Darius M. Moshfeghi, MD's Profile
Darius M. Moshfeghi, MD is part of Stanford Profiles, official site for faculty, postdocs, students and staff information (Expertise, Bio, Research, Publications, and more). The site facilitates research and collaboration in academic endeavors.
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Abstract

Treatment outcomes in retinopathy of prematurity (ROP) are closely correlated with the location (i.e. zone) of disease, with more posterior zones having poorer outcomes. The most posterior zone, Zone I, is defined as a circle centered on the optic nerve with radius twice the distance from nerve to fovea, or subtending an angle of 30 degrees. Because the eye enlarges and undergoes refractive changes during the period of ROP screening, the absolute area of Zone I according to these definitions may likewise change. It is possible that these differences may confound accurate assessment of risk in patients with ROP. In this study, we estimated the area of Zone I in relation to different ocular parameters to determine how variability in the size and refractive power of the eye may affect zoning. Using Gaussian optics, a model was constructed to calculate the absolute area of Zone I as a function of corneal power, anterior chamber depth, lens power, lens thickness, and axial length (AL), with Zone I defined as a circle with radius set by a 30-degree visual angle. Our model predicted Zone I area to be most sensitive to changes in AL; for example, an increase of AL from 14.20 to 16.58mm at postmenstrual age 32weeks was calculated to expand the area of Zone I by up to 72%. These findings motivate several hypotheses which upon future testing may help optimize treatment decisions for ROP.

View details for DOI 10.1038/s41598-022-08680-5

View details for PubMedID 35304549

Abstract

To describe a database of longitudinally graded telemedicine retinal images to be used as a comparator for future studies assessing grader recall bias and ability to detect typical progression (e.g. International Classification of Retinopathy of Prematurity (ICROP) stages) as well as incremental changes in retinopathy of prematurity (ROP). Cohort comprised of retinal images from 84 eyes of 42 patients who were sequentially screened for ROP over 6 consecutive weeks in a telemedicine program and then followed to vascular maturation or treatment, and then disease stabilization. De-identified retinal images across the 6 weekly exams (2520 total images) were graded by an ROP expert based on whether ROP had improved, worsened, or stayed the same compared to the prior week's images, corresponding to an overall clinical "gestalt" score. Subsequently, we examined which parameters might have influenced the examiner's ability to detect longitudinal change; images were graded by the same ROP expert by image view (central, inferior, nasal, superior, temporal) and by retinal components (vascular tortuosity, vascular dilation, stage, hemorrhage, vessel growth), again determining if each particular retinal component or ROP in each image view had improved, worsened, or stayed the same compared to the prior week's images. Agreement between gestalt scores and view, component, and component by view scores was assessed using percent agreement, absolute agreement, and Cohen's weighted kappa statistic to determine if any of the hypothesized image features correlated with the ability to predict ROP disease trajectory in patients. The central view showed substantial agreement with gestalt scores (kappa=0.63), with moderate agreement in the remaining views. Of retinal components, vascular tortuosity showed the most overall agreement with gestalt (kappa=0.42-0.61), with only slight to fair agreement for all other components. This is a well-defined ROP database graded by one expert in a real-world setting in a masked fashion that correlated with the actual (remote in time) exams and known outcomes. This provides a foundation for subsequent study of telemedicine's ability to longitudinally assess ROP disease trajectory, as well as for potential artificial intelligence approaches to retinal image grading, in order to expand patient access to timely, accurate ROP screening.

View details for DOI 10.1038/s41598-021-84723-7

View details for PubMedID 33686091

Abstract

Detection of diabetic retinopathy (DR) outside of specialized eye care settings is an important means of access to vision-preserving health maintenance. Remote interpretation of fundus photographs acquired in a primary care or other nonophthalmic setting in a store-and-forward manner is a predominant paradigm of teleophthalmology screening programs. Artificial intelligence (AI)-based image interpretation offers an alternative means of DR detection. IDx-DR (Digital Diagnostics Inc) is a Food and Drug Administration-authorized autonomous testing device for DR. We evaluated the diagnostic performance of IDx-DR compared with human-based teleophthalmology over 2 and a half years. Additionally, we evaluated an AI-human hybrid workflow that combines AI-system evaluation with human expert-based assessment for referable cases.Prospective cohort study and retrospective analysis.Diabetic patients ≥ 18 years old without a prior DR diagnosis or DR examination in the past year presenting for routine DR screening in a primary care clinic.Macula-centered and optic nerve-centered fundus photographs were evaluated by an AI algorithm followed by consensus-based overreading by retina specialists at the Stanford Ophthalmic Reading Center. Detection of more-than-mild diabetic retinopathy (MTMDR) was compared with in-person examination by a retina specialist.Sensitivity, specificity, accuracy, positive predictive value, and gradability achieved by the AI algorithm and retina specialists.The AI algorithm had higher sensitivity (95.5% sensitivity; 95% confidence interval [CI], 86.7%-100%) but lower specificity (60.3% specificity; 95% CI, 47.7%-72.9%) for detection of MTMDR compared with remote image interpretation by retina specialists (69.5% sensitivity; 95% CI, 50.7%-88.3%; 96.9% specificity; 95% CI, 93.5%-100%). Gradability of encounters was also lower for the AI algorithm (62.5%) compared with retina specialists (93.1%). A 2-step AI-human hybrid workflow in which the AI algorithm initially rendered an assessment followed by overread by a retina specialist of MTMDR-positive encounters resulted in a sensitivity of 95.5% (95% CI, 86.7%-100%) and a specificity of 98.2% (95% CI, 94.6%-100%). Similarly, a 2-step overread by retina specialists of AI-ungradable encounters improved gradability from 63.5% to 95.6% of encounters.Implementation of an AI-human hybrid teleophthalmology workflow may both decrease reliance on human specialist effort and improve diagnostic accuracy.Proprietary or commercial disclosure may be found after the references.

View details for DOI 10.1016/j.xops.2023.100330

View details for PubMedID 37449051

View details for PubMedCentralID PMC10336195

Abstract

Myopia is a known risk factor for rhegmatogenous retinal detachment (RRD). Given global trends of increasing myopia, we aimed to determine the absolute risk (incidence rate) of RRD in non-myopes, myopes and high myopes in the United States over ten years. We performed a retrospective cohort study of 85,476,781 commercially insured patients enrolled in the Merative Marketscan Research Database. The incidence rate of RRD in phakic patients inthe United States was 39-fold higher in high myopes than non-myopes (868.83 per 100,000 person-years versus 22.44 per 100,000 person-years)and three-fold higher in myopes than non-myopes (67.51 per 100,000 person-yearsversus22.44 per 100,000 person-years). The incidence rate was significantly higher in males in each category (P<0.01). Combined, the incidence rate of RRD in phakic patients inthe United States from 2007 to 2016was 25.27 RRDs per 100,000 person-years, a rate higherthan those in prior published studies in North America, South America, Europe, Asia, and Australia.The absolute risk of myopia and high myopia increased from 2007 to 2016. Therisk of RRD in phakichigh myopes rosewith increasing age. Notably, the magnitude of increased risk of RRD in myopes varied substantially according to the minimum follow-up period in our models and should be accounted for when interpreting data analyses.

View details for DOI 10.1038/s41598-023-35520-x

View details for PubMedID 37296124

Abstract

PURPOSE: To investigate causes of childhood blindness in the United States using the IRIS Registry (Intelligent Research in Sight).DESIGN: Cross-Sectional Study.PARTICIPANTS: Patients ≤18 years of age with visual acuity 20/200 or worse in their better seeing eye in the IRIS Registry during 2018.METHODS: Causes of blindness were classified by anatomical site and specific diagnoses.MAIN OUTCOME MEASURES: Percentages of causes of blindness.RESULTS: Of 81,164 children with 2018 visual acuity data in the IRIS Registry, 961 (1.18%) had visual acuity 20/200 or worse in their better-seeing eye. Leading causes of blindness were retinopathy of prematurity (ROP) in 301 (31.3%), nystagmus in 78 (8.1%), and cataract in 64 (6.7%) patients. The retina was the leading anatomic site (47.7%) followed by optic nerve (11.6%) and lens (10.0%). A total of 52.4% of patients had treatable causes of blindness.CONCLUSIONS: This analysis offers a unique cross-sectional view of childhood blindness in the US using a clinical data registry. More than one-half of blind patients had a treatable cause of blindness.

View details for DOI 10.1016/j.ophtha.2023.04.004

View details for PubMedID 37037315

Abstract

Purpose: To report different biometric measurements in high myopia associated with different underlying ocular and genetic conditions.Design: Retrospective study.Subjects: Patients with high myopia.Methods: We searched the Stanford Research Repository tool to identify patients with the diagnosis of high myopia who were seen by a single provider at Byers Eye Institute at Stanford from January 2019 to March 2022. We performed a chart review and included eyes that had high myopia and ocular biometric measurements at any time point after January 2019. We divided our cohort into 5 different groups: (1) isolated high myopia (IHM) (control group); (2) retinopathy of prematurity (ROP); (3) familial exudative vitreoretinopathy; (4) Marfan syndrome; and (5) Stickler syndrome.Main Outcome Measures: Biometric measurements.Results: A total of 246 patients (432 eyes) were included as follows: 202 patients (359 eyes) in the IHM group, 17 patients (27 eyes) in the ROP group, 7 patients (12 eyes) in the familial exudative vitreoretinopathy group, 8 patients (14 eyes) in the Marfan group, and 12 patients (20 eyes) in the Stickler group. The ROPgroup showed significantly shorter axial lengths, shallower anterior chambers, and thicker lenses compared with the IHM group. The Marfan group showed significantly flatter corneas and thicker lenses compared with the IHM group. The Stickler group showed significantly longer axial lengths compared with the IHM group.Conclusions: High myopia is associated with variable biometric measurements according to underlying ocular or genetic conditions. Retinopathy of prematurity-associated high myopia is primarily lenticular, while Stickler syndrome-associated high myopia is axial. Marfan syndrome-associated high myopia is derived from both axial and lenticular mechanisms.

View details for DOI 10.1016/j.xops.2022.100236

View details for PubMedID 36545263

Abstract

Five-field 130° wide-angle imaging is the standard of care for retinopathy of prematurity (ROP) screening with an ideal hypothetical composite field-of-view (FOV) of 180°. We hypothesized that in many real-world scenarios the effective composite FOV is considerably less than ideal. This observational retrospective study analyzed the effective FOV of fundus photos of patients screened for ROP as part of the Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) initiative. Five fundus photos were selected from each eye per image session. Effective FOV was defined as the largest circular area centered on the optic disc that encompassed retina in each of the four cardinal views. Seventy-three subjects were analyzed, 35 without ROP and 34 with ROP. Mean effective FOV was 144.55±6.62° ranging from 130.00 to 153.71°. Effective FOV was not correlated with the presence or absence of ROP, gestational age, birth weight, or postmenstrual age. Mean effective FOV was wider in males compared to females. Standard five-field 130° fundus photos yielded an average effective FOV of 144.54° in the SUNDROP cohort. This implies that an imaging FOV during ROP screening considerably less than the hypothetical ideal of 180° is sufficient for detecting treatment warranted ROP.

View details for DOI 10.1038/s41598-022-22964-w

View details for PubMedID 36369465

Abstract

PURPOSE: To report a novel finding of retinal arterial tortuosity (RAT) associated with Ehlers-Danlos syndromes (EDS).METHODS: We queried the STAnford Research Repository (STARR) database to identify patients diagnosed with EDS. We included patients with a confirmed diagnosis of any subtype of EDS who had any form of readable retinal imaging including colour fundus photos, autofluorescence, red-free photos, red-free optical coherence tomography photos and fluorescein angiography. Patients who had no retinal imaging and those with no confirmed EDS diagnosis were excluded. Retinal images were reviewed for RAT and were graded into no, possible and definite RAT. Eyes with definite RAT were further graded into mild, moderate and severe. Eyes with definite RAT were again subclassified according to the type of involved vessels into first-order arteriolar, macular and arteriovenous.RESULTS: A total of 307 patients were identified using the STARR tool and 142 patients were included. Mean age was 40.9±18.1 years and 87% were female. Underlying EDS subtypes were hypermobile EDS (69.7%), classical EDS (2.8%), vascular EDS (2.1%), myopathic EDS (0.7%) and not specified (24.6%). We graded 37.3% of patients with definite RAT, 10.6% with possible RAT and 52.1% with no RAT. In patients with definite RAT, we graded 39.2% of eyes with mild RAT, 40.2% with moderate RAT and 20.6% with severe RAT. In all, 84.9% showed involvement of first-order retinal arterioles, 35.8% showed involvement of macular arterioles and 1.9% showed arteriovenous involvement.CONCLUSIONS: Variable degrees of RAT are associated with EDS.

View details for DOI 10.1038/s41433-022-02278-x

View details for PubMedID 36241846

Abstract

Importance: Laser photocoagulation, which is the standard treatment for retinopathy of prematurity (ROP), can have adverse events. Studies of anti-vascular endothelial growth factor injections have suggested efficacy in the treatment of ROP, but few studies have directly compared them with laser treatments.Objective: To compare intravitreal aflibercept vs laser photocoagulation in infants with ROP requiring treatment.Design, Setting, and Participants: This noninferiority, phase 3, 24-week, randomized clinical trial was conducted in 27 countries (64 hospital sites) throughout Asia, Europe, and South America. Overall, 118 infants (gestational age ≤32 weeks at birth or birth weight ≤1500 g) with ROP severity (zone I stage 1+ [stage 1 plus increased disease activity], zone I stage 2+, zone I stage 3, zone I stage 3+, zone II stage 2+, or zone II stage 3+) requiring treatment or with aggressive posterior ROP in at least 1 eye were enrolled between September 25, 2019, and August 28, 2020 (the last visit occurred on February 12, 2021).Interventions: Infants were randomized 2:1 to receive a 0.4-mg dose of intravitreal aflibercept (n=75) or laser photocoagulation (n=43) at baseline. Additional treatment was allowed as prespecified.Main Outcomes and Measures: The primary outcome was the proportion of infants without active ROP and unfavorable structural outcomes 24 weeks after starting treatment (assessed by investigators). The requirement for rescue treatment was considered treatment failure. Intravitreal aflibercept was deemed noninferior if the lower limit of the 1-sided 95% bayesian credible interval for the treatment difference was greater than -5%.Results: Among 118 infants randomized, 113 were treated (mean gestational age, 26.3 [SD, 1.9] weeks; 53 [46.9%] were female; 16.8% had aggressive posterior ROP, 19.5% had zone I ROP, and 63.7% had zone II ROP) and 104 completed the study. Treatment (intravitreal aflibercept: n=75; laser photocoagulation: n=38) was mostly bilateral (92.9%), and 82.2% of eyes in the intravitreal aflibercept group received 1 injection per eye. Treatment success was 85.5% with intravitreal aflibercept vs 82.1% with laser photocoagulation (between-group difference, 3.4% [1-sided 95% credible interval, -8.0% to ]). Rescue treatment was required in 4.8% (95% CI, 1.9% to 9.6%) of eyes in the intravitreal aflibercept group vs 11.1% (95% CI, 4.9% to 20.7%) of eyes in the laser photocoagulation group. The serious adverse event rates were 13.3% (ocular) and 24.0% (systemic) in the intravitreal aflibercept group compared with 7.9% and 36.8%, respectively, in the laser photocoagulation group. Three deaths, which occurred 4 to 9 weeks after intravitreal aflibercept treatment, were considered unrelated to aflibercept by the investigators.Conclusions and Relevance: Among infants with ROP, intravitreal aflibercept compared with laser photocoagulation did not meet criteria for noninferiority with respect to the primary outcome of the proportion of infants achieving treatment success at week 24. Further data would be required for more definitive conclusions regarding the comparative effects of intravitreal aflibercept and laser photocoagulation in this population.Trial Registration: ClinicalTrials.gov Identifier: NCT04004208.

View details for DOI 10.1001/jama.2022.10564

View details for PubMedID 35881122

Abstract

OBJECTIVE OR PURPOSE: To utilize a deep learning (DL) model trained via federated learning (FL), a method of collaborative training without sharing patient data, to delineate institutional differences in clinician diagnostic paradigms and disease epidemiology in retinopathy of prematurity (ROP).DESIGN: Evaluation of a diagnostic test or technology SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: 5,245 patients with wide-angle retinal imaging from the neonatal intensive care units of 7 institutions as part of the Imaging and Informatics in ROP (i-ROP) study. Images were labeled with the clinical diagnosis of plus disease (plus, pre-plus, no plus) that was documented in the chart, and a reference standard diagnosis (RSD) determined by three image-based ROP graders and the clinical diagnosis.METHODS, INTERVENTION OR TESTING: Demographics (birthweight [BW], gestational age [GA]), and clinical diagnoses for all eye exams were recorded from each institution. Using a FL approach, a DL model for plus disease classification was trained using only the clinical labels. The three class probabilities were then converted into a vascular severity score (VSS) for each eye exam, as well as an "institutional VSS" in which the average of the VSS values assigned to patients' higher severity ("worse") eyes at each exam was calculated for each institution.MAIN OUTCOME MEASURES: We compared demographics, clinical diagnosis of plus disease, and institutional VSS between institutions using the McNemar Bowker test, two-proportion Z test and one-way ANOVA with post-hoc analysis by Tukey-Kramer test. Single regression analysis was performed to explore the relationship between demographics and VSS.RESULTS: We found that the proportion of patients diagnosed with pre-plus disease varied significantly between institutions (p<0.00l). Using the DL-derived VSS trained on the data from all institutions using FL, we observed differences in the institutional VSS, as well as level of vascular severity diagnosed as no plus (p<0.001) across institutions. A significant, inverse relationship between the institutional VSS and the mean GA was found (p=0.049, adjusted R2=0.49).CONCLUSIONS: A DL-derived ROP VSS developed without sharing data between institutions using FL identified differences in the clinical diagnosis of plus disease, and overall levels of ROP severity between institutions. FL may represent a method to standardize clinical diagnosis and provide objective measurement of disease for image-based diseases.

View details for DOI 10.1016/j.oret.2022.03.005

View details for PubMedID 35304305

Abstract

OBJECTIVE: To compare the performance of deep learning (DL) classifiers for the diagnosis of plus disease in retinopathy of prematurity (ROP) trained using two methods of developing models on multi-institutional datasets: centralizing data versus federated learning (FL) where no data leaves each institution.DESIGN: Evaluation of a diagnostic test or technology.SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: DL models were trained, validated, and tested on 5,255 wide-angle retinal images in the neonatal intensive care units of 7 institutions as part of the Imaging and Informatics in ROP (i-ROP) study. All images were labeled for the presence of plus, pre-plus, or no plus disease with a clinical label, and a reference standard diagnosis (RSD) determined by three image-based ROP graders and the clinical diagnosis.METHODS, INTERVENTION OR TESTING: We compared the area under the receiver operating characteristic curve (AUROC) for models developed on multi-institutional data, using a central approach, then FL, and compared locally trained models to either approach. We compared model performance (kappa) with label agreement (between clinical and RSD), dataset size and number of plus disease cases in each training cohort using Spearman's correlation coefficient (CC).MAIN OUTCOME MEASURES: Model performance using AUROC and linearly-weighted kappa.RESULTS: Four settings of experiment: FL trained on RSD against central trained on RSD, FL trained on clinical labels against central trained on clinical labels, FL trained on RSD against central trained on clinical labels, and FL trained on clinical labels against central trained on RSD (p=0.046, p=0.126, p=0.224, p=0.0173, respectively). 4/7 (57%) of models trained on local institutional data performed inferiorly to the FL models. Model performance for local models was positively correlated with label agreement (between clinical and RSD labels, CC = 0.389, p=0.387), total number of plus cases (CC=0.759, p=0.047), overall training set size (CC=0.924, p=0.002).CONCLUSIONS: We show that a FL model trained performs comparably to a centralized model, confirming that FL may provide an effective, more feasible solution for inter-institutional learning. Smaller institutions benefit more from collaboration than larger institutions, showing the potential of FL for addressing disparities in resource access.

View details for DOI 10.1016/j.oret.2022.02.015

View details for PubMedID 35296449

Abstract

OBJECTIVE: To validate a vascular severity score as an appropriate output for artificial intelligence (AI) Software as a Medical Device (SaMD) for retinopathy of prematurity (ROP) through comparison with ordinal disease severity labels for stage and plus disease assigned by the International Classification of ROP, 3rd edition (ICROP3) committee.DESIGN: Validation study of an AI-based ROP vascular severity score Subjects, Participants, and/or Controls: 34 ROP experts from the ICROP3 committee.METHODS: Two separate datasets of 30 fundus photographs each for stage (0-5) and plus disease (plus, pre-plus, neither) were labeled by members of the ICROP3 committee using an open-source platform. Averaging these results produced a continuous label for plus (1-9) and stage (1-3) for each image. Experts were also asked to compare each image to each other in terms of relative severity for plus disease. Each image was also labelled with a vascular severity score from the Imaging and Informatics in ROP deep learning (i-ROP DL) system, which was compared with each grader's diagnostic labels for correlation, as well as the ophthalmoscopic diagnosis of stage.MAIN OUTCOME MEASURES: Weighted kappa and Pearson correlation coefficients (CC) were calculated between each pair of grader classification labels for stage and plus disease. The Elo algorithm was also used to convert pairwise comparisons for each expert into an ordered set of images from least to most severe.RESULTS: The mean weighted kappa and CC for all inter-observer pairs for plus disease image comparison was 0.67 and 0.88 respectively. The vascular severity score was found to be highly correlated with both the average plus disease classification (CC = 0.90, p < 0.001) and the ophthalmoscopic diagnosis of stage (p < 0.001 by ANOVA) among all experts.CONCLUSIONS: The ROP vascular severity score correlates well with the ICROP committee member's labels for plus disease and stage, which had significant inter-grader variability. Generation of a consensus for a validated scoring system for ROP SaMD can facilitate global innovation and regulatory authorization of these technologies.

View details for DOI 10.1016/j.ophtha.2022.02.008

View details for PubMedID 35157950

Abstract

To examine whether new cases of retinal artery occlusion (RAO) or retinal vein occlusion (RVO) increased during the coronavirus 209 (COVID-19) pandemic.This was a retrospective cohort study of patients visiting retina clinics with a new diagnosis in two time periods: between January 1, 2019, and February 29, 2020 (the pre-COVID-19 period), and between March 1, 2020, and December 31, 2020 (the COVID-19 period). The key outcome was the percentage of newly diagnosed central RAO (CRAO), branch RAO (BRAO), central RVO (CRVO), and branch RVO (BRVO) seen in each period.The study population included 285,759 new patients in the pre-COVID-19 period and 156,427 new patients in the COVID-19 period. The overall number of new patients dropped dramatically during the first few months of the COVID-19 pandemic (24%, 66%, and 51% less new patients in March, April, and May 2020 than in the same months in 2019; P < .0001 for all 3 months). However, the decrease in the number of newly diagnosed patients with CRAO, CRVO, and BRAO during these months was less dramatic. As most states reopened in June and the number of patients in retina clinics started to increase, the newly diagnosed patients with these conditions as a percentage of all new diagnoses returned to similar trends as seen in the pre-COVID-19 period.The percentage of new cases of RAO and RVO with respect to all new diagnoses in retina clinics remained stable for the majority of the COVID-19 period. There was an increase in these percentages during the first few months of the COVID-19 pandemic, particularly for CRAO, CRVO, and BRAO, which may have led to the presumption that more patients presented with these conditions during the COVID-19 period evaluated in this study. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:22-30.

View details for DOI 10.3928/23258160-20211209-01

View details for PubMedID 34982005

Abstract

Importance: Telemedicine is accelerating the remote detection and monitoring of medical conditions, such as vision-threatening diseases. Meaningful deployment of smartphone apps for home vision monitoring should consider the barriers to patient uptake and engagement and address issues around digital exclusion in vulnerable patient populations.Objective: To quantify the associations between patient characteristics and clinical measures with vision monitoring app uptake and engagement.Design, Setting, and Participants: In this cohort and survey study, consecutive adult patients attending Moorfields Eye Hospital receiving intravitreal injections for retinal disease between May 2020 and February 2021 were included.Exposures: Patients were offered the Home Vision Monitor (HVM) smartphone app to self-test their vision. A patient survey was conducted to capture their experience. App data, demographic characteristics, survey results, and clinical data from the electronic health record were analyzed via regression and machine learning.Main Outcomes and Measures: Associations of patient uptake, compliance, and use rate measured in odds ratios (ORs).Results: Of 417 included patients, 236 (56.6%) were female, and the mean (SD) age was 72.8 (12.8) years. A total of 258 patients (61.9%) were active users. Uptake was negatively associated with age (OR, 0.98; 95% CI, 0.97-0.998; P=.02) and positively associated with both visual acuity in the better-seeing eye (OR, 1.02; 95% CI, 1.00-1.03; P=.01) and baseline number of intravitreal injections (OR, 1.01; 95% CI, 1.00-1.02; P=.02). Of 258 active patients, 166 (64.3%) fulfilled the definition of compliance. Compliance was associated with patients diagnosed with neovascular age-related macular degeneration (OR, 1.94; 95% CI, 1.07-3.53; P=.002), White British ethnicity (OR, 1.69; 95% CI, 0.96-3.01; P=.02), and visual acuity in the better-seeing eye at baseline (OR, 1.02; 95% CI, 1.01-1.04; P=.04). Use rate was higher with increasing levels of comfort with use of modern technologies (beta=0.031; 95% CI, 0.007-0.055; P=.02). A total of 119 patients (98.4%) found the app either easy or very easy to use, while 96 (82.1%) experienced increased reassurance from using the app.Conclusions and Relevance: This evaluation of home vision monitoring for patients with common vision-threatening disease within a clinical practice setting revealed demographic, clinical, and patient-related factors associated with patient uptake and engagement. These insights inform targeted interventions to address risks of digital exclusion with smartphone-based medical devices.

View details for DOI 10.1001/jamaophthalmol.2021.5269

View details for PubMedID 34913967

Abstract

Purpose: Generative adversarial networks (GANs) are deep learning (DL) models that can create and modify realistic-appearing synthetic images, or deepfakes, from real images. The purpose of our study was to evaluate the ability of experts to discern synthesized retinal fundus images from real fundus images and to review the current uses and limitations of GANs in ophthalmology.Design: Development and expert evaluation of a GAN and an informal review of the literature.Participants: A total of 4282 image pairs of fundus images and retinal vessel maps acquired from a multicenter ROP screening program.Methods: Pix2Pix HD, a high-resolution GAN, was first trained and validated on fundus and vessel map image pairs and subsequently used to generate 880 images from a held-out test set. Fifty synthetic images from this test set and 50 different real images were presented to 4 expert ROP ophthalmologists using a custom online system for evaluation of whether the images were real or synthetic. Literature was reviewed on PubMed and Google Scholars using combinations of the terms ophthalmology, GANs, generative adversarial networks, ophthalmology, images, deepfakes, and synthetic. Ancestor search was performed to broaden results.Main Outcome Measures: Expert ability to discern real versus synthetic images was evaluated using percent accuracy. Statistical significance was evaluated using a Fisher exact test, with P values ≤ 0.05 thresholded for significance.Results: The expert majority correctly identified 59% of images as being real or synthetic (P= 0.1). Experts 1 to 4 correctly identified 54%, 58%, 49%, and 61% of images (P= 0.505, 0.158, 1.000, and 0.043, respectively). These results suggest that the majority of experts could not discern between real and synthetic images. Additionally, we identified 20 implementations of GANs in the ophthalmology literature, with applications in a variety of imaging modalities and ophthalmic diseases.Conclusions: Generative adversarial networks can create synthetic fundus images that are indiscernible from real fundus images by expert ROP ophthalmologists. Synthetic images may improve dataset augmentation for DL, may be used in trainee education, and may have implications for patient privacy.

View details for DOI 10.1016/j.xops.2021.100079

View details for PubMedID 36246951

Abstract

STUDY OBJECTIVES: To investigate the association between daytime napping and retinal microcirculation.METHODS: This is a cross-sectional study from a prospective population-based cohort. 2,662 participants were recruited after quota sampling. Information on napping was collected through face-to-face interviews. Retinal vascular calibers (RVCs), including central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), and arterio-to-venous ratio (AVR), were obtained from fundus photography. Multivariate regression and restricted cubic spline curve were performed to determine the association between RVCs and daytime napping duration.RESULTS: 56.4% participants reported daytime napping regularly. Compared to no nap, daytime nap was related to higher CRAE, with nap duration of 0.5-1 h showing the most significant association. 0.5-1 h daytime nappers displayed an average of 4.18 m (95% confidence interval [CI] 2.45-5.91, p < 0.001) wider CRAE than non-nappers after adjustment. No significant association was found between CRVE and daytime napping. Moreover, individuals with 0.5-1 h daytime napping had a lower risk for AVR reduction (odds ratio [OR] 0.70, 95% confidence interval [CI] 0.56-0.86, p = 0.001) than non-nappers. Similar association persisted in non-hypertensive population. Restricted cubic spline indicated a J-shaped relationship between AVR reduction and nap duration.CONCLUSION: Retinal microcirculation was positively associated with self-reported 0.5-1 h daytime napping. Better indicators of retinal microcirculation were probably related to nap duration in a J-shaped manner. Also, the possibly beneficial role of 0.5-1 h daytime napping on retinal microcirculation might be independent of clinically diagnosed vascular diseases.

View details for DOI 10.1093/sleep/zsab277

View details for PubMedID 34875091

Abstract

Current retinal tamponade strategies are limited by anatomic considerations (retinal break location), durability (short-term vs need for removal), and patient adherence (positioning, travel/altitude restrictions). Here we describe the preclinical safety and toxicology of a novel biodegradable hydrogel tamponade agent (PYK-1105) with the potential to improve both patient experience and outcomes after retina surgery.We studied in vitro performance to assess hydrogel gelation time, modulus, viscosity, degradation time, refractive index, and transmittance. In addition to studying in vitro and in vivo (mice and rabbits) biocompatibility, testing was performed to assess cytotoxicity, intraocular irritation, acute systemic toxicity, genotoxicity, and pyrogenicity. Furthermore, clinical safety was assessed using in vivo (rabbits and minipigs) response to vitrectomy with PYK-1105 insertion with the following measures: clinical examination, multimodal imaging, full-field electroretinography, and histopathology.PYK-1105 met the predefined performance testing criteria for optimal tamponade and demonstrated excellent biocompatibility. Animal studies showed the PYK-1105 formulation to be well tolerated and nontoxic in mice, rabbits, and pigs.PYK-1105 holds promise as a new biodegradable tamponade agent that has the potential to improve both the patient experience and outcomes after retina surgery. Human pilot studies are warranted to further assess for safety and efficacy.

View details for DOI 10.1177/2474126420946632

View details for PubMedID 37009585

View details for PubMedCentralID PMC9976048

Abstract

OBJECTIVE: Vision changes can precipitate falls in the elderly resulting in significant morbidity and mortality. We hypothesized that pseudophakic monovision and ensuing anisometropia and aniseikonia impact elderly fall risk. This study assessed fall risk in patients with pseudophakic monovision, pseudophakic single vision distance (classic cataract surgery), and cataracts with no surgery.DESIGN: Retrospective single-institution cohort study PARTICIPANTS: Patients with bilateral cataracts diagnosed at 60 years of age or older who underwent bilateral cataract surgery (monovision or single vision distance) or did not undergo any cataract surgery (n = 13 385). Patients with unilateral surgery or a fall prior to cataract diagnosis were excluded.METHODS: Data were obtained from the Stanford Research Repository. Time-to-fall analysis was performed across all 3 groups. Primary outcome was hazard ratio (HR) for fall after second eye cataract surgery or after bilateral cataract diagnosis.RESULTS: Of 13 385 patients (241 pseudophakic monovision, 2809 pseudophakic single vision, 10 335 no surgery), 850 fell after cataract diagnosis. Pseudophakic monovision was not associated with fall risk after controlling for age, sex, and myopia. Pseudophakic single-vision patients had a decreased time to fall compared with no-surgery patients (log rank, p < 0.001). Older age at cataract diagnosis (HR =1.05, 95% confidence interval [CI] 1.04-1.06, p < 0.001) or at time of surgery (HR = 1.05, 95% CI 1.03-1.07, p < 0.001) increased fall risk, as did female sex (HR = 1.29, 95% CI 1.10-1.51, p = 0.002) and preexisting myopia (HR = 1.31, 95% CI 1.01-1.71, p = 0.046) among nonsurgical patients.CONCLUSIONS: Pseudophakic monovision did not impact fall risk, but pseudophakic single vision may increase falls compared with patients without cataract surgery.

View details for DOI 10.1016/j.jcjo.2021.07.010

View details for PubMedID 34419423

Abstract

PURPOSE: To compare neonatal eye screening using the red reflex test (RRT) versus the wide-field digital imaging (WFDI) system.METHODS: Prospective cohort study. Newborns (n=380, 760 eyes) in the Maternity Ward of Irmandade Santa Casa de Misericordia de Sao Paulo hospital from May to July 2014 underwent RRT by a paediatrician and WFDI performed by the authors. Wide-field digital imaging (WFDI) images were analysed by the authors. Validity of the paediatrician's RRT was assessed by unweighted kappa [kappa] statistic, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).RESULTS: While WFDI showed abnormalities in 130 eyes (17.1%), RRT was only abnormal in 13 eyes (1.7%). Wide-field digital imaging (WFDI) detected treatable retina pathology that RRT missed including hyphema, CMV retinitis, FEVR and a vitreous haemorrhage. The sensitivity of the paediatrician's RRT to detect abnormalities was poor at 0.77% (95% confidence interval, CI, 0.02%-4.21%) with a PPV of only 7.69% (95% CI, 1.08%-38.85%). Overall, there was no agreement between screening modalities (kappa=-0.02, 95% CI, -0.05 to 0.01). The number needed to screen to detect ocular abnormalities using WFDI was 5.9 newborns and to detect treatable abnormalities was 76 newborns.CONCLUSION: While RRT detects gross abnormalities that preclude visualization of the retina (i.e. media opacities and very large tumours), only WFDI consistently detects subtle treatable retina and optic nerve pathology. With a higher sensitivity than the current gold standard, universal WFDI allows for early detection and management of potentially blinding ophthalmic disease missed by RRT.

View details for DOI 10.1111/aos.14759

View details for PubMedID 34032022

Abstract

PURPOSE: Whether intravitreal anti-vascular endothelial growth factors (VEGFs) cause retinal atrophy is still a subject of debate. We reported 13 eyes that received several injections of anti-VEGF for wet age-related macular degeneration (AMD) with good visual acuity despite geographic atrophy on imaging.METHODS: This is a case series study conducted at Byers Eye Institute at Stanford University. Patients of three retina specialists with wet AMD who received six or more intravitreal injection of anti-VEGFs with visual acuity of 20/60 or better and incomplete RPE and outer retina atrophy (iRORA) or complete RPE and outer retinal atrophy (cRORA) were enrolled in this case series. Different imaging modalities were reviewed by three retina specialists comparing the baseline with the most recent exam.RESULTS: About 13 eyes of 10 patients met the selection criteria. Eleven eyes were classified as iRORA and 2 as cRORA. Despite the development of macular atrophy on imaging after an average of 38.1 injections, eyes maintained stable visual acuity.CONCLUSION: The discrepancy between structural and functional findings in this cohort suggests that patients treated by anti-VEGF drugs exhibit divergent clinical outcomes for currently unknown reasons. The authors propose anti-VEGF may affect melanosomes within RPE without disrupting RPE and photoreceptors function completely. This requires further investigation.

View details for DOI 10.1177/11206721211001708

View details for PubMedID 33781106

Abstract

BACKGROUND/AIMS: To determine whether timing of ophthalmic screening influences prevalence of neonatal fundus haemorrhages. We compared the prevalence of fundus haemorrhages in two populations: term newborns screened early (less than 72 hours) and preterm newborns screened late (4-11 weeks). Additionally, we reviewed the literature on timing and prevalence of newborn haemorrhages.METHODS: Retrospective observational cohort study. Infants who underwent wide-angle ophthalmic digital imaging over one overlapping year in the Newborn Eye Screen Testing (NEST) or Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) programme were included. The PubMed database was filtered to include English-language articles dating back to 1950. Nine articles were selected for review based on inclusion of the prevalence of newborn fundus haemorrhages at multiple time points.RESULTS: A total of 202 patients received early imaging in the NEST cohort and 73 patients received late imaging in the SUNDROP cohort. In the NEST cohort, 20.2% of newborns had haemorrhages. In contrast, we found haemorrhages in only one case or 1.4% of the SUNDROP cohort. Using prevalence data from nine additional studies, we developed a predicted probabilities model of newborn haemorrhages. Per this model, the probability of seeing a haemorrhage if you screen an infant at 1 hour is 18.8%, at 2 weeks is 2.9% and at 1 month is 0.28%.CONCLUSION: We found a significant difference in the prevalence of fundus haemorrhages between the early-screened NEST cohort and the late-screened, preterm SUNDROP cohort. Likely, this difference is due to the transient nature of most newborn haemorrhages.

View details for DOI 10.1136/bjophthalmol-2020-317908

View details for PubMedID 33514529

Abstract

To study the effect of statin exposure on the progression from non-exudative to exudative age-related macular degeneration (AMD).Retrospective cohort study of commercially insured patients diagnosed with non-exudative AMD (n = 231,888) from 2007 to 2015. Time-to-event analysis of the association between exposure to lipid-lowering medications and time from non-exudative AMD to exudative AMD diagnosis was conducted. Outcome measures included progression to exudative AMD, indicated by diagnosis codes for exudative AMD or procedural codes for intravitreal injections.In the year before and after first AMD diagnosis, 11,330 patients were continuously prescribed lipid-lowering medications and 31,627 patients did not take any lipid-lowering medication. Of those taking statins, 21 (1.6%) patients were on very-high-dose lipophilic statins, 644 (47.6%) on high-dose lipophilic statins, and 689 (50.9%) on low-dose lipophilic statins. We found no statistically significant relationship between exposure to low (HR 0.89, 95% CI 0.83 to 1.38) or high-dose lipophilic statins (HR 1.12, 95% CI 0.86 to 1.45) and progression to exudative AMD. No patients taking very-high-dose lipophilic statins converted from non-exudative to exudative AMD, though this difference was not statistically significant due to the subgroup size (p = .23, log-rank test).No statistically significant relationship was found between statin exposure and risk of AMD progression. Interestingly, no patients taking very-high-dose lipophilic statins progressed to exudative AMD, a finding that warrants further exploration.

View details for DOI 10.1371/journal.pone.0252878

View details for PubMedID 34347799

Abstract

PURPOSE: To determine if migraine is associated with increased risk of retinal artery occlusion (RAO).DESIGN: Retrospective cohort study METHODS: Setting: A large insurance claims database.PARTICIPANTS: Patients with migraine and matched controls without migraine between 2007 to 2016.PROCEDURES: Cox proportional hazard regression models were used to investigate the association between migraine and risk of all RAO, central RAO (CRAO), branch RAO (BRAO), and "other" RAO, which includes transient and partial RAO.MAIN OUTCOME MEASURES: Incidence of all RAO, including CRAO, BRAO, and other RAO, following first migraine diagnosis.RESULT: There were 418,965 patients with migraine who met study criteria and were included in the analysis with the appropriate matched controls. Among the 418,965 patients with migraine, 1,060 (0.25%) were subsequently diagnosed with RAO, whereas only 335 (0.08%) of the patients without migraine were diagnosed with RAO. The hazard ratio (HR) for incident all RAO in patients with migraine compared with those without migraine was 3.48 (95% Confidence Interval (CI): 3.07 - 3.94; P <0.0001]. This association was consistent across all types of RAO, including CRAO (HR = 1.62; 95% CI: 1.15 - 2.28; P=0.004) BRAO (HR 2.09; 95% CI 1.60 - 2.72; P <0.001), and other types of RAO (HR 4.61; 95% CI 3.94 - 5.38; P <0.001). Patients with migraine with aura had a higher risk for incident RAO compared with those with migraine without aura (HR = 1.58; 95% CI: 1.40 - 1.79; P <0.001). This association was consistent for BRAO (HR = 1.43; 95% CI 1.04 - 1.97; P <0.03) and other types of RAO (HR = 1.67; 95% CI 1.45 - 1.91; P <0.001), but was not statistically significant for CRAO (HR = 1.18; 95% CI 0.75 - 1.87; P = 0.475). Significant risk factors for this association included increased age, male sex, acute coronary syndrome, valvular disease, carotid disease, hyperlipidemia, hypertension, retinal vasculitis and/or inflammation, and systemic lupus erythematosus.CONCLUSIONS: Migraine is associated with increased risk of all types of RAO and migraine with aura is associated with increased risk of RAO compared with migraine without aura.

View details for DOI 10.1016/j.ajo.2020.11.004

View details for PubMedID 33359716

Abstract

BACKGROUND: Aicardi syndrome is an X-linked condition that is associated with multiple ophthalmic malformations. Here, we report the first published fluorescein angiography (FA) study of a morning glory optic nerve in a patient with Aicardi syndrome and contralateral persistent fetal vasculature (PFV).CASE DESCRIPTION: A 12-day old full-term baby girl with a normal neurological exam was referred for evaluation of microphthalmia. The posterior segment of the right eye demonstrated chorioretinal lacunae typical of Aicardi syndrome and microphthalmos with a stalk consistent with PFV. The right eye imaging could not be captured due to the severe microphthalmos and cataract, however, fluorescein angioscopy was performed. The left eye demonstrated a morning glory appearing optic disc with peripapillary chorioretinal lacunae. Fluorescein angiography of the eye showed and late staining in the areas of ellipsoid chorioretinal lacunae emanating from the optic nerve and extensive peripapillary staining and late leakage of the optic nerve.CONCLUSION: Patients with Aicardi syndrome can have morning glory optic nerve anomaly and PFV. Using FA under anesthesia to detect these abnormalities help in estimating the extend of the disease and its complications, which allows for better management of the complications.

View details for DOI 10.1177/1120672120942702

View details for PubMedID 32674592

Abstract

Importance: Identifying disparities in uveal melanoma (UM) treatment patterns and survival across racial, ethnic, and socioeconomic (SES) groups reveals possible inequities in ophthalmologic health care.Objective: To examine the association of race, ethnicity, and SES with UM treatment and survival.Design, Setting, and Participants: A retrospective cohort analysis of 28% of the US population using the Surveillance, Epidemiology, and End Results (SEER) 18 registries from January 1, 2004, to December 31, 2014, was conducted. Data analysis was performed from April to July 2018. SEER identified 4475 individuals using International Classification of Diseases for Oncology, Third Edition site and morphology codes.Exposures: Race, ethnicity, and SES estimated by tertile using Yost Index composite scores.Main Outcomes and Measures: Treatment odds ratios (ORs), 1-year and 5-year survival estimates, mortality hazard ratios (HRs), and Kaplan-Meier survival curves. Hypothesis was formulated before data collection.Results: Multivariate analyses of 4475 individuals (2315 [51.7%] men; non-Hispanic white, 4130 [92.3%]; nonwhite, 345 [7.7%]) showed that patients who were nonwhite (OR, 1.45; 95% CI, 1.12-1.88) and socioeconomically disadvantaged (lower SES: OR, 2.21; 95% CI, 1.82-2.68; middle SES: OR, 1.86; 95% CI, 1.56-2.21) were more likely to receive primary enucleation. No interactions were observed between race/ethnicity, SES, and stage at diagnosis. From 2004 to 2014, rates of primary enucleation decreased across all racial/ethnic and SES groups, but disparities persisted. Socioeconomically disadvantaged patients had lower 5-year all-cause survival rates (lower SES: 69.2%; middle SES: 68.1%; and upper SES: 73.8%), although disease-specific survival did not vary significantly by racial/ethnic or SES strata. Mortality risk was associated with older age at diagnosis (56-68 years: HR, 1.70; 95% CI, 1.44-2.01; ≥69 years: HR, 3.32; 95% CI, 2.85-3.86), advanced stage of UM (stage 2: HR, 1.40; 95% CI, 1.19-1.65; stage 3: HR, 2.26; 95% CI, 1.87-2.73; and stage 4: HR, 10.09; 95% CI, 7.39-13.77), and treatment with primary enucleation (HR, 2.14; 95% CI, 1.88-2.44) with no racial/ethnic or SES variation.Conclusions and Relevance: In this study, SEER data from 2004 to 2014 suggest that nonwhite and socioeconomically disadvantaged patients with UM are more likely to be treated with primary enucleation, although no such variation appears to exist in disease-specific survival. These differences reveal opportunities to address issues regarding treatment choice in UM.

View details for DOI 10.1001/jamaophthalmol.2020.2254

View details for PubMedID 32614376

Abstract

BACKGROUND: Optic disc pits frequently lead to visual deterioration due to macular retinoschisis or serous retinal detachment. Here, we report a case of optic disc pit-associated macular retinoschisis due to intraretinal fluid accumulation that resolved with improvement in visual acuity after treatment with topical dorzolamide.CASE DESCRIPTION: A 56-year-old otherwise healthy female with no ocular history presented with 2weeks of slowly worsening blurry vision in her right eye. Visual acuity was 20/30 in the right eye. Posterior segment examination revealed posterior vitreous detachment, an optic disc pit at 9 o'clock, macular edema and foveoschisis with fluid extending from the optic nerve, and a normal peripheral retina. Optical coherence tomography imaging of the macula showed central subfield thickness of 526m. The patient preferred no surgical intervention, so topical dorzolamide 2% three times daily was initiated. Over the next 2 years, the central subfield thickness steadily declined from 526 to 262m, and her vision improved to 20/20 with improvement in the macular retinoschisis.CONCLUSION: Our report presents a case of resolution of optic disc pit-associated macular retinoschisis due to intraretinal fluid accumulation with possible role for dorzolamide as a potential treatment option.

View details for DOI 10.1177/1120672120904664

View details for PubMedID 32019335

Abstract

To evaluate the efficacy and safety of iTEAR, a novel, portable, sonic external neuromodulation device, for the treatment of dry eye disease (DED).This was a multicenter, open-label, single-arm clinical trial that included adult patients with DED with a Schirmer score of ≤10 mm in at least one eye. Enrolled subjects were instructed to apply the study device at least twice per day for 30 seconds bilaterally to the external nasal nerve. After the initial baseline visit, patients were followed up at days 3, 14, 30, 90, and 180. The primary efficacy endpoint was the Schirmer index (change from unstimulated to stimulated tear production as measured by the Schirmer test) at day 30. The major secondary endpoint was the change in symptoms of DED at day 30 evaluated using the Ocular Surface Disease Index (OSDI).A total of 101 subjects evaluated at day 30 had a mean Schirmer index of 9.4 mm (95% confidence interval [CI], 7.4-11.3), and the baseline OSDI improved by an average of 14.4 (95% CI, 11.1-17.7). Both endpoints were highly statistically and clinically significant at all time points. There were two mild unanticipated adverse events definitely related to the device.The safety and efficacy of the iTEAR device observed in this study support its indication for treating DED.Neurostimulation has the potential to improve signs and symptoms of DED.

View details for DOI 10.1167/tvst.9.12.23

View details for PubMedID 33244443

View details for PubMedCentralID PMC7683850

Abstract

To investigate whether surgical management of newly diagnosed rhegmatogenous retinal detachment (RRD) varies if patients are diagnosed during a major national ophthalmology conference.This retrospective cohort study included 34,759 patients with incident RRD, of whom, 1,246 (3.6%) were diagnosed during dates of three national ophthalmology conferences, and 1,170 (3.4%) underwent surgery during conference dates. The authors identified patients with primary repair with cryotherapy, laser, scleral buckle, pneumatic retinopexy, or pars plana vitrectomy. Multinomial logistic regression models were used to determine patients' likelihood of receiving each type of repair within 30 days of their diagnosis depending on whether they were diagnosed during a national ophthalmology conference. Linear regression models were used to determine the relationship between the date patients were diagnosed and how long they waited to receive a repair. Main outcome measures included days between diagnosis with RRD and RRD repair, receiving repair on the same day of diagnosis, and reoperation rate within 30 days of the primary repair.Mean time from diagnosis to repair was 1.5 days (standard deviation: ± 2.4 days), and 71% of patients underwent repair within a day of diagnosis. Repairs were followed by a second surgery within 30 days in 11.1% of patients. Patients diagnosed during conferences waited 0.23 days longer between diagnosis and repair compared with patients diagnosed outside of conference dates (P = .001). Patients diagnosed with RRD during conferences were less likely to receive surgical repair within a day of diagnosis compared to patients diagnosed during non-conference dates (P = .037). Patients who were diagnosed with RRD during a conference date and also received surgery during a conference date were more likely to undergo a second surgery within 30 days of the primary procedure (P = .006) CONCLUSIONS: Patients diagnosed with RRD during national ophthalmology conference dates waited slightly longer for surgery, were slightly less likely to receive surgery within a day, and were more likely to undergo a second surgery within 30 days of the primary procedure. The "national meeting effect" phenomenon is present in ophthalmology, albeit to a lesser degree that is likely not visually significant. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:328-337.].

View details for DOI 10.3928/23258160-20200603-03

View details for PubMedID 32579691

Abstract

To determine differences between women and men in the repair of rhegmatogenous retinal detachments (RRD) in the United States.Retrospective cohort study.SETTING: A large insurance claims database.Subjects with an incident RRD between 2007-2015.Demographic data, comorbid ocular conditions associated with RRD,systemic comorbidities,and surgical intervention (pneumatic retinopexy (PR), pars plana vitrectomy (PPV), laser barricade, or scleral buckle (SB)) were collected.Odds of receipt of surgical intervention for incident RRD, time to repair, type of intervention, and the rate of reoperation by sex.The study period included 133 million eligible records with 61,071 cases of incident RRD meeting inclusion criteria among which 43% (n = 26,289) were women. Women had 34% reduced odds of receipt of surgical repairof an RRD (OR 0.66, 95% CI 0.59 - 0.73, p<0.001) after adjusting for confounders. This effect persisted in all sensitivity models. Among patients that received repair, women were more often delayed (0.17 days, p = 0.04). Women were more likely to undergo primary laser barricade (RRR 1.68, p < 0.001), primary SB (RRR 1.15, p < 0.001), and PR (RRR 1.07, p < 0.04) than men. The odds of reoperation were lower in women (OR 0.91, 95% CI 0.85 - 0.96, p=0.002) after adjustment.Insured women are less likely than insured men to receive surgical intervention for an RRD. If the odds of repair were equal between women and men in the U.S. then 781 more women would receive surgery each year, or 7,029 more during the study period. Women are more likely to have the repair performed with scleral buckle and laser barricade. The reason for thesesex differences in RRD repair remains unknown and requires further investigation.

View details for DOI 10.1016/j.ajo.2020.06.039

View details for PubMedID 32640255

Abstract

To determine if fluorescein angiographic (FA) findings after intravitreal ranibizumab (IVR) for retinopathy of prematurity (ROP) conform to a class effect previously described with bevacizumab.Single-center retrospective case series of all infants treated with 0.2 mg (0.02 mL) IVR for Type 1 ROP from July 2016 to November 2018. FA were obtained at 40, 52, 62, and 72 weeks of postmenstrual age (PMA) using wide-angle photography. FA images were analyzed and the peripheral avascular areas measured with ImageJ using a reference disc diameter (DD). Based on the extent of the avascular area and tortuosity of the retinal vessels all eyes were classified into four categories: complete vascular maturity (vascularization within 2 DD of the ora serrata), VAA (avascular area >2 DD of the ora serrata), VAT (avascular area >2 DD of the ora serrata and posterior tortuosity), and reactivation (recurrence of stage disease).About 13 infants were enrolled and 24 eyes were available in this study. None of the eyes reached complete vascular maturity at an average PMA of 60 weeks, 7 (29%) eyes presented with VAA, 8 (33%) with VAT, and 9 (37.5%) reactivated. The reactivated eyes presented with the largest area of peripheral ischemia, followed by the VAT and then the VAA groups (p = 0.02).IVR conforms to the previously described regression patterns following intravitreal bevacizumab for ROP indicative of a class effect. Follow-up using FA might help to optimize the management of these infants after injection of the drug.

View details for DOI 10.1177/1120672120945101

View details for PubMedID 32722932

Abstract

Purpose: To describe new cases of sclopetaria and evaluate the risk factors, management, and visual prognosis of all reported cases in the literature.Observations: We performed a retrospective, observational case series. This study included six cases (median age 23, interquartile range 33) of sclopetaria. Additionally, literature searches were conducted in the PubMed and Cochrane Library databases to uncover risk factors associated with all published cases of sclopetaria. Main outcome measure was best corrected visual acuity (BCVA) worse than 20/20. Sixty-seven cases (71 eyes) of sclopetaria have been reported, of which 59 cases (61 eyes) met inclusion criteria in this study. Most were young (median age 19.5 years) men (51/59, 88.1%). Thirty-seven eyes were observed while 24 underwent immediate surgery including six pars plana vitrectomies and three scleral buckles. Compared to initial presentation, BCVA improved in 31/48 (64.6%) eyes, remained stable in 12/48 eyes (25.0%), and worsened in 5/48 eyes (10.4%). Ten patients (16.4%) achieved a final BCVA of 20/20 with median follow up time of seven months. In a multivariate model, location of sclopetaria in the macula, temporal retina, or immediate orbital foreign body removal predicted poor final BCVA with an area under receiver operating characteristic curve of 0.767.Conclusions and importance: Traumatic chorioretinitis sclopetaria is rare, but reports have increased dramatically over the past two decades. While pars plana vitrectomy may be required for the management of retinal detachments and non-clearing vitreous hemorrhage, close observation is appropriate in most cases. Visual prognosis is poor with most patients attaining 20/200 vision or worse.

View details for PubMedID 30834355

Abstract

PURPOSE: To evaluate the utility of standard postoperative visit (POV) intervals in pars plana vitrectomy (PPV) as a function of adverse events (AEs) identified.DESIGN: Retrospective case review.METHODS: The medical records of all patients undergoing 23-, 25-, and 27-gauge PPV from January 1, 2016 to December 31, 2016 were reviewed. Each POV was assessed as a standard (s-POV), physicianadjusted (a-POV), or patient-initiated visit (p-POV). Preoperative features, diagnoses, and surgical procedures were evaluated to determine protective and risk factors for AEs.RESULTS: A total of 256 patients (310 PPVs) were included in this study. The most common cumulative postoperative AEs were elevated intraocular pressure (>30 mm Hg) (12.3%), cystoid macular edema (6.1%), and retinal detachment (5.8%). Patients with the diagnosis of macular hole or epiretinal membrane had the lowest relative risk of AEs [0.30; 95% confidence interval (CI), 0.12-0.75 and 0.36; 95% CI, 0.21-0.63, respectively]. There was no difference in time to AE among different vitrectomy gauge sizes (P = 0.733). Patients in a-POV and p-POV groups had a statistically significant higher incidence of AEs in the POV day 5-10 window (P = 0.004).CONCLUSIONS: The utility of standard POVs in detecting AEs is dependent on the indication for PPV. Specifically patients undergoing isolated macular surgery (epiretinal membrane peel or macular hole repair) had the lowest relative risk of postoperative AEs and may warrant a less-intensive follow-up regimen.

View details for PubMedID 30628767

Abstract

To determine the association and cumulative dose-response pattern between pentosan polysulfate sodium (PPS) use for interstitial cystitis (IC) and maculopathy.Large, multicenter, retrospective cohort study of commercially insured patients in the MarketScan database (Truven Health Analytics, San Jose, CA).Two hundred twenty-seven thousand three hundred twenty-five patients with IC who were enrolled continuously in the MarketScan database.Cox proportional hazards models (controlling for patient gender, age at index diagnosis of IC, and diagnosis with diabetes mellitus) followed up patients from index diagnosis of IC for 5 years, or until patients discontinued insurance coverage, or until patients' first diagnosis with a maculopathy. As a sensitivity analysis, we re-estimate all models after excluding all patients with diabetes. To assess for dose response, we calculated the total days of PPS prescriptions filled and created a categorical variable indicating total exposure.The primary outcome measure was association between binary PPS exposure and any maculopathy. Secondary outcome measures included exposure between binary and categorical, time-dependent, exposure to PPS and to drusen, nonexudative age-related macular degeneration (AMD), exudative AMD, hereditary maculopathy, and toxic maculopathy.The most common diagnoses of maculopathy in patients with IC were exudative AMD (1.5%), drusen (0.8%), nonexudative AMD (0.3%), toxic maculopathy (0.1%), and hereditary dystrophy (0.04%). In unadjusted analyses, the percentage of patients who filled a PPS prescription and were diagnosed later with a maculopathy (2.37%) was very similar to the percentage of patients who did not fill a prescription (2.77%). Survival models using a binary variable indicating PPS exposure showed no significant associations between PPS exposure and diagnosis of drusen, nonexudative AMD, exudative AMD, toxic maculopathy, hereditary dystrophy, or an aggregate variable of any maculopathy. Similarly, there was no dose-dependent relationship between PPS exposure and diagnosis of any maculopathy. These findings remained stable in sensitivity analysis models that excluded patients with diabetes mellitus.In this large, commercial claims database analysis, no association was found between PPS exposure and subsequent diagnosis of maculopathy.

View details for DOI 10.1016/j.ophtha.2019.10.036

View details for PubMedID 31899034

Abstract

To understand changes in disease activity as assessed by leakage and retinal fluid status in patients with neovascular age-related macular degeneration (nAMD) receiving fixed dosing with an anti-vascular endothelial growth factor (anti-VEGF) agent.In the phase III VIEW 1 (NCT00509795) and VIEW 2 (NCT00637377) studies, eyes with nAMD were treated with intravitreal aflibercept or ranibizumab. Independent, masked reading centres determined the presence/absence of leakage (fluorescein angiography) and retinal fluid (optical coherence tomography) at baseline, week 24 and week 52. In this integrated, post hoc analysis of the VIEW studies, the relationship between leakage/fluid status and best-corrected visual acuity (BCVA) was assessed. The impact of baseline lesion type (predominantly classic (PC), minimally classic (MC), occult) was also evaluated. Data from all treatment groups were pooled.2373 eyes were included in this analysis. At baseline, 95.4% of eyes presented with both leakage and fluid. By week 52, leakage and fluid were present in 16.0% of eyes. Mean BCVA gains at week 52 were numerically greater in eyes without leakage and fluid versus eyes with both leakage and fluid (10.3 vs 9.2 letters). At week 52, 11.6%, 15.3% and 20.1% of eyes with PC, MC and occult lesions, respectively, had both leakage and fluid present.In this post hoc analysis, fixed dosing with an anti-VEGF agent over 52 weeks eliminated disease activity (absence of both leakage and fluid) in most eyes. The effect of anti-VEGF treatment on leakage/fluid status favoured PC versus occult lesions.

View details for DOI 10.1136/bjophthalmol-2019-315021

View details for PubMedID 31826853

Abstract

To evaluate the impact of lipid-lowering medications on diabetic retinopathy and diabetic complications requiring intervention in the U.S.Retrospective cohort analysis.Administrative insurance claims drawn from the Truven MarketScan Commercial Claims and Encounters database.Beneficiaries with Type 2 diabetes mellitus (T2DM).Any signs of diabetic retinopathy, as measured by diagnosis codes for non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), diabetic macular edema (DME), and procedure codes for retinopathy treatments (anti-VEGF injections, laser therapy, and vitrectomy).We analyzed a population of 269,782 patients diagnosed with T2DM between 2008 and 2015. 99,233 (37%) of patients were undergoing treatment with lipid-lowering medications. Approximately 6% of patients on lipid-lowering medications had a diagnosis code for NPDR, PDR, or DME, or a procedural code for intravitreal injections, PPV, or laser in their record following diagnosis with diabetes, compared to 6.5% of patients who did not take lipid-lowering medications (p<0.01). In adjusted time-to-event analyses, patients who took lipid-lowering medications prior to diagnosis with T2DM were less likely to progress to any retinopathy diagnosis (HR 0.60, 95% CI 0.55-0.65) and less likely to receive any treatment for retinopathy (HR 0.81, 95% CI 0.78-0.84). These findings were significant at the aggregate level, as well as at the level of individual diagnosis (NPDR HR 0.63, 95% CI 0.57-0.69; PDR HR 0.45, 95% CI 0.37-0.54; DME HR 0.39, 95% CI 0.33-0.45), and at the level of each treatment category (anti-VEGF injection HR 0.81, 95% CI 0.78-0.84; laser HR 0.62, 95% CI 0.47-0.81; vitrectomy HR 0.71, 95% CI 0.59-0.85).We find consistent evidence that patients on lipid-lowering medications are less likely to develop NPDR, PDR, or DME, and modest evidence that these patients are less likely to receive intravitreal injections of anti-VEGF medication, laser treatments, or vitrectomy. Our study validates the findings of studies that have used claims databases in East Asia in relatively homogeneous populations to estimate an association between statin use and retinopathy, replicating them in a U.S. context in a large commercial claims database.

View details for DOI 10.1016/j.ajo.2019.05.029

View details for PubMedID 31194953

Abstract

To determine the effect of race, ethnicity, and census-tract-level composite socioeconomic status (SES) on retinoblastoma enucleation. This study augments Truong et al., providing multivariate analyses combining sociodemographic and clinical characteristics with more accurate SES measures. We hypothesized children from non-white, Hispanic, and lower socioeconomic backgrounds would have increased adjusted odds of enucleation.Retrospective cohort analysis.Setting: Multicenter population-based study using the Surveillance, Epidemiology, and End Results (SEER) 18 Registries.Children aged 18 and under diagnosed with retinoblastoma between 2000-2014. Subjects were identified using International Classification of Diseases Oncology (ICD-O) site and morphology codes.Enucleation Odds Ratios and 95% Confidence Intervals RESULTS: Analysis of 959 retinoblastoma patients revealed that 70.8% were enucleated. Adjusted analyses showed associations between enucleation and Asian (Odds Ratio (OR) 2.00, Confidence Interval (CI) 1.08-3.71) or Black (2.42, 1.41-4.16) race, Hispanic ethnicity (1.69, 1.16-2.46), and low SES (1.68, 1.09-2.58). Significantly increased enucleation risk was associated with older age at diagnosis (Age 1-2 years 2.55, 1.80-3.61; >2 years 4.88, 2.57-9.25), unilateral disease (5.00, 3.45-7.14), and advanced stage (Regional 4.71, 2.51-8.84; Distant 3.15, 1.63-6.08). No interactions were observed between race, ethnicity, SES, and stage at diagnosis. Enucleation rates decreased over time across all racial, ethnic, and socioeconomic groups.Children from non-white, Hispanic, and lower socioeconomic backgrounds are more likely to receive enucleation. These associations are independent of stage of diagnosis, suggesting larger systemic disparities in retinoblastoma care. The origin of these differences requires further study and attention by clinicians and policy-makers.

View details for PubMedID 31077666

Abstract

PURPOSE: To determine if final visual acuity (VA) is affected by duration of macular detachment (DMD) within the first week of macula-off retinal detachment (RD).METHODS: This is a retrospective study of eyes that underwent repair within 7 days with vitrectomy or vitrectomy with scleral buckle for macula-off RD at Stanford University Hospital between 1 May 2007 and 1 May 2017. A generalised linear model was constructed using DMD, postoperative lens status, preoperative VA, patient age and surgeon as the independent variables and the final VA as the dependent variable. The main outcome measure was the final VA.RESULTS: Seventy-nine eyes met the entry criteria. Group 1 included 52 eyes with RD repaired within 3 days of DMD, and group 2 included 27 eyes repaired between 4 and 7 days of DMD. The average final VA in group 1 eyes was logarithm of the minimum angle of resolution (logMAR) 0.21 (Snellen 20/33) and in group 2 eyes was logMAR 0.54 (Snellen 20/69). In group 1 and group 2 eyes, preoperative VA (p=0.017and p=0.007), DMD (p=0.004 and p=0.041) and final lens status (p<0.0001and p<0.001) predicted postoperative VA. Post-hoc analysis showed significant differences in final VA between detachments of 1day vs 3 days (p=0.0009).CONCLUSION: DMD affects the final VA even among patients whose DMD is <3 days. Based on these results, interventions that shorten DMD, including those occurring within the first 3days, may result in improved long-term VA outcomes.

View details for PubMedID 30504489

Abstract

INTRODUCTION:: To evaluate the adverse event rate following pars plana vitrectomy as a function of surgical start time and the presence of a vitreoretinal fellow.METHODS:: Single-institution retrospective cohort study of patients undergoing pars plana vitrectomy from 1 January 2016 to 31 December 2016 at Stanford University School of Medicine (Palo Alto, CA, USA). Records were reviewed for surgical start time, the presence of vitreoretinal fellow, and postoperative adverse events defined as any finding deviating from the expected postoperative course requiring observation or intervention.RESULTS:: A total of 310 pars plana vitrectomies were performed. There was no statistical difference in the rate of any adverse event when comparing cases starting after 16:01 (9/13, 69.2%) and after 12:01 (42/99, 42.4%) to a morning start time (69/198, 34.9%, adjusted p=0.083). There was a statistically significant increase in the risk of postoperative vitreous hemorrhage with afternoon and evening cases as compared to morning cases (adjusted p=0.021). In addition, there was no difference in any adverse event with a fellow present (93/244, 38.1%) compared to without (27/66, 40.9%, adjusted p=0.163). There was a higher risk of postoperative hypotony when a fellow was involved (6.6% vs 0%, p=0.028), though this difference disappeared after adjusting for confounders (adjusted p=0.252). There was no difference in the length of surgery with and without a fellow (49 vs 54min, respectively; p=0.990).DISCUSSION:: Afternoon start time and the presence of a fellow were not independent risk factors for postoperative adverse events.

View details for PubMedID 30426767

Abstract

PURPOSE: To describe an improved understanding of the regression patterns following off-label intravitreal bevacizumab (IVB) treatment for retinopathy of prematurity (ROP).DESIGN: Retrospective cohort study. MethodsAll infants treated with IVB for Type 1 ROP at a single institution from June 2013 to March 2018 were retrospectively reviewed and the amount of retinal non-perfusion on fluorescein angiogram was calculated. ResultsOnly 3 eyes (3.3%) reached full vascular maturity in the 92 eyes of 46 patients analyzed. Of the 89 eyes not reaching maturity, 39 eyes (43.8%) had vascular arrest alone (VAA), 34 eyes (38.2%) had vascular arrest with persistent tortuosity (VAT), and 16 (18.0%) had ROP reactivation. Those eyes that reactivated were more likely to be initially classified as aggressive posterior ROP (p = 0.004) and of Asian ethnicity (p = 0.008). There were greater areas of ischemia in eyes with reactivation as compared to VAT and VAA (112.1 mm2 vs 72.5 mm2 vs. 56.6 mm2, respectively, p = 0.007). Younger gestational age at birth was found to be an independent predictor of persistent tortuosity (VAT vs. VAA) in a logistic regression model. ConclusionsIncomplete vascularization following IVB is very common and is associated with a younger gestational age at birth, Asian ethnicities, and aggressive posterior ROP. The presence of tortuosity following IVB may be indicative of persistently elevated VEGF levels and an early indicator of potential reactivation.

View details for PubMedID 30312578

Abstract

PURPOSE: High myopia and pathologic myopia are common causes of visual morbidity. Myopic pathology can affect all regions of the retina, though there is currently no classification system to distinguish anterior (peripheral) and posterior (macular) pathology. We hypothesize that these classifications are characterized by distinct demographic and refractive features, highlighting the disparity in types of pathologic myopia.METHODS: Institutional retrospective cohort study. The Stanford University Medical Center Clinical Data Warehouse was used to identify patients with high myopia by ICD-9 and ICD-10 codes. Predetermined ICD diagnoses were then used to classify patients with high myopia into isolated high myopia (IHM), anterior pathologic myopia (APM), posterior pathologic myopia (PPM), and combined pathologic myopia (CPM). A cohort of this population was then manually reviewed to gather refractive data and confirm accuracy of ICD coding.RESULTS: Patients (3274) were identified with high myopia. Overall, 22.1% individuals met criteria for APM, 10.7% for PPM, 17.0% for CPM, and 50.2% for IHM. We identified a significantly higher frequency of females with PPM compared to APM (62.3 vs. 48.3%; OR, 1.73; 95% CI, 1.34 to 2.25), Asian patients with PPM as compared to APM (42.9 vs. 33.3%; OR, 1.50; 95% CI, 1.16 to 1.95), and younger patients with APM compared to PPM (median 45.3 vs. 63.4years). The refractive error was significantly more myopic in the CPM (median -9.8D; interquartile range,IQR 6.7) and PPM (median -10.5D; IQR 9.8) subgroups as compared to the APM (median -8.1D; IQR 3.5), and IHM (median - 8.2D; IQR 4.1) subgroups (p=0.003).CONCLUSIONS: High myopia may be divided into four distinct subgroups based on presence and location of pathology, which is associated with differences in age, gender, race, and refractive error.

View details for PubMedID 30030628

Abstract

This review highlights the common areas of medicolegal risk during retinopathy of prematurity (ROP) screening.Most malpractice risk in ROP comes from systemic errors that ultimately result in failure to screen the patient in a timely fashion, resulting in failures to intervene and/or refer in a timely fashion. Currently, the emphasis is engaging the family members, the hospital staff, and clinic staff to pro-actively manage ROP patients and ensure that they are screened in a timely fashion. Coordinating care between multiple caregivers can minimize risk. Risk increases when practitioners do not stay up to date on current screening and treatment guidelines or on the most recent study recommendations. Finally, it is important to maintain a high level of suspicion when dealing with infants is known to be predisposed to poor outcomes.Premature infants with short gestation and very low birthweights need to have structured screening coordinated between the hospital, the clinic, the physicians, and the family in order to minimize medicolegal risk and maximize beneficial outcomes.

View details for PubMedID 29561286

Abstract

The validity of the red reflex exam has yet to be tested against new methods of wide-angle imaging that may improve early detection of neonatal ocular pathology. The authors aimed to determine the validity of the pediatrician's red reflex exam using 130° wide-angle external and fundus digital imaging as a gold standard.This was a prospective cohort study of 194 healthy, term newborns enrolled in the Newborn Eye Screening Test study at Lucile Packard Children's Hospital from July 25, 2013, to July 25, 2014. Red reflex screening was performed by a pediatrician in the newborn nursery and wide-angle fundus digital imaging was performed by a neonatal intensive care unit-certified nurse. The main outcome measure was the validity of the pediatrician's red reflex exam (unweighted kappa [κ] statistic, sensitivity, specificity).Compared to no subjects with abnormal red reflex exams reported in the pediatrician's notes, 49 subjects demonstrated one or multiple ocular abnormalities on 130° wide-angle fundus imaging (κ = 0.00). The pediatrician's red reflex exam had a sensitivity of 0.0% (95% CI, 0.0%-7.3%) and specificity of 100.0% (95% CI, 97.5%-100.0%) for the detection of ocular abnormalities.This study demonstrates the ability of wide-angle fundus imaging to detect fundus abnormalities not otherwise identified by standard newborn red reflex screening prior to hospital discharge. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:103-110.].

View details for DOI 10.3928/23258160-20180129-04

View details for PubMedID 29443359

Abstract

To describe a technique that reduces patient discomfort by using a valved 25-gauge trocar for vitreous tap and intravitreal injection of medications in previously vitrectomized eyes with suspected infectious endophthalmitis.A commercially available 25-gauge valved entry system is used to enter the vitreous cavity. A 25-gauge needle attached to a syringe is used to obtain a vitreous specimen for microbiological access and administer intravitreal injections of antibiotics and steroids. No vitreous volume is lost during these procedures because of the cannula's valve. At the completion of the tap and injections, the cannula is removed with forceps and the single wound tamponaded with a cotton-tipped applicator.With this method, a vitreous tap and injection of pharmacologic agents only requires one piercing through the sclera, instead of the usual four piercings.With this new technique, it is possible to enhance patient comfort, decreased pain, and reduce trauma to the conjunctiva. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:916-917.].

View details for DOI 10.3928/23258160-20171030-07

View details for Web of Science ID 000418012200007

View details for PubMedID 29121361

Abstract

This study evaluates the annual incidence of syphilitic uveitis in the US and trends in hospital admissions over time.Retrospective, longitudinal incidence rate analysis of the National Inpatient Sample (NIS) data from 1998 to 2009.The NIS is a de-identified, random sample dataset of inpatient hospitalizations from 46 states. The number of cases of syphilitic uveitis was defined by (1) International Classification of Diseases, 9th Revision (ICD-9) code for syphilis and uveitis or (2) ICD-9 code for syphilitic uveitis. Annual case count, incidence rate, and trend over time were calculated. Multivariate logistic regression was used to evaluate associated factors for a syphilitic uveitis diagnosis.The study included 455 310 286 hospitalizations during a 12-year study period with a mean of 37 942 524 patients annually. Syphilis and uveitis was recorded for 1861 patients (155 annually) and syphilitic uveitis was diagnosed in 204 subjects (average of 17 cases annually). There was no change in the incidence of syphilitic uveitis, using either definition, over the study period (P for trend = .46). The mean annual incidence of syphilis and uveitis was 0.0004%, or 4 per million. Syphilitic uveitis had an annual incidence of 0.000045%, or 0.45 per million. The odds of syphilitic uveitis were lower among women (odds ratio [OR] 0.40, CI 0.28-0.57) and increased with comorbid acquired immunodeficiency syndrome (OR 4.52, CI 3.01-6.79).We report the first incidence of syphilitic uveitis in the United States. Fortunately, this remains a rare condition. The results demonstrate no change in the number of inpatient admissions for syphilitic uveitis during the study period.

View details for DOI 10.1016/j.ajo.2017.05.013

View details for PubMedID 28549847

Abstract

The Stanford University Network for the Diagnosis of Retinopathy of Prematurity (SUNDROP) initiative-an ongoing telemedicine-based initiative for in-hospital screening of high-risk infants for treatment-warranted ROP (TW-ROP)-has been shown to be a safe, reliable, and cost-effective supplement to the efforts of ROP specialists. We utilized data collected in the SUNDROP initiative to determine demographic (birth weight, sex, multiplicity), weight gain, and ocular imaging (media haze, peripapillary atrophy, fundus pigmentation) predictors of TW-ROP.This was a retrospective nested case-control study. Cases and controls were selected from a cohort of 843 low birth weight, premature newborns who survived to an estimated gestational age of 31 weeks and underwent screening through the SUNDROP initiative. Infants were screened at one of six neonatal intensive care units from December 1, 2005, to April 1, 2016. Cases (n = 37) were newborns with TW-ROP who underwent retinal ablative therapy. Two controls (n = 74) without TW-ROP were matched to each case by gestational age. One reviewer graded media haze, presence of peripapillary atrophy, and fundus pigmentation in images taken at the baseline exam for each newborn. The main outcome measure was association of TW-ROP with predictive factors.In the SUNDROP trial, 37 out of 843 (4.4%) newborns developed TW-ROP. In a multivariable model, birth weight (OR, 0.32; 95% CI, 0.15-0.70) was inversely associated with TW-ROP. In contrast to prior reports, we found no significant difference in sex, multiplicity, or fundus pigmentation at baseline exam in those with TW-ROP as compared to controls. High levels of media haze (>2, scale 0 to 5) were found in the majority of cases (67.6%, 25/37) and controls (65.7%, 44/67). Presence of peripapillary atrophy did not improve prediction of the development of TW-ROP compared to birth weight and weight gain rate alone.The finding of high levels of media haze at baseline ROP screening exams is novel. This study supports the current model for detection of TW-ROP using birth weight, gestational age, and weight gain rate. We found no significant difference between newborns with TW-ROP and controls in baseline presence of media haze, fundus pigmentation or peripapillary atrophy.

View details for PubMedID 28782073

Abstract

To summarize the literature addressing subthreshold or nondamaging retinal laser therapy (NRT) for central serous chorioretinopathy (CSCR) and to discuss results and trends that provoke further investigation.Analysis of current literature evaluating NRT with micropulse or continuous wave lasers for CSCR.Sixteen studies including 398 patients consisted of retrospective case series, prospective nonrandomized interventional case series, and prospective randomized clinical trials. All studies but one evaluated chronic CSCR, and laser parameters varied greatly between studies. Mean central macular thickness decreased, on average, by ∼80 μm by 3 months. Mean best-corrected visual acuity increased, on average, by about 9 letters by 3 months, and no study reported a decrease in acuity below presentation. No retinal complications were observed with the various forms of NRT used, but six patients in two studies with micropulse laser experienced pigmentary changes in the retinal pigment epithelium attributed to excessive laser settings.Based on the current evidence, NRT demonstrates efficacy and safety in 12-month follow-up in patients with chronic and possibly acute CSCR. The NRT would benefit from better standardization of the laser settings and understanding of mechanisms of action, as well as further prospective randomized clinical trials.

View details for PubMedID 27841848

Abstract

To describe a pattern of retinopathy of prematurity (ROP) disease regression and chronic vascular arrest after intravitreal bevacizumab treatment that is not observed after peripheral laser ablation.Single-institution retrospective cohort study.Consecutive sample of 58 eyes in 30 patients treated for type 1 ROP.Initial treatment with either a single intravitreal injection of bevacizumab in off-label use (n = 33 eyes) or peripheral laser ablation (n = 25 eyes) as part of standard clinical care. There was bias in recommending off-label bevacizumab for smaller infants with type 1 ROP.Reactivation or persistence of ROP, as determined by clinical examination, fundus photography, and fluorescein angiography.All eyes treated initially with bevacizumab demonstrated irregular progression of the leading vascular edge in a stereotyped pattern, suggestive of scalloped regression. Recurrence, based on angiographic demonstration of leakage, or chronic vascular arrest, confirmed based on angiographic demonstration of peripheral ischemia, was noted in 30 eyes (91%) in the bevacizumab group, at a median interval of 14.9 weeks after injection (corrected gestational age, 49.3 weeks). Univariate logistic regression indicated that the need for rescue treatment was associated with decreased birth weight (odds ratio [OR], -0.007; P = 0.04) and age of initial treatment (OR, -0.35; P = 0.05), but not gender, race, or gestational age. Multivariate logistic regression indicated that only decreased birth weight (OR, -0.018; P = 0.04) was associated with need for rescue treatment.Treating ROP with intravitreal bevacizumab results in a characteristic scalloped regression pattern that is highly associated with treatment using biologic anti-vascular endothelial growth factor agents. The presence of this pattern in conjunction with chronic vascular arrest and peripheral retinal ischemia persisting beyond standard screening timelines has significant implications for the management of ROP. Fluorescein angiography is important in assessing vascular maturation in these infants.

View details for DOI 10.1016/j.ophtha.2016.06.055

View details for PubMedID 27506484

Abstract

This study aims to assess the birth prevalence of iris colour among newborns in a prospective, healthy, full-term newborn cohort.The Newborn Eye Screening Test (NEST) study is a prospective cohort study conducted at Lucile Packard Children's Hospital at Stanford University School of Medicine. A paediatric vitreoretinal specialist (DMM) reviewed images sent to the Byers Eye Institute telemedicine reading centre and recorded eye colour for every infant screened. Variables were graphed to assess for normality, and frequencies per subject were reported for eye colour, sex, ethnicity and race.Among 192 subjects screened in the first year of the NEST study with external images of appropriate quality for visualization of the irides, the birth prevalence of iris colour was 63.0% brown, 20.8% blue, 5.7% green/hazel, 9.9% indeterminate and 0.5% partial heterochromia. The study population was derived from a quaternary care children's hospital. We report the birth prevalence of iris colour among full-term newborns in a diverse prospective cohort.The study demonstrates a broad range of iris colour prevalence at birth with a predominance of brown iris coloration. Future studies with the NEST cohort will assess the change in iris colour over time and whether the frequencies of eye colour change as the child ages.

View details for DOI 10.1111/aos.13006

View details for PubMedID 27061128

Abstract

To describe the ocular findings of 3 cases of suspected congenital Zika viral infection with microcephaly and maculopathy.Retrospective, consecutive case series.Three male infants born in northern Brazil whose mothers demonstrated a viral syndrome during the first trimester and who subsequently were born with microcephaly.Observational report of macular findings.Continued observation.Three male infants were born with microcephaly to mothers who had a viral syndrome during the first trimester of gestation in an area that subsequently has demonstrated epidemic Zika infection, a flavivirus related to Dengue. Ocular examination was performed. All 6 eyes demonstrated a pigmentary maculopathy ranging from mild to pronounced. In 4 eyes, well-delineated macular chorioretinal atrophy with a hyperpigmented ring developed. Three eyes demonstrated vascular tortuosity and 2 eyes demonstrated a pronounced early termination of the retinal vasculature on photographic evaluation. Two eyes demonstrated a washed out peripheral retina with a hypolucent spot. One eye had scattered subretinal hemorrhages external to the macula. Finally, 1 eye demonstrated peripheral pigmentary changes and clustered atrophic lesions resembling grouped congenital albinotic spots (polar bear tracks).Zika virus has been linked to microcephaly in children of mothers with a viral syndrome during the first trimester of pregnancy. Ocular findings previously described a pigmentary retinopathy and atrophy that now can be expanded to include torpedo maculopathy, vascular changes, and hemorrhagic retinopathy. Ophthalmologic screening guidelines need to be defined to determine which children would benefit from newborn screening in affected regions.

View details for DOI 10.1016/j.ophtha.2016.05.001

View details for PubMedID 27236271

Abstract

Retinopathy of Prematurity (ROP) is a leading cause of childhood blindness. The incidence of ROP is rising, placing greater demands on the healthcare providers that serve these patients and their families. Telemedicine remote digital fundus imaging (TM-RDFI) plays a pivotal role in ROP management, and has allowed for the expansion of ROP care into previously underserved areas.A broad literature review through the pubmed index was undertaken with the goal of summarizing the current state of ROP and guidelines for its screening . Furthermore, all currently used telemedicine remote digital fundus imaging devices were analyzed both via the literature and the companies' websites/brochures. Finally, the PanoCam LT™ and PanoCam™ Pro created by Visunex Medical were analyzed via the company website/brochures. Expert commentary: The PanoCam LT™ and PanoCam™ Pro have recently been approved for use within the USA and CE marked for international commercialization in European Union and other countries requiring CE mark. These wide-field imaging systems have the intended use of ophthalmic imaging of all newborn babies and meet the requirements for ROP screening, thereby serving as competition within the ROP screening market previously dominated by one camera imaging system.

View details for DOI 10.1080/17434440.2016.1208560

View details for PubMedID 27424884

Abstract

Diabetic retinopathy (DR) is the leading cause of blindness among working-age adults. DR often leads to diabetic macular edema (DME), which often goes unnoticed until a patient presents with vision loss. However, treatment options and data for DME are continually improving. We know that vascular endothelial growth factor (VEGF) plays a key role in DME progression; therapies that act by inhibiting VEGF production seem to improve visual acuity in patients with DME. Of the anti-VEGF therapies available, two have been approved by the U.S. Food and Drug Administration to treat DME: ranibizumab (Lucentis; Genentech, South San Francisco, CA) and aflibercept (Eylea; Regeneron, Tarrytown, NY). Bevacizumab (Avastin; Genentech, South San Francisco, CA), which is approved for the treatment of certain types of cancer, is occasionally used off-label to treat DME. Anti-VEGF therapy can stop vision loss and even improve visual acuity. Other treatments remain effective, and these various treatment options fuel a need for new data and discussion. This roundtable discussion, which took place during the 2015 annual meeting of the American Academy of Ophthalmology, outlines the current protocols used to treat DME and provides clinical opinions about selecting and treating with an appropriate anti-VEGF therapy. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:S5-14.].

View details for DOI 10.3928/23258160-20160415-01

View details for Web of Science ID 000393099700001

View details for PubMedID 27348433

Abstract

To assess the accuracy of best-corrected visual acuity (BCVA) measured by non-ophthalmic emergency department (ED) staff with a standard Snellen chart versus an automated application (app) on a handheld smartphone (Paxos Checkup, San Francisco, CA, USA).The study included 128 subjects who presented to the Stanford Hospital ED for whom the ED requested an ophthalmology consultation. We conducted the study in two phases. During phase 1 of the study, ED staff tested patient BCVA using a standard Snellen test at 20 feet. During phase 2 of the study, ED staff tested patient near BCVA using the app. During both phases, ophthalmologists measured BCVA with a Rosenbaum near chart, which was treated as the gold standard. ED BCVA measurements were benchmarked prospectively against ophthalmologists' measurements and converted to logMAR.ED logMAR BCVA was 0.21 ± 0.35 (approximately 2 Snellen lines difference ± 3 Snellen lines) higher than that of ophthalmologists when ED staff used a Snellen chart (p = .0.00003). ED BCVA was 0.06 ± 0.40 (less than 1 Snellen line ± 4 Snellen lines) higher when ED staff used the app (p = 0.246). Inter-observer difference was therefore smaller by more than 1 line (0.15 logMAR) with the app (p = 0.046).BCVA measured by non-ophthalmic ED staff with an app was more accurate than with a Snellen chart. Automated apps may provide a means to standardize and improve the efficiency of ED ophthalmologic care.

View details for DOI 10.1007/s00417-016-3291-4

View details for PubMedID 26931323

Abstract

To report the birth prevalence, risk factors, characteristics, and location of fundus hemorrhages (FHs) of the retina and optic nerve present in newborns at birth.Prospective cohort study at Stanford University School of Medicine.All infants who were 37 weeks postmenstrual age or older and stable were eligible for screening. Infants with known or suspected infectious conjunctivitis were excluded.Infants born at Lucile Packard Children's Hospital (LPCH) from July 25, 2013, through July 25, 2014, were offered universal newborn screening via wide-angle digital retinal photography in the Newborn Eye Screen Test study. Maternal, obstetric, and neonatal factors were obtained from hospital records. The location, retinal layer, and laterality of FH were recorded by 1 pediatric vitreoretinal specialist.Birth prevalence of FH. Secondary outcomes included rate of adverse events, risk factors for FH, hemorrhage characteristics, and adverse events.The birth prevalence of FH in this study was 20.3% (41/202 infants). Ninety-five percent of FHs involved the periphery, 83% involved the macula, and 71% involved multiple layers of the retina. The fovea was involved in 15% of FH cases (birth prevalence, 3.0%). No cases of bilateral foveal hemorrhage were found. Fundus hemorrhages were more common in the left eye than the right. Fundus hemorrhages were most commonly optic nerve flame hemorrhages (48%) and white-centered retinal hemorrhages (30%). Retinal hemorrhages were found most frequently in all 4 quadrants (35%) and more often were multiple than solitary. Macular hemorrhages most often were intraretinal (40%). Among the risk factors examined in this study, vaginal delivery compared with cesarean section (odds ratio [OR], 9.34; 95% confidence interval [CI], 2.57-33.97) showed the greatest level of association with FH. Self-identified ethnicity as Hispanic or Latino showed a protective effect (OR, 0.43; 95% CI, 0.20-0.94). Other study factors were not significant.Fundus hemorrhages are common among newborns. They often involve multiple areas and layers of the retina. Vaginal delivery was associated with a significantly increased risk of FH, whereas self-identified Hispanic or Latino ethnicity was protective against FH in this study. The long-term consequences of FH on visual development remain unknown.

View details for DOI 10.1016/j.ophtha.2016.01.004

View details for PubMedID 26875004

Abstract

To report the birth prevalence, risk factors, characteristics, and location of fundus hemorrhages (FHs) of the retina and optic nerve present in newborns at birth.Prospective cohort study at Stanford University School of Medicine.All infants who were 37 weeks postmenstrual age or older and stable were eligible for screening. Infants with known or suspected infectious conjunctivitis were excluded.Infants born at Lucile Packard Children's Hospital (LPCH) from July 25, 2013,