African Descent and Glaucoma Evaluation Study (ADAGES): Racial Differences in Optic Disc Hemorrhage and Beta-Zone Parapapillary Atrophy.

PURPOSE: To investigate the differences in the frequency of optic disc hemorrhage (DH) and prevalence of beta-zone parapapillary atrophy (ßPPA) between individuals of African descent (AD) and European descent (ED). DESIGN: Prospective, multicenter, observational cohort. PARTICIPANTS: A total of 1950 eyes of 1172 participants of the African Descent and Glaucoma Evaluation Study (ADAGES). METHODS: Stereoscopic disc photographs of subjects with and without glaucomatous optic neuropathy (GON) followed during the first 13 years of the ADAGES underwent masked review searching for DH and ßPPA. A total of 928 eyes (non-GON, 581; GON, 347) of 551 AD patients (non-GON, 334; GON, 217) and 1022 eyes (non-GON, 568; GON, 454) of 611 ED patients (non-GON, 334; GON, 277) were included. We compared the number of eyes with detected DH at any time during follow-up and eyes with ßPPA between the AD and ED groups. The analyses were then adjusted for clinical parameters using multivariable logistic regression. MAIN OUTCOME MEASURES: Differences in frequency of DH and prevalence of ßPPA. RESULTS: A total of 9395 stereoscopic disc photographs were reviewed. More ED eyes experience DH than AD eyes (49/1022 [4.8%] vs. 10/928 eyes [1.1%], respectively; P < 0.001), whereas ßPPA had higher prevalence in AD eyes (675 eyes [72%] vs. 659 eyes [64%]; P < 0.001). In the final multivariable model, after controlling for confounders, AD eyes were less likely to have at least 1 detected DH than ED eyes (odds ratio [OR], 0.21; 95% CI, 0.10-0.45; P < 0.001) but were more likely to have ßPPA than ED eyes (OR, 1.55; 95% CI, 1.12-2.14; P = 0.008). CONCLUSIONS: Subjects of ED are at higher risk for developing DH compared with AD subjects, whereas AD subjects have greater prevalence of ßPPA. These findings suggest that there are structural differences within the optic nerve complex between these groups. Further research is needed to determine whether racial differences in the frequency of DH and prevalence of ßPPA affect the likelihood of glaucomatous progression.

The African Descent and Glaucoma Evaluation Study (ADAGES): predictors of visual field damage in glaucoma suspects.

PURPOSE: To evaluate racial differences in the development of visual field (VF) damage in glaucoma suspects. DESIGN: Prospective, observational cohort study. METHODS: Six hundred thirty-six eyes from 357 glaucoma suspects with normal VF at baseline were included from the multicenter African Descent and Glaucoma Evaluation Study (ADAGES). Racial differences in the development of VF damage were examined using multivariable Cox proportional hazard models. RESULTS: Thirty one of 122 African-descent participants (25.4%) and 47 of 235 European-descent participants (20.0%) developed VF damage (P = .078). In multivariable analysis, worse baseline VF mean deviation, higher mean arterial pressure during follow-up, and a race ∗ mean intraocular pressure (IOP) interaction term were significantly associated with the development of VF damage, suggesting that racial differences in the risk of VF damage varied by IOP. At higher mean IOP levels, race was predictive of the development of VF damage even after adjusting for potentially confounding factors. At mean IOPs during follow-up of 22, 24, and 26 mm Hg, multivariable hazard ratios (95% confidence intervals) for the development of VF damage in African-descent compared to European-descent subjects were 2.03 (1.15-3.57), 2.71 (1.39-5.29), and 3.61 (1.61-8.08), respectively. However, at lower mean IOP levels (below 22 mm Hg) during follow-up, African descent was not predictive of the development of VF damage. CONCLUSION: In this cohort of glaucoma suspects with similar access to treatment, multivariate analysis revealed that at higher mean IOP during follow-up, individuals of African descent were more likely to develop VF damage than individuals of European descent.

Rates of retinal nerve fiber layer thinning in glaucoma suspect eyes.

PURPOSE: To compare the rates of retinal nerve fiber layer (RNFL) loss in patients suspected of having glaucoma who developed visual field damage (VFD) with those who did not develop VFD and to determine whether the rate of RNFL loss can be used to predict the development of VFD. DESIGN: Prospective, observational cohort study. PARTICIPANTS: Glaucoma suspects, defined as having glaucomatous optic neuropathy or ocular hypertension (intraocular pressure, >21 mmHg) without repeatable VFD at baseline, from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. METHODS: Global and quadrant RNFL thickness (RNFLT) were measured with the Spectralis spectral-domain optical coherence tomography (SD-OCT; Spectralis HRA+OCT [Heidelberg Engineering, Heidelberg, Germany]). Visual field damage was defined as having 3 consecutive abnormal visual fields. The rate of RNFL loss in eyes developing VFD was compared to eyes not developing VFD using multivariate linear mixed-effects models. A joint longitudinal survival model used the estimated RNFLT slope to predict the risk of developing VFD, while adjusting for potential confounding variables. MAIN OUTCOME MEASURES: The rate of RNFL thinning and the probability of developing VFD. RESULTS: Four hundred fifty-four eyes of 294 glaucoma suspects were included. The average number of SD-OCT examinations was 4.6 (range, 2-9), with median follow-up of 2.2 years (0.4-4.1 years). Forty eyes (8.8%) developed VFD. The estimated mean rate of global RNFL loss was significantly faster in eyes that developed VFD compared with eyes that did not develop VFD (-2.02 µm/year vs. -0.82 µm/year; P<0.001). The joint longitudinal survival model showed that each 1-µm/year faster rate of global RNFL loss corresponded to a 2.05-times higher risk of developing VFD (hazard ratio, 2.05; 95% confidence interval, 1.14-3.71; P = 0.017). CONCLUSIONS: The rate of global RNFL loss was more than twice as fast in eyes that developed VFD compared with eyes that did not develop VFD. A joint longitudinal survival model showed that a 1-µm/year faster rate of RNFLT loss corresponded to a 2.05-times higher risk of developing VFD. These results suggest that measuring the rate of SD-OCT RNFL loss may be a useful tool to help identify patients who are at a high risk of developing visual field loss.

Detecting glaucoma progression from localized rates of retinal changes in parametric and nonparametric statistical framework with type I error control.

PURPOSE: We evaluated three new pixelwise rates of retinal height changes (PixR) strategies to reduce false-positive errors while detecting glaucomatous progression. METHODS: Diagnostic accuracy of nonparametric PixR-NP cluster test (CT), PixR-NP single threshold test (STT), and parametric PixR-P STT were compared to statistic image mapping (SIM) using the Heidelberg Retina Tomograph. We included 36 progressing eyes, 210 nonprogressing patient eyes, and 21 longitudinal normal eyes from the University of California, San Diego (UCSD) Diagnostic Innovations in Glaucoma Study. Multiple comparison problem due to simultaneous testing of retinal locations was addressed in PixR-NP CT by controlling family-wise error rate (FWER) and in STT methods by Lehmann-Romano's k-FWER. For STT methods, progression was defined as an observed progression rate (ratio of number of pixels with significant rate of decrease; i.e., red-pixels, to disk size) > 2.5%. Progression criterion for CT and SIM methods was presence of one or more significant (P < 1%) red-pixel clusters within disk. RESULTS: Specificity in normals: CT = 81% (90%), PixR-NP STT = 90%, PixR-P STT = 90%, SIM = 90%. Sensitivity in progressing eyes: CT = 86% (86%), PixR-NP STT = 75%, PixR-P STT = 81%, SIM = 39%. Specificity in nonprogressing patient eyes: CT = 49% (55%), PixR-NP STT = 56%, PixR-P STT = 50%, SIM = 79%. Progression detected by PixR in nonprogressing patient eyes was associated with early signs of visual field change that did not yet meet our definition of glaucomatous progression. CONCLUSIONS: The PixR provided higher sensitivity in progressing eyes and similar specificity in normals than SIM, suggesting that PixR strategies can improve our ability to detect glaucomatous progression. Longer follow-up is necessary to determine whether nonprogressing eyes identified as progressing by these methods will develop glaucomatous progression. (ClinicalTrials.gov number, NCT00221897).

African descent and glaucoma evaluation study: asymmetry of structural measures in normal participants.

PURPOSE: The purpose of the study is to determine the degree of intereye asymmetry of optic disc topography and retinal nerve fiber layer (RNFL) thickness in healthy individuals of African descent (AD) and European descent (ED). DESIGN: Observational, clinical study. METHODS: Five hundred nineteen healthy individuals (AD, n=262, mean age=44.9 years; ED, n=257, mean age=47.1 years) from the African Descent and Glaucoma Evaluation Study and Diagnostic Innovations in Glaucoma Study were tested using Heidelberg retina romograph (HRT), GDx variable corneal compensation (GDx-VCC), and standard, automated perimetry within 6 months of one another. HRT-II measurements included cup area, cup volume, rim area, and rim volume. GDx-VCC measurements included average RNFL thickness. Intereye asymmetry was calculated as the absolute value of the differences in measurements between the right and left eye. RESULTS: AD participants showed significantly higher median asymmetry in cup volume and rim volume (P<0.001 and 0.033, respectively) compared with ED participants. The effect of race lost significance after adjustment for mean disc area and disc area asymmetry in multivariable models. Axial length asymmetry was not correlated with increased asymmetry in any of this study's asymmetry parameters. Normal ranges of asymmetry for the HRT-II measurements of cup area (up to 0.39 mm), cup volume (up to 0.15 mm), rim area (up to 0.45 mm), and rim volume (up to 0.22 mm) were derived, as were asymmetry ranges for GDx-VCC-measured average RNFL thickness (up to 6.25 µm). CONCLUSIONS: The effect of race was no longer significant after adjustment for mean disc area and disc area asymmetry. Individuals with asymmetries with magnitudes greater than those of the normal ranges could be considered as suspicious for glaucoma.

Progression of patterns (POP): a machine classifier algorithm to identify glaucoma progression in visual fields.

PURPOSE: We evaluated Progression of Patterns (POP) for its ability to identify progression of glaucomatous visual field (VF) defects. METHODS: POP uses variational Bayesian independent component mixture model (VIM), a machine learning classifier (MLC) developed previously. VIM separated Swedish Interactive Thresholding Algorithm (SITA) VFs from a set of 2,085 normal and glaucomatous eyes into nine axes (VF patterns): seven glaucomatous. Stable glaucoma was simulated in a second set of 55 patient eyes with five VFs each, collected within four weeks. A third set of 628 eyes with 4,186 VFs (mean ± SD of 6.7 ± 1.7 VFs over 4.0 ± 1.4 years) was tested for progression. Tested eyes were placed into suspect and glaucoma categories at baseline, based on VFs and disk stereoscopic photographs; a subset of eyes had stereophotographic evidence of progressive glaucomatous optic neuropathy (PGON). Each sequence of fields was projected along seven VIM glaucoma axes. Linear regression (LR) slopes generated from projections onto each axis yielded a degree of confidence (DOC) that there was progression. At 95% specificity, progression cutoffs were established for POP, visual field index (VFI), and mean deviation (MD). Guided progression analysis (GPA) was also compared. RESULTS: POP identified a statistically similar number of eyes (P > 0.05) as progressing compared with VFI, MD, and GPA in suspects (3.8%, 2.7%, 5.6%, and 2.9%, respectively), and more eyes than GPA (P = 0.01) in glaucoma (16.0%, 15.3%, 12.0%, and 7.3%, respectively), and more eyes than GPA (P = 0.05) in PGON eyes (26.3%, 23.7%, 27.6%, and 14.5%, respectively). CONCLUSIONS: POP, with its display of DOC of progression and its identification of progressing VF defect pattern, adds to the information available to the clinician for detecting VF progression.

Arterial spin labeling fMRI measurements of decreased blood flow in primary visual cortex correlates with decreased visual function in human glaucoma.

PURPOSE: Altered metabolic activity has been identified as a potential contributing factor to the neurodegeneration associated with primary open angle glaucoma (POAG). Consequently, we sought to determine whether there is a relationship between the loss of visual function in human glaucoma and resting blood perfusion within primary visual cortex (V1). METHODS: Arterial spin labeling (ASL) functional magnetic resonance imaging (fMRI) was conducted in 10 participants with POAG. Resting cerebral blood flow (CBF) was measured from dorsal and ventral V1. Behavioral measurements of visual function were obtained using standard automated perimetry (SAP), short-wavelength automated perimetry (SWAP), and frequency-doubling technology perimetry (FDT). Measurements of CBF were compared to differences in visual function for the superior and inferior hemifield. RESULTS: Differences in CBF between ventral and dorsal V1 were correlated with differences in visual function for the superior versus inferior visual field. A statistical bootstrapping analysis indicated that the observed correlations between fMRI responses and measurements of visual function for SAP (r=0.49), SWAP (r=0.63), and FDT (r=0.43) were statistically significant (all p<0.05). CONCLUSIONS: Resting blood perfusion in human V1 is correlated with the loss of visual function in POAG. Altered CBF may be a contributing factor to glaucomatous optic neuropathy, or it may be an indication of post-retinal glaucomatous neurodegeneration caused by damage to the retinal ganglion cells.

Localized glaucomatous change detection within the proper orthogonal decomposition framework.

PURPOSE: To detect localized glaucomatous structural changes using proper orthogonal decomposition (POD) framework with false-positive control that minimizes confirmatory follow-ups, and to compare the results to topographic change analysis (TCA). METHODS: We included 167 participants (246 eyes) with ≥4 Heidelberg Retina Tomograph (HRT)-II exams from the Diagnostic Innovations in Glaucoma Study; 36 eyes progressed by stereo-photographs or visual fields. All other patient eyes (n = 210) were non-progressing. Specificities were evaluated using 21 normal eyes. Significance of change at each HRT superpixel between each follow-up and its nearest baseline (obtained using POD) was estimated using mixed-effects ANOVA. Locations with significant reduction in retinal height (red pixels) were determined using Bonferroni, Lehmann-Romano k-family-wise error rate (k-FWER), and Benjamini-Hochberg false discovery rate (FDR) type I error control procedures. Observed positive rate (OPR) in each follow-up was calculated as a ratio of number of red pixels within disk to disk size. Progression by POD was defined as one or more follow-ups with OPR greater than the anticipated false-positive rate. TCA was evaluated using the recently proposed liberal, moderate, and conservative progression criteria. RESULTS: Sensitivity in progressors, specificity in normals, and specificity in non-progressors, respectively, were POD-Bonferroni = 100%, 0%, and 0%; POD k-FWER = 78%, 86%, and 43%; POD-FDR = 78%, 86%, and 43%; POD k-FWER with retinal height change ≥50 µm = 61%, 95%, and 60%; TCA-liberal = 86%, 62%, and 21%; TCA-moderate = 53%, 100%, and 70%; and TCA-conservative = 17%, 100%, and 84%. CONCLUSIONS: With a stronger control of type I errors, k-FWER in POD framework minimized confirmatory follow-ups while providing diagnostic accuracy comparable to TCA. Thus, POD with k-FWER shows promise to reduce the number of confirmatory follow-ups required for clinical care and studies evaluating new glaucoma treatments. (ClinicalTrials.gov number, NCT00221897.).

Comparison of visual field severity classification systems for glaucoma.

PURPOSE: To compare categorical severity classification systems for glaucoma. METHODS: This cross-sectional study included 1,921 eyes (49.5% right eye) from 1,137 participants from the Diagnostic Innovations in Glaucoma Study and African Descent and Glaucoma Evaluation Study. Standard automated perimetry fields were classified using the: (1) Advanced Glaucoma Intervention Study scoring system (AGIS), (2) Glaucoma Severity Staging system (GSS), and (3) Enhanced Glaucoma Severity Staging system (eGSS). Systems were characterized using the following continuous measures of severity: mean deviation, pattern standard deviation, and visual field index. Classifications between systems and with optic disc stereophotograph assessment were compared (κ) and some stages were consolidated to evaluate severity classification across systems (Wilcoxon test). RESULTS: Mean deviation, pattern standard deviation, and visual field index were significantly different between GSS and AGIS, and GSS and eGSS in normal and abnormal fields (P<0.005). Agreement between AGIS and eGSS was substantial (κ=0.715±0.012); agreement between GSS and eGSS (κ=0.559±0.014) and AGIS (κ=0.519±0.016) was moderate. eGSS tended to stage abnormal fields most severely followed by GSS and then AGIS (P<0.001). CONCLUSIONS: The presence of glaucomatous optic neuropathy increases with staging severity for all systems. However, different systems led to different severity staging. Of the systems examined in this study, eGSS may be the better choice for its ease of use for both clinicians and researchers.

Structure-function relationship in glaucoma using spectral-domain optical coherence tomography.

OBJECTIVES: To determine the structure-function relationship in glaucoma using spectral-domain optical coherence tomography (SDOCT)-derived structural measurements and to evaluate this relationship using a linear model. METHODS: In a cross-sectional study, structure-function relationships were determined for all the participants in the DIGS (Diagnostic Innovations in Glaucoma Study) and the ADAGES (African Descent and Glaucoma Evaluation Study) who had undergone standard automated perimetry (SAP) and SDOCT within 6 months of each other. Strength of relationship was reported as coefficient of determination (R(2)). The relationship was also evaluated using a previously described linear model. RESULTS: The results of 579 SAP and SDOCT examinations from 80 eyes of 47 control subjects, 199 eyes of 130 patients with suspected glaucoma, and 213 eyes of 146 patients with glaucoma were analyzed. The R(2) for the association between SAP total deviation and SDOCT variables ranged from 0.01 (P = .02) for the nasal rim area to 0.30 (P < .001) for inferior inner retinal thickness at the macula. The linear model fitted the data well. CONCLUSIONS: The strongest structure-function associations using SDOCT were found for retinal nerve fiber layer measurements at arcuate areas and inner retinal thickness at the macula measurements. The linear model is useful in studying the structure-function relationship in glaucoma.

Pattern recognition can detect subtle field defects in eyes of HIV individuals without retinitis under HAART.

OBJECTIVES: To use machine learning classifiers (MLCs) to seek differences in visual fields (VFs) between normal eyes and eyes of HIV+ patients; to find the effect of immunodeficiency on VFs and to compare the effectiveness of MLCs to commonly-used Statpac global indices in analyzing standard automated perimetry (SAP). METHODS: The high CD4 group consisted of 70 eyes of 39 HIV-positive patients with good immune status (CD4 counts were never <100/ml). The low CD4 group had 59 eyes of 38 HIV-positive patients with CD4 cell counts <100/ml at some period of time lasting for at least 6 months. The normal group consisted of 61 eyes of 52 HIV-negative individuals. We used a Humphrey Visual Field Analyzer, SAP full threshold program 24-2, and routine settings for evaluating VFs. We trained and tested support vector machine (SVM) machine learning classifiers to distinguish fields from normal subjects and high and CD4 groups separately. Receiver operating characteristic (ROC) curves measured the discrimination of each classifier, and areas under ROC were statistically compared. RESULTS: Low CD4 HIV patients: with SVM, the AUROC was 0.790 ± 0.042. SVM and MD each significantly differed from chance decision, with p < .00005. High CD4 HIV patients: the SVM AUROC of 0.664 ± 0.047 and MD were each significantly better than chance (p = .041, p = .05 respectively). CONCLUSIONS: Eyes from both low and high CD4 HIV+ patients have VFs defects indicating retinal damage. Generalized learning classifier, SVM, and a Statpac classifier, MD, are effective at detecting HIV eyes that have field defects, even when these defects are subtle.

Effect of disease severity and optic disc size on diagnostic accuracy of RTVue spectral domain optical coherence tomograph in glaucoma.

PURPOSE: To evaluate the effect of disease severity and optic disc size on the diagnostic accuracies of optic nerve head (ONH), retinal nerve fiber layer (RNFL), and macular parameters with RTVue (Optovue, Fremont, CA) spectral domain optical coherence tomography (SDOCT) in glaucoma. METHODS: 110 eyes of 62 normal subjects and 193 eyes of 136 glaucoma patients from the Diagnostic Innovations in Glaucoma Study underwent ONH, RNFL, and macular imaging with RTVue. Severity of glaucoma was based on visual field index (VFI) values from standard automated perimetry. Optic disc size was based on disc area measurement using the Heidelberg Retina Tomograph II (Heidelberg Engineering, Dossenheim, Germany). Influence of disease severity and disc size on the diagnostic accuracy of RTVue was evaluated by receiver operating characteristic (ROC) and logistic regression models. RESULTS: Areas under ROC curve (AUC) of all scanning areas increased (P < 0.05) as disease severity increased. For a VFI value of 99%, indicating early damage, AUCs for rim area, average RNFL thickness, and ganglion cell complex-root mean square were 0.693, 0.799, and 0.779, respectively. For a VFI of 70%, indicating severe damage, corresponding AUCs were 0.828, 0.985, and 0.992, respectively. Optic disc size did not influence the AUCs of any of the SDOCT scanning protocols of RTVue (P > 0.05). Sensitivity of the rim area increased and specificity decreased in large optic discs. CONCLUSIONS: Diagnostic accuracies of RTVue scanning protocols for glaucoma were significantly influenced by disease severity. Sensitivity of the rim area increased in large optic discs at the expense of specificity.

Agreement among spectral-domain optical coherence tomography instruments for assessing retinal nerve fiber layer thickness.

PURPOSE: To assess the agreement of parapapillary retinal nerve fiber layer (RNFL) thickness measurements among 3 spectral-domain optical coherence tomography (SD-OCT) instruments. DESIGN: Observational, cross-sectional study. METHODS: Three hundred thirty eyes (88 with glaucoma, 206 glaucoma suspects, 36 healthy) from 208 individuals enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) were imaged using RTVue, Spectralis and Cirrus in a single visit. Agreement among RNFL thickness measurements was assessed using Bland-Altman plots. The influence of age, axial length, disc size, race, spherical equivalent, and disease severity on the pairwise agreements between different instruments was assessed by regression analysis. RESULTS: Although RNFL thickness measurements between different instruments were highly correlated, Bland-Altman analyses indicated the presence of fixed and proportional biases for most of the pairwise agreements. In general, RTVue measurements tended to be thicker than Spectralis and Cirrus measurements. The agreement in average RNFL thickness measurements between RTVue and Spectralis was affected by age (P = .001) and spherical equivalent (P < .001), whereas the agreement between Spectralis and Cirrus was affected by axial length (P = .004) and spherical equivalent (P < .001). Disease severity influenced the agreement between Spectralis and both RTVue and Cirrus (P = .001). Disc area and race did not influence the agreement among the devices. CONCLUSIONS: RNFL thickness measurements obtained by different SD-OCT instruments were not entirely compatible and therefore they should not be used interchangeably. This may be attributable in part to differences in RNFL detection algorithms. Comparisons with histologic measurements could determine which technique is most accurate.

Imaging and Perimetry Society standards and guidelines.

PURPOSE: To provide readers with standards, recommendations, guidelines, and requirements for the application of perimetry to clinical ophthalmic practice and scientific study. METHODS: A working group of perimetry and visual field specialists from many parts of the world constructed a document that would allow current and future perimeters to be assessed by the same criteria. Because hardware and software technology, statistical procedures and clinical conditions are constantly changing, the characteristics in this paper emphasize general concepts rather than specific implementations employed by current devices. RESULTS: Critical aspects of perimetry included indications for perimetry, perimetric techniques, stimulus characteristics, test administration, patient preparation, data display, statistical analysis, interpretation of visual field findings, a glossary of terms and definitions, and standards for comparison of different perimetric tests. Each of these topics is discussed, along with their advantages and disadvantages. CONCLUSIONS: These guidelines serve as a basis for practitioners to evaluate their perimetric needs in relation to their clinical practice and patient population so that informed decisions can be made for visual field testing. In addition, these issues should be used as a cornerstone for future technological and practical improvements to the visual field diagnostic procedures.

Comparison of corneal biomechanical properties between healthy blacks and whites using the Ocular Response Analyzer.

PURPOSE: To analyze and compare corneal biomechanical properties in healthy black and white subjects using the Ocular Response Analyzer (ORA) and to evaluate their relationship with other ocular parameters. DESIGN: Observational cross-sectional study. METHODS: One hundred eighty one eyes (46 in blacks, 135 in whites) of 119 patients (37 blacks, 82 whites) were recruited from the longitudinal Diagnostic Innovations in Glaucoma Study (DIGS) and from the African Descent and Glaucoma Evaluation Study (ADAGES) at the University of California, San Diego. Corneal curvature, axial length, central corneal thickness (CCT), corneal hysteresis (CH), and corneal resistance factor (CRF) were obtained from all participants. Univariable and multivariable regression analyses were used to evaluate the associations between ORA measurements and age, CCT, axial length, corneal curvature, and race. RESULTS: Black subjects had significantly lower values of CH (9.7 mm Hg vs 10.4 mm Hg; P = .033), CRF (9.84 mm Hg vs 10.70 mm Hg; P = .028), and CCT (534 mum vs 562 mum; P = .001) compared to white subjects. A significant relationship was found between CH and CCT (R(2) = 0.25; P < .001) and between CRF and CCT (R(2) = 0.42; P < .001). After adjusting for CCT, age, axial length, and corneal curvature, the difference between blacks and whites in CH (P = .077) and CRF (P = .621) measurements lost statistical significance. CONCLUSION: Black subjects tended to have lower measurements of corneal hysteresis compared to white subjects; however, this was largely explained by differences in corneal thickness. Therefore, it is unlikely that CH would have an independent effect in explaining differences in susceptibility of disease between these 2 racial groups.

Spatial pattern of glaucomatous visual field loss obtained with regionally condensed stimulus arrangements.

PURPOSE: To assess the spatial distribution of glaucomatous visual field defects (VFDs) obtained with regionally condensed stimulus arrangements. METHODS: Sixty-three eyes of 63 glaucoma subjects were examined with threshold-estimating automated static perimetry (full threshold 4-2-1 dB strategy with at least three reversals) on an automatic campimeter or a full-field perimeter. Stimuli were added by the examiner to regionally enhance spatial resolution in regions that were suspicious for a glaucomatous VFD. These regions were characterized by contiguous local VFDs, attributable to the retinal nerve fiber bundle course according to the impression of the examiner. The added stimulus locations were subsets of a predefined, dense perimetric grid. All VFD locations with P < 0.05 (total deviation plots) were assessed by superimposing the visual field records of all participants. RESULTS: Glaucomatous VFD loss occurred more frequently in the upper than in the lower hemifield, with a typical retinal nerve fiber-related pattern and a preference of the nasal step region. More than 50% of the eyes with predominantly mild to moderate glaucomatous field loss showed defective locations in the immediate superior paracentral region within an eccentricity of 3°. CONCLUSIONS: Conventional thresholding white-on-white perimetry with regionally enhanced spatial resolution reveals that glaucomatous visual field loss affects the immediate paracentral area, especially the upper hemifield, in many eyes with only mild to moderate glaucomatous visual field loss. Detailed knowledge about the spatial pattern and the local frequency distribution of glaucomatous VFDs is an essential prerequisite for creating regionally condensed stimulus arrangements for adequate detection and follow-up of functional glaucomatous damage.

The relationship between intraocular pressure reduction and rates of progressive visual field loss in eyes with optic disc hemorrhage.

PURPOSE: To evaluate rates of visual field progression in eyes with optic disc hemorrhages and the effect of intraocular pressure (IOP) reduction on these rates. DESIGN: Observational cohort study. PARTICIPANTS: The study included 510 eyes of 348 patients with glaucoma who were recruited from the Diagnostic Innovations in Glaucoma Study (DIGS) and followed for an average of 8.2 years. METHODS: Eyes were followed annually with clinical examination, standard automated perimetry visual fields, and optic disc stereophotographs. The presence of optic disc hemorrhages was determined on the basis of masked evaluation of optic disc stereophotographs. Evaluation of rates of visual field change during follow-up was performed using the visual field index (VFI). MAIN OUTCOME MEASURES: The evaluation of the effect of optic disc hemorrhages on rates of visual field progression was performed using random coefficient models. Estimates of rates of change for individual eyes were obtained by best linear unbiased prediction (BLUP). RESULTS: During follow-up, 97 (19%) of the eyes had at least 1 episode of disc hemorrhage. The overall rate of VFI change in eyes with hemorrhages was significantly faster than in eyes without hemorrhages (-0.88%/year vs. -0.38%/year, respectively, P<0.001). The difference in rates of visual field loss pre- and post-hemorrhage was significantly related to the reduction of IOP in the post-hemorrhage period compared with the pre-hemorrhage period (r = -0.61; P<0.001). Each 1 mmHg of IOP reduction was associated with a difference of 0.31%/year in the rate of VFI change. CONCLUSIONS: There was a beneficial effect of treatment in slowing rates of progressive visual field loss in eyes with optic disc hemorrhage. Further research should elucidate the reasons why some patients with hemorrhages respond well to IOP reduction and others seem to continue to progress despite a significant reduction in IOP levels. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Determinants of agreement between the confocal scanning laser tomograph and standardized assessment of glaucomatous progression.

PURPOSE: To estimate the agreement of confocal scanning laser tomograph (CSLT), topographic change analysis (TCA) with assessment of stereophotographs, and standard automated perimetry (SAP) for detecting glaucomatous progression and to identify factors associated with agreement between methods. DESIGN: Observational cohort study. PARTICIPANTS: We included 246 eyes of 167 glaucoma patients, glaucoma suspects, and ocular hypertensives. METHODS: We included CSLT series (n ≥ 4 tests; mean follow-up, 4 years), stereophotographs, and SAP results in the analysis. The number of progressors by guided progression analysis (GPA, "likely progression"), progressors by masked stereophotographs assessment and progressors by TCA as determined for 3 parameters related to the number of progressed superpixels within the disc margin was determined. Agreement between progression by each TCA parameter, stereophotographs and GPA was assessed using the Kappa test. Analysis of variance with post hoc analysis was applied to identify baseline factors including image quality (standard deviation of the mean topography), disc size and disease severity (pattern standard deviation [PSD] and cup area) associated with agreement/nonagreement between methods. MAIN OUTCOME MEASURES: Agreement in assessing glaucomatous progression between the methods including factors associated with agreement/nonagreement between methods. RESULTS: Agreement between progression by TCA and progression by stereophotographs and/or GPA was generally poor regardless of the TCA parameter and specificity cutoffs applied. For the parameters with the strongest agreement, cluster size in disc (CSIZE(disc)) and cluster area in disc (CAREA(disc)), kappa values were 0.16 (63.9%, agreement on 134 nonprogressing eyes and 23 progressing eyes) and 0.15 (64.1%, agreement on 135 nonprogressing eyes and 22 progressing eyes) at 99% cutoff. Most of the factors evaluated were not significantly associated with agreement/nonagreement between methods (all P > 0.07). However, SAP PSD was greater in the progressors by stereophotography only group compared with the progressors by TCA only group (5.8 ± 4.7 and 2.6 ± 2.2, respectively [P = 0.003] for CSIZE(disc) at 95% specificity and 5.4 ± 4.6 and 2.5 ± 2.3, respectively [P = 0.002] for CAREA(disc) at 99% specificity). CONCLUSIONS: Agreement for detection of longitudinal changes between TCA, stereophotography, and SAP GPA is poor. Progressors by stereophotography only tended to have more advanced disease at baseline than progressors by TCA only.

African Descent and Glaucoma Evaluation Study (ADAGES): II. Ancestry differences in optic disc, retinal nerve fiber layer, and macular structure in healthy subjects.

OBJECTIVE: To define differences in optic disc, retinal nerve fiber layer, and macular structure between healthy participants of African (AD) and European descent (ED) using quantitative imaging techniques in the African Descent and Glaucoma Evaluation Study (ADAGES). METHODS: Reliable images were obtained using stereoscopic photography, confocal scanning laser ophthalmoscopy (Heidelberg retina tomography [HRT]), and optical coherence tomography (OCT) for 648 healthy subjects in ADAGES. Findings were compared and adjusted for age, optic disc area, and reference plane height where appropriate. RESULTS: The AD participants had significantly greater optic disc area on HRT (2.06 mm(2); P < .001) and OCT (2.47 mm(2); P < .001) and a deeper HRT cup depth than the ED group (P < .001). Retinal nerve fiber layer thickness was greater in the AD group except within the temporal region, where it was significantly thinner. Central macular thickness and volume were less in the AD group. CONCLUSIONS: Most of the variations in optic nerve morphologic characteristics between the AD and ED groups are due to differences in disc area. However, differences remain in HRT cup depth, OCT macular thickness and volume, and OCT retinal nerve fiber layer thickness independent of these variables. These differences should be considered in the determination of disease status.

African Descent and Glaucoma Evaluation Study (ADAGES): III. Ancestry differences in visual function in healthy eyes.

OBJECTIVE: To investigate differences in visual function between the healthy eyes of people of African (AD) and European descent (ED). METHODS: Visual function was assessed in 393 AD and 367 ED participants selected from the African Descent and Glaucoma Evaluation Study and the Diagnostic Innovations in Glaucoma Study. Participants had normal appearance of the optic disc and intraocular pressure of less than 22 mm Hg. Each participant had 2 reliable 24-2 standard automated perimetry tests, and most had short-wavelength automated perimetry and frequency-doubling technology tests. The generalized estimating equation was used to adjust for intereye correlations. Results were adjusted for age, vertical cup-disc ratio, disc size, central corneal thickness, and presence of high blood pressure. RESULTS: The AD participants were younger (mean [SD] age, 46.2 [13.2] years) than the ED participants (age, 49.5 [16.6] years) (P = .003). The AD participants had worse mean deviation and pattern standard deviation and more points triggered as abnormal on the total and pattern deviation plots compared with ED participants on all tests (P < .05). A larger percentage of AD participants had confirmed abnormal glaucoma hemifield test results on standard automated perimetry only. CONCLUSIONS: People of AD have significantly worse performance than people of ED on all tests of visual function. Additional research using longitudinal data is needed to determine the cause of these small but significant ancestry differences in visual function.