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Doxorubicin (DOX) is a potent chemotherapeutic agent used to treat multiple types of cancer, but its clinical application is limited by cardiotoxicity, mainly due to oxidative stress. Curcumin (CUR) is a natural polyphenolic compound with strong antioxidant properties, but its potential protective effects against DOX-induced cardiotoxicity need further investigation. This study aimed to evaluate CUR's efficacy in mitigating DOX-induced oxidative stress in the hearts of BALB/c mice. Mice received a DOX dose of 9 mg/kg or 16 mg/kg; half of the mice received daily doses of 100 mg/kg CUR for 15 days. Survival analysis, histopathological examination, and oxidative stress markers were assessed to determine the cardioprotective effects of CUR. Results showed that CUR significantly reduced oxidative damage and improved survival rates, particularly at the lower DOX dose (9 mg/kg). Mice treated with DOX-9 mg/kg plus CUR showed improved health conditions and reduced levels of reactive oxygen species (ROS), lipid peroxidation, sulfhydryl production, and protein carbonylation. Histopathological analysis confirmed reduced cardiac tissue damage. In conclusion, CUR combined with a lower dose of DOX effectively reduces oxidative stress and cardiac injury, enhancing survival in BALB/c mice. These findings suggest that CUR is a promising adjunct therapy to mitigate DOX-induced cardiotoxicity, potentially improving the DOX therapeutic index in cancer treatment.

Young people in vulnerable situations tend to have more difficulties realizing successful formal education trajectories. It is extremely important to conduct studies that explore the key dimensions that can help young people overcome the conditioning of vulnerable situations, assisting in the achievement of academic success. According to the existing literature, one of these key dimensions is psychosocial well-being. Thus, this qualitative research aims to identify and analyze psychosocial factors that favor successful school pathways among young people in vulnerable situations. Through a case study approach, 12 in-depth interviews were carried out with 12 young Spanish people who not only have a vulnerable background but also successful formal education trajectories. The data were explored through qualitative content analysis-NVivo11. The results revealed that young people generally associate their successful educational trajectory with the positive impact of psychosocial factors, such as the following: positive caregivers' valuation of formal education and positive school experiences and support networks. Young people also point to many negative school experiences that have been overcome via positive attitudes and individual protective factors. The youngsters suggest changes in the educational system and teachers' skills in order to improve the levels of psychosocial support in formal education contexts. The study's implications and limitations and recommendations for future research are discussed.

(1) There are several patients with asthma-COPD overlap (ACO). A peptide derived from the primary sequence of a kallikrein inhibitor isolated from Bauhinia bauhinioides (pep-BbKI) has potent anti-inflammatory and antioxidant effects. Purpose: To investigate the effects of pep-BbKI treatment in an ACO model and compare them with those of corticosteroids. (2) BALB/c mice were divided into groups: SAL (saline), OVA (ovalbumin), ELA (elastase), ACO (ovalbumin + elastase), ACO-pep-BbKI (treated with inhibitor), ACO-DX (dexamethasone treatment), ACO-DX-pep-BbKI (both treatments), and SAL-pep-BbKI (saline group treated with inhibitor). We evaluated: hyperresponsiveness to methacholine, bronchoalveolar lavage fluid (BALF), exhaled nitric oxide (eNO), IL-1β, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, IFN-γ, TNF-α, MMP-9, MMP-12, TGF-β, collagen fibers, iNOS, eNO, linear mean intercept (Lm), and NF-κB in airways (AW) and alveolar septa (AS). (3) ACO-pep-BbKI reversed ACO alterations and was similar to SAL in all mechanical parameters, Lm, neutrophils, IL-5, IL-10, IL-17, IFN-γ, TNF-α, MMP-12 (AW), collagen fibers, iNOS (AW), and eNO ( p > 0.05). ACO-DX reversed ACO alterations and was similar to SAL in all mechanical parameters, Lm, total cells and differentials, IL-1β(AS), IL-5 (AS), IL-6 (AS), IL-10 (AS), IL-13 (AS), IFN-γ, MMP-12 (AS), TGF-β (AS), collagen fibers (AW), iNOS, and eNO ( p > 0.05). SAL was similar to SAL-pep-BbKI for all comparisons ( p > 0.05). (4) Pep-BbKI was similar to dexamethasone in reducing the majority of alterations of this ACO model.

Jewel tetra ( Hyphessobrycon eques ) is a freshwater fish found in several rivers and basins in South America. The present study is the first study to create a panel of microsatellite markers for detecting genetic diversity in H. eques and evaluating the application of these markers in Serrapinnus notomelas . In total, 44 individuals were genotyped from the natural (WIL, n  = 20) and stock in captivity (CAP, n  = 24) population. Moreover, 19 microsatellite markers were obtained, of which only 8 loci presented a high degree polymorphism. In total, 45 alleles were detected, ranging from 126 bp (Hype2G2) to 420 bp (Hype2E2). The Hardy-Weinberg equilibrium ( p  < 0.05) revealed significant difference in one locus in WIL (Hype1G4) and three loci in CAP (Hype1F4, Hype2C3, and Hype2G2). Null alleles ( p  < 0.05) were present in only one locus (Hype1G4). The WIL and CAP populations revealed high genetic diversity during F ST analysis. The cross-amplification test for S. notomelas revealed that only two loci (Hype2C3 and Hype2G2B) presented satisfactory transferability results. The developed microsatellite primers will be useful in studying the genetic diversity and population structure of H. eques in wild populations and fish farms in the Brazilian and other South American basins.

Variance components and heritabilities for daily weight gain (DWG) were estimated for Nile tilapia farmed in cages across nine generations (G1-G9) of selection in a breeding program in Brazil. DWG was measured in 16,272 accumulated tagged animals representing 535 full- and half-sib families of Nile tilapia under cage farming. The additive genetic variance showed a slight variation (0.051-0.066), and heritability estimates ranged from 0.20 to 0.33. The common environmental effect accounted for a higher proportion of the total variance in DWG, especially in the last generations (6%-24%). A genetic trend based on all data available showed a substantial increase in the DWG (about 3.3% per generation) of Nile tilapia across nine generations of selection. Furthermore, our results demonstrate ample scope for further genetic improvement., (© 2021 Wiley-VCH GmbH.)

Aim: To investigate the effect of resistance training (RT) on hepatocardiovascular and muscle mitochondrial parameters in rats that were fed a high-calorie diet for 12 weeks., Main Methods: The animals were divided into four groups: control (C), exercise (E), obese (O), and obese plus exercise (OE). Group E and OE rats performed resistance training by climbing on a vertical ladder with load attached to the end of the tail (1×/day, 3×/week, for 12 weeks). Group O and OE rats were fed a high-calorie diet containing chow and a cafeteria diet for 12 weeks. Under anesthesia, the heart and liver were removed for histopathological analysis, and the gastrocnemius muscle was removed for Western blotting., Key Findings: Group O rats were heavier, with increased fat mass, elevated fasting glycemia, and total triglycerides, and exhibited a significant number of Kupffer cells and diffuse steatosis in the liver. Group O rats also showed increased thickness of the right ventricle, septum, and pulmonary artery. All of these parameters were attenuated by RT. PGC1-α protein levels were increased in both exercise groups. The protein levels of OXPHOS complexes III, IV, and V were reduced in Group O, while RT prevented this alteration., Significance: RT exerts a protective effect against hepato-cardiac alterations and prevents changes in the muscle mitochondrial protein profile induced by a high-calorie diet., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s).)

Digital image analysis is a practical, non-invasive, and relatively low-cost tool that may assist in the evaluation of body traits in Nile tilapia, being particularly useful for assessing difficult-to-measure variables, such as body areas. In this study, we aimed to estimate variance components and genetic parameters for body areas of Nile tilapia obtained by digital images. The data set comprised body weight (BW) records of 1,917 pond-reared fish at 366 days of age. Of this total, 656 animals were photographed and subjected to image analysis of trunk area (TA), head area (HA), caudal fin area (CFA) and fillet area (FA). Heritabilities and genetic correlations were estimated through multiple-trait models based on Bayesian inference. Heritability estimates for BW, TA, HA, CFA and FA were 0.25, 0.23, 0.26, 0.21 and 0.25, respectively. Genetic correlations between the traits were high and positive, ranging from 0.70 to 0.98. We highlight the genetic correlation between BW and TA (r G  = 0.98) and FA (r G  = 0.97). In view of the observed results, it can be concluded that trunk and fillet areas obtained by digital image analysis can lead to indirect genetic gains in weight and other body areas. In addition, the areas studied have potential as a selection criterion and may assist in studies on changes in the body shape in Nile tilapia., (© 2021 Wiley-VCH GmbH.)

Purpose: This study was conducted to analyze the profile and publication rate of abstracts in indexed journals presented in the cornea section at the Association for Research in Vision and Ophthalmology Annual Meeting and to further identify potential predictive factors for better outcomes., Methods: Abstracts accepted for presentation at the 2013 Association for Research in Vision and Ophthalmology Annual Meeting in the cornea section were sought via PubMed and Scopus to identify whether they had been published as full-text manuscripts. First author's name, time of publication, journal's name, and impact factor were recorded. A multivariate regression was performed to explore the association between variables and both the likelihood of publication and the journal's impact factor. A Kaplan-Meier analysis was performed to evaluate the time course of publication of abstracts., Results: Of the 939 analyzed abstracts, 360 (38.3%) were published in journals with a median impact factor of 3.4. The median time interval between abstract submission and article publication was 22 months. The multivariate analysis revealed that abstracts were more likely to be published if they were funded (OR=1.482, p=0.005), had a control group (OR=1.511, p=0.016), and had a basic science research scope (OR=1.388, p=0.020). The journal's impact factor was higher in funded studies (β=0.163, p=0.002) but lower in multicenter studies (β=-0.170, p=0.001). The Kaplan-Meier analyses revealed significant differences in the publication time distribution for basic science vs clinical abstracts (χ2=7.636), controlled vs uncontrolled studies (χ2=6.921), and funded vs unfunded research (χ2=13.892) (p<0.05)., Conclusion: Almost 40% of Association for Research in Vision and Ophthalmology abstracts were published within 5 years from submission. Funding support, basic research scope, and controlled design were the determinants of better outcomes of publication.

Purpose: To analyze the comparative safety and efficacy of two techniques of corneal neurotization (CN) (direct corneal neurotization [DCN] vs indirect corneal neurotization [ICN]) for the treatment of neurotrophic keratopathy (NK)., Design: Multicenter interventional prospective comparative case series., Methods: This study took place at ASST Santi Paolo e Carlo University Hospital, Milan; S.Orsola-Malpighi University Hospital, Bologna; and Santa Maria alle Scotte University Hospital, Siena, Italy. The study population consisted of consecutive patients with NK who underwent CN between November 2014 and October 2019. The intervention procedures included DCN, which was was performed by transferring contralateral supraorbital and supratrochlear nerves. ICN was performed using a sural nerve graft. The main outcome measures included NK healing, corneal sensitivity, corneal nerve fiber length (CNFL) measured by in vivo confocal microscopy (IVCM), and complication rates., Results: A total of 26 eyes in 25 patients were included: 16 eyes were treated with DCN and 10 with ICN. After surgery, NK was healed in all patients after a mean period of 3.9 months without differences between DCN and ICN. Mean corneal sensitivity improved significantly 1 year after surgery (from 3.07 to 22.11 mm; P < .001) without differences between the 2 groups. The corneal sub-basal nerve plexus that was absent before surgery in all patients, except 4, become detectable in all cases (mean CNFL: 14.67 ± 7.92 mm/mm 2 1 year postoperatively). No major complications were recorded in both groups., Conclusions: CN allowed the healing of NK in all patients as well as improvement of corneal sensitivity in most of them thanks to nerve regeneration documented by IVCM. One year postoperatively, DCN and ICN showed comparable outcomes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Nile tilapia (Oreochromis niloticus) is the major fish species produced in Brazil, a country with a vast territory and great climate diversity. This study assessed the effects of the genotype × environment interaction on heritability estimates and selection responses in Nile tilapia (Tilamax strain) cultivated in earthen ponds and net cages. The weight at harvest, trunk length, and head percentage of 4400 individuals were determined. Trait heritabilities were higher in pond fish (0.27-0.52) than in caged fish (0.09-0.33). Genetic correlations between farming systems were lower than 0.5 for the three traits. The rank position of the top 10 families differed according to the environment, as did the response to direct and indirect selection. The results revealed significant genotype × environment effects on the heritability of Nile tilapia farmed under different systems.

Although the tambaqui (Colossoma macropomum) is the most cultivated native fish species in Brazil, estimated breeding values for growth traits are rarely used for selection of superior individuals in commercial fingerling production. This study aimed to estimate the (co)variance components of growth traits. Body weight, length and width of 2500 tambaqui were determined at tagging and at 6 and 12 months after tagging in a commercial breeding programme in Brazil. Heritability estimates were low for traits measured at tagging (0.10 to 0.19) and moderate to high for traits measured at 6 and 12 months (0.23 to 0.81). Common full-sib effects were high at tagging (>73%), low at 6 months and negligible at 12 months. Positive genetic correlations were found among growth traits at 12 months (0.84 to 0.99) and between growth traits at 6 and 12 months (0.80 to 0.92). These results show that animal selection can be performed at 6 months after tagging. Expected genetic gains for growth traits ranged from 8% to 31%. A simulation of the sex ratio was performed, as individuals did not reach sexual maturity during the experimental period. Because of the sexual dimorphism, more accurate heritability estimates were obtained when considering the female proportion to be 90% in the high-weight group. The findings indicate that it is possible to obtain considerable genetic gains in growth by selecting for growth traits. The development of a tool to determine the sex of animals at early stages can improve the response to selection in tambaqui.

Purpose: To use an automated morphometric analysis system of in vivo confocal microscopy (IVCM) images for evaluating reinnervation occurring at the subbasal nerve plexus (SNP) after direct corneal neurotization (DCN) and to further report neurophysiological and histopathological findings., Methods: Prospective interventional case series including 3 eyes with neurotrophic keratitis that underwent DCN. Deep anterior lamellar keratoplasty was performed 18 months after DCN in patient 1. The following evaluations were performed before and at 3, 6, and 12 months after DCN: clinical evolution of keratitis; corneal sensitivity; IVCM images of the SNP analyzed with "ACCMetrics;" neurophysiological study of corneal reflex. Protein gene product 9.5 immunofluorescence staining assay and transmission electron microscopy were conducted on the neurotized button excised during deep anterior lamellar keratoplasty., Results: Complete healing was obtained in all patients by 3 months postoperatively. Corneal sensitivity was absent preoperatively in all eyes and improved after surgery, reaching an average value of 30 mm 1 year postoperatively. The corneal SNP was not visible at IVCM in any of the cases preoperatively and became visible by 3 months postoperatively, showing IVCM metrics comparable to normal contralateral eyes at 1 year. In all cases, neurophysiological evaluation showed a partial recovery of the electrical activity of the cornea. In patient 1, protein gene product (PGP) 9.5 staining of neurotized cornea showed nerve fascicles at the SNP, whereas transmission electron microscopy showed amyelinic nerve axons and nerve endings., Conclusions: The corneal SNP exhibited IVCM metrics comparable to the normal contralateral eye 1 year after DCN. Ex vivo histopathological assessment of neurotized corneas confirmed the presence of nerves with normal ultrastructure.

Background and Aims: Expansion and morphological dysregulation of the bronchial vascular network occurs in asthmatic airways. Interleukin (IL) -17 and Rho-kinase (ROCK) are known to act in inflammation control and remodeling. Modulation of Rho-kinase proteins and IL-17 may be a promising approach for the treatment of asthma through the control of angiogenesis. Our objective was to analyze the effects of treatment with anti-IL17 and/or Rho-kinase inhibitor on vascular changes in mice with chronic allergic pulmonary inflammation., Methods: Sixty-four BALB/c mice, with pulmonary inflammation induced by ovalbumin were treated with anti-IL17A (7.5/µg per dose, intraperitoneal) and/or Rho-kinase inhibitor (Y-27632-10 mg/kg, intranasal), 1 h before each ovalbumin challenge (22, 24, 26, and 28/days). Control animals were made to inhale saline. At the end of the protocol, lungs were removed, and morphometric analysis was performed to quantify vascular inflammatory, remodeling, and oxidative stress responses., Results: Anti-IL17 or Rho-kinase inhibitor reduced the number of CD4 + , CD8 + , dendritic cells, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, Rho-kinase 1 and 2, transforming growth factor (TGF-β), vascular endothelial growth factor (VEGF), nuclear factor (NF)-KappaB, iNOS, metalloproteinase (MMP)-9, MMP-12, metalloproteinase inhibitor-1 (TIMP-1), FOXP-3, signal transducer and activator of transcription 1 (STAT1) and phospho-STAT1-positive cells, and actin, endothelin-1, isoprostane, biglycan, decorin, fibronectin and the collagen fibers volume fraction compared with the ovalbumin group ( p  < 0.05). The combination treatment, when compared with anti-IL17, resulted in potentiation of decrease in the number of IL1β- and dendritic cells-positive cells. When we compared the OVA-RHO inhibitor-anti-IL17 with OVA-RHO inhibitor we found a reduction in the number of CD8 + and IL-17, TGF-β, and phospho-STAT1-positive cells and endothelin-1 in the vessels ( p  < 0.05). There was an attenuation in the number of ROCK 2-positive cells in the group with the combined treatment when compared with anti-IL17 or Rho-kinase inhibitor-treated groups ( p  < 0.05)., Conclusion: We observed no difference in angiogenesis after treatment with Rho-kinase inhibitor and anti-IL17. Although the treatments did not show differences in angiogenesis, they showed differences in the markers involved in the angiogenesis process contributing to inflammation control and vascular remodeling. The reviews of this paper are available via the supplemental material section.

Purpose: To investigate the comparative effect of allogeneic peripheral blood serum (allo-PBS) and cord blood serum (CBS) eye drops on the status of the corneal subbasal nerve plexus in patients with dry eye disease by using an automated analysis system of in vivo confocal microscopy images., Methods: This prospective, randomized, double-blind study included 30 patients with severe dry eye disease assigned to receive allo-PBS (group 1) or CBS (group 2) eye drops 8 times a day for 30 days. The following in vivo confocal microscopy parameters were calculated with ACCMetrics before (visit 1 [V1]) and after treatment (visit 2 [V2]): corneal nerve fiber density, corneal nerve branch density, corneal nerve fiber length, corneal nerve total branch density, corneal nerve fiber area, corneal nerve fiber width, and corneal nerve fractal dimension (CNFrD)., Results: In overall patients, the values of corneal nerve fiber density, corneal nerve fiber length, and CNFrD significantly increased, whereas the value of corneal nerve fiber width significantly decreased at V2 compared with V1 (respectively, 20.4 ± 7.9 vs. 17.4 ± 10.1 n/mm; 13.5 ± 4.0 vs. 12.0 ± 5.1 mm/mm; 1.466 ± 0.046 vs. 1.475 ± 0.033; and 0.022 ± 0.002 vs. 0.023 ± 0.002; all P < 0.05). In the subanalysis according to the treatment type, the increase of CNFrD value from V1 to V2 was higher in group 2 compared with group 1 (respectively, from 1.455 ± 0.041 to 1.471 ± 0.030 and from 1.479 ± 0.050 to 1.481 ± 0.035; P = 0.030)., Conclusions: Overall, both treatments significantly improved corneal subbasal nerve plexus parameters, and in particular, nerve density, length, width, and fractal dimension. Treatment with CBS eye drops was associated with a higher increase of CNFrD compared with allo-PBS.

Objectives : To investigate longitudinally corneal sub-basal nerve plexus (SNP) by means of in vivo confocal microscopy (IVCM) in the contralateral eye (CE) of patients with unilateral neurotrophic keratitis (NK) secondary to central nervous system (CNS) diseases who underwent different treatments. Methods : Ten patients with NK and 10 matched controls were included. In 7 NK patients, conservative treatment maintained unchanged the clinical picture over the 1-year follow-up (Group 1), while NK progressed in 3 patients who underwent direct corneal neurotization (Group 2). IVCM scans of SNP of NK patients were acquired in CE at baseline (V0) ad after 1-year follow-up (V1). All images were analyzed with the automated software "ACCMetrics" and compared with controls. The following IVCM corneal nerve parameters were calculated at V0 and V1 with ACCMetrics: fiber density (CNFD), branch density (CNBD), fiber length (CNFL), total branch density (CTBD), fiber area (CNFA), fiber width (CNFW), and fractal dimension (CNFrD). Results : At V0, significantly lower mean values of CNFD and CNBD, and higher values of CNFW were detected in CE of NK patients compared to controls (respectively, 16.9 ± 8.7 vs 25.0 ± 8.3 n/mm 2 , P = .029; 19.3 ± 13.8 vs 33.8 ± 18.9 n/mm 2 , P = .023; 0.022 ± 0.002 vs 0.020 ± 0.001 mm/mm 2 , P < .001). From V0 to V1, all IVCM metrics of CE remained unchanged in Group 1, while they improved in Group 2. Conclusions : Contralateral eye of patients with unilateral NK secondary to CNS disease showed lower CNFD and CNBD and higher CNFW compared to controls. Unlike conservative treatment, direct corneal neurotization was able to improve SNP metrics also in CE.

Purpose: To compare choroidal vascularity index (CVI) in patients with arteritic anterior ischemic optic neuropathy (A-AION), nonarteritic anterior ischemic optic neuropathy (NA-AION), and control subjects., Design: Retrospective cross-sectional study., Methods: This study was conducted at the Ophthalmology Unit of the S.Orsola-Malpighi University Hospital (Bologna, Italy). Macular and optic nerve head optical coherence tomography (OCT) scans of 20 patients with A-AION secondary to giant cell arteritis (biopsy-proven), 20 patients with NA-AION, and 20 control subjects were acquired with Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany). Images were binarized using ImageJ software, and total choroid area (TCA), luminal area (LA), and stromal area (SA) were segmented. The main outcome measure was CVI, defined as the ratio of LA to TCA., Results: Patients with A-AION showed a significantly lower macular and peripapillary CVI compared to both patients with NA-AION (respectively, 67.17 ± 2.35 vs 69.66 ± 4.18, P = .048; 63.51 ± 3.29 vs 67.67 ± 3.07, P < .001) and control subjects (respectively, 67.17 ± 2.35 vs 70.00 ± 2.95, P = .021; 63.51 ± 3.29 vs 68.69 ± 3.19, P = .002). Conversely, no significant difference in macular and peripapillary CVI was found between patients with NA-AION and controls (respectively, P = .942 and P = .570). After adjustment for age, the difference of peripapillary CVI among groups remained statistically significant (P < .001), while the difference in macular CVI did not (P = .060)., Conclusions: Macular and peripapillary CVI are reduced in patients with A-AION. These parameters may be useful to quantitatively evaluate choroidal vascular dysfunction in A-AION, serving as a new additional diagnostic tool to distinguish A-AION from NA-AION., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To assess whether omega-3 fatty acid (FA) supplementation is more efficacious than placebo in amelioration of signs and symptoms of dry eye disease., Methods: We performed a systematic literature search in PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases. We included randomized clinical trials comparing omega-3 FA supplementation with placebo in patients with dry eye disease. The outcome measures were dry eye symptoms, breakup time (BUT), Schirmer test, and corneal fluorescein staining. The pooled effect sizes were estimated using a random-effects model. Heterogeneity was evaluated using the Q and I tests. Sensitivity analysis and assessment of publication bias were performed. Meta-regression was performed to evaluate the source of heterogeneity., Results: Seventeen randomized clinical trials involving 3363 patients were included. Compared with placebo, omega-3 FA supplementation decreased dry eye symptoms [standardized difference in mean values (SDM) = 0.968; 95% confidence interval (CI) 0.554-1.383; P < 0.001] and corneal fluorescein staining (SDM = 0.517; 95% CI, 0.043-0.991; P = 0.032), whereas it increased the BUT (SDM = 0.905; 95% CI, 0.564-1.246; P < 0.001) and Schirmer test values (SDM = 0.905; 95% CI, 0.564-1.246; P < 0.001). No evidence of publication bias was observed, and sensitivity analyses indicated the robustness of results obtained. Meta-regression analysis showed a higher improvement of dry eye symptoms and BUT in studies conducted in India., Conclusions: This meta-analysis provides evidence that omega-3 FA supplementation significantly improves dry eye symptoms and signs in patients with dry eye disease. Therefore, our findings indicate that omega-3 FA supplementation may be an effective treatment for dry eye disease.

Purpose: To compare corneal biomechanics between patients with ocular graft versus-host disease (oGVHD) and healthy subjects (controls), and to further correlate these values with ocular and hematological characteristics., Materials and Methods: The following procedures were performed in oGVHD patients and controls: Schirmer test (ST), break-up time (BUT), corneal and conjunctival staining, tear matrix metalloproteinase-9 (MMP-9) assay (InflammaDry test, Rapid Pathogen Screening, Inc, Sarasota, FL). Corneal biomechanics were calculated by using ocular response analyzer (ORA, Reichert Instruments, Depew, New York, USA). The Mann-Whitney U test was used to compare continuous variables between oGVHD patients and controls. Correlations of corneal biomechanics with ocular and hematological parameters were examined using Spearman's correlation., Results: A total of 45 oGVHD patients (mean age ± SD, 51.5 ± 7.1 years) and 34 controls (47.8 ± 6.1 years) were included. Patients with oGVHD showed significantly lower values of corneal hysteresis (CH) and corneal resistance factor (CRF) compared to controls (respectively, 9.4 ± 1.8 mmHg vs 11.6 ± 1.6 and 9.7 ± 1.4 mmHg vs 12.3 ± 1.3; always p<0.001). Twenty-nine of the oGVHD eyes (64.4%) were strong-positive for MMP-9, while 16 (35.6%) were weak-positive. Conversely, only 4 of the control eyes (11.8%) were weak-positive for MMP-9. In patients with oGVHD, CH was significantly correlated with corneal staining (Rs = -0.316, p = 0.035), conjunctival staining (Rs = -0.437, p = 0.003), ST (Rs = 0.390, p = 0.008), BUT (Rs = 0.423, p = 0.004), oGVHD severity grade (Rs = -0.383, p = 0.009), and MMP-9 positivity grade (Rs = -0.429, p = 0.003), while CRF was correlated only with corneal staining (Rs = -0.317, p = 0.034)., Conclusions: Corneal biomechanics are reduced in patients with oGVHD, and CH is negatively correlated with disease severity grade and MMP-9 tear levels., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To evaluate refractive, binocular vision and ocular alignment outcomes of photorefractive keratectomy (PRK) for the treatment of hyperopia in esotropic patients., Methods: Medical charts of hyperopic patients with full or partial accommodative esotropia (FAE or PAE) or consecutive exotropia (CE) undergone PRK from 2011 to 2014 were reviewed. The primary outcome was to assess the efficacy of PRK in improving ocular alignment. The secondary outcomes were the assessments of uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), spherical equivalent (SE) and stereoacuity., Results: Sixty-four eyes of 32 hyperopic patients were included. Three patients were affected by FAE, 24 by PAE and 5 by CE. All FAE patients and 4 PAE patients underwent only PRK; the remaining 25 patients underwent PRK plus strabismus surgery. After PRK, the mean corrected esodeviation decreased significantly in the overall esotropic population [7.15 ± 9.42 prism diopters (PD) vs. 5.04 ± 8.83 PD; p = 0.03] and in particular in the group with small-angle esodeviation (< 20 PD). Conversely, the only 2 patients with an angle of strabismus ≥ 20 PD as well as all CE patients did not show any postoperative variation of the deviation angle. Mean preoperative BCVA did not differ from postoperative UCVA (p = 0.19), while the mean postoperative SE decreased significantly after PRK (p < 0.0001)., Conclusions: Our study confirmed that PRK eliminates the accommodative component of the deviation. In addition, this procedure seems to reduce or eliminate also the non-accommodative component of esodeviation (especially in small-angle deviation), thus suggesting to postpone strabismus surgery after PRK when esotropia and hyperopia coexist.

Purpose: To evaluate in vivo confocal microscopy (IVCM) features of corneal subbasal nerve plexus (SNP) in the setting of dry eye disease (DED) using fully automated software "ACCMetrics," and to further investigate its diagnostic performance in discriminating DED patients., Methods: IVCM exams of SNP in DED patients and matched control subjects were performed using Heidelberg Retina Tomograph with the Rostock Cornea Module. The following parameters were obtained with ACCMetrics: corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), corneal nerve total branch density (CTBD), corneal nerve fiber area (CNFA), corneal nerve fiber width (CNFW), and corneal nerve fractal dimension (CNFrD). The Mann-Whitney U test was used to compare variables. Receiver operating characteristic curves with calculations of the area under the curve (AUC) were used to describe the accuracy of IVCM parameters for discriminating DED patients from controls., Results: Thirty-nine DED patients and 30 control subjects were included. Significantly, lower values of CNFD, CNBD, and CNFL and higher value of CNFW were found in DED patients compared to controls (respectively, 20.5 ± 8.7 vs 25.4 ± 6.7 n/mm 2 ; 25.6 ± 20.1 vs 37.6 ± 21.5 n/mm 2 ; 12.6 ± 4.4 vs 14.5 ± 2.9 mm/mm 2 ; 0.021 ± 0.001 vs 0.019 ± 0.001 mm/mm 2 ; always p < 0.024). CNFW value had the highest diagnostic power in discriminating DED patients (AUC = 0.828). When the diagnosis of DED was made based on either CNFW or CNBD, the sensitivity was 97.4% and the specificity 46.7%., Conclusions: The software ACCMetrics was able to rapidly detect SNP alterations occurring in the setting of DED and showed good diagnostic performance in discriminating DED patients.

This is a prospective interventional clinical study evaluating intraocular inflammation developed after Ultrasound Cyclo Plasty (UCP) for the treatment of glaucoma. Eighteen eyes of 18 patients were treated with UCP second-generation probes (Eye OP1). After treatment, the mean intraocular pressure (IOP) significantly decreased from 26.8±7.2 to 18.8±6.1 mm Hg at day 1 and to 14.7±3.4 mm Hg at month 6 (all P <0.001). Mean laser flare-cell photometry value steeply increased after surgery from 12.1±7.5 to 64.1±53.9 ph/ms ( P =0.001) at day 1, and then progressively decreased to respectively 60.6±49.7 at day 7, 43.5±38.5 at day 14 and 28.2±18.3 at month 1 (all P <0.05), returning at levels similar to baseline ones at month 3 and month 6 (respectively 16.7±6.2 and 12.8±10.2, both P >0.05). A significant negative correlation was found between postoperative increase of aqueous flare values and anterior chamber depth ( R =-0.568, P =0.014). This timeframe may be considered reasonable for repeating UCP treatment, when required.

Doxorubicin (DOX) is a cytostatic antibiotic from the class of anthracyclines widely used in chemotherapeutic cancer treatments. Despite the efficiency against several types of cancer, the use of DOX remains limited due to the side effects, especially cardiotoxicity. Among the DOX administration strategies, there are the "classic players" such as nanoparticles and polymers, which are capable of DOX delivery directly to interesting neoplastic regions. On the other hand, the "new players" such as phytochemicals and probiotics emerged with the proposal to react with DOX free radicals, reducing the oxidative stress, inflammatory and apoptotic process. Thus, this review aims to report the studies involving these classics and new players along the years that focus on improved administration and reduction of DOX-induced cardiotoxicity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: The aim of this study was to evaluate the safety and efficacy of ultrasound cyclo-plasty (UCP) for reducing intraocular pressure (IOP) in patients with glaucoma., Methods: This is a multicentre prospective study conducted in 3 Italian glaucoma centres. UCP was performed by EyeOP1, which delivers ultrasound beams using 6 piezoelectric transducers activated for 4/6 s (first generation) or 8 s (second generation). Primary outcomes were the mean IOP reduction and the rates of success after 1 year. Secondary outcomes were the mean IOP reduction at each follow-up, and the reduction of the number of hypotensive medications., Results: In total, 49 eyes from 47 patients were treated. One year postoperatively, the mean IOP had decreased from 27.7 ± 9.2 to 19.8 ± 6.9 mm Hg (p < 0.001), and the mean number of hypotensive drops and tablets had decreased from 3.2 and 0.5 to 2.3 and 0.2, respectively (p < 0.05). Postoperative IOP reduction was significantly related to preoperative IOP (r2 = 0.5034; p < 0.0001). Second-generation probes determined a significantly higher IOP reduction (p < 0.05). Qualified success was achieved in 25 eyes (51.1%) and complete success in 21 (42.9%), while failure was recorded in 12 (24.5%)., Conclusions: UCP is safe and effective for reducing IOP. The procedure determines a greater IOP reduction in patients with higher preoperative IOP. Second-generation probes improve outcomes without detrimental effects on safety., (© 2018 S. Karger AG, Basel.)

Purpose: To compare the proportion and the agreement rate in the diagnosis of chronic ocular graft-versus-host disease (GVHD) among three criteria applied with and without ophthalmological examination before hematopoietic stem cell transplantation (HSCT)., Methods: National Institutes of Health (NIH), International Consensus Criteria on ocular GVHD (ICCGVHD) and TFOS Dry Eye Workshop (DEWS) II criteria were used for the diagnosis of ocular GVHD according to two protocols: ophthalmological examination after HSCT (Protocol A), or before and after HSCT (Protocol B). Proportion of GVHD diagnosis and inter-rate agreement coefficient Kappa (K) among the criteria were calculated., Results: One hundred nine patients undergone HSCT were included. NIH, ICCGVHD and DEWS II criteria diagnosed ocular GVHD in 14.7%, 17.4% and 59.6% of the patients (Protocol A), whereas in 11.9%, 15.6% and 33.0% of the HSCT patients (Protocol B). The coefficient K for the proportion of patients diagnosed with ocular GVHD by NIH and ICCGVHD criteria was K = 0.626 (Protocol A) and K = 0.615 (Protocol B). The K coefficient by NIH and DEWS II criteria was K = 0.144 (Protocol A), and K = 0.233 (Protocol B). The K coefficient by ICCGVHD and DEWS II criteria was K = 0.250 (Protocol A) and K = 0.499 (Protocol B). The K coefficient for ocular GVHD diagnosis applying Protocol A and B was K = 0.881 if NIH criteria were used, K = 0.933 if ICCGVHD criteria were used and K = 0.501 if DEWS II criteria were used., Conclusions: The diagnosis of ocular GVHD varied significantly in our cohort of hematological patients according to both the diagnostic criteria used and the visit protocols applied.

Purpose: To compare the efficacy and tolerability of diclofenac and bromfenac ophthalmic solutions as adjunctive therapy after cataract surgery., Materials and Methods: This prospective randomized controlled study included 130 patients who underwent cataract surgery. One hundred patients were randomized to receive postoperatively diclofenac 0.1% (four times daily for 28 days, Group 1) or bromfenac 0.09% (twice daily for 14 days, Group 2) ophthalmic solutions in addition to steroid-antibiotic combination. Thirty patients instilled only steroid-antibiotic combination (Control Group 3). Laser flare-cell photometry and optical coherence tomography scans with central foveal thickness (CFT) measurement were performed before (V0) and 7 (V1), 14 (V2) and 28 days (V3) after surgery. Treatment tolerability was scored using the Ocular Comfort Grading Assessment., Results: Laser flare-cell photometry values were significantly higher at V1, V2 and V3 compared to V0 in all the groups (respectively 13.3 ± 1.0, 12.7 ± 0.9 and 9.6 ± 0.9 vs 8.4 ± 0.6 ph/ms for Group 1; 13.4 ± 1.0, 12.7 ± 0.9 and 12.7 ± 1.0 vs 8.1 ± 0.6 for Group 2; 15.9 ± 0.8, 15.4 ± 0.7 and 14.5 ± 0.7 vs 7.5 ± 0.5 for Group 3) (p < 0.001); flare increase was significantly lower in Group 1 compared to Groups 2 and 3 (p < 0.001). CFT values were higher after surgery in all the three groups; the increase was significantly lower in Group 1 compared to Groups 2 and 3 (p < 0.0002). The percentage of symptoms-free patients after study treatment was significantly higher in Group 2 compared to Group 1 (respectively 74% vs 14% of the total; p < 0.001)., Conclusion: The addition of diclofenac or bromfenac ophthalmic solutions contributed to further reduce both inflammation and cystoid macular edema after cataract surgery compared to steroid-antibiotic combination alone. Diclofenac appeared to be more effective in reducing postoperative intraocular inflammation with a more intense and prolonged regimen, while bromfenac more tolerated with lower daily dose and treatment duration.

Background The contribution of tear protein expression in patients with presumed diagnosis of Sjögren syndrome is underestimated. We aimed to evaluate the role of tear proteins in the Sjögren syndrome early diagnosis. Methods Charts from 110 patients suspected of Sjögren syndrome were analysed and the subsequent diagnosis retrieved. Subjective symptoms (ocular surface disease index, OSDI), tear film break-up time (TFBUT), Schirmer test, Jones test, tear clearance (TC), corneal (NEI score) and conjunctival staining (van Bjerstelveldt score), esthesiometry, cytology, tear protein analysis (total protein [TP] content, lysozyme-C [LYS-C], lactoferrin [LACTO], lipocalin-1 [LIPOC-1] and albumin [ALB]) were analysed. The diagnostic performance with area under the curve (AUC) and odds ratio (OR) for each parameter were calculated. Results Thirty-five patients (31.8%) had been diagnosed as affected by Sjögren syndrome. Clinical tests showed lower diagnostic performance (OSDI > 44 [AUC 0.57], Schirmer ≤ 5 mm [0.59], TFBUT ≤ 3 s [0.72], TC > 1/16 [0.68], Jones ≤ 4 mm [0.68], corneal staining > 2 [0.51], conjunctival staining > 2 [0.78]) compared with tear proteins (LYS-C ≤ 1.5 mg/mL [0.79], LACTO ≤ 20% [0.94], LIPOC-1 ≤ 10% [0.89], ALB ≥ 15% [0.79]). LYS-C, LACTO, LIPOC-1 and ALB showed a significant association in predicting Sjögren syndrome vs. not-Sjögren syndrome dry eye (OR, respectively, 4.9, 5.5, 7.2, 6.7). Conclusions Tear proteins' concentrations showed a significant higher accuracy compared with the traditional ocular clinical tests for reaching Sjögren syndrome's diagnosis. In particular, LACTO and LIPOC-1 provided an excellent diagnostic performance and thus could likely be considered promising biomarkers of Sjögren syndrome.

Introduction: Various blood-derived products have been proposed for the topical treatment of ocular surface diseases. The aim of the study was to compare the different content of Growth Factors (GFs) and Interleukins (ILs) in peripheral blood (PB-S) and Cord Blood (CB-S) sera., Materials and Methods: Sera were obtained from 105 healthy adult donors (PB-S) and 107 umbilical/placental veins at the time of delivery (CB-S). The levels of epithelial-GF (EGF), fibroblast-GF (FGF), platelet-derived-GF (PDGF), insulin-GF (IGF), transforming-GF alpha (TGF-α,) and beta 1-2-3 (TGF-β1-β2-β3), vascular endothelial-GF (VEGF), nerve-GF (NGF), Interleukin (IL)-1β,IL-4,IL-6,IL-10, and IL-13 were assessed by Bio-Plex Protein Array System (Bio-Rad Laboratories, CA, USA). The Mann-Whitney test for unpaired data was applied to compare GFs and ILs levels in the two sources. The associations among each GF/IL level and the obstetric data for CB-S and hematological characteristics for PB-S were also investigated., Results: The levels of EGF, TGF-α, TGF-β2, FGF, PDGF, VEGF, NGF, IL-1B, IL-4, IL-6, IL-10, and IL-13 were significantly higher in CB-S compared to PB-S. Conversely, the levels of IGF-1, IGF-2, and TGF-β1 were significantly higher in PB-S. The female sex and the weight of the child showed a significant association in predicting EGF and PDGF levels., Conclusion: A significantly different content in those GFs and ILs was demonstrated in the two blood sources. Since each GF/IL selectively regulates different cellular processes involved in corneal healing, the use of PB-S or CB-S should be chosen on the basis of the cellular mechanism to be promoted in each clinical case., (Copyright © 2018. Published by Elsevier Ltd.)

Purpose: To evaluate the rate and outcomes of immunologic stromal rejection occurring after large deep anterior lamellar keratoplasty (DALK) and the effect of the underlying disease on the cumulative probability of rejection., Methods: This was a retrospective chart review of all eyes that underwent a 9-mm DALK at Ospedali Privati Forlì (Forlì, Italy). On the basis of preoperative diagnosis, eyes were assigned to group 1: keratoconus, group 2: stromal disease with a low risk for rejection, or group 3: stromal disease with a high risk for rejection. The cumulative probability of experiencing a rejection episode over time was assessed by Kaplan-Meier analysis and was compared among the 3 groups using the log-rank test. Values of corrected distance visual acuity, central corneal thickness, and endothelial cell density before and 6 months after rejection were compared., Results: Twenty of 377 eyes (5.3%) experienced an episode of stromal rejection [17/265 (6.4%) in group 1, 2/71 (2.8%) in group 2, and 1/41 (2.4%) in group 3]. The mean time interval between DALK and the rejection onset was 11.8 months (range 1-24). The cumulative probability of rejection episodes did not differ significantly among the 3 groups. All episodes resolved within 6 months after the onset, with no significant differences between prerejection and 6-month postrejection values of corrected distance visual acuity, central corneal thickness, and endothelial cell density., Conclusions: The rate of immunologic stromal rejection after large 9-mm DALK is within the range reported in the literature for conventional DALK, regardless of the indication for surgery.

Fusional vergence is a disjunctive movement of the eyes that is made in order to obtain single vision. The aim of the study was to provide a quantitative and objective approach for analyzing the fusional convergence response using eye tracking (ET) technology and automatic data analysis provided by the intuitive SacLab toolbox previously developed by our group. We evaluated the proposed approach in a population of 26 subjects with normal binocular vision, who were tested with base-out prisms (magnitudes 4Δ, 6Δ, and 10Δ) in order to elicit fusional convergence response. Eye movements were recorded using the Viewpoint ET and analyzed using SacLab. Parameters describing both the vergence and the version components of the fusional response (convergence duration, CD; peak convergence velocity, PCV; number of intrusive saccades, NS; and mean saccadic amplitude, MSA) were automatically calculated and provided to clinicians for an objective evaluation. Results showed that the number of subjects achieving fusional convergence decreased with prism magnitude. For subjects achieving fusion CD and PCV increased significantly ( p < 0.05) when increasing the prism magnitude. For NS and MSA, there were no significant changes when passing to 6Δ, but a significant increase resulted when passing to 10Δ ( p < 0.05). Noninvasive ET associated with the intuitive SacLab toolbox may represent a valid option to objectively characterize the fusional vergence response in clinical setting. The analysis may be extended to patients with vergence disorders.

Neurotrophic keratitis (NK) is a degenerative corneal disease caused by damage of trigeminal corneal innervation, which leads to spontaneous epithelial breakdown and corneal ulceration. The impairment of corneal sensory innervation causes the reduction of both protective reflexes and trophic neuromodulators that are essential for the vitality, metabolism, and wound healing of ocular surface tissues. A wide range of ocular and systemic conditions, including herpetic keratitis, ocular chemical burns, corneal surgery, diabetes, multiple sclerosis, and neurosurgical procedures, can cause NK by damaging trigeminal innervation. Diagnosis of NK requires careful investigation of any ocular and systemic condition associated with the disease, complete ocular surface examination, and quantitative measurement of corneal sensitivity. The clinical stages of NK range from corneal epithelial alterations (stage 1) to persistent epithelial defect (stage 2) and ulcer (stage 3), which may progress to corneal perforation. Management of NK is based on clinical severity, and the aim of the therapy is to halt the progression of corneal damage and promote epithelial healing. Although several medical and surgical treatments have been proposed, no therapies are currently available to restore corneal sensitivity, and thus, NK remains difficult and challenging to treat. The purpose of this review is to summarize available evidence on the pathogenesis, diagnosis, and treatment of NK. Novel medical and surgical therapies including the topical administration of nerve growth factor and corneal neurotization are also described., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Purpose: To investigate the biomechanical response of the cornea, lamina cribrosa (LC), and prelaminar tissue (PT) to an acute intraocular pressure (IOP) increase in patients with markedly asymmetrical glaucoma and in healthy controls., Patients and Methods: A total of 24 eyes of 12 patients with markedly asymmetrical primary open-angle glaucoma (POAG) and 12 eyes of 12 healthy patients were examined with spectral-domain optical coherence tomography (SD-OCT) and ocular response analyzer (ORA) at baseline and during acute IOP elevation by means of an ophthalmodynamometer. The displacement of the LC and PT and the change in corneal hysteresis (CH) and corneal resistance factor (CRF) were evaluated., Results: Following a mean IOP increase of 12.3±2.4 mmHg, eyes with severe glaucoma demonstrated an overall mean anterior displacement of the LC (-6.58±26.09 µm) as opposed to the posterior laminar displacement in eyes with mild glaucoma (29.08±19.28 µm) and in healthy eyes (30.3±10.9; p ≤0.001 and p =0.001, respectively). The PT displaced posteriorly during IOP elevation in all eyes. The CH decreased in eyes with severe glaucoma during IOP elevation (from 9.30±3.65 to 6.92±3.04 mmHg; p =0.012), whereas the CRF increased markedly in eyes with mild glaucoma (from 8.61±2.30 to 12.38±3.64; p =0.002) and in eyes with severe glaucoma (from 9.02±1.48 to 15.20±2.06; p =0.002). The increase in CRF correlated with the anterior displacement of the LC in eyes with severe glaucoma., Conclusion: Eyes with severe glaucoma exhibited a mean overall anterior displacement of the anterior laminar surface, while eyes with mild glaucoma and healthy eyes showed a posterior displacement of the LC during IOP elevation. The CH decreased significantly from baseline only in eyes with severe glaucoma, but the CRF increased significantly in all glaucomatous eyes. The CRF increase correlated with the anterior displacement of the LC in eyes with severe glaucoma., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Objective: To determine whether weight loss in women with morbid obesity subjected to bariatric surgery alters lung function, respiratory muscle strength, functional capacity and the level of habitual physical activity and to investigate the relationship between these variables and changes in both body composition and anthropometrics., Methods: Twenty-four women with morbid obesity were evaluated with regard to lung function, respiratory muscle strength, functional capacity, body composition, anthropometrics and the level of habitual physical activity two weeks prior to and six months after bariatric surgery., Results: Regarding lung function, mean increases of 160 mL in slow vital capacity, 550 mL in expiratory reserve volume, 290 mL in forced vital capacity and 250 mL in forced expiratory volume in the first second as well as a mean reduction of 490 mL in inspiratory capacity were found. Respiratory muscle strength increased by a mean of 10 cmH2O of maximum inspiratory pressure, and a 72-meter longer distance on the Incremental Shuttle Walk Test demonstrated that functional capacity also improved. Significant changes also occurred in anthropometric variables and body composition but not in the level of physical activity detected using the Baecke questionnaire, indicating that the participants remained sedentary. Moreover, correlations were found between the percentages of lean and fat mass and both inspiratory and expiratory reserve volumes., Conclusion: The present data suggest that changes in body composition and anthropometric variables exerted a direct influence on functional capacity and lung function in the women analyzed but exerted no influence on sedentarism, even after accentuated weight loss following bariatric surgery.

Glaucoma is a chronic disease caused by the progressive degeneration of the optical nerve fibers, resulting in decreased visual field that can lead to severe visual impairment, and eventually blindness. This manuscript describes a simple, surgeon-friendly, non-incisional technique, named Ultrasound Cyclo Plasty (UCP), for reducing intraocular pressure (IOP) in glaucoma patients. The technique determines a selective coagulation necrosis of the ciliary body; in addition, the stimulation of supra-choroidal and trans-scleral portions of the uveo-scleral outflow pathway has been recently proposed. UCP shows several technical improvements in ultrasound technology compared to previous techniques, providing more precise focusing on the target zone. The procedure is performed in the operating room under peribulbar anesthesia. Briefly, the coupling cone is put in contact with the eye and the ring probe, that contains six piezoelectric transducers which produce the ultrasound beams, is inserted inside it. Their proper centering over the ocular surface represents a crucial step for the correct targeting of the ciliary body. Sterile balanced salt solution is used to fill the empty spaces to ensure ultrasound acoustic propagation. Surgical treatment consists in the sequential automatic activation of each of the six transducers, for a total duration of less than 3 min. The patient leaves the hospital 1 h after the procedure with the treated eye patched. In the present study, 10 patients with open-angle glaucoma were followed-up during at least 12 months after the procedure. IOP was reduced at each interval compared to pre-operative, as well as the number of hypotensive medications. Twenty percent of patients did not respond to the treatment, and needed subsequent surgery to better control IOP. Treatment tolerability was good, with no cases of hypotony or phthisis. The UCP procedure is simpler, faster, safer, and less invasive than traditional cyclodestructive procedures with similar results in reducing IOP.

Purpose: To evaluate the outcomes of early intra-trochlear steroid injections in patients with acquired Brown syndrome secondary to trochleitis (ABSST)., Methods: Retrospective analysis from medical charts of patients diagnosed as affected by unilateral ABSST from January 2008 to June 2015, and treated according to our Institution protocol: intra-trochlear injection of 1ml of triamcinolone acetonide 40 mg/ml is performed under sterile conditions. In cases of no resolution/improvement within 1 month, further monthly injections are performed up to a maximum number of three. Non-responder patients after three injections undergo recession of the superior oblique muscle., Results: Thirteen patients were diagnosed as affected by unilateral ABSST, and were included in the analysis (seven F, six M; median age at diagnosis 30.38 ± 25.56 years). The mean time interval from ABSST diagnosis to the first steroid injection was 7.84 ± 5.40 days (range 2-17). After a median number of 1.30 injections per patient, 11 patients (84.6% of the total) showed complete remission of symptoms and signs within 22.45 ± 13.85 days after the first injection. None of these responder patients referred to diplopia in primary gaze after injections. The remaining two non-responder patients after three injections underwent superior oblique muscle recession of 8.0 mm., Conclusions: Early intra-trochlear steroid injections are effective in patients with acquired Brown syndrome secondary to trochleitis, leading to a complete recovery of signs and symptoms in the majority of treated patients. Surgical treatment should be limited only to patients non-responding to serial steroid injections.

PurposeTo evaluate ocular surface parameters before and after hematopoietic stem cell transplantation (HSCT) and to correlate them with clinical and transplant variables.MethodsThis is a retrospective analysis of data from 93 patients affected by hematological malignancies undergoing HSCT. Values from Ocular Surface Disease Index, Schirmer test, Break-up Time, ocular surface staining, and Meibomian Gland Dysfunction score obtained before HSCT and 3-6 months after were retrieved from charts. Diagnosis and staging of dry eye (DE) disease was performed according to Dry Eye WorkShop criteria. Graft-versus-host-disease (GVHD) was classified according to the NIH criteria. Odds ratios for DE onset after HSCT were estimated for demographic, ocular, hematological and transplant variables.ResultsDE was diagnosed before HSCT in 50 (53%) of the patients, mostly of hyperevaporative profile. After HSCT, all ocular parameters significantly worsened with no change in DE profile. A 51% incident cases (22 of the 43 non-DE subjects) were reported. Increasing recipient age and female sex, higher CD34+ cells infused, donor-recipient sex mismatch (males receiving from females), related donors, and peripheral blood cells as stem cell source were associated with a significant higher incidence of DE after HSCT. Systemic chronic GVHD was diagnosed in 42% while ocular GVHD in 35.5% of the patients, which decreased to 12% when taking into account only incident cases.ConclusionsHigh DE prevalence was shown already before HSCT. A pre-HSCT ocular surface assessment is recommended for early DE diagnosis and treatment. This new protocol also influences the prevalence of ocular GVHD.

PurposeThe aim of this study is to assess the importance of magnetic resonance imaging (MRI) before surgery in highly myopic patients, evaluating the capability of imaging to identify muscles displacement and orbital pulley abnormalities and their role in the pathogenesis of heavy eye syndrome (HES).MethodsWe reviewed the medical records and high-resolution orbital MRIs of highly myopic adults with HES, who underwent surgery for strabismus at the Sant'Orsola-Malpighi University Hospital of Bologna from January 2007 to June 2016. The measure of the angle of dislocation between lateral rectus and superior rectus and lateral rectus-superior rectus band (LR-SR band) were evaluated on coronal MRI imaging.ResultsA total of 54 patients with HES were evaluated by MRI. Mean axial length was 30.5±3 mm. Mean distance esotropia was 49.2±14.4 prism diopters (PD) and the mean hypotropia was 4.3±4.4 PD. All subjects exhibited severe superotemporal globe prolapse that displaced the lateral rectus inferiorly and the superior rectus muscle medially with mean angle of dislocation of 167.5±12.9° on MRI. The LR-SR band was thinned in 56 eyes, ruptured in 8 and not evaluable in 1 case.ConclusionsIn our study, we detected muscles displacement in all subjects and we discovered alteration of the LR-SR band in patients with HES, suggesting a possible role in the pathogenesis of this disease. The evaluation of preoperative orbital MRI imaging in patients with highly myopic strabismus is helpful to detect different anatomical etiology and eventually to drive the choice of appropriate surgery.

The use of blood derived eye drops for the treatment of ocular surface disorders has become increasingly popular in recent years. The mechanism of action is the stimulation of cellular proliferation and migration by supplying an active mixture of growth factors and cytokines at the ocular surface, thus mimicking the function of the lacking natural tears. Blood derived eye drops have been used in the last decades for the treatment of a variety of ocular surface diseases, including mainly dry eye disease, persistent corneal epithelial defect, corneal ulcer, ocular surface burn, recurrent corneal erosion and limbal stem-cell deficiency. Among overall blood derived eye drops, both autologous (from the patients themselves) and homologous (from donors) products exist, with different advantages and disadvantages. Autologous serum, obtained from the patient's own peripheral blood, is the first introduced and most commonly used product. Despite several randomized clinical trials showed its safety and efficacy, a recent Cochraine meta-analysis failed to show significant results due to low evidence. Homologous sources including allogeneic serum obtained from healthy donors, and umbilical cord blood serum collected at the time of delivery, are efficient alternatives, especially when autologous serum therapy is contraindicated or not appropriate. Platelet-derived eye drops are prepared and used in various but poor standardized preparations, namely platelet-rich plasma, plasma rich in growth factors, and platelet lysate. Future perspectives of blood-derived products include the introduction of tailored eye drops, screened for the proper content of growth factors and cytokines according to each patient and ocular surface disease., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate early changes in multifocal electroretinogram (mfERG) and subclinical aqueous humor flare and cellularity in patients receiving hydroxychloroquine (HCQ) as treatment for rheumatoid arthritis., Methods: Ten patients receiving treatment with HCQ and no ophthalmic symptoms were enrolled. After complete ocular examination, mfERG and laser flare-cell photometry were performed. Patients were also divided into two subgroups with HCQ cumulative dose (CD) higher or lower than 500 g. Results obtained were compared with a control group of ten healthy subjects and statistical analysis was performed., Results: In patients receiving HCQ treatment, mfERG P1-wave in ring 2 showed a significant reduction in amplitude and a significant increase in latency compared to healthy control subjects, respectively resulting in 1.143 μV vs 1.316 μV ( P =0.040) and 38.611 ms vs 36.334 ms ( P =0.024). These changes are highly related to CD. Furthermore, when using the laser flare-cell photometry, a significant increase in aqueous humor flare and cellularity was shown in patients with CD higher than 500 g, resulting in a mean value of 14.4 ph/ms compared to 8.1 ph/ms in patients with CD lower than 500 g ( P =0.0029). These reports appear highly related to CD ( P =0.001). Receiver operating characteristic curve analysis showed mfERG P1-wave amplitude in ring 2 as the most sensitive value in detecting early HCQ-related retinopathy., Conclusion: MfERG was shown to be a very sensitive test in detecting early retinal toxicity and should be used for the screening of patients receiving HCQ treatment. Although less sensitive, laser flare-cell photometry can provide further information to evaluate early toxic retinal cell damage., Competing Interests: Disclosure The authors do not have a financial relationship with any organization and declare that there are no conflicts of interest in this work.

Objectives: Doxorubicin (DXR), an anthracyclic antineoplastic agent, is one of the most commonly drug utilized to induce dilated cardiomyopathy (DCM) and heart failure (HF), but the well optimized protocol for cardiomyopathy induction leading to development of cardiac systolic dysfunction is unclear. This study aims to critically compare short-term and long-term DXR injection protocols for the induction of DCM in rats., Methods: Animals were allocated into 3 experimental groups: a ST (short-term DXR injection) group, in which animals received 6 intraperitoneal (i.p.) injections of DXR (2.5mg/kg per dose) over a period of 2 weeks (cumulative dose of 15mg/kg); a LT (long-term DXR injection) group in which animals received weekly i.p. injections of DXR (2mg/kg per dose) over a period of 9 weeks (cumulative dose of 18mg/kg); and a control group in which animals received an appropriate volume of 0.9% saline i.p. All animals were submitted to echocardiography analysis at baseline and after completion treatment. Afterwards, the hearts were collected for conventional light microscopy and collagen quantification., Results: Morphological myocardial analysis of both DXR-treated groups showed an identical pattern of swollen and vacuolated cardiomyocytes and disorganization of myofibrils. There was pronounced interstitial fibrosis in both groups of DXR-treated hearts as compared to controls, as assessed by the interstitial collagen volume fraction. There was no difference in interstitial fibrosis between the ST and LT groups. The echocardiography analysis of the LT group showed structural and functional findings compatible with DCM, including increased left ventricular systolic (5.02±0.96mm) and diastolic (7.68±0.96mm) dimensions and reduction of ejection fraction (69.40±8.51%) as compared to the ST group (4.10±0.89mm, 7.32±0.84, and 79.68±7.23%, respectively) and control group (4.07±0.72mm, 7.17±0.68mm and 80.08±4.71%, respectively), ANOVA p<0.01., Conclusions: These results indicate that LT injection of DXR is more effective than ST injection in inducing left ventricular dysfunction and structural cardiac changes resembling those found in dilated cardiomyopathy., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Surgeries to correct congenital heart diseases are increasing in Brazil and worldwide. However, even with the advances in surgical techniques and perfusion, some cases, especially the more complex ones, can develop heart failure and death. A retrospective study of patients who underwent surgery for correction of congenital heart diseases with cardiopulmonary bypass (CPB) in a university tertiary-care hospital that died, showed infarction in different stages of evolution and scattered microcalcifications in the myocardium, even without coronary obstruction. CPB is a process routinely used during cardiac surgery for congenital heart disease. However, CPB has been related to increased endogenous catecholamines that can lead to major injuries in cardiomyocytes. The mechanisms involved are not completely understood. The aim of this study was to evaluate the alterations induced in the β-adrenergic receptors and GRK-2 present in atrial cardiomyocytes of infants with congenital heart disease undergoing surgical repair with CPB and correlate the alterations with functional and biochemical markers of ischemia/myocardial injury. The study consisted of right atrial biopsies of infants undergoing surgical correction in HC-FMRPUSP. Thirty-three cases were selected. Atrial biopsies were obtained at the beginning of CPB (group G1) and at the end of CPB (group G2). Real-time PCR, Western blotting, and immunofluorescence analysis were conducted to evaluate the expression of β 1 , β 2 -adrenergic receptors, and GRK-2 in atrial myocardium. Cardiac function was evaluated by echocardiography and biochemical analysis (N-terminal pro-brain natriuretic peptide (NT-ProBNP), lactate, and cardiac troponin I). We observed an increase in serum lactate, NT-proBNP, and troponin I at the end of CPB indicating tissue hypoxia/ischemia. Even without major clinical consequences in cardiac function, these alterations were followed by a significant increase in gene expression of β 1 and β 2 receptors and GRK-2, suggesting that this is one of the mechanisms responsible for the exacerbated response of cardiomyocytes to circulating catecholamines. These alterations could explain the irreversible myocardial damage and lipid peroxidation of membranes classically attributed to catecholamine excess, observed in some infants who develop heart failure and postoperative death. Although other factors may be involved, this study confirms that CPB acts as a potent inducer of increased gene expression of β- adrenergic receptors and GRK-2, making the myocardium of these infants more susceptible to the effects of circulating endogenous catecholamines, which may contribute to the development of irreversible myocardial damage and death.

Purpose: To assess the safety and efficacy of ultrasound coagulation of the ciliary body in refractory glaucoma., Methods: This prospective multicenter interventional study was conducted in two Italian university-affiliated glaucoma centers: St. Orsola-Malpighi Teaching Hospital (Bologna, Italy) and University Eye Clinic of Genoa (Genoa, Italy). The main inclusion criterion was the diagnosis of glaucoma with a baseline intraocular pressure (IOP) ≥ 21 mmHg while on maximum topical and systemic medical hypotensive treatment. The EyeOP1 device (Eye Tech Care, Rillieux-la-Pape, France), which was employed in the study, uses miniaturized transducers to produce high-intensity focused ultrasound (HIFU). Treatment consisted of the sequential activation of each transducer lasting 4 s (group 1), 6 s (group 2) or 8 s (group 3). Hypotensive medications were interrupted after surgery and then prescribed only if postoperative IOP was ≥ 21 mmHg during follow-up visits. Patients were assessed before and 1, 7, 14, 30, 90 and 180 days after the procedure. Primary outcomes were the mean IOP reduction in the overall population and in groups 1, 2 and 3, and the rates of complete success, qualified success and failure., Results: Thirty eyes (16 open-angle, 10 angle-closure and 4 neovascular glaucoma) of 30 patients were included. The mean preoperative IOP was 30.1 ± 10.5 mmHg. Twenty-nine patients completed the entire study follow-up; one patient exited from the study 3 months after HIFU and underwent trabeculectomy. At days 1 and 180, the mean IOP was significantly reduced (18.4 ± 7.2 and 20.2 ± 6.2 mmHg, respectively; all p < 0.0001). Group 3 patients (8-s ultrasound exposure time) showed a greater IOP reduction than the other two groups (-16.2 ± 8.3 for group 3 vs. -8.8 ± 6.6 for group 2 and -3.7 ± 6.5 for group 1; p = 0.02 and p < 0.001, respectively). Qualified and complete success was achieved in 23.3 and 46.7% of patients, respectively; treatment failure was recorded in 6.6%., Conclusions: Ultrasonic coagulation of the ciliary body is a safe and effective procedure for reducing IOP in refractory glaucoma. The increase in ultrasound exposure time appears to improve the response rate and the global efficacy of the procedure, with no detrimental effect on safety.

Cardiac dysfunction caused by the impairment of myocardial contractility has been recognized as an important factor contributing to the high mortality in sepsis. Calpain activation in the heart takes place in response to increased intracellular calcium influx resulting in proteolysis of structural and contractile proteins with subsequent myocardial dysfunction. The purpose of the present study was to test the hypothesis that increased levels of calpain in the septic heart leads to disruption of structural and contractile proteins and that administration of calpain inhibitor-1 (N-acetyl-leucinyl-leucinyl-norleucinal (ALLN)) after sepsis induced by cecal ligation and puncture prevents cardiac protein degradation. We also tested the hypothesis that calpain plays a role in the modulation of protein synthesis/degradation through the activation of proteasome-dependent proteolysis and inhibition of the mTOR pathway. Severe sepsis significantly increased heart calpain-1 levels and promoted ubiquitin and Pa28β over-expression with a reduction in the mTOR levels. In addition, sepsis reduced the expression of structural proteins dystrophin and β-dystroglycan as well as the contractile proteins actin and myosin. ALLN administration prevented sepsis-induced increases in calpain and ubiquitin levels in the heart, which resulted in decreased of structural and contractile proteins degradation and basal mTOR expression levels were re-established. Our results support the concept that increased calpain concentrations may be part of an important mechanism of sepsis-induced cardiac muscle proteolysis., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Acute acquired distance esotropia (AADE) is a poorly understood moderate-angle strabismus, affecting young adult myopes and determining bothersome diplopia. Symptoms can be intermittent in the early stages, becoming constant in long-lasting disease. Symptomatic therapy includes prism correction, while surgery is the only curative treatment. However, the latter is affected by high rate of symptoms recurrence with the frequent need for reoperation., Hypothesis: We hypothesize that AADE could be caused by the increase of the accommodative demand, often secondary to a myopic overcorrection. This condition could determine an increase in induced hyperopia at near, dominated by an excess of accommodation and therefore of convergence. The latter cannot be relaxed at distance and diplopia develops. We speculate that early-stage AADE could be successfully treated by cycloplegic eye drops slowly tapered within three months. On the other hand, surgery remains the only option in long-lasting AADE. In these cases, we propose a new pre-operative assessment of esotropia by asking the patient to fix alternatively a stimulus at near and at distance in order to stimulate the accommodative convergence. This technique allows to unmask the total amount of the angle of deviation and to plan a wider bilateral medial rectus muscle recession avoiding long-term residual esotropia., Discussion: Currently, AADE curative therapy is surgical regardless of onset time but it is usually affected by poor outcomes. If our hypothesis was to be confirmed, pharmacological treatment could solve early-stage AADE, avoiding any surgery. Furthermore, a wide bilateral medial rectus muscle recession, quantified on the basis of the above mentioned test for measuring the total amount of the strabismus angle, could improve outcomes eliminating the need for reoperation in long-lasting AADE., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Epitheliotrophic growth factors (GF) can be supplied topically to patients with severe keratopathy through a variety of blood-derived products. We compared GF content in adult peripheral blood serum (PB-S) and cord blood serum (CB-S) as potential sources of GF. To limit inter-individual variability the assessment was performed in maternal-child pairs at the time of delivery., Material and Methods: The amounts of epidermal GF (EGF), insulin-like GF (IGF), transforming GF-beta (TGF-β), vascular endothelial GF (VEGF) in CB units collected from the umbilical vein and PB from mothers (each group n=30) were estimated by enzyme-linked immunosorbent assays. Obstetric characteristics and haematological data were recorded from the archives of the Emilia Romagna Cord Blood Bank. Statistical evaluations were performed by Wilcoxon's test and correlations between variables were determined using Spearman's (ρ) coefficient; p-values <0.05 were considered statistically significant., Results: EGF, TGF-β and VEGF levels were significantly higher in CB-S than in PB-S (median 1,254.4 vs 646.0 pg/mL, 51.3 vs 38.4 μg/mL and 686.8 vs 30 pg/mL, respectively; all p<0.0001) whereas IGF content was significantly higher in PB-S than in CB-S (159.9 vs 53.5 pg/mL, respectively; p<0.0001). In CB-S, the CD34(+) cell concentration appeared to be related to EGF, IGF and TGF-β levels whereas white blood cell count appeared to be related to EGF and TGF-β levels. VEGF levels showed no relation to the haematological parameters considered. Platelet counts were not related to GF level in either CB or PB., Discussion: The GF content in the two blood sources was different, with CB containing larger amounts. Each GF selectively regulates cellular processes involved in corneal healing, so the use of PB or CB should be targeted to supply specific GF on the basis of the type and severity of the keratopathy.

Purpose: To measure the corneal temperature in patients with dry eye (DE) and to correlate the values with subjective discomfort symptoms., Methods: Twenty-four patients with DE (scored as DEWS severity grade 2 to 3) and 15 age-matched normal control subjects were enrolled. Subjective symptoms of discomfort were scored with an Ocular Surface Disease Index questionnaire, and a 100-mm horizontal visual analog scale (VAS) technique was used to measure symptom intensity. Schirmer I test, tear film breakup time (TFBUT), and Oxford grade scoring were performed in all subjects. Dynamic infrared noncontact thermal imaging (Tomey TG 1000) was used to measure the central corneal temperature (CCT). After training, subjects were asked to maintain their eyes forcedly open and to signal the discomfort onset time (DOT). The temperature was measured at eye opening (T0) and every second during 10 seconds of sustained eye opening (T10). The first discomfort sensation onset time (DOT) was also recorded. Temperature values were correlated with the clinical tests, Ocular Surface Disease Index, VAS, and DOT, and data were statistically evaluated (significance P < 0.05)., Results: The corneal temperature immediately after eye opening was significantly lower in patients with DE than in controls, in correlation to the subject age, VAS, and TFBUT. A 3-phase cooling profile in patients with DE and a point of highest decrease (HD) in both groups were identified. DOT occurred earlier in patients with DE than in controls (5.9 vs. 15.9 seconds) and was strongly correlated to the VAS, TFBUT, and CCT-HD., Conclusions: Subjective sensation of discomfort occurred earlier in patients with DE than in controls, in correlation to low corneal temperatures and enhanced tear evaporation.

Purpose: To analyze visual and refractive outcomes of photorefractive keratectomy (PRK) in adult patients with infantile nystagmus syndrome., Setting: Ophthalmology Unit, Department of Experimental Diagnostic and Specialty Medicine, Saint Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy., Design: Retrospective case series., Methods: Photorefractive keratectomy was performed in both eyes of patients with infantile nystagmus syndrome under topical anesthesia using an eye-tracking excimer laser. Patient satisfaction was tested using a questionnaire. The main outcomes were a decrease in refractive error, an improvement in postoperative corrected distance visual acuity (CDVA), and an uncorrected distance visual acuity (UDVA) equal to or better than the preoperative UDVA., Results: Twenty-two eyes of 11 patients with infantile nystagmus syndrome were evaluated. The mean patient age was 30.82 years (range 22 to 42 years). All eyes had simple, compound, or mixed astigmatism (mean -3.40 D; range -0.75 to -6.00 diopters [D]). The mean postoperative astigmatism (-0.70 D ± 0.81 [SD]) and spherical equivalent (-0.420 ± 0.652 D) were statistically significantly better than the preoperative values (-3.40 ± 1.31 D and -3.426 ± 3.343 D, respectively (P < .0001 and P = .0002, respectively). The mean monocular postoperative CDVA (0.24 ± 0.19 logMAR) and UDVA (0.25 ± 0.18 logMAR) were better than the mean preoperative CDVA (0.32 ± 0.28 logMAR) (P = .0045 and P = .0338, respectively). The mean binocular postoperative UDVA was better than the mean preoperative CDVA (0.15 ± 0.14 logMAR versus 0.23 ± 0.23 logMAR) (P = .05). No patient required repeat surgery., Conclusions: Nystagmus patients are eligible for PRK. The results were promising; gaining a few Snellen lines in visual acuity can be very important to these patients for their daily life., Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned., (Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Dry eye (DE) is a multifactorial disorder of the ocular surface unit that results in eye discomfort, visual disturbance and ocular surface damage. It is one of the most common complaints in daily ophthalmic practice. The risk of DE increases with age in both sexes, while its incidence is higher among females. In addition, the condition of menopause in aging women may also contribute to DE onset or worsening as a consequence of an overall hormonal imbalance. Sex hormones play a key role in ocular surface physiology and they impact differently on ocular surface tissues. Reduced estrogen levels were historically thought to be responsible in age-related DE onset but more recent investigations have reconsidered the role of androgens that are present and exert a protective function on the ocular surface. Hormone levels themselves, withdrawal changes in hormone levels, and the changes in hormone-receptor responsiveness are all important factors but it remains to be fully elucidated how estrogen or androgen insufficiency act alone or together in a combined imbalance or interplay to raise the risk of disease. The purpose of this review is to briefly outline current scientific evidence on the influence of androgens and estrogens, on the Lachrymal and Meibomian glands and on ocular surface epithelia including conjunctival goblet cells during reproductive and menopausal periods. The role of sex steroids is also discussed in relation to the pathogenesis of different forms of DE and Sjogren's syndrome (SS). The impact of systemic hormone therapy (HT) in DE post-menopausal women still appears as a controversial issue, despite the many clinical studies. Finally, the outcomes of topical applications of steroid-based products are summarized, underlying the need for potential (tear) biomarker(s) in the rationale of DE-targeted therapy.

Purpose. To assess endothelin-1 (ET-1) plasma levels, choroidal thickness, and aqueous flare in patients with early stage retinitis pigmentosa (RP) and to search for possible correlations. Methods. We compared 24 RP patients with 24 healthy controls. Choroidal thickness and aqueous flare were measured, respectively, by using a spectral domain optical coherence tomography and a laser flare-cell meter, whereas plasma samples were obtained from each patient to evaluate ET-1 plasma levels. Results. Notably, RP subjects showed significantly increased ET-1 plasma levels and reduced choroidal thickness compared with controls: 2.143 ± 0.258 versus 1.219 ± 0.236 pg/mL, P < 0.002, and 226.75 ± 76.37 versus 303.9 ± 39.87 μm, P < 0.03, respectively. Higher aqueous flare values were also demonstrated in RP compared to controls: in detail, 10.51 ± 3.97 versus 5.66 ± 1.29 photon counts/ms, P < 0.0001. Spearman's correlation test highlighted that the increase of ET-1 plasma levels was related with the decrease of choroidal thickness (r = -0.702; P < 0.023) and the increase of aqueous flare (r = 0.580; P < 0.007). Conclusions. Early stage RP patients show a breakdown of blood-ocular barrier and increased ET-1 plasma levels and these findings may contribute to the reduction of choroidal thickness.

Aim: To assess the relationship between both photoreceptor function and choroidal thickness and endothelin-1 (ET-1) plasma levels in patients with early stage retinitis pigmentosa (RP)., Main Methods: We compared 24 RP patients (14 males and 10 females), 25 to 42 years of age (mean age: 34±7 years) with 24 healthy controls (12 males and 12 females) aged between 28 and 45 years (mean 36±6.8 years). All patients underwent visual field test, electroretinogram and multifocal-electroretinogram and choroidal thickness measurement by using spectral domain optical coherence tomography., Key Findings: RP patients had a visual acuity of 0.95, a mean defect of the visual field of -7.90±1.75 dB, a pattern standard deviation index of 6.09±4.22 dB and a b-wave ERG amplitude of 45.08±8.24 μV. Notably RP subjects showed significantly increased ET-1 plasma levels and reduced choroidal thickness compared with controls: respectively, 2.143±0.258 pg/ml vs. 1.219±0.236 pg/ml; p<0.002 and 226.75±76.37 μm vs. 303.9±39.87 μm; p<0.03. Spearman's correlation test highlighted that the increase of ET-1 plasma levels was related with the decrease of choroidal thickness (r=-0.702; p<0.023) and the increase of implicit time in both ring 2 (r=-0.669; p<0.034) and ring 3 (r=-0.883; p<0.007) of mfERG., Significance: Increased ET-1 plasma levels may play a key role in the impairment of retinal and choroidal blood flow due to the vasoconstriction induced by ET-1. This could lead to worsening of the abiotrophic process of the macular photoreceptors., (Copyright © 2014 Elsevier Inc. All rights reserved.)