We have investigated the occurrence of attenuated extracolonic manifestations (AEMs) of familial ... more We have investigated the occurrence of attenuated extracolonic manifestations (AEMs) of familial adenomatous polyposis (FAP) in patients with non-polyposis colorectal cancer. In a prospective case-control study, we observed that significantly more colorectal cancer patients exhibited AEM than did age and sexmatched controls (19.5% vs 7.5%, P<0.004). However patients with AEMs do not have occult FAP, as we found no heterozygous adenomatous polyposis coli (APC) gene mutations despite extensive analysis of constitutional DNA. Genome-wide DNA replication errors (RERs) occur in a proportion of colorectal cancers, particularly right-sided lesions and in almost all tumours from hereditary non-polyposis colorectal cancer (HNPCC) patients. As AEMs have been reported in familial colon cancer cases, we investigated the relationship of AEMs to tumour RER phenotype. There was indeed an excess of AEMs in patients with rightsided tumours (30.2% of 53 patients vs 14.7% of 116 patients, P<0.03) and in those with RER tumours (3 out of 12 patients with RER tumours vs none out of 21 patients with non-RER tumours, P<0.05). Two patients with AEM were from HNPCC families compared with none of those without AEM (P< 0.05). The association of AEMs with colorectal cancer is intriguing, and we speculate that it may be a manifestation of mutational mosaicism of the APC gene, perhaps associated with a constitutional defect in DNA mismatch pair.
Translational Vision Science & Technology, 2021
To examine the feasibility of saccadic vector optokinetic perimetry (SVOP), an automated eye trac... more To examine the feasibility of saccadic vector optokinetic perimetry (SVOP), an automated eye tracking perimeter, as a tool for visual field (VF) assessment in infants. Methods: Thirteen healthy infants aged between 3.5 and 12.0 months were tested binocularly using an adapted SVOP protocol. SVOP uses eye tracking technology to measure gaze responses to stimuli presented on a computer screen. Modifications of SVOP for testing infants included adjusting the fixation target to display a short animation, increasing the stimulus size to equivalent to Goldmann V, and introducing a tiered test pattern strategy. Binocular, single-quadrant confrontation VF testing and Keeler preferential looking cards visual acuity testing was also performed. Results: Using multiple test attempts when required, all but the youngest infant (12 of 13 [92.3%]) successfully completed a 4-point screening test. Seven infants (53.8%) successfully completed the 12-point test, four (30.8%) successfully completed the 20-point test, and three (23.1%) successfully completed the 40-point test. The effect of multiple test attempts and the complexity of the test pattern (number of test points) on performance was investigated, including test completion rate, percentage of correctly seen stimuli, and average time per tested stimulus. Conclusions: The modified SVOP test strategy allowed successful assessment of binocular VFs in healthy infants. Future data collection from larger cohorts of infants is needed to derive normative limits of detection and assess accuracy in detecting and monitoring infant VF abnormalities. Translational Relevance: Eye tracking perimetry may provide a useful method of automated VF assessment in infants.
To explore the feasibility of using Saccadic Vector Optokinetic Perimetry (SVOP) to differentiate... more To explore the feasibility of using Saccadic Vector Optokinetic Perimetry (SVOP) to differentiate glaucomatous and healthy eyes. A prospective case–control study was performed using a convenience sample recruited from a single university glaucoma clinic and a group of healthy controls. SVOP and standard automated perimetry (SAP) was performed with testing order randomised. The reference standard was a diagnosis of glaucoma based a comprehensive ophthalmic examination and abnormality on standard automated perimetry (SAP). The index test was SVOP. 31 patients with glaucoma and 24 healthy subjects were included. Mean SAP mean deviation (MD) in those with glaucoma was − 8.7 ± 7.4 dB, with mean SAP and SVOP sensitivities of 23.3 ± 0.9 dB and 22.1 ± 4.3 dB respectively. Participants with glaucoma were significantly older. On average, SAP sensitivity was 1.2 ± 1.4 dB higher than SVOP (95% limits of agreement = − 1.6 to 4.0 dB). SVOP sensitivity had good ability to differentiate healthy and...
Conclusions An ICU stay can have significant, long-lasting impacts on young people and their fami... more Conclusions An ICU stay can have significant, long-lasting impacts on young people and their families. This is the first pan-European survey to investigate ICU care for this group. We identified significant variation in adherence to quality standards. Some of this may be culturally influenced but there are also differences in less obviously controversial measures e.g. DVT prophylaxis. Further qualitative work is planned.
Background To examine the speed and accuracy of saccadic eye movements during a novel eye trackin... more Background To examine the speed and accuracy of saccadic eye movements during a novel eye tracking threshold visual field assessment and determine whether eye movement parameters may improve ability to detect glaucoma. Methods A prospective study including both eyes of 31 patients with glaucoma and 23 controls. Standard automated perimetry (SAP) and eye tracking perimetry (saccadic vector optokinetic perimetry, SVOP) was performed. SVOP provided data on threshold sensitivity, saccade latency, and two measures of accuracy of saccades (direction bias and amplitude bias). The relationship between eye movement parameters and severity of glaucoma was examined and Receiver Operating Characteristic curves were used to assess ability to detect glaucoma. Results Patients with glaucoma had significantly slower saccades (602.9 ± 50.0 ms versus 578.3 ± 44.6 ms for controls, P = 0.009) and reduced saccade accuracy (direction bias = 7.4 ± 1.8 versus 6.5 ± 1.5 degrees, P = 0.006). There was a sign...
ObjectiveTo determine the time to resolution of different-layered retinal haemorrhages (RHs), and... more ObjectiveTo determine the time to resolution of different-layered retinal haemorrhages (RHs), and to describe the main patterns of their resolution in a group of children with encephalopathies.Methods and analysisFrom a prospective study of 114 children with traumatic and non-traumatic encephalopathies, 429 selected individual RHs (iRHs) from 18 children were serially imaged from admission using a RetCam. Photoshop and Scion Imaging software allowed calculation of RH area in pixels.ResultsTwo patterns of the resolution were recognised on the basis of area measurements: a progressive decrease (pattern A, 60% of iRHs), and a form of asymmetrical decay in which iRHs first increased in size before then progressively decreasing (pattern B, 35% of iRHs). Within the pattern A group, the Kaplan-Meier median survival time (MST) (95% CI) was 10 (9.3 to 10.7) days for intra-RHs (IRHs) and 38 (10.8 to 65.2) days for pre-RHs (PRHs), log rank (Mantel-Cox) p=0.001. The mean percentage reduction in...
To determine the ability of Saccadic Vector Optokinetic Perimetry (SVOP) to detect and characteri... more To determine the ability of Saccadic Vector Optokinetic Perimetry (SVOP) to detect and characterise visual field defects in children with brain tumours using eye-tracking technology, as current techniques for assessment of visual fields in young children can be subjective and lack useful detail. Case-series study of children receiving treatment and follow-up for brain tumours at the Royal Hospital for Sick Children in Edinburgh from April 2008 to August 2013. Patients underwent SVOP testing and the results were compared with clinically expected visual field patterns determined by a consensus panel after review of clinical findings, neuroimaging, and where possible other forms of visual field assessment. Sixteen patients participated in this study (mean age of 7.2 years; range 2.9-15 years; 7 male, 9 female). Twelve children (75%) successfully performed SVOP testing. SVOP had a sensitivity of 100% and a specificity of 50% (positive predictive value of 80% and negative predictive valu...
Translational Vision Science & Technology, 2017
Purpose: We compared patterns of visual field loss detected by standard automated perimetry (SAP)... more Purpose: We compared patterns of visual field loss detected by standard automated perimetry (SAP) to saccadic vector optokinetic perimetry (SVOP) and examined patient perceptions of each test. Methods: A cross-sectional study was done of 58 healthy subjects and 103 with glaucoma who were tested using SAP and two versions of SVOP (v1 and v2). Visual fields from both devices were categorized by masked graders as: 0, normal; 1, paracentral defect; 2, nasal step; 3, arcuate defect; 4, altitudinal; 5, biarcuate; and 6, end-stage field loss. SVOP and SAP classifications were cross-tabulated. Subjects completed a questionnaire on their opinions of each test. Results: We analyzed 142 (v1) and 111 (v2) SVOP and SAP test pairs. SVOP v2 had a sensitivity of 97.7% and specificity of 77.9% for identifying normal versus abnormal visual fields. SAP and SVOP v2 classifications showed complete agreement in 54% of glaucoma patients, with a further 23% disagreeing by one category. On repeat testing, 86% of SVOP v2 classifications agreed with the previous test, compared to 91% of SAP classifications; 71% of subjects preferred SVOP compared to 20% who preferred SAP. Conclusions: Eye-tracking perimetry can be used to obtain threshold visual field sensitivity values in patients with glaucoma and produce maps of visual field defects, with patterns exhibiting close agreement to SAP. Patients preferred eye-tracking perimetry compared to SAP. Translational relevance: This first report of threshold eye tracking perimetry shows good agreement with conventional automated perimetry and provides a benchmark for future iterations.
Translational Vision Science & Technology, 2017
Purpose: We evaluated threshold saccadic vector optokinetic perimetry (SVOP) and compared results... more Purpose: We evaluated threshold saccadic vector optokinetic perimetry (SVOP) and compared results to standard automated perimetry (SAP). Methods: A cross-sectional study was done including 162 subjects (103 with glaucoma and 59 healthy subjects) recruited at a university hospital. All subjects underwent SAP and threshold SVOP. SVOP uses an eye tracker to monitor eye movement responses to stimuli and determines if stimuli have been perceived based on the vector of the gaze response. The test pattern used was equivalent to SAP 24-2 and stimuli were presented at Goldmann III. Average and pointwise sensitivity values obtained from both tests were compared using Pearson's correlation coefficient. Two versions of SVOP were evaluated. Results: A total of 124 tests were performed with SAP and SVOP version 2. There was excellent agreement between mean threshold values obtained using SVOP and SAP (r ¼ 0.95, P , 0.001). Excluding the blind spot, correlation between SVOP and SAP individual test point sensitivity ranged from 0.61 to 0.90, with 48 of 54 (89%) test points. 0.70. Overall SVOP showed good repeatability with a Pearson correlation of 0.88. The repeatability on a point-by-point basis ranged from 0.66 to 0.98, with 45 of 54 points (83%). 0.80. Repeatability of SAP was 0.87, ranging from 0.69 to 0.96, with 47 of 54 (87%) points. 0.80. Conclusion: Eye-tracking perimetry is repeatable and compares well with the current gold standard of SAP. The technique has advantages over conventional perimetry and could be useful for evaluating glaucomatous visual field loss, particularly in patients who may struggle with conventional perimetry.
Developmental medicine and child neurology, Jan 29, 2017
To explore the relationship between raised intracranial pressure (RICP) and retinal haemorrhages ... more To explore the relationship between raised intracranial pressure (RICP) and retinal haemorrhages in traumatic and non-traumatic childhood encephalopathies. A prospective study of 112 children (35 females and 77 males, age range 0.01mo-17y 8.3mo; mean 5y 8.6mo, median 4y 5.6mo) included 57 accidental traumatic brain injuries (ATBIs), 21 inflicted traumatic brain injuries (ITBIs), and 34 non-traumatic encephalopathy cases. Measurements included intracranial pressure (ICP), cerebral perfusion pressure, pressure-time index of ICP, and number, zone, and layer of retinal haemorrhages on retinal imaging. Group I had measured elevated ICP (n=42), Group II had clinical and/or radiological signs of RICP (n=21), and Group III had normal ICP (n=49). In the combined Groups I and II, 38% had retinal haemorrhages. Multiple logistic regression confirmed that the presence of retinal haemorrhages was significantly related to the presence of RICP independent of age and aetiology; however, the occurren...
Translational Vision Science & Technology, 2016
To evaluate feasibility, accuracy, and repeatability of suprathreshold Saccadic Vector Optokineti... more To evaluate feasibility, accuracy, and repeatability of suprathreshold Saccadic Vector Optokinetic Perimetry (SVOP) by comparison with Humphrey Field Analyzer (HFA) perimetry. Methods: The subjects included children with suspected field defects (n ¼ 10, age 5-15 years), adults with field defects (n ¼ 33, age 39-78 years), healthy children (n ¼ 12, age 6-14 years), and healthy adults (n ¼ 30, age 16-61 years). The test protocol comprised repeat suprathreshold SVOP and HFA testing with the C-40 test pattern. Feasibility was assessed by protocol completeness. Sensitivity, specificity, and accuracy of SVOP was established by comparison with reliable HFA tests in two ways: (1) visual field pattern results (normal/abnormal), and (2) individual test point outcomes (seen/unseen). Repeatability of each test type was assessed using Cohen's kappa coefficient. Results: Of subjects, 82% completed a full protocol. Poor reliability of HFA testing in child patients limited the robustness of comparisons in this group. Sensitivity, specificity, and accuracy across all groups when analyzing the visual field pattern results was 90.9%, 88.5%, and 89.0%, respectively, and was 69.1%, 96.9%, and 95.0%, respectively, when analyzing the individual test points. Cohen's kappa coefficient for repeatability of SVOP and HFA was excellent (0.87 and 0.88, respectively) when assessing visual field pattern results, and substantial (0.62 and 0.74, respectively) when assessing test point outcomes. Conclusions: SVOP was accurate in this group of adults. Further studies are required to assess SVOP in child patient groups. Translational Relevance: SVOP technology is still in its infancy but is used in a number of centers. It will undergo iterative improvements and this study provides a benchmark for future iterations.
We report molecular genetic analysis of 42 affected individuals referred with a diagnosis of anir... more We report molecular genetic analysis of 42 affected individuals referred with a diagnosis of aniridia who previously screened as negative for intragenic PAX6 mutations. Of these 42, the diagnoses were 31 individuals with aniridia and 11 individuals referred with a diagnosis of Gillespie syndrome (iris hypoplasia, ataxia and mild to moderate developmental delay). Array-based comparative genomic hybridization identified six whole gene deletions: four encompassing PAX6 and two encompassing FOXC1. Six deletions with plausible cis-regulatory effects were identified: five that were 3' (telomeric) to PAX6 and one within a gene desert 5' (telomeric) to PITX2. Sequence analysis of the FOXC1 and PITX2 coding regions identified two plausibly pathogenic de novo FOXC1 missense mutations (p.Pro79Thr and p.Leu101Pro). No intragenic mutations were detected in PITX2. FISH mapping in an individual with Gillespie-like syndrome with an apparently balanced X;11 reciprocal translocation revealed ...
The safest ranges of oxygen saturation in preterm infants have been the subject of debate. In two... more The safest ranges of oxygen saturation in preterm infants have been the subject of debate. In two trials, conducted in Australia and the United Kingdom, infants born before 28 weeks' gestation were randomly assigned to either a lower (85 to 89%) or a higher (91 to 95%) oxygen-saturation range. During enrollment, the oximeters were revised to correct a calibration-algorithm artifact. The primary outcome was death or disability at a corrected gestational age of 2 years; this outcome was evaluated among infants whose oxygen saturation was measured with any study oximeter in the Australian trial and those whose oxygen saturation was measured with a revised oximeter in the U.K. trial. After 1135 infants in Australia and 973 infants in the United Kingdom had been enrolled in the trial, an interim analysis showed increased mortality at a corrected gestational age of 36 weeks, and enrollment was stopped. Death or disability in the Australian trial (with all oximeters included) occurred ...
BACKGROUND:Retinal hemorrhages (RHs) occur in inflicted traumatic brain injury (ITBI), accidental... more BACKGROUND:Retinal hemorrhages (RHs) occur in inflicted traumatic brain injury (ITBI), accidental traumatic brain injury (ATBI), and some medical conditions, although the reported number, distribution, type, and frequency vary greatly between these different etiologies. We hypothesize that these RH characteristics reliably help to distinguish ITBI from ATBI and nontraumatic etiologies.METHODS:A 6-year prospective observational study using wide-field retinal imaging (RetCam) was conducted within 24 hours of admission to PICU, on serially recruited children with traumatic and nontraumatic encephalopathies. “Definite” and “probable” ITBI cases were confirmed by multiagency child protection case conferences. Image analysis used digital color and grayscale images for retinal “zoning” and “layering” of hemorrhages.RESULTS:Significant differences were found between the mean numbers of hemorrhages in ATBI/ITBI, and ITBI/nontraumatic etiologies for the 3 retinal zones (range, P = .003–.009) ...
Journal of Pediatric Ophthalmology & Strabismus, 2012
Purpose: To investigate nystagmus and other visual system abnormalities among children exposed to... more Purpose: To investigate nystagmus and other visual system abnormalities among children exposed to opiates and benzodiazepines in utero. Methods: Retrospective case series comprising clinical examination and case note review of 25 children with nystagmus and reduced vision who were exposed to controlled drugs during pregnancy. Results: Twenty-four children were exposed to opiates, of whom 13 were also exposed to diazepam. One child was exposed to diazepam alone. All children had horizontal nystagmus, which was either fine pendular or jerk type. The nystagmus had a latent element in 4 children and 8 adopted a compensatory head posture. Where the time of onset of nystagmus was known, it was always prior to 6 months of age. At least 9 children (36%) had delayed visual maturation. The mean initial logarithm of the minimum angle of resolution binocular best-corrected visual acuity (BCVA) was 0.54 at an average of 22 months of age. Thirteen children were followed up for 6 months or longer ...
We report an epidemiological and genetic study attempting complete ascertainment of subjects with... more We report an epidemiological and genetic study attempting complete ascertainment of subjects with microphthalmia, anophthalmia, and coloboma (MAC) born in Scotland during a 16 year period beginning on 1 January 1981. A total of 198 cases were confirmed giving a minimum live birth prevalence of 19 per 100 000. One hundred and twenty-two MAC cases (61.6%) from 115 different families were clinically examined and detailed pregnancy, medical, and family histories obtained. A simple, rational, and apparently robust classification of the eye phenotype was developed based on the presence or absence of a defect in closure of the optic (choroidal) fissure. A total of 85/122 (69.7%) of cases had optic fissure closure defects (OFCD), 12/122 (9.8%) had non-OFCD, and 25/122 (20.5%) had defects that were unclassifiable owing to the severity of the corneal or anterior chamber abnormality. Segregation analysis assuming single and multiple incomplete ascertainment, respectively, returned a sib recurrence risk of 6% and 10% in the whole group and 8.1% and 13.3% in the OFCD subgroup. Significant recurrence risks were found in both unilateral and bilateral disease. In four families, one parent had an OFCD, two of which were new diagnoses in asymptomatic subjects. All recurrences in first degree relatives occurred in the OFCD group with a single first cousin recurrence seen in the non-OFCD group. A total of 84/122 of the MAC cases were screened for mutations in the coding regions of PAX6, CHX10, and SIX3. No pathogenic mutations were identified in the OFCD cases. A single PAX6 homeodomain missense mutation was identified in a subject with partial aniridia that had been initially misclassified as coloboma.
Aims-To compare the relative antiinflammatory potency and safety of topical diclofenac-gentamicin... more Aims-To compare the relative antiinflammatory potency and safety of topical diclofenac-gentamicin with betamethasone-neomycin following strabismus surgery. Methods-A single centre, single observer, prospective, randomised, and double masked clinical trial of 25 children undergoing bilateral symmetrical horizontal strabismus surgery was carried out. One eye received diclofenacgentamicin and the contralateral eye received betamethasone-neomycin; both treatments were instilled four times a day for 4 weeks postoperatively. Ocular inflammation was assessed at 1 and 4 weeks postoperatively, objectively by comparison with a photographic chart and subjectively by questionnaire. Results-There was no statistically significant diVerence in the rate of resolution of the inflammatory response between each group at both visits. Conclusion-Diclofenac appears to be as eVective as betamethasone in controlling postoperative inflammation following strabismus surgery and may oVer a safer alternative to the use of topical steroids.
A photometric study of the effect of pupil dilatation on Nd:YAG laser iridotomy area was performe... more A photometric study of the effect of pupil dilatation on Nd:YAG laser iridotomy area was performed in 21 eyes of 21 patients. The iridotomy area was 0-075 (0.055) mm'2 (mean
We have investigated the occurrence of attenuated extracolonic manifestations (AEMs) of familial ... more We have investigated the occurrence of attenuated extracolonic manifestations (AEMs) of familial adenomatous polyposis (FAP) in patients with non-polyposis colorectal cancer. In a prospective case-control study, we observed that significantly more colorectal cancer patients exhibited AEM than did age and sexmatched controls (19.5% vs 7.5%, P<0.004). However patients with AEMs do not have occult FAP, as we found no heterozygous adenomatous polyposis coli (APC) gene mutations despite extensive analysis of constitutional DNA. Genome-wide DNA replication errors (RERs) occur in a proportion of colorectal cancers, particularly right-sided lesions and in almost all tumours from hereditary non-polyposis colorectal cancer (HNPCC) patients. As AEMs have been reported in familial colon cancer cases, we investigated the relationship of AEMs to tumour RER phenotype. There was indeed an excess of AEMs in patients with rightsided tumours (30.2% of 53 patients vs 14.7% of 116 patients, P<0.03) and in those with RER tumours (3 out of 12 patients with RER tumours vs none out of 21 patients with non-RER tumours, P<0.05). Two patients with AEM were from HNPCC families compared with none of those without AEM (P< 0.05). The association of AEMs with colorectal cancer is intriguing, and we speculate that it may be a manifestation of mutational mosaicism of the APC gene, perhaps associated with a constitutional defect in DNA mismatch pair.
Translational Vision Science & Technology, 2021
To examine the feasibility of saccadic vector optokinetic perimetry (SVOP), an automated eye trac... more To examine the feasibility of saccadic vector optokinetic perimetry (SVOP), an automated eye tracking perimeter, as a tool for visual field (VF) assessment in infants. Methods: Thirteen healthy infants aged between 3.5 and 12.0 months were tested binocularly using an adapted SVOP protocol. SVOP uses eye tracking technology to measure gaze responses to stimuli presented on a computer screen. Modifications of SVOP for testing infants included adjusting the fixation target to display a short animation, increasing the stimulus size to equivalent to Goldmann V, and introducing a tiered test pattern strategy. Binocular, single-quadrant confrontation VF testing and Keeler preferential looking cards visual acuity testing was also performed. Results: Using multiple test attempts when required, all but the youngest infant (12 of 13 [92.3%]) successfully completed a 4-point screening test. Seven infants (53.8%) successfully completed the 12-point test, four (30.8%) successfully completed the 20-point test, and three (23.1%) successfully completed the 40-point test. The effect of multiple test attempts and the complexity of the test pattern (number of test points) on performance was investigated, including test completion rate, percentage of correctly seen stimuli, and average time per tested stimulus. Conclusions: The modified SVOP test strategy allowed successful assessment of binocular VFs in healthy infants. Future data collection from larger cohorts of infants is needed to derive normative limits of detection and assess accuracy in detecting and monitoring infant VF abnormalities. Translational Relevance: Eye tracking perimetry may provide a useful method of automated VF assessment in infants.
To explore the feasibility of using Saccadic Vector Optokinetic Perimetry (SVOP) to differentiate... more To explore the feasibility of using Saccadic Vector Optokinetic Perimetry (SVOP) to differentiate glaucomatous and healthy eyes. A prospective case–control study was performed using a convenience sample recruited from a single university glaucoma clinic and a group of healthy controls. SVOP and standard automated perimetry (SAP) was performed with testing order randomised. The reference standard was a diagnosis of glaucoma based a comprehensive ophthalmic examination and abnormality on standard automated perimetry (SAP). The index test was SVOP. 31 patients with glaucoma and 24 healthy subjects were included. Mean SAP mean deviation (MD) in those with glaucoma was − 8.7 ± 7.4 dB, with mean SAP and SVOP sensitivities of 23.3 ± 0.9 dB and 22.1 ± 4.3 dB respectively. Participants with glaucoma were significantly older. On average, SAP sensitivity was 1.2 ± 1.4 dB higher than SVOP (95% limits of agreement = − 1.6 to 4.0 dB). SVOP sensitivity had good ability to differentiate healthy and...
Conclusions An ICU stay can have significant, long-lasting impacts on young people and their fami... more Conclusions An ICU stay can have significant, long-lasting impacts on young people and their families. This is the first pan-European survey to investigate ICU care for this group. We identified significant variation in adherence to quality standards. Some of this may be culturally influenced but there are also differences in less obviously controversial measures e.g. DVT prophylaxis. Further qualitative work is planned.
Background To examine the speed and accuracy of saccadic eye movements during a novel eye trackin... more Background To examine the speed and accuracy of saccadic eye movements during a novel eye tracking threshold visual field assessment and determine whether eye movement parameters may improve ability to detect glaucoma. Methods A prospective study including both eyes of 31 patients with glaucoma and 23 controls. Standard automated perimetry (SAP) and eye tracking perimetry (saccadic vector optokinetic perimetry, SVOP) was performed. SVOP provided data on threshold sensitivity, saccade latency, and two measures of accuracy of saccades (direction bias and amplitude bias). The relationship between eye movement parameters and severity of glaucoma was examined and Receiver Operating Characteristic curves were used to assess ability to detect glaucoma. Results Patients with glaucoma had significantly slower saccades (602.9 ± 50.0 ms versus 578.3 ± 44.6 ms for controls, P = 0.009) and reduced saccade accuracy (direction bias = 7.4 ± 1.8 versus 6.5 ± 1.5 degrees, P = 0.006). There was a sign...
ObjectiveTo determine the time to resolution of different-layered retinal haemorrhages (RHs), and... more ObjectiveTo determine the time to resolution of different-layered retinal haemorrhages (RHs), and to describe the main patterns of their resolution in a group of children with encephalopathies.Methods and analysisFrom a prospective study of 114 children with traumatic and non-traumatic encephalopathies, 429 selected individual RHs (iRHs) from 18 children were serially imaged from admission using a RetCam. Photoshop and Scion Imaging software allowed calculation of RH area in pixels.ResultsTwo patterns of the resolution were recognised on the basis of area measurements: a progressive decrease (pattern A, 60% of iRHs), and a form of asymmetrical decay in which iRHs first increased in size before then progressively decreasing (pattern B, 35% of iRHs). Within the pattern A group, the Kaplan-Meier median survival time (MST) (95% CI) was 10 (9.3 to 10.7) days for intra-RHs (IRHs) and 38 (10.8 to 65.2) days for pre-RHs (PRHs), log rank (Mantel-Cox) p=0.001. The mean percentage reduction in...
To determine the ability of Saccadic Vector Optokinetic Perimetry (SVOP) to detect and characteri... more To determine the ability of Saccadic Vector Optokinetic Perimetry (SVOP) to detect and characterise visual field defects in children with brain tumours using eye-tracking technology, as current techniques for assessment of visual fields in young children can be subjective and lack useful detail. Case-series study of children receiving treatment and follow-up for brain tumours at the Royal Hospital for Sick Children in Edinburgh from April 2008 to August 2013. Patients underwent SVOP testing and the results were compared with clinically expected visual field patterns determined by a consensus panel after review of clinical findings, neuroimaging, and where possible other forms of visual field assessment. Sixteen patients participated in this study (mean age of 7.2 years; range 2.9-15 years; 7 male, 9 female). Twelve children (75%) successfully performed SVOP testing. SVOP had a sensitivity of 100% and a specificity of 50% (positive predictive value of 80% and negative predictive valu...
Translational Vision Science & Technology, 2017
Purpose: We compared patterns of visual field loss detected by standard automated perimetry (SAP)... more Purpose: We compared patterns of visual field loss detected by standard automated perimetry (SAP) to saccadic vector optokinetic perimetry (SVOP) and examined patient perceptions of each test. Methods: A cross-sectional study was done of 58 healthy subjects and 103 with glaucoma who were tested using SAP and two versions of SVOP (v1 and v2). Visual fields from both devices were categorized by masked graders as: 0, normal; 1, paracentral defect; 2, nasal step; 3, arcuate defect; 4, altitudinal; 5, biarcuate; and 6, end-stage field loss. SVOP and SAP classifications were cross-tabulated. Subjects completed a questionnaire on their opinions of each test. Results: We analyzed 142 (v1) and 111 (v2) SVOP and SAP test pairs. SVOP v2 had a sensitivity of 97.7% and specificity of 77.9% for identifying normal versus abnormal visual fields. SAP and SVOP v2 classifications showed complete agreement in 54% of glaucoma patients, with a further 23% disagreeing by one category. On repeat testing, 86% of SVOP v2 classifications agreed with the previous test, compared to 91% of SAP classifications; 71% of subjects preferred SVOP compared to 20% who preferred SAP. Conclusions: Eye-tracking perimetry can be used to obtain threshold visual field sensitivity values in patients with glaucoma and produce maps of visual field defects, with patterns exhibiting close agreement to SAP. Patients preferred eye-tracking perimetry compared to SAP. Translational relevance: This first report of threshold eye tracking perimetry shows good agreement with conventional automated perimetry and provides a benchmark for future iterations.
Translational Vision Science & Technology, 2017
Purpose: We evaluated threshold saccadic vector optokinetic perimetry (SVOP) and compared results... more Purpose: We evaluated threshold saccadic vector optokinetic perimetry (SVOP) and compared results to standard automated perimetry (SAP). Methods: A cross-sectional study was done including 162 subjects (103 with glaucoma and 59 healthy subjects) recruited at a university hospital. All subjects underwent SAP and threshold SVOP. SVOP uses an eye tracker to monitor eye movement responses to stimuli and determines if stimuli have been perceived based on the vector of the gaze response. The test pattern used was equivalent to SAP 24-2 and stimuli were presented at Goldmann III. Average and pointwise sensitivity values obtained from both tests were compared using Pearson's correlation coefficient. Two versions of SVOP were evaluated. Results: A total of 124 tests were performed with SAP and SVOP version 2. There was excellent agreement between mean threshold values obtained using SVOP and SAP (r ¼ 0.95, P , 0.001). Excluding the blind spot, correlation between SVOP and SAP individual test point sensitivity ranged from 0.61 to 0.90, with 48 of 54 (89%) test points. 0.70. Overall SVOP showed good repeatability with a Pearson correlation of 0.88. The repeatability on a point-by-point basis ranged from 0.66 to 0.98, with 45 of 54 points (83%). 0.80. Repeatability of SAP was 0.87, ranging from 0.69 to 0.96, with 47 of 54 (87%) points. 0.80. Conclusion: Eye-tracking perimetry is repeatable and compares well with the current gold standard of SAP. The technique has advantages over conventional perimetry and could be useful for evaluating glaucomatous visual field loss, particularly in patients who may struggle with conventional perimetry.
Developmental medicine and child neurology, Jan 29, 2017
To explore the relationship between raised intracranial pressure (RICP) and retinal haemorrhages ... more To explore the relationship between raised intracranial pressure (RICP) and retinal haemorrhages in traumatic and non-traumatic childhood encephalopathies. A prospective study of 112 children (35 females and 77 males, age range 0.01mo-17y 8.3mo; mean 5y 8.6mo, median 4y 5.6mo) included 57 accidental traumatic brain injuries (ATBIs), 21 inflicted traumatic brain injuries (ITBIs), and 34 non-traumatic encephalopathy cases. Measurements included intracranial pressure (ICP), cerebral perfusion pressure, pressure-time index of ICP, and number, zone, and layer of retinal haemorrhages on retinal imaging. Group I had measured elevated ICP (n=42), Group II had clinical and/or radiological signs of RICP (n=21), and Group III had normal ICP (n=49). In the combined Groups I and II, 38% had retinal haemorrhages. Multiple logistic regression confirmed that the presence of retinal haemorrhages was significantly related to the presence of RICP independent of age and aetiology; however, the occurren...
Translational Vision Science & Technology, 2016
To evaluate feasibility, accuracy, and repeatability of suprathreshold Saccadic Vector Optokineti... more To evaluate feasibility, accuracy, and repeatability of suprathreshold Saccadic Vector Optokinetic Perimetry (SVOP) by comparison with Humphrey Field Analyzer (HFA) perimetry. Methods: The subjects included children with suspected field defects (n ¼ 10, age 5-15 years), adults with field defects (n ¼ 33, age 39-78 years), healthy children (n ¼ 12, age 6-14 years), and healthy adults (n ¼ 30, age 16-61 years). The test protocol comprised repeat suprathreshold SVOP and HFA testing with the C-40 test pattern. Feasibility was assessed by protocol completeness. Sensitivity, specificity, and accuracy of SVOP was established by comparison with reliable HFA tests in two ways: (1) visual field pattern results (normal/abnormal), and (2) individual test point outcomes (seen/unseen). Repeatability of each test type was assessed using Cohen's kappa coefficient. Results: Of subjects, 82% completed a full protocol. Poor reliability of HFA testing in child patients limited the robustness of comparisons in this group. Sensitivity, specificity, and accuracy across all groups when analyzing the visual field pattern results was 90.9%, 88.5%, and 89.0%, respectively, and was 69.1%, 96.9%, and 95.0%, respectively, when analyzing the individual test points. Cohen's kappa coefficient for repeatability of SVOP and HFA was excellent (0.87 and 0.88, respectively) when assessing visual field pattern results, and substantial (0.62 and 0.74, respectively) when assessing test point outcomes. Conclusions: SVOP was accurate in this group of adults. Further studies are required to assess SVOP in child patient groups. Translational Relevance: SVOP technology is still in its infancy but is used in a number of centers. It will undergo iterative improvements and this study provides a benchmark for future iterations.
We report molecular genetic analysis of 42 affected individuals referred with a diagnosis of anir... more We report molecular genetic analysis of 42 affected individuals referred with a diagnosis of aniridia who previously screened as negative for intragenic PAX6 mutations. Of these 42, the diagnoses were 31 individuals with aniridia and 11 individuals referred with a diagnosis of Gillespie syndrome (iris hypoplasia, ataxia and mild to moderate developmental delay). Array-based comparative genomic hybridization identified six whole gene deletions: four encompassing PAX6 and two encompassing FOXC1. Six deletions with plausible cis-regulatory effects were identified: five that were 3' (telomeric) to PAX6 and one within a gene desert 5' (telomeric) to PITX2. Sequence analysis of the FOXC1 and PITX2 coding regions identified two plausibly pathogenic de novo FOXC1 missense mutations (p.Pro79Thr and p.Leu101Pro). No intragenic mutations were detected in PITX2. FISH mapping in an individual with Gillespie-like syndrome with an apparently balanced X;11 reciprocal translocation revealed ...
The safest ranges of oxygen saturation in preterm infants have been the subject of debate. In two... more The safest ranges of oxygen saturation in preterm infants have been the subject of debate. In two trials, conducted in Australia and the United Kingdom, infants born before 28 weeks' gestation were randomly assigned to either a lower (85 to 89%) or a higher (91 to 95%) oxygen-saturation range. During enrollment, the oximeters were revised to correct a calibration-algorithm artifact. The primary outcome was death or disability at a corrected gestational age of 2 years; this outcome was evaluated among infants whose oxygen saturation was measured with any study oximeter in the Australian trial and those whose oxygen saturation was measured with a revised oximeter in the U.K. trial. After 1135 infants in Australia and 973 infants in the United Kingdom had been enrolled in the trial, an interim analysis showed increased mortality at a corrected gestational age of 36 weeks, and enrollment was stopped. Death or disability in the Australian trial (with all oximeters included) occurred ...
BACKGROUND:Retinal hemorrhages (RHs) occur in inflicted traumatic brain injury (ITBI), accidental... more BACKGROUND:Retinal hemorrhages (RHs) occur in inflicted traumatic brain injury (ITBI), accidental traumatic brain injury (ATBI), and some medical conditions, although the reported number, distribution, type, and frequency vary greatly between these different etiologies. We hypothesize that these RH characteristics reliably help to distinguish ITBI from ATBI and nontraumatic etiologies.METHODS:A 6-year prospective observational study using wide-field retinal imaging (RetCam) was conducted within 24 hours of admission to PICU, on serially recruited children with traumatic and nontraumatic encephalopathies. “Definite” and “probable” ITBI cases were confirmed by multiagency child protection case conferences. Image analysis used digital color and grayscale images for retinal “zoning” and “layering” of hemorrhages.RESULTS:Significant differences were found between the mean numbers of hemorrhages in ATBI/ITBI, and ITBI/nontraumatic etiologies for the 3 retinal zones (range, P = .003–.009) ...
Journal of Pediatric Ophthalmology & Strabismus, 2012
Purpose: To investigate nystagmus and other visual system abnormalities among children exposed to... more Purpose: To investigate nystagmus and other visual system abnormalities among children exposed to opiates and benzodiazepines in utero. Methods: Retrospective case series comprising clinical examination and case note review of 25 children with nystagmus and reduced vision who were exposed to controlled drugs during pregnancy. Results: Twenty-four children were exposed to opiates, of whom 13 were also exposed to diazepam. One child was exposed to diazepam alone. All children had horizontal nystagmus, which was either fine pendular or jerk type. The nystagmus had a latent element in 4 children and 8 adopted a compensatory head posture. Where the time of onset of nystagmus was known, it was always prior to 6 months of age. At least 9 children (36%) had delayed visual maturation. The mean initial logarithm of the minimum angle of resolution binocular best-corrected visual acuity (BCVA) was 0.54 at an average of 22 months of age. Thirteen children were followed up for 6 months or longer ...
We report an epidemiological and genetic study attempting complete ascertainment of subjects with... more We report an epidemiological and genetic study attempting complete ascertainment of subjects with microphthalmia, anophthalmia, and coloboma (MAC) born in Scotland during a 16 year period beginning on 1 January 1981. A total of 198 cases were confirmed giving a minimum live birth prevalence of 19 per 100 000. One hundred and twenty-two MAC cases (61.6%) from 115 different families were clinically examined and detailed pregnancy, medical, and family histories obtained. A simple, rational, and apparently robust classification of the eye phenotype was developed based on the presence or absence of a defect in closure of the optic (choroidal) fissure. A total of 85/122 (69.7%) of cases had optic fissure closure defects (OFCD), 12/122 (9.8%) had non-OFCD, and 25/122 (20.5%) had defects that were unclassifiable owing to the severity of the corneal or anterior chamber abnormality. Segregation analysis assuming single and multiple incomplete ascertainment, respectively, returned a sib recurrence risk of 6% and 10% in the whole group and 8.1% and 13.3% in the OFCD subgroup. Significant recurrence risks were found in both unilateral and bilateral disease. In four families, one parent had an OFCD, two of which were new diagnoses in asymptomatic subjects. All recurrences in first degree relatives occurred in the OFCD group with a single first cousin recurrence seen in the non-OFCD group. A total of 84/122 of the MAC cases were screened for mutations in the coding regions of PAX6, CHX10, and SIX3. No pathogenic mutations were identified in the OFCD cases. A single PAX6 homeodomain missense mutation was identified in a subject with partial aniridia that had been initially misclassified as coloboma.
Aims-To compare the relative antiinflammatory potency and safety of topical diclofenac-gentamicin... more Aims-To compare the relative antiinflammatory potency and safety of topical diclofenac-gentamicin with betamethasone-neomycin following strabismus surgery. Methods-A single centre, single observer, prospective, randomised, and double masked clinical trial of 25 children undergoing bilateral symmetrical horizontal strabismus surgery was carried out. One eye received diclofenacgentamicin and the contralateral eye received betamethasone-neomycin; both treatments were instilled four times a day for 4 weeks postoperatively. Ocular inflammation was assessed at 1 and 4 weeks postoperatively, objectively by comparison with a photographic chart and subjectively by questionnaire. Results-There was no statistically significant diVerence in the rate of resolution of the inflammatory response between each group at both visits. Conclusion-Diclofenac appears to be as eVective as betamethasone in controlling postoperative inflammation following strabismus surgery and may oVer a safer alternative to the use of topical steroids.
A photometric study of the effect of pupil dilatation on Nd:YAG laser iridotomy area was performe... more A photometric study of the effect of pupil dilatation on Nd:YAG laser iridotomy area was performed in 21 eyes of 21 patients. The iridotomy area was 0-075 (0.055) mm'2 (mean
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Papers by Brian Fleck