ABSTRACT
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.
Subject(s)
Autoimmune Diseases , Leukocytes, Mononuclear , Alleles , Autoimmune Diseases/genetics , Gene Expression Regulation , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Polymorphism, Single Nucleotide , Precursor Cells, B-Lymphoid , Quantitative Trait Loci , Sequence Analysis, RNAABSTRACT
PURPOSE: To investigate the effects of vitrectomy (Vy) with or without same time cataract surgery and membrane plus internal limiting membrane peeling (MP+ILMP) on retinal oxygenation and choroidal volume and their role on postoperative outcome. METHODS: Thirty-two eyes were included in this prospective clinical study. All patients received 23 gauge Vy+MP+ILMP without endotamponade. Additional cataract surgery was performed in 14 patients. Follow-up visits were scheduled at day 1, week 1, month 1 and month 3. At each visit, best corrected visual acuity (BCVA) using ETDRS charts (except at day 1), oxygenation of retinal vessels using the Oxymap T1, and optical coherence tomography (OCT, Heidelberg Spectralis) was performed. RESULTS: Mean BCVA increased significantly from 73 ± 11 letters to 77 ± 7 letters at month 3 (p = 0.02). Mean central retinal thickness (CRT) decreased from 456 ± 84 µm at baseline to 418±58µm (p = 0.01 baseline versus month 3). In the cataract surgery group, CRT was higher at month 3 than in the group without (400 ± 58 µm versus 441 ± 51 µm; p = 0.007). There was no statistically significant difference in choroidal volume or oxygenation of retinal vessels between groups (additional cataract surgery versus vitrectomy alone). Oxygenation of retinal arteries tended to decrease at day 1 followed by an increase, but the changes did not reach the level of significance (p = 0.29 baseline versus month 3). Oxygenation of retinal veins increased significantly (p = 0.02 baseline versus month 1; p = 0.04 baseline versus month 3, accordingly). There was a significant negative correlation (Spearman correlation coefficient rs = -0.35, p = 0.047) between visual acuity and oxygenation of retinal veins at month 3. No statistically significant correlation was found between CRT and oxygenation of neither retinal arteries nor veins. Choroidal volume (CV) of the central mm did not change significantly during the study period (baseline: 0.203 ± 0.04 mm3 , median: 0.206, month 3: 0.205 ± 0.04 mm3 , p = 0.54). There was no statistically significant effect of choroidal volume at baseline on postoperative clinical outcomes (change in BCVA estimate [95% CI]: 7 [-76; 90], p = 0.86; change in CRT: 147 [-577; 871], p = 0.68). CONCLUSION: Oxygen saturation may affect the visual acuity outcome but not the CRT in patients after vitrectomy for epiretinal membrane. Choroidal thickness had no statistically significant influence on the study outcomes. Further studies are needed to evaluate if the measurement of retinal oxygenation may be helpful in the decision for surgery.
Subject(s)
Cataract , Epiretinal Membrane , Epiretinal Membrane/diagnosis , Epiretinal Membrane/surgery , Humans , Oxygen Saturation , Prospective Studies , Retrospective Studies , Tomography, Optical Coherence/methods , Visual Acuity , Vitrectomy/methodsABSTRACT
PURPOSE: To prospectively evaluate the outcomes of different subtypes of neovascular age-related macular degeneration during intravitreal aflibercept monotherapy. METHODS: Forty-four eyes of 44 patients with treatment-naïve polypoidal choroidal vasculopathy (PCV, n = 12), hemorrhagic choroidal neovascularization (hCNV, n = 12), pigment epithelium detachment (PED, n = 11), or retinal angiomatous proliferation (RAP, n = 9) were included and followed for 12 months. All patients received intravitreal aflibercept monotherapy. RESULTS: Mean visual acuity at baseline in PCV was 67 ± 16 Early Treatment Diabetic Retinopathy Study letters (20/50 Snellen equivalent), in hCNV 55 ± 21 (20/80), in RAP lesions 64 ± 11 (20/50), and in PED 74 ± 7 (20/32). At Month 12, visual acuity in PCV was 66 ± 16 (20/50), in hCNV 69 ± 17 (20/40), in RAP 68 ± 12 (20/50), and in PED 69 ± 18 (20/40). At the 12-month follow-up, visual acuity improved or was stable (±5 letters from baseline) in 84% of eyes (37/44 patients), with hCNV showing the greatest mean visual acuity gain. Mean central retinal thickness in patients with PCV was 523 ± 251 µm, in hCNV 497 ± 171, in RAP lesions 573 ± 132, and in PED 541 ± 158 and decreased to 310 ± 91 µm in PCV, 323 ± 75 µm in hCNV, 357 ± 173 µm in RAP lesions, and 422 ± 150 µm in PED. The mean area of atrophy increased from 2.0 ± 3.6 mm2 at baseline to 4.6 ± 8.6 mm2 at Month 12 (mean difference [95% confidence interval] -0.8 [-8.5 to 7.0], P = 0.8), with the greatest atrophy in patients with PED at Month 12. CONCLUSION: All subtypes of neovascular age-related macular degeneration showed anatomical improvement and stabilization of visual function during intravitreal treatment.
Subject(s)
Receptors, Vascular Endothelial Growth Factor/administration & dosage , Recombinant Fusion Proteins/administration & dosage , Retinal Pigment Epithelium/pathology , Visual Acuity , Wet Macular Degeneration/drug therapy , Aged , Angiogenesis Inhibitors/administration & dosage , Female , Fluorescein Angiography/methods , Fundus Oculi , Humans , Intravitreal Injections , Male , Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors , Retrospective Studies , Tomography, Optical Coherence/methods , Treatment Outcome , Wet Macular Degeneration/diagnosisABSTRACT
Optical coherence tomography is a non-invasive ocular imaging technique that is frequently used in the diagnosis and monitoring of optic nerve or retinal disease. Advances in optical coherence tomography speed and image processing capability allow increased use of the modality in clinical practice, especially in younger children. This review outlines the challenges involved in imaging children, highlights the technological progress, the importance of acquiring normative data and, finally, focuses on the clinical applicability of optical coherence tomography in our paediatric population with various ocular conditions.
