Faculty Bibliography

Purpose : To compare the discrimination accuracy for glaucoma diagnosis using the OCT RNFL clock hours compared with average RNFL. Methods : In a large, ongoing, longitudinal cohort of healthy subjects and subjects with glaucoma, all subjects underwent visual field (VF) and OCT testing. Principal component (PC) analysis was used to reduce the dimensionality of clock hour measurements while maintaining maximum information variability for diagnostic performance. The first four PCs with linear regression were used as predictors of VF mean deviation (MD) and to classify glaucoma diagnosis. The prediction accuracy and discrimination power using cross validation were compared to the models using only average RNFL as a predictor. All models were adjusted for age, signal strength, and intra-subject correlation. Results : 1317 healthy and glaucomatous eyes (717 subjects) were included in the study. A PC analysis was built on the 9 clock hours while excluding non-informative sectors (clock hours 3, 4, and 9). The first PC explained 51% of the total variance, and the first four PCs explained 82% of the total variance and thus were used for subsequent regression models. A PC regression for glaucoma discrimination showed that clock hours 1, 5, 6, 7, 10, 11, 12 were significantly association with diagnosis. The PC showed better glaucoma diagnosis performance compared to average RNFL, with 10-fold cross-validation AUCs of 0.898 and 0.877, respectively (p<0.001). The PC regression for MD improved the model fit measured by R² by 9% compared to a regression using average RNFL. PC showed that clock hours 2, 5, 6, 7, 10, 11, 12 were significantly associated with MD. Conclusions : Using PCs with RNFL clock hours improved classification performance for glaucoma diagnosis and model fit for MD, compared to using average RNFL. This method improves discrimination performance by both considering all sectoral RNFL information and removing locations with low diagnostic yield

Purpose : In mild glaucoma, RNFL thinning and visual field (VF) loss are often localized, but structure-function modeling is impeded by variability due to individual eye anatomy. We perform high-resolution spatial correlations of RNFLT maps for each VF location to identify relevant areas and study further improvements by geometrically aligning RNFLT maps based on artery trajectories. Methods : In 419 SITA Standard 24-2 Humphrey VFs with at most mild glaucoma (mean deviation >=-3dB) with accompanying circumpapillary Cirrus HD-OCT RNFLT maps, we computed pixel-wise correlations (52 VF locations x 40401 pixels). We then performed an alignment operation, ensuring that the two major retinal arteries follow the same lines in all scans. We piecewise linearly approximated the trajectories of the arteries on 4 concentric circles around ONH (Fig. 1a), determined the necessary rotation for each pixel, and morphed the images accordingly (Fig. 1b). Results : For the pre-alignment RNFLT (correlation maps Fig. 2 top) we observed: (1) relatively high correlations (max 0.29); (2) most of the high-correlation regions are highly localized around the median trajectories of the major arteries at most VF locations, possibly due to the stacked character of the fiber bundles close to ONH, which impedes precise spatial mapping to the VF. This observation suggests general retinal vulnerability zones rather than highly VF location-specific areas as assumed by many previous structure-function models. Accordingly, morphing the RNFLT maps by aligning the eyespecific artery locations increased the maximal correlations on 25 of the 52 VF locations (Fig. 2 bottom, marked in green), particularly in nasal and inferior VF, with improvements of up to 0.1 (inferior arcuate region of VF). At many locations, aligned vulnerability areas become substantially more conspicuous (e.g. the location enlarged on the top left) and might have been missed without aligning. Conclusions : High-resolution structure-function correlations reveal retinal vulnerability zones in mild glaucoma. At many VF locations, these zones become better correlated with VF regions when RNFLT maps are aligned along the arteries. Specific attention to RNFL thinning in these zones in glaucoma suspects may improve the detection of initial VF loss glaucoma

Purpose : Predicting progression of primary open angle glaucoma (POAG) continues to be a challenge. Recent studies have shown that macular parameters may predict glaucoma progression and disease onset equally as well or even better than the traditionally used optic nerve head (ONH) retinal nerve fiber layer (RNFL) thickness. We performed a retrospective longitudinal study to identify structural parameters which best predicted visual field (VF) loss. Methods : Subjects with POAG with at least 5 qualified Cirrus OCT (Zeiss, Dublin, CA) macular and optic nerve head (ONH) scans and 5 qualified 24-2 Humphrey VF tests (Zeiss) were enrolled to this study. All parameters from the OCT's report of the macula and ONH scans were used in the analysis. We identified subjects who were OCT ONH progressors or VF progressors using both event and trend based definitions of progression based on the Guided Progression Analyses. Students t-test was used to assess differences in baseline characteristics between groups, and mixed-effects model was used in longitudinal analysis to compare the rate of parameter change between groups. Results : 263 eyes (180 subjects) with a mean follow-up time of 2.4+/-1.8 years were included in the study. Twenty-three eyes were identified as ONH progressors, 25 eyes were identified as VF progressors, and of these, 6 eyes were both VF and ONH progressors. At baseline, only macular average RNFL and macular inferior RNFL were significantly thinner in ONH progressors compared to non-progressors. Between the VF progressors and non-progressor groups, all OCT parameters were significantly thinner at baseline in the progressors except for four focal macular measurements and disc area. Mixed-effects modeling showed that both focal macular and ONH parameters thinned at a significantly greater rate in VF progressors compared to non-progressors (Table 1). Conclusions : Focal macular retinal segmentations and focal ONH parameters thin significantly more per year in VF progressors, and VF progressors tend to have thinner baseline structural parameters

Observational studies in glaucoma patients can provide important evidence on treatment effects, especially for combination therapies which are often used in reality. But the success relies on the reduction of selection bias through methods such as propensity score (PS) weighting. The objective of this study was to assess the effects of five glaucoma treatments (medication, laser, non-laser surgery (NLS), laser + medication, and NLS + medication) on 1-year intraocular pressure (IOP) change. Data were collected from 90 glaucoma subjects who underwent a single laser, or NLS intervention, and/or took the same medication for at least 6 months, and had IOP measures before the treatment and 12-months after. Baseline IOP was significantly different across groups (p = 0.007) and this unbalance was successfully corrected by the PS weighting (p = 0.81). All groups showed statistically significant PS-weighted IOP reductions, with the largest reduction in NLS group (-6.78 mmHg). Baseline IOP significantly interacted with treatments (p = 0.03), and at high baseline IOP medication was less effective than other treatments. Our findings showed that the 1-year IOP reduction differed across treatment groups and was dependent on baseline IOP. The use of PS-weighted methods reduced treatment selection bias at baseline and allowed valid assessment of the treatment effect in an observational study.

We present a technique to reduce speckle in visible-light optical coherence tomography (vis-OCT) that preserves fine structural details and is robust against sample motion. Specifically, we locally modulate B-scans orthogonally to their axis of acquisition. Such modulation enables acquisition of uncorrelated speckle patterns from similar anatomical locations, which can be averaged to reduce speckle. To verify the effectiveness of speckle reduction, we performed in-vivo retinal imaging using modulated raster and circular scans in both mice and humans. We compared speckle-reduced vis-OCT images with the images acquired with unmodulated B-scans from the same anatomical locations. We compared contrast-to-noise ratio (CNR) and equivalent number of looks (ENL) to quantify the image quality enhancement. Speckle-reduced images showed up to a 2.35-dB improvement in CNR and up to a 3.1-fold improvement in ENL with more discernable anatomical features using eight modulated A-line averages at a 25-kHz A-line rate.

Purpose : OCT Angiography (OCTA) can be used to measure retinal vessel density (VD). These scans can be of various sizes and may be centered on the optic nerve head (ONH) or macula. In this study, we examined the glaucoma discrimination performance of VD using different scanning sizes and locations and compared it with the performance of conventional structural and functional biomarkers to identify the best glaucoma discrimination scanning protocol. Methods : 79 healthy and glaucomatous eyes (50 subjects) were included in the study. Subjects with diabetes, vascular disease, or who were using medications known to affect retinal thickness were excluded. 3x3 and 6x6mm ONH and macula OCTA images were obtained using Cirrus HD-OCT Angioplex (Zeiss, Dublin, CA). Global and sectoral VD was calculated using native software on the device. Area under the receiver operating characteristics (AUC) was used to determine the discrimination ability of VD, retinal nerve fiber layer (RNFL) thickness, rim area, cup-to-disc (C/D) ratio, ganglion cell inner plexiform layer (GCIPL) thickness, and visual field mean deviation (MD). Bootstrapping was used for comparison between the AUCs. Results : Subjects with glaucoma had statistically significantly different measurements than healthy individuals for all tested parameters except for the majority of macula VD (both 3x3 and 6x6 scanning sizes; Table). VD measurements that had the best glaucoma discrimination ability were acquired from the ONH from all sectors of the 3x3 scans and in the outer and full sectors in the 6x6 scans (Table). For these ONH parameters, no significant difference was detected from the best discriminating parameter (average RNFL and rim area). All macula VD measurements had significantly worse discrimination performance. Conclusions : Among VD scanning options, the ONH scans are the most suitable for glaucoma discrimination. However, the coarse sampling in the larger scan (6x6mm) reduces this capability inside and immediately adjacent to the ONH

Purpose : To examine the effect of varying levels of intraocular (IOP) and intracranial pressure (ICP) on the reproducibility of lamina cribrosa (LC) microstructure measurements. Methods : Spectral-domain OCT scans of the optic nerve head (ONH) were obtained from adult healthy rhesus macaque monkeys while IOP and ICP were changed in a controlled environment. Gravity-based perfusion through a needle inserted into the anterior chamber controlled IOP (low, medium, high settings). Perfusion through the lateral ventricle controlled ICP (low, high settings). Scans were registered in 3D and LC microstructure measurements (beam thickness, pore diameter) were calculated from shared regions among scans acquired at each setting using a previously described segmentation algorithm. Microstructure measurement results were used to calculate the beam/pore ratio of each scan, and a 2-way ANOVA test compared the effect of different IOP and ICP settings on measurement reproducibility. Results : The results of 2 eyes were analyzed. For average beam thickness IOP had a significant effect on measurement reproducibility but ICP did not (p=0.005, p=0.66, respectively). For average pore diameter IOP also had a significant effect on measurement reproducibility but ICP did not (p=0.009, p=0.97, respectively). The effect of IOP and ICP on beam/pore ratio reproducibility was not significant (p=0.23, p=0.80, respectively). Results are summarized in Figure 1. Conclusions : Our study provides evidence that beam/pore ratio measurements are reproducible regardless of acquisition at different IOP and ICP settings. This parameter is less influenced by scanning angle and image quality than other measurements. This information supports direct comparison of beam/pore ratio measurements obtained in varying pressure settings

PURPOSE/OBJECTIVE:The suprachoroidal space (SCS) has been a successful target to lower intraocular pressure (IOP) in glaucoma patients. We present the results of 4 patients who underwent a novel glaucoma surgical procedure to lower IOP: Intrascleral Ciliary Sulcus-Suprachoroidal Microtube. METHODS:A sterile medical grade silicone microtube (Tube extender, New World Medical) was surgically placed to drain aqueous from the posterior chamber ciliary sulcus of the eye to the SCS. The internal diameter of the tube was 300 um and the length varied from 8-10mm. After informed consent was obtained and witnessed, this procedure was performed in glaucoma patients with pseudophakia. The tube was placed intrasclerally beneath an inferotemporal sclera flap (50% thickness approximately 4mm x 4mm). The anterior end of the tube was inserted into the ciliary sulcus approximately 2mm from the limbus and the posterior end was placed into the SCS approximately 4mm from the limbus. The microtube was sutured to the sclera with a 10-0 nylon suture. 8-0 vicryl sutures were used to close the sclera flap and the conjunctiva inferotemporally. RESULTS:All 4 patients had lower IOP. The average reduction of IOP was 36% at 3 months. The amount of glaucoma medications per patient at 3 months dropped from an average of 3 to 0.25. The risks are similar to traditional glaucoma incisional surgery. CONCLUSION/CONCLUSIONS:This new technique of Intrascleral Ciliary Sulcus-Suprachoroidal Microtube in all four patients with mild, moderate, and advanced glaucoma demonstrated a significant lowering of IOP and a decrease in the number of medications. Further research is required to assess long term efficacy and safety.

Purpose : To examine the effect of co-variables commonly used in ocular structure models on ocular vessel density (VD) measurements provided by OCT angiography (OCTA) Methods : Healthy subjects with a normal comprehensive ophthalmic examination, axial length (AL) measurements, qualified visual fields (VF; Humphrey Field Analyzer; Zeiss, Dublin, CA), and optic nerve head (ONH) and macula OCT and OCTA scans (Cirrus HD-OCT 200x200 cube scans and 3x3 mm/ 6x6 mm Angioplex; Zeiss) were included. Subjects with comorbidities affecting the systemic or local micro or macro vasculature and subjects taking medications that modify vessel diameter were excluded. Peripapillary, ONH, and macular VD were calculated using the device's native software. Mixed-effects models were used accounting for age, gender, signal strength, AL, and inter- and intra-subject correlation. Results : 72 eyes (46 subjects) with a mean age of 45.1 (+/-13.9) years, mean AL of 23.82 (+/-1.03) mm, and mean signal strength of 8.32 (+/-1.04) were included in the study for ONH analysis and a subset of 33 eyes were included for macular analysis. The 3x3 and 6x6 ONH inner VD measurements decrease as age advances (-0.1 +/-0.02 mm/mm2, p=0.005; -0.07 +/-0.02 mm/mm2, p=0.0026, respectively). The central and inner measurements in the 3x3 macular scans decrease with age (-0.14 +/-0.03 mm/mm2, p=0.0006; -0.06 +/-0.01mm/mm2, p=0.0003, respectively). ONH and macula VD in both scanning sizes were not associated with AL, except for the macula 6x6 outer region (0.41 +/-0.05 mm/mm2, p=0.05). Only macular VD measurements were associated with signal strength. Conclusions : When analyzing ocular VD, the variables of age, AL, and image quality, should be considered

Background/UNASSIGNED:The capabilities of visible-light optical coherence tomography (vis-OCT) in noninvasive anatomical and functional retinal imaging have been demonstrated by multiple groups in both rodents and healthy human subjects. Translating laboratory prototypes to an integrated clinical-environment-friendly system is required to explore the full potential of vis-OCT in disease management. Methods/UNASSIGNED:We developed and optimized a portable vis-OCT system for human retinal imaging in clinical settings. We acquired raster- and circular-scan images from both healthy and diseased human eyes. Results/UNASSIGNED:The new vis-OCT provided high-quality retinal images of both subjects without any known eye diseases and patients with various retinal diseases, including retinal occlusive disease and diabetic retinopathy (DR) over a broad range of ages. Conclusions/UNASSIGNED:A newly designed vis-OCT system is sufficiently optimized to be suited for routine patients' examinations in clinics. Vis-OCT has the potential to add new anatomical and functional imaging capabilities to ophthalmic clinical care.