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Biomedical subjects

D F Garway-Heath

Publications and source records attributed to D F Garway-Heath.

At least 19 recordsLinked to original sources

Quantification of optic nerve head topography in optic neuritis: a pilot study.

AIMS: To investigate optic nerve head topography in patients with optic neuritis compared to controls using the Heidelberg retina tomograph-II (HRT-II) and to determine if detected changes are related to visual function and electrophysiology. METHODS: 25 patients with a previous single episode of unilateral optic neuritis and 15 controls were studied with HRT-II, visual evoked potentials, and pattern electroretinogram. Patients also had testing of visual acuity, visual field, and colour vision. RESULTS: In affected eyes compared to fellow eyes, there was reduction of both the mean retinal nerve fibre layer (RNFL) thickness at the disc edge (p = 0.009) and the neuroretinal rim volume (p = 0.04). In affected eyes compared to control eyes, the three dimensional optic cup shape measure was increased (p = 0.01), indicative of an abnormal cup shape. There were no other significant differences in HRT-II measures. Within patient interocular difference correlation was used to investigate the functional relevance of these changes and demonstrated associations between RNFL thickness change and changes in visual acuity, visual field, and colour vision. Colour vision change was also associated with change in neuroretinal rim volume. CONCLUSIONS: HRT detects functionally relevant changes in RNFL thickness and neuroretinal rim volume between eyes affected by optic neuritis and unaffected fellow eyes.

Adult↗

Factors affecting the test-retest variability of Heidelberg retina tomograph and Heidelberg retina tomograph II measurements.

AIMS: To evaluate the test-retest variability of stereometric parameter measurements made with the Heidelberg retina tomograph (HRT) and Heidelberg retina tomograph-II (HRT-II), and to establish which parameter(s) provided the most repeatable and reliable measurements with both devices. An investigation into the factors affecting the repeatability of the measurements of this parameter(s) was conducted. METHODS: 43 ocular hypertensive and 31 glaucoma subjects were recruited to a test-retest study. One eye from each subject underwent HRT and HRT-II imaging by two observers on each of two occasions within 6 weeks of each other. Lens grading was carried out by LOCS III grading and Scheimpflug camera generated densitogram analysis. RESULTS: Rim area (RA) and mean cup depth measurements were found to be least variable. Both inter-test reference height difference and image quality had a strong relation (R(2)>0.5, p<0.0001) with inter-test RA difference and, together, are responsible for 70% of RA measurement variability. Image quality was influenced by lens opacity, cylindrical error, and age. Inter-test RA measurement differences were unrelated to the observer or visit interval. CONCLUSIONS: RA represents an appropriate measure for monitoring glaucomatous progression. Reference height difference and image quality were the factors that most influenced RA measurement variability. Image analysis strategies that address these factors may reduce test-retest variability.

Adult↗

Improving the repeatability of Heidelberg retina tomograph and Heidelberg retina tomograph II rim area measurements.

AIMS: To devise and test strategies for improving Heidelberg retina tomograph (HRT and HRT-II) rim area (RA) repeatability and assess the benefit of the strategies in time series of HRT images. METHODS: The effect of the standard and 320 microm reference planes and image quality on RA repeatability was assessed in a test-retest HRT image dataset from 74 subjects. A longitudinal HRT image dataset from 30 ocular hypertensive subjects was analysed by linear regression of RA over time, with each of the reference planes and using a manual image alignment facility. RA variability was estimated by comparing the standard deviation of residuals (RSD) generated by each linear regression. RESULTS: RA repeatability was better with the 320 microm reference plane (repeatability coefficient 0.17 mm(2)), improving further with only good quality images (repeatability coefficient 0.08 mm(2)). For the longitudinal data, a significant (p<0.0001) reduction in the RSD from 0.10 to 0.05 mm(2) was obtained with the 320 microm reference plane. Manual alignment led to a further significant (p<0.0001) reduction in the RSD to 0.04 mm(2). CONCLUSIONS: The findings support the use of a 320 microm reference plane and manual image alignment to analyse RA over time. The estimates of RA repeatability may be used to define thresholds for glaucomatous change.

Adult↗

The relative effects of corneal thickness and age on Goldmann applanation tonometry and dynamic contour tonometry.

AIMS: To establish the effects of central corneal thickness (CCT) on intraocular pressure (IOP) measured with a prototype Pascal dynamic contour tonometer (DCT), to evaluate the effect of CCT and age on the agreement between IOP measured with the Pascal DCT and Goldmann applanation tonometer (GAT), and to compare the interobserver and intraobserver variation of the DCT with the GAT. METHODS: GAT and DCT IOP measurements were made on 130 eyes of 130 patients and agreement was assessed by means of Bland-Altman plots. The effect of CCT and age on GAT/DCT IOP differences was assessed by linear regression analysis. Interobserver and intraobserver variations for GAT and DCT were assessed in 100 eyes of 100 patients. RESULTS: The mean difference (95% limits of agreement) between GAT and DCT was -0.7 (-6.3 to 4.9) mm Hg. GAT/DCT IOP differences increased with thicker CCT (slope 0.017 mm Hg/microm, 95% CI 0.004 to 0.03, r2 = 0.05, p = 0.01), and with greater age, slope 0.05 mm Hg/year (95% CI 0.012 to 0.084, r2 = 0.05, p = 0.01). The intraobserver variability of GAT and DCT was 1.7 mm Hg and 3.2 mm Hg, respectively. The interobserver variability was (mean difference (95% limits of agreement)) 0.4 (-3.5 to 4.2) mm Hg for GAT and 0.2 (-4.9 to 5.3) mm Hg for DCT. CONCLUSIONS: GAT is significantly more affected than DCT by both CCT and subject age. The effect of age suggests an age related corneal biomechanical change that may induce measurement error additional to that of CCT. The prototype DCT has greater measurement variability than the GAT.

Adult↗

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↗

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↗

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↗

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↗

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↗

Relationship between structural abnormalities and short-wavelength perimetric defects in eyes at risk of glaucoma.

PURPOSE: To determine the relative prevalence of blue-yellow perimetric defects and structural abnormalities of the optic nerve and nerve fiber layer in eyes at risk of glaucoma. METHODS: Seventy-two eyes (of 72 patients) at risk of glaucoma, with normal white-on-white full threshold perimetry, were examined prospectively with blue-yellow full-threshold perimetry (Humphrey). Structural evaluations were conducted with qualitative assessment of stereoscopic color optic disk photographs and monochromatic nerve fiber layer photographs performed independently by three masked examiners (a glaucoma specialist and two glaucoma fellows), and statistical analysis of summary parameters was obtained with scanning confocal laser tomography (abnormal defined as values outside 95% confidence limits established in normal control subjects). RESULTS: Kappa values for interobserver agreement were 0.64, 0.88, and 0.79 for optic disk evaluation and 0.59, 0.60, and 0.61 for nerve fiber layer evaluation. Thirteen (18%) of 72 eyes had blue-yellow abnormalities. A total of 30 eyes (42%) were identified as having a structural abnormality; 29 (40%) had qualitatively determined optic disk abnormalities, 21 (29%) had qualitatively determined nerve fiber layer defects, and 26 (36%) had statistically significant structural abnormalities. Twelve of 13 eyes with blue-yellow defects had a detectable structural abnormality; all 12 had abnormalities identified with disk photography, nine with nerve fiber layer photography, and 12 by scanning laser tomography. CONCLUSIONS: Clinically detectable structural abnormalities frequently coexist with blue-yellow perimetric defects in patients with ocular hypertension. A substantial proportion of patients with ocular hypertension with normal blue-yellow perimetry has early detectable glaucomatous structural abnormalities.

Glaucoma, Open-Angle↗

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↗

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↗

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↗

Use of sequential Heidelberg retina tomograph images to identify changes at the optic disc in ocular hypertensive patients at risk of developing glaucoma.

AIM: To determine if global and segmental changes in optic disc parameters of sequential Heidelberg retina tomograph (HRT) images develop in individual ocular hypertensive (OHT) patients without white on white visual field defects. METHODS: Patients and normal controls were recruited from a prospective ocular hypertension treatment trial. The subject groups consisted of 21 OHT patients who had converted to early glaucoma on the basis of visual field criteria (24-2 program on the Humphrey perimeter), 164 OHT subjects with normal visual fields, and 21 normal controls. Sequential HRT images 16-21 months apart were obtained for each subject and segmental optic disc parameters were measured to determine if any change had occurred. From the analysis of sequential HRT images of the 21 normal eyes we established normal limits of interimage variation. Individual discs in each group showing changes above the 95% limit of normal variability were then sought. RESULTS: Several segmental and global optic disc parameters were found to show significant change in the converter group before confirmed visual field change, confirming our previously published results. Individual optic disc analysis using the 95% limit of normal variability data demonstrated glaucomatous change in 13 out of 21 converter eyes. 47 of the 164 OHT eyes with normal visual fields showed change in global and segmental parameters in a "glaucomatous" direction above the level expected for normal variability. The parameters which changed most frequently in the OHT eyes were: global cup volume (6.7% of discs), inferonasal cup volume (11%), inferotemporal cup volume (8.5%), and superotemporal cup area (7.3%). CONCLUSIONS: We have identified change in a subset of ocular hypertensive patients which could predate the development of glaucomatous visual field loss. The HRT could be of value in the sequential follow up of those suspected of having glaucoma by identifying eyes at risk of developing glaucoma. However, further refinement of the technique is required to eliminate some of the inherent variability of the analysis method described, and to increase the ability to detect at risk individuals.

Adult↗

Scaling the hill of vision: the physiological relationship between light sensitivity and ganglion cell numbers.

PURPOSE: Differential light sensitivity (DLS) in white-on-white perimetry is used as a measure of ganglion cell function to estimate the amount of neuronal damage in glaucoma. The physiological relationship between DLS and ganglion cell numbers is poorly understood. Within small retinal areas, brightness information is summated, so that A * L = C, or A = C/L, where A is target area, L is threshold luminance, and C is a constant. In larger illuminated areas, as with a Goldmann size III target in perimetry, summation is incomplete, so that A(k) = C/L, where k is the coefficient of summation, and 0 < k < 1. This study tests the hypothesis that the target area (A) can be represented by the number of underlying ganglion cells (G) to give G(k) = C/L. METHODS: Normative human data for ganglion cell density within 30 degrees of retinal eccentricity were taken from the literature and corrected for lateral displacement of ganglion cells from the fovea to estimate ganglion cell receptive field density (g). The number of ganglion cell receptive fields within a Goldmann size III target (G) was calculated from target area (A) and receptive field density (g) [G = A (g)]. Normative data for DLS in the central 30 degrees (Humphrey 30-2) were taken from the literature. The coefficient summation (k) was measured empirically at each Humphrey 30-2 test point in 8 normal subjects. The relationship between DLS and G was investigated by plotting DLS as decibels (dB) against G and DLS as 1/L (1/Lamberts) against G(k). The physiological relationship was extrapolated to glaucomatous ganglion cell loss by calculating hypothetical cell losses for 3 and 6 dB sensitivity defects at each test point. RESULTS: Spatial summation increased with eccentricity. The relationship between DLS (dB) and G was curvilinear. The relationship between DLS (1/L) and G(k) was linear (r2 = 0.73). The extrapolation to glaucomatous ganglion cell loss indicated that a proportionally greater loss of ganglion cells is required in the central compared with peripheral visual field for equal losses in dB sensitivity. CONCLUSIONS: The number of underlying ganglion cells, adjusted for local spatial summation, is better reflected by the DLS scale of 1/L than by dB. If spatial summation is unchanged in glaucoma, this scale more accurately reflects the amount of neuronal damage.

Adult↗

Detection of optic disc change with the Heidelberg retina tomograph before confirmed visual field change in ocular hypertensives converting to early glaucoma.

AIM: To determine whether analysis of sequential optic disc images obtained with the Heidelberg retina tomograph (HRT) is able to demonstrate optic disc change before the development of reproducible field defects in a group of ocular hypertensive (OHT) patients converting to early glaucoma. METHODS: Two groups were analysed: (1) 13 eyes of 13 OHT patients who subsequently developed reproducible field defects (converters); and (2) 13 eyes of 11 normal control subjects. Two sequential optic disc images were obtained using the HRT (median separation between images was 12 months for the converters and 13 months for the normals). The second image in the converter group was obtained before confirmed visual field loss. The optic disc variables were analysed both globally and segmentally using HRT software version 1.11. The Wilcoxon signed rank test was used to determine if there were any significant differences between the variables of the two image sets. RESULTS: Significant optic disc change was demonstrated in the group of converters: (1) global variables: the cup area increased by 9.7%, the C/D area ratio increased by 10.5%, and the rim area decreased by 6.9%; (2) segmental variables: the superonasal cup area increased by 11.0%, the superonasal C/D area ratio increased 11.7%, and the inferonasal cup volume increased by 28.4%. The temporal rim volume decreased by 15.6%, the inferotemporal rim volume decreased by 23.6%, and the rim area in the superonasal and superotemporal segments decreased by 6.6% and 6.9% respectively. CONCLUSION: Analysis of sequential optic disc images on the HRT allowed the detection of glaucomatous change before confirmed visual field change in a group of OHT patients converting to early glaucoma.

Aged↗