The Metabolomic Profile in Amyotrophic Lateral Sclerosis Changes According to the Progression of the Disease: An Exploratory Study

Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative pathology of the upper or lower motor neuron. Evaluation of ALS progression is based on clinical outcomes considering the impairment of body sites. ALS has been extensively investigated in the pathogenetic mechanisms and the clinical profile; however, no molecular biomarkers are used as diagnostic criteria to establish the ALS pathological staging. Using the source-reconstructed magnetoencephalography (MEG) approach, we demonstrated that global brain hyperconnectivity is associated with early and advanced clinical ALS stages. Using nuclear magnetic resonance (1H-NMR) and high resolution mass spectrometry (HRMS) spectroscopy, here we studied the metabolomic profile of ALS patients’ sera characterized by different stages of disease progression—namely early and advanced. Multivariate statistical analysis of the data integrated with the network analysis indicates that metabolites related to energy deficit, abnormal concentrations of neurotoxic metabolites and metabolites related to neurotransmitter production are pathognomonic of ALS in the advanced stage. Furthermore, analysis of the lipidomic profile indicates that advanced ALS patients report significant alteration of phosphocholine (PCs), lysophosphatidylcholine (LPCs), and sphingomyelin (SMs) metabolism, consistent with the exigency of lipid remodeling to repair advanced neuronal degeneration and inflammatio

Outcomes of Abrupt Switch to Bevacizumab of Patients Undergoing Aflibercept Intravitreal Injections for Neovascular Age-Related Macular Degeneration in a Tertiary Center in Lombardy, Italy: A Real-Life Retrospective Analysis

To assess real-life anatomical and functional outcomes of switch to bevacizumab in patients undergoing aflibercept intravitreal injections for nAMD

Trans-Scleral Plugs Fixated FIL SSF IOL: A Review of the Literature and Comparison with Other Secondary IOL Implants

Purpose. To revise the current literature on FIL SSF (Carlevale) intraocular lens, previously known as Carlevale lens, and to compare their outcomes with those from other secondary IOL implants. Methods. We performed a peer review of the literature regarding FIL SSF IOLs until April 2021 and analyzed the results only of articles with a minimum of 25 cases and a follow-up of at least 6 months. The searches yielded 36 citations, 11 of which were abstracts of meeting presentations that were not included in the analysis because of their limited data. The authors reviewed 25 abstracts and selected six articles of possible clinical relevance to review in full text. Of these, four were considered to be sufficiently clinically relevant. Particularly, we extrapolated data regarding the pre- and postoperative best corrected visual acuities (BCVA) and the complications related to the procedure. The complication rates were then compared with those from a recently published Ophthalmic Technology Assessment by the American Academy of Ophthalmology (AAO) on secondary IOL implants. Results. Four studies with a total of 333 cases were included for results analysis. The BCVA improved in all cases after surgery, as expected. Cystoid macular edema (CME) and increased intraocular pressure were the most common complications, with an incidence of up to 7.4% and 16.5%, respectively. Other IOL types from the AAO report included anterior chamber IOLs, iris fixation IOLs, sutured iris fixation IOLs, sutured scleral fixation IOLs, and sutureless scleral fixation IOLs. There was no statistically significant difference in the rates of postoperative CME (p = 0.20), and vitreous hemorrhage (p = 0.89) between other secondary implants and the FIL SSF IOL, whereas the rate of retinal detachment was significantly less with FIL SSF IOLs (p = 0.04). Conclusion. The results of our study suggest the implantation of FIL SSF IOLs is an effective and safe surgical strategy in cases where there is a lack of capsular support. In fact, their outcomes seem to be comparable to those obtained with the other available secondary IOL implants. According to published literature, the FIL SSF (Carlevale) IOL provides favorable functional results with a low rate of postoperative complications

Curcumin-Based Treatment for Macular Edema from Uncommon Etiologies: Efficacy and Safety Assessment

The aim of this study was to investigate the efficacy and safety of curcumin formulation with a polyvinylpyrrolidone-hydrophilic carrier (CHC*; Diabec®-AlfaIntes, Italy) for the treatment of macular edema (ME) from uncommon etiologies. We conducted retrospective interventional case series, reviewing the medical records of patients referred to the Eye Center, Humanitas Hospital, Bergamo due to persistent ME related to uncommon causes and treated by oral administration of CHC. The main outcomes assessed were best-corrected visual acuity (BCVA), central macular thickness (CMT), and the presence of intraretinal and/or subretinal fluid (SRF). Only patients with a minimum follow-up (f/u) of 6 months were included. The occurrence of any adverse effect was registered. Thirty-one eyes of 30 patients were included, with a mean f/u of 8.32 ± 1.77 months. Of them, 9 patients (10 eyes) were affected by postoperative ME and 21 by chronic central serous chorioretinopathy. Median BCVA significantly improved after treatment, changing from 0.3 [0.16-0.5] to 0.1 [0-0.3] logarithm of the minimum angle of resolution (P < .001). Also CMT was significantly improved, as it decreased from 400 [364-438] μm before treatment to 280 [242-307] μm at the last f/u visit (P < .001). The complete absorption of intraretinal/SRF was detected in 23 of 31 eyes (74%) at the final f/u. No adverse effects were registered. In conclusion, treatment with CHC was effective and safe for eyes affected by ME of various uncommon etiologies, resulting in significant improvement of both functional and anatomical outcomes, with the complete resolution of the edema in the majority of cases (74%)

Swept-Source Optical Coherence Tomography-Based Biometry: A Comprehensive Overview

The purpose of this study was to summarize the results related to ocular biometry performed using swept-source optical coherence tomography (SS-OCT). A literature search was conducted to search articles reporting the clinical outcomes of patients who underwent examinations with commercially available SS-OCT machines. The available data were thoroughly analyzed, with a particular focus on all the biometric factors used to calculate the power of intraocular lenses (IOLs) implanted during cataract surgery. The agreement, repeatability, and reproducibility of several parameters among different devices were examined. The variations found for parameters obtained from agreement testing were evaluated in order to promote the interchangeability of devices. Swept-source optical coherence tomography biometers usually produce highly repeatable and reproducible results. The excellent results obtained led us to the conclusion that optical biometers based on SS-OCT technology will probably take the lead in ocular biometry

Swept-Source Optical Coherence Tomography-Based Biometry: A Comprehensive Overview

The purpose of this study was to summarize the results related to ocular biometry performed using swept-source optical coherence tomography (SS-OCT). A literature search was conducted to search articles reporting the clinical outcomes of patients who underwent examinations with commercially available SS-OCT machines. The available data were thoroughly analyzed, with a particular focus on all the biometric factors used to calculate the power of intraocular lenses (IOLs) implanted during cataract surgery. The agreement, repeatability, and reproducibility of several parameters among different devices were examined. The variations found for parameters obtained from agreement testing were evaluated in order to promote the interchangeability of devices. Swept-source optical coherence tomography biometers usually produce highly repeatable and reproducible results. The excellent results obtained led us to the conclusion that optical biometers based on SS-OCT technology will probably take the lead in ocular biometry

Genetic Aspects of Age-Related Macular Degeneration and Their Therapeutic Potential

Age-related macular degeneration (AMD) is a complex and multifactorial disease, resulting from the interaction of environmental and genetic factors. The continuous discovery of associations between genetic polymorphisms and AMD gives reason for the pivotal role attributed to the genetic component to its development. In that light, genetic tests and polygenic scores have been created to predict the risk of development and response to therapy. Still, none of them have yet been validated. Furthermore, there is no evidence from a clinical trial that the determination of the individual genetic structure can improve treatment outcomes. In this comprehensive review, we summarize the polymorphisms of the main pathogenetic ways involved in AMD development to identify which of them constitutes a potential therapeutic target. As complement overactivation plays a major role, the modulation of targeted complement proteins seems to be a promising therapeutic approach. Herein, we summarize the complement-modulating molecules now undergoing clinical trials, enlightening those in an advanced phase of trial. Gene therapy is a potential innovative one-time treatment, and its relevance is quickly evolving in the field of retinal diseases. We describe the state of the art of gene therapies now undergoing clinical trials both in the field of complement-suppressors and that of anti-VEGF

The effect of optical degradation from cataract using a new Deep Learning optical coherence tomography segmentation algorithm

Purpose: To assess the validity of the results of a freely available online Deep Learning segmentation tool and its sensitivity to noise introduced by cataract. Methods: The OCT images were collected with a Spectralis SD-OCT (Heidelberg Engineering, Heidelberg, Germany) as part of normal clinical practice. Data were segmented using a freely available online tool called Relayer ( https://www.relayer.online/ ), based on a cross-platform Deep Learning segmentation architecture specifically adapted for retinal OCT images. The segmentations were read into MATLAB (The MathWorks, Natick, MA, USA) and analyzed. Results: There was an excellent agreement between the ETDRS measurements obtained from the two algorithms. Upon visual inspection, the segmentation based on Deep Learning obtained with Relayer appeared more accurate except in one case of apparent good quality image showing interrupted segmentations in some of the B-scans. Conclusion: A freely available online Deep Learning segmentation tool showed good and promising performance in healthy retinas before and after cataract surgery, proving robust to optical degradation of the image from media opacities

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

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