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Purpose: The lamina cribrosa (LC) is hypothesized to be the site of initial axonal damage in glaucoma with the circumpapillary retinal nerve fiber layer thickness (RNFL-T) widely used as a standard metric for quantifying the glaucomatous damage. The purpose of this study was to determine in vivo, 3-dimensional (3D) differences in the microstructure of the LC in eyes of nonhuman primates (NHPs) with naturally occurring glaucoma., Methods: Spectral-domain optical coherence tomography (OCT) scans (Leica, Chicago, IL, USA) of the optic nerve head were acquired from a colony of 50 adult rhesus monkeys suspected of having high prevalence of glaucoma. The RNFL-T was analyzed globally and in quadrants using a semi-automated segmentation software. From a set of 100 eyes, 18 eyes with the thinnest global RNFL-T were selected as the study group and 18 eyes with RNFL-T values around the 50th percentile were used as controls. A previously described automated segmentation algorithm was used for LC microstructure analysis. Parameters included beam thickness, pore diameter and their ratio (beam-to-pore ratio [BPR]), pore area and shape parameters, beam and pore volume, and connective tissue volume fraction (CTVF; beam volume/total volume). The LC microstructure was analyzed globally and in the following volumetric sectors: quadrants, central and peripheral lamina, and three depth slabs (anterior, middle, and posterior)., Results: Although no significant difference was detected between groups for age, weight, or disc size, the study group had significantly thinner RNFL than the control group (P < 0.01). The study group had significantly smaller global and sectoral pore diameter and larger BPR compared with the control group. Across eyes, the global RNFL-T was associated positively with pore diameter globally. BPR and CTVF were significantly and negatively associated with the corresponding RNFL-T in the superior quadrant., Conclusions: Global and sectoral microstructural differences were detected when comparing thin and normal RNFL-T eyes. Whether these LC differences are the cause of RNFL damage or the result of remodeling of the LC requires further investigation., Translational Relevance: Our findings indicate structural alterations in the LC of NHP exhibiting natural thinning of the RNFL, a common characteristic of glaucomatous damage.

Purpose: To determine whether peripapillary atrophy (PPA) area is an indicator of glaucomatous structural and functional damage and progression., Methods: In this retrospective longitudinal analysis from ongoing prospective study we qualified 71 eyes (50 subjects) with glaucoma. All subjects had a comprehensive ophthalmic examination, visual field (VF), and spectral-domain optical coherence tomography (OCT) testing in at least three visits. PPA was manually delineated on en face OCT optic nerve head scans, while observing the corresponding cross-sectional images, as the hyper-reflective area contiguous with the optic disc., Results: The mean follow-up duration was 4.4 ± 1.4 years with an average of 6.8 ± 2.2 visits. At baseline, PPA area was significantly associated only with VF's mean deviation (MD; P = 0.041), visual field index (VFI; P = 0.041), superior ganglion cell inner plexiform layer (GCIPL; P = 0.011), and disc area (P = 0.011). Longitudinally, PPA area was negatively and significantly associated with MD (P = 0.015), VFI (P = 0.035), GCIPL (P = 0.009), superior GCIPL (P = 0.034), and disc area (P = 0.007, positive association)., Conclusions: Longitudinal change in PPA area is an indicator of glaucomatous structural and functional progression but PPA area at baseline cannot predict future progression., Translational Relevance: Longitudinal changes in peripapillary atrophy area measured by OCT can be an indicator of structural and functional glaucoma progression.

Background: Retinal oxygen saturation (sO 2 ) provides essential information about the eye's response to pathological changes that can result in vision loss. Visible-light optical coherence tomography (vis-OCT) is a noninvasive tool that has the potential to measure retinal sO 2 in a clinical setting. However, its reliability is currently limited by unwanted signals referred to as spectral contaminants (SCs), and a comprehensive strategy to isolate true oxygen-dependent signals from SCs in vis-OCT is lacking., Methods: We develop an adaptive spectroscopic vis-OCT (ADS-vis-OCT) technique that can adaptively remove SCs and accurately measure sO 2 under the unique conditions of each vessel. We also validate the accuracy of ADS-vis-OCT using ex vivo blood phantoms and assess its repeatability in the retina of healthy volunteers., Results: In ex vivo blood phantoms, ADS-vis-OCT agrees with a blood gas machine with only a 1% bias in samples with sO 2 ranging from 0% to 100%. In the human retina, the root mean squared error between sO 2 values in major arteries measured by ADS-vis-OCT and a pulse oximeter is 2.1% across 18 research participants. Additionally, the standard deviations of repeated ADS-vis-OCT measurements of sO 2 values in smaller arteries and veins are 2.5% and 2.3%, respectively. Non-adaptive methods do not achieve comparable repeatabilities from healthy volunteers., Conclusions: ADS-vis-OCT effectively removes SCs from human images, yielding accurate and repeatable sO 2 measurements in retinal arteries and veins with varying diameters. This work could have important implications for the clinical use of vis-OCT to manage eye diseases., (© 2023. The Author(s).)

Purpose: Lamina cribrosa (LC) deformation is hypothesized to play a major role in glaucoma pathogenesis. The purpose of this study was to determine in vivo how varying intraocular pressure (IOP) under fixed intracranial pressure (ICP), and vice versa, deforms the pore paths throughout the LC volume., Methods: Spectral-domain optical coherence tomography scans of the optic nerve head were acquired from healthy adult rhesus monkeys under different pressures. IOP and ICP were controlled with gravity-based perfusion systems into the anterior chamber and lateral ventricle, respectively. IOP and ICP were modulated from baseline to high (19-30 mmHg) and highest (35-50 mmHg) levels while maintaining a fixed ICP of 8 to 12 mmHg and IOP of 15 mmHg, respectively. After three-dimensional registration and segmentation, the paths of pores visible in all settings were tracked based on their geometric centroids. Pore path tortuosity was defined as the measured distance divided by the minimal distance between the most anterior and posterior centroids., Results: The median pore tortuosity at baseline varied among the eyes (range, 1.16-1.68). For the IOP effect under fixed ICP (six eyes, five animals), two eyes showed statistically significant increased tortuosity and one showed a decrease (P < 0.05, mixed-effects model). No significant change was detected in three eyes. When modulating ICP under fixed IOP (five eyes, four animals), a similar response pattern was detected., Conclusions: Baseline pore tortuosity and the response to acute pressure increase vary substantially across eyes., Translational Relevance: LC pore path tortuosity could be associated with glaucoma susceptibility.

Purpose: Growing evidence suggests that dendrite retraction or degeneration in a subpopulation of the retinal ganglion cells (RGCs) may precede detectable soma abnormalities and RGC death in glaucoma. Visualization of the lamellar structure of the inner plexiform layer (IPL) could advance clinical management and fundamental understanding of glaucoma. We investigated whether visible-light optical coherence tomography (vis-OCT) could detect the difference in the IPL sublayer thicknesses between small cohorts of healthy and glaucomatous subjects., Method: We imaged nine healthy and five glaucomatous subjects with vis-OCT. Four of the healthy subjects were scanned three times each in two separate visits, and five healthy and five glaucoma subjects were scanned three times during a single visit. IPL sublayers were manually segmented using averaged A-line profiles., Results: The mean ages of glaucoma and healthy subjects are 59.6 ± 13.4 and 45.4 ± 14.4 years (P = 0.02.) The visual field mean deviations (MDs) are -26.4 to -7.7 dB in glaucoma patients and -1.6 to 1.1 dB in healthy subjects (P = 0.002). Median coefficients of variation (CVs) of intrasession repeatability for the entire IPL and three sublayers are 3.1%, 5.6%, 6.9%, and 5.6% in healthy subjects and 1.8%, 6.0%, 7.7%, and 6.2% in glaucoma patients, respectively. The mean IPL thicknesses are 36.2 ± 1.5 µm in glaucomatous and 40.1 ± 1.7 µm in healthy eyes (P = 0.003)., Conclusions: IPL sublayer analysis revealed that the middle sublayer could be responsible for the majority of IPL thinning in glaucoma. Vis-OCT quantified IPL sublayers with good repeatability in both glaucoma and healthy subjects.

Purpose: To test the hypothesis that the fovea-Bruch's membrane opening (FoBMO) axis angle influences the thickness symmetry of the macular ganglion cell/inner plexiform layer (GCIPL) across the temporal horizontal meridian in normal subjects., Design: Cross-sectional diagnostic study at a tertiary academic center., Methods: One hundred sixteen eyes of 60 normal subjects aged 40 to 85 years underwent spectral domain optical coherence tomography(SD-OCT) imaging. The FoBMO angle was estimated on en face infrared SD-OCT images. Posterior Pole algorithm images acquired with Spectralis SD-OCT were used to define vertical asymmetry as follows. The average thickness difference between the 3 most temporal superpixels above and below the horizontal meridian, the second row of superpixels from the horizontal meridian, and 3 central superpixels above and below the horizontal meridian were calculated. Factors influencing GCIPL thickness asymmetry were explored and changes in thickness asymmetry as a function of FoBMO angle were investigated., Results: No demographic or clinical factors affected temporal GCIPL asymmetry (P>0.05 for all). A more (negatively) tilted FoBMO angle was associated with relatively thinner inferior compared with superior GCIPL thickness in superpixels immediately adjacent to the temporal raphe (P<0.001). The second row of temporal superpixels from the horizontal meridian (P=0.349) or central superpixels (P=0.292) did not show this tendency., Conclusions: Vertical GCIPL symmetry across the horizontal meridian is influenced by the FoBMO angle. SD-OCT algorithms using vertical asymmetry as a diagnostic index should be adjusted for the FoBMO angle.

Segmentation of retinal anatomical features such as optic nerve head (ONH) and optic cup, the brightest area in the center of ONH which is devoid of neural elements, is a prerequisite for computer-aided diagnosis and follow-up of glaucoma. The ONH segmentation methods, which imposed shape and intensity constraints, are unable to identify ONH and optic cup boundaries at the same time. On the other hand, recent efficient supervised learning-based methods, which provide a unified system, require combination of many informative features as their inputs, as well as ground truth for the training phase. This paper uses a saliency map including color, intensity and orientation contrasts as the input of a winner-take-all neural network, and color visual features as the input of a self-organizing map neural network to segment ONH and optic cup, simultaneously. Our method is evaluated on a database of 205 ocular fundus images provided by local eye hospitals and publicly available image databases RIMONE and DIARETDB0 comprising 60 non-glaucomtous and 145 glaucomatous images. The ground truth is provided by two expert ophthalmologists. The method attained an average overlapping error of 9.6% and 25.1% for ONH and cup segmentation, respectively. Cup-to-disc area ratio (CDR) is computed for glaucoma assessment. The mean and standard deviation of the CDR differences between our method and the ground truth in all images are 0.11 and 0.09, respectively.