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IMPORTANCE: Estimating the rate of glaucomatous visual field change provides practical assessment of disease progression and has implications for management decisions. OBJECTIVE: To assess the rates of visual field change in patients receiving treatment for glaucoma compared with healthy individuals over an extensive follow-up period and to quantify the impact of important covariates for these rates. DESIGN, SETTING, AND PARTICIPANTS: This prospective longitudinal cohort study was conducted in a hospital-based setting from January 1991 to February 2020. The study included 40 patients receiving treatment for open-angle glaucoma and 29 healthy participants. One eye of each participant was randomly selected as the study eye. EXPOSURES: Patients with glaucoma and healthy participants received testing with standard automated perimetry every 6 months. Individual rates of mean sensitivity change were computed using ordinary least-squares regression analysis, and linear mixed-effects modeling was used to estimate the mean rates of mean sensitivity change in the 2 groups and the impact of baseline mean sensitivity, baseline age, and follow-up intraocular pressure for rate estimates. MAIN OUTCOMES AND MEASURES: Rate of mean sensitivity change in patients with glaucoma and healthy participants. RESULTS: A total of 40 patients with glaucoma (median age, 53.07 years [IQR, 48.34-57.97 years]; 21 men [52%]) and 29 healthy participants (median age, 48.80 years [IQR, 40.40-59.07 years], 17 women [59%]) were followed up for a median of 25.65 years (IQR, 22.49-27.02 years) and 19.56 years (IQR, 16.19-26.21 years), respectively. Most participants (65 individuals [94%]) self-identified as White, with the exception of 2 patients with glaucoma (1 self-identified as Black and 1 as South Asian) and 2 healthy participants (both self-identified as South Asian). The mean follow-up intraocular pressure of patients with glaucoma (median, 15.83 mm Hg [IQR, 13.05-17.33 mm Hg]) was similar to that of healthy participants (median, 14.94 mm Hg [IQR, 13.28-16.01 mm Hg]; P = .25). In an ordinary least-squares regression analysis, 31 patients (78%) with glaucoma had rates of mean sensitivity change within the range of healthy participants (ie, between −0.20 dB/y and 0.15 dB/y). Linear mixed-effects modeling revealed that the mean (SE) rate of mean sensitivity change in healthy participants was 0.003 (0.033) dB/y (95% CI, −0.062 to 0.068; P = .93). In comparison, patients with glaucoma had a mean (SE) rate of mean sensitivity change that was −0.032 (0.052) dB/y faster, but this difference was not statistically significant (95% CI, −0.134 to 0.070; P = .53). Among covariates, only baseline mean sensitivity was associated with the rate of mean sensitivity change (mean [SE], 0.021 [0.010] dB/y/dB; 95% CI, 0.002-0.041; P = .03). CONCLUSIONS AND RELEVANCE: The results of this cohort study suggest that over a median follow-up of more than 25 years, the rate of visual field change in patients receiving treatment for glaucoma was comparable to that of healthy individuals. These findings could guide practitioners in making management decisions.

Purpose To determine whether the 10-2 test of the Humphrey Field Analyzer detected a higher proportion of abnormal visual fields compared with the 24-2 test in the central 10° of patients with early glaucomatous visual field damage. Design Prospective observational study. Participants Patients with open-angle glaucoma and healthy control participants. Methods All participants underwent a 24-2 and 10-2 test. Only the 12 central test locations of the 24-2 test were included to analyze equivalent visual field areas. The performance of the 2 tests was compared across 4 pointwise criteria: total deviation (TD) and pattern deviation (PD) analyses at the 5% and 2% levels. Analyses also were conducted for 2 pairs of follow-up tests, each performed 4 months apart. Main Outcome Measures (1) Area under the receiver operating characteristic curve (AUC), (2) sensitivity at identically matched specificity for the 4 criteria, (3) overlap (entire field and by quadrant) of abnormal visual fields with both tests, and (4) repeatability of the findings in 2 subsequent follow-up tests. Results One eye each of 97 glaucoma patients (median mean deviation, –2.31 dB) and 65 control participants were included in the study. The AUCs for the 24-2 and 10-2 tests were not significantly different for any of the 4 criteria and ranged from 0.88 to 0.93 and from 0.91 to 0.94, respectively. At matched specificity, the sensitivity of the 24-2 test was significantly higher for all criteria except for PD analysis at 5%. In patients with an abnormal field with either test, the overlap varied from 60% to 86% depending on the criterion, whereas by quadrant, concordance ranged from 70% to 87%. Over the follow-up, the repeatability of test results (both 24-2 and 10-2 abnormal, either abnormal, or both normal) was achieved in 55% to 70% of patients. Conclusions In this study of glaucoma patients with early damage with the 24-2 test, there was little evidence that adding the 10-2 test revealed additional undetected defects in the central visual field. It may be more prudent to reserve 10-2 testing for following up selected patients with higher risk of central visual field progression.

Correction of automated retinal layer segmentation in the peripapillary retina led to significant differences in perfusion density measured with optical coherence tomography angiography in the retinal plexuses. Segmentation accuracy should be checked prior to interpretation.

To determine the impact of glaucoma severity on rates of change of minimum rim width (MRW), peripapillary retinal nerve fiber layer (RNFL), and macular ganglion cell layer (GCL) thickness.Prospective, cohort study.Glaucoma patients and healthy subjects had optical coherence tomography scans at 6-month intervals. Individual rates of change for MRW, RNFL, and GCL thickness were estimated with ordinary least-squares regression. Linear mixed-effect models were used to estimate the rate of change of each parameter and evaluate the impact of glaucoma severity (expressed by visual field mean deviation, MD) and age on these rates.A total of 132 glaucoma patients and 57 healthy subjects were followed for a median of 4.3 years and 3.7 years, respectively. Healthy subjects had a statistically significant deterioration in MRW (-1.66 µm/year), RNFL (-0.46 µm/year), and GCL thickness (-0.22 µm/year). While glaucoma patients had a faster rate of change in each parameter compared with healthy subjects, only GCL thickness showed a statistically significant group difference (mean difference: -0.17 µm/year; P = .03). Older baseline age was associated with faster GCL thickness change (-0.07 µm/year; P = .03), but not other parameters. Baseline MD had no impact on the subsequent rates of change in any of the parameters.The rates of MRW, RNFL, and GCL thickness change were not significantly influenced by glaucoma severity at baseline; however, GCL thickness was able to statistically contrast the rate of change between healthy subjects and glaucoma patients throughout the disease spectrum.

Purpose To determine whether: (1) change in lamina cribrosa depth occurs more frequently than change in neuroretinal parameters in glaucoma, and (2) Bruch's membrane or anterior sclera should be used as a reference plane when measuring laminar depth. Design Prospective observational study. Participants One hundred fifty-five glaucoma patients and 35 healthy controls. Methods Anterior laminar depth from a Bruch's membrane (LD-BM) or anterior sclera (LD-AS) reference plane were measured with optical coherence tomography. Two neuroretinal parameters, minimum rim width and retinal nerve fiber layer thickness, in addition to peripapillary choroidal thickness were measured. Factors related to laminar depth were determined with mixed-effects modeling. Cutoffs for significant change in each parameter were estimated from variability in healthy controls over 1 year. The occurrences of significant change in laminar depth and neuroretinal parameters were compared with survival models. Because normal aging has a clear effect on neuroretinal parameters, but not on laminar depth, changes in neuroretinal parameters were adjusted for age-related reduction. Main Outcome Measures Longitudinal changes in laminar depth and neuroretinal parameters. Results Glaucoma patients were followed up for a mean of 3.90 years (range, 2.03–5.44 years). The LD-BM was influenced significantly more by choroidal thickness (1.14 μm/μm; 95% confidence interval, 1.07–1.21) than was the LD-AS (0.15 μm/μm; 95% confidence interval, 0.08–0.22). Posterior movement of the lamina (LD-BM increase or LD-AS increase) occurred with the same frequencies as thinning in neuroretinal parameters. Anterior movement of the lamina was detected more frequently with the Bruch's membrane (LD-BM decrease) compared with the anterior sclera (LD-AS decrease) reference plane (hazard ratio, 3.23; P Conclusions Lamina cribrosa depth should be measured from an anterior sclera reference plane to reduce the influence of choroidal thickness changes. In glaucoma patients, lamina cribrosa depth changes are detected with similar frequency as neuroretinal parameter changes.

PURPOSE To compare the visibility of deep optic nerve head (ONH) structures and the visible area of the anterior surface of the lamina cribrosa (ASLC) with spectral-domain optical coherence tomography (SD-OCT) and swept-source OCT (SS-OCT). MATERIALS AND METHODS In total, 33 glaucoma patients were imaged with SD-OCT (Spectralis, 24 radial B-scans centered on the ONH) and SS-OCT (Atlantis, 12 radial and a horizontal and vertical raster scan pattern containing 5 lines each, centered on the ONH). One of the SS-OCT horizontal and vertical scans that was best matching with the horizontal and vertical scan lines with those of SD-OCT was selected. All B-scans were then exported and deidentified. An independent observer determined whether the posterior choroid, border tissue, anterior scleral canal opening, and LC insertion into the sclera were detectable in the matched scan lines. Bruch membrane opening (BMO) and ASLC were segmented manually in radial scans. The segmented points were combined into a single plane and a linear interpolation was used to define BMO and ASLC areas. RESULTS The posterior choroid, border tissue, and anterior scleral canal opening were detectable in most patients (94% to 100%, 88% to 100%, and 76% to 100%, respectively) and were not different between SD-OCT and SS-OCT. The LC insertion detection rate was nonstatistically higher for SS-OCT compared with SD-OCT (58% to 85% vs. 42% to 73%; P>0.10). The mean (SD) ASLC visible area (percentage of the respective BMO area) was 124 (30%) with SD-OCT and 135 (32%) with SS-OCT (P

Background/aimsQuantitative analysis of optical coherence tomography angiography (OCT-A) images requires a reproducible approach that accounts for sectoral loss. The objective of this study was to determine whether an index that accounts for both global (perfusion density, PD) and asymmetric loss of perfusion, rather than PD alone, more reliably measures loss of perfusion in patients with glaucoma.MethodsWe analysed macular OCT-A scans of 95 glaucoma patients and 59 control subjects. Two-dimensional projection images corresponding to the superficial vascular plexus were exported and analyses performed to calculate global PD and image asymmetry. An unsigned perfusion asymmetry index (PAI) that included PD and asymmetry (with 1:1 wt) was calculated. Perfusion density and PAI were compared with 10-2 visual field mean deviation and ganglion cell layer (GCL) thickness.ResultsMedian (IQR) visual field mean deviation was −1.73 (−3.76, 0.30) dB for the glaucoma group and 0.67 (0.16, 1.18) dB for the control group. The strength of the correlation with mean deviation was stronger for PAI (r=0.47), compared with PD (r=0.35), whereas with GCL thickness they were comparable (r=0.45 and 0.43, respectively). Compared with controls, mean PD was 12% lower in patients with glaucoma (0.27 vs 0.30), while PAI was 17% lower (0.40 vs 0.48). However, diagnostic accuracy of either PD or PAI was worse than GCL thickness.ConclusionsWhile PAI yielded better correlation with mean deviation and GCL thickness, and a slightly improved separation between patients with glaucoma and healthy controls, diagnostic accuracy was inferior compared with GCL thickness.

Purpose To determine whether the glaucoma diagnostic accuracy of age- and Bruch membrane opening area (BMOA)-adjusted normative classifications of minimum rim width (MRW) and retinal nerve fiber layer thickness (RNFLT) is dependent on BMOA, in a European descent population. Design Retrospective, cross-sectional study. Methods We included 182 glaucoma patients and 166 healthy controls for the primary study, and 105 glaucoma patients in a second sample used for a replication study. Optical coherence tomography (Spectralis) measurements of BMOA, global MRW, and RNFLT and normative classifications from the device software were exported for analysis. Sensitivity and specificity were calculated for a conservative criterion (abnormal = “outside normal limits” classification) and a liberal criterion (abnormal = “outside normal limits” or “borderline” classifications). The dependence of sensitivity and specificity on BMOA was analyzed with comparison among subgroups divided by tertiles of BMOA, and with logistic regression. Results For the conservative criterion, MRW sensitivity was independent of BMOA (P ≥ .76), while RNFLT sensitivity increased in the large BMOA subgroup (P = .04, odds ratio: 1.2 per mm2 [P = .02]). For the liberal criterion, MRW and RNFLT sensitivities were independent of BMOA (P ≥ .53). Specificities were independent of BMOA (P ≥ .07). For the replication sample, which included younger patients with larger BMOA and worse visual field damage than the primary sample, sensitivities were independent of BMOA for both criteria (P ≥ .10). Conclusions RNFLT sensitivity was higher in eyes with larger BMOA; however, age and visual field damage may influence that association. MRW diagnostic accuracy was not dependent on BMOA.

Background/aimsOptical coherence tomography (OCT) imaging of the optic nerve head minimum rim width (MRW) has recently been shown to sometimes contain components besides extended retinal nerve fibre layer (RNFL). This study was conducted to determine whether excluding these components, termed protruded retinal layers (PRLs), from MRW increases diagnostic accuracy for detecting glaucoma.MethodsIn this cross-sectional study, we included 123 patients with glaucoma and 123 normal age-similar controls with OCT imaging of the optic nerve head (24 radial scans) and RNFL (circle scan). When present, PRLs were manually segmented, and adjusted MRW measurements were computed. We compared diagnostic accuracy of adjusted versus unadjusted MRW measurement. We also determined whether adjusted MRW correlates better with RNFL thickness compared with unadjusted MRW.ResultsThe median (IQR) visual field mean deviation of patients and controls was −4.4 (−10.3 to −2.1) dB and 0.0 (−0.6 to 0.8) dB, respectively. In the 5904 individual B-scans, PRLs were identified less frequently in patients (448, 7.6%) compared with controls (728, 12.3%; pConclusionWhile layers besides the RNFL are sometimes included in OCT measurements of MRW, subtracting these layers does not impact clinical utility.

Background/AimsTo determine the effect of glaucoma on outer retinal layer thickness in eyes with horizontal hemifield visual field (VF) defects.MethodsWe conducted a cross-sectional study in glaucomatous eyes with repeatable (in three or examinations) horizontal hemifield VF (programme 24–2) defect defined as: all five nasal VF locations immediately either above or below the horizontal midline abnormal in the pattern deviation plot with pResultsWe included 10 eyes of 8 patients with median age of 67 years and median VF mean deviation of −8.85 dB. The nerve fibre, ganglion cell and inner plexiform layers were significantly thinner in the perimetrically abnormal hemimacula (median asymmetry of –6.4, –11.5 and −3.8 µm, (corresponding to –27.7, –40.5 and −15.7 %), respectively, all p≤0.01). The inner nuclear layer was slightly thicker in the perimetrically abnormal hemimacula (median asymmetry of 1.3 µm (5.0 %), p=0.01). The outer plexiform, outer nuclear and photoreceptor layers asymmetry values were negligible.ConclusionOur study showed no evidence that glaucoma has an effect on the outer retinal layer thickness. In contrast, a large impact was observed in inner layer thickness.

Purpose To describe longitudinal rates of change of neuroretinal parameters in patients with glaucoma and healthy controls, and to evaluate the influence of covariates. Design Prospective longitudinal study. Participants Treated patients with glaucoma (n = 192) and healthy controls (n = 37). Methods Global disc margin–based neuroretinal rim area (DMRA) was measured with confocal scanning laser tomography, while Bruch's membrane opening-minimum rim width (BMO-MRW), BMO area (BMOA), and peripapillary retinal nerve fiber layer thickness (RNFLT) were measured with optical coherence tomography at 6-month intervals. Individual rates of change were estimated with ordinary least-squares regression, and linear mixed effects modeling was used to estimate the average rate of change and differences between the groups, and to evaluate the effects of baseline measurement and baseline age on rates of change. Main Outcome Measures Rates of change for each parameter. Results Subjects were followed for a median (range) of 4 (2–6) years. The proportion of controls who had significant reduction of neuroretinal parameters was 35% for BMO-MRW, 31% for RNFLT, and 11% for DMRA. The corresponding figures for patients with glaucoma were not statistically different (42%, P = 0.45; 31%, P = 0.99; 14%, P = 0.99, respectively). Controls had a significant reduction of BMO-MRW (mean: −1.92 μm/year, P P = 0.01), but not DMRA (mean: −0.22×10 −2 mm 2 /year, P = 0.41). After adjusting for covariates, patients with glaucoma had faster, but not statistically different, rates of deterioration compared with controls, by −1.26 μm/year ( P = 0.07) for BMO-MRW, −0.40 μm/year ( P = 0.11) for RNFLT, and −0.38×10 −2 mm 2 /year ( P = 0.23) for DMRA. Baseline BMO-MRW and RNFLT significantly influenced the respective rates of change, with higher baseline values relating to faster reductions. Older age at baseline was associated with a slower reduction in rates of BMO-MRW. Reductions in intraocular pressure were related to increases in BMO-MRW and DMRA. There was a tendency for BMOA to decrease over time (−0.38×10 −2 mm 2 /year; P = 0.04). Conclusions Age-related loss of neuroretinal parameters may explain a large proportion of the deterioration observed in treated patients with glaucoma and should be carefully considered in estimating rates of change.

PURPOSE: To evaluate the structure-function relationship between disc margin-based rim area (DM-RA) obtained with confocal scanning laser tomography (CSLT), Bruch's membrane opening-based horizontal rim width (BMO-HRW), minimum rim width (BMO-MRW), peripapillary retinal nerve fiber layer thickness (RNFLT) obtained with spectral-domain optical coherence tomography (SD-OCT), and visual field sensitivity. METHODS: We examined 151 glaucoma patients with CSLT, SD-OCT, and standard automated perimetry on the same day. Optic nerve head (ONH) and RNFL with SD-OCT were acquired relative to a fixed coordinate system (acquired image frame [AIF]) and to the eye-specific fovea-BMO center (FoBMO) axis. Visual field locations were mapped to ONH and RNFL sectors with fixed Garway-Heath (VF(GH)) and patient-specific (VF(PS)) maps customized for various biometric parameters. RESULTS: Globally and sectorally, the structure-function relationships between DM-RA and VF(GH), BMO-HRW(AIF) and VF(GH), and BMO-HRW(FoBMO) and VF(PS) were equally weak. The R(2) for the relationship between DM-RA and VF(GH) ranged from 0.1% (inferonasal) to 11% (superotemporal) whereas that between BMO-HRW(AIF) and VF(GH) ranged from 0.1% (nasal) to 10% (superotemporal). Relatively stronger global and sectoral structure-function relationships with BMO-MRW(AIF) and with BMO-MRW(FoBMO) were obtained. The R(2) between BMO-MRW(AIF) and VF(GH) ranged from 5% (nasal) to 30% (superotemporal), whereas that between BMO-MRW(FoBMO) and VF(PS) ranged from 5% (nasal) to 25% (inferotemporal). The structure-function relationship with RNFLT was not significantly different from that with BMO-MRW, regardless of image acquisition method. CONCLUSIONS: The structure-function relationship was enhanced with BMO-MRW compared with the other neuroretinal rim measurements, due mainly to its geometrically accurate properties.

Objective Neuroretinal rim assessment based on the clinical optic disc margin (DM) lacks a sound anatomic basis for 2 reasons: (1) The DM is not reliable as the outer border of rim tissue because of clinically and photographically invisible extensions of Bruch's membrane (BM) inside the DM and (2) nonaccountability of rim tissue orientation in the optic nerve head (ONH). The BM opening-minimum rim width (BMO-MRW) is a parameter that quantifies the rim from its true anatomic outer border, BMO, and accounts for its variable orientation. We report the diagnostic capability of BMO-MRW. Design Case control. Participants Patients with open-angle glaucoma (n = 107) and healthy controls (n = 48). Methods Spectral-domain optical coherence tomography (SD-OCT) with 24 radial and 1 circumpapillary B-scans, centered on the ONH, and confocal scanning laser tomography (CSLT) were performed. The internal limiting membrane (ILM) and BMO were manually segmented in each radial B-scan. Three SD-OCT parameters were computed globally and sectorally: (1) circumpapillary retinal nerve fiber layer thickness (RNFLT); (2) BMO-horizontal rim width (BMO-HRW), the distance between BMO and ILM in the BMO reference plane; and (3) BMO-MRW, the minimum distance between BMO and ILM. Moorfields Regression Analysis (MRA) with CLST was performed globally and sectorally to yield MRA1 and MRA2, where "borderline" was classified as normal and abnormal, respectively. Main Outcome Measures Sensitivity, specificity, and likelihood ratios (LRs) for positive and negative test results (LR+/LR−). Results The median (interquartile range) age and mean deviation of patients and controls were 69.9 (64.3–76.9) and 65.0 (58.1–74.3) years and −3.92 (−7.87 to −1.62) and 0.33 (−0.32 to 0.98) dB, respectively. Globally, BMO-MRW yielded better diagnostic performance than the other parameters. At 95% specificity, the sensitivity of RNFLT, BMO-HRW, and BMO-MRW was 70%, 51%, and 81%, respectively. The corresponding LR+/LR− was 14.0/0.3, 10.2/0.5, and 16.2/0.2. Sectorally, at 95% specificity, the sensitivity of RNFLT ranged from 31% to 59%, of BMO-HRW ranged from 35% to 64%, and of BMO-MRW ranged from 54% to 79%. Globally and in all sectors, BMO-MRW performed better than MRA1 or MRA2. Conclusions The higher sensitivity at 95% specificity in early glaucoma of BMO-MRW compared with current BMO methods is significant, indicating a new structural marker for the detection and risk profiling of glaucoma. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

To determine whether: (1) change in lamina cribrosa depth occurs more frequently than change in neuroretinal parameters in glaucoma, and (2) Bruch's membrane or anterior sclera should be used as a reference plane when measuring laminar depth.Prospective observational study.One hundred fifty-five glaucoma patients and 35 healthy controls.Anterior laminar depth from a Bruch's membrane (LD-BM) or anterior sclera (LD-AS) reference plane were measured with optical coherence tomography. Two neuroretinal parameters, minimum rim width and retinal nerve fiber layer thickness, in addition to peripapillary choroidal thickness were measured. Factors related to laminar depth were determined with mixed-effects modeling. Cutoffs for significant change in each parameter were estimated from variability in healthy controls over 1 year. The occurrences of significant change in laminar depth and neuroretinal parameters were compared with survival models. Because normal aging has a clear effect on neuroretinal parameters, but not on laminar depth, changes in neuroretinal parameters were adjusted for age-related reduction.Longitudinal changes in laminar depth and neuroretinal parameters.Glaucoma patients were followed up for a mean of 3.90 years (range, 2.03-5.44 years). The LD-BM was influenced significantly more by choroidal thickness (1.14 μm/μm; 95% confidence interval, 1.07-1.21) than was the LD-AS (0.15 μm/μm; 95% confidence interval, 0.08-0.22). Posterior movement of the lamina (LD-BM increase or LD-AS increase) occurred with the same frequencies as thinning in neuroretinal parameters. Anterior movement of the lamina was detected more frequently with the Bruch's membrane (LD-BM decrease) compared with the anterior sclera (LD-AS decrease) reference plane (hazard ratio, 3.23; P0.01). Significant choroidal thinning occurred in most patients (25/28 [89%]) in whom anterior movement of the lamina occurred with the Bruch's membrane, but not the anterior sclera, reference plane (LD-BM decrease without LD-AS decrease). Patients had a wide range of individual rates of change of choroidal thickness, from -20.00 to 17.09 μm/year (mean, -1.62 μm/year).Lamina cribrosa depth should be measured from an anterior sclera reference plane to reduce the influence of choroidal thickness changes. In glaucoma patients, lamina cribrosa depth changes are detected with similar frequency as neuroretinal parameter changes.

To examine the rates of retinal nerve fibre layer thickness (RNFLT) change in glaucoma patients and healthy, age-similar control subjects with three techniques: scanning laser polarimetry with variable corneal compensation (VCC) and enhanced corneal compensation (ECC), and time-domain optical coherence tomography (OCT). Sixty-one patients and thirty-three controls were examined with each technique and with standard automated perimetry (SAP) every 6 months. Rates of global RNFLT change and SAP mean deviation (MD) change were estimated with linear mixed-effects models. The median (interquartile range) baseline age was 64.4 (58.2, 71.0) years for patients and 62.4 (56.3, 70.1) years for controls (P=0.56). There was a median of seven examinations over 3.1 years for patients and six examinations in 3.0 years for controls. Baseline visual field MD and RNFLT for all imaging modalities were significantly lower (P

Objective To determine the response of the anterior lamina cribrosa and prelaminar tissue to acute elevation of intraocular pressure (IOP) in glaucoma patients and healthy subjects. Design Prospective case-control series. Participants and Controls Patients with open-angle glaucoma (n = 12; mean age±standard deviation [SD], 66.8±6.0 years), age-matched healthy controls (n = 12; mean age±SD, 67.1±6.2 years), and young controls (n = 12; mean age±SD, 36.1±11.7 years). Methods One eye was imaged with spectral-domain optical coherence tomography to obtain 12 high-resolution radial scans centered on the optic disc. Imaging was repeated at precisely the same locations with an ophthalmodynamometer held perpendicular to the globe via the inferior lid to raise the IOP. A line joining Bruch's membrane opening in 4 radial scans was used as reference in the baseline and elevated IOP images. The vertical distance from the reference line to the anterior prelaminar tissue surface and anterior laminar surface was measured at equidistant points along the reference line in the 2 sets of images. The difference between the 2 sets of corresponding measurements were used to determine laminar displacement (LD) and prelaminar tissue displacement (PTD). Main Outcome Measures Laminar displacement and PTD. Results Intraocular pressure elevation among patients, age-matched controls, and young controls was similar (mean±SD, 12.4±3.2 mmHg). The mean±SD LD and PTD were 0.5±3.3 μm and 15.7±15.5 μm, respectively. The LD was not statistically different from 0 ( P = 0.366), but PTD was ( P P = 0.366), whereas the mean±SD PTD was different (6.8±13.7 μm, 20.8±17.5 μm, and 19.6±11.8 μm, respectively; P = 0.045). In all subjects, the PTD was greater than LD. In multivariate regression analyses, LD was negatively associated with optic disc size ( P = 0.007), whereas PTD was positively associated with the degree of IOP elevation ( P = 0.013). Conclusions In glaucoma patients and controls, the anterior laminar surface is noncompliant to acute IOP elevation. Acute optic disc surface changes represent compression of prelaminar tissue and not laminar displacement. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

Purpose To determine whether structural abnormalities of the lamina cribrosa explain the presence of optic disc hemorrhages, we determined the spatial concordance between disc hemorrhages and laminar disinsertions from the sclera. Design Prospective noninterventional study. Participants From open-angle glaucoma patients followed up prospectively, we identified 52 eyes of 46 open-angle glaucoma patients with optic disc hemorrhage (ODH+ group) in at least 1 optic disc photograph during follow-up. We also identified 52 control eyes of 46 glaucoma patients in whom no disc hemorrhage was detected (ODH− group). Methods Enhanced depth imaging optical coherence tomography of the optic nerve head (24 radial scans) was performed. The scans were de-identified and a trained observer masked to all clinical information determined the presence of laminar disinsertions in each of the 48 positions with a confidence score of 1 (least certain) to 5 (most certain). Only disinsertions with a score of 3 or more were included in the analysis. Main Outcome Measures Frequency and spatial concordance between disc hemorrhages and laminar disinsertions. Results The median age, visual field mean deviation, and follow-up period of the ODH+ and ODH− groups was 77.5 and 70.8 years, −5.20 and −4.70 dB, and 10.4 and 9.9 years, respectively. There were 84 hemorrhages recorded in the ODH+ group. There were laminar disinsertions in 50 eyes (96%) in the ODH+ group and in 27 eyes (52%) in the ODH− group, with 2 or more disinsertions in 30 eyes (58%) and 5 eyes (10%), respectively. Most hemorrhages and disinsertions were located in the inferotemporal and superotemporal sectors. However, in individual patients, only 33 of the ODHs (39%) were located within a laminar disinsertion. Conclusions Laminar disinsertions occurred twice as frequently in eyes with ODHs; however, in individual patients, the spatial concordance between ODHs and laminar disinsertions was poor.

Importance: A new analysis method called permutation of pointwise linear regression measures the significance of deterioration over time at each visual field location, combines the significance values into an overall statistic, and then determines the likelihood of change in the visual field. Because the outcome is a single P value, individualized to that specific visual field and independent of the scale of the original measurement, the method is well suited for comparing techniques with different stimuli and scales.\ud \ud Objective: To test the hypothesis that frequency-doubling matrix perimetry (FDT2) is more sensitive than standard automated perimetry (SAP) in identifying visual field progression in glaucoma.\ud \ud Design, Setting, and Participants: Patients with open-angle glaucoma and healthy controls were examined by FDT2 and SAP, both with the 24-2 test pattern, on the same day at 6-month intervals in a longitudinal prospective study conducted in a hospital-based setting. Only participants with at least 5 examinations were included.\ud \ud Intervention: Data were analyzed with permutation of pointwise linear regression.\ud \ud Main Outcome and Measure: Permutation of pointwise linear regression is individualized to each participant, in contrast to current analyses in which the statistical significance is inferred from population-based approaches. Analyses were performed with both total deviation and pattern deviation.\ud \ud Results: Sixty-four patients and 36 controls were included in the study. The median age, SAP mean deviation, and follow-up period were 65 years, −2.6 dB, and 5.4 years, respectively, in patients and 62 years, +0.4 dB, and 5.2 years, respectively, in controls. Using total deviation analyses, statistically significant deterioration was identified in 17% of patients with FDT2, in 34% of patients with SAP, and in 14% of patients with both techniques; in controls these percentages were 8% with FDT2, 31% with SAP, and 8% with both. Using pattern deviation analyses, statistically significant deterioration was identified in 16% of patients with FDT2, in 17% of patients with SAP, and in 3% of patients with both techniques; in controls these values were 3% with FDT2 and none with SAP.\ud \ud Conclusions and Relevance: No evidence was found that FDT2 is more sensitive than SAP in identifying visual field deterioration. In about one-third of healthy controls, age-related deterioration with SAP reached statistical significance.

Objective: To examine peripapillary choroidal thickness in healthy controls and in patients with glaucoma who have focal, diffuse, and sclerotic optic disc damage. Methods: Healthy controls (n=92) and patients with glaucoma who have focal (n=34), diffuse (n=35), and sclerotic (n=34) optic disc damage were imaged with spectral-domain optical coherence tomography (12 circular scan protocol centered on optic nerve head). Peripapillary choroidal thickness was measured as the distance between the automatically segmented retinal pigment epithelium/Bruch's membrane and the manually outlined interface between the posterior choroid and the anterior border of the sclera in eyes in which the anterior scleral border was visible over more than 85% of the scan circumference. Results: The anterior scleral border was visible in 76 controls (83%) and 89 patients (86%). Peripapillary choroidal thickness in healthy controls decreased linearly with age (-11 mu m/decade; P < .001; r(2)=0.16), with a predicted value of 137 mu m at age 70 years (95% prediction interval, 62-212 mu m). While this value was similar in patients with focal and diffuse optic disc damage (126 and 130 mu m, respectively; P=.22 compared with controls), it was approximately 30% lower in patients with sclerotic optic disc damage (96 mu m; P

Background/aim:To compare the ability of confocal scanning laser tomography (CSLT), scanning laser polarimetry (SLP) and optical coherence tomography (OCT) in recognising localised retinal nerve fibre layer (RNFL) defects.Methods:51 eyes from 43 patients with glaucoma were identified by two observers as having RNFL defects visible on optic disc photographs. 51 eyes of 32 normal subjects were used as controls. Three masked observers evaluated CSLT, SLP and OCT images to determine subjectively the presence of localised RNFL defects.Results:Interobserver agreement was highest with OCT, followed by SLP and CSLT (mean kappa: 0.83, 0.69 and 0.64, respectively). RNFL defects were identified in 58.8% of CSLT, 66.7% of SLP and 54.9% of OCT (p = 0.02 between SLP and OCT) by at least two observers. In the controls, 94.1% of CSLT, 84.3% of SLP and 94.1% of OCT scans, respectively, were rated as normal (p = 0.02 between CSLT and SLP, and SLP and OCT).Conclusion:Approximately 20–40% of localised RNFL defects identified by colour optic disc photographs are not detected by CSLT, SPL or OCT. SLP showed a higher number of false-positive results than the other techniques, but also had a higher proportion of correctly identified RNFL defects in the glaucoma population.

Purpose To compare the diagnostic accuracy of conventional sector-based analysis with a method devised to detect the smallest localized neuroretinal rim and retinal nerve fiber layer thickness (RNFLT) damage. Methods One eye of 151 glaucoma patients and 83 healthy controls (median age and MD, 71.7 and 66.7 years, and -3.6 and -0.3 dB, respectively) was imaged with spectral-domain optical coherence tomography (OCT). Bruch's membrane opening-minimum rim width (BMO-MRW) and RNFLT were determined at 1° intervals and also averaged for each sector. A classification of glaucoma was made with sectoral analysis when the sectoral value was below the 1%, 5%, or 10% normative limit (from an independent normative dataset); and with total analysis when a given number of measurements was below the 1%, 5%, or 10% normative limit. Results With the 1% normative limit, BMO-MRW sectoral analysis yielded sensitivity of 87% and specificity of 92%; while at the same specificity (92%), total analysis yielded sensitivity of 88%. With RNFLT, sectoral analysis yielded sensitivity of 85% and specificity of 95%; while at the same specificity (95%), total analysis yielded sensitivity of 83%. The results for the 5% and 10% normative limits yielded lower specificity but higher sensitivity. In the whole glaucoma population, none of the sensitivity values of the sectoral and total analysis at the same specificities were statistically different. Conclusions The diagnostic accuracy of sectoral analysis was equivalent to total analysis. These results indicate that BMO-MRW and RNFLT defects were wide and deep enough for detection by conventional sectoral analysis.

Aims: To determine whether central corneal thickness (CCT) is a significant predictor of visual field and optic disc progression in open angle glaucoma. Methods: Data were obtained from a prospective study of glaucoma patients tested with static automated perimetry and confocal scanning laser tomography every 6 months. Progression was determined using a trend based approach called evidence of change (EOC) analysis in which sectoral ordinal scores based on the significance of regression coefficients of visual field pattern deviation and neuroretinal rim area over time are summed. Visual field progression was also determined using the event based glaucoma change probability (GCP) analysis using both total and pattern deviation. Results: The sample contained 101 eyes of 54 patients (mean (SD) age 56.5 (9.8) years) with a mean follow up of 9.2 (0.7) years and 20.7 (2.3) sets of examinations every 6 months. Lower CCT was associated with worse baseline visual fields and lower mean IOP in the follow up. In the longitudinal analysis CCT was not correlated with the EOC scores for visual field or optic disc change. In the GCP analyses, there was a tendency for groups classified as progressing to have lower CCT compared to non-progressing groups. In a multivariate analyses accounting for IOP, the opposite was found, whereby higher CCT was associated with visual field progression. None of the independent factors were predictive of optic disc progression. Conclusions: In this cohort of patients with established glaucoma, CCT was not a useful index in the risk assessment of visual field and optic disc progression.

PURPOSE . To compare frequency-doubling technology (FDT) perimetry with standard automated perimetry (SAP) for detecting glaucomatous visual field progression in a longitudinal prospective study. METHODS . One eye of patients with open-angle glaucoma was tested every 6 months with both FDT and SAP. A minimum of 6 examinations with each perimetric technique was required for inclusion. Visual field progression was determined by two methods: glaucoma change probability (GCP) analysis and linear regression analysis (LRA). For GCP, several criteria for progression were used. The number of locations required to classify progression with FDT compared with SAP, respectively, was 1:2 (least conservative), 1:3, 2:3, 2:4, 2:6, 2:7, 3:6, 3:7, and 3:10 (most conservative). The number of consecutive examinations required to confirm progression was 2-of-3, 2-of-2, and 3-of-3. For LRA, the progression criterion was any significant decline in mean threshold sensitivity over time in each of the following three visual field subdivisions: (1) all test locations, (2) locations in the central 10° and the superior and inferior hemifields, and (3) locations in each quadrant. Using these criteria, the proportion of patients classified as showing progression with each perimetric technique was calculated and, in the case of progression with both, the differences in time to progression were determined. RESULTS . Sixty-five patients were followed for a median of 3.5 years (median number of examinations, 9). For the least conservative GCP criterion, 32 (49%) patients were found to have progressing visual fields with FDT and 32 (49%) patients with SAP. Only 16 (25%) patients showed progression with both methods, and in most of those patients, FDT identified progression before SAP (median, 12 months earlier). The majority of GCP progression criteria (15/27), classified more patients as showing progression with FDT than with SAP. Contrary to this, more patients showed progression with SAP than FDT, when analysed with LRA; e.g., using quadrant LRA 20 (31%) patients showed progression with FDT, 23 (35%) with SAP, and only 10 (15%) with both. CONCLUSIONS . FDT perimetry detected glaucomatous visual field progression. However, the proportion of patients who showed progression with both FDT and SAP was small, possibly indicating that the two techniques identify different subgroups of patients. Using GCP, more patients showed progression with FDT than with SAP, yet the opposite occurred using LRA. As there is no independent qualifier of progression, FDT and SAP progression rates vary depending on the method of analysis and the criterion used.

PURPOSE. To quantify and characterize the difference between automated and manual segmentation of optic nerve head structures with spectral-domain optical coherence tomography (SD-OCT). METHODS. Optic nerve head radial scans in 107 glaucoma patients and 48 healthy controls were conducted with SD-OCT. Independent segmentations of the internal limiting membrane (ILM) and Bruch's membrane opening (BMO) were performed manually with custom software and with an automated algorithm in each radial scan. The minimum distance between BMO and ILM, termed BMO-minimum rim width (BMO-MRW) was calculated with each segmentation method. Absolute differences between automated and manual segmentations of ILM (Delta ILM) and BMO (Delta BMO), and the resulting computation of BMO-MRW (Delta BMO-MRW) were computed. Finally, the relationship between image quality score and Delta ILM and Delta BMO was explored. RESULTS. The median (interquartile range, IQR) Delta ILM was 8.9 (6.5, 13.4) mu m in patients and 7.3 (5.3, 9.9) mu m in controls. The corresponding values for Delta BMO were 11.5 (6.6, 22.1) mu m and 12.4 (6.8, 25.4) mu m. Subject-averaged Delta ILM was higher in patients than controls (P < 0.01); however, mean Delta BMO was not (P = 0.09). The median (IQR) subject-averaged absolute Delta BMO-MRW was 13.4 (10.6, 16.8) mu m in patients and 12.1 (10.0, 16.8) mu m in controls and not statistically different (P = 0.21). Mean image quality score was statistically higher in controls than patients (P = 0.03) but not related to subject-averaged Delta ILM or Delta BMO. CONCLUSIONS. In individual scans, the median difference in ILM and BMO segmentations was < 2 and < 3 image pixels, respectively. There were no differences between patients and controls in Delta BMO-MRW.

Purpose. To compare the properties of the visual field index (VFI) to those of mean deviation (MD) in patients with glaucoma. Methods. MD and VFI were calculated in data obtained from an ongoing longitudinal study in which patients with glaucoma (N = 109, 204 eyes) were observed for 9.8 years (median, 21 tests) with static automated perimetry. MD and VFI were compared in one test of each eye, and a subset of 30 tests were selected to compare the VFI with the judgments of eight experts who judged the percentage of the remaining visual field. In series of tests obtained over time, rates of change, statistical significance, evidence of nonlinearity, and variability were compared between both indices. Results. In single tests, MD and VFI were closely related (r = 0.88, P < 0.001). The relationship between both indices appeared linear, except in visual fields with MDs better than -5.0 dB where 29 (22%) of 129 eyes exhibited a ceiling effect (VFI = 100%). Based on this relationship, the predicted VFIs for visual fields with MDs of -5, -10, and -15 dB were 91%, 76%, and 60%, respectively. The percentage of remaining visual field suggested by the VFI exceeded the range of the experts' subjective judgments in 16 (53%) of 30 eyes. In series of tests obtained over time, rates of change with the two indices were closely related (r = 0.79, P < 0.001), and statistically significant reductions over time (P < 0.05) occurred in a similar number of eyes (92 [45%] with MD, and 87 [43%] with VFI). Of the 105 eyes with statistically significant (P < 0.05) negative trend in either MD or VFI, 74 (70%) showed such trends with both indices (κ = 0.69). The variability of MD and VFI increased with damage, and there was no evidence that change over time was more linear with VFI than with MD. Conclusions. The VFI provides a simple and understandable metric of visual field damage, but its estimates of remaining visual field were more optimistic than those of the experts. Rates of change over time with both indices were closely related, but the reliance of the VFI on pattern deviation probability maps caused a ceiling effect that may have reduced its sensitivity to change in eyes with early damage. In this group of patients there was no evidence to suggest that the VFI is either superior or inferior to the MD as a summary measure of visual field damage.

PURPOSE: To compare confocal scanning laser tomography (CSLT) to optic disc photography for detecting progressive glaucomatous disc changes. METHODS: Four expert observers first examined a training set of 40 pairs of monoscopic disc photographs to help set a criterion for change. They then classified 44 pairs of monoscopic photographs of patients followed prospectively as having either definitely no change, probably no change, probably change, or definitely change (score, 0, 1, 2, or 3, respectively). Observers were unaware that 10 pairs were photographs of fellow eyes obtained the same day to measure specificity. These patients were imaged with the Heidelberg Retina Tomograph every 6 months. Topographic change analysis (TCA) software with three criteria (yielding specificity of 81%, 94%, or 97%) was used. Comparisons between the TCA results and those of observers were made for a range of liberal to conservative criteria and for individual and combined observer scores. RESULTS: The median follow-up was 9.0 years with 18 CSLT images. Observer specificity varied from 50% to 90% (using score 0) and 60% to 100% (using score 0 or 1). Interobserver kappa ranged from 0.22 to 0.38 from the most liberal to conservative criterion and was generally higher than corresponding TCA-observer agreement. For most criteria, observers had either a high hit rate with low specificity or high specificity with a low hit rate compared with the TCA. Similar results were obtained when observer scores were combined to derive a broader range of criteria. CONCLUSIONS: The results indicate that the TCA performs at least as well as either the individual or best combination of observer classifications of disc photographs.

PURPOSE: To compare test results from second-generation Frequency-Doubling Technology perimetry (FDT2, Humphrey Matrix; Carl-Zeiss Meditec, Dublin, CA) and standard automated perimetry (SAP) in patients with glaucoma. Specifically, to examine the relationship between visual field sensitivity and test-retest variability and to compare total and pattern deviation probability maps between both techniques. METHODS: Fifteen patients with glaucoma who had early to moderately advanced visual field loss with SAP (mean MD, -4.0 dB; range, +0.2 to -16.1) were enrolled in the study. Patients attended three sessions. During each session, one eye was examined twice with FDT2 (24-2 threshold test) and twice with SAP (Swedish Interactive Threshold Algorithm [SITA] Standard 24-2 test), in random order. We compared threshold values between FDT2 and SAP at test locations with similar visual field coordinates. Test-retest variability, established in terms of test-retest intervals and standard deviations (SDs), was investigated as a function of visual field sensitivity (estimated by baseline threshold and mean threshold, respectively). The magnitude of visual field defects apparent in total and pattern deviation probability maps were compared between both techniques by ordinal scoring. RESULTS: The global visual field indices mean deviation (MD) and pattern standard deviation (PSD) of FDT2 and SAP correlated highly (r > 0.8; P 25 dB with SAP), threshold estimates from FDT2 and SAP exhibited a close, linear relationship, with a slope of approximately 2.0. However, at test locations with lower sensitivity, the relationship was much weaker and ceased to be linear. In comparison with FDT2, SAP showed a slightly larger proportion of test locations with absolute defects (3.0% vs. 2.2% with SAP and FDT2, respectively, P < 0.001). Whereas SAP showed a significant increase in test-retest variability at test locations with lower sensitivity (P < 0.001), there was no relationship between variability and sensitivity with FDT2 (P = 0.46). In comparison with SAP, FDT2 exhibited narrower test-retest intervals at test locations with lower sensitivity (SAP thresholds

C. perfringens degraded chenodeoxycholic acid (CDC) into two major products: 7α-hydroxy-3-oxo-5β-cholanoic acid and 3β,7α-dihydroxy-5β-cholanoic acid, the latter appearing very quickly and the former very slowly in whole cell cultures. Yields of about 60 and 16% were obtained for the respective products. Both products, as substrates in C. perfringens cultures, were quickly transformed back to CDC (about 84%) and 3β,7α-dihydroxy-5β-cholanoic acid (about 16%), whereas 7α-hydroxy-3-oxo-5β-cholanoic acid was formed slowly (4–5 days). In contrast to CDC, cholic acid was not epimerized at 3α-OH position; however, 7α, 12α-dihydroxy-3-oxo-cholanoic acid was formed slowly. When 7α,12α-dihydroxy-3-oxo cholanoic acid was substrate, rapid quantitative reduction, back to cholic acid then slow oxidation back to the 3-oxo product was observed. Thirty-six strains of C. perfringens (18 from a culture collection and 18 isolated from human feces) were screened for 3α-OH epimerization and oxidation of the primary bile acids. All but three strains epimerized CDC (yields 14–20%), while none epimerized cholic acid. Oxidation at the 3 position varied from 0–30% for CDC and 0–90% for cholic acid. Cell-free preparations of C. perfringens in the presence of NADP produced both 3-oxo and 3β-hydroxyl products with CDC, but only the 3-oxo product with cholic acid; these activities were non-inducible. The authors propose that 3α-OH isomerization takes place early in log phase via a 3α- and 3β-hydroxysteroid dehydrogenase (HSDH) system. Accumulation of 3-oxo product occurs late in stationary phase as the Redox (Eh) value rises above —100 mV.

Primary bile acids, chenodeoxycholic (3 alpha,7 alpha-dihydroxy-5 beta-cholan-24-oic) and cholic (3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholan-24-oic) were included in cultures of (a) Clostridium absonum alone (b) a mixture of C. absonum and a 7-dehydroxylating organism, Eubacterium sp. (c) a mixture of C. absonum and fecal bacteria, and (d) fecal bacteria alone. C. absonum, when added to Eubacterium sp. cultures totally prevented lithocholic acid formation when the substrate was chenodeoxycholic acid and halved deoxycholic acid formation when the substrate was cholic acid. As expected, formation of 7 beta-hydroxy- and 7-keto-bile acids took precedence over formation of 7 alpha-dehydroxylated bile acids. However, the addition of C. absonum to mixed fecal cultures containing chenodeoxycholic acid did not alter production of lithocholic (3 alpha-hydroxy-5 beta-cholan-24-oic) acid; instead it enhanced formation of ursodeoxycholic acid (3 alpha,7 beta-dihydroxy-5 beta-cholan-24-oic acid) at the expense of 7-keto-lithocholic acid (3 alpha-hydroxyl-7-oxo-5 beta-cholan-24-oic acid). Similarly, the addition of C. absonum to mixed fecal cultures containing cholic acid promoted production of ursocholic acid (3 alpha,7 beta,12 alpha-trihydroxy-5 beta-cholan-24-oic acid) which did not take place when C. absonum was not added. Surprisingly, deoxycholic acid formation was somewhat enhanced when C. absonum was added to fecal cultures. These studies suggest that successful introduction of "foreign" 7 alpha-epimerizing organisms into animal or human intestines may influence bile acid metabolism in vivo.

Eight strains of Clostridium absonum were shown to form ursocholic acid (UC) from cholic acid (C) and ursodeoxycholic acid (UDC) from chenodeoxycholic acid (CDC) but did not transform deoxycholic acid (DC) in whole cell cultures. The structures of UC and UDC were verified by mass spectroscopy, and by thin-layer chromatography using Komarowsky's spray reagent. The organism transformed C and CDC at concentrations below 1.5. 10(-3) M and 5.0. 10(-4) M, respectively; higher concentrations were inhibitory. Optimal yields of the final products were realized at about 15-22 hr and 9-15 hr of incubation, respectively, and were in the range of 60-70%. Additionally, the 7 keto-derivatives, 7 keto-deoxycholic acid (7K-DC) or 7 keto-lithocholic acid (7K-LC) were also formed from C and CDC. With longer periods of incubation, increasing yields of 7K-DC and 7K-LC and decreasing yields of UC and UDC were observed. These time course studies suggest that 7K-DC and 7K-LC are intermediates in the formation of UC and UDC from the primary bile acids. We propose the occurrence of C right harpoon over left harpoon 7K-DC right harpoon over left harpoon UC and CDC right harpoon over left harpoon 7K-LC right harpoon over left harpoon UDC with increasing dominance of back reaction of the second step on aging of the culture. When the initial pH value of the medium was manipulated within the range of 5.8-9.0, increasing yields of UDC from CDC were obtained at higher pH values (maximum yield at pH 9.0 was 83%), with total inhibition of growth and transformation at pH 5.8. In contrast, UC was produced from C at all pH values studied, with marginal differences in yields (maximum yield at pH 8.0 was 50%). In all cases, formation of UC from C was much slower than that of UDC from CDC. In contrast, C. paraperfringens transformed none of the above bile acids. We propose that C. absonum, or a biochemically similar species, may be present in the human gut and give rise to UDC (and UC) in vivo.-Macdonald, I. A., D. M. Hutchison, and T. P. Forrest. Formation of urso- and ursodeoxycholic acids from primary acids by Clostridium absonum.