Balwantray C. Chauhan

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.

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).

Optic Disc Margin Anatomy in Patients with Glaucoma and Normal Controls with Spectral Domain Optical Coherence Tomography

OBJECTIVE To characterize optic nerve head (ONH) anatomy related to the clinical optic disc margin with spectral domain-optical coherence tomography (SD-OCT). DESIGN Cross-sectional study. PARTICIPANTS Patients with open-angle glaucoma with focal, diffuse, and sclerotic optic disc damage, and age-matched normal controls. METHODS High-resolution radial SD-OCT B-scans centered on the ONH were analyzed at each clock hour. For each scan, the border tissue of Elschnig was classified for obliqueness (internally oblique, externally oblique, or nonoblique) and the presence of Bruchs membrane overhanging the border tissue. Optic disc stereophotographs were co-localized to SD-OCT data with customized software. The frequency with which the disc margin identified in stereophotographs coincided with (1) Bruchs membrane opening (BMO), defined as the innermost edge of Bruchs membrane; (2) Bruchs membrane/border tissue, defined as any aspect of either outside BMO or border tissue; or (3) border tissue, defined as any aspect of border tissue alone, in the B-scans was computed at each clock hour. MAIN OUTCOME MEASURES The SD-OCT structures coinciding with the disc margin in stereophotographs. RESULTS There were 30 patients (10 with each type of disc damage) and 10 controls, with a median (range) age of 68.1 (42-86) years and 63.5 (42-77) years, respectively. Although 28 patients (93%) had 2 or more border tissue configurations, the most predominant one was internally oblique, primarily superiorly and nasally, frequently with Bruchs membrane overhang. Externally oblique border tissue was less frequent, observed mostly inferiorly and temporally. In controls, there was predominantly internally oblique configuration around the disc. Although the configurations were not statistically different between patients and controls, they were among the 3 glaucoma groups. At most locations, the SD-OCT structure most frequently identified as the disc margin was some aspect of Bruchs membrane and border tissue external to BMO. Bruchs membrane overhang was regionally present in the majority of patients with glaucoma and controls; however, in most cases it was not visible as the disc margin. CONCLUSIONS The clinically perceived disc margin is most likely not the innermost edge of Bruchs membrane detected by SD-OCT. These findings have important implications for the automated detection of the disc margin and estimates of the neuroretinal rim.

From Clinical Examination of the Optic Disc to Clinical Assessment of the Optic Nerve Head: A Paradigm Change

PURPOSE To review and interpret the anatomy of the optic nerve head (ONH) detected with spectral-domain optical coherence tomography (SD OCT) pertaining to the clinical examination of the optic disc and to propose that a paradigm change for clinical assessment of the ONH is necessary. DESIGN Perspective. METHODS Presently, the clinician evaluates neuroretinal rim health according to the appearance of the optic disc, the clinically visible surface of the ONH. Recent anatomic findings with SD OCT have challenged the basis and accuracy of current rim evaluation. We demonstrate why incorporation of SD OCT imaging of the ONH into the clinical examination of the disc is required. RESULTS Disc margin-based rim evaluation lacks a solid anatomic basis and results in variably inaccurate measurements for 2 reasons. First, the clinically visible disc margin is an unreliable outer border of rim tissue because of clinically and photographically invisible extensions of Bruchs membrane. Second, rim tissue orientation is not considered in width measurements. We propose alternative anatomically and geometrically accurate SD OCT-based approaches for rim assessment that have enhanced detection of glaucoma. We also argue for new data acquisition and analysis strategies with SD OCT that account for the large interindividual variability in the angle between the fovea and ONH. CONCLUSIONS We propose a 4-point paradigm change for clinical assessment of the ONH that is anchored to the eye-specific anatomy and geometry of the ONH and fovea. Our approach is designed to enhance the accuracy and consistency of rim width, as well as of peripapillary and macular intraretinal thickness measurements.

Laminar and Prelaminar Tissue Displacement During Intraocular Pressure Elevation in Glaucoma Patients and Healthy Controls

OBJECTIVE To determine the response of the anterior lamina cribrosa and prelaminar tissue to acute elevation of intraocular pressure (IOP) in glaucoma patients and healthy subjects. DESIGN Prospective case-control series. PARTICIPANTS AND CONTROLS Patients with open-angle glaucoma (n = 12; mean age ± standard deviation [SD], 66.8 ± 6.0 years), age-matched healthy controls (n = 12; mean age ± SD, 67.1 ± 6.2 years), and young controls (n = 12; mean age ± SD, 36.1 ± 11.7 years). METHODS One eye was imaged with spectral-domain optical coherence tomography to obtain 12 high-resolution radial scans centered on the optic disc. Imaging was repeated at precisely the same locations with an ophthalmodynamometer held perpendicular to the globe via the inferior lid to raise the IOP. A line joining Bruchs membrane opening in 4 radial scans was used as reference in the baseline and elevated IOP images. The vertical distance from the reference line to the anterior prelaminar tissue surface and anterior laminar surface was measured at equidistant points along the reference line in the 2 sets of images. The difference between the 2 sets of corresponding measurements were used to determine laminar displacement (LD) and prelaminar tissue displacement (PTD). MAIN OUTCOME MEASURES Laminar displacement and PTD. RESULTS Intraocular pressure elevation among patients, age-matched controls, and young controls was similar (mean ± SD, 12.4 ± 3.2 mmHg). The mean ± SD LD and PTD were 0.5 ± 3.3 μm and 15.7 ± 15.5 μm, respectively. The LD was not statistically different from 0 (P = 0.366), but PTD was (P < 0.001). The mean ± SD LD was similar among the groups (-0.5 ± 3.7 μm, 0.2 ± 2.0 μm, and 2.0 ± 3.6 μm, respectively; P = 0.366), whereas the mean ± SD PTD was different (6.8 ± 13.7 μm, 20.8 ± 17.5 μm, and 19.6 ± 11.8 μm, respectively; P = 0.045). In all subjects, the PTD was greater than LD. In multivariate regression analyses, LD was negatively associated with optic disc size (P = 0.007), whereas PTD was positively associated with the degree of IOP elevation (P = 0.013). CONCLUSIONS In glaucoma patients and controls, the anterior laminar surface is noncompliant to acute IOP elevation. Acute optic disc surface changes represent compression of prelaminar tissue and not laminar displacement.

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.

The Role of Glia, Mitochondria, and the Immune System in Glaucoma

Author(s): Tezel, Gulgun; Fourth ARVO/Pfizer Ophthalmics Research Institute Conference Working Group

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.

The relationship between intraocular pressure and visual field progression in glaucoma

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 Tübinger 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.

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.