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Purpose: To compare the lens tilt after apex-centered capsulotomy with standard pupil-centered capsulotomy., Setting: Clinical practice., Design: Prospective, randomized, investigator-masked trial., Methods: This prospective, randomized, investigator masked study included 40 patients with age-related cataract scheduled for femtosecond laser-assisted cataract surgery (FLACS) in both eyes. The main outcome was the tilt of the intraocular lens (IOL), measured with the IOLMaster 700., Results: The study enrolled 80 eyes of 40 patients. The mean distance from the center of the apex-centered capsulotomy to the pupil-centered capsulotomy was 175.8 ± 97.2 μm. The amount of IOL tilt was not significantly reduced with the new technique (P > .05). Tilt orientation was more stable in eyes treated with apex-centered capsulotomy., Conclusions: Centration of the capsulotomy on the lens apex in FLACS does not influence the amount of IOL tilt but the orientation stability. The clinical importance of this finding has to be further elucidated., (Copyright © 2021 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Glaucomatous optic neuropathies have been regarded as diseases caused by high intraocular pressure for a long time, despite the concept of vascular glaucoma dating back to von Graefe in 1854. Since then, a tremendous amount of knowledge about the ocular vasculature has been gained; cohort studies have established new vascular risk factors for glaucoma as well as identifying protective measures acting on blood vessels. The knowledge about the physiology and pathophysiology of the choroidal, retinal, as well as ciliary and episcleral circulation has also advanced. Only recently have novel drugs based on that knowledge been approved for clinical use, with more to follow. This review provides an overview of the current vascular concepts in glaucoma, ranging from novel pathogenesis insights to promising therapeutic approaches, covering the supply of the optic nerve head as well as the aqueous humor production and drainage system.

Purpose: To investigate the possibility and consequences of false positive testing for Leber's hereditary optic neuropathy (LHON) using repeated testing., Methods: In three cases of suspected LHON, initial mutation analysis using restriction fragment length polymorphism (RFLP) and direct sequencing showed rare mtDNA mutations at nt 14482 in two cases and a mutation in nt 14484 in the third case which has been associated with a mild variant of LHON. All three patients consulted a specialized neuro-ophthalmology center for a second opinion. During the examinations the clinical diagnosis of LHON was questioned. Therefore the initial DNA samples were reevaluated again using the same probes., Results: The reevaluation by the testing laboratory of the DNA samples of the three patients revealed misinterpreted initial results and could show that there were no LHON typical mutations in none of the three patients., Conclusion: A high level of suspicion is important when an accumulation of rare mutations occurs. It is only because of the attentiveness of a specialized neuro-ophthalmologist and the testing laboratory that the diagnosis of LHON was averted. Every laboratory testing can produce false positive results. Therefore, we emphasize that a positive test should be confirmed by a second independent laboratory, at least if the clinical findings seem not to be typical for LHON.

Purpose: Swept Source Optical coherence tomography angiography (SS-OCTA) is a novel technique to visualize perfusion and vascular changes like ischemia in patients with diabetic retinopathy. The aim of this study was to compare non-perfusion areas on conventional fluorescein angiography (FA) with those on SS-OCTA using detailed manual annotation in patients with diabetic macular edema (DME) and to evaluate possible artifacts caused by DME on SS-OCTA., Methods: 27 eyes of 21 patients with DME were analyzed in this prospective, cross-sectional study; on all, standard ophthalmological examination, SS-OCTA and FA imaging were performed. Early-phase FA and SS-OCTA images were analyzed for capillary dropout and foveal avascular zone (FAZ) was measured on both modalities. Artifacts in SS-OCTA imaging caused by DME were marked and analyzed., Results: The mean age of the patients was 62.6 ± 11.5 years. On FA the mean size of the annotated non-perfusion areas was 0.14 ± 0.31 mm2 whereas the mean size in SS-OCTA was 0.04 ± 0.13 mm2; areas marked on FA were statistically significantly larger than on SS-OCTA (p<0.01). Mean size of FAZs was similar between FA and OCTA images. (p = 0.91). Seven eyes (25.9 percent) showed imaging artifacts due to DME in SS-OCTA., Conclusion: SS-OCTA is a valid tool to analyze capillary perfusion status of patients with DME, although areas of non-perfusion were measured smaller than in conventional FA. More non-perfusion areas were found on SS-OCTA images. FAZ measurements were similar using the two modalities. However, SS-OCTA is prone to artifacts and therefore requires reviewing of imaging results: up to 25 percent of the analyzed eyes showed artifacts on OCTA, which occurred in the areas of diabetic macular edema and did not correspond to capillary drop out., Competing Interests: “Lukas Fischer is an employee at the company Software Competence Center Hagenberg GmbH. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The other authors declare that there is no conflict of interest regarding the publication of this paper.

The purpose of the study was to evaluate the retinal blood flow in patients with acute central serous chorioretinopathy (CSC) over an observational period of 1 month using swept-source optical coherence tomography (SS-OCTA), focusing especially on changes in the area of subretinal fluid (A-SRF). We correlated these findings with conventional indocyanine green angiography (ICGA). ICGA and SS-OCTA images were collected and analyzed of 12 eyes of 12 patients. The A-SRF was annotated and a qualitative analysis of choriocapillaris, the vessel density (VD) and perfusion density (PD) of the retinal superficial capillary plexus (SCP) and the deep capillary plexus (DCP) was performed in A-SRF and the unaffected remaining area (RA). The VD and PD in the DCP were statistically significantly lower in A-SRF than in the RA at baseline. (VD: p = 0.014; PD: p = 0.036). After 1 month, there was a statistically significant difference in the VD and PD of the DCP (VD: p = 0.015; PD: p = 0.014), and for the PD of the SCP between the A-SRF and the RA (p = 0.015), with lower values in the A-SRF. We found low perfused areas in choriocapillaris corresponding to hypofluorescent areas on ICGA. In conclusion there is a difference in VD and VD of the DCP in the area of SRF in acute CSC. These alterations may lead to a chronic change in the microvasculature and potentially to morphological changes.

Buruli ulcer (BU) is an emerging ulcerative skin disease caused by infection with Mycobacterium ulcerans. Efforts to control its spread have been hampered by our limited understanding of M. ulcerans reservoirs and transmission, and the factors leading to the emergence of BU disease in a particular region. In this report we investigate an anecdotal link between damming the Mapé River in Cameroon and the emergence of BU in the Health Districts bordering Lake Bankim, the impoundment created by the Mapé dam. We used bacterial population genomics and molecular dating to find compelling support for a 2000 M. ulcerans introduction event that followed about 10 years after the filling of the newly created impoundment in 1988. We compared the genomic reconstructions with high-resolution satellite imagery to investigate what major environmental alterations might have driven the emergence of the new focus., Competing Interests: The authors have declared that no competing interests exist.

Aim of the Study: The purpose of the present study was to determine if swept-source optical coherence tomography angiography (OCTA) of the superficial plexus in the macular region can detect differences between high-tension open-angle glaucoma (HTG) and normal-tension glaucoma (NTG)., Materials and Methods: In this prospective study 60 eyes from 60 patients (40 HTG; 20 NTG) underwent fovea centred 3 × 3 mm cube macula OCTA imaging by a swept-source OCTA device (Plex Elite, Zeiss, Jena, Germany). Quantitative analysis of the vasculature at the superficial plexus was performed by assessing the Perfusion Density (PD), defined as the total area of perfused vasculature per unit area in a region of measurement, for each group, respectively. Besides, macular ganglion cell layer thickness and mean deviation from visual field testing was assessed and correlated with PD., Results: Average superficial PD of the measured 3 × 3 mm field was comparable between HTG and NTG ( P = .567). In both groups a significant relation of PD and age (HTG: r = -0.48, p = .002; NTG: r = -0.615; p = .004) was shown, indicating reduced PD with increasing age. For both groups a positive correlation between PD and mean deviation (MD) (HTG: r = 0.492, p = .003; NTG: r = 0.530, p = .029) as well as PD and GCL thickness was shown (r = 0.486, p = .002 vs. r = 0.389; p = .09). However, the latter did not reach statistical significance in the NTG group., Conclusion: PD at the central 3 mm around the fovea is comparable between HTG and NTG. Significant correlation with age and MD was shown in both groups.

Dysregulation of miRNAs is connected with a multitude of diseases for which antagomirs and miRNA replacement are discussed as therapeutic options. Here, we suggest an alternative concept based on the redirection of RISCs to non-native target sites. Metabolically stable DNA-LNA mixmers are used to mediate the binding of RISCs to mRNAs without any direct base complementarity to the presented guide RNA strand. Physical redirection of a dye-labeled miRNA model and of specific miRNA-programmed RISC fractions present in HeLa extracts is demonstrated by pull-down experiments with biotinylated capture oligonucleotides., (© 2020 The Authors. Published by Wiley-VHCA AG, Zurich, Switzerland.)

Purpose: To determine the effect of intravitreal ranibizumab and a dexamethasone implant on aqueous humour cytokine, protein and enzyme levels and to correlate findings to morphologic and functional changes., Methods: In a prospective, randomized, controlled, double-blind study, patients with clinically significant diabetic macular oedema (CSME) were randomly allocated to receive either monthly intravitreal injections of ranibizumab (Lucentis, Novartis Pharma) or a single dexamethasone implant (Ozurdex, Pharm-Allergan) at baseline (BL). Aqueous humour samples were collected at BL and weeks 2, 8 and 20., Results: The study included 18 eyes of 18 patients. In the dexamethasone implant group, soluble intercellular adhesion molecule 1 (sICAM-1) (weeks 2 and 8), CXCL9/monokine induced by gamma interferon (MIG) (weeks 2 and 8), soluble vascular cell adhesion protein 1 (sVCAM-1) (weeks 2 and 8) and monocyte chemo-attractant protein 1 (MCP-1) (week 2) levels were significantly decreased compared with baseline. In the ranibizumab group, placental growth factor (PIGF) (week 2) and vascular endothelial growth factor (VEGF) (week 2 and 8) levels were significantly decreased compared with baseline. No significant changes in central retinal thickness (CRT) or Early Treatment Diabetic Retinopathy Study (ETDRS) best corrected visual acuity (BCVA) were observed in the Ozurdex group at any time-points. ETDRS scores significantly increased at week 20 (84.88 ± 8.88 letters) compared with baseline (74.78 ± 14.85 letters), and the CRT decreased significantly at week 4 (381.00 ± 114.64 μm) compared with baseline (440 ± 144 μm) in the Lucentis group., Conclusion: The dexamethasone implant affected the aqueous cytokines and proteins MCP-1, sICAM-1, sVCAM-1 and MIG, whereas ranibizumab treatments reduced VEGF and PIGF levels. Morphological changes may diverge from cytokine changes. Results may indicate a rationale for a combination therapy for CSME using both agents, the dexamethasone implant and repeatedly administered ranibizumab injections., (© 2019 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: We sought to describe and evaluate patients with clinically significant diabetic macular oedema (CSME) according to the improved SAVE II protocol and correlate findings with visual acuity and systemic parameters in the outpatient clinic for DR (diabetic retinopathy) management., Methods: This was a cross-sectional case series study of patients with CSME, regardless of prior treatment. Visual acuity testing was performed according to the Early Treatment of Diabetic Retinopathy Study (ETDRS) protocol. Optical coherence tomography (OCT) and fluorescence angiography (FA) were performed. All imaging data were evaluated according to an improved version of the SAVE grading protocol for CSME (SAVE II). The main outcome measures were SAVE II oedema types and best-corrected visual acuity. Additional parameters of a blood sample (fasting glucose, haemoglobin A1c, serum creatinine, triglycerides, cholesterol, low-density lipoproteins, and high-density lipoproteins) were taken., Results: In total, 66 eyes of 66 patients were included. The mean age of the patients was 64.9 ± 8.2 years. Two eyes were classified as SAVE oedema type 1, 19 eyes as SAVE oedema type 2, 28 eyes as SAVE oedema type 3, and 28 eyes as SAVE oedema type 4, respectively. Central retinal thickness and laboratory parameters were not significantly different between the groups. There was a statistically significant difference in ETDRS visual acuity between the SAVE groups 2 and 4 (p < 0.001) with lower vision in group 4. There was no statistically significant difference between oedema types 2 and 3 (p = 0.065) and oedema types 3 and 4 (p = 0.13)., Conclusion: There was a significant correlation between the four defined oedema types and visual acuity. Morphologic findings did not correlate with any of the evaluated blood parameters., (© 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht.

Aims: To investigate changes in ocular perfusion following three consecutive intravitreal injections with aflibercept for treatment of neovascular age-related macular degeneration (nAMD)., Methods: The study included 20 eyes from 20 Caucasian patients with unilateral nAMD and 20 fellow eyes. All nAMD eyes were treated with standard intravitreal injection of aflibercept (IVA; 2 mg). Measurements of ocular perfusion at the optic nerve head (ONH) and the choroid were performed with laser speckle flowgraphy (LSFG). Measurements were conducted at baseline, 1 week after the first injection, at the time point of the second and third injection as well as 1 month after the third injection., Results: In treated eyes, mean blur rate (the main output parameter of LSFG) in the ONH microvasculature and in the choroid was significantly reduced 1 week after the first IVA treatment. The effect persisted throughout the entire follow-up period (p<0.001). No change in ocular perfusion was observed in fellow eyes., Conclusions: IVA for treatment of nAMD leads to a reduction in perfusion of the ONH and the choroid in the treated eye with no apparent effect on the fellow eye., Competing Interests: Competing interests: The Department of Ophthalmology, Kepler University Clinic, Johannes Kepler University has received a research grant from Nidek. ASME has received lecture fees from Nidek., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Purpose: To study the intraocular pressure (IOP) variation during vacuum and docking of femtosecond laser application., Setting: Department for Ophthalmology, Kepler University Hospital, Johannes Kepler University Linz, Austria., Design: Experimental study., Methods: Intracameral intraocular pressure (IOP) was monitored in 30 porcine ex vivo models using a dual femtosecond laser platform (VICTUS). Five different baseline IOP levels (10 to 30 mm Hg) were assessed during fluid-filled (liquid) docking, full-contact (applanating) docking, and vacuum application without docking., Results: Raising the baseline intracameral IOP from 10 to 30 mm Hg increased the IOP from 27.55 mm Hg ± 5.93 (SD) to 56.85 ± 6.10 mm Hg in the fluid-filled docking group, and from 60.91 ± 8.41 mm Hg to 90.11 ± 6.64 mm Hg in the full-contact docking group. The full-contact docking procedure per se (excluding vacuum effect) increased the IOP by 61.7% (+36.58 ± 5.84 mm Hg). In contrast, fluid-filled docking (excluding vacuum effect) raised the IOP by only 3.1% (+0.72 ± 2.71 mm Hg). Each 5 mm Hg reduction of baseline IOP resulted in a mean IOP reduction of 7.33 ± 3.05 mm Hg in the fluid-filled group, and 7.30 ± 6.88 mm Hg in the full-contact docking group (P < .001). Decreasing baseline intracameral IOP from 15 to 10 mm Hg resulted in the highest IOP reduction between all subgroups (P < .01)., Conclusions: Baseline IOP, docking procedures, and vacuum influenced IOP during femtosecond laser application in a synergistic manner. Lowering the baseline intracameral IOP resulted in a significantly lower IOP during fluid-filled docking for cataract surgery and full-contact docking for refractive surgery. Full-contact (applanating) docking resulted in a significantly higher IOP elevation compared with similar IOP values found during fluid-filled (liquid) docking and the application of the suction ring alone without docking., (Copyright © 2019 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the effect of preoperative intraocular pressure (IOP) and the vacuum level on IOP during femtosecond laser-assisted cataract surgery., Methods: Intraocular pressure was measured in 40 enucleated porcine eyes by intracameral manometry prior, during and after vacuum application using the VICTUS femtosecond laser platform (Bausch&Lomb, Technolas Perfect Vision GmbH, Germany). Twenty combinations of different preoperative IOP levels (12, 16, 20 and 24 mmHg) and different vacuum levels (350-550 mbar) were investigated., Results: Multivariate regression analysis indicated that both the vacuum level (beta = 0.138; p < 0.001) but much stronger the preoperative IOP (beta = 0.861; p < 0.001) were predictive factors for IOP rise during vacuum application. Mean IOP was 28.23 ± 3.86, 34.23 ± 3.92, 40.35 ± 4.41 and 46.82 ± 4.11 mmHg in groups with baseline IOP of 12, 16, 20 and 24 mmHg, respectively. In the 350, 450 and 550 mbar group, and mean IOP was 35.85 ± 7.85, 37.33 ± 7.90 and 39.00 ± 8.04 mmHg, respectively. Lowering the preoperative IOP by 2 mmHg and reducing the vacuum from maximum to minimum resulted in a similar reduction in IOP during vacuum application (-3.10 ± 0.79 mmHg versus -3.15 ± 0.88 mmHg; p = 0.015). Furthermore, decreasing the baseline IOP from 20 to 12 mmHg resulted in a 30.0% reduction in intraoperative IOP., Conclusion: Preoperative IOP was a stronger predictive factor for intraoperative IOP rise than the applied vacuum level. Measurements and critical interpretation of preoperative IOP in a preliminary examination could help estimating the individual risk of significant IOP rise during femtosecond laser-assisted cataract surgery and could help taking early countermeasures in selected cases. Due to the porcine ex vivo model, further studies are needed to verify these findings., (© 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht.

Purpose: Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) is the standard treatment for neovascular age-related macular degeneration (AMD). As VEGF is a physiological key player for regulating retinal vascular tone, questions have been raised whether the application of anti-VEGF could induce alterations in ocular perfusion., Methods: The study included 20 eyes from 20 Caucasian patients with unilateral neovascular AMD and 20 fellow eyes. All eyes were treated with standard intravitreal injection of aflibercept (IVA). Measurements of blood flow at the optic nerve head (ONH) and the choroid were performed with laser speckle flowgraphy (LSFG). The intraocular pressure (IOP), systolic and diastolic blood pressure, heart rate, mean arterial pressure (MAP) and ocular perfusion pressure (OPP) were analysed. Measurements were performed at baseline and repeated immediately after the injection and 30 and 45 min later., Results: Mean time between injection of aflibercept and first follow-up was 8:56 ± 4:25 min. The injection led to significant rise in IOP. In the injected eyes, mean blur rate (MBR, i.e. a relative measure of perfusion and the main outcome parameter of LSFG) within the major vessels of the ONH as well as at the entire ONH region decreased significantly (p < 0.001). No change in MBR was observed in the fellow eye. Choroidal blood flow was maintained stable in both eyes., Conclusion: Intravitreal injection of aflibercept (IVA) led to a short-term reduction in perfusion only in the treated eye. This was independent from IOP, indicating a direct pharmacological effect. No changes in choroidal perfusion were observed during the first 45 min after the injection., (© 2019 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

A 46-year-old patient presented with a flip-folded partially dislocated flap after trauma caused by a sheet of paper, four years after a reportedly uneventful laser in situ keratomileusis procedure using microkeratome. Flap re-lift, mechanical debridement, and flap stretching were performed in a first interventional approach. Due to epithelial ingrowth two month after the first intervention, a flap re-lift and mechanical removal of epithelial cells from the stroma bed and flap were performed. In addition, triamcinolone was applied subconjunctivally. Thereafter, best corrected visual acuity of 20/20 was regained and no more epithelial ingrowth was observed. Only few cases of flap dislocation with epithelial ingrowth have been described in the literature following trauma, though none of a permanently inward folded flap. The use of subconjunctival triamcinolone is a new approach to prevent recurrent epithelial ingrowth., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2019 by S. Karger AG, Basel.)

PRéCIS:: Optic nerve head (ONH) perfusion was not significantly altered in subjects with normal tension glaucoma (NTG) nor in healthy individuals after performing the water drinking test (WDT), because of its limited effect on ocular perfusion pressure (OPP)., Purpose: ONH blood flow can be maintained stable in healthy individuals because of a physiological phenomenon called autoregulation. Impairment of autoregulation has been shown especially under condition of NTG. The purpose of this study was to investigate the ONH blood flow autoregulation in patients with NTG by influencing the OPP with the WDT., Methods: The study included 9 eyes from 9 white patients with a diagnosis of NTG and 9 eyes from age-matched and sex-matched healthy individuals. In the glaucoma group, the antiglaucomatous therapy was paused 3 weeks before the investigations. Measurements of ONH blood flow were performed with laser speckle flowgraphy. After baseline measurements, individuals ingested 800 mL of water in <5 minutes. Measurements were repeated after 15, 30, and 45 minutes., Results: The water ingestion led to a significant rise in intraocular pressure (P<0.001) but also mean arterial pressure (P<0.001) in both groups. This resulted in stable OPP (P=0.051) with no significant difference between the groups (P=0.43). ONH blood flow remained stable over time in both groups (P=0.719). No significant interaction of time and group was shown for all parameters., Conclusions: Our findings show that the WDT does not significantly influence the OPP and therefore has to be considered inferior to other methods used to assess blood flow autoregulation.

Diabetes mellitus can cause diabetic retinopathy, diabetic macular edema, optic neuropathy, cataract or dysfunction of the eye muscles. The incidence of these defects correlates with disease duration and quality of metabolic control. Recommendations of the Austrian Diabetes Association for diagnosis, therapeutic procedures and requirements for adequate follow-up depending on stage of diabetic eye disease are summarized.

Secretion of specific proteins contributes to pathogenesis and immune responses in tuberculosis and other bacterial infections, yet the kinetics of protein secretion and fate of secreted proteins in vivo are poorly understood. We generated new monoclonal antibodies that recognize the Mycobacterium tuberculosis secreted protein Ag85B and used them to establish and characterize a sensitive enzyme-linked immunosorbent assay (ELISA) to quantitate Ag85B in samples generated in vitro and in vivo We found that nutritional or culture conditions had little impact on the secretion of Ag85B and that there is considerable variation in Ag85B secretion by distinct strains in the M. tuberculosis complex: compared with the commonly used H37Rv strain (lineage 4), Mycobacterium africanum (lineage 6) secretes less Ag85B, and two strains from lineage 2 secrete more Ag85B. We also used the ELISA to determine that the rate of secretion of Ag85B is 10- to 100-fold lower than that of proteins secreted by Gram-negative and Gram-positive bacteria, respectively. ELISA quantitation of Ag85B in lung homogenates of M. tuberculosis H37Rv-infected mice revealed that although Ag85B accumulates in the lungs as the bacterial population expands, the amount of Ag85B per bacterium decreases nearly 10,000-fold at later stages of infection, coincident with the development of T cell responses and arrest of bacterial population growth. These results indicate that bacterial protein secretion in vivo is dynamic and regulated, and quantitation of secreted bacterial proteins can contribute to the understanding of pathogenesis and immunity in tuberculosis and other infections. IMPORTANCE Bacterial protein secretion contributes to host-pathogen interactions, yet the process and consequences of bacterial protein secretion during infection are poorly understood. We developed a sensitive ELISA to quantitate a protein (termed Ag85B) secreted by M. tuberculosis and used it to find that Ag85B secretion occurs with slower kinetics than for proteins secreted by Gram-positive and Gram-negative bacteria and that accumulation of Ag85B in the lungs is markedly regulated as a function of the bacterial population density. Our results demonstrate that quantitation of bacterial proteins during infection can reveal novel insights into host-pathogen interactions., (Copyright © 2019 Ernst et al.)

Background/aims: There is considerable interest in novel techniques to quantify choroidal blood flow (CBF) in humans. In the present study, we investigated a novel technique to measure CBF based on laser speckle flowgraphy (LSFG) in healthy subjects., Methods: This study included 31 eyes of 31 healthy, non-smoking subjects aged between 19 and 74 years. A commercial LSFG instrument was used to measure choroidal vessel diameter (CVD) and relative flow volume (RFV) in choroidal vessels that were identified on fundus photos, an approach that was used previously only for retinal vessels. The reproducibility and the effect of isometric exercise on these parameters were investigated. The latter was compared with measurement of subfoveal CBF using laser Doppler flowmetry (LDF)., Results: Intraclass correlation coefficients for CVD and RFV were higher than 0.8 indicating excellent reproducibility. During isometric exercise, we observed an increase in ocular perfusion pressure of approximately 60% (P<0.001). The increase in RFV and CBF was lower, but also highly significant versus baseline (at minute 6 of isometric exercise: RFV 10.5%±4.2%, CBF 8.3%±3.6%; P<0.001 each) indicating choroidal autoregulation., Conclusion: LSFG may be a novel approach to study blood flow in choroidal vessels. Data are reproducible and show good agreement with LDF data., Trial Registration Number: NCT02102880, Results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: The coupling between neural activity and blood flow is a physiological key principle of ocular blood flow regulation. The current study was performed to investigate whether Laser speckle flowgraphy (LSFG), a commercially available technique for measuring blood flow, is capable to assess flicker-induced haemodynamic changes in the retinal and optic nerve head (ONH) circulation., Methods: Twenty healthy subjects were included in this cross sectional study. A commercial LSFG instrument was used to measure blood flow at the ONH as well as in retinal vessels before and during stimulation with flickering light. Mean blur rate (MBR), a measure of relative blood flow velocity, was obtained for the ONH and relative flow volume (RFV) a measure of relative blood flow of the respective retinal vessels., Results: Stimulation with flicker light increased ONH MBR by +17.5%±6.6% (p<0.01). In retinal arteries, flicker stimulation led an increase of +23.8±10.0% (p<0.05) in total RFV. For retinal veins, an increase of +23.1%±11.0 (p<0.05) in total RFV was observed during stimulation. A higher response was observed in nasal RFV compared to temporal RFV in retinal arteries (nasal: +28.9%±20.0%; temporal: +20.4%±17.6%, p<0.05) and veins (nasal: +28.3%±19.6%; temporal +17.8%±18.9%, p<0.05)., Conclusion: As shown previously with other techniques, flicker stimulation leads to an increase in retinal and optic nerve head blood flow. Our results indicate that LSFG is an appropriate method for the quantification of retinal and ONH blood flow during visual stimulation and may be used as a non-invasive, easy to use tool to assess neuro-vascular coupling in humans., Competing Interests: The authors have declared that no competing interests exist.

Background: The aim of the study was to investigate the accuracy of ultrasound-derived estimated fetal weight (EFW) and to determine its impact on management and outcome of delivery., Methods: In this single-center cohort analysis, women with a singleton term pregnancy in the beginning stages of labor were included. Women with immediately antepartum EFW (N = 492) were compared to women without ultrasound (N = 515)., Results: EFW was correct (deviation from birth weight ≤ 10%) in 72.2% (355/492) of patients with fetal biometry; 19.7% (97/492) were underestimated, and 8.1% (40/492) were overestimated. Newborns with a lower birth weight were more frequently overestimated, and newborns with higher birth weight were more frequently underestimated. The mean difference between EFW and real birth weight was - 114.5 g (standard deviation ±313 g, 95% confidence interval 87.1-142.0). The rate of non-reassuring fetal heart tracing (9.8% vs. 1.9%, P < 0.001) and of caesarean delivery (9.1% vs. 5.0%, P = 0.013) was higher in women with EFW. Overestimation was associated with an increased risk for delivery by caesarean section (odds ratio 2.80; 95% confidence interval 1.2-6.5, P = 0.017). After adjustment, EFW remained associated with increased non-reassuring fetal heart tracing (odds ratio 4.73; 95% confidence interval 2.3-9.6) and caesarean delivery (odds ratio 1.86; 95% confidence interval 1.1-3.1). The incidence of perineal tears of grade 3/4, shoulder dystocia, postnatal depression and neonatal acidosis did not differ between groups., Conclusions: Antepartum ultrasound-derived EFW does not improve maternal and fetal outcome and is therefore not recommended.

Background: The central control of the autonomic nervous system (ANS) and the complex interplay of its components can be described by a functional integrated mode - the central autonomic network (CAN). CAN represents the integrated functioning and interaction between the central nervous system (CNS) and ANS (parasympathetic and sympathetic activity)., Objective: This study investigates the central cardiovascular network (CCVN) as a part of the CAN, during which heart rate (HR), systolic blood pressure (SYS) and frontal EEG activity in 21 healthy subjects (CON) will be analysed. The objective of this study is to determine how these couplings (central-cardiovascular) are composed by the different regulatory aspects of the CNS-ANS interaction., Methods: To quantify the short-term instantaneous causal couplings within the CCVN, the normalized short time partial directed coherence (NSTPDC) approach was applied. It is based on an m-dimensional MAR process to determine Granger causality in the frequency domain., Results: We found that CCVN were of bidirectional character, and that the causal influences of central activity towards HR were stronger than those towards systolic blood pressure. This suggests that the central-cardiac closed-loop regulation process in CON focuses mainly on adapting the heart rate via the sinoatrial node rather than focusing on SYS. The CNS-ANS coupling directions with respect to central spectral power bands were characterized as mostly bidirectional, where HR and SYS acted as drivers in nearly every frequency band (unidirectional for α, α 1 and α 2 )., Conclusion: This study provides a more indepth understanding of the interplay of neuronal and autonomic cardiovascular regulatory processes in healthy subjects, as well as a greater insight into the complex CAN., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Schattauer GmbH.)

The purpose of this prospective, case control study was to investigate the differences in optic nerve head blood flow measured with Laser Speckle Flowgraphy (LSFG) between Caucasian patients with normal tension glaucoma and healthy subjects. It included 20 eyes from 20 Caucasian patients with diagnosis of normal tension glaucoma and 20 eyes from age- and sex-matched healthy individuals. In the glaucoma group the antiglaucomatous therapy was paused 3 weeks prior to the investigations. Measurement of optic nerve head blood flow was performed with LSFG. The mean blur rate was obtained for different vascular compartments of the optic nerve head. Parameters for the characterization of pulse-waveform of the mean blur rate were calculated. It was shown that the mean blur rate was significantly lower in the glaucoma group compared to the control group (P < 0.001). The significant differences in the pulse-waveform parameters blow out time (P = 0.028) and flow acceleration time index (P < 0.001) indicate a flatter curve in NTG patients. In conclusion, LSFG can detect differences in optic nerve head blood flow between eyes with normal tension glaucoma and healthy eyes.

Background/aims: To identify characteristic retinal pigment epithelium (RPE) changes in fellow eyes of patients with neovascular age-related macular degeneration (nAMD) using polarisation-sensitive optical coherence tomography (PS-OCT)., Methods: Thirty-one fellow eyes of 31 patients with unilateral nAMD were evaluated in this cohort study of a prospective interventional trial. PS-OCT as well as conventional imaging including spectral-domain (SD)-OCT and fluorescein angiography (FA) were performed using a standardised protocol. Monitoring visits were performed continuously at 1-month intervals. Morphological RPE features associated with the development of choroidal neovascularisation (CNV) were systematically analysed., Results: Mean follow-up was 29 months (±17, SD). Thirteen (42%) of 31 eyes developed de novo CNV: 9 eyes type I CNV, 2 eyes type II CNV, 2 eyes a retinal angiomatous proliferation lesion. RPE thickening and reticular pseudodrusen (RPD) were observed significantly more often in eyes that developed CNV than in eyes without CNV development (p<0.01). Monthly increase in drusen volume was higher in the CNV group with a median increase of +2.2% in area and +2.9% in volume compared with +0.8% and +0.6% in the non-progressing group. RPE migration within the neurosensory retina and at the level of the RPE resulting in RPE thickening was seen topographically and chronologically associated with CNV development., Conclusions: Conversion to CNV is associated with RPE-related changes such as RPE migration, RPE thickening, drusen volume or the presence of RPD. Early detection of these features may allow more efficient screening in risk eyes and timely vision-preserving treatment in eyes developing neovascular disease., Competing Interests: Competing interests: US-E receives consultancy, lecture fees and travel support from Alcon Laboratories (Fort Worth, Texas), Bayer Healthcare (Vienna, Austria), Novartis (Basel, Switzerland), Allergan (Irvine, California) and Boehringer (Ingelheim, Germany). PKR, CKH, MP and BB have received support from Canon (Tokyo, Japan)., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Two recent studies (Cambier et al., 2017; Madigan et al., 2017) reveal in vivo functions for specific phenolic glycolipids (PGLs) in the mycobacteria that cause tuberculosis or leprosy. M. tuberculosis (and M. marinum) PGL promotes bacterial spread to growth-permissive macrophages, while M. leprae PGL-1 induces macrophages to cause nerve demyelination characteristic of human leprosy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The treatment of pregnant women who have illnesses unrelated to pregnancy can cause uncertainty among physicians., Methods: We searched the PubMed database and specialty guidelines from Germany and abroad (the guidelines of the German Society for Gynecology and Obstetrics, the American Congress of Obstetri cians and Gynecologists, and the Royal College of Obstetricians and Gynaecologists) over the period 2007-2016 for information on standards for the diagnosis and treatment of five illnesses that can arise in pregnancy: bronchial asthma, migraine, hypothyroidism, hyperthyroidism, and varicose veins., Results: Any diagnostic tests that are carried out in pregnant women should be simple and goal-directed. The choice of drugs that can be used is limited. For many drugs, no embryotoxic or teratogenic effect is suspected, but the level of evidence is low., Conclusion: When illnesses unrelated to pregnancy arise in pregnant women, attention must be paid to potential diver gences from the typical disease course and to pos sible drug side effects on the fetus in order to prevent serious complications for both mother and child.

The aim of the present study was to investigate regulation of blood flow (BF) in the optic nerve head (ONH) and a peripapillary region (PPR) during an isometric exercise-induced increase in ocular perfusion pressure (OPP) using laser speckle flowgraphy (LSFG) in healthy subjects. For this purpose, a total of 27 subjects was included in this study. Mean blur rate in tissue (MT) was measured in the ONH and in a PPR as well as relative flow volume (RFV) in retinal arteries (ART) and veins (VEIN) using LSFG. All participants performed isometric exercise for 6 minutes during which MT and mean arterial pressure were measured every minute. From these data OPP and pressure/flow curves were calculated. Isometric exercise increased OPP, MTONH and MTPRR. The relative increase in OPP (78.5 ± 19.8%) was more pronounced than the increase in BF parameters (MTONH: 18.1 ± 7.7%, MTPRR: 21.1 ± 8.3%, RFVART: 16.5 ±12.0%, RFVVEIN: 17.7 ± 12.4%) indicating for an autoregulatory response of the vasculature. The pressure/flow curves show that MTONH, MTPRR, RFVART, RFVVEIN started to increase at OPP levels of 51.2 ± 2.0%, 58.1 ± 2.4%, 45.6 ± 1.9% and 45.6 ± 1.9% above baseline. These data indicate that ONHBF starts to increase at levels of approx. 50% increase in OPP: This is slightly lower than the values we previously reported from LDF data. Signals from the PPR may have input from both, the retina and the choroid, but the relative contribution is unknown. In addition, retinal BF appears to increase at slightly lower OPP values of approximately 45%. LSFG may be used to study ONH autoregulation in diseases such as glaucoma., Trial Registration: ClinicalTrials.gov NCT02102880.

Synchronization is a central key feature of neural information processing and communication between different brain areas. Disturbance of oscillatory brain rhythms and decreased synchronization have been associated with different disorders including schizophrenia. The aim of this study was to investigate whether synchronization (in relaxed conditions with no stimuli) between different brain areas within the delta, theta, alpha (alpha1, alpha2), beta (beta1, beta2), and gamma bands is altered in patients with a neurological disorder in order to generate significant cortical enhancements. To achieve this, we investigated schizophrenic patients (SZO; N=17, 37.5±10.4 years, 15 males) and compared them to healthy subjects (CON; N=21, 36.7±13.4 years, 15 males) applying the phase locking value (PLV). We found significant differences between SZO and CON in different brain areas of the theta, alpha1, beta2 and gamma bands. These areas are related to the central and parietal lobes for the theta band, the parietal lobe for the alpha1, the parietal and frontal for the beta2 and the frontal-central for the gamma band. The gamma band revealed the most significant differences between CON and SZO. PLV were 61.7% higher on average in SZO in most of the clusters when compared to CON. The related brain areas are directly related to cognition skills which are proved to be impaired in SZO. The results of this study suggest that synchronization in SZO is also altered when the patients were not asked to perform a task that requires their cognitive skills (i.e., no stimuli are applied - in contrast to other findings).

Introduction: In Germany the rate of deliveries by cesarean section is continually increasing. Many different reasons have been put forward to explain this trend. The aim of this study was to examine how the C-section rate developed at the University Gynecology Clinic Rostock, one of the biggest maternity hospitals and level I perinatal centers in Germany, based on various maternal and neonatal parameters. The aim was also to identify potential risk factors for C-sections., Material and Method: Various obstetric parameters were obtained from the birth cohort (2008 to 2014; n = 20 091) of the University Gynecology Clinic Rostock. The data was used to calculate parameter-specific C-section rates. Potential risk factors for C-section were identified by regression analysis., Results: The C-section rate dropped from 26.24% to 23.57%. The rate of repeat C-sections also declined. The mean age of the pregnant women increased. Nevertheless, the frequency of cesarean sections in pregnant women aged more than 35 years declined. Rates of being overweight or obese preconception increased. C-section rates increased as BMI values preconception increased. There was a perceptible trend towards attempting the vaginal delivery of children in breech presentation and of twins. The frequency of depressed neonates after vaginal delivery and after C-section decreased. Rates for mild and advanced acidosis increased after both C-sections and vaginal deliveries. Previous C-section, older maternal age, overweight and obesity prior to conception, breech presentation and multiple pregnancies all increased the risk of cesarean sections., Conclusion: This study showed that reducing the rates of C-sections without a deterioration in neonatal outcomes can be achieved even in a large maternity hospital that cares for many high-risk pregnancies.

Purpose: To prospectively characterize the stromal thickness changes during the first year after myopic small-incision lenticule extraction using spectral-domain optical coherence tomography (SD-OCT)., Setting: Department of Ophthalmology, Kepler University Hospital, Linz, Austria., Design: Prospective case series., Methods: This study evaluated eyes that had small-incision lenticule extraction to treat myopia or myopic astigmatism. A high-resolution SD-OCT system (RS 3000 Advance) in conjunction with a custom image-segmentation algorithm was applied to directly measure stromal thickness within the central 5.0 mm corneal zone. Measurements were obtained preoperatively and postoperatively at 1 day, 1 week, 6 weeks, 3 months, 6 months, and 1 year., Results: The study enrolled 42 eyes of 21 patients. The mean surgical refractive correction was -4.94 diopters ± 1.75 (SD). Postoperatively, the stromal thickness showed a significant decrease during the first 6 weeks, which amounted to a mean of 10.4 ± 6.3 μm at the apex (P < .001). Subsequently, the central stroma thickened by a mean of 8.8 ± 5.9 μm up until the 1-year follow-up (P < .001). One year postoperatively, the mean observed central stromal thickness reduction was 18.7 ± 5.7 μm smaller than the planned lenticule thickness. This difference was smallest 6 weeks postoperatively (mean 9.8 ± 7.8 μm)., Conclusions: Significant anatomic changes in the corneal stroma were detected during the first year after small-incision lenticule extraction. The achieved lenticule thickness was systematically lower than planned, and the mismatch was more pronounced with higher lenticule thickness. Refractive outcomes did not appear to be influenced by lenticule thickness accuracy., (Copyright © 2017 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare the safety and efficacy between femtosecond laser-assisted cataract surgery using the Victus laser system and conventional cataract surgery., Setting: Department of Ophthalmology, Kepler University Hospital, Linz, Austria., Design: Prospective randomized case series., Methods: Both eyes of patients with age-related cataract were randomized to conventional cataract surgery or femtosecond laser-assisted cataract surgery, both with intraocular lens (IOL) implantation. Postoperative follow-up was at 1 day, 1 week, 1 month, 3 months, and 6 months and comprised corrected distance visual acuity, endothelial cell density (ECD), central corneal thickness (CCT), and central retinal thickness. The main outcomes were intraoperative and postoperative complications and the effective phacoemulsification time (EPT). Intraocular lens and capsulotomy centration were evaluated using retroillumination slitlamp photography., Results: The study enrolled 50 patients. No intraoperative complications occurred in either group. The ECD, CCT, and central retinal thickness were similar between the groups at all follow-up examinations (P > .05). The EPT was not statistically significantly different between the groups (P = .22). The IOL centration was similar between the groups (P = .93)., Conclusion: Femtosecond laser-assisted and conventional cataract surgery using the mentioned system were equally safe and effective., (Copyright © 2017 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the feasibility and reliability of Laser Speckle Flowgraphy (LSFG) to measure ocular perfusion in a sample of healthy white subjects and to elucidate the age-dependence of the parameters obtained., Methods: This cross-sectional study included 80 eyes of 80 healthy, non-smoking white subjects of Western European descent between 19 and 79 years of age. A commercial LSFG instrument was applied to measure ocular blood flow at the optic nerve head (ONH) three successive times before and after pharmacological pupil dilation. The mean blur rate (MBR), a measure of relative blood flow velocity, was obtained for different regions of the ONH. Eight parameters of ocular perfusion derived from the pulse-waveform analysis of MBR including blowout time (BOT) and falling rate (FR) were also recorded., Results: Artifact-free LSFG images meeting the quality criteria for automated image analysis were obtainable in 93.8% without pupil dilation and in 98.8% with pharmacological pupil dilation. Measurements of MBR showed excellent repeatability with intraclass correlation coefficients ≥ 0.937 and were barely affected by pupil dilation. The majority of pulse-waveform derived variables exhibited equally high repeatability. MBR-related blood flow indices exhibited significant age dependence (p<0.001). FR (r = 0.747, p<0.001) and BOT (r = -0.714, p<0.001) most strongly correlated with age., Conclusions: LSFG represents a reliable method for the quantitative assessment of ocular blood flow in white subjects. Our data affirms that the LSFG-derived variables FR and BOT may be useful biomarkers for age-related changes in ocular perfusion., Competing Interests: Leopold Schmetterer and Nikolaus Luft have received honoraria from NIDEK Co. Ltd. for speaking at a scientific meeting at a symposium. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Aims: Manifestation of preeclampsia is characterized by an inflammatory response and altered expression of acute-phase proteins. In this study, we examined the predictive value of serum amyloid A, progranulin, transthyretin, C-reactive protein and interleukin-6. Soluble endoglin was used as control., Methods: Maternal serum levels of the putative biomarkers were measured in 49 women with a midtrimester bilateral abnormal uterine artery Doppler velocimetry., Results: Preeclampsia developed in 26.5 %. 75.0 % had an early-onset disease (<34 + 0 weeks). Delivery <34 + 0 weeks was indicated in 16.3 %. 12.2 % of patients developed a normotensive intrauterine growth restriction. All of the putative biomarkers were not predictive for preeclampsia. But serum levels of progranulin and also of soluble endoglin were increased in cases with development of a severe normotensive intrauterine growth restriction. Only soluble endoglin was predictive for the development of preeclampsia with an area under curve in the receiver operating curve analysis of 0.761 (P = 0.006). Using a cut-off level of ≥9.14 ng/mL, sensitivity, specificity, positive predictive value and negative predictive value were 53.9, 88.9, 63.6 and 84.2 %, respectively., Conclusions: Inflammation is a late event during development of preeclampsia, and acute-phase proteins are not predictive for the disease in a high-risk population without clinical symptoms during the second trimester. Progranulin is a putative new biomarker for an early detection of intrauterine growth restriction in women without concomitant hypertensive disorders. Soluble endoglin improved predictive values for preeclampsia in patients with abnormal uterine Doppler.

Purpose: This study evaluated the validity of retinal perfusion measurements using laser speckle flowgraphy (LSFG) by means of in vitro experiments and direct comparison with dual-beam Doppler optical coherence tomography (D-OCT) in a healthy Caucasian population., Methods: The flow velocity of scattering solution pumped through a glass capillary was measured at 17 different flow velocities (range, 0.5-47 mm/s) using LSFG. The flow within the glass capillary was produced by a computer-controlled infusion pump. In vivo, three consecutive LSFG scans were obtained in 20 eyes of 20 healthy Caucasian subjects before and after pharmacological pupil dilation. Relative flow volume (RFV), the primary output parameter of LSFG, was comparatively validated relative to absolute measurements of retinal blood flow and velocity as obtained from D-OCT., Results: In the in vitro experiments, RFV was found to saturate at a level of approximately 700 arbitrary units (au) or 23.5 mm/s of actual velocity. In vivo, RFV was in significant agreement with absolute blood flow measurements as obtained from D-OCT in arteries (r = 0.69, P = 0.001) and veins (r = 0.74, P < 0.001). However, linear regression analysis revealed significant positive zero offset values for RFV of 223.4 and 282.7 au in arteries and veins, respectively., Conclusions: Measurements of RFV were successfully obtainable, reproducible, and not influenced by pharmacological pupil dilation. Nevertheless, our data revealed flaws in the LSFG method of measuring retinal perfusion in Caucasians. Adjustment to the technique is required to address apparent issues with RFV, especially saturation effects with higher arterial flow rates. The present dataset may provide a valuable tool to do so. (Clinicaltrials.gov number NCT02582411).

Background: To evaluate a recently established grading protocol for diabetic macular edema (DME) over the course of intravitreal anti-VEGF treatment with ranibizumab., Methods: Fluorescein angiography images and optical coherence tomography scans before treatment and after 3 monthly applied intravitreal ranibizumab injections were retrospectively graded for each included study eye according to the recently introduced "SAVE" grading protocol ("S"= subretinal fluid; "A"= "area of retinal thickening"; "V"="vitreo-retinal abnormalities"; "E"="etiology of leakage focal versus non-focal") and correlated with best-corrected visual acuity (BCVA) in letters (lett)., Results: Five of the 39 included study eyes had subretinal fluid ("S") before treatment which resolved during treatment. BCVA of study eyes with an initial retinal thickening smaller than one disc diameter ("A") was non-significantly higher compared to patients with a retinal thickening greater than one disc diameter (34.0 ± 17.9 lett versus 25.3 ± 13.3 lett, p=0.236) but became significant during treatment (40.5 ± 10.0 lett versus 28.3 ± 13.1 lett, p=0.004). No difference in BCVA was observed between patients with or without vitreo-retinal abnormalities ("V") before and during therapy. BCVA in patients with focal leakage ("E") was significantly higher than in patients with non-focal leakage before (33.1 ± 12.3 lett versus 23.3 ± 13.3 lett, p=0.017) and during (38.9 ± 10.9 lett versus 26.3 ± 12.6 lett, p=0.002) therapy., Conclusions: Applying the grading protocol "SAVE", focal leakage ("E") was the only retrospectively observed parameter which significantly correlated with a better BCVA before therapy and over the course of treatment in patients with fovea-involving DME.

Purpose: To test the reliability of a novel algorithm for measuring corneal epithelial thickness (ET) and stromal thickness of normal eyes and post-small incision lenticule extraction (SMILE) corneas with spectral-domain optical coherence tomography., Methods: In this prospective observational study, a customized semiautomated software algorithm was developed and applied to measure corneal ET and stromal thickness along the horizontal corneal meridian. Measurements were performed by 2 examiners in a randomized fashion on a sample of 40 eyes with previous SMILE for treatment of myopia and a control group composed of 40 normal eyes. The intrauser repeatability and interuser reproducibility were analyzed by calculating typical indices including the coefficient of variation and intraclass correlation coefficient. Corneal sublayer thickness profiles were compared between normal and post-SMILE eyes., Results: In both groups, coefficients of variation were 3.2% or lower and intraclass correlation coefficients were 0.929 or higher indicating excellent reliability of the measurement method. Central ET was on an average 6 μm greater in post-SMILE corneas (58.8 ± 5.4 μm) compared with normal eyes (52.8 ± 4.0 μm), with P < 0.01. Also, there was greater interindividual variability in ET in post-SMILE corneas and their horizontal epithelial profile seemed to show a lenticular appearance., Conclusions: Highly favorable indices of measurement reliability were achieved for this novel method of measuring corneal sublayer pachymetry not only in normal eyes but also in eyes with previous SMILE. The corneal ET profile was significantly altered in post-SMILE eyes compared with normal corneas.

Purpose: To assess the reactive changes of the corneal epithelial thickness (ET) profile induced by small incision lenticule extraction (SMILE) for treatment of myopia., Methods: This prospective observational study included 46 eyes of 23 patients that were scheduled for myopic SMILE. High-resolution spectral-domain optical coherence tomography (SD-OCT) and a custom image segmentation algorithm were applied to measure corneal ET at multiple time points within the central 5-mm zone. Postoperative ET alterations were correlated with treatment parameters and refractive outcomes., Results: Mean age was 33 ± 6 years and mean spherical equivalent of surgical refractive correction was -4.78 ± 1.75 diopters. The average ET (averaged over the central 5-mm zone) increased from 52.3 ± 3.6 μm preoperatively to 57.7 ± 5.1 μm 6 months postoperatively (P < 0.01). Average ET was 101.9% of the preoperative thickness at 24 hours postoperatively, 103.2% at 1 week, 106.7% at 6 weeks, 109.3% at 3 months, and 110.4% at 6 months postoperatively. The epithelial thickening response could be modeled by an exponential recovery function and stabilized after 3 months. The extent of epithelial hyperplasia was highly dependent on the magnitude of the induced refractive correction (P = 0.002)., Conclusions: In this initial study of corneal ET remodeling after myopic SMILE, significant epithelial thickening was detected as a function of the extent of surgical refractive correction. Moreover, the epithelial remodeling response to the corneal refractive change appeared to decrease with higher age. In our hands, the observed epithelial changes did not appear to affect the refractive outcome of SMILE. (ClinicalTrials.gov number, NCT02614625).

Background: Current laboratory diagnosis of Buruli ulcer (BU) is based on microscopic detection of acid fast bacilli, quantitative real-time PCR (qPCR), histopathology or cultivation. Insertion sequence (IS) 2404 qPCR, the most sensitive method, is usually only available at reference laboratories. The only currently available point-of-care test, microscopic detection of acid fast bacilli (AFB), has limited sensitivity and specificity., Methodology/ Principal Findings: Here we analyzed AFB positive tissue samples (n = 83) for the presence, distribution and amount of AFB. AFB were nearly exclusively present in the subcutis with large extracellular clusters being most frequently (67%) found in plaque lesions. In ulcerative lesions small clusters and dispersed AFB were more common. Beside this, 151 swab samples from 37 BU patients were analyzed by IS2404 qPCR and ZN staining in parallel. The amount of M. ulcerans DNA in extracts from swabs correlated well with the probability of finding AFB in direct smear microscopy, with 56.1% of the samples being positive in both methods and 43.9% being positive only in qPCR. By analyzing three swabs per patient instead of one, the probability to have at least one positive swab increased from 80.2% to 97.1% for qPCR and from 45% to 66.1% for AFB smear examination., Conclusion / Significance: Our data show that M. ulcerans bacteria are primarily located in the subcutis of BU lesions, making the retrieval of the deep subcutis mandatory for examination of tissue samples for AFB. When laboratory diagnosis is based on the recommended less invasive collection of swab samples, analysis of three swabs from different areas of ulcerative lesions instead of one increases the sensitivity of both qPCR and of smear microscopy substantially.

Purpose: To identify the effects of pan-retinal laser treatment on the integrity of neurosensory retinal layers., Methods: Patients were examined with fluorescence angiography after a standardized examination for diabetic retinopathy and a peripapillary ring scan with spectral domain optical coherence tomography. A single-session pan-retinal photocoagulation was performed using the PASCAL pattern scanning argon laser applying a minimum of 1,500 spots. Optical coherence tomography was evaluated more than 6 months., Results: Eighteen eyes of 12 consecutive patients with new onset, treatment-naive proliferative diabetic retinopathy secondary to diabetes Type 2 were treated and retinal optical coherence tomography morphology evaluated. Retinal nerve fiber layer thickness increased statistically significantly from baseline to week 1, when it reached its peak. The combined thickness of the outer plexiform and the inner nuclear layers and the combined thickness of the inner plexiform and the ganglion cell layers showed no relevant changes. The combined thickness of the retinal pigment epithelium and the photoreceptor cell layers decreased at month 1 followed by a steady increase in thickness, which remained below baseline values over time., Conclusion: Pan-retinal photocoagulation in proliferative diabetic retinopathy leads to a slowly reversible, marked biological response with statistically significant morphometric changes detected by spectral domain optical coherence tomography. Swelling of the retinal nerve fiber and outer nuclear layers induce an increase in peripapillary total retinal thickness. Simultaneously, the photoreceptor and retinal pigment epithelium layers decrease in thickness. These changes indicate diffuse retinal inflammation after pan-retinal laser therapy.

The autonomic nervous system (ANS) dysfunction has been well described in schizophrenia (SZ), a severe mental disorder. Nevertheless, the coupling between the ANS and central brain activity has been not addressed until now in SZ. The interactions between the central nervous system (CNS) and ANS need to be considered as a feedback-feed-forward system that supports flexible and adaptive responses to specific demands. For the first time, to the best of our knowledge, this study investigates central-autonomic couplings (CAC) studying heart rate, blood pressure and electroencephalogram in paranoid schizophrenic patients, comparing them with age-gender-matched healthy subjects (CO). The emphasis is to determine how these couplings are composed by the different regulatory aspects of the CNS-ANS. We found that CAC were bidirectional, and that the causal influence of central activity towards systolic blood pressure was more strongly pronounced than such causal influence towards heart rate in paranoid schizophrenic patients when compared with CO. In paranoid schizophrenic patients, the central activity was a much stronger variable, being more random and having fewer rhythmic oscillatory components. This study provides a more in-depth understanding of the interplay of neuronal and autonomic regulatory processes in SZ and most likely greater insights into the complex relationship between psychotic stages and autonomic activity., (© 2016 The Author(s).)