Faculty Bibliography

PURPOSE/OBJECTIVE:Previously, we introduced a state-based 2-dimensional continuous-time hidden Markov model (2D CT HMM) to model the pattern of detected glaucoma changes using structural and functional information simultaneously. The purpose of this study was to evaluate the detected glaucoma change prediction performance of the model in a real clinical setting using a retrospective longitudinal dataset. DESIGN/METHODS:Longitudinal, retrospective study. PARTICIPANTS/METHODS:One hundred thirty-four eyes from 134 participants diagnosed with glaucoma or as glaucoma suspects (average follow-up, 4.4±1.2 years; average number of visits, 7.1±1.8). METHODS:A 2D CT HMM model was trained using OCT (Cirrus HD-OCT; Zeiss, Dublin, CA) average circumpapillary retinal nerve fiber layer (cRNFL) thickness and visual field index (VFI) or mean deviation (MD; Humphrey Field Analyzer; Zeiss). The model was trained using a subset of the data (107 of 134 eyes [80%]) including all visits except for the last visit, which was used to test the prediction performance (training set). Additionally, the remaining 27 eyes were used for secondary performance testing as an independent group (validation set). The 2D CT HMM predicts 1 of 4 possible detected state changes based on 1 input state. MAIN OUTCOME MEASURES/METHODS:Prediction accuracy was assessed as the percentage of correct prediction against the patient's actual recorded state. In addition, deviations of the predicted long-term detected change paths from the actual detected change paths were measured. RESULTS:Baseline mean ± standard deviation age was 61.9±11.4 years, VFI was 90.7±17.4, MD was -3.50±6.04 dB, and cRNFL thickness was 74.9±12.2 μm. The accuracy of detected glaucoma change prediction using the training set was comparable with the validation set (57.0% and 68.0%, respectively). Prediction deviation from the actual detected change path showed stability throughout patient follow-up. CONCLUSIONS:The 2D CT HMM demonstrated promising prediction performance in detecting glaucoma change performance in a simulated clinical setting using an independent cohort. The 2D CT HMM allows information from just 1 visit to predict at least 5 subsequent visits with similar performance.

Glaucoma is the second leading cause of blindness world-wide. Despite active research efforts driven by the importance of diagnosis and treatment of the optic degenerative neuropathy, the relationship between structural and functional changes along the glaucomateous evolution are still not clearly understood. Dynamic changes of the lamina cribrosa (LC) in the presence of intraocular pressure (IOP) were suggested to play a significant role in optic nerve damage, which motivates the proposed research to explore the relationship of changes of the 3D structure of the LC collagen meshwork to clinical diagnosis. We introduce a framework to quantify 3D dynamic morphological changes of the LC under acute IOP changes in a series of swept-source optical coherence tomography (SS-OCT) scans taken under different pressure states. Analysis of SS-OCT images faces challenges due to low signal-to-noise ratio, anisotropic resolution, and observation variability caused by subject and ocular motions. We adapt unbiased diffeomorphic atlas building which serves multiple purposes critical for this analysis. Analysis of deformation fields yields desired global and local information on pressure-induced geometric changes. Deformation variability, estimated with repeated images of a healthy volunteer without IOP elevation, is found to be a magnitude smaller than pressure-induced changes and thus illustrates feasibility of the proposed framework. Results in a clinical study with healthy, glaucoma suspect, and glaucoma subjects demonstrate the potential of the proposed method for non-invasive in vivo analysis of LC dynamics, potentially leading to early prediction and diagnosis of glaucoma.

Purpose/UNASSIGNED:To determine if inner retinal layer reflectivity in eyes with acute central retinal vein occlusion (CRVO) correlates with visual acuity at 12 months. Methods/UNASSIGNED:Macular optical coherence tomography (OCT) scans were obtained from 22 eyes of 22 patients with acute CRVO. Optical intensity ratios (OIRs), defined as the mean OCT reflectivity of the inner retinal layers normalized to the mean reflectivity of the RPE, were measured from the presenting and 1-month OCT image by both manual measurements of grayscale B-scans and custom algorithmic measurement of raw OCT volume data. OIRs were assessed for association with final visual outcome. Cohort subgroup division for analysis was determined statistically. Results/UNASSIGNED:Eyes with poorer final visual acuity (≥20/70) at 1 year were more likely to have a higher ganglion cell layer OIR than eyes with better final visual acuity (<20/70) at 1 month (manually: 0.591 to 0.735, P = 0.006, algorithmically: 0.663 to 0.799, P = 0.014). At 1 month, eyes with a poorer final visual acuity demonstrated a higher variance of OIR measurements (algorithmically: 0.087 vs. 0.160, P = 0.002) per scan than eyes with better final visual acuity. Conclusions/UNASSIGNED:In acute CRVO, ganglion cell layer changes at 1 month, including increased reflectivity and increased heterogeneity of reflectivity signal as expressed as OIR and OIR variance, were associated with a poorer visual prognosis at 1 year. Technique calibration with larger sample sizes and automated integration into OCT platforms will be necessary to determine if OIR can be a clinically useful prognostic tool.

Purpose: Most reported information regarding the in vivo prelaminar tissue is based on a limited number of sampling planes on OCT volumes. In this study we used whole volume data to compute a global mean prelaminar thickness and examined its association with structural and functional parameters in subjects with moderate to advanced glaucoma. Given the low reliability of OCT and visual field (VF) to detect progression in advanced subjects, this study focuses on this subset as it could benefit most from a novel structural parameter.
Method(s): Subjects with moderate to advanced glaucoma, as indicated by a baseline spectral-domain(SD) OCT's mean RNFL thickness <=70mum, were included. All subjects had a baseline prototype swept-source(SS) OCT, VF (Humphrey Field Analyzer, Zeiss), and at least one follow-up SD-OCT (Cirrus HD-OCT, Zeiss). SS-OCT raster scan of the optic nerve head (ONH) (3.5 mmx3.5mm;400x400x861sampling points) was performed. The prelaminar tissue was manually delineated in each SS-OCT cross-section and the mean distance between the vitreous/ONH interface and the anterior lamina surface was automatically computed by averaging the thickness in every sampling point within the ONH. A random mixed effects model was used for assessing the association between baseline prelaminar thickness and cross-sectional variables, and longitudinal changes in structural and functional parameters.
Result(s): 31 eyes from 27 subjects were available for analysis (mean follow-up=20 months). Baseline prelaminar thickness was positively associated with baseline RNFL (average, superior, inferior), GCIPL (average, superior, inferior), rim area, vertical cup to disc ratio (C/D ratio), VFI and MD (p<=0.02) and negatively associated with baseline average C/D ratio and cup volume (p<=0.002;Table). Longitudinal analysis demonstrated that thicker baseline prelaminar tissue was associated with faster rate of progression for average and inferior RNFL thickness and faster enlargement of average and vertical C/D ratio (p<=0.03).
Conclusion(s): Prelaminar tissue thickness is significantly associated with ONH, peripapillary, macular and VF parameters on cross-sectional analysis. On longitudinal analysis prelaminar thickness showed association with faster rate of RNFL progression. Thorough sampling of the prelaminar tissue thickness has the potential to serve as a biomarker for both disease status and risk of progression in subjects with glaucoma. (Table presented)

Purpose: The optic nerve and peripapillary sclera undergo mechanical stresses and strains due to tractional forces as the eyes move. In this study, gaze as a potential cause of lamina cribrosa (LC) deformation was explored in a well-controlled in-vivo animal model at normal and elevated intracranial pressure (ICP).
Method(s): An adult healthy macaque was anesthetized, and OCT (Leica Microsystems, Chicago, IL) scans of the optic nerve head (ONH) (3x3mm; 400x400x1024 pixels) were obtained. A baseline scan was acquired at normal ICP (9mmHg) with the eye at neutral position followed by adduction and abduction positions. ICP was raised to 25mmHg via a ventricular cannula, and scanning was repeated in all gaze settings and locations. All scans were acquired after a 10-minute pause to allow for dissipation of tissue viscoelastic changes. Scans were registered in 3D using our own algorithm and evaluated for macroand microstructure deformation. Lamina microstructure measurements were generated from shared regions among all scanning setting using our own 3D segmentation algorithm.
Result(s): At baseline and elevated ICPs, the IOPs were10 and 19mmHg, respectively. Gaze shifts from the neutral position were associated with a seesaw movement of the macrostructure - nasal elevation and temporal depression in adduction and the reverse effect in abduction (Fig. 1). This effect was more pronounced in elevated ICP condition. At both pressure settings, the ratio of beam thickness to pore diameter increased when gaze deviated from midline (Table 1). The changes seen from neutral to abduction were greater than those seen from neutral to adduction; both findings were more pronounced under elevated ICP.
Conclusion(s): We demonstrated that gaze can induce noticeable macrostructure deformation of the ONH region and a measurable effect on global LC microstructural parameters. Microstructure effects are more pronounced in abduction and in elevated ICP. The magnitude of gaze effect as well as the potential damage to the lamina and its associated axons should be studied further. (Figure presented)