Elena Antoniazzi

Risk of dissection in thoracic aneurysms associated with mutations of smooth muscle alpha-actin 2 (ACTA2)

Objective To evaluate the prevalence and phenotype of smooth muscle alpha-actin (ACTA2) mutations in non-syndromic thoracic aortic aneurysms and dissections (TAAD). Design Observational study of ACTA2 mutations in TAAD. Setting Centre for Inherited Cardiovascular Diseases. Patients A consecutive series of 100 patients with TAAD. Exclusion criteria included genetically confirmed Marfan syndrome, Loeys–Dietz type 2, familial bicuspid aortic valve and Ehlers–Danlos type IV syndromes. Interventions Multidisciplinary clinical and imaging evaluation, genetic counselling and testing of ACTA2, and family screening. Main outcome measures Prevalence of ACTA2 mutations and corresponding phenotypes. Results TAAD was familial in 43 cases and sporadic in 57 cases. Five mutations in the familial TAAD group (12%) were identified that were absent in controls. The known p.Arg149Cys and the novel p.Asp82Glu, p.Glu243Lys and p.Val45Leu mutations affected evolutionarily conserved residues. The IVS4+1G>A mutation was novel. Of 14 affected relatives, 13 were carriers of the mutation identified in the corresponding proband while one deceased relative had no genetic test. Type A dissection was the first manifestation of aortic aneurysm in four probands and occurred unexpectedly in five relatives. The aortic aneurysm was age dependent and absent in mutated children. Of nine patients who had acute dissection, five died following surgery. At dissection, the size of the aortic aneurysm ranged from 40 mm to 95 mm. Extravascular, ocular, skeletal, nervous and pulmonary traits were variably associated with TAAD, with iris flocculi being most common. Conclusions Timely diagnosis of TAAD in the probands, genetic counselling and family screening identify predisposed relatives and prevent catastrophic aortic dissections.

Antibiotic-Impregnated Fibrin Glue in Ocular Surgery:In vitro Antibacterial Activity

A strategy to reduce postoperative ocular infections might consist in maintaining a high antibiotic concentration in the eye by using a topical slow-release drug formulation. Fibrin glue is widely used in ocular surgery. Vancomycin, teicoplanin, cephalothin and gentamicin were added to a 500 IU/ml thrombin solution, their concentrations in 1 g fibrin glue being 500 µg for vancomycin and 400 µg for the other drugs. The in vitro antibacterial activity of antibiotic-impregnated fibrin glue was evaluated against a recent clinical isolate of Staphylococcus epidermidis. Moreover the antibiotic elution from fibrin discs in saline was assayed for up to 96 h. Fibrin glue properties were maintained when thrombin was reconstituted with a CaCl2 solution additioned with the antibiotics tested. All antibiotic fibrin mixtures exhibited good antistaphylococcal activity immediately after the preparation. A prolonged inhibition (4 days) of S. epidermidis growth was observed with teicoplanin discs. Gentamicin and teicoplanin levels were higher than those of the other antibiotics. The results suggest that the fibrin glycopeptide and/or gentamicin mixtures can be used, both prophylactically and therapeutically, in ocular surgery.

Autologous platelet lysate for treatment of refractory ocular GVHD

Current treatment of ocular GVHD (oGVHD), represented by systemic immunosuppressive regimens and local therapies (mainly artificial tears and corticosteroids), gives unsatisfactory results. We investigated the safety and efficacy of autologous plasma rich in PDGFs to treat oGVHD unresponsive to standard medications. A total of 23 patients with refractory oGVHD (grade II–IV) unresponsive to standard therapy were treated with autologous plasma rich in PDGFs eye drops (PRGD) four times/day for 6 months. Symptoms and signs (best visual acuity, Schirmer’s test and tear break up time (TBUT), evaluation of the anterior segment and fluorescein and lissamine staining) were always assessed by the same ophthalmologist. Patients were defined as ‘responders’ when showing improvement for total complaints and at least one sign. At 30 days of treatment, 17 patients (73.9%) were classified as responders. The symptom that improved most was photophobia (improved in 19 patients, 82.6%). TBUT improved in 20 patients (86.9%) and anterior segment score in 19 patients (82.6%). Response was maintained over time. No serious adverse events occurred. PRGD proved to be safe and effective in treating oGVHD and may be a valid treatment option from the early stages of the disease to avoid irreversible ocular damage.

Anterior chamber measurements taken with Pentacam: An objective tool in laser iridotomy

Purpose. Laser iridotomy is the standard first-line intervention in both acute and chronic forms of angle closure because it prevents the recurrence of acute attacks and virtually eliminates the risk of an acute attack in the fellow eye. Pentacam is a new imaging modality which does not require probe contact or an immersion bath. The instrument will allow anterior segment morphology before and after laser peripheral iridotomy (LPI) to be quantified. The aim of the study is to evaluate the objective difference in changes of anterior chamber morphology after LPI with Pentacam. Methods. Twenty eyes with a high risk of angle closure were evaluated with Pentacam rotating Scheimpflug camera before and after LPI. We measured anterior chamber volume, anterior chamber depth, and chamber angle before and after laser treatment. Results. Statistically significant difference before and after LPI was noted in all anterior chamber measurements except central anterior chamber depth. Conclusions. This study confirms previous reports of increased anterior chamber volume and angle after LPI and Pentacam is a good objective instrument to demonstrate the efficacy of LPI.

Pentacam sensitivity and specificity in detecting occludable angles

Purpose To assess the sensitivity and specificity of Pentacam measurements in detection of occludable angles and to provide cutoff values. Methods Observational, single-center, cross-sectional study on 64 Caucasian eyes: 28 (43.7%) primary narrow angles or primary angle-closure glaucoma, and 36 (56.2%) controls: all subjects were evaluated and classified by gonioscopy (Shaffer classification). The following measurements have been considered: superior and inferior anterior chamber angle (ACA), temporal and nasal ACA, anterior chamber depth (ACD) using 5 value representation (central, superior, inferior, nasal, temporal), and anterior chamber volume (ACV). Validity of Pentacam parameters to detect patients in Shaffer 0 or I class was assessed by receiver operating characteristic (ROC) curves analysis; cutoffs were chosen as to maximize sensitivity and specificity. Results All the considered Pentacam measures were statistically different between the 2 groups (p<0.0001). All Shaffer grade groups differed in all parameters (p<0.001), except for grade 0 and I, which did not differ in any. Area under the curve ROC analysis revealed high discriminant power of all Pentacam measures: ACA = 0.94; ACD = 0.91; ACD central = 0.89; and ACV = 0.89. Chosen cutoff values (ACA = 22.4°; ACD = 1.12 mm; ACD central = 1.93 mm; ACV = 84 mm3) allowed correct classification of narrow angles. Conclusions The study pointed out a high power of Pentacam AVA, ACV, and ACD in detecting occludable angles. Pentacam is simple to use, reliable, and noncontact, provides parameters in a short period, and represents a possible screening tool.

Ocular Infections: Antibiotics and Bacterial Adhesion on Biomaterials Used in Ocular Surgery

The in vitro antibacterial activity of ofloxacin, sagamycin and other antibiotics was evaluated against 85 bacterial isolates [coagulase-negative staphylococci (CNS), n = 37, Staphylococcus aureus, n = 28, and Pseudomonas aeruginosa, n = 20] obtained from patients with ocular infections. The antistaphylococcal activity of ofloxacin was quite elevated with a 90% minimal inhibitory concentration (MIC90) of 1.56 mg/l against CNS and S. aureus. Rokitamycin and erythromycin showed a good activity against methicillin-sensitive staphylococci, but were less active than ofloxacin and sagamycin against methicillin-resistant strains (MIC90 > 100 mg/l). Sagamycin was highly effective against staphylococci (MIC90 0.78 mg/l) and appeared to be the most active compound against P. aeruginosa (MIC90 6.25 mg/l), followed by ofloxacin, tobramycin and gentamicin. In a successive part of the study, the adhesive properties of slime-producing staphylococci were tested on biomaterials used in ocular surgery. Intraocular lenses, Silastic sheetings, circling bands and grooved strips showed a high affinity for slime-producing strains, while round silicone sponges were not covered by bacterial biofilm. In the last part of our study, we demonstrated how subMIC levels of ofloxacin increased the adhesion of slime-producing staphylococci. Our data confirmed the excellent activity of ofloxacin and sagamycin against ocular pathogens and the key role of adhesion in promoting colonization and infections of biomaterials.

A cross-sectional study on vision-related quality of life in patients with ocular GvHD

Ocular GvHD affects about 40–60% of patients receiving bone marrow transplantation. Ocular complaints worsen quality of life (QoL), which, besides survival time, is a primary end point in a patients follow-up. The aim of our study was to assess the ocular surface status and vision-related QoL (VRQoL) and explore the potential determinants in VRQoL in patients with chronic GvHD with ocular involvement. In this cross-sectional study, we investigated 40 patients with ocular GvHD after allogeneic hematopoietic stem cell transplantation assessing ocular symptoms and signs, VRQoL and ophthalmologic parameters. The median age was 52.1 years; 32.5% were females. Most of them presented a multiple organ involvement. Ophthalmological parameter examinations were on average abnormal. Corneal staining was severe/very severe in 25%; conjunctival staining in 10% of subjects. The worse QoL scores were on ‘general vision’, ‘ocular pain’, ‘vision-specific mental health’ and ‘vision-specific role difficulties’. Both symptoms and sign scores indicate poor VRQoL. A lower VRQoL was related to schooling level, job position, underlying disease and extracorporeal photopheresis. Corneal staining, Schirmer and tear film breakup time were negatively associated to visual function-related subscales. An accurate ophthalmological and VRQoL assessment should be mandatory for a long time to promptly recognize early signs of ocular suffering, and to prevent irreversible ocular complications.

Longitudinal analysis of serum cytokines in a Behcet's patient during 9 months of IVIG infusions: how does CXCL8 bridge the immune and neuroendocrine systems?

Behcet’s Disease (BD) is a systemic vasculitis of unknown aetilogy with a protean range of manifestations and diagnosed only n the basis of clinical criteria [1,2]. A specific laboratory test has not yet been validated to idenify BD, however, starting from 1993, several studies have reported hat in serum of BD patients the levels of CXCL8 directly correlated o both severity and duration of symptoms, including the numer of involved organs and active clinical manifestations [3,4]. In articular, CXCL8 levels have been found to be high in sera of BD atients who showed mucosal and neurological signs [5]. CXCL8 is n inflammatory cytokine that attracts and activates neutrophils to he site of infection or tissue damage and, although the pathogenic echanisms are still unknown, BD is in fact a systemic neurophilic perivasculitis characterised by recurrent inflammatory ares, mainly due to the hyper-activation of circulating neutrophils 6,7] Here we report for the first time a long term longitudinal nalysis of 7 serum cytokines in a 39-years old female affected y BD treated with cyclic IntraVenous ImmunoGlobulins (IVIG) nfusions. The patient presented mucocutaneous, articular, ocular nd intestinal manifestations, without clear signs of neurological nvolvement. After the failure of the first-line treatment based on rednisone (25 mg/day) and colchicine (1 mg/day), any immunouppressive therapy was contraindicated because of recurrent evere Varicella-Zoster Virus reactivations. Besides the well-known se of IVIG for protecting patients with primary or secondary mmunodeficiency from infections, IVIG are a recognized treatent for several immune-mediated diseases, including BD. Then, he therapeutic choice fell on IVIG, that the patient started at the osage of 0.4 g/kg/day for three consecutive days in a month for 3 onths, then fortnightly for 3 times, then every three weeks for 9 onths. The inflammatory milieu was monitored by measuring the erum levels of IL-1, IL-2, IL 6, IL-10, CXCL8, IFN, and TNF. Before ach IVIG infusion, the cytokine concentrations were assessed by nzyme-linked immunosorbent assay kits following the manufacurer’s instructions (R&D Systems, USA). Before treatment, mucocutaneous and articular symptoms were resent and we found high levels of CXCL8 (253.83 pg/ml; normal alue: 0–31 pg/ml), detectable levels of IL-6, IL-10, IFN, whereas L-1 and IL-2 were undetectable. After 15 days from the first infuion, CXCL8 rapidly decreased (7.82 pg/ml) and symptoms started o improve. During the nine months of therapy, the use of cyclic infusions of VIG maintained the remission of BD symptoms, and cytokines levls only slightly increased even during an upper airways infection [

Cataracts and Dupuytren disease: a case report and review of the literature

Purpose. Dupuytren disease is an inherited proliferative and progressive connective disease. Ectopic disease may, however, be located distant from the palmar fascia. Methods. Case report and review of the literature. Results. We describe a case of symmetric bilateral posterior subcapsular cataracts associated with symmetric bilateral Dupuytren disease and symmetric bilateral Ledderhose disease in a 56-year-old Caucasian man. His medical history was negative for glucocorticoids intake, diabetes, and exposure to radiation. Serum transforming growth factor β (TGF-β)1 concentration has been evaluated and was found to be almost double compared to the controls. Conclusions. We speculate that the TGF-β plays an important role for ocular and connective tissue disorders.

An easy method for intraoperative confirmation of lacrimal sac patency in endoscopic dacryocystorhinostomy

Purpose Few studies have focused on the intranasal localization of the lacrimal sac during endoscopic dacryocystorhinostomy: landmarks in order to find the medial wall of the lacrimal sac have been described, but there is a lack of description of methods for the verification of the complete marsupialization of the lacrimal sac during surgery. In this report, we propose an easy and effective method for certain intraoperative identification of lacrimal sac. Methods A method in order to verify the effective marsupialization of the lacrimal sac is applied and described: to ensure that the opening of the sac in the nasal cavity is complete, the surgeon should identify the Rosenmuller valve, which is the end of the common canaliculus in the lacrimal sac. Continuous irrigation with saline solution through the inferior canaliculus can be useful to obtain a clean surgical area and to permit easy intraoperative identification of the valve. Results Between 2007 and 2015, 193 endoscopic dacryocystorhinostomies were performed in our institutions. Postoperative surgical success at last follow-up (minimum 12 months) was 93.8% (181 out of 193 of cases). No major complications were observed. Conclusions Correct and complete exposure of the lacrimal sac during surgery is crucial for a good outcome: when the opening of the common canaliculus is identified, the surgeon is assured that the sac has been correctly and completely marsupialized inside the nasal cavity.