Biomedical subjects

Carol Westall

Publications and source records attributed to Carol Westall.

9 recordsLinked to original sources

PubMed2007

Enolase autoantibodies and retinal function in multiple sclerosis patients.

BACKGROUND: Electroretinographic (ERG) abnormalities have been reported in multiple sclerosis (MS), as well as the presence of circulating antiretinal antibodies. We and others have reported cases of impaired vision and diminished ERGs in MS patients with alpha-enolase autoantibodies. Anti-enolase antibodies have been implicated in autoimmune retinopathy. We performed this study to further explore the relationship between antiretinal antibodies and ERG changes in patients with MS. METHODS: Patients with clinically definite MS and normal visual acuity were recruited for this study, along with healthy controls. All patients and controls had ERG testing done according to ISCEV standards. Patient and control sera were analyzed for the presence of antiretinal antibodies using Western blot and ELISA techniques, and HLA class II typing was performed using polymerase chain reaction. RESULTS: We found a statistically significant difference between MS patients and controls in the rod-cone b-wave implicit time (p < 0.005). We found autoantibodies against alpha-enolase in 38% of MS patients and 11% of controls (p < 0.02). There was no statistically significant difference between ERG parameters of MS patients with alpha-enolase autoantibodies compared to those without alpha-enolase antibodies. Furthermore, the presence of alpha-enolase did not associate with a particular HLA haplotype. CONCLUSIONS: Factors affecting the retina other than alpha-enolase antibodies may account for the delayed rod-cone b-wave implicit times observed in MS patients in this study. Anti-enolase antibodies are likely an epiphenomenon of autoimmune disease, and are not causing retinopathy in MS patients with normal visual acuity. However, the possibility of rare cases of patients with pathogenic alpha-enolase autoantibodies can not be excluded. The pathogenic contribution of these antibodies in MS patients with visual impairment deserves further investigation.

Adult↗

PubMed2006

Electroretinographic abnormalities in multiple sclerosis: possible role for retinal autoantibodies.

BACKGROUND: Multiple sclerosis (MS) has been associated with inflammation of the uveal tract, suggesting an immunological link between the uvea and central nervous system (CNS) in this disease. The retina is embryologically derived from the CNS, and it is conceivable that retinal antigens may also be recognized by the immune system in MS. Electroretinographic abnormalities, as well as retinal autoantibodies, have previously been described in MS. We performed this study to further explore the possibility of retinal autoimmunity in MS. METHODS: Thirty-four patients with clinically definite MS and thirty-seven healthy controls were recruited. All patients and controls had standard electroretinographic (ERG) testing done, as well as a brightflash ERG protocol to isolate rod photoreceptor function. Patient and control sera were analyzed for the presence of antiretinal antibodies using Western blot techniques. RESULTS: We found statistically significant differences between MS patients and controls in four ERG parameters. In the MS group, implicit times of the rod-cone b-wave response, cone b-wave response, and rod photoreceptor response were increased. The amplitudes of the photopic oscillatory potentials were reduced in the MS group. Patients with the highest titres of retinal autoantibodies had delayed rod-cone b-wave implicit times and diminished photopic oscillatory potential amplitudes. CONCLUSIONS: We report ERG evidence of retinal dysfunction in patients with MS. We also report the first use of the brightflash ERG protocol in MS, which demonstrated rod photoreceptor dysfunction. Patients with the highest antiretinal antibody titres had abnormal ERG recordings. Retinal autoimmunity is a possible explanation for these observed ERG abnormalities in MS patients.

Adult↗

PubMed2006

Utility of the National Eye Institute VFQ-25 questionnaire in a heterogeneous group of multiple sclerosis patients.

PURPOSE: To investigate the utility of the 25-Item National Eye Institute Visual Function Questionnaire (VFQ-25) in assessing visual function in a heterogeneous group of multiple sclerosis (MS) patients and to identify correlations of VFQ-25 scores with clinically relevant objective visual parameters. DESIGN: Comparative cohort study. METHODS: The VFQ-25 was distributed to 34 patients with clinically definite MS. Patients underwent a comprehensive ophthalmic examination, including Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (V(A)), Pelli-Robson contrast sensitivity (CS), Humphrey visual field 30 to 2 (HVF), and Farnsworth-Munsell 100-Hue color vision (100-Hue). Expanded Disability Status Scores (EDSS) were recorded for each patient. Comparative analyses using chi2 tests and t tests were performed. Spearman rank correlation coefficients were computed to identify relationships between VFQ-25 scores and the aforementioned visual parameters. RESULTS: In comparison with a published reference group without ocular disease, MS patients had considerably worse VFQ-25 composite scores (P < .01), being similar to published cohorts of glaucoma and cataract patients. VFQ-25 composite scores were found to be modestly and significantly correlated with several clinical parameters, including: V(A) (r = -0.63, P < .001), CS (r = 0.60, P < .001), HVF (r = 0.53, P = .003), and 100-Hue (r = -0.48, P = .01). EDSS scores, the use of disease modifying agents, and having a history of previous optic neuritis did not correlate significantly with VFQ-25 composite scores. CONCLUSIONS: The VFQ-25 questionnaire is a sensitive and useful tool in assessing visual function in MS patients. Such patients have quality of life indices similar to glaucoma and cataract patients, underscoring the significance of visual symptoms in MS.

Adult↗

PubMed2006

Saccadic adaptation in Chiari type II malformation.

BACKGROUND: Saccadic adaptation corrects errors in saccadic amplitude. Experimentally-induced saccadic adaptation provides a method for studying motor learning. The cerebellum is a major participant in saccadic adaptation. Chiari type II malformation (CII) is a developmental deformity of the cerebellum and brainstem that is associated with spina bifida. We investigated the effects of CII on saccadic adaptation. METHOD: We measured eye movements using an infrared eye tracker in 21 subjects with CII (CII group) and 39 typically developing children (control group), aged 8-19 years. Saccadic adaptation was induced experimentally using targets that stepped horizontally 120 to the right and then stepped backward 3 degrees during saccades. RESULTS: Saccadic adaptation was achieved at the end of the adaptation phase in participants in each group. Saccadic amplitude gain decreased by 6.9% in the CII group and 9.3% in the control group. The groups did not differ significantly (p = 0.27). Amplitude gain reduction was significantly less in the CII participants who had multiple shunt revisions. Regression analyses revealed no effects of spinal lesion level, presence of nystagmus, or cerebellar vermis dysmorphology on saccadic adaptation. CONCLUSION: The neural circuits involved in saccadic adaptation appear to be functionally intact in CII.

Adaptation, Physiological↗

PubMed2006

Saccadic adaptation in children.

Saccades are fast-orienting eye movements. Saccadic adaptation, a form of motor learning, is a corrective change in the amplitude of saccades in response to error. The aim of the study was to ascertain whether saccadic adaptation occurs in typically developing children. We recorded saccades with an infrared eye tracker in 39 children, aged 8 to 19 years, at baseline to 12-degree horizontal target steps and after an adaptive task. During the adaptive task, a saccadic hypometric error was induced. This task consisted of 200 12-degree target steps that stepped backward 3 degrees during the initial saccade and without the participants' awareness. The initial saccade triggered the back-step. This paradigm required a corrective reduction of the amplitude of the initial saccades in response to the induced error. Saccadic adaptation was achieved in 26 participants, whose mean saccadic amplitudes decreased by 13% (P < .05). Saccadic adaptation was not influenced by age. We conclude that children as young as 8 years old have established functions of the neural circuits responsible for the motor learning required for saccadic adaptation.

Adaptation, Physiological↗

PubMed2005

Saccades in children.

Saccades are necessary for optimal vision. Little is known about saccades in children. We recorded saccades using an infrared eye tracker in 39 children, aged 8-19 years. Participants made saccades to visual targets that stepped 10 degrees or 15 degrees horizontally and 5 degrees or 10 degrees vertically at unpredictable time intervals. Saccadic latency decreased significantly with increasing age, while saccadic gain and peak velocity did not vary with age. Saccadic gains and peak velocities in children are similar to reported adult values. This implies maturity of the neural circuits responsible for making saccades accurate and fast. Saccade latency decreases as the brain matures.

Adolescent↗

PubMed2005

Ocular phenotypes of three genetic variants of Bardet-Biedl syndrome.

Bardet-Biedl syndrome is a genetically heterogeneous multisystem disorder that causes severe visual impairment. Retinitis pigmentosa (RP), hypogonadism, digit and renal anomalies, obesity, and a variable degree of mental retardation characterize the disorder. Eight different loci have been identified on 2q31(BBS5), 3p13 (BBS3), 4q27 (BBS7), 11q13 (BBS1), 14q32 (BBS8), 15q22.3 (BBS4), 16q21 (BBS2), and 20p12 (BBS6). The ocular manifestations of Bardet-Biedl syndrome include an early and severe rod-cone dystrophy causing legal blindness in the second decade. Features of systemic phenotypic variability were proposed to distinguish patients mapped to either the BBS2, BBS3, or BBS4 loci but no phenotype-genotype correlation has been established for the ocular phenotype. We studied the three original families used for the identification of BBS2, BBS3, and BBS4 loci to define the ocular phenotypes of patients (n = 34) and obligate carriers (n = 32) using clinical examination and electroretinography (ERG). RP was severe and early in all cases. Myopia was associated with BBS3 and BBS4, but not BBS2. One patient with Bardet-Biedl syndrome also had iris and chorioretinal colobomata, features suggestive of Biemond syndrome.

Adolescent↗

PubMed2003

Visual acuity assessment: a comparison of two tests for measuring children's vision.

PURPOSE: To compare the Kay Picture Test and the logMAR Crowded Test. METHODS: Monocular visual acuity measurement was attempted on 103 paediatric subjects (aged between 2.5 and 16 years) attending eye clinics, using each of the visual acuity tests. RESULTS: The results obtained with the two tests were found to be comparable as confirmed with the Intra-class Correlation Coefficient, which revealed good agreement between the two tests. There was significant correlation between the visual acuity results measured and high conformity in the results from the weaker eye. There was a statistical difference in acuity scores between the tests; the Kay Picture Test gave a lower logMAR score with a mean difference of 0.08 logMAR. This 0.08 difference represents an actual difference of less than one line of acuity measure which can be considered to be clinically insignificant. There was a significant difference in the ability to perform each of the tests under binocular conditions, with more of the 50 children, aged 5 and under, able to perform the Kay Picture Test than the logMAR Crowded Test. CONCLUSIONS: The results obtained with the two tests are comparable. Both tests can be considered to be appropriate for amblyopia detection and the use of picture-based logMAR tests should be considered for younger children.

Adolescent↗

PubMed2002

VSX1: a gene for posterior polymorphous dystrophy and keratoconus.

We identified mutations in the VSX1 homeobox gene for two distinct inherited corneal dystrophies; posterior polymorphous dystrophy (PPD) and keratoconus. One of the mutation (R166W) responsible for keratoconus altered the homeodomain and impaired DNA binding. Two other sequence changes (L159M and G160D) were associated with keratoconus and PPD, respectively, and involved a region adjacent to the homeodomain. The G160D substitution, and a fourth defect affecting the highly conserved CVC domain (P247R), occurred in a child with very severe PPD who required a corneal transplant at 3 months of age. In this family, relatives with the G160D change alone had mild to moderate PPD, while P247R alone caused no corneal abnormalities. However, with either the G160D or P247R mutation, electroretinography detected abnormal function of the inner retina, where VSX1 is expressed. These data define the molecular basis of two important corneal dystrophies and reveal the importance of the CVC domain in the human retina.

Adult↗