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In vascularized organ transplants, gender mismatches have higher rates of immunological rejection. We investigated the influence of gender incompatibility, including H‐Y incompatibility, on corneal transplant graft rejection and failure. Patients were included who had undergone a first corneal transplant for keratoconus (KC), Fuchs endothelial dystrophy (FED), pseudophakic bullous keratopathy (PBK), infection and other indications. A Cox regression model was fitted for each indication to determine factors affecting graft failure and rejection at 5 years. The impact of gender, including H‐Y, matching was analyzed after accounting for other factors, including known risk factors. Of 18 171 patients, 4314 had undergone a transplant for FED, 4783 for KC, 3669 for PBK, 1903 for infection and 3502 for other disorders. H‐Y mismatched (male [M]→female [F]) corneas were at greater risk of graft failure or rejection. For FED, F→F were 40% less likely to fail (p < 0.0001) and 30% less likely to reject (p = 0.01); M→M were 20% less likely to fail (p = 0.04) and 30% less likely to reject (p = 0.01). For KC, M→M matched corneas were 30% less likely to fail (p = 0.05) and 20% less likely to reject (p = 0.01) compared with H‐Y mismatches. H‐Y antigen mismatched (M→F) patients were at greater risk of rejection or graft failure.

PURPOSE.To investigate the rate of recurrent bacterial keratitis, associated bacteria, and surgical intervention. METHODS.Patients with suspected bacterial keratitis were identified from microbiological requests over a 16-year period between 1995 and 2010. Recurrences and number of surgical interventions were analyzed according to bacterial type. RESULTS.A total of 2418 patients were included, of whom 2124 (87.84%) had only one episode of keratitis, 294 (12.15%) at least two, 88 (3.63%) at least three, 40 (1.65%) at least four, and 22 (0.91%) five or more episodes. The bacterial isolation rate was 35.74% (SD 9.41%), increasing to 56.01% in patients with two or more episodes. There was an increase in the isolation of Staphylococcus aureus with increasing number of episodes (P ¼ 0.008), and S. aureus occurred more commonly in patients with recurrent disease due to the same bacterial group (P ¼ 0.04). Patients whose recurrent keratitis was associated with S. aureus had a higher rate of requiring subsequent corneal transplantation (7 of 10) compared to those with Enterobacteriaceae (2 of 7), Pseudomonas aeruginosa (2 of 4), streptococci (2 of 5), or coagulase-negative staphylococci (none of 8) (P ¼ 0.02).CONCLUSIONS. S. aureus is particularly associated with recurrent keratitis. Identification and treatment of the possible source of the infection may be necessary to reduce the risk of recurrent disease. The potential for the autocthonous S. aureus colonizing the nasopharynx or conjunctiva or lid margin to be a reservoir for recurrent keratitis suggests that decolonization of S. aureus could be considered as a potential intervention in those patients with recurrent disease.

Severe, chronic eye allergy is an understudied, vision-threatening condition. Treatments remain limited. We used a mouse model of severe allergic eye disease (AED) to determine if topical application of the pro-resolution mediator Resolvin D1 (RvD1) terminates the response. AED was induced by injection of ovalbumin (OVA) followed by topical challenge of OVA daily. RvD1 was applied topically prior to OVA. Clinical symptoms were scored. Eye washes were assayed for MUC5AC. After 7 days, eyes were removed and the number of goblet cells, T helper cell responses and presence of immune cells in draining lymph nodes and conjunctiva determined. Topical RvD1 treatment significantly reduced symptoms of AED. RvD1 did not alter the systemic type 2 immune response in the lymph nodes. AED increased the total amount of goblet cell mucin secretion, but not the number of goblet cells. RvD1 prevented this increase, but did not alter goblet cell number. Absolute numbers of CD4+ T cells, total CD11b+ myeloid cells, eosinophils, neutrophils, and monocytes, but not macrophages increased in AED versus RvD1 treated mice. We conclude that topical application of RvD1 reduced the ocular allergic response by a local actions in conjunctival immune response and a decrease in goblet cell mucin secretion.

Purpose: To identify interactions of the epidermal growth factor receptor (EGFR) with the proresolving mediator receptors for RvD1 and RvE1 to stimulate an increase in intracellular [Ca 2+ ] ([Ca 2+ ] i ) and mucin secretion from cultured human and rat conjunctival goblet cells.Methods: Goblet cells from human and rat conjunctiva were grown in culture using RPMI media. Cultured goblet cells were pre-incubated with inhibitors, and then stimulated with RvD1, RvE1, EGF or the cholinergic agonist carbachol (Cch). Increase in [Ca 2+ ] i was measured using fura-2/AM. Goblet cell secretion was measured using an enzyme-linked lectin assay with UEA-1. Western blot analysis was performed with antibodies against AKT and ERK 1/2. Results:In cultured human conjunctival goblet cells RvE1 -stimulated an increase in [Ca 2+ ] i . The RvD1-, but not the RvE1-, stimulated increase in [Ca 2+ ] i and mucin secretion was blocked by the EGFR inhibitor AG1478 and siRNA for the EGFR. RvD1-, but not RvE1-stimulated an increase in [Ca 2+ ] i that was also inhibited by TAPI-1, an inhibitor of the matrix metalloprotease ADAM 17. Inhibition of the EGFR also blocked RvD1-stimulated increase in AKT activity and

To effectively reduce vision loss due to age-related macular generation (AMD) on a global scale, knowledge of its genetic architecture in diverse populations is necessary. A critical element, AMD risk profiles in African and Hispanic/Latino ancestries, remains largely unknown due to lower lifetime prevalence. We combined genetic and clinical data in the Million Veteran Program with five other cohorts to conduct the first multi-ancestry genome-wide association study of AMD and discovered 63 loci (30 novel). We observe marked cross-ancestry heterogeneity at major risk loci, especially in African-ancestry populations which demonstrate a primary signal in a Major Histocompatibility Complex Class II haplotype and reduced risk at the established CFH and ARMS2/HTRA1 loci. Broadening efforts to include ancestrally-distinct populations helped uncover genes and pathways which boost risk in an ancestry-dependent manner, and are potential targets for corrective therapies.

At best, mortality monitoring can act as a backstop to detect a particularly prolific serial killer when other means of detection have failed. Policy should focus on changes likely to improve detection of individual murders, such as reform of death certification and the coroner system. Keywords family practice; homicide; outcome and process assessment (health care); quality assurance, health care; regulation. B Guthrie, PhD, MRCGP, professor of primary care medicine;