Agreement among clinicians in the recognition of patterns of optic disk damage in glaucoma.

PURPOSE: To determine the interobserver and intraobserver agreement in the recognition of different patterns of glaucomatous optic disk damage and evaluate if these patterns changed over time in patients followed for a number of years. METHODS: Patients with early to moderate glaucoma (n = 105) were consecutively enrolled to participate in a prospective observational study. In the first part of the present study, optic disk photographs obtained closest to patient's entry date in the prospective study were classified in a masked fashion by three observers according to the pattern of optic disk damage into one of the following: (1) focal, (2) myopic, (3) senile sclerotic, (4) concentric cup enlargement, (5) normal appearance, or (6) miscellaneous (those disks that did not qualify for any of the other groups). The observers were also asked to assign a confidence score for each classification, ranging from 1 (low confidence) to 5 (highest confidence). The three observers reclassified the photographs after a minimal period of 2 months, in order to assess intraobserver agreement. In a second part of the study, one observer reviewed, in a masked fashion, all the optic disk photographs that had been taken during the routine follow-up of the 105 patients in order to evaluate whether the classification of disk pattern changed over time. RESULTS: Intraobserver agreement yielded kappa values (95% confidence interval [CI]) from 0.51 (CI, 0.40 to 0.62) to 0.85 (CI, 0.77 to 0.93) depending on the observer. Interobserver agreement kappa values between all three observers was 0.40 (CI, 0.35 to 0.46), but it improved if photographs classified with moderate or higher degrees of confidence were included (0.52 [CI, 0.44 to 0.60]). During a mean follow-up period of 8.2 +/- 4.8 years, 41.6% of the eyes were always classified into the same group and 23.6% of the eyes were classified at least once into two or more of the four patterns of damage (groups 1 to 4). CONCLUSIONS: Intraobserver agreement on the pattern of optic disk damage was generally very good, with some variation among the observers. Interobserver agreement was reasonable and increased proportionally with the confidence in the classification. During long-term follow-up, the pattern of optic disk damage usually did not change. This type of classification can probably be used accurately in clinical practice.

Natural history of normal-tension glaucoma.

OBJECTIVE: A recently reported randomized study described the role of intraocular pressure (IOP) in normal-tension glaucoma (NTG) pathogenesis and the effect of therapeutic lowering of IOP. This is a report of an analysis of the natural course of NTG during the time eyes were not receiving therapy, either in the time interval awaiting randomization or after being randomly assigned not to receive treatment to lower the IOP. DESIGN: Analysis of prospectively collected data on the long-term course of a cohort of untreated subjects with normal-tension glaucoma, a subset of subjects enrolled in a randomized controlled clinical trial. RANDOMIZATION AND SUBJECT SELECTION: If the field defect in the study eye threatened the point of fixation, the subject was randomly assigned to start on treatment immediately or to be observed without treatment until progression was documented. Otherwise, an eye was randomly assigned only when and if, subsequent to enrollment, it showed visual field progression, progression of optic disc cupping, or a new disc hemorrhage. PARTICIPANTS: Data were collected for this report on 160 subjects observed without treatment among a total enrollment of 260. They consist of 49 subjects who were randomly assigned on enrollment not to receive therapy, 24 followed without treatment for a time until later being randomly assigned to treatment, 31 similarly followed without treatment and who were later randomly assigned to be followed for an additional time without treatment, and 56 who enrolled but were never randomly assigned. MAIN OUTCOME MEASURES: Visual field data were used in this report only from the interval during which the eye had not been assigned to receive therapy and were analyzed by two measures of progression: the "survival" time to meeting a criterion of confirmed localized progression and the rate of change in the mean deviation (MD) index over time. RESULTS: The four subgroups just described were similar at baseline, except that the average MD index was slightly better for the 56 eyes that never progressed during the period of follow-up. By Kaplan-Meier analysis of all untreated subjects combined, approximately one third showed localized progression within 3 years and about half within 5 to 7 years. Of subjects followed for 3 years or more, 62 of 109 did not show a statistically significant negative slope of MD regressed over time, whereas the others showed a statistically significant MD decline, mainly between -0.2 and -2 db per year. CONCLUSIONS: Some cases of NTG progress more rapidly than others. Although approximately half of cases showed a confirmed localized visual field deterioration by 7 years, the change is typically small and slow, often insufficient to measurably affect the MD index.

Nocturnal hypotension: role in glaucoma progression.

The role of systemic blood pressure in glaucomatous damage remains undefined, with systemic hypertension and hypotension being implicated in different studies. We have previously reported that the physiologic nocturnal blood pressure "dip" may be exaggerated in some glaucoma patients with progressive field loss. A 24-hour ambulatory blood pressure recording was originally performed on 84 patients with glaucoma. The mean result across all our glaucoma patients were within the ranges reported in the literature for normal subjects. The normal-tension glaucoma and primary open-angle glaucoma groups did not differ significantly in blood pressure variables. Nocturnal blood pressure variables were lower in the patients with progressive field defects compared to those with stable visual fields. To determine long-term outcomes in these patients, we reevaluated the visual fields of the original 84 patients studied. In 70 patients with long-term visual field data (mean, 5.1 years), those who had shown greater nocturnal blood pressure dips were more likely to have shown field progression at some stage, despite good intraocular pressure control. Patients who had field progression showed significantly lower nocturnal blood pressure variables, with the dips of the systolic, diastolic, and mean arterial pressure significantly larger (systolic dip, P = 0.01). They also had a greater history of disk hemorrhages. A review of other 24-hour blood pressure studies in the literature shows that most are in agreement with these findings. The nocturnal reduction in blood pressure may, therefore, be an additional risk factor in glaucoma patients.

Optic disk appearances in primary open-angle glaucoma.

Primary open-angle glaucoma almost certainly develops in a multifactorial manner, with interplay between numerous risk factors affecting the disease. These risk factors, in addition to intraocular pressure, include a number of cardiovascular factors. Some of these factors may determine the appearance of the damaged glaucomatous optic nerve head. Patients with four specific optic disk appearances have been investigated, and differences have been identified in their demographic characteristics, prevalence of certain risk factors, the pattern of visual field damage, and circulatory abnormalities in their retrobulbar vessels. The findings provide evidence of the existence of subgroups of primary open-angle glaucoma with correlations between risk factor and type of optic disk. A reliable method by which the different disk appearances could be distinguished in an objective manner would be clinically valuable, and the scanning laser ophthalmoscope has shown potential promise to achieve this. The results of studies relating to various glaucomatous optic disk appearances are presented and discussed.

Glaucoma and vasospasm.

AIMS/BACKGROUND: To study the vasoactivity of glaucoma patients with four previously described and distinct disc appearances potentially representative of primary open angle glaucoma subgroups. METHODS: Patients with pure examples of four glaucomatous optic disc types--focal ischaemic, myopic glaucomatous, senile sclerotic, and those with generalised cup enlargement, were selected. A detailed ophthalmic, systemic, drug, and smoking history was taken from the patients who, in addition, underwent assessment of peripheral vasospasm with a laser Doppler flowmeter. Differences between the groups were evaluated using an analysis of variance, Student's t test, Pearson's chi 2 test, Fisher's exact test together with Spearman's and Pearson's correlation tests. RESULTS: 38 patients with focal ischaemic, 37 with myopic glaucomatous, 24 with senile sclerotic, and 24 with discs characterised by generalised cup enlargement met the selection criteria. The group of patients with focal ischaemic discs contained more women (66% versus 32%-50% in the other three groups; p = 0.01) and had a higher prevalence of vasospasm (63% versus 25%-49%; p = 0.01), migraine (32% versus 8%-19%; p = 0.02), and cold extremities (66% versus 17%-30%; p = 0.00003). The group of patients with senile sclerotic discs had a higher prevalence of systemic cardiovascular disease (58% versus 21%-30% in the other three groups; p = 0.01) and thyroid disease (21% cf 0%-8%; p = 0.01) and although their mean age was greater (76 years cf 55-65 years; p < 0.00001) the findings were independent of age. Smoking was unrelated to optic disc type. CONCLUSION: Vasospasm, previously associated with normal tension glaucoma, and generalised cardiovascular disease both appear to be specific risk factors for the development of particular subgroups of glaucoma and may be independent of absolute intraocular pressure levels exerting effects in patients with both "normal" or "raised" intraocular pressure. The simple assessment as to whether a glaucoma patient suffers from colder extremities than average appeared to be better at distinguishing the focal ischaemic type of glaucoma than the more complex determination of vasospasm using the laser Doppler flowmeter.

A comparison of the effects of betaxolol, timolol, and pilocarpine on visual function in patients with open-angle glaucoma.

PURPOSE: The author compares the effect of betaxolol, timolol, and pilocarpine on visual functions in patients with glaucoma. METHODS: Sixty-eight patients with early glaucoma were randomly allocated to betaxolol, timolol, or pilocarpine treatment and their visual fields, motion detection, and contrast sensitivity were studied over a 24-month period. A subset of the betaxolol and timolol group were also followed with short-wave automated perimetry. One eye of each patient was used in the analysis. RESULTS: All three drugs reduced pressure effectively. Pilocarpine and timolol were not significantly different from each other and both produced a more marked pressure reduction than betaxolol. There were no significant differences between the drugs on the visual fields, contrast sensitivity, or motion detection. Betaxolol appeared to have a better impact on the blue-yellow sensitivity of the upper nasal and upper temporal visual field quadrants than timolol. CONCLUSIONS: In spite of a greater pressure reduction, timolol did not have a more favorable effect on visual function. In the short-wave automated perimetry, the betaxolol did marginally better than timolol. The apparent dissociation between pressure reduction and protection of visual function deserves further study.

Comparison of the effect of latanoprost 0.005% and timolol 0.5% on the calculated ocular perfusion pressure in patients with normal-tension glaucoma.

PURPOSE: To compare the calculated mean ocular perfusion pressure at the end of 3 weeks' treatment with latanoprost 0.005% once daily or timolol 0.5% twice daily in normal-tension glaucoma patients. METHODS: In a three-center, double-masked, randomized, crossover study, 36 patients were allocated to two treatment groups; one received 3 weeks each of placebo, latanoprost, placebo, and timolol, whereas the other group had placebo, timolol, placebo, and latanoprost. Intraocular pressure and resting systemic blood pressure were measured at 9 AM, 12 noon, and 4 PM. Ocular perfusion pressure was calculated for each time period as well as the mean of three values (daytime average). Systemic blood pressure and heart rate were also recorded at 30-minute intervals during the last 24 hours of each treatment period. RESULTS: The average daytime mean ocular perfusion pressure (mean +/- SEM) following latanoprost treatment was 53.2 +/- 1.4 mm Hg, an increase of 8% from the latanoprost run-in period, compared with 50.9 +/- 1.1 mm Hg following timolol treatment, an increase of 2% from the timolol run-in period (P < .05, ANOVA). Timolol reduced the blood pressure. The difference in mean daytime and nighttime systolic blood pressure measurements as well as nighttime diastolic blood pressure was about 5 mm Hg between the latanoprost and timolol treatments. The daytime and nighttime heart rates were also slower during the timolol treatment. CONCLUSION: Because ocular perfusion pressure may be important in some glaucomatous patients, latanoprost appears to affect ocular perfusion pressure more favorably than timolol does in patients with normal-tension glaucoma.

The ability of scanning laser ophthalmoscopy to identify various glaucomatous optic disk appearances.

PURPOSE: To compare four distinct glaucomatous disk appearances using scanning laser ophthalmoscopy and determine the ability of a previously described discriminant analysis to detect glaucomatous damage for each group. METHODS: Two thousand three hundred eighty-eight stereoscopic optic disk photographs of 2,388 subjects with glaucoma or suspicion of glaucoma were reviewed to select four pure glaucomatous optic disk types. Twenty-three topographic, volumetric, and morphometric scanning laser ophthalmoscopic variables from one optic disk of each selected subject were compared. Differences between the groups were evaluated using an analysis of variance and the Pearson chi-square test. RESULTS: Forty-four focal ischemic disks, 38 myopic glaucomatous disks, 30 senile sclerotic disks, and 28 disks characterized by generalized cup enlargement were studied. Significant intergroup differences were found for the majority of the evaluated optic disk variables. The accuracy with which the discriminant analysis model was able to detect disks with glaucomatous visual field damage was 93.2% for focal ischemic disks, 81.6% for myopic disks, 66.7% for senile sclerotic disks, and 78.6% for disks with generalized cup enlargement. CONCLUSIONS: By comparing mean values for certain optic disk variables, scanning laser ophthalmoscopic optic disk assessment can distinguish groups of disks with specific appearances. However, the ability of presently available software to detect glaucomatous damage varied considerably with disk appearance. Expert clinical optic disk evaluation remains an important part of the assessment of patients suspected of having glaucoma, although refinement of computerized scanning laser ophthalmoscopic disk assessment may eventually make this easier.

A multicenter comparison study of the Humphrey Field Analyzer I and the Humphrey Field Analyzer II.

PURPOSE: The purpose of the study is to determine the comparability of the 30-2 full-threshold program in the original Humphrey Field Analyzer (HFA) I to the same test procedure in the new Humphrey Field Analyzer II. METHODS: At each of five clinical centers, one eye of patients with ocular hypertension and normal visual fields, patients with early glaucomatous visual field loss, and patients with more advanced visual field loss were tested with the two instruments plus a retest on a separate HFA I. All participants had undergone at least one prior visual field examination. To minimize the influence of any residual learning or fatigue effects, the order of testing for the three visual field examinations was counterbalanced across subjects. A total of 250 patients were tested (81 patients with ocular hypertension, 81 patients with early glaucomatous visual field loss, and 88 patients with more advanced glaucomatous visual field loss). RESULTS: No statistically significant differences were observed between thresholds, visual field indices, or reliability indices obtained with the HFA I and the HFA II. The small differences between the two instruments were equivalent to the variation observed for test-retest measures using only the HFA I. These results were consistent across the range of visual field characteristics shown by the ocular hypertensive, early glaucoma, and moderate glaucoma patient groups. CONCLUSIONS: The authors' results indicate that there are no differences in the visual field results obtained with the HFA I and the HFA II. These findings suggest that with careful attention to test protocols, the HFA I and HFA II may be used interchangeably to observe patients, even within the context of multicenter clinical trials.

Automated perimetry in detecting threats to fixation.

PURPOSE: To study in glaucoma patients the threat to fixation on a Humphrey field analyzer program 10-2 when one of the four innermost paracentral points is defective on program 30-2. METHODS: Forty-five eyes of 45 patients with chronic open-angle glaucoma in whom at least one of the innermost four defective paracentral points was reproducibly defective on program 30-2 of the Humphrey perimeter, with a size 3 target, on two consecutive tests, were studied with program 10-2. RESULTS: Of the 45 eyes with an abnormal paracentral point of program 30-2, 30 (66%) also showed involvement of a paracentral point on program 10-2, which was considered a threat to fixation. The remaining 15 were considered not to threaten fixation imminently. CONCLUSIONS: In about one third of glaucomatous fields considered to threaten fixation on the standard programs 30-2 and 24-2, the threat was not imminent. The extra evaluation is therefore useful before making radical and precipitous changes in management of the disease.

ROC analysis of Heidelberg Retina Tomograph optic disc shape measures in glaucoma.

OBJECTIVE: To determine the capacity of the Heidelberg Retina Tomograph (HRT) optic disc shape measures to detect glaucomatous damage. DESIGN: Prospective study. SETTING: Department of ophthalmology at a university-affiliated hospital in Vancouver. PATIENTS: Ninety-seven consecutive patients from the glaucoma centre and 129 healthy subjects selected from volunteers and employees of the department. One eye of each subject was chosen randomly. OUTCOME MEASURES: Visual fields, as assessed with the Humphrey perimeter, program 30-2, and 12 HRT shape characteristics: disc area, cup area cup/disc area ratio, rim area, cup volume, rim volume, mean cup depth, maximum cup depth, cup shape measure, height variation contour, mean retinal nerve fibre layer thickness and retinal nerve fiber layer cross-section area. ROC (receiver operating characteristic) curves were used to analyse the capacity of each HRT characteristic to detect glaucoma. RESULTS: Statistically significant difference were found between the control and glaucoma groups in age, cup area, cup/disc ratio, rim area, cup volume, rim volume, mean cup depth, cup shape measure, mean retinal nerve fibre layer thickness and retinal nerve fibre layer cross-section area (p < or = 0.003, t-test). The largest (i.e., best) ROC curve area was found for cup shape measure (area = 0.812), rim area (0.809), cup/disc area ratio (0.804) and rim volume (0.768). The mean reference height was 0.31 mm (standard deviation [SD] 0.14 mm) for the control group and 0.29 mm (SD 0.12 mm) for the glaucoma group, a nonsignificant difference. CONCLUSIONS: Cup shape measure was the most predictive HRT shape characteristic.

The ability of Medmont M600 automated perimetry to detect threats to fixation.

PURPOSE: The authors studied the sensitivity and specificity of the Medmont M600 central 10 degrees program (Medmont PTY Ltd., Camberwell, Victoria, Australia) in identifying paracentral threats to fixation mapped on the Humphrey program 10-2 (Humphrey Inst. Inc., San Leandro, CA, U.S.A.). METHODS: Humphrey automated threshold perimetry (program 10-2) and Medmont M600 automated threshold perimetry (central 10 degrees program) were performed on 62 eyes of 62 patients with glaucoma, and their paracentral point defects on the field were investigated. The sensitivity and specificity of Medmont central 10 degrees program were analyzed. RESULTS: The sensitivity and specificity of Medmont M600 central 10 degrees field was 78% and 81% within 1 degree, and 95% and 83% within 3 degrees in detecting the field defects on the Humphrey program 10-2. The Medmont M600 central 10 degrees threshold visual field test took 36% of the testing time required for the Humphrey threshold 10-2 visual field examination. CONCLUSION: The Medmont perimeter seems to be efficient in its performance of central threshold testing and significantly cuts down the test time.

Reproducibility of retinal and optic nerve head blood flow measurements with scanning laser Doppler flowmetry.

PURPOSE: To evaluate the interobserver variability and the reproducibility of retinal and optic nerve head capillary blood flow measurements performed with a new noninvasive equipment, the scanning laser Doppler flowmeter (Heidelberg Engineering, Heidelberg, Germany). METHODS: Blood flow measurements were performed during three independent sessions in six patients with glaucoma and five normal subjects using the scanning laser Doppler flowmeter (SLDF), which allows the visualization of perfused capillaries and vessels of the retina and optic nerve head and enables the quantification of capillary blood volume, flow, and velocity in any selected area of the perfusion map. To evaluate the interobserver variability in selecting the areas in the perfusion map to be measured, three observers tried to locate the same areas in the perfusion map of images obtained during the first session. To evaluate the reproducibility of the measurements, the observers measured correspondent areas in the peripapillary retina and in the optic nerve head of images from the three sessions. Areas of different sizes (10 x 10 pixels and 4 x 4 pixels) were measured. RESULTS: The agreement between readings performed by the three observers was very good, with the reliability coefficient for the various parameters varying from 0.90 to 0.98. The reproducibility of retinal and lamina cribrosa measurements with the 10 x 10 pixel square target was good (reliability coefficient for the different parameters ranging from 0.70 to 0.85) and much better than the reproducibility of the 4 x 4 pixel target. The measurements performed in the neuroretinal rim area also had poor reproducibility. The measurements from the patients with glaucoma tended to be more reproducible than those from normal subjects. CONCLUSIONS: The SLDF allows reproducible blood perfusion measurements of retinal and lamina cribrosa areas when a target square of 10 x 10 pixels is used.

Correlation between the visual field indices and Heidelberg retina tomograph parameters.

PURPOSE: We wished to determine whether a relationship exists between Heidelberg retina tomograph (HRT) parameters and the visual field indices. METHODS: One eye was randomly chosen from 59 normal patients [normal visual field and normal optic nerve head (ONH) and intraocular pressure (IOP) < 21 mm Hg], 64 ocular hypertensive patients (normal visual field and normal OHN and IOP > 22 mm Hg), 124 high-tension glaucoma patients (abnormal visual field and/or abnormal optic nerve and IOP > 22 mm Hg) and 47 low-tension glaucoma patients (abnormal visual field and or optic disc and IOP < 21 mm Hg). All the patients were examined with Humphrey Perimeter, program 30-2, and HRT. Findings were assessed by analysis of variance, Pearson's correlation coefficient, and multiple linear regression. RESULTS: Among all subjects, we noted a statistically significant correlation (Pearson's r, p < 0.001) between cup area, cup/disc area ratio, rim area, rim volume, cup shape measure, and retinal nerve fiber layer cross-section area with mean deviation and corrected pattern SD. Multiple linear regression analysis demonstrated that rim area was the most important predictor of mean deviation and corrected pattern SD. CONCLUSIONS: The presence of significant correlations between some HRT parameters, such as rim area and cup shape measure and visual field indices, suggests that these HRT parameters could be good indicators of the degree of glaucomatous ONH damage.