Rare variants in the complement factor I (CFI) gene, associated with low serum factor I (FI) levels, are strong risk factors for developing the advanced stages of age‐related macular degeneration (AMD). No studies have been undertaken on the prevalence of disease‐causing CFI mutations in patients with geographic atrophy (GA) secondary to AMD. A multicenter, cross‐sectional, noninterventional study was undertaken to identify the prevalence of pathogenic rare CFI gene variants in an unselected cohort of patients with GA and low FI levels. A genotype‐phenotype study was performed. Four hundred and sixty‐eight patients with GA secondary to AMD were recruited to the study, and 19.4% (n = 91) demonstrated a low serum FI concentration (below 15.6 μg/ml). CFI gene sequencing on these patients resulted in the detection of rare CFI variants in 4.7% (n = 22) of recruited patients. The prevalence of CFI variants in patients with low serum FI levels and GA was 25%. Of the total patients recruited, 3.2% (n = 15) expressed a CFI variant classified as pathogenic or likely pathogenic. The presence of reticular pseudodrusen was detected in all patients with pathogenic CFI gene variants. Patients with pathogenic CFI gene variants and low serum FI levels might be suitable for FI supplementation in therapeutic trials.

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.

PurposeTo determine whether visual-tactile sensory substitution utilizing the Low-vision Enhancement Optoelectronic (LEO) Belt prototype is suitable as a new visual aid for those with reduced peripheral vision by assessing mobility performance and user opinions.MethodsSighted subjects (n = 20) and subjects with retinitis pigmentosa (RP) (n = 6) were recruited. The LEO Belt was evaluated on two cohorts: normally sighted subjects wearing goggles to artificially reduce peripheral vision to simulate stages of RP progression, and subjects with advanced visual field limitation from RP. Mobility speed and accuracy was assessed using simple mazes, with and without the LEO Belt, to determine its usefulness across disease severities and lighting conditions.ResultsSighted subjects wearing most narrowed field goggles simulating most advanced RP had increased mobility accuracy (44% mean reduction in errors, p = 0.014) and self-reported confidence (77% mean increase, p = 0.004) when using the LEO Belt. Additionally, use of LEO doubled mobility accuracy for RP subjects with remaining visual fields between 10° and 20°. Further, in dim lighting, confidence scores for this group also doubled. By patient reported outcomes, subjects largely deemed the device comfortable (100%), easy to use (92.3%) and thought it had potential future benefit as a visual aid (96.2%). However, regardless of severity of vision loss or simulated vision loss, all subjects were slower to complete the mazes using the device.ConclusionsThe LEO Belt improves mobility accuracy and therefore confidence in those with severely restricted peripheral vision. The LEO Belt’s positive user feedback suggests it has potential to become the next generation of visual aid for visually impaired individuals. Given the novelty of this approach, we expect navigation speeds may improve with experience.

Many individuals with advanced glaucoma and retinal dystrophies have functional difficulty due to a loss of their peripheral vision. These individuals may have sufficient central vision to read and perform visual tasks in a controlled situation, but are often unable to function in a cluttered, unstructured or chaotic environment (i.e. a normal social situation). This is because they lack the ability to be visually alerted to an incentive or threat outside the narrowed region of their central vision. Some groups of these patients, for example those with a diagnosis of retinitis pigmentosa, also experience nyctalopia (night blindness) meaning that time of day can alter their functional ability. Currently, there are limited options to aid these patients. Intel Corporation has developed a computer-based assistive device that may be useful for these individuals. Intel has recently made the design details and software available via the internet. The device consists of a vest or shirt with an attached depth-sensing camera, a computer and vibration transducers (6 on the vest and one on each foot). The transducers vibrate to alert the wearer to objects that are approaching them, or if they are walking, alert them to objects that they may be approaching. We propose to test subjects wearing the device to determine its usefulness. This will consist of participants with known reduced peripheral vision walking through simple maze scenarios first using their normal visual aid (if required) and then wearing the vibration vest. Variations of the maze will be carried out in both bright and dim lighting, equalling four mazes per subject. Each subject will also answer two short questionnaires, one before and one after using the device, to help determine the possible benefits and drawbacks of the device. The results will then be analysed to conclude whether an electronic device such as this could be useful to patients with reduced peripheral vision.