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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.

Background and ObjectivesPatients with multiple sclerosis (MS) may seek fertility treatment (FT)—including in vitro fertilization (IVF). Variable relapse risk after IVF has been reported in small historical cohorts, with more recent studies suggesting no change in annualized relapse rate (ARR). The objective of this study was to evaluate ARR 12 months pre-FT and 3 months post-FT in a multicenter cohort and identify factors associated with an increased risk of relapse.MethodsPatients with clinically isolated syndrome (CIS) or MS aged 18–45 years with at least 1 FT from January 1, 2010, to October 14, 2021, were retrospectively identified at 4 large academic MS centers. The exposed period of 3 months after FT was compared with the unexposed period of 12 months before FT. FTs included controlled ovarian stimulation followed by fresh embryo transfer (COS-ET), COS alone, embryo transfer (ET) alone, and oral ovulation induction (OI). The Wilcoxon signed rank test and mixed Poisson regression models with random effects were used to compare ARR pre-FT vs post-FT, with the incidence rate ratio (IRR) and 95% CI reported.ResultsOne hundred twenty-four FT cycles among 65 patients with MS (n = 56) or CIS (n = 9) were included: 61 COS-ET, 19 COS alone, 30 ET alone, and 14 OI. The mean age at FT was 36.5 ± 3.8 years, and the mean disease duration was 8.2 ± 5.0 years. Across 80 cycles with COS, only 5 relapses occurred among 4 unique patients within 3 months of treatment. The mean ARR after COS and before was not different (0.26 vs 0.25,p= 0.37), and the IRR was 0.95 (95% CI: 0.52–1.76,p= 0.88). No cycles with therapeutic disease-modifying therapies (DMTs) during COS had 3 months relapse (ARR 0 post-COS vs 0.18 pre-COS,p= 0.02, n = 34). Relapse rates did not vary by COS protocol. Among COS-ET cycles that achieved pregnancy (n = 43), ARR decreased from 0.26 to 0.09 (p= 0.04) within the first trimester of pregnancy. There were no relapses 3 months after ET alone and 1 relapse after OI.DiscussionIn this modern multicenter cohort of patients with MS undergoing diverse FTs, which included 43% on DMTs, we did not observe an elevated relapse risk after FT.

PURPOSE: To formulate an Epithelial Modulation index to differentiate between eyes with contact lens warpage and keratoconus. METHODS: Normal eyes and eyes with either contact lens warpage or keratoconus were scanned by a Fourier-domain optical coherence tomography (OCT) system. Maps of epithelial thickness and anterior surface mean curvature were generated and converted to deviation maps by subtracting the average maps from a healthy population. The Epithelial Modulation index was defined as the covariance between the two types of deviation maps. A logistic regression model was used to classify eyes as non-keratoconus (normal or warp-age) or keratoconus (manifest, subclinical, or forme fruste). RESULTS: The average Epithelial Modulation index value for normal eyes was −0.6 ± 1.0 µm/m. Eyes with keratoconus were characterized by coincident high anterior surface mean curvature and low epithelial thickness, resulting in a high Epithelial Modulation index (manifest: 103.0 ± 82.9 µm/m, subclinical: 37.0 ± 23.0 µm/m, forme fruste: 7.3 ± 13.2 µm/m). The Epithelial Modulation index was closer to normal for eyes with warpage (−1.9 ± 4.0 µm/m). The classification accuracy of the Epithelial Modulation index during five-fold cross-validation of the logistic regression model was 100 ± 0% for normal eyes and 99.0 ± 2.0% for eyes with warpage. The accuracy was 100 ± 0%, 100 ± 0%, and 53.1 ± 1.5% for the manifest, subclinical, and forme fruste keratoconus groups, respectively. CONCLUSIONS: The Epithelial Modulation index is useful in distinguishing eyes with secondary epithelial modulation (keratoconus) from those with primary epithelial deformation (contact lens–related warpage). [ J Refract Surg . 2022;38(2):112–119.]

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

The purpose of this study was to correct refractive error-associated bias in optical coherence tomography (OCT) and OCT angiography (OCTA) glaucoma diagnostic parameters.OCT and OCTA imaging were obtained from participants in the Hong Kong FAMILY cohort. The Avanti/AngioVue OCT/OCTA system was used to measure the peripapillary nerve fiber layer thickness (NFLT), peripapillary nerve fiber layer plexus capillary density (NFLP-CD), macular ganglion cell complex thickness (GCCT), and macular superficial vascular complex vascular density (SVC-VD). Healthy eyes, including ones with axial ametropia, were enrolled for analysis.A total of 1346 eyes from 792 participants were divided into 4 subgroups: high myopia (-6D), low myopia (-6D to -1D), emmetropia (-1D to 1D), and hyperopia (1D). After accounting for age, sex, and signal strength, multivariable regression showed strong dependence in most models for NFLT, GCCT, and NFLP-CD on axial eye length (AL), spherical equivalent (SE) refraction, and apparent optic disc diameter (DD). Optical analysis indicated that AL-related transverse optical magnification variations predominated over anatomic variations and were responsible for these trends. Compared to the emmetropic group, the false positive rates were significantly (Chi-square test P0.003) elevated in both myopia groups for NFLT, NFLP-CD, and GCCT. Regression-based adjustment of these diagnostic parameters with AL or SE significantly (McNemar test P0.03) reduced the elevated false positive rates.Myopic eyes are biased to have lower NFLT, GCCT, and NFLP-CD measurements. AL- and SE-based adjustments were effective in mitigating this bias.Adoption of these adjustments into commercial OCT systems may reduce false positive rates related to refractive error.

PURPOSE: To quantify the abnormal corneal thinning and posterior surface steepening that is observed in keratoconus with an Ectasia Index. METHODS: Optical coherence tomography (OCT) was used to image the corneas of normal individuals and patients with varying stages of keratoconus (manifest, subclinical, and forme fruste). Maps of corneal pachymetry and posterior surface mean curvature were generated, and an Ectasia Index was calculated by multiplying Gaussian fits obtained from the two types of maps. Repeated five-fold cross-validation was used to evaluate the ability of the Ectasia Index to differentiate between normal and keratoconic eyes. The classification performance of the Ectasia Index was compared to minimum pachymetry and maximum posterior mean curvature. RESULTS: Thirty-two eyes from 16 normal individuals, 89 eyes from 63 patients with manifest keratoconus, 16 eyes from 15 patients with subclinical keratoconus, and 26 eyes from 26 patients with forme fruste keratoconus were included in the study. During cross-validation, 100% of the eyes with manifest (89 of 89) and subclinical (16 of 16) keratoconus were correctly classified by the Ectasia Index. The average classification accuracy for the forme fruste keratoconus group was 63 ± 21% (16.4 of 26). The specificity for the normal group was 91 ± 10% (29.1 of 32). The Ectasia Index had a higher sensitivity for keratoconus detection and similar specificity in comparison to minimum pachymetry and maximum posterior mean curvature. CONCLUSIONS: The Ectasia Index could be a valuable additional metric for clinicians to consider when screening for keratoconus. [ J Refract Surg . 2022;38(8):502–510.]

PurposeTo assess the effects of algorithms and covariates in glaucoma diagnosis with optical coherence tomography angiography (OCTA).MethodsIn this prospective cross-sectional study, one eye each of 36 normal controls and 64 patients with glaucoma underwent 4.5 mm disc-centred and 6 mm macula-centred OCTA scans. The peripapillary nerve fibre layer plexus capillary density (NFLP-CD) and macular superficial vascular complex vessel density (SVC-VD) were measured using both a commercial algorithm (AngioAnalytics) and a custom algorithm (Center for Ophthalmic Optics & Lasers Angiography Reading Toolkit (COOL-ART)). The nerve fibre layer and ganglion cell complex thicknesses were measured on structural OCT.ResultsThe overall peripapillary NFLP-CD and macular SVC-VD measured with the two algorithms were highly correlated but poorly agreed. Among the normal controls, the perfusion measurements made by both algorithms were significantly correlated with age. AngioAnalytics measurements were also correlated with signal strength index, while COOL-ART measurements were not. These covariates were adjusted. The diagnostic accuracy, measured as the area under the receiver operating characteristic curve for glaucoma detection, was not significantly different between algorithms, between structural and perfusion parameters and between the peripapillary and macular regions (All p>0.05). The macular SVC-VD in the 6 mm square had a significantly higher diagnostic accuracy than that of the central 3 mm square area (p=0.005).ConclusionsAngioAnalytics and COOL-ART vessel density measurements are not interchangeable but potentially interconvertible. Age and signal strength are significant covariates that need to be considered. Both algorithms and both peripapillary and macular perfusion parameters have similarly good diagnostic accuracy comparable to structural OCT. A larger macular analytic area provides higher diagnostic accuracy.

Background Approximately 3.8% of adults worldwide have used cannabis in the past year. Understanding how cannabis use is associated with other health conditions is crucial for healthcare providers seeking to understand the needs of their patients, and for health policymakers. This paper analyzes the relationship between documented cannabis use disorders (CUD), cannabis use (CU) and other health diagnoses among primary care patients during a time when medical use of marijuana was permitted by state law in California, United States of America. Methods The study utilized primary care electronic health record (EHR) data from an academic health system, using a case–control design to compare diagnoses among individuals with CUD/CU to those of matched controls, and those of individuals with CUD diagnoses with individuals who had CU otherwise documented. Associations of documented CU and CUD with general medical conditions and health conditions associated with cannabis use (both medical and behavioral) were analyzed using conditional logistic regression. Results Of 1,047,463 patients with ambulatory encounters from 2013–2017, 729 (0.06%) had CUD diagnoses and 3,731 (0.36%) had CU documented in their EHR. Patients with documented CUD and CU patients had significantly (p Conclusion The prevalence of CUD and CU notation in EHR data from an academic health system was low, highlighting the need for improved screening in primary care. CUD and CU documentation were associated with increased risk for many health conditions, with the most elevated risk for behavioral health disorders and HIV/AIDS (among CUD-documented, but not CU-documented patients). Given the strong associations of CUD and CU documentation with health problems, it is important for healthcare providers to be prepared to identify CU and CUD, discuss the pros and cons of cannabis use with patients thoughtfully and empathically, and address cannabis-related comorbidities among these patients.

PURPOSE: To develop a coincident thinning (CTN) index to differentiate between keratoconic and healthy corneas using optical coherence tomography (OCT) measurements of pachymetry and epithelial thickness. METHODS: Pattern deviation maps of pachymetry and epithelial thickness were generated using Fourier-domain OCT images of the cornea. The co-localized thinning of the two maps was quantified using a novel CTN index, which was calculated from Gaussian fits of the regions of maximum relative thinning. The CTN index was validated using k-fold cross-validation, and its classification performance was compared to minimum pachymetry and maximum keratometry. RESULTS: A total of 82 normal eyes and 133 eyes within three groups of keratoconus severity were evaluated. The pattern deviation maps for the keratoconic eyes showed relative thinning that was larger in magnitude and more strongly correlated with the Gaussian function compared to normal eyes (all P < .01). The distance between the pachymetric and epithelial maximum relative thinning locations was significantly smaller for the keratoconic eyes than for the normal eyes (all P < .02). The CTN index was significantly larger for all three keratoconus groups compared to normal eyes (all P < .0001). The CTN index demonstrated a sensitivity of 100% in detecting manifest keratoconus, 100% for subclinical keratoconus, and 56% for forme fruste keratoconus. The overall classification accuracy was better for the CTN index (93%) than for minimum pachymetry (86%) and maximum keratometry (86%). CONCLUSIONS: The CTN index is a highly sensitive measure of coincident pachymetric and epithelial thinning. It provides valuable information for detecting and monitoring early to moderate keratoconus. [ J Refract Surg . 2020;36(11):757–765.]

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 To simulate 24-2 visual field (VF) using optical coherence tomographic angiography (OCTA) for glaucoma evaluation. Design Cross-sectional study. Methods One eye each of 39 glaucoma and 31 age-matched normal participants was scanned using 4.5-mm OCTA scans centered on the disc. The peripapillary retinal nerve fiber layer plexus capillary density (NFLP-CD, %area) was measured. The NFLP-CD and 24-2 VF maps were divided into 8 corresponding sectors using an extension of Garway-Heath scheme. Results Sector NFLP-CD was transformed to a logarithmic dB scale and converted to sector simulated VF deviation maps. Comparing simulated and actual 24-2 VF maps, the worst sector was in the same or adjacent location in the same hemisphere 97% of the time. VF mean deviation (VF-MD) was simulated by NFLP mean deviation (NFLP-MD). The differences between NFLP-MD and VF-MD in early, moderate, and severe glaucoma stages were −0.9 ± 2.0, 0.9 ± 2.9, and 5.8 ± 3.2 dB. NFLP-MD had better (P = .015) between-visit reproducibility (0.63 dB pooled standard deviation) than VF-MD (1.03 dB). NFLP-MD had a significantly higher sensitivity than VF-MD (P Conclusions OCTA-based simulated VF agreed well with actual 24-2 VF in terms of both the location and severity of glaucoma damage, with the exception of severe glaucoma in which the simulation tended to underestimate severity. The NFLP-MD had better reproducibility than actual VF-MD and holds promise for improving glaucoma monitoring. The NFLP-MD had better diagnostic accuracy than both VF-MD and overall NFL thickness and may be useful for early glaucoma diagnosis.

PURPOSE: To study longitudinal changes in retinal capillary circulation in eyes treated with iodine 125 (I(125)) plaque brachytherapy for uveal melanoma using OCT angiography (OCTA). DESIGN: Longitudinal prospective study of 21 patients undergoing treatment for uveal melanoma with I(125) plaque brachytherapy. Eyes with melanoma were imaged with OCTA before treatment and at 12-month intervals until 2 years after brachytherapy. PARTICIPANTS: After institutional review board approval, participants were enrolled prospectively from an academic ocular oncology clinic. METHODS: Peripapillary (4.5 × 4.5-mm) and macular (3 × 3-mm) OCTA scans were acquired with AngioVue (Optovue, Inc, Fremont, CA). MAIN OUTCOME MEASURES: The peripapillary nerve fiber layer plexus capillary density (NFLP_CD), macular superficial vascular complex vessel density (mSVC_VD), and foveal avascular zone (FAZ) area were calculated. RESULTS: Before treatment, no significant difference was found in the NFLP_CD, mSVC_VD, or FAZ area between eyes with melanoma and normal fellow eyes. By 24 months, 11 eyes had developed clinical signs of radiation retinopathy, radiation optic neuropathy, or both. In treated eyes, the NFLP_CD (48.4 ±.44.1%) was reduced at 12 months (46.7±5.0%; P = 0.04, Wilcoxon signed-rank test) and 24 months (44.5±6.1%; P < 0.001). Similarly, the mSVC_VD (48.4 2±3.6%) was reduced in treated eyes at 12 months (43.5±5.9%; P = 0.01) and 24 months (37.4±9.1%; P < 0.001). The FAZ area (0.26±0.11 mm(2)) increased in treated eyes at 12 months (0.35±0.22 mm(2); P = 0.009) and 24 months (0.81±1.03 mm(2); P = 0.001). When only eyes with clinically evident radiation changes were evaluated, the changes in NFLP_CD, mSVC_VD, and FAZ area were more pronounced. OCT angiography measurements correlated with both radiation dose and visual acuity. The mSVC_VD measured at 12 months was found to predict the development of clinically apparent radiation retinopathy within 1 year. CONCLUSIONS: OCT angiography demonstrated early emergence of peripapillary and macular capillary vasculature changes after I(125) plaque brachytherapy. OCT angiography provided a quantitative measurement of retinal capillary changes associated with ischemia that correlated with visual acuity and radiation dose and may predict future development of radiation-induced retinal toxicity.

PURPOSE: To assess the repeatability and accuracy of corneal astigmatism measurement with a spectral-domain optical coherence tomography (OCT) system (Avanti, Optovue) and compare them with Scheimpflug imaging (Pentacam HR, Oculus) and swept-source optical biometry (IOLMaster 700, Carl Zeiss Mediatec AG). SETTING: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA DESIGN: Prospective cross-sectional observational study. METHODS: Sixty pseudophakic eyes with monofocal non-toric intraocular lens that previously had refractive surgery were analyzed. To assess accuracy, simulated keratometric (SimK) and net corneal astigmatism, obtained from each device were compared with subjective manifest refraction astigmatism. Repeatability for corneal astigmatism was assessed for OCT and Pentacam HR by the coefficient of repeatability from three repeated measures. RESULTS: Compared to manifest refraction, SimK readings produced with-the-rule (WTR) astigmatic bias which was reduced for net astigmatism for all the three devices. Except for OCT net astigmatism, all instruments significantly overestimated the magnitude of the astigmatism (linear mixed-effects model (LMM), P < .05). OCT net astigmatism showed the highest accuracy for manifest astigmatism prediction with the smaller 95% confidence ellipse for the mean difference vector. OCT net mean absolute difference was 0.57 D, significantly smaller than that of the other modalities (LMM, P

This study reports the development of prototype swept-source optical coherence tomography (SS-OCT) technology for imaging the anterior eye. Advances in vertical-cavity surface-emitting laser (VCSEL) light sources, signal processing, optics and mechanical designs, enable a unique combination of high speed, long range, and deep penetration that addresses the challenges of anterior eye imaging. We demonstrate SS-OCT with a 325 kHz A-scan rate, 12.2 µm axial resolution (in air), and 15.5 mm depth range (in air) at 1310 nm wavelength. The ultrahigh 325 kHz A-scan rate not only facilitates biometry measurements by minimizing acquisition time and thus reducing motion, but also enables volumetric OCT for comprehensive structural analysis and OCT angiography (OCTA) for visualizing vasculature. The 15.5 mm (~ 11.6 mm in tissue) depth range spans all optical surfaces from the anterior cornea to the posterior lens capsule. The 1310 nm wavelength range enables structural OCT and OCTA deep in the sclera and through the iris. Achieving high speed and long range requires linearizing the VCSEL wavenumber sweep to efficiently utilize analog-to-digital conversion bandwidth. Dual channel recording of the OCT and calibration interferometer fringe signals, as well as sweep to sweep wavenumber compensation, is used to achieve invariant 12.2 µm (~ 9.1 µm in tissue) axial resolution and optimum point spread function throughout the depth range. Dynamic focusing using a tunable liquid lens extends the effective depth of field while preserving the lateral resolution. Improved optical and mechanical design, including parallax “split view” iris cameras and stable, ergonomic patient interface, facilitates accurate instrument positioning, reduces patient motion, and leads to improved imaging data yield and measurement accuracy. We present structural and angiographic OCT images of the anterior eye, demonstrating the unique imaging capabilities using representative scanning protocols which may be relevant to future research and clinical applications.

To measure net corneal astigmatism using optical coherence tomography (OCT) (Avanti) in individuals with keratoconus and compare the repeatability and accuracy with those obtained using Scheimpflug imaging (Pentacam HR).Casey Eye Institute, Portland, Oregon.Prospective cross-sectional observational study.Net corneal astigmatism was calculated in keratoconic and normal eyes using OCT and Scheimpflug imaging with 4 settings-pupil or vertex centration settings with a 3 or 4 mm circular analytical zone. Corneal elevation maps were obtained from OCT images and fitted with the Zernike polynomials to obtain net corneal astigmatism. Manifest refraction astigmatism was used to evaluate the accuracy of net corneal astigmatism measurements. The coefficient of repeatability from 2 repeated measures was calculated.46 eyes with manifest or subclinical keratoconus and 52 normal control eyes were analyzed. For OCT measurements in keratoconus, better accuracy was achieved with pupil centration and 3 mm analytical zone; however, better repeatability was achieved with vertex centration and 4 mm analytical zone (coefficient of repeatability = 0.53 diopters, the Fligner-Killeen test with Bonferroni adjustment Pamp;lt; .0017). Agreement with manifest refraction was significantly better with OCT compared with that using Pentacam HR (generalized mixed-effect model with Bonferroni adjustment Pamp;lt; .00625). No statistically significant difference was found between instruments or settings in control eyes.OCT was able to measure net corneal astigmatism with better accuracy and precision in keratoconic eyes than the Pentacam HR. Measurements may be more accurate using pupil centration and a smaller analytical zone in patients with keratoconus.

We demonstrate a handheld swept-source optical coherence tomography (OCT) system with a 400 kHz vertical-cavity surface-emitting laser (VCSEL) light source, a non-contact approach, and an unprecedented single shot 105° field of view (FOV). We also implemented a spiral scanning pattern allowing real-time visualization with improved scanning efficiency. To the best of our knowledge, this is the widest FOV achieved in a portable non-contact OCT retinal imaging system to date. Improvements to the FOV may aid the evaluation of retinal diseases such as retinopathy of prematurity, where important vitreoretinal changes often occur in the peripheral retina.

PLG0206 is an engineered antimicrobial peptide that has completed phase 1 clinical studies. A prospective study was completed on explanted implants from chronic periprosthetic joint infections (n = 17). At a concentration of 1 mg/mL for 15 min, there was a mean 4-log10 reduction (range, 1 to 7) in the bacterial CFU identified from the implants. IMPORTANCE Chronically infected prosthetics of the knee were exposed to PLG0206, an engineered antimicrobial peptide, at a concentration of 1 mg/mL for 15 min. A mean 4-log10 reduction (range, 1 to 7) in the number of bacteria occurred, which may translate to improved clinical outcomes for persons with prosthetic joint infection of the knee.

Background Differentiated service delivery (DSD) models are recommended for stable people living with HIV on antiretroviral therapy (ART) but there are few rigorous evaluations of patient outcomes. Methods Adherence clubs (ACs) are a form of DSD run by community health workers at community venues with 2–4 monthly ART refills and annual nurse assessments). Clinic-based care involves 2-monthly ART refills and 4-monthly nurse/doctor assessments. We compared virologic outcomes in stable adults randomised to ACs at four months post-ART initiation to those randomised to primary health care (PHC) ART clinics through 12 months on ART in Cape Town, South Africa (NCT03199027). We hypothesised that adults randomised to ACs would be more likely to be virally suppressed at 12 months post-ART initiation, versus adults randomised to continued PHC care. We enrolled consecutive adults on ART for 3–5 months who met local DSD [‘adherence clubs’ (AC)] eligibility (clinically stable, VL Results Between January 2017 and April 2018, 220 adults were randomised (mean age 35 years; 67% female; median ART duration 18 weeks); 85% and 94% of participants randomised to ACs and PHCs attended their first service visit on schedule respectively. By 12 months on ART, 91% and 93% randomised to ACs and PHCs had a VL Conclusion Stable adults referred to DSDs at 4 months post-ART initiation had comparable virologic outcomes at 12 months on ART versus PHC clinics, with no evidence of superiority. Further research on long-term outcomes is required.

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

To quantify the level of decision regret in women ≥42 years of age after autologous in vitro fertilization (IVF) and identify factors associated with moderate-to-severe regret.Cross-sectional survey.Academic center.Ninety-four women ≥42 years of age who underwent autologous IVF between 2012 and 2018.None.Decision regret score, with25 as threshold for moderate-to-severe regret.The overall response rate was 22%. Respondents had a median age of 43 years at the time of IVF. The median and mean decision regret scores were 10 and 17.1 (range, 0-75), respectively. Seventy-three percent (n = 69) had absent-to-mild regret (score, 0-25), and 27% (n = 25) had moderate-to-severe regret (score,25) after IVF. Having no live births was associated with increased regret (odds ratio [OR], 22 [95% confidence interval {CI}, 2.82-171.82]). Among those who were unsuccessful, 40% (n = 24) had moderate-to-severe regret. Predictors for moderate-to-severe regret in this group included the lack of insurance coverage (OR, 0.33 [95% CI, 0.12-0.99]). Conversely, the perceived adequacy of information/counseling (OR, 0.44 [95% CI, 0.2-0.77]) and the perceived adequacy of emotional support (OR, 0.29 [95% CI, 0.15-0.55]) were protective factors inversely correlated with regret.Autologous IVF carries a low success rate and a considerable risk of decision regret in women ≥42 years of age. In those who were unsuccessful, the perceived adequacy of information and that of emotional support were protective factors against increased regret. Although concluding from a small, selected pool, our results strongly suggest that ample counseling and psychological support should be particularly emphasized within this patient population.

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

To construct an optical coherence tomography (OCT) nerve fiber layer (NFL) parameter that has maximal correlation and agreement with visual field (VF) mean deviation (MD). The NFL_MD parameter in dB scale was calculated from the peripapillary NFL thickness profile nonlinear transformation and VF area-weighted averaging. From the Advanced Imaging for Glaucoma study, 245 normal, 420 pre-perimetric glaucoma (PPG), and 289 perimetric glaucoma (PG) eyes were selected. NFL_MD had significantly higher correlation (Pearson R: 0.68 vs 0.55, p

PURPOSE: To detect plexus-specific peripapillary retinal perfusion defects in glaucoma using projection-resolved optical coherence tomography angiography (PR-OCTA). DESIGN: Prospective cross-sectional study. METHODS: One eye each of 45 perimetric glaucoma participants and 37 age-matched normal participants were scanned using 4.5-mm OCTA scans centered on the disc. The PR-OCTA algorithm removed flow projection artifacts in OCT angiograms. Five en face OCTA slabs were analyzed: nerve fiber layer plexus (NFLP), ganglion cell layer plexus (GCLP), superficial vascular complex (SVC = NFLP + GCLP), deep vascular complex (DVC), and all plexuses combined. Peripapillary retinal capillary density (CD) and vessel density (VD) were calculated using a reflectance-compensated algorithm. RESULTS: Focal capillary dropout could be visualized more clearly in the NFLP than the other slabs. The NFLP, SVC and all-plexus CD in the glaucoma group were significantly lower (P

Background Nationwide efforts seek to address the opioid epidemic by increasing access to medications for opioid use disorder (OUD), particularly with buprenorphine. A poorly understood challenge is that among individuals with OUD who do receive buprenorphine, many do not adhere to the pharmacotherapy long enough to achieve sustained benefits. We aimed to identify factors associated with buprenorphine treatment utilization over time. Methods We used random-intercept modeling to identify factors associated with buprenorphine treatment utilization over 2 years after first follow-up by 789 individuals with OUD who had participated in a multi-site randomized clinical trial of buprenorphine compared to methadone. Key predictors were participants' reports of buprenorphine treatment accessibility and acceptability (assessed at first follow-up) and their interaction effects, controlling for baseline randomization status, sociodemographics, and other covariates. Results Approximately 9.3–11.2% of participants utilized buprenorphine treatment over the 2 years of follow-up. Interaction effects indicated that individuals who perceived buprenorphine to be both accessible and acceptable were most likely to use buprenorphine during follow-up, controlling for other factors. In contrast, individuals who perceived buprenorphine to be unacceptable were least likely to use buprenorphine, regardless the level of perceived access to the medication. Buprenorphine treatment utilization was also negatively associated with Hispanic ethnicity, West coast context, and cumulative months receiving methadone treatment and incarceration during follow-up. Conclusions To engage more individuals with OUD in long-term treatment with buprenorphine, interventions should target buprenorphine treatment acceptability, in addition to increasing buprenorphine access, and tailor efforts to meet the needs of vulnerable populations. Trial registration The START Follow-up Study on ClinicalTrials.gov ( NCT01592461 ).

Author(s): Fung, Constance H; Martin, Jennifer L; Hays, Ron D; Col, Nananda; Patterson, Emily S; Josephson, Karen; Mitchell, Michael N; Grinberg, Austin; Aysola, Ravi; Song, Yeonsu; Dzierzewski, Joseph M; Liang, Li-Jung; Huang, David; Zeidler, Michelle; Alessi, Cathy

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

BackgroundBiological tissues consist of heterogenous populations of cells. Because gene expression patterns from bulk tissue samples reflect the contributions from all cells in the tissue, understanding the contribution of individual cell types to the overall gene expression in the tissue is fundamentally important. We recently developed a computational method, CDSeq, that can simultaneously estimate both sample-specific cell-type proportions and cell-type-specific gene expression profiles using only bulk RNA-Seq counts from multiple samples. Here we present an R implementation of CDSeq (CDSeqR) with significant performance improvement over the original implementation in MATLAB and an added new function to aid cell type annotation. The R package would be of interest for the broader R community.ResultWe developed a novel strategy to substantially improve computational efficiency in both speed and memory usage. In addition, we designed and implemented a new function for annotating the CDSeq estimated cell types using single-cell RNA sequencing (scRNA-seq) data. This function allows users to readily interpret and visualize the CDSeq estimated cell types. In addition, this new function further allows the users to annotate CDSeq-estimated cell types using marker genes. We carried out additional validations of the CDSeqR software using synthetic, real cell mixtures, and real bulk RNA-seq data from the Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) project.ConclusionsThe existing bulk RNA-seq repositories, such as TCGA and GTEx, provide enormous resources for better understanding changes in transcriptomics and human diseases. They are also potentially useful for studying cell-cell interactions in the tissue microenvironment. Bulk level analyses neglect tissue heterogeneity, however, and hinder investigation of a cell-type-specific expression. The CDSeqR package may aid in silico dissection of bulk expression data, enabling researchers to recover cell-type-specific information.

The emergence and rapid global spread of SARS-CoV-2 demonstrates the importance of infectious disease surveillance, particularly during the early stages. Viral genomes can provide key insights into transmission chains and pathogenicity. Nasopharyngeal swabs were obtained from thirty-two of the first SARS-CoV-2 positive cases (March 18–30) in Kingston Ontario, Canada. Viral genomes were sequenced using Ion Torrent (n = 24) and MinION (n = 27) sequencing platforms. SARS-CoV-2 genomes carried forty-six polymorphic sites including two missense and three synonymous variants in the spike protein gene. The D614G point mutation was the predominate viral strain in our cohort (92.6%). A heterozygous variant (C9994A) was detected by both sequencing platforms but filtered by the ARTIC network bioinformatic pipeline suggesting that heterozygous variants may be underreported in the SARS-CoV-2 literature. Phylogenetic analysis with 87,738 genomes in the GISAID database identified global origins and transmission events including multiple, international introductions as well as community spread. Reported travel history validated viral introduction and transmission inferred by phylogenetic analysis. Molecular epidemiology and evolutionary phylogenetics may complement contact tracing and help reconstruct transmission chains of emerging diseases. Earlier detection and screening in this way could improve the effectiveness of regional public health interventions to limit future pandemics.

STUDY OBJECTIVES: Person-centered obstructive sleep apnea (OSA) care is a collaborative approach that is respectful of an individual’s health priorities. Informed decision-making is essential to person-centered care, especially as patients age. In a feasibility study, we evaluated the effects of a new decision aid (Decide2Rest) on OSA treatment decision-making in older adults. METHODS: Patients (aged ≥ 60 years) with newly diagnosed OSA were recruited from two health care systems and randomized either to Decide2Rest or to a control program. Postintervention outcomes included 1) Decisional Conflict Scale (0–100, where 0 = low and 100 = high conflict), which measures perceptions of uncertainty, whether decisions reflect what matters most to patients, and whether patients feel supported in decision-making; 2) Preparation for Decision-Making scale (0–100, where 0 = least and 100 most prepared); and 3) OSA knowledge (0–100, where 0 = poor and 100 = outstanding). Multivariable linear regression models examined relationships between Decide2Rest and outcomes (Decisional Conflict Scale, Preparation for Decision-Making, OSA knowledge). RESULTS: Seventy-three patients were randomized to Decide2Rest (n = 36; mean age, 69 years; 72% male) vs control (n = 37; mean age, 69 years; 70% male). Results from the regressions, controlling for study site, indicate that the Decide2Rest program resulted in less decisional conflict (20.5 vs 32.7 on the Decisional Conflict Scale; P = .014), more preparedness for decision-making (87.8 vs 66.2 on the Preparation for Decision-Making scale; P < .001), and greater OSA knowledge (75.1 vs 65.3 OSA knowledge score; P = .04) scores than in the control group. CONCLUSIONS: The Decide2Rest program promotes person-centered OSA decision-making for older patients with newly diagnosed OSA. Future studies are needed to optimize implementation of the program. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov, Name: Improving Older Adults’ Decision-Making for OSAT (eDecide2Rest); URL: https://clinicaltrials.gov/ct2/show/NCT03138993; Identifier: NCT03138993. CITATION: Fung CH, Martin JL, Liang LJ, et al. Efficacy of a patient decision aid for improving person-centered decision-making by older adults with obstructive sleep apnea. J Clin Sleep Med. 2021;17(2):121–128.

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.

PRECIS An association between macular vessel density (VD) and total retinal blood flow (TRBF) was demonstrated in subjects with primary open-angle glaucoma (POAG) and visual field (VF) loss. PURPOSE The purpose of this study was to report relationships of macular VD metrics and TRBF in POAG. MATERIALS AND METHODS A total of 24 POAG and 19 healthy control subjects participated in the study. Subjects underwent optical coherence tomography and angiography for measurements of inner retinal thickness (IRT), VD, and spacing between large vessels (SLV) and small vessels (SSV). Doppler optical coherence tomography imaging was performed for TRBF measurement. In POAG subjects, automated perimetry was performed and VF loss expressed as mean deviation was measured. RESULTS Compared with the control group, POAG group had decreased VD, TRBF, IRT, and increased SLV (P

Background With the expansion of online patient portals linked to electronic health records in safety-net health care settings, we need more data on the use of these websites by patients with limited English proficiency (LEP) in order to guide their continued design, implementation, and evaluation as portals for the underserved. Methods Cross-sectional portal data for the Los Angeles County Department of Health Services, the second largest safety-net system in the nation. We examined differences in portal use across language (English vs. non-English/LEP), covering four years since implementation. Results Of 425,281 patients assigned to primary care as of March 2019, 55,190 (13%) unique portal enrollments were registered. Among 54,981 portal users, LEP users had lower adjusted odds of using an active portal function (e.g., medication refill) vs. English-speakers. Conclusions Even among those registered to access portals, these websites are underused, particularly by LEP patients. All systems must facilitate use for these populations, especially for time-saving active functions, which can improve outcomes. Health systems must prioritize design/usability as a factor to counter LEP underuse.

Significance Many environmental pollutants act as endocrine disruptors that interfere with normal endocrine regulation and promote adverse effects in humans. As a major target of xenobiotics, the pregnane X receptor (PXR) is known to play opposite roles by both facilitating their clearance and mediating their toxic effects. Here, we use structural and functional approaches to describe two converging mechanisms leading to a robust synergistic stimulation of the PXR pathway by mixtures of three chemicals exhibiting very low efficacy when administered separately. This “cocktail effect” relies on two cooperative binding processes that enhance both ligand binding affinity and recruitment of transcriptional coactivators. Our findings show how chemical mixtures may alter physiology and homeostasis at concentrations where individual components are considered safe., Humans are chronically exposed to mixtures of xenobiotics referred to as endocrine-disrupting chemicals (EDCs). A vast body of literature links exposure to these chemicals with increased incidences of reproductive, metabolic, or neurological disorders. Moreover, recent data demonstrate that, when used in combination, chemicals have outcomes that cannot be predicted from their individual behavior. In its heterodimeric form with the retinoid X receptor (RXR), the pregnane X receptor (PXR) plays an essential role in controlling the mammalian xenobiotic response and mediates both beneficial and detrimental effects. Our previous work shed light on a mechanism by which a binary mixture of xenobiotics activates PXR in a synergistic fashion. Structural analysis revealed that mutual stabilization of the compounds within the ligand-binding pocket of PXR accounts for the enhancement of their binding affinity. In order to identify and characterize additional active mixtures, we combined a set of cell-based, biophysical, structural, and in vivo approaches. Our study reveals features that confirm the binding promiscuity of this receptor and its ability to accommodate bipartite ligands. We reveal previously unidentified binding mechanisms involving dynamic structural transitions and covalent coupling and report four binary mixtures eliciting graded synergistic activities. Last, we demonstrate that the robust activity obtained with two synergizing PXR ligands can be enhanced further in the presence of RXR environmental ligands. Our study reveals insights as to how low-dose EDC mixtures may alter physiology through interaction with RXR–PXR and potentially several other nuclear receptor heterodimers.

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.

Importance Data on the efficacy of hydroxychloroquine for the treatment of coronavirus disease 2019 (COVID-19) are needed. Objective To determine whether hydroxychloroquine is an efficacious treatment for adults hospitalized with COVID-19. Design, Setting, and Participants This was a multicenter, blinded, placebo-controlled randomized trial conducted at 34 hospitals in the US. Adults hospitalized with respiratory symptoms from severe acute respiratory syndrome coronavirus 2 infection were enrolled between April 2 and June 19, 2020, with the last outcome assessment on July 17, 2020. The planned sample size was 510 patients, with interim analyses planned after every 102 patients were enrolled. The trial was stopped at the fourth interim analysis for futility with a sample size of 479 patients. Interventions Patients were randomly assigned to hydroxychloroquine (400 mg twice daily for 2 doses, then 200 mg twice daily for 8 doses) (n = 242) or placebo (n = 237). Main Outcomes and Measures The primary outcome was clinical status 14 days after randomization as assessed with a 7-category ordinal scale ranging from 1 (death) to 7 (discharged from the hospital and able to perform normal activities). The primary outcome was analyzed with a multivariable proportional odds model, with an adjusted odds ratio (aOR) greater than 1.0 indicating more favorable outcomes with hydroxychloroquine than placebo. The trial included 12 secondary outcomes, including 28-day mortality. Results Among 479 patients who were randomized (median age, 57 years; 44.3% female; 37.2% Hispanic/Latinx; 23.4% Black; 20.1% in the intensive care unit; 46.8% receiving supplemental oxygen without positive pressure; 11.5% receiving noninvasive ventilation or nasal high-flow oxygen; and 6.7% receiving invasive mechanical ventilation or extracorporeal membrane oxygenation), 433 (90.4%) completed the primary outcome assessment at 14 days and the remainder had clinical status imputed. The median duration of symptoms prior to randomization was 5 days (interquartile range [IQR], 3 to 7 days). Clinical status on the ordinal outcome scale at 14 days did not significantly differ between the hydroxychloroquine and placebo groups (median [IQR] score, 6 [4-7] vs 6 [4-7]; aOR, 1.02 [95% CI, 0.73 to 1.42]). None of the 12 secondary outcomes were significantly different between groups. At 28 days after randomization, 25 of 241 patients (10.4%) in the hydroxychloroquine group and 25 of 236 (10.6%) in the placebo group had died (absolute difference, −0.2% [95% CI, −5.7% to 5.3%]; aOR, 1.07 [95% CI, 0.54 to 2.09]). Conclusions and Relevance Among adults hospitalized with respiratory illness from COVID-19, treatment with hydroxychloroquine, compared with placebo, did not significantly improve clinical status at day 14. These findings do not support the use of hydroxychloroquine for treatment of COVID-19 among hospitalized adults. Trial Registration ClinicalTrials.gov:NCT04332991

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: To evaluate nerve fiber layer (NFL) reflectance for glaucoma diagnosis. Methods: Participants were imaged with 4.5X4.5-mm volumetric disc scans using spectral-domain optical coherence tomography (OCT). The normalized NFL reflectance map was processed by an azimuthal filter to reduce directional reflectance bias due to variation of beam incidence angle. The peripapillary area of the map was divided into 160 superpixels. Average reflectance was the mean of superpixel reflectance. Low-reflectance superpixels were identified as those with NFL reflectance below the 5 percentile normative cutoff. Focal reflectance loss was measure by summing loss in low-reflectance superpixels. Results: Thirty-five normal, 30 pre-perimetric and 35 perimetric glaucoma participants were enrolled. Azimuthal filtering improved the repeatability of the normalized NFL reflectance, as measured by the pooled superpixel standard deviation (SD), from 0.73 to 0.57 dB (p, pages: 31; Tables: 6; Figures: 9

Purpose To detect keratoconus using optical coherence tomography (OCT) corneal map parameters and patterns. Setting Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA DESIGN:: Cross-sectional observational study. Methods A spectral-domain OCT was used to acquire corneal and epithelial thickness maps in normal, manifest keratoconic, subclinical keratoconic, and forme fruste keratoconic (FFK) eyes. A two-step decision tree was designed. An eye will be classified as keratoconus if both decision tree conditions are met: First, at least one of the four quantitative corneal thickness (minimum, minimum-maximum, superonasal-inferotemporal) and epithelial thickness (standard deviation) map parameters exceed cutoff values. Second, presence of both concentric thinning pattern on the epithelial thickness map and coincident thinning patterns on corneal and epithelial thickness maps by visual inspection. Results The study was compromised of 54 eyes from 29 normal participants, 91 manifest keratoconic eyes from 65 patients, 12 subclinical keratoconic eyes from 11 patients, and 19 FFK eyes from 19 patients. The decision tree correctly classified all normal eyes (100% specificity), and had good sensitivities for detecting manifest keratoconus (97.8%), subclinical keratoconus (100.0%), and FFK (73.7%). Conclusions The two-step decision tree provided a useful tool to detect keratoconus including cases at early disease stages (subclinical keratoconus and FFK). OCT corneal and epithelial thickness map parameters and patterns can be used in conjunction with topography to improve keratoconus screening.

Purpose The Medicare cost savings from the use of bevacizumab in the United States for the treatment of exudative age-related macular degeneration (AMD) were estimated by replacing the use of bevacizumab with ranibizumab and aflibercept. Design Retrospective trend study. Methods Main outcome measures were spending by Medicare as tracked by Current Procedural Terminology (CPT) codes for intravitreal injections (67028) and treatment-specific J-codes (J0178, J2778, J9035, J3490, and J3590) for inhibitors of vascular endothelial growth factor. These claims were identified from the Medicare Provider Utilization and Payment Data from the Centers for Medicare and Medicaid Services among fee-for-service (FFS) Medicare beneficiaries from 2012 to 2015. The 2008 claims were acquired from the 100% fee-for-service (FFS) Part B Medicare Claims File. Results The use of bevacizumab from 2008 to 2015 resulted in an estimated savings of $17.3 billion, which corresponded to a $13.8 billion savings to Medicare and a $3.5 billion savings to patients. This amount underestimated the actual cost savings to Medicare providers, since approximately 30% of Medicare-eligible recipients received care within Medicare Advantage plans and were not included in this analysis. Conclusions The cost savings from the use of bevacizumab from 2008 to 2015 for Medicare fee-for-service patients undergoing treatment for exudative AMD was estimated at $17.3 billion. Additional savings over the $17.3 billion would have accrued from the use of bevacizumab if diagnostic categories such as diabetic macular edema and retinal vein occlusion were included in this study.

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 compare patient and Medicare savings from the use of optical coherence tomography (OCT) in guiding therapy for neovascular age-related macular degeneration (nvAMD) to the research investments made in developing OCT by the National Institutes of Health (NIH) and the National Science Foundation (NSF). Design Observational cohort study. Methods Main outcome measures were spending by Medicare as tracked by Current Procedural Terminology codes on intravitreal injections (67028), retinal OCT imaging (92134), and anti–vascular endothelial growth factor (anti-VEGF) treatment–specific J-codes (J0178, J2778, J9035, J3490, and J3590). These claims were identified from the Medicare Provider Utilization and Payment Data from the Centers for Medicare and Medicaid Services among fee-for-service (FFS) Medicare beneficiaries from 2012 to 2015; 2008 claims were acquired from the 100% FFS Part B Medicare Claims File. OCT research costs were determined by searching for grants awarded by NIH and NSF from inception to 2015. All costs and savings were discounted by 3% annually and adjusted for inflation to 2015 dollars. Results From 2008 to 2015, the United States government and nvAMD patients have accrued an estimated savings of $9.0 billion and $2.2 billion, respectively, from the use of OCT to guide personalized anti-VEGF treatment. The $9.0 billion represents a 21-fold return on government investment into developing the technology through NIH and NSF grants. Conclusions Although an overall cost-benefit ratio of government-sponsored research is difficult to estimate because the benefit may be diffuse and delayed, the investment in OCT over 2 decades has been recouped many times over in just a few years through better personalized therapy.

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 compare longitudinal glaucoma progression detection using optical coherence tomography (OCT) and visual field (VF).Validity assessment.We analyzed subjects with more than 4 semi-annual follow-up visits (every 6 months) in the multicenter Advanced Imaging for Glaucoma Study. Fourier-domain optical coherence tomography (OCT) was used to map the thickness of the peripapillary retinal nerve fiber layer (NFL) and ganglion cell complex (GCC). OCT-based progression detection was defined as a significant negative trend for either NFL or GCC. VF progression was reached if either the event or trend analysis reached significance.The analysis included 356 glaucoma suspect/preperimetric glaucoma (GS/PPG) eyes and 153 perimetric glaucoma (PG) eyes. Follow-up length was 54.1 ± 16.2 months for GS/PPG eyes and 56.7 ± 16.0 for PG eyes. Progression was detected in 62.1% of PG eyes and 59.8% of GS/PPG eyes by OCT, significantly (P .001) more than the detection rate of 41.8% and 27.3% by VF. In severity-stratified analysis of PG eyes, OCT had significantly higher detection rate than VF in mild PG (63.1% vs. 38.7%, P.001), but not in moderate and advanced PG. The rate of NFL thinning slowed dramatically in advanced PG, but GCC thinning rate remained relatively steady and allowed good progression detection even in advanced disease. The Kaplan-Meier time-to-event analyses showed that OCT detected progression earlier than VF in both PG and GS/PPG groups.OCT is more sensitive than VF for the detection of progression in early glaucoma. While the utility of NFL declines in advanced glaucoma, GCC remains a sensitive progression detector from early to advanced stages.

PURPOSE: To measure the change of peripapillary retinal vessel density (VD) in eyes with a history of acute primary angle-closure glaucoma (PACG). DESIGN: Case-control study. METHODS: Twenty-one consecutive Chinese patients with history of unilateral acute PACG were enrolled. Eyes with acute PACG constituted the case group, while the contralateral eyes without attack constituted the control. All patients underwent ophthalmic examinations including best-corrected visual acuity, intraocular pressure, and visual field (VF). Spectral-domain optical coherence tomography (SD-OCT) was used to obtain both structural OCT and OCT angiography (OCTA). Structural OCT scans provided thickness measurements of the peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell complex (GCC). OCTA was used to measure all-plexus peripapillary retinal VD. RESULTS: In unaffected eyes, a dense microvascular network surrounded the disc on all-plexus retinal OCTA. The vascular network was visibly attenuated and focal capillary dropout was evident in acute PACG eyes. The peripapillary VD in acute PACG eyes was 66.6% ± 17.3% (mean ± standard deviation), which was significantly (P < .01) reduced compared to 87.2% ± 8.6% in the unaffected eyes. In acute PACG eyes, peripapillary retinal VD was positively correlated with RNFL and GCC thicknesses (P < .001 each) and negatively correlated with VF mean deviation (P = .002) and cup-to-disc ratio (P = .0064). In unaffected eyes, there were no correlations between peripapillary retinal VD and glaucoma-related parameters. CONCLUSIONS: In acute PACG eyes, peripapillary retinal VD decreased significantly compared with the contralateral unaffected eyes. Peripapillary retinal VD was significantly correlated with other glaucomatous changes.

BACKGROUND: After a single-center trial and observational studies suggesting that early, goal-directed therapy (EGDT) reduced mortality from septic shock, three multicenter trials (ProCESS, ARISE, and ProMISe) showed no benefit. This meta-analysis of individual patient data from the three recent trials was designed prospectively to improve statistical power and explore heterogeneity of treatment effect of EGDT. METHODS: We harmonized entry criteria, intervention protocols, outcomes, resource-use measures, and data collection across the trials and specified all analyses before unblinding. After completion of the trials, we pooled data, excluding the protocol-based standard-therapy group from the ProCESS trial, and resolved residual differences. The primary outcome was 90-day mortality. Secondary outcomes included 1-year survival, organ support, and hospitalization costs. We tested for treatment-by-subgroup interactions for 16 patient characteristics and 6 care-delivery characteristics. RESULTS: We studied 3723 patients at 138 hospitals in seven countries. Mortality at 90 days was similar for EGDT (462 of 1852 patients [24.9%]) and usual care (475 of 1871 patients [25.4%]); the adjusted odds ratio was 0.97 (95% confidence interval, 0.82 to 1.14; P=0.68). EGDT was associated with greater mean (±SD) use of intensive care (5.3±7.1 vs. 4.9±7.0 days, P=0.04) and cardiovascular support (1.9±3.7 vs. 1.6±2.9 days, P=0.01) than was usual care; other outcomes did not differ significantly, although average costs were higher with EGDT. Subgroup analyses showed no benefit from EGDT for patients with worse shock (higher serum lactate level, combined hypotension and hyperlactatemia, or higher predicted risk of death) or for hospitals with a lower propensity to use vasopressors or fluids during usual resuscitation. CONCLUSIONS: In this meta-analysis of individual patient data, EGDT did not result in better outcomes than usual care and was associated with higher hospitalization costs across a broad range of patient and hospital characteristics. (Funded by the National Institute of General Medical Sciences and others; PRISM ClinicalTrials.gov number, NCT02030158.)

Purpose To examine the prevalence of comorbid chronic pain among patients with opioid use disorder (OUD) and to compare other comorbidities (substance use disorder (SUD), mental health disorders, health/disease conditions) among patients in four categories: no chronic pain (No Pain), OUD prior to pain (OUD First), OUD and pain at the same time (Same Time), or pain condition prior to OUD (Pain First). Methods Using an electronic health record (EHR) database from 2006–2015, the study assessed 5307 adult patients with OUD in a large healthcare system; 35.6% were No Pain, 9.7% were OUD First, 14.9% were Same Time, and 39.8% were Pain First. Results Most OUD patients (64.4%) had chronic pain conditions, and among them 61.8% had chronic pain before their first OUD diagnosis. Other SUDs occurred more frequently among OUD First patients than among other groups in terms of alcohol (33.4% vs. 25.4% for No Pain, 20.7% for Same Time, and 20.3% for Pain First), cocaine (19.0%, vs. 13.8%, 9.4%, 7.1%), and alcohol or drug-induced disorders. OUD First patients also had the highest rates of HIV (4.7%) and hepatitis C virus (HCV; 28.2%) among the four groups. Pain First patients had the highest rates of mental disorder (81.7%), heart disease (72.0%), respiratory disease (68.4%), sleep disorder (41.8%), cancer (23.4%), and diabetes (19.3%). Conclusions The alarming high rates of chronic pain conditions occurring before OUD and the associated severe mental health and physical health conditions require better models of assessment and coordinated care plans to address these complex medical conditions.

The three‐dimensional dose (3D) distribution of intensity‐modulated radiation therapy (IMRT) was verified based on electronic portal imaging devices (EPIDs), and the results were analyzed. Thirty IMRT plans of different lesions were selected for 3D EPID‐based dose verification. The gamma passing rates of the 3D dose verification‐based EPID system (Edose, Version 3.01, Raydose, Guangdong, China) and Delta4 measurements were then compared with treatment planning system (TPS) calculations using global gamma criteria of 5%/3 mm, 3%/3 mm, and 2%/2 mm. Furthermore, the dose–volume histograms (DVHs) for planning target volumes (PTVs) as well as organs at risk (OARs) were analyzed using Edose. For dose verification of the 30 treatment plans, the average gamma passing rates of Edose reconstructions under the gamma criteria of 5%/3 mm, 3%/3 mm, and 2%/2 mm were (98.58 ± 0.93)%, (95.67 ± 1.97)%, and (83.13 ± 4.53)%, respectively, whereas the Delta4 measurement results were (99.14% ± 1.16)%, (95.81% ± 2.88)%, and (84.74% ± 7.00)%, respectively. The dose differences between Edose reconstructions and TPS calculations were within 3% for D95%, D98%, and Dmean in each PTV, with the exception that the D98% of the PTV‐clinical target volume (CTV) in esophageal carcinoma cases was (3.21 ± 2.33)%. However, the larger dose deviations in OARs (such as lens, parotid gland, optic nerve, and spinal cord) can be determined based on DVHs. The difference was particularly obvious for OARs with small volumes; for example, the maximum dose deviation for the lens reached (−6.12 ± 5.28)%. A comparison of the results obtained with Edose and Delta4 indicated that the Edose system could be applied for 3D pretreatment dose verification of IMRT. This system could also be utilized to evaluate the gamma passing rate of each treatment plan. Furthermore, the detailed dose distributions of PTVs and OARs could be indicated based on DVHs, providing additional reliable data for quality assurance in a clinic setting.

To analyze transepithelial phototherapeutic keratectomy (PTK) results using optical coherence tomography (OCT) and develop a model to guide the laser dioptric and depth settings.Casey Eye Institute, Portland, Oregon, USA.Prospective nonrandomized case series.Patients with superficial corneal opacities and irregularities had transepithelial PTK with a flying-spot excimer laser by combining wide-zone myopic and hyperopic astigmatic ablations. Optical coherence tomography was used to calculate corneal epithelial lenticular masking effects, guide refractive laser settings, and measure opacity removal. The laser ablation efficiency and the refractive outcome were investigated using multivariate linear regression models.Twenty-six eyes of 20 patients received PTK to remove opacities and irregular astigmatism due to scar, dystrophy, radial keratotomy, or previous corneal surgeries. The uncorrected distance visual acuity and corrected distance visual acuity were significantly improved (P .01) by 3.7 Snellen lines and 2.0 Snellen lines, respectively, to a mean of 20/41.2 and 20/22.0, respectively. Achieved laser ablation depths were 31.3% (myopic ablation) and 63.0% (hyperopic ablation) deeper than the manufacturer's nomogram. The spherical equivalent of the corneal epithelial lenticular masking effect was 0.73 diopter ± 0.61 (SD). The refractive outcome highly correlated to the laser settings and epithelial lenticular masking effect (Pearson R = 0.96, P .01). The ablation rate of granular dystrophy opacities appeared to be slower. Smoothing ablation under masking fluid was needed to prevent focal steep islands in these cases.The OCT-measured ablation depth efficiency could guide opacity removal. The corneal epithelial lenticular masking effect could refine the spherical refractive nomogram to achieve a better refractive outcome after transepithelial ablation.

The advent of super‐resolution microscopy allowed for new insights into cellular and physiological processes of normal and diseased cells. In this study, we report for the first time on the super‐resolved DNA structure of buccal cells from patients with Alzheimer's disease (AD) versus age‐ and gender‐matched healthy, non‐caregiver controls. In this super‐resolution study cohort of 74 participants, buccal cells were collected and their spatial DNA organization in the nucleus examined by 3D Structured Illumination Microscopy (3D‐SIM). Quantitation of the super‐resolution DNA structure revealed that the nuclear super‐resolution DNA structure of individuals with AD significantly differs from that of their controls (p

Purpose To evaluate tumor vasculature with optical coherence tomography angiography (OCTA) in malignant iris melanomas and benign iris lesions. Design Cross-sectional observational clinical study. Participants Patients with iris lesions and healthy volunteers. Methods Eyes were imaged using OCTA systems operating at 1050- and 840-nm wavelengths. Three-dimensional OCTA scans were acquired. Iris melanoma patients treated with radiation therapy were imaged again after I-125 plaque brachytherapy at 6 and 18 months. Main Outcome Measures OCT and OCTA images, qualitative evaluation of iris and tumor vasculature, and quantitative vessel density. Results One eye each of 8 normal volunteers and 9 patients with iris melanomas or benign iris lesions, including freckles, nevi, and an iris pigment epithelial (IPE) cyst, were imaged. The normal iris has radially oriented vessels within the stroma on OCTA. Penetration of flow signal in normal iris depended on iris color, with best penetration seen in light to moderately pigmented irides. Iris melanomas demonstrated tortuous and disorganized intratumoral vasculature. In 2 eyes with nevi there was no increased vascularity; in another, fine vascular loops were noted near an area of ectropion uveae. Iris freckles and the IPE cyst did not have intrinsic vascularity. The vessel density was significantly higher within iris melanomas (34.5%±9.8%, P < 0.05) than in benign iris nevi (8.0%±1.4%) or normal irides (8.0%±1.2%). Tumor regression after radiation therapy for melanomas was associated with decreased vessel density. OCTA at 1050 nm provided better visualization of tumor vasculature and penetration through thicker tumors than at 840 nm. But in very thick tumors and highly pigmented lesions even 1050-nm OCTA could not visualize their full thickness. Interpretable OCTA images were obtained in 82% of participants in whom imaging was attempted. Conclusions This is the first demonstration of OCTA in iris tumors. OCTA may provide a dye-free, no-injection, cost-effective method for monitoring a variety of tumors, including iris melanocytic lesions, for growth and vascularity. This could be helpful in evaluating tumors for malignant transformation and response to treatment. Penetration of the OCT beam remains a limitation for highly pigmented tumors, as does the inability to image the entire iris in a single field., National Institutes of Health (U.S.) (Grants R01 EY023285, R01 EY024544, R01 EY018184, DP3 DK104397, UL1TR000128, and P30 EY010572