Redmer van Leeuwen

Age-related macular degeneration (AMD) shows substantial clinical heterogeneity that remains unexplained despite extensive genetic and clinical characterization. We evaluated whether proteomic stratification could provide insight beyond clinical phenotype and genetic risk. We performed 384-plex plasma proteomics in a cohort of 215 individuals, including patients with early and late neovascular AMD, other complement-associated retinal diseases, and age-matched controls. Proteome-based reclassification identified four disease-overarching clusters. Neovascular AMD cases were partitioned almost exclusively between two clusters (30/36). Early AMD cases were predominantly assigned to one of these clusters (10/18), whereas only two localized to the other (2/18). Both AMD-associated clusters shared elevated levels of a protein module enriched for lipoprotein-related functions compared to the other clusters. However, the cluster containing both early and neovascular AMD cases showed higher levels of additional protein modules enriched for complement pathways and cellular stress-response pathways compared with the other AMD-associated cluster. Importantly, this molecular divergence in neovascular AMD could not be explained by genetic predisposition (i.e., 52-variant AMD genetic risk score), signatures of biological ageing, nor by other clinical features. Together, these findings support two proteomic endotypes of neovascular AMD with distinct involvement of cellular stress pathways.

Retinal artery and vein occlusions can both lead to significant vision loss. Vein occlusions are much more common, while visual acuity is usually more severely affected in artery occlusions. In addition to ophthalmological treatment, both types of occlusions require a multidisciplinary approach, in which cardiovascular risk management is important. In the event of an artery occlusion, an urgent search for the source of the embolism must be carried out. We discuss two cases. First, a 71-year-old man with a central retinal artery occlusion who presented three hours after the event and was treated successfully. Second, a 37-year-old obese man with a central retinal vein occlusion for which he has undergone long-term treatment with intravitreal anti-VEGF injections for persistent macular edema.

Background: Healthcare is responsible for 4-10% of carbon dioxide (CO₂) emissions worldwide, with travel-related emissions accounting for approximately 22%. Telemedicine has emerged as a potential solution, but there is a lack of comprehensive approaches to estimate carbon footprint savings, limiting our understanding of its environmental impact. The aim of this paper is to conduct a systematic review to evaluate how the carbon footprint of telemedicine is measured, report the impact of a telemedicine program, and propose an open-access calculator to estimate CO₂ emissions for healthcare providers. Methods: We conducted a systematic literature search following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in the PubMed, Medline, Embase and Scopus databases to identify articles estimating the carbon footprint savings of telemedicine. We evaluated publications based on various categories, with ground travel and streamlined life cycle assessment (LCA) being the most important. Based on our findings and an example case in eyecare, we developed a Carbon Calculator for remote Care (CCrC) and applied this model to the papers included for ground travel analysis. Results: Based on a search of 1,117 records, 30 articles were included for quantitative or qualitative analysis. The median roundtrip travel distance for each patient in 23 papers examining ground transportation emissions was 131 km (interquartile range [IQR]:52-386), resulting in 26.3 kilograms CO₂ (kgCO₂) (IQR:10.6-94.4) emissions. Calculations including LCA had a mean emission of 2.5% less than estimates excluding LCA. In our remote eyecare example, we estimated that 411,000 kgCO₂/year could be saved from travel alone, or 401,000 kgCO₂/year when accounting for LCA. Conclusions: To prevent overestimation of CO₂ emissions savings due to telemedicine, including LCA should be considered, although travel distance as a variable is the biggest contributor. Our CCrC is a preliminary attempt to roughly capture these factors and furthers the debate for structural measurement and calculation of CO₂ in telemedicine.

Background: Pseudoxanthoma elasticum (PXE), a monogenic disorder resulting in calcification affecting the skin, eyes and peripheral arteries, is caused by mutations in the ABCC6 gene, and is associated with low plasma inorganic pyrophosphate (PP_i). It is unknown how ABCC6 genotype affects plasma PP_i. Methods: We studied the association of ABCC6 genotype (192 patients with biallelic pathogenic ABCC6 mutations) and PP_i levels, and its association with the severity of arterial and ophthalmological phenotypes. ABCC6 variants were classified as truncating or non-truncating, and three groups of the 192 patients were formed: those with truncating mutations on both chromosomes (n = 121), those with two non-truncating mutations (n = 10), and a group who had one truncating and one non-truncating ABCC6 mutation (n = 61). The hypothesis formulated before this study was that there was a negative association between PP_i level and disease severity. Results: Our findings confirm low PP_i in PXE compared with healthy controls (0.53 ± 0.15 vs. 1.13 ± 0.29 µM, p < 0.01). The PP_i of patients correlated with increasing age (β: 0.05 µM, 95% CI: 0.03–0.06 per 10 years) and was higher in females (0.55 ± 0.17 vs. 0.51 ± 0.13 µM in males, p = 0.03). However, no association between PP_i and PXE phenotypes was found. When adjusted for age and sex, no association between PP_i and ABCC6 genotype was found. Conclusions: Our data suggest that the relationship between ABCC6 mutations and reduced plasma PP_i may not be as direct as previously thought. PP_i levels varied widely, even in patients with the same ABCC6 mutations, further suggesting a lack of direct correlation between them, even though the ABCC6 protein-mediated pathway is responsible for ~60% of this metabolite in the circulation. We discuss potential factors that may perturb the expected associations between ABCC6 genotype and PP_i and between PP_i and disease severity. Our findings support the argument that predictions of pathogenicity made on the basis of mutations (or on the structure of the mutated protein) could be misleading.

The aim of this paper is to summarize all available evidence from systematic reviews, randomized controlled trials (RCTs) and comparative nonrandomized studies (NRS) on the association between nutrition and antioxidant, vitamin, and mineral supplements and the development or progression of age‐related macular degeneration (AMD). The Cochrane Database of Systematic Reviews, Cochrane register CENTRAL, MEDLINE and Embase were searched and studies published between January 2015 and May 2021 were included. The certainty of evidence was assessed according to the GRADE methodology. The main outcome measures were development of AMD, progression of AMD, and side effects. We included 7 systematic reviews, 7 RCTs, and 13 NRS. A high consumption of specific nutrients, i.e. β‐carotene, lutein and zeaxanthin, copper, folate, magnesium, vitamin A, niacin, vitamin B6, vitamin C, docosahexaenoic acid, and eicosapentaenoic acid, was associated with a lower risk of progression of early to late AMD (high certainty of evidence). Use of antioxidant supplements and adherence to a Mediterranean diet, characterized by a high consumption of vegetables, whole grains, and nuts and a low consumption of red meat, were associated with a decreased risk of progression of early to late AMD (moderate certainty of evidence). A high consumption of alcohol was associated with a higher risk of developing AMD (moderate certainty of evidence). Supplementary vitamin C, vitamin E, or β‐carotene were not associated with the development of AMD, and supplementary omega‐3 fatty acids were not associated with progression to late AMD (high certainty of evidence). Research in the last 35 years included in our overview supports that a high intake of specific nutrients, the use of antioxidant supplements and adherence to a Mediterranean diet decrease the risk of progression of early to late AMD.

A rhegmatogenous retinal detachment (RRD) is one of the most common sight-threatening emergencies in the Western world. An RRD develops from retinal breaks occurring at points of firm vitreoretinal adhesion and dynamic traction on the retina, eg, during posterior vitreous detachment.¹ Even with timely surgery, an RRD may result in severe visual impairment.² The incidence of RRD has been studied in many populations around the world.³ The earliest published figures come from admission data from English national hospital statistics.⁴ Later, population-based studies were performed in numerous regions, cities, and countries all around the world. During the 1970s, the annual incidence of RRD ranged from 6.9 to 11.0 cases per 100 000 persons and increased to 8.0 to 17.9 cases per 100 000 in the 1990s and early 2000.^5-8 Recent studies from Denmark and the Netherlands reported even higher incidence rates of 22.0 and 18.2 cases per 100 000, respectively.^9-11 This variability in RRD incidence may be explained by differences in study design, definitions, and the prevalence of risk factors, such as age, male sex, cataract extraction, and myopia.^3,12,13