Progressive Changes in the Neuroretinal Rim and Retinal Nerve Fiber Layer in Glaucoma: Impact of Baseline Values and Floor Effects.

PURPOSE: To determine whether more severe baseline damage impedes measurement of minimum rim width (MRW) and peripapillary retinal nerve fiber layer thickness (RNFLT) change in glaucoma patients because of a floor effect. DESIGN: Prospective, longitudinal cohort study in a hospital-based setting. PARTICIPANTS: The study included patients with open-angle glaucoma and healthy control subjects. Participants had at least 5 years of follow-up with OCT every 6 months. METHODS: Baseline global and sectorial MRW and RNFLT values were classified as within normal limits, borderline, or outside normal limits based on reference normative values. Regression analysis was used to determine the magnitude and significance of MRW and RNFLT change. Additionally, the follow-up period for each participant was divided into 2 equal halves (first and second periods) to determine whether there was attenuation of MRW and RNFLT change with follow-up time. MAIN OUTCOME MEASURES: Rates of global and sectoral MRW and RNFLT changes (slopes). RESULTS: A total of 97 patients with glaucoma (median age, 70.3 years) and 42 healthy subjects (median age, 64.8 years) were followed for a median of 6.9 years and 7.0 years, respectively. The median mean deviation of the visual field in glaucoma patients was -4.30 decibels (dB) (interquartile range, -7.81 to -2.06 dB; range, -20.68 to 1.37 dB). Statistically significant changes in global and sectoral MRW and RNFLT were detected across all baseline classifications; however, there was a tendency for less change with increasing baseline damage. In glaucoma patients, RNFLT slopes, but not MRW slopes, were significantly more positive (less change) in the second period compared with the first. There were also no differences in MRW or RNFLT slopes in the first and second periods in healthy subjects. CONCLUSIONS: Significant MRW and RNFLT changes were detected at all levels of baseline damage. However, an attenuation in the rate of RNFLT change compared with MRW indicates an earlier floor effect in RNFLT measurements globally and in equivalent sectors. Because the axonal component of these measurements should be equivalent, our results suggest important differences in tissue remodeling at the level of the optic nerve head and peripapillary retina. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Value of 10-2 Visual Field Testing in Glaucoma Patients with Early 24-2 Visual Field Loss.

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.

Association of Rare CYP39A1 Variants With Exfoliation Syndrome Involving the Anterior Chamber of the Eye.

Importance: Exfoliation syndrome is a systemic disorder characterized by progressive accumulation of abnormal fibrillar protein aggregates manifesting clinically in the anterior chamber of the eye. This disorder is the most commonly known cause of glaucoma and a major cause of irreversible blindness. Objective: To determine if exfoliation syndrome is associated with rare, protein-changing variants predicted to impair protein function. Design, Setting, and Participants: A 2-stage, case-control, whole-exome sequencing association study with a discovery cohort and 2 independently ascertained validation cohorts. Study participants from 14 countries were enrolled between February 1999 and December 2019. The date of last clinical follow-up was December 2019. Affected individuals had exfoliation material on anterior segment structures of at least 1 eye as visualized by slit lamp examination. Unaffected individuals had no signs of exfoliation syndrome. Exposures: Rare, coding-sequence genetic variants predicted to be damaging by bioinformatic algorithms trained to recognize alterations that impair protein function. Main Outcomes and Measures: The primary outcome was the presence of exfoliation syndrome. Exome-wide significance for detected variants was defined as P < 2.5 × 10-6. The secondary outcomes included biochemical enzymatic assays and gene expression analyses. Results: The discovery cohort included 4028 participants with exfoliation syndrome (median age, 78 years [interquartile range, 73-83 years]; 2377 [59.0%] women) and 5638 participants without exfoliation syndrome (median age, 72 years [interquartile range, 65-78 years]; 3159 [56.0%] women). In the discovery cohort, persons with exfoliation syndrome, compared with those without exfoliation syndrome, were significantly more likely to carry damaging CYP39A1 variants (1.3% vs 0.30%, respectively; odds ratio, 3.55 [95% CI, 2.07-6.10]; P = 6.1 × 10-7). This outcome was validated in 2 independent cohorts. The first validation cohort included 2337 individuals with exfoliation syndrome (median age, 74 years; 1132 women; n = 1934 with demographic data) and 2813 individuals without exfoliation syndrome (median age, 72 years; 1287 women; n = 2421 with demographic data). The second validation cohort included 1663 individuals with exfoliation syndrome (median age, 75 years; 587 women; n = 1064 with demographic data) and 3962 individuals without exfoliation syndrome (median age, 74 years; 951 women; n = 1555 with demographic data). Of the individuals from both validation cohorts, 5.2% with exfoliation syndrome carried CYP39A1 damaging alleles vs 3.1% without exfoliation syndrome (odds ratio, 1.82 [95% CI, 1.47-2.26]; P < .001). Biochemical assays classified 34 of 42 damaging CYP39A1 alleles as functionally deficient (median reduction in enzymatic activity compared with wild-type CYP39A1, 94.4% [interquartile range, 78.7%-98.2%] for the 34 deficient variants). CYP39A1 transcript expression was 47% lower (95% CI, 30%-64% lower; P < .001) in ciliary body tissues from individuals with exfoliation syndrome compared with individuals without exfoliation syndrome. Conclusions and Relevance: In this whole-exome sequencing case-control study, presence of exfoliation syndrome was significantly associated with carriage of functionally deficient CYP39A1 sequence variants. Further research is needed to understand the clinical implications of these findings.

Selective Laser Trabeculoplasty versus Argon Laser Trabeculoplasty in Glaucoma Patients Treated Previously with 360° Selective Laser Trabeculoplasty: A Randomized, Single-Blind, Equivalence Clinical Trial.

PURPOSE: The effectiveness of selective laser trabeculoplasty (SLT) was compared with argon laser trabeculoplasty (ALT) in a randomized clinical trial for patients with medically uncontrolled open-angle glaucoma who have previously received 360° SLT. DESIGN: An active equivalence parallel armed randomized control trial. PARTICIPANTS: Patients with open-angle glaucoma including pigmentary dispersion syndrome and pseudoexfoliation syndrome were enrolled into the study from 7 different sites across Canada. METHODS: One setting of 180° of either SLT or ALT was assigned randomly and applied to each participant. MAIN OUTCOME MEASURES: The change in intraocular pressure (IOP) from baseline to 12 months was compared between the 2 groups. RESULTS: A total of 132 patients were recruited, 2 of which dropped out early in the study, leaving 130 patients who completed the study as per protocol. For those, the study's primary outcome was calculated. The IOP change at 1 year in comparison to baseline for SLT vs. ALT was found to be different by 0.33 mmHg between the 2 groups (3.16 for SLT and 2.83 for ALT) and was not statistically significant (P = 0.71) Further analysis, though, showed that SLT had a significantly lower IOP reduction at early time points: 1 week and 1 month, but this effect was lost by 3 months. Corresponding to this finding was the strong trend for ALT to fail more quickly than SLT. Although repeatable, the first repeat SLT reduced IOP to only about half compared with initial SLT treatment. CONCLUSIONS: The comparison at 12 months following the laser therapy showed that both modalities lowered the IOP with approximately 3 mmHg, yet essentially all of the time-to-failure analyses favored SLT over ALT. The repeat SLT effect was found to be half of the initial treatment.

Serial Changes in Lamina Cribrosa Depth and Neuroretinal Parameters in Glaucoma: Impact of Choroidal Thickness.

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 < 0.01). 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). 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.

Diagnostic Accuracy of Optical Coherence Tomography and Scanning Laser Tomography for Identifying Glaucoma in Myopic Eyes.

PURPOSE: Ruling out glaucoma in myopic eyes often poses a diagnostic challenge because of atypical optic disc morphology and visual field defects that can mimic glaucoma. We determined whether neuroretinal rim assessment based on Bruch's membrane opening (BMO), rather than conventional optic disc margin (DM)-based assessment or retinal nerve fiber layer (RNFL) thickness, yielded higher diagnostic accuracy in myopic patients with glaucoma. DESIGN: Case-control, cross-sectional study. PARTICIPANTS: Myopic patients with glaucoma (n = 56) and myopic normal controls (n = 74). METHODS: Myopic subjects with refraction error greater than -2 diopters (D) (spherical equivalent) and typical myopic optic disc morphology, with and without glaucoma, were recruited from a glaucoma clinic and a local optometry practice. The final classification of myopic glaucoma or myopic control was based on consensus assessment by 3 clinicians of visual fields and optic disc photographs. Participants underwent imaging with confocal scanning laser tomography for measurement of DM rim area (DM-RA) and with spectral domain optical coherence tomography (SD OCT) for quantification of a BMO-based neuroretinal rim parameter, minimum rim width (BMO-MRW), and RNFL thickness. MAIN OUTCOME MEASURES: Sensitivity of DM-RA, BMO-MRW, and RNFL thickness at a fixed specificity of 90% and partial area under the curves (pAUCs) for global and sectoral parameters for specificities ≥90%. RESULTS: Sensitivities at 90% specificity were 30% for DM-RA and 71% for both BMO-MRW and RNFL thickness. The pAUC was higher for the BMO-MRW compared with DM-RA (P < 0.001), but similar to RNFL thickness (P > 0.5). Sectoral values of BMO-MRW tended to have a higher, but nonsignificant, pAUC across all sectors compared with RNFL thickness. CONCLUSIONS: Bruch's membrane opening MRW is more sensitive than DM-RA and similar to RNFL thickness for the identification of glaucoma in myopic eyes and offers a valuable diagnostic tool for patients with glaucoma with myopic optic discs.

Optic Disc Hemorrhages and Laminar Disinsertions in Glaucoma.

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 of Normal Aging in Estimating the Rate of Glaucomatous Neuroretinal Rim and Retinal Nerve Fiber Layer Loss.

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 < 0.01) and RNFLT (mean: -0.44 µm/year, 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.

Visual field progression in glaucoma: what is the specificity of the Guided Progression Analysis?

PURPOSE: To estimate the specificity of the Guided Progression Analysis (GPA) (Carl Zeiss Meditec, Dublin, CA) in individual patients with glaucoma. DESIGN: Observational cohort study. PARTICIPANTS: Thirty patients with open-angle glaucoma. METHODS: In 30 patients with open-angle glaucoma, 1 eye (median mean deviation [MD], -2.5 decibels [dB]; interquartile range, -4.4 to -1.3 dB) was tested 12 times over 3 months (Humphrey Field Analyzer, Carl Zeiss Meditec; SITA Standard, 24-2). "Possible progression" and "likely progression" were determined with the GPA. These analyses were repeated after the order of the tests had been randomly rearranged (1000 unique permutations). MAIN OUTCOME MEASURES: Rate of false-positive alerts of "possible progression" and "likely progression" with the GPA. RESULTS: On average, the specificity of the GPA "likely progression" alert was high-for the entire sample, the mean rate of false-positive alerts after 10 follow-up tests was 2.6%. With "possible progression," the specificity was considerably lower (false-positive rate, 18.5%). Most important, the cumulative rate of false-positive alerts varied substantially among patients, from <1% to 80% with "possible progression" and from <0.1% to 20% with "likely progression." Factors associated with false-positive alerts were visual field variability (standard deviation of MD, Spearman's rho = 0.41, P<0.001) and the reliability indices (proportion of false-positive and false-negative responses, fixation losses, rho>0.31, P≤0.10). CONCLUSIONS: On average, progression criteria currently used in the GPA have high specificity, but some patients are more likely to show false-positive alerts than others. This is a natural consequence of population-based change criteria and may not matter in clinical trials and studies in which large groups of patients are compared. However, it must be considered when the GPA is used in clinical practice where specificity needs to be controlled for individual patients.

OCT Optic Nerve Head Morphology in Myopia IV: Neural Canal Scleral Flange Remodeling in Highly Myopic Eyes.

PURPOSE: To compare the prevalence, location and magnitude of optic nerve head (ONH) OCT-detected, exposed neural canal (ENC), externally oblique choroidal border tissue (EOCBT) and exposed scleral flange (ESF) regions in 122 highly myopic (Hi-Myo) versus 362 nonhighly myopic healthy (Non-Hi-Myo-Healthy) eyes. DESIGN: Cross-sectional study. METHODS: After OCT radial B-scan, ONH imaging, Bruch's membrane opening (BMO), the anterior scleral canal opening (ASCO), and the scleral flange opening (SFO) were manually segmented in each B-scan and projected to BMO reference plane. The direction and magnitude of BMO/ASCO offset and BMO/SFO offset as well as the location and magnitude of ENC, EOCBT and ESF regions, perineural canal (pNC) retinal nerve fiber layer thickness (RNFLT) and pNC choroidal thickness (CT) were calculated within 30° sectors relative to the Foveal-BMO (FoBMO) axis. Hi-ESF eyes were defined to be those with an ESF region ≥100 µms in at least 1 sector. RESULTS: Hi-Myo eyes more frequently demonstrated Hi-ESF regions (87/122) than Non-Hi-myo-Healthy eyes (73/362) and contained significantly larger ENC, EOCBT, and ESF regions (P < .001) which were greatest in magnitude and prevalence within the inferior-temporal FoBMO sectors where Hi-Myo pNC-RNFLT and pNCCT were thinnest. BMO/ASCO offset and the BMO/SFO offset were both significantly increased (P < .001) in the Hi-Myo eyes, with the latter demonstrating a greater increase. CONCLUSIONS: ENC region tissue remodeling that includes the scleral flange is enhanced in Hi-Myo compared to Non-Hi-Myo-Healthy eyes. Longitudinal studies are necessary to determine whether the presence of an ENC region influences ONH susceptibility to aging and/or glaucoma.

Enhanced detection of open-angle glaucoma with an anatomically accurate optical coherence tomography-derived neuroretinal rim parameter.

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.

Non-arteritic anterior ischemic and glaucomatous optic neuropathy: Implications for neuroretinal rim remodeling with disease severity.

PURPOSE: Post-acute non-arteritic ischemic optic neuropathy (NAION) and glaucomatous optic neuropathy (GON) can be difficult to differentiate clinically. Our objective was to identify optical coherence tomography (OCT) parameters to help differentiate these optic neuropathies. METHODS: We compared 12 eyes of 8 patients with NAION and 12 eyes of 12 patients with GON, matched for age and visual field mean deviation (MD). All patients underwent clinical assessment, automated perimetry (Humphrey Field Analyzer II; Carl Zeiss Meditec, Dublin, CA, USA), and OCT imaging (Spectralis OCT2; Heidelberg Engineering, Heidelberg, Germany) of the optic nerve head and macula. We derived the neuroretinal minimum rim width (MRW), peripapillary retinal nerve fibre layer (RNFL) thickness, central anterior lamina cribrosa depth, and macular retinal thickness. RESULTS: MRW was markedly thicker, both globally and in all sectors, in the NAION group compared to the GON group. There was no significant group difference in RFNL thickness, globally or in any sector, with the exception of the temporal sector that was thinner in the NAION group. The group difference in MRW increased with increasing visual field loss. Other differences observed included lamina cribrosa depth significantly greater in the GON group and significantly thinner central macular retinal layers in the NAION group. The ganglion cell layer was not significantly different between the groups. CONCLUSIONS: The neuroretinal rim is altered in a dissimilar manner in NAION and GON and MRW is a clinically useful index for differentiating these two neuropathies. The fact that the difference in MRW between the two groups increased with disease severity suggests distinct remodelling patterns in response to differing insults with NAION and GON.

Variability of scan quality and perfusion density in longitudinal optical coherence tomography angiography imaging.

BACKGROUND/AIMS: Optical coherence tomography angiography (OCT-A) images are subject to variability, but the extent to which learning impacts OCT-A measurements is unknown. We determined whether there is a learning effect in glaucoma patients and healthy controls imaged with OCT-A. METHODS: Ninety-one open-angle glaucoma patients and 54 healthy controls were imaged every 4 months over a period of approximately 1 year in this longitudinal cohort study. We analysed 15°×15° scans, centred on the fovea, in one eye of each participant. Two-dimensional projection images for the superficial, intermediate and deep vascular plexuses were exported and binarised after which perfusion density was calculated. Linear mixed-effects models were used to investigate the association between perfusion density and follow-up time. RESULTS: The mean (SD) age of glaucoma patients and healthy controls was 67.3 (8.1) years and 62.1 (9.0) years, respectively. There was a significant correlation between perfusion density and scan quality in both glaucoma patients (r=0.50 (95% CI 0.42 to 0.58); p<0.05) and healthy controls (r=0.41 (95% CI 0.29 to 0.52); p<0.05). An increase in perfusion density occurred over time and persisted, even after adjustment for scan quality (1.75% per year (95% CI 1.14 to 2.37), p<0.01). CONCLUSIONS: Perfusion density measurements are subject to increasing experience of either the operator or participant, or a combination of both. These findings have implications for the interpretation of longitudinal measurements with OCT-A.

OCT Optic Nerve Head Morphology in Myopia II: Peri-Neural Canal Scleral Bowing and Choroidal Thickness in High Myopia-An American Ophthalmological Society Thesis.

PURPOSE: To use optical coherence tomography (OCT) to characterize optic nerve head (ONH) peri-neural canal (pNC) scleral bowing (pNC-SB) and pNC choroidal thickness (pNC-CT) in 69 highly myopic and 138 healthy, age-matched, control eyes. DESIGN: Cross-sectional, case control study. METHODS: Within ONH radial B-scans, Bruch membrane (BM), BM opening (BMO), anterior scleral canal opening (ASCO), and pNC scleral surface were segmented. BMO and ASCO planes and centroids were determined. pNC-SB was characterized within 30° foveal-BMO (FoBMO) sectors by 2 parameters: pNC-SB-scleral slope (pNC-SB-SS), measured within 3 pNC segments (0-300, 300-700, and 700-1000 µm from the ASCO centroid); and pNC-SB-ASCO depth relative to a pNC scleral reference plane (pNC-SB-ASCOD). pNC-CT was calculated as the minimum distance between the scleral surface and BM at 3 pNC locations (300, 700, and 1100 µm from the ASCO). RESULTS: pNC-SB increased and pNC-CT decreased with axial length (P < .0133; P < .0001) and age (P < .0211; P < .0004) among all study eyes. pNC-SB was increased (P < .001) and pNC-CT was decreased (P < .0279) in the highly myopic compared to control eyes, and these differences were greatest in the inferior quadrant sectors (P < .0002). Sectoral pNC-SB was not related to sectoral pNC-CT in control eyes, but was inversely related to sectoral pNC-CT (P < .0001) in the highly myopic eyes. CONCLUSIONS: Our data suggest that pNC-SB is increased and pNC-CT is decreased in highly myopic eyes and that these phenomena are greatest in the inferior sectors. They support the hypothesis that sectors of maximum pNC-SB may predict sectors of greatest susceptibility to aging and glaucoma in future longitudinal studies of highly myopic eyes. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Rates of change in the visual field and optic disc in patients with distinct patterns of glaucomatous optic disc damage.

PURPOSE: To investigate the rate of visual field and optic disc change in patients with distinct patterns of glaucomatous optic disc damage. DESIGN: Prospective longitudinal study. PARTICIPANTS: A total of 131 patients with open-angle glaucoma with focal (n = 45), diffuse (n = 42), and sclerotic (n = 44) optic disc damage. METHODS: Patients were examined every 4 months with standard automated perimetry (SAP, SITA Standard, 24-2 test, Humphrey Field Analyzer, Carl Zeiss Meditec, Dublin, CA) and confocal scanning laser tomography (CSLT, Heidelberg Retina Tomograph, Heidelberg Engineering GmbH, Heidelberg, Germany) for a period of 4 years. During this time, patients were treated according to a predefined protocol to achieve a target intraocular pressure (IOP). Rates of change were estimated by robust linear regression of visual field mean deviation (MD) and global optic disc neuroretinal rim area with follow-up time. MAIN OUTCOME MEASURES: Rates of change in MD and rim area. RESULTS: Rates of visual field change in patients with focal optic disc damage (mean -0.34, standard deviation [SD] 0.69 dB/year) were faster than in patients with sclerotic (mean -0.14, SD 0.77 dB/year) and diffuse (mean +0.01, SD 0.37 dB/year) optic disc damage (P = 0.003, Kruskal-Wallis). Rates of optic disc change in patients with focal optic disc damage (mean -11.70, SD 25.5 ×10(-3) mm(2)/year) were faster than in patients with diffuse (mean -9.16, SD 14.9 ×10(-3) mm(2)/year) and sclerotic (mean -0.45, SD 20.6 ×10(-3) mm(2)/year) optic disc damage, although the differences were not statistically significant (P = 0.11). Absolute IOP reduction from untreated levels was similar among the groups (P = 0.59). CONCLUSIONS: Patients with focal optic disc damage had faster rates of visual field change and a tendency toward faster rates of optic disc deterioration when compared with patients with diffuse and sclerotic optic disc damage, despite similar IOP reductions during follow-up.

Optic disc margin anatomy in patients with glaucoma and normal controls with spectral domain optical coherence tomography.

OBJECTIVE: To characterize optic nerve head (ONH) anatomy related to the clinical optic disc margin with spectral domain-optical coherence tomography (SD-OCT). DESIGN: Cross-sectional study. PARTICIPANTS: Patients with open-angle glaucoma with focal, diffuse, and sclerotic optic disc damage, and age-matched normal controls. METHODS: High-resolution radial SD-OCT B-scans centered on the ONH were analyzed at each clock hour. For each scan, the border tissue of Elschnig was classified for obliqueness (internally oblique, externally oblique, or nonoblique) and the presence of Bruch's membrane overhanging the border tissue. Optic disc stereophotographs were co-localized to SD-OCT data with customized software. The frequency with which the disc margin identified in stereophotographs coincided with (1) Bruch's membrane opening (BMO), defined as the innermost edge of Bruch's membrane; (2) Bruch's membrane/border tissue, defined as any aspect of either outside BMO or border tissue; or (3) border tissue, defined as any aspect of border tissue alone, in the B-scans was computed at each clock hour. MAIN OUTCOME MEASURES: The SD-OCT structures coinciding with the disc margin in stereophotographs. RESULTS: There were 30 patients (10 with each type of disc damage) and 10 controls, with a median (range) age of 68.1 (42-86) years and 63.5 (42-77) years, respectively. Although 28 patients (93%) had 2 or more border tissue configurations, the most predominant one was internally oblique, primarily superiorly and nasally, frequently with Bruch's membrane overhang. Externally oblique border tissue was less frequent, observed mostly inferiorly and temporally. In controls, there was predominantly internally oblique configuration around the disc. Although the configurations were not statistically different between patients and controls, they were among the 3 glaucoma groups. At most locations, the SD-OCT structure most frequently identified as the disc margin was some aspect of Bruch's membrane and border tissue external to BMO. Bruch's membrane overhang was regionally present in the majority of patients with glaucoma and controls; however, in most cases it was not visible as the disc margin. CONCLUSIONS: The clinically perceived disc margin is most likely not the innermost edge of Bruch's membrane detected by SD-OCT. These findings have important implications for the automated detection of the disc margin and estimates of the neuroretinal rim.

Elucidating macular structure-function correlations in glaucoma.

Correlation between structural data from optical coherence tomography and functional data from the visual field may be suboptimal because of poor mapping of OCT measurement locations to VF stimuli. We tested the hypothesis that stronger structure-function correlations in the macula can be achieved with fundus-tracking perimetery, by precisely mapping OCT measurements to VF sensitivity at the same location. The conventional 64 superpixel (3° × 3°) OCT grid was mapped to VF sensitivities averaged in 40 corresponding VF units with standard automated perimetry (conventional mapped approach, CMA) in 38 glaucoma patients and 10 healthy subjects. Similarly, a 144 superpixel (2° × 2°) OCT grid was mapped to each of the 68 locations with fundus-tracking perimetry (localized mapped approach, LMA). For each approach, the correlation between sensitivity at each VF unit and OCT superpixel was computed. Vector maps showing the maximum correlation between each VF unit and OCT pixel was generated. CMA yielded significantly higher structure-function correlations compared to LMA. Only 20% of the vectors with CMA and < 5% with LMA were within corresponding mapped OCT superpixels, while most were directed towards loci with structural damage. Measurement variability and patterns of structural damage more likely impact correlations compared to precise mapping of VF stimuli.

Rates of Visual Field Change in Patients With Glaucoma and Healthy Individuals: Findings From a Median 25-Year Follow-up.

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.