acuity outcomes ranged from 6/5 to no perception of light. Twenty-five patients (34%) achieved 6/12 or better in the injured eye, 23 patients (31%) achieved between 6/15 and 6/60, and 14 patients (19%) had visual acuity of less than 6/60. Twelve patients (16%) were lost to follow-up.
In a paediatric population, cataract formation as a result of trauma requiring lensectomy is not uncommon. Males are more likely to suffer from such injury. A variety of sharp and blunt objects are the primary mechanism by which the injury is sustained with variable visual outcomes.
Clinical and Experimental Ophthalmology 04/2010; 38(3):237-41. · 1.98 Impact Factor
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James A Poulter,
Manir Ali,
David F Gilmour,
Aine Rice,
Hiroyuki Kondo,
Kenshi Hayashi,
David A Mackey,
Lisa S Kearns, Jonathan B Ruddle,
Jamie E Craig,
Eric A Pierce,
Louise M Downey,
Moin D Mohamed,
Alexander F Markham,
Chris F Inglehearn,
Carmel Toomes
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ABSTRACT: Familial exudative vitreoretinopathy (FEVR) is an inherited blinding disorder of the retinal vascular system. Although mutations in three genes (LRP5, FZD4, and NDP) are known to cause FEVR, these account for only a fraction of FEVR cases. The proteins encoded by these FEVR genes form part of a signaling complex that activates the Norrin-beta-catenin signaling pathway. Recently, through a large-scale reverse genetic screen in mice, Junge and colleagues identified an additional member of this signaling complex, Tspan12. Here, we report that mutations in TSPAN12 also cause autosomal-dominant FEVR. We describe seven mutations identified in a cohort of 70 FEVR patients in whom we had already excluded the known FEVR genes. This study provides further evidence for the importance of the Norrin-beta-catenin signaling pathway in the development of the retinal vasculature and also indicates that more FEVR genes remain to be identified.
The American Journal of Human Genetics 02/2010; 86(2):248-53. · 10.60 Impact Factor
