REGIONAL POPULATION MOBILITY AND OUTPATIENT RETINA VISITS IN THE UNITED STATES DURING THE COVID-19 PANDEMIC.

PURPOSE: To characterize how community mobility patterns across the United States correlate with local changes in retina visits during the pandemic. METHODS: Outpatient retina clinic visits were linked to population mobility by combining multiple public data sets, including the Google Community Mobility Reports and data from the Centers for Disease Control and Infection. Percentage change from baseline in daily-average number of retina visits by county and mobility were measured by county. RESULTS: A total of 2,159,689 patient visits were examined across 332 counties. Daily-average retina visits decreased by 7.0%, 19.0%, 5.0%, and 4.0% from Quarter 1 to 4 of 2020. This decrease was negatively correlated with increased incident of COVID-19 deaths for Quarters 1 to 3 (r = -0.13, r = -0.16, and r = -0.15, respectively, P < 0.001) and increased incident cases for Quarters 1 and 2 (r = -0.18, r = -0.13, respectively, P < 0.001). Daily-average retina visits relative to baseline were significantly lower for metropolitan counties in Quarters 1 and 2, compared with urban and rural (P < 0.001). The decline in retina visits had greatest association with decline in workplace visits in Quarters 1 to 3 (r = 0.27, r = 0.09, r = 0.12, respectively, P < 0.001 for all). CONCLUSION: This study provides insight into how regional mobility patterns may help to explain and predict patient behaviors and retina outpatient visit responses during the COVID-19 pandemic.

Real-Time RT-PCR Allelic Discrimination Assay for Detection of N501Y Mutation in the Spike Protein of SARS-CoV-2 Associated with B.1.1.7 Variant of Concern.

The N501Y amino acid mutation caused by a single point substitution A23063T in the spike gene of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is possessed by three variants of concern (VOCs), B.1.1.7, B.1.351, and P.1. A rapid screening tool using this mutation is important for surveillance during the coronavirus disease 2019 (COVID-19) pandemic. We developed and validated a single nucleotide polymorphism real-time reverse transcription PCR assay using allelic discrimination of the spike gene N501Y mutation to screen for potential variants of concern and differentiate them from SARS-CoV-2 lineages without the N501Y mutation. A total of 160 clinical specimens positive for SARS-CoV-2 were characterized as mutant (N501Y) or N501 wild type by Sanger sequencing and were subsequently tested with the N501Y single nucleotide polymorphism real-time reverse transcriptase PCR assay. Our assay, compared to Sanger sequencing for single nucleotide polymorphism detection, demonstrated positive percent agreement of 100% for all 57 specimens displaying the N501Y mutation, which were confirmed by Sanger sequencing to be typed as A23063T, including one specimen with mixed signal for wild type and mutant. Negative percent agreement was 100% in all 103 specimens typed as N501 wild type, with A23063 identified as wild type by Sanger sequencing. The identification of circulating SARS-CoV-2 lineages carrying an N501Y mutation is critical for surveillance purposes. Current identification methods rely primarily on Sanger sequencing or whole-genome sequencing, which are time consuming, labor intensive, and costly. The assay described herein is an efficient tool for high-volume specimen screening for SARS-CoV-2 VOCs and for selecting specimens for confirmatory Sanger or whole-genome sequencing. IMPORTANCE During the coronavirus disease 2019 (COVID-19) pandemic, several variants of concern (VOCs) have been detected, for example, B.1.1.7, B.1.351, P.1, and B.1.617.2. The VOCs pose a threat to public health efforts to control the spread of the virus. As such, surveillance and monitoring of these VOCs is of the utmost importance. Our real-time RT-PCR assay helps with surveillance by providing an easy method to quickly survey SARS-CoV-2 specimens for VOCs carrying the N501Y single nucleotide polymorphism (SNP). Samples that test positive for the N501Y mutation in the spike gene with our assay can be sequenced to identify the lineage. Thus, our assay helps to focus surveillance efforts and decrease turnaround times.

ACUTE MACULAR NEURORETINOPATHY AFTER SARS-COV-2 VACCINATION.

PURPOSE: To present the rare case of a patient who developed acute macular neuroretinopathy (AMN) after administration of a single-dose adenovector coronavirus vaccine. METHODS: Retrospective chart review. RESULTS: A 26-year-old woman presented with paracentral scotomas in both eyes that acutely developed 2 days after administration of a single-dose adenovector SARS-CoV-2 vaccine (Johnson & Johnson, New Brunswick, NJ). She had previously received the seasonal influenza immunization without any symptoms and denied having any recent history of viral illnesses. On examination, optical coherence tomography showed parafoveal hyperreflective bands in the outer retina of both eyes without retinal thickening and near-infrared reflectance showed wedge-shaped parafoveal lesions pointing to the fovea, both classic findings in acute macular neuroretinopathy. DISCUSSION: This report highlights the development of acute macular neuroretinopathy after a SARS-CoV-2 vaccination in an otherwise healthy female patient. A single case cannot establish cause and effect, and millions of COVID-19 vaccines have been administered safely at the time of writing. However, this may be a rare association, and clinicians can consider inquiring about recent vaccination history in patients presenting with acute macular neuroretinopathy.

Impact of coronavirus disease 2019 (COVID-19) pre-test probability on positive predictive value of high cycle threshold severe acute respiratory coronavirus virus 2 (SARS-CoV-2) real-time reverse transcription polymerase chain reaction (RT-PCR) test results.

OBJECTIVES: Performance characteristics of SARS-CoV-2 nucleic acid detection assays are understudied within contexts of low pre-test probability, including screening asymptomatic persons without epidemiological links to confirmed cases, or asymptomatic surveillance testing. SARS-CoV-2 detection without symptoms may represent presymptomatic or asymptomatic infection, resolved infection with persistent RNA shedding, or a false-positive test. This study assessed the positive predictive value of SARS-CoV-2 real-time reverse transcription polymerase chain reaction (rRT-PCR) assays by retesting positive specimens from 5 pre-test probability groups ranging from high to low with an alternate assay. METHODS: In total, 122 rRT-PCR positive specimens collected from unique patients between March and July 2020 were retested using a laboratory-developed nested RT-PCR assay targeting the RNA-dependent RNA polymerase (RdRp) gene followed by Sanger sequencing. RESULTS: Significantly fewer (15.6%) positive results in the lowest pre-test probability group (facilities with institution-wide screening having ≤3 positive asymptomatic cases) were reproduced with the nested RdRp gene RT-PCR assay than in each of the 4 groups with higher pre-test probability (individual group range, 50.0%-85.0%). CONCLUSIONS: Large-scale SARS-CoV-2 screening testing initiatives among low pre-test probability populations should be evaluated thoroughly prior to implementation given the risk of false-positive results and consequent potential for harm at the individual and population level.

The Influence of Universal Face Mask Use on Endophthalmitis Risk after Intravitreal Anti-Vascular Endothelial Growth Factor Injections.

PURPOSE: Routine use of face masks for patients and physicians during intravitreal anti-vascular endothelial growth factor (VEGF) injections has increased with the emergence of the coronavirus disease 2019 pandemic. This study evaluates the impact of universal face mask use on rates and outcomes of post-injection endophthalmitis (PIE). DESIGN: Retrospective, multicenter, comparative cohort study. PARTICIPANTS: Eyes receiving intravitreal anti-VEGF injections from October 1, 2019, to July 31, 2020, at 12 centers. METHODS: Cases were divided into a "no face mask" group if no face masks were worn by the physician or patient during intravitreal injections or a "universal face mask" group if face masks were worn by the physician, ancillary staff, and patient during intravitreal injections. MAIN OUTCOME MEASURES: Rate of endophthalmitis, microbial spectrum, and visual acuity (VA). RESULTS: Of 505 968 intravitreal injections administered in 110 547 eyes, 85 of 294 514 (0.0289%; 1 in 3464 injections) cases of presumed endophthalmitis occurred in the "no face mask" group, and 45 of 211 454 (0.0213%; 1 in 4699) cases occurred in the "universal face mask" group (odds ratio [OR], 0.74; 95% confidence interval [CI], 0.51-1.18; P = 0.097). In the "no face mask" group, there were 27 cases (0.0092%; 1 in 10 908 injections) of culture-positive endophthalmitis compared with 9 cases (0.004%; 1 in 23 494) in the "universal face mask" group (OR, 0.46; 95% CI, 0.22-0.99; P = 0.041). Three cases of oral flora-associated endophthalmitis occurred in the "no face mask" group (0.001%; 1 in 98 171 injections) compared with 1 (0.0005%; 1 in 211 454) in the "universal face mask" group (P = 0.645). Patients presented a mean (range) 4.9 (1-30) days after the causative injection, and mean logarithm of the minimum angle of resolution (logMAR) VA at endophthalmitis presentation was 2.04 (~20/2200) for "no face mask" group compared with 1.65 (~20/900) for the "universal face mask" group (P = 0.022), although no difference was observed 3 months after treatment (P = 0.764). CONCLUSIONS: In a large, multicenter, retrospective study, physician and patient face mask use during intravitreal anti-VEGF injections did not alter the risk of presumed acute-onset bacterial endophthalmitis, but there was a reduced rate of culture-positive endophthalmitis. Three months after presentation, there was no difference in VA between the groups.

Barriers to Follow-Up Retinal Care During the COVID-19 Pandemic: A Survey Study.

BACKGROUND AND OBJECTIVE: To characterize patient-identified barriers to care in those non-compliant with retina appointments during the coronavirus disease 2019 (COVID-19) pandemic. PATIENTS AND METHODS: Inclusion criteria included non-compliant patients from March 1, 2020 to May 1, 2020. Ultimately, 1,345 patients were invited to complete a 14-question survey. A retrospective chart review correlated clinical and demographic information. Univariate logistic regression, independent-samples t-test, and Pearson correlation coefficient identified differences among subgroups. RESULTS: Of the 1,345 patients, 181 (13.5%) completed the survey. The most significant barriers to care included fear of COVID (76/181; 42.0%), wait times (21/181; 11.6%), and costs (11/181; 6.1%). Patients who got their COVID information from the Centers for Disease Control and Prevention (7.8 ± 2.4) and televised news (8.0 ± 2.0) had higher levels of fear. Finally, patients with diabetic retinopathy and higher Charlson Comorbidity Index scores had greater concerns of COVID (P = .034 and P = .047, respectively). CONCLUSION: This survey study suggests fear of COVID-19 is a prominent new barrier to retinal care. Identifying those at risk for loss to follow-up can guide practices as the pandemic continues. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:526-533.].

Characteristics of SARS-CoV-2 testing for rapid diagnosis of COVID-19 during the initial stages of a global pandemic.

Accurate SARS-CoV-2 diagnosis is essential to guide prevention and control of COVID-19. Here we examine SARS-CoV-2 molecular-based test performance characteristics and summarize case-level data related to COVID-19 diagnosis. From January 11 through April 22, 2020, Public Health Ontario conducted SARS-CoV-2 testing of 86,942 specimens collected from 80,354 individuals, primarily using real-time reverse-transcription polymerase chain reaction (rRT-PCR) methods. We analyzed test results across specimen types and for individuals with multiple same-day and multi-day collected specimens. Nasopharyngeal compared to throat swabs had a higher positivity (8.8% vs. 4.8%) and an adjusted estimate 2.9 Ct lower (SE = 0.5, p<0.001). Same-day specimens showed high concordance (98.8%), and the median Ct of multi-day specimens increased over time. Symptomatic cases had rRT-PCR results with an adjusted estimate 3.0 Ct (SE = 0.5, p<0.001) lower than asymptomatic/pre-symptomatic cases. Overall test sensitivity was 84.6%, with a negative predictive value of 95.5%. Molecular testing is the mainstay of SARS-CoV-2 diagnosis and testing protocols will continue to be dynamic and iteratively modified as more is learned about this emerging pathogen.

Temporal Dynamics and Evolution of SARS-CoV-2 Demonstrate the Necessity of Ongoing Viral Genome Sequencing in Ontario, Canada.

Genome-wide variation in SARS-CoV-2 reveals evolution and transmission dynamics which are critical considerations for disease control and prevention decisions. Here, we review estimates of the genome-wide viral mutation rates, summarize current COVID-19 case load in the province of Ontario, Canada (5 January 2021), and analyze published SARS-CoV-2 genomes from Ontario (collected prior to 24 November 2020) to test for more infectious genetic variants or lineages. The reported mutation rate (∼10-6 nucleotide [nt]-1 cycle-1) for SARS-CoV-2 is typical for coronaviruses. Analysis of published SARS-CoV-2 genomes revealed that the G614 spike protein mutation has dominated infections in Ontario and that SARS-CoV-2 lineages present in Ontario have not differed significantly in their rate of spread. These results suggest that the SARS-CoV-2 population circulating in Ontario has not changed significantly to date. However, ongoing genome monitoring is essential for identification of new variants and lineages that may contribute to increased viral transmission.

Bacterial Dispersion Associated With Various Patient Face Mask Designs During Simulated Intravitreal Injections.

PURPOSE: We sought to investigate bacterial dispersion with patient face mask use during simulated intravitreal injections. DESIGN: Prospective cross-sectional study. METHODS: Fifteen healthy subjects were recruited for this single-center study. Each participant was instructed not to speak for 2 minutes, simulating a "no-talking" policy, while in an ophthalmic examination chair with an blood agar plate secured to the forehead and wearing various face masks (no mask, loose fitting surgical mask, tight-fitting surgical mask without tape, tight-fitting surgical mask with adhesive tape securing the superior portion of the mask, N95 mask, and cloth mask). Each scenario was then repeated while reading a 2-minute script, simulating a talking patient. The primary outcome measures were the number of colony-forming units (CFUs) and microbial species. RESULTS: During the "no-talking" scenario, subjects wearing a tight-fitting surgical mask with tape developed fewer CFUs compared with subjects wearing the same mask without tape (difference 0.93 CFUs [95% confidence interval 0.32-1.55]; P = .003). During the speech scenarios, subjects wearing a tight-fitting surgical mask with tape had significantly fewer CFUs compared with subjects without a face mask (difference 1.07 CFUs; P = .001), subjects with a loose face mask (difference 0.67 CFUs; P = .034), and subjects with a tight face mask without tape (difference 1.13 CFUs; P < .001). There was no difference between those with a tight-fitting surgical mask with tape and an N95 mask in the "no-talking" (P > .99) and "speech" (P = .831) scenarios. No oral flora were isolated in "no-talking" scenarios but were isolated in 8 of 75 (11%) cultures in speech scenarios (P = .02). CONCLUSION: The addition of tape to the superior portion of a patient's face mask reduced bacterial dispersion during simulated intravitreal injections and had no difference in bacterial dispersion compared with wearing N95 masks.

The Impact of Physician Face Mask Use on Endophthalmitis After Intravitreal Anti-Vascular Endothelial Growth Factor Injections.

PURPOSE: To evaluate the effect of physician face mask use on rates and outcomes of postinjection endophthalmitis. DESIGN: Retrospective, comparative cohort study. METHODS: Setting: Single-center. StudyPopulation: Eyes receiving intravitreal anti-vascular endothelial growth factor injections from July 1, 2013, to September 1, 2019. INTERVENTION: Cases were divided into "Face Mask" group if face masks were worn by the physician during intravitreal injections or "No Talking" group if no face mask was worn but a no-talking policy was observed during intravitreal injections. MainOutcomeMeasures: Rate of endophthalmitis, visual acuity, and microbial spectrum. RESULTS: Of 483,622 intravitreal injections administered, 168 out of 453,460 (0.0371%) cases of endophthalmitis occurred in the No Talking group, and 9 out of 30,162 (0.0298%) cases occurred in the Face Mask group (odds ratio, 0.81; 95% confidence interval, 0.41-1.57; P = .527). Sixteen cases of oral flora-associated endophthalmitis were found in the No Talking group (1 in 28,341 injections), compared to none in the Face Mask group (P = .302). Mean logMAR visual acuity at presentation in cases that developed culture-positive endophthalmitis was significantly worse in the No Talking group compared to the Face Mask group (17.1 lines lost from baseline acuity vs 13.4 lines lost; P = .031), though no difference was observed at 6 months after treatment (P = .479). CONCLUSION: Physician face mask use did not influence the risk of postinjection endophthalmitis compared to a no-talking policy. However, no cases of oral flora-associated endophthalmitis occurred in the Face Mask group. Future studies are warranted to assess the role of face mask use to reduce endophthalmitis risk, particularly attributable to oral flora.

Evolutionary and structural analyses of SARS-CoV-2 D614G spike protein mutation now documented worldwide.

The COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), was declared on March 11, 2020 by the World Health Organization. As of the 31st of May, 2020, there have been more than 6 million COVID-19 cases diagnosed worldwide and over 370,000 deaths, according to Johns Hopkins. Thousands of SARS-CoV-2 strains have been sequenced to date, providing a valuable opportunity to investigate the evolution of the virus on a global scale. We performed a phylogenetic analysis of over 1,225 SARS-CoV-2 genomes spanning from late December 2019 to mid-March 2020. We identified a missense mutation, D614G, in the spike protein of SARS-CoV-2, which has emerged as a predominant clade in Europe (954 of 1,449 (66%) sequences) and is spreading worldwide (1,237 of 2,795 (44%) sequences). Molecular dating analysis estimated the emergence of this clade around mid-to-late January (10-25 January) 2020. We also applied structural bioinformatics to assess the potential impact of D614G on the virulence and epidemiology of SARS-CoV-2. In silico analyses on the spike protein structure suggests that the mutation is most likely neutral to protein function as it relates to its interaction with the human ACE2 receptor. The lack of clinical metadata available prevented our investigation of association between viral clade and disease severity phenotype. Future work that can leverage clinical outcome data with both viral and human genomic diversity is needed to monitor the pandemic.

Ocular trauma during COVID-19 stay-at-home orders: a comparative cohort study.

PURPOSE OF REVIEW: The aim of this study was to report characteristics of patients presenting with serious ocular injuries during the COVID-19 stay-at-home orders. RECENT FINDINGS: Of 1058 patients presenting for emergency evaluation during the stay-at-home order, 62 (5.9%) patients [mean (SD) age, 41.1 (19.2) years; 19 (31%) women; 31 (50%) white] presented with severe ocular trauma. The daily mean (SD) number of patients who presented for emergency evaluation decreased from 49.0 (9) to 36.4 (6) during the quarantine (P < 0.001). Patients presenting during the stay-at-home order were less likely to have health insurance [odds ratio (OR), 0.33; 95% confidence interval (95% CI), 0.13-0.90, P = 0.024], more likely to have a delayed presentation (difference, 22.7 h, 95% CI, 5.8-39.5, P < 0.001, more likely to travel farther to seek emergency care (difference, 10.4 miles, 95% CI, 2.6-18.2, P < 0.001) and more likely to have an injury occur at home (OR, 22.8; 95% CI, 9.6-54.2, P < 0.001). Of injuries occurring at home, there was a significant increase in injuries arising from home improvement projects during the stay-at-home order (28 vs. 0%, P = 0.02). SUMMARY: During the COVID-19 pandemic, patients with ocular trauma were more likely to have injuries sustained at home and have additional barriers to care. These changes underscore a need for targeted interventions to optimize emergent eye care during a pandemic.