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To quantify ellipsoid zone (EZ) changes in integrity after epiretinal membrane (ERM) surgery, correlate findings to visual acuity, and determine predictors for prognosis.A post hoc analysis of eyes undergoing ERM surgery pooled from the prospective DISCOVER intraoperative optical coherence tomography study and eyes undergoing conventional ERM surgery without intraoperative optical coherence tomography. Quantitative EZ features were extracted using a multilayer machine learning enabled automated segmentation platform after image analyst review/correction for segmentation accuracy. Visual acuity and EZ integrity were quantitatively assessed and correlated before and after ERM surgery. Multiple linear regression was performed to assess preoperative visual acuity and EZ features as predictors for improvement in visual acuity or EZ integrity.There were 177 eyes from 177 subjects that underwent ERM surgery from the DISCOVER and conventional arms. Improvement in visual acuity and multiple EZ integrity features was noted after ERM surgery, including EZ partial attenuation and EZ-retinal pigment epithelium (RPE) volume (P0.05). A reduction in EZ partial attenuation and increase in EZ-RPE central subfield thickness (EZ-RPE CST) was significantly correlated with improved visual acuity after ERM surgery (P0.05). More robust EZ-RPE CST at baseline predicted visual acuity improvement after ERM peel in regression modeling (β = 0.005, P0.05).Longitudinal assessment of EZ features demonstrates significant postoperative improvement in multiple EZ integrity metrics after ERM surgery. Improving EZ integrity was correlated to improving the visual acuity. Ellipsoid zone integrity and visual acuity were significant predictors in regression modeling and may have value in clinical prognostication.

BackgroundThis study investigates the association of intraocular cytokine expression and ultrawide-field fluorescein angiography (UWFA) quantitative imaging biomarkers and their association with angiographical feature response after antivascular endothelial growth factor (VEGF) therapy in diabetic macular oedema (DME).MethodsThe IMAGINE DME study is a post hoc imaging biomarker and intraocular cytokine assessment from the DAVE study, a prospective DME clinical trial that included aqueous humour sampling and UWFA imaging. Fifty-four cytokines associated with inflammation and angiogenesis were evaluated through multiplex arrays. UWFA parameters were assessed using an automated feature analysis platform to determine ischaemic and leakage indices and microaneurysm (MA) count. Eyes were classified into UWFA responder or non-responder groups based on longitudinal quantitative UWFA parameter improvement. Cytokine expression was correlated with UWFA metrics and evaluated in the context of therapeutic response.ResultsTwenty-one eyes were included with a mean age of 55±10 years. Increased panretinal leakage index correlated with VEGF (r=0.70, p=0.0005), angiopoietin-like 4 (r=0.77, p=4.6E-5) and interleukin (IL)-6 (r=0.64, p=0.002). Panretinal ischaemic index was associated with tissue inhibitor of metalloproteinases 1 (TIMP-1, r=0.49, p=0.03) and peripheral ischaemia correlated with VEGF (r=0.45, p=0.05). MA count correlated with increased monocyte chemotactic protein-4 (MCP-4, r=0.60, p=0.004) and platelet and endothelial cell adhesion molecule 1 (PECAM-1, r=0.58, p=0.005). Longitudinal MA reduction was associated with decreased baseline VEGF and urokinase receptor (uPAR) (pConclusionsBaseline and longitudinal quantitative UWFA imaging parameters correlated with multiple aqueous humour cytokine concentrations, including VEGF and IL-6. Further research is needed to assess the possible implications of using these findings for evaluating treatment response.

To assess the safety and efficacy of as-needed (PRN) intravitreal aflibercept injections (IAI) in managing diabetic retinopathy (DR) guided by the real-time DR severity scale (DRSS) level or panretinal leakage index (PLI) assessment among eyes without diabetic macular edema (DME).Prospective, randomized phase 2 trial (PRIME).A total of 40 eyes with nonproliferative (NPDR) or proliferative DR (PDR) received monthly IAIs until a DRSS improvement of ≥2 steps was achieved and eyes were randomized (1:1) to DRSS-guided or PLI-guided management strategies graded by a central reading center. Main outcome measurements included safety and changes in DRSS and PLI.Through week 52, 95% of eyes achieved a DRSS improvement of ≥2 steps. Following DRSS improvement, 97% of eyes required at least 1 PRN IAI. In eyes requiring PRN IAI and completing week 52, 100% and 59% experienced DRSS worsening (P = .01) in the DRSS- and PLI-guided arms, respectively. Through week 52, mean PLI decreased 18.2% (P = .49) and 54.6% (P.0001), respectively, in the DRSS- and PLI-guided arms. NPDR versus PDR eyes at baseline achieved a DRSS improvement of ≥2 steps after a mean 4.9 and 3.6 IAIs (P = .03). Two eyes developed a PDR event at week 52 following 5 months of quiescence.The randomized PRIME study analyzed 2 imaging-based biomarkers to guide PRN management with IAI of DR without DME: DRSS level and PLI. Within the context of this study with limitations, most patients required IAI re-treatment every 3-4 months, and deterioration of PLI appeared to precede DRSS level worsening. Finally, these findings reaffirm the fact that close clinical follow-up is important even among eyes that achieve substantial DRSS improvements with apparently quiescent disease.

PURPOSE To evaluate association of the baseline macular hole (MH) geometric features and longitudinal ellipsoid zone integrity with the visual acuity outcome after surgical repair. METHODS This was a post-hoc analysis of eyes in the DISCOVER study undergoing vitrectomy repair for MH. Anatomical and functional data were collected through one year postoperatively. An automated retinal layer segmentation platform was used for the assessment of outer retinal metrics and volumetric reconstruction of MH. Association of longitudinal ellipsoid zone features and baseline MH height, width, and volume with VA outcomes were investigated. RESULTS Eighty-four eyes with MH were included. The mean baseline VA was 20 of 114 and increased to 20 of 45 (P < 0.001) at postoperative Month 12 (N = 45). Successful MH closure was achieved in 98.8% of cases. Ellipsoid zone integrity metrics significantly improved from baseline (P = 0.002) and postoperative Month 1 (P < 0.001) to post-operative Month 12. Ellipsoid zone metrics independently correlated with VA at all follow-up visits (P < 0.05). Increased baseline MH width and volume negatively correlated with the VA at postoperative Month 12 (P < 0.001). Preoperative VA and EZ integrity on optical coherence tomography were predictors for postoperative VA. CONCLUSION Baseline MH volumetric parameters and EZ parameters were associated with VA outcomes after repair.

Purpose To identify biomarkers for predicting response to anti−vascular endothelial growth factor (VEGF) therapy in diabetic macular edema (DME) and evaluate any links between cytokine expression and optical coherence tomography (OCT) phenotype. Design The IMAGINE is a post hoc image analysis and cytokine expression assessment of the Efficacy & Safety Trial of Intravitreal Injections Combined With PRP for CSME Secondary to Diabetes Mellitus (DAVE) randomized clinical trial. Methods Subjects were categorized as anatomical responders or nonresponders, and within the responder group as rebounders and non-rebounders based on quantitative, longitudinal OCT criteria. Retinal layer and fluid features were extracted using an OCT machine-learning augmented segmentation platform. Responders were further sub-classified by rapidity of response. Aqueous concentrations of 54 cytokines were measured at multiple timepoints. Expression was compared between responder groups and correlated with OCT imaging biomarkers. Results Of the 24 eyes studied, 79% were anatomical responders with 38% super responders, 17% early responders, and 25% slow responders. Twenty-one percent were nonresponders. Super responders had increased baseline vascular endothelial growth factor (VEGF) (880.0 pg/mL vs 245.4 pg/mL; P = .012) and decreased monocyte chemotactic protein-1 (MCP-1) (513.3 pg/mL vs 809.5 pg/mL; P = .0.042) concentrations compared with nonresponders. Interleukin-6 (−24.9 pg/mL vs 442.8 pg/mL; P = .032) concentrations increased among nonresponders during therapy. VEGF concentrations correlated with central subfield thickness (r = 0.49; P = .01). Panmacular retinal volume correlated with increased interleuckin-6 (r = 0.47; P = .02) and decreased MCP-1 (r = −0.45; P = .03). Matrix metallopeptidase-1 correlated with subretinal fluid volume (r = 0.50; P = .01). Conclusions OCT imaging biomarkers correlated with both intraocular cytokines and responsiveness to anti-VEGF therapy, which indicated a possible link to underlying pathways and their relevance to DME prognosis. Baseline concentrations of VEGF and MCP-1 are associated with anatomic response to anti-VEGF therapy.

PurposeTo evaluate longitudinal quantitative ischaemic and vasculature parameters, including ischaemic index, vessel area, length and geodesic distance in sickle cell retinopathy (SCR) on ultra-widefield fluorescein angiography (UWFA).MethodsOptimal UWFA images from two longitudinal timepoints of 74 eyes from 45 patients with SCR were aligned and a common region of interest was determined. A deep-learning augmented ischaemia and vascular segmentation platform was used for feature extraction. Geodesic distance maps demonstrating the shortest distance within the vascular masks from the centre of the optic disc were created. Ischaemic index, vessel area, vessel length and geodesic distance were measured. Paired t-test and linear mixed effect model analysis were performed.ResultsOverall, 25 (44 eyes) patients with HbSS, 14 (19 eyes) with HbSC, 6 (11 eyes) with HbSthal and other genotypes were included. Mean age was 40.1±11.0 years. Mean time interval between two UWFA studies was 23.0±15.1 months (range: 3–71.3). Mean panretinal ischaemic index increased from 10.0±7.2% to 10.9±7.3% (pConclusionLongitudinal ischaemic index and retinal vascular parameter measurements demonstrate statistically significant progression in SCR. The clinical significance of these relatively small magnitude changes remains unclear but may provide insights into the progression of retinal ischaemia in SCR.

Purpose: This work evaluated the longitudinal dynamics of ellipsoid zone (EZ) integrity in retinal vein occlusion (RVO) with macular edema and their relation to outcomes. Methods: Clinical characteristics and optical coherence tomography data of patients with RVO and associated macular edema were collected at baseline and at 3 and 12 months. Macular cube scans were exported into EZ and retinal-layer analysis software. Longitudinal EZ parameters and visual acuity (VA) outcomes were regressed and correlated. Results: The study included 108 eyes of 108 patients; all eyes were treated with antivascular endothelial growth factor therapy at the baseline visit. VA improved from 20/97 at baseline to 20/52 at 3 months and 12 months ( P Conclusions: EZ and outer retinal integrity are correlated with functional outcomes in RVO. Following treatment, EZ integrity improves and is associated with functional improvement. In RVO baseline, EZ features were not associated with 1-year VA outcomes, but evaluation of EZ integrity at 3 months was linked to 1-year outcomes.

Background/aimsThis study aimed to characterise the clinical outcomes and utility of intraoperative optical coherence tomography (iOCT)-assisted macular hole (MH) repair.MethodsThis was a post hoc analysis of eyes in the Determination of feasibility of Intraoperative Spectral domain microscope Combined/integrated OCT Visualization during En face Retinal and ophthalmic surgery (DISCOVER) study undergoing surgical MH repair with use of iOCT. Functional and surgical outcome data were collected through 12 months postoperatively. MH closure rate, postoperative visual acuity (VA), percentage of cases in which iOCT provided valuable feedback and altered surgical decision making were measured.ResultsEighty-four eyes were included in this study. The mean preoperative VA measured 20/114. The mean postoperative VA improved to 20/68 (pConclusionThis study suggests that iOCT may have important utility in MH surgery, including impacting surgical decision making. iOCT-assisted MH surgery resulted in significant improvement in VA and high single-surgery success rate.

Purpose To compare optical coherence tomography angiography (OCTA) review strategies for optimizing choroidal neovascularization (CNV) detection. Methods Eyes with CNV in the differential diagnosis were imaged with the Avanti RTVue XR HD (Optovue, Fremont, CA). Three modalities of review for CNV presence were used in each case: a single report generated using automated segmentation within Avanti software; a continuous slab descent video OCTA export; and a manual segmentation approach using cross-sectional OCT with decorrelation signal overlay. Scans were reviewed by two masked expert reviewers; a third reviewer was used for discrepancies. Results The study included 421 eyes, and 350 eyes had reports deemed sufficient quality for interpretation. Choroidal neovascularization was in the differential diagnosis in 107 of 350 patients. Overall CNV was identified in 55% (59/107) eyes. In those eyes with CNV, the automated segmentation identified CNV in 56% (33/59) of cases, continuous slab descent method identified CNV in 53% (31/59) of cases, and the manual segmentation group identified CNV in 92% (54/59) of cases. Conclusion Review strategies for detection of CNV on OCTA were highest using the manual segmentation method as compared to both the automated report and continuous slab descent methods. Although the manual segmentation method had a higher rate of detection, the practical aspects of the time required for segmentation make this method challenging in routine clinical practice.

Purpose: To determine the association between diabetic retinopathy (DR) severity and quantitative retinal vascular features. Design: Retrospective image analysis study. Participants: Eyes with DR and eyes with no posterior segment disease (normal eyes) that had undergone ultra-widefield fluorescein angiography (UWFA) with associated color fundus photography. Exclusion criteria were any previous laser photocoagulation, low image quality, intravitreal or periocular pharmacotherapy within 6 months of imaging, and any other significant retinal disease including posterior uveitis, retinal vein occlusion, and choroidal neovascularization. Methods: The centered early mid-phase UWFA frame that captured the maximum vessel area was selected using automated custom software for each eye. Panretinal and zonal vascular features were extracted using a machine learning algorithm. Eyes with DR were graded for DR severity as mild nonproliferative DR (NPDR), moderate NPDR, severe NPDR, and proliferative DR (PDR). Parameters of normal eyes were compared with age- and gender-matched patients with DR using the t test. Differences between severity groups were evaluated by the analysis of variance and Kruskal-Wallis tests, generalized linear mixed-effects models, and random forest regression models. Main Outcome Measures: Diabetic retinopathy severity and vascular features (panretinal and zonal vessel area, length and geodesic distance, panretinal area index, tortuosity measures, vascular density measures, and zero vessel density rate). Results: Ninety-seven eyes from 60 patients with DR and 12 normal eyes from 12 patients that underwent UWFA for evaluation of fellow eye pathology had images of sufficient quality to be included in this analysis. The mean age was 60 ± 10 years in DR eyes and 46 ± 17 years in normal eyes. Panretinal vessel area, mean geodesic distance, skewness, and kurtosis of local vessel density was significantly higher in normal eyes compared with the age- and gender-matched eyes with DR (P < 0.05). Zero vessel density rate, skewness of vessel density, and mean mid-peripheral geodesic distance were among the most important features for distinguishing mild NPDR from advanced forms of DR and PDR versus eyes without PDR. Conclusions: Automated analysis of retinal vasculature demonstrated associations with DR severity and visual and subvisual vascular biomarkers. Further studies are needed to evaluate the clinical significance of these parameters for DR prognosis and therapeutic response.

The current study describes the development and assessment of innovative, machine learning (ML)-based approaches for automated detection and pixel-accurate measurements of regions with geographic atrophy (GA) in late-stage age-related macular degeneration (AMD) using optical coherence tomography systems. 900 OCT volumes, 100266 B-scans, and en face OCT images from 341 non-exudative AMD patients with or without GA were included in this study from both Cirrus (Zeiss) and Spectralis (Heidelberg) OCT systems. B-scan and en face level ground truth GA masks were created on OCT B-scan where the segmented ellipsoid zone (EZ) line, retinal pigment epithelium (RPE) line, and bruchs membrane (BM) line overlapped. Two deep learning-based approaches, B-scan level and en face level, were trained. The OCT B-scan model had detection accuracy of 91% and GA area measurement accuracy of 94%. The en face OCT model had detection accuracy of 82% and GA area measurement accuracy of 96% with primary target of hypertransmission on en face OCT. Accuracy was good for both devices tested (92–97%). Automated lesion size stratification for CAM cRORA definition of 250um minimum lesion size was feasible. High-performance models for automatic detection and segmentation of GA area were achieved using OCT systems and deep learning. The automatic measurements showed high correlation with the ground truth. The en face model excelled at identification of hypertransmission defects. The models performance generalized well across device types tested. Future development will include integration of both models to enhance feature detection across GA lesions as well as isolating hypertransmission defects without GA for pre-GA biomarker extraction.

BACKGROUND AND OBJECTIVES: To characterize the clinical and ellipsoid zone (EZ) integrity outcomes in surgical intervention for symptomatic vitreomacular traction (VMT), and to evaluate the utility of intraoperative optical coherence tomography (OCT) during VMT surgery. PATIENTS AND METHODS: This was a post-hoc analysis of eyes in the DISCOVER study undergoing pars plana vitrectomy (PPV) with intraoperative OCT for VMT-related macular disease. Data were collected prospectively on feasibility and utility of intraoperative OCT, with follow-up lasting 12 months. RESULTS: Forty-three eyes of 41 patients were included and mean visual acuity improved from 20/96 to 20/45 ( P < .001). Intraoperative OCT provided information that impacted surgical decision-making in eight patients (18.6%). EZ integrity metrics significantly improved from baseline to 12 months and directly correlated with functional outcomes ( P < .001). CONCLUSIONS: Retinal function and morphology improved significantly following PPV for VMT. Intraoperative OCT provided surgeon-perceived valuable information in select cases. Further research is needed to determine whether this information impacts overall surgical outcomes. [ Ophthalmic Surg Lasers Imaging Retina . 2021;52:544–550.]

The prospective PRIME trial applied real-time, objective imaging biomarkers to determine individualized retreatment needs with intravitreal aflibercept injections (IAI) among eyes with diabetic retinopathy (DR). 40 eyes with nonproliferative or proliferative DR without diabetic macular edema received monthly IAI until a DR severity scale (DRSS) level improvement of ≥2 steps was achieved. Eyes were randomized 1:1 to DRSS- or PLI- guided management. At the final 2-year visit, DRSS level was stable or improved compared to baseline in all eyes, and mean PLI decreased by 11% (p = 0.73) and 23.6% (p = 0.25) in the DRSS- and PLI-guided arms. In both arms, the percent of pro re nata (PRN) visits requiring IAI was significantly higher in year 2 versus 1 (p &lt, 0.0001). The percent of PRN visits receiving IAI during year 1 was significantly correlated with the percent of PRN visits with IAI during year 2 (p &lt, 0.0001). Through week 104, 77.4% of instances of DRSS level worsening in the DRSS-guided arm were preceded by or occurred alongside an increase of PLI. Overall, consistent IAI re-treatment interval requirements were observed longitudinally among individual patients. Additionally, PLI increases appeared to precede DRSS level worsening, highlighting PLI as a valuable biomarker in the management of DR.

Purpose To characterize the longitudinal panretinal retinal vascular dynamics in diabetic macular edema (DME) and retinal vein occlusion (RVO) over a 12-month period while being treated with intravitreal aflibercept injections (IAIs). Design Prospective open-label study ( clinicaltrials.gov identifier, NCT02503540 ). Participants Thirty-one treatment-naive eyes with foveal-involving retinal edema secondary to DME and RVO. Methods Participants received 2 mg IAI every 4 weeks for the first 6 months, followed by 2 mg every 8 weeks. Ultra-widefield fluorescein angiography (UWFA; California Optos [Optos, Dunfermline, United Kingdom]) and spectral-domain OCT (Cirrus; Zeiss, Oberkochen, Germany) scans were obtained and analyzed using a novel quantitative assessment platform. Visual acuity, central subfield thickness, and adverse events also were collected. Main Outcome Measures The primary end point was the mean change in panretinal leakage index at month 12 from baseline as measured by UWFA. Results Mean age was 67.1 years. At month 12, visual acuity significantly improved by a mean of 18.4±21.4 letters (P Conclusions Intravitreal aflibercept injections resulted in a dramatic reduction in panretinal leakage index. Panretinal ischemic index did not improve and trended toward worsening.

BACKGROUND AND OBJECTIVE: To evaluate the impact of drusen burden on the detection of subclinical choroidal neovascularization (CNV) on optical coherence tomography angiography (OCTA) in nonexudative age-related macular degeneration (AMD). PATIENTS AND METHODS: A subanalysis of the AVATAR study, subjects diagnosed with nonexudative AMD without subfoveal atrophy were included. Subclinical CNV was assessed using OCTA software, and drusen burden was graded utilizing the advanced retinal pigment epithelium (RPE) analysis. RESULTS: Among eligible 58 eyes, 26 eyes (45%) had high drusen burden. Of the three eyes (5%) that demonstrated subclinical CNV, only one eye had high drusen burden, and all three eyes had neovascular AMD in the fellow eye. Extrafoveal RPE atrophy (odds ratio [OR] = 20.0; 95% confidence interval [CI], 1.53–261) and older age (OR = 1.27; 95% CI, 1.01–1.59) were predictive factors for subclinical CNV. CONCLUSION: Extrafoveal RPE atrophy, older age, and fellow-eye CNV were significant risk factors for underlying subclinical CNV in nonexudative AMD. [ Ophthalmic Surg Lasers Imaging Retina . 2020;51:22–30.]

Purpose To investigate the relationship between the diabetic retinopathy (DR) severity and quantitative ultra-widefield angiographic metrics, including leakage index, ischemic index, and microaneurysm count. Design Retrospective image analysis study. Methods Eyes with DR that had undergone ultra-widefield fluorescein angiography (UWFA) with associated color photography were identified. All eyes were laser-naive and had not received any intravitreal pharmacotherapy within 6 months of UWFA. Each eye was graded for DR severity. Quantitative angiographic parameters were evaluated with a semiautomated analysis platform with expert reader correction, as needed. Angiographic parameters included panretinal leakage index, ischemic index, and microaneurysm count. Clinical characteristics analyzed included age, gender, race, hemoglobin A1C level, hypertension, systolic blood pressure, diastolic blood pressure, and smoking history. Main Outcome Measures Association of DR severity with panretinal leakage index, ischemic index, and microaneurysm count. Results Three hundred thirty-nine eyes were included with mean age of 62±13 years. Forty-two percent of eyes were from women and 57.5% were from men. Distribution of DR severity was as follows: mild NPDR in 11.2%, moderate NPDR in 23.9%, severe NPDR in 40.1%, and PDR with 24.8%. Panretinal leakage index [mild NPDR (mean = 0.51%), moderate NPDR mean = 1.20%, severe NPDR (mean = 2.75%), and PDR (mean = 5.84%); P Conclusions Panretinal leakage index, panretinal ischemic index, and panretinal microaneurysm count are associated with DR severity. Additional research is needed to understand the clinical implications of these parameters related to progression risk, prognosis, and implications for therapeutic response.

Background/aimsUltra-widefield fluorescein angiography (UWFA) provides unique opportunities for panretinal assessment of retinal diseases. The objective quantification of UWFA features is a labour-intensive manual process, limiting its utility. The present study assesses the consistency/repeatability of an automated assessment platform for the characterisation of retinal vascular features, quantification of microaneurysms (MA) and leakage foci in UWFA images.MethodsAn Institutional Review Board-approved retrospective image analysis study was performed on UWFA images. For each eye, two arteriovenous-phase images and two late-phase images were selected. Automated assessment was performed for retinal vascular features, MA identification and leakage segmentation. Panretinal and zonal assessment of metrics was performed.ResultsThere was a significant correlation between paired time points for retinal vessel area and vessel length on early images (Pearson r=0.92, pConclusionThis automated algorithm demonstrated very strong intrastudy correlation between paired time points in the same phases of the angiogram for quantifying retinal vascular characteristics, MA count and leakage parameters in UWFA images. These findings suggest significant flexibility in the platform for consistency in evaluating metrics over time and is encouraging for longitudinal assessment opportunities.

BackgroundOcriplasmin is approved for the treatment of symptomatic vitreomacular traction (VMT). However, several retrospective reports have identified ellipsoid zone (EZ) alterations on spectral domain optical coherence tomography (SDOCT) after ocriplasmin injection. This report quantitatively analysed outer retinal changes after intravitreal ocriplasmin.MethodsOcriplasmin Research to Better Inform Treatment is a prospective, observational phase IV clinical study where subjects received a single intravitreal injection of ocriplasmin for symptomatic VMT. Macular cube scans were imported into a semiautomated EZ mapping and fluid feature extraction software for SDOCT analysis. Change in visual acuity, VMT release, macular hole (MH) closure, EZ integrity/volume and subretinal fluid (SRF) volume on SDOCT macular cube scans were recorded and analysed.ResultsThis analysis included 55 participants with 6 months of follow-up. Intravitreal ocriplasmin injection caused VMT release in 67% and MH closure in 82% of participants. Visual acuity improved by 4.5 letters (pConclusionOcriplasmin treatment resulted in VMT release, MH closure and visual acuity gains in a significant portion of eyes. EZ volume was significantly reduced at week 1, but recovered to baseline levels by final follow-up and was not associated with final visual acuity.

Purpose The purpose of this study was to evaluate the feasibility of assessing quantitative longitudinal fluid dynamics and total retinal fluid indices (TRFIs) with higher-order optical coherence tomography (OCT) for neovascular age-related macular degeneration (nAMD). Methods A post hoc image analysis study was performed using the phase II OSPREY clinical trial comparing brolucizumab and aflibercept in nAMD. Higher-order OCT analysis using a machine learning-enabled fluid feature extraction platform was used to segment intraretinal fluid (IRF) and subretinal fluid (SRF) volumetric components. TRFI, the proportion of fluid volume against total retinal volume, was calculated. Longitudinal fluid metrics were evaluated for the following groups: all subjects (i.e. treatment agnostic), brolucizumab, and aflibercept. Results Mean IRF and SRF volumes were significantly reduced from baseline at each timepoint for all groups. Fluid feature extraction allowed high-resolution assessment of quantitative fluid burden. A greater proportion of brolucizumab participants achieved true zero and minimal fluid (total fluid volume between 0.0001 and 0.001mm3) versus aflibercept participants at week 40. True zero fluid during q12 brolucizumab dosing was achieved in 36.6% to 38.5%, similar to the 25.6% to 38.5% during the corresponding q8 aflibercept cycles. TRFI was significantly reduced from baseline in all groups. Conclusions Higher-order OCT analysis demonstrates the feasibility of fluid feature extraction and longitudinal volumetric fluid burden and TRFI characterization in nAMD, supporting a unique opportunity for fluid burden assessment and the impact on outcomes. Translational relevance Detection and characterization of disease activity is vital for optimal treatment of nAMD. Longitudinal assessment of fluid dynamics and the TRFI provide important proof of concept for future automated tools in characterizing disease activity.

To evaluate the association of fluid volatility with ellipsoid zone (EZ) integrity and subretinal hyperreflective material (SHRM) volume during anti-vascular endothelial growth factor (VEGF) therapy in neovascular age-related macular degeneration (nAMD).This study was a post hoc analysis of the OSPREY study. Retinal volatility was quantified as the standard deviation across weeks 12 to 56 for six optical coherence tomography (OCT) metrics: central subfield thickness (CST), total fluid (TF) volume, subretinal fluid (SRF) volume, intraretinal fluid (IRF) volume, macular total retinal fluid index (TRFI), and central macular TRFI. Eyes with volatility ≤ 25th or ≥ 75th percentile values were compared.Eyes with low volatility in several exudative metrics showed greater change from baseline in SHRM volume at week 12 than eyes with high volatility. During the maintenance phase (weeks 12-56), eyes exhibiting high SRF volatility demonstrated increased SHRM volume compared to eyes with low SRF volatility (P = 0.027). Eyes exhibiting high volatility in CST, TF, and SRF demonstrated less improvement in EZ total attenuation (P0.001, P = 0.033, and P = 0.043, respectively) than eyes with low volatility. Early exudative instability (i.e., between weeks 4-8 or weeks 8-12) in multiple parameters (i.e., CST, TF, IRF, macular TRFI, or central macular TRFI) was associated with greater volatility during the maintenance phase (P0.05).Greater volatility in exudative OCT metrics, particularly SRF volatility, was associated with a greater increase in SHRM and less improvement in EZ integrity, suggesting that volatility is detrimental to multiple anatomic features in nAMD. Early exudative instability during the loading phase of treatment was associated with longer-term volatility in exudation.

To provide a comparative assessment of clinical outcomes between patients undergoing intraoperative OCT (iOCT) and conventional surgery for pars plana vitrectomy (PPV) with epiretinal membrane (ERM) peel.Case-control retrospective, comparative assessment.Patients undergoing PPV with membrane peel for ERM with eyes pooled from the prospective Determination of Feasibility of Intraoperative Spectral Domain Microscope Combined/Integrated OCT Visualization During En Face Retinal and Ophthalmic Surgery (DISCOVER) iOCT study and eyes undergoing conventional ERM surgery without iOCT.Visual acuity and OCT assessment before ERM surgery and at 1-, 3-, 6-, and 12-month follow-up after standard small-gauge PPV with iOCT feedback (iOCT DISCOVER group) or PPV with compulsory internal limiting membrane (ILM) peeling (conventional group). Visual acuity, central subfield thickness (CST), reoperation rate, and ERM recurrence were determined by record review and post hoc assessment of clinical OCTs after ERM peel.Visual acuity and ERM recurrence.A total of 262 eyes were included. Visual acuity (VA) improved 11.9 letters in the iOCT group (P 0.0001) and 12.1 letters in the conventional group (P0.0001) at 12 months after ERM surgery. Visual acuity improvement did not differ between the iOCT and conventional groups at 1, 3, 6, or 12 months after surgery (P 0.05 for each time point). Preoperative mean CST decreased in the iOCT group (P0.0001) and conventional group (P0.0001) with no difference between groups in CST reduction at 12 months (P = 0.36). No reoperations or visually significant recurrent ERMs occurred in either cohort.Intraoperative OCT-guided ERM removal without mandated ILM peeling provided similar VA and anatomic results to conventional ILM peeling for ERM. Future randomized prospective studies are needed to assess fully the possible role of iOCT in ERM surgery and to evaluate the potential impact of nonfoveal ERM persistence or recurrence in comparison with conventional surgery.

Objectives To demonstrate the feasibility of a deep learning-based vascular segmentation tool for UWFA and evaluate its ability to automatically identify quality-optimized phase-specific images. Methods Cumulative retinal vessel areas (RVA) were extracted from all available UWFA frames. Cubic splines were fitted for serial vascular assessment throughout the angiographic phases of eyes with diabetic retinopathy (DR), sickle cell retinopathy (SCR), or normal retinal vasculature. The image with maximum RVA was selected as the optimum early phase. A late phase frame was selected at a minimum of 4 min that most closely mirrored the RVA from the selected early image. Trained image analysts evaluated the selected pairs. Results A total of 13,980 UWFA sequences from 462 sessions were used to evaluate the performance and 1578 UWFA sequences from 66 sessions were used to create cubic splines. Maximum RVA was detected at a mean of 41 ± 15, 47 ± 27, 38 ± 8 s for DR, SCR, and normals respectively. In 85.2% of the sessions, appropriate images for both phases were successfully identified. The individual success rate was 90.7% for early and 94.6% for late frames. Conclusions Retinal vascular characteristics are highly phased and field-of-view sensitive. Vascular parameters extracted by deep learning algorithms can be used for quality assessment of angiographic images and quality optimized phase selection. Clinical applications of a deep learning-based vascular segmentation and phase selection system might significantly improve the speed, consistency, and objectivity of UWFA evaluation.

PURPOSE: To longitudinally assess the effect of anti-vascular endothelial growth factor (VEGF) treatment on ellipsoid zone (EZ) integrity, subretinal hyperreflective material (SHRM), and the sub-retinal pigment epithelium (sub-RPE) compartment in eyes with neovascular age-related macular degeneration (nAMD). DESIGN: This study was a post hoc analysis of the OSPREY clinical trial, a prospective, double-masked, phase 2 study comparing brolucizumab 6 mg with aflibercept 2 mg over 56 weeks. PARTICIPANTS: Participants with treatment-naïve nAMD at the initiation of the trial were included in the analysis. METHODS: Eyes were evaluated with spectral domain optical coherence tomography (SD-OCT) at 4-week intervals in the OSPREY trial (n=81). SD-OCT scans collected from each visit were automatically. segmented using a proprietary, machine learning enabled higher-order feature-extraction platform for retinal layer, SHRM, and sub-RPE boundary lines, which were evaluated and corrected as needed by masked trained graders. The current analysis focused only on subjects evaluated with Cirrus (Zeiss) platform, n=28). MAIN OUTCOME MEASURES: Outcome measures included change from baseline in EZ-RPE volume, EZ-RPE central subfield thickness (CST), total EZ attenuation, SHRM volume, SHRM CST, and total sub-RPE volume. The correlation between each of these measures and best corrected visual acuity (BCVA) at each visit was evaluated. RESULTS: EZ-RPE volume and EZ-RPE CST showed significant increases, and total EZ attenuation, SHRM volume, SHRM CST, and total sub-RPE volume showed significant decreases from baseline at each visit from Week 4–56 (P

Purpose Numerous angiographic images with high variability in quality are obtained during each ultra-widefield fluorescein angiography (UWFA) acquisition session. This study evaluated the feasibility of an automated system for image quality classification and selection using deep learning. Methods The training set was comprised of 3543 UWFA images. Ground-truth image quality was assessed by expert image review and classified into one of four categories (ungradable, poor, good, or best) based on contrast, field of view, media opacity, and obscuration from external features. Two test sets, including randomly selected 392 images separated from the training set and an independent balanced image set composed of 50 ungradable/poor and 50 good/best images, assessed the model performance and bias. Results In the randomly selected and balanced test sets, the automated quality assessment system showed overall accuracy of 89.0% and 94.0% for distinguishing between gradable and ungradable images, with sensitivity of 90.5% and 98.6% and specificity of 87.0% and 81.5%, respectively. The receiver operating characteristic curve measuring performance of two-class classification (ungradable and gradable) had an area under the curve of 0.920 in the randomly selected set and 0.980 in the balanced set. Conclusions A deep learning classification model demonstrates the feasibility of automatic classification of UWFA image quality. Clinical application of this system might greatly reduce manual image grading workload, allow quality-based image presentation to clinicians, and provide near-instantaneous feedback on image quality during image acquisition for photographers. Translational relevance The UWFA image quality classification tool may significantly reduce manual grading for clinical- and research-related work, providing instantaneous and reliable feedback on image quality.

Background In 2017, the Addendum Guidelines for the Prevention of Peanut Allergy were published with recommendations on early introduction of peanut-containing foods based on infants' clinical history. Objective We sought to conduct a nationwide US survey to assess Guidelines implementation among allergists and immunologists who manage infants for food allergy. Methods Survey invitations were delivered to 3281 nonretired, US members of the American Academy of Asthma, Allergy & Immunology, board certified in allergy and immunology. The survey assessed awareness and implementation of the Guidelines and barriers to implementation. Descriptive statistics were generated. Results Twenty-nine percent (946 of 3281) of surveyed allergists/immunologists responded, and 87.1% (825 of 946) of responders met eligibility criteria. Among eligible responders, 97.1% were aware of the Guidelines. Of these, 64.5% reported full implementation of the Guidelines as published, 34.4% reported partial implementation, and 1.1% reported using none of the Guidelines. Barriers to Guidelines use included parental (47.6%) and self (21.8%) concerns about allergic reactions, lack of referrals (33.6%), parents uninterested in early feeding (28.2%), and lack of clinic time (20.9%). The 2 most common deviations from the Guidelines were considering additional factors not specified in the Guidelines such as family history (50.2%) and conducting skin prick testing in non–high-risk children (43.9%). Of respondents using the Guidelines, 45.7% indicated they needed more education or training. Conclusions Essentially all allergists/immunologists who responded to the survey reported full or partial Guidelines implementation. Parental concerns and lack of referrals are major identifiable barriers. Improved Guidelines messaging to parents and referring physicians is warranted.

Purpose To evaluate the use of OCT angiography (OCTA) to detect choroidal neovascularization (CNV) in eyes with indeterminate CNV features on conventional imaging. Design Prospective observational study of OCTA in patients undergoing routine spectral-domain optical coherence tomography (SD-OCT) for macular disease. Participants Participants enrolled in the Observational Assessment of Visualizing and Analyzing Vessels with Optical Coherence Tomography Angiography in Retinal Diseases for which CNV was considered as part of a differential diagnosis based on clinical examination, prior imaging, or both, but in whom the presence of CNV was not definitive on SD-OCT and fluorescein angiography (FA) imaging. Methods All patients underwent imaging with the Avanti RTVue XR HD (Optovue, Fremont, CA) and the Cirrus HD-OCT (Zeiss, Oberkochen, Germany) systems. Main Outcome Measures OCT angiography scans were assessed for the presence or absence of CNV. Spectral-domain OCT scans were assessed for the presence of fluid, hyperreflective material, serous pigment epithelial detachment (PED), shallow irregular PED, vitreomacular adhesion, epiretinal membrane, retinal pigment epithelium (RPE) atrophy, and central subfield retinal thickness. Univariate and multivariate logistic regression analyses were performed to identify features on SD-OCT associated with the presence of CNV on OCTA. Results Twenty-nine eyes of 29 patients met the criteria for inclusion. A CNV lesion was detected on OCTA in 8 eyes (28%); 21 eyes (72%) showed negative results for CNV. After adjusting for age, gender, and central subfield retinal thickness, the presence of shallow irregular PED (odds ratio [OR], 148; 95% confidence interval [CI], 3.22–6830; P = 0.011), as well as the combinations of intraretinal fluid and sub-RPE material (OR, 16.8; 95% CI, 1.43–198; P = 0.025) on SD-OCT were associated significantly with the presence of CNV on OCTA. Conclusions OCT angiography enabled the identification of CNV that was otherwise indeterminate with prior imaging in select eyes. The presence of a shallow irregular PED as well as intraretinal fluid combined with sub-RPE material both were associated with the presence of CNV. OCT angiography may be a valuable adjunct to conventional SD-OCT and FA imaging in the detection and surveillance of CNV, particularly in diagnostic dilemmas.

To assess the relationship of dissociated optic nerve fiber layer (DONFL) and intraoperative membrane-peeling dynamics as visualized using intraoperative optical coherence tomography (OCT), and to evaluate the functional implications of DONFL.This was a post hoc analysis of eyes undergoing membrane peeling for vitreomacular interface disorders in the prospective PIONEER intraoperative OCT study. Retinal layer measurements in preincision and postpeel intraoperative OCT images were obtained. The primary outcome was development of DONFL appearance on spectral domain OCT at 6-month follow-up. Secondary outcomes included correlation of DONFL with surgical technique, surgical indication, intraoperative OCT findings, and retinal sensitivity.Ninety-five eyes were included. The prevalence of DONFL at 6 months was 36%. Increased inner retinal layer thickness on intraoperative OCT immediately after membrane peeling was associated with development of DONFL (P0.01). Macular hole repair was significantly associated with DONFL appearance. Peel technique (forceps vs. diamond-dusted membrane scraper) was not associated with DONFL. There was no difference in retinal sensitivity or visual acuity between eyes with or without DONFL.Acute postpeel increase in inner retinal thickness and macular hole repair were associated with development of DONFL appearance. However, it is unclear whether the surgical indication (e.g., macular hole) or the surgical manipulations performed (e.g., internal limiting membrane peeling) is the major factor that has an impact on DONFL appearance. Overall, these findings suggest that one mechanism in the development of DONFL appearance may be intraoperative trauma to the inner retina, potentially during internal limiting membrane peeling (e.g., macular hole repair).

Purpose To report the 3-year assessment of feasibility and usefulness of microscope-integrated intraoperative OCT (iOCT) during ophthalmic surgery. Design Prospective, consecutive case series. Participants Adult participants undergoing incisional ophthalmic surgery with iOCT imaging who consented to be enrolled in the Determination of Feasibility of Intraoperative Spectral-Domain Microscope Combined/Integrated OCT Visualization during En Face Retinal and Ophthalmic Surgery (DISCOVER) study. Methods The DISCOVER study is a single-site, multisurgeon, institutional review board-approved investigational device prospective study. Participants included patients undergoing anterior or posterior segment surgery who underwent iOCT imaging with 1 of 3 prototype microscope-integrated iOCT systems (i.e., Zeiss Rescan 700, Leica EnFocus, or Cole Eye iOCT systems). Clinical characteristics were documented, iOCT was directed by the operating surgeon at predetermined surgical time points, and each surgeon completed a questionnaire after surgery to evaluate the usefulness of iOCT during surgery. Main Outcome Measures Feasibility of iOCT based ability to obtain an OCT image during surgery and usefulness of iOCT based on surgeon reporting during surgery. Results Eight hundred thirty-seven eyes (244 anterior segment cases and 593 posterior segment cases) were enrolled in the DISCOVER study. Intraoperative OCT demonstrated feasibility with successful image acquisition in 820 eyes (98.0%; 95% confidence interval [CI], 96.8%–98.8%). In 106 anterior segment cases (43.4%; 95% CI, 37.1%–49.9%), the surgeons indicated that the iOCT information impacted their surgical decision making and altered the procedure. In posterior segment procedures, surgeons reported that iOCT enabled altered surgical decision making during the procedure in 173 cases (29.2%; 95% CI, 25.5%–33.0%). Conclusions The DISCOVER iOCT study demonstrated both generalized feasibility and usefulness based on the surgeon-reported impact on surgical decision making. This large-scale study confirmed similar findings from other studies on the potential value and impact of iOCT on ophthalmic surgery.

Purpose To assess the efficacy of ranibizumab for persistent diabetic macular edema (DME) previously treated with bevacizumab and compare monthly versus treat-and-extend (TREX) dosing. Design Twelve-month open-label prospective, randomized, comparative dosing study. Participants Twenty-seven participants with persistent foveal-involving DME recently treated with bevacizumab. Methods All participants were to receive 3 initial monthly 0.3-mg ranibizumab injections before randomization to monthly (n = 15) or TREX (n = 12) injection protocols over 12 months. The treatment interval was extended by 2 weeks up to a maximum interval of 12 weeks in the TREX group if central subfield thickness (CST) was 300 μm or less or complete absence of intraretinal or subretinal fluid on the macular cube was observed. The follow-up interval was decreased by 2 weeks if CST increased to 300 μm or more with associated intraretinal or subretinal fluid, or both. Main Outcome Measures Change in Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA), CST, and adverse events. Results Before study enrollment, participants received an average of 8.6 bevacizumab injections. At month 12, mean ETDRS BCVA improved by +5.3 letters (P Conclusions After conversion to ranibizumab in eyes with persistent DME refractory to bevacizumab, significant functional and anatomic improvements were noted. Visual and anatomic outcomes were similar in TREX and monthly treatment protocols.

Eyes with proliferative diabetic retinopathy (PDR) have been shown to improve in the leakage index and microaneurysm (MA) count after intravitreal aflibercept (IAI) treatment. The authors investigated these changes via automatic segmentation on ultra-widefield fluorescein angiography (UWFA). Forty subjects with PDR were randomized to receive either 2 mg IAI every 4 weeks (Arm 1) or every 12 weeks (Arm 2) through Year 1. After Year 1, Arm 1 switched to quarterly IAI and Arm 2 to monthly IAI through Year 2. By Year 2, the Arm 1 leakage index decreased by 43% from Baseline (p = 0.03) but increased by 59% from Year 1 (p = 0.04). Arm 2 decreased by 61% from Baseline (p = 0.008) and by 31% from Year 1 (p = 0.12). Both cohorts exhibited a significant decline in MAs from Baseline to Year 2 (871 to 410, p &lt, 0.001, 776 to 207, 0.001, respectively). Subjects with an improved leakage and MA count showed a more significant improvement in the Diabetic Retinopathy Severity Scale (DRSS) score. Moreover, central subfield thickness (CST) was positively associated with changes in the leakage index. In conclusion, the leakage index and MA counts significantly improved from Baseline following IAI treatment, and monthly injections provided a more rapid and sustained reduction in these parameters compared with quarterly injections.

The purpose of this study is to evaluate intraoperative OCT (iOCT) utility and outcomes during retinal detachment (RD) repair.The Determination of Feasibility of Intraoperative Spectral-Domain Microscope Combined/Integrated OCT Visualization during En Face Retinal and Ophthalmic Surgery (DISCOVER) intraoperative OCT study is a prospective Institutional Review Board-approved study.Participants in the DISCOVER study undergoing surgical repair for RD.This was a post hoc analysis of eyes in the DISCOVER study undergoing surgical repair for RDs. Inclusion criteria included iOCT after perfluorocarbon liquid placement and at least 6 months follow-up. Exclusion criteria included severe retinal pathology unrelated to RD. Surgeons completed standardized questionnaires after each case evaluating the iOCT instrument's utility. Functional and surgical outcome data were collected at the latest available time point between 6 and 12 months. Outcomes were evaluated in 2 groups: uncomplicated primary and complex cases.Intraoperative OCT utility, single-surgery success, and visual acuity outcomes.A total of 103 eyes were included in this study: 51 uncomplicated primary and 52 complex cases. Intraoperative OCT provided valuable information in 36% of cases. In 12% of cases, iOCT data directly altered surgical decision making. There was a significantly higher rate of valuable iOCT feedback in complex cases compared with primary cases (50% vs. 22%, P0.01). Among primary cases, 48 (94%) had successful single surgery repair with a mean postoperative visual acuity of 20/47 compared with the complex group's 75% single surgery success (n=39) and mean postoperative visual acuity of 20/92.This study affirms the potential impact of iOCT in assisting select cases of RD repair, particularly with complex pathology. The single surgery success rate was good with more than 80% of cases successfully repaired with 1 surgery.

BACKGROUND AND OBJECTIVE: To compare conventional microscope-integrated intraoperative optical coherence tomography (iOCT) and digitally enabled microscope-integrated iOCT in vitreoretinal surgery. PATIENTS AND METHODS: In this post-hoc analysis of the DISCOVER prospective iOCT study, two surgical groups were compared: (1) conventional iOCT and (2) digitally enabled iOCT. Surgeon questionnaires were collected immediately following surgery. RESULTS: A total of 187 subjects were included in the study: 91 in the conventional iOCT group and 96 in the digitally enabled iOCT group. There were no differences in surgeon-perceived iOCT utility between the two groups. There was significantly higher surgical field-based visualization of the iOCT datastream in the digitally enabled iOCT group (67.7% vs. 3.3%; P < .0001). Reported significant back discomfort (1.0% vs. 18.7%; P < .0001) and headaches (5.2% vs. 20.9%; P < .002) were lower in the digitally enabled iOCT group. CONCLUSIONS: Feasibility and utility of iOCT were similar in both groups. Digitally enabled iOCT datastream enabled increased attention on the surgical field during OCT review. [ Ophthalmic Surg Lasers Imaging Retina . 2020;51:S37–S43.]

BACKGROUND AND OBJECTIVE: To compare optical coherence tomography angiography (OCTA) capillary perfusion density (CPD) measurements of normal eyes and eyes with macular ischemia (MI). PATIENTS AND METHODS: AVATAR is an institutional review board-approved, prospective, observational imaging study using the Avanti RTVue XR HD. OCTA reports were reviewed for the presence of MI. Qualitative MI grading was performed, and CPD metrics in the superficial and deep fovea and parafovea were analyzed. A normal eye cohort was identified for comparative assessment. RESULTS: The MI and normal cohorts included 55 and 58 eyes, respectively. Compared to normal eyes, eyes with MI had significantly lower CPD values in all regions. There was a statistically significant correlation between qualitative MI grade and VA in the superficial ( P = .003) and deep plexuses ( P = .029). Only deep parafoveal CPD values demonstrated correlation with VA ( P = .043). CONCLUSIONS: Eyes with MI determined by masked qualitative OCTA grading demonstrated significantly reduced CPD values compared to normal eyes. Categorical assessment of MI severity correlated with VA. [ Ophthalmic Surg Lasers Imaging Retina. 2020;51:S30–S36.]

PURPOSE: To examine the relationship between diabetic macular edema (DME) and quantitative ultra-widefield fluorescein angiography (UWFA) metrics of ischemia, leakage, and microaneurysms (MAs). DESIGN: Retrospective image analysis study SUBJECTS: Eyes with diabetic retinopathy that had undergone spectral-domain optical coherence tomography (OCT), UWFA, and ultra-widefield fundus photography. METHODS: OCT images were analyzed to determine the presence or absence of DME, central subfield thickness (CST), and subretinal fluid (SRF). Utilizing a semi-automated analysis platform, UWFA images were segmented for ischemia, leakage, and MAs with manual correction as needed. Clinical variables, including age, sex, race, hemoglobin A1C, blood pressure, cholesterol levels, use of blood thinners, smoking status, and lens status were also evaluated. MAIN OUTCOME MEASURES: Factors associated with the presence and severity of DME RESULTS: A total of 304 eyes (156 OD, 148 OS) from 178 diabetic patients were analyzed in the study. Panretinal leakage index, MA count, and ischemic index were not significantly different between eyes with and without DME in univariate assessment. Zonal assessments of macular MAs and macular leakage index values revealed that eyes with DME had a significantly higher MA count (p=0.001) and leakage index (p

PURPOSE: To characterize the longitudinal panretinal retinal vascular dynamics in diabetic macular edema (DME) and retinal vein occlusion (RVO) over a 12-month period while being treated with intravitreal aflibercept injections (IAI). DESIGN: Prospective open-label study (clinicaltrials.org identifier, ). PARTICIPANTS: Thirty-one treatment-naïve eyes with foveal-involving retinal edema secondary to DME and RVO. METHODS: Subjects received 2mg IAI q4 weeks for the first 6 months, followed by 2 mg q8 weeks. Ultra-widefield angiograms (UWFA, California Optos) and SD-OCT (Cirrus, Zeiss) scans were obtained and analyzed using a novel quantitative assessment platform. Visual acuity, central subfield thickness, and adverse events were also collected. MAIN OUTCOME MEASURES: The primary study endpoint was the mean change in panretinal leakage index at month 12 from baseline as measured by UWFA. RESULTS: Baseline mean age was 67.1 years (range, 46-84). At month 12, visual acuity significantly improved by a mean of 18.4 ± 21.4 letters (P < 0.0001), and CST also significantly improved with a mean reduction of 301.3 ± 250.3 μm (P < 0.0001). Mean panretinal leakage index significantly improved, decreasing from 3.4% at baseline to 0.5% at month 6 (P < 0.0001) and 0.4% at month 12 (P < 0.0001). Panretinal ischemic index did not demonstrate any significant change but showed a nonsignificant increase from 5.5% at baseline to 6.1% at month 6 (P = 0.315) and 8.7% at month 12 (P = 0.193). Subjects diagnosed with DME showed a decrease in leakage index from 3.5 ± 2.7% at baseline to 1.6 ± 0.8% at month 12 (P = 0.018) and overall stability in ischemic index from 5.0 ± 4.1% at baseline to 4.7 ± 3.5% at month 12 (P = 0.689). Subjects with RVO presented a decrease in leakage index from 3.3 ± 1.1% at baseline to 0.02 ± 0.03% at 12 months (P < 0.0001) and a non-significant increase in ischemic index from 5.9 ± 4.5% at baseline to 12.6 ± 9.8% at month 12 (P = 0.172). CONCLUSIONS: Therapy with IAI resulted in a dramatic reduction in panretinal leakage index. Panretinal ischemic index did not improve and trended towards worsening.

This survey study describes the self-reported level of adherence, familiarity, and implementation needs associated with national peanut allergy prevention recommendations among pediatricians caring for infants., Key Points Question What is the current rate of implementation of the 2017 Addendum Guidelines for the Prevention of Peanut Allergy in the United States, and what are the barriers to implementation among pediatricians who provide care for infants aged 12 months or younger? Findings In this study survey of 1781 US pediatricians, 93% of respondents were aware of the guideline. Of those who had knowledge of the guidelines, 29% were fully implementing them and 64% were partially implementing them. Meaning These findings suggest that understanding implementation barriers and needs among pediatricians is necessary to increase adherence and reduce peanut allergy incidence in infants., Importance The 2017 Addendum Guidelines for the Prevention of Peanut Allergy in the United States recommend that pediatricians assess infant peanut allergy risk and introduce peanut in the diet at age 4 to 6 months. Early introduction has the potential to prevent peanut allergy development. Objectives To measure the rates of guideline awareness and implementation and to identify barriers to and factors associated with implementation among US pediatricians. Design, Setting, and Participants This population-based study survey used a 29-item electronic survey instrument that was administered to pediatricians practicing across the United States from June 1, 2018, to December 1, 2018. Invitations to complete a survey were emailed to all pediatricians in the American Academy of Pediatrics vendor database. Eligible participants were nonretired US-based pediatricians providing general care to infants aged 12 months or younger. Main Outcomes and Measures The primary outcome was the prevalence of guideline implementation, which was measured by 1 survey item about awareness followed by a second item about implementation. Secondary outcomes included identification of guidelines-focused services provided by pediatricians, knowledge of the guidelines (measured with 3 clinical scenarios), barriers to guideline implementation, need for training, and facilitators of guideline implementation. Results A total of 1781 pediatricians were eligible to participate and completed the entire survey. Most respondents self-identified as white (1287 [72.5%]) and female (1210 [67.4%]) individuals. Overall, 1725 (93.4%; 95% CI, 92.2%-94.5%) pediatricians reported being aware of the guidelines. Of those pediatricians who had knowledge of the guidelines, 497 (28.9%; 95% CI, 26.8%-31.1%) reported full implementation and 1105 (64.3%; 95% CI, 62.0%-66.6%) reported partial implementation. Common barriers to implementation included parental concerns about allergic reactions (reported by 575 respondents [36.6%; 95% CI, 34.3%-39.1%]), uncertainty in understanding and correctly applying the guidelines (reported by 521 respondents [33.2%; 95% CI, 30.9%-35.6%]), and conducting in-office supervised feedings (reported by 509 respondents [32.4%; 95% CI, 30.1%-34.8%]). Many pediatricians (1175 [68.4%; 95% CI, 66.1%-70.5%]) reported a need for further training on the guidelines. Conclusions and Relevance This survey found that most pediatrician respondents appeared to know of the 2017 guidelines, but less than one-third of respondents reported full implementation. Results of this study may inform future efforts to eliminate barriers to guideline implementation and adherence, thereby reducing the incidence of peanut allergy in infants.

PURPOSE: To compare review strategies for optical coherence tomography angiography (OCT-A) for multiple disease features found in common diseases of the choroid and retina. DESIGN: Prospective, observational study. PARTICIPANTS: Patients with macular disease undergoing routine spectral-domain optical coherence tomography (SDOCT). METHODS: Eyes were imaged with the Avanti RTVue XR HD (Optovue, Fremont, CA), and the split-spectrum amplitude decorrelation angiography (SSADA) algorithm software was utilized for OCT-A performance. Scans were reviewed by 2 masked expert reviewers. A third masked reviewer was utilized in cases of reviewer disagreement. A single report using automated segmentation within the Avanti software to represent the superficial retina capillary plexus, deep retina capillary plexus, outer retina, and choroid capillary layer was generated. A continuous slab descent video export was also reviewed for each OCT-A scan. This video consisted of a continuous (e.g., line-by-line) review of the en face OCT- data. Each dataset was reviewed for the presence of three pathologic features: choroidal neovascularization, microaneurysms, and macular ischemia. MAIN OUTCOME MEASURES: Comparison of identification rates of retinal and choroidal microvascular abnormalities using different review strategies. RESULTS: Four hundred twenty-one eyes were included in the study. Of those, 350 eyes had reports that were deemed sufficient quality for interpretation and analysis by both reviewers. Identification rates of choroidal neovascularization, microaneurysms, and macular ischemia on the report were 90.5%, 84.5%, and 95.4% respectively compared to the overall presence. Likewise, rates of identification in the continuous slab descent review video were 88.1%, 96.4%, and 95.4% for choroidal neovascularization, microaneurysms, and macular ischemia respectively compared to the overall presence. Cohen’s kappa values ranged from 0.80 to 0.96, corresponding to very good agreement between the report and continuous slab descent review for each variable. CONCLUSIONS: Defining an optimal reporting strategy for OCT-A is important for diagnostic accuracy and optimizing workflow in retina clinics. In this study, OCT-A report using automated segmentation was comparable to continuous slab descent review for identifying microvascular abnormalities of the retina and choroid.

Purpose Intraoperative OCT (iOCT) has enabled visualization of subtle structural details during surgical interventions, including retinal detachment repair. The purpose of this study was to evaluate iOCT findings during retinal detachment repair and to assess their impact on anatomic and functional outcomes, including outer retinal integrity. Design The PIONEER Intraoperative and Perioperative OCT Study is a prospective cohort, institutional review board-approved study. Participants Participants in the PIONEER undergoing surgical repair for primary macula-involving retinal detachment. Methods This was a post hoc analysis of all eyes in the PIONEER undergoing surgical repair with primary macula-involving retinal detachments. Inclusion criteria included iOCT after perfluorocarbon liquid (PFO) placement, visualization of the foveal center on iOCT, and images of sufficient quality for quantitative assessment of submacular fluid volume. Exclusion criteria included recurrent retinal detachment, proliferative vitreoretinopathy, and a lack of postoperative OCT data after gas bubble resolution. Subretinal fluid volume on iOCT imaging was quantified. Qualitative review of iOCT images was performed for visualization of outer retinal bands, fluid, and retinal corrugations. Postoperative OCT images were analyzed using an ellipsoid zone (EZ) mapping platform to evaluate and quantify outer retinal metrics. Postoperative OCT images also were reviewed qualitatively for persistent subretinal fluid. Associations between various anatomic and functional outcomes were assessed. Main Outcome Measures Presence of intraoperative subretinal fluid under PFO tamponade, postoperative persistent subretinal fluid, postoperative visual acuity at 1 year, and EZ integrity at 1 year. Results Fifteen eyes of 15 patients were analyzed. All 15 eyes (100%) showed subretinal fluid on iOCT. All eyes demonstrated spontaneous fluid resolution on follow-up OCT imaging. Increased intraoperative subretinal fluid volume under PFO tamponade trended toward significantly worse visual acuity outcome (P = 0.07). Postoperative quantitative EZ integrity at 12 months directly correlated with visual outcome (P = 0.01). Conclusions Intraoperative subretinal fluid persists under PFO tamponade with high frequency in eyes undergoing retinal detachment repair, but this fluid does not seem to be associated with persistent postoperative subretinal fluid. Postoperative EZ integrity is associated with visual acuity outcome, and intraoperative subretinal fluid volume under PFO tamponade also may be linked to visual outcomes.

Purpose To delineate the feasibility and role of intraoperative OCT (iOCT) in surgical decision-making during vitreoretinal surgical interventions for proliferative diabetic retinopathy (PDR). Design Prospective, single-site, multisurgeon consecutive case series. Participants Patients enrolled in the DISCOVER study (Determination of Feasibility of Intraoperative Spectral Domain Microscope Combined/Integrated OCT Visualization during En Face Retinal and Ophthalmic Surgery) who underwent vitreoretinal surgery for sequelae of PDR. Methods Subjects were identified from participants in the first 2 years of the DISCOVER study who underwent vitreoretinal surgery for complications of PDR. Intraoperative imaging with a microscope-integrated iOCT system was performed at surgical milestones as determined by the surgeon. Data collected included clinical characteristics, image features, and survey-based surgeon feedback. Main Outcome Measures Main outcomes were (1) the percentage of cases with successful acquisition of iOCT (feasibility) and (2) the percentage of cases in which iOCT altered surgical decision making (usefulness). Results Eighty-one eyes with PDR underwent vitreoretinal surgery in the DISCOVER study. Successful iOCT imaging was obtained for 80 of 81 eyes (98.8%). Of these, 36 (44.4%) were female and 44 (54.3%) were male. The surgeon preferred real-time feedback in 47 cases (58.6%) and static review in 29 cases (36.3%); it was indeterminate in 4 cases (5%). Surgeons reported that in 2 cases (2.5%) the iOCT interfered with the surgery (e.g., microscope malfunction). In 41 of the 81 cases (50.6%), surgeons reported that iOCT provided valuable information (e.g., identification of dissection planes, identification of retinal hole). In addition, the iOCT data provided information that specifically altered the surgeon's decision making (e.g., determination of peel completion, choice of tamponade) in 21 of 81 cases (26%). No adverse events were attributed to the iOCT system. Conclusions The results suggest that iOCT is feasible during complex vitreoretinal surgeries in patients with PDR using a microscope-integrated OCT platform. Using iOCT seems to frequently offer key information that may impact surgical decision making and, potentially, patient outcomes.

PURPOSE: To assess the retinal architecture changes which occur during epiretinal membrane (ERM) surgery, utilizing intraoperative optical coherence tomography (iOCT). DESIGN: Prospective multi-surgeon single center study. SUBJECTS/PARTICIPANTS: Subjects from the PIONEER iOCT study who underwent surgical intervention for management of ERM. METHODS: All subjects underwent vitrectomy with ERM peeling with optional internal limiting membrane (ILM) peeling. Preoperative, intraoperative, and postoperative quantitative and qualitative OCT assessments were performed. Clinical characteristics including visual acuity outcomes, central subfield thickness and complications including ERM recurrence and need for reoperation were assessed at 3, 6 and 12 months following surgery for membrane peeling, as available. MAIN OUTCOME MEASURES: Visual acuity outcomes, anatomic outcomes and complications including ERM recurrence. Microarchitectural alterations (i.e. retinal layer changes) following membrane peeling visualized with iOCT. RESULTS: Seventy-six were identified and included in this analysis of clinical outcomes and quantitative OCT assessment. Twenty-four eyes were excluded due to insufficient intraoperative OCT quality for quantitative assessment. The mean preoperative VA measured 20/63. The mean postoperative VA at 3 months was 20/41 (p

BACKGROUND AND OBJECTIVE: Optimal placement of the Argus II Retinal Prosthesis System (Second Sight Medical Products, Sylmar, CA) is critical. Intraoperative optical coherence tomography (OCT) allows for intrasurgical visualization and confirmation of array placement. In this study, two different OCT systems were evaluated to assess the feasibility and utility of this technology during Argus II surgery. PATIENTS AND METHODS: Intraoperative OCT was performed on five patients undergoing Argus II implantation at Cole Eye Institute from June 2015 to July 2016. The EnVisu portable OCT (Bioptigen, Morrisville, NC) and microscope-integrated RESCAN 700 (Zeiss, Oberkochen, Germany) intraoperative OCT systems were utilized. The EnVisu was used in three patients and the RESCAN 700 in three of the five patients. Following array tacking, intraoperative OCT was performed over the entire array including the edges and tack. RESULTS: Intraoperative OCT allowed for visualization of the array/retina interface. Microscope integration of the OCT system facilitated ease of focusing, real-time feedback, surgeon-directed OCT scanning to the areas of interest, and enhanced image quality at points of interest. CONCLUSIONS: Intraoperative imaging of the Argus II electrode array is feasible and provides information about electrode array-retina interface and distance to help guide a surgeon. Microscope integration of OCT appears to provide an optimal and efficient approach to intraoperative OCT during Argus II array placement. [ Ophthalmic Surg Lasers Imaging Retina . 2016;47:999–1003.]

PURPOSE:Ellipsoid zone (EZ) and outer retinal integrity are strongly linked to visual prognosis, but quantitative normative data is lacking. This study evaluates the EZ, outer retina, and inner retina in eyes without macular disease across a wide age spectrum. METHODS:An IRB-approved study was performed for eyes without macular pathology undergoing Spectral Domain Optical Coherence Tomography (SD-OCT) scans on the Cirrus HD-OCT system (Carl Zeiss Meditec, Oberkochen, Germany). Scans were analyzed using a previously described automated EZ mapping tool with line-by-line manual verification. Segmentation included internal limiting membrane (ILM), outer nuclear layer/Henle fiber layer complex (ONL/HFL), EZ, and the retinal pigment epithelium (RPE). The output included metrics for the inner retina (ILM-OPL/HFL), outer retina (ONL/HFL-RPE), EZ-RPE area and volume, and en face EZ mapping. EZ-RPE attenuation on en face mapping was defined as EZ-RPE thickness < 20 um, and total attenuation was 0 um. Imaging parameters were assessed for the group and compared to age, sex, visual acuity and spherical equivalent. RESULTS:167 eyes from 167 subjects were included. Mean age was 49.7 years (range 10-84 years). The mean foveal retinal thickness was 200.58 ± 19.22 um. Mean inner retinal thickness was 21.47 ± 13.60 um. Mean outer retinal thickness was 179.11 ± 18.52 um. Mean EZ-RPE thickness was 50.58 ± 6.01um. The mean EZ-RPE volume was 1.20 ± 0.10 mm3. Mean EZ attenuation percentage per macular map area was 0.87% ± 1.13% and mean percentage total attenuation was 0.12% ± 0.14%. Total and inner retinal thickness metrics decreased with age. Mean outer retinal thickness increased with age. EZ-RPE parameters were unchanged with age. However, EZ attenuation was negatively correlated with age. CONCLUSION:This study provides important information for inner and outer retinal parameters. Future research on quantitative EZ integrity can utilize this data for comparison.

Purpose To evaluate alterations on optical coherence tomography angiography (OCT-A) and quantitatively assess alterations in the ellipsoid zone (EZ) in eyes with macular telangiectasia type 2 (MacTel type 2). Methods The Observational Assessment of Visualizing and Analyzing Vessels With Optical Coherence Tomography Angiography in Retinal Diseases study is an institutional review board-approved prospective, observational study investigating OCT-A in macular disease. Patients underwent spectral-domain (SD)-OCT and OCT-A imaging at a single visit. SD-OCT data were analyzed using a novel OCT EZ-mapping software to obtain linear, area, and volumetric measurements of the EZ-retinal pigment epithelium (RPE) complex across the macular cube. OCT-A retinal capillary density was measured using the Optovue Avanti split-spectrum amplitude-decorrelation angiography algorithm. EZ-RPE parameters were compared to age-matched, sex-matched controls. Results Fourteen eyes of seven patients (mean age, 59 ± 6.5 years) were analyzed. Mean visual acuity was 20/45 (range, 20/20–20/150). EZ-RPE central foveal mean thickness was 27.8 ± 6.7 μm, EZ-RPE central foveal thickness was 22.1 ± 21.6 μm, EZ-RPE central foveal area was 0.17 ± 0.04 mm2, and EZ-RPE central subfield volume was 0.017 ± 0.012 mm3. Each of these measurements was significantly inversely correlated with visual acuity (P < 0.02). In addition, all of these measurements were significantly reduced compared to controls (all P ≤ 0.005). OCT-A showed a reduced parafoveal vessel density of 50.8% temporally compared to 53.8% nasally (P = 0.01) in the superficial vascular plexus. In the deep vascular plexus, similar findings were noted with a parafoveal vessel density of 56.7% temporally and 58.8% nasally (P = 0.01). Conclusions Abnormalities in EZ-RPE thickness, area, and volume are correlated with visual acuity in MacTel type 2, and may provide quantitative markers to measure disease progression and treatment response. OCT-A was a useful adjunct for determining disease severity.

A subset of subjects with atopic dermatitis (AD) are susceptible to serious infections with herpes simplex virus, called eczema herpeticum, or vaccina virus, called eczema vaccinatum.This National Institute of Allergy and Infectious Diseases-funded multicenter study was performed to establish a database of clinical information and biologic samples on subjects with AD with and without a history of eczema herpeticum (ADEH(+) and ADEH(-) subjects, respectively) and healthy control subjects. Careful phenotyping of AD subsets might suggest mechanisms responsible for disseminated viral infections and help identify at-risk individuals.We analyzed the data from 901 subjects (ADEH(+) subjects, n = 134; ADEH(-) subjects, n = 419; healthy control subjects, n = 348) enrolled between May 11, 2006, and September 16, 2008, at 7 US medical centers.ADEH(+) subjects had more severe disease based on scoring systems (Eczema Area and Severity Index and Rajka-Langeland score), body surface area affected, and biomarkers (circulating eosinophil counts and serum IgE, thymus and activation-regulated chemokine, and cutaneous T cell-attracting chemokine) than ADEH(-) subjects (P.001). ADEH(+) subjects were also more likely to have a history of food allergy (69% vs 40%, P.001) or asthma (64% vs 44%, P.001) and were more commonly sensitized to many common allergens (P.001). Cutaneous infections with Staphylococcus aureus or molluscum contagiosum virus were more common in ADEH(+) subjects (78% and 8%, respectively) than in ADEH(-) subjects (29% and 2%, respectively; P.001).Subjects with AD in whom eczema herpeticum develops have more severe T(H)2-polarized disease with greater allergen sensitization and more commonly have a history of food allergy, asthma, or both. They are also much more likely to experience cutaneous infections with S. aureus or molluscum contagiosum.