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Latanoprost, a prostaglandin analogue, was given topically to 20 patients with normal pressure glaucoma in a double masked randomized study. Either latanoprost 0.006% or placebo (vehicle) was administered twice a day for 14 days. Latanoprost caused a statistically significant (p < 0.001) reduction in intraocular pressure from a diurnal baseline level of 16.8 to 14.3 mmHg, as measured on day 14. Latanoprost was well tolerated.

The author has been involved in 3 studies, the multicentre collaborative normal-tension glaucoma study, a study of 4 phenotypes of glaucomatous disc appearances and their associations, and a study reporting on biostatistical evidence for 2 distinct chronic open-angle glaucoma populations. These studies have some common threads whose clinical implications are discussed.

Purpose To compare rim area rates in patients with and without the visual field (VF) progression endpoint in the Canadian Glaucoma Study and determine whether intraocular pressure (IOP) reduction following the endpoint altered rim area rate. Design Prospective multicenter cohort study. Methods setting: University hospitals. patient population: Two hundred and six patients with open-angle glaucoma were examined at 4-month intervals with standard automated perimetry and confocal scanning laser tomography. intervention: After the endpoint, IOP was reduced by ≥20%. outcome measures: Univariate analysis for change in rim area rate and multivariable analysis to adjust for independent covariates (eg, age, sex, and IOP). Results Patients with an endpoint (n = 59) had a worse rim area rate prior to the endpoint compared to those without (n = 147; median [interquartile range]: −14 [−32, 11] × 10 −3 mm 2 /y and −5 [−14, 5] × 10 −3 mm 2 /y, respectively, P = .02). In univariate analysis, there was no difference in rim area rate before and after the endpoint (median difference [95% CI], 8 (−10, 24) × 10 −3 mm 2 /y), but the muItivariate analysis showed that IOP reduction >2 mm Hg after the endpoint was strongly linked to a reduction in rim area rate decline (8 × 10 −3 mm 2 /y for each additional 1 mm Hg reduction). Conclusions Patients with a VF endpoint had a median rim area rate that was nearly 3 times worse than those without an endpoint. Lower mean follow-up IOP was independently associated with a slower decline in rim area.

Objective To evaluate the incidence of visual field and optic disc progression in glaucoma patients with distinct patterns of optic disc damage. Design Prospective, observational case series. Participants One hundred five patients with open-angle glaucoma. Methods Baseline optic disc photographs of 105 study eyes of 105 patients were reviewed by 2 masked observers and classified according to patterns of disc damage into the following categories: focal, myopic, senile sclerotic, and generalized disc damage. Patients were followed up every 6 months with standard automated perimetry (SAP), high-pass resolution perimetry (HRP), and scanning laser tomography (SLT) with the Heidelberg Retina Tomograph. Main outcome measures Visual field (SAP and HRP) and optic disc (SLT) progression were determined according to predefined criteria. Results Twenty-four eyes were classified into the focal, 8 into the myopic, 12 into the senile sclerotic, and 28 into the generalized group. Eyes from 33 patients could not be classified by the observers into any of these groups and were excluded from further analysis. Although intraocular pressure during follow-up was similar among the four groups, some differences in frequency of progression were observed. Patients with senile sclerotic discs had the lowest rates of visual field progression (both with SAP and HRP) and optic disc progression, although the differences were significant only for optic disc progression ( P = 0.05). Conclusions Patients with senile sclerotic discs showed a tendency towards less visual field and optic disc progression when compared with patients with other types of disc damage.

PURPOSE: To uncover risk factors for the highly variable individual rates of progression in cases of untreated normal-tension glaucoma. METHODS: Visual field data were assembled from 160 subjects (160 eyes) enrolled in the collaborative normal-tension glaucoma study during intervals in which the eye under study was not receiving intraocular pressure–lowering treatment during prerandomization and postrandomization intervals. Analyses included multivariate analysis of time-dependent Cox proportional hazard, Kaplan-Meier analysis of "survival" without an increment of visual field worsening, and comparison of slopes of change in mean deviation global index over time. RESULTS: Most migraine occurred in women, but analysis demonstrated that gender and presence of migraine contribute separately to the overall risk. The risk ratio for migraine, adjusted for the other variables was 2.58 ( P = .0058), for disk hemorrhage was 2.72 ( P = .0036), and for female gender 1.85 ( P = .0622). The average fall in the mean deviation index was faster in nonmigrainous women than in nonmigrainous men ( P = .05). Suggesting genetic influence, Asians had a slower rate of progression ( P = .005), and the few black patients enrolled had a tendency for faster progression. However, self-declared history of family with glaucoma or treated for glaucoma did not affect the rate of progression. Neither age nor the untreated level of intraocular pressure affected the rate of untreated disease progression, despite their known influence on prevalence. CONCLUSIONS: Whereas risk factors for prevalence help select populations within which to screen for glaucoma, the factors that affect the rate of progression help decide the expected prognosis of the individual's untreated disease and thereby the frequency of follow-up and aggressiveness of the therapy to be undertaken.

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.

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.

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.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.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.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.

Purpose: The purpose of this study was to observe the blood flow velocity in the retrobulbar vessels of patients with glaucoma with different appearances of optic discs. Methods: Patients with four different disc appearances (focal ischemic discs, myopic glaucomatous discs, senile sclerotic discs, and discs with a generalized enlargement of the cup) were selected from a pool of optic discphotographs. No clinical information from the patients was available during the selection. Color Doppler imaging (CDI) was performed in those patients whose discs clearly belonged to one of the disc patterns. The peak systolic and end diastolic velocity were measured and the resistance index calculated from the central retinal artery, short posterior ciliary arteries and ophthalmic artery. Results: Color Doppler imaging was performed in 24 patients with focal ischemic discs, 26 patients with myopic glaucomatous discs, 16 patients with senile sclerotic discs, and 16 patients with generalized enlargements of the cup. The patients with senile sclerotic discs had statistically significantly lower diastolic velocity and a higher resistance index in their ophthalmic, central retinal and the mean of the short posterior ciliary arteries sampled. These statistical differences persisted for the ophthalmic artery even after correcting the values for the age differences between the groups. Conclusions: Patients with senile sclerotic discs seem to have greater circulatory abnormalities in their retrobulbar vessels studied with color Doppler imaging that are compatible with a higher downstream resistance in these vessels. These circulatory abnormalities could be related to the pathogenesis of the glaucoma in these patients.

Purpose: To study the prevalence of risk factors for glaucoma as well as the pattern of visual field defects and their progression in patients with open angle glaucoma with different and distinct optic nerve appearances. Methods: One thousand seven hundred eleven optic disc stereo photographs of patients with glaucoma and ocular hypertension and of those suspected of having glaucoma were reviewed to identify pure examples of discs with four different optic disc appearances: focal ischemic discs, myopic glaucomatous discs, senile sclerotic discs, and generalized enlargement of the optic cup discs. The clinical charts of the selected patients were reviewed, with emphasis on the presence of predetermined ocular and systemic risk factors. Their automated visual fields also were analyzed. Results: Thirty-four patients with focal ischemic discs, 38 with myopic glaucomatous discs, 22 with senile sclerotic discs, and 23 with generalized enlargement of the optic cup discs were selected. Patients with myopic glaucoma and generalized enlargement of the optic cup discs were significantly younger than patients with focal ischemic and senile sclerotic discs. There were more women in the focal ischemic group. Patients with senile sclerotic discs had a significantly higher prevalence of ischemic heart disease; they also had a higher prevalence of systemic hypertension, which did not reach statistical significance. Migraine was 2.5 times more frequent in the focal ischemic group than in the other groups. Intraocular pressure was significantly higher in the generalized enlargement group. The pattern of visual field defect in the four groups also was distinctly different. Conclusions: Patients with different disc appearances, selected only from their disc photographs, showed differences in their demographic characteristics, prevalence of certain systemic risk factors, intraocular pressure levels, and the pattern of their visual field damage. These findings suggest that these various disc appearances probably represent different populations of patients with glaucoma with, possibly, different pathogenic mechanisms.

We used color Doppler imaging to study blood flow velocity in the central retinal artery and the short posterior ciliary arteries in patients with glaucoma.Fifty-two patients with chronic open-angle glaucoma, 24 patients with normal-tension glaucoma, and 28 normal subjects were studied. The mean of the peak systolic velocity, the end diastolic velocity, and the resistive index were compared in the three groups.Compared with the normal subjects, the patients with chronic open-angle glaucoma showed a statistically significant (P.05) decrease in the mean end diastolic velocity and an increase in the mean resistive index in all vessels studied. The patients with normal-tension glaucoma showed similar changes, achieving significance most prominently in the central retinal arteries, compared with normal subjects (P.05). There were no statistically significant differences between the patients with chronic open-angle glaucoma and those with normal-tension glaucoma.Open-angle glaucoma appears to be associated with a decreased mean flow velocity and an increased mean resistive index in the ocular vasculature. These changes are in keeping with possibly compromised circulation in this region.

In a 1973 study of risk factors, it was shown that the condition very rarely progressed for normal pressure glaucoma patients with a history of a major shock-like state preceding the diagnosis of their glaucoma; whereas patients without such a history of shock usually did have their glaucoma worsen over time.

82 eyes of 82 patients with different types of glaucoma were examined with various psychophysical tests assessing central and paracentral function, including foveal temporal contrast sensitivity function, FM 100-Hue test, and foveal and parafoveal blue-on-yellow-sensitivity. For all eyes visual field tests were performed with the Humphrey-Field-Analyzer, program 30-2. Global visual field indices were calculated as follows: Mean Sensitivity MS, Mean Deviation MD, and Corrected Pattern Standard Deviation CPSD. Linear regression analysis and multiple regression analysis correcting for a possible influence of age between the central and paracentral criteria and the global indices was performed. For the entire study population highly significant correlations are present between foveal and parafoveal blue-on-yellow-sensitivity and MS, MD and CPSD. Whereas in the Normal Tension Glaucoma subgroup (19/82 eyes) no significant correlations are found, the subgroup of 35/82 eyes with markedly elevated intraocular pressure (> or = 30 mmHg) shows highly statistically significant correlations between the low- and high-frequency end of the foveal temporal contrast sensitivity function and foveal and parafoveal blue-on-yellow-sensitivity and the global field indices. The results of the present study support the idea that there are two different mechanisms of glaucomatous damage, one which is pressure-dependent and one which may be pressure-independent. The pressure-dependent mechanism is responsible for deficits of central or paracentral function which are correlated to overall visual field damage.

Sir William Bowman died in 1892 exactly one hundred years ago. His singularly productive life has already been chronicled in detail by many. William Bowman, Franz Come1is Donders and Albrecht Von Graefe were close friends and undoubtedly the outstanding ophthalmologists of the 19th century, responsible among other things for giving ophthalmology its scientific tradition. There can be no greater tribute to Bowman's own greatness than to have been admitted to membership of the Royal Society of Science at the age of 25 for his work on muscle, liver and kidney. He was awarded the Society's medal a year later for his scientific achievement. The esteem with which he was held by his peers resulted in his being made the first president of the Ophthalmological Society of the United Kingdom. In 1884 a year after he stepped down from the presidency the Bowman Lecture was instituted. He was the first surgeon in England to perform and recognise the value of iridectomy in the management of the glaucomas in 1857. His defence of that procedure against an attack from Dublin remains a classic in diplomacy and can be found in Hirschberg's History of Ophthalmology. In his last publication in 1891, which was the obituary to his good friend Donders, Bowman wrote: 'He had the fortune to have contributed to the advancement of his speciality and lived long enough to see the fruit of his work uni­ versally recognised.' Hirschberg, who knew Bowman well said that this obituary could also be applied to the life of Sir William Bowman. The work of McKenzie in 1835 linked high pressure in the eye with what was then known as glaucoma.l Helm­ holtz invented the ophthalmoscope2 in 1852 and by 1857 von Graefe recognised cupping of the optic nerve. He div­ ided glaucoma into an acute congestive glaucoma, chronic congestive glaucoma, secondary congestive glaucoma and amaurosis with excavation of the optic nerve.3 This classi­ fication was made at a time when tonometry was not avail­ able. Donders4 first linked all these groups as glaucoma simplex associated with elevated intraocular pressure. Schnabel5 argued that glaucoma was an intrinsic disease

A LTHOUGH LOWERING OF INTRAOCULAR PRESSURE is a principal guide for therapy of chronic glaucoma and for determining the efficacy of treatment in scientific studies, it is really the preservation of axons (structure) or visual capabilities (function) that matters to the glaucoma patient in the long run. The authors met to try to define progression of the disease using old and new methods used to quantify the structural and functional status of glaucoma. We considered this in the context of clinical care and scientific studies, especially as treatment modalities intended to affect blood flow or neural survival (rather than simply lowering the intraocular pressure) are emerging. We hoped to develop concrete criteria that might be suggested for widespread use to create uniformity in scientific studies and clinical practice. When we considered what methods and criteria of measured parameters might be suitable to judge glaucomatous deterioration, it quickly became apparent that the needs differed according to purpose. For example, evaluation of the course of the disease in an individual patient is different from identifying small differences in the average course between two or more study groups and also different from ascertaining the safety of each individual enrolled in a clinical trial. In some circumstances, the progression of one parameter may be more appropriate than others, particularly because scientific studies may vary in purposes. The demonstration of adequate axonal nutrition, for example, may require progression in a parameter that is different than the protection from the parameter used to assess protection from harm caused by an ischemic insult. Finally, emerging or new technology may provide a means of evaluation of special advantage. Therefore, no single current method, measured parameter, or criterion appeared suitable for all these circumstances. Indeed, most clinical studies devise new criteria to meet their particular needs or use new methods that became available since prior studies were designed,1 which makes comparison between studies difficult. For this reason, we abandoned the effort to define specific parameters to be measured, particular methods of examination currently available or in use, or particular criteria to be applied to available measurements that we might suggest as “the standard” to be used for all clinical and research purposes. Instead, we considered the characteristics that would make a determination of glaucoma progression acceptable. The following guidelines and considerations are proposed: 1. The measurement and criteria used in clinical studies should have good performance in recognizing progression and in separating the groups being compared (stable versus unstable, rapid deterioration versus less rapid, and so forth). This requires good reproducibility of the tests and that the parameter used have small and known biological fluctuation in an individual from one time to another. 2. The measured values and criteria that provide good sensitivity and specificity in recognizing progression of the disease may very well differ from those that are sensitive and specific in recognizing the presence or absence of the disease. 3. The measurement should be accepted as relevant to the course of the disease and its clinical outcome. This may include direct measurements of structure (axon count) or function (vision) exemplified, for example, by retinal nerve fiber measurements, optic disk parameters, electrophysiologic measurements of ganglion cell activity, visual field as well as other visual psychophysical testing. 4. In principle, an acceptable measurement may also be a short-term surrogate of long-term outcome, that is, some predictive parameter for which there has been documented linkage to future progression and outcome. Currently, intraocular pressure is accepted as a surrogate for expected Accepted for publication July 18, 2000. From the Bascom Palmer Eye Institute, University of Miami, Miami, Florida (Dr Anderson); Department of Ophthalmology, University of British Columbia, Vancouver, BC, Canada (Dr Drance); Director of Diagnostic Research Discoveries in Sight Research Labs, Devers Eye Institute, Portland, Oregon (Dr Johnson); Departments of Ophthalmology and Physiology & Biophysics Dalhousie University, Halifax, N.S. Canada (Dr Chauhan); Zeiss Humphrey Systems, Dublin, California (Dr Patella); Division of Disease Control, Department of International Health, Johns Hopkins University, Baltimore, Maryland (Dr Katz). Reprint requests to Stephen M. Drance, OC, MD, 1561 Wesbrook Crescent, Vancouver, BC V6T 1V9, Canada.

The authors studied the effect of multiple threshold determinations on local and global (root-mean-square) short-term fluctuation in 30 subjects (10 controls, 10 glaucoma suspects, and 10 glaucoma patients) with a mean age of 56.70 years. Five custom programs were designed on the Octopus perimeter in which the total number of threshold determinations was equal but in which thresholds at 2 principal locations were determined between 2 and 15 times. One randomly selected eye of each subject was first tested with the standard Octopus programs G1 and 31 followed by the custom programs. Local fluctuation initially increased with the number of threshold determinations and then stabilized after five determinations. Global fluctuation was not influenced by the number of determinations and the values obtained by the shorter custom programs were not significantly different from those obtained by the standard programs. Programs that determine thresholds only twice at a given location may underestimate local fluctuation. Furthermore, local fluctuation is de-emphasized by the "watering-down" effect of estimating global fluctuation.

A total of 106 eyes of 106 patients with different types of glaucoma were examined by automated light-sense, flicker and resolution perimetry (Humphrey Field Analyzer, program 30-2; flicker perimeter as described by Lachenmayr [16, 18]; resolution perimeter as devised by Fris'en [4, 6, 8–11]). The fields were classified in a masked fashion as being normal or as having purely diffuse loss, purely localized loss or diffuse as well as localized loss. As compared with light-sense perimetry, resolution perimetry had a markedly lower sensitivity in the detection of glaucomatous damage (77%) but a high specificity (93%); the comparison of resolution perimetry with flicker perimetry showed similar results (sensitivity, 75%; specificity, 85%). When flicker perimetry was compared with light-sense perimetry and vice versa, the sensitivity was high (95% and 94%, respectively), but the specificity was low (57% and 62%, respectively). The prevalence of detection of diffuse loss by both light-sense and resolution perimetry was related to visual acuity, whereas flicker perimetry did not show such a relationship.

One hundred forty-three patients with intraocular pressures (IOPs) above 22 mmHg and without visual field defects or any obvious evidence of optic nerve damage were randomly assigned to either a timolol treatment group or no treatment in a 6-year prospective clinical trial. Endpoints were defined as reproducible visual field defects on automatic perimetry, disc hemorrhages, or stereophotographically documented optic nerve head changes. Endpoints developed in 42 patients: 28 visual field defects, 8 changes in disc appearance, and 6 disc hemorrhages. Of the 42 patients, 20 were treated and 22 were not. Survival analysis showed no statistically significant differences in failure time to any endpoints between the two groups. In the untreated group, the time to failure of disc change was related to the mean IOP during the study and also to the changes in the IOP from baseline. A significant correlation was found between initial cup-to-disc ratio and survival time to visual field defects in the untreated group.

Traditionally, the sensitivity and specificity of a new diagnostic test are derived from its application to two groups of individuals known to have or not to have met the criterion to be detected as judged by means of a "gold standard", some external time-honored test. In this study, a test with unknown accuracy parameters was used to detect an end-point criterion in an ongoing ophthalmological clinical trial. Since no external test method was available to assess the accuracy of this test, equations were derived relating the unknown sensitivity and specificity of the test to data frequencies based on replicate measurements. The solutions to these equations also provided estimates of the incidence rate of the criterion under investigation in the group tested, and of the predictive values of the test. The validity of this method of estimation is discussed, and applications to other situations are suggested.

Twenty-six eyes of 26 patients with low-tension glaucoma and 34 eyes of 34 patients with high-tension glaucoma were studied. Fifty-one measurements were available on each patient, including visual field indices, finger blood flow measurements, as well as haematological, coagulation, and biochemical and rheological variables. Multivariate analysis revealed two statistically distinct groups of patients, with low and high tension glaucoma cases equally distributed in both. The smaller group (15 patients) showed a suggestion of vasospastic finger blood flow measurements, and had a high positive correlation between the mean deviation (MD) index of field severity and the highest intraocular pressure (r = 0.715, p = 0.0008). The second, larger group (45 patients) showed disturbed coagulation and biochemical measurements, suggestive of vascular disease, and had no correlation between the MD index and the highest intraocular pressure.

This is to present the results of randomized multicenter normal tension glaucoma study. The primary aim of the study was to establish whether a 30% or greater pressure reduction altered the course of NTG compared to untreated controls. Our study confirms that in glaucoma patients even with normal intraocular pressures the pressure is involved in its pathogenesis and that pressure reduction favourably affects its course in a significant proportion of cases. Moreover, it identifies a great variability of the untreated disease. Over 7 years nearly half appeared to show no progression, the other half showed progression of their damaged area but this was slow and often did not result in a change of their MD index. There was a small group, who showed rapidly advancing disease, which was likely lead to visual handicap. Moreover, it was then attempted to study risk factors, other than intraocular pressure. Gender, ethnic background, migraine and the presence of disc hemorrhage adversely influence the course of the disease and may therefore account for some of the variability in the course of the disease. normal tension glaucoma, randomized multicenter study.

To study whether the benefit of lowering of intraocular pressure (IOP) varies according to certain traits.Randomized clinical trial, secondary analysis.Visual field data were analyzed from 144 subjects (144 eyes) randomized not to receive IOP-lowering treatment or to have the IOP lowered by 30%. Survival analyses were applied to compare times to progression between groups. Changes in mean deviation global index over time were compared with multilevel random effects models.By univariate analysis, the most readily demonstrated treatment benefit occurred in patients without baseline disk hemorrhage, of female gender, with family history of glaucoma, without family history of stroke, without personal history of cardiovascular disease, and with mild disk excavation; IOP lowering benefited females with migraine (P.05) but perhaps without eliminating all migraine-associated risk.It is suggested that different factors may contribute to the glaucomatous optic neuropathy in different cases of normal tension glaucoma, interacting with IOP to different degrees and, thereby, affecting the magnitude of benefit of IOP lowering. Further study is required to establish interactions that would have implications for understanding the disease mechanisms in glaucomatous cupping, for guiding development of new treatment modalities, and for making clinical decisions regarding prognosis and management of individual patients.

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.

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.

The pharmacologic differences between the betablockers currently used for pressure reduction in patients suffering from glaucoma have become of more than academic interest since Flammer and his group reported that the visual fields of betaxololtreated glaucoma patients fared better than the fields of timolol-treated patients. 13 There are a number of reported studies that support the fact that risk factors other than intraocular pressure, including a number of vascular risk factors, are involved in the pathogenesis of the open-angle glaucomas. The results of some of the vascular studies are conflicting, which is not surprising, as the methods of examination and, above all, the patient selection are strikingly different. It is generally thought that the lower the intraocular pressure levels in a given glaucoma patient, the more likely it is that these other factors, including the vascular ones, may be involved in the pathologic process. 19

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 χ2 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

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.

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.

Currently used ocular hypotensive agents do not effectively lower intraocular pressure (IOP) in some normal-tension glaucoma (NTG) patients. The prostaglandin F2 alpha analogue, latanoprost, has been shown to reduce IOP in normal subjects and ocular hypertensive glaucoma patients by increasing uveoscleral outflow. This mechanism is expected to be particularly effective in the lower IOP range that is typical of NTG. To date, three dose regimens of latanoprost have been shown to reduce IOP significantly in NTG. The IOP reductions of 14.2% and 15% obtained with twice-daily application of 0.0015% and 0.006% latanoprost, respectively, were comparable to the modest IOP reduction that has been reported for other glaucoma drugs in NTG. In contrast, once-daily application of 0.005% latanoprost resulted in a 21.4% IOP reduction. In another study that included 24-hour monitoring of systemic blood pressure and heart rate in NTG patients, the ocular perfusion pressure was found to improve more on once-daily 0.005% latanoprost than on twice-daily treatment with 0.5% timolol. Thus, once-daily 0.005% latanoprost appears to be a more effective and more convenient ocular hypotensive agent for treating NTG than currently used glaucoma drugs. However, long-term studies will ultimately be needed to establish the efficacy of this new drug to delay or prevent the progression of visual field loss in normal tension glaucoma.

PURPOSE To compare the optic discs of 62 healthy individuals 68 patients who have ocular hypertension (OH), and 182 patients with primary open-angle glaucoma (132 high-tension glaucoma (HTG) and 50 normal-tension glaucoma (NTG)), and determine whether disc size exerted an influence on the group differentiation. PATIENTS AND METHODS Standard criteria were used to define glaucoma and normality. Ocular hypertension was defined as having raised intraocular pressure, a normal visual field, and a healthy optic disc/retinal nerve fiber layer (RNFL). The optic disc of one eye from each individual was analyzed using a confocal scanning laser ophthalmoscope (Heidelberg Retina Tomograph software version 1.11, Heidelberg Engineering, Heidelberg, Germany). Thirteen topographical, volumetric, and shape parameters were compared between the three diagnostic groups. In addition, the individuals were divided into subgroups on the basis of disc size to determine any effect of disc size on the differentiating ability of the confocal scanning laser ophthalmoscope. Differences between the groups were evaluated using an analysis of variance. RESULTS Glaucomatous optic discs were found to differ from both healthy and OH discs, although no differences in disc area between the groups were identified. On the basis of disc size, differentiating the glaucomatous discs was best for midsized discs of 2 mm2 to 3 mm2. However, no difference was found between healthy and OH discs, even when allowing for disc size. CONCLUSIONS Ocular hypertensive optic discs (with a clinically normal appearance) could not be distinguished from healthy discs using a confocal scanning laser ophthalmoscopic technique. Glaucomatous optic discs were found to differ from both healthy and OH discs, with a limited effect of disc size.

To examine blood flow in the retina and optic nerve head of patients with primary open-angle glaucoma.Retinal and optic nerve head blood flow of glaucoma patients and control subjects of similar age and gender were measured in arbitrary units with the Heidelberg Retina Flowmeter, a scanning laser Doppler flowmeter (Heidelberg Engineering, Heidelberg, Germany). A total of 33 glaucoma patients and 29 control subjects were included in this study. Microvascular blood volume, flow, and velocity were analyzed in four areas of the retina approximately 100 microns from the edge of the optic disk (two temporal, one superior, and one inferior), in one area of the neuroretinal rim, and in the lamina cribrosa.The glaucoma patients had significantly decreased blood volume, flow, and velocity in one temporal retinal area (P.006) and in blood volume in the inferior retinal area (P = .04). They also had significantly decreased blood volume, flow, and velocity in the lamina cribrosa (P.0004), which also had more areas the investigators judged to be avascular compared to control subjects (P.0001). No differences between glaucoma and control subjects in the blood flow measurements of the neuroretinal rim were found.These findings suggest that glaucoma patients tend to have less blood volume, flow, and velocity in the lamina cribrosa and upper temporal peripapillary retina. The temporal area below the horizontal, corresponding to the papillomacular bundle, did not show this difference. The findings may be significant in the pathogenesis of primary open-angle glaucoma.

Purpose To examine the effects of topical timolol and latanoprost on retrobulbar vessel blood velocity in patients with glaucoma or ocular hypertension. Methods Nine patients with primary open-angle glaucoma and six patients with ocular hypertension were enrolled for this study. All patients were treated topically with 0.5% timolol or 0.005% latanoprost, using a double-masked crossover design with a 3-week washout before administration of each drug. Each patient had a baseline color Doppler imaging ultrasound of the central retinal artery, short posterior ciliary arteries, and ophthalmic artery and two other ultrasound examinations during the 1-week treatment with each drug, performed 12 hours after the first dose of the drug and 12 hours after the last dose, 7 days later. Results Both topical timolol and topical latanoprost significantly reduced the intraocular pressure. The only significant change observed in the retrobulbar blood velocity with timolol was a reduction of end diastolic velocity in the ophthalmic artery 12 hours after the first dose, accompanied by a trend toward a decrease in the peak systolic velocity and an increase in the resistance index in the same vessel. No change in blood velocity was observed with latanoprost. Conclusion Topical timolol and latanoprost significantly reduced the intraocular pressure in ocular hypertensive and glaucoma patients without creating substantial hemodynamic changes in the retrobulbar vessels.

• Purpose: To determine whether lower blood velocities and high resistive index in the retrobulbar arteries are primary or secondary to glaucomatous damage in patients with open-angle glaucoma. • Methods: Color Doppler imaging was performed in 32 glaucomatous patients with unilateral visual field loss and in 31 control subjects. Peak systolic velocity and end diastolic velocity were measured, and resistive index was calculated in the central retinal artery and short posterior ciliary arteries. • Results: In patients with glaucoma, both the more affected and the contralateral eyes with normal visual fields had significantly lower peak systolic velocity and end diastolic velocity in their central retinal artery and short posterior ciliary arteries than did the control subjects of similar age (P ≤ .03). The resistive index of the central retinal artery of both eyes of patients with glaucoma was also significantly higher than in the control subjects (P = .001). When considering the 16 patients who had the greatest visual field asymmetry, the more affected eyes had lower peak systolic velocity and end diastolic velocity in the central retinal artery than the contralateral eyes did (P = .02). • Conclusions: Even eyes with normal visual fields in patients with asymmetric disease had decreased blood velocities in their retrobulbar vessels, suggesting that these circulatory changes probably precede detectable damage. Furthermore, the finding of lower central retinal artery blood velocities in the more affected eye of asymmetric patients suggests that low blood velocities may be one of the lateralizing factors in those patients and that they have a possible role in the pathogenesis of the disease.

The first two visual field examinations of each of 16 glaucoma suspects and 16 glaucoma patients, who were followed up for a median of 7.46 years with seven examinations, were averaged. Three-dimensional color-coded images of the visual field were then generated. After correcting for test-retest variability, the images, as well as additional interpolated images, were aligned and presented in rapid succession to create an animation sequence. Five glaucoma specialists trained themselves to classify the visual fields as either progressing or not progressing. The interobserver and intraobserver agreement rates were then calculated. Perfect agreement (100% concordance) between the observers was obtained for 18 (56.3%) subjects, and at least 80% concordance was obtained for 27 (84.4%) subjects. Of the eight sequences that were repeated to test intraobserver agreement, four of the five observers had a value of at least 87.5%.

Background: Despite strictly defined criteria for visual field progression in the ongoing Normal-tension Glaucoma Study, the authors noted a surprisingly large number of patients reaching the endpoint. Traditional methods could not be used to check the diagnostic accuracy of their criteria, because no "gold standard" was established for distinguishing true change from physiologic long-term fluctuation. Methods: The authors developed a statistical method based on the results of duplicate tests for progression in their subjects. This method allowed the authors to assess the sensitivity, specificity, and predictive values of their diagnostic criterion. It also estimated the true incidence of progression and provided standard errors for the estimates. Results: The authors found that their original strict criteria for progression, based on duplicate testing, produced false calls of progression 57% of the time. By raising the requirement for deterioration and by repeating the entire sequence of duplicate testing once more, the authors have successfully reduced the rate of false calls to 2%. Conclusion: Accuracy in recognizing progression is improved by not accepting small changes as evidence of progression and by confirming the findings on repeat testing.

Cigarette smoking is associated with glaucoma. Nicotine from cigarette smoking is known to produce hemodynamic changes. We studied the effect of nicotine on the ophthalmic artery flow velocity using transcranial Doppler ultrasound to measure noninvasively the Peak (systolic) flow velocity (VP), mean-envelope flow velocity (VM) and end-diastolic flow velocity, as well as using a laser Doppler flowmeter on the finger blood flow of the finger prior to and after administration of 2-4 mg nicotine in a gum base. In a pilot project a group of 18 glaucoma patients and 8 normal subjects were tested with nicotine, and another group of 11 glaucoma patients were tested with placebo. VP, VM, and systolic blood pressure were significantly increased while finger blood flow was significantly decreased when comparing the nicotine-tested glaucoma group with the placebo-tested group (P = 0.02074, 0.01479, 0.02185, and 0.04209, respectively). The nicotine-tested group of normals also showed significant changes in VM, systolic blood pressure, and finger blood flow compared to a placebo group. The responses to the small doses of nicotine used in this study (approximately one-third that of cigarette smoking) were not significantly different between the glaucoma and the normal groups.

The purpose of this study was to determine the intraocular pressure characteristics in glaucoma suspects and patients whose visual fields were classified as stable or progressing over a long-term follow-up. We present data from 64 patients who received either medical or laser treatment and who were followed up for a median of 7.4 years. The visual fields of 27 patients were classified as stable and 37 as progressing using pre-determined criteria on either the Tubinger or Goldmann perimeter. Patients with initially normal and initially abnormal fields were analysed separately to avoid bias. There were no significant group differences in the mean, highest or interquartile range of intraocular pressure in the follow-up. The largely overlapping distributions over a wide spectrum of the pressure variables in patients with stable and progressing fields show that intraocular pressure alone cannot separate these two groups of patients. Our study does not suggest that pressure reduction in glaucoma has no beneficial effect, but that there may be other factors which determine the fate of the visual field in glaucoma.

In 61 eyes of 61 patients with glaucoma, semiquantitative assessment of retinal nerve-fiber-layer (RNFL) loss and neuroretinal rim measurement of the optic nerve head by means of the Optic Nerve Head Analyzer were correlated to the outcomes of automated light-sense, flicker and resolution perimetry and the Farnsworth-Munsell (FM) 100-Hue test. A significant influence of age on total RNFL and total diffuse RNFL scores was found, but there was no measurable effect of age on neuroretinal rim area. Total RNFL and total diffuse RNFL scores showed a good correlation to the various visual field indices: total RNFL score vs mean flicker frequency as determined by flicker perimetry, r = -0.606, P less than 0.0001; total RNFL score vs mean sensitivity as determined by light-sense perimetry, r = -0.385, P = 0.002; and total RNFL score vs mean ring score as determined by resolution perimetry, r = 0.341, P = 0.007. There was no significant correlation between RNFL scores and the FM 100-Hue score. Correlation between the neuroretinal rim area and the various psychophysical indices was poor and mostly not statistically significant. The high correlation of flicker scores with RNFL loss provides interest for future applications of this perimetric technique.

A total of 75 eyes in 75 patients with different types of glaucoma (21 eyes with low-tension glaucoma, 49 with primary open-angle glaucoma and 5 with pigmentary glaucoma) were examined by automated light-sense, flicker and resolution perimetry. All fields were classified in a masked fashion as being “normal” (N) or as having “diffuse loss” (D), “localized loss” (L) or “diffuse plus localized loss” (DL). The frequency distributions for the various field loss categories were plotted against the highest intraocular pressure ever reported in the patients' records. The frequency distributions for the purely localized defects showed a peak at 20 mmHg and were markedly skewed to low pressure values, whereas those for both diffuse plus localized damage and purely diffuse loss peaked at about 30 mmHg. The data suggest that diffuse field loss may be an indicator of pressure-induced damage.

Increased intraocular pressure is accepted as a primary etiologic factor for the atrophy of the optic nerve head and visual field defects of high-tension glaucoma. Other factors must be present to explain these findings in low-tension glaucoma. One of the current theories is that low-tension glaucoma is the result of decreased optic nerve perfusion on the basis of vascular disease or other factors such as altered blood viscosity. This study compared the non-invasive vascular profiles, coagulation tests, and rheological profiles of 46 consecutive cases of low-tension glaucoma with 69 similarly unselected cases of high-tension glaucoma and 47 age-matched controls. Despite the multifactorial approach and the use of previously validated objective tests, no significant group differences were detected with any of the above investigations. If vascular disease is important in the etiology of low-tension glaucoma, then it must be localized or vasospastic since this study does not support the concept of a generalized vascular etiology, either of an atheromatous or hyperviscous nature, for the genesis of low-tension glaucoma.

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.

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.

PURPOSE To compare the orbital blood flow velocities of patients with long-standing ocular hypertension and patients with primary open-angle glaucoma. METHODS Twenty patients with ocular hypertension were recruited from our clinic and underwent color Doppler imaging evaluation of their retrobulbar vessels. The blood flow velocities and resistance index of their central retinal artery, temporal short posterior ciliary artery, and ophthalmic artery were compared with those of 20 glaucoma patients individually matched for age and level of the highest untreated intraocular pressure ever recorded. RESULTS Glaucoma patients had significantly lower peak systolic velocity and end-diastolic velocity than did patients with ocular hypertension in their central retinal artery (p < 0.001). No significant difference between the groups was observed in the other vessels studied. CONCLUSIONS Glaucoma patients had lower blood flow velocity in the central retinal artery compared with that of ocular hypertension patients of similar age and level of untreated intraocular pressure. This might be important in the development of glaucomatous damage in those patients.

PURPOSE Psychophysical testing was used to assess the effects of early glaucomatous damage on visual functions mediated by the magnocellular and parvocellular pathways. METHODS We studied 57 eyes with early glaucoma, 92 eyes suspect for glaucoma, and 88 normal eyes. Tests were designed to target the functions of the magnocellular (M) or the parvocellular (P) pathways, and included measurements of contrast sensitivity for letter recognition, using both static presentation, and counterphase modulation at 25 Hz. We assumed that ability to perform the latter task would depend on the integrity of the M-cell pathway. To evaluate P-cell function we measured spatial acuity for a green letter presented against an isoluminant white background. Tests were carried out in the fovea, and at 3 degrees nasal, superior, temporal and inferior to the fovea. RESULTS Glaucomatous eyes showed, on average, defects in almost all of the functions tested. Threshold elevations for static and isoluminant presentations were generally as large as those for flickering stimuli. The inferior paracentral part of the retina was generally more severely affected than the other locations tested. The defects observed in the suspect population were similar to, although smaller in magnitude than, those found in eyes with glaucoma. A discriminant analysis identified a subset of five tests, including P as well as M pathway tests, which was able to correctly classify 89% of normal and 79% of glaucomatous eyes. CONCLUSIONS Putative M- and P-cell functions are both impaired at a relatively early stage of glaucoma. Deficits for both types of test are most severe in the inferior paracentral area of the retina (superior visual fields). Psychophysically based detection of the condition can benefit if results from different tests, done at different retinal locations, are combined.

Purpose This study was designed to assess the correlation between flow velocity, the resistive index and visual field defects in patients with chronic open angle glaucoma in comparison with a nonglaucomatous control population. Methods Color Doppler imaging was used to study flow velocity in the central retinal artery and short posterior ciliary arteries of 76 patients with chronic open angle glaucoma and 28 normal subjects. Velocity and resistive index were correlated with visual field abnormalities. Results The chronic open angle glaucoma patients showed a statistically significant lowering of the end diastolc velocity and a raised resistive index in all vessels studied. The end diastolic velocity of the central retinal arteries of glaucoma patients were significantly correlated with the Mean Deviation of the visual field (right eye, p = 0.0041; left eye, p = 0.0167). The glaucoma patients showed a statistically significant lowering of the end diastolc velocity and a raised resistive index in all vessels supplying those parts of the optic disc that corresponded to visual hemifield defects. Conclusion Open angle glaucoma is associated with changes in central retinal and ciliary artery flow velocity and resistive index which suggest a compromised circulation in this region.