Faculty Bibliography

Purpose/UNASSIGNED:The purpose was to establish the position of the fovea centralis to the optic nerve via en-face, near-infrared spectral domain optical coherence tomography (NIR-OCT) in healthy patients. This may shed light on physiological variability and be used for studying subtle cases of foveal ectopia in macular pathology and after retinal detachment. Methods/UNASSIGNED:SD-OCT data of 890 healthy eyes were retrospectively analyzed. Exclusion criteria included axial myopia causing tilting of the optic disc, peripapillary atrophy >1/3 the width of the disc, macular images excluding greater than half of the optic disc, and patients unable to maintain vertical head positioning. Two independent reviewers measured the horizontal and vertical distance from the fovea to the optic disc center and optic disc diameter via cross-sectional and en-face scanning laser ophthalmoloscopy OCT imaging. Results/UNASSIGNED:890 eyes were included in the study. The right and left eyes differed in the horizontal distance from the fovea to the disc center (4359 vs. 4248 µm, P < 0.001) and vertical distance from the fovea to the disc center (464 µm vs. 647, P < 0.001). This corresponded to a smaller angle between the right and left eyes (6.07° vs. 8.67°, P < 0.001). Older age was associated with a larger horizontal (P = 0.008) and vertical distance (0.025). These differences persisted after correcting for axial length in the 487 patients with axial-length data. Conclusions/UNASSIGNED:This study compares the position of the fovea centralis among individuals without macular pathology on a micron level basis. The significant variability between right and left eyes indicates that contralateral eye evaluation cannot be reliably used. Rather, true foveal ectopia requires assessments of preoperative and postoperative NIR-OCT scans. This finding is relevant to retinal detachment cases and evaluation of subtle foveal ectopia. Translational Relevance/UNASSIGNED:This finding is relevant to retinal detachment cases and evaluation of subtle foveal ectopia.

PURPOSE/OBJECTIVE:To determine which spectral domain optical coherence tomography biomarkers of idiopathic macular hole (MH) correlate with the postoperative best-corrected visual acuity (BCVA) in anatomically closed MH. METHODS:Retrospective analysis of spectral domain optical coherence tomography scans of 44 patients presenting with MH followed for a mean of 17 months. Widths of MH aperture, base, and ellipsoid zone disruption were calculated from presenting foveal spectral domain optical coherence tomography B-scans. Macular hole base area and ellipsoid zone disruption area were calculated through the custom in-house software. RESULTS:Poorer postoperative BCVA correlated with increased preoperative choroidal hypertransmission (r = 0.503, P = 0.0005), minimum diameter (r = 0.491, P = 0.0007), and base diameter (r = 0.319, P = 0.0348), but not with preoperative ellipsoid zone width (r = 0.199, P = 0.2001). Applying en-face analysis, the BCVA correlated weakly with preoperative ellipsoid zone loss area (r = 0.380, P = 0.013), but not with preoperative MH base area (r = 0.253, P = 0.1058). CONCLUSION/CONCLUSIONS:Increased MH minimum diameter, base diameter, base area, and choroidal hypertransmission are correlated with a poorer postoperative BCVA. Ellipsoid zone loss measurements were not consistently correlated with a BCVA. Choroidal hypertransmission width may be an easy-to-visualize predictive imaging biomarker in MH surgery.

AIMS/OBJECTIVE:To evaluate the associations between retinal blood flow (RBF) and optical coherence tomography (OCT) structural measurements in normal-tension glaucoma (NTG) eyes with single-hemifield visual field (VF) damage by the Doppler OCT. METHODS:The Doppler OCT was used to measure temporal artery (TA) RBF and temporal vein (TV) RBF. Retinal nerve fibre layer thickness (RNFLT) was measured by spectral-domain OCT. RESULTS:Forty-three consecutive eyes of 43 patients with NTG with VF defect confined to a single hemifield and 24 eyes of 24 age-matched healthy subjects were studied. TA and TV RBF and RNFLT were reduced in the damaged hemisphere compared with the normal hemisphere (mean (SD), 3.61 (1.68) vs 5.86 (2.59) µL/min, p<0.001; 5.61 (2.51) vs 6.94 (2.83) µL/min, p=0.010; 69.0 (19.7) vs 99.7 (22.8) µm, p<0.001). Those values in the normal hemisphere of NTG eyes also decreased compared with the healthy hemisphere of the healthy eyes (8.40 (3.36) µL/min, p<0.001; 9.28 (4.47) µL/min, p<0.002; 122.8 (20.2) µm, p<0.001). Multivariate model showed that normal and damaged hemispheres and RNFLT were associated with RBF reduction. In addition, the RBF in the normal hemisphere was lower than that in the healthy hemisphere even after adjusting for RNFLT. CONCLUSION/CONCLUSIONS:In NTG eyes with single-hemifield damage, the RBF was significantly reduced in the damaged hemisphere compared with the normal one. The RBF decreased in the normal and damaged hemispheres of NTG eyes compared with the healthy hemisphere independent from RNFLT.

PURPOSE/OBJECTIVE:To evaluate the accuracy at which visual field global indices could be estimated from OCT scans of the retina using deep neural networks and to quantify the contributions to the estimates by the macula (MAC) and the optic nerve head (ONH). DESIGN/METHODS:Observational cohort study. PARTICIPANTS/METHODS:A total of 10 370 eyes from 109 healthy patients, 697 glaucoma suspects, and 872 patients with glaucoma over multiple visits (median = 3). METHODS:Three-dimensional convolutional neural networks were trained to estimate global visual field indices derived from automated Humphrey perimetry (SITA 24-2) tests (Zeiss, Dublin, CA), using OCT scans centered on MAC, ONH, or both (MAC + ONH) as inputs. MAIN OUTCOME MEASURES/METHODS:Spearman's rank correlation coefficients, Pearson's correlation coefficient, and absolute errors calculated for 2 indices: visual field index (VFI) and mean deviation (MD). RESULTS:The MAC + ONH achieved 0.76 Spearman's correlation coefficient and 0.87 Pearson's correlation for VFI and MD. Median absolute error was 2.7 for VFI and 1.57 decibels (dB) for MD. Separate MAC or ONH estimates were significantly less correlated and less accurate. Accuracy was dependent on the OCT signal strength and the stage of glaucoma severity. CONCLUSIONS:The accuracy of global visual field indices estimate is improved by integrating information from MAC and ONH in advanced glaucoma, suggesting that structural changes of the 2 regions have different time courses in the disease severity spectrum.

BACKGROUND:Glaucoma filtration surgery (GFS) is limited by subconjunctival, episcleral and scleral fibrosis sealing the trabeculectomy and scarring the filtering bleb. Mitomycin-C (MMC) is commonly applied intraoperatively to the subconjunctival and/or intrascleral space to reduce scarring and promotes GFS success but is associated with postoperative scleral melting and bleb leaks. IP-10 peptide (IP-10p), an ELR-negative CXC chemokine mimetic and inhibitor of fibroblast function, may be an alternative or adjunct to current postoperative GFS treatments. This study sought to determine if IP-10p produces histological changes in tissue remodelling, vascularity and fibrosis that enhance bleb survival after GFS. METHODS:Rabbits underwent tube-assisted filtration surgery on the right eye with either: (a) IP-10p injected into bleb at time of surgery and postoperative days 2, 4 and 7, (b) intraoperative MMC or (c) intraoperative MMC plus IP-10p injected into bleb at time of surgery and postoperative days 2, 4 and 7. Left contralateral eyes were treated with balanced salt solution (BSS). RESULTS:IP-10p-treated blebs demonstrated reduced collagen deposition, cellularity and overall reduction of scar formation compared to BSS-control. Bleb vascularity was reduced compared to BSS-control and MMC treatment groups. Additionally, IP-10p/MMC treated eyes demonstrated an increased number of conjunctival goblet cells in bleb histology compared to the dramatic loss seen with MMC treatment alone. CONCLUSIONS:This study demonstrates that IP-10p significantly reduces histological scarring compared to BSS or MMC alone, does not damage the conjunctiva to the extent of current standards, and may be an alternative or adjunct to MMC for those undergoing GFS.

The direct analysis of 3D Optical Coherence Tomography (OCT) volumes enables deep learning models (DL) to learn spatial structural information and discover new bio-markers that are relevant to glaucoma. Downsampling 3D input volumes is the state-of-art solution to accommodate for the limited number of training volumes as well as the available computing resources. However, this limits the network's ability to learn from small retinal structures in OCT volumes. In this paper, our goal is to improve the performance by providing guidance to DL model during training in order to learn from finer ocular structures in 3D OCT volumes. Therefore, we propose an end-to-end attention guided 3D DL model for glaucoma detection and estimating visual function from retinal structures. The model consists of three pathways with the same network architecture but different inputs. One input is the original 3D-OCT cube and the other two are computed during training guided by the 3D gradient class activation heatmaps. Each pathway outputs the class-label and the whole model is trained concurrently to minimize the sum of losses from three pathways. The final output is obtained by fusing the predictions of the three pathways. Also, to explore the robustness and generalizability of the proposed model, we apply the model on a classification task for glaucoma detection as well as a regression task to estimate visual field index (VFI) (a value between 0 and 100). A 5-fold cross-validation with a total of 3782 and 10,370 OCT scans is used to train and evaluate the classification and regression models, respectively. The glaucoma detection model achieved an area under the curve (AUC) of 93.8% compared with 86.8% for a baseline model without the attention-guided component. The model also outperformed six different feature based machine learning approaches that use scanner computed measurements for training. Further, we also assessed the contribution of different retinal layers that are relevant to glaucoma. The VFI estimation model achieved a Pearson correlation and median absolute error of 0.75 and 3.6%, respectively, for a test set of size 3100 cubes.