Factors Influencing Optical Coherence Tomography Peripapillary Choroidal Thickness: A Multicenter Study.

Purpose:To quantify peripapillary choroidal thickness (PCT) and the factors that influence it in healthy participants who represent the racial and ethnic composition of the U.S. population. Methods:A total of 362 healthy participants underwent optical coherence tomography (OCT) enhanced depth imaging of the optic nerve head with a 24 radial B-scan pattern aligned to the fovea to Bruch's membrane opening axis. Bruch's membrane, anterior scleral canal opening (ASCO), and the anterior scleral surface were manually segmented. PCT was measured at 100, 300, 500, 700, 900, and 1100 μm from the ASCO globally and within 12 clock-hour sectors. The effects of age, axial length, intraocular pressure, ethnicity, sex, sector, and ASCO area on PCT were assessed by ANOVA and univariable and multivariable regressions. Results:Globally, PCT was thicker further from the ASCO border and thinner with older age, longer axial length, larger ASCO area, European descent, and female sex. Among these effectors, age and axial length explained the greatest proportion of variance. The rate of age-related decline increased further from the ASCO border. Sectorally, the inferior-temporal sectors were thinnest (10.7%-20.0% thinner than the thickest sector) and demonstrated a higher rate of age-related loss (from 15.6% to 20.7% faster) at each ASCO distance. Conclusions:In healthy eyes, PCT was thinnest in the inferior temporal sectors and thinner PCT was associated with older age, European descent, longer axial length, larger ASCO area, and female sex. Among these associations, age had the strongest influence, and its effect was greatest within the inferior temporal sectors

Viscoelastic material properties of the peripapillary sclera in normal and early-glaucoma monkey eyes

PURPOSE. To test the hypothesis that changes in the viscoelastic material properties of peripapillary sclera are present within monkey eyes at the onset of early experimental glaucoma detected by confocal scanning laser tomography (CSLT). METHODS. Short-term (3-9 weeks), moderate (Յ44 mm Hg) intraocular pressure (IOP) elevation was induced in one eye of each of eight male monkeys by lasering the trabecular meshwork. This procedure generated early experimental glaucoma, defined as the onset of CSLT-detected optic nerve head (ONH) surface change, in the treated eye. Scleral tensile specimens from the superior and inferior quadrants of the eight earlyglaucoma eyes were subjected to uniaxial stress relaxation and tensile tests to failure and the results compared with similar data obtained in a previous study of 12 normal (nonglaucomatous) eyes. Linear viscoelastic theory was used to characterize viscoelastic material property parameters for each specimen. Differences in each parameter due to quadrant and treatment were assessed by analysis of variance (ANOVA). RESULTS. Peripapillary sclera from the early-glaucoma eyes exhibited an equilibrium modulus (7.46 Ϯ 1.58 MPa) that was significantly greater than that measured in normal eyes (4.94 Ϯ 1.22 MPa; mean Ϯ 95% confidence interval, P Ͻ 0.01, ANOVA). Quadrant differences were not significant for the viscoelastic parameters within each treatment group. CONCLUSIONS. The long-term viscoelastic material properties of monkey peripapillary sclera are altered by exposure to moderate, short-term, chronic IOP elevations and these alterations are present at the onset of CSLT-detected glaucomatous damage to the ONH. Damage to and/or remodeling of the extracellular matrix of these tissues may underlie these changes in scleral material properties. (Invest Ophthalmol Vis Sci. 2005;46: 540 -546 1 The finite element method is a computer-based engineering technique that estimates the stresses (force/cross-sectional area) and strains (local deformation under those stresses) within a complex load-bearing structure. 2 The important aspects of a finite element model are the three-dimensional geometry and material properties of the load-bearing structure and the appropriate boundary and mechanical loading conditions. 2 Within such models of the monkey ONH, scleral material properties are needed to characterize accurately the important transition between the peripapillary sclera and the peripheral laminar beams. To characterize the material properties of peripapillary sclera, we constructed a controlled-environment testing apparatus capable of performing uniaxial biomechanical testing of soft tissues in tension. The overall response of a tissue to a load is the combination of instantaneous (elastic) and time-dependent (viscous) responses, which are governed by its viscoelastic material properties. All soft tissues are viscoelastic, and the characterization of the instantaneous and time-dependent aspects of these material properties is important in understanding a tissue's behavior as a load-bearing structure and its response to short-and long-term changes in the applied load. Accurate characterization of a tissue's material properties can lead to a broader understanding of the mechanisms that underlie tissue damage, as well as determine the resultant altered load-bearing behavior of a remodeled or healed tissue. In a previous report we performed quadrant-based uniaxial tensile testing of peripapillary sclera from normal rabbit and normal monkey eyes 3 and found no differences in the viscoelastic material properties of the peripapillary sclera by quadrant (superior, inferior, nasal, and temporal to the ONH) in either species. In addition, when normal rabbit and monkey sclera were compared with one another, peripapillary sclera from monkey eyes was stiffer and showed slower stress relaxation than sclera from rabbit eyes. The present study tests the hypothesis that changes in the viscoelastic material properties of monkey peripapillary sclera are present at the earliest detectable stage of glaucomatous damage to the ONH, defined as the onset of confocal scanning laser tomography (CSLT)-detected ONH surface change. MATERIALS AND METHODS Animals, Scleral Specimens, and Study Design All animals were treated in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. In the present study, a single scleral tensile specimen was generated from either the superior or inferior quadrant of eight eyes with experimental early glaucoma, yielding four early-glaucoma specimens for each quadrant. Each specimen underwent a multistage uniaxial tensile test. ViscoelasFrom th

The Morphological Difference Between Glaucoma and Other Optic Neuropathies (Video)

The defining features of a "glaucomatous" optic neuropathy include "glaucomatous" "cupping" which is difficult to describe and therefore phenotype except when "deep" cupping is present and is accompanied by some degree of excavation of the rim tissues beneath Bruch's Membrane Opening (BMO) and/or the anterior scleral canal opening. Discussion of what constitutes "glaucomatous" cupping are made difficult by the fact that "cupping" is a clinical term which is used to describe optic nerve head (ONH) structural change in all forms of optic neuropathy, however "cupping" is also used as a synonym for the pathophysiology of glaucomatous damage to the ONH. Because the clinical and pathophysiologic contexts for "cupping" are seldom clarified there is a confusing literature regarding the presence, importance and meaning of "cupping" in a variety of disorders.KBDdoonglaucoma; KBDglaucoma; KBDcuppedopticnerve; Medical Knowledge; Patient Care; Practice-Based Learning and Improvemen

The Morphological Difference Between Glaucoma and Other Optic Neuropathies

The defining features of a "glaucomatous" optic neuropathy include "glaucomatous" "cupping" which is difficult to describe and therefore phenotype except when "deep" cupping is present and is accompanied by some degree of excavation of the rim tissues beneath Bruch's Membrane Opening (BMO) and/or the anterior scleral canal opening. Discussion of what constitutes "glaucomatous" cupping are made difficult by the fact that "cupping" is a clinical term which is used to describe optic nerve head (ONH) structural change in all forms of optic neuropathy, however "cupping" is also used as a synonym for the pathophysiology of glaucomatous damage to the ONH. Because the clinical and pathophysiologic contexts for "cupping" are seldom clarified there is a confusing literature regarding the presence, importance and meaning of "cupping" in a variety of disorders.KBDdoonglaucoma; KBDglaucoma; KBDcuppedopticnerve; Medical Knowledge; Patient Care; Practice-Based Learning and Improvement; ICopticdisccuppin

The Morphological Difference Between Glaucoma and Other Optic Neuropathies

The defining features of a glaucomatous optic neuropathy include glaucomatous cupping which is difficult to describe and therefore phenotype except when deep cupping is present and is accompanied by some degree of excavation of the rim tissues beneath Bruchs Membrane Opening (BMO) and/or the anterior scleral canal opening. Discussion of what constitutes glaucomatous cupping are made difficult by the fact that cupping is a clinical term which is used to describe optic nerve head (ONH) structural change in all forms of optic neuropathy, however cupping is also used as a synonym for the pathophysiology of glaucomatous damage to the ONH. Because the clinical and pathophysiologic contexts for cupping are seldom clarified there is a confusing literature regarding the presence, importance and meaning of cupping in a variety of disorders

Does optic nerve head surface topography change prior to loss of retinal nerve fiber layer thickness: a test of the site of injury hypothesis in experimental glaucoma.

PURPOSE:To test the hypothesis that optic nerve head (ONH) deformation manifesting as changes in its mean surface height precedes thinning of the peripapillary retinal nerve fiber layer (RNFL) in experimental glaucoma (EG). METHODS:68 rhesus macaque monkeys each had three or more baseline imaging sessions under manometric intraocular pressure (IOP) control to obtain average RNFL thickness (RNFLT) and the ONH surface topography parameter mean position of the disc (MPD). Laser photocoagulation was then applied to the trabecular meshwork of one eye to induce chronic, mild-to-moderate IOP elevation and bi-weekly imaging continued. Event analysis was applied to determine for each parameter when an 'endpoint' occurred (signficant change from baseline) for eight different endpoint criteria. Specificity was assessed in the group of 68 fellow control eyes. Classical signal detection theory and survival analysis were used to compare MPD with RNFLT. RESULTS:Regardless of the endpoint criterion, endpoints were always more frequent for MPD than for RNFLT. The discriminability index (d') was 2.7 ± 0.2 for MPD and 1.9 ± 0.2 for RNFLT (p<0.0001). Endpoints were reached by MPD an average of 1-2 months earlier than by RNFLT (p<0.01). At the onset of the first specific, detectable MPD change in EG eyes, there was still no significant change in RNFLT on average (p=0.29) and only 25% of individual eyes exhibited signficant reduction. In contrast, at onset of signficant RNFLT change, MPD had already changed an average of 101 µm from baseline (p<0.0001) and 71% of the individual eyes had exhibited significant change. The magnitude of MPD change was more than could be explained on the basis of axon loss alone. CONCLUSIONS:This study demonstrates that the average surface height of the ONH changes prior to any detectable loss of average peripapillary RNFL thickness in non-human primate eyes with experimental glaucoma

L: Structural and functional abnormalities of retinal ganglion cells measured in vivo at the onset of optic nerve head surface change in experimental glaucoma. Invest Ophthalmol Vis Sci 2012

PURPOSE. To compare peripapillary retinal nerve fiber layer thickness (RNFLT), RNFL retardance, and retinal function at the onset of optic nerve head (ONH) surface topography change in experimental glaucoma (EG). METHODS. Thirty-three rhesus macaques had three or more weekly baseline measurements in both eyes of ONH surface topography, peripapillary RNFLT, RNFL retardance, and multifocal electroretinography (mfERG). Laser photocoagulation was then applied to the trabecular meshwork of one eye to induce chronic elevation of IOP and weekly recordings continued alternating between ONH surface topography and RNFLT during one week and RNFL retardance and mfERG the next week. Data were pooled for the group at the onset of ONH surface topography change in each EG eye, which was defined as the first date when either the mean position of the disc (MPD) fell below the 95% confidence limit of each eye&apos;s individual baseline range and/or when the topographic change analysis (TCA) map was subjectively judged as having demonstrated change, whichever came first. Analysis of variance with post hoc tests corrected for multiple comparisons were used to assess parameter changes. RESULTS. At onset of ONH surface topography change, there was no significant difference for RNFLT versus baseline or fellow control eyes. RNFL retardance and mfERG were significantly reduced in the recordings just prior (median of 9 days) to ONH onset (P &lt; 0.01) and had progressed significantly (P &lt; 0.001) an average of 17 days later (median of 7 days after ONH onset). RNFLT did not exhibit significant thinning until 15 days after onset of ONH surface topography change (P &lt; 0.001). CONCLUSIONS. These results support the hypothesis that during the course of glaucomatous neurodegeneration, axonal cytoskeletal and retinal ganglion cell functional abnormalities exist before thinning of peripapillary RNFL axon bundles begins. (Invest Ophthalmol Vis Sci

Lamina Cribrosa Microarchitecture in Monkey Early Experimental Glaucoma: Global Change

PURPOSE. The purpose of this study was to characterize experimental glaucoma (EG) versus control eye differences in lamina cribrosa (LC), beam diameter (BD), pore diameter (PD), connective tissue volume fraction (CTVF), connective tissue volume (CTV), and LC volume (LV) in monkey early EG. METHODS. Optic nerve heads (ONHs) of 14 unilateral EG and 6 bilateral normal (BN) monkeys underwent three-dimensional reconstruction and LC beam segmentation. Each beam and pore voxel was assigned a diameter based on the largest sphere that contained it before transformation to a common cylinder with inner, middle, and outer layers. Full-thickness and layer averages for BD, PD, CTVF, CTV, and LV were calculated for each ONH. Beam diameter and PD distributions for each ONH were fit to a gamma distribution and summarized by scale and shape parameters. Experimental glaucoma and depth effects were assessed for each parameter by linear mixed-effects (LME) modeling. Animal-specific EG versus control eye differences that exceeded the maximum intereye difference among the six BN animals were considered significant. RESULTS. Overall EG eye mean PD was 12.8% larger (28.2 6 5.6 vs. 25.0 6 3.3 lm), CTV was 26.5% larger (100.06 6 47.98 vs. 79.12 6 28.35 3 10 6 lm 3 ), and LV was 40% larger (229.29 6 98.19 vs. 163.63 6 39.87 3 10 6 lm 3 ) than control eyes (P 0.05, LME). Experimental glaucoma effects were significantly different by layer for PD (P ¼ 0.0097) and CTVF (P &lt; 0.0001). Pore diameter expanded consistently across all PDs. Experimental glaucoma eyespecific parameter change was variable in magnitude and direction. CONCLUSIONS. Pore diameter, CTV, and LV increase in monkey early EG; however, EG eyespecific change is variable and includes both increases and decreases in BD and CTVF