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Biomedical subjects

R A Hitchings

Publications and source records attributed to R A Hitchings.

At least 19 recordsLinked to original sources
PubMed2003

The phenotype of normal tension glaucoma patients with and without OPA1 polymorphisms.

AIM: Polymorphisms in OPA1, the gene responsible for autosomal dominant optic atrophy, were recently found to be strongly associated with normal tension glaucoma (NTG). The aim of this study was to determine whether OPA1 polymorphisms affect the phenotype of NTG patients. METHODS: A retrospective analysis was performed of 108 well characterised NTG patients who had been genotyped for OPA1 variations, and who had previously undergone automated perimetry and Heidelberg retina tomography (HRT). 25 NTG patients had the at-risk OPA1 genotype (IVS 8 +4 C/T; +32 T/C) and 83 NTG patients did not. Differences between groups were sought in a wide range of structural, psychophysical, and demographic factors. These included sex, age at diagnosis, family history of glaucoma, history of ischaemic risk factors and vasospasm, laterality of glaucoma, presenting and highest diurnal intraocular pressure (IOP), initial cup-disc (CD) ratio, baseline visual field global indices, and optic disc parameters as measured by HRT. For a subgroup of patients with at least 5 years of follow up and 10 visual field tests, pointwise linear regression analysis (PROGRESSOR for Windows software) was applied to the visual field series. RESULTS: There was no significant difference in the two groups with respect to sex, age at diagnosis, family history of glaucoma, history of ischaemic risk factors and vasospasm, or laterality of glaucoma. The comparison of IOP, CD ratio and visual field global indices, MD and CPSD in the two groups showed no significant difference. There were no differences in the mean values for any of the HRT parameters analysed. For the subgroup of patients with at least 5 years of follow up, there was also no significant difference in the number of patients with progressing locations, the mean number of progressing locations per subject, the mean slope of the progressing locations or the mean slope for whole visual field. CONCLUSIONS: The absence of phenotypic differences in normal tension glaucoma patients with and without the OPA1 polymorphisms IVS 8 +4 C/T; +32 T/C suggest that these OPA1 polymorphisms do not underlie any major phenotypic diversity in these patients.

Age of Onset↗
PubMed2003

Variability across the optic nerve head in scanning laser tomography.

AIM: To characterise measurement variability in scanning laser tomography of the optic nerve head. METHODS: 21 normal and 21 glaucoma subjects underwent same and separate day test-retest Heidelberg retina tomograph imaging by the same and different operators. RESULTS: Rim area was most reproducible among parameters. Its variability tended to be highest temporally and increased (p<0.05) with testing involving different operators and visits. Nature of regional variability differed between glaucoma and normal eyes and between standard and 320 micro m reference planes. CONCLUSIONS: Rim area is reproducible and potentially useful as a marker of progression. Pattern of variability and the influence of different reference planes, disease, operators, and visits should be considered when evaluating progression.

Case-Control Studies↗
PubMed2003

Interobserver agreement on visual field progression in glaucoma: a comparison of methods.

AIM: To examine the level of agreement between clinicians in assessing progressive deterioration in visual field series using two different methods of analysis. METHODS: Each visual field series satisfied the following criteria: more than 19 reliable fields, patient age over 40 years, macular threshold at least 30 dB. The first three fields in each series were excluded to minimise learning effects: the following 16 were studied. Five expert clinicians assessed the progression status of each series using both standard Humphrey printouts and pointwise linear regression (PROGRESSOR). The level of agreement between the clinicians was evaluated using a weighted kappa statistic. RESULTS: A total of 432 tests comprising 27 visual field series of 16 tests each were assessed by the clinicians. The level of agreement on progression status between the clinicians was always higher when they used PROGRESSOR (median kappa = 0.59) than when they used Humphrey printouts (median kappa = 0.32). This was statistically significant (p = 0.006, Wilcoxon matched pairs signed rank sum test). CONCLUSIONS: Agreement between expert clinicians about visual field progression status is poor when standard Humphrey printouts are used, even when the field series studied are long and consist solely of reliable fields. Under these ideal conditions, clinicians agree more closely about patients' visual field progression status when using PROGRESSOR than when inspecting series of Humphrey printouts.

Adult↗
PubMed2002

Effect of treatment by medicine or surgery on intraocular pressure and pulsatile ocular blood flow in normal-pressure glaucoma.

PURPOSE: To study the effect of trabeculectomy and monotherapy with topical betaxolol, brimonidine and latanoprost on intraocular pressure (IOP) and pulsatile ocular blood flow (POBF) in patients with normal-pressure glaucoma (NPG). METHODS: In this retrospective study NPG patients attending the glaucoma research unit at Moorfields Eye Hospital were reviewed. Patients treated by surgery or topical medication (betaxolol, brimonidine or latanoprost) who had pre- and post-treatment IOP and POBF measurements were studied. For those patients who were having treatment to both eyes, one eye was selected at random for analysis. RESULTS: A total of 147 patients were reviewed. Forty-three eyes were receiving betaxolol 0.5%, 58 eyes latanoprost 0.005%, 23 eyes brimonidine 0.2% and 23 eyes had undergone trabeculectomy surgery. There were more female than male patients in all four groups, and the groups were similar with regards age. Pre-treatment IOP and POBF values were similar among the groups ( P=0.27, P=0.08 respectively). Post-treatment IOP values tended to be lower than pre-treatment values for all four groups. All groups had an increased POBF except for betaxolol, where POBF decreased. CONCLUSION: Patients treated by trabeculectomy and those receiving topical latanoprost and brimonidine had lower IOP and higher POBF following treatment. The betaxolol-treated group, despite a slight decrease in IOP, had a decreased POBF. Lowering IOP by treatment may not necessarily be associated with an increase in POBF.

Administration, Topical↗
PubMed2002

Use of high spatial resolution perimetry to identify scotomata not apparent with conventional perimetry in the nasal field of glaucomatous subjects.

AIM: To examine whether high spatial resolution perimetry (HSRP) could identify fine scale scotomata which may not be apparent with conventional perimetry. The HSRP was performed in the nasal field, as this location is a recognised site for the early occurrence of glaucomatous defects. METHOD: 16 early glaucoma eyes, 17 glaucoma suspect eyes, and 20 age matched healthy control eyes underwent conventional automated perimetry using the 24-2 program of the Humphrey field analyser (HFA) and HSRP. The HSRP was performed in the nasal field by testing 9 x 9 degrees of 100 tested points separated by 1 degree and the results compared with the HFA 24-2 program. RESULTS: Mean HSRP thresholds were significantly abnormal in the suspect and glaucoma eyes, with elevated levels of asymmetry between the superior and inferior nasal field. Overall, 7/17 (41%) suspect eyes (95% confidence interval 5/17 (29%) to 7/17 (41%)) had nasal scotomata on HSRP, although their HFA 24-2 fields failed to identify any defects. In glaucomatous eyes, 15/16 (94%) eyes had HSRP scotomata (95% CI 14/16 (88%) to 15/16 (94%)). In 12 these coexisted with HFA 24-2 defects at the same location, while in three eyes only HSRP identified scotomata in the nasal field. CONCLUSION: HSRP can identify scotoma in glaucomatous eyes in the nasal field which may be missed with the lower spatial resolution of conventional perimetry.

Aged↗
PubMed2001

The ability of the GDx nerve fibre analyser neural network to diagnose glaucoma.

PURPOSE: To evaluate the neural network used by the GDx in a group of normal subjects, patients with ocular hypertension (OHT) and patients with normal-pressure glaucoma (NPG). METHODS: The GDx neural network produces a "number" that indicates the likelihood that glaucoma is present. This number was compared in three groups representing different stages of health and disease, namely, normal controls (n = 101), OHT (n = 102) and NPG (105). The GDx number's ability to differentiate between normal and glaucoma individuals was then investigated. We also studied the relationship between the GDx number and retinal nerve fibre layer (RNFL) average thickness and visual field status to examine how well the GDx number reflects disease severity. RESULTS: The GDx number was significantly different among the groups (P < 0.01); it was highest in NPG and lowest in normal controls. The GDx number differentiated between glaucoma and normal with sensitivity of 92.3% and specificity of 96%. When combined with the parameter of RNFL average thickness, sensitivity and specificity were 88.5% and 100% respectively. In NPG a significant correlation was found between the GDx number and RNFL average thickness(rho = -0.88, P < 0.001) and visual field mean deviation (rho = -0.64, P < 0.001). CONCLUSION: The GDx number is able to differentiate between groups of normal, OHT and NPG subjects. Its close relationship with RNFL average thickness and visual field status in glaucoma indicates that it is able to reflect disease severity. Furthermore, its measured ability to distinguish between normal individuals and those with glaucoma demonstrates potential for use in glaucoma diagnosis.

Adult↗
PubMed2001

Glaucoma surgery with or without adjunctive antiproliferatives in normal tension glaucoma: 2 Visual field progression.

BACKGROUND: Reduction of intraocular pressure by 20-30% with glaucoma drainage surgery slows disease progression in normal tension glaucoma (NTG). It is not clear whether adjunctive antiproliferative agents are necessary or safe in eyes at low risk for scarring. METHOD: 61 eyes of 61 white patients with NTG who had undergone a primary guarded fistulising procedure were reviewed. 20 eyes had no antiproliferatives (nil), 29 had peroperative 5-fluorouracil (5-FU), and 12 had peroperative mitomycin C (MMC). Pointwise linear regression analysis (PROGRESSOR for Windows software) was applied to their visual field series starting with the first visual field following surgery and adding subsequent visual fields one at a time. Progression of visual field loss was defined as the appearance of a regression slope 1 dB per year or more with a significance of p<0.01 at one or more visual field locations which remained consistent with the addition of two of three successive visual fields. Time updated covariate analysis was used to determine the relation between variables that changed with time, such as IOP, and the risk of progression. RESULTS: The median percentage IOP reduction was 24.4 for the nil group, 38.0 for the 5-FU group, and 47.5 for the MMC group (p=0.001). There was a statistically significant relation between percentage change in IOP and risk of visual field progression in the subsequent 6 month period for all patients analysed as one group, hazard ratio = -0.021 (p=0.002). There was a statistically significantly increase in the risk of visual field progression for the MMC group compared with the 5-FU group, hazard ratio = 1.51 (p=0.02). CONCLUSION: In NTG patients, the IOP reduction produced by drainage surgery reduces the risk that visual field progression may be reduced after drainage surgery; this is related to the level of IOP reduction. The percentage drop in IOP during a given time is related to the risk of subsequent visual field progression. However, the use of MMC is associated with a greater risk of visual field progression despite a greater fall in IOP. This visual field deterioration may be related to the functional loss produced by late postoperative complications which have been reported at a higher rate in this group. The use of adjunctive perioperative 5-FU should maintain a suitable target IOP with preservation of visual function without the additional complications and associated visual deterioration seen with adjunctive MMC.

Aged↗
PubMed2001

Optic disc changes following trabeculectomy: longitudinal and localisation of change.

AIMS: To determine whether there were any changes in the optic disc at 2 years after trabeculectomy. To determine the factors that most influenced change and whether change was localised to any region of the optic disc. METHODS: 95 patients undergoing routine trabeculectomy as part of the ongoing Moorfields/MRC 5-fluorouracil trial were recruited into the study. Eyes were imaged preoperatively (4 (SD 3) weeks) with the Heidelberg retina tomograph (HRT, Heidelberg Engineering), and at 3 months (SD 2 weeks), 1 year (SD 1 month), and 2 years (SD 1 month) after surgery. Parameters investigated for change were rim area, rim volume, and maximum cup depth. The predefined segment analysis available on the HRT analysis software was used to determine segmental change. RESULTS: The images of 70 patients were analysed. Intraocular pressure reduced from 22.25 (SD 3.76) mm Hg, at the time of preoperative imaging to 15.27 (SD 4.96) mm Hg at 3 months, 14.38 (SD 3.89) mm Hg at 1 year, and 13.80 (SD 3.54) mm Hg at 2 years after trabeculectomy. An increase in rim area and rim volume was present at all time points after surgery, but was only found to be statistically significant at 2 years after surgery. Maximum depth of cup reduced by month 3 and month 12, but showed a slight increase at 2 years after surgery, although this was still lower than the preoperative measure. Segmental analysis found a significant change in rim volume in the nasal, inferonasal, superonasal, and superotemporal regions at 2 years after surgery. No significant regional localisation for change was found at any other time point or in any other parameter investigated. CONCLUSIONS: Reversal of disc cupping is present at 2 years after trabeculectomy. The factor most influencing change is reduction of intraocular pressure. Segmental analysis showed that change in rim volume was greatest in the nasal, inferonasal, superonasal and superotemporal regions at 2 years.

Aged↗
PubMed2000

Chromosomal duplication involving the forkhead transcription factor gene FOXC1 causes iris hypoplasia and glaucoma.

The forkhead transcription factor gene FOXC1 (formerly FKHL7) is responsible for a number of glaucoma phenotypes in families in which the disease maps to 6p25, although mutations have not been found in all families in which the disease maps to this region. In a large pedigree with iris hypoplasia and glaucoma mapping to 6p25 (peak LOD score 6.20 [recombination fraction 0] at D6S967), no FOXC1 mutations were detected by direct sequencing. However, genotyping with microsatellite repeat markers suggested the presence of a chromosomal duplication that segregated with the disease phenotype. The duplication was confirmed in affected individuals by FISH with markers encompassing FOXC1. These results provide evidence of gene duplication causing developmental disease in humans, with increased gene dosage of either FOXC1 or other, as yet unknown genes within the duplicated segment being the probable mechanism responsible for the phenotype.

Chromosomes, Human, Pair 6↗
PubMed2000

Longitudinal nerve fibre layer thickness change in normal-pressure glaucoma.

PURPOSE: To investigate longitudinal retinal nerve fibre layer (RNFL) thickness change in patients with normal-pressure glaucoma (NPG) and to assess how this may be related to visual fields. METHODS: NPG patients and normal subjects who had had serial GDx nerve fibre layer Analyzer II imaging and Humphrey visual fields performed at least 18 months apart were selected for study. These measurements were compared between groups at baseline and at subsequent follow-up, for change over time. RESULTS: Seventy-five NPG patients and 35 normal subjects were studied. Significant differences in RNFL thickness were found between NPG patients and normal controls at baseline (P < or = 0.001). Over the same time, there was greater RNFL thinning in NPG patients than in normal subjects (P < or = 0.0001). RNFL thinning in NPG was negatively correlated with visual field log MD at baseline (P < 0.001) and change in MD over time (P < 0.001). CONCLUSION: Reduction of RNFL thickness over time was significantly greater in NPG patients than in normal subjects, indicating that NPG patients' RNFL had thinned at a faster rate. NPG patients with initially better visual fields had a greater reduction in RNFL thickness than did those with initially more advanced visual field defects, suggesting that more RNFL change may be observed when glaucoma is at an earlier stage. There was a direct relationship between RNFL thinning and visual field deterioration.

Aged↗
PubMed2000

Mapping the visual field to the optic disc in normal tension glaucoma eyes.

PURPOSE: To establish the anatomical relationship between visual field test points in the Humphrey 24-2 test pattern and regions of the optic nerve head (ONH) DESIGN: Cross-sectional study. PARTICIPANTS: Glaucoma patients and suspects from the Normal Tension Glaucoma Clinic at Moorfields Eye Hospital. METHODS: Sixty-nine retinal nerve fiber layer (RNFL) photographs with well-defined RNFL defects and/or prominent bundles were digitized. An appropriately scaled Humphrey 24-2 visual field grid and an ONH reference circle, divided into 30 degrees sectors, were generated digitally. These were superimposed onto the RNFL images. The relationship of visual field test points to the circumference of the ONH was estimated by noting the proximity of test points to RNFL defects and/or prominent bundles. The position of the ONH in relation to the fovea was also noted. MAIN OUTCOME MEASURES: The sector at the ONH corresponding to each visual field test point, the position of the ONH in relation to the fovea, and the effect of the latter on the former. RESULTS: A median 22 (range, 4-58), of a possible 69, ONH positions were assigned to each visual field test point. The standard deviation of estimations was 7.2 degrees. The position of the ONH was 15.5 degrees (standard deviation 0.9 degrees ) nasal and 1.9 degrees (standard deviation 1.0 degrees ) above the fovea. The location of the ONH had a significant effect on the corresponding position at the ONH for 28 of 52 visual field test points. CONCLUSIONS: A clinically useful map that relates visual field test points to regions of the ONH has been produced. The map will aid clinical evaluation of glaucoma patients and suspects, as well as form the basis for investigations of the relationship between retinal light sensitivity and ONH structure.

Cross-Sectional Studies↗
PubMed2000

Glaucomatous optic disc changes in the contralateral eye of unilateral normal pressure glaucoma patients.

OBJECTIVE: To evaluate the optic disc for structural abnormalities in the contralateral eye of unilateral normal pressure glaucoma patients. DESIGN: Cross-sectional study. PARTICIPANTS: Fifty-three unilateral normal pressure glaucoma patients. TESTING: Optic disc imaging with the Heidelberg Retina Tomograph (HRT). MAIN OUTCOME MEASURES: Optic disc structural parameters. RESULTS: Of the contralateral (normal visual field) eyes, 79.2% were found to have an abnormal optic disc by HRT analysis. Of the glaucomatous (abnormal visual field) eyes, 94.3% were found to have an abnormal disc. The patterns of disc abnormality were defined as marked or moderate diffuse thinning of the neuroretinal rim (NRR) or broad or narrow focal thinning of the NRR. The most common pattern in the contralateral eyes was moderate diffuse thinning of the NRR (45.2%). The most frequently abnormal segments were the nasal superior (73. 8%) followed by the nasal inferior and the global NRR parameter (both 54.8%). CONCLUSIONS: A high frequency of NRR thinning was found in the contralateral (normal visual field) eyes of unilateral normal pressure glaucoma patients by HRT analysis. Knowing whether these abnormalities predict future progression to the development of visual field abnormality must wait until longitudinal studies are completed. If a disc abnormality is shown to predict future field loss, then early identification will allow early treatment.

Aged↗
PubMed2000

Identifying early glaucomatous changes. Comparison between expert clinical assessment of optic disc photographs and confocal scanning ophthalmoscopy.

OBJECTIVE: To compare the ability of expert clinicians, using qualitative assessment of stereoscopic optic disc photographs, and confocal scanning laser ophthalmoscope imaging to discriminate between healthy persons and patients with early glaucoma. DESIGN: Comparative instrument validation study. PARTICIPANTS: Seventy-two healthy persons and 51 patients with early glaucoma (average visual field mean deviation, -3.6 dB). Early glaucoma was defined as a history of ocular hypertension and a reproducible visual field defect scoring 5 or less in the Advanced Glaucoma Intervention Study classification, regardless of optic disc appearance. INTERVENTION: Stereoscopic optic nerve head (ONH) photography and Heidelberg Retina Tomograph (HRT) imaging, (Heidelberg Engineering GmbH, Dossenheim, Germany). MAIN OUTCOME MEASURES: Ability of clinical assessment of stereoscopic ONH photographs and analysis of HRT parameters, taking into account the optic disc size, to detect early glaucomatous optic disc changes. RESULTS: The specificity of the majority opinion of five observers to detect early glaucomatous optic disc changes was 94.4%, with a sensitivity of 70.6%. Using the HRT analysis, the specificity was 95.8% and the sensitivity was 84. 3%. CONCLUSIONS: Heidelberg Retina Tomograph image analysis that takes into account the optic disc size is more sensitive than clinical assessment of stereoscopic optic disc photographs in distinguishing between healthy persons and patients with early glaucoma.

Aged↗
PubMed2000

Use of the GDx to detect differences in retinal nerve fibre layer thickness between normal, ocular hypertensive and early glaucomatous eyes.

PURPOSE: The GDx is a scanning laser polarimeter that has been developed to allow the quantitative analysis of retinal nerve fibre layer (RNFL) thickness. The purpose of this study was to determine whether differences in the RNFL thickness between normal, ocular hypertensive and glaucomatous eyes could be detected using the GDx. METHODS: RNFL analysis was carried out using the GDx on 33 normal, 145 ocular hypertensive (OHT) and 44 glaucomatous (POAG) eyes. The inclusion criteria for entry into the study did not include the clinical appearance of the RNFL or optic disc, thus eliminating an important source of selection bias. The Kruskal-Wallis one-way analysis of variance was used to determine whether any significant differences existed among the groups in mean total and quadrantic RNFL thickness. When significant differences were found, specific inter-group analysis was carried out using the Mann-Whitney U-test. RESULTS: Significant differences in RNFL thickness were found for the mean total, superior and inferior quadrant values between normals and OHT eyes as compared with POAG eyes. No significant differences were found for these values between the normal and OHT eyes. CONCLUSION: Analysis of RNFL thickness using the GDx was able to detect differences between POAG eyes compared with normal and OHT eyes, although there was considerable overlap between groups. Further assessment of the technique is required to determine whether it may be useful in screening for the presence of early glaucomatous damage.

Aged↗
PubMed2000

Response time prolongation for a motion stimulus in patients with glaucoma and its relationship with elevation of the motion threshold.

PURPOSE: To investigate whether response times for a motion stimulus are prolonged in glaucoma and to investigate the relationship between response time prolongation and motion threshold elevation in glaucoma. METHOD: Motion displacement thresholds and response times were measured in 15 patients with glaucoma and 18 age-matched control subjects. RESULTS: Mean test response times were significantly prolonged in the glaucomatous eyes than in the control eyes, with a mean delay of 200 milliseconds. After correcting for threshold elevation, response times at the motion threshold showed no significant difference between the groups. CONCLUSIONS: Response times for motion detection are significantly prolonged in glaucoma and are accounted for by the threshold elevation in patients with glaucoma. The implications of these results are discussed in terms of the use of response time analysis to determine subject reliability.

Adult↗