Open-source deep learning-based automatic segmentation of mouse Schlemm's canal in optical coherence tomography images.

The purpose of this study was to develop an automatic deep learning-based approach and corresponding free, open-source software to perform segmentation of the Schlemm's canal (SC) lumen in optical coherence tomography (OCT) scans of living mouse eyes. A novel convolutional neural network (CNN) for semantic segmentation grounded in a U-Net architecture was developed by incorporating a late fusion scheme, multi-scale input image pyramid, dilated residual convolution blocks, and attention-gating. 163 pairs of intensity and speckle variance (SV) OCT B-scans acquired from 32 living mouse eyes were used for training, validation, and testing of this CNN model for segmentation of the SC lumen. The proposed model achieved a mean Dice Similarity Coefficient (DSC) of 0.694 ± 0.256 and median DSC of 0.791, while manual segmentation performed by a second expert grader achieved a mean and median DSC of 0.713 ± 0.209 and 0.763, respectively. This work presents the first automatic method for segmentation of the SC lumen in OCT images of living mouse eyes. The performance of the proposed model is comparable to the performance of a second human grader. Open-source automatic software for segmentation of the SC lumen is expected to accelerate experiments for studying treatment efficacy of new drugs affecting intraocular pressure and related diseases such as glaucoma, which present as changes in the SC area.

VALIDATION OF A DEEP LEARNING-BASED ALGORITHM FOR SEGMENTATION OF THE ELLIPSOID ZONE ON OPTICAL COHERENCE TOMOGRAPHY IMAGES OF AN USH2A-RELATED RETINAL DEGENERATION CLINICAL TRIAL.

PURPOSE: To assess the generalizability of a deep learning-based algorithm to segment the ellipsoid zone (EZ). METHODS: The dataset consisted of 127 spectral-domain optical coherence tomography volumes from eyes of participants with USH2A-related retinal degeneration enrolled in the RUSH2A clinical trial (NCT03146078). The EZ was segmented manually by trained readers and automatically by deep OCT atrophy detection, a deep learning-based algorithm originally developed for macular telangiectasia Type 2. Performance was evaluated using the Dice similarity coefficient between the segmentations, and the absolute difference and Pearson's correlation of measurements of interest obtained from the segmentations. RESULTS: With deep OCT atrophy detection, the average (mean ± SD, median) Dice similarity coefficient was 0.79 ± 0.27, 0.90. The average absolute difference in total EZ area was 0.62 ± 1.41, 0.22 mm2 with a correlation of 0.97. The average absolute difference in the maximum EZ length was 222 ± 288, 126 µm with a correlation of 0.97. CONCLUSION: Deep OCT atrophy detection segmented EZ in USH2A-related retinal degeneration with good performance. The algorithm is potentially generalizable to other diseases and other biomarkers of interest as well, which is an important aspect of clinical applicability.

Fast and robust active neuron segmentation in two-photon calcium imaging using spatiotemporal deep learning.

Calcium imaging records large-scale neuronal activity with cellular resolution in vivo. Automated, fast, and reliable active neuron segmentation is a critical step in the analysis workflow of utilizing neuronal signals in real-time behavioral studies for discovery of neuronal coding properties. Here, to exploit the full spatiotemporal information in two-photon calcium imaging movies, we propose a 3D convolutional neural network to identify and segment active neurons. By utilizing a variety of two-photon microscopy datasets, we show that our method outperforms state-of-the-art techniques and is on a par with manual segmentation. Furthermore, we demonstrate that the network trained on data recorded at a specific cortical layer can be used to accurately segment active neurons from another layer with different neuron density. Finally, our work documents significant tabulation flaws in one of the most cited and active online scientific challenges in neuron segmentation. As our computationally fast method is an invaluable tool for a large spectrum of real-time optogenetic experiments, we have made our open-source software and carefully annotated dataset freely available online.

In vivo measurement of trabecular meshwork stiffness in a corticosteroid-induced ocular hypertensive mouse model.

Ocular corticosteroids are commonly used clinically. Unfortunately, their administration frequently leads to ocular hypertension, i.e., elevated intraocular pressure (IOP), which, in turn, can progress to a form of glaucoma known as steroid-induced glaucoma. The pathophysiology of this condition is poorly understood yet shares similarities with the most common form of glaucoma. Using nanotechnology, we created a mouse model of corticosteroid-induced ocular hypertension. This model functionally and morphologically resembles human ocular hypertension, having titratable, robust, and sustained IOPs caused by increased resistance to aqueous humor outflow. Using this model, we then interrogated the biomechanical properties of the trabecular meshwork (TM), including the inner wall of Schlemm's canal (SC), tissues known to strongly influence IOP and to be altered in other forms of glaucoma. Specifically, using spectral domain optical coherence tomography, we observed that SC in corticosteroid-treated mice was more resistant to collapse at elevated IOPs, reflecting increased TM stiffness determined by inverse finite element modeling. Our noninvasive approach to monitoring TM stiffness in vivo is applicable to other forms of glaucoma and has significant potential to monitor TM function and thus positively affect the clinical care of glaucoma, the leading cause of irreversible blindness worldwide.

BiconNet: An Edge-preserved Connectivity-based Approach for Salient Object Detection.

Salient object detection (SOD) is viewed as a pixel-wise saliency modeling task by traditional deep learning-based methods. A limitation of current SOD models is insufficient utilization of inter-pixel information, which usually results in imperfect segmentation near edge regions and low spatial coherence. As we demonstrate, using a saliency mask as the only label is suboptimal. To address this limitation, we propose a connectivity-based approach called bilateral connectivity network (BiconNet), which uses connectivity masks together with saliency masks as labels for effective modeling of inter-pixel relationships and object saliency. Moreover, we propose a bilateral voting module to enhance the output connectivity map, and a novel edge feature enhancement method that efficiently utilizes edge-specific features. Through comprehensive experiments on five benchmark datasets, we demonstrate that our proposed method can be plugged into any existing state-of-the-art saliency-based SOD framework to improve its performance with negligible parameter increase.

Integral role for lysyl oxidase-like-1 in conventional outflow tissue function and behavior.

Lysyl oxidase-like-1 (LOXL1), a vital crosslinking enzyme in elastin fiber maintenance, is essential for the stability and strength of elastic vessels and tissues. Variants in the LOXL1 locus associate with a dramatic increase in risk of exfoliation syndrome (XFS), a systemic fibrillopathy, which often presents with ocular hypertension and exfoliation glaucoma (XFG). We examined the role of LOXL1 in conventional outflow function, the prime regulator of intraocular pressure (IOP). Using Loxl1-/- , Loxl1+/- , and Loxl1+/+ mice, we observed an inverse relationship between LOXL1 expression and IOP, which worsened with age. Elevated IOP in Loxl1-/- mice was associated with a larger globe, decreased ocular compliance, increased outflow facility, extracellular matrix (ECM) abnormalities, and dilated intrascleral veins, yet, no dilation of arteries or capillaries. Interestingly, in living Loxl1-/- mouse eyes, Schlemm's canal (SC) was less susceptible to collapse when challenged with acute elevations in IOP, suggesting elevated episcleral venous pressure (EVP). Thus, LOXL1 expression is required for normal IOP control, while ablation results in altered ECM repair/homeostasis and conventional outflow physiology. Dilation of SC and distal veins, but not arteries, is consistent with key structural and functional roles for elastin in low-pressure vessels subjected to cyclical mechanical stress.

COMPARISON OF SINGLE DRUSEN SIZE ON COLOR FUNDUS PHOTOGRAPHY AND SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To determine the relationship of drusen size as determined by spectral-domain optical coherence tomography (SD-OCT) with that measured on registered color fundus photography (CFP) images and to derive an OCT-based classification system that was comparable with that determined by CFP. METHODS: Custom software was developed to register CFP images to the scanning laser ophthalmoscopy fundus images obtained simultaneously with the corresponding SD-OCT images, so that individual drusen observed on CFP could be matched with those seen on SD-OCT. Single druse size (diameter, area, volume, and height) on CFP and SD-OCT images from a phase two clinical trial was determined with the Duke OCT Retinal Analysis Program. RESULTS: The sizes of 213 individual drusen were measured on CFP and SD-OCT. The drusen diameter measured on CFP was significantly correlated with those determined on SD-OCT (R: 0.879, P < 0.001). Based on the corresponding formula: drusen diameter on SD-OCT = 0.77 × (drusen diameter on CFP) + 50.67 µm, large drusen defined as ≥125 µm on CFP had a diameter ≥145 µm on OCT, medium drusen defined as 63 µm to 124 µm on CFP had diameters 100 µm to 144 µm on OCT, and small drusen defined as <63 µm on CFP had diameters <100 µm on OCT. CONCLUSION: With our registration software and imaging processing algorithms, we were able to correlate individual druse sizes measured on CFP with those determined on SD-OCT. These data can be used to develop an SD-OCT-based grading scale, analogous to the CFP Age-Related Eye Disease Study drusen scale that may be useful in the clinic and in clinical trials.

Beyond Performance Metrics: Automatic Deep Learning Retinal OCT Analysis Reproduces Clinical Trial Outcome.

PURPOSE: To validate the efficacy of a fully automatic, deep learning-based segmentation algorithm beyond conventional performance metrics by measuring the primary outcome of a clinical trial for macular telangiectasia type 2 (MacTel2). DESIGN: Evaluation of diagnostic test or technology. PARTICIPANTS: A total of 92 eyes from 62 participants with MacTel2 from a phase 2 clinical trial (NCT01949324) randomized to 1 of 2 treatment groups METHODS: The ellipsoid zone (EZ) defect areas were measured on spectral domain OCT images of each eye at 2 time points (baseline and month 24) by a fully automatic, deep learning-based segmentation algorithm. The change in EZ defect area from baseline to month 24 was calculated and analyzed according to the clinical trial protocol. MAIN OUTCOME MEASURE: Difference in the change in EZ defect area from baseline to month 24 between the 2 treatment groups. RESULTS: The difference in the change in EZ defect area from baseline to month 24 between the 2 treatment groups measured by the fully automatic segmentation algorithm was 0.072±0.035 mm2 (P = 0.021). This was comparable to the outcome of the clinical trial using semiautomatic measurements by expert readers, 0.065±0.033 mm2 (P = 0.025). CONCLUSIONS: The fully automatic segmentation algorithm was as accurate as semiautomatic expert segmentation to assess EZ defect areas and was able to reliably reproduce the statistically significant primary outcome measure of the clinical trial. This approach, to validate the performance of an automatic segmentation algorithm on the primary clinical trial end point, provides a robust gauge of its clinical applicability.

Spectroscopic optical coherence refraction tomography.

In optical coherence tomography (OCT), the axial resolution is often superior to the lateral resolution, which is sacrificed for long imaging depths. To address this anisotropy, we previously developed optical coherence refraction tomography (OCRT), which uses images from multiple angles to computationally reconstruct an image with isotropic resolution, given by the OCT axial resolution. On the other hand, spectroscopic OCT (SOCT), an extension of OCT, trades axial resolution for spectral resolution and hence often has superior lateral resolution. Here, we present spectroscopic OCRT (SOCRT), which uses SOCT images from multiple angles to reconstruct a spectroscopic image with isotropic spatial resolution limited by the OCT lateral resolution. We experimentally show that SOCRT can estimate bead size based on Mie theory at simultaneously high spectral and isotropic spatial resolution. We also applied SOCRT to a biological sample, achieving axial resolution enhancement limited by the lateral resolution.

Multimodal handheld adaptive optics scanning laser ophthalmoscope.

Non-confocal adaptive optics scanning laser ophthalmoscopy (AOSLO) has enhanced the study of human retinal photoreceptors by providing complementary information to standard confocal AOSLO images. Previously we developed the first confocal handheld AOSLO (HAOSLO) capable of in vivo cone photoreceptor imaging in supine and non-cooperative patients. Here, we introduce the first multimodal (M-)HAOSLO for confocal and non-confocal split-detection (SD) imaging to allow for more comprehensive patient data collection. Aside from its unprecedented miniature size and weight, M-HAOSLO is also the first system to perform sensorless wavefront-corrected SD imaging of cone photoreceptors.

Effect of Ciliary Neurotrophic Factor on Retinal Neurodegeneration in Patients with Macular Telangiectasia Type 2: A Randomized Clinical Trial.

PURPOSE: To test the effects of an encapsulated cell-based delivery of a neuroprotective agent, ciliary neurotrophic factor (CNTF), on progression of macular telangiectasia type 2, a neurodegenerative disease with no proven effective therapy. DESIGN: Randomized sham-controlled clinical trial. PARTICIPANTS: Ninety-nine study eyes of 67 eligible participants were enrolled. METHODS: Single-masked randomized clinical trial of 24 months' duration conducted from May 2014 through April 2017 in 11 clinical centers of retinal specialists in the United States and Australia. Participants were randomized 1:1 to surgical implantation of intravitreal sustained delivery of human CNTF versus a sham procedure. MAIN OUTCOME MEASURES: The primary outcome was the difference in the area of neurodegeneration as measured in the area of the ellipsoid zone disruption (or photoreceptor loss) measured on spectral-domain (SD) OCT images at 24 months from baseline between the treated and untreated groups. Secondary outcomes included comparison of visual function changes between treatment groups. RESULTS: Among the 67 participants who were randomized (mean age, 62±8.9 years; 41 women [61%]; 58 white persons [86%]), 65 (97%) completed the study. Two participants (3 study eyes) died and 3 participants (4 eyes) were found ineligible. The eyes receiving sham treatment had 31% greater progression of neurodegeneration than the CNTF-treated eyes. The difference in mean area of photoreceptor loss was 0.05±0.03 mm2 (P = 0.04) at 24 months. Retinal sensitivity changes, measured using microperimetry, were correlated highly with the changes in the area of photoreceptor loss (r = 0.86; P < 0.0001). The mean retinal sensitivity loss of the sham group was 45% greater than that of the treated group (decrease, 15.81±8.93 dB; P = 0.07). Reading speed deteriorated in the sham group (-13.9 words per minute) with no loss in the treated group (P = 0.02). Serious adverse ocular effects were found in 2 of 51 persons (4%) in the sham group and 2 of 48 persons (4%) in the treated group. CONCLUSIONS: In participants with macular telangiectasia type 2, a surgical implant that released CNTF into the vitreous cavity, compared with a sham procedure, slowed the progression of retinal degeneration. Further research is needed to assess longer-term clinical outcomes and safety.

Demonstration of anatomical development of the human macula within the first 5 years of life using handheld OCT.

PURPOSE: To demonstrate the anatomical development of the human macula using handheld spectral domain optical coherence tomography (SD-OCT) during the first 5 years of life. METHODS: This study is a cross-sectional, observational case series. Thirty-five normal eyes of 35 full-term/late preterm infants and children under 5 years of age were included. Handheld SD-OCT was used to image the macula of each eye. The data were analyzed using the Duke OCT Retinal Analysis Program v17 software. Retinal thickness maps were generated for the total retinal thickness (TRT), the inner retinal layers thickness (IRL), and the photoreceptor layer thickness (PRL). Based on the early treatment diabetic retinopathy study macular map, average thickness measurements were taken at 4 circles centered on the fovea (diameter): the foveal center (0.5 mm), sector 1 (S1) (1 mm), sector 2 (S2) (3 mm), sector 3 (S3) (6 mm). RESULTS: The median age at participation was 24 months (range 5-52 months). The TRT increased throughout the first 5 years of life, and this increase was statistically significant at the foveal center and S1 (p = 0.01, p = 0.016, respectively). The IRL did not show any significant change in thickness from birth and throughout the first 5 years of life. The PRL thickness showed thickening in the first 24 months of age at the foveal center and S1 which was statistically significant at S1 (p = 0.066, p = 0.016, respectively). Interestingly, this PRL thickness increase plateaus beyond 24 months of age. The photoreceptors inner segment/outer segment (IS/OS) band was identified as a distinct layer in all our subjects. CONCLUSION: Our findings conform with the literature that the anatomical development of the macular IRL completes before 5 months of age and hence before the PRL. We also identify 24 months of age as an important developmental milestone for photoreceptors development in the human macula.

Effects of aging and environmental tobacco smoke exposure on ocular and plasma circulatory microRNAs in the Rhesus macaque.

Purpose: To identify changes induced by environmental tobacco smoke (ETS) in circulatory microRNA (miRNA) in plasma and ocular fluids of the Rhesus macaque and compare these changes to normal age-related changes. Tobacco smoke has been identified as the leading environmental risk factor for age-related macular degeneration (AMD). Methods: All Rhesus macaques were housed at the California National Primate Research Center (CNPRC), University of California, Davis. Four groups of animals were used: Group 1 (1-3 years old), Group 2 (19-28 years old), Group 3 (10-16 years old), and Group 4 (middle aged, 9-14 years old). Group 4 was exposed to smoke for 1 month. Ocular fluids and plasma samples were collected, miRNAs isolated, and expression data obtained using Affymetrix miRNA GeneTitan Array Plates 4.0. Bioinformatics analysis was done on the Affymetrix Expression Console (EC), Transcriptome Analysis Software (TAS) using ANOVA for candidate miRNA selection, followed by Ingenuity Pathway Analysis (IPA). Results: The expression of circulatory miRNAs showed statistically significant changes with age and ETS. In the plasma samples, 45 miRNAs were strongly upregulated (fold change >±1.5, p<0.05) upon ETS exposure. In the vitreous, three miRNAs were statistically significantly downregulated with ETS, and two of them (miR-6794 and miR-6790) were also statistically significantly downregulated with age. Some retinal layers exhibited a thinning trend measured with optical coherence tomography (OCT) imaging. The pathways activated were IL-17A, VEGF, and recruitment of eosinophils, Th2 lymphocytes, and macrophages. Conclusions: ETS exposure of Rhesus macaques resulted in statistically significant changes in the expression of the circulatory miRNAs, distinct from those affected by aging. The pathways activated appear to be common for ETS and AMD pathogenesis. These data will be used to develop an animal model of early dry AMD.

Comparison of chorioretinal layers in rhesus macaques using spectral-domain optical coherence tomography and high-resolution histological sections.

Nonhuman primates are important preclinical models of retinal diseases because they uniquely possess a macula similar to humans. Ocular imaging technologies such as spectral-domain optical coherence tomography (SD-OCT) allow noninvasive, in vivo measurements of chorioretinal layers with near-histological resolution. However, the boundaries are based on differences in reflectivity, and detailed correlations with histological tissue layers have not been explored in rhesus macaques, which are widely used for biomedical research. Here, we compare the macular anatomy and thickness measurements of chorioretinal layers in rhesus macaque eyes using SD-OCT and high-resolution histological sections. Images were obtained from methylmethacrylate-embedded histological sections of 6 healthy adult rhesus macaques, and compared with SD-OCT images from 6 age-matched animals. Thicknesses of chorioretinal layers were measured across the central 3 mm macular region using custom semi-automated or manual software segmentation, and compared between the two modalities. We found that histological sections provide better distinction between the ganglion cell layer (GCL) and inner plexiform layer (IPL) than SD-OCT imaging. The first hyperreflective band between the external limiting membrane (ELM) and retinal pigment epithelium (RPE) appears wider on SD-OCT than the junction between photoreceptor inner and outer segments seen on histology. SD-OCT poorly distinguishes Henle nerve fibers from the outer nuclear layer (ONL), while histology correctly identifies these fibers as part of the outer plexiform layer (OPL). Overall, the GCL, inner nuclear layer (INL), and OPL are significantly thicker on histology, especially at the fovea; while the ONL, choriocapillaris (CC), and outer choroid (OC) are thicker on SD-OCT. Our results show that both SD-OCT and high-resolution histological sections allow reliable measurements of chorioretinal layers in rhesus macaques, with distinct advantages for different sublayers. These findings demonstrate the effects of tissue processing on chorioretinal anatomy, and provide normative values for chorioretinal thickness measurements on SD-OCT for future studies of disease models in these nonhuman primates.

Optical Coherence Tomography Predictors of Risk for Progression to Non-Neovascular Atrophic Age-Related Macular Degeneration.

PURPOSE: Appearance of geographic atrophy (GA) on color photography (CP) is preceded by specific features on spectral-domain optical coherence tomography (SD OCT). We aimed to build SD OCT-based risk assessment models for 5-year new onset of GA and central GA on CP. DESIGN: Prospective, longitudinal study. PARTICIPANTS: Age-Related Eye Disease Study 2 Ancillary SD OCT study participants with age-related macular degeneration (AMD) with bilateral large drusen or noncentral GA and at least 1 eye without advanced disease (n = 317). METHODS: For 1 eye per participant, qualitative and quantitative SD OCT variables were derived from standardized grading and semiautomated segmentation, respectively, at baseline. Up to 7 years later, annual outcomes were extracted and analyzed to fit multivariate logistic regression models and build a risk calculator. MAIN OUTCOME MEASURES: New onset of CP-visible GA and central GA. RESULTS: Over a follow-up median of 4.0 years and among 292 AMD eyes (without advanced disease at baseline) with complete outcome data, 46 (15.8%) developed central GA. Among 265 eyes without any GA on baseline CP, 70 (26.4%) developed CP-visible GA. Final multivariate models were adjusted for age. In the model for GA, the independent predicting SD OCT factors (P < 0.001-0.03) were: hyperreflective foci and retinal pigment epithelium (RPE) layer atrophy or absence, followed by choroid thickness in absence of subretinal drusenoid deposits, photoreceptor outer segment loss, RPE drusen complex volume, and RPE drusen complex abnormal thinning volume. For central GA, the factors (P < 0.001) were RPE drusen complex abnormal thinning volume, intraretinal fluid or cystoid spaces, hyperreflective foci, and RPE layer atrophy or absence. The models yielded a calculator that computes the probabilities of CP-visible, new-onset GA and central GA after 1 to 5 years. CONCLUSIONS: For AMD eyes with large drusen and no advanced disease, we built a novel risk assessment model-based on age and SD OCT segmentation, drusen characteristics, and retinal pathology-for progression to CP-visible GA over up to 5 years. This calculator may simplify SD OCT grading and with future validation has a promising role as a clinical prognostic tool.

Enhanced visualization of peripheral retinal vasculature with wavefront sensorless adaptive optics optical coherence tomography angiography in diabetic patients.

Optical coherence tomography angiography (OCTA) is a promising technique for non-invasive visualization of vessel networks in the human eye. We debut a system capable of acquiring wide field-of-view (>70°) OCT angiograms without mosaicking. Additionally, we report on enhancing the visualization of peripheral microvasculature using wavefront sensorless adaptive optics (WSAO). We employed a fast WSAO algorithm that enabled wavefront correction in <2 s by iterating the mirror shape at the speed of OCT B-scans rather than volumes. Also, we contrasted ∼7° field-of-view OCTA angiograms acquired in the periphery with and without WSAO correction. On average, WSAO improved the sharpness of microvasculature by 65% in healthy eyes and 38% in diseased eyes. Preliminary observations demonstrated that the location of 7° images could be identified directly from the wide field-of-view angiogram. A pilot study on a normal subject and patients with diabetic retinopathy showed the impact of utilizing WSAO for OCTA when visualizing peripheral vasculature pathologies.

Drusen Volume and Retinal Pigment Epithelium Abnormal Thinning Volume Predict 2-Year Progression of Age-Related Macular Degeneration.

PURPOSE: To analyze the value of novel measures of retinal pigment epithelium-drusen complex (RPEDC) volume to predict 2-year disease progression of intermediate age-related macular degeneration (AMD). DESIGN: Prospective, observational study. PARTICIPANTS: Three hundred forty-five AMD and 122 non-AMD participants enrolled in the Age Related Eye Disease Study 2 Ancillary Spectral-Domain (SD) Optical Coherence Tomography (OCT) study. METHODS: High-density SD OCT macular volumes were obtained at yearly study visits. The RPEDC abnormal thickening (henceforth, OCT drusen) and RPEDC abnormal thinning (RAT) volumes were generated by semiautomated segmentation of total RPEDC within a 5-mm-diameter macular field. MAIN OUTCOME MEASURES: Volume change and odds ratio (OR) with 95% confidence intervals (CI) for progression to advanced AMD with choroidal neovascularization (CNV) or central geographic atrophy (GA). RESULTS: Complete volumes were obtained in 265 and 266 AMD eyes and in 115 and 97 control eyes at baseline and at year 2, respectively. In AMD eyes, mean (standard deviation) OCT drusen volume increased from 0.08 mm(3) (0.16 mm(3)) to 0.10 mm(3) (0.23 mm(3); P < 0.001), and RAT volume increased from 8.3 × 10(-4) mm(3) (20.8 × 10(-4) mm(3)) to 18.4 × 10(-4) mm(3) (46.6 × 10(-4) mm(3); P < 0.001). Greater baseline OCT drusen volume was associated with 2-year progression to CNV (P = 0.002). Odds of developing CNV increased by 31% for every 0.1-mm(3) increase in baseline OCT drusen volume (OR, 1.31; 95% CI, 1.06-1.63; P = 0.013). Greater baseline RAT volume was associated with significant 2-year increase in RAT volume (P < 0.001), noncentral GA (P < 0.001), and progression to central GA (P < 0.001). Odds of developing central GA increased by 32% for every 0.001-mm(3) increase in baseline RAT volume (OR, 1.32; 95% CI, 1.14-1.53; P < 0.001). In non-AMD eyes, all volumes were significantly lower than AMD eyes and showed no significant 2-year change. CONCLUSIONS: Macular OCT drusen and RAT volumes increased significantly in AMD eyes over 2 years. These quantitative SD OCT biomarkers predict 2-year AMD progression and may serve as useful biomarkers for future clinical trials.

Validation of Macular Choroidal Thickness Measurements from Automated SD-OCT Image Segmentation.

PURPOSE: Spectral domain optical coherence tomography (SD-OCT) imaging permits in vivo visualization of the choroid with micron-level resolution over wide areas and is of interest for studies of ocular growth and myopia control. We evaluated the speed, repeatability, and accuracy of a new image segmentation method to quantify choroid thickness compared to manual segmentation. METHODS: Two macular volumetric scans (25 × 30°) were taken from 30 eyes of 30 young adult subjects in two sessions, 1 hour apart. A single rater manually delineated choroid thickness as the distance between Bruch's membrane and sclera across three B-scans (foveal, inferior, and superior-most scan locations). Manual segmentation was compared to an automated method based on graph theory, dynamic programming, and wavelet-based texture analysis. Segmentation performance comparisons included processing speed, choroid thickness measurements across the foveal horizontal midline, and measurement repeatability (95% limits of agreement (LoA)). RESULTS: Subjects were healthy young adults (n = 30; 24 ± 2 years; mean ± SD; 63% female) with spherical equivalent refractive error of -3.46 ± 2.69D (range: +2.62 to -8.50D). Manual segmentation took 200 times longer than automated segmentation (780 vs. 4 seconds). Mean choroid thickness at the foveal center was 263 ± 24 µm (manual) and 259 ± 23 µm (automated), and this difference was not significant (p = 0.10). Regional segmentation errors across the foveal horizontal midline (±15°) were ≤9 µm (median) except for nasal-most regions closest to the nasal peripapillary margin-15 degrees (19 µm) and 12 degrees (16 µm) from the foveal center. Repeatability of choroidal thickness measurements had similar repeatability between segmentation methods (manual LoA: ±15 µm; automated LoA: ±14 µm). CONCLUSIONS: Automated segmentation of SD-OCT data by graph theory and dynamic programming is a fast, accurate, and reliable method to delineate the choroid. This approach will facilitate longitudinal studies evaluating changes in choroid thickness in response to novel optical corrections and in ocular disease.

Multimodal characterization of proliferative diabetic retinopathy reveals alterations in outer retinal function and structure.

PURPOSE: To identify changes in retinal function and structure in persons with proliferative diabetic retinopathy (PDR), including the effects of panretinal photocoagulation (PRP). DESIGN: Cross-sectional study. PARTICIPANTS: Thirty adults who underwent PRP for PDR, 15 adults with untreated PDR, and 15 age-matched controls. METHODS: Contrast sensitivity, frequency doubling perimetry (FDP), Humphrey visual fields, photostress recovery, and dark adaptation were assessed. Fundus photography and macular spectral-domain optical coherence tomography (SD OCT) were performed. To quantify retinal layer thicknesses, SD OCT scans were segmented semiautomatically. MAIN OUTCOME MEASURES: Visual function measures were compared among patients with PDR and PRP, untreated patients with PDR, and controls. Mean retinal layer thicknesses were compared between groups. Correlation analyses were performed to evaluate associations between visual function measures and retinal layer thicknesses. RESULTS: A significant reduction of FDP mean deviation (MD) was exhibited in PRP-treated patients with PDR (MD ± standard deviation, -8.20±5.76 dB; P < 0.0001) and untreated patients (-5.48±4.48 dB; P < 0.0001) relative to controls (1.07±2.50 dB). Reduced log contrast sensitivity compared with controls (1.80±0.14) also was observed in both PRP-treated patients (1.42±0.17; P < 0.0001) and untreated patients (1.56±0.20; P = 0.001) with PDR. Compared with controls, patients treated with PRP demonstrated increased photostress recovery time (151.02±104.43 vs. 70.64±47.14 seconds; P = 0.001) and dark adaptation speed (12.80±5.15 vs. 9.74±2.56 minutes; P = 0.022). Patients who underwent PRP had diffusely thickened nerve fiber layers (P = 0.024) and diffusely thinned retinal pigment epithelium (RPE) layers (P = 0.009) versus controls. Untreated patients with PDR also had diffusely thinned RPE layers (P = 0.031) compared with controls. CONCLUSIONS: Patients with untreated PDR exhibited inner retinal dysfunction, as evidenced by reduced contrast sensitivity and FDP performance, accompanied by alterations in inner and outer retinal structure. Patients who underwent PRP had more profound changes in outer retinal structure and function. Distinguishing the effects of PDR and PRP may guide the development of restorative vision therapies for patients with advanced diabetic retinopathy.

Optical coherence tomography accurately measures corneal power change from laser refractive surgery.

PURPOSE: To determine the ability of motion-corrected optical coherence tomography (OCT) to measure the corneal refractive power change due to LASIK. DESIGN: Evaluation of a diagnostic test or technology in a cohort. SUBJECTS: A total of 70 eyes from 37 subjects undergoing LASIK were measured preoperatively. A total of 39 eyes from 22 subjects were measured postoperatively and completed the study. METHODS: Consecutive patients undergoing LASIK at the Duke Eye Center who consented to participate were imaged with Placido-ring topography, Scheimpflug photography, and OCT on the day of their surgery. Patients were then reimaged with the same imaging systems at the postoperative month 3 visit. Change in preoperative to postoperative corneal refractive power as measured by each of the imaging modalities was compared with the preoperative to postoperative change in manifest refraction (MRx) using the t test with generalized estimating equations. MAIN OUTCOME MEASURES: Corneal refractive power change due to LASIK as measured by Placido-ring topography, Scheimpflug photography, and OCT compared with the MRx change vertexed to the corneal plane. The change in MRx should correspond to the change in the corneal refractive power from LASIK and was considered the reference measurement. RESULTS: In 22 individuals (39 eyes) returning after LASIK, we found no significant difference between the clinically measured pre- to post-LASIK change in MRx and both Scheimpflug photography (P = 0.714) and OCT (P = 0.216). In contrast, keratometry values from Placido-ring topography were found to be significantly different from the measured refractive change (P < 0.001). In addition, of the 3 imaging modalities, OCT recorded the smallest mean absolute difference from the reference measurement with the least amount of variability. CONCLUSIONS: Motion-corrected OCT more accurately measures the change in corneal refractive power due to laser refractive surgery than other currently available clinical devices. By offering accurate corneal refractive power measurements in normal and surgically modified subjects, OCT offers a compelling alternative to current clinical devices for determining corneal refractive power.