Raymond P. LeBlanc

Test-Retest Variability of Topographic Measurements With Confocal Scanning Laser Tomography in Patients With Glaucoma and Control Subjects

Using confocal scanning laser tomography, we studied the test-retest variability of topographic measurements of the optic nerve head and parapapillary retina in 30 patients with glaucoma and 30 normal control subjects. We obtained three independent images, separated by between one and six hours, centered on the optic nerve head. We condensed each original 256 x 256-pixel image to a 64 x 64-pixel image, thereby allowing a realistic estimate of the empiric 90% confidence interval of testretest variability at each condensed pixel. Confidence interval maps generated for each subject showed highest measurement variability along the cup border and blood vessels. The mean standard deviation equivalents of test-retest variability in the patients and controls were 31.20 and 25.94 microns, respectively. These differences were statistically significant (P = .010). Variability increased with age (P < .001). When the analysis was repeated for discrete parapapillary areas, the group differences were not statistically significant (P = .100).

Canadian Glaucoma Study: 2. Risk Factors for the Progression of Open-angle Glaucoma

OBJECTIVE To determine systemic and ocular risk factors for visual field progression in open-angle glaucoma. METHODS In the Canadian Glaucoma Study, a multicenter prospective longitudinal study of 258 patients (131 men and 127 women; median age, 65.0 years), baseline systemic measures included assessment of peripheral vasospasm and markers for hematopathology, coagulopathy, and immunopathology. Patients were followed up at 4-month intervals with perimetry, optic disc imaging, and a standardized interventional protocol for intraocular pressure control. Univariate and proportional hazards models were used to identify factors that predicted progression. MAIN OUTCOME MEASURE Visual field progression with standard automated perimetry. RESULTS Median follow-up was 5.3 years, with 167 patients (64.7%) completing 5 years or more and 67 patients (26.0%) completing 7 years or more. Abnormal baseline anticardiolipin antibody levels (hazard ratio [HR], 3.86; 95% confidence interval [CI], 1.60-9.31), higher baseline age (HR per year, 1.04; 95% CI, 1.01-1.07), female sex (HR, 1.94; 95% CI, 1.09-3.46), and higher mean follow-up intraocular pressure (HR per 1 mm Hg, 1.19; 95% CI, 1.05-1.36) before progression were associated with progression. CONCLUSIONS The Canadian Glaucoma Study identified 4 independent predictive factors for glaucomatous field progression. Application to Clinical Practice While confirming the importance of intraocular pressure in glaucoma progression, this study determined other risk factors that merit awareness.

Glaucoma and On-Road Driving Performance

PURPOSE To investigate the on-road driving performance of patients with glaucoma. METHODS The sample comprised 20 patients with glaucoma and 20 subjects with normal vision, all licensed drivers, matched for age and sex. Driving performance was tested over a 10-km route incorporating 55 standardized maneuvers and skills through residential and business districts of Halifax, Nova Scotia, Canada. Testing was conducted by a professional driving instructor and assessed by an occupational therapist certified in driver rehabilitation, masked to participant group membership and level of vision. Main outcome measures were total number of satisfactory maneuvers and skills, overall rating, and incidence of at-fault critical interventions (application of the dual brake and/or steering override by the driving instructor to prevent a potentially unsafe maneuver). Measures of visual function included visual acuity, contrast sensitivity, and visual fields (Humphrey Field Analyzer; Carl Zeiss Meditec, Inc., Dublin, CA; mean deviation [MD] and binocular Esterman points). RESULTS There was no significant difference between patients with glaucoma (mean MD = -1.7 dB [SD 2.2] and -6.5 dB [SD 4.9], better and worse eyes, respectively) and control subjects in total satisfactory maneuvers and skills (P = 0.65), or overall rating (P = 0.60). However, 12 (60%) patients with glaucoma had one or more at-fault critical interventions, compared with 4 (20%) control subjects (odds ratio = 6.00, 95% CI, 1.46-24.69; higher still after adjustment for age, sex, medications and driving exposure), the predominant reason being failure to see and yield to a pedestrian. In the glaucoma group, worse-eye MD was associated with the overall rating of driving (r = 0.66, P = 0.002). CONCLUSIONS This sample of patients with glaucoma with slight to moderate visual field impairment performed many real-world driving maneuvers safely. However, they were six times as likely as subjects with normal vision to have a driving instructor intervene for reasons suggesting difficulty with detection of peripheral obstacles and hazards and reaction to unexpected events.

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.

Canadian Glaucoma Study: 3. Impact of risk factors and intraocular pressure reduction on the rates of visual field change.

OBJECTIVES To determine rates of visual field change associated with risk factors for progression in the Canadian Glaucoma Study (abnormal anticardiolipin antibody level, age, female sex, and mean follow-up intraocular pressure [IOP]), and to evaluate the effect of IOP reduction on subsequent rates of visual field change in progressing patients. METHODS Two hundred sixteen patients (median age, 65.2 years) were followed up at 4-month intervals with perimetry and were monitored for progression. Patients reaching an end point based on total deviation analysis underwent 20% or greater reduction in IOP. Rates of mean deviation (MD) change were calculated. RESULTS Patients with 0, 1, and 2 end points had a median of 18, 23, and 25 examinations, respectively. The median MD rate in progressing patients prior to the first end point was significantly worse compared with those with no progression (-0.35 and 0.05 dB/y, respectively). An abnormal anticardiolipin antibody level was associated with a significantly worse MD rate compared with a normal anticardiolipin antibody level (-0.57 and -0.03 dB/y, respectively). Increasing age was associated with a worse MD rate, but female sex and mean follow-up IOP were not. After the first end point, the median IOP decreased from 18.0 to 14.8 mm Hg (20% in individual patients), resulting in a significant MD rate change from -0.36 to -0.11 dB/y. CONCLUSIONS Patients with abnormal anticardiolipin antibody levels and increasing age had faster visual field change. Modest IOP reduction in progressing patients significantly ameliorated the rate of visual field decline. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00262626.

Visual field and optic disc progression in patients with different types of optic disc damage: A longitudinal prospective study

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.

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.

Optic disc progression in glaucoma: comparison of confocal scanning laser tomography to optic disc photographs in a prospective study.

PURPOSE To compare confocal scanning laser tomography (CSLT) to optic disc photography for detecting progressive glaucomatous disc changes. METHODS Four expert observers first examined a training set of 40 pairs of monoscopic disc photographs to help set a criterion for change. They then classified 44 pairs of monoscopic photographs of patients followed prospectively as having either definitely no change, probably no change, probably change, or definitely change (score, 0, 1, 2, or 3, respectively). Observers were unaware that 10 pairs were photographs of fellow eyes obtained the same day to measure specificity. These patients were imaged with the Heidelberg Retina Tomograph every 6 months. Topographic change analysis (TCA) software with three criteria (yielding specificity of 81%, 94%, or 97%) was used. Comparisons between the TCA results and those of observers were made for a range of liberal to conservative criteria and for individual and combined observer scores. RESULTS The median follow-up was 9.0 years with 18 CSLT images. Observer specificity varied from 50% to 90% (using score 0) and 60% to 100% (using score 0 or 1). Interobserver kappa ranged from 0.22 to 0.38 from the most liberal to conservative criterion and was generally higher than corresponding TCA-observer agreement. For most criteria, observers had either a high hit rate with low specificity or high specificity with a low hit rate compared with the TCA. Similar results were obtained when observer scores were combined to derive a broader range of criteria. CONCLUSIONS The results indicate that the TCA performs at least as well as either the individual or best combination of observer classifications of disc photographs.

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.

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 patients 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.