Optic Nerve Head Tissue Research Articles

Association between esodeviation and primary open-angle glaucoma: the 2010–2011 Korea National Health and Nutrition Examination Survey

Background/AimsTo evaluate the association between strabismus and primary open-angle glaucoma (POAG) in a representative Korean population.MethodsA total of 11 114 participants aged 20 years or older in the Korea National...

Imaging video plethysmography shows reduced signal amplitude in glaucoma patients in the area of the microvascular tissue of the optic nerve head

PurposeTo measure parameters of the cardiac cycle-induced pulsatile light absorption signal (plethysmography signal) of the optic nerve head (ONH) and to compare parameters between normal subjects and patients with different stages of glaucoma.Patients and methodsA recently developed video ophthalmoscope was used to acquire short video sequences (10 s) of the ONH. After image registration and trend correction, the pulsatile changing light absorption at the ONH tissue (excluding large vessels) was calculated. The changing light absorption depends on the pulsatile changing blood volume. Various parameters, including peak amplitude, steepness, time-to-peak, full width at half maximum (FWHM), and pulse duration, were calculated for averaged individual pulses (heartbeats) of the plethysmography signal. This method was applied to 19 healthy control subjects and 91 subjects with ocular hypertension, as well as different stages of primary open-angle glaucoma (17 subjects with ocular hypertension, 24 with preperimetric glaucoma, and 50 with perimetric glaucoma).ResultsCompared to the normal subjects, significant reductions (p < 0.001) in peak amplitude and steepness were observed in the group of perimetric glaucoma patients, but no significant difference was found for time-to-peak, FWHM, and pulse duration. Peak amplitude and steepness showed high correlations with RNFL thickness (p < 0.001).ConclusionsThe presented low-cost video-ophthalmoscope permits measurement of the plethysmographic signal of the ONH tissue and calculation of different blood flow-related parameters. The reduced values of the amplitude and steepness parameters in perimetric glaucoma patients suggest decreased ONH perfusion and blood volume. This outcome is in agreement with results from other studies using OCT angiography and laser speckle flowgraphy, which confirm reduced capillary density in these patients.Registration site: www.clinicaltrials.gov, Trial registration number: NCT00494923

Expression profile analysis to predict potential biomarkers for glaucoma: BMP1, DMD and GEM.

PurposeGlaucoma is the second commonest cause of blindness. We assessed the gene expression profile of astrocytes in the optic nerve head to identify possible prognostic biomarkers for glaucoma.MethodA total of 20 patient and nine normal control subject samples were derived from the GSE9944 (six normal samples and 13 patient samples) and GSE2378 (three normal samples and seven patient samples) datasets, screened by microarray-tested optic nerve head tissues, were obtained from the Gene Expression Omnibus (GEO) database. We used a weighted gene coexpression network analysis (WGCNA) to identify coexpressed gene modules. We also performed a functional enrichment analysis and least absolute shrinkage and selection operator (LASSO) regression analysis. Genes expression was represented by boxplots, functional geneset enrichment analyses (GSEA) were used to profile the expression patterns of all the key genes. Then the key genes were validated by the external dataset.ResultsA total 8,606 genes and 19 human optic nerve head samples taken from glaucoma patients in the GSE9944 were compared with normal control samples to construct the co-expression gene modules. After selecting the most common clinical traits of glaucoma, their association with gene expression was established, which sorted two modules showing greatest correlations. One with the correlation coefficient is 0.56 (P = 0.01) and the other with the correlation coefficient is −0.56 (P = 0.01). Hub genes of these modules were identified using scatterplots of gene significance versus module membership. A functional enrichment analysis showed that the former module was mainly enriched in genes involved in cellular inflammation and injury, whereas the latter was mainly enriched in genes involved in tissue homeostasis and physiological processes. This suggests that genes in the green–yellow module may play critical roles in the onset and development of glaucoma. A LASSO regression analysis identified three hub genes: Recombinant Bone Morphogenetic Protein 1 gene (BMP1), Duchenne muscular dystrophy gene (DMD) and mitogens induced GTP-binding protein gene (GEM). The expression levels of the three genes in the glaucoma group were significantly lower than those in the normal group. GSEA further illuminated that BMP1, DMD and GEM participated in the occurrence and development of some important metabolic progresses. Using the GSE2378 dataset, we confirmed the high validity of the model, with an area under the receiver operator characteristic curve of 85%.ConclusionWe identified several key genes, including BMP1, DMD and GEM, that may be involved in the pathogenesis of glaucoma. Our results may help to determine the prognosis of glaucoma and/or to design gene- or molecule-targeted drugs.

IOP-induced regional displacements in the optic nerve head and correlation with peripapillary sclera thickness

Mechanical insult induced by intraocular pressure (IOP) is likely a driving force in the disease process of glaucoma. This study aimed to evaluate regional displacements in human optic nerve head (ONH) and peripapillary tissue (PPT) in response to acute IOP elevations, and their correlations with morphological characteristics of the posterior eye. Cross-sectional (2D) images of the ONH and PPT in 14 globes of 14 human donors were acquired with high-frequency ultrasound during whole globe inflation from 5 to 30 mm Hg. High-frequency ultrasound has a spatial resolution of tens of micrometers and is capable of imaging through the ONH and PPT thickness. Tissue displacements were calculated using a correlation-based speckle tracking algorithm for a dense matrix of kernels covering the 2D imaging plane. The ONH was manually segmented in the ultrasound B-mode images acquired at 5 mmHg based on echogenicity. The lamina cribrosa (LC) boundaries were visible in eight of the fourteen eyes and the LC region was segmented using a semi-automated superpixel-based method. The ONH had larger radial displacement than the PPT in all tested eyes and the difference increased with increasing IOP. A significant negative correlation was found between ONH-PPT displacement difference and PPT thickness (p < 0.05), while no significant correlations were found between ONH-PPT displacement difference and other morphological parameters including PPT radius of curvature, scleral canal size, LC thickness and anterior LC surface depth. Within the ONH, the radial displacement decreased in the region anterior to and across LC but not in the region posterior to LC. Finite element models using simplified geometry and material properties confirmed the role of LC in reducing the overall ONH radial displacements, but did not predict the displacement gradient change observed experimentally. These results suggested that a thinner PPT may be associated with a larger relative posterior motion of the ONH with respect to the surrounding PPT and the LC may play a major role in preventing excessive posterior displacement of ONH during acute IOP elevations.

Role of radially aligned scleral collagen fibers in optic nerve head biomechanics

Collagen fibers organized circumferentially around the canal in the peripapillary sclera are thought to provide biomechanical support to the sensitive tissues within the optic nerve head (ONH). Recent studies have demonstrated the existence of a family of fibers in the innermost sclera organized radially from the scleral canal. Our goal was to determine the role of these radial fibers in the sensitivity of scleral canal biomechanics to acute increases in intraocular pressure (IOP). Following the same general approach of previous parametric sensitivity studies, we created nonlinear generic finite element models of a posterior pole with various combinations of radial and circumferential fibers at an IOP of 0 mmHg. We then simulated the effects of normal and elevated IOP levels (15 and 30 mmHg). We monitored four IOP-induced geometric changes: peripapillary sclera stretch, scleral canal displacement, lamina cribrosa displacement, and scleral canal expansion. In addition, we examined the radial (maximum tension) and through-thickness (maximum compression) strains within the ONH tissues. Our models predicted that: 1) radial fibers reduced the posterior displacement of the lamina, especially at elevated IOP; 2) radial fibers reduced IOP-induced radial strain within the peripapillary sclera and retinal tissue; and 3) a combination of radial and circumferential fibers maintained strains within the ONH at a level similar to those conferred by circumferential fibers alone. In conclusion, radial fibers provide support for the posterior globe, additional to that provided by circumferential fibers. Most importantly, a combination of both fiber families can better protect ONH tissues from excessive IOP-induced deformation than either alone.

Ocular hypertension suppresses homeostatic gene expression in optic nerve head microglia of DBA/2\u2009J mice

Glaucoma is the leading cause of irreversible vision loss. Ocular hypertension is a major risk factor for glaucoma and recent work has demonstrated critical early neuroinflammatory insults occur in the optic nerve head following ocular hypertension. Microglia and infiltrating monocytes are likely candidates to drive these neuroinflammatory insults. However, the exact molecular identity / transcriptomic profile of microglia following ocular hypertensive insults is unknown. To elucidate the molecular identity of microglia after long-term exposure to ocular hypertension, we used a mouse model of glaucoma (DBA/2 J). We performed RNA-sequencing of microglia mRNA from the optic nerve head at a time point following ocular hypertensive insults, but preceding detectable neurodegeneration (with microglia identified as being CD45lo/CD11b+/CD11c−). Furthermore, RNA-sequencing was performed on optic nerve head microglia from mice treated with radiation therapy, a potent therapy preventing neuroinflammatory insults. Transcriptomic profiling of optic nerve head microglia mRNA identifies metabolic priming with marked changes in mitochondrial gene expression, and changes to phagocytosis, inflammatory, and sensome pathways. The data predict that many functions of microglia that help maintain tissue homeostasis are affected. Comparative analysis of these data with data from previously published whole optic nerve head tissue or monocyte-only samples from DBA/2 J mice demonstrate that many of the neuroinflammatory signatures in these data sets arise from infiltrating monocytes and not reactive microglia. Finally, our data demonstrate that prophylactic radiation therapy of DBA/2 J mice potently abolishes these microglia metabolic transcriptomic changes at the same time points. Together, our data provide a unique resource for the community to help drive further hypothesis generation and testing in glaucoma.

Finite element analysis of trans-lamina cribrosa pressure difference on optic nerve head biomechanics: the Beijing Intracranial and Intraocular Pressure Study.

The present study aims to assess the potential difference of biomechanical response of the optic nerve head to the same level of trans-lamina cribrosa pressure difference (TLCPD) induced by a reduced cerebrospinal fluid pressure (CSFP) or an elevated intraocular pressure (IOP). A finite element model of optic nerve head tissue (pre- and post-laminar neural tissue, lamina cribrosa, sclera, and pia mater) was constructed. Computed stresses, deformations, and strains were compared at each TLCPD step caused by reduced CSFP or elevated IOP. The results showed that elevating TLCPD increased the strain in optic nerve head, with the largest strains occurring in the neural tissue around the sclera ring. Relative to a baseline TLCPD of 10 mmHg, at a same TLCPD of 18 mmHg, the pre-laminar neural tissue experienced 11.10% first principal strain by reduced CSFP and 13.66% by elevated IOP, respectively. The corresponding values for lamina cribrosa were 6.09% and 6.91%. In conclusion, TLCPD has a significant biomechanical impact on optic nerve head tissue and, more prominently, within the pre-laminar neural tissue and lamina cribrosa. Comparatively, reducing CSFP showed smaller strain than elevating IOP even at a same level of TLCPD on ONH tissue, indicating a different potential role of low CSFP in the pathogenesis of glaucoma.

Translaminar Autonomous System Model for the Modulation of Intraocular and Intracranial Pressure in Human Donor Posterior Segments.

There is a current unmet need for a new preclinical human model that can target disease etiology ex vivo using intracranial pressure (ICP) and intraocular pressure (IOP) whichcan identify various pathogenic paradigms related to the glaucoma pathogenesis. Ex vivo human anterior segment perfusion organ culture models have previously been successfully utilized and applied as effective technologies for the discovery of glaucoma pathogenesis and testing of therapeutics. Preclinical drug screening and research performed on ex vivo human organ systems can be more translatable to clinical research. This article describes in detail the generation and operation of a novel ex vivo human translaminar pressure model called the translaminar autonomous system (TAS). The TAS model can independently regulate ICP and IOP using human donor posterior segments. The model allows for studying pathogenesis in a preclinical manner. It can reduce the use of living animals in ophthalmic research. In contrast to in vitro experimental models, optic nerve head (ONH) tissue structure, complexity, and integrity can also be maintained within the ex vivo TAS model.

Sub-region-Specific Optic Nerve Head Glial Activation in Glaucoma.

Glaucoma, a multifactorial neurodegenerative disease characterized by progressive loss of retinal ganglion cells and their axons in the optic nerve, is a leading cause of irreversible vision loss. Intraocular pressure (IOP) is a risk factor for axonal damage, which initially occurs at the optic nerve head (ONH). Complex cellular and molecular mechanisms involved in the pathogenesis of glaucomatous optic neuropathy remain unclear. Here we define early molecular events in the ONH in an inherited large animal glaucoma model in which ONH structure resembles that of humans. Gene expression profiling of ONH tissues from rigorously phenotyped feline subjects with early-stage glaucoma and precisely age-matched controls was performed by RNA-sequencing (RNA-seq) analysis and complementary bioinformatic approaches applied to identify molecular processes and pathways of interest. Immunolabeling supported RNA-seq findings while providing cell-, region-, and disease stage-specific context in the ONH in situ. Transcriptomic evidence for cell proliferation and immune/inflammatory responses is identifiable in early glaucoma, soon after IOP elevation and prior to morphologically detectable axon loss, in this large animal model. In particular, proliferation of microglia and oligodendrocyte precursor cells is a prominent feature of early-stage, but not chronic, glaucoma. ONH microgliosis is a consistent hallmark in both early and chronic stages of glaucoma. Molecular pathways and cell type-specific responses strongly implicate toll-like receptor and NF-κB signaling in early glaucoma pathophysiology. The current study provides critical insights into molecular pathways, highly dependent on cell type and sub-region in the ONH even prior to irreversible axon degeneration in glaucoma.

In Vivo Measurements of Prelamina and Lamina Cribrosa Biomechanical Properties in Humans

PurposeTo develop and use a custom virtual fields method (VFM) to assess the biomechanical properties of human prelamina and lamina cribrosa (LC) in vivo.MethodsClinical data of 20 healthy, 20 ocular hypertensive (OHT), 20 primary open-angle glaucoma, and 16 primary angle-closure glaucoma eyes were analyzed. For each eye, the intraocular pressure (IOP) and optical coherence tomography (OCT) images of the optic nerve head (ONH) were acquired at the normal state and after acute IOP elevation. The IOP-induced deformation of the ONH was obtained from the OCT volumes using a three-dimensional tracking algorithm and fed into the VFM to extract the biomechanical properties of the prelamina and the LC in vivo. Statistical measurements and P values from the Mann-Whitney-Wilcoxon tests were reported.ResultsThe average shear moduli of the prelamina and the LC were 64.2 ± 36.1 kPa and 73.1 ± 46.9 kPa, respectively. The shear moduli of the prelamina of healthy subjects were significantly lower than those of the OHT subjects. Comparisons between healthy and glaucoma subjects could not be made robustly due to a small sample size.ConclusionsWe have developed a methodology to assess the biomechanical properties of human ONH tissues in vivo and provide preliminary comparisons in healthy and OHT subjects. Our proposed methodology may be of interest for glaucoma management.

The optic nerve head vasoreactive response to systemic hyperoxia and visual field defect progression in open-angle glaucoma, a pilot study.

To investigate the effect of optic nerve head (ONH) tissue vasoreactivity on glaucoma visual field defect progression. This prospective, longitudinal study comprised 28 eyes of 16 patients with open-angle glaucoma. Baseline data were obtained from oxygen inhalation testing, including laser speckle flowgraphy measurements of tissue-area mean blur rate (MT), which represents ONH tissue blood flow, and the mean percentage change in MT (MT-change). Follow-up data were collected for at least 2years, including at least 5 reliable visual field tests. The average total deviation (TD) was calculated in each sector of the Garway-Heath map; in this study, superior, central and inferior TD corresponded to inferior, temporal and superior MT or MT-change, respectively. MT and MT-change in three sectors per eye were included as explanatory variables in a multivariable linear mixed-effects model, with TD slope set as the response variable. At baseline, lower MT and higher diastolic blood pressure were associated with lower MT-change (p<0.05). Additionally, MT-change significantly contributed to TD slope in the corresponding sectors (β=0.41, p=0.01). Weaker ONH tissue vasoreactivity to systemic hyperoxia, assessed with laser speckle flowgraphy, was associated with lower baseline ONH tissue blood flow, higher diastolic blood pressure and rapid visual field defect progression. Laser speckle flowgraphy variables during oxygen provocation testing may represent potentially useful predictive biomarkers of glaucoma progression.

A neuroglia-based interpretation of glaucomatous neuroretinal rim thinning in the optic nerve head.

Neuroretinal rim thinning (NRR) is a characteristic glaucomatous optic disc change. However, the precise mechanism of the rim thinning has not been completely elucidated. This review focuses on the structural role of the glioarchitecture in the formation of the glaucomatous NRR thinning. The NRR is a glia-framed structure, with honeycomb geometry and mechanically reinforced astrocyte processes along the transverse plane. When neural damage selectively involves the neuron and spares the glia, the gross structure of the tissue is preserved. The disorganization and loss of the glioarchitecture are the two hallmarks of optic nerve head (ONH) remodeling in glaucoma that leads to the thinning of NRR tissue upon axonal loss. This is in contrast to most non-glaucomatous optic neuropathies with optic disc pallor where hypertrophy of the glioarchitecture is associated with the seemingly absent optic disc cupping. Arteritic anterior ischemic optic neuropathy is an exception where pan-necrosis of ONH tissue leads to NRR thinning. Milder ischemia indicates selective neuronal loss that spares glia in non-arteritic anterior ischemic optic neuropathy. The biological reason is the heterogeneous glial response determined by the site, type, and severity of the injury. The neuroglial interpretation explains how the cellular changes underlie the clinical findings. Updated understandings on glial responses illustrate the mechanical, microenvironmental, and microglial modulation of activated astrocytes in glaucoma. Findings relevant to the possible mechanism of the astrocyte death in advanced glaucoma are also emerging. Ultimately, a better understanding of glaucomatous glial response may lead to glia-targeting neuroprotection in the future.

A Deep Learning Approach to Denoise Optical Coherence Tomography Images of the Optic Nerve Head

Optical coherence tomography (OCT) has become an established clinical routine for the in vivo imaging of the optic nerve head (ONH) tissues, that is crucial in the diagnosis and management of various ocular and neuro-ocular pathologies. However, the presence of speckle noise affects the quality of OCT images and its interpretation. Although recent frame-averaging techniques have shown to enhance OCT image quality, they require longer scanning durations, resulting in patient discomfort. Using a custom deep learning network trained with 2,328 ‘clean B-scans’ (multi-frame B-scans; signal averaged), and their corresponding ‘noisy B-scans’ (clean B-scans + Gaussian noise), we were able to successfully denoise 1,552 unseen single-frame (without signal averaging) B-scans. The denoised B-scans were qualitatively similar to their corresponding multi-frame B-scans, with enhanced visibility of the ONH tissues. The mean signal to noise ratio (SNR) increased from 4.02 ± 0.68 dB (single-frame) to 8.14 ± 1.03 dB (denoised). For all the ONH tissues, the mean contrast to noise ratio (CNR) increased from 3.50 ± 0.56 (single-frame) to 7.63 ± 1.81 (denoised). The mean structural similarity index (MSSIM) increased from 0.13 ± 0.02 (single frame) to 0.65 ± 0.03 (denoised) when compared with the corresponding multi-frame B-scans. Our deep learning algorithm can denoise a single-frame OCT B-scan of the ONH in under 20 ms, thus offering a framework to obtain superior quality OCT B-scans with reduced scanning times and minimal patient discomfort.

Genome-wide association analysis of 95 549 individuals identifies novel loci and genes influencing optic disc morphology.

Optic nerve head morphology is affected by several retinal diseases. We measured the vertical optic disc diameter (DD) of the UK Biobank (UKBB) cohort (N = 67 040) and performed the largest genome-wide association study (GWAS) of DD to date. We identified 81 loci (66 novel) for vertical DD. We then replicated the novel loci in International Glaucoma Genetic Consortium (IGGC, N = 22 504) and European Prospective Investigation into Cancer-Norfolk (N = 6005); in general the concordance in effect sizes was very high (correlation in effect size estimates 0.90): 44 of the 66 novel loci were significant at P < 0.05, with 19 remaining significant after Bonferroni correction. We identified another 26 novel loci in the meta-analysis of UKBB and IGGC data. Gene-based analyses identified an additional 57 genes. Human ocular tissue gene expression analysis showed that most of the identified genes are enriched in optic nerve head tissue. Some of the identified loci exhibited pleiotropic effects with vertical cup-to-disc ratio, intraocular pressure, glaucoma and myopia. These results can enhance our understanding of the genetics of optic disc morphology and shed light on the genetic findings for other ophthalmic disorders such as glaucoma and other optic nerve diseases.

Increased Optic Nerve Head Capillary Blood Flow in Early Primary Open-Angle Glaucoma.

PurposeBlood flow in the optic nerve head (ONH) is known to be reduced in eyes with advanced glaucoma. However, experimental results from non-human primates suggest an initial increase in ONH blood flow at the earliest stages of damage. This study assesses flow and pulsatile hemodynamics across a range of severities to test the hypothesis that this also occurs in human glaucoma.MethodsLaser speckle flowgraphy was used to measure average mean blur rate (MBRave) within ONH tissue (a correlate of capillary blood flow) and the pulsatile waveform in 93 eyes with functional loss and 74 glaucoma suspect/fellow eyes without functional loss. These were compared against results from 92 healthy control eyes. Parameters produced by the instrument's software were age-corrected, then compared between groups using generalized estimating equation models.ResultsThe mean MBRave in the control eyes was 12.5 units. In glaucoma suspect/fellow eyes, the mean was 16.4 units, higher with P < 0.0001. In eyes with functional loss, the mean was 13.8 units, lower than eyes without functional loss with P < 0.0001, although still higher than control eyes with P = 0.0096. Analysis of the pulsatile waveform suggested that the deceleration in flow as it approaches its maximum across the cardiac cycle was delayed in glaucoma.ConclusionsBlood flow within ONH capillaries was higher in glaucoma suspect eyes than in healthy controls. It was less elevated in eyes that had developed functional loss. The mechanisms causing these changes and their relation to concurrent changes in pulsatile hemodynamics remain under investigation.

Compressive mechanical properties of rat and pig optic nerve head

Glaucoma is the leading cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP), the primary risk factor for glaucoma, is thought to induce abnormally high strains in optic nerve head (ONH) tissues, which ultimately result in retinal ganglion cell damage and vision loss. The mechanisms by which excessive deformations result in vision loss remain incompletely understood. The ability of computational and in vitro models of the ONH to provide insight into these mechanisms, in many cases, depends on our ability to replicate the physiological environment, which in turn requires knowledge of tissue biomechanical properties. The majority of mechanical data published to date regarding the ONH has been obtained from tensile testing, yet compression has been shown to be the main mode of deformation in the ONH under elevated IOP. We have thus tested pig and rat ONH tissue using unconfined cyclic compression. The material constants C1, obtained from fitting the stress vs. strain data with a neo-Hookean material model, were 428 [367, 488] Pa and 64 [53, 76] Pa (mean [95% Confidence Interval]) for pig and rat optic nerve head, respectively. Additionally, we investigated the effects of strain rate and tissue storage on C1 values. These data will inform future efforts to understand and replicate the in vivo biomechanical environment of the ONH.

Sectoral Differences in the Association of Optic Nerve Head Blood Flow and Glaucomatous Visual Field Defect Severity and Progression.

To investigate sectoral differences in the relationship between optic nerve head tissue blood flow, anatomically corresponding visual field defect severity, and future progression. This retrospective longitudinal medical chart review comprised 508 eyes of 319 open-angle glaucoma patients (mean deviation: -9.2 ± 7.0 dB), followed for an average of 4.7 ± 1.1 years; an average 11.7 ± 3.7 visual field tests were performed. Average total deviation (TD) was calculated in the superior, central, and inferior sectors of the Humphrey 24-2 program. The optic nerve head was divided to obtain inferior, temporal, and superior tissue-area mean blur rate (MT), derived from laser speckle flowgraphy. At baseline, the correlation between MT and TD was compared in anatomically corresponding sectors. We performed a multivariate analysis to determine the contribution of baseline MT to corresponding TD slope and to determine background factors influencing superior to temporal MT. We used a linear-mixed effect model for the statistical analysis. At baseline, the highest β coefficients were found between MT-superior and TD-inferior, MT-temporal and TD-central, and between MT-inferior and TD-superior, in that order (β = 0.38, β = 0.27, β = 0.26, respectively). MT-superior and MT-temporal independently contributed to corresponding TD slope (P < 0.05). Male sex, high body mass index, and the prevalence of sleep apnea syndrome were contributing factors to lower superior to temporal MT (P < 0.05). Review of medical history, measurements of systemic variables, and laser speckle flowgraphy parameters might help clinicians to predict visual field defect severity and progression.

Mechanical Deformation of Human Optic Nerve Head and Peripapillary Tissue in Response to Acute IOP Elevation.

PurposeTo measure the deformation of the human optic nerve head (ONH) and peripapillary tissue (PPT) in response to acute intraocular pressure (IOP) elevation.MethodsThe ONH and PPT of 14 human donor globes were imaged with high-frequency ultrasonography during inflation testing from 5 to 30 mm Hg. A correlation-based speckle tracking algorithm was used to compute tissue displacements, and the through-thickness, in-plane, and shear strains were calculated by using least-squares strain estimation methods. The ONH and PPT were segmented along the anterior-posterior direction and the nasal-temporal direction. Regional displacements and strains were analyzed and compared.ResultsThe ONH displaced more posteriorly than the PPT in response to an acute IOP increase. Scleral canal expansion was minimal but correlated with ONH posterior displacement at all IOP levels. Through-thickness compression was concentrated in the anterior of both the ONH and the PPT. Shear was concentrated in the vicinity of the canal with higher shear in the peripheral ONH than the central ONH and higher shear in the PPT near the scleral canal than that further away from the canal.ConclusionsHigh-resolution ultrasound speckle tracking showed a displacement mismatch between the ONH and the PPT, larger compressive strains in the direction of IOP loading in the anterior ONH and PPT, and higher shear strains in the periphery of ONH in response to acute IOP elevation in the human eye. These findings delineate the deformation patterns within and around the ONH and may help understand IOP-associated optic nerve damage.

Changes in the optic nerve head induced by horizontal eye movements.

PurposeTo investigate the effect of eye movement on the optic nerve head (ONH) using swept-source optical coherence tomography (SS-OCT), and to measure the degree of ONH changes.MethodsWe enrolled 52 healthy subjects, 20 to 40 years of age, and performed a prospective observational study. Both ONH and macula were imaged simultaneously using wide volume scan of the SS-OCT in the primary and different gaze positions. Horizontal eye movements were used to obtain OCT images in abducted and adducted eyeball positions. Multilateral 3-dimensional registration was used to process and analyze the images to measure the degree of ONH changes.ResultsThe mean axial length (AXL) was 25.73 ± 1.42mm and the mean spherical equivalents was -4.49 ± 2.94 D (The proportion of high myopia was 39.4%). Significant morphologic changes were observed in the ONH during both abduction and adduction. In abduction, the overall ONH tissues were elevated, and the mean area of elevation was 115,134 ± 9,424 μm2 (p<0.001). In adduction, the mean areas from two perspectives, which were nasal or temporal, and peripapillary tissues or optic nerve cupping were 95,277 ± 73,846 μm2, 34,450 ± 44,948 μm2, -108,652 ± 91,246 μm2, and -30,581 ± 46,249 μm2, respectively. Elevation in abduction (overall, nasal cup segment, and temporal cup segment; R = 0.204, 0.195 and 0.225, p = 0.038, 0.047 and 0.021, respectively) and elevation of nasal peripapillary segments in adduction were positively correlated with AXL (R = 0.346, p<0.001).ConclusionWe found significant morphologic changes in the ONH in both abduction and adduction and these changes were associated with AXL. Considering these morphologic changes as physical properties, it allows a better understanding of the biomechanical characteristics of the ONH.

Microvascular Changes in Peripapillary and Optic Nerve Head Tissues After Trabeculectomy in Primary Open-Angle Glaucoma.

To determine microvasculature changes in the deep optic nerve head (ONH) and peripapillary tissues after trabeculectomy, and to correlate these with changes in the lamina cribrosa (LC) curvature. Fifty-six eyes with primary open-angle glaucoma that underwent trabeculectomy were included. The optic nerve and peripapillary microvasculature were evaluated in en face images obtained using optical coherence tomography (OCT) angiography (OCTA) before and 3 months after trabeculectomy. The OCTA-derived vessel density (VD) was calculated in each layer segmented into the prelaminar tissue (PLT), LC, peripapillary retina (PR), and peripapillary choroid (PPC). Swept-source OCT volume scanning of ONH was performed on the same day as OCTA to examine the change in LC curvature quantified as the LC curve index (LCCI). At 3 months postoperative, the IOP and LCCI had significantly decreased (both P < 0.001). OCTA images revealed a significant increase in VD in the LC (P = 0.006), but not in the PLT, PR, or PPC. Twenty-six eyes showed both significant LCCI decrease and VD increase based on 95% Bland-Altman limits of agreement. The VD increase in the LC was significantly associated with larger percentage reductions in IOP (P = 0.040) and LCCI (P < 0.001) in the univariate analysis. Multivariate analysis revealed that only the LCCI reduction was a significant factor affecting the VD increase in the LC. A significant increase in VD was observed at the level of the LC after trabeculectomy. The VD increase was more strongly associated with the reduction in the LC curvature than with the reduction of IOP.