Severity and stability of glaucoma: patient perception compared with objective measurement.

OBJECTIVE: To elucidate the relationship between the subjective assessment in patients with glaucoma of (1) the severity of their visual loss, and (2) any deterioration in their visual function and their objective visual fields as measured by computed perimetry. DESIGN: First, patients completed a questionnaire relating to perceived visual disability and underwent binocular visual field testing. Second, a separate group of patients answered a question about perceived visual deterioration: their monocular visual field tests were analyzed retrospectively by pointwise linear regression to establish stability or deterioration. SETTING: The Glaucoma Service of a specialist eye hospital, which is a tertiary referral center and serves the local community. SUBJECTS: One hundred twenty-three patients with glaucoma including 62 for the severity arm of the study and 61 for the progression arm. MAIN OUTCOME MEASURES: Questionnaire responses, Esterman binocular disability score, and objective visual field deterioration. RESULTS: Questions strongly associated with Esterman binocular disability scores related to bumping into things, problems with stairs, and finding things that have been dropped. There was a strong association between perceived visual deterioration and measured bilateral visual field deterioration (P<.01). CONCLUSIONS: There is a strong association between some types of perceived visual disability and the severity of binocular field loss. A patient who notices gradual visual deterioration is twice as likely to have bilateral visual field deterioration as not. The findings in this sample of patients with mild-to-moderate glaucoma challenge the belief that glaucoma is an insidious process in which the symptoms do not appear until the end stage of the disease.

Colour vision in patients with chronic simple glaucoma and ocular hypertension.

Normal subjects and patients with chronic simple glaucoma and ocular hypertension were examined with the Farnsworth-Munsell 100 hue test. Two groups of glaucoma patients were studied, one group having field defects in both eyes and the other being 'unilateral' in the sense that one eye had a full visual field. The stage of the disease was assessed by the amount of field loss or by the amount of optic disc damage as expressed by the vertical cup:disc ratio. Hue discrimination in eyes with glaucomatous field defects was worse than in eyes of normal subjects, but there was no clear indication of one range of colours being more affected than another. In glaucoma patients with field defects in both eyes the difference in error scores between the 2 eyes was greater than in normal subjects. There was a significant correlation between the degree of impairment of hue discrimination, expressed as the error score, and the amount of glaucomatous field loss. There was also a significant correlation between error score and the amount of glaucomatous damage to the optic disc, expressed by the vertical cup:disc ratio. Findings in a group of patients with ocular hypertension suggested that some of these were cases of incipient glaucoma.

Ocular effects of acute hyperglycaemia.

Intraocular pressure and levels of glucose in plasma were recorded during a standard glucose tolerance test for 54 patients with chronic simple or low-tension glaucoma, and osmolality in plasma was also recorded for 12 patients. Significant correlations between the rates of change of these variables were not obtained, but the overall response of intraocular pressure correlated with the overall increase of plasma glucose, which also correlated with the increase of osmolality. These results show that the changes in refraction associated with acute hyperglycaemia arise from adjustments in fluid balance between intraocular compartments.

Double-masked cross-over comparison of Ganda 1.02 (guanethidine 1% and adrenaline 0.2% mixture) with gutt. adrenaline 1% (Simplene 1%) and with pilocarpine 1% (Sno-Pilo 1%).

A trial of the efficacy of low-concentration nonmiotic therapy was carried out, the aim being to minimise the side effects produced by 1% adrenaline or pilocarpine. A total of 77 eyes with open-angle glaucoma were studied in both parts of the trial. Thirty-nine eyes had a base-line pressure of over 28 mmHg and 28 eyes a pressure of 30 mmHg or over. In the comparison between Ganda 1.02 and adrenaline 1% (Simplene) the mean lowering of intraocular pressure was 8.6 mmHg with Ganda and 7.69 mmHg with Simplene. In the comparison between Ganda 1.02 and pilocarpine 1% (Sno-Pilo) the mean decrease was 6.34 mmHg with Ganda and 6.13 mmHg with Sno-Pilo. The resulting falls in intraocular pressure were highly significant statistically, but the differences between the effects of the 3 drugs were not significant. No significant side effects were reported with Ganda 1.02, and in particular no ptosis or superficial punctate staining of the cornea was noted.

Effect of pilocarpine on visual acuity and on the dimensions of the cornea and anterior chamber.

The effect of pilocarpine on visual acuity and on the dimensions of the cornea, anterior chamber, and lens were studied in two groups of subjects. Significant changes in ocular tension, corneal curvature, anterior chamber depth, and lens anterior radius were found in a group of 55 glaucomatous eyes as a result of pilocarpine treatment, but there was no change in corneal thickness. Out of 102 glaucomatous eyes 78 became relatively myopic, and this appears to be due to changes in the dimensions of the lens of the eye similar to those occurring in accommodation, as a result of the effect of the drug on the ciliary muscle. The effect of pilocarpine on anterior chamber depth, area, and volume was studied in 125 eyes using a photographic method, and a significant reduction in the dimensions of the anterior chamber was observed as a result of the administration of pilocarpine. A significant correlation between depth and volume was also noted and the implications of this are discussed.

Regression analysis of visual field progression in low tension glaucoma.

Eighty four patients (168 eyes) with low tension glaucoma were retrospectively reviewed (mean follow-up was 28 months). The mean age was 66 years, and 69% were females. Regression analysis of their automated Humphrey fields (a mean of eight fields per eye) showed progression in 50% of patients and in 37% of eyes. There was no statistically significant difference between patients with progression and non-progression with respect to age (p less than 0.05) or intraocular pressure (p less than 0.5). Visual field defects were located most frequently in the superior hemifield in both groups of patients. A considerable proportion of patients had advanced field loss at the time of diagnosis.

Glaucoma surgery with or without adjunctive antiproliferatives in normal tension glaucoma: 1 intraocular pressure control and complications.

BACKGROUND: Reduction of intraocular pressure (IOP) 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: 86 eyes of 73 white NTG patients who had undergone a primary guarded fistulising procedure were reviewed. 25 eyes had no antiproliferatives, 36 had peroperative 5-fluorouracil (5-FU) and 25 had peroperative mitomycin C (MMC). Their postoperative IOPs, complications, and changes in visual acuity were recorded. RESULTS: Eyes that had no adjunctive antiproliferative less commonly maintained a 20-30% reduction in IOP (47.4% at 2 years) compared with either the 5-FU group (69.4%at 2 years, p=0.01) or the MMC group (64.9% at 2 years, p=0.04). Eyes that had adjunctive MMC more often had late hypotony (28%, p=0.02) and late bleb leak (12%, p<0.001). Eyes that had adjunctive MMC also more often had a two lines loss of Snellen visual acuity (39.8% by 2 years) compared with those that had adjunctive 5-FU (14.7% by 2 years), p=0.06. CONCLUSION: For NTG patients at low risk of scarring trabeculectomy with adjunctive peroperative 5-FU should maintain a suitable target IOP without the additional sight threatening complications seen with adjunctive MMC.

Surgery for normal tension glaucoma.

The long term follow up of surgery in normal tension glaucoma is presented. One eye of 18 patients with bilateral progressive disease underwent fistulising surgery. Over follow up periods ranging from 2 to 7 years (50% > or = 5 years) the operated eye showed on average a 30% reduction in intraocular pressure (IOP). This was associated with a marked difference in the rate and number of retinal locations showing a progressive decline in retinal function, suggesting some protective function for lowering IOP in patients with normal tension glaucoma.

Evaluation of the Humphrey FASTPAC threshold program in glaucoma.

The makers of the Humphrey perimeter have developed a rapid thresholding program, FASTPAC, to address the problems of fatigue and poor test performance associated with prolonged perimetry. The performance of FASTPAC was compared with the standard threshold program of the Humphrey visual field analyser (program 24-2) in 44 glaucoma patients. FASTPAC reduced the mean test time by 35% (from 12.6 to 8.2 minutes), owing to a reduction in the number of stimulus presentations. FASTPAC underestimated the mean deviation (MD) (Wilcoxon, p = 0.007) and corrected pattern standard deviation (CPSD) (Wilcoxon, p = 0.005). The sum of the differences between FASTPAC and the standard program was -1.19 (SD 2.37) dB for MD and 0.97 (2.14) dB for CPSD. The measured difference between the two methods was independent of the value of either MD or CPSD, indicating that the measurement error was just as likely to occur with either early or advanced visual field loss. No difference was noted in short term fluctuation or in the reliability indices of test performance. These results indicate that FASTPAC, while considerably faster, is not as accurate as the standard threshold program at measuring retinal sensitivity in glaucoma. This inaccuracy may be offset in practical terms by greater patient acceptability and by increasing the number of patients capable of performing reliable threshold perimetry because of the reduction in duration of the FASTPAC program.

Addition of timolol maleate to routine medical therapy: a clinical trial.

A double-blind cross-over trial of timolol maleate (Timoptol) while routine medical therapy was continued gave the result that pressure was reduced by 3.22 mmHg is compared to placebo and 5.01 compared to pre-timolol levels in 24 patients. There was also a small (1.858 mmHg) drop in pressure in placebo treated eyes, a small and statistically significant drop in resting pulse rate, 76.67 to 71.39/min, and a small but not statistically significant drop in diastolic blood pressure.

Association between optic disc haemorrhages in glaucoma and abnormal glucose tolerance.

Data concerning the results of glucose tolerance tests and levels of intraocular pressure were analysed for 120 patients with primary open-angle glaucoma, many of whom had been under observation for a period of four to five years. The patients consisted of two groups: in 62 patients a disc haemorrhage had been recorded at some time during the observation period, and in 58 no haemorrhages had been seen. Patients with disc haemorrhages had a higher incidence of abnormal glucose tolerance or frank diabetes and lower intraocular pressures than those without haemorrhages.

Addition of pindolol to routine medical therapy: a clinical trial.

A double-blind study of pindolol eye drops 0.5% was carried out on 24 patients with primary open-angle glaucoma. Pressures were taken once weekly during three 3-week periods. In one of the periods placebo was given in both eyes, during another pindolol was given in one eye, and during another it was given in the other eye. A drop in pressure averaging 2.79% was found in eyes receiving pindolol compared with the period when they were receiving saline. Substantial placebo effects were found when in-trial pressures were compared with pretrial, but the placebo effects were avoided in the analysis of the pindolol effect. Blood pressure and pulse rates were not significantly affected. There was slight evidence of pindolol in one eye affecting the contralateral eye but little evidence of persistence of hypotensive effects after cessation of treatment.

Clinical factors influencing the visual prognosis of the fellow eyes of normal tension glaucoma patients with unilateral field loss.

AIM: To investigate the influence of several clinical variables on the development of visual field loss in the "second eye" of patients with normal tension glaucoma (NTG) presenting with unilateral field loss. METHODS: Patients with NTG and unilateral field loss at presentation were selected from a cohort of 403 consecutive diagnoses of NTG. The state of the visual field "normal" or with a visual field defect was defined using the Advanced Glaucoma Intervention Study (AGIS) template. Where available, optic disc planimetry was carried out on stereo photographs taken at presentation. Measurements of the topography of each of these optic discs were compared with morphometric values from a group of normal subjects, allowing for differences in age and disc size. For each patient the percentage of the relative neuroretinal rim (NRR) area was calculated. The time taken to develop a visual field defect was related to clinical factors including age, sex, peak and mean diurnal intraocular pressure (IOP), refraction, relative NRR area, and the AGIS score of the fellow eye at presentation RESULTS: 54 patients were included in the study. The median (range) follow up time was 49.2 (11.1-116.7) months. 14 (26%) patients developed field loss in the eyes with an initially normal field. The estimate of the median time to field loss onset was 95.1 months. Field damage developed more rapidly in women and in patients with greater AGIS score in the contralateral eye at the beginning of follow up ((adjusted hazard ratio, HR (95% confidence interval, CI) 0.20 (0. 04; 0.93); 1.19 (1.02; 1.41) respectively)). Little evidence of any association was found between time to onset of field loss and each of age, refraction, and peak or mean diurnal IOP. Planimetric disc analysis was carried out in 33 (61%) patients. Of these 10 (30%) developed field loss in the eyes with initial normal field at a median follow up of 95.1 months. After adjustment for sex and AGIS, relative NRR area was found to be significantly related to the time of onset of field damage, the greater the reduction in relative NRR area, the shorter the time to visual field loss (HR 0.93 (0.89; 0. 99)). CONCLUSIONS: NTG patients with unilateral field loss are at high risk of developing field damage in the eyes with an initially normal visual field. In this study, the visual prognosis of the eye with the normal visual field at presentation was found to be influenced by the extent of the reduction in relative NRR area together with the severity of field damage in the contralateral eye at presentation.

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 microns to a maximum of 105.3 microns, with a mean thickness value of 78.2 (SD 10.6) microns. 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.

Pulsatile ocular blood flow investigation in asymmetric normal tension glaucoma and normal subjects.

AIMS: This study was designed to investigate pulsatile ocular blood flow (POBF) in normal tension glaucoma (NTG) patients and in normal controls. NTG patients with unilateral field loss were evaluated to compare POBF values between eyes with and without field loss. METHODS: POBF measurements from more than 1500 subjects were collected during a period of 6 months from six optometric centres. Subjects with systemic vascular diseases (such as systemic hypertension and diabetes), ophthalmic diseases, a positive family history of glaucoma, and those individuals receiving treatment with systemic beta blockers were excluded on the basis of a questionnaire. For comparison, 95 NTG patients with unilateral field loss, selected from 403 consecutive patients with NTG, underwent POBF testing. For each individual age, sex, intraocular pressure, refraction, and pulse rate were entered into a database. RESULTS: Data from 777 subjects were included in the analysis. POBF measurements of patients and subjects were compared allowing for differences in age, sex, intraocular pressure, refraction, and pulse rate. POBF was significantly lower in eyes of NTG patients with and without field loss (p < 0.001 and p = 0.01 respectively). Eyes of NTG patients with field loss showed significantly lower POBF than the contralateral eyes with normal field (p < 0.001). CONCLUSIONS: POBF was significantly lower in eyes of NTG patients with and without field loss than in normal subjects, suggesting that differences in ocular blood perfusion are relevant to the development of NTG and are detectable from the early stage of the disease. Furthermore, the finding of lower POBF in NTG eyes with field loss than in the contralateral eyes with normal field suggests that haemodynamic differences between fellow eyes contribute to determine the side of onset of the disease.

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.

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.

Comparison of visual field progression in patients with normal pressure glaucoma between eyes with and without visual field loss that threatens fixation.

AIM: To compare the frequency and site of visual field progression and changes in visual acuity in patients with normal pressure glaucoma (NPG) with and without pre-existing visual field loss. METHOD: Patients with normal tension glaucoma were selected who had at least 10 visual fields over 5 or more years of follow up and no other condition that might influence the visual field or visual acuity. Alternate left and right eyes were selected from patients in random order. These eyes were then subdivided according to visual field defect threatening fixation, visual field defect not threatening fixation, and no visual field defect (fellow eyes). Eyes were defined as showing a threat to fixation according to the presence of a visual field defect involving one of more of four paracentral visual field locations. Pointwise linear regression analysis was applied to each visual field series using PROGRESSOR software. 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, which remained consistent with the addition of two of three successive visual fields to the series. The number of patients showing progression and the number where progression occurred in one of the four paracentral visual field locations was noted. The number of eyes losing two or more lines of Snellen visual acuity over the follow up period was also noted. RESULTS: 174 eyes of 174 patients were selected. 106 eyes had visual field loss threatening fixation, 46 eyes had visual field loss that did not threaten fixation, and 22 were fellow eyes with normal visual fields. The median follow up was 7.2 years. Eight eyes (36.4%) in the "normal visual fields" group, 31 eyes (67.4%) in the "visual field loss away from fixation" group, and 87 eyes (82.1%) in the "threat to fixation" group showed progression in any part of the visual field. Two eyes (9.1%) in the "normal visual fields" group, nine eyes (19.6%) in the "visual field loss away from fixation" group, and 45 eyes (42.5%) in the "threat to fixation" group showed progression at "threat to fixation". The Cox proportional hazards regression model showed an increased risk of progression at any part of the visual field for female sex and a decreased risk for eyes with normal visual fields. For progression at threat to fixation this model showed an increased risk with pre-existing threat to fixation. Eyes from older patients and those that went on to have progressive visual field loss at fixation were more likely to lose two lines of Snellen visual acuity over the follow up period. CONCLUSION: Since 20-30% of previously field damaged eyes and over 60% without prior field loss fail to demonstrate progressive visual field damage over a long follow up it is recommended that normal pressure glaucoma patients be monitored for progression and that potentially harmful therapy be withheld until progression is demonstrated. Although the presence of visual field loss that threatens fixation does not constitute an increased risk of visual field progression it does indicate an increased risk of further loss of visual field close to fixation which is in turn associated with loss of central acuity. In the light of this finding, patients with visual field loss that threatens fixation should be managed more aggressively.

Motion detection threshold and field progression in normal tension glaucoma.

Psychophysical tests may demonstrate abnormalities of visual function before the appearance of conventional visual field loss in glaucoma. Motion detection thresholds (MDT) were measured in the normal fellow eye of 51 patients with confirmed normal tension glaucoma and initially unilateral field loss. Humphrey visual fields from the initially normal eye covering a mean follow up of 3.4 years were assessed using pointwise linear regression analysis. In 22 of the 51 eyes with normal visual fields at presentation, field deterioration occurred at one or more Humphrey locations within a mean of 1.7 (SD 1.6) years. An initially abnormal MDT test showed a sensitivity of 73% and a specificity of 90% in predicting field deterioration within the cluster of four Humphrey locations closest to the original MDT test site. Sensitivity was lower (40%) in predicting progression at retinal locations distant from the MDT test site, though specificity remained high (90%).

Simulating binocular visual field status in glaucoma.

AIMS: To simulate the central binocular visual field using results from merged left and right monocular Humphrey fields. To assess the agreement between the simulation and the binocular Humphrey Esterman visual field test (EVFT). METHOD: 59 consecutive patients with bilateral glaucoma each recorded Humphrey 24-2 fields for both eyes and binocular EVFT on the same visit. EVFT results were used to identify patients exhibiting at least one defect (< 10 dB) within the central 20 degrees of the binocular field. This criterion is relevant to a patient's legal fitness to drive in the UK. Individual sensitivity values from monocular fields are merged to generate a simulated central binocular field. Results are displayed as a grey scale and as symbols representing defects at the < 10 dB level. Agreement between patients failing the criterion using the simulation and the EVFT was evaluated. RESULTS: Substantial agreement was observed between the methods in classifying patients with at least one defect (< 10 dB) within the central binocular field (kappa 0.81; SE 0.09). Patients failing this criterion using the EVFT results were identified by the binocular simulation with high levels of sensitivity (100%) and specificity (86%). CONCLUSIONS: Excellent agreement exists between the simulated binocular results and EVFT in classifying glaucomatous patients with central binocular defects. A rapid estimate of a patient's central binocular field and visual functional capacity can be ascertained without extra perimetric examination.