OnyxTMGel or Coil versus Hydrogel as Embolic Agents in Endovascular Applications: Review of the Literature and Case Series.

This review focuses on the use of conventional gel or coil and "new" generation hydrogel used as an embolic agent in endovascular applications. In general, embolic agents have deep or multidistrict vascular penetration properties as they ensure complete occlusion of vessels by exploiting the patient's coagulation system, which recognises them as substances foreign to the body, thus triggering the coagulation cascade. This is why they are widely used in the treatment of endovascular corrections (EV repair), arteriovenous malformations (AVM), endoleaks (E), visceral aneurysms or pseudo-aneurysms, and embolisation of pre-surgical or post-surgical (iatrogenic) lesions. Conventional gels such as Onyx or coils are now commercially available, both of which are frequently used in endovascular interventional procedures, as they are minimally invasive and have numerous advantages over conventional open repair (OR) surgery. Recently, these agents have been modified and optimised to develop new embolic substances in the form of hydrogels based on alginate, chitosan, fibroin and other polymers to ensure embolisation through phase transition phenomena. The main aim of this work was to expand on the data already known in the literature concerning the application of these devices in the endovascular field, focusing on the advantages, disadvantages and safety profiles of conventional and innovative embolic agents and also through some clinical cases reported. The clinical case series concerns the correction and exclusion of endoleak type I or type II appeared after an endovascular procedure of exclusion of aneurysmal abdominal aortic (EVAR) with a coil (coil penumbra released by a LANTERN microcatheter), the exclusion of renal arterial malformation (MAV) with a coil (penumbra coil released by a LANTERN microcatheter) and the correction of endoleak through the application of Onyx 18 in the arteries where sealing by the endoprosthesis was not guaranteed.

Synthetic Haemostatic Sealants: Effectiveness, Safety, and In Vivo Applications.

Rapid haemostasis during surgery is essential when one wants to reduce the duration of operations, reduce the need for transfusions, and above all when one wants to achieve better patient management. The use of haemostatic agents, sealants, and adhesives improves the haemostatic process by offering several advantages, especially in vascular surgery. These agents vary widely in their mechanism of action, composition, ease of application, adhesion to wet or dry tissue, immunogenicity, and cost. The most used are cyanoacrylate-based glues (Glubran 2) or polysaccharide hydrogel-microsphere powder (AristaTMAH). This work is based on a retrospective study carried out on a sample of patients with different vascular diseases (FAV, pseudoaneurysm, and PICC application) in which two different haemostatic sealants were used. The aim was to assess the safety, the advantages, and the ability of both sealants to activate the haemostatic process at the affected site, also in relation to their chemical-physical characteristics. The obtained results showed that the application of Glubran 2 and AristaTMAH as surgical wound closure systems is effective and safe, as the success achieved was ≥94% on anastomoses of FAV, 100% on stabilization of PICC catheters, and ≤95% on pseudoaneurysms.

Retinal phakomatosis and Von Hippel-Lindau peripheral capillary hemangioblastoma: proposal for staged surgery.

PURPOSE: Retinal capillary hemangioblastoma (RCH) is present in about half of the carriers of the VHL (von Hippel-Lindau) gene mutation and can lead to the evolution of blindness. Herewith is a proposal for surgical intraretinal feeder vessel ligature to induce ischemia the phakoma and to resolve the exudative secondary retinal detachment, with satisfying results at the 6 months follow-up end point. METHODS: The patient underwent a chandelier-assisted 23 G pars plana vitrectomy with valved trocars. A bimanual transretinal ligature of the hemangioblastoma's feeder vessel was performed, followed by localized endolaser to ablate the surrounding retina and capillaries, and a Polydimethylsiloxane 1000 (PDMS 1000) final tamponade. After 3 months, exchange PDMS/air/balanced salt solution (BSS), phacoemulsification, and in-the-bag intraocular lens (IOL) implantation were performed. RESULTS: At sixth month, fundus fluorescein angiography (FFA) showed a significant reduction of blood flow in the phakoma. Final best-corrected visual acuity (BCVA) was 6/6 (9 lines gain obtained compared to the baseline time). CONCLUSIONS: This surgical technique seems to be effective and promising for the treatment of VHL retinal capillary hemangioblastomas and their related retinal complications.

Expanded Polytetrafluoroethylene Membranes for Vascular Stent Coating: Manufacturing, Biomedical and Surgical Applications, Innovations and Case Reports.

Coated stents are defined as innovative stents surrounded by a thin polymer membrane based on polytetrafluoroethylene (PTFE)useful in the treatment of numerous vascular pathologies. Endovascular methodology involves the use of such devices to restore blood flow in small-, medium- and large-calibre arteries, both centrally and peripherally. These membranes cross the stent struts and act as a physical barrier to block the growth of intimal tissue in the lumen, preventing so-called intimal hyperplasia and late stent thrombosis. PTFE for vascular applications is known as expanded polytetrafluoroethylene (e-PTFE) and it can be rolled up to form a thin multilayer membrane expandable by 4 to 5 times its original diameter. This membrane plays an important role in initiating the restenotic process because wrapped graft stent could be used as the treatment option for trauma devices during emergency situations and to treat a number of pathological vascular disease. In this review, we will investigate the multidisciplinary techniques used for the production of e-PTFE membranes, the advantages and disadvantages of their use, the innovations and the results in biomedical and surgery field when used to cover graft stents.

Genetic Basis and Molecular Mechanisms of Uveal Melanoma Metastasis: A Focus on Prognosis.

Uveal melanoma (UM) is the most frequently found primary intraocular tumor, although it accounts for only 5% of all melanomas. Despite novel systemic therapies, patient survival has remained poor. Indeed, almost half of UM patients develop metastases from micro-metastases which were undetectable at diagnosis. Genetic analysis is crucial for metastatic risk prediction, as well as for patient management and follow-up. Several prognostic parameters have been explored, including tumor location, basal dimension and thickness, histopathologic cell type, vascular mimicry patterns, and infiltrating lymphocytes. Herein, the Authors review the available literature concerning cytogenetic prognostic markers and biochemical pathways correlated to UM metastasis development.

Impact of COVID-19 on surgical activities and personnel: lessons for the future.

BACKGROUND: COVID-19 pandemic has impacted professional, economic and social activities. In the surgical field, it has brought changes to operating activities, the organization of workforces, the protection measures for patients and personnel against possible intraoperative transmissions as well as training young surgeons. This study intends to assess the extent of this impact in our institution. METHODS: The patients operated on in nine Operating Units (OUs) in the period February 1 - March 31, 2020, with follow-ups on April 30, 2020, were evaluated both retrospectively and prospectively. Organizational, clinical and impact parameters on staff were evaluated. RESULTS: Of the 833 consecutive admitted patients, 742 were operated on, 705 of whom were recruited for the study. Compared to the same period in 2019 there was a decrease in the number of operations (742 compared to 1187), similar use of intensive care unit (ICU), a diagnostic activity only for symptomatic patients, heterogeneity in organizational behaviors, an impact on staff who highlighted concerns about getting sick or passing the infection on to others (87.64%) or their family members (75.14%). CONCLUSIONS: The present study made it possible to detect the need to make significant changes in the clinical, organizational and teaching fields, for which some operational proposals are suggested.

Visual Performance and Quality of Life after Femtosecond Laser-Assisted Cataract Surgery with Trifocal IOLs Implantation.

PURPOSE: To assess visual performance and quality of life after implantation of diffractive trifocal IOLs with enhanced depth of focus (Acriva Reviol Tri-ED) compared to monofocal IOLs. SETTING: Ophthalmology Clinic, Department of Medicine and Science of Ageing, University "G. d'Annunzio" Chieti-Pescara, Italy. DESIGN: Prospective clinical study. METHODS: This study comprised 36 eyes of 18 patients with senile cataract candidates for phacoemulsification and implantation of the Acriva Reviol Tri-ED (Group 1-18 eyes) and the AcrySof IQ Monofocal IOL SN60WF (Group 2-18 eyes). The main outcome measures, over a 6-month follow-up period, were uncorrected and corrected visual acuity at different distances (40, 60 cm and 4 m), defocus curve, contrast sensitivity and wavefront error. Patient satisfaction was evaluated by means of the NEI-RQL-42 questionnaire. RESULTS: At 180 days postoperatively, the difference of the UCDVA and CDVA between the groups was not statistically significant (p = 0.888 and p = 0.843, respectively). The difference between the groups was statistically significant for UCIVA (p = 0.019) and UCNVA (p = 0.036). The mean values of contrast sensitivity under photopic and mesopic conditions were not significantly different between the groups. The RMS of spherical aberration was significantly lower in Group 1 compared to Group 2. The NEI-RQL-42 questionnaire showed statistically significant differences between the groups for the dependence on correction (p < 0.001). CONCLUSIONS: The diffractive trifocal IOL with enhanced depth of focus Acriva Reviol Tri-ED was effective in improving functional capacity for intermediate and near vision compared to monofocal IOLs and provided a good quality of vision due to a significant reduction in spherical aberration.

Virtual learning solutions in COVID-19 era: University Italian Ophthalmology department perspective.

INTRODUCTION: Few months after the COVID-19 pandemic burst, many aspects of the human life, including education, dramatically changed. Because of the lockdown measures taken to limit the virus spread in Italy, in-person teaching and learning have been interrupted in all health care disciplines and readapted in virtual formulae. METHODS: As academic ophthalmology departments, we had to maintain the educational needs of medical and orthoptic students, internships, surgical training of residents, as well as to cover the scientific update of health care personnel (HCPs), and the continuation of research and academic activities. To assure these needs we ideated an educational strategy and a team, which was then translated on a multichannel virtual platform created with Microsoft Teams. RESULTS: In this platform there were 21 channels organized in a public view mode, open to all Team members, or in private view mode to separate non-permanent HCPs, internships, residents, and students' tasks, from permanent HCPs tasks. Virtual channels were dedicated to provide theoretical lessons, clinical cases, surgical video, internal meetings and webinar, to offer news from scientific societies, requests of appointments from biomedical companies, links with ophthalmological websites, to move forward research projects, to participate at institutional academic duties, and to obtain feedbacks from users. Residents continued their training on surgery using a surgical simulator, after consulting an agenda uploaded into the dedicated virtual channel. CONCLUSION: These positive initial results should represent a boost to rapidly proceed with the development of even more versatile virtual learning solutions, given that the forecasts for the duration of the COVID-19 pandemic are not encouraging.

New Insights into Molecular Oncogenesis and Therapy of Uveal Melanoma.

Uveal melanoma (UM), which is the most common cancer of the eye, was investigated in recent years by many teams in the field of biomedical sciences and eye clinicians. New knowledge was acquired on molecular pathways found to be dysregulated during the multistep process of oncogenesis, whereas novel therapeutic approaches gave significant results in the clinical applications. Uveal melanoma-affected patients greatly benefited from recent advances of the research in this eye cancer. Tumour biology, genetics, epigenetics and immunology contributed significantly in elucidating the role of different genes and related pathways during uveal melanoma onset/progression and UM treatments. Indeed, these investigations allowed identification of new target genes and to develop new therapeutic strategies/compounds to cure this aggressive melanoma of the eye. Unfortunately, the advances reported in the treatment of cutaneous melanoma have not produced analogous benefits in metastatic uveal melanoma. Nowadays, no systemic adjuvant therapy has been shown to improve overall survival or reduce the risk of metastasis. However, the increasing knowledge of this disease, and the encouraging results seen in clinical trials, offer promise for future effective therapies. Herein, different pathways/genes involved in uveal melanoma onset/progression were taken into consideration, together with novel therapeutic approaches.

Topical Anesthesia in Children With Intraoperative Adjustable Strabismus Surgery.

PURPOSE: To evaluate strabismus surgery with intraoperative adjustment of sutures under topical anesthesia in children. METHODS: Nineteen children with horizontal deviation underwent a one-stage surgical technique performed under topical anesthesia. Surgery consisted of unilateral or bilateral recession and/or resection of horizontal muscles or the medial or lateral rectus muscles, with intraoperative adjustment of sutures based on alternate prism cover test. Follow-up was done at 1 day and 1, 3, and 6 months postoperatively. RESULTS: Mean age at surgery was 12.68 ± 2.50 years (range: 8 to 16 years). Mean preoperative angle of deviation was 24.21 ± 11.20 prism diopters (PD) (range: -50 to +30 PD) at distance. Mean postoperative angle of deviation at 6 months was 4.11 ± 2.87 PD (range: -10 to +10 PD) at distance. In esotropic patients, the average angle of deviation decreased from +23.80 ± 5.89 PD preoperatively to +4.80 ± 3.35 PD at 6 months, whereas in exotropic patients it decreased from -24.36 ± 12.76 to -3.86 ± 2.77 PD. Seventeen of 19 patients (89%) remained comfortable during surgery, whereas 2 needed an intravenous injection of propofol. The success rate, defined by a postoperative residual angle of deviation of ±8 PD or less, was 89% at 6 months. CONCLUSIONS: Strabismus surgery with intraoperative suture adjustment under topical anesthesia in children is a tolerable procedure with encouraging outcomes, representing an alternative to general anesthesia in well-selected children. Clinical evaluation of children and parents is fundamental to predict a likely poor collaboration of the child during surgery, which, if present, would require surgery under general anesthesia. [J Pediatr Ophthalmol Strabismus. 2019;56(3):173-177.].

High prevalence of serum IgG antibodies reacting to specific mimotopes of BK polyomavirus, a human oncogenic polyomavirus, in patients affected by uveal melanoma.

The uveal melanoma (UM) is the most common human intraocular tumor. The BK polyomavirus (BKPyV) is a small DNA tumor virus whose footprints have been detected in different human cancers. BKPyV has oncogenic potential. Indeed, BKPyV, when inoculated into experimental animals, induces tumors of different histotypes, whereas in vitro, it transforms mammalian cells, including human cells from distinct tissues. In this investigation, the association between UM and BKPyV was studied employing indirect enzyme-linked immunosorbent assays (ELISAs) using synthetic peptides that mimic BKPyV viral capsid 1 (VP1) antigens. Indirect ELISAs were used to detect serum IgG antibodies against this polyomavirus with oncogenic potential in samples from patients with UM and controls, represented by healthy subjects (HS). It was found that serum samples from patients with UM had a higher prevalence of BKPyV antibodies, 85% (51/60), compared with that detected in HS1, 62% (54/87), and HS2, 57% (68/120). The different prevalence of BKPyV antibodies detected in UM versus the two control groups, HS1 and HS2, is statistically significant (p < 0.005). Our immunologic data suggest a significantly higher prevalence of antibodies against BKPyV VP1 epitopes in serum samples from patients with UM compared with HS. These results indicate an association between UM and BKPyV, suggesting that this small DNA tumor virus may be a cofactor in the UM onset or progression.

Comparison of the Efficacy of Dexamethasone, Nepafenac, and Bromfenac for Preventing Pseudophakic Cystoid Macular Edema: an Open-label, Prospective, Randomized Controlled Trial.

PURPOSE: To evaluate the incidence of pseudophakic cystoid macular edema (PCMO) in patients treated with corticosteroids alone or in combination with bromfenac or nepafenac eyedrops after uneventful cataract surgery. MATERIALS AND METHODS: Prospective, randomized, open-label, placebo-controlled clinical trial. Patients who underwent routine cataract surgery with intraocular lens (IOL) implant were randomly divided into three groups receiving either bromfenac or nepafenac in association with dexamethasone or dexamethasone alone (control group) postoperatively. Best-corrected visual acuity (BCVA) measurement, slit lamp and fundus examination and optical coherence tomography (OCT) were performed preoperatively, 1 and 5 weeks after surgery. Primary outcome was defined as patients (%) in whom macular edema developed within 5 weeks after cataract surgery; secondary end points were patients (%) with BCVA improvement from pre-op through 5 weeks after surgery and corneal toxicity. RESULTS: A total of 144 patients completed the study, 48 for each group. In all groups, mean central subfield thickness at OCT increased significantly 5 weeks after surgery (p < 0.01). However, at this time point, four patients (8.3%) of the control group and none in nepafenac and bromfenac groups developed PCMO (p = 0.016). Compared with baseline, mean BCVA significantly improved both at 1 and 5 weeks in all groups (p < 0.01). At 1 week, the nepafenac group showed a mean BCVA significantly lower compared with both the control (p = 0.038) and bromfenac group (p = 0.002). CONCLUSIONS: Co-administration of nepafenac or bromfenac and steroids in patients who underwent routine cataract surgery is associated with a lower incidence of PCMO compared with steroid monotherapy.

Specific Detection of Serum Antibodies against BKPyV, A Small DNA Tumour Virus, in Patients Affected by Choroidal Nevi.

Ocular or choroidal nevus (CN) is a rare benign neoplastic lesion of the eye. The cause of CN onset/progression, which arises from the transformation of ocular melanocytes, is not known. A fraction of CN patients may develop uveal melanoma. The objective of this study was to investigate the association between CN and BK polyomavirus (BKPyV), a small DNA tumor virus. Serum IgG antibodies which react with BKPyV antigens were analyzed. An indirect E.L.I.S.A. using synthetic peptides that mimic BKPyV antigens was employed. Serum antibodies against BKPyV were also investigated by haemagglutination inhibition (HAI) assay. Sera were from CN patients and healthy subject (HS) were the control. A statistically significant higher prevalence of antibodies against BKPyV capsid protein antigens in serum samples from CN patients was detected, compared to HS, using two independent techniques, indirect E.L.I.S.A. and HAI (87.3% CN vs. 62.1% HS and 91.5% CN vs. 64.4% HS, respectively; p < 0.005). Our data suggest an association exists between CN and BKPyV indicating that this small DNA tumor virus could be responsible in the onset of this benign neoplastic lesion affecting eye melanocytes. This investigation reports the association between choroidal nevi and BKPyV infection for the first time. These data are innovative in this field and may represent a starting point for further investigation into the putative role of BKPyV in CN onset/progression.

Early Deep Anterior Lamellar Keratoplasty (DALK) for Acanthamoeba Keratitis Poorly Responsive to Medical Treatment.

PURPOSE: To evaluate the success (eradication of infection) or failure (recurrence of infection in the cornea or sclera, or endophthalmitis) of early therapeutic deep anterior lamellar keratoplasty (DALK) for active Acanthamoeba keratitis (AK) poorly responsive to medical treatment. METHODS: Retrospective, noncomparative case series of 11 patients (11 eyes) affected by active AK poorly responsive to medical treatment who underwent early therapeutic DALK. Surgery was performed in all cases within 30 to 60 days from the onset of symptoms. Corneal ulcer depth was less than 300 µm in all cases. A 3-drug combination (chlorhexidine gluconate, propamidine isethionate, and neomycin sulfate) was the antiamoebic protocol used preoperatively and postoperatively. Cannula big bubble and "layer-by-layer" manual dissection techniques were performed. Eradication of infection, episodes of rejection, postoperative endothelial cell density, and the best spectacle-corrected visual acuity were evaluated. Histologic examination of surgical margins was performed, and margin clearance was assessed. Mean follow-up was approximately 2 years. RESULTS: Four descemetic DALK and 7 predescemetic DALK were performed. One small Descemet membrane rupture occurred. Peripheral surgical margins were free of infection in all cases. Deep surgical margins not free from infection were found in 2 cases. However, no episode of infection recurrence was observed. The postoperative average best spectacle-corrected visual acuity was 0.8 (range, 0.6-1.0). No case of rejection was recorded. CONCLUSIONS: Early therapeutic DALK could be considered a new approach to eradicate active infection in AK cases poorly responsive to medical treatment, with significant ulcer in the optical zone. Further studies are needed to validate this new indication for DALK.

Extracellular matrix assessment of infected chronic venous leg ulcers: role of metalloproteinases and inflammatory cytokines.

Chronic venous ulcer (CVU) represents a dreaded complication of chronic venous disease (CVD). The onset of infection may further delay the already precarious healing process in such lesions. Some evidences have shown that matrix metalloproteinases (MMPs) are involved and play a central role in both CVUs and infectious diseases. Two groups of patients were enrolled to evaluate the expression of MMPs in infected ulcers and the levels of inflammatory cytokines as well as their prevalence. Group I comprised 63 patients (36 females and 27 males with a median age of 68·7 years) with infected CVUs, and group II (control group) comprised 66 patients (38 females and 28 males with a median age of 61·2 years) with non-infected venous ulcers. MMP evaluation and dosage of inflammatory cytokines in plasma and wound fluid was performed by means of enzyme-linked immunosorbent assay test; protein extraction and immunoblot analysis were performed on biopsied wounds. The first three most common agents involved in CVUs were Staphylococcus aureus (38·09%), Corynebacterium striatum (19·05%) and Pseudomonas aeruginosa (12·7%). In this study, we documented overall higher levels of MMP-1 and MMP-8 in patients with infected ulcers compared to those with uninfected ulcers that showed higher levels of MMP-2 and MMP-9. We also documented higher levels of interleukin (IL)-1, IL-6, IL-8, vascular endothelial growth factor and tumour necrosis factor-alpha in patients with infected ulcers with respect to those with uninfected ulcers, documenting a possible association between infection, MMP activation, cytokine secretions and symptoms. The present results could represent the basis for further studies on drug use that mimic the action of tissue inhibitors of metalloproteinases in order to make infected CVU more manageable.

Anti-VEGF Therapy for Retinal Vein Occlusions.

Retinal vein occlusion (RVO) is the second most common cause of visual loss in the Western World. RVO is usually classified into branch RVO (BRVO) and central RVO (CRVO) according to the anatomical site of the vascular occlusion. The pathogenesis of RVO is not yet fully understood, however an important event is the intraluminal thrombus formation, which is usually secondary to several conditions such as hypertension, hyperlipidemia, diabetes and thrombophilia. The blockage of venous circulation causes an elevation of intraluminal pressure in the capillaries, leading to hemorrhages and leakage of fluid within the retina, increase of interstitial pressure and a consequent reduction of retinal perfusion. Ischemia may develop resulting in secretion of vascular endothelial growth factor (VEGF) that causes further vascular leakage and retinal oedema. VEGF has therefore a leading role in RVO pathogenesis and symptoms. As a consequence use of anti-VEGF agents by intravitreal injections has become very common with the aim to improve the clinical outcomes in these patients. Currently 2 anti-VEGF agents (ranimizumab and aflibercept) have been FDA (Food and Drug Administration) and EMA (European Medicine Agency) approved for the treatment of RVO, while another VEGF inhibitor (bevacizumab) is often used "off-label" in clinical practice. Many treatment regimens have been suggested in the clinical trials with these drugs, as monthly injections or injections when needed, however the ideal regimen has not been defined yet. We conducted a systematic review searching MEDLINE for the following terms: retinal vein occlusion, ranibizumab, bevacizumab, aflibercept, vascular endothelial growth factor, macular oedema. Data were extracted by one author (AG and BE) and checked by a second (BPM, CC). Aim of this article was to review available data for each drug, focusing on their efficacy and safety trying to compare their advantages and limits.

Endovascular repair for acute traumatic transection of the descending thoracic aorta: experience of a single centre with a 12-years follow up.

BACKGROUND: Most blunt aortic injuries occur in the proximal proximal descending aorta causing acute transection of this vessel. Generally, surgical repair of the ruptured segment of aorta is associated with high rates of morbidity and mortality and in this view endovascular treatment seems to be a valid and safer alternative. Aim of this article is to review our experience with endovascular approach for the treatment of acute traumatic rupture of descending thoracic aorta. METHODS: From April 2002 to November 2014, 11 patients (9 males and 2 females) were referred to our Department with a diagnosis of acute transection of thoracic aorta. Following preoperative Computed Tomography (CT) evaluation, thoracic endovascular aortic repair (TEVAR) with left subclavian artery coverage was performed. Follow-up consisted clinical and instrumental (CT, Duplex ultrasound) controls at discharge, 1, 3 and 6 months and yearly thereafter. RESULTS: At 12-year follow up, the overall survival for the entire patients cohort was 100 %, no major or minor neurological complications and no episode of left arm claudication occurred. Cardiovascular, respiratory and bleeding complications, in the early period, was represented by minor, non fatal events. No stent graft failure, collapse, leak or distal migration were detected at CT scan during the entire follow up period. CONCLUSIONS: According to our experience, despite the small number of patient population, TEVAR procedure with with left subclavian artery coverage, performed in emergency settings, seems to provide excellent long term results. TRIALS REGISTRATION: The protocol was registered at a public trials registry, www.clinicaltrials.gov (trial identifier NCT02376998 ).

Kinetic Profiles of Inflammatory Mediators in the Conjunctival Sac Fluid of Patients upon Photorefractive Keratectomy.

Photorefractive keratectomy (PRK) represents a therapeutic option to remodel corneal stroma and to compensate refractive errors, which involves inflammatory and/or regenerative processes. In this context, the modulation of cytokines/chemokines in the conjunctival sac fluid and their role in the maintenance of the corneal microenvironment during the healing process upon refractive procedures has not been deeply investigated. In this study, serial samples of conjunctival sac fluid of patients (n = 25) undergoing PRK were harvested before and at different time points after surgery. The levels of 29 cytokines/chemokines/growth factors involved in inflammatory/immune processes were measured with a multiplex array system. The results have firstly highlighted the different pattern of cytokine expression between the microenvironment at the anterior surface of the eye and the systemic circulation. More importantly, the kinetic of modulation of cytokines/chemokines at the conjunctival level following PRK revealed that while the majority of cytokines/chemokines showed a significant decrease, MCP-1 emerged in light of its pronounced and significant increase soon after PRK and during the follow-up. This methodological approach has highlighted the role of MCP-1 in the healing process following PRK and has shown a potential for the identification of expression/modulation of soluble factors for biomarker profiling in ocular surface diseases.

TNF-related apoptosis inducing ligand in ocular cancers and ocular diabetic complications.

TNF-related apoptosis inducing ligand (TRAIL) is an intensively studied cytokine, in particular for its anticancer activity. The discovery that conjunctival sac fluid contains extremely high levels of soluble TRAIL as compared to other body fluids suggested important implications in the context of the immunological surveillance of the eye, in particular of the anterior surface. In this review, we discuss the potential physiopathologic and therapeutic role of the TRAIL/TRAIL receptor system in a variety of ocular cancers. Moreover, since an increasing amount of data has indicated the important biological activities of the TRAIL/TRAIL receptor systems also in a completely different pathologic context such as diabetes mellitus, in the second part of this review we summarize the currently available data on the involvement of TRAIL in the ocular complications of diabetes mellitus as modulator of the inflammatory and angiogenic response in the eye.

Low molecular weight heparin improves healing of chronic venous ulcers especially in the elderly.

Venous ulcers are common, especially in the elderly, accounting for more than 50% of all lower extremity ulcers with important socioeconomic problems. Improving extracellular matrix functioning, by heparin administration, seems to be a way to support wound healing. A total of 284 patients with venous ulcers were recruited in a 4-year period. All patients were subjected to the most appropriate treatment after considering their preference (compression therapy followed or not by vein surgery). Patients were randomised into two groups of 142 persons in each (group A and group B as cases and controls, respectively). Patients of group A, in addition to the basic treatment as described earlier, received administration of nadroparin 2850 IU/0.3 ml through subcutaneous injection once a day for 12 months, whereas group B patients received basic treatment alone. Healing was assessed by means of direct ulcer tracing with computerised planimetry. Group A showed a healing rate of 83·80% at 12 months, whereas that of group B was 60·56%. Results by age group surprisingly showed that the group of older patients took the most advantage from long-term treatment with low molecular weight heparin; this group also had lowest recurrence rate.