Faculty Bibliography

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/OBJECTIVE:To evaluate the ability of OCT optic nerve head (ONH) and macular parameters to detect disease progression in eyes with advanced structural glaucomatous damage of the circumpapillary retinal nerve fiber layer (cRNFL). DESIGN/METHODS:Longitudinal study. PARTICIPANTS/METHODS:Forty-four eyes from 37 patients with advanced average cRNFL damage (≤60 μm) followed up for an average of 4.0 years. METHODS:All patients were examined with spectral-domain OCT and visual field (VF) assessment during at least 4 visits. MAIN OUTCOME MEASUREMENTS/METHODS:Visual field mean deviation (MD) and VF index. OCT cRNFL (average, superior, and inferior quadrants), ganglion cell-inner plexiform layer (GCIPL) (average, superior, and inferior), rim area, cup volume, average cup-to-disc (C:D) ratio, and vertical C:D ratio. RESULTS:/year). CONCLUSIONS:Macula GCIPL and ONH parameters may be useful in tracking progression in patients with advanced glaucoma.

Purpose/UNASSIGNED:To introduce an experimental approach for direct comparison of the primate optic nerve head (ONH) before and after death by exsanguination. Method/UNASSIGNED:The ONHs of four eyes from three monkeys were imaged with spectral-domain optical coherence tomography (OCT) before and after exsanguination under controlled IOP. ONH structures, including the Bruch membrane (BM), BM opening, inner limiting membrane (ILM), and anterior lamina cribrosa (ALC) were delineated on 18 virtual radial sections per OCT scan. Thirteen parameters were analyzed: scleral canal at BM opening (area, planarity, and aspect ratio), ILM depth, BM depth; ALC (depth, shape index, and curvedness), and ALC visibility (globally, superior, inferior, nasal, and temporal quadrants). Results/UNASSIGNED:All four ALC quadrants had a statistically significant improvement in visibility after exsanguination (overall P < 0.001). ALC visibility increased by 35% globally and by 36%, 37%, 14%, and 4% in the superior, inferior, nasal, and temporal quadrants, respectively. ALC increased 4.1%, 1.9%, and 0.1% in curvedness, shape index, and depth, respectively. Scleral canals increased 7.2%, 25.2%, and 1.1% in area, planarity, and aspect ratio, respectively. ILM and BM depths averaged -7.5% and -55.2% decreases in depth, respectively. Most, but not all, changes were beyond the repeatability range. Conclusions/UNASSIGNED:Exsanguination allows for improved lamina characterization, especially in regions typically blocked by shadowing in OCT. The results also demonstrate changes in ONH morphology due to the loss of blood pressure. Future research will be needed to determine whether there are differences in ONH biomechanics before and after exsanguination and what those differences would imply.

The lamina cribrosa is a primary site of damage in glaucoma. While mechanical distortion is hypothesized to cause reduction of axoplasmic flow, little is known about how the pores, which contains the retinal ganglion cell axons, traverse the lamina cribrosa. We investigated lamina cribrosa pore paths in vivo to quantify differences in tortuosity of pore paths between healthy and glaucomatous eyes. We imaged 16 healthy, 23 glaucoma suspect and 48 glaucomatous eyes from 70 subjects using a swept source optical coherence tomography system. The lamina cribrosa pores were automatically segmented using a previously described segmentation algorithm. Individual pore paths were automatically tracked through the depth of the lamina cribrosa using custom software. Pore path convergence to the optic nerve center and tortuosity was quantified for each eye. We found that lamina cribrosa pore pathways traverse the lamina cribrosa closer to the optic nerve center along the depth of the lamina cribrosa regardless of disease severity or diagnostic category. In addition, pores of glaucoma eyes take a more tortuous path through the lamina cribrosa compared to those of healthy eyes, suggesting a potential mechanism for reduction of axoplasmic flow in glaucoma.

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.

Although elevated intraocular pressure (IOP) and age are major risk factors for glaucoma, their effects on glaucoma pathogenesis remain unclear. This study examined the onset and progression of glaucomatous changes to ocular anatomy and physiology, structural and physiological brain integrity, and visuomotor behavior in the DBA/2J mice via non-invasive tonometry, multi-parametric magnetic resonance imaging (MRI) and optokinetic assessments from 5 to 12 months of age. Using T2-weighted MRI, diffusion tensor MRI, and manganese-enhanced MRI, increasing IOP elevation at 9 and 12 months old coincided with anterior chamber deepening, altered fractional anisotropy and radial diffusivity of the optic nerve and optic tract, as well as reduced anterograde manganese transport along the visual pathway respectively in the DBA/2J mice. Vitreous body elongation and visuomotor function deterioration were observed until 9 months old, whereas axial diffusivity only decreased at 12 months old in diffusion tensor MRI. Under the same experimental settings, C57BL/6J mice only showed modest age-related changes. Taken together, these results indicate that the anterior and posterior visual pathways of the DBA/2J mice exhibit differential susceptibility to glaucomatous neurodegeneration observable by in vivo multi-modal examinations.

Purpose/UNASSIGNED:Sex hormones may be associated with primary open-angle glaucoma (POAG), although the mechanisms are unclear. We previously observed that gene variants involved with estrogen metabolism were collectively associated with POAG in women but not men; here we assessed gene variants related to testosterone metabolism collectively and POAG risk. Methods/UNASSIGNED:We used two datasets: one from the United States (3853 cases and 33,480 controls) and another from Australia (1155 cases and 1992 controls). Both datasets contained densely called genotypes imputed to the 1000 Genomes reference panel. We used pathway- and gene-based approaches with Pathway Analysis by Randomization Incorporating Structure (PARIS) software to assess the overall association between a panel of single nucleotide polymorphisms (SNPs) in testosterone metabolism genes and POAG. In sex-stratified analyses, we evaluated POAG overall and POAG subtypes defined by maximum IOP (high-tension [HTG] or normal tension glaucoma [NTG]). Results/UNASSIGNED:In the US dataset, the SNP panel was not associated with POAG (permuted P = 0.77), although there was an association in the Australian sample (permuted P = 0.018). In both datasets, the SNP panel was associated with POAG in men (permuted P ≤ 0.033) and not women (permuted P ≥ 0.42), but in gene-based analyses, there was no consistency on the main genes responsible for these findings. In both datasets, the testosterone pathway association with HTG was significant (permuted P ≤ 0.011), but again, gene-based analyses showed no consistent driver gene associations. Conclusions/UNASSIGNED:Collectively, testosterone metabolism pathway SNPs were consistently associated with the high-tension subtype of POAG in two datasets.

The choroid is vascular tissue located underneath the retina and supplies oxygen to the outer retina; any damage to this tissue can be a precursor to retinal diseases. This paper presents an automated method of choroidal segmentation from Enhanced Depth Imaging Optical Coherence Tomography (EDI-OCT) images. The Dijkstra shortest path algorithm is used to segment the choroid-sclera interface (CSI), the outermost border of the choroid. A novel intensity-normalisation technique that is based on the depth of the choroid is used to equalise the intensity of all non-vessel pixels in the choroid region. The outer boundary of choroidal vessel and CSI are determined approximately and incorporated to the edge weight of the CSI segmentation to choose optimal edge weights. This method is tested on 190 B-scans of 10 subjects against choroid thickness (CTh) results produced manually by two graders. For comparison, results obtained by two state-of-the-art automated methods and our proposed method are compared against the manual grading, and our proposed method performed the best. The mean root-mean-square error (RMSE) for finding the CSI boundary by our method is 7.71±6.29 pixels, which is significantly lower than the RMSE for the two other state-of-the-art methods (36.17±11.97 pixels and 44.19±19.51 pixels). The correlation coefficient for our method is 0.76, and 0.51 and 0.66 for the other two state-of-the-art methods. The interclass correlation coefficients are 0.72, 0.43 and 0.56 respectively. Our method is highly accurate, robust, reliable and consistent. This identification can enable to quantify the biomarkers of the choroidin large scale study for assessing, monitoring disease progression as well as early detection of retinal diseases. Identification of the boundary can help to determine the loss or change of choroid, which can be used as features for the automatic determination of the stages of retinal diseases.