Stuart L. Graham

Ability of the heidelberg retina tomograph to detect early glaucomatous visual field loss.

PurposeThe Heidleberg Retina Tomograph provides rapid, reproducible measurements of optic disc topography as well as calculations of disc parameters. We used a stepwise discriminant analysis to determine which parameters were most useful in detecting individuals with early glaucomatous visual field loss. MethodsWe studied one eye in each of 45 normal individuals and one eye in each of 46 individuals with early glaucomatous visual field loss. The appearance of the optic disc was not used for classification purposes so as not to bias the diagnostic determination obtained by the instrument. The data were analyzed using the reference plane of the software version 1.10 and using a method incorporating the height of the papillomacular bundle as reference level with and without age correction. ResultsWe obtained an 89% sensitivity and 78% specificity for the detection of early visual field loss using the standard reference level. The jackknife classification revealed lower sensitivity of 87% and an unchanged specificity of 78%. With the method incorporating the height of the papillomacular bundle as reference level, the sensitivity was 87% and the specificity was 84% for detecting early visual field loss. The jackknife classification revealed a sensitivity of 87% and a specificity of 82%. With the age correction, the sensitivity was 87%, specificity 84% with regular and jackknife classification. With the standard reference level, the important parameters were the third moment and the maximum depth, with the papillomacular bundle reference level volume above reference level added as important, and with age correction, height variation in contour replaced maximum depth in the analysis. ConclusionThree significant shape parameters of the optic disc can be used to detect early glaucomatous visual field loss.

Multifocal objective perimetry in the detection of glaucomatous field loss.

PURPOSE To test the ability of a new type of multifocal objective perimetry to identify glaucomatous visual field defects. METHODS A multichannel visual evoked potential was recorded using the ObjectiVision Accumap perimeter. One hundred patients (age, 62.2 +/- 9.8 years, mean MD -6.5 +/- 4.17 dB) with open-angle glaucoma and confirmed glaucomatous visual field defects were tested and compared with the normal database of 100 normal subjects (age, 58.9 +/- 10.7 years). Both eyes were tested, but for determining sensitivity the eye with the lesser field defect was chosen if both qualified. The amplitude and intereye asymmetry coefficient for each zone of the field were calculated. A mean amplitude and multifocal objective perimetry severity index was calculated for each subject. RESULTS In 95 of 100 (95%) patients with glaucoma Humphrey field defects were correlated with visual evoked potential amplitude reductions identifying a cluster of three or more abnormal zones. In two of five remaining patients with glaucoma the defect was detected on the intereye asymmetry analysis. Topographic location was well correlated with Humphrey fields. Mean amplitude was significantly reduced in 86 of the glaucoma cases (86%). The glaucoma severity index was abnormal in 93 glaucoma cases and showed a correlation with Humphrey MD (r = 0.67 right eyes, 0.69 left eyes). In 37 glaucoma cases with no scotoma by definition in the fellow eye, 22 (59.4%) had an abnormal multifocal objective perimetry, whereas only eight had some other aspect of their Humphrey visual field flagged as abnormal. CONCLUSIONS Multifocal objective perimetry can assess the visual field and identify glaucomatous visual field defects. It may have the potential for identifying defects earlier than conventional perimetry.

Objective perimetry in glaucoma

PURPOSE Objective perimetry in glaucoma is described using the multifocal pattern visually evoked potential (VEP). A multichannel recording technique was used to improve signal detection in healthy volunteers and assess its ability to detect glaucoma and early changes in patients with suspected glaucoma. DESIGN Prospective, case-control study. PARTICIPANTS Thirty healthy volunteers, 30 patients with suspected glaucoma, and 30 patients with glaucomatous visual field defects were tested. METHOD The VEP was recorded using cortically scaled, multifocal, pseudorandomly alternated pattern stimuli with the VERIS system (Electro-Diagnostic Imaging, Inc., San Francisco, CA). An array of four bipolar occipital electrodes provided four differently oriented channels for simultaneous recording. Signals were compared for different locations within the field up to 26 degrees of eccentricity. Healthy volunteers, patients with suspected glaucoma, and glaucoma patients with established visual field defects were tested, and results were compared with Humphrey visual fields (Humphrey Systems, Dublin, CA) performed on the same day. For reproducibility, five healthy volunteers were each tested on four separate days. The patients with suspected glaucoma and the established glaucoma patients were analyzed for intereye asymmetry of signals, and these data were compared with the asymmetry values of the healthy volunteers. RESULTS Multiple recording channels significantly enhanced the recording of signals from parts of the visual field not reliably sampled with a single channel technique in all healthy volunteers, particularly along the horizontal meridian (P: < 0.001). Signal amplitude did not decline with age in healthy volunteers. Recordings showed good reproducibility within individuals. In all 30 glaucoma patients, the Humphrey visual field defects were well demonstrated by the VEP, and topographic location was strongly correlated (r(s) = 0.79). Despite large interindividual variations in amplitude, scotomas were well demonstrated when compared with normal values. In the patients with suspected glaucoma, smaller changes in signal amplitude could be identified in parts of the field still normal on perimetry using intereye asymmetry analysis. CONCLUSIONS The multifocal, multichannel VEP can objectively detect glaucomatous visual field defects. The nasal step region can be more reliably tested using multiple channels. Asymmetry analysis has the potential to detect early defects. This technique represents a significant step toward the clinical application of objective perimetry in glaucoma.

Axonal loss and myelin in early ON loss in postacute optic neuritis

To investigate the relation between retinal nerve fiber layer (RNFL) thickness and latency and amplitude of multifocal visual‐evoked potentials (mfVEPs) in the postacute stage of optic neuritis in patients with early or possible multiple sclerosis.

Objective VEP perimetry in glaucoma: asymmetry analysis to identify early deficits.

Purpose: The multifocal visual evoked potential (VEP) shows markedly symmetrical responses between the two eyes of control subjects. Patients with glaucoma and patients considered at high risk for glaucoma were examined to determine if VEP asymmetry could be identified and used for diagnosis and detection of early damage. Methods: Multifocal pattern VEP recordings were performed using a single channel bipolar occipital electrode position and the Visual Evoked Response Imaging System (VERIS). There were 125 subjects: 24 control subjects, 70 patients with glaucoma, and 31 patients considered at high risk for glaucoma. A between‐eye relative asymmetry coefficient (RAC) was determined for each of the 60 test points in the VEP field. The RAC for patients with glaucoma and patients considered at risk for glaucoma were compared with values from control subjects. Correlation between Humphrey thresholds and RAC scores was performed. Results: Patients with glaucoma and patients considered at risk for glaucoma both showed significantly larger mean quadrant RAC values. When point by point analysis was performed, 69 out of 70 scotomas were identified with a cluster of at least 3 points of P < 0.05. For those considered at high risk for glaucoma, 10 out of 31 patients had abnormal areas in the VEP field. There was a strong correlation (r = 0.82) between quadrantic RAC mean values and Humphrey quadrant threshold scores in an asymmetric glaucoma subgroup. Abnormal VEP responses were identified in parts of the visual field that were still normal on perimetry. Conclusions: Asymmetry analysis correctly identifies patients with glaucomatous field loss and shows abnormalities in many patients considered at high risk for glaucoma who still have normal fields. Asymmetry analysis is able to identify objectively the extent of glaucomatous damage and may be able to detect changes before subjective field loss occurs.

Analysis of risk factors that may be associated with progression from ocular hypertension to primary open angle glaucoma

Background: As a multifactorial disease, glaucoma may be associated with pressure‐dependent and pressure‐independent factors. Ocular hypertension (OHT) may develop into primary open angle glaucoma (POAG) for many patients. Groups with OHT and POAG were compared for pressure‐dependent and independent risk factors. A high prevalence of any factor(s) could indicate a contribution to progression from OHT to POAG.

Central corneal thickness, tonometry, and ocular dimensions in glaucoma and ocular hypertension.

PurposeTo assess possible correlations between central corneal thickness, tonometry, and ocular dimensions. Patients and MethodsOne hundred seventeen eyes of 117 patients who were not taking any intraocular pressure–lowering medications were studied prospectively. Forty-one patients had ocular hypertension; 13 patients had primary open-angle glaucoma; and 10 patients had normal-pressure glaucoma. Twenty-three healthy eyes were included. Thirty glaucoma suspects (10 patients monitored for possible normal-pressure glaucoma and 20 patients with intermittent ocular hypertension) were included for correlation analysis. Tonometry was performed with Goldmann applanation and pneumotonometry, and central corneal thickness, anterior chamber depth, lens thickness, and axial length were measured ultrasonically. ResultsCentral corneal thickness was lowest in eyes with normal-pressure glaucoma (538 ± 51 &mgr;m), highest in eyes with ocular hypertension (570 ± 32 &mgr;m), and intermediate and similar in eyes with primary open-angle glaucoma and healthy eyes (547 ± 34 &mgr;m and 554 ± 32 &mgr;m, respectively). These differences were significant (P = 0.028). Goldmann applanation tonometry and central corneal thickness were weakly correlated (r = 0.12, P = 0.205), with a 0.2-mm Hg change per 10-&mgr;m variation in central corneal thickness. Pneumotonometry measurements were more strongly correlated with central corneal thickness (r = 0.21, P < 0.05). Lens thickness was strongly correlated with age (r = 0.57, P < 0.001). Anterior chamber depth was negatively correlated with lens thickness and age (r = −0.29, P < 0.005 and r = −0.25, P < 0.01). Axial length was correlated with anterior chamber depth and age (r = 0.5, P <.001 and r = −0.19, P < 0.05). ConclusionEyes diagnosed as having ocular hypertension have thicker corneas and eyes labeled as having normal-pressure glaucoma have thinner corneas, when compared with healthy eyes or eyes with primary open-angle glaucoma. The effect of central corneal thickness on Goldmann applanation tonometry accuracy appears to be small and usually not clinically relevant. When corneal thickness is markedly different from normal, the clinician may need to factor this into diagnosis and management.

Assessing quality of life in patients with glaucoma using the Glaucoma Quality of Life-15 (GQL-15) questionnaire.

PurposeTo measure and compare quality of life in patients with and without glaucoma using the Glaucoma Quality of Life-15 Questionnaire, and to determine the association between glaucoma-related quality of life and clinical indices of glaucoma. Patients and MethodsUsing a prospective, cross-sectional study, we collected demographic information via interviews and administered the questionnaire to assess glaucoma-related quality of life in 121 patients with glaucoma and 31 subjects without glaucoma. Visual function was measured objectively by clinical examination. Group differences and the association between questionnaire scores and clinical indices were evaluated using nonparametric analysis of variance and correlation coefficients, respectively. The relationship between the likelihood of reporting vision-related dysfunction and glaucoma severity was examined using logistic regression. ResultsPatients with glaucoma had significantly poorer glaucoma-related quality of life than controls (P<0.001). Summary scores differed significantly among patients with mild, moderate, and severe glaucoma demonstrating a trend of poorer quality of life with increasing disease severity. Activities involving glare and dark adaptation were most problematic for all, but patients with glaucoma felt significantly more compromised in central and near vision, peripheral vision, and outdoor mobility (all P<0.001). Glaucoma-related quality of life scores correlated moderately and significantly with visual acuity, disease severity, and visual field measurements, but only severe glaucoma was a significant predictor of self-perceived deficits in glaucoma-related quality of life (P=0.038). ConclusionsThe Glaucoma Quality of Life-15 Questionnaire correlated well with objective measures of visual function and discriminated between quality of life in patients with glaucoma and subjects without glaucoma.

Flash and pattern electroretinogram changes with optic atrophy and glaucoma

We investigated recent reports that, contrary to common belief, glaucoma can affect flash as well as pattern electroretinograms. An extensive flash and pattern electroretinogram test protocol was used in a large sample of glaucoma patients and age-matched controls who were either visually normal or had other optic nerve diseases. All electroretinogram parameters were reduced and delayed in normal people > 55 years of age. The effect did not increase in later decades. In patients aged < or = 55 years, flash electroretinograms showed mild reductions and delays from optic atrophy alone. Glaucomatous ERG changes were larger and increased with disease severity. Pattern electroretinograms and oscillatory potentials were almost equally reduced in optic atrophy and all degrees of glaucoma. Mildly affected patients > 55 years of age had similar electroretinogram change to age-matched normals in most conditions. Advanced glaucoma patients showed similar differences from normal irrespective of age. This suggests that direct diagnostic application of these results to older patients will be difficult, that the ERG changes in glaucoma cannot be attributed simply to optic atrophy and that additional widespread outer retinal damage occurs in glaucoma.

Common variants near ABCA1 , AFAP1 and GMDS confer risk of primary open-angle glaucoma

Primary open-angle glaucoma (POAG) is a major cause of irreversible blindness worldwide. We performed a genome-wide association study in an Australian discovery cohort comprising 1,155 cases with advanced POAG and 1,992 controls. We investigated the association of the top SNPs from the discovery stage in two Australian replication cohorts (932 cases and 6,862 controls total) and two US replication cohorts (2,616 cases and 2,634 controls total). Meta-analysis of all cohorts identified three loci newly associated with development of POAG. These loci are located upstream of ABCA1 (rs2472493[G], odds ratio (OR) = 1.31, P = 2.1 × 10−19), within AFAP1 (rs4619890[G], OR = 1.20, P = 7.0 × 10−10) and within GMDS (rs11969985[G], OR = 1.31, P = 7.7 × 10−10). Using RT-PCR and immunolabeling, we show that these genes are expressed within human retina, optic nerve and trabecular meshwork and that ABCA1 and AFAP1 are also expressed in retinal ganglion cells.