Anterior Lamina Cribrosa Research Articles

Evaluation of Lamina Cribrosa by Using Enhanced Depth Imaging Optical Coherence Tomography in Ocular Sarcoidosis during Quiescent Phase.

Enhanced depth imaging optical coherence tomography is a useful method to allow for the evaluation of deep ocular structures, such as choroid and lamina cribrosa (LC), which are affected by ocular diseases. We hypothesized that choroidal and optic nerve inflammation in patients with ocular sarcoidosis (OS) might affect the LC structure. This study aimed to evaluate changes in the LC and anterior LC depth (ALCD) in patients with OS. Forty-eight eyes of 26 patients with OS who received the treatment of panuveitis and were in the quiescent phase for at least 6 months were included in the study. Thirty healthy subjects' randomly selected eyes were selected as a control group. Eyes with OS were divided into two subgroups according to the presence (OS eyes with glaucoma [OSWG], n = 23) or absence of glaucoma (OS eyes without glaucoma [OSWOG], n = 25). The LC thickness, ALCD, and peripapillary choroidal thickness were measured using enhanced depth imaging optical coherence tomography in eyes with OS and in controls. The mean LC thickness was found significantly thinner in both OSWG and OSWOG eyes compared with the healthy controls (P < .001 and P = .001, respectively). The mean ALCD was found significantly higher in OSWG eyes (462 ± 65 μm) compared with OSWOG eyes (417 ± 58 μm) and the healthy control eyes (397 ± 59 μm; P = .03 and P = .001, respectively). The average peripapillary choroidal thickness was found to be significantly thinner in OSWG eyes compared with the control eyes (P = .05). The present study revealed that OS is associated with a thinned LC independent of the presence of glaucoma. The degenerative changes in the LC, which is the transition point of the retinal nerve fibers, may cause long-term visual dysfunction in OS. These degenerative changes should be prevented by controlling inflammation with early diagnosis and treatment in patients with OS.

Longitudinal assessment of optic nerve head changes using optical coherence tomography in a primate microbead model of ocular hypertension

In humans, the longitudinal characterisation of early optic nerve head (ONH) damage in ocular hypertension (OHT) is difficult as patients with glaucoma usually have structural ONH damage at the time of diagnosis. Previous studies assessed glaucomatous ONH cupping by measuring the anterior lamina cribrosa depth (LCD) and minimal rim width (MRW) using optical coherence tomography (OCT). In this study, we induced OHT by repeated intracameral microbead injections in 16 cynomolgus primates (10 unilateral; 6 bilateral) and assessed the structural changes of the ONH longitudinally to observe early changes. Elevated intraocular pressure (IOP) in OHT eyes was maintained for 7 months and serial OCT measurements were performed during this period. The mean IOP was significantly elevated in OHT eyes when compared to baseline and compared to the control eyes. Thinner MRW and deeper LCD values from baseline were observed in OHT eyes with the greatest changes seen between month 1 and month 2 of OHT. Both the mean and maximum IOP values were significant predictors of MRW and LCD changes, although the maximum IOP was a slightly better predictor. We believe that this model could be useful to study IOP-induced early ONH structural damage which is important for understanding glaucoma pathogenesis.

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.

Lamina Cribrosa Moves Anteriorly After Trabeculectomy in Myopic Eyes.

PurposeThe purpose of this study was to investigate changes in lamina cribrosa (LC) depth after trabeculectomy in myopic eyes using enhanced depth imaging (EDI) spectral-domain optical coherence tomography (SD-OCT).MethodsSerial horizontal B-scans of the optic nerve head of 41 myopic eyes with primary open-angle glaucoma (POAG) were obtained before and 3 months after trabeculectomy using EDI SD-OCT. LC depth, defined as the distance from the opening plane of Bruch's membrane to the level of the anterior LC surface, was measured before and 3 months after trabeculectomy at 7 locations spaced equidistantly across the vertical optic disc diameter on B-scan images. The mean of the measurements at these seven planes was defined as the average LC depth. Factors associated with changes in LC depth were identified by linear regression.ResultsIntraocular pressure (IOP) decreased from 26.3 ± 9.3 millimeters of mercury (mm Hg) preoperatively to 10.6 ± 3.5 mm Hg 3 months after trabeculectomy. LC depth was significantly lower 3 months after trabeculectomy than preoperatively (P < 0.001, all planes). The magnitude of LC depth reduction was significantly associated with younger age, higher preoperative LC depth, and greater magnitude of IOP reduction (all P ≤ 0.016).ConclusionsLC depth reduction was observed after trabeculectomy in myopic eyes. The degree of LC depth reduction was not related to the degree of myopia.

The optic nerve head, lamina cribrosa, and nerve fiber layer in non-myopic and myopic children

The purpose of this study was to evaluate the optic nerve head, lamina cribrosa, retina, and choroid in school age children using spectral domain optical coherence tomography (SD-OCT) and to assess these structural parameters in relation to age, axial length, and refractive error. Healthy children, ages 11.15 ± 2.62 years (range 6–15 years, n = 53), underwent cycloplegic autorefraction, biometry, and SD-OCT imaging in both eyes. Images were analyzed using custom written programs in MATLAB, after adjustment for lateral magnification. Peripapillary retinal nerve fiber layer (RNFL) thickness, retinal and choroidal thicknesses, Bruch's membrane opening (BMO) area, minimum rim width (MRW), and anterior lamina cribrosa surface depth (ALCSD) were determined and analyzed with age, axial length, and refraction. Results show that axial length increased and refractive error became more myopic with increasing age (R2 = 0.25, β = 0.18, P < 0.0001 and R2 = 0.27, β = −0.37, P < 0.0001, respectively). Minimum foveal thickness and central 1 mm retinal thickness increased with increasing age (R2 = 0.15, β = 2.38, P < 0.01 and R2 = 0.11, β = 3.16, P < 0.05, respectively). Age-adjusted raw values for peripapillary RNFL thickness decreased with increasing axial length (R2 = 0.11, β = −3.18, P < 0.05); however, this relationship was not present when image magnification was corrected (R2 = 0.07, β = 2.72, P = 0.09). BMO area increased with myopic refractive error (R2 = 0.16, β = −0.10, P < 0.01). Age-adjusted vertical cup-to-disc ratio decreased with increasing axial length and myopic refractive error (R2 = 0.12, β = −0.05, P < 0.05 and R2 = 0.11, β = 0.03, P = 0.05, respectively). Mean MRW, mean ALCSD, and peripapillary choroidal thickness were not associated with age, axial length, or refraction. Mean MRW was significantly thinner in eyes with deeper ALCS (R2 = 0.41, β = −0.83, P < 0.0001). These findings provide normal values for retinal and optic nerve head parameters in school age children, and also suggest that ocular remodeling occurs in some structures in school age children with normal eye growth and during early stages of myopia development.

Clinical Assessment of Scleral Canal Area in Glaucoma Using Spectral-Domain Optical Coherence Tomography

To investigate anterior scleral canal (ASC) area in the eyes with glaucoma using spectral-domain optical coherence tomography (SDOCT). Cross-sectional study. This study included 206 eyes of 103 patients with glaucoma, classified as 66 eyes of 33 patients with unilateral glaucoma and 140 eyes of 70 patients with bilateral glaucoma. Radial scan enhanced depth imaging SDOCT centered on the optic disc was performed, and parameters that present ASC area such as ASC opening and the largest ASC area were obtained in each eye. The largest ASC area was the largest cross-sectional area of the ASC region identified between the ASC opening and anterior lamina cribrosa insertion. These parameters were compared between eyes with and without glaucoma in unilateral glaucoma, and eyes with worse and better visual field defect (VFD) in bilateral glaucoma. In the patients with unilateral glaucoma, ASC opening and largest ASC area were significantly larger in the eyes with glaucoma than in those without glaucoma (both P < .001). In bilateral glaucoma, these parameters were significantly larger in the eyes with worse VFD than in those with better VFD (P= .0080 and P= .0018, respectively). Intereye differences of the ASC parameters in the glaucoma patients were significantly greater than that in the normal subjects. Significantly larger ASC area was first observed in the living human eyes with glaucoma compared to the normal eyes. Further longitudinal studies are required to determine if the ASC area is useful in the prevention and treatment of glaucoma.

Neuroretinal rim response to transient changes in intraocular pressure in healthy non-human primate eyes

Optic nerve head (ONH) neuroretinal rim thickness, quantified as minimum rim width (BMO-MRW), is a sensitive measure for assessing early glaucomatous disease. The BMO-MRW is sensitive to transient fluctuations in intraocular pressure (IOP), but the time course over which BMO-MRW decreases and recovers with changes in IOP remains unknown. The goal of this study was to investigate the dynamics of BMO-MRW changes over 2-h periods of mild or moderate IOP elevation, and subsequent recovery, in healthy non-human primate eyes. Eight non-human primates were included in the study. For each animal, in two different sessions separated by at least 2 weeks, the anterior chamber IOP of one eye was maintained at either 25 mmHg or 40 mmHg for 2 h and, subsequently, at 10 mmHg for 2 h. For the duration of anterior chamber cannulation, optical coherence tomography (OCT) radial scans centered on the ONH were acquired every 5 min and used to quantify BMO-MRW. An exponential decay or rise to maximum function was used to determine the extent and rate of structural change. Additionally, Bruch's membrane opening (BMO) area, BMO height/displacement, and BMO-referenced anterior lamina cribrosa surface depth (BMO-ALCSD) were computed from radial scans. A circular scan was used to quantify retinal nerve fiber layer thickness (RNFLT) and circumpapillary choroid thickness. The primary results demonstrated that the BMO-MRW changed over an extended duration, while BMO displacement was rapid and remained stable with sustained IOP. The mean maximum predicted BMO-MRW thinning following 2 h of IOP elevation was significantly related to pressure (34.2 ± 13.8 μm for an IOP of 25 mmHg vs 40.5 ± 12.6 μm for 40 mmHg, p = 0.03). The half-life for BMO-MRW thinning was 21.9 ± 9.2 min for 25 mmHg and 20.9 ± 4.2 min for 40 mmHg, not significantly different between IOP levels (p = 0.76). Subsequently, after 2 h of IOP at 10 mmHg, all animals exhibited partial recovery of BMO-MRW with similar degrees of persistent residual thinning for the two IOP levels (21.5 ± 13.7 vs 21.0 ± 12.3 μm, p = 0.88). Similar to BMO-MRW, choroid thickness exhibited gradual thinning with IOP elevation and residual thinning following IOP reduction. However, there was no significant change in BMO area or BMO-ALCSD in either experimental session. The RNFLT gradually decreased over the duration of IOP elevation, with continued decreases following IOP reduction for the 40 mmHg session, resulting in total changes from baseline of −2.24 ± 0.81 and −2.45 ± 1.21 μm for 25 and 40 mmHg, respectively (p < 0.001). The sum of the results demonstrate that the ONH neural tissue is sensitive to changes in IOP, the effects of which are gradual over an extended time course and different for increased vs. decreased pressure. Understanding the duration over which IOP influences BMO-MRW has important implications for studies investigating the effects of IOP on the ONH. Additionally, individual variability in ONH response to IOP may improve our understanding of the risk and progression of disease.

Association of lamina cribrosa morphometry with retinal nerve fiber layer loss and visual field defects in primary open angle glaucoma.

Objectives:To calculate the anterior lamina cribrosa depth (ALCD) and lamina cribrosa thickness (LCT) in primary open angle glaucoma (POAG) patients and controls and to correlate lamina cribrosa (LC) parameters to retinal nerve fiber layer thickness (RNFLT) and visual field (VF) defects.Methods:The study was conducted from November 2018 to March 2019. A total of 60 correspondents (30 cases and 30 controls) were assessed for general ophthalmological investigations including intraocular pressure (IOP), axial length AXL, ophthalmoscopy, visual field (VF) testing and spectral domain ocular computed tomography (SDOCT).Results:The mean age of subjects was 62 years (Cases 67.30±1.2, controls 57.32±1.1) with more male participants. Intraocular pressure [IOP (19.85 ±1.4)], AXL (22.85 ± 1.6), VF defects (8.30 ± 4.5), RNFLT (72.58 ± 13.2) and LCT (162.51 ± 64.62) were statistically significant in POAG patients as compared to the controls.Conclusion:A thinner LC in POAG correlated significantly with the RNFLT and VF defects. LC anatomical parameters can be estimated with precision using SDOCT with enhanced depth imaging (EDI).

In Vivo anterior Optic Nerve Head changes as a function of Visual Field loss in Glaucoma

AbstractPurposeTo correlate regional measures of prelamina (preL) depth and thickness, anterior lamina cribrosa (LC) depth and nerve fibre layer (NFL) thicknesses with change in visual field sensitivity in primary open angle glaucoma, using enhanced depth imaging optical coherence tomography (OCT).MethodsThree‐dimensional image datasets were acquired as 20° scans centred on the optic nerve head (ONH) of glaucoma (n=111) and control (n=39) eyes, using a custom built OCT at 1040nm (spectral bandwidth 70nm). ONH measurements of regional (superior [S], inferior [I], nasal [N], temporal [T], and central [C]) preL and anterior LC depth were performed using Bruch’s membrane opening as a reference plane. PreL thickness was calculated from these surface measures. Border (above BMO) and peripapillary (pp) NFL were also measured. Intraclass correlation coefficients (ICC) were used to determine intra‐session repeatability.ResultsPreL depth (S: r=0.339, I: r=0.363, and N: r=0.317; p&lt;0.001, T: r=0.219, p=0.007, central: r=0.202, p=0.013) and anterior LC depth (S: r=0.232, p=0.006, I: r=0.229, p=0.006, N: r=0.246, p=0.009, T: r=0.169, p=0.04, central: r=0.226, p=0.006) significantly increased with increasing VF loss in all ONH regions. PreL thickness significantly decreased with increasing VF loss in all ONH regions, (S: r=‐0.295 and I: r=‐0.346; p&lt;0.001, N: r=‐0.218, p=0.026, temporal: r=‐0.177, p=0.031), except for the centre (r=‐0.106, p=0.199). ICCs &gt;0.9 were calculated for all ONH measures and intra‐session differences in the ONH parameters were not identified within triplicate image datasets (p&gt;0.05). BNFL and ppNFL thicknesses significantly decreased with VF loss (p&lt;0.001).ConclusionsSignificant correlations were found between preL depth and thickness, and anterior LC depth with VF function, indicating that these quantitative (and repeatable) measures are useful in monitoring glaucomatous optic neuropathy.

Relationship of Corneal Hysteresis and Anterior Lamina Cribrosa Displacement in Glaucoma

To investigate the relationship between corneal hysteresis (CH) and anterior lamina cribrosa surface (ALCS) displacement over time in a cohort of patients with glaucoma. Prospective observational case series. In this study, 147 eyes from 96 glaucoma or glaucoma suspect patients were followed for a mean of 3.5 years and 7.9 visits. Baseline CH measurements were obtained using the Ocular Response Analyzer (ORA; Reichert Ophthalmic Instruments Inc, Depew, New York, USA). The mean anterior lamina cribrosa surface depth (ALCSD) and choroidal thickness were by automated segmentation of spectral-domain optical coherence tomography (SD-OCT) scans. The rate of change of ALCSD was calculated using linear mixed effects models. Relationship between baseline CH and follow-up ALCSD rate of change was adjusted for confounding factors, including age, intraocular pressure (IOP), and choroidal thickness. The mean baseline CH was 9.4mm Hg (95% confidence interval [CI] 9.1-9.7). Overall, the ALCS was displaced posteriorly at a rate of 0.78μm/y (95% CI-1.82, 0.26). Seventeen eyes (11.5%) showed a significant posterior displacement of ALCS, whereas 22 eyes (15.0%) showed a significant anterior displacement of ALCS. The choroidal thickness thinned at a rate of-1.09μm/y during the follow-up (P= .001). Multivariable mixed modeling showed that choroidal thinning, lower IOP change, and lower corneal hysteresis were significantly associated with posterior ALCS displacement over time (P= .034, P= .037, and P= .048). Each 1mm lower CH was associated with 0.66μm/y posterior displacement of the ALCS. Lower corneal hysteresis was significantly associated with posterior displacement of the anterior lamina cribrosa over time. These data provide additional support for lower corneal hysteresis being a risk factor for glaucoma progression.

Deep learning based noise reduction method for automatic 3D segmentation of the anterior of lamina cribrosa in optical coherence tomography volumetric scans

A deep-learning (DL) based noise reduction algorithm, in combination with a vessel shadow compensation method and a three-dimensional (3D) segmentation technique, has been developed to achieve, to the authors best knowledge, the first automatic segmentation of the anterior surface of the lamina cribrosa (LC) in volumetric ophthalmic optical coherence tomography (OCT) scans. The present DL-based OCT noise reduction algorithm was trained without the need of noise-free ground truth images by utilizing the latest development in deep learning of de-noising from single noisy images, and was demonstrated to be able to cover more locations in the retina and disease cases of different types to achieve high robustness. Compared with the original single OCT images, a 6.6 dB improvement in peak signal-to-noise ratio and a 0.65 improvement in the structural similarity index were achieved. The vessel shadow compensation method analyzes the energy profile in each A-line and automatically compensates the pixel intensity of locations underneath the detected blood vessel. Combining the noise reduction algorithm and the shadow compensation and contrast enhancement technique, medical experts were able to identify the anterior surface of the LC in 98.3% of the OCT images. The 3D segmentation algorithm employs a two-round procedure based on gradients information and information from neighboring images. An accuracy of 90.6% was achieved in a validation study involving 180 individual B-scans from 36 subjects, compared to 64.4% in raw images. This imaging and analysis strategy enables the first automatic complete view of the anterior LC surface, to the authors best knowledge, which may have the potentials in new LC parameters development for glaucoma diagnosis and management.

Association of Corneal Hysteresis With Lamina Cribrosa Curvature in Primary Open Angle Glaucoma.

To investigate whether corneal biomechanical properties are associated with the lamina cribrosa (LC) curvature in eyes with primary open angle glaucoma (POAG). Corneal biomechanical properties and LC curvature were assessed in 65 treatment-naïve POAG patients. Corneal biomechanical properties, including corneal hysteresis (CH), corneal resistance factor (CRF), and corneal-compensated intraocular pressure (IOPcc), were measured using an ocular response analyzer (ORA; Reichert Ophthalmic Instruments). LC curvature was assessed by measuring the LC curvature index (LCCI) on B-scan images obtained using spectral-domain optical coherence tomography (OCT). The LCCI was determined by measuring LC curve depth on the anterior LC surface and the width of the reference line. The LCCI was correlated with CH (P = 0.001), CRF (P = 0.012) and IOPcc (P = 0.001) in the univariate analysis. To adjust multicollinearity, principal component analysis was performed, and multivariate regression analyses were conducted using one variable from each component. The larger LCCI was associated with larger IOPcc (P < 0.001), smaller CRF (P = 0.001) and smaller CH (P < 0.001). Lower CH was associated with a more posteriorly curved LC in treatment naïve POAG patients. This finding may provide a basic explanation for the reported association between CH and an increased risk for glaucoma development and progression, and support a potential value of CH for risk assessment for glaucoma.

Effect of Trabeculectomy on OCT Measurements of the Optic Nerve Head Neuroretinal Rim Tissue

Ophthalmologists commonly perform glaucoma surgery to treat progressive glaucoma. Few studies have examined the stability of OCT neuroretinal rim parameters after glaucoma surgery for ongoing detection of glaucoma progression. Longitudinal cohort study. 20 eyes (16 subjects) with primary open angle glaucoma who had undergone a trabeculectomy. We calculated the change in OCT parameters (minimum rim area (MRA), minimum rim width (MRW), Bruch's membrane opening (BMO) area, mean cup depth (MCD), anterior lamina cribrosa surface depth (ALCSD), prelaminar tissue thickness (PLTT), retinal nerve fiber layer thickness (RFNLT) during an interval from the visit before the surgery to the visit after the surgery, a span of approximately 6-months. We also calculated changes in the same eyes over two separate 6-month intervals that did not contain trabeculectomy to serve as control. We compared these intervals using a generalized linear model (with compound symmetry correlation structure), accounting for the correlation between time intervals for the same eye. MRW, MRA, angle above the reference plane for MRW and MRA, BMO area, MCD, mean ALCSD, PLTT, RNFLT and visual field parameters (mean deviation (MD), pattern standard deviation (PSD), and visual field index (VFI)). The intervals containing trabeculectomy showed a significant decrease in intraocular pressure (-9.2 mmHg, p<.001) when compared to control intervals. Likewise, the following neuroretinal rim parameters showed significant changes with trabeculectomy: increased MRW (+6.04μm, p=.001), increased MRA (+0.014mm2, p=.024), increased angle above reference plane of MRW (+2.64°, p<.001), decreased MCD (-11.6μm, p=.007), and decreased mean ALCSD (-18.91μm, p=.006). This is consistent with an increase in rim tissue thickness and a more anterior position of the ILM and ALCS relative to the BMO plane. Conversely, RNFLT change was not significantly different between trabeculectomy and control intervals (p=.37). Trabeculectomy resulted in anatomical changes to the ONH rim associated with reduced glaucomatous cupping. The RNFL thickness may be a more stable measure of disease progression that clinicians can use to monitor across time intervals containing glaucoma surgery.

In vivo characterization of the deformation of the human optic nerve head using optical coherence tomography and digital volume correlation

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 SignificanceGlaucoma 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.

Investigation of the Optic Nerve Head Morphology Influence to the Optic Nerve Head Biomechanics - Patient Specific Model.

Glaucoma is associated with damage and death of optic nerve fibers within the Lamina Cribrosa (LC) region of the Optic Nerve Head. The pathogenesis of the disease is unclear, and the anterior LC surface morphology of different individuals can be one of the possible contributor of glaucoma development and progression. The current study evaluates the relationship between the LC surface curvature and distribution of shear stresses on the LC surface. The patient-specific reconstructed ocular model was developed and analyzed in a finite element analysis software. In addition, the effect of elastic modulus of both sclera and LC on the shear stress was examined. Results showed that there is a correlation between the shear stress distribution and the curvature of the anterior LC surface. This finding highlights the potential significance of the LC morphology on the distribution of LC shear stress and require further investigation.

Investigation of the Optic Nerve Head Morphology Influence to the Optic Nerve Head Biomechanics - Population Specific Model.

Glaucoma is an eye disorder potentially leading to permanent blindness through the damage of optic nerves at the optic nerve head (ONH). As a critical region of optic nerve damage, the porous Lamina Cribrosa (LC) in the ONH plays a critical role in determining whether optic nerves passing through will experience apoptosis in response to shear stress. The primary cause of shear stress to the LC is the increase in intraocular pressure (IOP). Since morphology governs how mechanical stresses distributes, LC morphology could be an important factor in determining the risks of glaucoma development and progression. The current project aims at investigating how anterior LC surface morphology impacts its response to shear stress caused by IOP. Results of the current study show that steeper LC morphologies could be associated with increased average shear stress on the anterior LC surface. The effect of LC morphology was comparable to that of IOP. This highlights the potential significance of LC morphology on the distribution of IOP-induced shear stress and calls for further investigation in this area.

Evaluation of lamina cribrosa in angioid streaks using spectral-domain optical coherence tomography enhanced depth imaging

To investigate retinal nerve fiber layer (RNFL) thickness, anterior lamina cribrosa depth (ALD) and laminar thickness (LT) in eyes with angioid streaks (AS) in comparison with healthy eyes. Patients with AS (n=32 eyes) and age-matched healthy subjects (n=42 eyes) underwent enhanced depth imaging with spectral domain optical coherence tomography of the optic nerve head. RNFL thickness was obtained automatically by using the Heidelberg software. The ALD was defined as the vertical distance between the Bruch's membrane openings as reference plane and the anterior border of the lamina cribrosa. The LT was measured as the distance between the anterior and posterior borders of the lamina cribrosa. RNFL thickness, ALD and LT were compared between the AS and healthy eyes adjusting for axial length. The mean age was 51.7±8.0 years for AS patients and 53.8±10.2 years for control subjects (P=0.34). The mean RNFL thickness was 88.6±17.6μm in AS eyes and 102.1±8.3μm in control eyes; the difference between the groups was significantly significant. ALD was 350.9±70.8μm in AS eyes and 432.5±82.1μm in control eyes, while LT was 166.3±41.0μm in AS eyes and 241.3±43.2μm in control eyes. ALD and LT were also significantly thinner in AS eyes than control eyes (P=0.003, P<0.001; respectively). Enhanced depth imaging revealed that eyes with AS demonstrate thinner RNFL, ALD and LT compared with normal eyes. Further studies with a larger sample size are needed to understand the relationship between these findings and the morphologic changes and pathogenesis of AS.

Changes in the Anterior Lamina Cribrosa Morphology with Glaucoma Severity

This study was designed to evaluate if primary open angle glaucoma (POAG) and its severity are associated with the shape of the lamina cribrosa (LC) as measured by a global shape index (LC-GSI), or other indices of LC curvature or depth. Optical coherence tomography (OCT) scans of the optic nerve head (OHN) were obtained from subjects with POAG (n = 99) and non-glaucomatous controls (n = 76). ONH structures were delineated, the anterior LC morphology reconstructed in 3D, and the LC-GSI calculated (more negative values denote greater posterior concavity). Anterior LC depth and 2D-curvature were also measured. Severity of glaucoma was defined by the extent of visual field loss, based on the Hodapp-Parrish-Anderson grading. Linear regression analyses compared LC characteristics between controls, mild-moderate, and advanced POAG groups. After adjusting for age, gender, ethnicity, intraocular pressure, axial length and corneal curvature, the LC-GSI was most negative in the advanced POAG group (mean [standard error] = −0.34 [0.05]), followed by the mild-moderate POAG group (−0.31 [0.02]) and then controls (−0.23 [0.02], PTrend = 0.01). There was also a significant trend of increasing LC depth and greater LC horizontal curvature with increasing severity of glaucoma (PTrend = 0.04 and 0.02, respectively). Therefore, with more severe glaucoma, the LC-GSI was increasingly more negative, and the anterior LC depth and curvature greater. These observations collectively correspond to greater cupping of the ONH at the level of the LC. As the LC-GSI describes the 3D anterior LC morphology, its potential usage may be complementary to existing ONH parameters measured on OCT.

Swept-Source OCT for Evaluating the Lamina Cribrosa: A Report by the American Academy of Ophthalmology

To review the published literature on the use of swept-source (SS) OCT for evaluating the lamina cribrosa in glaucoma. A PubMed and Cochrane Library literature search initially conducted on March 3, 2017, and updated on June 26, 2018, yielded a total of 64 articles. Articles that were reviews or that were not published in English were excluded, and 29 were found to fit the inclusion criteria. The panel methodologist then assigned a level of evidence rating to each study. Fifteen studies were rated level III, 14 studies were rated level II, and no studies were rated level I. Different aspects of the lamina cribrosa were studied using SS-OCT, including the anterior lamina cribrosa curvature, anterior lamina cribrosa depth, anterior lamina cribrosa insertions, laminar thickness, focal lamina cribrosa defects (FLCDs), and lamina cribrosa microarchitecture. In general, imaging of the anterior lamina can be achieved reliably, although shadowing from blood vessels at the neuroretinal rim remains an issue. Imaging of the posterior lamina can be achieved with varying levels of success. In glaucoma, there is posterior migration of the anterior lamina cribrosa insertions as well as increased thinning and posterior curvature of the lamina cribrosa. Focal lamina cribrosa defects appear more commonly in glaucoma, and this may hint at the pathogenesis of axonal damage. In addition, there may be remodeling of the microarchitecture of the lamina, resulting in more variable laminar pores. There are limited studies comparing SS-OCT with spectral-domain (SD) OCT with regard to imaging of the lamina, but the difference in image quality between enhanced depth imaging (EDI) with SD-OCT and SS-OCT seems minimal. Imaging of the lamina cribrosa using SS-OCT has demonstrated that the lamina cribrosa is likely biomechanically active and that significant changes occur in glaucoma. The diagnostic utility of SS-OCT for lamina cribrosa imaging is promising, but standardized nomenclature, automated measurements, and longitudinal studies with larger and more diverse sample sizes are needed.

Structure-function relationships in glaucoma using enhanced depth imaging optical coherence tomography-derived parameters: a cross-sectional observational study

BackgroundTo investigate structural and functional correlations in glaucoma patients using enhanced depth imaging spectral-domain optical coherence tomography (EDI OCT)-derived parameters.MethodsWe prospectively enrolled healthy participants and glaucomatous patients with a wide range of disease stages. All participants underwent visual field (VF) testing (SITA - Standard 24–2; Carl Zeiss Meditec, Dublin, CA) and EDI OCT imaging (Spectralis; Heidelberg Engineering Co., Heidelberg, Germany). The following optic nerve head parameters were measured on serial vertical EDI OCT B-scans by two experienced examiners masked to patients clinical data: lamina cribrosa (LC) thickness and area, prelaminar neural tissue thickness and area, anterior LC depth, Bruch’s membrane opening (BMO) and average, superior, and inferior BMO-minimum rim width (BMO-MRW). Only good quality images were considered, and whenever both eyes were eligible, one was randomly selected for analysis. Scatter plots were constructed to investigate correlations between each anatomic parameter and patient’s VF status (based on VF index [VFI] values).ResultsA total of 73 eyes of 73 patients were included. All EDI OCT parameters evaluated differed significantly between glaucomatous and control eyes (P ≤ 0.045). A secondary analysis, in which glaucomatous patients were divided according to VF mean deviation index values into 3 groups (mild [G1; > − 6 dB], moderate [G2; − 6 to − 12 dB] and advanced [G3; <− 12 dB] glaucoma), revealed that average BMO-MRW was the EDI OCT parameter that presented more significant differences between the different stages of glaucoma. Significant structure-function correlations were found between VFI values and prelaminar neural tissue area (R2 = 0.20, P = 0.017), average BMO-MRW (R2 = 0.35, P ≤ 0.001), superior BMO-MRW (R2 = 0.21, P = 0.012), and inferior BMO-MRW (R2 = 0.27, P = 0.002). No significant correlations were found for LC area and anterior LC depth (P ≥ 0.452).ConclusionsEvaluating the distribution pattern and structure-function correlations of different laminar and prelaminar EDI OCT-derived parameters in glaucomatous patients, we found better results for neural tissue-based indexes (compared to LC-derived parameters). The diagnostic utility of each parameter deserves further investigations.