Deepa A Taranath

Anterior segment biometry with the pentacam: comprehensive assessment of repeatability of automated measurements

PURPOSE: To comprehensively assess the reliability of automated Pentacam (Oculus, Inc.) measurements. SETTING: Flinders Eye Centre, Flinders Medical Centre, Bedford Park, South Australia, Australia. METHODS: Both eyes of 35 normal volunteers were tested twice on the same day by 2 different observers. All automated values were recorded, and manual analysis of topographic maps was performed only to overrule variance in corneal thickness due to pupil decentration altering the central reference point. Repeatability was determined with Bland‐Altman limits of agreement and reported as the coefficient of repeatability (COR = ±1.96 standard deviation of differences). Relative repeatability (RR) was calculated as a percentage of the ratio of COR to the mean. RESULTS: Overall, repeatability was good. Corneal curvature, reported in diopters, showed good repeatability anteriorly (simulated keratometry mean COR±0.28D; RR=0.64%) and posteriorly (COR±011D; RR=1.85%). Peripheral corneal curvature was more reliable when calculated by the sagittal (axial) method (RR=1.57%) than by the tangential (meridional) method (RR=2.38%). Keratometric power deviation was less reliable (RR=16.39%). Anterior chamber measurements showed good reliability (RR=3.07%‐5.68%) except for anterior chamber angle (RR=14.41%). Pupil diameter showed poor reliability (RR=25.77%). Central corneal thickness was comparable at pupil center and corneal vertex, but peripheral repeatability was much better when centered on the corneal vertex (COR±16.00μm; RR=2.56%) than at pupil center (COR±26.28μm; RR=4.23%). CONCLUSIONS: Pentacam corneal curvature and anterior chamber parameters were highly repeatable, but pupil measurements had poor repeatability. Peripheral pachymetry readings were affected by pupil decentration and required manual analysis using the corneal vertex as the point of reference to achieve good repeatability.

Repeatability of corneal first-surface wavefront aberrations measured with Pentacam corneal topography

PURPOSE: To assess the repeatability of corneal wavefront aberrations derived from Pentacam (Oculus) corneal topography. SETTING: Flinders Eye Centre, Flinders Medical Centre, Bedford Park, South Australia, Australia. METHODS: Forty‐five normal participants and 10 participants with keratoconus were tested. Intraobserver and interobserver repeatability was determined using 4 observers within and between sessions. Topographical maps were exported to external software, and corneal first‐surface wavefront aberrations were calculated using a 10th‐order Zernike expansion over a 6.0 mm optical zone. Repeatability was determined with Bland‐Altman limits of agreement and expressed as the coefficient of repeatability (COR). RESULTS: Initial data showed high wavefront aberrations in normal participants and poor repeatability. Topographical maps showed extrapolated topography in zones without data acquisition; maps with less than 6.0 mm of complete data were excluded in the final analysis. The mean wavefront aberrations for normal participants remained high, but repeatability improved. The COR relative to the magnitude of wavefront aberrations was high (average 100%) across all modal pairs and orders, although best for total higher‐order root mean square. Participants with keratoconus had higher magnitude wavefront aberrations and poorer repeatability but similar COR to average wavefront aberration ratios. Examination of raw elevation data showed poor repeatability. CONCLUSIONS: Wavefront aberrations calculated from Pentacam corneal topography were large in magnitude, and reliability was poor, largely due to variability in corneal elevation data. Intraobserver and interobserver reliability within and between sessions was comparable. The Pentacam was not reliable in measuring corneal wavefront aberrations.

Mutations in the EPHA2 gene are a major contributor to inherited cataracts in South-Eastern Australia.

Congenital cataract is the most common cause of treatable visual impairment in children worldwide. Mutations in many different genes lead to congenital cataract. Recently, mutations in the receptor tyrosine kinase gene, EPHA2, have been found to cause congenital cataract in six different families. Although these findings have established EPHA2 as a causative gene, the total contribution of mutations in this gene to congenital cataract is unknown. In this study, for the first time, a population-based approach was used to investigate the frequency of disease causing mutations in the EPHA2 gene in inherited cataract cases in South-Eastern Australia. A cohort of 84 familial congenital or juvenile cataract index cases was screened for mutations in the EPHA2 gene by direct sequencing. Novel changes were assessed for segregation with the disease within the family and in unrelated controls. Microsatellite marker analysis was performed to establish any relationship between families carrying the same mutation. We report a novel congenital cataract causing mutation c.1751C>T in the EPHA2 gene and the previously reported splice mutation c.2826-9G>A in two new families. Additionally, we report a rare variant rs139787163 potentially associated with increased susceptibility to cataract. Thus mutations in EPHA2 account for 4.7% of inherited cataract cases in South-Eastern Australia. Interestingly, the identified rare variant provides a link between congenital and age-related cataract.

A comparison between the amblyopic eye and normal fellow eye ocular architecture in children with hyperopic anisometropic amblyopia

PURPOSE To compare the anterior and posterior ocular architecture of amblyopic and normal fellow eyes in children with hyperopic anisometropic amblyopia. METHODS Fourteen subjects with hyperopic anisometropic amblyopia were examined using the Pentacam and optical coherence tomography. For each participant, the amblyopic eye was compared to the fellow non-amblyopic eye. RESULTS There were no significant differences (P > 0.05) in the anterior corneal curvature, posterior corneal curvature, central corneal thickness, corneal volume, anterior chamber depth, anterior chamber volume, peripapillary retinal nerve fiber layer, central macular thickness, and macular volume between the amblyopic eye and fellow eye of the study participants. CONCLUSIONS The Pentacam and optical coherence tomography revealed no differences in the anterior and posterior ocular architecture between the amblyopic eye and fellow eye in children with hyperopic anisometropic amblyopia.

Ocular malformation in a newborn secondary to maternal hypovitaminosis A

We report a case of microphthalmia, inferior adherent leukoma, and optic nerve hypoplasia in an infant whose mother underwent biliopancreatic diversion surgery for obesity 7 years before his birth. The pregnancy was complicated by severe, maternal hypovitaminosis A despite oral supplementation. The infant was found to have undetectable serum vitamin A levels in the perinatal period. At 8 weeks of age, the infant underwent sector iridectomies. At 9 months of age, electroretinography suggested rod dysfunction. His visual performance is poor.

High-throughput genetic screening of 51 pediatric cataract genes identifies causative mutations in inherited pediatric cataract in South Eastern Australia

Pediatric cataract is a leading cause of childhood blindness. This study aimed to determine the genetic cause of pediatric cataract in Australian families by screening known disease-associated genes using massively parallel sequencing technology. We sequenced 51 previously reported pediatric cataract genes in 33 affected individuals with a family history (cases with previously known or published mutations were excluded) using the Ion Torrent Personal Genome Machine. Variants were prioritized for validation if they were predicted to alter the protein sequence and were absent or rare with minor allele frequency <1% in public databases. Confirmed mutations were assessed for segregation with the phenotype in all available family members. All identified novel or previously reported cataract-causing mutations were screened in 326 unrelated Australian controls. We detected 11 novel mutations in GJA3, GJA8, CRYAA, CRYBB2, CRYGS, CRYGA, GCNT2, CRYGA, and MIP; and three previously reported cataract-causing mutations in GJA8, CRYAA, and CRYBB2. The most commonly mutated genes were those coding for gap junctions and crystallin proteins. Including previous reports of pediatric cataract-associated mutations in our Australian cohort, known genes account for >60% of familial pediatric cataract in Australia, indicating that still more causative genes remain to be identified.

Glaucoma spectrum and age-related prevalence of individuals with FOXC1 and PITX2 variants

Variation in FOXC1 and PITX2 is associated with Axenfeld-Rieger syndrome, characterised by structural defects of the anterior chamber of the eye and a range of systemic features. Approximately half of all affected individuals will develop glaucoma, but the age at diagnosis and the phenotypic spectrum have not been well defined. As phenotypic heterogeneity is common, we aimed to delineate the age-related penetrance and the full phenotypic spectrum of glaucoma in FOXC1 or PITX2 carriers recruited through a national disease registry. All coding exons of FOXC1 and PITX2 were directly sequenced and multiplex ligation-dependent probe amplification was performed to detect copy number variation. The cohort included 53 individuals from 24 families with disease-associated FOXC1 or PITX2 variants, including one individual diagnosed with primary congenital glaucoma and five with primary open-angle glaucoma. The overall prevalence of glaucoma was 58.5% and was similar for both genes (53.3% for FOXC1 vs 60.9% for PITX2, P=0.59), however, the median age at glaucoma diagnosis was significantly lower in FOXC1 (6.0±13.0 years) compared with PITX2 carriers (18.0±10.6 years, P=0.04). The penetrance at 10 years old was significantly lower in PITX2 than FOXC1 carriers (13.0% vs 42.9%, P=0.03) but became comparable at 25 years old (71.4% vs 57.7%, P=0.38). These findings have important implications for the genetic counselling of families affected by Axenfeld-Rieger syndrome, and also suggest that FOXC1 and PITX2 contribute to the genetic architecture of primary glaucoma subtypes.

Intense pulsed light therapy (IPL) induced iritis following treatment for a medial canthal capillary malformation

The popularity of intense pulsed light (IPL) therapy continues to increase due to its relative safety, high skin coverage rate and ability to treat both vascular and pigmented lesions. An often‐overlooked risk is the potential for IPL‐induced ocular damage. The damage sustained can cause significant, persistent morbidity and can occur even with very limited IPL exposure to the eye.

Objective monitoring of papilloedema using confocal scanning laser ophthalmoscopy

Idiopathic intracranial hypertension can cause severe optic nerve damage with irreversible visual loss. Heidelberg retina tomography is a sensitive and reproducible tool that can be used in the monitoring of optic disc swelling due to IIH. We demonstrate that the three‐dimensional images produced are easy to interpret, indicate progression or resolution and improve the timing of intervention in multidisciplinary settings by facilitating communication between specialists.

Partial duplication of the CRYBB1-CRYBA4 locus is associated with autosomal dominant congenital cataract

Congenital cataract is a rare but severe paediatric visual impediment, often caused by variants in one of several crystallin genes that produce the bulk of structural proteins in the lens. Here we describe a pedigree with autosomal dominant isolated congenital cataract and linkage to the crystallin gene cluster on chromosome 22. No rare single nucleotide variants or short indels were identified by exome sequencing, yet copy number variant analysis revealed a duplication spanning both CRYBB1 and CRYBA4. While the CRYBA4 duplication was complete, the CRYBB1 duplication was not, with the duplicated CRYBB1 product predicted to create a gain of function allele. This association suggests a new genetic mechanism for the development of isolated congenital cataract.