Aims Age-related macular degeneration (AMD) is characterised by a progressive loss of central vision. Intermediate AMD is a risk factor for progression to advanced stages categorised as geographic atrophy (GA) and neovascular AMD. However, rates of progression to advanced stages vary between individuals. Recent advances in imaging and computing technologies have enabled deep phenotyping of intermediate AMD. The aim of this project is to utilise machine learning (ML) and advanced statistical modelling as an innovative approach to discover novel features and accurately quantify markers of pathological retinal ageing that can individualise progression to advanced AMD. Methods The PINNACLE study consists of both retrospective and prospective parts. In the retrospective part, more than 400,000 optical coherent tomography (OCT) images collected from four University Teaching Hospitals and the UK Biobank Population Study are being pooled, centrally stored and pre-processed. With this large dataset featuring eyes with AMD at various stages and healthy controls, we aim to identify imaging biomarkers for disease progression for intermediate AMD via supervised and unsupervised ML. The prospective study part will firstly characterise the progression of intermediate AMD in patients followed between one and three years; secondly, it will validate the utility of biomarkers identified in the retrospective cohort as predictors of progression towards late AMD. Patients aged 55–90 years old with intermediate AMD in at least one eye will be recruited across multiple sites in UK, Austria and Switzerland for visual function tests, multimodal retinal imaging and genotyping. Imaging will be repeated every four months to identify early focal signs of deterioration on spectral-domain optical coherence tomography (OCT) by human graders. A focal event triggers more frequent follow-up with visual function and imaging tests. The primary outcome is the sensitivity and specificity of the OCT imaging biomarkers. Secondary outcomes include sensitivity and specificity of novel multimodal imaging characteristics at predicting disease progression, ROC curves, time from development of imaging change to development of these endpoints, structure-function correlations, structure-genotype correlation and predictive risk models. Conclusions This is one of the first studies in intermediate AMD to combine both ML, retrospective and prospective AMD patient data with the goal of identifying biomarkers of progression and to report the natural history of progression of intermediate AMD with multimodal retinal imaging.

Background: Acute myocardial injury (AMJ), assessed by elevated levels of cardiac troponin, is associated with fatal outcome in coronavirus disease 2019 (COVID-19). However, the role of acute cardiovascular (CV) events defined by clinical manifestation rather than sole elevations of biomarkers is unclear in hospitalized COVID-19 patients. Objective: The aim of this study was to investigate acute clinically manifest CV events in hospitalized COVID-19 patients. Methods: From 1 March 2020 to 5 January 2021, we conducted a multicenter, prospective, epidemiological cohort study at six hospitals from Hamburg, Germany (a portion of the state-wide 45-center CORONA Germany cohort study) enrolling all hospitalized COVID-19 patients. Primary endpoint was occurrence of a clinically manifest CV-event. Results: In total, 132 CV-events occurred in 92 of 414 (22.2%) patients in the Hamburg-cohort: cardiogenic shock in 10 (2.4%), cardiopulmonary resuscitation in 12 (2.9%), acute coronary syndrome in 11 (2.7%), de-novo arrhythmia in 31 (7.5%), acute heart-failure in 43 (10.3%), myocarditis in 2 (0.5%), pulmonary-embolism in 11 (2.7%), thrombosis in 9 (2.2%) and stroke in 3 (0.7%). In the Hamburg-cohort, mortality was 46% (42/92) for patients with a CV-event and 33% (27/83) for patients with only AMJ without CV-event (OR 1.7, CI: (0.94–3.2), p = 0.077). Mortality was higher in patients with CV-events (Odds ratio(OR): 4.8, 95%-confidence-interval(CI): [2.9–8]). Age (OR 1.1, CI: (0.66–1.86)), atrial fibrillation (AF) on baseline-ECG (OR 3.4, CI: (1.74–6.8)), systolic blood-pressure (OR 0.7, CI: (0.53–0.96)), potassium (OR 1.3, CI: (0.99–1.73)) and C-reactive-protein (1.4, CI (1.04–1.76)) were associated with CV-events. Conclusion: Hospitalized COVID-19 patients with clinical manifestation of acute cardiovascular events show an almost five-fold increased mortality. In this regard, the emergence of arrhythmias is a major determinant.

Intraocular lens (IOL) power calculation after corneal refractive surgery (CRS) becomes an expanding challenge for ophthalmologists as more and more cataract surgeries after CRS are required. These patients typically also have high expectations as to visual performance. Conventional IOL power calculation schemes frequently provide inaccurate results in these cases. This review aims to summarize and recommend currently available IOL power calculation methods for eyes with the most common CRS methods: radial keratotomy (RK), photorefractive keratectomy (PRK), laser in situ keratomileusis (LASIK), and small incision lenticule extraction (SMILE). To this end, biometry measuring methods and IOL formulas will be explained and combinations of both are proposed. In synopsis, it is evident that the latest generation of vergence formulas exhibit favorable IOL power prediction accuracy in post-CRS eyes, even though the predictive precision of methods in eyes without CRS is not attained. Ray tracing computation, intraoperative aberrometry, and machine learning–based formulas hold potential to further improve refractive outcomes in post-CRS eyes.

Purpose: To assess potential differences between central and eccentric cones in the aberrometric corneal profile and in visual and keratometric outcomes 6 months after intracorneal ring segment (ICRS) implantation for keratoconus. Methods: This study compared two groups consisting of 12 patients each, with central or eccentric keratoconus who were treated with femtosecond laser-assisted Keraring implantation. Uncorrected (UDVA) and corrected (CDVA) distance visual acuity, keratometric readings and higher order aberrations (HOAs) including high order aberrations root mean square (HOARMS), coma, spherical aberration and trefoil were measured preoperatively and 6 months after ICRS implantation. Results: Trefoil and spherical aberration were significantly reduced after ICRS implantation compared to preoperative values in eccentric keratoconus (Trefoil, p = 0.0049; Spherical aberration, p < 0.0001). In central keratoconus spherical aberration was reduced not significantly after ICRS implantation compared to preoperative values ( p = 0.087). Coma showed a significant reduction in central ( p = 0.0001) and in eccentric keratoconus ( p = 0.0001). The reduction of spherical aberration in central keratoconus was significantly positively correlated to improvement in UDVA (Pearson’s correlation coefficient, r = −0.66; p = 0.02). In eccentric keratoconus there was a significant positive correlation between reduction of trefoil and improvement in UDVA (Spearmans R, r = −0.69; p = 0.01). Conclusion: Patients both with central and eccentric keratoconus benefit from ICRS implantation. Specifically, our data provide a slightly higher gain in visual performance for eccentric cones 6 month after ICRS implantation, which is accentuated by a greater reduction in spherical aberration and trefoil. Improvements in UDVA are positively correlated with reductions in HOAs.