Circumpapillary retinal nerve fiber layer thickness, anterior lamina cribrosa depth, and lamina cribrosa thickness in neovascular glaucoma secondary to proliferative diabetic retinopathy: a cross-sectional study.
ABSTRACT: To compare the lamina cribrosa between eyes with and without neovascular glaucoma (NVG) using enhanced depth imaging spectral-domain optical coherence tomography.Forty-six patients with proliferative diabetic retinopathy were enrolled in this cross-sectional study. The patients were divided into two groups based on the absence or presence of NVG (the non-NVG group and the NVG group, respectively). The intraocular pressure (IOP), circumpapillary retinal nerve fiber layer (cpRNFL) thickness, anterior lamina cribrosa depth (ALD), and laminar thickness (LT) were compared between the groups.In the non-NVG group, the mean age was 66.2 ± 2.4 (mean ± standard error) years, mean maximum IOP was 18.8 ± 1.8 mmHg, mean cpRNFL thickness was 91.2 ± 3.9 ?m, mean ALD was 407.0 ± 22.9 ?m, and mean LT was 155.0 ± 4.7 ?m. In the NVG group, the mean age was 61.4 ± 2.1 years, mean maximum IOP was 33.1 ± 1.6 mmHg, mean cpRNFL thickness was 73.6 ± 3.4 ?m, mean ALD was 403.9 ± 20.1 ?m, and mean LT was 156.9 ± 4.2 ?m. The IOP was significantly higher and the cpRNFL was significantly thinner in the NVG group (P < 0.001 and P = 0.002, respectively). However, the age, ALD, and LT were not statistically different between the groups (P = 0.151, 0.919, and 0.757, respectively).Although the cpRNFL was thinner, the structure of the lamina cribrosa was unchanged in the NVG eyes. Axonal loss of the retinal ganglion cells in NVG patients was prior to lamina cribrosa deformation.
Project description:To determine the factors influencing the anterior lamina cribrosa (LC) surface depth (LCD) in patients with open-angle glaucoma (OAG), focusing on the association between LCD and the position of the central retinal vessel trunk (CRVT) at the anterior LC surface.Optic nerve heads of 205 OAG eyes were scanned using swept-source optical coherence tomography (SS-OCT). After processing the images using adaptive compensation, the LCD was determined from 11 horizontal B-scan images that divided the optic disc vertically into 12 equal parts. Eyes were divided into two groups (central or peripheral) according to where the CRVT exits from the anterior LC surface. The influence of CRVT position on LCD was evaluated, taking into account age, gender, untreated intraocular pressure (IOP), IOP at optic-disc scanning, retinal nerve fiber layer (RNFL) thickness, visual-field mean deviation, central corneal thickness, and axial length.Patients in the peripheral CRVT group were younger and more myopic, and had a larger mean LCD and thinner global RNFL than those in the central CRVT group (all P?0.023). On multivariate analysis, the peripheral CRVT location was significantly associated with a larger LCD (P = 0.002), together with the significant association of younger age (P<0.001), higher untreated IOP (P = 0.010), and thinner RNFL (P = 0.003) on the larger LCD.In OAG, CRVT location was an independent factor influencing the LCD, together with age, untreated IOP, and global RNFL thickness. The data indicate that the CRVT may contribute to the resistance of the LC against deformation. A longitudinal prospective observation is required to clarify this relationship.
Project description:PURPOSE:To investigate the variation of lamina cribrosa (LC) structure based on the baseline intraocular pressure (IOP) in eyes with primary open-angle glaucoma (POAG) and healthy individuals using swept-source optical coherence tomography. METHODS:A total of 108 eyes with POAG and 61 healthy eyes were recruited. Based on the baseline IOP, the POAG eyes were divided into higher-baseline IOP (HTG; baseline IOP > 21 mmHg, n = 38 eyes) and lower-baseline IOP (NTG; baseline IOP ? 21 mmHg, n = 70 eyes). The anterior laminar insertion depth (ALID), mean LC depth (mLCD), and the LC curvature index (mLCD-ALID) were measured, and compared among the three groups. The regional variation of LC structure was evaluated by vertical-horizontal ALID difference. RESULTS:The mLCD and LC curvature index were greatest in HTG eyes (520.3 ± 123.0 and 80.9 ± 30.7 ?m), followed by NTG (463.2 ± 110.5 and 64.5 ± 30.7 ?m) and healthy eyes (382.9 ± 107.6 and 47.6 ± 25.7 ?m, all P < 0.001). However, there were no significant difference in ALID between HTG and NTG eyes. The vertical-horizontal ALID difference was larger in NTG eyes (72.8 ± 56.2 ?m) than in HTG (32.7 ± 61.4 ?m, P = 0.004) and healthy eyes (25.5 ± 34.8 ?m, P < 0.001). CONCLUSIONS:Lamina cribrosa position and curvature differed in POAG eyes with low and high IOP. This would support the theory that IOP induced biomechanical effects on the optic play a role on glaucoma.
Project description:We developed a method to measure the 3-dimensional (3D) strain field in the optic nerve head (ONH) in vivo between two intraocular pressures (IOP). Radial optical coherence tomography (OCT) scans were taken of the ONH of 5 eyes from 5 glaucoma patients before and after IOP-lowering surgery and from 5 eyes from 3 glaucoma suspect patients before and after raising IOP by wearing tight-fitting swimming goggles. Scans taken at higher and lower IOP were compared using a custom digital volume correlation (DVC) algorithm to calculate strains in the anterior lamina cribrosa (ALC), retina, and choroid. Changes in anterior lamina depth (ALD) relative to Bruch's membrane were also analyzed. Average displacement error was estimated to be subpixel and strain errors were smaller than 0.37%. Suturelysis decreased IOP by 9-20?mmHg and decreased compressive anterior-posterior strain Ezz in the ALC by 0.76% (p=0.002,n=5). Goggle-wearing increased IOP by 3-4?mmHg and produced compressive Ezz in the ALC (-0.32%,p=0.001,n=5). Greater IOP decrease was associated with greater ALD change (p=0.047,n=10) and greater strains in the ALC (Ezz:p=0.002,n=10). A deepening of ALD was associated with lower IOP and greater ALC strains (p?0.045,n=10). A DVC-based method to measure strains from OCT images caused by IOP changes as small as 2.3?mmHg provides preliminary evidence that ALD is shallower and ALC strains are less compressive at higher IOP and that ALD change is associated with ALC strains. STATEMENT OF SIGNIFICANCE: Glaucoma causes vision loss through progressive damage of the retinal ganglion axons at the lamina cribrosa, a connective tissue structure in the optic nerve head that supports the axons as they pass through the eye wall. It is hypothesized that strains caused by intraocular pressure (IOP) may initiate this damage, but few studies have measured the strain response to pressure of the optic nerve head in patients. We present a method to measure the 3D displacement and strain field in the optic nerve head caused by IOP alteration in glaucoma patients using clinically available images. We used this method to measure strain within the optic nerve head from IOP changes caused by glaucoma surgery and wearing tight-fitting swimming goggles.
Project description:There is increasing clinical evidence that the eye is not only affected by intraocular pressure (IOP), but also by intracranial pressure (ICP). Both pressures meet at the optic nerve head of the eye, specifically the lamina cribrosa (LC). The LC is a collagenous meshwork through which all retinal ganglion cell axons pass on their way to the brain. Distortion of the LC causes a biological cascade leading to neuropathy and impaired vision in situations such as glaucoma and idiopathic intracranial hypertension. While the effect of IOP on the LC has been studied extensively, the coupled effects of IOP and ICP on the LC remain poorly understood. We investigated in-vivo the effects of IOP and ICP, controlled via cannulation of the eye and lateral ventricle in the brain, on the LC microstructure of anesthetized rhesus monkeys eyes using the Bioptigen spectral-domain optical coherence tomography (OCT) device (Research Triangle, NC). The animals were imaged with their head upright and the rest of their body lying prone on a surgical table. The LC was imaged at a variety of IOP/ICP combinations, and microstructural parameters, such as the thickness of the LC collagenous beams and diameter of the pores were analyzed. LC microstructure was confirmed by histology. We determined that LC microstructure deformed in response to both IOP and ICP changes, with significant interaction between the two. These findings emphasize the importance of considering both IOP and ICP when assessing optic nerve health.
Project description:The lamina cribrosa is a primary site of damage in glaucoma. While mechanical distortion is hypothesized to cause reduction of axoplasmic flow, little is known about how the pores, which contains the retinal ganglion cell axons, traverse the lamina cribrosa. We investigated lamina cribrosa pore paths in vivo to quantify differences in tortuosity of pore paths between healthy and glaucomatous eyes. We imaged 16 healthy, 23 glaucoma suspect and 48 glaucomatous eyes from 70 subjects using a swept source optical coherence tomography system. The lamina cribrosa pores were automatically segmented using a previously described segmentation algorithm. Individual pore paths were automatically tracked through the depth of the lamina cribrosa using custom software. Pore path convergence to the optic nerve center and tortuosity was quantified for each eye. We found that lamina cribrosa pore pathways traverse the lamina cribrosa closer to the optic nerve center along the depth of the lamina cribrosa regardless of disease severity or diagnostic category. In addition, pores of glaucoma eyes take a more tortuous path through the lamina cribrosa compared to those of healthy eyes, suggesting a potential mechanism for reduction of axoplasmic flow in glaucoma.
Project description:PURPOSE:To assess changes in the position of lamina cribrosa pores (LCPs) induced by acute intraocular pressure (IOP) elevation. METHODS:A prospective observational study. Acute angle-closure suspects who underwent the 2-hour dark room prone provocative test (DRPPT) were included. At baseline and within 5?min after the DRPPT end, tonometry, fundus photography and optical coherence tomography were performed. Optic disc photos taken before and after the DRPPT were aligned and moving distance of each visible LCP was measured (LCPMD). RESULTS:38 eyes from 27 participants (age: 52.5±10.8 years) were included. The IOP rose from 16.7±3.2?mm Hg at baseline to 23.9±4.3?mm Hg at the DRPPT end. The mean lateral LCPMD was 28.1±14.6?µm (range: 5.0-77.2?µm), which increased with higher IOP rise (p=0.01) and deeper optic cup (p=0.02) in multivariate analysis. The intralamina range and SD of the LCPMD increased with younger age (p=0.01?and p=0.02, respectively) and with wider optic cup (p=0.01?and p=0.02, respectively). The LCP movements were headed to the superior direction in 12 (33%) eyes, inferior direction in 10 (28%) eyes, temporal direction in 9 (25%) eyes, and nasal direction in 5 (14%) eyes. CONCLUSIONS:IOP rise is associated with LCP movements in the frontal plane, which are more pronounced with higher IOP rise and deeper optic cup. The intralamina variability in the IOP rise-associated LCPMD increased with younger age and wider optic cup. IOP variation-associated lateral LCP movements may be of interest to elucidate glaucomatous optic nerve damage.
Project description:<h4>Purpose</h4>To investigate peripheral lamina cribrosa depth (PLCD) and its vertical-horizontal difference in eyes with primary open-angle glaucoma (POAG).<h4>Methods</h4>Patients with POAG (n=90 eyes) and age-matched healthy individuals (n=90 eyes) underwent swept-source optical coherence tomography (SS-OCT) scans centered at the optic discs. The PLCD was defined as the vertical distance between the most peripheral visible end of anterior lamina cribrosa (LC) surface and the reference plane connecting the Bruch's membrane openings. The PLCD in each quadrant region and the vertical-horizontal PLCD difference were compared between the POAG and healthy eyes. The clinical factors associated with increased PLCD were evaluated.<h4>Results</h4>The PLCD was significantly larger in the POAG eyes than the control eyes at the horizontal (P=0.034) and vertical (P=0.001) meridians. The vertical PLCD was significantly larger than the horizontal PLCD, both in the POAG eyes (P<0.001) and in the control eyes (P=0.003). However, the vertical-horizontal PLCD difference was significantly larger in the POAG eyes (47±60??m) than in the control eyes (18±54??m, P=0.001). Multivariate regression showed a significant association of male gender (P=0.005), increased baseline IOP (P=0.043), and decreased MD of VF (P=0.025) with increased PLCD.<h4>Conclusions</h4>The peripheral LC was displaced more posteriorly in the POAG eyes compared with the age-matched healthy eyes. In the POAG eyes, the peripheral LC was displaced more posteriorly at the vertical meridian than at the horizontal meridian. The peripheral LC in the vertical meridian might have increased IOP-related strain (deformation) compared with horizontal meridian in glaucomatous eyes.
Project description:It is widely considered that intraocular pressure (IOP)-induced deformation within the neural tissue pores of the lamina cribrosa (LC) contributes to neurodegeneration and glaucoma. Our goal was to study how the LC microstructure and mechanical properties determine the mechanical insult to the neural tissues within the pores of the LC. Polarized light microscopy was used to measure the collagen density and orientation in histology sections of three sheep optic nerve heads (ONH) at both mesoscale (4.4?m) and microscale (0.73?m) resolutions. Mesoscale fiber-aware FE models were first used to calculate ONH deformations at an IOP of 30mmHg. The results were then used as boundary conditions for microscale models of LC regions. Models predicted large insult to the LC neural tissues, with 95th percentile 1st principal strains ranging from 7 to 12%. Pores near the scleral boundary suffered significantly higher stretch compared to pores in more central regions (10.0±1.4% vs. 7.2±0.4%; p=0.014; mean±SD). Variations in material properties altered the minimum, median, and maximum levels of neural tissue insult but largely did not alter the patterns of pore-to-pore variation, suggesting these patterns are determined by the underlying structure and geometry of the LC beams and pores. To the best of our knowledge, this is the first computational model that reproduces the highly heterogeneous neural tissue strain fields observed experimentally. STATEMENT OF SIGNIFICANCE:The loss of visual function associated with glaucoma has been attributed to sustained mechanical insult to the neural tissues of the lamina cribrosa due to elevated intraocular pressure. Our study is the first computational model built from specimen-specific tissue microstructure to consider the mechanics of the neural tissues of the lamina separately from the connective tissue. We found that the deformation of the neural tissue was much larger than that predicted by any recent microstructure-aware models of the lamina. These results are consistent with recent experimental data and the highest deformations were found in the region of the lamina where glaucomatous damage first occurs. This study provides new insight into the complex biomechanical environment within the lamina.
Project description:Purpose:To determine if variation in anterior lamina cribrosa surface depth (ALCSD) differs between glaucoma patients of African (AD) and European descent (ED). Methods:A 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. Results:A deeper ALCSD-Scl was found in males (52.4 ?m, P = 0.0401), AD individuals (78.6 ?m, P = 0.0004), younger individuals (-3.1 ?m/year, P < 0.0213), and eyes with larger discs (81.0 ?m/mm2, P = 0.024), increased visual field loss (mean defect, MD: -6.4 ?m/dB [decibel], P = 0.0106), and higher intraocular pressure (IOP: 14.1 ?m/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 ?m/year, P = 0.0213), while there was no significant association in the ED group (2.1 ?m/mm Hg, P < 0.2026). Conclusions:This 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.
Project description:Based on biomechanical theory, lamina cribrosa (LC) displacement, the key component of progressive glaucomatous change, is presumed to be dependent on intraocular pressure (IOP) as well as tissue stiffness of LC. In the performance of the Valsalva maneuver, both IOP and cerebrospinal fluid pressure can increase. The present study investigated the age-dependent variation of LC displacement during the standardized Valsalva maneuver in healthy subjects. Sixty-three (63) eyes (age range: 20-76 years) were prospectively underwent IOP measurement and Cirrus HD-OCT optic disc scans before and during the standardized Valsalva maneuver. During the standardized Valsalva maneuver, the IOP significantly increased from 13.2 ± 2.9 mmHg to 18.6 ± 5.2 mmHg (P < 0.001). The maximal LC depth significantly decreased in the younger age groups (age: 20 s to 40 s) but not in the older age groups (age: over 50). The BMO distance did not change significantly. Younger age (P = 0.009), a smaller increase of IOP during the Valsalva maneuver (P = 0.002), and greater baseline maximal LC depth (P = 0.013) were associated with more anterior displacement of the LC during the standardized Valsalva maneuver. Taken together, age as well as translaminar pressure dynamics seems to play a crucial role in LC biomechanics.