Epidemic intelligence data of Crimean-Congo haemorrhagic fever, European Region, 2012 to 2022: a new opportunity for risk mapping of neglected diseases.

BackgroundThe Epidemic Intelligence from Open Sources (EIOS) system, jointly developed by the World Health Organisation (WHO), the Joint Research Centre (JRC) of the European Commission and various partners, is a web-based platform that facilitate the monitoring of information on public health threats in near real-time from thousands of online sources.AimsTo assess the capacity of the EIOS system to strengthen data collection for neglected diseases of public health importance, and to evaluate the use of EIOS data for improving the understanding of the geographic extents of diseases and their level of risk.MethodsA Bayesian additive regression trees (BART) model was implemented to map the risk of Crimean-Congo haemorrhagic fever (CCHF) occurrence in 52 countries and territories within the European Region between January 2012 and March 2022 using data on CCHF occurrence retrieved from the EIOS system.ResultsThe model found a positive association between all temperature-related variables and the probability of CCHF occurrence, with an increased risk in warmer and drier areas. The highest risk of CCHF was found in the Mediterranean basin and in areas bordering the Black Sea. There was a general decreasing risk trend from south to north across the entire European Region.ConclusionThe study highlights that the information gathered by public health intelligence can be used to build a disease risk map. Internet-based sources could aid in the assessment of new or changing risks and planning effective actions in target areas.

PERSEUS-IT 24-month analysis: a prospective observational study to assess the effectiveness of intravitreal aflibercept in routine clinical practice in Italy in patients with neovascular age-related macular degeneration.

PURPOSE: PERSEUS-IT (NCT02289924) was a prospective, observational, 2-year study evaluating the effectiveness and treatment patterns of intravitreal aflibercept (IVT-AFL) in patients with neovascular age-related macular degeneration (nAMD) in routine clinical practice in Italy. METHODS: Treatment-naïve patients with nAMD receiving IVT-AFL per routine clinical practice were enrolled. The primary endpoint was mean change in visual acuity (VA; decimals) from baseline to month (M) 12 and M24. Outcomes were evaluated for the overall study population and independently for the 2 treatment cohorts: regular (3 initial monthly doses, ≥ 7 injections by M12, and ≥ 4 injections between M12 and M24) and irregular (any other pattern). RESULTS: Of 813 patients enrolled, 709 were included in the full analysis set (FAS); VA assessments were available for 342 patients at M12 (FAS1Y, 140 regular and 202 irregular) and 233 patients at M24 (FAS2Y, 37 regular and 196 irregular). In the overall FAS, the mean ± SD change in VA from baseline to M12 and M24 was + 0.09 ± 0.24 and + 0.02 ± 0.25 decimals, and there was a statistically significant difference between the regular and irregular cohorts in both FAS1Y (p = 0.0034) and FAS2Y (p = 0.0222). Ocular treatment-emergent adverse events were reported in 4.1% (n = 33/810 [safety set]) of patients. CONCLUSION: In PERSEUS-IT, clinically relevant functional and anatomic improvements were observed within the first 12 months of IVT-AFL treatment in routine clinical practice in Italy in patients with treatment-naïve nAMD. These gains were generally maintained across the 2-year study. The safety profile of IVT-AFL was consistent with prior studies. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT02289924. DATE OF REGISTRATION: November 13, 2014.

Tailoring Superconductivity in Large-Area Single-Layer NbSe2 via Self-Assembled Molecular Adlayers.

Two-dimensional transition metal dichalcogenides (TMDs) represent an ideal testbench for the search of materials by design, because their optoelectronic properties can be manipulated through surface engineering and molecular functionalization. However, the impact of molecules on intrinsic physical properties of TMDs, such as superconductivity, remains largely unexplored. In this work, the critical temperature (TC) of large-area NbSe2 monolayers is manipulated, employing ultrathin molecular adlayers. Spectroscopic evidence indicates that aligned molecular dipoles within the self-assembled layers act as a fixed gate terminal, collectively generating a macroscopic electrostatic field on NbSe2. This results in an ∼55% increase and a 70% decrease in TC depending on the electric field polarity, which is controlled via molecular selection. The reported functionalization, which improves the air stability of NbSe2, is efficient, practical, up-scalable, and suited to functionalize large-area TMDs. Our results indicate the potential of hybrid 2D materials as a novel platform for tunable superconductivity.

Beneficial effect of low-dose radioiodine ablation for Graves' orbitopathy: results of a retrospective study.

OBJECTIVE: Graves' orbitopathy (GO) reflects an autoimmune response against antigens expressed by the thyroid and orbital tissues. Elimination of thyroid antigens may be beneficial for GO. Total thyroid ablation (TTA) [thyroidectomy (Tx), followed by 30 mCi of radioiodine] was shown to exert a beneficial effect on GO following intravenous glucocorticoids (ivGC) compared with Tx alone. Here, we investigated retrospectively whether TTA performed with a 15 mCi of radioiodine still maintains advantages over Tx. METHODS: Thirty-two subjects, 13 treated with TTA (performed with 15 mCi of radioiodine) and 19 with Tx alone, all with moderately severe, active GO, treated with ivGC, were studied. The primary objective was the outcome of GO at 24 weeks based on a composite evaluation. RESULTS: The two groups did not differ at baseline in terms of sex, age, smoking habits, TSH, anti-TSH receptor autoantibodies, GO duration and eye features. The proportion of GO responders at 24 weeks was greater in the TTA (61.5%) than in the Tx group (26.3%, P = 0.046). In contrast, GO outcome at 48 weeks did not differ between the two groups (69.2% vs 52.6% of responder in TTA and Tx group, respectively). The outcome of the individual GO features did not differ between the two groups both a 24 and 48 months. CONCLUSIONS: The advantage of total thyroid ablation seems to be a more rapid response for GO to ivGC treatment. Prospective, randomized studies in a larger number of subjects are needed to confirm our findings.

Secondary epiretinal membrane after Ex-Press glaucoma filtration device implant.

PURPOSE: To estimate the frequency of epiretinal membrane (ERM) in eyes with primary open-angle glaucoma (POAG) treated with Ex-Press shunt implant. Secondarily, we aimed to assess the role of concomitant cataract surgery and the impact of the ERM on central foveal thickness and macular volume. METHODS: In this prospective, consecutive, case-control study, we enrolled 54 patients affected by PAOG and scheduled for Ex-Press device implant with or without contemporary phacoemulsification. Contralateral eyes affected by POAG and receiving anti-glaucomatous eyedrops constituted the control group. Complete ophthalmologic evaluation and spectral-domain optical coherence tomography (OCT) were performed before and 1, 3 and 6 months after surgery. RESULTS: Twenty-six eyes received the Ex-Press implant alone, and 28 eyes underwent the combined procedure. Six months postoperatively, we observed 18 (33%) cases of ERM: 15 (28%) of cellophane macular reflex (CMR) and 3 (6%) of pre-macular fibrosis (PMF). In the control group, 9 (17%) eyes developed an ERM: 8 (15%) were CMR, and 1 (2%) was PMF. The frequency of ERM statistically differs between treated and contralateral eyes (P = 0.032, χ2 test). The ERM frequency did not statically differ between eyes subjected to simple or combined surgery (P = 0.846, χ2 test). Mean central foveal thickness and mean macular volume did not significantly differ between groups. CONCLUSION: The Ex-Press glaucoma shunt may increase the risk of ERM onset regardless of the concomitant cataract surgery; however, most cases were cellophane macular reflex with limited functional and anatomical impact.

Aqueous humour concentrations after topical apPlication of combinEd levofloxacin-dexamethasone eye dRops and of its single components: a randoMised, assEssor-blinded, parallel-group study in patients undergoing cataract surgery: the iPERME study.

PURPOSE: To evaluate the penetration of levofloxacin and dexamethasone sodium phosphate into the aqueous humour (AH) after administration in combination and as single molecules. Evaluation of the penetration of those agents in the site of action and their pharmacodynamic potential activity in view of the intended clinical use after cataract surgery. METHODS: Randomised, assessor-blinded, parallel-group. Patients scheduled for cataract surgery were assigned in a 1:1:1 ratio to: levofloxacin + dexamethasone sodium phosphate (L-DSP), Levofloxacin (L) or Dexamethasone sodium phosphate (DSP) eye drops. Either test or reference drugs were instilled in the cul-de-sac twice, 90 and 60 min before paracentesis. RESULTS: A total of 125 patients completed the study. Fraction of dose absorbed in the anterior chamber was 3.8-4.2 · 10-4 for levofloxacin and 0.3-0.4 · 10-4 for dexamethasone, respectively. No notable differences in concentration of levofloxacin were found between L-DSP arm (1.970 nmol/ml) and L arm (2.151 nmol/ml). The concentrations of levofloxacin were well above the MICs for the most frequent Gram-positive and Gram-negative eye pathogens. Dexamethasone concentrations were slightly lower in L-DSP arm (0.030 nmol/ml) than in DSP arm (0.042 nmol/ml), but still in the pharmacodynamically active range in the site of action. The difference was not clinically relevant. DSP was not detected in any HA sample, suggesting its full hydrolysis to free dexamethasone. CONCLUSION: Our results confirm that no interaction is evident on the corneal penetration of levofloxacin and dexamethasone which reach pharmacologically active concentrations when instilled as fixed combination eye drops to patients undergoing cataract surgery. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03740659.

Pachychoroid neovasculopathy: a type-1 choroidal neovascularization belonging to the pachychoroid spectrum-pathogenesis, imaging and available treatment options.

PURPOSE: The purpose of this paper is to provide a meaningful literature review about the epidemiology, pathogenesis, imaging and treatment of pachychoroid neovasculopathy (PNV). METHODS: A computerized search from inception up to December 2019 of the online electronic database PubMed was performed using the following search string: "pachychoroid neovasculopathy". The reference list in each article was scanned for additional relevant publications. RESULTS: PNV is a type-1 choroidal neovascularization, overlying focal areas of choroidal thickening and dilated choroidal vessels. It can develop in patients affected by pachychoroid pigment epitheliopathy or chronic central serous chorioretinopathy. The absence of drusen, the presence of pachydrusen, younger age of onset and choroidal thickening distinguish it from neovascular age-related macular degeneration (AMD). PNV incidence and prevalence data are lacking. Its pathophysiology is not fully understood, but angiogenic mechanisms involved in neovascular AMD may be different from those in PNV. Due to optical coherence tomography (OCT) improvements, PNV can be diagnosed more easily than before. In particular, PNV shows a shallow pigment epithelium detachment with an undulating retinal pigment epithelium over a subfoveal choroidal thickening, associated with vein enlargement in Haller's layer (named pachyvessels) and choriocapillaris thinning. On OCT angiography, PNV reveals tangled hyper-reflective filamentous neovessels in the choriocapillaris itself. The current first-line PNV treatment is intravitreal anti-VEGF (vascular endothelial growth factor) injections with a treat-and-extend regimen. In particular, aflibercept shows a higher rate of fluid absorption than others. In the case of fluid recurrence or persistence, photodynamic therapy is a valid alternative. CONCLUSION: Ongoing research into pathophysiology and imaging improvements may be helpful in defining prognostic criteria and stratifying patient risk, allowing responsible monitoring and management of PNV.

Seroprevalence of Rift Valley fever virus in cattle in the Democratic Republic of the Congo.

This study aimed at assessing the serological and virological status of Rift Valley fever virus (RVFV) in cattle from four climatically diverse zones of the Democratic Republic of the Congo (DRC). A total of 1675 sera samples collected between 2014 and 2015 from cattle without clinical manifestation of RVF infection were tested using competitive and capture enzyme ELISA to detect both IgG and IgM. RT-PCR was used for the detection of nucleic acid of RVFV. Out of the 1675 cattle sera tested, 203 were found to be IgG-positive, giving an overall true seroprevalence of 12.37% (95% CI 10.86-14.05). This seroprevalence varied between the four zones with a seroprevalence of 16.16% (95% CI 12.86-20.12), 14.70% (95% CI 11.72-18.29), 10.82% (95% CI 7.19-14.19), and 7.34% (95% CI 5.13-10.41) recorded in cattle sampled in the mountainous, humid savannah, dry savannah, and forest zones, respectively (p < 0.05, χ2 = 17.26). A higher true seroprevalence of 14.58% (95% CI 9.3-22.13) was found in animals aged 1 year compared to 10.43% (95% CI 8.12-13.30) and 13.16% (95% CI 11.19-15.42) in groups aged between 2-3 and > 3 years, respectively, although the difference was not statistically significant (p > 0.05, χ2 = 2.95). Similarly, no statistically significant difference (p > 0.05, χ2 = 0.04) was found between the sexes of the animals. Among the IgG-positive samples screened for anti-RVFV IgM, only 1.47% (3/203) was IgM-positive. One of the IgM-positive samples was positive by RT-PCR. These findings reveal country-wide distribution of RVF in the DRC for the first time.

Lithography-Free Miniaturization of Resistive Nonvolatile Memory Devices to the 100 nm Scale by Glancing Angle Deposition.

The scaling of nonvolatile memory (NVM) devices based on resistive filament switching to below a 100 nm2 footprint area without employing cumbersome lithography is demonstrated. Nanocolumns of the organic semiconductor 4,4-bis[N-(1-naphthyl)-N-phenyl-amino]diphenyl (α-NPD) were grown by glancing angle deposition on a silver electrode. Individual NVM devices were electrically characterized by conductive atomic force microscopy with the tip of a conductive cantilever serving as second electrode. The resistive switching mechanism is unambiguously attributed to Ag filament formation between the electrodes. This sets the upper limit for the filament diameter to well below 100 nm. Full functionality of these NVM nanodevices is evidenced, revealing a potential memory density of >1 GB/cm2 in appropriate architectures.

Analysis of Choroidal Thickness Change after 25-Gauge Vitrectomy for Idiopathic Epiretinal Membrane with or without Phacoemulsification and Intraocular Lens Implantation.

PURPOSE: This study aimed to evaluate choroidal thickness modifications before and after vitrectomy with or without phacoemulsification for idiopathic epiretinal membrane in the operated eye and in the unaffected fellow eye. METHODS: In total, 53 eyes of 53 patients underwent 25-gauge pars plana vitrectomy plus internal limiting membrane peeling and air tamponade. Twenty-seven eyes underwent combined surgery with phacoemulsification and intraocular lens implantation. Choroidal thickness was measured using enhanced deep image spectral-domain optical coherence tomography at the fovea and at 500 and 2,500 µm from the fovea. Fellow eyes without any previous ocular surgery history served as controls. RESULTS: Baseline comparison did not show significant differences between study and fellow eyes (p > 0.05). Choroidal thickness significantly decreased in the subfoveal area (p = 0.004) as well as at 500 µm (p = 0.026) and 2,500 µm nasally (p = 0.019) and at 500 µm (p = 0.039) and 2,500 µm (p = 0.005) temporally to the fovea. No significant changes were observed postoperatively in the superior and inferior areas (p > 0.05). No differences were found between eyes which underwent combined surgery and those which underwent vitrectomy alone (p > 0.05). The unaffected eyes did not show any significant changes (p > 0.05). CONCLUSIONS: Comparison of baseline values did not show any differences between affected and unaffected eyes, meaning that choroidal thickness was not influenced by the development of epiretinal membrane. Vitrectomy plus epiretinal and inner limiting membrane removal may influence choroidal homeostasis, leading to a decrease in choroidal thickness in the subfoveal, nasal, and temporal areas. Combined surgery did not show significant differences when compared to vitrectomy alone.

Electronic structures of CuTPP and CuTPP(F) complexes. A combined experimental and theoretical study I.

Copper complexes of tetraphenylporphyrin (H2TPP) and tetrakis(pentafluorophenyl)porphyrin (H2TPP(F)) deposited as thin films on Au(111) have been studied experimentally and theoretically. Core level emissions from C 1s, N 1s, F 1s and Cu 2p as well as valence states of CuTPP and CuTPP(F) have been investigated using surface photoelectron spectroscopy. The interpretation of experimental results has been guided by theoretical calculations carried out on isolated species in the habit of the density functional theory. Reference to experimental and theoretical outcomes pertaining to H2TPP and H2TPP(F) allowed a confident and detailed assignment of the title molecules' X-ray and ultraviolet photoemission data. With specific reference to the latter, similar to copper phthalocyanine (CuPc), whose coordinative pocket mirrors the CuTPP/CuTPP(F) ones, the lowest ionization energy of the title compounds implies electron ejection from a ring orbital rather than from the Cu 3d-based singly occupied molecular orbital. Moreover, analogous to CuPc, the ionic contribution appears to play an important role in the Cu-N bonding. Nevertheless, differences in the number, symmetry, nature and relative position of CuTPP/CuTPP(F) occupied frontier orbitals compared to CuPc may be stated only by considering in great detail the Cu-ligand covalent interactions.

Electronic structure of CuTPP and CuTPP(F) complexes: a combined experimental and theoretical study II.

The unoccupied electronic structure of thick films of tetraphenylporphyrin and tetrakis(pentafluorophenyl)porphyrin Cu(ii) complexes (hereafter, CuTPP and CuTPP(F)) deposited on Au(111) has been studied by combining the outcomes of near-edge X-ray absorption fine structure (NEXAFS) spectroscopy with those of spin-unrestricted time-dependent density functional (TD-DFT) calculations carried out either within the scalar relativistic zeroth order regular approximation (ZORA) framework (C, N and F K-edges) or by using the Tamm-Dancoff approximation coupled to ZORA and including spin-orbit effects (Cu L2,3-edges). Similarly to the modelling of NEXAFS outcomes pertaining to other Cu(ii) complexes, the agreement between theory and experiment is more than satisfactory, thus confirming the open-shell TD-DFT to be a useful tool to look into NEXAFS results pertinent to Cu(ii) compounds. The combined effect of metalation and phenyl (Ph) fluorine decoration is found to favour an extensive mixing between (Ph)σ* and pristine porphyrin macrocyle (pmc) (pmc)π* virtual levels. The lowest lying excitation in the C and N K-edge spectra of both CuTPP and CuTPP(F) is associated with a ligand-to-metal-charge-transfer transition, unambiguously revealed in the (CuTPP)N K-edge spectral pattern. Moreover, the comparison with literature data pertaining to the modelling of the (Cu(II))L2,3 features in the phthalocyanine-Cu(ii) (CuPc) complex provided further insights into how metal-to-ligand-charge-transfer transitions associated with excitations from 2p(Cu(II)) AOs to low-lying, ligand-based π* MOs may contribute to the Cu(ii) L2,3-edge intensity and thus weaken its believed relationship with the Cu(ii)-ligand symmetry-restricted covalency. Despite the coordinative pocket of CuTPP/CuTPP(F) mirroring CuPc, the ligand-field strength exerted by the phthalocyanine ligand on the Cu(ii) centre is experimentally found and theoretically confirmed to be slightly stronger than that experienced by Cu in CuTPP and CuTPP(F). On the whole, the obtained results complement those published in the near past by the same group on the occupied and empty states of the H2TPP and H2TPP(F) free ligands as well as on the occupied states of both CuTPP and CuTPP(F), thus providing the final piece to get a thorough description of electronic perturbations associated with the metalation and the Ph halogen decoration of H2TPP.

VARIABLES AFFECTING THE LONG-TERM OUTCOME OF GRAVES ORBITOPATHY FOLLOWING HIGH-DOSE INTRAVENOUS GLUCOCORTICOID PULSE THERAPY IN PATIENTS NOT TREATED WITH ORBITAL RADIOTHERAPY.

OBJECTIVE: Intravenous (iv) glucocorticoids (GC) (ivGC) are used for active Graves orbitopathy (GO), but factors affecting GO outcome are poorly understood. We performed a retrospective study to investigate the variables affecting GO after ivGC. METHODS: We evaluated 83 consecutive GO patients treated with ivGC but not orbital radiotherapy (ORT) and re-examined them after a median of 47 months. The endpoints were the relationships between GO outcome or additional treatments with age, sex, smoking habits, thyroid volume, thyroid treatment, time since thyroid treatment, antithyroid-stimulating hormone receptor antibodies (TRAb), GO duration, GO features, and follow-up time. RESULTS: GO features improved after treatment, resulting in moderate and marked amelioration in ~75% and ~41% of patients respectively. By multivariate analysis, a moderate GO improvement correlated with diplopia at first observation, which was more severe in responders. A marked GO improvement correlated with time between first and last observation and time after thyroid treatment, which were longer in responders. This likely reflected the combination of an early effect of GC and a late, spontaneous improvement of GO, as shown by analyses of GO outcome at various time points. Additional treatments after ivGC correlated by multivariate analysis with eyelid aperture, diplopia and NOSPECS score (NOSPECS stands for no GO signs [N], only eyelid sign [O], soft tissue involvement [S], proptosis [P], extraocular motility restriction [E], corneal involvement [C], and sight loss [S]) at first observation, which were more severe in responders. CONCLUSION: Our study shows that response to ivGC increases with time, likely reflecting the known tendency of GO to improve spontaneously, and is more pronounced when GO is more severe to begin with, which is associated with more additional treatments. ABBREVIATIONS: ANOVA = analysis of variance CAS = clinical activity score GC = glucocorticoids GO = Graves orbitopathy 131I = radioactive iodine iv = intravenous ivGC = high-dose intravenous glucocorticoid pulse therapy MMI = methimazole OD = orbital decompression ORT = orbital radiotherapy TRAb = antithyroid-stimulating hormone receptor antibodies.

ADJUSTABLE MACULAR BUCKLING FOR FULL-THICKNESS MACULAR HOLE WITH FOVEOSCHISIS IN HIGHLY MYOPIC EYES: Long-Term Anatomical and Functional Results.

PURPOSE: To assess functional and structural outcome after adjustable macular buckling for the treatment of foveoschisis (FS), associated with full-thickness macular hole (FTMH) in highly myopic eyes. METHODS: Eighteen consecutive patients who underwent adjustable macular buckling for FS associated with FTMH were included in this prospective study. Three cases were not included in the analysis due to short follow-up period (less than 3 months). Outcome measures included anatomical success rate with FS resolution and FTMH closure, best-corrected visual acuity, mean retinal sensitivity, central retinal thickness, and fixation site and stability. RESULTS: Foveoschisis resolution and FTMH closure were observed in all cases between 1 month to 3 months after surgery. At 24 months of follow-up visit visual acuity improved in 13/15 eyes (86.7%) and remained stable in 2 (13.3%). Mean retinal sensitivity showed significant improvement from baseline 5.69 ± 3.52 dB to final 8.35 ± 3.86 dB; P < 0.001. Fixation stability inside central 4° improved from baseline 58.5 ± 17.8% to final 73.7 ± 23.0%; P = 0.009. Central retinal thickness did not change significantly throughout follow-up. No FTMH or FS recurrence occurred and no surgical complications arose. CONCLUSION: Adjustable macular buckling exoplant may represent an effective surgical option for the treatment of FS associated with FTMH in highly myopic eyes. Adjustable macular buckling showed high closure rate and virtually no tendency to recur. Functional results and safety are also interesting because vision improved and retinal thickness did not reduce significantly at 24 months of follow-up.

Tuning the Magnetic Properties of Carbon by Nitrogen Doping of Its Graphene Domains.

Here we present the formation of predominantly sp(2)-coordinate carbon with magnetic- and heteroatom-induced structural defects in a graphene lattice by a stoichiometric dehalogenation of perchlorinated (hetero)aromatic precursors [hexachlorobenzene, C6Cl6 (HCB), and pentachloropyridine, NC5Cl5 (PCP)] with transition metals such as copper in a combustion synthesis. This route allows the build-up of a carbon lattice by a chemistry free of hydrogen and oxygen compared to other pyrolytic approaches and yields either nitrogen-doped or -undoped graphene domains depending on the precursor. The resulting carbon was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Raman spectroscopy, photoelectron spectroscopy (XPS), and SQUID magnetometry to gain information on its morphological, chemical, and electronic structure and on the location of the nitrogen atoms within the carbon lattice. A significant lowering of the magnetization was observed for the nitrogen-doped carbon obtained by this method, which exhibits less ordered graphene domains in the range of approximately 10-30 nm as per TEM analysis compared to the nondoped carbon resulting from the reaction of HCB with larger graphene domains as per TEM and the presence of a 2D mode in the Raman spectra. The decrease of the magnetization by nitrogen doping within the sp(2)-coordinate carbon lattice can be attributed to an increase in pyrrole-type defects along with a reduction in radical defects originating from five-membered carbon ring structures as well as changes in the π-electron density of edge states.

Aflibercept administration in neovascular age-related macular degeneration refractory to previous anti-vascular endothelial growth factor drugs: a critical review and new possible approaches to move forward.

PURPOSE: The recent introduction of anti-VEGF drugs has widely changed the prognosis of exudative age-related macular degeneration (AMD), even if a variable percentage of patients showed an insufficient response. Aflibercept is a new anti-VEGF drug approved by FDA for the treatment of exudative AMD with a wider binding capacity than either bevacizumab or ranibizumab. Therefore, the purposes were as follows: (i) to report anatomical and functional outcomes of switching from bevacizumab/ranibizumab to aflibercept previously described in the scientific literature, (ii) to hypothesize the possible pathophysiological mechanisms of the resistance and tachyphylaxis to anti-VEGF drugs, and (iii) to suggest possible clinical actions to increase the chances of success for such difficult cases. METHODS: We reviewed the available scientific literature in Medline, Cochrane database, Current Contents, PubMed, and cross-referencing from identified articles, regarding the treatment of exudative AMD patients refractory to bevacizumab and/or ranibizumab and switched to aflibercept monotherapy. We included in this review all the cases in which the diagnosis of refractory or resistant exudative AMD was properly made, and the results of at least one aflibercept injection were described. FINDINGS: We reported the outcomes of 21 papers for a total of 1066 eyes affected by exudative AMD resistant to previous anti-VEGF drug injections and switched to aflibercept. Enrolled reports were divided into two groups: 5 prospective reports and 16 retrospective reports. All the reported papers conclude their analysis, stating that switching from bevacizumab/ranibizumab to aflibercept injections can improve outcomes successfully in refractory neovascular AMD patients. IMPLICATIONS: Analysis of the papers reported in this review demonstrates that switching from bevacizumab/ranibizumab to aflibercept injections can improve outcomes successfully in refractory neovascular AMD patients. The mechanism for these effects is not yet completely understood.

Organic semiconductor/gold interface interactions: from physisorption on planar surfaces to chemical reactions with metal nanoparticles.

The interaction of gold nanoparticles (AuNPs) with prototypical organic semiconductors used in optoelectronics, namely, tris(8-hydroxyquinoline)aluminium (Alq3 ) and 4,4-bis[N-(1-naphthyl)-N-phenylamino]diphenyl (α-NPD), is investigated in situ by X-ray photoelectron spectroscopy (XPS). These AuNPs-on-molecule experiments are compared with the reversed molecule-on-Au cases. The molecules-on-Au systems show only weak interactions, and the evolution of the XP spectra is dominated by final-state effects. In contrast, in the AuNPs-on-molecules cases, both initial-state effects and final-state effects occur. Spectral features arising for both molecules and metal indicate charge transfer and the formation of organometallic complexes (initial-state effects). The energy shift in the metal emission underlines the size-induced nanometric nature of the molecule/Au interaction (final-state effects). Consequently, the chemical interaction between metals and organic semiconductors likely depends strongly on the deposition sequence in general.

XAS of tetrakis(phenyl)- and tetrakis(pentafluorophenyl)-porphyrin: an experimental and theoretical study.

The unoccupied electronic structure of tetrakis(phenyl)- and tetrakis(pentafluorophenyl)-porphyrin thick films deposited on SiO2/Si(100) native oxide surfaces has been thoroughly studied by combining the outcomes of near-edge X-ray absorption fine structure spectroscopy at the C, N, and F K-edges with those of scalar relativistic zeroth order regular approximation time-dependent density functional theory calculations carried out on isolated molecules. Both experimental and theoretical results concur to stress the electronic inertness of pristine porphyrin macrocycle based 1s(C)→π* and 1s(N)→π* transitions whose excitation energies are substantially unaffected upon fluorination. The obtained results complement those published by the same group about the occupied states of both molecules, thus providing the missing tile to get a thorough description of the halide decoration effects on the electronic structure of the tetrakis(phenyl)-porphyrin.

Macular pucker: to peel or not to peel the internal limiting membrane? A microperimetric response.

BACKGROUND: To compare functional and anatomical outcomes after idiopathic macular pucker removal between eyes that underwent internal limiting membrane (ILM) peeling and eyes that did not. METHODS: In this multicentric, randomized clinical trial, 60 eyes of 60 patients affected with idiopathic macular pucker were enrolled. Thirty eyes underwent 23-gauge pars plana vitrectomy associated with ILM peeling ("ILM peeling group"), whereas 30 eyes did not undergo ILM peeling ("ILM not peeling group"). Retinal sensitivity, frequency of microscotomas, and all the other microperimetric parameters were tested by MP1 microperimetry. Best-corrected visual acuity was investigated with the Early Treatment Diabetic Retinopathy Study chart. Anatomical outcomes were analyzed with spectral domain optical coherence tomography. RESULTS: After a 12-month follow-up, the mean retinal sensitivity in the 4° central area showed a greater and faster recovery in the ILM not peeling group than in the ILM peeling group (P = 0.041). The number of absolute microscotomas (0 dB) within the 12° central retinal area was significantly higher in the ILM peeling group than in the ILM not peeling group (P = 0.044). CONCLUSION: The ILM not peeling group seems to show better outcomes than the ILM peeling group as measured by mean retinal sensitivity and number of microscotomas after a 12-month follow-up.

Intravitreal ranibizumab for predominantly hemorrhagic choroidal neovascularization in age-related macular degeneration.

PURPOSE: To evaluate the effects of intravitreal ranibizumab monotherapy on predominantly hemorrhagic choroidal neovascularization with foveal involvement associated with age-related macular degeneration. MATERIALS AND METHODS: Twenty-two consecutive eyes with hemorrhagic neovascularization were treated with 3 monthly intravitreal ranibizumab injections. Additional injections were administered according to retreatment criteria during 12 months of follow-up. RESULTS: A mean of 6.64 ± 1.36 injections was administered. Overall, the mean visual acuity increased from 10.90 ± 6.02 to 12.81 ± 8.34 ETDRS letters (p > 0.05) at 12 months. The 'early treatment group' gained a mean of 2.83 ± 2.24 ETDRS letters (p < 0.05), while the 'late treatment group' gained a mean of 0.30 ± 1.25 ETDRS letters (p > 0.05) with significant differences between the groups (p < 0.05). A progressive resolution of macular bleeding was registered in 20 patients (mean time: 5.3 ± 1.6 months). CONCLUSIONS: Ranibizumab injections can be considered a beneficial approach for the management of predominantly hemorrhagic choroidal neovascularization with foveal involvement associated with age-related macular degeneration. Furthermore, the time interval between hemorrhage and the first injection seems to be an important predicting factor of final visual acuity.