Roger A. Hitchings

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.

Identification of early glaucoma cases with the scanning laser ophthalmoscope.

PURPOSE This study aimed to define the confocal laser scanning ophthalmoscope (Heidelberg Retina Tomograph [HRT]) parameters that best separate patients with early glaucoma from normal subjects. STUDY DESIGN A cross-sectional study. PARTICIPANTS A total of 80 normal subjects and 51 patients with early glaucoma participated (average visual field mean deviation = -3.6 dB). INTERVENTION Imaging of the optic nerve head with the HRT and analysis using software version 1.11 were performed. MAIN OUTCOME MEASURES The relation between neuroretinal rim area and optic disc area, and cup-disc area ratio and optic disc area, was defined by linear regression of data derived from the normal subjects. The normal ranges for these two parameters were defined by the 99% prediction intervals of the linear regression between the parameter and optic disc area, for the whole disc, and for each of the predefined segments. Normal subjects and patients were labeled as abnormal if the parameter for either the whole disc or any of the predefined segments was outside the normal range. The sensitivity and specificity values of the method were calculated. RESULTS The highest specificity (96.3%) and sensitivity (84.3%) values to separate normal subjects and those patients with early glaucoma were obtained using the 99% prediction interval from the linear regression between the optic disc area and the log of the neuroretinal rim area. Similar specificity (97.5%) and lower sensitivity (74.5%) values were obtained with the 99% prediction interval derived from regression between the disc area and cup-disc area ratios. Poor separation between groups was obtained with the other parameters. CONCLUSIONS The HRT, using the technique of linear regression to account for the relationship between optic disc size and rim area or cup-disc area ratio, provides good separation between control subjects and patients with early glaucoma in this population.

Long-term Functional Outcome after Early Surgery Compared with Laser and Medicine in Open-angle Glaucoma

PURPOSE This randomly allocated prospective clinical study was designed to assess the relative efficacy of laser trabeculoplasty, medical therapy, and trabeculectomy used as the primary treatment in open-angle glaucoma, with particular regard to the level of intraocular pressure control and the amount of visual field decay. No patient had received any antiglaucoma treatment before entry into the trial. METHODS One hundred sixty-eight patients were entered into the trial and randomly allocated into one of the three treatment groups--laser, medicine, or surgery. Follow-up was for a minimum of 5 years. The patients were monitored in the standard way, including intraocular pressure estimations and visual field tests (initially using the Friedmann analyzer and later including Humphrey automated perimetry). RESULTS Despite similar initial composition of the three treatment groups, primary surgery resulted in the lowest mean intraocular pressures. The perimeter Friedmann visual fields were shown to have deteriorated in patients in the medicine-treated group and to a lesser extent in patients in the laser-treated group, but not in patients in the surgery-treated group. Multivariate linear regression analysis showed that the difference in field changes between laser and surgical treatments could be explained entirely by the difference between the intraocular pressure values at 6 months between the two groups. The same was not true for the medicine-treated group. CONCLUSION Primary trabeculectomy appears to have the desired effect in preserving visual function in patients with high-tension glaucoma. This may be related to laser treatment might be expected to have the same effect.

Long-term Morphologic Effects of Antiglaucoma Drugs on the Conjunctiva and Tenon's Capsule in Glaucomatous Patients

Conjunctival and Tenons capsule biopsies from two patient groups were quantitatively analyzed by light microscopy. Group A consisted of 20 patients with a primary glaucoma for whom surgery was a planned primary treatment modality. Group B was comprised of 20 patients with a primary glaucoma who had received at least two types of antiglaucoma topical medication, for a minimum of 1 year (mean, 7.7 years) before surgery. All slides were examined by two masked observers. A significant increase in the number of macrophages, lymphocytes, mast cells, and fibroblasts in the conjunctiva and Tenons capsule and a significant decrease in the number of epithelial goblet cells were seen in the group that received long-term drop therapy. These results suggest that exhaustive medical therapy, before surgery is offered, increases the number of tissue inflammatory cells. It is possible this may enhance the risk of external bleb scarring and filtration surgery failure.

Variation of nerve fibre layer thickness measurements with age and ethnicity by scanning laser polarimetry

AIMS Scanning laser polarimetry is a new technique allowing quantitative analysis of the retinal nerve fibre layer in vivo. This technique was employed to investigate the variation of the retinal nerve fibre layer thickness in a group of normal subjects of different ages and ethnic groups. METHODS 150 normal volunteers of different ages and ethnic groups were recruited for this study. Three consecutive 15 degree polarimetric maps were acquired for each subjects. Nerve fibre layer thickness measurements were obtained at 1.5 disc diameters from the optic nerve. Four 90 degree quadrants were identified. RESULTS The mean nerve fibre layer thickness varied from a minimum of 55.4 μm to a maximum of 105.3 μm, with a mean thickness value of 78.2 (SD 10.6) μm. Superior and inferior quadrants showed a comparatively thicker nerve fibre layer than nasal and temporal quadrants. Retinal nerve fibre layer thickness is inversely correlated with age (p < 0.001). White people showed thicker nerve fibre layers than Afro-Caribbeans (p = 0.002). CONCLUSION The results indicate a progressive reduction of the nerve fibre layer thickness with increasing age. This may be due to a progressive loss of ganglion axons with age as suggested in postmortem studies. A racial difference in nerve fibre layer thickness is present between whites and Afro-Caribbeans.

Analysis of visual field progression in glaucoma.

BACKGROUND: Despite the widespread use of computerised perimetry the diagnosis of visual field deterioration in following glaucoma patients over time remains particularly difficult. A new method of analysis using a novel graphical display of longitudinal field data is presented. METHODS: A linear regression model of the luminance sensitivity at each stimulus location against time of follow up transforms the quantitative data from a series of fields into a colour coded form which illustrates the spatial configuration of change to aid the interpretation of field loss. The method of analysis and the developed computer software (PROGRESSOR) is described. Comparison with STATPAC-2 glaucoma change probability analysis is given including levels of agreement between the techniques using series of fields of 10 eyes from patients with normal tension glaucoma. RESULTS: Examples of this new method compare well with STATPAC-2 analysis. The level of agreement between the techniques to separate progressing from stable retinal locations is good (kappa = 0.62; SE = 0.04). CONCLUSIONS: This new technique, which combines the change in perimetric sensitivity over time with colour coding of significant change into one image may provide an efficient method to detect true progression in glaucomatous field loss.

Frequency of asymmetric visual field defects in normal-tension and high-tension glaucoma

OBJECTIVE The purpose of the study was to evaluate the frequency of asymmetric visual field loss at presentation in patients with normal-tension glaucoma (NTG) and high-tension glaucoma (HTG). DESIGN A retrospective cross-sectional study design was used. PARTICIPANTS Four hundred and three NTG patients and 337 consecutive HTG patients (consecutive diagnoses between 1986 and 1996). INTERVENTION Analysis of the frequency of unilateral field loss presentations in NTG and HTG. The visual fields of fellow eyes were compared to determine the side of more severe field loss. For the NTG patients, the relationship between the side with greater field loss and corresponding intraocular pressure (IOP) was investigated. MAIN OUTCOME MEASURES Humphrey field analyzer mean defect (MD) and mean diurnal IOP. RESULTS In the NTG group, 101 (25%) patients presented with unilateral field loss. The proportion of cases with unilateral field loss decreased with increasing age of presentation (chi-square test for trend = 26.9; P < 0.0001). Sixty-four percent of the patients had unilateral field loss in the left eye. Sixty-eight percent of the cases with bilateral field loss had a higher MD in the left eye. The diurnal IOP was estimated as 0.23 +/- 0.068 mmHg (mean +/- SE) higher in the left eye (P = 0.001). In the HTG group, 104 (31%) patients presented with unilateral field loss. The proportion of cases with unilateral field loss decreased with increasing age of presentation (chi-square test for trend = 4.6; P = 0.03). Right and left eyes had an equal chance of having field loss in unilateral cases and of being the side of more advanced field damage in bilateral cases. CONCLUSIONS The frequency of cases with unilateral field loss was similar in HTG and NTG patients. Patients with unilateral field loss at presentation were more likely to be at the younger end of the age range. In the NTG population we studied, the left eye was more frequently the side of onset of field loss and 2.1 times more likely to present with a greater field defect than the right eye. In HTG patients, right and left eyes showed an equal chance of being the side of onset of field damage and the more affected side.

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.

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.

Direct costs of glaucoma and severity of the disease: a multinational long term study of resource utilisation in Europe

Background: Resource utilisation and direct costs associated with glaucoma progression in Europe are unknown. As population progressively ages, the economic impact of the disease will increase. Methods: From a total of 1655 consecutive cases, the records of 194 patients were selected and stratified by disease severity. Record selection was based on diagnoses of primary open angle glaucoma, glaucoma suspect, ocular hypertension, or normal tension glaucoma; 5 years minimum follow up were required. Glaucoma severity was assessed using a six stage glaucoma staging system based on static threshold visual field parameters. Resource utilisation data were abstracted from the charts and unit costs were applied to estimate direct costs to the payer. Resource utilisation and estimated direct cost of treatment, per person year, were calculated. Results: A statistically significant increasing linear trend (p = 0.018) in direct cost as disease severity worsened was demonstrated. The direct cost of treatment increased by an estimated €86 for each incremental step ranging from €455 per person year for stage 0 to €969 per person year for stage 4 disease. Medication costs ranged from 42% to 56% of total direct cost for all stages of disease. Conclusions: These results demonstrate for the first time in Europe that resource utilisation and direct medical costs of glaucoma management increase with worsening disease severity. Based on these findings, managing glaucoma and effectively delaying disease progression would be expected to significantly reduce the economic burden of this disease. These data are relevant to general practitioners and healthcare administrators who have a direct influence on the distribution of resources.