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.

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.

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.

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.

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.

Comparison of different spectral domain optical coherence tomography scanning areas for glaucoma diagnosis.

PURPOSE: To evaluate retinal nerve fiber layer (RNFL), optic nerve head (ONH), and macular thickness measurements for glaucoma detection using the RTVue spectral domain optical coherence tomograph. DESIGN: Diagnostic, case-control study. PARTICIPANTS: One hundred forty eyes of 106 glaucoma patients and 74 eyes of 40 healthy subjects from the Diagnostic Innovations in Glaucoma Study (DIGS). METHODS: All patients underwent ocular imaging with the commercially available RTVue. Optic nerve head, RNFL thickness, and macular thickness scans were obtained during the same visit. Receiver operating characteristic (ROC) curves and sensitivities at fixed specificities (80% and 95%) were calculated for each parameter. MAIN OUTCOME MEASURES: Areas under the ROC curves (AUC) and sensitivities at fixed specificities of 80% and 95%. RESULTS: The AUC for the RNFL parameter with best performance, inferior quadrant thickness, was significantly higher than that of the best-performing ONH parameter, inferior rim area (0.884 vs 0.812, respectively; P = 0.04). There was no difference between ROC curve areas of the best RNFL thickness parameters and the best inner macular thickness measurement, ganglion cell complex root mean square (ROC curve area = 0.870). CONCLUSIONS: The RTVue RNFL and inner retinal macular thickness measurements had good ability to detect eyes with glaucomatous visual field loss and performed significantly better than ONH parameters.

Agreement for detecting glaucoma progression with the GDx guided progression analysis, automated perimetry, and optic disc photography.

PURPOSE: To evaluate the ability of the GDx Variable Corneal Compensation (VCC) Guided Progression Analysis (GPA) software for detecting glaucomatous progression. DESIGN: Observational cohort study. PARTICIPANTS: The study included 453 eyes from 252 individuals followed for an average of 46+/-14 months as part of the Diagnostic Innovations in Glaucoma Study. At baseline, 29% of the eyes were classified as glaucomatous, 67% of the eyes were classified as suspects, and 5% of the eyes were classified as healthy. METHODS: Images were obtained annually with the GDx VCC and analyzed for progression using the Fast Mode of the GDx GPA software. Progression using conventional methods was determined by the GPA software for standard automated achromatic perimetry (SAP) and by masked assessment of optic disc stereophotographs by expert graders. MAIN OUTCOME MEASURES: Sensitivity, specificity, and likelihood ratios (LRs) for detection of glaucoma progression using the GDx GPA were calculated with SAP and optic disc stereophotographs used as reference standards. Agreement among the different methods was reported using the AC(1) coefficient. RESULTS: Thirty-four of the 431 glaucoma and glaucoma suspect eyes (8%) showed progression by SAP or optic disc stereophotographs. The GDx GPA detected 17 of these eyes for a sensitivity of 50%. Fourteen eyes showed progression only by the GDx GPA with a specificity of 96%. Positive and negative LRs were 12.5 and 0.5, respectively. None of the healthy eyes showed progression by the GDx GPA, with a specificity of 100% in this group. Inter-method agreement (AC(1) coefficient and 95% confidence intervals) for non-progressing and progressing eyes was 0.96 (0.94-0.97) and 0.44 (0.28-0.61), respectively. CONCLUSIONS: The GDx GPA detected glaucoma progression in a significant number of cases showing progression by conventional methods, with high specificity and high positive LRs. Estimates of the accuracy for detecting progression suggest that the GDx GPA could be used to complement clinical evaluation in the detection of longitudinal change in glaucoma.

Diagnostic accuracy of pattern electroretinogram optimized for glaucoma detection.

PURPOSE: To assess the ability of the new pattern electroretinogram optimized for glaucoma detection (PERGLA) paradigm to discriminate between healthy individuals and individuals with glaucomatous optic neuropathy (GON). DESIGN: Cross-sectional study. PARTICIPANTS: One hundred forty-two eyes of 71 participants (42 healthy and 29 with GON in at least 1 eye) enrolled in the University of California, San Diego, Diagnostic Innovations in Glaucoma Study were studied. Healthy individuals were those recruited as healthy with healthy-appearing optic disc by examination and masked stereoscopic optic disc photograph evaluation. Glaucomatous optic neuropathy was defined based on stereophotograph evaluation. METHODS: The PERGLA (Glaid Elettronica, Pisa, Italy) recordings were obtained within 6 months of standard automated perimetry (SAP) testing. Dependent variables were PERGLA amplitude, phase, amplitude asymmetry, phase asymmetry, and SAP pattern standard deviation (PSD) and mean deviation (MD). MAIN OUTCOME MEASURES: Diagnostic accuracy (sensitivity and specificity) of the PERGLA normative database for classifying healthy and glaucomatous individuals was determined. In addition, performance (areas under receiver operating characteristic curves [AUCs]) of PERGLA amplitude and phase for classifying healthy (n=84) and GON (n=50) eyes was determined. Results from both analyses were compared with those from SAP. RESULTS: Sensitivity and specificity of the PERGLA normative database were 0.76 and 0.59, respectively, compared with 0.83 and 0.77 for SAP. The AUCs for PERGLA amplitude and phase were 0.75 and 0.50 (chance performance), respectively. The AUCs for SAP PSD and MD were 0.83 and 0.78, respectively. CONCLUSIONS: Pattern electroretinograms recorded using the PERGLA paradigm can discriminate between healthy and glaucoma eyes, although this technique performed no better than SAP at this task. Low specificity of the PERGLA normative database suggests that the distribution of recordings included in the database is not ideal.

The Relationship between intraocular pressure and progressive retinal nerve fiber layer loss in glaucoma.

PURPOSE: To evaluate the relationship between intraocular pressure (IOP) and progressive retinal nerve fiber layer (RNFL) loss, as measured by scanning laser polarimetry with enhanced corneal compensation (GDx ECC), in a cohort of glaucoma patients and individuals suspected of having the disease followed over time. DESIGN: Observational cohort study. PARTICIPANTS: The study included 344 eyes of 204 patients recruited from the Diagnostic Innovations in Glaucoma Study (DIGS). There were 98 eyes (28%) with a diagnosis of glaucoma and 246 (72%) were considered glaucoma suspects at baseline. METHODS: Images were obtained annually with the GDx ECC scanning laser polarimeter, along with stereophotographs and SAP. The study included a total of 1211 GDx ECC visits with an average of 3.5 visits per eye. Progression was determined by the Guided Progression Analysis software for SAP and by masked assessment of stereophotographs performed by expert graders. MAIN OUTCOME MEASURES: Random coefficient models were used to evaluate the relationship between IOP and RNFL thickness measurements over time in progressors and nonprogressors. Models were adjusted for baseline diagnosis and central corneal thickness. RESULTS: For all 344 eyes, the overall rate of change for the GDx ECC average thickness at an average IOP of 17 mmHg was -0.25 microm per year (P = 0.002). Each 1-mmHg higher IOP was associated with an additional loss of 0.05 microm per year of RNFL (P = 0.001). Twenty-nine eyes (8%) showed progression on SAP and/or optic disc stereophotographs. These eyes had a significantly higher rate of RNFL change (-0.95 microm/year) than nonprogressors (-0.17 microm/year; P = 0.001). For progressors, each 1-mmHg higher IOP was associated with an additional loss of 0.13 microm per year of RNFL. CONCLUSIONS: Higher levels of IOP during follow-up were significantly related to higher rates of progressive RNFL loss detected by the GDx ECC. These findings suggest that the GDx ECC may be helpful in monitoring progression and estimating rates of change in patients with glaucoma or suspected of having the disease. Also, they may contribute to a better understanding of the relationship between IOP and structural deterioration in glaucoma. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Specification of progression in glaucomatous visual field loss, applying locally condensed stimulus arrangements.

PURPOSE: The goal of this work was to (i) determine patterns of progression in glaucomatous visual field loss, (ii) compare the detection rate of progression between locally condensed stimulus arrangements and conventional 6 degrees x 6 degrees grid, and (iii) assess the individual frequency distribution of test locations exhibiting a local event (i.e., an abrupt local deterioration of differential luminance sensitivity (DLS) by more than -10 dB between any two examinations). METHODS: The visual function of 41 glaucomatous eyes of 41 patients (16 females, 25 males, 37 to 75 years old) was examined with automated static perimetry (Tuebingen Computer Campimeter or Octopus 101-Perimeter). Stimuli were added to locally enhance the spatial resolution in suspicious regions of the visual field. The minimum follow-up was four subsequent sessions with a minimum of 2-month (median 6-month) intervals between each session. Progression was identified using a modified pointwise linear regression (PLR) method and a modified Katz criterion. The presence of events was assessed in all progressive visual fields. RESULTS: Eleven eyes (27%) showed progression over the study period (median 2.5 years, range 1.3-8.6 years). Six (55%) of these had combined progression in depth and size and five eyes (45%) progressed in depth only. Progression in size conformed always to the nerve fiber course. Seven out of 11 (64%) of the progressive scotomata detected by spatially condensed grids would have been missed by the conventional 6 degrees x 6 degrees grid. At least one event occurred in 64% of all progressive eyes. Five of 11 (46%) progressive eyes showed a cluster of events. CONCLUSIONS: The most common pattern of progression in glaucomatous visual fields is combined progression in depth and size of an existing scotoma. Applying individually condensed test grids remarkably enhances the detection rate of glaucomatous visual field deterioration (at the expense of an increased examination time) compared to conventional stimulus arrangements.

Diagnostic accuracy of the Matrix 24-2 and original N-30 frequency-doubling technology tests compared with standard automated perimetry.

PURPOSE: To compare the diagnostic accuracy of the Matrix frequency-doubling technology (FDT) 24-2, first-generation FDT N-30 (FDT N-30), and standard automated perimetry (SAP) tests of visual function. METHODS: One eye of each of 85 glaucoma patients and 81 healthy controls from the Diagnostic Innovations in Glaucoma Study was included. Evidence of glaucomatous optic neuropathy on stereophotographs was used to classify the eyes. Matrix FDT 24-2, first-generation FDT N-30, and SAP-SITA 24-2 tests were performed on all participants within 3 months. Receiver operating characteristic (ROC) curves were generated and used to determine sensitivity levels at 80% and 90% specificity for mean deviation (MD), pattern standard deviation (PSD), number of total deviation (TD), and pattern deviation (PD) points triggered at less than 5% and 1%. The tests were compared using the best parameter for each test (that with the highest area under the ROC curve) and with the PSD. RESULTS: The best parameters were MD for SAP (0.680), PSD for FDT N-30 (0.733), and number of TD less than 5% points for FDT 24-2 (0.774). Using the best parameter, the area under the ROC curve was significantly larger for FDT 24-2 than for SAP (P = 0.01). No statistically significant differences were observed between SAP and FDT N-30 (P = 0.21) and FDT N-30 and FDT 24-2 (P = 0.26). Similar results were obtained when the PSD was used to compare the tests, with the exception that the area under the ROC curve for the FDT N-30 test (0.733) was significantly larger than that of the SAP-SITA (0.641; P = 0.03). CONCLUSIONS: The performance of the Matrix FDT 24-2 was similar to that of the first-generation FDT N-30. The Matrix FDT 24-2 test was consistently better than SAP at discriminating between healthy and glaucomatous eyes. Further studies are needed to evaluate the ability of the Matrix FDT 24-2 to monitor glaucoma progression.

Comparison of HRT-3 glaucoma probability score and subjective stereophotograph assessment for prediction of progression in glaucoma.

PURPOSE: To assess whether baseline Glaucoma Probability Score (GPS; HRT-3; Heidelberg Engineering, Dossenheim, Germany) results are predictive of progression in patients with suspected glaucoma. The GPS is a new feature of the confocal scanning laser ophthalmoscope that generates an operator-independent, three-dimensional model of the optic nerve head and gives a score for the probability that this model is consistent with glaucomatous damage. METHODS: The study included 223 patients with suspected glaucoma during an average follow-up of 63.3 months. Included subjects had a suspect optic disc appearance and/or elevated intraocular pressure, but normal visual fields. Conversion was defined as development of either repeatable abnormal visual fields or glaucomatous deterioration in the appearance of the optic disc during the study period. The association between baseline GPS and conversion was investigated by Cox regression models. RESULTS: Fifty-four (24.2%) eyes converted. In multivariate models, both higher values of GPS global and subjective stereophotograph assessment (larger cup-disc ratio and glaucomatous grading) were predictive of conversion: adjusted hazard ratios (95% CI): 1.31 (1.15-1.50) per 0.1 higher global GPS, 1.34 (1.12-1.62) per 0.1 higher CDR, and 2.34 (1.22-4.47) for abnormal grading, respectively. No significant differences (P > 0.05 for all comparisons) were found between the c-index values (equivalent to area under ROC curve) for the multivariate models (0.732, 0.705, and 0.699, respectively). CONCLUSIONS: GPS values were predictive of conversion in our population of patients with suspected glaucoma. Further, they performed as well as subjective assessment of the optic disc. These results suggest that GPS could potentially replace stereophotograph as a tool for estimating the likelihood of conversion to glaucoma.

Bayesian machine learning classifiers for combining structural and functional measurements to classify healthy and glaucomatous eyes.

PURPOSE: To determine whether combining structural (optical coherence tomography, OCT) and functional (standard automated perimetry, SAP) measurements as input for machine learning classifiers (MLCs; relevance vector machine, RVM; and subspace mixture of Gaussians, SSMoG) improves diagnostic accuracy for detecting glaucomatous eyes compared with using each measurement method alone. METHODS: Sixty-nine eyes of 69 healthy control subjects (average age, 62.0, SD 9.7 years; visual field mean deviation [MD], -0.70, SD 1.41 dB) and 156 eyes of 156 patients with glaucoma (average age, 66.4, SD 10.2 years; visual field MD, -3.12, SD 3.43 dB) were imaged with OCT (Stratus OCT, Carl Zeiss Meditec, Inc., Dublin, CA) and tested with SAP (Humphrey Field Analyzer II with Swedish Interactive Thresholding Algorithm, SITA; Carl Zeiss Meditec, Inc.) within 3 months of each other. RVM and SSMoG MLCs were trained and tested on OCT-determined RNFL thickness measurements from 32 sectors ( approximately 11.25 degrees each) obtained in the circumpapillary area under the instrument-defined measurement ellipse and SAP pattern deviation values from 52 points from the 24-2 grid, independently and in combination. Tenfold cross-validation was used to train and test classifiers on unique subsets of the full 225-eye data set, and areas under the receiver operating characteristic curve (AUROC) for the classification of eyes in the test set were generated. AUROC results from classifiers trained on OCT and SAP alone and those trained on OCT and SAP in combination were compared. In addition, these results were compared to currently available OCT measurements (mean retinal nerve fiber layer [RNFL] thickness, inferior RNFL thickness, and superior RNFL thickness) and SAP indices (MD and pattern standard deviation [PSD]). RESULTS: The AUROCs for RVM trained on OCT parameters alone, SAP parameters alone and OCT and SAP parameters combined were 0.809, 0.815, and 0.845, respectively. The AUROCs for SSMoG trained on OCT parameters alone, SAP parameters alone, and OCT and SAP parameters combined were 0.817, 0.841, and 0.869, respectively. Combining techniques using both RVM and SSMoG significantly improved on MLC analysis of OCT, but not SAP, measurements alone. Classification performance using RVM and SSMoG was statistically similar. CONCLUSIONS: RVM and SSMoG Bayesian MLCs trained on OCT and SAP data can successfully discriminate between healthy and early glaucomatous eyes. Combining OCT and SAP measurements using RVM and SSMoG increased diagnostic performance marginally compared with MLC analysis of data obtained using each technology alone.

Comparison of retinal nerve fiber layer and optic disc imaging for diagnosing glaucoma in patients suspected of having the disease.

PURPOSE: To compare retinal nerve fiber layer (RNFL) and optic disc topographic imaging for detection of optic nerve damage in patients suspected of having glaucoma. DESIGN: Observational cohort study. PARTICIPANTS: A cohort of 82 patients suspected of having glaucoma based on the appearance of the optic nerve. METHODS: All patients were imaged using the GDx VCC scanning laser polarimeter and HRT (software version 3.0) confocal scanning laser ophthalmoscope. All patients had normal standard automated perimetry visual fields at the time of imaging and were classified based on history of documented stereophotographic evidence of progressive glaucomatous change in the appearance of the optic nerve occurring before the imaging sessions. MAIN OUTCOME MEASURES: Areas under the receiver operating characteristic (ROC) curves were used to evaluate the diagnostic accuracies of GDx VCC and the HRT. RESULTS: Forty eyes with progressive glaucomatous optic nerve change were included in the glaucoma group, and 42 eyes without any evidence of progressive damage to the optic nerve followed untreated for an average time of 8.97+/-3.08 years were included in the normal group. The area under the ROC curve for the best parameter from GDx VCC (nerve fiber indicator [NFI]) was significantly larger than that of the best parameter from the HRT (rim volume) (0.83 vs. 0.70; P = 0.044). The NFI parameter also had a larger ROC curve area than that of the contour line-independent parameter glaucoma probability score (0.83 vs. 0.68; P = 0.023). Assuming borderline results as normal, the Moorfields regression analysis classification had a sensitivity of 48% for specificity of 69%. For a similar specificity (70%), the parameter NFI had a significantly larger sensitivity (83%) (P = 0.003). CONCLUSIONS: Retinal nerve fiber layer imaging with GDx VCC had a superior performance versus topographic optic disc assessment with the HRT for detecting early damage in patients suspected of having glaucoma. For glaucoma diagnosis, these results suggest that GDx VCC may offer advantage over the HRT when these tests are combined with clinical examination of the optic nerve.

Long-term intraocular pressure fluctuations and risk of conversion from ocular hypertension to glaucoma.

PURPOSE: To investigate whether long-term intraocular pressure (IOP) fluctuations are a risk factor for conversion from ocular hypertension to glaucoma. DESIGN: Observational cohort study. PARTICIPANTS: The study included 252 eyes of 126 patients with ocular hypertension observed untreated as part of the Diagnostic Innovations in Glaucoma Study. At baseline, ocular hypertensive eyes had elevated IOP, normal visual fields (VFs) on standard automated perimetry, and normal optic discs as evaluated by stereophotograph assessment. METHODS: Glaucoma conversion was defined as development of reproducible VF loss or optic disc damage. Analyses included all IOP measurements from the baseline visit to time of progression (for converters) and last follow-up (for nonconverters). Mean IOP and IOP fluctuation were calculated as the arithmetic mean and standard deviation (SD), respectively, of all available IOP measurements per eye. MAIN OUTCOME MEASURES: Univariable and multivariable Cox regression analyses were used to evaluate the association between IOP fluctuation and time to progression. Multivariable models adjusted for age, mean IOP, central corneal thickness, vertical cup-to-disc ratio, and pattern SD. RESULTS: Forty eyes of 31 subjects developed glaucoma during follow-up. Mean IOPs during follow-up were 25.4+/-4.2 mmHg for the eyes that converted to glaucoma and 24.1+/-3.5 mmHg for the eyes that did not. Corresponding values for IOP fluctuation were 3.16+/-1.35 mmHg and 2.77+/-1.11 mmHg, respectively. Intraocular pressure fluctuation was not a risk factor for conversion to glaucoma both in univariable analysis (hazard ratio [HR], 1.30 per 1 mmHg higher; 95% confidence interval [CI], 0.76-1.96; P = 0.092) and in multivariable analysis (adjusted HR, 1.08 per 1 mmHg higher; 95% CI, 0.79-1.48; P = 0.620). Mean IOP during follow-up was a significant risk factor for progression both in univariable analysis (HR = 1.16 per 1 mmHg higher; 95% CI, 1.04-1.31; P = 0.010) and in multivariable analysis (adjusted HR, 1.20 per 1 mmHg higher; 95% CI, 1.06-1.36; P = 0.005). CONCLUSION: Long-term IOP fluctuations do not appear to be significantly associated with the risk of developing glaucoma in untreated ocular hypertensive subjects.

Retinotopic organization of primary visual cortex in glaucoma: Comparing fMRI measurements of cortical function with visual field loss.

Primary open angle glaucoma (POAG) is a progressive optic neuropathy characterized by retinal ganglion cell loss. Experimental primate glaucoma indicates neuronal degeneration of the lateral geniculate nucleus (LGN) and activity changes in the visual cortex (V1). Neuronal degeneration has also been shown in a post-mortem human study of the optic nerve, LGN and visual cortex. Functional magnetic resonance imaging (fMRI), a non-invasive means of inferring function-specific neuronal activity, provides an opportunity to evaluate glaucomatous changes in neuronal activity throughout the visual pathway in vivo. The purpose of this study is to demonstrate that the relationship between visual field loss in human POAG and the functional organization of V1 can be measured using novel fMRI analysis methods. Visual field defects were measured using standard automated perimetry (SAP). A retinotopic map of visual space was obtained for V1, and the retinotopy data was fit with a template. The template was used to project regions within the visual field onto a flattened representation of V1. Viewing through the glaucomatous vs. fellow eye was compared by alternately presenting each eye with a scotoma-mapping stimulus. The resulting blood oxygen level dependent (BOLD) fMRI response was compared to interocular differences in thresholds for corresponding regions of the visual field. The spatial pattern of activity observed in the flattened representation agreed with the pattern of visual field loss. Furthermore, the amplitude of the BOLD response was correlated on a pointwise basis with the difference in sensitivity thresholds between the glaucomatous and fellow eyes (r = 0.53, p < 0.0001). The BOLD signal in human V1 is altered for POAG patients in a manner consistent with the loss of visual function. FMRI of visual brain areas is a potential means for quantifying glaucomatous changes in neuronal activity. This should enhance our understanding of glaucoma, and could lead to new diagnostic techniques and therapies.

Diagnostic tools for glaucoma detection and management.

Early diagnosis of glaucoma is critical to prevent permanent structural damage and irreversible vision loss. Detection of glaucoma typically relies on examination of structural damage to the optic nerve combined with measurements of visual function. To aid the clinician in evaluation of visual function and structure, computer-based devices such as confocal scanning laser ophthalmoscopy, scanning laser polarimetry, and optical coherence tomography provide quantitative assessments of structural damage, and visual function testing includes standard automated perimetry as well as selective techniques, including short-wavelength automated perimetry and frequency-doubling technology perimetry are available. This article will review current literature on diagnostic modalities available for glaucoma with emphasis on the best evidence available in the literature to support their use in clinical practice.

Vision function in HIV-infected individuals without retinitis: report of the Studies of Ocular Complications of AIDS Research Group.

PURPOSE: To evaluate the prevalence and risk factors for vision loss in patients with clinical or immunologic AIDS without infectious retinitis. DESIGN: A prospective, multicenter cohort study of patients with AIDS. METHODS: One thousand three hundred and fifty-one patients (2,671 eyes) at 19 clinical trials centers diagnosed with AIDS but without major ocular complications of HIV. Standardized measurements of visual acuity, automated perimetry, and contrast sensitivity were analyzed and correlated with measurements of patients' health and medical data relating to HIV infection. We evaluated correlations between vision function testing and HIV-related risk factors and medical testing. RESULTS: There were significant (P<.05) associations between measures of decreasing vision function and indices of increasing disease severity, including Karnofsky score and hemoglobin. A significant relationship was seen between low-contrast sensitivity and decreasing levels of CD4+ T-cell count. Three percent of eyes had a visual acuity worse than 20/40 Snellen equivalents, which was significantly associated with a history of opportunistic infections and low Karnofsky score. When compared with external groups with normal vision, 39% of eyes had abnormal mean deviation on automated perimetry, 33% had abnormal pattern standard deviation, and 12% of eyes had low contrast sensitivity. CONCLUSIONS: This study confirms that visual dysfunction is common in patients with AIDS but without retinitis. The most prevalent visual dysfunction is loss of visual field; nearly 40% of patients have some abnormal visual field. There is an association between general disease severity and less access to care and vision loss. The pathophysiology of this vision loss is unknown but is consistent with retinovascular disease or optic nerve disease.

The effects of study design and spectrum bias on the evaluation of diagnostic accuracy of confocal scanning laser ophthalmoscopy in glaucoma.

PURPOSE: To assess the effects of study design and spectrum bias on the evaluation of diagnostic accuracy of confocal scanning laser ophthalmoscopy (CSLO) in glaucoma. METHODS: Analysis 1 included 67 eyes with glaucomatous visual field loss and 56 eyes of normal volunteers. Estimates of diagnostic accuracy in this analysis were compared to those obtained from analysis 2, which included a cohort of patients with suspected glaucoma, but without visual field loss at the time of CSLO imaging. For analysis 2, 40 eyes with progressive glaucomatous optic disc change were included in the glaucoma group and 43 eyes without any evidence of progressive damage to the optic nerve that were observed untreated for an average time of 9.01 +/- 3.09 years were included in the normal group. Areas under the receiver operating characteristic (ROC) curves (AUC) were used to evaluate diagnostic accuracy of CSLO parameters. RESULTS: There was a statistically significant difference between the performance of the parameter with largest AUC, discriminant function Bathija, in analysis 1 (AUC = 0.91) compared with its performance in analysis 2 (AUC = 0.71; P = 0.002). For the contour-line-independent parameter glaucoma probability score, a statistically significant difference was also observed in the performance obtained in analysis 1 (AUC = 0.89) compared with analysis 2 (AUC = 0.65; P < 0.001). CONCLUSIONS: Estimates of diagnostic accuracy of CSLO in glaucoma can be largely different depending on the population studied and the reference standard used to define disease. Diagnostic accuracy estimates obtained from case-control studies including well-defined groups of subjects with or without disease may not be applicable to the clinically relevant population.