Search

Glaucoma is one of the world’s leading causes of blindness, and its management is challenging. The main objective is to lower intraocular pressure through medical, para-surgical, and surgical therapy. Medical therapy often represents the first line of treatment. Although effective in many cases, the eye drops are accompanied by significant problems. They require high patient compliance and can be associated with various side effects, limiting their efficacy. Consequently, the research for new drug delivery systems trying to overcome these limitations is ongoing: numerous devices are developing and gradually entering clinical practice. These new therapeutic options may offer better control of the intraocular pressure, with fewer side effects, and are less dependent on patients’ compliance. Hence, the research in this field continues to flourish. This review summarizes the most recent findings in the scientific literature, underlines the role and possible limitations of the new glaucoma drug delivery systems in clinical practice, and recognizes their new horizons and perspectives.

Introduction:The purine analog 6-thioguanine (6TG), an old drug approved in the 60s to treat acute myeloid leukemia (AML), was tested in the diabetic retinopathy (DR) experimental in vivo setting along with a molecular modeling approach.Methods:A computational analysis was performed to investigate the interaction of 6TG with MC1R and MC5R. This was confirmed in human umbilical vein endothelial cells (HUVECs) exposed to high glucose (25 mM) for 24 h. Cell viability in HUVECs exposed to high glucose and treated with 6TG (0.05–0.5–5 µM) was performed. To assess tube formation, HUVECs were treated for 24 h with 6TG 5 µM and AGRP (0.5–1–5 µM) or PG20N (0.5–1–5–10 µM), which are MC1R and MC5R antagonists, respectively. For the in vivo DR setting, diabetes was induced in C57BL/6J mice through a single streptozotocin (STZ) injection. After 2, 6, and 10 weeks, diabetic and control mice received 6TG intravitreally (0.5–1–2.5 mg/kg) alone or in combination with AGRP or PG20N. Fluorescein angiography (FA) was performed after 4 and 14 weeks after the onset of diabetes. After 14 weeks, mice were euthanized, and immunohistochemical analysis was performed to assess retinal levels of CD34, a marker of endothelial progenitor cell formation during neo-angiogenesis.Results:The computational analysis evidenced a more stable binding of 6TG binding at MC5R than MC1R. This was confirmed by the tube formation assay in HUVECs exposed to high glucose. Indeed, the anti-angiogenic activity of 6TG was eradicated by a higher dose of the MC5R antagonist PG20N (10 µM) compared to the MC1R antagonist AGRP (5 µM). The retinal anti-angiogenic effect of 6TG was evident also in diabetic mice, showing a reduction in retinal vascular alterations by FA analysis. This effect was not observed in diabetic mice receiving 6TG in combination with AGRP or PG20N. Accordingly, retinal CD34 staining was reduced in diabetic mice treated with 6TG. Conversely, it was not decreased in diabetic mice receiving 6TG combined with AGRP or PG20N.Conclusion:6TG evidenced a marked anti-angiogenic activity in HUVECs exposed to high glucose and in mice with DR. This seems to be mediated by MC1R and MC5R retinal receptors.

Background: Ureaplasma parvum (UP) is a causative agent of non-gonococcal urethritis, involved in the pathogenesis of prostatitis and epididymitis, and it could impair human fertility. Although UP infection is a frequent cause of male infertility the study evidence assessing their prevalence and the association in patients with infertility is still scarce. The molecular processes leading to defects in spermatozoa quality are not completely investigated. MicroRNAs (miRNAs) have been extensively reported as gene regulatory molecules on post-transcriptional levels involved in various biological processes such as gametogenesis, embryogenesis, and the quality of sperm, oocyte, and embryos. Methods: Therefore, the study design was to demonstrate that miRNAs in body fluids like sperm could be utilized as non-invasive diagnostic biomarkers for pathological and physiological conditions such as infertility. A post-hoc bioinformatics analysis was carried out to predict the pathways modulated by the miRNAs dysregulated in the differently motile spermatozoa. Results: Here it is shown that normospermic patients infected by UP had spermatozoa with increased quantity of superoxide anions, reduced expression of miR-122-5p, miR-34c-5, and increased miR-141-3p compared with non-infected normospermic patients. This corresponded to a reduction of sperm motility in normospermic infected patients compared with normospermic non-infected ones. A target gene prediction presumed that an essential role of these miRNAs resided in the regulation of lipid kinase activity, accounting for the changes in the constitution of spermatozoa membrane lipids caused by UP. Conclusions: Altogether, the data underline the influence of UP on epigenetic mechanisms regulating spermatozoa motility.

Acanthamoeba keratitis (AK) is a rare but potentially sight-threatening corneal infection caused by the Acanthamoeba parasite. This microorganism is found ubiquitously in the environment, often in freshwater, soil, and other sources of moisture. Despite its low incidence, AK presents significant challenges due to delayed diagnosis and the complex nature of therapeutic management. Early recognition is crucial to prevent severe ocular complications, including corneal ulceration and vision loss. Diagnostic modalities and treatment strategies may vary greatly depending on the clinical manifestation and the available tools. With the growing reported cases of Acanthamoeba keratitis, it is essential for the ophthalmic community to thoroughly understand this condition for its effective management and improved outcomes. This review provides a comprehensive overview of AK, encompassing its epidemiology, risk factors, pathophysiology, clinical manifestations, diagnosis, and treatment.

Background and Objectives: The role and the levels of ghrelin in diabetes-induced retinal damage have not yet been explored. The present study aimed to measure the serum levels of total ghrelin (TG), and its acylated (AG) and des-acylated (DAG) forms in patients with the two stages of diabetic retinopathy (DR), non-proliferative (NPDR) and proliferative (PDR). Moreover, the correlation between serum ghrelin and neutrophil elastase (NE) levels was investigated. Materials and Methods: The serum markers were determined via enzyme-linked immunosorbent assays in 12 non-diabetic subjects (CTRL), 15 diabetic patients without DR (Diabetic), 15 patients with NPDR, and 15 patients with PDR. Results: TG and AG serum levels were significantly decreased in Diabetic (respectively, p < 0.05 and p < 0.01 vs. CTRL), NPDR (p < 0.01 vs. Diabetic), and in PDR patients (p < 0.01 vs. NPDR). AG serum levels were inversely associated with DR abnormalities (microhemorrhages, microaneurysms, and exudates) progression (r = −0.83, p < 0.01), serum neutrophil percentage (r = −0.74, p < 0.01), and serum NE levels (r = −0.73, p < 0.01). The latter were significantly increased in the Diabetic (p < 0.05 vs. CTRL), NPDR (p < 0.01 vs. Diabetic), and PDR (p < 0.01 vs. PDR) groups. Conclusions: The two DR stages were characterized by decreased AG and increased NE levels. In particular, serum AG levels were lower in PDR compared to NPDR patients, and serum NE levels were higher in the PDR vs. the NPDR group. Together with the greater presence of retinal abnormalities, this could underline a distinctive role of AG in PDR compared to NPDR.

Diabetic macular edema (DME)’s therapeutic approach can frequently be challenging. The purpose of the review is to propose evidence-based recommendations on the employment of intravitreal dexamethasone implants (DEX) when approaching patients suffering from DME. Seven national consensuses redacted by different groups of retina specialists from Europe and Asia were examined and confronted. Each consensus was redacted utilizing a Delphi approach, in person meetings, or by reviewing the literature. DEX can be studied as a first-line strategy in individuals suffering from DME with inflammatory OCT biomarkers, in vitrectomized eyes, in patients with recent cardiovascular events, in pregnant women, in patients scheduled to undergo cataract surgery or with poor compliance. The other parameters considered were the indications to the DME treatment, when to switch to DEX, the definition of non-responder to anti-VEGFs agents and to the DEX implant, whether to combine DEX with laser photocoagulation, the association between glaucoma and DEX, and the management of DEX and the cataract. Although several years have passed since the introduction of DEX implants in the DME treatment, there is still not a unified agreement among retina specialists. This paper compares the approach in the DME treatment between countries from different continents and provides a broader and worldwide perspective of the topic.

Fungi represent a very important cause of microbial eye infections, especially in tropical and developing countries, as they could cause sight-threating disease, such as keratitis and ocular candidiasis, resulting in irreversible vision loss. Candida species are among the most frequent microorganisms associated with fungal infection. Although Candida albicans is still the most frequently detected organism among Candida subspecies, an important increase in non-albicans species has been reported. Mycotic infections often represent an important diagnostic-clinical problem due to the difficulties in performing the diagnosis and a therapeutic problem due to the limited availability of commercial drugs and the difficult penetration of antifungals into ocular tissues. The ability to form biofilms is another feature that makes Candida a dangerous pathogen. In this review, a summary of the state-of-the-art panorama about candida ocular pathology, diagnosis, and treatment has been conducted. Moreover, we also focused on new prospective natural compounds, including nanoparticles, micelles, and nanocarriers, as promising drug delivery systems to better cure ocular fungal and biofilm-related infections. The effect of the drug combination has also been examined from the perspective of increasing efficacy and improving the course of infections caused by Candida which are difficult to fight.

L’autore analizza le diverse anime europee a partire dal documento della sua prima concettualizzazione: il manifesto di Ventotene sino a toccare i problemi della crisi politica europea e dei diritti fondamentali.

L’autore analizza le diverse anime europee a partire dal documento della sua prima concettualizzazione: il manifesto di Ventotene sino a toccare i problemi della crisi politica europea e dei diritti fondamentali

Background: Vitamin D deficiency has been associated with dry eye development during Sjögren’s syndrome (SS). Here, we investigated whether repeated oral vitamin D3 supplementation could prevent the corneal epithelium damage in an SS mouse model. Methods: 30 female mouse knock-out for the thrombospondin 1 gene were randomized (six per group) in untreated mice euthanized at 6 weeks as negative control (C−) or at 12 weeks as the positive control for dry eye (C+). Other mice were sacrificed after 6 weeks of oral vitamin D3 supplementation in the drinking water (1000, 8000, and 20,000 IU/kg/week, respectively). Results: The C+ mice showed alterations in their corneal epithelial morphologies and thicknesses (p < 0.01 vs. C−), while the mice receiving 8000 (M) and 20,000 (H) IU/kg/week of vitamin D3 showed preservation of the corneal epithelium morphology and thickness (p < 0.01 vs. C+). Moreover, while the C+ mice exhibited high levels and activity of corneal tumor necrosis factor alpha converting enzyme (TACE), neovascularization and fibrosis markers; these were all reduced in the M and H mice. Conclusions: Oral vitamin D3 supplementation appeared to counteract the negative effect of TACE on corneal epithelium in a mouse model of SS-associated dry eye.

Ocular viral infections are common and widespread globally. These infectious diseases are a major cause of acute red eyes and vision loss. The eye and its nearby tissues can be infected by several viral agents, causing infections with a short course and limited ocular implications or a long clinical progression and serious consequences for the function and structure of the ocular region. Several surveillance studies underline the increased emergence of drug resistance among pathogenic viral strains, limiting treatment options for these infections. Currently, in the event of resistant infections, topical or systemic corticosteroids are useful in the management of associated immune reactions in the eye, which contribute to ocular dysfunction. Many cases of viral eye infections are misdiagnosed as being of bacterial origin. In these cases, therapy begins late and is not targeted at the actual cause of the infection, often leading to severe ocular compromises, such as corneal infiltrates, conjunctival scarring, and reduced visual acuity. The present study aims at a better understanding of the viral pathogens that cause eye infections, along with the treatment options available.

L’articolo studia la costruzione concettuale del giurista in Emilio Betti come un rappresentante organico della società. Non è un rappresentante politico, con o senza vincolo di mandato, né un rappresentante legale, che trasferisce interessi e li relaziona. Il rappresentante organico è una longa manus, un’estensione autorevole del meglio della società. La sua autorevolezza, disinteressandosi del potere politico, può contemperare gli interessi in gioco, dire il diritto con la sentenza, riequilibrando gli squilibri sociali, provocati anche dalle stesse leggi. La funzione di riequilibrio sociale, capace di coniugarsi con l’equità, nella potenzialità di quest’ultima di porsi non solo come giustizia formale, ma sostanziale, è ciò che rende capace la tensione teoretica bettiana di divenire strumento metodologico possibile per tutte le scienze del sapere, ma anche per la vita associata, sulle orme dell’Etica nicomachea, della Politica e della Retorica di Aristotele. La scelta decisionale del giurista emerge come una delle più rilevanti questioni giuridiche del nostro tempo, quella del giusto processo. La sua soluzione necessaria, sia sul piano della legislazione di ciascuno stato, sia sul piano di tutte le singole narrazioni di ciascuna vicenda processuale, può trovare riferimenti solidi negli studi romanistici di Betti, a partire da quelli sui Sette Re di Roma, fino a giungere a quelli sul Pretore romano. Permette di distinguere il decisionismo gnoseologico e ponderato del giurista da quello che mette fine allo stato d’eccezione del politico, teorizzato da Carl Schmitt. E permette anche di distinguere una logica fondata su una visione etica e culturale ampia della società, da una logica svuotata di deontologia e fondata soltanto sull’argomentazione sillogistica, nella quale il mezzo può sostituire il fine.

This study aimed to investigate the interactions between fingolimod, a sphingosine 1-phosphate receptor (S1PR) agonist, and melanocortin receptors 1 and 5 (MCR1, MCR5). In particular, we investigated the effects of fingolimod, a drug approved to treat relapsing-remitting multiple sclerosis, on retinal angiogenesis in a mouse model of diabetic retinopathy (DR). We showed, by a molecular modeling approach, that fingolimod can bind with good-predicted affinity to MC1R and MC5R. Thereafter, we investigated the fingolimod actions on retinal MC1Rs/MC5Rs in C57BL/6J mice. Diabetes was induced in C57BL/6J mice through streptozotocin injection. Diabetic and control C57BL/6J mice received fingolimod, by oral route, for 12 weeks and a monthly intravitreally injection of MC1R antagonist (AGRP), MC5R antagonist (PG20N), and the selective S1PR1 antagonist (Ex 26). Diabetic animals treated with fingolimod showed a decrease of retinal vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor receptors 1 and 2 (VEGFR1 and VEGFR2), compared to diabetic control group. Fingolimod co-treatment with MC1R and MC5R selective antagonists significantly (p < 0.05) increased retinal VEGFR1, VEGFR2, and VEGFA levels compared to mice treated with fingolimod alone. Diabetic animals treated with fingolimod plus Ex 26 (S1PR1 selective blocker) had VEGFR1, VEGFR2, and VEGFA levels between diabetic mice group and the group of diabetic mice treated with fingolimod alone. This vascular protective effect of fingolimod, through activation of MC1R and MC5R, was evidenced also by fluorescein angiography in mice. Finally, molecular dynamic simulations showed a strong similarity between fingolimod and the MC1R agonist BMS-470539. In conclusion, the anti-angiogenic activity exerted by fingolimod in DR seems to be mediated not only through S1P1R, but also by melanocortin receptors.

HSV-1 can be associated with severe and recurrent eye infections characterized by a strong inflammatory response that leads to blepharoconjunctivitis, epithelial and stromal keratitis, and retinal necrosis. The incidence of HSV-1 keratitis is 1.5 million every year worldwide, including more than 40,000 new cases exhibiting serious visual failures. Generally, the therapy uses antiviral drugs to promote healing; however, there are currently no compounds that are able to completely eradicate the virus. In addition, the phenomenon of resistance is rapidly spreading among HSV-1 strains, creating mutants developing resistance to the common antiviral drugs; therefore, deep research on this issue is warranted. The efficacy of different ophthalmic solutions already on the market was evaluated for reducing HSV-1 infection. Different plaque assays were set up on epithelial cells, revealing that two ophthalmic solutions were able to inhibit viral replication in the early stages of infection. The data were further confirmed by molecular tests analyzing the expression levels of the principal genes involved in HSV-1 infection, and a strong reduction was observed after only 1 min of eye-drop treatment. Collectively, these results suggested the use of ophthalmic solutions as potential antiviral options for the treatment of ocular herpetic infection.

The ocular microbiome is of fundamental importance for immune eye homeostasis, and its alteration would lead to an impairment of ocular functionality. Little evidence is reported on the composition of the ocular microbiota of term infants and on the impact of antibiotic prophylaxis. Methods: A total of 20 conjunctival swabs were collected from newborns at birth and after antibiotic treatment. Samples were subjected to 16S rRNA sequencing via system MiSeq Illumina. The data were processed with the MicrobAT software and statistical analysis were performed using two-way ANOVA. Results: Antibiotic prophylaxis with gentamicin altered the composition of the microbiota. In detail, a 1.5- and 2.01-fold reduction was recorded for Cutibacterium acnes (C. acnes) and Massilia timonae (M. timonae), respectively, whereas an increase in Staphylococcus spp. of 6.5 times occurred after antibiotic exposure. Conclusions: Antibiotic prophylaxis altered the ocular microbiota whose understanding could avoid adverse effects on eye health.

Diabetic retinopathy (DR) is a neurovascular disease characterized by the reduction of retina integrity and functionality, as a consequence of retinal pigment epithelial cell fibrosis. Although galectin-1 (a glycan-binding protein) has been associated with dysregulated retinal angiogenesis, no evidence has been reported about galectin-1 roles in DR-induced fibrosis. ARPE-19 cells were cultured in normal (5 mM) or high glucose (35 mM) for 3 days, then exposed to the selective galectin-1 inhibitor OTX008 (2.5–5–10 μM) for 6 days. The determination of cell viability and ROS content along with the analysis of specific proteins (by immunocytochemistry, Western blotting, and ELISA) or mRNAs (by real time-PCR) were performed. OTX008 5 μM and 10 μM improved cell viability and markedly reduced galectin-1 protein expression in cells exposed to high glucose. This was paralleled by a down-regulation of the TGF-β/, NF-kB p65 levels, and ROS content. Moreover, epithelial–mesenchymal transition markers were reduced by OTX008 5 μM and 10 μM. The inhibition of galectin-1 by OTX008 in DR may preserve retinal pigment epithelial cell integrity and functionality by reducing their pro-fibrotic phenotype and epithelial–mesenchymal transition phenomenon induced by diabetes.

PurposeTo investigate the vascular status of the macula in psoriasis patients without history of ocular inflammation by Optical Coherence Tomography Angiography (OCTA).MethodsThis prospective cross-sectional multicenter study included 55 psoriasis patients and 55 control healthy subjects. A complete eye examination and 6 mm × 6 mm OCTA imaging were performed. Retinal vascular status was evaluated by analyzing vascular density (VD) of superficial vascular plexus (superficial wVD) and deep vascular plexuses (deep wVD) in a 6 mm × 6 mm area and in foveal (superficial fVD and deep fVD) and parafoveal sectors (superficial pVD and deep pVD). In addition, foveal thickness (FT) and foveal avascular zone (FAZ) and clinical variables, including best corrected visual acuity (BCVA), intraocular pressure and refractive condition, were collected.ResultsBCVA, intraocular pressure and refractive condition were comparable between cases and controls. OCTA imaging showed that superficial wVD and superficial pVD were lower in the psoriasis group in comparison with controls (p = 0.009 and p = 0.01, respectively). Similarly, deep wVD and pVD were lower in the psoriasis group in comparison with control subjects (p = 0.03 and p = 0.01, respectively). In a sub-analysis of 47 patients affected by psoriasis without psoriatic arthritis, lower values of wVD and pVD in both superficial and deep capillary plexuses were registered.ConclusionOCTA is a useful tool which provides data on vascular status of the retina in psoriasis with no ocular involvement. VD data may suggest that vascular changes may occur earlier than clinical onset of posterior inflammation.

Purpose. To evaluate the efficacy of intravitreal dexamethasone implant (DEX) for the treatment of macular oedema secondary to vitrectomy for epiretinal membrane (ERM) and retinal detachment (RD) by conducting a systematic review with meta-analysis of published studies. Methods. Studies reporting clinical outcomes of DEX use for the treatment of macular oedema secondary to ERM and RD vitrectomy were searched on PubMed and Embase databases. The primary outcome was best-corrected visual acuity (BCVA) change between baseline and post-DEX treatment, reported as mean difference (MD) with 95% confidence interval (CI). Mean central macular thickness (CMT) change was assessed as a secondary outcome. Postimplant adverse events, including intraocular pressure rise and cataract development, were reported as well. Results. Five uncontrolled studies, 1 nonrandomized controlled study, and 1 randomized controlled study were included, with a total of 5 cohorts and 3 cohorts in the ERM group and RD group, respectively. Considering the last available follow-up, a significant improvement in postimplant BCVA was found in the overall population, irrespective of the indication for vitrectomy (MD = −0.28, 95% CI = −0.37, −0.20; p

Retinal hypoxia is one of the causative factors of diabetic retinopathy and is also one of the triggers of VEGF release. We hypothesized that specific dysregulated miRNAs in diabetic retinopathy could be linked to hypoxia-induced damage in human retinal endothelial cells (HRECs). We investigated in HRECs the effects of chemical (CoCl2) hypoxia on the expression of HIF-1α, VEGF, PlGF, and of a focused set of miRNAs. We found that miR-20a-5p, miR-20b-5p, miR-27a-3p, miR-27b-3p, miR-206-3p, miR-381-3p correlated also with expression of TGFβ signaling pathway genes in HRECs, challenged with chemical hypoxic stimuli. In conclusion, our data suggest that retinal angiogenesis would be promoted, at least under HIF-1α activation, by upregulation of PlGF and other factors such as miRNAs, VEGFA, and TGFβ1.

Stimulation of retinal photoreceptors with elevated glucose concentration (30 mM) for 96 h, served as diabetic retinopathy in vitro model to study Resolvin D1 (50 nM) effects on neovascularization. VEGF and anti-angiogenic miR-20a-3p, miR-20a-5p, miR-106a-5p, and miR-20b expression was assessed either in photoreceptors exposed to HG or in exosomes released by those cells. High glucose increased VEGF levels and concurrently decreased anti-angiogenic miRNAs content in photoreceptors and exosomes. RvD1 reverted the effects of glucose damage in photoreceptors and exosomal pro-angiogenic potential, tested with the HUVEC angiogenesis assay. By activating FPR2 receptor, RvD1 modulated both the expression of anti-angiogenic miRNA, which decrease VEGF, and the pro-angiogenic potential of exosomes released by primary retinal cells. HUVEC transfection with miR-20a-3p, miR-20a-5p, miR-106a-5p, and miR-20b antagomirs, followed by exposure to exosomes from photoreceptors, confirmed the VEGF-related miRNAs mechanism and the anti-angiogenic effects of RvD1.

Eye infections caused by bacteria are a serious public health problem among pediatric patients. These diseases, if not properly treated, can cause blindness and impaired vision. The study aimed to evaluate the antimicrobial resistance profiles of the main pathogens involved in eye infections. This study involved pediatric patients enrolled at the “Luigi Vanvitelli” University Hospital of Campania in Naples, Italy, between 2017 and 2019. Of a total of 228 pediatric patients, 73 (32%) tested positive for bacterial infection. In terms of strain distribution, 85% were Gram-positive bacteria, while 15% were Gram-negative bacteria. The most frequently isolated strains were coagulase-negative Staphylococci (60.4%), followed by Staphylococcus aureus (16.4%). The isolated bacteria showed a significant percentage of resistance to multiple antibiotics. Therefore, the identification of the causal bacteria and antimicrobial sensitivity tests are mandatory to select the effective drug for the treatment of eye infections and prevent the development of antibiotic-resistant bacteria.

In 2020, a global pandemic was declared following the spread of SARS-CoV-2, the pathogen responsible for COVID-19. The risk of infection is high due to the ease of transmission, which can occur orally, through droplets, or via contact with contaminated surfaces and objects. It has also been demonstrated that the ocular surface can constitute a transmission route, especially in hospital settings, where health care workers can become a dangerous source of infection. In order to increase prevention and reduce the spread of the virus on the ocular surface, the antiviral activity of already-marketed eye drops against SARS-CoV-2 was evaluated. Iodim, Ozodrop, Septavis, and Dropsept were tested against SARS-CoV-2 in plaque-assay experiments at different stimulation times. Furthermore, the expression levels of early and late genes were evaluated through molecular assays. Results indicated that three of the four ophthalmic solutions showed a considerable dose-dependent inhibition of viral replication, highlighting their use as potential antiviral drugs against SARS-CoV-2 and preventing other ocular infections.

Topical administration is the most convenient route for ocular drug delivery, but only a minor fraction is retained in the precorneal pocket. To overcome this limitation, numerous drug delivery systems (DDS) have been developed. The protein corona (PC) is the layer of biomolecules (e.g., proteins, sugars, lipids, etc.) that forms around DDS in physiological environments by non-covalent interaction. The PC changes the DDS physical–chemical properties, providing them with a completely novel biological identity. The specific involvement of PC in ocular drug delivery has not been addressed so far. To fulfill this gap, here we explored the interaction between a library of four cationic liposome-DNA complexes (lipoplexes) and mucin (MUC), one of the main components of the tear film. We demonstrate that MUC binds to the lipoplex surface shifting both their size and surface charge and reducing their absorption by primary corneal epithelial cells. To surpass such restrictions, we coated lipoplexes with two different artificial PCs made of Fibronectin (FBN) and Val-Gly-Asp (VGA) tripeptide that are recognized by receptors expressed on the ocular surface. Both these functionalizations remarkedly boosted internalization in corneal epithelial cells with respect to pristine (i.e., uncoated) lipoplexes. This opens the gateway for the exploitation of artificial protein corona in targeted ocular delivery, which will significantly influence the development of novel nanomaterials.

Ocular bacterial infections represent a serious problem that affecting people of all age and genders. These infections can lead to visual impairment and blindness if not properly treated. The current study evaluates the antimicrobial resistance profiles and the resistance trend of both Staphylococcus aureus (S. aureus) and coagulase-negative staphylococci (CoNS), the main pathogens involved in eye infections. A total of 322 isolates of S. aureus and CoNS, were collected from patients with bacterial conjunctivitis and keratitis at the “Luigi Vanvitelli” University Hospital of Campania in Naples, Italy, between 2017 and 2020. The isolated bacteria showed a high percentage of resistance to methicillin and other antibiotics commonly used for the treatment of ocular infections. Trends in antibiotic resistance were not encouraging, recording—especially among CoNS strains—an increase of more than 20% in resistance to methicillin and aminoglycosides during the study period. Instead, the resistance rates to tetracycline had a significant decrease in CoNS isolates while no changes in their susceptibility to fluoroquinolones and macrolides were observed. However, all isolates showed no resistance to trimethoprim/sulfamethoxazole and chloramphenicol. In this scenario, preventive identification of the infection causative agents and the evaluation of the antimicrobial susceptibility patterns are essential to set up an ocular infection effective drug treatment and also prevent antibiotic resistance.

Abstract Legal positivism of modernity, built on the will of the legislature, today is interesting, considering its differences with the logical legal positivism, because it is based on a political decision. Because of its construction on willed decision, is intertwined with the need a constant recourse to the courts of justice to settle questions pre or post legal, reguarding radical anthropological or existential problems of one man or of the whole policy society. The Swedish example can be used as an important model for understanding where a possible corrective methodology legal-hermeneutics of the high courts of justice is going. It also helps to better understand the recent security legislations, in some countries - including European countries - against terrorism, without any opposition of national and supranational political and legal systems. Key words: Legal-positivism of modernity, Legal-hermeneutics, Security state. Riassunto Il positivismo giuridico della modernità, costruito sulla volontà del legislatore, trova nuovo interesse, se considerato nelle sue differenze con il positivismo giuridico logico, proprio per il suo affondare le radici nella decisione politica. Il suo fondamento volitivo-decisionista lo vede intrecciarsi con la necessità odierna del ricorso costante alle Corti di Giustizia per risolvere questioni pre-giuridiche o post-giuridiche, attinenti, per esempio, a radicali problematiche antropologiche o esistenziali di soggetti singoli, ma anche di intere società politiche. L'esempio svedese si rivela modello di forte rilievo per cogliere fino in fondo la direzione di senso della metodologia giuridico-ermeneutica correttiva possibile delle alte Corti di Giustizia, ma anche per comprendere fino in fondo, dal punto di vista giuridico oltre che politico, il recente ricorso da parte di alcuni stati, anche europei, a legislazionidi sicurezza contro il terrorismo, senza resistenza da parte degli ordinamenti giuridico-politici nazionali e sovranazionali. Parole chiave: Positivismo giuridico della modernità, ermeneutica giuridica, sicurezza dello Stato

Exogenous fungal endophthalmitis (EXFE) represents a rare complication after penetrating ocular trauma of previously unresolved keratitis or iatrogenic infections, following intraocular surgery such as cataract surgery. The usual latency period between intraocular inoculation and presentation of symptoms from fungal endophthalmitis is several weeks to months as delayed-onset endophthalmitis. Aspergillus spp., is the most common causative mould pathogen implicated in this ocular infection and early diagnosis and prompt antimicrobial treatment, concomitantly in most cases with expert surgical attention, reduce unfavorable complications and increase the possibility of eye function preservation. Topical, intravitreal and systemic antifungal molecules are the mainstay of a medical approach to the disease and azoles, polyenes and in particular cases echinocandins are the pharmacological classes most commonly used in clinical practice. This review discusses pharmacokinetics and pharmacodynamic of antifungal agents in their principal modes of administration with a focus on their ability to achieve high drug concentration in the vitreous and ocular tissues.

The ocular surface microbiota refers to the resident non-pathogenic microorganisms that colonize conjunctiva and cornea. Several studies have shown that ocular surface epithelial cells can respond selectively to specific components of ocular pathogenic bacteria by producing pro-inflammatory cytokines and, in contrast, they do not respond to non-pathogenic bacteria, thus supporting the colonization by a real microbiota. However, the analysis of the ocular microbiome composition is essential for understanding the pathophysiology of various ophthalmic diseases. In this scenario, the first studies, which used microbiological culture techniques, reported a less diverse profile of the ocular microbiota compared with that recently discovered using new molecular-based methods. Indeed, until a few years ago, the microbiota of the ocular surface appeared to be dominated by Gram-positive and a few Gram-negative bacteria, as well as some fungal strains. In contrast, genomics has nowadays detected a remarkable diversity in the ocular surface microorganisms. Furthermore, recent studies suggest that the microbiota of other areas of the body, such as the gut and oral microbiota, are involved in the pathophysiology of several ophthalmic diseases. The aim of the present study is to highlight the current evidence on the ocular surface microbiota to better understand it and to investigate its potential role in the development of ophthalmic diseases.

Sin resumen disponible