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Purpose: To evaluate the lamina cribrosa, retinal nerve fiber layer (RNFL), and macula in patients with primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PEXG) and healthy individuals using enhanced depth imaging (EDI) of spectral-domain optical coherence tomography (SD-OCT). Methods: A total of 158 eyes were included in the study, comprising 58 eyes of 29 patients with POAG, 50 eyes of 25 patients with PEXG, and 50 eyes of 25 healthy individuals. The lamina cribrosa thickness (LCT) (at three locations), lamina cribrosa depth (LCD), RNFL thickness, and the macular thickness were measured using the EDI mode of the SD-OCT. The results were compared among the three groups. Results: In both POAG and PEXG groups, the LCT was significantly thinner in the center, mid-superior, and mid-inferior areas in both eyes than in the control group (p < 0.001). However, no statistically significant difference was observed between the POAG and PEXG groups in terms of LCT at all three measurement locations in both eyes (p > 0.05). The LCD was significantly lower in the control group compared to the POAG and PEXG groups (p < 0.05), but there was no significant difference between the POAG and PEXG groups (p > 0.05). The RNFL thickness was significantly lower in both the POAG and PEXG groups compared to the control group in both eyes (p < 0.05). Conclusion: The LCT and LCD of patients with POAG and PEXG were thinner than those of healthy individuals, but there was no significant difference between the patients with POAG and PEXG. [ABSTRACT FROM AUTHOR]

Purpose: Glaucoma, one of the leading causes of irreversible blindness, is a common progressive optic neuropathy characterised by visual field defects and structural changes to the optic nerve head (ONH). There is extracellular matrix (ECM) accumulation and fibrosis of the lamina cribrosa (LC) in the ONH, and consequently increased tissue stiffness of the LC connective tissue. Integrins are cell surface proteins that provide the key molecular link connecting cells to the ECM and serve as bidirectional sensors transmitting signals between cells and their environment to promote cell adhesion, proliferation, and remodelling of the ECM. Here, we investigated the expression of αVβ3 integrin in glaucoma LC cell, and its effect on stiffness-induced ECM gene transcription and cellular proliferation rate in normal (NLC) and glaucoma (GLC) LC cells, by down-regulating αVβ3 integrin expression using cilengitide (a known potent αVβ3 and αVβ5 inhibitor) and β3 integrin siRNA knockdown. Methods: GLC cells were compared to age-matched controls NLC to determine differential expression levels of αVβ3 integrin, ECM genes (Col1A1, α-SMA, fibronectin, vitronectin), and proliferation rates. The effects of αVβ3 integrin blockade (with cilengitide) and silencing (with a pool of four predesigned αVβ3 integrin siRNAs) on ECM gene expression and proliferation rates were evaluated using both reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting in the human NLC cells cultured on soft (4 kPa) and stiff (100 kPa) substrate and in GLC cells grown on standard plastic plates. Results: αVβ3 integrin gene and protein expression were enhanced (p < 0.05) in GLC cells as compared to NLC. Both cilengitide and siRNA significantly reduced αVβ3 expression in GLC. When NLC were grown in the stiff substrate, cilengitide and siRNA also significantly reduced the increased expression in αVβ3, ECM components, and proliferation rate. Conclusions: Here, we provide evidence of cilengitide- and siRNA-mediated silencing of αVβ3 integrin expression, and inhibition of ECM synthesis in LC cells. Therefore, αVβ3 integrin may be a promising target for the development of novel anti-fibrotic therapies for treating the LC cupping of the ONH in glaucoma. [ABSTRACT FROM AUTHOR]

Glaucoma, a leading cause of blindness, is a multifactorial condition that leads to progressive loss of retinal ganglion cells (RGCs) and vision. Therapeutic interventions based on reducing ocular hypertension are not always successful. Emerging features of glaucoma include mitochondrial dysfunction and oxidative stress. In the current study, NDI1-based gene therapy, which improves mitochondrial function and reduces reactive oxygen species, was delivered intraocularly via an adeno-associated viral vector (AAV). This AAV-NDI1 therapy protected RGCs from cell death in treated (1552.4 ± 994.0 RGCs/mm2) versus control eyes (1184.4 ± 978.4 RGCs/mm2, p < 0.05) in aged DBA/2J mice, a murine model of glaucoma. The photonegative responses (PhNRs) of RGCs were also improved in treated (6.4 ± 3.3 µV) versus control eyes (5.0 ± 3.1 µV, p < 0.05) in these mice. AAV-NDI1 also provided benefits in glaucomatous human lamina cribrosa (LC) cells by significantly increasing basal and maximal oxygen consumption rates and ATP production in these cells. Similarly, NDI1 therapy significantly protected H2O2-insulted primary porcine LC cells from oxidative stress. This study highlights the potential utility of NDI1 therapies and the benefits of improving mitochondrial function in the treatment of glaucoma. [ABSTRACT FROM AUTHOR]

Yiwei Wang,1 Yanzhi Guo,1 Yang Zhang,1 Shouyue Huang,1 Yisheng Zhong1,2 1Author Affiliations Department of Ophthalmology, Ruijin Hospital Affiliated Medical School, Shanghai Jiao tong University, Shanghai, 200025, People’s Republic of China; 2Author affiliations Department of Ophthalmology, Wuxi Branch of Ruijin Hospital Affiliated Medical School, Shanghai Jiao tong University, Wuxi, People’s Republic of ChinaCorrespondence: Yisheng Zhong; Shouyue Huang, Email yszhong68@126.com; yachtjj@hotmail.comAbstract: Glaucoma is the leading cause of irreversible blindness worldwide. It is an ocular disease characterized by an increase in intraocular pressure or, in some cases, normal intraocular pressure, which leads to optic nerve damage and progressive constriction of the visual field (VF). Primary Open-Angle Glaucoma (POAG) and Primary Angle-Closure Glaucoma (PACG) represent the predominant forms of glaucoma. Numerous hypotheses have been posited to elucidate the pathogenic mechanisms underlying these conditions. There is an emerging understanding of the distinct pathological processes that differentiate the various types of glaucoma. While some similarities in the mechanisms between PACG and POAG have been suggested, evidence indicates that there are also significant differences between the two. This review synthesizes the similarities and differences in the etiology of optic neuropathy caused by POAG and PACG, considering their respective pathophysiological mechanisms, the morphology of the optic disc and surrounding tissues, genetic characteristics, optical coherence tomography angiography, optical coherence tomography, and structural and functional features from VF examinations. These characteristics may contribute to a deeper comprehension of the underlying pathogenesis of glaucoma and enhance the management of different types of this ocular condition.Keywords: pathophysiology, lamina cribrosa, optic nerve head, visual field

Purpose: We report a patient with recurrent optic disc pit (ODP) maculopathy after Valsalva's maneuver and discuss its pathophysiology. We also hypothesize the role of Valsalva's maneuver in its genesis. Method: Case report of one patient, male, 12 years old. Results: Serous retinal detachment may occur in association with the ODP, a developmental anomaly of the optic nerve head. Histopathologically, it consists of a dysplastic retina herniation into a pocket extending posteriorly through a defect in the lamina cribrosa into the subarachnoid space. These three different compartments--intraocular space, optic nerve head, and subarachnoid space--and the dynamic interactions among them should be understood as the key factors for the occurrence of ODP-related serous retinal detachment. Conclusion: Based on the possibility that serous retinal detachment secondary to the ODP could be related to the Valsalva's maneuver, we strongly recommend that patients with ODP be advised to avoid intense physical or work activities that may increase abdominal, thoracic, and cerebral pressure and to refrain from playing wind instruments to avoid pretreatment, per treatment, and post-treatment intercurrences. [ABSTRACT FROM AUTHOR]

Rapidly increasing intraocular pressure(IOP)is a typical manifestation of acute angle-closure glaucoma and an important cause of ocular tissue damage, vision loss and even blindness in glaucoma patients. The sharp increase of intraocular pressure in a short period of time in acute angle-closure glaucoma will cause characteristic damage to the structure and function of retina, choroid and optic nerve. Currently, the diagnosis and evaluation of the course of glaucoma is largely dependent on the state of high IOP, changes in the optic nerve and visual field damage, but irreversible damage to the fundus has already been made in glaucoma patients by this time. The microstructural changes in the posterior segment of the eye are more sensitive to high IOP and often appear before optic nerve and visual field damage, which can indicate the damage of high IOP to the eye earlier. Through the evaluation of the imaging characteristics of the posterior segment of the eye, the morphological characteristics that affect the prognosis of glaucoma can be explored, which is clinically important for the early diagnosis of glaucoma.

Purpose: To compare the differences between eyes with pseudoexfoliative glaucoma (PXG) when they are divided into two groups (hypertensive PXG and normotensive PXG) according to the intraocular pressure (IOP). Methods: This is a retrospective study. Data from 86 hypertensive PXG eyes and 80 normotensive PXG eyes were included. Hypertensive PXG was defined as PXG with IOP ≥ 22 mmHg, and normotensive PXG was defined as with IOP ≤ 21 mmHg). Central corneal thickness (CCT) was measured by ultrasound pachymetry. Lamina cribrosa thickness (LT) was evaluated using swept-source optical coherence tomography. Results: No significant differences were observed between hypertensive and normotensive PXG in terms of age, gender, axial length, hypertension, or diabetes. Normotensive PXG eyes had thinner CCT than hypertensive PXG eyes (p = 0.02). To compare LT, a sub-analysis was performed after matching age, VF MD and retinal nerve fiber layer thickness. The normotensive PXG group (n = 32) demonstrated significantly thinner LT compared with the hypertensive PXG group (n = 32) at similar ages and levels of glaucoma severity (p < 0.001). Conclusions: Eyes with normotensive PXG demonstrated thinner CCT and LT compared with those with hypertensive PXG, suggesting structural vulnerability to glaucoma. [ABSTRACT FROM AUTHOR]

PurposeThe purpose of this study was to test if optic nerve head (ONH) myelin basic protein (MBP), 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), glial fibrillary acidic protein (GFAP), and ionized calcium binding adaptor molecule 1 (Iba1) proteins are altered in non-human primate (NHP) early/moderate experimental glaucoma (EG).MethodsFollowing paraformaldehyde perfusion, control and EG eye ONH tissues from four NHPs were paraffin embedded and serially (5 µm) vertically sectioned. Anti-MBP, CNPase, GFAP, Iba1, and nuclear dye-stained sections were imaged using sub-saturating light intensities. Whole-section images were segmented creating anatomically consistent laminar (L) and retrolaminar (RL) regions/sub-regions. EG versus control eye intensity/pixel-cluster density data within L and two RL regions (RL1 [1-250 µm]/RL2 [251-500 µm] from L) were compared using random effects models within the statistical program "R."ResultsEG eye retinal nerve fiber loss ranged from 0% to 20%. EG eyes' MBP and CNPase intensity were decreased within the RL1 (MBP = 31.4%, P < 0.001; CNPase =62.3%, P < 0.001) and RL2 (MBP = 19.6%, P < 0.001; CNPase = 56.1%, P = 0.0004) regions. EG eye GFAP intensity was decreased in the L (41.6%, P < 0.001) and RL regions (26.7% for RL1, and 28.4% for RL2, both P < 0.001). Iba1+ and NucBlue pixel-cluster density were increased in the laminar (28.2%, P = 0.03 and 16.6%, P = 0.008) and both RL regions (RL1 = 37.3%, P = 0.01 and 23.7%, P = 0.0002; RL2 = 53.7%, P = 0.002 and 33.2%, P < 0.001).ConclusionsRetrolaminar myelin disruption occurs early in NHP EG and may be accompanied by laminar and retrolaminar decreases in astrocyte process labeling and increases in microglial/ macrophage density. The mechanistic and therapeutic implications of these findings warrant further study.

Purpose: Glaucoma, one of the leading causes of irreversible blindness, is a common progressive optic neuropathy characterised by visual field defects and structural changes to the optic nerve head (ONH). There is extracellular matrix (ECM) accumulation and fibrosis of the lamina cribrosa (LC) in the ONH, and consequently increased tissue stiffness of the LC connective tissue. Integrins are cell surface proteins that provide the key molecular link connecting cells to the ECM and serve as bidirectional sensors transmitting signals between cells and their environment to promote cell adhesion, proliferation, and remodelling of the ECM. Here, we investigated the expression of αVβ3 integrin in glaucoma LC cell, and its effect on stiffness-induced ECM gene transcription and cellular proliferation rate in normal (NLC) and glaucoma (GLC) LC cells, by down-regulating αVβ3 integrin expression using cilengitide (a known potent αVβ3 and αVβ5 inhibitor) and β3 integrin siRNA knockdown. Methods: GLC cells were compared to age-matched controls NLC to determine differential expression levels of αVβ3 integrin, ECM genes (Col1A1, α-SMA, fibronectin, vitronectin), and proliferation rates. The effects of αVβ3 integrin blockade (with cilengitide) and silencing (with a pool of four predesigned αVβ3 integrin siRNAs) on ECM gene expression and proliferation rates were evaluated using both reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting in the human NLC cells cultured on soft (4 kPa) and stiff (100 kPa) substrate and in GLC cells grown on standard plastic plates. Results: αVβ3 integrin gene and protein expression were enhanced (p < 0.05) in GLC cells as compared to NLC. Both cilengitide and siRNA significantly reduced αVβ3 expression in GLC. When NLC were grown in the stiff substrate, cilengitide and siRNA also significantly reduced the increased expression in αVβ3, ECM components, and proliferation rate. Conclusions: Here, we provide evidence of cilengitide- and siRNA-mediated silencing of αVβ3 integrin expression, and inhibition of ECM synthesis in LC cells. Therefore, αVβ3 integrin may be a promising target for the development of novel anti-fibrotic therapies for treating the LC cupping of the ONH in glaucoma.

Abstract Introduction To evaluate the characteristics of optic nerve head (ONH) in highly myopic eyes and its role in predicting intraocular pressure (IOP) spikes after cataract surgery. Methods Patients who are highly myopic and were scheduled for cataract surgery were enrolled in this prospective case series study. IOP was measured preoperatively and at 1 day and 3 days postoperatively. ONH characteristics including area, tilt ratio, lamina cribrosa (LC) thickness, and depth, and the presence of LC defects were evaluated with enhanced depth imaging optical coherence tomography. Factors influencing LC defects and early IOP spike were investigated using multivariate stepwise logistic regression. Results In total, 200 highly myopic eyes of 200 patients were analyzed: 35.00% had small ONH, 53.00% had ONH tilt, and 14.00% had LC defects. Multivariate analysis demonstrated female patients with larger ONH area and deeper LC tended to have LC defects (all P 0.05), higher (all P 28 mm was a risk factor (all P

The lamina cribrosa (LC) is a connective tissue in the optic nerve head (ONH). The objective of this study was to measure the curvature and collagen microstructure of the human LC, compare the effects of glaucoma and glaucoma optic nerve damage, and investigate the relationship between the structure and pressure-induced strain response of the LC in glaucoma eyes. Previously, the posterior scleral cups of 10 normal eyes and 16 diagnosed glaucoma eyes were subjected to inflation testing with second harmonic generation (SHG) imaging of the LC and digital volume correlation (DVC) to calculate the strain field. In this study, we applied a custom microstructural analysis algorithm to the maximum intensity projection of SHG images to measure features of the LC beam and pore network. We also estimated the LC curvatures from the anterior surface of the DVC-correlated LC volume. Results showed that the LC in glaucoma eyes had larger curvatures p=0.03), a smaller average pore area (p = 0.001), greater beam tortuosity (p < 0.0001), and more isotropic beam structure (p = 0.01) than in normal eyes. The difference measured between glaucoma and normal eyes may indicate remodeling of the LC with glaucoma or baseline differences that contribute to the development of glaucomatous axonal damage. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the characteristics of optic nerve head (ONH) in highly myopic eyes and its role in predicting intraocular pressure (IOP) spikes after cataract surgery. Methods: Patients who are highly myopic and were scheduled for cataract surgery were enrolled in this prospective case series study. IOP was measured preoperatively and at 1 day and 3 days postoperatively. ONH characteristics including area, tilt ratio, lamina cribrosa (LC) thickness, and depth, and the presence of LC defects were evaluated with enhanced depth imaging optical coherence tomography. Factors influencing LC defects and early IOP spike were investigated using multivariate stepwise logistic regression. Results: In total, 200 highly myopic eyes of 200 patients were analyzed: 35.00% had small ONH, 53.00% had ONH tilt, and 14.00% had LC defects. Multivariate analysis demonstrated female patients with larger ONH area and deeper LC tended to have LC defects (all P < 0.05). As to postoperative IOP, IOP change, and incidence of IOP spikes, eyes with small ONH, ONH tilt, and LC defects had similar (all P > 0.05), higher (all P < 0.05), and lower (all P < 0.05) outcomes compared with those without the corresponding characteristic, respectively. Multivariate analysis showed that presence of LC defects and thicker LC were protective factors for early IOP spikes, and axial length > 28 mm was a risk factor (all P < 0.05). Conclusion: Female patients with larger ONH area and deeper LC tend to have LC defects, which, together with thicker LC, was correlated with less IOP spikes in highly myopic eyes. Trial Registration: This study was conducted as part of a larger project, the Shanghai High Myopia Study, registered at www.clinicaltrials.gov (accession number NCT03062085). [ABSTRACT FROM AUTHOR]

PurposeThe purpose of this study was to determine if the rate of change in the depth of the surface of the lamina cribrosa due to glaucomatous remodeling differs between glaucoma patients of African descent (AD) and European descent (ED).MethodsThere were 1122 images taken longitudinally over an average of 3 years (range = 0.9-4.1 years) from 122 patients with glaucoma followed in the African Descent and Glaucoma Evaluation Study (ADAGES) and Diagnostic Intervention and Glaucoma Study (DIGS) were automatically segmented to compute anterior lamina cribrosa surface depth (ALCSD). The rate of ALCSD change was compared across racial groups after adjusting for baseline characteristics known to be associated with ALCSD or disease progression (visual field, ALCSD, corneal thickness, optic disk size, and age).ResultsAfter adjusting for all other covariates, the ED group had significantly greater ALCSD posterior migration (deepening) than the AD group (difference = 2.57 µm/year, P = 0.035). There was a wider range of ALCSD change in the ED compared with the AD group, and more individuals had greater magnitude of both deepening and shallowing. No other covariates measured at baseline had independent effects on the longitudinal changes in ALCSD (baseline visual field severity, baseline ALCSD, corneal thickness, Bruch's membrane opening [BMO] area, or age).ConclusionsGlaucomatous remodeling of the lamina cribrosa differs between AD and ED patients with glaucoma. Unlike the cross-sectional associations seen with aging, in which a deeper ALCSD was seen with age in the ED group, glaucomatous remodeling in this longitudinal study resulted in more posterior migration of ALCSD in ED compared to AD patients.

Purpose: To compare the differences between eyes with pseudoexfoliative glaucoma (PXG) when they are divided into two groups (hypertensive PXG and normotensive PXG) according to the intraocular pressure (IOP). Methods: This is a retrospective study. Data from 86 hypertensive PXG eyes and 80 normotensive PXG eyes were included. Hypertensive PXG was defined as PXG with IOP ≥ 22 mmHg, and normotensive PXG was defined as with IOP ≤ 21 mmHg). Central corneal thickness (CCT) was measured by ultrasound pachymetry. Lamina cribrosa thickness (LT) was evaluated using swept-source optical coherence tomography. Results: No significant differences were observed between hypertensive and normotensive PXG in terms of age, gender, axial length, hypertension, or diabetes. Normotensive PXG eyes had thinner CCT than hypertensive PXG eyes (p = 0.02). To compare LT, a sub-analysis was performed after matching age, VF MD and retinal nerve fiber layer thickness. The normotensive PXG group (n = 32) demonstrated significantly thinner LT compared with the hypertensive PXG group (n = 32) at similar ages and levels of glaucoma severity (p < 0.001). Conclusions: Eyes with normotensive PXG demonstrated thinner CCT and LT compared with those with hypertensive PXG, suggesting structural vulnerability to glaucoma.

Purpose: To evaluate the relationship of the peripapillary retina nerve fiber layer (RNFL) and lamina cribrosa (LC) with diabetic retinopathy (DR) in type 2 diabetes mellitus (DM) cases. Study design: Prospective comparative study. Methods: This study included 50 non-DR (Group 1), 55 non-proliferative diabetic retinopathy (NPDR) (Group 2), 28 DM cases with proliferative diabetic retinopathy (PDR) (Group 3) and 45 healthy volunteers (Group 4). All participants were evaluated with visual acuity, intraocular pressure (IOP) with Goldman applanation tonometry, anterior segment biomicroscopy, 24 − 2 visual field testing, and dilated fundus examination. Retinal nerve fiber layer (RNFL) thickness, lamina cribrosa thickness (LCT) and anterior lamina cribrosa depth (ALCD) were examined by spectral-domain optical coherence tomography (OCT). Results: There was no difference between the groups in terms of age and gender. Visual acuity (p < 0.001) was significantly different between the groups, while IOP (p = 0.068) was similar. Mean (p = 0.010), superior-temporal (p = 0.024), and superior-nasal (p = 0.011) RNFL thickness decreased significantly in correlation with the stage of DR. LCT decreased significantly as the stage of DR progressed in both vertical and horizontal radial OCT scans (p < 0.001). ALCD was not different between groups (p = 0.954 for horizontal scan, p = 0.867 for vertical scan). Conclusion: Peripapillary RNFL and LCT significantly decreases as the DR stage progresses. The biomechanical effects of the LC may also be responsible for diabetes-induced neurodegeneration. [ABSTRACT FROM AUTHOR]

In this work, an attempt has been made to analyze the influence of pathological changes in eye globe dimensions towards the mechanical responses of optic nerve head tissues during eye adductions. For this study, a 3D baseline model geometry of posterior ocular tissues has been constructed. The eye globe diameters of the model are modified to mimic the changes in ocular globe morphology in control, glaucoma, myopia and glaucoma with myopia conditions. Adductions are simulated for each modified model as the rotation of the globe from 1o to 10o in steps of 1o. von Mises strain in lamina cribrosa (LC) and posterior displacement of LC are estimated. Results show that strains developed in LC and its posterior displacement are higher in diseased eyes compared to healthy eyes. It appears that eyes with higher axial length and globe anisotropy are more susceptible to optic nerve head damage. This study might be extended to assess the progression of glaucomatous optic neuropathy.

Purpose: The purpose of the study was to investigate whether the position of the central retinal vascular trunk (CRVT), as a surrogate for lamina cribrosa (LC) offset, is associated with the dominant hemisphere of visual field defect in primary angle‐closure glaucoma (PACG) eyes. Methods: Central retinal vascular trunk deviation was measured from Bruch's membrane opening (BMO) centre, which was delineated by OCT imaging, using the horizontal midline as a reference. The dominant hemisphere developing visual field defect was defined as three connected abnormal points (having a p‐value < 5% probability of being normal) appearing in only one hemisphere or each point of the hemisphere having a statistically worse value compared with its mirrored point in the opposite hemisphere on pattern deviation plots. Results: One hundred five (80%) of 132 eyes with PACG had dominant hemisphere of visual field defect initially: 70 eyes (67%) in the superior and 35 eyes (33%) in the inferior hemisphere. The CRVT was located superiorly in the dominant superior visual field defect group (p < 0.001). A logistic regression analysis revealed that superior deviation of the CRVT was the only factor associated with dominant superior visual field defect (p < 0.001). Externally oblique border (EOB) presence was associated with larger BMO (p = 0.005) and angular deviation of CRVT (p = 0.002). Conclusions: Central retinal vascular trunk deviation was associated with the dominant hemisphere of visual field defect in PACG eyes. This finding implies that the LC position relative to the BMO centre (LC/BMO offset) may incur structural vulnerability in the optic nerve head of PACG eyes. [ABSTRACT FROM AUTHOR]

PurposeTo determine if variation in anterior lamina cribrosa surface depth (ALCSD) differs between glaucoma patients of African (AD) and European descent (ED).MethodsA total of 178 eyes from 123 glaucoma patients in the African Descent and Glaucoma Evaluation Study (ADAGES) and Diagnostic Innovations in Glaucoma Study (DIGS) were included. ALCSD and choroidal thickness were measured using the San Diego Automated Layer Segmentation Algorithm (SALSA). ALCSD was defined by both Bruch's membrane opening (BMO)-based (ALCSD-BMO) and scleral-based (ALCSD-Scl) reference planes. Racial differences in ALCSD were evaluated using cross-sectional univariate and multivariable models.ResultsA deeper ALCSD-Scl was found in males (52.4 μm, P = 0.0401), AD individuals (78.6 μm, P = 0.0004), younger individuals (-3.1 μm/year, P < 0.0213), and eyes with larger discs (81.0 μm/mm2, P = 0.024), increased visual field loss (mean defect, MD: -6.4 μm/dB [decibel], P = 0.0106), and higher intraocular pressure (IOP: 14.1 μm/mm Hg, P = 0.0256). Significant deepening of ALSCD was observed with increasing IOP and visual field severity only in the AD group. Race modified the relationship between ALCSD-Scl and age (P = 0.0145) with ALCSD-Scl in AD individuals becoming more shallow with increasing age (-3.1 μm/year, P = 0.0213), while there was no significant association in the ED group (2.1 μm/mm Hg, P < 0.2026).ConclusionsThis study demonstrates that a deeper ALCSD, regardless of the ALCSD reference plane used, is associated with more severe glaucoma and higher IOP in the ADAGES cohort, particularly in individuals of AD. These results suggest that characterizing ALCSD morphology and its relationships to IOP, aging, and glaucoma progression may help explain racial differences in disease susceptibility.

Abstract Background To detect the superficial and buried optic disc drusen (ODD) with swept-source optical coherence tomography (SS-OCT). Methods Retrospective cross-sectional study. Twenty patients (age 18–74 years) diagnosed with ODD via B-scan ultrasonography were analysed. All patients underwent color fundus photography (CFP), B-scan ultrasonography, fundus autofluorescence (FAF), and SS-OCT. We defined each hyporeflective signal mass of SS-OCT as an ODD, recorded its location and relationship with Bruch’s membrane opening (BMO), and other ophthalmic imaging characteristics. Results Twenty (33 eyes) patients had 54 ODDs in all, except one eye did not show abnormal optic disc findings on SS-OCT. We classified ODD into three categories: ODD above BMO, ODD across BMO, and ODD below BMO. The ODDs across BMO were the largest, followed by ODDs below BMO, and those above BMO. The location of the ODDs: One (1.9%) was in the border tissue of Elschnig, 6 (11.1%) might span across the lamina cribrosa, 16 (29.6%) were above BMO located in the neuroepithelial layer, 9 (16.7%) spanned across BMO located near the center of the optic disc, 18 (33.3%) were below BMO located near the center of the optic disc, 4 (7.4%) were below BMO located within the optic disc rim. When the anterior margin was ≥ 100 μm from the BMO, clear autofluorescence could be seen. Conclusion Multimodal imaging provided a deeper understanding of ODD. SS-OCT illustrated more details about the relationship between the posterior surface of ODD, BMO and the lamina cribrosa.

PurposeTo better understand the relationship of lamina cribrosa (LC) and choroid features to the severity of pseudoexfoliation glaucoma (PXG).MethodsIn this cross-sectional study, 137 eyes of 122 subjects (47 eyes with moderate/advanced PXG [mean deviation (MD), -15.0 ± 7.7 dB], 34 eyes with mild PXG [MD, -2.7 ± 1.5 dB], 32 aged-matched pseudoexfoliation syndrome [PXS] eyes, and 24 aged-matched control eyes) were investigated. Optic discs, LC thickness, and anterior LC depth (ALD; midsuperior, center, and midinferior) as well as peripapillary choroidal thickness were determined. Linear mixed modeling was used to adjust for age, sex, and axial length.ResultsA progressive decrease in LC thickness was found when comparing controls (271.9 ± 61.3 μm), PXS (212.6 ± 51.5 μm), mild PXG (180.8 ± 24.6 μm), and moderate/advance PXG (138.9 ± 37.5 μm) (P < 0.001). ALD was greater (P < 0.001) in moderate/advance glaucoma (306.7 ± 105.3 μm) and mild PXG (209.5 ± 79.7 μm) compared with PXS (155 ± 86.7 μm) and healthy controls (149.2 ± 103 μm). Although eyes with moderate/advance PXG had the thinnest choroid (117.2 ± 36.6 μm), choroidal thickness was comparable in mild PXG, PXS, and controls (150.0 ± 46.1, 159.7 ± 65.5, and 157.5 ± 51.1 μm, respectively; P = 0.002). Worse MD was the only factor associated with thinner LC (β = 2.344, P < 0.001) and choroid (β = 1.717, P = 0.009 μm) in PXG eyes. Higher IOP (β = 4.305, P = 0.013) and worse MD (β = -6.390, P < 0.001) were associated with deeper ALD in PXG.ConclusionsIn pseudoexfoliation, LC thinning is an early sign, and there is progressive thinning with advancing glaucoma. Choroidal thinning is observable only with moderate/advanced glaucoma. In PXG eyes, LC thickness, depth, and peripapillary choroidal thickness are associated with glaucoma severity.

Glaucoma is one of the most common causes of treatable visual impairment in the developed world, affecting approximately 64 million people worldwide, some of whom will be bilaterally blind from irreversible optic nerve damage. The optic nerve head is a key site of damage in glaucoma where there is fibrosis of the connective tissue in the lamina cribrosa (LC) extracellular matrix. As a ubiquitous second messenger, calcium (Ca2+) can interact with various cellular proteins to regulate multiple physiological processes and contribute to a wide range of diseases, including cancer, fibrosis, and glaucoma. Our research has shown evidence of oxidative stress, mitochondrial dysfunction, an elevated expression of Ca2+ entry channels, Ca2+-dependent pumps and exchangers, and an abnormal rise in cytosolic Ca2+ in human glaucomatous LC fibroblast cells. We have evidence that this increase is dependent on Ca2+ entry channels located in the plasma membrane, and its release is from internal stores in the endoplasmic reticulum (ER), as well as from the mitochondria. Here, we summarize some of the molecular Ca2+-dependent mechanisms related to this abnormal Ca2+-signalling in human glaucoma LC cells, with a view toward identifying potential therapeutic targets for ongoing optic neuropathy. [ABSTRACT FROM AUTHOR]

To study the associations between optic nerve head (ONH) strains under intraocular pressure (IOP) elevation with retinal sensitivity in patients with glaucoma. Clinic-based cross-sectional study. Two hundred twenty-nine patients with primary open-angle glaucoma (subdivided into 115 patients with high-tension glaucoma [HTG] and 114 patients with normal-tension glaucoma [NTG]). For 1 eye of each patient, we imaged the ONH using spectral-domain OCT under the following conditions: (1) primary gaze and (2) primary gaze with acute IOP elevation (to approximately 35 mmHg) achieved through ophthalmodynamometry. A 3-dimensional strain-mapping algorithm was applied to quantify IOP-induced ONH tissue strain (i.e., deformation) in each ONH. Strains in the prelaminar tissue (PLT), the retina, the choroid, the sclera, and the lamina cribrosa (LC) were associated (using linear regression) with measures of retinal sensitivity from the 24-2 Humphrey visual field test (Carl Zeiss Meditec). This was performed globally, then locally according to a previously published regionalization scheme. Associations between ONH strains and values of retinal sensitivity from visual field testing. For patients with HTG, we found (1) significant negative linear associations between ONH strains and retinal sensitivity (P < 0.001; on average, a 1% increase in ONH strains corresponded to a decrease in retinal sensitivity of 1.1 decibels [dB]), (2) that high-strain regions colocalized with anatomically mapped regions of high visual field loss, and (3) that the strongest negative associations were observed in the superior region and in the PLT. In contrast, for patients with NTG, no significant associations between strains and retinal sensitivity were observed except in the superotemporal region of the LC. We found significant negative associations between IOP-induced ONH strains and retinal sensitivity in a relatively large glaucoma cohort. Specifically, patients with HTG who experienced higher ONH strains were more likely to exhibit lower retinal sensitivities. Interestingly, this trend in general was less pronounced in patients with NTG, which could suggest a distinct pathophysiologic relationship between the two glaucoma subtypes. [ABSTRACT FROM AUTHOR]

This initial methods study presents the initial immunohistochemical and transcriptomic changes in the optic nerve head and retina from three research-consented brain-dead organ donors following prolonged and transient intraocular pressure (IOP) elevation. In this initial study, research-consented brain-dead organ donors were exposed to unilateral elevation of IOP for 7.5 h (Donor 1), 30 h (Donor 2), and 1 h (Donor 3) prior to organ procurement. Optic nerve tissue and retinal tissue was obtained following organ procurement for immunohistological and transcriptomic analysis. Optic nerve sections in Donor 1 exposed to 7.5-hours of unilateral sub-ischemic IOP elevation demonstrated higher levels of protein expression of the astrocytic marker, glial fibrillary acidic protein (GFAP), within the lamina cribrosa with greatest expression inferior temporally in the treated eye compared to control. Spatial transcriptomic analysis performed on optic nerve head tissues from Donor 2 exposed to 30 h of unilateral IOP elevation demonstrated differential transcription of mRNA across laminar and scleral regions. Immunohistochemistry of retinal sections from Donor 2 exhibited higher GFAP and IBA1 expression in the treated eye compared with control, but this was not observed in Donor 3, which was exposed to only 1-hour of IOP elevation. While there were no differences in GFAP protein expression in the retina following the 1-hour IOP elevation in Donor 3, there were higher levels of transcription of GFAP in the inner nuclear layer, and CD44 in the retinal ganglion cell layer, indicative of astrocytic and Müller glial reactivity as well as an early inflammatory response, respectively. We found that transcriptomic differences can be observed across treated and control eyes following unilateral elevation of IOP in brain dead organ donors. The continued development of this model affords the unique opportunity to define the acute mechanotranscriptomic response of the optic nerve head, evaluate the injury and repair mechanisms in the retina in response to IOP elevation, and enable correlation of in vivo imaging and functional testing with ex vivo cellular responses for the first time in the living human eye. [ABSTRACT FROM AUTHOR]

This study aimed to develop and evaluate a guinea pig model for glaucoma, comparing resultant eyeball enlargement with an existing myopia model. Thirty guinea pigs underwent intracameral injection of magnetic microspheres to induce chronic ocular hypertension (COH). Intraocular pressure (IOP) was systematically monitored, revealing a successful induction of COH in 73.33% of the guinea pigs. The mean IOP increased from a baseline of 18.04 ± 1.33 mmHg, reaching a peak at week 3 (36.31 ± 6.13 mmHg) and remaining elevated for at least 7 weeks. All data are presented as mean ± standard deviation of the mean. Subsequently, detailed assessments were conducted to validate the established glaucoma model. Immunofluorescent staining demonstrated a significant decrease in the density of retinal ganglion cells (RGC) in the glaucoma group. Optic disc excavation and notable thinning of the lamina cribrosa (LC) were observed. The quantity of optic nerve ax·ons in glaucoma group gradually decreased from baseline (44553 ± 3608/mm2) to week 4 (28687 ± 2071/mm2) and week 8 (17977 ± 3697/mm2). Moreover, regarding the global enlargement of eyeballs, both the transverse and longitudinal axis in glaucomatous eyes were found to be significantly larger than that in myopic eyes, particularly in the anterior chamber depth (1.758 ± 0.113 mm vs. 1.151 ± 0.046 mm). These findings indicate distinct patterns of structural changes associated with glaucoma and myopia in the guinea pig model. This guinea pig model holds promise for future research aimed at exploring biomechanical mechanisms, therapeutic interventions, and advancing our understanding of the relationship between glaucoma and myopia. • Successful induction of glaucoma in guinea pigs via intracameral injection of magnetic microspheres. • Guinea pigs feature a collagen-based lamina cribrosa, superior to current rodent models. • Distinct patterns of eyeball enlargement exist in glaucomatous and myopic eyes. [ABSTRACT FROM AUTHOR]

The optic nerve head (ONH) is a complex structure wherein the axons of the retinal ganglion cells extrude from the eyeball through three openings: 1) the Bruch's membrane opening (BMO) in the retinal layer, 2) the anterior scleral canal opening in the anterior scleral layer, and 3) the lamina cribrosa (LC). Eyeball expansion during growth induces an offset among openings, since the expansion affects the inner retinal and outer scleral layers differently: the posterior polar retinal structure is preserved by the preferential growth in the equatorial region, whereas no such regional difference is observed in the scleral layer. The various modes and extents of eyeball expansion result in diverse directionality and amount of offset among openings, which causes diverse ONH morphology in adults, especially in myopia. In this review, we summarize the ONH changes that occur during myopic axial elongation. These changes were observed prospectively in our previous studies, wherein LC shift and subsequent offset from the BMO center could be predicted by tracing the central retinal vascular trunk position. This offset induces the formation of γ-zone parapapillary atrophy or externally oblique border tissue. As a presumptive site of glaucomatous damage, the LC/BMO offset may render the LC pores in the opposite direction more vulnerable. To support such speculation, we also summarize the relationship between LC/BMO offset and glaucomatous damage. Indeed, LC/BMO offset is not only the cause of diverse ONH morphology in adults, but is also, potentially, an important clinical marker for assessment of glaucoma. [Display omitted] • The lamina cribrosa/Bruch's membrane opening offset during eyeball growth. • The three-dimensional eyeball shape is associated with the offset. • The lamina cribrosa offset explains the characteristic shape of the myopic optic disc. • The offset is associated with the initial location of glaucomatous damage. • The lamina cribrosa offset theory offers new insight into myopia and glaucoma. [ABSTRACT FROM AUTHOR]

AIM: To determine the prevalence of focal lamina cribrosa (LC) defect among patients with pachychoroid disease spectrum (PDS) in the absence of peripapillary retinoschisis. METHODS: This retrospective, cross-sectional study comprised of 180 patients with PDS, including polypoidal choroidal vasculopathy (PCV), central serous chorioretinopathy, and pachychoroidal neovasculopathy. Medical records and optic nerve head evaluations conducted using spectral-domain optical coherence tomography with enhanced depth imaging were reviewed. As a control group, 236 patients who underwent ophthalmologic evaluation for vitreous floaters, without obvious ocular disease, were also included. RESULTS: The mean age of the PDS group, which included 118 male patients (65.6%), was 57.4±11.1y. There was no significant difference between the two groups in age (P=0.710) or sex (P=0.248). Six patients (3.3%) in the PDS group and none in the control group showed focal LC defect (P=0.318). Among the six patients with focal LC defect in the PDS group, four eyes had PCV, one eye was the fellow eye of a PCV eye, and one eye had pachychoroidal neovasculopathy. CONCLUSION: Focal LC defect can be defected in patients with PDS in the absence of peripapillary retinoschisis. However, the prevalence of focal LC defect was not different significantly between PDS patients and those who did not have PDS.

Ahmed El Basty, Raouf Gaber, Ahmed Elmaria, Moataz Sabry, Tarek R Hussein Department of Ophthalmology, Tanta University, Tanta, Gharbeya Province, EgyptCorrespondence: Raouf GaberTanta University Eye Hospital, The Faculty of Medicine, El-Gash St. Medical Campus, Tanta, Gharbeya Province, 31527, EgyptTel +201557673775Email Raouf.a.gaber@gmail.comPurpose: To investigate the correlation between changes in lamina cribrosa (LC) structure using enhanced depth imaging (EDI) and severity of visual field (VF) affection in primary open-angle glaucoma (POAG).Patients and Methods: This prospective cross-sectional study was carried out on 52 glaucomatous eyes of 28 POAG patients who attended Tanta University Eye Hospital and 40 normal eyes of 20 age-matched normal subjects from April 2020 to March 2021. POAG patients were classified according to the modified Hodapp–Anderson–Parrish grading scale based on the MD of the standard automated perimetry (SAP) visual field into two groups: group (1) – mild-to-moderate POAG patients (MD ≤ 12 dB), group (2) – severe POAG patients (MD ≥ 12 dB) and the third group included normal (control) age- and gender-matched individuals.Results: There was no statistically significant difference between the three groups regarding lamina cribrosa thickness nor lamina cribrosa area and there was no statistically significant correlation between MD and LC thickness, LC area (P-value=0.395 and 0.644). There was a statistically significant correlation between MD and anterior lamina cribrosa surface depth (P-value=0.002) and there was a statistically significant positive correlation between MD and prelaminar neural tissue (PLNT) thickness and prelaminar neural tissue (PLNT) area (P-value= 0.023 and < 0.001, respectively).Conclusion: EDI-OCT is a useful biomarker of structural changes in ONH and LC, and we recommended it to be a part of the routine monitoring of patients with POAG.Keywords: EDI, blindness, biomarker, lamina cribrosa, PLNT thickness

Glaucomatous optic neuropathy is the leading cause of irreversible blindness in the world. The chronic disease is characterized by optic nerve degeneration and vision field loss. The reduction of intraocular pressure remains the only proven glaucoma treatment, but it does not prevent further neurodegeneration. There are three major classes of cells in the human optic nerve head (ONH): lamina cribrosa (LC) cells, glial cells, and scleral fibroblasts. These cells provide support for the LC which is essential to maintain healthy retinal ganglion cell (RGC) axons. All these cells demonstrate responses to glaucomatous conditions through extracellular matrix remodeling. Therefore, investigations into alternative therapies that alter the characteristic remodeling response of the ONH to enhance the survival of RGC axons are prevalent. Understanding major remodeling pathways in the ONH may be key to developing targeted therapies that reduce deleterious remodeling. [ABSTRACT FROM AUTHOR]

Insufficient oxygenation in the lamina cribrosa (LC) may contribute to axonal damage and glaucomatous vision loss. To understand the range of susceptibilities to glaucoma, we aimed to identify key factors influencing LC oxygenation and examine if these factors vary with anatomical differences between eyes. We reconstructed 3D, eye-specific LC vessel networks from histological sections of four healthy monkey eyes. For each network, we generated 125 models varying vessel radius, oxygen consumption rate, and arteriole perfusion pressure. Using hemodynamic and oxygen supply modeling, we predicted blood flow distribution and tissue oxygenation in the LC. ANOVA assessed the significance of each parameter. Our results showed that vessel radius had the greatest influence on LC oxygenation, followed by anatomical variations. Arteriole perfusion pressure and oxygen consumption rate were the third and fourth most influential factors, respectively. The LC regions are well perfused under baseline conditions. These findings highlight the importance of vessel radius and anatomical variation in LC oxygenation, providing insights into LC physiology and pathology. Pathologies affecting vessel radius may increase the risk of LC hypoxia, and anatomical variations could influence susceptibility. Conversely, increased oxygen consumption rates had minimal effects, suggesting that higher metabolic demands, such as those needed to maintain intracellular transport despite elevated intraocular pressure, have limited impact on LC oxygenation., Competing Interests: Conflict of Interest: none

Purpose: Although the mechanisms underlying glaucomatous neurodegeneration are not yet well understood, cellular and small animal models suggest that LC astrocytes undergo early morphologic and functional changes, indicating their role as early responders to glaucomatous stress. These models, however, lack the LC found in larger animals and humans, leaving the in situ morphology of LC astrocytes and their role in glaucoma initiation underexplored. In this work, we aimed to characterize the morphology of LC astrocytes in situ and determine differences and similarities with astrocytes in the mouse glial lamina (GL), the analogous structure in a prominent glaucoma model., Methods: Astrocytes in the LCs of twenty-two eyes from goats, sheep, and pigs were stochastically labeled via Multicolor DiOlistics and imaged in situ using confocal microscopy. 3D models of DiOlistically-labeled LC astrocytes and hGFAPpr-GFP mouse GL astrocytes were constructed to quantify morphological features related to astrocyte functions. LC and GL astrocyte cross-pore contacts, branching complexity, branch tortuosity, and cell and branch span were compared., Results: LC astrocytes displayed distinct spatial relationships with collagen, greater branching complexity, and higher branch tortuosity compared to GL astrocytes. Despite substantial differences in their anatomical environments, LC and GL astrocytes had similar cell and branch spans., Conclusions: Astrocyte morphology in the LC was characterized through Multicolor DiOlistic labeling. LC and GL astrocytes have both distinct and shared morphological features. Further research is needed to understand the potentially unique roles of LC astrocytes in glaucoma initiation and progression.

Purpose: Our goal is to evaluate how lamina cribrosa (LC) oxygenation is affected by the tissue distortions resulting from elevated IOP., Design: Experimental study on monkeys., Subjects: Four healthy monkey eyes with OCT scans with IOP of 10 to 50 mmHg, and then with histological sections of LC., Methods: Since in-vivo LC oxygenation measurement is not yet possible, we used 3D eye-specific numerical models of the LC vasculature which we subjected to experimentally-derived tissue deformations. We reconstructed 3D models of the LC vessel networks of 4 healthy monkey eyes from histological sections. We also obtained in-vivo IOP-induced tissue deformations from a healthy monkey using OCT images and digital volume correlation analysis techniques. The extent that LC vessels distort under a given OCT-derived tissue strain remains unknown. We biomechanics-based mapping techniques: cross-sectional and isotropic. The hemodynamics and oxygenations of the four vessel networks were simulated for deformations at several IOPs up to 60mmHg. The results were used to determine the effects of IOP on LC oxygen supply, assorting the extent of tissue mild and severe hypoxia., Main Outcome Measures: IOP-induced deformation, vasculature structure, blood supply, and oxygen supply for LC region., Result: IOP-induced deformations reduced LC oxygenation significantly. More than 20% of LC tissue suffered from mild hypoxia when IOP reached 30 mmHg. Extreme IOP(>50mmHg) led to large severe hypoxia regions (>30%) in the isotropic mapping cases., Conclusion: Our models predicted that moderately elevated IOP can lead to mild hypoxia in a substantial part of the LC, which, if sustained chronically, may contribute to neural tissue damage. For extreme IOP elevations, severe hypoxia was predicted, which would potentially cause more immediate damage. Our findings suggest that despite the remarkable LC vascular robustness, IOP-induced distortions can potentially contribute to glaucomatous neuropathy.

Background: To detect the superficial and buried optic disc drusen (ODD) with swept-source optical coherence tomography (SS-OCT).Methods: Retrospective cross-sectional study. Twenty patients (age 18-74 years) diagnosed with ODD via B-scan ultrasonography were analysed. All patients underwent color fundus photography (CFP), B-scan ultrasonography, fundus autofluorescence (FAF), and SS-OCT. We defined each hyporeflective signal mass of SS-OCT as an ODD, recorded its location and relationship with Bruch's membrane opening (BMO), and other ophthalmic imaging characteristics.Results: Twenty (33 eyes) patients had 54 ODDs in all, except one eye did not show abnormal optic disc findings on SS-OCT. We classified ODD into three categories: ODD above BMO, ODD across BMO, and ODD below BMO. The ODDs across BMO were the largest, followed by ODDs below BMO, and those above BMO. The location of the ODDs: One (1.9%) was in the border tissue of Elschnig, 6 (11.1%) might span across the lamina cribrosa, 16 (29.6%) were above BMO located in the neuroepithelial layer, 9 (16.7%) spanned across BMO located near the center of the optic disc, 18 (33.3%) were below BMO located near the center of the optic disc, 4 (7.4%) were below BMO located within the optic disc rim. When the anterior margin was ≥ 100 μm from the BMO, clear autofluorescence could be seen.Conclusion: Multimodal imaging provided a deeper understanding of ODD. SS-OCT illustrated more details about the relationship between the posterior surface of ODD, BMO and the lamina cribrosa. [ABSTRACT FROM AUTHOR]

PurposeThe purpose of this study was to determine how the architecture of the lamina cribrosa (LC) microstructure, including the shape and size of the lamina pores, influences the IOP-induced deformation of the neural tissues within the LC pores using computational modeling.MethodsWe built seven specimen-specific finite element models of LC microstructure with distinct nonlinear anisotropic properties for LC beams and neural tissues based on histological sections from three sheep eyes. Changes in shape (aspect ratio and convexity) and size (area and perimeter length) due to IOP-induced hoop stress were calculated for 128 LC pores. Multivariate linear regression was used to determine if pore shape and size were correlated with the strain in the pores. We also compared the microstructure models to a homogenized model built following previous approaches.ResultsThe LC microstructure resulted in focal tensile, compressive, and shear strains in the neural tissues of the LC that were not predicted by homogenized models. IOP-induced hoop stress caused pores to become larger and more convex; however, pore aspect ratio did not change consistently. Peak tensile strains within the pores were well predicted by a linear regression model considering the initial convexity (negative correlation, P < 0.001), aspect ratio (positive correlation, P < 0.01), and area (negative correlation, P < 0.01). Significant correlations were also found when considering the deformed shape and size of the LC pores.ConclusionsThe deformation of the LC neural tissues was largely dependent on the collagenous LC beams. Simple measures of LC pore shape and area provided good estimates of neural tissue biomechanical insult.

The incidences of open angle glaucoma (OAG) and high myopia are increasing concomitantly. Considering the aging population and concurrent rapid increase in the number of individuals with myopia, the risk of visual defects caused by highly myopic OAG is likely to increase dramatically over the next few decades. However, precise screening and diagnosis of OAG is challenging because of the tilt and rotation of the optic disc, as well as extensive β-zone parapapillary atrophy in highly myopic eyes. Recent advances in optical coherence tomography (OCT) and OCT angiography (OCTA) technologies imply that both modalities are promising tools for the detection of highly myopic OAG. Notably, the diagnosis of OAG remains to be determined with the longitudinal changes of functional damages (e.g. visual field defect, visual electrophysiological changes). We herein describe some aspects of microvascular and microstructural pathology in patients with highly myopic OAG and proposes a framework for the development of novel diagnostic and therapeutic strategies.

Aim: To evaluate the behavior of the lamina cribrosa (LC) following successful phacoemulsification (PE) surgery in non-glaucomatous PXS cases with cataract. Methods: A total of 25 bilateral PXS and 56 non-PXS cataract patients were included in this prospective, interventional, and controlled study. The lamina cribrosa thickness (LCt) and anterior laminar depth (ALD) were measured horizontally and vertically from two sections using EDI-OCT. The measurements were taken preoperatively, and the LCt and ALD measurements were repeated at week one (W1), month one (M1), month two (M2), and month three (M3) postoperatively. Results: The baseline horizontal and vertical LCt values were found to be significantly thinner in the PXS group (p = 0.001, p = 0.006 respectively). The horizontal section ALD values were 463.32 ± 98.82 µm and 383.88 ± 85.8 µm (p < 0.001) for the PXS and non-PXS groups, respectively, and this significance continued during follow-up. The vertical ALD values were 469.64 ± 117.83 µm and 390.3 ± 98.1 µm (p = 0.002) in the PXS and non-PXS groups, respectively. There was no significant change in the PXS group for the depth following PE, but a statistically significant depth increase response was observed in the non-PXS group during follow-up. Conclusion: It is possible to conclude that the bending capacity of the lamina cribrosa may be lower than seen in the normal population, but we do not know how this lack of flexibility will affect the eye. [ABSTRACT FROM AUTHOR]

The lamina cribrosa (LC) is a layer of fenestrated connective tissue tethered to the posterior sclera across the scleral canal in the optic nerve head (ONH). It is located at the interface of intracranial and intraocular compartments and is exposed to intraocular pressure (IOP) anteriorly and intracranial pressure (ICP) or Cerebrospinal fluid (CSF) pressure (CSFP) posteriorly. We hypothesize that the pressure difference across LC will determine LC position and meridional diameter of scleral canal (also called Bruch's membrane opening diameter; BMOD). We enrolled 19 human subjects undergoing a medically necessary lumbar puncture (LP) to lower CSFP and 6 anesthetized pigs, whose ICP was increased in 5 mm Hg increments using a lumbar catheter. We imaged ONH using optical coherence tomography and measured IOP and CSFP/ICP at baseline and after each intervention. Radial tomographic ONH scans were analyzed by two independent graders using ImageJ, an open-source software. The following ONH morphological parameters were obtained: BMOD, anterior LC depth and retinal thickness. We modeled effects of acute CSFP/ICP changes on ONH morphological parameters using ANOVA (human study) and generalized linear model (pig study). For 19 human subjects, CSFP ranged from 5 to 42 mm Hg before LP and 2 to 19.4 mm Hg after LP. For the six pigs, baseline ICP ranged from 1.5 to 9 mm Hg and maximum stable ICP ranged from 18 to 40 mm Hg. Our models showed that acute CSFP/ICP changes had no significant effect on ONH morphological parameters in both humans and pigs. We conclude that ONH does not show measurable morphological changes in response to acute changes of CSFP/ICP. Proposed mechanisms include compensatory and opposing changes in IOP and CSFP/ICP and nonlinear or nonmonotonic effects of IOP and CSFP/ICP across LC. [ABSTRACT FROM AUTHOR]

INTRODUCTION[|]To measure lamina cribrosa thickness (LCT), lamina cribrosa depth (LCD) and subfoveal choroidal thickness (SFCT) by imaging posterior ocular structures in pediatric cases with isolated unilateral iris coloboma and to determine the differences as compared with healthy contralateral eyes of these cases (fellow eyes) and healthy control eyes.[¤]METHODS[|]This cross-sectional, comparative prospective study included seven children (age range, 9-17 years) with unilateral isolated iris coloboma. The healthy contralateral eyes of these cases formed the fellow group. An age-matched (age range 8-17 years) control group (n = 9) including children with both eyes having either normal or corrected-to-normal visual acuity was formed. A detailed ophthalmic examination was performed. The posterior ocular segments were evaluated using spectral domain-optical coherence tomography (SD-OCT) with enhanced depth imaging (EDI) technique.[¤]RESULTS[|]The SFCT was 372.0 +- 48.8 µm, 375.3 +- 44.0 µm, and 386.5 +- 71.8 µm, respectively and the LCD was 362.4 +- 68.3 µm, 354.4 +- 47.1 µm, and 350.7 +- 38.1 µm, respectively, in the coloboma, fellow, and control eyes. There was no difference between the groups regarding SFCT and LCD. The mean LCT was significantly thinner in the coloboma eyes (200.2 +- 9.5 µm) than in the fellow (238.8 +- 26.7 µm; p = 0.023) and control eyes (240.0 +- 12.9 µm; p < 0.001). The LCT showed no significant correlation with age, axial length or spherical equivalent.[¤]DISCUSSION AND CONCLUSION[|]Better visual prognosis is expected in isolated iris coloboma. Nevertheless, detailed examinations using new technologies such as SD-OCT may reveal some structural changes. Longitudinal studies are required to understand if a thinner LCT in coloboma eyes is associated with any future problems.[¤]

The guinea pig is becoming an increasingly popular model for studying human myopia, which carries an increased risk of glaucoma. As a step towards understanding this association, this study sought to characterize the normal, developmental intraocular pressure (IOP) profiles, as well as the anatomy of the optic nerve head (ONH) and adjacent sclera of young guinea pigs. IOP was tracked in pigmented guinea pigs up to 3 months of age. One guinea pig was imaged in vivo with OCT and one with a fundus camera. The eyes of pigmented and albino guinea pigs (ages 2 months) were enucleated and sections from the posterior segment, including the ONH and surrounding sclera, processed for histological analyses - either hematoxylin and eosin (H&E) staining of paraffin embedded, sectioned tissue (n = 1), or cryostat sectioned tissue, processed for immunohistochemistry (n = 3), using primary antibodies against collagen types I-V, elastin, fibronectin and glial fibrillary acidic protein (GFAP). Transmission and scanning electron microscopy (TEM, SEM) studies of ONHs were also undertaken (n = 2 & 5 respectively). Mean IOPs ranged from 17.33 to 22.7 mmHg, increasing slightly across the age range studied, and the IOPs of individual animals also exhibited diurnal variations, peaking in the early morning (mean of 25.8, mmHg, ∼9 am), and decreasing across the day. H&E-stained sections showed retinal ganglion cell axons organized into fascicles in the prelaminar and laminar region of the ONHs, with immunostained sections revealing collagen types I, III, IV and V, as well as elastin, GFAP and fibronectin in the ONHs. SEM revealed a well-defined lamina cribrosa (LC), with radially-oriented collagen beams. TEM revealed collagen fibrils surrounding non-myelinated nerve fiber bundles in the LC region, with myelination and decreased collagen posterior to the LC. The adjacent sclera comprised mainly crimped collagen fibers in a crisscross arrangement. Both the sclera and LC were qualitatively similar in structure in pigmented and albino guinea pigs. The well-organized, collagen-based LC of the guinea pig ONH is similar to that described for tree shrews and more similar to the human LC than that of other rodents that lack collagen. Based on these latter structural similarities the guinea pig would seem a promising model for investigating the relationship between myopia and glaucoma.

Glaucoma is a chronic and progressive optic neuropathy characterized by the death of retinal ganglion cells and corresponding visual field loss. Despite the growing number of studies on the subject, the pathogenesis of the disease remains unclear. Notwithstanding, several studies have shown that the lamina cribrosa (LC) is considered an anatomic site of glaucomatous optic nerve injury, thus having a key role in the pathophysiology of glaucoma development and progression. Different morphological alterations of the LC have been described in vivo in glaucomatous eyes after the evolution of optical coherence tomography (OCT) devices. The most relevant findings were the reduction of laminar thickness, the presence of localized defects, and the posterior LC displacement. These new laminar parameters documented through OCT are not only promising as possible additional tools for glaucoma diagnosis and monitoring, but also as predictors of disease progression. In spite of the advance of technology, however, proper evaluation of the LC is not yet viable in all eyes. We describe OCT-identified LC changes related to the development and progression of glaucoma and provide future directions based on a critical data analysis, focusing on its clinical relevance and applicability. [ABSTRACT FROM AUTHOR]