Paul H. Artes

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.

Face recognition in age related macular degeneration: perceived disability, measured disability, and performance with a bioptic device.

Aims: (1) To explore the relation between performance on tasks of familiar face recognition (FFR) and face expression difference discrimination (FED) with both perceived disability in face recognition and clinical measures of visual function in subjects with age related macular degeneration (AMD). (2) To quantify the gain in performance for face recognition tasks when subjects use a bioptic telescopic low vision device. Methods: 30 subjects with AMD (age range 66–90 years; visual acuity 0.4–1.4 logMAR) were recruited for the study. Perceived (self rated) disability in face recognition was assessed by an eight item questionnaire covering a range of issues relating to face recognition. Visual functions measured were distance visual acuity (ETDRS logMAR charts), continuous text reading acuity (MNRead charts), contrast sensitivity (Pelli-Robson chart), and colour vision (large panel D-15). In the FFR task, images of famous people had to be identified. FED was assessed by a forced choice test where subjects had to decide which one of four images showed a different facial expression. These tasks were repeated with subjects using a bioptic device. Results: Overall perceived disability in face recognition did not correlate with performance on either task, although a specific item on difficulty recognising familiar faces did correlate with FFR (r = 0.49, p<0.05). FFR performance was most closely related to distance acuity (r = −0.69, p<0.001), while FED performance was most closely related to continuous text reading acuity (r = −0.79, p<0.001). In multiple regression, neither contrast sensitivity nor colour vision significantly increased the explained variance. When using a bioptic telescope, FFR performance improved in 86% of subjects (median gain = 49%; p<0.001), while FED performance increased in 79% of subjects (median gain = 50%; p<0.01). Conclusion: Distance and reading visual acuity are closely associated with measured task performance in FFR and FED. A bioptic low vision device can offer a significant improvement in performance for face recognition tasks, and may be useful in reducing the handicap associated with this disability. There is, however, little evidence for a correlation between self rated difficulty in face recognition and measured performance for either task. Further work is needed to explore the complex relation between the perception of disability and measured performance.

Repeatability of automated perimetry: a comparison between standard automated perimetry with stimulus size III and V, matrix, and motion perimetry.

PURPOSE Standard automated perimetry (SAP) shows a marked increase in variability in damaged areas of the visual field. This study was conducted to test the hypothesis that larger stimuli are associated with more uniform variability, by investigating the retest variability of four perimetry tests: standard automated perimetry size III (SAP III), with the SITA standard strategy; SAP size V (SAP V), with the full-threshold strategy; Matrix (FDT II), and Motion perimetry. METHODS One eye each of 120 patients with glaucoma was examined on the same day with these four perimetric tests and retested 1 to 8 weeks later. The decibel scales were adjusted to make the tests scales numerically similar. Retest variability was examined by establishing the distributions of retest threshold estimates, for each threshold level observed at the first test. The 5th and 95th percentiles of the retest distribution were used as point-wise limits of retest variability. Regression analyses were performed to quantify the relationship between visual field sensitivity and variability. RESULTS With SAP III, the retest variability increased substantially with reducing sensitivity. Corresponding increases with SAP V, Matrix, and Motion perimetry were considerably smaller or absent. With SAP III, sensitivity explained 22% of the retest variability (r(2)), whereas corresponding data for SAP V, Matrix, and Motion perimetry were 12%, 2%, and 2%, respectively. CONCLUSIONS Variability of Matrix and Motion perimetry does not increase as substantially as that of SAP III in damaged areas of the visual field. Increased sampling with the larger stimuli of these techniques is the likely explanation for this finding. These properties may make these stimuli excellent candidates for early detection of visual field progression.

Incidence and Rates of Visual Field Progression after Longitudinally Measured Optic Disc Change in Glaucoma

OBJECTIVE To determine whether glaucoma patients with progressive optic disc change have subsequent visual field progression earlier and at a faster rate compared with those without disc change. DESIGN Prospective, longitudinal, cohort study. PARTICIPANTS AND CONTROLS Eighty-one patients with open-angle glaucoma. METHODS Patients underwent confocal scanning laser tomography and standard automated perimetry every 6 months. The complete follow-up was divided into initial and subsequent periods. Two initial periods-first 3 years (Protocol A) and first half of the total follow-up (Protocol B)-were used, with the respective remainder being the subsequent follow-up. Disc change during the initial follow-up was determined with liberal, moderate, or conservative criteria of the Topographic Change Analysis. Subsequent field progression was determined with significant pattern deviation change in >or=3 locations (criterion used in the Early Manifest Glaucoma Trial). As a control analysis, field change during the initial follow-up was determined with significant pattern deviation change in >or=1, >or=2, or >or=3 locations. MAIN OUTCOME MEASURES Survival time to subsequent field progression, rates of mean deviation (MD) change, and positive and negative likelihood ratios. RESULTS The median (interquartile range) total follow-up was 11.0 (8.0-12.0) years with 22 (18-24) examinations. More patients had disc changes during the initial follow-up compared with field changes. The mean time to field progression was consistently shorter (protocol A, 0.8-1.7 years; protocol B, 0.3-0.7 years) in patients with prior disc change. In the control analysis, patients with prior field change had statistically earlier subsequent field progression (protocol A, 2.9-3.0 years; protocol B, 0.7-0.9). Similarly, patients with either prior disc or field change always had worse mean rates of subsequent MD change, although the distributions overlapped widely. Patients with subsequent field progression were up to 3 times more likely to have prior disc change compared with those without, and up to 5 times more likely to have prior field change compared with those without. CONCLUSIONS Longitudinally measured optic disc change is predictive of subsequent visual field progression and may be an efficacious end point for functional outcomes in clinical studies and trials in glaucoma.

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.

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.

The repeatability of mean defect with size III and size V standard automated perimetry.

PURPOSE The mean defect (MD) of the visual field is a global statistical index used to monitor overall visual field change over time. Our goal was to investigate the relationship of MD and its variability for two clinically used strategies (Swedish Interactive Threshold Algorithm [SITA] standard size III and full threshold size V) in glaucoma patients and controls. METHODS We tested one eye, at random, for 46 glaucoma patients and 28 ocularly healthy subjects with Humphrey program 24-2 SITA standard for size III and full threshold for size V each five times over a 5-week period. The standard deviation of MD was regressed against the MD for the five repeated tests, and quantile regression was used to show the relationship of variability and MD. A Wilcoxon test was used to compare the standard deviations of the two testing methods following quantile regression. RESULTS Both types of regression analysis showed increasing variability with increasing visual field damage. Quantile regression showed modestly smaller MD confidence limits. There was a 15% decrease in SD with size V in glaucoma patients (P = 0.10) and a 12% decrease in ocularly healthy subjects (P = 0.08). CONCLUSIONS The repeatability of size V MD appears to be slightly better than size III SITA testing. When using MD to determine visual field progression, a change of 1.5 to 4 decibels (dB) is needed to be outside the normal 95% confidence limits, depending on the size of the stimulus and the amount of visual field damage.

Longitudinal and cross-sectional analyses of visual field progression in participants of the ocular hypertension treatment study

OBJECTIVE To assess agreement between longitudinal and cross-sectional analyses for determining visual field progression in data from the Ocular Hypertension Treatment Study. METHODS Visual field data from 3088 eyes of 1570 participants (median follow-up, 7 years) were analyzed. Longitudinal analyses were performed using change probability with total and pattern deviation, and cross-sectional analyses were performed using the glaucoma hemifield test, corrected pattern standard deviation, and mean deviation. The rates of mean deviation and general height change were compared to estimate the degree of diffuse loss in emerging glaucoma. RESULTS Agreement on progression in longitudinal and cross-sectional analyses ranged from 50% to 61% and remained nearly constant across a wide range of criteria. In contrast, agreement on absence of progression ranged from 97.0% to 99.7%, being highest for the stricter criteria. Analyses of pattern deviation were more conservative than analyses of total deviation, with a 3 to 5 times lesser incidence of progression. Most participants developing field loss had both diffuse and focal changes. CONCLUSIONS Despite considerable overall agreement, 40% to 50% of eyes identified as having progressed with either longitudinal or cross-sectional analyses were identified with only one of the analyses. Because diffuse change is part of early glaucomatous damage, pattern deviation analyses may underestimate progression in patients with ocular hypertension.

Visual Field Progression in Glaucoma: Estimating the Overall Significance of Deterioration with Permutation Analyses of Pointwise Linear Regression (PoPLR)

PURPOSE To establish a method for estimating the overall statistical significance of visual field deterioration from an individual patients data, and to compare its performance to pointwise linear regression. METHODS The Truncated Product Method was used to calculate a statistic S that combines evidence of deterioration from individual test locations in the visual field. The overall statistical significance (P value) of visual field deterioration was inferred by comparing S with its permutation distribution, derived from repeated reordering of the visual field series. Permutation of pointwise linear regression (PoPLR) and pointwise linear regression were evaluated in data from patients with glaucoma (944 eyes, median mean deviation -2.9 dB, interquartile range: -6.3, -1.2 dB) followed for more than 4 years (median 10 examinations over 8 years). False-positive rates were estimated from randomly reordered series of this dataset, and hit rates (proportion of eyes with significant deterioration) were estimated from the original series. RESULTS The false-positive rates of PoPLR were indistinguishable from the corresponding nominal significance levels and were independent of baseline visual field damage and length of follow-up. At P < 0.05, the hit rates of PoPLR were 12, 29, and 42%, at the fifth, eighth, and final examinations, respectively, and at matching specificities they were consistently higher than those of pointwise linear regression. CONCLUSIONS In contrast to population-based progression analyses, PoPLR provides a continuous estimate of statistical significance for visual field deterioration individualized to a particular patients data. This allows close control over specificity, essential for monitoring patients in clinical practice and in clinical trials.