The risk of development and progression of diabetic retinopathy in a group of ethnically diverse pregnant women with diabetes attending three regional Diabetic Eye Screening Programs in the UK.

BACKGROUND/OBJECTIVES: Currently, all pregnant women with diabetes are asked to attend screening at least twice during pregnancy, even if no retinopathy is detected in early pregnancy. We hypothesise that for women with no diabetic retinopathy in early pregnancy, the frequency of retinal screening may be safely reduced. SUBJECTS/METHODS: In this retrospective cohort study, data for 4718 pregnant women attending one of three UK Diabetic Eye Screening (DES) Programmes between July 2011 and October 2019 was extracted. The women's UK DES grades at 13 weeks gestation (early pregnancy) and 28 weeks gestation (late pregnancy) were recorded. Descriptive statistics were used to report baseline data. Ordered logistic regression was used to control for covariates, such as age, ethnicity, diabetes duration, and diabetes type. RESULTS: Of the women with grades recorded for both early and late pregnancy, a total of 3085 (65.39%) women had no retinopathy in early pregnancy, and 2306 (74.7%) of these women did not develop any retinopathy by 28 weeks. The number of women without retinopathy in early pregnancy who developed referable retinopathy was 14 (0.45%), none of whom required treatment. Diabetic Retinopathy in early pregnancy remained a significant predictor of DES grade in late pregnancy when covariates of Age, Ethnicity, and Diabetes Type were controlled for (P < 0.001). CONCLUSIONS: In summary, this study has demonstrated that the burden of managing diabetes for pregnant mothers may be safely reduced by limiting the number of diabetic eye screening appointments in women who have no retinal changes in early pregnancy. Screening of women with retinopathy in early pregnancy should continue in line with current UK guidance.

Automated image curation in diabetic retinopathy screening using deep learning.

Diabetic retinopathy (DR) screening images are heterogeneous and contain undesirable non-retinal, incorrect field and ungradable samples which require curation, a laborious task to perform manually. We developed and validated single and multi-output laterality, retinal presence, retinal field and gradability classification deep learning (DL) models for automated curation. The internal dataset comprised of 7743 images from DR screening (UK) with 1479 external test images (Portugal and Paraguay). Internal vs external multi-output laterality AUROC were right (0.994 vs 0.905), left (0.994 vs 0.911) and unidentifiable (0.996 vs 0.680). Retinal presence AUROC were (1.000 vs 1.000). Retinal field AUROC were macula (0.994 vs 0.955), nasal (0.995 vs 0.962) and other retinal field (0.997 vs 0.944). Gradability AUROC were (0.985 vs 0.918). DL effectively detects laterality, retinal presence, retinal field and gradability of DR screening images with generalisation between centres and populations. DL models could be used for automated image curation within DR screening.

Cilioretinal Artery Territory Infarction Associated With Papilledema in a Patient With Neurofibromatosis Type 2.

Cilioretinal artery territory infarction can occur in isolation or in association with other vascular compromise of the retinal circulation. Our patient, an 18-year-old woman with neurofibromatosis type 2, developed a cilioretinal artery territory infarction in the setting of papilledema. Our case, together with one previous report, suggests that cilioretinal artery territory infarction in the context of papilledema, although rare, is a real entity.

Genome-wide association study of age-related macular degeneration identifies associated variants in the TNXB-FKBPL-NOTCH4 region of chromosome 6p21.3.

Age-related macular degeneration (AMD) is a leading cause of visual loss in Western populations. Susceptibility is influenced by age, environmental and genetic factors. Known genetic risk loci do not account for all the heritability. We therefore carried out a genome-wide association study of AMD in the UK population with 893 cases of advanced AMD and 2199 controls. This showed an association with the well-established AMD risk loci ARMS2 (age-related maculopathy susceptibility 2)-HTRA1 (HtrA serine peptidase 1) (P =2.7 × 10(-72)), CFH (complement factor H) (P =2.3 × 10(-47)), C2 (complement component 2)-CFB (complement factor B) (P =5.2 × 10(-9)), C3 (complement component 3) (P =2.2 × 10(-3)) and CFI (P =3.6 × 10(-3)) and with more recently reported risk loci at VEGFA (P =1.2 × 10(-3)) and LIPC (hepatic lipase) (P =0.04). Using a replication sample of 1411 advanced AMD cases and 1431 examined controls, we confirmed a novel association between AMD and single-nucleotide polymorphisms on chromosome 6p21.3 at TNXB (tenascin XB)-FKBPL (FK506 binding protein like) [rs12153855/rs9391734; discovery P =4.3 × 10(-7), replication P =3.0 × 10(-4), combined P =1.3 × 10(-9), odds ratio (OR) = 1.4, 95% confidence interval (CI) = 1.3-1.6] and the neighbouring gene NOTCH4 (Notch 4) (rs2071277; discovery P =3.2 × 10(-8), replication P =3.8 × 10(-5), combined P =2.0 × 10(-11), OR = 1.3, 95% CI = 1.2-1.4). These associations remained significant in conditional analyses which included the adjacent C2-CFB locus. TNXB, FKBPL and NOTCH4 are all plausible AMD susceptibility genes, but further research will be needed to identify the causal variants and determine whether any of these genes are involved in the pathogenesis of AMD.

Complement factor H genetic variant and age-related macular degeneration: effect size, modifiers and relationship to disease subtype.

BACKGROUND: Variation in the complement factor H gene (CFH) is associated with risk of late age-related macular degeneration (AMD). Previous studies have been case-control studies in populations of European ancestry with little differentiation in AMD subtype, and insufficient power to confirm or refute effect modification by smoking. METHODS: To precisely quantify the association of the single nucleotide polymorphism (SNP rs1061170, 'Y402H') with risk of AMD among studies with differing study designs, participant ancestry and AMD grade and to investigate effect modification by smoking, we report two unpublished genetic association studies (n = 2759) combined with data from 24 published studies (26 studies, 26,494 individuals, including 14,174 cases of AMD) of European ancestry, 10 of which provided individual-level data used to test gene-smoking interaction; and 16 published studies from non-European ancestry. RESULTS: In individuals of European ancestry, there was a significant association between Y402H and late-AMD with a per-allele odds ratio (OR) of 2.27 [95% confidence interval (CI) 2.10-2.45; P = 1.1 x 10(-161)]. There was no evidence of effect modification by smoking (P = 0.75). The frequency of Y402H varied by ancestral origin and the association with AMD in non-Europeans was less clear, limited by paucity of studies. CONCLUSION: The Y402H variant confers a 2-fold higher risk of late-AMD per copy in individuals of European descent. This was stable to stratification by study design and AMD classification and not modified by smoking. The lack of association in non-Europeans requires further verification. These findings are of direct relevance for disease prediction. New research is needed to ascertain if differences in circulating levels, expression or activity of factor H protein explain the genetic association.

The symmetry of phenotype between eyes of patients with early and late bilateral age-related macular degeneration (AMD).

BACKGROUND: Macular degeneration is known to be a bilateral disease. This study set out to determine the symmetry of phenotype between eyes of patients with bilateral early AMD (or drusen) or late-stage AMD. This may be important information when considering the likelihood of anti-VEGF treatment. METHODS: This prospective, observational, cross-sectional study graded the color fundus photographs of both eyes of 1,114 Caucasian patients with either early or late-stage AMD. Patients were recruited from a tertiary referral UK population. The main outcomes were phenotype, comparison of number, type and overall area of drusen in early AMD and symmetry of late AMD. RESULTS: The overall agreement of phenotype in the entire cohort of patients was 53%, kappa statistic (κ)=0.31, (95% CI = 0.27-0.36). Within this group, a total of 271 patients were identified with bilateral soft and hard drusen (early AMD). Symmetry of phenotype within this group was high in terms of total of area of drusen (agreement = 79%, weighted κ = 0.75) and number of drusen. In those with bilateral geographic atrophy (GA), symmetry between area of GA was moderate (agreement 72%, weighted κ = 0.54), and in those with bilateral neovascular disease (choroidal neovascularization or pigment epithelial detachment), symmetry was poor (agreement 45%, weighted κ = 0.16). Out of the entire cohort, 62% (n = 688) had neovascular disease in at least one eye and 37.5% of these had bilateral disease. CONCLUSIONS: The observed symmetry of phenotype between eyes with drusen appears to reduce in GA and neovascular forms of AMD. Overall, 53% of the cohort had symmetrical disease in terms of phenotype, 23% had neovascular disease in both eyes, 9.3% had GA in both eyes, and 39% of patients had neovascular disease in one eye and non-neovascular disease in the other. This may have implications for the potential need for anti-VEGF treatment of AMD in second eye involvement.