Effect of Ultrasound Radiation Force on the Choroid

Purpose: While visualization of the retina and choroid has made great progress, functional imaging techniques have been lacking. Our aim was to utilize acoustic radiation force impulse (ARFI) response to probe functional properties of these tissues. Methods: A single element 18-MHz ultrasound transducer was focused upon the retina of the rabbit eye. The procedure was performed with the eye proptosed and with the eye seated normally in the orbit. The transducer was excited to emit ARFI over a 10-ms period with a 25% duty cycle. Phase resolved pulse/echo data were acquired before, during, and following ARFI. Results: In the proptosed eye, ARFI exposure produced tissue displacements ranging from 0 to 10 lm, and an immediate increase in choroidal echo amplitude to over 6 dB, decaying to baseline after about 1 second. In the normally seated eye, ultrasound phase shifts consistent with flow were observed in the choroid, but enhanced backscatter following ARFI rarely occurred. ARFI-induced displacements of about 10um were observed at the choroidal margins. Larger displacements occurred within the choroid and in orbital tissues. Conclusions: We hypothesize that elevated intraocular pressure occurring during proptosis induced choroidal ischemia and that acoustic radiation force produced a transient local decompression and reperfusion. With the eye normally seated, choroidal flow was observed and little alteration in backscatter resulted from exposure. Clinical application of this technique may provide new insights into diseases characterized by altered choroidal hemodynamics, including maculopathies, diabetic retinopathy, and glaucoma

Pulse-Encoded Ultrasound Imagine of the Vitreous With an Annular Array

The vitreous body is nearly transparent both optically and ultrasonically. Conventional 10- to 12-MHz diagnostic ultrasound can detect vitreous inhomogeneities at high gain settings, but has limited resolution and sensitivity, especially outside the fixed focal zone near the retina. To improve visualization of faint intravitreal fluid/gel interfaces, the authors fabricated a spherically curved 20-MHz five-element annular array ultrasound transducer, implemented a synthetic-focusing algorithm to extend the depth-of-field, and used a pulse-encoding strategy to increase sensitivity. The authors evaluated a human subject with a recent posterior vitreous detachment and compared the annular array with conventional 10-MHz ultrasound and spectral-domain optical coherence tomography. With synthetic focusing and chirp pulse-encoding, the array allowed visualization of the formed and fluid components of the vitreous with improved sensitivity and resolution compared with the conventional B-scan. Although optical coherence tomography allowed assessment of the posterior vitreoretinal interface, the ultrasound array allowed evaluation of the entire vitreous body

Age-related macular degeneration: choroidal ischaemia?

Aim: Our aim is to use ultrasound to non-invasively detect differences in choroidal microarchitecture possibly related to ischaemia among normal eyes and those with wet and dry age-related macular degeneration (AMD). Design Prospective case series of subjects with dry AMD, wet AMD and age-matched controls. Methods: Digitized 20 MHz B-scan radiofrequency ultrasound data of the region of the macula were segmented to extract the signal from the retina and choroid. This signal was processed by a wavelet transform, and statistical modelling was applied to the wavelet coefficients to examine differences among dry, wet and non-AMD eyes. Receiver operating characteristic (ROC) analysis was used to evaluate a multivariate classifier. Results: In the 69 eyes of 52 patients, 18 did not have AMD, 23 had dry AMD and 28 had wet AMD. Multivariate models showed statistically significant differences between groups. Multiclass ROC analysis of the best model showed an excellent volume-under-curve of 0.892±0.17. The classifier is consistent with ischaemia in dry AMD. Conclusions: Wavelet augmented ultrasound is sensitive to the organisational elements of choroidal microarchitecture relating to scatter and fluid tissue boundaries such as seen in ischaemia and inflammation, allowing statistically significant differentiation of dry, wet and non-AMD eyes. This study further supports the association of ischaemia with dry AMD and provides a rationale for treating dry AMD with pharmacological agents to increase choroidal perfusion

Measurement of choroidal perfusion and thickness following systemic sildenafil (Viagra)

Purpose: To demonstrate anatomic and physiologic changes in the human choroid following systemic sildenafil citrate (Viagra) using enhanced depth imaging spectral domain–optical coherence tomography (EDI-OCT) and swept-scan high-frequency digital ultrasound. Methods: Seven healthy male subjects (mean age 32.7 years) were evaluated at baseline and 2 hr after ingesting 50 mg of sildenafil. Swept-scan high-frequency digital ultrasound and EDI-OCT were utilized to measure choroidal perfusion and thickness, respectively. Results were read by masked observers. The Wilcoxon signed-rank test and t-test were used to analyse differences in choroidal flow and thickness at baseline and 2 hr after ingestion of sildenafil. Results: Two hours following sildenafil, increased choroidal perfusion was observed in 11 of 12 eyes measured by swept-scan high-frequency digital ultrasound. The mean increase was 3.46 (±2.00) times baseline with a range of 0.47–7.80 times baseline (p = 0.004). Increased choroidal thickness was observed in 12 of 12 eyes measured with EDI-OCT. The average choroidal thickness increased by 11.6% temporal to the fovea, 9.3% nasal to the fovea and 10.7% underneath the fovea (p < 0.001 for all values). Conclusions: Choroidal perfusion and thickness both increase in response to systemic sildenafil. These changes could secondarily affect retinal function, explain previously reported clinical symptoms and potentially be a useful adjunct for treatment of ocular diseases that would benefit from increased choroidal blood flow

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Effect of Ultrasound Radiation Force on the Choroid

Objetivo: Identificar e discutir os riscos ocupacionais a que estão expostos o trabalhador naval. Método: Trata-se de uma pesquisa bibliográfica, com características descritivo-analíticas. A seleção dos textos se deu a partir da leitura dos resumos encontrados, a partir de 1990, objetivando a elaboração de um quadro demonstrativo. Posteriormente realizou-se a análise bibliográfica dos artigos selecionados. Resultados: Os riscos encontrados foram riscos físicos relacionados a exposição ao ruído, riscos químicos relacionado a exposição a agentes cancerígenos e a inalação da sílica. Conclusão: Alertamos para importância do estudo dos riscos ocupacionais na área do trabalho naval, considerando seu grau de periculosidade para a saúde do trabalhador. A enfermagem deve estar preparada para identificar se a doença é secundária ao risco ocupacional, desta forma estará capacitada para que junto do paciente encontre a melhor maneira de evitar a exposição ou de pelo menos amenizar os riscos

High-resolution photoacoustic imaging with focused laser and ultrasonic beams

We report a photoacoustic imager that utilizes a focused laser beam in combination with a 20 MHz ultrasound focusing transducer to obtain micron-resolution tissue images over a long working distance. The imager is based on a ring transducer that combines ultrasonic and laser beams collinearly and confocally in a monolithic element. The combination of focused laser beam and short pulse irradiation led to significant improvement in lateral and axial resolutions compared to the pulse-echo ultrasonic imaging technique or photoacoustic imaging with an unfocused laser. Potential applications include clinical examination of the eye and characterization of thin and superficial tissues