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Fedele Passidomo,1 Francesco Pignatelli,1 Giuseppe Addabbo,1 Ciro Costagliola2 1Comprehensive Ophthalmology Unit, S.S. Annunziata Hospital, Taranto, Italy; 2Department of Medicine and Health Sciences “V. Tiberio”, University of Molise, Campobasso, ItalyCorrespondence: Fedele PassidomoComprehensive Ophthalmology Unit, S.S. Annunziata Hospital, Via Francesco Bruno, 1, Taranto, 74121, ItalyTel +393288569125Email dotpaoli@yahoo.itAbstract: Infectious and traumatic corneal diseases require adequate therapy against infection and promote re-epithelialization. The appearance of multidrug-resistant bacterial strains, induced by excessive use of antibiotics in the treatment of infectious diseases, has urged researchers to study new antimicrobial formulations. Ozonated oils have demonstrated antiseptic (antibacterial, antifungal and antiviral) and reparative properties and can be proposed for the prevention and treatment of acute and chronic local infections, as an alternative to conventional topical antimicrobials. In ocular treatment, ozonated oil can exert tissue repair and anti‐inflammatory and bactericidal activity. Moreover, its specific formulation makes it well tolerated and biocompatible with the ocular surface. Herein, we report on three cases of corneal inflammation (dendritic epithelial keratitis, corneal injuries caused by olive leaves, and neurotrophic corneal ulcer), treated with liposomal ozonated oil (Ozodrop®, FB VISION S.p.a. San Benedetto del Tronto, Italy), successfully resolved using topical liposomal ozonated oil.Keywords: corneal trauma, corneal ulcers, corneal wound healing, infectious keratitis, ozonated oil

Ciro Costagliola,1 Mario Sbordone,2 Stefano Gandolfi,3 Luca Cesari,4 Gianluca Furneri,5 Antonio Maria Fea6 1Department of Medicine & Health Sciences “V. Tiberio”, University of Molise, Campobasso, Italy; 2Ophthalmology Unit, Santa Maria Delle Grazie Hospital, Pozzuoli, Naples, Italy; 3Ophthalmology Unit, Department of Biological, Biotechnological and Translational Sciences, University of Parma, Parma, Italy; 4UOC Ophthalmology - Area 5, Ascoli Piceno, San Benedetto del Tronto, Italy; 5EBMA Consulting SRL, Melegnano, Milan, Italy; 6Department of Surgical Sciences, University of Turin, Turin, ItalyCorrespondence: Gianluca FurneriEBMA Consulting SRL, Via per Carpiano, 2 – 20077, Melegnano, MI ItalyEmail gianluca.furneri@ebmaconsulting.comAbstract: Medical therapy is the first treatment choice for most patients with glaucoma; however, in a relevant proportion of patients, intraocular pressure (IOP) reduction is achieved with multi-therapy and/or high therapeutic doses. Conventional surgery is the standard alternative to medical therapy when this is not effective or not tolerated. Recently, selective laser trabeculoplasty (SLT) has been advocated as first-line therapy, and “minimally invasive glaucoma surgery” (MIGS) has been developed as safer and less traumatic surgical intervention for patients with glaucoma. Schlemm’s canal surgery has emerged as one of the approaches with the most favorable risk-benefit profile for glaucoma patients in need of cataract surgery. However, despite the promising results, use of MIGS in Italy has been extremely low. We aimed to investigate the reasons of the lower-than-expected use of Schlemm’s canal-based MIGS devices in Italy, share our perspective on their potential place in therapy, and give practical suggestions to improve the management of glaucoma patients.Keywords: minimally invasive surgery, glaucoma, IOP reduction, trabecular bypass, cataract surgery

Francesco Semeraro,1 Francesco Morescalchi,1 Andrea Russo,1 Elena Gambicorti,1 Andrea Pilotto,2 Francesco Parmeggiani,3 Silvia Bartollino,4 Ciro Costagliola4 1Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy; 2Department of Clinical and Experimental Sciences, Neurology Unit, University of Brescia, Brescia, Italy; 3Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy; 4Department of Medicine and Health Science “V. Tiberio”, University of Molise, Campobasso, ItalyCorrespondence: Silvia BartollinoDepartment of Medicine and Health Science “V. Tiberio”, University of Molise, Via de Santis, Campobasso 86100, ItalyEmail silvia.bartollino@unimol.itAbstract: Central serous chorioretinopathy (CSC) is a common retina disease and has a relative high recurrence rate, etiology, and pathogenesis of which remains largely ambiguous. The effects on the retina are usually self-limited, although some people are left with permanent vision loss due to progressive and irreversible photoreceptor damage or retinal pigment epithelium atrophy. There have been a number of interventions used in CSC, including, but not limited to, laser treatment, photodynamic therapy (PDT), intravitreal injection of anti-vascular endothelial growth factor agents, and subthreshold lasers. It is not clear whether there is a clinically important benefit to treating acute CSC, which often resolves spontaneously as part of its natural history. Of the interventions studied to date, PDT and micropulse laser treatment appear the most promising. Keywords: central serous chorioretinopathy, acute central serous chorioretinopathy, chronic central serous chorioretinopathy

Silvia Bartollino,1 Flavia Chiosi,1 Silvio di Staso,2 Maurizio Uva,3 Arduino Pascotto,1 Michele Rinaldi,4 Jan M Keppel Hesselink,5 Ciro Costagliola1 1Eye Clinic, Department of Medicine and Health Sciences “V. Tiberio,” University of Molise, Campobasso, Italy; 2Department of Surgical Science, Ophthalmic Clinic, University of L’Aquila, L’Aquila, Italy; 3Eye Clinic, University of Catania, Catania, Italy; 4Department of Ophthalmology, University della Campania Luigi Vanvitelli, Naples, Italy; 5Department of Health, University of Witten/Herdecke, Witten, Germany Abstract: Phenytoin is a non-sedative barbiturate derivate and has been recently rediscovered as a neuroprotective and retinoprotective compound in patients affected by optic neuritis secondary to multiple sclerosis. However, currently there are still no neuroprotective compounds registered and available in the clinic. We reviewed the literature supporting the retinoprotective properties of phenytoin and analyzed the various approaches and definitions from the first research periods onwards. The retinoprotective role of phenytoin was already known in the 1970s, but only recently has this effect been rediscovered, confirming that it could indeed provide structural protection of the retinal cells. Keywords: phenytoin, neuroprotection, retinoprotection, optic neuritis, multiple sclerosis

Andrea Russo,1 Nicolò Scaroni,1 Elena Gambicorti,1 Raffaele Turano,1 Francesco Morescalchi,1 Ciro Costagliola,2 Francesco Semeraro1 1Eye Clinic, Department of Neurological and Vision Sciences, University of Brescia, Brescia, 2Eye Clinic, Department of Health Sciences, University of Molise, Campobasso, Italy Purpose: The aim of this study was to evaluate whether indomethacin eye drops and intravitreal ranibizumab (IVR) injections would provide additional benefit over ranibizumab alone in the treatment of choroidal neovascularization (CNV). Participants and methods: This was a randomized, prospective pilot study of eyes with new-onset CNV. Fifty-eight patients were randomized 1:1 into a ranibizumab monotherapy (RM) group and a ranibizumab plus indomethacin (RI) group. All patients received monthly 0.5 mg IVR injections for 3 months, followed by monthly injections administered as needed. RI group patients also self-administered one drop of 0.5% indomethacin three times a day for 12 months. All patients were followed up for 12 months. Results: At 12 months, both groups showed significant improvement in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). The mean BCVA change from baseline to 12 months was -0.12±0.04 LogMAR and -0.20±0.04 LogMAR in the RM and RI groups, respectively, with the degree of change being significantly different between the two groups (P=0.04). At 12 months, the mean CRT in the RM group (316±41.2 µm) was significantly higher than that in the RI group (287±31.5 µm; P=0.004). The mean required number of IVR injections was 7.38±0.78 and 6.34±0.67 in the RM and RI groups, respectively (P

Jan M Keppel Hesselink,1 Flavia Chiosi,2 Ciro Costagliola2 1University of Witten/Herdecke, Witten, Germany; 2Eye Clinic, Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy Abstract: Resolvins are a novel class of lipid-derived endogenous molecules (autacoids) with potent immunomodulating properties, which regulate the resolution phase of an active immune response. These modulating factors are locally produced, influencing the function of cells and/or tissues, which are produced on demand and subsequently metabolized in the same cells and/or tissues. This review is focused on certain lipid autacoids with putative relevance for ophthalmology in general and for dry eye more specifically. We also briefly investigate the concept of aliamides and the role of palmitoylethanolamide in ophthalmology, and analyze in more detail the putative role and the preclinical and clinical development of resolvins as emerging treatments for dry eye and related disorders, with a focus on one of the lead resolvin derivatives – RX-10045. Keywords: resolvins, autacoids, aliamides, dry eye, palmitoylethanolamide, inflammation, ophthalmology, protection

Francesco Semeraro,1 Barbara Arcidiacono,2 Giuseppe Nascimbeni,1 Martina Angi,1 Barbara Parolini,2 Ciro Costagliola31Eye Clinic, Department of Neurological Sciences and Vision, University of Brescia, Brescia, Italy; 2Department of Ophthalmology, S. Anna Hospital, Brescia, Italy; 3Eye Clinic, Department of Health Sciences, University of Molise, Campobasso, ItalyAbstract: Juvenile idiopathic arthritis-related uveitis is the most common type of uveitis in childhood and one of the main causes of visual impairment in children. The introduction of biological treatment has widened the range of therapeutic options for children with uveitis refractory to standard nonbiologic immunosuppressants. Data from clinical trials suggest that both adalimumab and infliximab have demonstrated effectiveness and safety in open-label studies, although no large, randomized, controlled trials have been reported so far. The role of etanercept in treating juvenile idiopathic arthritis-related uveitis is not yet well defined. In our experience, anti-tumor necrosis factor therapy has been shown to be more effective than steroids and/or methotrexate in treating uveitis. Up to now, tumor necrosis factor blocking compounds have been reserved for the treatment of the most severe cases of refractory uveitis, and larger prospective clinical trials are required in order to better assess the safety of these new compounds.Keywords: adalimumab, etanercept, infliximab

F Semeraro,1 F Morescalchi,1 S Duse,1 F Parmeggiani,2 E Gambicorti,1 C Costagliola31Department of Medical and Surgical Specialties, Radiological Specialties and Public Health, Ophthalmology Clinic, University of Brescia, Brescia, Italy; 2Department of Ophthalmology, University of Ferrara, Ferrara, Italy; 3Department of Health Science, Ophthalmology Clinic, University of Molise, Campobasso, ItalyBackground: Vascular endothelial growth factor (VEGF) is a naturally occurring glycoprotein in the body that acts as a growth factor for endothelial cells. It regulates angiogenesis, enhances vascular permeability, and plays a major role in wet age-related macular degeneration. The consistent association between choroidal neovascularization and increased VEGF expression provides a strong reason for exploring the therapeutic potential of anti-VEGF agents in the treatment of this disorder. Blockade of VEGF activity is currently the most effective strategy for arresting choroidal angiogenesis and reducing vascular permeability, which is frequently the main cause of visual acuity deterioration. In recent years, a number of other molecules have been developed to increase the efficacy and to prolong the durability of the anti-VEGF effect. Aflibercept (EYLEA®; Regeneron Pharmaceutical Inc and Bayer), also named VEGF Trap-eye, is the most recent member of the anti-VEGF armamentarium that was approved by the US Food and Drug Administration in November 2011. Because of its high binding affinity and long duration of action, this drug is considered to be a promising clinically proven anti-VEGF agent for the treatment of wet maculopathy.Objective: This article reviews the current literature and clinical trial data regarding the efficacy and the pharmacological properties of VEGF-Trap eye and describes the possible advantages of its use over the currently used "older" anti-VEGF drugs.Methods: For this review, a search of PubMed from January 1989 to May 2013 was performed using the following terms (or combination of terms): vascular endothelial growth factors, VEGF, age-related macular degeneration, VEGF-Trap eye in wet AMD, VEGF-Trap eye in diabetic retinopathy, VEGF-Trap eye in retinal vein occlusions, aflibercept. Studies were limited to those published in English.Results and conclusion: Two Phase III clinical trials, VEGF Trap-eye Investigation of Efficacy and Safety in Wet AMD (VIEW) 1 and 2, comparing VEGF Trap-eye to ranibizumab demonstrated the noninferiority of this novel compound. The clinical equivalence of this compound against ranibizumab is maintained even when the injections are administered at 8-week intervals, which indicates the potential to reduce the risk of monthly intravitreal injections and the burden of monthly monitoring.Keywords: aflibercept, AMD, neovascularization, VEGF, VEGF inhibition, VEGF-Trap eye

Based on the observation of the course of callosal fibres and of their artero-venous support as appearing in a microanatomic study, the Authors propose a variant of standard callosotomy procedure by the introduction of the transverse section of callosal fibres. This technique would allow the surgeon to spare a larger number of callosal fibres by the combined effect of a lower direct mechanical traction on fibres and a lower impact on artero-venous microcircle. The neuropsychological outcome of the patients who underwent this kind of procedure was evaluated. Fourteen patients affected by occupying-space lesions involving the anterior and middle third ventricle were included in the study. Ten patients underwent transverse callosotomy, four subjects received standard sagittal callosotomy. A control group was also included in the study. All patients underwent a pre-operative and six months post-operative neuropsychological evaluation focused on performance at cognitive and attentional tasks. No disturbances in executive function were observed in either group. Patients receiving transverse callosotomy performed as well as control group subjects in attentive tasks, which is not the case of patients undergoing sagittal callosotomy who show a marked deficit in selective attention for left side visual field. The observed more favourable neuropsychological outcome supports transverse callosotomy as a valid alternative method to standard longitudinal callosotomy in third ventricle surgery.