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To evaluate intraretinal cystoid spaces in patients with idiopathic macular hole (MH).Retrospective cohort study included consecutive patients with full-thickness MH who underwent successful MH surgery and 12 months of follow-up. Custom software was applied to preoperative optical coherence tomography scans to generate fluid volume. Inner fluid volume was defined as cystoid spaces in the inner nuclear layer, and outer fluid volume was defined as cystoid spaces in Henle fiber layer of the outer nuclear layer.Thirty-nine eyes from 39 participants were included. Postoperative 12-month visual acuity correlated with both inner fluid volume and minimum MH size (both P0.05) but not outer fluid volume. Inner fluid volume positively correlated with minimum MH size ( P = 0.0003). After accounting for minimum MH size with multivariable analysis, inner fluid volume effect on VA remained significant ( P = 0.025). After dividing inner fluid volume into tertiles, mean baseline visual acuity was 20/50 in eyes with small inner fluid volume, and was 20/125 in eyes with large inner fluid volume ( P = 0.0039). Mean postoperative 12-month visual acuity was 20/20 in eyes with small inner fluid volume compared with 20/32 in eyes with large inner fluid volume ( P = 0.019).Increased inner fluid volume was associated with worse postoperative VA.

This study was designed to evaluate iVue Spectral-domain optical coherence tomography (SD-OCT) effectiveness in screening for eye disease compared to clinical examination. Subjects were recruited from the Casey Eye Community Outreach Program Mobile Clinic during its routinely scheduled outreach clinics to indigent, underserved populations throughout Oregon. Macular optical coherence tomography interpretation and automated optical coherence tomography analysis were compared to the clinical examination, with specific attention to findings indicative of retinal abnormalities, risks for glaucoma, and narrow angles. As a result, a total of 114 subjects were included in this study. In diabetics, optical coherence tomography and clinical exam were in fair agreement (kappa = 0.39), with 22% of eyes having abnormal findings on macular optical coherence tomography and 26% of eyes having diabetic retinopathy or diabetic macular edema on fundus exam. In non-diabetics, optical coherence tomography and clinical exam were in fair agreement (kappa = 0.28), with 11% of eyes having abnormal findings on macular optical coherence tomography and 9% on fundus exam. Using optical coherence tomography ganglion cell complex and retinal nerve fiber layer analysis, 18% of eyes were found to be glaucoma suspects, whereas clinical exam of cup-to-disc ratio detected 8% and intraocular pressure 5%. Agreements between optical coherence tomography and other methods were poor (kappa

SynopsisA deep-learning-based macular extrafoveal avascular area (EAA) on a 6×6 mm optical coherence tomography (OCT) angiogram is less dependent on the signal strength and shadow artefacts, providing better diagnostic accuracy for diabetic retinopathy (DR) severity than the commercial software measured extrafoveal vessel density (EVD).AimsTo compare a deep-learning-based EAA to commercial output EVD in the diagnostic accuracy of determining DR severity levels from 6×6 mm OCT angiography (OCTA) scans.MethodsThe 6×6 mm macular OCTA scans were acquired on one eye of each participant with a spectral-domain OCTA system. After excluding the central 1 mm diameter circle, the EAA on superficial vascular complex was measured with a deep-learning-based algorithm, and the EVD was obtained with commercial software.ResultsThe study included 34 healthy controls and 118 diabetic patients. EAA and EVD were highly correlated with DR severity (ρ=0.812 and −0.577, respectively, both pConclusionMacular EAA on 6×6 mm OCTA measured with a deep learning-based algorithm is less dependent on the signal strength and shadow artefacts, and provides better diagnostic accuracy for DR severity than EVD measured with the instrument-embedded software.

A limitation of conventional optical coherence tomography angiography (OCTA) is the limited field of view normally used in data acquisition. As the technology improves, larger fields of view that capture information away from the macular are being explored in order to provide an enhanced ability to detect pathology. However, normative measurements for important OCTA metrics like vessel density and intercapillary distance are not currently well-characterized in the peripheral retina. In this prospective study, we measured vessel density and intercapillary distance of the superficial vascular complex, ganglion cell layer plexus, and deep capillary plexus in montaged macular/temporal scans from 53 (33 men) healthy volunteers. Vessel density and intercapillary distance were also compared across different regions of the retina, including along arcs at separate distance from the fovea. Compared to the central macular region, the temporal retina had significantly lower vessel density, decreased thickness, and greater intercapillary distance in the superficial vascular complex, GCLP ganglion cell layer plexus, and deep capillary plexus (Wilcoxon rank sum test P

Purpose To evaluate wide-field optical coherence tomography angiography (OCTA) for detection of clinically unsuspected neovascularization (NV) in diabetic retinopathy (DR). Methods This prospective observational single-center study included adult patients with a clinical diagnosis of nonproliferative DR. Participants underwent a clinical examination, standard 7-field color photography, and OCTA with commercial and prototype swept-source devices. The wide-field OCTA was achieved by montaging five 6 × 10-mm scans from a prototype device into a 25 × 10-mm image and three 6 × 6-mm scans from a commercial device into a 15 × 6-mm image. A masked grader determined the retinopathy severity from color photographs. Two trained readers examined conventional and wide-field OCTA images for the presence of NV. Results Of 27 participants, photographic grading found 13 mild, 7 moderate, and 7 severe nonproliferative DR. Conventional 6 × 6-mm OCTA detected NV in 2 eyes (7%) and none with 3 × 3-mm scans. Both prototype and commercial wide-field OCTA detected NV in two additional eyes. The mean area of NV was 0.38 mm (range 0.17-0.54 mm). All eyes with OCTA-detected NV were photographically graded as severe nonproliferative DR. Conclusion Wide-field OCTA can detect small NV not seen on clinical examination or color photographs and may improve the clinical evaluation of DR.

Purpose We propose a deep learning-based image reconstruction algorithm to produce high-resolution optical coherence tomographic angiograms (OCTA) of the intermediate capillary plexus (ICP) and deep capillary plexus (DCP). Methods In this study, 6-mm × 6-mm macular scans with a 400 × 400 A-line sampling density and 3-mm × 3-mm scans with a 304 × 304 A-line sampling density were acquired on one or both eyes of 180 participants (including 230 eyes with diabetic retinopathy and 44 healthy controls) using a 70-kHz commercial OCT system (RTVue-XR; Optovue, Inc., Fremont, California, USA). Projection-resolved OCTA algorithm removed projection artifacts in voxel. ICP and DCP angiograms were generated by maximum projection of the OCTA signal within the respective plexus. We proposed a deep learning-based method, which receives inputs from registered 3-mm × 3-mm ICP and DCP angiograms with proper sampling density as the ground truth reference to reconstruct 6-mm × 6-mm high-resolution ICP and DCP en face OCTA. We applied the same network on 3-mm × 3-mm angiograms to enhance these images further. We evaluated the reconstructed 3-mm × 3-mm and 6-mm × 6-mm angiograms based on vascular connectivity, Weber contrast, false flow signal (flow signal erroneously generated from background), and the noise intensity in the foveal avascular zone. Results Compared to the originals, the Deep Capillary Angiogram Reconstruction Network (DCARnet)-enhanced 6-mm × 6-mm angiograms had significantly reduced noise intensity (ICP, 7.38 ± 25.22, P < 0.001; DCP, 11.20 ± 22.52, P < 0.001), improved vascular connectivity (ICP, 0.95 ± 0.01, P < 0.001; DCP, 0.96 ± 0.01, P < 0.001), and enhanced Weber contrast (ICP, 4.25 ± 0.10, P < 0.001; DCP, 3.84 ± 0.84, P < 0.001), without generating false flow signal when noise intensity lower than 650. The DCARnet-enhanced 3-mm × 3-mm angiograms also reduced noise, improved connectivity, and enhanced Weber contrast in 3-mm × 3-mm ICP and DCP angiograms from 101 eyes. In addition, DCARnet preserved the appearance of the dilated vessels in the reconstructed angiograms in diabetic eyes. Conclusions DCARnet can enhance 3-mm × 3-mm and 6-mm × 6-mm ICP and DCP angiogram image quality without introducing artifacts. Translational Relevance The enhanced 6-mm × 6-mm angiograms may be easier for clinicians to interpret qualitatively.

PURPOSE: In diabetic macular edema (DME), the correlation between visual acuity (VA) and central subfield thickness (CST) is weak. We hypothesize that fluid volume (FV) in inner nuclear layer (INL) may correlate more strongly with VA. DESIGN: Retrospective, cross-sectional study METHOD: One eye each of diabetic patients with DME were included. We measured intraretinal fluid volume that detected by automated fluid detection algorithm on 3×3-mm optical coherence tomography angiogram volume scans. The detected fluid was subdivided into inner FV, bounded by the inner nuclear layer (INL), and outer FV, the fluid between outer border of INL to ellipsoid zone. RESULT: We enrolled 125 patients with DME (60 women, mean 61-year-old). The mean detected inner FV was 0.013 mm(3) in 109 eyes (87%). The mean detected outer FV was 0.042 mm(3) in 124 eyes (99%). Univariate analysis demonstrated that the VA significantly correlated with the inner FV (P

PURPOSE: To compare retinal vessel density in eyes with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) to age-matched healthy eyes using projection-resolved optical coherence tomography angiography (PR-OCTA). DESIGN: Prospective cross-sectional study. METHODS: Study participants underwent macular 3×3-mm OCTA scans with spectral domain OCTA. Reflectance-compensated retinal vessel densities were calculated on projection-resolved superficial vascular complex (SVC), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). Quantitative analysis using normalized deviation compared the retinal vessel density in GA regions, 500 μm GA rim regions, and non-GA regions to similar macular locations in control eyes. RESULTS: Ten eyes with GA and 10 control eyes were studied. Eyes with GA had significantly lower vessel density in the SVC (54.8±2.4% vs. 60.8±3.1%, P

Importance Diabetic macular edema (DME) is the predominant cause of visual impairment in patients with type 1 or 2 diabetes. Automated fluid volume measurements using optical coherence tomography (OCT) may improve the diagnostic accuracy of DME screening. Objective To assess the diagnostic accuracy of an automated central macular fluid volume (CMFV) quantification using OCT for DME. Design, Setting, and Participants A cross-sectional observational study was conducted at a tertiary academic center among 215 patients with diabetes (1 eye each) enrolled from January 26, 2015, to December 23, 2019. All participants underwent comprehensive examinations, 6 × 6-mm macular structural OCT horizontal raster scans, and 6 × 6-mm macular OCT angiography volumetric scans. From January 1 to March 30, 2020, 2 retinal specialists reviewed the structural OCT scans independently and diagnosed DME if intraretinal or subretinal fluid was present. Diabetic macular edema was considered center involved if fluid was present within the central fovea (central 1-mm circle). A third retinal specialist arbitrated any discrepancy. The mean central subfield thickness (CST) within the central fovea was measured on structural OCT horizontal raster scans. A deep learning algorithm automatically quantified fluid volumes on 6 × 6-mm OCT angiography volumetric scans and within the central foveas (CMFV). Main Outcomes and Measures The area under the receiver operating characteristic curve (AUROC) and the sensitivity and specificity of CST and CMFV for DME diagnosis. Results We enrolled 1 eye each of 215 patients with diabetes (117 women [54.4%]; mean [SD] age, 59.6 [12.4] years). Diabetic macular edema was present in 136 eyes; 93 cases of DME were center involved. The AUROC of CMFV for diagnosis of center-involved DME (0.907 [95% CI, 0.861-0.954]) was greater than the AUROC of CST (0.832 [95% CI, 0.775-0.889]; P = .02). With the specificity set at 95%, the sensitivity of CMFV for detection of center-involved DME (78.5% [95% CI, 68.8%-86.3%]) was higher than that of CST (53.8% [95% CI, 43.1%-64.2%]; P = .002). Center-involved DME cases not detected by CST but detected by CMFV were associated with a thinner CST (290.8 μm [95% CI, 282.3-299.3 μm] vs 369.4 μm [95% CI, 347.1-391.7 μm]; P

Reliable classification of referable and vision threatening diabetic retinopathy (DR) is essential for patients with diabetes to prevent blindness. Optical coherence tomography (OCT) and its angiography (OCTA) have several advantages over fundus photographs. We evaluated a deep-learning-aided DR classification framework using volumetric OCT and OCTA.Four hundred fifty-six OCT and OCTA volumes were scanned from eyes of 50 healthy participants and 305 patients with diabetes. Retina specialists labeled the eyes as non-referable (nrDR), referable (rDR), or vision threatening DR (vtDR). Each eye underwent a 3 × 3-mm scan using a commercial 70 kHz spectral-domain OCT system. We developed a DR classification framework and trained it using volumetric OCT and OCTA to classify eyes into rDR and vtDR. For the scans identified as rDR or vtDR, 3D class activation maps were generated to highlight the subregions which were considered important by the framework for DR classification.For rDR classification, the framework achieved a 0.96 ± 0.01 area under the receiver operating characteristic curve (AUC) and 0.83 ± 0.04 quadratic-weighted kappa. For vtDR classification, the framework achieved a 0.92 ± 0.02 AUC and 0.73 ± 0.04 quadratic-weighted kappa. In addition, the multiple DR classification (non-rDR, rDR but non-vtDR, or vtDR) achieved a 0.83 ± 0.03 quadratic-weighted kappa.A deep learning framework only based on OCT and OCTA can provide specialist-level DR classification using only a single imaging modality.The proposed framework can be used to develop clinically valuable automated DR diagnosis system because of the specialist-level performance showed in this study.

Optical coherence tomographic angiography (OCTA) is a non-invasive imaging modality that provides three-dimensional, information-rich vascular images. With numerous studies demonstrating unique capabilities in biomarker quantification, diagnosis, and monitoring, OCTA technology has seen rapid adoption in research and clinical settings. The value of OCTA imaging is significantly enhanced by image analysis tools that provide rapid and accurate quantification of vascular features and pathology. Today, the most powerful image analysis methods are based on artificial intelligence (AI). While AI encompasses a large variety of techniques, machine learning-based, and especially deep-learning-based, image analysis provides accurate measurements from a variety of contexts, including different diseases and regions of the eye. Here, we discuss the principles of both OCTA and AI that make their combination capable of answering new questions. We also review contemporary applications of AI in OCTA, which include accurate detection of pathologies such as choroidal neovascularization, precise quantification of retinal perfusion, and reliable disease diagnosis.

Objective: Optical coherence tomography (OCT) and its angiography (OCTA) have several advantages for the early detection and diagnosis of diabetic retinopathy (DR). However, automated, complete DR classification frameworks based on both OCT and OCTA data have not been proposed. In this study, a convolutional neural network (CNN) based method is proposed to fulfill a DR classification framework using en face OCT and OCTA. Methods: A densely and continuously connected neural network with adaptive rate dropout ( DcardNet ) is designed for the DR classification. In addition, adaptive label smoothing was proposed and used to suppress overfitting. Three separate classification levels are generated for each case based on the International Clinical Diabetic Retinopathy scale. At the highest level the network classifies scans as referable or non-referable for DR. The second level classifies the eye as non-DR, non-proliferative DR (NPDR), or proliferative DR (PDR). The last level classifies the case as no DR, mild and moderate NPDR, severe NPDR, and PDR. Results: We used 10-fold cross-validation with 10% of the data to assess the network's performance. The overall classification accuracies of the three levels were 95.7%, 85.0%, and 71.0% respectively. Conclusion/Significance: A reliable, sensitive and specific automated classification framework for referral to an ophthalmologist can be a key technology for reducing vision loss related to DR.

ObjectiveTo detect the plexus-specific retinal capillary avascular area in exudative age-related macular degeneration (EAMD) with projection-resolved optical coherence tomography angiography (PR-OCTA).Methods and analysisIn this prospective cross-sectional single centre study, eyes with treatment-naïve EAMD underwent macular 3×3 mm OCTA with AngioVue system. OCTA scans were analysed and processed including three-dimensional projection artefact removal, retinal layer semi-automated segmentation and en face angiogram generation. Automated quantification of extrafoveal (excluding the central 1 mm circle) avascular area (EAA) were calculated on projection-resolved superficial vascular complex (SVC), intermediate capillary plexus (ICP) and deep capillary plexus (DCP), respectively.ResultsNineteen eyes with EAMD and 19 age-matched healthy control eyes were included. There was no significant difference between the EAMD and control eyes in terms of age, sex, axial length and mean ocular perfusion pressure (all p>0.05). Compared with control eyes, EAMD eyes had significantly larger EAA in SVC (median 0.125 vs 0.059 mm2, p=0.006), ICP (0.016 vs 0.000 mm2, p=0.004) and DCP (0.033 vs 0.000 mm2, p＜0.001).ConclusionPR-OCTA showed that EAMD is associated with focal avascular area in all the three retinal vascular plexuses.

PURPOSE Stickler syndrome is associated with open-angle glaucoma, but no reports exist of adults presenting with acute angle closure. Here, we report the clinical associations and short-term outcomes in 2 patients with Stickler syndrome who presented with acute angle closure at a single tertiary referral center. OBSERVATIONS A 36-year-old female with Stickler syndrome presented with acute onset of red and painful left eye with cloudy vision. Initial intraocular pressure (IOP) was measured to be 54 mm Hg. Gonioscopy revealed no angle structures or peripheral anterior synechiae in the left eye. Two laser peripheral iridotomies were created 5 days apart without adequate IOP lowering. Left eye cataract extraction with intraocular lens implantation and Ahmed glaucoma drainage device implantation were performed with resolution of ocular hypertension.A 35-year-old male with Stickler syndrome presented with intermittent right eye pain and blurry vision. IOP was 42 mm Hg and gonioscopy revealed 270 degrees of angle closure in the right eye. The patient underwent laser peripheral iridotomy in the right eye with resolution of ocular hypertension by the next day. CONCLUSIONS Recognizing angle closure as a potential feature of Stickler syndrome can help providers adequately screen and manage patients with Stickler syndrome presenting with acutely elevated IOP.

Purpose We proposed a deep convolutional neural network (CNN), named Retinal Fluid Segmentation Network (ReF-Net), to segment retinal fluid in diabetic macular edema (DME) in optical coherence tomography (OCT) volumes. Methods The 3- × 3-mm OCT scans were acquired on one eye by a 70-kHz OCT commercial AngioVue system (RTVue-XR; Optovue, Inc., Fremont, CA, USA) from 51 participants in a clinical diabetic retinopathy (DR) study (45 with retinal edema and six healthy controls, age 61.3 ± 10.1 (mean ± SD), 33% female, and all DR cases were diagnosed as severe NPDR or PDR). A CNN with U-Net-like architecture was constructed to detect and segment the retinal fluid. Cross-sectional OCT and angiography (OCTA) scans were used for training and testing ReF-Net. The effect of including OCTA data for retinal fluid segmentation was investigated in this study. Volumetric retinal fluid can be constructed using the output of ReF-Net. Area-under-receiver-operating-characteristic-curve, intersection-over-union (IoU), and F1-score were calculated to evaluate the performance of ReF-Net. Results ReF-Net shows high accuracy (F1 = 0.864 ± 0.084) in retinal fluid segmentation. The performance can be further improved (F1 = 0.892 ± 0.038) by including information from both OCTA and structural OCT. ReF-Net also shows strong robustness to shadow artifacts. Volumetric retinal fluid can provide more comprehensive information than the two-dimensional (2D) area, whether cross-sectional or en face projections. Conclusions A deep-learning-based method can accurately segment retinal fluid volumetrically on OCT/OCTA scans with strong robustness to shadow artifacts. OCTA data can improve retinal fluid segmentation. Volumetric representations of retinal fluid are superior to 2D projections. Translational relevance Using a deep learning method to segment retinal fluid volumetrically has the potential to improve the diagnostic accuracy of diabetic macular edema by OCT systems.

Purpose The purpose of this study was to assess the associations between baseline choriocapillaris (CC) flow deficits and geographic atrophy (GA) progression. Methods In this prospective cohort study, patients with GA underwent 3 × 3-mm macular spectral-domain optical coherence tomographic angiography (OCTA) at baseline and follow-up visits. Annual GA enlargement rate was defined as change of square root of GA area in 12 months. Shadow areas due to iris, media opacity, retinal vessels, and drusen were excluded. CC vessel density (CC-VD) in non-GA areas was measured using a validated machine-learning-based algorithm. Low perfusion area (LPA) was defined as capillary density below the 0.1 percentile threshold of the same location of 40 normal healthy control eye. Focal perfusion loss (FPL) was defined as percentage of CC loss within LPA compared with normal controls. Results Ten patients with GA were enrolled and followed for 26 months on average. At baseline, the mean GA area was 0.84 ± 0.70 mm2. The mean CC-VD was 44.5 ± 15.2%, the mean LPA was 4.29 ± 2.6 mm2, and the mean FPL was 50.4 ± 28.2%. The annual GA enlargement rate was significantly associated with baseline CC-VD (r = −0.816, P = 0.004), LPA (r = 0.809, P = 0.005), and FPL (r = 0.800, P = 0.005), but not with age (r = 0.008, P = 0.98) and GA area (r = −0.362, P = 0.30). Conclusions Baseline CC flow deficits were significantly associated with a faster GA enlargement over the course of 1 year, suggesting the choriocapillaris perfusion outside of a GA area may play a role in GA progression.

Purpose To describe an automated algorithm to quantify the foveal avascular zone (FAZ), using optical coherence tomography angiography (OCTA), and to compare its performance for diagnosis of diabetic retinopathy (DR) and association with best-corrected visual acuity (BCVA) to that of extrafoveal avascular area (EAA). Methods We obtained 3 × 3-mm macular OCTA scans in diabetic patients with various levels of DR and healthy controls. An algorithm based on a generalized gradient vector flow (GGVF) snake model detected the FAZ, and metrics assessing FAZ size and irregularity were calculated. We compared the automated FAZ segmentation to manual delineation and tested the within-visit repeatability of FAZ metrics. The correlations of two conventional FAZ metrics, two novel FAZ metrics, and EAA with DR severity and BCVA, as determined by Early Treatment Diabetic Retinopathy Study (ETDRS) charts, were assessed. Results Sixty-six eyes from 66 diabetic patients and 19 control eyes from 19 healthy participants were included. The agreement between manual and automated FAZ delineation had a Jaccard index > 0.82, and the repeatability of automated FAZ detection was excellent in eyes at all levels of DR severity. FAZ metrics that incorporated both FAZ size and shape irregularity had the strongest correlation with clinical DR grade and BCVA. Of all the tested OCTA metrics, EAA had the greatest sensitivity in differentiating diabetic eyes without clinical evidence of retinopathy, mild to moderate nonproliferative DR (NPDR), and severe NPDR to proliferative DR from healthy controls. Conclusions The GGVF snake algorithm tested in this study can accurately and reliably detect the FAZ, using OCTA data at all DR severity grades, and may be used to obtain clinically useful information from OCTA data regarding macular ischemia in patients with diabetes. While FAZ metrics can provide clinically useful information regarding macular ischemia, and possibly visual acuity potential, EAA measurements may be a better biomarker for DR.

To assess the association between optical coherence tomography angiography (OCTA)-quantified avascular areas (AAs) and diabetic retinopathy (DR) severity, progression, and treatment requirement in the following year.Prospective cohort study.We recruited patients with diabetes from a tertiary academic retina practice and obtained 3-mm × 3-mm macular OCTA scans with the AngioVue system and standard 7-field color photographs at baseline and at a 1-year follow-up visit. A masked grader determined the severity of DR from the color photographs using the Early Treatment of Diabetic Retinopathy scale. A custom algorithm detected extrafoveal AA (EAA) excluding the central 1-mm circle in projection-resolved superficial vascular complex (SVC), intermediate capillary plexus (ICP), and deep capillary plexus (DCP).Of 138 patients, 92 (41 men, ranging in age from 26-84 years [mean 59.4 years]) completed 1 year of follow-up. At baseline, EAAs for SVC, ICP, and DCP were all significantly correlated with retinopathy severity (P.0001). DCP EAA was significantly associated with worse visual acuity (r = -0.24, P = .02), but SVC and ICP EAA were not. At 1 year, 11 eyes progressed in severity by at least 1 step. Multivariate logistic regression analysis demonstrated the progression was significantly associated with baseline SVC EAA (odds ratio = 8.73, P = .04). During the follow-up period, 33 eyes underwent treatment. Multivariate analysis showed that treatment requirement was significantly associated with baseline DCP EAA (odds ratio = 3.39, P = .002). No baseline metric was associated with vision loss at 1 year.EAAs detected by OCTA in diabetic eyes are significantly associated with baseline DR severity, disease progression, and treatment requirement over 1 year.

Purpose Thinning of the inner layers of the retina occurs in patients with central retinal artery occlusion (CRAO). The mechanism for such thinning may be partially due to proteolysis by a calcium-activated protease called calpain. Calpain inhibitor SNJ-1945 ameliorated the proteolysis in a past series of model experiments. The purposes of the present retrospective study were to: 1) use segmentation analysis of optical coherence tomography (OCT) images to mathematically model the loss of specific retinal layers in CRAO patients, and 2) predict the number of patients and days of observation needed for clinical trials of inhibitors against CRAO. Methods A retrospective case control study was conducted by computer-aided search for CRAO (ICD10 H43.1) with at least one OCT procedure (CPT: 92134) in the OHSU Epic patient data base. Results After initial swelling, thinning of the inner retinal layers, especially the ganglion cell (GCL) layer followed exponential decay curves. Using sample size statistics and GCL thickness as a marker in a 30-day clinical trial, 19 eyes/group could theoretically detect a 20% beneficial effect of an inhibitor against CRAO. Other markers, such as the whole retinal thickness and combined inner layers could also be used as less-specific markers. Conclusions Using thickness changes in the GCL layer to monitor the efficacy of potential inhibitors against CRAO is practical in human trials requiring a reasonable number of patients and relatively short trial period. Translational relevance Measurement of GCL thickness would be a useful indicator of CRAO progression in a clinical trial of putative inhibitors.

Purpose To characterize the density and distribution of the radial peripapillary capillary plexus (RPCP) and its relationship with retinal nerve fiber layer (NFL) thickness in healthy subjects. Methods Using spectral-domain optical coherence tomography (OCT), split-spectrum amplitude decorrelation angiography algorithm and automated montaging, wide-field OCT angiography (OCTA) was used to measure the RPCP capillary density (CD) and NFL thickness. Polar sector-average CD and thickness maps were also created on each eye. Results Wide-field OCTA (8 × 8 mm) in 10 healthy eyes from 10 subjects demonstrated the distribution of the RPCP throughout the posterior pole. RPCP-CD decreases with distance from the disc, but along the arcuate nerve fiber bundles relatively dense (> half maximum density) RPCP extends more than 5 mm from the disc and includes regions superior to and inferior to the macula. The RPCP-CD and NFL thickness are highly correlated (R2 = 0.85, P < 0.001) and fit well with a nonlinear stacked-layer model. The model fit suggests that the RPCP is present when the NFL is thicker than 17.9 μm and reaches a ceiling area density of 84% and that the RPCP has an apparent volume density of 19% at the current instrument transverse resolution. This indicates that capillary overlap can be expected to occur when NFL thickness reaches 40 μm. Conclusions The wide distribution of dense overlapping RPCP suggests that wider (up to 8 mm vertical and 7 mm horizontal) OCTA scans may be better investigate capillary loss in the early stages of glaucoma or other optic neuropathies.

Purpose To evaluate the morphological structure of ill-defined choroidal neovascularisation (CNV) with traditional fluorescein angiography (FA) compared with optical coherence tomographic angiography (OCTA). Methods A retrospective case series study of 11 eyes with ill-defined CNV on FA was performed. Eyes were scanned with commercially available spectral-domain optical coherence tomography (OCT) (70 000 A-scans/s). The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm was used to distinguish blood flow from static tissue. En face OCT angiograms were compared with FA. Results Eleven cases of ill-defined CNV on FA were identified from 10 study participants. Mean age of the participants was 74.5±6.8 years. Six cases had late leakage from undetermined source (LLUS) and five had fibrovascular pigment epithelial detachment (FVPED). Combining cross-sectional structural OCT with OCT angiograms, all cases were found to have type 1 CNV that corresponded to occult CNV with FA. In all cases of occult CNV on FA, distinct vascular structures were visible with OCTA in the outer retinal/retinal pigment epithelium slab. The mean CNV vessel area was 2.61±3.65 mm 2 . The mean CNV vessel area in cases with FVPED was larger than that in cases with LLUS (4.69±4.72 mm 2 compared with 0.85±0.90 mm 2 , Mann-Whitney p value=0.04). Conclusions Although the sample size is small to draw conclusions and the nature of work is retrospective and descriptive, OCTA has the potential to improve visualisation of ill-defined CNV with dye-based angiography, including occult CNV.

Optical coherence tomographic angiography (OCTA) is a novel technology capable of imaging retinal vasculature three-dimensionally at capillary scale without the need to inject any extrinsic dye contrast. However, projection artifacts cause superficial retinal vascular patterns to be duplicated in deeper layers, thus interfering with the clean visualization of some retinal plexuses and vascular pathologies. Projection-resolved OCTA (PR-OCTA) uses post-processing algorithms to reduce projection artifacts. With PR-OCTA, it is now possible to resolve up to 4 distinct retinal vascular plexuses in the living human eye. The technology also allows us to detect and distinguish between various retinal and optic nerve diseases. For example, optic nerve diseases such as glaucoma primarily reduces the capillary density in the superficial vascular complex, which comprises the nerve fiber layer plexus and the ganglion cell layer plexus. Outer retinal diseases such as retinitis pigmentosa primarily reduce the capillary density in the deep vascular complex, which comprises the intermediate capillary plexus and the deep capillary plexus. Retinal vascular diseases such as diabetic retinopathy and vein occlusion affect all plexuses, but with different patterns of capillary loss and vascular malformations. PR-OCTA is also useful in distinguishing various types of choroidal neovascularization and monitoring their response to anti-angiogenic medications. In retinal angiomatous proliferation and macular telangiectasia type 2, PR-OCTA can trace the pathologic vascular extension into deeper layers as the disease progress through stages. Plexus-specific visualization and measurement of retinal vascular changes are improving our ability to diagnose, stage, monitor, and assess treatment response in a wide variety of optic nerve and retinal diseases. These applications will be further enhanced with the continuing improvement of the speed and resolution of the OCT platforms, as well as the development of software algorithms to reduce artifacts, improve image quality, and make quantitative measurements.

PURPOSE: With the current wide adoption of electronic health records (EHRs) by ophthalmologists, there are widespread concerns about the amount of time spent using the EHR. The goal of this study was to examine how the amount of time spent using EHRs as well as related documentation behaviors changed 1 decade after EHR adoption. DESIGN: Single-center cohort study. PARTICIPANTS: Six hundred eighty-five thousand three hundred sixty-one office visits with 70 ophthalmology providers. METHODS: We calculated time spent using the EHR associated with each individual office visit using EHR audit logs and determined chart closure times and progress note length from secondary EHR data. We tracked and modeled how these metrics changed from 2006 to 2016 with linear mixed models. MAIN OUTCOME MEASURES: Minutes spent using the EHR associated with an office visit, chart closure time in hours from the office visit check-in time, and progress note length in characters. RESULTS: Median EHR time per office visit in 2006 was 4.2 minutes (interquartile range [IQR], 3.5 minutes), and increased to 6.4 minutes (IQR, 4.5 minutes) in 2016. Median chart closure time was 2.8 hours (IQR, 21.3 hours) in 2006 and decreased to 2.3 hours (IQR, 18.5 hours) in 2016. In 2006, median note length was 1530 characters (IQR, 1435 characters) and increased to 3838 characters (IQR, 2668.3 characters) in 2016. Linear mixed models found EHR time per office visit was 31.9±0.2% (P < 0.001) greater from 2014 through 2016 than from 2006 through 2010, chart closure time was 6.7±0.3 hours (P < 0.001) shorter from 2014 through 2016 versus 2006 through 2010, and note length was 1807.4±6.5 characters (P < 0.001) longer from 2014 through 2016 versus 2006 through 2010. CONCLUSIONS: After 1 decade of use, providers spend more time using the EHR for an office visit, generate longer notes, and close the chart faster. These changes are likely to represent increased time and documentation pressure for providers. Electronic health record redesign and new documentation regulations may help to address these issues.

BACKGROUND AND OBJECTIVE: To report on the microbiology, management, and visual outcomes of intravitreal injection (IVI)-associated, culture-proven endophthalmitis. PATIENTS AND METHODS: All patients seen at a tertiary referral center with culture-proven endophthalmitis associated with an IVI between June 2007 and July 2017 were included in this retrospective analysis. RESULTS: Thirty-five patients with culture-positive endophthalmitis following IVI were identified. All gram-positive organisms (34 of 35) were susceptible to vancomycin. Cases due to pathogens associated with oral or respiratory flora were common (31.4%, n = 11), presented earlier (2.0 days vs. 4.6 days, P < .001), were more likely to undergo pars plana vitrectomy (81.8% vs. 25.0%, P = .002) and had worse visual acuity outcomes. CONCLUSION: IVI-associated endophthalmitis pathogens and anti-microbial susceptibilities in the Pacific Northwest are similar to those reported from other geographic locations. Bacteria associated with the oral and respiratory flora are common isolates that result in a more aggressive course and worse visual outcomes. [ Ophthalmic Surg Lasers Imaging Retina . 2019;50:33–38.]

OBJECTIVE: To investigate ophthalmologists’ rate of attestation to meaningful use of their electronic health record (EHR) systems in the Medicare EHR Incentive program and their continuity and success in receiving payments in comparison to other specialties. DESIGN: Administrative database study PARTICIPANTS: Eligible professionals participating in the Medicare EHR Incentive Program METHODS: Based on publicly available data sources, subsets of payment and attestation data were created for ophthalmologists and for other specialties. The number of eligible professionals attesting was determined using the attestation data for each year and stage of the program. The proportion of attestations by EHR vendor was calculated using all attestations for each vendor. MAIN OUTCOME MEASURES: Numbers of ophthalmologists attesting by year and stage of the Medicare EHR Incentive program, incentive payments, and number of attestations by EHR vendor RESULTS: 51.6% of ophthalmologists successfully attested to meaningful use in the peak year of participation, compared to 37.1% of optometrists, 50.2% of dermatologists, 54.5% of otolaryngologists, and 64.4% of urologists. Across the six years of the program, ophthalmologists received an average of $US 17,942 in incentive payments compared to $US 11,105 for optometrists, $US 16,617 for dermatologists, $US 20,203 for otolaryngologists, and $US 23,821 for urologists. Epic and Nextgen were the most frequently used EHRs for attestation by ophthalmologists. CONCLUSIONS: Ophthalmology as a specialty performed better than optometry and dermatology but worse than otolaryngology and urology in terms of the proportion of eligible professionals attesting to meaningful use of EHRs. Ophthalmologists were more likely to remain in the program after their initial year of attestation compared to all eligible providers. The top 4 vendors accounted for 50% of attestations by ophthalmologists.

Importance Diabetic retinopathy (DR) is a leading cause of vision loss that is managed primarily through qualitative clinical examination of the retina. Optical coherence tomography angiography (OCTA) may offer an objective and quantitative method of evaluating DR. Objective To quantify capillary nonperfusion in 3 vascular plexuses in the macula of eyes patients with diabetes of various retinopathy severity using projection-resolved OCTA (PR-OCTA). Design, Setting, and Participants Cross-sectional study at a tertiary academic center comprising 1 eye each from healthy control individuals and patients with diabetes at different severity stages of retinopathy. Data were acquired and analyzed between January 2015 and December 2017. Main Outcomes and Measures Foveal avascular zone area, extrafoveal avascular area (EAA), and the sensitivity of detecting levels of retinopathy. Results The study included 39 control individuals (20 women [51%]; mean [SD] age, 43.41 [19.37] years); 16 patients with diabetes without retinopathy (8 women [50%]; mean [SD] age, 56.50 [12.43] years); 23 patients with mild to moderate nonproliferative DR (18 women [78%] ; mean [SD] age, 62.48 [10.55] years); and 32 patients with severe nonproliferative DR or proliferative DR (12 women [38%]; mean age, 53.41 [14.05] years). Mean (SD) foveal avascular zone area was 0.203 (0.103) mm2for control individuals, 0.192 (0.084) mm2for patients with diabetes without retinopathy, 0.243 [0.079] mm2for mild to moderate nonproliferative DR, and 0.359 (0.275) mm2for severe nonproliferative DR or proliferative DR. Mean (SD) EAA in whole inner retinal slab in these groups, respectively, were 0.020 (0.031) mm2, 0.034 (0.047) mm2, 0.038 (0.040) mm2, and 0.237 (0.235) mm2. The mean (SD) sum of EAA from 3 segmented plexuses in each of the respective groups were 0.103 (0.169) mm2, 0.213 (0.242) mm2, 0.451 (0.243) mm2, and 1.325 (1.140) mm2. With specificity fixed at 95%, using EAA in inner retinal slab, the sensitivity of detecting patients with diabetes from healthy control individuals was 28% (95% CI, 18%-40%), 31% for patients with DR (95% CI, 19%-45%), and 47% for patients with severe DR (95% CI, 29%-65%) from whole inner retinal EAA. With the sum of EAA from 3 individual plexuses, the sensitivities were 69% (95% CI, 57%-80%), 82% (95% CI, 70%-91%), and 97% (95% CI, 85%-100%), respectively. Avascular areas were not associated with signal strength index. The commercial vessel density from the 2-plexus scheme distinguished the groups with lower sensitivity and were dependent on SSI. Conclusions and Relevance Automatically quantified avascular areas from a 3-layer segmentation scheme using PR-OCTA distinguished levels of retinopathy with a greater sensitivity than avascular areas from unsegmented inner retinal slab or measurements from a commercially available vessel density in 2-layer scheme. Additional studies are needed to investigate the applicability of nonperfusion parameters in clinical settings.

Diabetic retinopathy is a microangiopathy that causes capillary occlusion, vascular hyperpermeability, and neovascularization in the retinal vasculature.1 Detailed clinical examination for grading disease severity for risk of progression and vision loss is the standard of care2, but ophthalmic angiography has played a critical role in understanding and care of the disease. Early Treatment of Diabetic Retinopathy Study (ETDRS) examined the fluorescein angiographic features of the posterior pole of patients with non-proliferative diabetic retinopathy and correlated the specific features with their risk of disease progression. 3,4 Fluorescein angiography (FA) is also used to identify retinal neovascularization (RNV) in situations where clinical examination cannot detect RNV or distinguish from other anomalous appearing vessels on the retinal surface. While angiography provides valuable additional information compared to clinical examination or fundus photography, it is not part of the routine diabetic eye examination. FA requires venipuncture and intravenous injection of a dye that has a moderate risk of nausea and a rare but well documented risk of anaphylaxis and death. 5 Also, a standard protocol FA acquires images over 10 minutes with repeated exposure to a very bright light source, 6 which can cause significant discomfort for patients. Optical coherence tomography (OCT) angiography, a novel imaging technique that uses decorrelation between resampled images to detect flow to construct 2- and 3-dimensional images of blood flow within the eye, offers an alternative angiographic technique without some of the drawbacks of FA. Our group has developed the split-spectrum amplitude decorrelation algorithm (SSADA) for efficiently detecting flow signals for angiography. 7 Applying this algorithm, an OCT angiogram in areas up to 6 × 6 mm area can be acquired in 3.5 seconds without intravenous injection. This study describes features of diabetic retinopathy as seen on OCT angiography.

PURPOSE Recent studies have suggested that the use of systemic beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers can induce regression of choroidal neovascularization in rodent models. The purpose of this study is to evaluate if these agents have a protective effect against the development of choroidal neovascularization in patients with age-related macular degeneration. METHODS In this single-center retrospective case-control study, the charts of 250 patients with neovascular age-related macular degeneration were compared with those of 250 controls with dry age-related macular degeneration. Charts were reviewed for current and past use of beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers. Frequency tables were generated, and associations were examined using chi-square tests, t-tests, and multivariate logistic regression. RESULTS There was no statistically significant difference between rates of beta-blocker use (P = 0.57), angiotensin-converting enzyme inhibitors use (P = 0.20), or angiotensin receptor blockers use (P = 0.61) between the 2 groups. Additionally, there was no statistically significant difference between rates of use of combinations of the above drugs between the two groups. CONCLUSION Although there is growing evidence that beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers can induce regression of choroidal neovascularization in rodent models, these medications do not seem to confer a protective effect against the development of choroidal neovascularization in patients with age-related macular degeneration.

Optical coherence tomography angiography (OCTA) is a noninvasive method of 3D imaging of the retinal and choroidal circulations. However, vascular depth discrimination is limited by superficial vessels projecting flow signal artifact onto deeper layers. The projection-resolved (PR) OCTA algorithm improves depth resolution by removing projection artifact while retaining in-situ flow signal from real blood vessels in deeper layers. This novel technology allowed us to study the normal retinal vasculature in vivo with better depth resolution than previously possible. Our investigation in normal human volunteers revealed the presence of 2 to 4 distinct vascular plexuses in the retina, depending on location relative to the optic disc and fovea. The vascular pattern in these retinal plexuses and interconnecting layers are consistent with previous histologic studies. Based on these data, we propose an improved system of nomenclature and segmentation boundaries for detailed 3-dimensional retinal vascular anatomy by OCTA. This could serve as a basis for future investigation of both normal retinal anatomy, as well as vascular malformations, nonperfusion, and neovascularization.

We propose a three-dimensional (3-D) registration method to correct motion artifacts and construct the volume structure for angiographic and structural optical coherence tomography (OCT). This algorithm is particularly suitable for the nonorthogonal wide-field OCT scan acquired by a ultrahigh-speed swept-source system ( > 200 ?? kHz A-scan rate). First, the transverse motion artifacts are corrected by the between-frame registration based on en face OCT angiography (OCTA). After A-scan transverse translation between B-frames, the axial motions are corrected based on the rebuilt boundary of inner limiting membrane. Finally, a within-frame registration is performed for local optimization based on cross-sectional OCTA. We evaluated this algorithm on retinal volumes of six normal subjects. The results showed significantly improved retinal smoothness in 3-D-registered structural OCT and image contrast on en face OCTA.

BACKGROUND AND OBJECTIVE: Acute retinal necrosis (ARN) may lead to severe visual loss because of its rapid progression and high likelihood of retinal detachment (RD). This study investigates whether combination systemic and intravitreal antiviral therapy is superior to systemic antiviral therapy alone. PATIENTS AND METHODS: Single-center, interventional, comparative case series of patients with ARN treated with combination systemic antiviral and intravitreal foscarnet injection therapy or systemic antiviral therapy alone. Survival analysis and incidence rates of visual acuity (VA) gain of two lines or greater, severe visual loss of 20/200 or worse, and RD were assessed. RESULTS: Twelve patients received combination therapy and 12 received systemic therapy alone. Patients receiving combination therapy were more likely to gain two or more lines of VA and showed decreased incidences of severe visual loss and RD. CONCLUSION: Combination oral and intravitreal antiviral therapy may improve the likelihood for VA gain and decrease the risk of RD in patients with ARN. Clinicians should consider administering combination systemic and intravitreal antiviral therapy for patients with the ARN syndrome. [ Ophthalmic Surg Lasers Imaging Retina . 2014;45:399–407.]

Projection artifacts in optical coherence tomography angiography (OCTA) blur the retinal vascular plexuses together and limit visualization of the individual plexuses.To describe projection-resolved (PR) OCTA in eyes with diabetic retinopathy (DR) and healthy eyes.In this case-control study, patients with DR and healthy controls were enrolled in this observational study from January 26, 2015, to December 4, 2015, at a tertiary academic center. Spectral-domain, 70-kHz OCT obtained 3 × 3-mm macular scans. The PR algorithm suppressed projection artifacts. A semiautomated segmentation algorithm divided PR-OCTA into superficial, intermediate, and deep retinal plexuses. Two masked graders examined 3-layer PR-OCTA and combined angiograms for nonperfusion and abnormal capillaries.Retinal nonperfusion and capillary abnormalities and the diagnostic accuracy of detecting DR.Twenty-nine eyes of 15 healthy individuals (mean [SD] age, 36.2 [13.4] years; 11 women) and 47 eyes of 29 patients with DR (mean [SD] age, 55.5 [11.9]; 10 women) underwent imaging. PR-OCTA revealed 3 distinct retinal plexuses in their known anatomical locations in all eyes. The intermediate and deep plexuses of healthy eyes revealed capillary networks of uniform density and caliber, whereas the superficial plexus revealed vessels in the familiar centripetal branching pattern. In eyes with DR, 3-layer PR-OCTA disclosed incongruent areas of nonperfusion and varied vessel caliber and density in the deeper plexuses. Masked grading of capillary nonperfusion on 3-layer PR-OCTA detected DR with 100% sensitivity (95% CI, 90.8%-100%) and 100% specificity (95% CI, 85.4%-100%). With unsegmented retinal angiograms, the sensitivity and specificity were 78.7% (95% CI, 63.9%-88.8%) and 100% (95% CI, 85.4%-100%), respectively (P = .002 for sensitivity). On 3-layer PR-OCTA, sensitivity was 72.2% (95% CI, 54.6%-85.2%) for severe nonproliferative DR and proliferative DR eyes with generalized nonperfusion in 2 or more individual plexuses, but on combined angiogram, sensitivity was 25.0% (95% CI, 12.7%-42.5%) for generalized nonperfusion (P .001). PR-OCTA disclosed dilated vessels in the intermediate and deep plexuses in 23 eyes (100%) with proliferative DR, 13 eyes (100%) with severe nonproliferative DR, 8 eyes (73%) with mild to moderate nonproliferative DR, and 0 control eyes.By presenting 3 retinal vascular plexuses distinctly, PR-OCTA reveals capillary abnormalities in deeper layers with clarity and may distinguish DR from healthy eyes and severe DR from mild DR with greater accuracy compared with conventional OCTA.

Purpose Structural and compositional heterogeneity within drusen comprising lipids, carbohydrates, and proteins have been previously described. We sought to detect and define phenotypic patterns of drusen heterogeneity in the form of optical coherence tomography–reflective drusen substructures (ODS) and examine their associations with age-related macular degeneration (AMD)–related features and AMD progression. Design Retrospective analysis in a prospective study. Participants Patients with intermediate AMD (n = 349) enrolled in the multicenter Age-Related Eye Disease Study 2 (AREDS2) ancillary spectral-domain optical coherence tomography (SD OCT) study. Methods Baseline SD OCT scans of 1 eye per patient were analyzed for the presence of ODS. Cross-sectional and longitudinal associations of ODS presence with AMD-related features visible on SD OCT and color photographs, including drusen volume, geographic atrophy (GA), and preatrophic features, were evaluated for the entire macular region. Similar associations were also made locally within a 0.5-mm-diameter region around individual ODS and corresponding control region without ODS in the same eye. Main Outcome Measures Preatrophy SD OCT changes and GA, central GA, and choroidal neovascularization (CNV) from color photographs. Results Four phenotypic subtypes of ODS were defined: low reflective cores, high reflective cores, conical debris, and split drusen. Among the 349 participants, there were 307 eligible eyes and 74 (24%) had at least 1 ODS. The ODS at baseline were associated with (1) greater macular drusen volume at baseline ( P P = 0.001–0.01), and (3) development of macular GA ( P = 0.005) and preatrophic changes at year 3 ( P = 0.002–0.008), but not development of CNV. The ODS at baseline in a local region were associated with (1) presence of preatrophy changes at baseline ( P = 0.02–0.03) and (2) development of preatrophy changes at years 2 and 3 within the region ( P = 0.008–0.05). Conclusions Optical coherence tomography–reflective drusen substructures are optical coherence tomography–based biomarkers of progression to GA, but not to CNV, in eyes with intermediate AMD. Optical coherence tomography–reflective drusen substructures may be a clinical entity helpful in monitoring AMD progression and informing mechanisms in GA pathogenesis.

Purpose To determine specific retinal precursor lesions and sequence of events preceding the onset of geographic atrophy (GA) in eyes with age-related macular degeneration (AMD). Design Retrospective review. Participants All participants in the Age-Related Eye Disease Study (AREDS) at 2 clinical centers (Devers Eye Institute, Portland, Oregon, and University of Wisconsin, Madison, Wisconsin) in whom GA initially appeared in at least one eye a minimum of 4 years after the baseline study visit. Methods All stereoscopic fundus photographs taken before the appearance of GA in the involved (study) eye were reviewed. Fundus features at the site of future GA were graded and recorded. Three graders reviewed photographs, with independent grading and adjudication by mutual agreement. Features graded included drusen (classified by size and confluence), focal hyperpigmentation, hypopigmentation, and refractile deposits. The time between first appearance of these features and initial appearance of GA was recorded. Main Outcome Measure Appearance of GA. Results Of all AREDS participants at the 2 sites, 95 eyes of 77 developed GA at least 4 years after entrance into the study. Average time from baseline to initial appearance of GA was 6.6 years (range, 4–11). Drusen were found in 100% of eyes at the site of later developing GA, drusen >125 μm in diameter in 96% of eyes, confluent drusen in 94%, hyperpigmentation in 96%, drusen > 250 μm in 83%, hypopigmentation in 82%, and refractile deposits in 23%. Time from lesion appearance to onset of GA varied by lesion type, ranging from 5.9 years for drusen confluence to 2.5 years for hypopigmentation or refractile deposits. Lesions generally followed a uniform sequence of appearance. Conclusions By focusing on the location of initial GA appearance and then retrospectively analyzing prior photographs, we were able to identify specific precursor lesions and the most common sequence of events leading to GA formation in eyes with AMD. The progression was usually characterized by large drusen formation and development of hyperpigmentation, followed by regression of drusen, appearance of hypopigmentation, and ultimately development of GA, sometimes preceded by the appearance of refractile deposits.

Purpose To report a case of retinal occlusive disease producing binasal visual field defects in a patient with sickle cell (SC) disease. Design Retrospective case report. Methods A 21-year-old man with SC disease presented with binasal field defects and 20/20 acuity in each eye. Results Initial ophthalmoscopy and fluorescein angiography revealed no abnormalities. Optical coherence tomography (OCT) demonstrated bilateral temporal inner retinal hyperreflectivity, and multifocal electroretinography (mfERG) confirmed retinal dysfunction. Several weeks later, ophthalmoscopy and angiography demonstrated macular arteriolar occlusive disease. Conclusions Simultaneous bilateral macular occlusive events are uncommon in patients particularly with SC disease. Although the binasal field defects raised the suspicion of a process affecting the optic nerves, the OCT and mfERG proved essential in diagnosing retinal rather than optic nerve disease.

Retinal vascular diseases are important causes of vision loss. A detailed evaluation of the vascular abnormalities facilitates diagnosis and treatment in these diseases. Optical coherence tomography (OCT) angiography using the highly efficient split-spectrum amplitude decorrelation angiography algorithm offers an alternative to conventional dye-based retinal angiography. OCT angiography has several advantages, including 3D visualization of retinal and choroidal circulations (including the choriocapillaris) and avoidance of dye injection-related complications. Results from six illustrative cases are reported. In diabetic retinopathy, OCT angiography can detect neovascularization and quantify ischemia. In age-related macular degeneration, choroidal neovascularization can be observed without the obscuration of details caused by dye leakage in conventional angiography. Choriocapillaris dysfunction can be detected in the nonneovascular form of the disease, furthering our understanding of pathogenesis. In choroideremia, OCT's ability to show choroidal and retinal vascular dysfunction separately may be valuable in predicting progression and assessing treatment response. OCT angiography shows promise as a noninvasive alternative to dye-based angiography for highly detailed, in vivo, 3D, quantitative evaluation of retinal vascular abnormalities.

To evaluate the clinical, anatomic and functional effects of conversion to aflibercept following ranibizumab and/or bevacizumab in patients with neovascular age-related macular degeneration (AMD).A retrospective review of patients with neovascular AMD treated with intravitreal ranibizumab and/or bevacizumab who were switched to aflibercept was performed. The primary outcome was change in injection frequency in the year following the change. Secondary outcomes included change in central macular thickness (CMT) at 6 months and 1 year, presence of intraretinal and subretinal fluid at 6 months and visual acuity at 1 year.A total of 109 eyes with neovascular AMD were switched to aflibercept and met inclusion criteria. Overall, aflibercept injection frequency was unchanged with patients receiving 7.4 antivascular endothelial growth factor (VEGF) injections the year prior to conversion compared with 7.2 aflibercept injections in the year following (p=0.47). However, the change to aflibercept was associated with improvement in CMT from 324 to 295 μm (p=0.0001) at 6 months and 299 μm (p=0.0047) at 1 year. There was no effect on visual acuity at 1 year. In a subgroup analysis, patients who had received ≥10 anti-VEGF injections in the year prior had fewer injections (11.1 to 8.4, p0.0001) and clinic visits (13.9 to 9.6, p0.0001) as well as a significant decrease in CMT (-35 μm, p=0.02).In our population, switching to aflibercept therapy was not associated with a change in injection frequency nor improved visual acuity, but was associated with improved CMT at 6 months and 1 year. In patients who received at least 10 anti-VEGF injections in the year prior, transitioning to aflibercept was associated with a reduced injection frequency and CMT, suggesting potential cost savings in this population.

To evaluate three measures related to electronic health record (EHR) implementation: clinical volume, time requirements, and nature of clinical documentation. Comparison is made to baseline paper documentation.An academic ophthalmology department implemented an EHR in 2006. A study population was defined of faculty providers who worked the 5 months before and after implementation. Clinical volumes, as well as time length for each patient encounter, were collected from the EHR reporting system. To directly compare time requirements, two faculty providers who utilized both paper and EHR systems completed time-motion logs to record the number of patients, clinic time, and nonclinic time to complete documentation. Faculty providers and databases were queried to identify patient records containing both paper and EHR notes, from which three cases were identified to illustrate representative documentation differences.Twenty-three faculty providers completed 120,490 clinical encounters during a 3-year study period. Compared to baseline clinical volume from 3 months pre-implementation, the post-implementation volume was 88% in quarter 1, 93% in year 1, 97% in year 2, and 97% in year 3. Among all encounters, 75% were completed within 1.7 days after beginning documentation. The mean total time per patient was 6.8 minutes longer with EHR than paper (P.01). EHR documentation involved greater reliance on textual interpretation of clinical findings, whereas paper notes used more graphical representations, and EHR notes were longer and included automatically generated text.This EHR implementation was associated with increased documentation time, little or no increase in clinical volume, and changes in the nature of ophthalmic documentation.

Purpose The purpose of this study was to evaluate an automated algorithm for detecting avascular area (AA) in optical coherence tomography angiograms (OCTAs) separated into three individual plexuses using a projection-resolved technique. Methods A 3 × 3 mm macular OCTA was obtained in 13 healthy and 13 mild nonproliferative diabetic retinopathy (NPDR) participants. A projection-resolved algorithm segmented OCTA into three vascular plexuses: superficial, intermediate, and deep. An automated algorithm detected AA in each of the three plexuses that were segmented and in the combined inner-retinal angiograms. We assessed the diagnostic accuracy of extrafoveal and total AA using segmented and combined angiograms, the agreement between automated and manual detection of AA, and the within-visit repeatability. Results The sum of extrafoveal AA from the segmented angiograms was larger in the NPDR group by 0.17 mm2 (P < 0.001) and detected NPDR with 94.6% sensitivity (area under the receiver operating characteristic curve [AROC] = 0.99). In the combined inner-retinal angiograms, the extrafoveal AA was larger in the NPDR group by 0.01 mm2 (P = 0.168) and detected NPDR with 26.9% sensitivity (AROC = 0.62). The total AA, inclusive of the foveal avascular zone, in the segmented and combined angiograms, detected NPDR with 23.1% and 7.7% sensitivity, respectively. The agreement between the manual and automated detection of AA had a Jaccard index of >0.8. The pooled SDs of AA were small compared with the difference in mean for control and NPDR groups. Conclusions An algorithm to detect AA in OCTA separated into three individual plexuses using a projection-resolved algorithm accurately distinguishes mild NPDR from control eyes. Automatically detected AA agrees with manual delineation and is highly repeatable.

Optical coherence tomography angiography (OCTA) is a noninvasive approach that can visualize blood vessels down to the capillary level. With the advent of high-speed OCT and efficient algorithms, practical OCTA of ocular circulation is now available to ophthalmologists. Clinical investigations that used OCTA have increased exponentially in the past few years. This review will cover the history of OCTA and survey its most important clinical applications. The salient problems in the interpretation and analysis of OCTA are described, and recent advances are highlighted.

Macular ischemia is a key feature of diabetic retinopathy (DR). Quantification of macular ischemia has potential as a biomarker for DR.To assess the feasibility of automated quantification of capillary nonperfusion as a potential sign of macular ischemia using optical coherence tomography (OCT) angiography.An observational study conducted in a tertiary, subspecialty, academic practice evaluated macular nonperfusion with 6 × 6-mm OCT angiography obtained with commercially available 70-kHz OCT and fluorescein angiography (FA). The study was conducted from January 22 to September 18, 2014. Data analysis was performed from October 1, 2014, to April 7, 2015. Participants included 12 individuals with normal vision serving as controls and 12 patients with various levels of DR.Preplanned primary measures were parafoveal and perifoveal vessel density, total avascular area, and foveal avascular zone as detected with 6 × 6-mm OCT angiography and analyzed using an automated algorithm. Secondary measures included the agreement of the avascular area between the OCT angiogram and FA.Compared with the 12 healthy controls (11 women; mean [SD] age, 54.2 [14.2] years), the 12 participants with DR (4 women; mean [SD] age, 55.1 [12.1] years) had reduced parafoveal and perifoveal vessel density by 12.6% (95% CI, 7.7%-17.5%; P .001) and 10.4% (95% CI, 6.8%-14.1%; P .001), respectively. Total avascular area and foveal avascular zone area were greater in eyes with DR by 0.82 mm2 (95% CI, 0.65-0.99 mm2; P = .02) and 0.16 mm2 (95% CI, 0.05-0.28 mm2; P .001). The agreement between the vascular areas in the OCT angiogram and FA had a κ value of 0.45 (95% CI, 0.21-0.70; P .001). Total avascular area in the central 5.5-mm-diameter area distinguished eyes with DR from control eyes with 100% sensitivity and specificity.Avascular area analysis with an automated algorithm using OCT angiography, although not equivalent to FA, detected DR reliably in this small pilot study. Further study is necessary to determine the usefulness of the automated quantification in clinical practice.

To evaluate quantitative and qualitative differences in documentation of the ophthalmic examination between paper and electronic health record (EHR) systems.Comparative case series.One hundred fifty consecutive pairs of matched paper and EHR notes, documented by 3 attending ophthalmologist providers.An academic ophthalmology department implemented an EHR system in 2006. Database queries were performed to identify cases in which the same problems were documented by the same provider on different dates, using paper versus EHR methods. This was done for 50 consecutive pairs of examinations in 3 different diseases: age-related macular degeneration (AMD), glaucoma, and pigmented choroidal lesions (PCLs). Quantitative measures were used to compare completeness of documenting the complete ophthalmologic examination, as well as disease-specific critical findings using paper versus an EHR system. Qualitative differences in paper versus EHR documentation were illustrated by selecting representative paired examples.(1) Documentation score, defined as the number of examination elements recorded for the slit-lamp examination, fundus examination, and complete ophthalmologic examination and for critical clinical findings for each disease. (2) Paired comparison of qualitative differences in paper versus EHR documentation.For all 3 diseases (AMD, glaucoma, PCL), the number of complete examination findings recorded was significantly lower with paper than the EHR system (P ≤ 0.004). Among the 3 individual examination sections (general, slit lamp, fundus) for the 3 diseases, 5 of the 9 possible combinations had significantly lower mean documentation scores with paper than EHR notes. For 2 of the 3 diseases, the number of critical clinical findings recorded was significantly lower using paper versus EHR notes (P ≤ 0.022). All (150/150) paper notes relied on graphical representations using annotated hand-drawn sketches, whereas no (0/150) EHR notes contained drawings. Instead, the EHR systems documented clinical findings using textual descriptions and interpretations.There were quantitative and qualitative differences in the nature of paper versus EHR documentation of ophthalmic findings in this study. The EHR notes included more complete documentation of examination elements using structured textual descriptions and interpretations, whereas paper notes used graphical representations of findings.The author(s) have no proprietary or commercial interest in any materials discussed in this article.

PURPOSE Macular hyperpigmentation is associated with progression from intermediate to advanced age-related macular degeneration (AMD). The purpose of this study was to accurately correlate hyperpigmentary changes with spectral domain optical coherence tomography (SDOCT) hyperreflective foci in eyes with non-advanced AMD. METHODS A prospective cross-sectional analysis of 314 eyes (314 subjects) with intermediate AMD was performed in the multicenter Age-Related Eye Disease Study 2 (AREDS2) Ancillary SDOCT Study to correlate hyperpigmentary changes on color fundus photographs (CFP) with abnormal morphology on SDOCT. Spatial coregistration was performed with an automated algorithm in two nonoverlapping subsets of 20 study eyes, which permitted double-masked CFP and SDOCT grading by certified investigators. RESULTS Macular CFP hyperpigmentation was significantly associated with SDOCT intraretinal hyperreflective foci in the 314 study eyes (P < 0.001). In a substudy of 40 eyes, automated intermodality spatial coregistration was successfully achieved in all 136 (100%) retinal regions selected for CFP and SDOCT grading. In one subset of 20 study eyes, 28 of 39 (71.8%) retinal CFP regions with hyperpigmentation were correlated with focal hyperreflectivity on SDOCT, versus seven of 39 (17.9%) control regions (P < 0.001). In another subset of 20 eyes, 21 of 29 (72.4%) SDOCT regions with hyperreflective foci were correlated with hyperpigmentary changes on CFP, versus two of 29 (6.9%) control regions (P < 0.001). CONCLUSIONS A novel algorithm achieves automated intermodality spatial coregistration for masked grading of regions selected on CFP and SDOCT. In intermediate AMD, macular hyperpigmentation has high spatial correlation to SDOCT hyperreflective foci and often represents the same anatomical lesion. (ClinicalTrials.gov number, NCT00734487.).

Purpose Describe qualitative spectral-domain optical coherence tomography (SD-OCT) characteristics of eyes classified as intermediate age-related macular degeneration (nonadvanced AMD) from Age-Related Eye Disease Study 2 (AREDS2) color fundus photography (CFP) grading. Design Prospective cross-sectional study. Participants We included 345 AREDS2 participants from 4 study centers and 122 control participants who lack CFP features of intermediate AMD. Methods Both eyes were imaged with SD-OCT and CFP. The SD-OCT macular volume scans were graded for the presence of 5 retinal, 5 subretinal, and 4 drusen characteristics. In all, 314 AREDS2 participants with ≥1 category-3 AMD eye and all controls each had 1 eye entered into SD-OCT analysis, with 63 eyes regraded to test reproducibility. Main Outcome Measures We assessed SD-OCT characteristics at baseline. Results In 98% of AMD eyes, SD-OCT grading of all characteristics was successful, detecting drusen in 99.7%, retinal pigment epithelium (RPE) atrophy/absence in 22.9%, subfoveal geographic atrophy in 2.5%, and fluid in or under the retina in 25.5%. Twenty-eight percent of AMD eyes had characteristics of possible advanced AMD on SD-OCT. Two percent of control eyes had drusen on SD-OCT. Vision loss was not correlated with foveal drusen alone, but with foveal drusen that were associated with other foveal pathology and with overlying focal hyperreflectivity. Focal hyperreflectivity over drusen, drusen cores, and hyper- or hyporeflectivity of drusen were also associated with RPE atrophy. Conclusions Macular pathologies in AMD can be qualitatively and reproducibly evaluated with SD-OCT, identifying pathologic features that are associated with vision loss, RPE atrophy, and even possibly the presence of advanced AMD not apparent on CFP. Qualitative and detailed SD-OCT analysis can contribute to the anatomic characterization of AMD in clinical studies of vision loss and disease progression. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

PURPOSE Accurate assessment of tumor size is crucial in the treatment of choroidal melanoma. Digital fundus photographic systems can create a montage that clearly documents the tumor margins. These images can be used to measure tumor maximal linear dimension (MLD). This study evaluates the potential value of a digital imaging system compared with echography in measuring the MLD of choroidal melanoma. METHODS Echographic measurements were performed in a standardized fashion following Collaborative Ocular Melanoma Study (COMS) methods. For photographic measurements, the tumor margin was outlined with an electronic pen and the MLD were calculated by software (ANKA-ProView, Topcon Medical Systems, Paramus, NJ). RESULTS The mean MLD before I-125 brachytherapy was 9.32 mm by echography and 10.57 mm by digital photography analysis. This difference was statistically significant (P < 0.001). The 2 measurements of MLD agreed within 1.1 mm for 11 eyes (52%) and 2.2 mm for 20 eyes (95%). Digital photographic analysis estimated a larger MLD in 19 of the 21 eyes compared with echography. CONCLUSION This discrepancy likely results from the photographic measurement more accurately assessing the flat portion of the tumor. Digital photographic analysis may allow clinicians to determine the MLD of tumors more accurately than echography. This could increase the rate of successful treatment with brachytherapy.

Retinal hemangioblastoma is a clinically and histopathologically distinct tumor that may occur sporadically or as a manifestation of von Hippel-Lindau (VHL) disease.1 von Hippel-Lindau disease is transmitted in an autosomal dominant fashion due to germline mutations in the VHL gene, a tumor suppressor gene on the short arm of chromosome 3 (3p25.5).2 It consists of 3 exons, which encode a messenger RNA (mRNA) transcript expressed in many tissues and translated into a 213-amino acid protein. Originally identified as a tumor suppressor, the VHL protein is now known to repress expression of mRNAs that are normally induced under hypoxic conditions.3,4 The hypoxia-inducible factor is a key transcription factor responsible for up-regulation of expression of hypoxia-inducible genes. When mutated, the VHL gene produces a protein that is unable to regulate hypoxia-inducible factor, permitting accumulation of hypoxia-inducible factor and subsequent activation of vascular endothelial growth factor and other hypoxiainducible genes.5,6 This can result in growth of retinal hemangioblastomas and other tumors associated with VHL disease. Clinically, retinal hemangioblastomas are characterized by their vascular appearance, often with dilated feeder vessels. They may increase in size with endophytic, exophytic, or sessile growth patterns. Vision loss may occur due to leakage of fluid and proteins from the tumor and traction retinal detachment secondary to associated vitreous and retinal changes. Various treatment options have been used, including observation, thermal laser, cryotherapy, brachytherapy, photodynamic therapy, transpupillary thermotherapy, external beam radiation therapy, and systemic and intravitreal vascular endothelial growth factor inhibitors.7-18 Treatment depends on the size and location of the tumor. Smaller tumors are generally treated using laser if posterior in location or using cryotherapy if in the retinal periphery. These methods are less effective on larger tumors (>4 mm in diameter), which may be more effectively treated using radiation therapy. However, tumors greater than 5 mm in diameter or with exudative or tractional retinal detachment have a poor prognosis even using radiation therapy. We describe the treatment of 3 patients with large solitary retinal hemangioblastomas using internal en bloc surgical resection. All patients lack a germline mutation in the VHL gene, as determined by sequence analysis of leukocyte cell DNA. To analyze the molecular basis for sporadically occurring retinal hemangioblastoma, 2 of the resected tumors were evaluated for loss of heterozygosity (LOH) and for VHL gene mutations.

Purpose To provide histopathologic correlation of the appearance of a stage 2 macular hole. Methods A 79-year-old woman presented with a recent onset of mildly decreased vision in the right eye. With slit-lamp biomicroscopic examination and fundus photography, she was diagnosed as having a stage 2 macular hole. Her vision remained stable thereafter without intervention for 15 months. She died 6 months after her final follow-up examination. Postmortem histopathologic examination of the right eye was carried out by light microscopy of conventional and immunoperoxidase-stained sections. Results The clinical appearance of a stage 2 macular hole in this patient corresponded with findings of intraretinal splitting, which extended beyond an area of surface retinal defect. Conclusion Surface retinal defects associated with intraretinal splitting are a pathway in the development of a macular hole.

In three patients, acute horizontal gaze pareses developed that could not be overcome with the oculocephalic maneuver, indicating a putative lesion of the ipsilateral abducens nerve nucleus. None of the patients had a facial nerve paresis or evidence of a trigeminal sensory neuropathy. Although most lesions that affect the abducens nerve nucleus also damage the ipsilateral fasciculus of the facial nerve, small lesions in this region can produce an isolated horizontal gaze paresis.