Predictive factors of graft detachment and rebubbling after descemet membrane endothelial keratoplasty.

PURPOSE: To identify risk and predictive factors associated with the need of rebubbling in the eye of patients who underwent a descemet membrane endothelial keratoplasty (DMEK). METHODS: The records of patients who underwent DMEK were retrospectively analyzed. Data regarding comorbidities, intraoperative characteristics, and postoperative treatments or complications were collected. The central corneal thickness (CCT) was measured by optical coherence tomography before and the day after DMEK. Univariate and multivariate analyses were performed. RESULTS: Of the 333 DMEK, rebubbling was performed in 119 cases (36%). Preoperative subepithelial fibrosis and a history of penetrating keratoplasty (PK) were associated with significantly more graft detachment [OR of 3.55 (2.02-6.32; P < 0.001) and 5.89 (2.00-21.86; P = 0.003), respectively]. A decreased CCT the day after surgery reduced by 5.7-fold the risk of rebubbling (sensitivity/specificity of 0.42/0.93). Conversely, a 20% increase in the CCT the day after surgery increased by 4.5-fold the risk of rebubbling (sensitivity/specificity of 0.42/0.91). CONCLUSION: Variation of the CCT could be used as a predictive factor of rebubbling after DMEK. Patients with a 20% increase of CCT the day after surgery are at higher risk of graft detachment. Conversely, a reduced CCT the day after the surgery is associated with a reduced risk of rebubbling. Subepithelial fibrosis and history of PK were also identified as risk factors for rebubbling. Those predictive factors may help develop a customized approach for patients undergoing DMEK surgery.

Classical swine fever virus Npro antagonises IRF3 to prevent IFN-independent TLR3 and RIG-I-mediated apoptosis.

Classical swine fever virus (CSFV) is the causative agent of classical swine fever, a notifiable disease of economic importance that causes severe leukopenia, fever and haemorrhagic disease in domesticated pigs and wild boar across the globe. CSFV has been shown to antagonise the induction of type I IFN, partly through a function of its N-terminal protease (Npro) which binds IRF3 and targets it for proteasomal degradation. Additionally, Npro has been shown to antagonise apoptosis triggered by the dsRNA-homolog poly(I:C), however the exact mechanism by which this is achieved has not been fully elucidated. In this study we confirm the ability of Npro to inhibit dsRNA-mediated apoptosis and show that Npro is also able to antagonise Sendai virus-mediated apoptosis in PK-15 cells. Gene edited PK-15 cell lines were used to show the dsRNA-sensing pathogen recognition receptors (PRRs) TLR3 and RIG-I specifically respond to poly(I:C) and SeV respectively, subsequently triggering apoptosis through pathways that converge on IRF3 and culminate in the cleavage of caspase-3. Importantly, this IRF3-mediated apoptosis was found to be dependent on transcription-independent functions of IRF3 and also on Bax, a pro-apoptotic Bcl-2 family protein, through a direct interaction between the two proteins. Deletion of IRF3, stable expression of Npro and infection with wild-type CSFV were found to antagonise the mitochondrial localisation of Bax, a key hallmark of the intrinsic, mitochondrial pathway of apoptosis. Together, these findings show that Npro's putative interaction with IRF3 is involved not only in its antagonism of type I IFN, but also dsRNA-mediated mitochondrial apoptosis.Importance Responsible for severe haemorrhagic disease in domestic pigs and wild boar, classical swine fever is recognised by the World Organisation for Animal Health (OIE) and European Union as a notifiable disease of economic importance. Persistent infection, immunotolerance and early dissemination of the virus at local sites of infection have been linked to the antagonism of type I IFN induction by Npro This protein may further contribute to these phenomena by antagonising the induction of dsRNA-mediated apoptosis. Ultimately, apoptosis is an important innate mechanism by which cells counter viruses at local sites of infection, thus preventing wider spread and dissemination within the host, potentially also contributing to the onset of persistence. Elucidation of the mechanism by which Npro antagonises the apoptotic response will help inform the development of rationally-designed live-attenuated vaccines and antivirals for control of outbreaks in typically CSFV-free countries.

PATTERNS OF CHORIOCAPILLARIS FLOW SIGNAL VOIDS IN CENTRAL SEROUS CHORIORETINOPATHY: An Optical Coherence Tomography Angiography Study.

PURPOSE: To investigate choriocapillaris flow signal void distribution on optical coherence tomography (OCT) angiography in central serous chorioretinopathy (CSCR) and its correlation to choroidal vessel morphology. METHODS: Fifty-three CSCR eyes (48 patients) and 34 healthy control eyes were included, retrospectively. Exclusion criteria were refractive error >2D, previous laser or photodynamic therapy, low-quality OCT angiography, or excessive shadowing artifacts. Choriocapillaris OCT angiography scans were processed by local-threshold binarization to identify signal voids, and extract their cumulative area. The locations of the two largest voids in each eye were reported on the corresponding enhanced depth imaging OCT raster scan. Choriocapillaris thickness and diameter of underlying outer choroidal vessels were measured at the level of flow voids and of adjacent outer choroidal vessels, not colocalizing with voids. RESULTS: There were 22 acute, 16 recurrent, and 15 chronic CSCR eyes. Total flow void area was larger in CSCR than control eyes. In univariate analysis, the total flow void area on OCT angiography increased with age (P = 0.0002), duration since CSCR diagnosis (P = 0.004), extension of autofluorescence alterations (P = 0.016), and CSCR severity (P < 0.0001). In multivariate analysis, age (P = 0.014) and CSCR type (P = 0.046) influenced independently the total flow void area. On enhanced depth imaging OCT, outer choroidal vessel diameter was higher (P < 0.0001), and choriocapillaris was thinner (P < 0.0001) at flow voids compared with adjacent sites, independently from eccentricity from the fovea. CONCLUSION: Choriocapillaris flow voids colocalize with choriocapillaris thinning and deep choroidal vessel dilation in CSCR eyes. Age and CSCR severity influence choriocapillaris flow, a key contributor to CSCR pathophysiology and clinical expression.

The Efficacy of Medical Marijuana in the Treatment of Cancer-Related Pain.

Background: The opioid epidemic has spurred investigations for nonopioid options, yet limited research persists on medical marijuana's (MMJ) efficacy in managing cancer-related symptoms. Objective: We sought to characterize MMJ's role on symptomatic relief and opioid consumption in the oncologic population. Design: Retrospective chart review of MMJ-certified oncology patients was performed. Divided patients into MMJ use [MMJ(+)] versus no use [MMJ(-)], and Edmonton Symptom Assessment System (ESAS)-reported pain cohorts: "mild-moderate" versus "severe." Measurements: Medical records were reviewed for ESAS, to measure physical and emotional symptoms, and opiate consumption, converted into morphine milligram equivalents (MME). Minimal clinically important differences were determined. Wilcoxon signed-rank tests determined statistical significance between MMJ-certification and most recent palliative care visit. Results: Identified 232 patients [95/232 MMJ(-); 137/232 MMJ(+)]. Pain, physical and total ESAS significantly improved for total MMJ(-) and MMJ(+); however, only MMJ(+) significantly improved emotional ESAS. MMJ(-) opioid consumption increased by 23% (97.5-120 mg/day MME, p = 0.004), while it remained constant (45-45 mg/day MME, p = 0.522) in MMJ(+). Physical and total ESAS improved in mild-moderate-MMJ(-) and MMJ(+). Pain and emotional symptoms worsened in MMJ(-); while MMJ(+)'s pain remained unchanged and emotional symptoms improved. MMJ(-) opioid consumption increased by 29% (90-126 mg/day MME, p = 0.012); while MMJ(+)'s decreased by 33% (45-30 mg/day MME, p = 0.935). Pain, physical, emotional, and total ESAS scores improved in severe-MMJ(-) and MMJ(+); opioid consumption reduced by 22% in MMJ(-) (135-106 mg/day MME, p = 0.124) and 33% in MMJ(+) (90-60 mg/day MME, p = 0.421). Conclusions: MMJ(+) improved oncology patients' ESAS scores despite opioid dose reductions and should be considered a viable adjuvant therapy for palliative management.