Intravitreal aflibercept for choroidal neovascularization secondary to angioid streaks in a non-responder to intravitreal ranibizumab

Olga E Makri, Foteini N Tsapardoni, Panagiotis Plotas, Athina Pallikari, Constantine D Georgakopoulos Department of Ophthalmology, University of Patras, Patras, Greece Purpose: To report the 12-month outcomes of a patient switching from intravitreal ranibizumab to aflibercept for choroidal neovascularization (CNV) associated with angioid streaks (AS).Results: A 42-year-old Caucasian female with CNV associated with AS underwent intensive treatment with ranibizumab without significant functional or anatomic change. Treatment was then switched to aflibercept and the patient received the proposed age-related macular degeneration treatment regimen. After 3 loading doses of aflibercept, best-corrected visual acuity (BCVA) improved from 3/10 to 6/10, while optical coherence tomography (OCT) demonstrated resolution of the subretinal fluid with a reduction of the intraretinal fluid. After 12 months and 7 intravitreal injections of aflibercept, BCVA returned to 3/10, while OCT had demonstrated further morphologic improvement.Conclusion: Our case shows that aflibercept may be an alternative treatment for advanced cases of CNV associated with AS that respond insufficiently to ranibizumab injections. Prospective studies are required to further evaluate the effect of aflibercept and to propose a standardized treatment protocol for this entity. Keywords: aflibercept, ranibizumab, angioid streaks, choroidal neovascularization, intravitrea

Orbital Cellulitis and Subperiosteal Abscess: A 5-year Outcomes Analysis

Purpose: Orbital cellulitis and subperiosteal abscess (SPA) are historically associated with poor outcomes. We seek to characterize current associations with abscess formation, surgical failure and vision loss. Methods: All cases of orbital cellulitis presenting to an affiliated hospital between April 2008 and 2013 were critically reviewed. Results: Thirty patients met inclusion criteria. Average age was 28.7 ± 24.4. The male to female ratio was 2:1. Abscesses were identified in 56.7% of patients. Adults were less likely than children to present with abscesses (28.6% vs. 81.3%, p = 0.008). Of the other factors analyzed, only antibiotic use before admission (70.5% vs. 23.1%, p = 0.03) and maximum restriction (−2.5 ± 1.2 vs. −0.9 ± 0.7, p = 0.008) were associated with SPA. Temperature at presentation (37.9 ± 0.9 vs. 37.1 ± 0.4, p = 0.04), relative proptosis (5.8 ± 3.3 mm vs. 2.1 ± 1.1, p = 0.002) and abscess volume (4.3 ± 1.3 mm 3 vs. 0.7 ± 0.5 mm 3 , p = 0.0004) were associated with progression to surgery. Reoperation was required in 26.7% of patients. Of these, two-thirds had combined superior/medial abscesses that re-accumulated after isolated endonasal surgery. Two of the 3 patients with profound vision loss had a dental etiology. Conclusions: Only young age, prior antibiotics and degree of restriction predicted the presence of an abscess. Re-accumulation was more common than anticipated, and drainage of superior/medial abscesses by endoscopic surgery alone had the strongest association with surgical failure. Patients with odontogenic abscesses must be treated with particular caution

Vascular inflammation and metabolic activity in hematopoietic organs and liver in familial combined hyperlipidemia and heterozygous familial hypercholesterolemia

BACKGROUND: Familial dyslipidemias of either heterozygous (heFH) or combined (FCH) type lead to accelerated atherogenesis and increased cardiovascular risk. OBJECTIVE: The aim of this study was to investigate in statin-naïve adult patients with familial dyslipidemias whether inflammatory activation and liver, spleen and bone marrow metabolic activity differ compared with normolipidemic subjects and between dyslipidemic groups. METHODS: Fourteen patients with FCH, 14 with heFH, and 14 normolipidemic individuals were enrolled. Serum lipids, high-sensitivity C-reactive protein, and fibrinogen levels were measured, followed by 18F-fluorodeoxyglucose positron-emission tomography/computed tomography imaging. Radiotracer uptake in the aortic wall, spleen, bone marrow, and liver was quantified as tissue-to-background ratio (TBR). RESULTS: Patients with heFH had significantly higher low-density lipoprotein levels compared with those with FCH and controls (P &lt; .001). However, aortic TBRs were higher in FCH compared with heFH patients and controls (P = .02 and P &lt; .001, respectively). FCH patients exhibited higher FDG uptake in the spleen compared with controls (P = .05). In addition, FCH exhibited higher bone marrow FDG uptake compared with heFH patients and controls (P = .03 and P = .02, respectively). FCH had higher liver uptake compared with heFH patients and controls (P &lt; .001 for both). Significant correlations were observed between inflammatory biomarkers and imaging indices as well as between aortic TBR and FDG uptake of hematopoietic organs and liver. CONCLUSIONS: Systemic, as well as vascular inflammation and spleen, bone marrow, and hepatic metabolic activity are increased in patients with FCH despite lower levels of low-density lipoprotein.</p

Vascular inflammation and metabolic activity in hematopoietic organs and liver in familial combined hyperlipidemia and heterozygous familial hypercholesterolemia

BACKGROUND: Familial dyslipidemias of either heterozygous (heFH) or combined (FCH) type lead to accelerated atherogenesis and increased cardiovascular risk. OBJECTIVE: The aim of this study was to investigate in statin-naand#239;ve adult patients with familial dyslipidemias whether inflammatory activation and liver, spleen and bone marrow metabolic activity differ compared with normolipidemic subjects and between dyslipidemic groups. METHODS: Fourteen patients with FCH, 14 with heFH, and 14 normolipidemic individuals were enrolled. Serum lipids, high-sensitivity C-reactive protein, and fibrinogen levels were measured, followed by 18F-fluorodeoxyglucose positron-emission tomography/computed tomography imaging. Radiotracer uptake in the aortic wall, spleen, bone marrow, and liver was quantified as tissue-to-background ratio (TBR). RESULTS: Patients with heFH had significantly higher low-density lipoprotein levels compared with those with FCH and controls (Pand#160;andlt;and#160;.001). However, aortic TBRs were higher in FCH compared with heFH patients and controls (Pand#160;=and#160;.02 and Pand#160;andlt;and#160;.001, respectively). FCH patients exhibited higher FDG uptake in the spleen compared with controls (Pand#160;=and#160;.05). In addition, FCH exhibited higher bone marrow FDG uptake compared with heFH patients and controls (Pand#160;=and#160;.03 and Pand#160;=and#160;.02, respectively). FCH had higher liver uptake compared with heFH patients and controls (Pand#160;andlt;and#160;.001 for both). Significant correlations were observed between inflammatory biomarkers and imaging indices as well as between aortic TBR and FDG uptake of hematopoietic organs and liver. CONCLUSIONS: Systemic, as well as vascular inflammation and spleen, bone marrow, and hepatic metabolic activity are increased in patients with FCH despite lower levels of low-density lipoprotein.</p

lentiMPRA and MPRAflow for high-throughput functional characterization of gene regulatory elements

Massively parallel reporter assays (MPRAs) can simultaneously measure the function of thousands of candidate regulatory sequences (CRSs) in a quantitative manner. In this method, CRSs are cloned upstream of a minimal promoter and reporter gene, alongside a unique barcode, and introduced into cells. If the CRS is a functional regulatory element, it will lead to the transcription of the barcode sequence, which is measured via RNA sequencing and normalized for cellular integration via DNA sequencing of the barcode. This technology has been used to test thousands of sequences and their variants for regulatory activity, to decipher the regulatory code and its evolution, and to develop genetic switches. Lentivirus-based MPRA (lentiMPRA) produces 'in-genome' readouts and enables the use of this technique in hard-to-transfect cells. Here, we provide a detailed protocol for lentiMPRA, along with a user-friendly Nextflow-based computational pipeline-MPRAflow-for quantifying CRS activity from different MPRA designs. The lentiMPRA protocol takes ~2 months, which includes sequencing turnaround time and data processing with MPRAflow