Corneal Biomechanical Changes Caused by Acute Elevation of IOP in Eyes with and without Glaucoma.

SIGNIFICANCE: Although corneal biomechanical parameters are well linked with glaucoma, their clinical utility has not yet been fully elucidated. This study was designed to provide unique evidence about the dynamic nature of corneal biomechanical parameters and their potential prognostic ability for glaucoma. PURPOSE: This study aimed to evaluate the effect of acute intraocular pressure (IOP) elevation on corneal hysteresis (CH) and corneal resistance factor (CRF) and the associations of these biomechanical parameters with glaucomatous disease. METHODS: Subjects participating in a prospective, longitudinal glaucoma research study had CH and CRF measured before and during ophthalmodynamometry during visits in the years 2011 to 2012. All participants were diagnosed with primary open-angle glaucoma, ocular hypertension, glaucoma suspect, or normal eyes and had a minimum of 3 years of study participation with at least five reliable visual field (VF) tests. Changes in CH, CRF, and IOP induced by ophthalmodynamometry were compared between diagnostic groups and evaluated for relationships with existing and future glaucomatous VF loss. RESULTS: In 248 eyes of 248 subjects followed up for 7.7 ± 2.3 years, ophthalmodynamometry induced a mean IOP increase from 15.1 to 29.9 mmHg, causing a mean 34 ± 28% increase in CRF and 21 ± 25% decrease in CH. Magnitude of CH change did not differ between diagnostic groups or between eyes that did (n = 20) and did not (n = 95) develop new VF loss during the study period, nor was it related to rate of future VF progression. CONCLUSIONS: Ophthalmodynamometry-induced IOP elevation resulted in significant acute changes in CH and CRF in this study; this suggests accounting for IOP may be important in clinical interpretation of these parameters. However, because the degree of CH change was not related to glaucoma or its progression, acute changes in CH and CRF do not seem to have a prognostic value for glaucoma.

Change in Intraocular Pressure and Ocular Perfusion Pressure Due to Trendelenburg Positioning.

SIGNIFICANCE: This study increases foundational knowledge about the dynamic relationships between intraocular pressure (IOP), blood pressure (BP), and mean ocular perfusion pressure (MOPP) in the setting of steep Trendelenburg positioning and may inform medical decision making for patients in which this positioning is planned. PURPOSE: The purpose of this study was to explore the demographic and clinical factors related to IOP, MOPP, and BP change during Trendelenburg positioning in a large sample of subjects. METHODS: A single-cohort interventional study was conducted at the American Academy of Optometry 2017 annual meeting. Baseline demographic data were collected by a secure survey tool. IOP and BP were then measured while seated and again after 1 and 2 minutes in a steep Trendelenburg position. Raw and percentage differences for each variable were compared between time points, and regression analyses demonstrated factors related to change in IOP, BP, and MOPP during steep Trendelenburg positioning. RESULTS: Median IOP increased from 16.3 mmHg (13.3 to 18.3 mmHg) at baseline to 25.0 mmHg (21.7 to 28.7 mmHg) at 1 minute after assuming the Trendelenburg position. More than 95% of individual eyes exhibited an IOP increase of at least 10%, and 45% had an IOP increase of 10 mmHg or greater. Correspondingly, MOPP fell from 50.3 mmHg (43.4 to 55.4 mmHg) at baseline to 36.3 mmHg (31.9 to 43.3 mmHg). Mean ocular perfusion pressure decreased by at least 10 in 90% of eyes. In multivariate regression analysis, factors independently related to percentage IOP increase were increasing weight, less myopic refractive error, lower baseline pulse, and lower baseline IOP (total r = 0.31, P < .001). Conversely, weight was the only variable independently related to percent MOPP change, and this relationship was weak (r = 0.05, P = .008). CONCLUSIONS: Our results confirm that steep Trendelenburg positioning causes an increase in IOP and a decrease in MOPP in almost all eyes. Considering the identified causative factors will inform clinical education and provide foundational knowledge for future investigations.

Differentiating Occult Branch Retinal Artery Occlusion from Primary Open-angle Glaucoma.

SIGNIFICANCE: Clinical findings in occult branch retinal artery occlusion (BRAO) can mimic those of primary open-angle glaucoma (POAG). Because management of these conditions substantially differs, accurate diagnosis is crucial. Our comparative analysis indicates that specific macular thickness variables reliably differentiate these conditions and that macular scanning may enhance routine glaucoma evaluation. PURPOSE: The aim of this study was to identify clinical factors that reliably and efficiently identify occult BRAO masquerading as POAG. METHODS: All subjects had comprehensive eye examinations including measurements of retinal nerve fiber layer and macular thickness (MT) using spectral-domain optical coherence tomography (SD-OCT). All subjects were asymptomatic for previous acute vision loss episodes, had optic nerve appearances suggestive of glaucoma, and exhibited SD-OCT retinal nerve fiber layer thinning with corresponding visual field loss. Macular thickness scans were divided into 64 individual thickness blocks with thin MT blocks defined by the lower 99% confidence interval from a group of normal eyes. We defined BRAO by the presence of regional inner retinal thinning with lack of inner-layer stratification on macular SD-OCT b-scan images that spatially corresponded with arteriolar distribution and visual field loss location. Primary open-angle glaucoma eyes were selected to match the BRAO eyes by age and disease severity. Pairwise and receiver operating characteristic curve analyses were used to compare occult BRAO and POAG eyes. RESULTS: Compared with POAG (n = 52), occult BRAO eyes (n = 11) demonstrated lower cup-disc ratio, greater intereye and intraeye (superior vs. inferior) MT asymmetry, and higher frequency of thin MT blocks (<200 µm). Area under the receiver operating characteristic curve (AUC) for differentiating these conditions was highest for intraeye MT asymmetry (AUC = 0.990 [95% confidence interval, 0.925 to 1.000]) and number of thin MT blocks (AUC = 0.993 [95% confidence interval, 0.929 to 1.000]). CONCLUSIONS: Macular thickness parameters provided accurate and efficient diagnostic capability in this study. Considering the clinical implications of inaccurate diagnosis, macular scanning may be important in baseline glaucoma evaluation.

Influence of Optic Disc Size on Identifying Glaucomatous Optic Neuropathy.

PURPOSE: The aim of this study was to use a large group of observers to test prior research findings that suggest optic disc size, clinical evaluation of the neuroretinal rim (ISNT rule), and practitioner characteristics influence the accuracy of differentiating normal from glaucomatous optic nerves. METHODS: Participant observers were optometrists, optometry students, and vision scientists/researchers attending the 2013 American Academy of Optometry Annual Meeting. Each observer viewed and judged six sets of stereoscopic photographs of normal and clinically confirmed glaucomatous optic nerves of different sizes presented in random order. Observers were queried on whether each nerve was glaucomatous or normal, whether the nerve followed the ISNT rule, and whether further evaluation with advanced imaging techniques was indicated. RESULTS: Of the 261 observers who participated, 59% were practicing optometrists, 7% were vision scientists, and 34% were residents or students. Of practicing optometrists and vision scientists, half (49%) had more than 15 years of experience, whereas 11% had less than 2 years of experience. Diagnostic accuracy differed based on optic nerve size: average-sized nerves were correctly identified by 90% of subjects, whereas small nerves and large nerves were correctly identified by 42% and 62%, respectively. Notably, only 9% of subjects correctly identified the small glaucomatous nerve, and only 34% correctly identified the large normal nerve. No practitioner characteristics were associated with diagnostic accuracy. CONCLUSIONS: Accurate identification of glaucomatous optic neuropathy was significantly influenced by optic disc size. This was particularly evident for the large normal nerve and the small glaucomatous nerve. The ISNT rule provided value for differentiating normal from glaucomatous nerves, but its subjective interpretation resulted in considerable intergrader variability. These findings agree with other studies utilizing smaller numbers of observers but larger numbers of optic nerve presentations that disc size and the ISNT rule have value for enhancing accuracy of optic nerve assessment.

Nongranulomatous Uveitis as the First Manifestation of Syphilis.

PURPOSE: The incidence of syphilis appears to be increasing in recent years. Although any structure of the eye can be involved in syphilis, isolated unilateral anterior uveitis as an initial sign of the disease is rare. We report a case of ocular syphilis presenting as a mild unilateral, nongranulomatous, anterior uveitis in an otherwise asymptomatic patient. CASE REPORT: A 64-year-old white male patient presented with a 3-day history of mildly reduced vision, photophobia, and pain in his left eye. The patient denied prior occurrences, and no contributing ocular or medical history was elicited. Entering corrected distance acuities were 20/25+ in the right eye and 20/20- in the left eye. Slit lamp examination of the left eye revealed a moderate circumlimbal flush, numerous fine keratic precipitates, and mild-to-moderate white blood cells in the anterior chamber. The patient was diagnosed as having acute, idiopathic, nongranulomatous, anterior uveitis, and topical steroid/cycloplegic treatment was initiated. Despite an initially positive, although somewhat sluggish response to treatment, the patient's uveitis suddenly worsened on day 44, exhibiting increased anterior chamber cells, several mutton-fat keratic precipitates, and elevated intraocular pressure. Systemic diagnostic workup led to the diagnosis of neurosyphilis, and the patient subsequently admitted to high-risk sexual behaviors. Treatment with intravenous aqueous penicillin-G 24 million units per day for 14 days led to complete resolution of uveitis. The case was reported to the local health department within 24 h of syphilis diagnosis. CONCLUSIONS: Syphilis, although an uncommon cause of ocular inflammation, is a highly contagious, but curable disease. Given its potentially devastating neurologic consequences, syphilis should be considered in all patients presenting with uveitis. A high index of clinical suspicion and a detailed sexual history are crucial for the accurate and timely diagnosis of ocular syphilis.

Baseline 10-2 Visual Field Loss as a Predictor for Future Glaucoma Progression.

PRCIS: Presence of baseline 10-2 visual field (VF) loss was the strongest predictor of future rate of 24-2 VF loss and development of new 24-2 progression events, suggesting a role for 10-2 VF testing in baseline glaucoma risk analysis. PURPOSE: The purpose of this study is to examine the relationship between baseline 10-2 VF loss and future 24-2 VF loss. MATERIALS AND METHODS: Subjects were participating in a prospective longitudinal study within a VA Medical Center outpatient eye clinic. Eligibility required 2 good quality baseline 10-2 VF tests followed by a minimum of 5 good quality 24-2 VF tests over at least 3 years. Longitudinal 24-2 VF testing was completed every 4-6 months after baseline 10-2 testing. Mixed model regression analyses and Cox Proportional Hazard regression analyses were completed to identify predictors of 24-2 mean deviation change rate and new VF loss events. RESULTS: We studied 394 eyes of 202 subjects (119 primary open angle glaucoma and 83 glaucoma suspect). Over 6.7 (±1.5) years, 9.9 (±2.3) good quality 24-2 VF tests were completed. In mixed model regression analyses, baseline variables that predicted faster rate of 24-2 VF loss in order of strength of association were presence of baseline 10-2 VF defect, lower 24-2 mean deviation, and higher age. When analyses were completed without 10-2 variables, predictive capability of the model was reduced compared with when 10-2 variables were included. In Cox Proportional Regression analyses evaluating progression events, baseline 10-2 VF defect demonstrated the largest hazard ratio (22 times greater risk for developing future VF loss event in eyes with vs. without baseline 10-2 VF loss). CONCLUSIONS: Baseline 10-2 VF defect was the most effective predictor of subsequent 24-2 VF progression in this study. These findings imply that presence of baseline 10-2 VF loss may provide unique value for predicting future glaucoma progression.

Relative importance of factors affecting corneal hysteresis measurement.

PURPOSE: To evaluate the relative influences of several demographic, ocular, and systemic parameters on corneal hysteresis (CH). METHODS: This is a prospective, observational, cross-sectional study using subjects recruited from consecutive Albuquerque VAMC eye clinic patients. We classified eligible subjects as primary open-angle glaucoma (POAG), ocular hypertension, glaucoma suspect, or normal. We used the Ocular Response Analyzer, Pascal Dynamic Contour Tonometer, and Goldmann applanation tonometer to obtain intraocular pressure (IOP), CH, corneal resistance factor, and ocular pulse amplitude values. We also obtained corneal curvature, central corneal thickness (CCT), axial length, retinal nerve fiber layer thickness, clinical cup/disc ratio (CDR) estimates, and standard automated perimetry metrics (mean defect, pattern standard deviation). We gathered glycosylated hemoglobin (A1C) data through chart review. Multivariate regression analyses were used to determine independent relationships between CH and the other parameters. RESULTS: Three hundred seventeen eyes in 317 subjects were studied (116 POAG, 87 ocular hypertension, 47 glaucoma suspect, and 67 normal). In univariate regression analysis, CH varied directly with CCT (ß = 0.39, p < 0.001), corneal curvature (ß = 0.16, p = 0.01), corneal resistance factor (ß = 0.57, p < 0.001), A1C (ß = 0.15, p = 0.01), mean defect (ß = 0.29, p < 0.001), and retinal nerve fiber layer (ß = 0.31, p < 0.001). Factors inversely related to CH were age (ß = -0.22, p < 0.001), IOP (ß = -0.29, p < 0.001), ocular pulse amplitude (ß = -0.11, p = 0.04), CDR (ß = -0.34, p < 0.001), and pattern standard deviation (ß = -0.29, p < 0.001). CH was lower in POAG compared with the other diagnostic groups. In multivariate analysis, CH was independently associated with age, IOP, CCT, A1C, glaucoma diagnosis, and CDR. Of these factors, CCT and IOP demonstrated twice as much influence on CH compared with the other four factors. CONCLUSIONS: Although this study identified six separate variables that independently influence CH values, the overall r value indicates that these variables together only explain 40% of CH variability. These results suggest that other significant sources of variability exist and deserve investigation.

Glaucoma Suspects: The Impact of Risk Factor-Driven Review Periods on Clinical Load, Diagnoses, and Healthcare Costs.

PURPOSE: To model the healthcare impact (clinical attendance time and financial cost) and clinical outcomes (glaucoma diagnoses) of different risk factor-driven review frequencies for glaucoma suspect patients up until the point of discharge or diagnosis. METHODS: Medical records of 494 glaucoma suspects were examined to extract the clinical diagnosis. Two criteria for review periods were defined, based on contrasting stringency from established clinical guidelines: American Academy of Ophthalmology (AAO), more stringent/less frequent; and the Australian National Health and Medical Research Council (NHMRC), less stringent/more frequent. We used these data to model patient outcomes and healthcare costs using a Markov model. RESULTS: The less stringent/more frequent criterion resulted in more high-risk glaucoma suspects requiring more frequent review compared with the more stringent/less frequent criterion. Across the 15 Markov cycles (7.5 years), the less stringent/more frequent review criterion resulted in 6.6% more diagnoses and fewer overall clinical visits (14.7%) and reduced cost per diagnosis by 12% to 32% (P < 0.0001). The number of glaucoma diagnoses made using each criterion converged at 2.5 to 3 years. CONCLUSIONS: The stringency of risk assessments for glaucoma suspects impacts review periods and therefore clinical load, healthcare costs, and diagnosis rates. Using current testing methods, more frequent review periods appear advantageous for diagnostic efficiency, with both lower clinic load and lower cost up until the point of discharge or glaucoma diagnosis. TRANSLATIONAL RELEVANCE: A less stringent criterion for assessing the risk of developing glaucoma potentially offers a more cost-effective method for reviewing glaucoma suspects, especially within the first 2.5 years.

Prediction of 10-2 Visual Field Loss Using Optical Coherence Tomography and 24-2 Visual Field Data.

PRECIS: Using standard glaucoma structural and functional tests, clinicians accurately predicted the presence/absence of 10-2 glaucomatous visual field (VF) loss in 90% of the eyes in this study. PURPOSE: To investigate how well clinicians with variable experience can predict the presence and location of 10-2 VF loss using structural and functional data that are routinely obtained for glaucoma assessment. METHODS: Within a test set of 416 eyes (210 subjects) who were diagnosed glaucoma suspect or primary open-angle glaucoma (with most eyes having mild disease), 6 clinicians were asked to predict the presence and hemispheric location of 10-2 VF loss using 24-2 VF and spectral-domain optical coherence tomography structural data. Prediction accuracies were calculated for each clinician and compared using the weighted κ-statistic. Receiver operating characteristic analyses were used to evaluate models for predicting 10-2 VF loss. RESULTS: Among the 6 clinicians, mean (range) accuracy, false negatives, and false positives for predicting presence/absence of 10-2 VF loss were 90% (87% to 92%), 4.7% (2.4% to 7.0%), and 5.4% (1.7% to 7.5%) respectively. The mean (range) weighted κ-statistic was 0.75 (0.64 to 0.83), suggesting good or very good inter-rater agreement between examiners. Mean accuracy for correctly predicting hemispheric location was 73% (range, 65% to 82%) with the most common error occurring in eyes with both superior and inferior 10-2 VF defects in which one hemisphere was correctly identified but the other missed. CONCLUSIONS: In this study, the presence/absence of 10-2 glaucomatous VF loss was highly predictable using standard functional and structural clinical metrics. These findings suggest that 10-2 VF testing is not needed to reliably recognize and confirm central VF involvement in most eyes with glaucoma. Whether error related to identifying second hemisphere involvement in 10-2 VF loss is important requires further study.

Clinical comparison of pascal dynamic contour tonometry and goldmann applanation tonometry in asymmetric open-angle glaucoma.

PURPOSE: To investigate and compare the relationships between glaucomatous visual field loss and intraocular pressure (IOP) as measured by both Pascal dynamic contour tonometry (DCT) and Goldmann applanation tonometry (GAT). PATIENTS AND METHODS: All primary open-angle glaucoma and normal tension glaucoma patients seen between July 2005 and June 2006 with at least 2 sets of good-quality, bilateral DCT and GAT measurements were retrospectively identified. Additional inclusion criteria required that all subjects had repeatable, asymmetric glaucomatous visual field loss that corresponded with asymmetric glaucomatous optic neuropathy. After mean IOP values were computed and visual fields were scored using Advanced Glaucoma Intervention Study (AGIS) criteria, paired-eye comparisons were conducted using right versus left eyes and higher versus lower AGIS-score eyes. RESULTS: Sixty-seven (42 primary open-angle glaucoma, 25 normal tension glaucoma) subjects met all criteria for study inclusion. Per paired t test, mean DCT-IOP was significantly higher in the higher AGIS-score eyes compared with the lower AGIS-score eyes (16.3 vs. 15.5 mm Hg, P=0.004), whereas GAT-IOP was not significantly different in these same eyes (14.5 vs. 14.4 mm Hg, P=0.56). Mean IOP difference between the 2 methods was significantly larger in higher versus lower AGIS-score eyes (P<0.001), and 72% of the subjects demonstrated larger intermethod IOP differences in their higher AGIS-score eye compared with their lower AGIS-score eye (P<0.001; 95% confidence interval: 0.59-0.82). Multivariate linear regression analysis revealed that AGIS-score differences between eyes were independently associated with both intermethod IOP differences between eyes (P=0.004) and central corneal thickness (CCT) differences between eyes (P=0.04). CCT, however, was not associated with intermethod IOP differences within or between eyes. CONCLUSIONS: These findings suggest that DCT-IOP is correlated with glaucomatous damage, and moreover, DCT-IOP is more closely related to extent of glaucoma damage than is GAT-IOP. The most likely explanation for these results is that GAT-IOP systematically underestimates IOP compared with DCT-IOP. Our findings also support the hypothesis that corneal biomechanical factors other than CCT are major confounders of applanation tonometry measurements.

Central corneal thickness and normal tension glaucoma: a cross-sectional study.

BACKGROUND: Recently published evidence has identified thinner central corneal thickness (CCT) as a strong predictive factor for the conversion from ocular hypertension (OHT) to primary open-angle glaucoma (POAG). The association between CCT and development of normal-tension glaucoma (NTG), however, is less clear. Accordingly, we designed this cross-sectional study to further explore the relationship between CCT and NTG. PATIENTS AND METHODS: All patients with a clinical diagnosis of NTG and NTG suspect (NTGS) who were seen from September 2002 through May 2003 at the Albuquerque VA Medical Center eye clinic were identified retrospectively. After eligible subjects were categorized into no, mild, moderate, and advanced visual field loss groups, analysis of variance (ANOVA) and regression analyses were used to determine group differences for several IOP variables, several systemic variables, and CCT. Additional analyses were completed after eligible subjects were recategorized into thin, intermediate, and thick CCT groups. RESULTS: Eighty-four eyes in 84 NTGS subjects and 56 eyes in 56 NTG subjects were studied. Mean CCT was significantly thicker in the no field loss group (NTGS) when compared with all 3 groups with glaucomatous visual field loss (NTG). In multivariate regression analysis, the association between CCT and the presence of NTG-related visual field loss was robust and independent. Conversely, no relationship was found between CCT and severity of NTG-related visual field loss. CONCLUSIONS: In eyes characterized by statistically normal intraocular pressure (IOP) measurements as measured by Goldmann applanation tonometry, we found a significant relationship between CCT and the presence, but not severity, of glaucomatous visual field loss. A prospective study is required to further explore and confirm these relationships.

Relationship between central corneal thickness and severity of glaucomatous visual field loss in a primary care population.

BACKGROUND: Although the ability of central corneal thickness (CCT) to predict development of primary open-angle glaucoma has become increasingly well recognized, the ability of CCT to predict severity of glaucoma remains uncertain. This study was designed to expand the available knowledge about the relationship between CCT and glaucoma severity. METHODS: Retrospective identification of all patients with a clinical diagnosis of either primary open angle glaucoma (POAG) or ocular hypertension who were seen from September 2002 through May 2003 at the Albuquerque VA Medical Center eye clinic was completed. Eligible subjects were segregated into no, mild, moderate, or advanced visual field loss groups based on Advanced Glaucoma Intervention Study (AGIS) visual field scoring criteria. Following statistical analyses comparing the visual field groups, the sample was divided into thin, intermediate, and thick CCT groups, and further analysis was performed. RESULTS: Mean CCT was significantly higher in the no field loss group compared with all 3 groups with glaucomatous visual field loss. Mean CCT was not statistically different, however, between the mild, moderate, and advanced visual field loss groups. In linear regression analyses, no significant relationship was found between CCT and severity of visual field loss. CONCLUSIONS: Although CCT was associated strongly with development of POAG-related visual field loss, CCT was not associated with severity of visual field loss in this study. These findings suggest that glaucoma patients with thinner corneas are just as likely to have advanced levels of field loss as glaucoma patients with thicker corneas. Prospective studies are needed to validate these findings.

Prevalence, Features, and Severity of Glaucomatous Visual Field Loss Measured With the 10-2 Achromatic Threshold Visual Field Test.

PURPOSE: To investigate the clinical characteristics of 10-2 visual field defects in subjects with a diagnosis of glaucoma or glaucoma suspicion. DESIGN: Prospective, observational cohort study. METHODS: From participants enrolled in an ongoing glaucoma research study at our institution, we identified 354 eyes in 180 subjects (97 with primary open-angle glaucoma, 83 with glaucoma suspicion) who had 2 or more reliable 24-2 and 10-2 visual field tests and good-quality spectral-domain optical coherence tomography (SDOCT) scans. Eyes with macular pathology, significant cataract, or nonglaucomatous vision loss were excluded. We applied previously published cluster criteria to define 10-2 visual field loss, and then calculated prevalence, location, severity, and pattern of 10-2 visual field loss as well as its relationships with various functional and structural parameters. RESULTS: Repeatable 10-2 visual field defects were present in 89 of 180 subjects (49%) and usually exhibited an arcuate or nasal pattern. In eyes with no, mild, moderate, and advanced 24-2 visual field loss, 15 of 236 (6%), 49 of 67 (73%), 25 of 26 (96%), and 25 of 25 (100%) had 10-2 visual field defects, respectively. Of the 114 eyes with 10-2 visual field loss, 93 (82%) demonstrated abnormal points within the central 10 degrees of the 24-2 visual field test. Mean defect on the 10-2 and 24-2 tests was highly correlated (r(2) = 0.72). CONCLUSIONS: Although central VF loss appears to be common in glaucoma and may have an important role in glaucoma management, additional study is warranted to more definitively determine the optimal methods to detect presence, severity, and functional impact of central glaucomatous visual field loss.

The relationship between central corneal thickness-adjusted intraocular pressure and glaucomatous visual-field loss.

BACKGROUND: Although measurement of central corneal thickness (CCT) is increasingly becoming an important component of glaucoma risk analysis, significant controversy exists regarding the benefit of calculating a corrected intraocular pressure (IOP) value from measured IOP and CCT data. METHODS: Three hundred forty-four male subjects were identified from a VA eye clinic with one of the following clinical diagnoses: ocular hypertension (OHT), primary open-angle glaucoma (POAG), normal tension glaucoma (NTG), and normal tension glaucoma suspect (NTGS). Using one eye per subject, multivariate logistic regression and correlational analyses were performed to determine relationships between glaucomatous visual-field loss and several glaucoma risk factors, including adjusted IOP values. RESULTS: Multivariate logistic regression analysis did not identify CCT-adjusted IOP values as independent risk factors for development of either NTG or POAG-related glaucomatous visual-field loss. CCT, however, was found to be strongly associated with both NTG and POAG-related visual-field loss. Correlational analysis revealed a weak correlation between Ehlers-adjusted pre-treatment IOP and severity of POAG-related visual-field loss, but no other adjusted IOP values significantly correlated with severity of visual-field loss in either POAG or NTG. CONCLUSIONS: Our results suggest that adjusted IOP, as calculated using current algorithms, is not useful within glaucoma risk analysis, since adjusted IOP was unable to predict either presence or severity of glaucomatous visual-field loss in this study. CCT, conversely, was found to be a robust and independent predictor of glaucomatous visual-field loss. These findings, while supporting routine CCT measurements for all glaucoma suspects, do not support routine clinical computation of adjusted IOP values using current algorithms.

Relationship Between Juxtapapillary Choroidal Volume and Beta-Zone Parapapillary Atrophy in Eyes With and Without Primary Open-Angle Glaucoma.

PURPOSE: To evaluate whether quantity of choroidal tissue directly adjacent to the optic nerve differs between eyes with and without glaucoma and whether beta-zone parapapillary atrophy influences this relationship. DESIGN: Prospective cohort study. METHODS: Subjects were enrolled in a longitudinal, observational study at our institution. We studied 1 eye of 63 primary open-angle glaucoma (POAG), 30 ocular hypertension (OH), and 48 control subjects. Using optical coherence tomography enhanced depth imaging, we acquired 12 radial scans centered on the optic nerve head with 15 degrees of separation between scans. After images were enhanced, segmented, and corrected for ocular magnification, juxtapapillary choroidal volumetric parameters were calculated using raw thickness measurements and standard interpolation techniques. Juxtapapillary choroidal volume was then compared by diagnosis and by beta-zone parapapillary atrophy status. RESULTS: Total juxtapapillary choroidal volume was significantly reduced in POAG vs OH and control eyes (1.057 vs 1.228 vs 1.255 µL, P = .04) and it was reduced in eyes with vs without beta-zone parapapillary atrophy (1.076 µL, n = 80 vs 1.306 µL, n = 61, P < .001). Juxtapapillary choroidal volume did not differ between POAG, OH, and control eyes when beta-zone parapapillary atrophy was absent, but juxtapapillary choroidal volume was significantly reduced in POAG vs control eyes when beta-zone parapapillary atrophy was present (0.957 vs 1.196 µL, P = .02). Furthermore, POAG eyes with beta-zone parapapillary atrophy had substantially lower juxtapapillary choroidal volume compared to POAG eyes without beta-zone parapapillary atrophy (0.957 vs 1.356 µL, P < .001). CONCLUSIONS: The volume of choroid adjacent to the optic nerve was significantly reduced in POAG eyes when beta-zone parapapillary atrophy was present, suggesting that beta-zone parapapillary atrophy may be a biomarker for juxtapapillary choroidal atrophy and associated vascular compromise in POAG.

Correspondence of Tono-Pen intraocular pressure measurements performed at the central cornea and mid-peripheral cornea.

BACKGROUND: As the awareness of the influence of central corneal thickness (CCT) on Goldmann tonometry has increased, many publications have questioned the accuracy of Goldmann intraocular pressure (IOP) measurement. The Tono-Pen, because it indents a much smaller surface area when compared to a Goldmann probe, may be less affected by corneal thickness variations when compared with Goldmann tonometry. METHODS: Forty human subjects with no history of refractive surgery participated in this study. The IOP of the right eye of each subject was measured with the Goldmann tonometer, the Tono-Pen at the central cornea, and the Tono-Pen at the mid-peripheral cornea. An ultrasonic DGH Pachette pachymeter was used to measure the central and mid-peripheral corneal thickness at the location of the IOP readings. RESULTS: Tono-Pen measurements at the central and mid-peripheral cornea highly correlated (r = 0.933), and did not significantly differ (p = 0.646). The IOP readings with the Goldmann tonometer (r= 0.406), the Tono-Pen at the central cornea (r = 0.453), and the Tono-Pen at the mid-peripheral cornea (r = 0.321) showed a positive correlation to corneal thickness. The Goldmann and Tono-Pen tonometers differed significantly in the measurement of IOP at the central cornea (p = 0.007), but were positively correlated (r = 0.674). CONCLUSIONS: The Tono-Pen IOP measurement at the central cornea highly approximated Tono-Pen IOP measurement at the mid-peripheral cornea. Furthermore, although not highly correlated, both the Goldmann and Tono-Pen tonometers showed a significantly positive correlation between IOP and corneal thickness measurements.

The relationship between retinal nerve fiber layer thickness and optic nerve head neuroretinal rim tissue in glaucoma.

PURPOSE: The purpose of this study was to determine the relationship between optical coherence tomography (OCT) measures of retinal nerve fiber layer (RNFL) and neuroretinal rim (NRR) in a nonhuman primate experimental glaucoma model, and in a population of clinical patients. METHODS: For nonhuman primates, normative data were collected from 44 healthy monkeys, and nine animals with unilateral experimental glaucoma that were followed longitudinally. Cross-sectional human subjects data were collected from 89 healthy, 74 glaucoma suspects, and 104 glaucoma patients. Individualized transverse scaling for OCT scans was calculated using a schematic eye that incorporated optical ocular biometry. Custom algorithms were used to quantify RNFL thickness with and without vessels removed, scaled minimum rim width (sMRW), and neural rim volume (NRV). RESULTS: For the experimental glaucoma group, NRR parameters showed the first changes with increased cumulative IOP. The data for both NRR and RNFL measures were best fit by an exponential rise model (NRV, R2=0.79, P<0.01, sMRW, R2=0.74, P<0.01). The major retinal vascular thickness contribution to the RNFL decreased (0.03 µm/µm, P<0.01) with RNFL loss, but the percent vascular contribution increased (-0.1%/µm, P<0.01) with disease progression. Overall, the findings for the cross-sectional human data were similar to those of the experimental model. CONCLUSIONS: The findings illustrate a nonlinear relationship between NRR and RNFL measures and provide support for the use of multiple OCT scaled morphological measures for the diagnosis and management of primary open angle glaucoma in humans.

Factors influencing intermethod agreement between goldmann applanation, pascal dynamic contour, and ocular response analyzer tonometry.

PURPOSE: To examine factors that influence intraocular pressure (IOP) measurement agreement between Goldmann applanation (GAT), Ocular Response Analyzer (ORA), and Pascal Dynamic Contour tonometers (DCT). PATIENTS AND METHODS: In subjects who were diagnosed with primary open-angle glaucoma, ocular hypertension, glaucoma suspect, and normal, we used ORA, DCT, and GAT to obtain corneal hysteresis (CH), corneal resistance factor (CRF), ocular pulse amplitude, and 4 IOP values (ORA-IOPcc; ORA-IOPg; DCT-IOP; and GAT-IOP.) We also obtained corneal curvature, corneal thickness, axial length, retinal nerve fiber layer thickness, visual field parameters, diabetes diagnostic status, and topical IOP-lowering treatment data. Analysis of variance, Bland-Altman, and regression analyses were used to examine IOP agreement and associated factors. RESULTS: In 243 eyes of the 243 subjects, mean DCT-IOP (18.73±4.92) was not different from mean ORA-IOPcc (18.96±5.41) but both were significantly higher than ORA-IOPg (16.97±5.49) and GAT-IOP (16.37±4.97). In multivariate regression models, intermethod differences between IOPg, IOPcc, and DCT-IOP were explained almost completely by variations in CH, CRF, and level of IOP (r(2)=0.98 to 0.99); conversely, intermethod variability between GAT-IOP and the other 3 IOP metrics was only partially explained by the factors evaluated in this study (r(2)=0.31 to 0.65). CONCLUSIONS: Consistent with other studies, we found that the 4 IOP variables examined in this study are not interchangeable. The most consistent confounders of IOP measurement agreement were the ORA-measured corneal parameters, CH and CRF. Thus, accounting for these factors may be important in efforts to obtain accurate transcorneal estimates of IOP.

Diagnostic precision of retinal nerve fiber layer and macular thickness asymmetry parameters for identifying early primary open-angle glaucoma.

PURPOSE: To evaluate the diagnostic capabilities of intereye and intraeye differences in retinal nerve fiber layer (RNFL) thickness and macular thickness for identifying early primary open-angle glaucoma (POAG). DESIGN: Prospective, cross-sectional cohort study. METHODS: All subjects were enrolled from an ongoing institutional glaucoma study. We used spectral-domain optical coherence tomography (Spectralis; Heidelberg Engineering) to obtain macular thickness (posterior pole asymmetry scan) and RNFL thickness (circumpapillary scan) in both eyes of 50 early POAG and 50 control subjects. Early POAG subjects had glaucomatous optic neuropathy with mild, reproducible visual field loss in at least 1 eye, and control subjects had normal intraocular pressures, visual fields, and optic nerves. We recorded total, superior, and inferior RNFL and macular thicknesses and then calculated intereye and intraeye differences (asymmetry parameters). Statistical evaluation included receiver operating characteristic and multivariate logistic regression analyses. RESULTS: Intereye macular thickness asymmetry had the highest diagnostic sensitivity (88% at 80% specificity; 83% at 95% specificity), followed by total RNFL thickness (88% at 80% specificity; 75% at 95% specificity). Parameters with the largest areas under the receiver operating characteristic curves were: total RNFL thickness (0.937), intereye RNFL asymmetry (0.921), intereye macular thickness asymmetry (0.913), inferior RNFL thickness (0.905), superior RNFL thickness (0.887), intereye inferior macular thickness asymmetry (0.872), and intraeye macular thickness asymmetry (0.860). These 7 values were not significantly different. In multivariate logistic regression analyses, intraeye macular thickness asymmetry, intereye macular thickness asymmetry, intereye RNFL thickness asymmetry, and total RNFL thickness were related independently to early POAG. CONCLUSIONS: Structural asymmetry parameters performed well, identifying early POAG as well as RNFL thickness. Further study is indicated to validate these results.