INTRAOCULAR EMULSION OF SILICONE OIL (ITEMS) GRADING SYSTEM: An Evidence-Based Expert-Led Consensus.

PURPOSE: To propose the InTraocular EMulsion of Silicone oil (ITEMS) grading system for the assessment of silicone oil (SiO) emulsion, applicable in a routine clinical setting and validated through an expert-led consensus procedure. METHODS: Seven experts on intraocular liquid tamponades, led by a facilitator, performed a literature review on the detection of SiO emulsion. Based on the proposed ideas, a questionnaire was developed and submitted to the experts on the methods to detect SiO emulsion and the items to grade. After 2 rounds of individual ranking using a 9-point scale and related discussion, the final grading system was developed including items that reached consensus (score ≥7 from ≥75% of members). RESULTS: The agreed ITEMS grading system includes the identification of SiO microbubbles and large SiO bubbles through slit-lamp biomicroscopy, gonioscopy, fundus examination under mydriasis, or ultra-wide-field fundus photography. Moreover, macular and disk optical coherence tomography are used to detect SiO-associated hyperreflective dots. CONCLUSION: An evidence-based expert-led consensus was conducted to develop grading system of SiO emulsion, allowing, for the first time, homogenous collection of data on SiO emulsion. This has the potential to improve the understanding of the role and clinical relevance of SiO emulsion, allowing comparisons between different studies.

Ex vivo evaluation of retinal cytotoxicity after the use of multiple medical devices in pars plana vitrectomy in porcine eyes.

This study aimed to evaluate viability of retinal cells after the use of multiple intraoperative devices, namely a vitreal dye (triamcinolone acetonide,TA), a ERM/ILM dye (solution of trypan blue 0.15% and brilliant blue 0.025%), and two intraocular tamponades, namely perfluoro-n-octane, (PFO) and silicone oil (SO 1000 cSt), with minimal and maximal removal of their residues, during a simulated pars plana vitrectomy (PPV) in porcine eyes ex-vivo. The in vitro cytotoxicity of each of these compounds was verified on ARPE-19 cells by direct tests according to the ISO 10993-5 (2009). Pars plana vitrectomy was performed on 25 enucleated porcine eyes divided in five groups according to the following conditions: Group A) No surgery control: eye bulbs were kept at room temperature for 40 min; Group B) Sham surgery: PPV with the sole use of BSS for 40 min; Group C) Cytotoxic control: PPV with BSS infusion (20 min) followed by intravitreal injection of 1H-PFO (contact time: 20 min); Group D) Surgery with residues: PPV with BSS infusion and sequential intravitreal injection of TA, ERM/ILM dye, PFO and SO, with minimal removal of each compound after a specified contact-time (overall duration: 40 min); Group E) Surgery with minimal residues: PPV performed as in group D, but with maximal removal of each compound (overall duration: 40 min). All the experimental procedures were performed at room temperature. Immediately after surgery, the retina was extracted from each eye bulb and samples of 3-mm diameter were prepared. Retinal viability was determined for each sample by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay. A cell viability <70% was considered the cytotoxicity threshold. Kruskal-Wallis test was used to evaluate the differences in retinal viability between groups. No cytotoxicity was detected in retinal samples in groups A, B and E. Samples from eye bulbs that had undergone surgery with minimal removal of residues (group D) and cytotoxic controls (group C) showed high retinal cytotoxicity. The tested conditions indicated that the combined use of TA, ERM/ILM dye, PFO and SO during PPV does not affect retinal cells viability if all the devices are properly removed, whereas the cytotoxicity detected in group D may suggest that the presence and accumulation of the residues of the compounds used intraoperatively could negatively impact retinal viability due to a cumulative and/or synergistic cytotoxic effect between them, supporting the crucial role of an optimal removal of the intraoperative medical devices to ensure a safe vitrectomy to the patient.

Safety of silicone oils as intraocular medical device: An in vitro cytotoxicity study.

This study aimed to assess the cytotoxic effect of low molecular weight components (LMWC) and conventional silicone oils (SOs) 1000 cSt with different degree of purification (raw, intermediate, and purified) using in vitro cytotoxicity tests. Direct contact cytotoxicity tests were performed in BALB 3T3 and human retinal pigment epithelial cells (ARPE-19) using quantitative and qualitative evaluation according to the ISO 10993-5 (2009) standards. Conventional SOs 1000 cSt in form of raw, intermediate (intermediate product obtained during distillation process), and purified SO (final product after distillation) and a concentrate of LMWC (including siloxane chains with molecular weight up to 1557 g/mol) were directly applied to 100% of cell layer area for 24 h. Cell viability was quantified using 3-(4,5-dimethylthiazole-2-yl)-2,5-28 diphenyltetrazolium bromide (MTT) and neutral red uptake assays in ARPE-19 and BALB3T3, respectively. All tested samples, including the concentrate of LMWC, resulted to be not cytotoxic according to ISO 10993-5 in both qualitative and quantitative evaluations. However, the cellular viability was significantly higher in the intermediate and purified SO compared with the raw SO in ARPE-19 cells. No reduction in cell viability was detected by LMWC. The absence of cytotoxicity was observed for all tested samples in both BALB3T3 and ARPE-19 after 24 h of application. A direct cytotoxic effect is not likely to be involved in the potential complications related to SO and LMWC. Long-term potential adverse effects of SO could be related to the raw material and to different concentrations of LMWC.

A Systematic Review on Organ-on-a-Chip in PDMS or Hydrogel in Dentistry: An Update of the Literature.

Organs-on-a-chip (OoCs) are microfluidic devices constituted by PDMS or hydrogel in which different layers of cells are separated by a semipermeable membrane. This technology can set many parameters, like fluid shear stress, chemical concentration gradient, tissue-organ interface, and cell interaction. The use of these devices in medical research permits the investigation of cell patterning, tissue-material interface, and organ-organ interaction, mimicking the complex structures and microenvironment of human and animal bodies. This technology allows us to reconstitute in vitro complex conditions that recapitulate in vivo environments. One of the main advantages of these systems is that they represent a very realistic model that, in many cases, can replace animal experimentation, eliminating costs and related ethical issues. Organ-on-a-chip can also contain bacteria or cancer cells. This technology could be beneficial in dentistry for testing novel antibacterial substances and biomaterials, performing studies on inflammatory disease, or planning preclinical studies. A significant number of publications and reviews have been published on this topic. Still, to our knowledge, they mainly focus on the materials used for fabrication and the different patterns of the chip applied to the experimentations. This review presents the most recent applications of organ-on-a-chip models in dentistry, starting from the reconstituted dental tissues to their clinical applications and future perspectives.

Topical Antiseptics in Minimizing Ocular Surface Bacterial Load Before Ophthalmic Surgery: A Randomized Controlled Trial.

PURPOSE: To investigate the reduction of the ocular surface bacterial load induced by 2 commercially available ophthalmic antiseptic formulations, povidone-iodine (PVI) 0.6% and chlorhexidine (CLX) 0.02%, before ocular surgery. DESIGN: Randomized controlled trial. METHODS: Seventy adult patients undergoing intraocular surgery (phacoemulsification) were randomized to receive in the index eye PVI (group A) 4 times a day for 3 days or CLX (group B) 4 times a day for 3 days before surgery. The untreated eye was used as control. A conjunctival swab was taken in both eyes before (T0) and after (T1) therapy. Microbial DNA was quantified with real-time polymerase chain reaction (PCR) analysis. The Mick algorithm was used to compare the abundance of each genus/genera against the distribution of abundances from the reference. At T1, patients filled a questionnaire to evaluate therapy-induced symptoms. Primary outcome was the reduction of bacterial DNA at T1 (microbial load), vs control arm, expressed as mean number of real-time PCR cycle times (CTs). Secondary outcomes were taxonomic composition, differential abundance, and therapy-induced ocular symptoms. RESULTS: The T0-T1 difference in CT was significant in group B, but not in group A (mean [95% CI], 0.99 [0.33] vs 0.26 [0.15], P < .001, and 0.65 [0.3] vs 0.45 [0.41], P = .09, respectively). The taxonomic composition, alpha, and beta diversity remained consistent at all time points in both groups. The rate of patients reporting therapy-induced ocular symptoms and the mean discomfort grade were greater in group A than in group B (97% vs 26% and 4.97±2.48 vs 0.66±1.53, respectively). CONCLUSIONS: Compared with PVI 0.6%, CLX 0.02% induced a greater reduction of ocular surface bacterial load, with no significant alterations of the taxonomic composition. Moreover, CLX was better tolerated than PVI.

Inflammation and macular oedema after pars plana vitrectomy.

Cystoid macular oedema (CMO) is a major cause of reduced vision following intraocular surgery. Although the aetiology of CMO is not completely clarified, intraocular inflammation is known to play a major role in its development. The macula may develop cytotoxic oedema when the primary lesion and fluid accumulation occur in the parenchymatous cells (intracellular oedema) or vasogenic oedema when the primary defect occurs in the blood-retinal barrier and leads to extracellular fluid accumulation (extracellular oedema). We report on the mechanisms of CMO formation after pars plana vitrectomy and associated surgical procedures and discuss possible therapeutic approaches.

Inosine triphosphatase genetic variants are protective against anemia during antiviral therapy for HCV2/3 but do not decrease dose reductions of RBV or increase SVR.

UNLABELLED: Two functional variants in the inosine triphosphatase (ITPA) gene causing inosine triphosphatase (ITPase) deficiency protect against ribavirin (RBV)-induced hemolytic anemia and the need for RBV dose reduction in patients with genotype 1 hepatitis C virus (HCV). No data are available for genotype 2/3 HCV. We evaluated the association between the casual ITPA variants and on-treatment anemia in a well-characterized cohort of genotype 2/3 patients treated with variable-duration pegylated interferon alfa-2b (PEG-IFN-α2b) and RBV. Two hundred thirty-eight Caucasian patients were included in this retrospective study [185 (78%) with genotype 2 and 53 (22%) with genotype 3]. Patients were treated with PEG-IFN-α2b plus weight-based RBV (1000/1200 mg) for 12 (n = 109) or 24 weeks (n = 129). The ITPA polymorphisms rs1127354 and rs7270101 were genotyped, and an ITPase deficiency variable was defined that combined both ITPA variants according to their effect on ITPase activity. The primary endpoint was hemoglobin (Hb) reduction in week 4. We also considered Hb reduction over the course of therapy, the need for RBV dose modification, and the rate of sustained virological response (SVR). The ITPA variants were strongly and independently associated with protection from week 4 anemia (P = 10(-6) for rs1127354 and P = 10(-7) for rs7270101). Combining the variants into the ITPase deficiency variable increased the strength of association (P = 10(-11) ). ITPase deficiency protected against anemia throughout treatment. ITPase deficiency was associated with a delayed time to an Hb level < 10 g/dL (hazard ratio = 0.25, 95% confidence interval = 0.08-0.84, P = 0.025) but not with the rate of RBV dose modification (required per protocol at Hb < 9.5 g/dL). There was no association between the ITPA variants and SVR. CONCLUSION: Two ITPA variants were strongly associated with protection against treatment-related anemia in patients with genotype 2/3 HCV, but they did not decrease the need for RBV dose reduction or increase the rate of SVR.

HCV genotype 1a shows a better virological response to antiviral therapy than HCV genotype 1b.

BACKGROUND: The impact of viral subtype on the rate of sustained virological response (SVR) to antiviral therapy in patients chronically infected with hepatitis C genotype 1 subtype 1a and 1b has not been extensively investigated. The aim of this study is to determine whether the HCV genotype 1 subtypes 1a and 1b respond differently to treatment with PEGylated interferon (PEG-IFN) plus ribavirin. METHODS: For 48 weeks, 388 "naïve"genotype 1 patients were treated weekly with PEG-IFN α-2a or PEG-INF α-2b combined with daily ribavirin (1000-1200 mg/day). The numbers of patients in whom HCV-RNA was undetectable were compared after 4 (rapid virological response, RVR), 12 (early virological response, EVR), and 48 (end treatment virological response, ETR) weeks of treatment as well as 24 weeks after the last treatment (sustained virological response, SVR). RESULTS: The rate of SVR was higher in subtype 1a patients than subtype 1b patients (55% vs. 43%; p < 0.02). Multiple logistic regression analysis showed that infection with genotype 1a (odds ratio(OR) : 1.8; 95% confidence interval (CI): 1.4 to 4.1), age < 50 years (OR:7.0; 95% CI 1.1 to 21.2), alanine aminotransferase level (ALT)<100 IU/ml (OR:2.1; 95% CI: 1.3 to3.5), HCV-RNA < 5.6 log10 IU/ml (OR: 3.2; 95% CI: 2.7 to 6.9) and fibrosis score < S3 (OR: 3.8; 95% CI:3.2 to 7.4), were all independent predictors of SVR. CONCLUSION: Dual antiviral therapy is more effective against HCV subtype 1a than against subtype 1b and this difference is independent of other factors that may favour viral clearance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01342003.

[Visual acuity reduction and silicone oil tamponade]. / Visusminderung und Silikonöltamponade.

Silicone oil is an established intraocular surgical aid, which enables the treatment of the most complex starting situations but no other alternative has been found; however, the available data indicate that an unclear loss of visual acuity during or after an intraocular silicone oil tamponade possibly occurs more frequently than assumed from the clinical routine. Various pathological mechanisms are under discussion as causes, but the exact causes are actually unclear. In addition to atrophic alterations in the optical coherence tomography (OCT) examination, there are a clear reduction in visual acuity and mostly a central scotoma with otherwise inconspicuous findings. Unclear loss of visual acuity can also occur after removal of the silicone oil. Whether this is caused by the same pathological mechanism is unclear. Furthermore, there are no reproducible risk factors that appear a priori to possibly cause an unclear loss of vision under silicone oil; however, oil removal as soon as possible and a good adjustment of the intraocular pressure are recommended by the authors. Overall, a silicone oil tamponade should be carefully weighed up even when using modern highly purified silicone oils and it should therefore continue to be reserved particularly for unfavorable initial situations or complicated courses with the necessity for a silicone oil tamponade. Against this background, a study for systematic recording and processing of cases of unclear loss of visual acuity after silicone oil tamponade seems to be meaningful.

Efficacy and tolerability of polyvinylpyrrolidone-iodine 0.6% treatment in adenoviral keratoconjunctivitis: a Prospective Randomized Controlled Study.

OBJECTIVES: To analyze the effect of the employment of polyvinylpyrrolidone-iodine (PVP-I) 0.6% eye drop on the clinical course of patients affected by Adenoviral Keratoconjunctivitis (AKC). METHODS: Consecutive patients with clinical signs of AKC and positive results of AdenoPlus test were enrolled from four Italian Centres. Patients were randomized to receive: PVP-I 0.6% eye drops four times/daily for 20 days (Group A) or hyaluronate-based tear substitutes four times/daily for 20 days (Group B). Best-corrected visual acuity (BCVA), optical coherence tomography (OCT) Optovue iVue pachymetry map; corneal haze; conjunctival injection and chemosis; subepithelial corneal infiltrates (SEIs); corneal and conjunctival staining and corneal densitometry were recorded at diagnosis and at every follow-up visit. The primary outcome was the resolution time of AKC. RESULTS: Overall, 59 AKC patients (34 for Group A and 25 for Group B) completed the study. Patients of Group A showed a significantly shorter resolution time and lower incidence of SEIs compared to patients of Group B. In particular, SEIs were present at the last visit in 3/34 (8.82%) patients of the Group A vs 11/25 (44%) of the Group B (p = 0.005). Patients of Group A showed a significantly lower incidence of corneal haze compared to patients of Group B (0/34 vs 3/25; p = 0.038). No side effects were reported for both groups. CONCLUSIONS: Although further clinical evaluations are needed, according to our data the use of PVP-I 0.6% eye drop in the setting of AKC reduces the risk of SEIs as well as the resolution time of the disease.

Twenty-three-gauge pars plana vitrectomy, Densiron-68, and 360° endolaser versus combined 20-gauge pars plana vitrectomy, scleral buckle, and SF6 for pseudophakic retinal detachment with inferior retinal breaks.

PURPOSE: To compare the anatomical and functional outcomes of 23-gauge pars plana vitrectomy (PPV) with Densiron-68 tamponade and 360° endolaser versus 20-gauge PPV with encircling scleral buckling (ESB) and an SF6 gas tamponade for the repair of primary pseudophakic retinal detachment with inferior retinal breaks. METHODS: Prospective, randomized, comparative, interventional study. Eighty-two eyes of 82 consecutive patients were randomly assigned to 1 of the 2 treatment groups: 23-gauge PPV/Densiron-68 (44 eyes, 54%) or 20-gauge PPV/ESB/SF6 (20%) (38 eyes, 46%). The inclusion criterion was the presence of primary pseudophakic retinal detachment with at least 1 retinal break between the 4- and 8-o'clock positions. The study protocol involved a minimum of 7 visits: baseline, day of surgery, 1 week, and 1, 3, 6, and 9 months postoperation. Densiron-68 removal was performed within 12 weeks of the initial surgery. Two surgical procedures were required in the Densiron group to remove the oil. RESULTS: After the primary procedure, the retina was reattached in 90% (40 of 44) of cases in the 23-gauge PPV/Densiron group and in 92% (35 of 38) of cases in the 20-gauge PPV/ESB/SF6 group (P = 0.2, Fisher's exact test). After resolution of redetachments, final anatomical success rate rose to 97% (43 of 44) in the 23-gauge PPV/Densiron group and 94% (36 of 38) in the 20-gauge PPV/SB/SF6 group (P = 0.32, Fisher's exact test). Mean final best-corrected visual acuity (logarithm of the minimum angle of resolution) was 0.40 in the 23-gauge PPV/Densiron group and 0.48 in the 20-gauge PPV/ESB/SF6 group (P = 0.31, t-test). Operative time was significantly less in the 23-gauge PPV/Densiron group (P = 0.002, t-test). No statistically significant difference in the complication rate between the two groups was recorded. CONCLUSION: Twenty-three-gauge PPV combined with Densiron-68 and 360° endolaser and 20-gauge PPV combined with ESB/SF6 seemed to have similar efficacy in the repair of primary pseudophakic retinal detachment. Supplementary scleral buckling can be avoided using a Densiron-68 tamponade for retinal detachment with inferior retinal breaks.

Biocompatibility of intraocular liquid tamponade agents: an update.

Intraocular liquids tamponade agents, such as perfluorocarbon liquids (PFCLs), semifluorinated alkanes (SFAs), silicone oils (SOs) and heavy silicone oils (HSOs), are a crucial intraoperative and/or postoperative tool in vitreoretinal surgery, in particular for the management of complex vitreoretinal diseases. However, their use is not without complications, which are potentially severe. Consequently, a growing interest has been devoted to the biocompatibility of these compounds and the adequacy of current regulations that should guarantee their safety. Obviously, an updated knowledge on research findings and potential risks associated to the use of intraocular liquid compounds is essential, not only for vitreoretinal surgeons, but also for any ophthalmologist involved in the management of patients receiving intraocular liquid tamponades. In light of this, the review provides a comprehensive characterisation of intraocular liquid tamponades, in terms of physical and chemical properties, current clinical use and possible complications. Moreover, this review focuses on the safety profile of these compounds, summarising the existing regulation and the available evidence on their biocompatibility.

Individualized treatment with combination of Peg-interferon alpha 2b and ribavirin in patients infected with HCV genotype 3.

BACKGROUND & AIMS: The benefit of individualizing treatment for patients with genotype 3 HCV infection on the basis of viral clearance at week 4 (wk4-R) has not been firmly established. METHODS: Four hundred and fourteen patients received Peg-interferon alpha-2b plus 1000-1200 mg of ribavirin daily according with body weight > or <75 kg. Patients were randomized to standard 24 weeks (Std24) or to a 12 or 36 weeks variable treatment duration (Var12/36). In the variable treatment arm, patients with or without wk4-R were allocated to either 12 or 36 weeks duration. RESULTS: At treatment week 4, HCV RNA was undetectable in 262 patients (63.3%), 136 in the Std24, and 126 in the Var12/36 group (p=0.41). In patients with wk4-R, end-of-treatment (EOT) responses were 80.4% (CI 85.4-95.3) and 97.6% (CI 94.9-99.9) in the two arms, respectively (p=0.019). In patients without wk4-R, corresponding rates were 61.9% (50.6-73.2) and 75.3% (CI 65.9-84.6) (p=0.08). SVR was attained in 302 patients, 71.4% (CI 65.3-77.6) in the St24 group and 74.3% (CI 58.4-80.3) in the variable 12/36 arm. Among patients with wk4-R, SVR was 81.6% (CI 75.1-88.1) and 82.5% (75.9-89.1), respectively. In patients without wk4-R, SVR amounted to 52.1% (CI 40.4-63.7) and 61.7 (CI 51.1-72.3) in the two arms (p=0.25). CONCLUSIONS: HCV genotype 3 patients with week4-R may be treated safely with 12 weeks of therapy, provided that sufficiently high doses of ribavirin are administered. For patients still viremic at treatment week 4, SVR rates were numerically higher after 36 weeks of treatment than after the currently recommended 24 weeks.

Determinants of relapse after a short (12 weeks) course of antiviral therapy and re-treatment efficacy of a prolonged course in patients with chronic hepatitis C virus genotype 2 or 3 infection.

UNLABELLED: In hepatitis C virus (HCV) genotypes 2 and 3 patients, the high rate of relapse after 12 to 16 weeks of antiviral therapy is the main concern for shortening treatment duration. This study was undertaken to delineate predictors of relapse after short treatment in patients with undetectable HCV RNA at treatment week 4 (RVR), and to report in RVR patients with relapse the sustained virological response (SVR) after a second 24-week course of therapy. RVR patients received pegylated interferon (Peg-IFN) alfa-2b (1.5 microg/kg) and ribavirin (1000-1200 mg/day) for 12 weeks; those who relapsed were re-treated with the same drug doses but for the extended standard duration of 24 weeks. Logistic regression analysis was applied to delineate predictors of relapse by using age, sex, route of transmission, body mass index (BMI), serum alanine aminotransferase (ALT), HCV genotypes, serum HCV RNA levels, and platelet counts as covariates. Of 718 patients with genotypes 2 and 3 who were started on therapy, 496 (69.1%) had undetectable HCV RNA at week 4. Of them, 409 patients (82.5%, CI 79.1-85.8) attained SVR, and 67 (14.1%, CI 10.4-16.5) relapsed. At regression analysis, only platelet count less than 140,000 mm(3) [odds ratio, 2.51; confidence interval (CI), 1.49-4.20] and BMI 30 or higher (odds ratio, 1.7; CI, 1.03-2.70) were independently associated with relapse. Forty-three of 67 patients with relapse agreed to be re-treated, and an SVR was achieved in 30 (70.0%) of them. CONCLUSION: We recommend 12 weeks course of therapy for patients with undetectable HCV RNA at treatment week 4, providing they present with no advanced fibrosis and low BMI.

Short versus standard treatment with pegylated interferon alfa-2A plus ribavirin in patients with hepatitis C virus genotype 2 or 3: the cleo trial.

BACKGROUND: In patients with chronic hepatitis C virus (HCV) genotype 2 or 3, 24 weeks' treatment with pegylated interferon alfa (PEG-IFN-alpha) and ribavirin induces a sustained virological response (SVR) in almost 80% of cases. Evidence suggests that a similar response rate may be obtained with shorter treatment periods, especially in patients with a rapid virological response (RVR). The aim of this study was to compare the efficacy of 12 or 24 weeks of treatment in patients with chronic HCV genotype 2 or 3 and to identify patients suitable for 12 weeks treatment. METHODS: Two hundred and ten patients received PEG-IFN-alpha-2a (180 ug/week) and ribavirin (800-1200 mg/day) for 4 weeks. Patients with a RVR (HCV RNA not detectable) were randomized (1:1) to either 12 (group A1) or 24 (group A2) weeks of combination therapy. Patients without a RVR continued with 24-weeks' combination therapy (group B). HCV RNA was monitored at weeks 4, 8, 12, and 24, and at week 24 post-treatment. RESULTS: At study end, end of treatment response (ETR) was observed in 62 (86%) patients of group A1 and in 55 (77%) patients of group A2 (p < 0.05) Relapse rate was 3% each in groups A1 and A2, and 6% in group B. Among patients with a HCVRNA test 24 weeks after the end of treatment, SVR was observed in 60 (83%) of group A1 patients and in 53 (75%) of group A2 patients. Rapid virological response, low baseline HCV RNA levels, elevated alanine aminotransferase levels and low fibrosis score, were the strongest covariates associated with SVR, independent of HCV genotype. No baseline characteristic was associated with relapse. CONCLUSION: In HCV patients with genotype 2 or 3, 12-week combination therapy is as efficacious as 24-week therapy and several independent covariates were predictive of SVR. TRIAL REGISTRATION: Trial number ISRCTN29259563.

Sutureless human sclera donor patch graft for Ahmed glaucoma valve.

PURPOSE: To report the safety and effectiveness of a sutureless human sclera donor patch graft covering the subconjunctival portion of glaucoma drainage implant tube to prevent its erosion throughout the overlying conjunctiva. METHODS: This was a prospective pilot study. Fifteen eyes of 15 consecutive patients not responsive to medical and to not-implant surgical glaucoma treatment underwent Ahmed glaucoma valve (AGV) implant surgery with sutureless human sclera donor patch graft. The surgical procedure included AVG implant placed 8 mm behind the corneal limbus and fixed to the sclera with two 9-0 black nylon sutures. The tube was passed through the scleral tunnel, parallel to the corneal limbus, and shortened at the desired length. The anterior part of the tube was covered with human donor scleral graft and kept in place with fibrin glue (Tissue Coll) under the conjunctiva. Examinations were scheduled at baseline and then at 1 week and 1, 3, 6, and 12 months after surgery. RESULTS: At 12-month follow-up, the best-corrected visual acuity did not significantly improve from baseline 0.78+/-1.2 logMAR, whereas mean intraocular pressure significantly decreased from preoperative values of 29.8 (SD 8.4) mmHg. In all cases, the scleral patch was found in place at each check during the follow-up period. No conjunctival erosion over the AGV tube nor sign of endophthalmitis was recorded at any time during the follow-up period. CONCLUSIONS: AVG implant surgery with sutureless human sclera donor patch graft represents an effective and relatively safe surgical procedure for complicated glaucomas, avoiding conjunctival erosions over the AGV tube.

The Role of Endogenous Proteins on the Emulsification of Silicone Oils Used in Vitreoretinal Surgery.

The present work is aimed at investigating the chemicophysical properties of the interface between silicone oils (SOs) used in vitreoretinal surgery and aqueous solutions, in the presence of surfactant biomolecules. Such molecules are thought to play an important role in the formation of SO emulsions in vitrectomised eyes, in which the natural vitreous body has been replaced with a SO. In particular, we have measured the interfacial tension (IT) and the interfacial dilational viscoelasticity (DV) of the interface between SO (Siluron 1000) and serum proteins (albumin and γ-globulins) at various concentrations in a Dulbecco alkaline buffer. The equilibrium IT value is relevant for the onset of emulsification, and the DV influences the stability of an emulsion, once formed. The study is complemented by preliminary emulsification tests. The experimental results show that, when proteins are dissolved in the aqueous solution, the rheological properties of the interface change. The IT decreases significantly for physiological protein concentrations, and the DV modulus achieves high values, even for small protein concentrations. The emulsification tests confirm that, in the presence of proteins, emulsions are stable on the time scale of months. We conclude that the measured values of IT in the presence of serum proteins are compatible with the promotion of droplet formation, which, in addition, are expected to be stable against coalescence. Adsorption of biomolecules at the interface with the SO is, therefore, likely to play an important role in the generation of an emulsion in eyes subjected to vitrectomy. These findings are relevant to identify strategies to avoid or control the formation of emulsions in eyes.

Individualized treatment duration for hepatitis C genotype 1 patients: A randomized controlled trial.

UNLABELLED: It was hypothesized that in hepatitis C virus (HCV) genotype 1 patients, variable treatment duration individualized by first undetectable HCV RNA is as effective as standard 48-week treatment. Patients (n = 696) received peginterferon alfa-2a, 180 mg/week, or peginterferon alfa-2b, 1.5 mg/kg/week, plus ribavirin, 1000-1200 mg/day, for 48 weeks (standard, n = 237) or for 24, 48, or 72 weeks if HCV-RNA-negative at weeks 4, 8, or 12, respectively (variable, n = 459). Sustained virologic response (SVR) was achieved in 45.1% [95% confidence interval (CI) 38.8-51.4] of the patients in the standard group and in 48.8% (CI 44.2-53.3) of the patients in the variable group (P = 0.37). The percentages of patients who first achieved undetectable HCV RNA at weeks 4, 8, or 12 were 26.7%, 27.8%, and 11.3%, respectively. In the standard treatment group, 87.1%, 70.3%, and 38.1% of patients who first achieved undetectable HCV RNA at 4, 8, or 12 weeks attained SVRs, respectively. In the variable group, corresponding SVR rates were 77.2%, 71.9%, and 63.5%. Low viremia levels and young age were independent predictors of response at week 4 [rapid virologic response (RVR)]. RVR patients with baseline viremia >or=400,000 IU/mL achieved higher SVR rates when treated for 48 weeks rather than 24 weeks (86.8% versus 73.1%, P = 0.14). The only predictive factor of SVR in RVR patients was advanced fibrosis. CONCLUSION: Variable treatment duration ensures SVR rates similar to those of standard treatment duration, sparing unnecessary side effects and costs.

Treatment of hepatitis C virus carriers with persistently normal alanine aminotransferase levels with peginterferon alpha-2a and ribavirin: a multicentric study.

BACKGROUND/AIMS: To evaluate, in clinical practice, the efficacy and safety of combined antiviral treatment in hepatitis C virus (HCV) carriers with normal alanine aminotransferase (ALT) levels. METHODS: Eighty-eight HCV carriers with persistently normal ALT levels were enrolled. All patients received peginterferon (PEG-IFN) alpha-2a 180 microg once weekly plus ribavirin (RBV) 800 mg/day for 24 weeks (HCV-2 and -3) or 1000-1200 mg/day for 48 weeks (HCV-1). RESULTS: Rapid virological response (RVR) was seen in 66/88 patients (75%): 19/32 HCV-1 (59%), 40/46 HCV-2 (87%) and 7/10 HCV-3 patients. Younger patients, leaner subjects and patients with non-1 genotype or lower baseline HCV RNA levels were more likely to achieve an RVR. Sustained virological response (SVR) was seen in 69/88 patients (78%): 20/32 HCV-1 patients (62%), 41/46 HCV-2 patients (89%) and 8/10 (80%) HCV-3 patients. The overall SVR rate was 88% in patients with RVR (58/66) and 50% in those without RVR. CONCLUSIONS: The combination of PEG-IFN alpha-2a and RBV produces, in patients with normal ALT, virological response rates that are comparable or even higher than those obtained in patients with elevated ALT levels. Thus, we suggest that in selected cases immediate therapy might be preferred to a 'wait-and-see' policy.

Comparative assessment of intraocular inflammation following standard or heavy silicone oil tamponade: a prospective study.

PURPOSE: To evaluate the inflammation associated with the use of standard silicone oil (polydimethylsiloxane; PDMS) and heavy silicone oil (HSO) Densiron-68™ in patients undergoing vitrectomy for retinal detachment. MATERIALS AND METHODS: A prospective study was performed involving 35 patients scheduled to undergo vitrectomy for retinal detachment. Patients received PDMS or Densiron-68™ HSO according to superior or inferior retinal localization of the tears, respectively. For assessing the inflammation, prostaglandin E2 (PGE2 ) and interleukin-1α (IL-1α) levels were evaluated in the aqueous. RESULTS: Thirty-five eyes of 35 patients completed the study: 20 eyes received HSO, and 15 eyes received PDMS. The mean aqueous PGE2 level was significantly higher in HSO patients than in PDMS patients (869.16 ± 242.83 pg/ml versus 369.38 ± 209.7 pg/ml, respectively; p < 0.0001). The mean aqueous IL-1α level was also significantly higher in HSO patients than in PDMS patients (81.40 ± 36.9 pg/ml versus 40.8 ± 32.5 pg/ml, respectively; p = 0.002). In HSO, a moderate positive correlation between the endotamponade duration and both PGE2 (r = 0.44; p = 0.05) and IL-1α (r = 0.48; p = 0.033) levels was observed. In PDMS, a strong positive correlation between the endotamponade duration and both PGE2 (r = 0.89; p < 0.0001) and IL-1α (r = 0.68; p = 0.006) levels was observed. CONCLUSION: Although both HSO and PDMS yielded favourable success rates in the surgical treatment of complicated retinal detachments, HSO triggered a more severe inflammatory reaction, in a time-dependent manner.