Bruch's Membrane Opening Area Research Articles

Reduction of Optic Disc Microvasculature and Retinal Nerve Fiber Layer Thinning in Patients With Glaucoma

PurposeTo assess the relationship between the change of optic disc vessel density (ODVD) and retinal nerve fiber layer (RNFL) thinning in primary open-angle glaucoma (POAG) patients. DesignRetrospective case series. MethodsFor 105 POAG patients, ≥ 5 consecutive optical coherence tomography (OCT) and OCT angiography (OCTA) images were obtained during ≥ 2 years of follow-up.Based on enface OCTA imaging, ODVD was calculated as the ratio of pixels occupied by vessels below the internal limiting membrane within the temporal area of the optic cup, and ODVD reduction was determined when there was a statistically significant negative slope (P < 0.05) for any of the global, superior, or inferior sectors. The association between the rates of ODVD change and RNFL thinning was assessed by multivariable longitudinal linear mixed-effects model vs. time. ResultsDuring 2.9 ± 0.3 years of follow-up on the 105 participants with visual field mean deviation at baseline of 5.7 ± 4.8 dB, 46 (43.8%) showed ODVD reduction. Faster global RNFL thinning was associated with the smaller Bruch's membrane opening area (ß = 0.381; 95% confidence interval (CI), 0.120 to 0.646; P = 0.006), optic disc hemorrhage (ß = -0.567; 95% CI, -0.909 to -0.228; P = 0.002) and faster rate of global ODVD change (ß = -0.090; 95% CI, -0.139 to -0.042; P = 0.001). ConclusionsReduction of optic disc microvasculature was associated with rapid RNFL thinning in POAG. This suggests a role for deep ONH circulation in the glaucoma pathogenesis.

Longitudinal Rates of Change in Structural Parameters of Optical Coherence Tomography in Primary Angle Closure Glaucoma following Laser Iridotomy along with Peripheral Iridoplasty.

This study aimed to investigate longitudinal rates of change (LRCs) of structural parameters from optical coherence tomography (OCT) in patients with primary angle closure glaucoma (PACG) after laser iridotomy (LI) along with laser peripheral iridoplasty (PI). Among 146 patients diagnosed with PACG, thirty-two subjects (32 eyes) who underwent LI plus PI and accomplished more than five times of reliable OCT tests were included in the current retrospective study. Retinal nerve fiber layer (RNFL) and Bruch's membrane opening-minimum rim width (BMO-MRW) were measured by spectral-domain OCT with three month interval. LRCs of global and six Garway-Heath sectors were investigated using the linear mixed-effects model which adjusted BMO area, sex, and age. Imaging of dual Scheimpflug analyzer was performed before and at 1 week after LI with PI and yearly thereafter. The mean follow-up period was 32.28 ± 13.34 months with a mean number of 10.18 ± 3.33 OCT images. Baseline characteristics are as follows: age, 63 ± 7.9 years; female, 62.5%; intraocular pressure(IOP), 15.48 ± 4.79 mmHg; anterior chamber depth, 2.09 ± 0.18 mm; and mean deviation, -7.97 ± 8.48 dB. Global LRC of BMO-MRW was 0.86 ± 1.34 μm/yr and RNFL was -0.64 ± 0.22 μm/yr. IOP decreased significantly to 13.06 ± 2.21 mmHg (p=0.001) while anterior chamber volume (p=0.011) and mean anterior chamber angle (p=0.022) increased significantly after LI along with PI compared to the baseline at the final visit. LRC of a new parameter, BMO-MRW, and LRC of RNFL were relatively low in patients with PACG, following LI along with PI. After widening of the anterior chamber angle and decrease of IOP due to LI plus PI, PACG might show stable structural prognosis assessed by OCT.

Effects of Deep Optic Nerve Head Structures on Bruch's Membrane Opening- Minimum Rim Width and Peripapillary Retinal Nerve Fiber Layer

PurposeTo explore the effects of deep optic nerve head (ONH) structures on Bruch's membrane opening (BMO)-minimum rim width (MRW) and peripapillary retinal nerve fiber layer thickness (pRNFLT) in healthy eyes. DesignProspective cross-sectional study MethodsTwo hundred five healthy eyes of 141 subjects (mean ± standard deviation of age and axial length (AXL): 46.9±10.0 years and 24.79±1.15 mm) were enrolled. Best fit multivariable linear mixed models identified factors associated with BMO-MRW and pRNFLT. Explanatory variables included age, sex, AXL, BMO and anterior scleral canal opening (ASCO) area and ovality, magnitude of BMO and ASCO shift, peripapillary choroidal thickness, lamina cribrosa (LC) parameters, prelaminar thickness and peripapillary scleral (PPS) angle. ResultsThinner BMO-MRW was associated with older age, smaller ASCO/BMO offset magnitude, larger BMO area, thinner prelaminar thickness, deeper LC, and thinner pRNFLT (p=0.011, <0.001, 0.004, <0.001, <0.001, <0.001 respectively). Thinner pRNFLT was associated with shorter AXL, smaller ASCO area, a more posteriorly bowed PPS, shallower LC and thinner BMO-MRW. (p=0.030, 0.002, 0.035, 0.012, <0.001 respectively) ConclusionsBMO-MRW and pRNFLT were influenced by several deep ONH structures such as BMO and ASCO position shift, BMO or ASCO area, prelaminar thickness, PPS bowing and LC depth in addition to patient characteristics such as age and AXL. The degree and/or direction of associations varied between deep ONH structures and BMO-MRW or pRNFLT. Despite both BMO-MRW and pRNFLT being surrogate parameters for RGC loss, a complex relationship with ONH deep-layer morphology was indicated.

Association of Bergmeister Papilla and Deep Optic Nerve Head Structures With Prelaminar Schisis of Normal and Glaucomatous Eyes

To investigate factors associated with the severity of prelaminar schisis (PLS) in heathy subjects and glaucoma patients. Prospective cross-sectional study METHODS: Two hundred seventeen eyes of 217 subjects (110 normal eyes and 107 open angle glaucoma eyes). Frequency and severity of PLS were compared between normal and glaucomatous eyes. Multivariate logistic models were used to assess factors associated with the severity of PLS. Factors considered were age, axial length, glaucomatous damage indices, Bruch's membrane opening (BMO) and anterior scleral canal opening parameters, tractional forces (posterior vitreous staging and the presence of Bergmeister's papilla), circumpapillary choroidal thickness, lamina cribrosa (LC) parameters and peripapillary scleral (PPS) angle. The frequency of PLS was 70.9% in normal eyes and 72.0% in glaucomatous eyes. There was no difference in frequency and severity between the groups. The presence of Bergmeister's papilla was the strongest predictor of a more severe PLS in both normal and glaucomatous eyes (OR: 9.78, 12.5; both p<0.001). A larger PPS angle in normal eyes (OR:1.19; p=0.003) and a larger BMO area and a deeper LC depth in glaucomatous eyes (OR: 1.08, 1.05; both p=0.038) were associated with severity of PLS. The severity of PLS was strongly associated with the presence of Bergmeister's papilla suggesting a traction-related phenomenon. Correlation of PLS severity with larger BMO area and deeper LC depth, which are ONH structures associated with glaucoma, suggested its possible relationship with glaucomatous damage.

Minimum Rim Width and Peripapillary Retinal Nerve Fiber Layer Thickness for Diagnosing Early to Moderate Glaucoma.

In a cross-sectional study from a Brazilian multiracial population, minimum rim width (MRW) and peripapillary retinal nerve fiber layer thickness measurements from OCT showed comparable diagnostic performance in discriminating early to moderate glaucoma from healthy eyes. The purpose of this study is to compare the ability of MRW and peripapillary retinal nerve fiber layer thickness (RNFLT) measurements in discriminating early to moderate glaucoma from healthy eyes in a Brazilian population. A total of 155 healthy controls and 118 patients with mild to moderate glaucoma (mean deviation >-12 dB) underwent MRW and RNFLT measurements with optical coherence tomography. Only 1 eye per patient was included in the analysis. A receiver operating characteristic (ROC) regression model was used to evaluate the diagnostic accuracy of MRW and RNFLT, whereas adjusting for age and Bruch membrane opening area. Sensitivities at fixed specificities of 95% were calculated for each parameter. Global RNFLT and MRW showed comparable area under the ROC curves [0.93 (0.91-0.96) and 0.93 (0.89-0.96), respectively; P =0.973]. Both parameters had similar sensitivities (75% vs. 74%, respectively; P =0.852) at a fixed specificity of 95%. The best sector for diagnosing glaucoma for both parameters was the temporal inferior sector, which showed an area under the ROC curve of 0.93 (0.87-0.96) for RNFLT and 0.91 (0.86-0.95) for MRW ( P =0.320). The temporal inferior sector showed similar sensitivities for RNFLT and MRW measurements (83% vs. 77%, respectively) at a fixed specificity of 95% (P =0.230). MRW and RNFLT measurements showed comparable diagnostic performance in discriminating early to moderate glaucoma from healthy eyes in a Brazilian multiracial population.

Identification of Factors Associated With the Development of Optic Disc Edema During Spaceflight

Approximately 70% of crew members who complete long-duration missions to the International Space Station develop signs of optic disc edema, a hallmark finding of spaceflight-associated neuro-ocular syndrome. The onset and magnitude of edema differ across individuals, and the reason for this variability remains unknown. Identifying risk factors for spaceflight-induced disc edema is important because this condition may become more severe during extended-duration missions to the moon and Mars and could be associated with irreversible vision loss. To assess whether preflight indicators of crowded optic nerve head morphology, other ocular measures (such as choroid thickness and axial length), body weight, body mass index, sex, age, and previous flight experience are associated with optic disc edema development. This cohort study analyzed ocular, body weight, and demographic data collected from 31 US and international crew members before, during, and after spaceflight at the NASA Johnson Space Center and International Space Station. Ocular factors assessed included preflight and in-flight peripapillary total retinal thickness, minimum rim width, optic cup volume, mean cup depth, mean cup width, cup-disc ratio, Bruch membrane opening area, retinal nerve fiber layer thickness, choroid thickness, axial length, and refractive error. In addition, body weight, body mass index, sex, age, and previous spaceflight experience were assessed for associations with optic disc edema development. The data were analyzed from August 2021 to June 2022. Approximately 6 to 12 months of spaceflight. In-flight increases in peripapillary total retinal thickness. Linear mixed models were used to assess for associations between a wide range of risk factors and in-flight increases in peripapillary total retinal thickness, which is a sensitive objective measure for detecting optic disc edema. This study included 31 International Space Station crew members with a mean (SD) age of 46.9 (6.0) years (25 men [80.6%]). During spaceflight, mean (SE) peripapillary total retinal thickness increased from 392.0 (5.8) μm to 430.2 (9.6) μm (P < .001), and greater individual changes were associated with smaller preflight cup volume (slope [SE], -62.8 [18.9]; P = .002), shallower preflight cup depth (slope [SE], -0.11 [0.03]; P < .001), and narrower preflight cup width (slope [SE], -0.03 [0.01]; P = .03). No associations were observed between changes in peripapillary total retinal thickness and any other variable evaluated. Findings of this cohort study suggest that smaller optic cup morphology may be associated with optic disc edema development during spaceflight. Crew members with this cup profile may benefit from enhanced ophthalmic monitoring during spaceflight and use of countermeasures against spaceflight-associated neuro-ocular syndrome.

Interplay between intraocular and intracranial pressure effects on the optic nerve head in vivo

Intracranial pressure (ICP) has been proposed to play an important role in the sensitivity to intraocular pressure (IOP) and susceptibility to glaucoma. However, the in vivo effects of simultaneous, controlled, acute variations in ICP and IOP have not been directly measured. We quantified the deformations of the anterior lamina cribrosa (ALC) and scleral canal at Bruch's membrane opening (BMO) under acute elevation of IOP and/or ICP.Four eyes of three adult monkeys were imaged in vivo with OCT under four pressure conditions: IOP and ICP either at baseline or elevated. The BMO and ALC were reconstructed from manual delineations. From these, we determined canal area at the BMO (BMO area), BMO aspect ratio and planarity, and ALC median depth relative to the BMO plane. To better account for the pressure effects on the imaging, we also measured ALC visibility as a percent of the BMO area. Further, ALC depths were analyzed only in regions where the ALC was visible in all pressure conditions. Bootstrap sampling was used to obtain mean estimates and confidence intervals, which were then used to test for significant effects of IOP and ICP, independently and in interaction.Response to pressure manipulation was highly individualized between eyes, with significant changes detected in a majority of the parameters. Significant interactions between ICP and IOP occurred in all measures, except ALC visibility. On average, ICP elevation expanded BMO area by 0.17 mm2 at baseline IOP, and contracted BMO area by 0.02 mm2 at high IOP. ICP elevation decreased ALC depth by 10 μm at baseline IOP, but increased depth by 7 μm at high IOP. ALC visibility decreased as ICP increased, both at baseline (−10%) and high IOP (−17%). IOP elevation expanded BMO area by 0.04 mm2 at baseline ICP, and contracted BMO area by 0.09 mm2 at high ICP. On average, IOP elevation caused the ALC to displace 3.3 μm anteriorly at baseline ICP, and 22 μm posteriorly at high ICP. ALC visibility improved as IOP increased, both at baseline (5%) and high ICP (8%).In summary, changing IOP or ICP significantly deformed both the scleral canal and the lamina of the monkey ONH, regardless of the other pressure level. There were significant interactions between the effects of IOP and those of ICP on LC depth, BMO area, aspect ratio and planarity. On most eyes, elevating both pressures by the same amount did not cancel out the effects. Altogether our results show that ICP affects sensitivity to IOP, and thus that it can potentially also affect susceptibility to glaucoma.

Clinical Utility of Bruch Membrane Opening-Minimum Rim Width for Detecting Early Glaucoma in Myopic Eyes.

Bruch membrane opening-minimum rim width (BMO-MRW) is overall a useful parameter for diagnosing early glaucoma in myopic eyes. The aim of this study was to determine the diagnostic value of BMO-MRW compared with peripapillary retinal nerve fiber layer (pRNFL) thickness for detecting early glaucoma in patients with moderate to severe myopia. One eye was randomly selected from each of the 253 subjects (127 normal controls, 82 with glaucoma suspect, and 44 with early glaucoma). All patients underwent visual acuity testing, refractive error assessment, slit-lamp inspection, intraocular pressure measurement, fundus photography, perimetry. BMO-MRW and pRNFL thickness data were obtained using spectral-domain optical coherence tomography. Area under the receiver operating characteristic curves (AUC) for global and sectoral thickness parameters were calculated. Global analyses for the discrimination of early glaucoma in all myopic subjects showed comparable AUCs between BMO-MRW and pRNFL thickness [AUC 0.952 (95% confidence interval, 0.918-0.975) and 0.934 (95% confidence interval, 0.896-0.961), respectively, P=0.345]. However, in sectoral analysis, BMO-MRW showed significantly better diagnostic performance than pRNFL thickness except for the superotemporal sector. The AUC for discriminating early glaucoma from glaucoma suspect, BMO-MRW showed statistically better diagnostic performance in the inferotemporal, inferonasal, superonasal, and nasal sectors. When dividing the subject based on a threshold Bruch membrane opening (BMO) area of 2.5 mm2, the diagnostic power of BMO-MRW was generally lower except for the inferonasal sector in the subgroup with a large BMO area. BMO-MRW was overall a useful parameter for diagnosing early glaucoma in myopic eyes. However, its diagnostic performance was decreased in myopic eyes with large BMO and there were no significant differences from pRNFL thickness.

Ultra-High Field Magnetic Resonance Imaging of the Retrobulbar Optic Nerve, Subarachnoid Space, and Optic Nerve Sheath in Emmetropic and Myopic Eyes.

PurposeWe aimed to image the optic nerve, subarachnoid space and optic nerve sheath in emmetropes and myopes ultra-high field (7-Tesla) magnetic resonance imaging (MRI). We targeted the retrobulbar distance of approximately 3 mm behind the eyeball, an area of clinical interest because of optic nerve sheath distensibility and pressure-related enlargement.MethodsEleven emmetropes (+0.75 to −0.50D, aged 20–41 years) and 10 myopes (−4.5 to −12D, aged 21–37 years) participated. Cross-sectional area of the optic nerve, subarachnoid space and optic nerve sheath at approximately 3 mm behind the eye were measured from two-dimensional T2-weighted coronal oblique MRI images obtained through the left optic nerve. Axial length of the left eye was measured from T2-weighted axial MRI images. In nine emmetropes and seven myopes, the optic nerve head was imaged with optical coherence tomography to compare retrobulbar and intraocular measures.ResultsRetrobulbar optic nerve, subarachnoid space and optic nerve sheath dimensions differed between myopes and emmetropes. Myopes tended to have smaller optic nerve and subarachnoid space. Longer MRI-derived axial length was associated with smaller optic nerve area (P = 0.03). Bruch's membrane opening area did not predict retrobulbar optic nerve area (P = 0.48).ConclusionsThis study demonstrates the feasibility of using 7-Tesla MRI to measure optic nerve, subarachnoid space, and optic nerve sheath dimensions behind the eye. In healthy adults, the retrobulbar optic nerve and subarachnoid space size are influenced by the degree of myopia.Translational Relevanceultra-high field MRI is a practical tool for assessing the morphometry of the optic nerve and surrounding anatomy behind the eye.

Rate of Change in Bruch's Membrane Opening-Minimum Rim Width and Peripapillary RNFL in Early Normal Tension Glaucoma.

Background: to investigate the rate of change (ROC) of Bruch’s membrane opening minimum rim width (BMO-MRW) and peripapillary retinal nerve fiber layer (RNFL) thickness in early normal tension glaucoma (NTG) patients. Methods: in this longitudinal cohort study, 115 subjects (115 eyes) diagnosed as early NTG (mean deviation > −6.0 dB) and who had completed more than five times of spectral-domain optical coherence tomography (OCT) tests with acceptable quality were included. Measurement of BMO-MRW and RNFL were performed at 3-month intervals by OCT. Linear mixed-effects model was employed to calculate the ROC in global region and six Garway-Heath sectors with adjusting age, sex, and BMO area. Results: Average follow-up was 20.99 ± 6.99 months with OCT number of 7.54 ± 2.12. Baseline intraocular pressure was 14.72 ± 2.70 mmHg and MD was −2.73 ± 2.26 dB. ROC of global BMO-MRW was −2.06 ± 0.65 µm/yr and RNFL was −0.96 ± 0.16 µm/yr (p = 0.098). The most rapid ROC was in inferotemporal sector (BMO-MRW: −3.02 ± 0.88 µm/yr, RNFL: −1.96 ± 0.36 µm/yr) followed by superotemporal sector. Conclusion: The ROC of BMO-MRW, the new parameter along with that of RNFL should be considered in the management of early NTG. BMO-MRW may show visible reduction ROC better than RNFL to detect early progression in early NTG when visual field may not show significant change.

Optical Coherence Tomography Optic Nerve Head Morphology in Myopia I: Implications of Anterior Scleral Canal Opening Versus Bruch Membrane Opening Offset

To measure the magnitude and direction of anterior scleral canal opening (ASCO) offset relative to the Bruch membrane opening (BMO) (ASCO/BMO offset) to characterize neural canal obliqueness and minimum cross-sectional area (NCMCA) in 69 highly myopic and 138 healthy, age-matched, control eyes. Cross-sectional study. Using optical coherence tomography (OCT) scans of the optic nerve head (ONH), BMO and ASCO were manually segmented and their centroids and size and shape were calculated. ASCO/BMO offset magnitude and direction were measured after projecting the ASCO/BMO centroid vector onto the BMO plane. Neural canal axis obliqueness was defined as the angle between the ASCO/BMO centroid vector and the vector perpendicular to the BMO plane. NCMCA was defined by projecting BMO and ASCO points onto a plane perpendicular to the neural canal axis and measuring their overlapping area. ASCO/BMO offset magnitude was greater (highly myopic eyes 264.3 ± 131.1μm; healthy control subjects 89.0 ± 55.8μm, P < .001, t test) and ASCO centroid was most frequently nasal relative to BMO centroid (94.2% of eyes) in the highly myopic eyes. BMO and ASCO areas were significantly larger (P < .001, t test), NCMCA was significantly smaller (P < .001), and all 3 were significantly more elliptical (P ≤ .001) in myopic eyes. Neural canal obliqueness was greater in myopic (65.17° ± 14.03°) compared with control eyes (40.91° ± 16.22°; P < .001, t test). Our data suggest that increased temporal displacement of BMO relative to the ASCO, increased BMO and ASCO area, decreased NCMCA, and increased neural canal obliqueness are characteristic components of ONH morphology in highly myopic eyes.

The optic nerve head, lamina cribrosa, and nerve fiber layer in non-myopic and myopic children

The purpose of this study was to evaluate the optic nerve head, lamina cribrosa, retina, and choroid in school age children using spectral domain optical coherence tomography (SD-OCT) and to assess these structural parameters in relation to age, axial length, and refractive error. Healthy children, ages 11.15 ± 2.62 years (range 6–15 years, n = 53), underwent cycloplegic autorefraction, biometry, and SD-OCT imaging in both eyes. Images were analyzed using custom written programs in MATLAB, after adjustment for lateral magnification. Peripapillary retinal nerve fiber layer (RNFL) thickness, retinal and choroidal thicknesses, Bruch's membrane opening (BMO) area, minimum rim width (MRW), and anterior lamina cribrosa surface depth (ALCSD) were determined and analyzed with age, axial length, and refraction. Results show that axial length increased and refractive error became more myopic with increasing age (R2 = 0.25, β = 0.18, P < 0.0001 and R2 = 0.27, β = −0.37, P < 0.0001, respectively). Minimum foveal thickness and central 1 mm retinal thickness increased with increasing age (R2 = 0.15, β = 2.38, P < 0.01 and R2 = 0.11, β = 3.16, P < 0.05, respectively). Age-adjusted raw values for peripapillary RNFL thickness decreased with increasing axial length (R2 = 0.11, β = −3.18, P < 0.05); however, this relationship was not present when image magnification was corrected (R2 = 0.07, β = 2.72, P = 0.09). BMO area increased with myopic refractive error (R2 = 0.16, β = −0.10, P < 0.01). Age-adjusted vertical cup-to-disc ratio decreased with increasing axial length and myopic refractive error (R2 = 0.12, β = −0.05, P < 0.05 and R2 = 0.11, β = 0.03, P = 0.05, respectively). Mean MRW, mean ALCSD, and peripapillary choroidal thickness were not associated with age, axial length, or refraction. Mean MRW was significantly thinner in eyes with deeper ALCS (R2 = 0.41, β = −0.83, P < 0.0001). These findings provide normal values for retinal and optic nerve head parameters in school age children, and also suggest that ocular remodeling occurs in some structures in school age children with normal eye growth and during early stages of myopia development.

Comparison of Rate of Change between Bruch's Membrane Opening Minimum Rim Width and Retinal Nerve Fiber Layer in Eyes Showing Optic Disc Hemorrhage

To investigate and compare the longitudinal rate of change of Bruch's membrane opening minimum rim width (BMO-MRW) and peripapillary retinal nerve fiber layer (RNFL) thickness in eyes showing optic disc hemorrhage(DH). Observational case series. A total of 82 subjects(82 eyes) showing DH who had undergone more than five reliable spectral-domain optical coherence tomography (OCT) tests were included. BMO-MRW and RNFL were measured with OCT at 3-month intervals. The rates of change in global and each Garway-Heath sector were calculated with a linear mixed-effects model after adjusting for age, sex, and BMO area. The mean follow-up period was 21.57 ± 7.88months with a mean number of 7.88 ± 2.39 OCT tests. Baseline demographics were age (58.37 ± 10.65 y); 46.3% were female; and the mean deviation was-4.41 ± 5.04 dB. The global rate of change in BMO-MRW was-3.507 ± 0.675μm/y and in-1.404 ± 0.208μm/y in RNFL. The rate of change was the greatest in the inferotemporal sector, which was-9.141 ± 1.254μm/y in BMO-MRW and-4.204 ± 0.490μm/y in the RNFL. The rate of change was significantly greater in BMO-MRW than in the RNFL in all sectors, except for the nasal sector (P < .05). Percentage of reduction was significantly greater in BMO-MRW than in RNFL in the inferotemporal and superotemporal sectors (P < .05). BMO-MRW showed a significantly greater rate of change than RNFL in eyes showing DH, especially in the inferotemporal and superotemporal sectors in percentage of reduction. Thus, it may be more advantageous to detect glaucomatous progression earlier in BMO-MRW than in the RNFL in eyes showing DH that are more likely to progress.

Neuroretinal rim response to transient changes in intraocular pressure in healthy non-human primate eyes

Optic nerve head (ONH) neuroretinal rim thickness, quantified as minimum rim width (BMO-MRW), is a sensitive measure for assessing early glaucomatous disease. The BMO-MRW is sensitive to transient fluctuations in intraocular pressure (IOP), but the time course over which BMO-MRW decreases and recovers with changes in IOP remains unknown. The goal of this study was to investigate the dynamics of BMO-MRW changes over 2-h periods of mild or moderate IOP elevation, and subsequent recovery, in healthy non-human primate eyes. Eight non-human primates were included in the study. For each animal, in two different sessions separated by at least 2 weeks, the anterior chamber IOP of one eye was maintained at either 25 mmHg or 40 mmHg for 2 h and, subsequently, at 10 mmHg for 2 h. For the duration of anterior chamber cannulation, optical coherence tomography (OCT) radial scans centered on the ONH were acquired every 5 min and used to quantify BMO-MRW. An exponential decay or rise to maximum function was used to determine the extent and rate of structural change. Additionally, Bruch's membrane opening (BMO) area, BMO height/displacement, and BMO-referenced anterior lamina cribrosa surface depth (BMO-ALCSD) were computed from radial scans. A circular scan was used to quantify retinal nerve fiber layer thickness (RNFLT) and circumpapillary choroid thickness. The primary results demonstrated that the BMO-MRW changed over an extended duration, while BMO displacement was rapid and remained stable with sustained IOP. The mean maximum predicted BMO-MRW thinning following 2 h of IOP elevation was significantly related to pressure (34.2 ± 13.8 μm for an IOP of 25 mmHg vs 40.5 ± 12.6 μm for 40 mmHg, p = 0.03). The half-life for BMO-MRW thinning was 21.9 ± 9.2 min for 25 mmHg and 20.9 ± 4.2 min for 40 mmHg, not significantly different between IOP levels (p = 0.76). Subsequently, after 2 h of IOP at 10 mmHg, all animals exhibited partial recovery of BMO-MRW with similar degrees of persistent residual thinning for the two IOP levels (21.5 ± 13.7 vs 21.0 ± 12.3 μm, p = 0.88). Similar to BMO-MRW, choroid thickness exhibited gradual thinning with IOP elevation and residual thinning following IOP reduction. However, there was no significant change in BMO area or BMO-ALCSD in either experimental session. The RNFLT gradually decreased over the duration of IOP elevation, with continued decreases following IOP reduction for the 40 mmHg session, resulting in total changes from baseline of −2.24 ± 0.81 and −2.45 ± 1.21 μm for 25 and 40 mmHg, respectively (p < 0.001). The sum of the results demonstrate that the ONH neural tissue is sensitive to changes in IOP, the effects of which are gradual over an extended time course and different for increased vs. decreased pressure. Understanding the duration over which IOP influences BMO-MRW has important implications for studies investigating the effects of IOP on the ONH. Additionally, individual variability in ONH response to IOP may improve our understanding of the risk and progression of disease.

Analysis of peripapillary vessel density and Bruch's membrane opening-based neuroretinal rim parameters in glaucoma using OCT and OCT-angiography.

To compare peripapillary vessel density (VD) measured by spectral domain optical coherence tomography angiography (SD-OCT-A) with morphometric parameters assessing the neuroretinal rim based on Bruch's membrane opening (BMO) by spectral domain optical coherence tomography (SD-OCT) in glaucoma. In this non-interventional cohort study, 50 eyes of 25 consecutively enrolled patients with diagnosis of glaucoma underwent SD-OCT and SD-OCT-A imaging of the optic nerve head (ONH). BMO minimum rim width (BMO-MRW) and area (BMO-MRA) as well as peripapillary retinal nerve fiber layer (RNFL) thickness were compared to peripapillary VD in the RNFL layer around the ONH. Mean BMO-MRW was 221.46 ± 81.5 µm, mean BMO-MRA was 1.05 ± 0.04 mm2, mean RNFL thickness was 72.46 ± 23.16 µm, and mean VD was 43.8 ± 11.4%. VD was significantly lower when morphometric parameters had lower thickness values (p < 0.01). Correlation coefficients and their 95%- confidence intervals (95%-CI) with VD were r = 0.53 (95%-CI: 0.21-0.77) for BMO-MRW, r = 0.55 (95%-CI: 0.21-0.77) for BMO-MRA, and r = 0.57 (95%-CI: 0.13-0.73) for RNFL thickness. Intra-individual VD in both eyes correlated with r = 0.72 (p < 0.001), mean VD was comparable (p = 0.6). Eyes with high global RNFL thickness (>90 µm) showed less VD variance (σ2 = 48.1) compared to eyes with highly reduced RNFL thickness (<65 µm; σ2 = 82.0). Best corrected visual acuity, perimetric mean defect, and PSD correlated significantly with VD (95%-CI: -0.66 to -0.10, 0.16 to 0.6, and -0.65 to -0.02, respectively). Peripapillary vessel density measured by SD-OCT angiography correlates significantly with Bruch's membrane opening-based parameters measured by SD-OCT in glaucoma patients.

Effect of Trabeculectomy on OCT Measurements of the Optic Nerve Head Neuroretinal Rim Tissue

Ophthalmologists commonly perform glaucoma surgery to treat progressive glaucoma. Few studies have examined the stability of OCT neuroretinal rim parameters after glaucoma surgery for ongoing detection of glaucoma progression. Longitudinal cohort study. 20 eyes (16 subjects) with primary open angle glaucoma who had undergone a trabeculectomy. We calculated the change in OCT parameters (minimum rim area (MRA), minimum rim width (MRW), Bruch's membrane opening (BMO) area, mean cup depth (MCD), anterior lamina cribrosa surface depth (ALCSD), prelaminar tissue thickness (PLTT), retinal nerve fiber layer thickness (RFNLT) during an interval from the visit before the surgery to the visit after the surgery, a span of approximately 6-months. We also calculated changes in the same eyes over two separate 6-month intervals that did not contain trabeculectomy to serve as control. We compared these intervals using a generalized linear model (with compound symmetry correlation structure), accounting for the correlation between time intervals for the same eye. MRW, MRA, angle above the reference plane for MRW and MRA, BMO area, MCD, mean ALCSD, PLTT, RNFLT and visual field parameters (mean deviation (MD), pattern standard deviation (PSD), and visual field index (VFI)). The intervals containing trabeculectomy showed a significant decrease in intraocular pressure (-9.2 mmHg, p<.001) when compared to control intervals. Likewise, the following neuroretinal rim parameters showed significant changes with trabeculectomy: increased MRW (+6.04μm, p=.001), increased MRA (+0.014mm2, p=.024), increased angle above reference plane of MRW (+2.64°, p<.001), decreased MCD (-11.6μm, p=.007), and decreased mean ALCSD (-18.91μm, p=.006). This is consistent with an increase in rim tissue thickness and a more anterior position of the ILM and ALCS relative to the BMO plane. Conversely, RNFLT change was not significantly different between trabeculectomy and control intervals (p=.37). Trabeculectomy resulted in anatomical changes to the ONH rim associated with reduced glaucomatous cupping. The RNFL thickness may be a more stable measure of disease progression that clinicians can use to monitor across time intervals containing glaucoma surgery.

Influence of Bruch's Membrane Opening Area in Diagnosing Glaucoma With Neuroretinal Parameters From Optical Coherence Tomography

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. Retrospective, cross-sectional study. 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. 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). 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.

Longitudinal Analysis of Bruch Membrane Opening Morphometry in Myopic Glaucoma.

To investigate longitudinal changes in morphologic characteristics of the BMO in control and glaucomatous subjects. A total of 53 myopic eyes (17 control, 6 suspect, 20 stable glaucoma, and 10 progressing glaucoma) were followed for an average of 4.2±1.4 years and imaged at the baseline and 2 follow-up appointments using a 1060 nm swept-source optical coherence tomography system. BM and BMO were segmented, and 4 morphometric BMO parameters (area, ellipse ratio, nonplanarity, and depth) were measured. There were no significant changes in BMO area or ellipse ratio for all groups. BMO nonplanarity was shown to increase in the glaucoma groups. BMO depth relative to BM increased in all groups except the suspects (control: 8.1 µm/y, P=0.0001; stable glaucoma: 3.5 µm/y, P=0.0001; progressing glaucoma: 14.0 µm/y, P=0.0026). In linear mixed-model analysis, axial length was positively associated with BMO area in all groups except for progressing glaucoma, and with BMO nonplanarity in stable glaucoma. It was not a significant factor to the slopes of the BMO parameters in the ANCOVA analysis of slopes. Longitudinally, BMO increased in nonplanarity in the glaucoma eyes, and its axial position relative to BM became more posterior in both control and glaucoma eyes.

Effect of optic disc size on correlation between Bruch's membrane opening-minimum rim width and peripapillary retinal nerve fibre layer thickness.

To investigate the effect of optic disc size on correlation between Bruch's membrane opening-minimum rim width (BMO-MRW) and peripapillary retinal nerve fibre layer (RNFL) thickness from three scan circles. In this retrospective, observational study, non-glaucomatous eyes without visible RNFL defect or visual field loss were included. A total of 101 subjects were distributed into three groups based on disc size: group 1 (n = 26), small disc (disc area < 1.63 mm2); group 2 (n = 40), regular size disc (disc area: 1.63~2.43 mm2); and group 3 (n = 35), large disc (disc area > 2.43 mm2). All patients underwent standard ophthalmic examinations including confocal scanning laser tomography and spectral-domain optical coherence tomography. Global BMO-MRW was the thickest in group 1 (314.96 ± 60.38 μm, BMO area: 1.72 ± 0.45 mm2), followed by that in group 2 (259.03 ± 40.04 μm, BMO area: 2.29 ± 0.31 mm2). It was the thinnest in group 3 (236.74 ± 31.21 μm, BMO area: 2.91 ± 0.31 mm2; p < 0.001, Kruskal-Wallis test). Correlation between global BMO-MRW value and RNFL thickness was the strongest in group 3 (Spearman's rho = 0.656), followed by that in group 2 (rho = 0.572). It was the weakest in group 1 (rho = 0.147). There was no significant difference in global RNFL thickness by disc size from either the 3.5 mm, 4.1 mm, or 4.7 mm diameter scan circles (all p > 0.05). Correlation between BMO-MRW values and RNFL thickness differed significantly according to disc size. Thus, when we assess BMO-MRW in relation to RNFL thickness, disc size may need to be taken into consideration.

OCT-Detected Optic Nerve Head Neural Canal Direction, Obliqueness, and Minimum Cross-Sectional Area in Healthy Eyes

To assess anterior scleral canal opening (ASCO) offset relative to Bruch's membrane opening (BMO) (ASCO/BMO offset) so as to determine neural canal direction, obliqueness, and minimum cross-sectional area (NCMCA) in 362 healthy eyes. Cross-sectional study. After optical coherence tomography optic nerve head and retinal nerve fiber layer thickness (RNFLT) imaging, BMO and ASCO were manually segmented. Planes, centroids, size, and shape were calculated. Neural canal direction was defined by projecting the neural canal axis vector (connecting BMO and ASCO centroids) onto the BMO plane. Neural canal obliqueness was defined by the angle between the neural canal axis and the BMO plane perpendicular vector. NCMCA was defined by projecting BMO and ASCO points onto a neural canal axis perpendicular plane and measuring the area of overlap. The angular distance between superior and inferior peak RNFLT was measured, and correlations between RFNLT, BMO, ASCO, ASCO/BMO offset, and NCMCA were assessed. Mean (SD) NCMCA was significantly smaller than either the BMO or ASCO area (1.33 (0.42), 1.82 (0.38), 2.22 (0.43) mm2, respectively), and most closely correlated to RNFLT (P < .001, R2= 0.158). Neural canal direction was most commonly superior-nasal (55%). Mean neural canal obliqueness was 39.4° (17.3°). The angular distance between superior and inferior peak RNFLT correlated to neural canal direction (P ≤ .008, R2= 0.093). ASCO/BMO offset underlies neural canal direction, obliqueness, and NCMCA. RNFLT is more strongly correlated to NCMCA than to BMO or ASCO, and its peripapillary distribution is influenced by neural canal direction.