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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.

Both plastic (permanent) and hypercompliant deformation of the lamina cribrosa and anterior scleral canal wall are present in young adult monkey eyes with early experimental glaucoma. These findings suggest that damage to the ONH connective tissues occurs early in the monkey model of experimental glaucoma.

Rosario Hernandez This article is dedicated to Rosario Hernandez for her warm support of my own work and her genuine enthusiasm for the work of her colleagues throughout her career. I first met Rosario as a research fellow in Harry Quigley’s laboratory between 1991 and 1993. Along with Harry, John Morrison, Elaine Johnson, Abe Clark, Colm O’Brien and many others, Rosario’s work has provided lamina cribrosa astrocyte cellular mechanisms that are biomechanically plausible and in so doing provided credibility to early notions of the optic nerve head (ONH) as a biomechanical structure. We owe a large intellectual debt to Rosario for her dogged persistence in the characterization of the ONH astrocyte and lamina cribrosacyte in age and disease. Two questions run through her work and remain of central importance today. First, how do astrocytes respond to and alter the biomechanical environment of the ONH and the physiologic stresses created therein? Second, how do these physiologic demands on the astrocyte influence their ability to deliver the support to retinal ganglion cell axon transport and flow against the translaminar pressure gradient? The purpose of this article is to summarize what is known about the biomechanical determinants of retinal ganglion cell axon physiology within the ONH in the optic neuropathy of aging and Glaucoma. My goal is to provide a biomechanical framework for this discussion. This framework assumes that the ONH astrocytes and glia fundamentally support and influence both the lamina cribrosa extracellular matrix and retinal ganglion cell axon physiology. Rosario Hernandez was one of the first investigators to recognize the implications of this unique circumstance. Many of the ideas contained herein have been initially presented within or derived from her work (Hernandez, M.R., 2000. The optic nerve head in glaucoma: role of astrocytes in tissue remodeling. Prog Retin Eye Res. 19, 297–321.; Hernandez, M.R., Pena, J.D., 1997. The optic nerve head in glaucomatous optic neuropathy. Arch Ophthalmol. 115, 389–395.).

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 Open-angle glaucoma patients 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 non-oblique), and presence of Bruch’s membrane overhang over border tissue. Optic disc stereo-photographs were co-localized to SD-OCT data with customized software. The frequency with which the disc margin identified in stereo-photographs coincided with (1) Bruch’s membrane opening, defined as the innermost edge of Bruch’s membrane; (2) Bruch’s membrane/border tissue, defined as any aspect of either, outside Bruch’s membrane opening 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 SD-OCT structures coinciding with the disc margin in stereo-photographs. Results There were 30 patients (10 with each type of disc damage) and 10 controls, with median (range) age 68.1 (42–86) and 63.5 (42–77) years respectively. Although 28 (93%) patients 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. While 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, outside Bruch’s membrane opening. Bruch’s membrane overhang was regionally present in the majority of glaucoma patients and controls, however, in most cases not visible as the disc margin. Conclusions The clinically perceived disc margin is most likely not the SD-OCT detected innermost edge of Bruch’s membrane. These findings have important implications for the automated detection of the disc margin and estimates of the neuroretinal rim.

Profound fixed posterior deformation and thickening of the lamina are accompanied by mild posterior deformation and thinning of the scleral flange and peripapillary sclera at the onset of confocal scanning laser tomography (CSLT)-detected ONH surface change in young adult monkey eyes with early experimental glaucoma.

Purpose To review and interpret optic nerve head (ONH) anatomy detected with spectral domain optical coherence tomography (SD-OCT) pertaining to the clinical examination of the optic disc and propose that a paradigm change for clinical assessment of the ONH is necessary. Design Perspective. Methods Presently, the clinician evaluates neuroretinal rim health according to the appearance of the optic disc, the clinically visible surface of the ONH. Recent anatomic findings with SD-OCT have challenged the basis and accuracy of current rim evaluation. We demonstrate why incorporation of SD-OCT imaging of the ONH into the clinical examination of the disc is required. Results Disc margin based rim evaluation lacks a solid anatomic basis and results in variably inaccurate measurements for two reasons. First, the clinically visible disc margin is an unreliable outer border of rim tissue due to clinically and photographically invisible extensions of Bruch’s membrane. Second, rim tissue orientation is not considered in width measurements. We propose alternative anatomically and geometrically accurate SD-OCT based approaches for rim assessment that have enhanced detection of glaucoma. We also argue for new data acquisition and analysis strategies with SD-OCT that account for the large inter-individual variability in the angle between the fovea and ONH. Conclusions We propose a 4-point paradigm change for clinical assessment of the ONH that is anchored to the eye-specific anatomy and geometry of the ONH and fovea. Our approach is designed to enhance the accuracy and consistency of rim width, as well as peripapillary and macular intraretinal thickness measurements.

Purpose To characterize the trabeculated connective tissue microarchitecture of the lamina cribrosa (LC) in terms of total connective tissue volume (CTV), connective tissue volume fraction (CTVF), predominant beam orientation, and material anisotropy in monkeys with early experimental glaucoma (EG). Methods The optic nerve heads from three monkeys with unilateral EG and four bilaterally normal monkeys were three dimensionally reconstructed from tissues perfusion fixed at an intraocular pressure of 10 mm Hg. A three-dimensional segmentation algorithm was used to extract a binary, voxel-based representation of the porous LC connective tissue microstructure that was regionalized into 45 subvolumes, and the following quantities were calculated: total CTV within the LC, mean and regional CTVF, regional predominant beam orientation, and mean and regional material anisotropy. Results Regional variation within the laminar microstructure was considerable within the normal eyes of all monkeys. The laminar connective tissue was generally most dense in the central and superior regions for the paired normal eyes, and laminar beams were radially oriented at the periphery for all eyes considered. CTV increased substantially in EG eyes compared with contralateral normal eyes (82%, 44%, 45% increases; P < 0.05), but average CTVF changed little (−7%, 1%, and −2% in the EG eyes). There were more laminar beams through the thickness of the LC in the EG eyes than in the normal controls (46%, 18%, 17% increases). Conclusions The substantial increase in laminar CTV with little change in CTVF suggests that significant alterations in connective and nonconnective tissue components in the laminar region occur in the early stages of glaucomatous damage.