Disparities in Visual Field Testing Frequency Among Subjects With Glaucoma.

Purpose: Prior evidence suggests racial disparities in the utilization of visual field testing (VFT) for the diagnosis and monitoring of glaucoma. In this study, we considered the effect of baseline glaucoma severity and socioeconomic disadvantage along with other potential confounders such as test reliability, ancillary tests, and glaucoma surgeries on racial disparity in the frequency of VFT. Methods: The records of all subjects with a diagnosis of glaucoma who received VFT at an academic, tertiary care facility from January 2018 to December 2021 were accessed. Analysis was performed to compare VFT frequency, the total number of office visits (DoS), and the ratio of VFT frequency to DoS (VFT/DoS) across self-reported races while controlling for sex, age, socioeconomic disadvantage (Area Deprivation Index), VF reliability indicators and baseline mean deviation, optical coherence tomography frequency, and glaucoma surgeries. Results: Among the 2654 subjects (1515 White, 782 Black, and 357 Asian) included in this study, Black subjects had the worst socioeconomic status and disease severity at baseline. They also experienced a 3% lower VFT/DoS ratio compared to White subjects (P = 0.031). Asian subjects had a 5% lower VFT/DoS ratio compared to White subjects (P = 0.015). Discussion: We identified racial disparity in performing VFT in subjects with glaucoma even when multiple confounders were considered. Further investigation is necessary to identify other race-associated factors to work toward reducing racial disparities in VFT. Translational Relevance: Black and Asian subjects with glaucoma receive fewer VFT per visit compared to White subjects even when considering socioeconomic disadvantage and disease severity.

Peripapillary Atrophy Area as an Indicator of Glaucomatous Structural and Functional Progression.

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.

Early inner plexiform layer thinning and retinal nerve fiber layer thickening in excitotoxic retinal injury using deep learning-assisted optical coherence tomography.

Excitotoxicity from the impairment of glutamate uptake constitutes an important mechanism in neurodegenerative diseases such as Alzheimer's, multiple sclerosis, and Parkinson's disease. Within the eye, excitotoxicity is thought to play a critical role in retinal ganglion cell death in glaucoma, diabetic retinopathy, retinal ischemia, and optic nerve injury, yet how excitotoxic injury impacts different retinal layers is not well understood. Here, we investigated the longitudinal effects of N-methyl-D-aspartate (NMDA)-induced excitotoxic retinal injury in a rat model using deep learning-assisted retinal layer thickness estimation. Before and after unilateral intravitreal NMDA injection in nine adult Long Evans rats, spectral-domain optical coherence tomography (OCT) was used to acquire volumetric retinal images in both eyes over 4 weeks. Ten retinal layers were automatically segmented from the OCT data using our deep learning-based algorithm. Retinal degeneration was evaluated using layer-specific retinal thickness changes at each time point (before, and at 3, 7, and 28 days after NMDA injection). Within the inner retina, our OCT results showed that retinal thinning occurred first in the inner plexiform layer at 3 days after NMDA injection, followed by the inner nuclear layer at 7 days post-injury. In contrast, the retinal nerve fiber layer exhibited an initial thickening 3 days after NMDA injection, followed by normalization and thinning up to 4 weeks post-injury. Our results demonstrated the pathological cascades of NMDA-induced neurotoxicity across different layers of the retina. The early inner plexiform layer thinning suggests early dendritic shrinkage, whereas the initial retinal nerve fiber layer thickening before subsequent normalization and thinning indicates early inflammation before axonal loss and cell death. These findings implicate the inner plexiform layer as an early imaging biomarker of excitotoxic retinal degeneration, whereas caution is warranted when interpreting the ganglion cell complex combining retinal nerve fiber layer, ganglion cell layer, and inner plexiform layer thicknesses in conventional OCT measures. Deep learning-assisted retinal layer segmentation and longitudinal OCT monitoring can help evaluate the different phases of retinal layer damage upon excitotoxicity.

Motion Contrast, Phase Gradient, and Simultaneous OCT Images Assist in the Interpretation of Dark-Field Images in Eyes with Retinal Pathology.

The cellular-level visualization of retinal microstructures such as blood vessel wall components, not available with other imaging modalities, is provided with unprecedented details by dark-field imaging configurations; however, the interpretation of such images alone is sometimes difficult since multiple structural disturbances may be present in the same time. Particularly in eyes with retinal pathology, microstructures may appear in high-resolution retinal images with a wide range of sizes, sharpnesses, and brightnesses. In this paper we show that motion contrast and phase gradient imaging modalities, as well as the simultaneous acquisition of depth-resolved optical coherence tomography (OCT) images, provide additional insight to help understand the retinal neural and vascular structures seen in dark-field images and may enable improved diagnostic and treatment plans.

LIMBARE: An Advanced Linear Mixed-Effects Breakpoint Analysis With Robust Estimation Method With Applications to Longitudinal Ophthalmic Studies.

Purpose: Broken stick analysis is a widely used approach for detecting unknown breakpoints where the association between measurements is nonlinear. We propose LIMBARE, an advanced linear mixed-effects breakpoint analysis with robust estimation, especially designed for longitudinal ophthalmic studies. LIMBARE accommodates repeated measurements from both eyes and over time, and it effectively addresses the presence of outliers. Methods: The model setup of LIMBARE and the computing algorithm for point and confidence interval estimates of the breakpoint were introduced. The performance of LIMBARE and other competing methods was assessed via comprehensive simulation studies and application to a longitudinal ophthalmic study with 216 eyes (145 subjects) followed for an average of 3.7 ± 1.3 years to examine the longitudinal association between structural and functional measurements. Results: In simulation studies, LIMBARE showed the smallest bias and mean squared error for estimating the breakpoint, with an empirical coverage probability of corresponding confidence interval estimates closest to the nominal level for scenarios with and without outlier data points. In the application to the longitudinal ophthalmic study, LIMBARE detected two breakpoints between visual field mean deviation (MD) and retinal nerve fiber layer thickness and one breakpoint between MD and cup-to-disc ratio, whereas the cross-sectional analysis approach detected only one and none, respectively. Conclusions: LIMBARE enhances breakpoint estimation accuracy in longitudinal ophthalmic studies, and the cross-sectional analysis approach is not recommended for future studies. Translational Relevance: Our proposed method and companion R package provide a valuable computational tool for advancing longitudinal ophthalmology research and exploring the association relationships among ophthalmic variables.

Reducing Ophthalmic Health Disparities Through Transfer Learning: A Novel Application to Overcome Data Inequality.

Purpose: Race disparities in the healthcare system and the resulting inequality in clinical data among different races hinder the ability to generate equitable prediction results. This study aims to reduce healthcare disparities arising from data imbalance by leveraging advanced transfer learning (TL) methods. Method: We examined the ophthalmic healthcare disparities at a population level using electronic medical records data from a study cohort (N = 785) receiving care at an academic institute. Regression-based TL models were usesd, transferring valuable information from the dominant racial group (White) to improve visual field mean deviation (MD) rate of change prediction particularly for data-disadvantaged African American (AA) and Asian racial groups. Prediction results of TL models were compared with two conventional approaches. Results: Disparities in socioeconomic status and baseline disease severity were observed among the AA and Asian racial groups. The TL approach achieved marked to comparable improvement in prediction accuracy compared to the two conventional approaches as evident by smaller mean absolute errors or mean square errors. TL identified distinct key features of visual field MD rate of change for each racial group. Conclusions: The study introduces a novel application of TL that improved reliability of the analysis in comparison with conventional methods, especially in small sample size groups. This can improve assessment of healthcare disparity and subsequent remedy approach. Translational Relevance: TL offers an equitable and efficient approach to mitigate healthcare disparities analysis by enhancing prediction performance for data-disadvantaged group.

Can Glaucoma Suspect Data Help to Improve the Performance of Glaucoma Diagnosis?

Purpose: The presence of imbalanced datasets in medical applications can negatively affect deep learning methods. This study aims to investigate how the performance of convolutional neural networks (CNNs) for glaucoma diagnosis can be improved by addressing imbalanced learning issues through utilizing glaucoma suspect samples, which are often excluded from studies because they are a mixture of healthy and preperimetric glaucomatous eyes, in a semi-supervised learning approach. Methods: A baseline 3D CNN was developed and trained on a real-world glaucoma dataset, which is naturally imbalanced (like many other real-world medical datasets). Then, three methods, including reweighting samples, data resampling to form balanced batches, and semi-supervised learning on glaucoma suspect data were applied to practically assess their impacts on the performances of the trained methods. Results: The proposed method achieved a mean accuracy of 95.24%, an F1 score of 97.42%, and an area under the curve of receiver operating characteristic (AUC ROC) of 95.64%, whereas the corresponding results for the traditional supervised training using weighted cross-entropy loss were 92.88%, 96.12%, and 92.72%, respectively. The obtained results show statistically significant improvements in all metrics. Conclusions: Exploiting glaucoma suspect eyes in a semi-supervised learning method coupled with resampling can improve glaucoma diagnosis performance by mitigating imbalanced learning issues. Translational Relevance: Clinical imbalanced datasets may negatively affect medical applications of deep learning. Utilizing data with uncertain diagnosis, such as glaucoma suspects, through a combination of semi-supervised learning and class-imbalanced learning strategies can partially address the problems of having limited data and learning on imbalanced datasets.

Age-Related Differences in Ocular Features of a Naturalistic Free-Ranging Population of Rhesus Macaques.

Purpose: Rhesus macaques (Macaca mulatta) are the premier nonhuman primate model for studying human health and disease. We investigated if age was associated with clinically relevant ocular features in a large cohort of free-ranging rhesus macaques from Cayo Santiago, Puerto Rico. Methods: We evaluated 120 rhesus macaques (73 males, 47 females) from 0 to 29 years old (mean ± SD: 12.6 ± 6.4) from September to December 2021. The ophthalmic evaluation included intraocular pressure (IOP) assessment, corneal pachymetry, biomicroscopy, A-scan biometry, automated refraction, and fundus photography after pupil dilation. The associations of age with the outcomes were investigated through multilevel mixed-effects models adjusted for sex and weight. Results: On average, IOP, pachymetry, axial length, and automated refraction spherical equivalent were 18.37 ± 4.68 mmHg, 474.43 ± 32.21 µm, 19.49 ± 1.24 mm, and 0.30 ± 1.70 diopters (D), respectively. Age was significantly associated with pachymetry (ß coefficient = -1.20; 95% confidence interval [CI], -2.27 to -0.14; P = 0.026), axial length (ß coefficient = 0.03; 95% CI, 0.01 to 0.05; P = 0.002), and spherical equivalent (ß coefficient = -0.12; 95% CI, -0.22 to -0.02; P = 0.015). No association was detected between age and IOP. The prevalence of cataracts in either eye was 10.83% (95% CI, 6.34-17.89) and was significantly associated with age (odds ratio [OR] = 1.20; 95% CI, 1.06-1.36; P = 0.004). Retinal drusen in either eye was observed in 15.00% (95% CI, 9.60-22.68) of animals, which was also significantly associated with age (OR = 1.14; 95% CI, 1.02-1.27; P = 0.020). Conclusions: Rhesus macaques exhibit age-related ocular associations similar to those observed in human aging, including decreased corneal thickness, increased axial length, myopic shift, and higher prevalence of cataract and retinal drusen.

GABA decrease is associated with degraded neural specificity in the visual cortex of glaucoma patients.

Glaucoma is an age-related neurodegenerative disease of the visual system, affecting both the eye and the brain. Yet its underlying metabolic mechanisms and neurobehavioral relevance remain largely unclear. Here, using proton magnetic resonance spectroscopy and functional magnetic resonance imaging, we investigated the GABAergic and glutamatergic systems in the visual cortex of glaucoma patients, as well as neural specificity, which is shaped by GABA and glutamate signals and underlies efficient sensory and cognitive functions. Our study shows that among the older adults, both GABA and glutamate levels decrease with increasing glaucoma severity regardless of age. Further, our study shows that the reduction of GABA but not glutamate predicts the neural specificity. This association is independent of the impairments on the retina structure, age, and the gray matter volume of the visual cortex. Our results suggest that glaucoma-specific decline of GABA undermines neural specificity in the visual cortex and that targeting GABA could improve the neural specificity in glaucoma.

Segmentation-Free OCT-Volume-Based Deep Learning Model Improves Pointwise Visual Field Sensitivity Estimation.

Purpose: The structural changes measured by optical coherence tomography (OCT) are related to functional changes in visual fields (VFs). This study aims to accurately assess the structure-function relationship and overcome the challenges brought by the minimal measurable level (floor effect) of segmentation-dependent OCT measurements commonly used in prior studies. Methods: We developed a deep learning model to estimate the functional performance directly from three-dimensional (3D) OCT volumes and compared it to the model trained with segmentation-dependent two-dimensional (2D) OCT thickness maps. Moreover, we proposed a gradient loss to utilize the spatial information of VFs. Results: Our 3D model was significantly better than the 2D model both globally and pointwise regarding both mean absolute error (MAE = 3.11 + 3.54 vs. 3.47 ± 3.75 dB, P < 0.001) and Pearson's correlation coefficient (0.80 vs. 0.75, P < 0.001). On a subset of test data with floor effects, the 3D model showed less influence from floor effects than the 2D model (MAE = 5.24 ± 3.99 vs. 6.34 ± 4.58 dB, P < 0.001, and correlation 0.83 vs. 0.74, P < 0.001). The gradient loss improved the estimation error for low-sensitivity values. Furthermore, our 3D model outperformed all prior studies. Conclusions: By providing a better quantitative model to encapsulate the structure-function relationship more accurately, our method may help deriving VF test surrogates. Translational Relevance: DL-based VF surrogates not only benefit patients by reducing the testing time of VFs but also allow clinicians to make clinical judgments without the inherent limitations of VFs.

Under Pressure: Lamina Cribrosa Pore Path Tortuosity in Response to Acute Pressure Modulation.

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.

Adaptive spectroscopic visible-light optical coherence tomography for clinical retinal oximetry.

BACKGROUND: Retinal oxygen saturation (sO2) 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 sO2 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 sO2 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 sO2 ranging from 0% to 100%. In the human retina, the root mean squared error between sO2 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 sO2 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 sO2 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.

Numerous diseases that cause blindness are associated with disrupted oxygen consumption in the retina, the part of the eye that senses light. This highlights the importance of accurately measuring oxygen consumption in the clinic. To address this challenge, we developed a method to analyze images of the retina which have been collected using visible-light optical coherence tomography, a non-invasive imaging method. Our approach achieves accurate oxygen level measurements in blood samples and in healthy volunteers. With further testing, our approach may prove useful in the clinical management of several diseases that cause blindness, allowing clinicians to more accurately diagnose disease and monitor the health of the eye.

Automated 360-degree goniophotography with the NIDEK Gonioscope GS-1 for glaucoma.

This study was registered with ClinicalTrials.gov (ID: NCT03715231). A total of 20 participants (37 eyes) who were 18 or older and had glaucoma or were glaucoma suspects were enrolled from the NYU Langone Eye Center and Bellevue Hospital. During their usual ophthalmology visit, they were consented for the study and underwent 360-degree goniophotography using the NIDEK Gonioscope GS-1. Afterwards, the three ophthalmologists separately examined the images obtained and determined the status of the iridocorneal angle in four quadrants using the Shaffer grading system. Physicians were masked to patient names and diagnoses. Inter-observer reproducibility was determined using Fleiss' kappa statistics. The interobserver reliability using Fleiss' statistics was shown to be significant between three glaucoma specialists with fair overall agreement (Fleiss' kappa: 0.266, p < .0001) in the interpretation of 360-degree goniophotos. Automated 360-degree goniophotography using the NIDEK Gonioscope GS-1 have quality such that they are interpreted similarly by independent expert observers. This indicates that angle investigation may be performed using this automated device and that interpretation by expert observers is likely to be similar. Images produced from automated 360-degree goniophotography using the NIDEK Gonioscope GS-1 are similarly interpreted amongst glaucoma specialists, thus supporting use of this technique to document and assess the anterior chamber angle in patients with, or suspected of, glaucoma and iridocorneal angle abnormalities.

In vivo Modulation of Intraocular and Intracranial Pressures Causes Nonlinear and Non-monotonic Deformations of the Lamina Cribrosa and Scleral Canal.

Purpose: To evaluate changes in monkey optic nerve head (ONH) morphology under acutely controlled intraocular pressure (IOP) and intracranial pressure (ICP). Methods: Seven ONHs from six monkeys were imaged via optical coherence tomography while IOP and ICP were maintained at one of 16 conditions. These conditions were defined by 4 levels for each pressure: low, baseline, high and very high. Images were processed to determine scleral canal area, aspect ratio, and planarity and anterior lamina cribrosa (ALC) shape index and curvature. Linear mixed effect models were utilized to investigate the effects of IOP, ICP and their interactions on ONH morphological features. The IOP-ICP interaction model was compared with one based on translaminar pressure difference (TLPD). Results: We observed complex, eye-specific, non-linear patterns of ONH morphological changes with changes in IOP and ICP. For all ONH morphological features, linear mixed effects models demonstrated significant interactions between IOP and ICP that were unaccounted for by TLPD. Interactions indicate that the effects of IOP and ICP depend on the other pressure. The IOP-ICP interaction model was a higher quality predictor of ONH features than a TLPD model. Conclusions: In vivo modulation of IOP and ICP causes nonlinear and non-monotonic changes in monkey ONH morphology that depend on both pressures and is not accounted for by a simplistic TLPD. These results support and extend prior findings. Translational Relevance: A better understanding of ICP's influence on the effects of IOP can help inform the highly variable presentations of glaucoma and effective treatment strategies.

LIMBARE: an Advanced Linear Mixed-effects Breakpoint Analysis with Robust Estimation Method with Applications to Longitudinal Ophthalmic Studies.

Purpose: Broken stick analysis is a widely used approach for detecting unknown breakpoints where association between measurements is non-linear. We propose LIMBARE, an advanced li near m ixed-effects b reakpoint a nalysis with r obust e stimation, especially designed for longitudinal ophthalmic studies. LIMBARE accommodates repeated measurements from both eyes and overtime, and effectively address the presence of outliers. Methods: The model setup of LIMBARE and computing algorithm for point and confidence interval estimates of the breakpoint was introduced. The performance of LIMBARE and other competing methods was assessed via comprehensive simulation studies and application to a longitudinal ophthalmic study with 216 eyes (145 subjects) followed for an average of 3.7±1.3 years to examine the longitudinal association between structural and functional measurements. Results: In simulation studies, LIMBARE showed the smallest bias and mean squared error (MSE) for estimating the breakpoint, with empirical coverage probability of corresponding CI estimate closest to the nominal level for scenarios with and without outlier data points. In the application to the longitudinal ophthalmic study, LIMBARE detected two breakpoints between visual field mean deviation (MD) and retinal nerve fiber layer thickness (RNFL) and one breakpoint between MD and cup to disc ratio (CDR), while the cross-sectional analysis approach only detected one and none, respectively. Conclusions: LIMBARE enhances breakpoint estimation accuracy in longitudinal ophthalmic studies, while cross-sectional analysis approach is not recommended for future studies. Translational Relevance: Our proposed method and companion software R package provides a valuable computational tool for advancing longitudinal ophthalmology research and exploring the association relationships between ophthalmic variables.

Modeling Longitudinal Optical Coherence Tomography Images for Monitoring and Analysis of Glaucoma Progression.

Glaucoma causes progressive visual field deterioration and is the leading cause of blindness worldwide. Glaucomatous damage is irreversible and greatly impacts quality of life. Therefore, it is critically important to detect glaucoma early and closely monitor progression to preserve functional vision. Glaucoma is routinely monitored in the clinical setting using optical coherence tomography (OCT) for derived measures such as the thickness of important visual structures. There is not a consensus of what measures represent the most relevant biomarkers of glaucoma progression. Further, despite the increasing availability of longitudinal OCT data, a quantitative model of 3D structural change over time associated with glaucoma does not exist. In this paper we present an algorithm that will perform hierarchical geodesic modeling at the imaging level, considering 3D OCT images as observations of structural change over time. Hierarchical modeling includes subject-wise trajectories as geodesics in the space of diffeomorphisms and population level (glaucoma vs control) trajectories are also geodesics which explain subject-wise trajectories as deviations from the mean. Our preliminary experiments demonstrate a greater magnitude of structural change associated with glaucoma compared to normal aging. Our algorithm has the potential application in patient-specific monitoring and analysis of glaucoma progression as well as a statistical model of population trends and population variability.

Comparing Acute IOP-Induced Lamina Cribrosa Deformations Premortem and Postmortem.

Purpose: Lamina cribrosa (LC) deformations caused by elevated intraocular pressure (IOP) are believed to contribute to glaucomatous neuropathy and have therefore been extensively studied, in many conditions, from in vivo to ex vivo. We compare acute IOP-induced global and local LC deformations immediately before (premortem) and after (postmortem) sacrifice by exsanguination. Methods: The optic nerve heads of three healthy monkeys 12 to 15 years old were imaged with spectral-domain optical coherence tomography under controlled IOP premortem and postmortem. Volume scans were acquired at baseline IOP (8-10 mm Hg) and at 15, 30, and 40 mm Hg IOP. A digital volume correlation technique was used to determine the IOP-induced three-dimensional LC deformations (strains) in regions visible premortem and postmortem. Results: Both conditions exhibited similar nonlinear relationships between IOP increases and LC deformations. Median effective and shear strains were, on average, over all eyes and pressures, smaller postmortem than premortem, by 14% and 11%, respectively (P's < 0.001). Locally, however, the differences in LC deformation between conditions were variable. Some regions were subjected premortem to triple the strains observed postmortem, and others suffered smaller deformations premortem than postmortem. Conclusions: Increasing IOP acutely caused nonlinear LC deformations with an overall smaller effect postmortem than premortem. Locally, deformations premortem and postmortem were sometimes substantially different. We suggest that the differences may be due to weakened mechanical support from the unpressurized central retinal vessels postmortem. Translational Relevance: Additional to the important premortem information, comparison with postmortem provides a unique context essential to understand the translational relevance of all postmortem biomechanics literature.

Virtual Reality Oculokinetic Perimetry Test Reproducibility and Relationship to Conventional Perimetry and OCT.

Purpose: Vivid Vision Perimetry (VVP; Vivid Vision, Inc) is a novel method for performing in-office and home-based visual field assessment using a virtual reality platform and oculokinetic perimetry. Here we examine the reproducibility of VVP Swift and compare results with conventional standard automated perimetry (SAP) and spectral-domain (SD) OCT. Design: Cross-sectional study. Participants: Fourteen eyes of 7 patients with open-angle glaucoma (OAG) (average age, 64.6 years; 29% women) and 10 eyes of 5 patients with suspected glaucoma (average age, 61.8 years; 40% women) were enrolled. Methods: Patients with OAG and suspected glaucoma were enrolled prospectively and underwent 2 VVP Swift examinations. Results were compared with 1 conventional SAP examination (Humphrey Visual Field [HVF]; Zeiss) and 1 SD OCT examination. Main Outcome Measures: Mean sensitivity (in decibels) obtained for each eye in 2 VVP Swift test sessions and a conventional SAP examination, thickness of the retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) for the SD OCT examination, and mean test durations of the VVP Swift and SAP examinations. Results: The mean test duration of VVP Swift in both eyes (8.5 minutes) was significantly shorter (P < 0.001) than SAP (12.2 minutes). The average absolute difference of the mean sensitivity between the 2 VVP Swift sessions was found to be 0.73 dB (95% confidence interval [CI], 0.40-1.06). A statistically significant association was found between average mean sensitivity measurements from the VVP and mean deviation (MD) measurements obtained by the HVF with a Pearson correlation coefficient of 0.86 (95% CI, 0.70-0.94; P < 0.001). Mean visual sensitivity measurements from the VVP Swift test were significantly associated with average RNFL thickness (r = 0.66; P = 0.014) and GCC thickness (r = 0.63; P = 0.02), whereas the correlation coefficients between HVF MD and RNFL and GCC were 0.86 (P < 0.001) and 0.83 (P < 0.001), respectively. Conclusions: Our results demonstrated that the VVP Swift test can generate reproducible results and is comparable with conventional SAP. This suggests that the device can be used by clinicians to assess visual function in glaucoma.

Normative Data and Conversion Equation for Spectral-Domain Optical Coherence Tomography in an International Healthy Control Cohort.

BACKGROUND: Spectral-domain (SD-) optical coherence tomography (OCT) can reliably measure axonal (peripapillary retinal nerve fiber layer [pRNFL]) and neuronal (macular ganglion cell + inner plexiform layer [GCIPL]) thinning in the retina. Measurements from 2 commonly used SD-OCT devices are often pooled together in multiple sclerosis (MS) studies and clinical trials despite software and segmentation algorithm differences; however, individual pRNFL and GCIPL thickness measurements are not interchangeable between devices. In some circumstances, such as in the absence of a consistent OCT segmentation algorithm across platforms, a conversion equation to transform measurements between devices may be useful to facilitate pooling of data. The availability of normative data for SD-OCT measurements is limited by the lack of a large representative world-wide sample across various ages and ethnicities. Larger international studies that evaluate the effects of age, sex, and race/ethnicity on SD-OCT measurements in healthy control participants are needed to provide normative values that reflect these demographic subgroups to provide comparisons to MS retinal degeneration. METHODS: Participants were part of an 11-site collaboration within the International Multiple Sclerosis Visual System (IMSVISUAL) consortium. SD-OCT was performed by a trained technician for healthy control subjects using Spectralis or Cirrus SD-OCT devices. Peripapillary pRNFL and GCIPL thicknesses were measured on one or both devices. Automated segmentation protocols, in conjunction with manual inspection and correction of lines delineating retinal layers, were used. A conversion equation was developed using structural equation modeling, accounting for clustering, with healthy control data from one site where participants were scanned on both devices on the same day. Normative values were evaluated, with the entire cohort, for pRNFL and GCIPL thicknesses for each decade of age, by sex, and across racial groups using generalized estimating equation (GEE) models, accounting for clustering and adjusting for within-patient, intereye correlations. Change-point analyses were performed to determine at what age pRNFL and GCIPL thicknesses exhibit accelerated rates of decline. RESULTS: The healthy control cohort (n = 546) was 54% male and had a wide distribution of ages, ranging from 18 to 87 years, with a mean (SD) age of 39.3 (14.6) years. Based on 346 control participants at a single site, the conversion equation for pRNFL was Cirrus = -5.0 + (1.0 × Spectralis global value). Based on 228 controls, the equation for GCIPL was Cirrus = -4.5 + (0.9 × Spectralis global value). Standard error was 0.02 for both equations. After the age of 40 years, there was a decline of -2.4 µm per decade in pRNFL thickness ( P < 0.001, GEE models adjusting for sex, race, and country) and -1.4 µm per decade in GCIPL thickness ( P < 0.001). There was a small difference in pRNFL thickness based on sex, with female participants having slightly higher thickness (2.6 µm, P = 0.003). There was no association between GCIPL thickness and sex. Likewise, there was no association between race/ethnicity and pRNFL or GCIPL thicknesses. CONCLUSIONS: A conversion factor may be required when using data that are derived between different SD-OCT platforms in clinical trials and observational studies; this is particularly true for smaller cross-sectional studies or when a consistent segmentation algorithm is not available. The above conversion equations can be used when pooling data from Spectralis and Cirrus SD-OCT devices for pRNFL and GCIPL thicknesses. A faster decline in retinal thickness may occur after the age of 40 years, even in the absence of significant differences across racial groups.

The Development and Clinical Application of Innovative Optical Ophthalmic Imaging Techniques.

The field of ophthalmic imaging has grown substantially over the last years. Massive improvements in image processing and computer hardware have allowed the emergence of multiple imaging techniques of the eye that can transform patient care. The purpose of this review is to describe the most recent advances in eye imaging and explain how new technologies and imaging methods can be utilized in a clinical setting. The introduction of optical coherence tomography (OCT) was a revolution in eye imaging and has since become the standard of care for a plethora of conditions. Its most recent iterations, OCT angiography, and visible light OCT, as well as imaging modalities, such as fluorescent lifetime imaging ophthalmoscopy, would allow a more thorough evaluation of patients and provide additional information on disease processes. Toward that goal, the application of adaptive optics (AO) and full-field scanning to a variety of eye imaging techniques has further allowed the histologic study of single cells in the retina and anterior segment. Toward the goal of remote eye care and more accessible eye imaging, methods such as handheld OCT devices and imaging through smartphones, have emerged. Finally, incorporating artificial intelligence (AI) in eye images has the potential to become a new milestone for eye imaging while also contributing in social aspects of eye care.