Assessing retinal ganglion cell damage.

Retinal ganglion cell (RGC) loss is the hallmark of optic neuropathies, including glaucoma, where damage to RGC axons occurs at the level of the optic nerve head. In experimental glaucoma, damage is assessed at the axon level (in the retinal nerve fibre layer and optic nerve head) or at the soma level (in the retina). In clinical glaucoma where measurements are generally limited to non-invasive techniques, structural measurements of the retinal nerve fibre layer and optic nerve head, or functional measurements with perimetry provide surrogate estimates of RGC integrity. These surrogate measurements, while clinically useful, are several levels removed from estimating actual RGC loss. Advances in imaging, labelling techniques, and transgenic medicine are making enormous strides in experimental glaucoma, providing knowledge on the pathophysiology of glaucoma, its progression and testing new therapeutic avenues. Advances are also being made in functional imaging of RGCs. Future efforts will now be directed towards translating these advances to clinical care.

Rates of glaucomatous visual field change after trabeculectomy.

BACKGROUND: Trabeculectomy is frequently performed in patients with glaucoma who are deteriorating, although its effects on rates of visual field (VF) progression are not fully understood. We studied the rate of VF progression post trabeculectomy comparing with medically treated patients matched for VF loss. METHODS: Medical records of patients who underwent trabeculectomy alone or combined with cataract extraction were reviewed. Patients with 5 or more 24-2 VF examinations post trabeculectomy were selected. The rate of mean deviation (MD) change after surgery was calculated for each patient. These patients were pairwise matched based on baseline MD with patients with glaucoma who were treated medically and had at least 5 VF tests. RESULTS: 180 surgical patients were identified and matched with 180 medically treated patients (baseline MD of -8.72 (5.24) dB and -8.71 (5.22) dB, respectively). Surgically and medically treated patients were followed for 7.4 (2.9) and 6.8 (3.1) years respectively. The MD slopes were -0.22 (0.55) dB/year and -0.08 (1.10) dB/year in the surgically and medically treated patients, respectively, and not statistically different (p=0.13, 95% CI -0.31 to 0.04). More patients in the surgical group had fast progression (rates worse than -1 dB/year) than in the medical group (17 and 7 patients, respectively, p=0.05). CONCLUSIONS: Our findings suggest that most patients who undergo trabeculectomy demonstrate relatively slow rates of VF progression postoperatively, similar to patients treated medically, although some patients can continue to progress despite adequate surgical control of intraocular pressure.

Rates of retinal nerve fibre layer thickness change in glaucoma patients and control subjects.

PURPOSE: To examine the rates of retinal nerve fibre layer thickness (RNFLT) change in glaucoma patients and healthy, age-similar control subjects with three techniques: scanning laser polarimetry with variable corneal compensation (VCC) and enhanced corneal compensation (ECC), and time-domain optical coherence tomography (OCT). METHODS: Sixty-one patients and thirty-three controls were examined with each technique and with standard automated perimetry (SAP) every 6 months. Rates of global RNFLT change and SAP mean deviation (MD) change were estimated with linear mixed-effects models. RESULTS: The median (interquartile range) baseline age was 64.4 (58.2, 71.0) years for patients and 62.4 (56.3, 70.1) years for controls (P=0.56). There was a median of seven examinations over 3.1 years for patients and six examinations in 3.0 years for controls. Baseline visual field MD and RNFLT for all imaging modalities were significantly lower (P<0.01) in patients compared with controls. Rates of RNFLT change were not significantly different between patients and controls (P≥0.19). Mean rates of VCC-measured RNFLT change were -0.18 and -0.37 µm per year in patients and controls, whereas the respective figures for ECC and OCT were -0.13 and -0.31 µm per year, and 0.04 and 0.61 µm per year. Mean rates of MD change were -0.20 and 0.03 dB per year in patients and controls, respectively (P=0.01). CONCLUSION: Rates of RNFLT change in glaucoma patients were not statistically different from control subjects for any modality. A significantly negative rate of MD change in patients suggests a genuine, continued deterioration in these patients not reflected by RNFLT changes.

Comparison between confocal scanning laser tomography, scanning laser polarimetry and optical coherence tomography on the ability to detect localised retinal nerve fibre layer defects in glaucoma patients.

BACKGROUND/AIM: To compare the ability of confocal scanning laser tomography (CSLT), scanning laser polarimetry (SLP) and optical coherence tomography (OCT) in recognising localised retinal nerve fibre layer (RNFL) defects. METHODS: 51 eyes from 43 patients with glaucoma were identified by two observers as having RNFL defects visible on optic disc photographs. 51 eyes of 32 normal subjects were used as controls. Three masked observers evaluated CSLT, SLP and OCT images to determine subjectively the presence of localised RNFL defects. RESULTS: Interobserver agreement was highest with OCT, followed by SLP and CSLT (mean kappa: 0.83, 0.69 and 0.64, respectively). RNFL defects were identified in 58.8% of CSLT, 66.7% of SLP and 54.9% of OCT (p = 0.02 between SLP and OCT) by at least two observers. In the controls, 94.1% of CSLT, 84.3% of SLP and 94.1% of OCT scans, respectively, were rated as normal (p = 0.02 between CSLT and SLP, and SLP and OCT). CONCLUSION: Approximately 20-40% of localised RNFL defects identified by colour optic disc photographs are not detected by CSLT, SPL or OCT. SLP showed a higher number of false-positive results than the other techniques, but also had a higher proportion of correctly identified RNFL defects in the glaucoma population.

Practical recommendations for measuring rates of visual field change in glaucoma.

To date, there has been a lack of evidence-based guidance on the frequency of visual field examinations required to identify clinically meaningful rates of change in glaucoma. The objective of this perspective is to provide practical recommendations for this purpose. The primary emphasis is on the period of time and number of examinations required to measure various rates of change in mean deviation (MD) with adequate statistical power. Empirical data were used to obtain variability estimates of MD while statistical modelling techniques derived the required time periods to detect change with various degrees of visual field variability. We provide the frequency of examinations per year required to detect different amounts of change in 2, 3 and 5 years. For instance, three examinations per year are required to identify an overall change in MD of 4 dB over 2 years in a patient with average visual field variability. Recommendations on other issues such as examination type, strategy and quality are also made.

Confocal laser Doppler flowmeter measurements in a controlled flow environment in an isolated perfused eye.

The aim of this study was to improve our ability to interpret and validate Heidelberg Retina Flowmeter (HRF) flow images by recording flow measurements from specific regions of the retinal vasculature by taking advantage of the ability to precisely regulate perfusion flow in an isolated eye preparation. The retinal vasculature in 16 isolated perfused pig eyes was perfused with a 50%/50% Krebs/RBC solution at known flow rates ranging from 0 to 300 microl min(-1). At each flow rate, HRF images were obtained at a location approximately two disc diameters from the disc. After HRF image acquisition, the retinal vasculature was perfused with fluorescein isothiocyanate for fluorescence microscopy. Using the standard HRF software and a 10 x 10pixel measurement window, flow rates were measured from a retinal artery, vein, arteriole, venule, and the retinal capillary bed and a capillary-free-zone. The relationship between HRF measured flow and perfusion flow in the different measurement locations was determined. At zero perfusion flow the measured HRF flow was consistently greater than zero ( approximately 170 arbitrary units (AU)), and not significantly different at each measurement location except for the retinal vein, which had a significantly higher HRF flow value ( approximately 230AU). At higher perfusion flow rates the flow signal from the larger vascular elements (arteries and veins) increased rapidly thereafter to reach several thousand AU at a total perfusate flow of 50 microlmin(-1) and increased less rapidly at higher flow rates. In arterioles, the HRF flow was more linear over a broader range of perfusate flow rates but the peak flow signal was an order of magnitude smaller than that from the retinal artery. Both the linearity and magnitude of the flow signal in venules was less than that in arterioles. In capillary areas and in the capillary free zone, the HRF flow showed only a very weak relationship to perfusion flow when compared to the background noise. The choice of location for HRF flow analysis greatly influences the ability of the technique to measure changes in retinal blood flow. The major arteries and veins provide the strongest signal and greatest signal to noise ratio. However, the retinal arterioles produce an HRF signal that is more linear over a wider range of perfusate flow rates.

Central corneal thickness and progression of the visual field and optic disc in glaucoma.

AIMS: To determine whether central corneal thickness (CCT) is a significant predictor of visual field and optic disc progression in open angle glaucoma. METHODS: Data were obtained from a prospective study of glaucoma patients tested with static automated perimetry and confocal scanning laser tomography every 6 months. Progression was determined using a trend based approach called evidence of change (EOC) analysis in which sectoral ordinal scores based on the significance of regression coefficients of visual field pattern deviation and neuroretinal rim area over time are summed. Visual field progression was also determined using the event based glaucoma change probability (GCP) analysis using both total and pattern deviation. RESULTS: The sample contained 101 eyes of 54 patients (mean (SD) age 56.5 (9.8) years) with a mean follow up of 9.2 (0.7) years and 20.7 (2.3) sets of examinations every 6 months. Lower CCT was associated with worse baseline visual fields and lower mean IOP in the follow up. In the longitudinal analysis CCT was not correlated with the EOC scores for visual field or optic disc change. In the GCP analyses, there was a tendency for groups classified as progressing to have lower CCT compared to non-progressing groups. In a multivariate analyses accounting for IOP, the opposite was found, whereby higher CCT was associated with visual field progression. None of the independent factors were predictive of optic disc progression. CONCLUSIONS: In this cohort of patients with established glaucoma, CCT was not a useful index in the risk assessment of visual field and optic disc progression.

Effects of minocycline and tetracycline on retinal ganglion cell survival after axotomy.

In the present study, we compared the in vivo neuroprotective efficacy of intraperitoneally administered tetracycline and minocycline to enhance the survival of retinal ganglion cells (RGCs) following unilateral axotomy of the adult rat optic nerve. We also examined the effects of the tetracycline drugs on the activation of retinal microglia. RGCs in retinal whole-mounts were visualized by retrograde labeling with fluorogold. The presence of activated microglia was confirmed immunohistochemically using OX-42 monoclonal antibodies. Optic nerve axotomy produced RGC death and increased activation of microglia. No significant RGC loss was seen prior to 5 days and approximately 50% and 80-90% cell loss occurred at 7 and 14 days, respectively. Examination of the effects of tetracycline and minocycline on RGC survival at 7 days post-axotomy, revealed increased numbers of RGCs in minocycline-treated animals (75% of non-axotomized control) compared with vehicle-only (52% of control) and tetracycline-treated (58% of control) animals. The densities of RGCs (RGCs/mm2+/-S.D.) for control, vehicle-, tetracycline- and minocycline-treated axotomized animals were 1996+/-81, 1029+/-186, 1158+/-190 and 1497+/-312, respectively. The neuroprotective effect of minocycline seen at 7 days was transient, since RGCs present in minocycline-treated animals at 14 days post-axotomy (281+/-43, 14% of control) were not significantly different to vehicle-treated animals (225+/-47, 11% of control). OX-42 staining of activated retinal microglia was reduced in tetracycline- and minocycline-treated axotomized animals compared with axotomized animals receiving vehicle-only. These results demonstrate that systemic administration of the second-generation tetracycline derivative, minocycline, delays the death of axotomized RGCs by a mechanism that may be associated with inhibition of microglia activation. The neuroprotective efficacy of minocycline following optic nerve axotomy was superior to that of tetracycline.

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.

Scanning laser polarimetry in a selected group of patients with glaucoma and normal controls.

PURPOSE: To evaluate the ability of scanning laser polarimetry to discriminate between subjects with glaucoma with specific patterns of visual field defect and normal controls. METHODS: This cross-sectional, prospective study in a glaucoma practice, focused on subjects with glaucoma with predefined types of visual field defect, including advanced (group A, n = 14), localized (group L, n = 46), or mixed (diffuse and localized) defects (group M, n = 22) and normal controls (n = 32). Scanning laser polarimetry was performed in one study eye per subject. Two methods of analysis were used: a subjective analysis, in which examination printouts with the image of the optic disk manually blocked were classified by two observers masked to the diagnosis, and a logistic regression analysis of the retardation parameters included in the printouts. RESULTS: The observers correctly identified 97% of the controls and 68% of subjects with glaucoma (overall correct classification of 77%), with 93%, 70%, and 47% of patients from groups A, L, and M, respectively, being correctly identified. The best discrimination obtained with the logistic regression correctly identified 69% of controls and 94% of glaucoma subjects (overall correct classification of 87%). The performance was only slightly better for cases from group A compared with L and M. CONCLUSIONS: Subjective assessment of the scanning laser polarimetry standard printout of single eyes might not be sensitive enough to detect cases of glaucoma with localized or milder mixed types of visual field defect. The discriminating ability of scanning laser polarimetry improves slightly when logistic regression analysis is employed.

Optic disc and visual field changes in a prospective longitudinal study of patients with glaucoma: comparison of scanning laser tomography with conventional perimetry and optic disc photography.

OBJECTIVE: To investigate the relationship between optic disc changes measured with scanning laser tomography and those measured with conventional perimetry and optic disc photography. METHODS: In a prospective longitudinal study, we followed up 77 patients with early glaucomatous visual field damage. Scanning laser tomography (using the Heidelberg Retina Tomograph) and conventional perimetry (using the Humphrey Field Analyzer) were carried out every 6 months. Disc progression was determined by a procedure recently described by us for scanning laser tomography, with confirmed progression requiring repeatable changes based on probability limits for both the depth (using individual test-retest variability values) and size of change (determined in a group of 37 healthy individuals also followed up prospectively). Field progression was determined with the Statpac Glaucoma Change Probability Analysis. The agreement between scanning laser tomography and conventional disc photography was determined in a subgroup of patients. RESULTS: Patients were followed up for a median of 5.5 years, with a median of 12 sets of examinations with scanning laser tomography and conventional perimetry. Twenty-one patients (27%) showed no progression with either technique. Thirty-one patients (40%) progressed with scanning laser tomography only, while 3 (4%) progressed with conventional perimetry only. Of the 22 patients (29%) who progressed with both techniques, 10 (45%) progressed with scanning laser tomography first (median, 18 month earlier) and 9 (41%) with conventional perimetry first (median, 12 months earlier), while 3 (14%) progressed at the same time. Of the 16 patients with disc photographs that closely overlapped the follow-up, there was concordance between scanning laser tomography and disc photography in 13 patients (81%). CONCLUSIONS: Glaucomatous disc changes determined with scanning laser tomography occur more frequently than field changes. Most patients with field changes also had disc changes; however, less than half of those with disc changes had field changes.

Comparison of conventional and pattern discrimination perimetry in a prospective study of glaucoma patients.

PURPOSE: To determine whether pattern discrimination perimetry detects progression of glaucomatous visual fields earlier than conventional static automated perimetry. METHODS: One hundred nine eyes of 109 patients with open angle glaucoma were enrolled in a longitudinal prospective study. Each patient underwent visual field examinations with conventional and pattern discrimination perimetry using the 30-2 program of the Humphrey Visual Field Analyzer (Humphrey Instruments Inc., San Leandro, CA) and a custom program for the pattern discrimination perimeter, respectively at 6-month intervals. Progression of glaucomatous visual field damage was assessed separately at each visit by predetermined criteria for conventional and pattern discrimination perimetry. The time to progression from baseline was calculated and the hemifield that showed progression first was documented for both conventional and pattern discrimination perimetry. RESULTS: Patients were followed for a mean of 5.1 years and a mean of 11.6 visits. Sixty-eight (62.3%) patients did not show progression with either technique. Of the remaining 41 patients, 15 (36.5%) showed progression with conventional perimetry alone, 9 (21.9%) with pattern discrimination perimetry alone, and 17 (41.4%) showed progression with both techniques. Of these 17 patients, 11 (64.7%) were detected earlier by conventional perimetry, and 6 (35.2%) were detected earlier by pattern discrimination perimetry. CONCLUSIONS: This study suggests that pattern discrimination perimetry is less effective than conventional perimetry in evaluating progressive glaucomatous visual field damage.

Simulation of longitudinal threshold visual field data.

PURPOSE: To describe and evaluate a computer model that simulates longitudinal visual field data. METHODS: A computer model was designed using factors that influence thresholds of normal and glaucomatous visual fields. The simulation model was used to quantify the effects of fluctuation on the outcomes of pointwise linear regression by comparison with simulated gold standard data with no variability. RESULTS: Serial sets of 10 stable and 10 progressive visual fields with different fluctuation levels were generated by simulation and were analyzed using pointwise linear regression. Regression outcome measures used were slopes of -1 dB/year or worse and slopes of -1 dB/year or worse that were also statistically significant. In stable visual fields, the number of locations with regression slopes worse than -1 dB/year increased with fluctuation and defect size and was inversely related to the number of fields. The number of locations with statistically significant slopes remained low and appeared unaffected by these variables. In progressive visual fields, analysis of a small number of visual field test results (<8) overestimated the number of locations with regression slopes worse than -1 dB/year and underestimated the number of locations with statistically significant slopes. CONCLUSIONS: Computer simulation may be used to provide a gold standard outcome that permits evaluation of statistical tools for monitoring progressive glaucomatous visual field loss.

The value of high-pass resolution perimetry in glaucoma.

High-pass resolution perimetry (HRP) is a perimetric technique that relies on low-contrast, high-spatial-frequency-filtered, ring-shaped test targets. It was devised as a quick and user-friendly technique that reflects the status of the retino-corneal pathway. Since its introduction in 1987, HRP has undergone substantial investigation, primarily in cross-sectional studies on patients with glaucoma, though it is also used in patients with neuro-ophthalmologic disorders. HRP has a shorter test time compared with conventional perimetry. Currently, evidence suggests that HRP is a viable test for the evaluation of the glaucomatous visual field.

The effect of brimonidine tartrate on retinal blood flow in patients with ocular hypertension.

PURPOSE: To study the effects of topical brimonidine tartrate 0.2%, an alpha(2)-agonist ocular hypotensive drug, on retinal capillary blood flow in patients with ocular hypertension. METHODS: The study was a double-masked, randomized, placebo-controlled trial set in a tertiary eye center. Ocular hypertensive patients with repeatable intraocular pressures greater than 21 mm Hg and normal visual fields and optic disks were consecutively recruited. After an eye examination, baseline retinal blood flow measurements were made with confocal scanning laser Doppler flowmetry in one study eye. Patients were then randomly assigned to receive either brimonidine or placebo (saline) twice daily for 8 weeks. Blood flow and intraocular pressure measurements were then repeated after 4 and 8 weeks. RESULTS: Seventeen patients were randomly assigned to receive brimonidine, and 14 received placebo. One patient in each group failed to complete the study. The mean group differences in baseline age and intraocular pressure were not statistically significant (59. 23 [+/-10.24] and 52.23 [+/-16.46] years, respectively, and 24.84 [+/-2.08] and 24.56 [+/-2.85] mm Hg, respectively). Brimonidine reduced intraocular pressure by 17.90% and 16.17% at 4 and 8 weeks, respectively, with a significant difference in treatment effect compared with the placebo group (P <.007). The group difference in treatment effect in any of the three hemodynamic parameters velocity, volume, and flow was within 8% and not significantly different at 4 or 8 weeks (P.360). Based on a type I error of 0.05, our study had a power greater than or equal to 75% to detect group differences in treatment effect of greater than or equal to 15% to 20%. CONCLUSIONS: Brimonidine reduces intraocular pressure without altering retinal capillary blood flow in patients with ocular hypertension.

Intraocular pressure and progression of glaucomatous visual field loss.

PURPOSE: To evaluate the relationship between intraocular pressure and visual field progression in patients with primary open-angle glaucoma. METHODS: We prospectively followed 113 patients with early to moderate glaucomatous field damage. Conventional automated static perimetry, high-pass resolution perimetry, and intraocular pressure measurements were carried out at 6-month intervals. The mean and the highest intraocular pressure in the follow-up were compared in stable and progressing patients with each perimetric technique. RESULTS: The mean (+/- SD) follow-up was 4.5 +/- 0.9 years. The mean (+/- SD) intraocular pressure in patients remaining stable with conventional perimetry [18.2 +/- 3.3 mm Hg, n = 81 (71.7%)] was not significantly different (P =.65) from those in whom it progressed (17.9 +/- 3.3 mm Hg, n = 32 [28.3%]). The mean intraocular pressure in patients remaining stable with high-pass resolution perimetry (17. 9 +/- 3.5 mm Hg, n = 63 [55.8%]) was not significantly different (P =.33) from those in whom it progressed (18.5 +/- 3.0 mm Hg, n = 50 [44.2%]). The mean (+/- SD) of the highest (single or three highest) pressure during follow-up for stable and progressing patients with conventional perimetry was not significantly different (22.6 +/- 5.0 and 23.0 +/- 4.6 mm Hg, respectively, P =.76). However, for high-pass resolution perimetry, the difference was highly significant (21.6 +/- 4.5 and 24.1 +/- 4.9 mm Hg, respectively, P <. 01). Furthermore, patients who progressed with high-pass resolution perimetry had more damaged baseline fields compared with those who remained stable (P <.01). CONCLUSIONS: The mean level of intraocular pressure does not differentiate glaucoma patients with progressive visual field loss from ones who remained stable. Baseline visual field status and peak intraocular pressure of patients who progress with high-pass resolution perimetry are significantly different from those who remain stable.

Technique for detecting serial topographic changes in the optic disc and peripapillary retina using scanning laser tomography.

PURPOSE: To describe and evaluate a new statistical technique for detecting topographic changes in the optic disc and peripapillary retina measured with confocal scanning laser tomography. METHODS: The 256x256-pixel array of topographic height values obtained with each image from the Heidelberg Retina Tomograph (Heidelberg Engineering, Heidelberg, Germany) was divided into an array of 64x64 superpixels, where each superpixel contained 16 (i.e., 4x4) pixels. An analysis of variance technique was developed to analyze each superpixel with three baseline and three follow-up images. The performance of the technique was tested with and without adjustment for spatial correlation of topographic values using computer simulations and with real data from a normal control subject and a patient with progressive glaucomatous disc change. RESULTS: Computer simulation with fixed population means and variance, and varying spatial correlation showed a monotonically increasing number of superpixels with significant test results (false positives), with 20% false-positives when the spatial correlation was 0.8 (the approximate median value in real patient data). The number of false-positive results was similar (17%) in serial images of a normal subject. When corrected for spatial correlation, the number of false-positives was independent of the level of spatial correlation and remained at the expected value of less than 5% in both simulations and real data. Although the number of significant test results in the patient with progressive glaucoma decreased after correction for spatial correlation, the change was readily apparent. Statistical power to detect mean differences in topographic values ranging from 0.5 to 4.0 SDs in computer simulation showed low power for changes of 1 SD or less, but increased dramatically with larger changes. CONCLUSIONS: This technique has a high level of sensitivity to detect changes in the optic disc while maintaining a high level of specificity.

The effect of brimonidine tartrate on retinal blood flow in patients with ocular hypertension [corrected].

PURPOSE: To study the effects of topical brimonidine tartrate 0.2%, an alpha2-agonist ocular hypotensive drug, on retinal capillary blood flow in patients with ocular hypertension. METHODS: The study was a double-masked, randomized, placebo-controlled trial set in a tertiary eye center. Ocular hypertensive patients with repeatable intraocular pressures greater than 21 mm Hg and normal visual fields and optic disks were consecutively recruited. After an eye examination, baseline retinal blood flow measurements were made with confocal scanning laser Doppler flowmetry in one study eye. Patients were then randomly assigned to receive either brimonidine or placebo (saline) twice daily for 8 weeks. Blood flow and intraocular pressure measurements were then repeated after 4 and 8 weeks. RESULTS: Seventeen patients were randomly assigned to receive brimonidine, and 14 received placebo. One patient in each group failed to complete the study. The mean group differences in baseline age and intraocular pressure were not statistically significant (59.23 [+/-10.24] and 52.23 [+/-16.46] years, respectively, and 24.84 [+/-2.08] and 24.56 [+/-2.85] mm Hg, respectively). Brimonidine reduced intraocular pressure by 17.90% and 16.17% at 4 and 8 weeks, respectively, with a significant difference in treatment effect compared with the placebo group (P < .007). The group difference in treatment effect in any of the three hemodynamic parameters velocity, volume, and flow was within 8% and not significantly different at 4 or 8 weeks (P > .360). Based on a type I error of 0.05, our study had a power greater than or equal to 75% to detect group differences in treatment effect of greater than or equal to 15% to 20%. CONCLUSIONS: Brimonidine reduces intraocular pressure without altering retinal capillary blood flow in patients with ocular hypertension.

Diffuse loss of sensitivity in early glaucoma.

PURPOSE: To establish whether there is significant diffuse loss of sensitivity in a population of patients with early glaucoma. METHODS: The differential light sensitivities at the 10 most sensitive locations from within the central 24 degrees of program 30-2 of the Humphrey Field Analyzer (Humphrey Instruments, San Leandro, CA) were compared in 38 pairs of age-matched subjects, one of each pair with early primary open-angle glaucoma (POAG) and the other with normal eyes. All subjects had had experience with automated perimetry and had clear media, visual acuity of 20/25 or better, and one or fewer false-positive or false-negative responses to catch trials. RESULTS: The mean difference in age between the subjects with glaucoma and normal subjects was 29 days (P = 0.44, maximum 1.42 years). The mean paired difference in pupil size was 0.16 mm (P = 0.26), and visual acuity was higher in the glaucoma-affected subjects (P = 0.044). The 10 highest sensitivity measurements in the POAG-affected subjects were found to be lower by a median of between 1.0 and 2.0 dB than those in the normal pair members (0.0001