Immediate sequential bilateral cataract surgery (ISBCS): A single-site experience of 41 patients during the COVID-19 pandemic.

Background: The practice of immediate sequential bilateral cataract surgery (ISBCS) was more widely adopted in the UK during the COVID-19 pandemic, in response to limited surgical capacity and the risk of nosocomial infection. This study reports on a single site experience of ISBCS in Northern Ireland. Methods: Data was collected prospectively between 17th November 2020 and 30th November 2021. The ISBCS surgical protocol, recommended by RCOphth and UKISCRS, was followed. Primary outcomes measures were: postoperative visual acuity (VA), refractive prediction accuracy, intraoperative and postoperative complications. Results: Of 41 patients scheduled, 39 patients completed ISBCS and two patients underwent unilateral surgery (n=80 eyes). Mean age at the time of surgery was 71.6 years (standard deviation (SD) ±11.8 years). Median preoperative VA was 0.8 logMAR (range: PL to 0.2 logMAR). Seventeen (20.9%) eyes were highly myopic and 9 (11.1%) eyes were highly hypermetropic. Median cumulative dissipated phacoemulsification energy was 15.7 sec (range: 1.8 sec to 83.4 sec). Median case time was 10.4 min (range: 4.3 min to 37.1 min).One eye (1.3%) developed iritis secondary to a retained tiny cortical fragment. Four eyes (5.0%, n=3 patients) developed cystoid macular oedema, with full resolution. On wide field imaging, an asymptomatic unilateral peripheral suprachoroidal haemorrhage was noted in two highly myopic patients (axial lengths of 27.01mm and 25.05mm respectively). The posterior pole was spared, and both resolved spontaneously without any visual impairment. Conclusions: In our initial experience, ISBCS was found to be a safe approach to cataract surgery. Our patient cohort included eyes with dense cataracts and high ametropia. Further studies are required to assess patient reported outcome measures and the possible economic benefits of ISBCS in our local population.

Inhibition of bradykinin in SARS-CoV-2 infection: a randomised, double-blind trial of icatibant compared with placebo (ICASARS).

SARS-CoV-2 binds to ACE2 receptors and enters cells. The symptoms are cough, breathlessness, loss of taste/smell and X-ray evidence of infiltrates on chest imaging initially caused by oedema, and subsequently by a lymphocytic pneumonitis. Coagulopathy, thrombosis and hypotension occur. Worse disease occurs with age, obesity, ischaemic heart disease, hypertension and diabetes.These features may be due to abnormal activation of the contact system. This triggers coagulation and the kallikrein-kinin system, leading to accumulation of bradykinin and its derivatives, which act on receptors B1R and B2R. Receptor activation causes cough, hypotension, oedema and release of the cytokine interleukin-6 (IL-6) which recruits lymphocytes. These effects are core features seen in early SARS CoV-2 infection. METHODS AND ANALYSIS: In this study, hypoxic patients with COVID-19 with symptom onset ≤7 days will be randomised to either a bradykinin inhibitor (icatibant) or placebo. Patients and investigators will be blinded. The primary outcome will be blood oxygenation, measured by arterial blood sampling. The secondary outcome will be cardiovascular status. Retinal imaging will be performed to assess vessel size. Blood samples will be taken for measurement of inflammatory analyses including IL-6. As a separate substudy, we will also take comparator blood inflammatory samples from a COVID-19-negative cohort. ETHICS AND DISSEMINATION: The study has received the following approvals: West Midlands-Edgbaston Research Ethics Committee. Medicines and Healthcare products Regulatory Agency has issued a clinical trial authorisation. Belfast Health and Social Care Trust is the study sponsor. Results will be made available to participants upon request and findings will be presented and published. TRIAL REGISTRATION NUMBER: NCT05407597.

Vascular risk factors for COVID-19 ARDS: endothelium, contact-kinin system.

SARS-CoV-2 binds to ACE2 receptors, expressed within the lungs. Risk factors for hospitalization include hypertension, diabetes, ischaemic heart disease and obesity-conditions linked by the presence of endothelial pathology. Viral infection in this setting causes increased conversion of circulating Factor XII to its active form (FXIIa). This is the first step in the contact-kinin pathway, leading to synchronous activation of the intrinsic coagulation cascade and the plasma Kallikrein-Kinin system, resulting in clotting and inflammatory lung disease. Temporal trends are evident from blood results of hospitalized patients. In the first week of symptoms the activated partial thromboplastin time (APTT) is prolonged. This can occur when clotting factors are consumed as part of the contact (intrinsic) pathway. Platelet counts initially fall, reflecting their consumption in coagulation. Lymphopenia occurs after approximately 1 week, reflecting the emergence of a lymphocytic pneumonitis [COVID-19 acute respiratory distress syndrome (ARDS)]. Intrinsic coagulation also induces the contact-kinin pathway of inflammation. A major product of this pathway, bradykinin causes oedema with ground glass opacities (GGO) on imaging in early COVID-19. Bradykinin also causes release of the pleiotrophic cytokine IL-6, which causes lymphocyte recruitment. Thromobosis and lymphocytic pneumonitis are hallmark features of COVID-19 ARDS. In this review we examine the literature with particular reference to the contact-kinin pathway. Measurements of platelets, lymphocytes and APTT should be undertaken in severe infections to stratify for risk of developing ARDS.