The role of the retinal vasculature in age-related macular degeneration: a spotlight on OCTA.

Age-related macular degeneration (AMD) remains a disease with high morbidity and an incompletely understood pathophysiological mechanism. The ocular blood supply has been implicated in the development of the disease process, of which most research has focused on the role of the choroid and choriocapillaris. Recently, interest has developed into the role of the retinal vasculature in AMD, particularly with the advent of optical coherence tomography angiography (OCTA), which enables non-invasive imaging of the eye's blood vessels. This review summarises the up-to-date body of work in this field including the proposed links between observed changes in the retinal vessels and the development of AMD and potential future directions for research in this area. The review highlights that the strongest evidence supports the observation that patients with early to intermediate AMD have reduced vessel density in the superficial vascular complex of the retina, but also emphasises the need for caution when interpreting such studies due to their variable methodologies and nomenclature.

Single-cell eQTL mapping identifies cell type-specific genetic control of autoimmune disease.

The human immune system displays substantial variation between individuals, leading to differences in susceptibility to autoimmune disease. We present single-cell RNA sequencing (scRNA-seq) data from 1,267,758 peripheral blood mononuclear cells from 982 healthy human subjects. For 14 cell types, we identified 26,597 independent cis-expression quantitative trait loci (eQTLs) and 990 trans-eQTLs, with most showing cell type-specific effects on gene expression. We subsequently show how eQTLs have dynamic allelic effects in B cells that are transitioning from naïve to memory states and demonstrate how commonly segregating alleles lead to interindividual variation in immune function. Finally, using a Mendelian randomization approach, we identify the causal route by which 305 risk loci contribute to autoimmune disease at the cellular level. This work brings together genetic epidemiology with scRNA-seq to uncover drivers of interindividual variation in the immune system.

Demyelinating Events Following Initiation of Anti-TNFα Therapy in the British Society for Rheumatology Biologics Registry in Rheumatoid Arthritis.

OBJECTIVE: To establish the incidence of demyelination in patients who have received anti-tumor necrosis factor alpha (anti-TNFα) therapy, through analysis of adverse events reported in a prospective cohort of patients receiving biological therapies. METHODS: A cohort study was performed on prospectively acquired data via the British Society for Rheumatology Biologics Register in Rheumatoid Arthritis. All potential demyelinating events during follow-up were extracted and classified as definite, probable, or possible blinded to treatment data. The point of starting an anti-TNF therapy in individuals with no prior reported demyelination was the time of exposure. Crude rates of demyelination and standardized incident rates (SIRs) compared with the general UK population were calculated. RESULTS: Thirty-five individuals with demyelinating events were identified from a total pool of 13,489. The median age at study entry was 44 years, and the median disease duration was 8 years; 71% were female. Events occurred a median of 3 (interquartile range 1-5) years from the start of the first anti-TNF therapy. Twenty-six events occurred in individuals still taking anti-TNFα therapy; of the other 9, 6 were within 90 days of drug withdrawal. The raw incidence of demyelination was 19.7/100,000 patient-years (95% CI 13.7-27.3). The SIR in the whole population was 1.38 (95% CI 0.96-1.92) and 0.83 (0.51-1.26) limited to definite/probable cases. CONCLUSIONS: Demyelination following anti-TNF therapy is uncommon. Patients receiving anti-TNFα therapy show a marginally increased SIR; this is lost in sensitivity analyses. Patients concerned about anti-TNFα-associated demyelination can be relatively reassured by these data.