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.

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 : Glaucoma affects task performance, a measure of ability in the context of performing daily tasks. Task factors affected by glaucoma are not well characterized for practical ophthalmic application. This study identifies domains of task performance associated with structure-function measures in order to characterize task factors relevant in the context of glaucoma. Methods : We recruited adults aged 50 years and older with glaucoma, with no other ocular comorbidities, who underwent ophthalmic evaluation. Eleven domains of task performance were analyzed (Table) using the standardized Assessment of Life Habits questionnaire to measure 1) ability to perform tasks (accomplishment, scale 0-10) and 2) satisfaction with task performance (satisfaction, scale 1-5). Better eye visual field mean deviation (MD) and OCT retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GCIPL) average thickness were analyzed. Multivariable regression analyses determined the association between task performance and MD, RNFL, and GCIPL, adjusting for age, race, glaucoma and depressive symptoms. Depressive symptoms were in the models due to their known association with vision loss. Results : 77 subjects of average age 68 +/- 9.2 years and baseline MD of -3.7 +/- 6.3 dB, RNFL of 76.1 +/- 13.3 mum and GCIPL of 69.8 +/- 10.7 mum were enrolled. Overall task performance scores were high (accomplishment 9.3 +/- 0.6, satisfaction 4.5 +/- 0.5). For accomplishment, MD, RNFL, and GCIPL were significant indicators for overall task performance scores (p < 0.001) and for >=6 domains (p <= 0.028, Table). For satisfaction, RNFL was a significant indicator for overall task performance scores (p = 0.037). Unlike accomplishment, satisfaction was less associated with structure-function (3 domains across measures). Depressive symptoms were significantly associated with task performance (p <= 0.05) in all domains except communication. Conclusions : Task performance affected by glaucoma is underrecognized in ophthalmic practice. Awareness of task performance accomplishment (ability) may be relevant in glaucoma more so than patients' satisfaction. Satisfaction is a measure of patients' perception and their reports often overestimate actual ability. Therefore, measuring accomplishment and its association with structure-function measures may guide future evaluation of those tasks most affected by glaucoma in order to enable timely treatment for task performance limitations

Purpose : Ganglion cell-inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL) thicknesses measured by OCT have been shown to be useful for glaucoma diagnosis and progression detection. The purpose of this study was to determine the disease severity threshold (tipping point) at which the longitudinal rate of change for RNFL and GCIPL thickness slows down; allowing to determine the preferred location to follow structural damage along the spectrum of the disease severity. Methods : Subjects with comprehensive ophthalmic examination and >= 5 visits with qualified visual field (VF; Humphrey Field Analyzer; Zeiss, Dublin, CA) and OCT (Cirrus HDOCT; Zeiss) optic nerve head and macular scans were enrolled. Piece-wise linear mixed effects model was used to identify the tipping points of RNFL and GCIPL vs. VF mean deviation (MD), respectively, and model with quadratic term for RNFL vs. GCIPL. To account for the difference in dynamic ranges, RNFL and GCIPL rate of change were standardized (normal distribution, mean=0 sd=1). Results : 177 eyes (125 open angle glaucoma, 45 glaucoma suspect, and 7 healthy eyes) of 114 subjects were analyzed. Subjects' mean age: 70 +/- 11 years, median VF MD: -1.78 dB ([Q1, Q3]; -5.8, -0.2), baseline average RNFL and GCIPL thicknesses: 73.2 +/- 14.9mum and 68.3 +/- 10.7mum, respectively, average follow-up time: 3.4 +/- 1 years, mean visits per subject: 5.6, with a grand total of 1,010 follow-up visits. Tipping point for RNFL occur at earlier stage of the disease and the rate of change is faster than for GCIPL (Table). However, after standardization, the slopes for RNFL and GCIPL were similar. When comparing the rate of change for RNFL and GCIPL, no tipping point was detected, but as RNFL and GCIPL decreased, the rate of change in RNFL became significantly smaller. Conclusions : Rate of RNFL thinning slows down at an earlier stage of functional damage than GCIPL. Different dynamic ranges give the impression that RNFL decreases faster, but accounting for the larger dynamic range, a similar rate of change to GCIPL is observed across the entire disease severity spectrum. Our results do not indicate whether RNFL or GCIPL is better for detecting progression except for very advanced stages of the disease where RNFL progression rate stalls

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)

Purpose : We previously described the two-dimensional continuous time hidden Markov model (2D CT-HMM) to model glaucoma progression using structural and functional measurements simultaneously. The purpose of this study was to validate the glaucoma progression prediction performance of a previously trained model on data collected from a different cohort. Methods : A 2D CT-HMM was trained using optical coherence tomography (OCT; Cirrus HD-OCT, Zeiss, Dublin, CA) mean circumpapillary retinal nerve fiber layer (cRNFL) thickness and visual field index (VFI; Humphrey Field Analyzer, Zeiss) obtained from 107 eyes of 107 subjects, including glaucoma and glaucoma suspect. Average observation period was 4.2 years (7.1 visits). Approximately 1 year of longitudinal data were collected from a separate cohort. 78 eyes of 39 subjects, glaucoma and glaucoma suspect, with an average of 2.2 +/- 0.4 visits were included. After matching the distribution of OCT and VF data on the training cohort, 19 eyes from 14 subjects were selected. The previously trained model was tested on these cases. One visit was used as an input to the model to predict the state at the next visit at least 6 months later, with 4 possible state changes (stable, OCT, VF, or OCT+VF progression). The percentage of correct prediction against the actual recorded state was reported as the prediction accuracy. Results : Baseline age of the test cohort was 58.4 +/- 13.9 years, VFI 93.6 +/- 8.3, mean cRNFL thickness 74.0 +/- 10.9mum. Figure 1 shows the trained model. The size of the circle (state) shows the number of subjects passing through the state. The grayscale of the state indicates the length of time spent there, increasing white to black. Lines indicate state changes, with the blue line being the most likely. This information is also shown in numerical form. The inset shows an example of model use. The calculated prediction accuracy of this pre-trained 2D CT-HMM on test data was 52.6%. Conclusions : Although the glaucoma progression prediction performance of the trained 2D CT-HMM was slightly lower than that previously reported, it is acceptable given the training and testing cohorts were different, and it exceeds the random chance of making a correct prediction, 25%. Furthermore, unlike conventional methods, this model requires only one visit as an input, which makes it a potentially useful tool in the clinical prediction of glaucoma progression. (Figure Presented)

Purpose: It has been shown that Asians have a high prevalence of normal tension glaucoma, while Caucasians and African-Americans have predominantly high tension glaucoma. This study compared the lamina cribrosa (LC) microstructure of a cohort of Korean and American eyes in order to discern microstructure differences between the cohorts that could contribute to this phenomenon.
Method(s): The optic nerve head of 53 healthy eyes (42 subjects; 38 Korean eyes and 15 American eyes, consisting of a mixture of Caucasian and African-American eyes) was scanned 3 times during the same session with Cirrus HD-OCT (Zeiss, Dublin CA). These scans were registered and averaged to increase LC visibility using a method we have previously described. The area of the ONH featuring clearly visible LC was delineated, and scans were semi-automatically analyzed within the delineated area to segment the LC microstructure in 3D. The LC measurements of beam thickness, pore diameter, and beam/pore ratio were compared using a hierarchical linear model taking ethnicity and age into account.
Result(s): Baseline characteristics were similar between the cohorts (Table 1). Mean pore diameter was on average 3.78mum bigger in Asian subjects compared to non-Asian subjects (p<0.001), and beam/pore ratio was 0.33 units smaller in Asian subjects (p<0.001). No differences were detected in beam thickness.
Conclusion(s): The in vivo microstructure of the LC varies among different ethnicities. Further research is needed to determine the cause, effect and clinical relevance of these differences. (Table presented)