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Francesco Oddone,1 Vincenzo Scorcia,2 Michele Iester,3 Dario Sisto,4 Stefano De Cilla,5 Paolo Bettin,6 Carlo Cagini,7 Michele Figus,8 Giorgio Marchini,9 Luca Rossetti,10 Gemma Rossi,11 Tommaso Salgarello,12,13 Gian Luca Scuderi,14 Giovanni Staurenghi15 On behalf of the VISIONARY Study Group (Italy)1Glaucoma Unit, IRCSS-Fondazione Bietti, Roma, Italy; 2Department of Ophthalmology, University Magna Græcia of Catanzaro, Catanzaro, Italy; 3Eye Clinic of Genoa, Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genova, Genova, Italy; 4Ophthalmology Department, University of Bari, Bari, Italy; 5Department of Health Sciences, Eye Clinic, University of Piemonte Orientale, Novara, Italy; 6Department of Ophthalmology, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milano, Italy; 7Department of Medicine and Surgery, Ophthalmology Section, University of Perugia, Perugia, Italy; 8Ophthalmology, Department of Surgery, Medicine, Molecular and Emergency, University of Pisa, Pisa, Italy; 9Ophthalmology Unit, Department of Neurosciences, Biomedicine and Movement, University of Verona, Verona, Italy; 10Eye Clinic, San Paolo Hospital, University of Milan, Milano, Italy; 11University Eye Clinic, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy; 12Ophthalmology Unit, Department of Ageing, Neurosciences, Head-Neck and Orthopaedics Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy; 13Institute of Ophthalmology, Università Cattolica del Sacro Cuore, Roma, Italy; 14NESMOS Department, Ophthalmology Unit, St. Andrea Hospital, Università di Roma La Sapienza, Roma, Italy; 15Eye Clinic, Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, Milano, ItalyCorrespondence: Francesco Oddone, Glaucoma Unit, IRCSS-Fondazione Bietti, Roma, Italy, Tel + 39 06 85356727, Email oddonef@gmail.comIntroduction: The VISIONARY study examined the intraocular pressure (IOP)-lowering efficacy and tolerability of the preservative-free fixed-dose combination of tafluprost (0.0015%) and timolol (0.5%) (PF tafluprost/timolol FC) in a real-world setting. The country-level data reported herein comprise the largest and first observational study of PF tafluprost/timolol FC therapy in Italy.Methods: An observational, multicenter, prospective study included adult Italian patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) demonstrating insufficient response or poor tolerability with topical prostaglandin analogue (PGA) or beta-blocker monotherapy. Treatment was switched to PF tafluprost/timolol FC therapy at baseline. Primary endpoint was the absolute mean IOP change from baseline at Month 6. Exploratory and safety endpoints included change in IOP at Weeks 4 and 12, ocular signs, symptom severity and reporting of adverse events (AEs).Results: Overall, 160 OAG/OHT patients were included. Mean ± standard deviation IOP was reduced from 19.6 ± 3.6 mmHg at baseline to 14.5 ± 2.6 mmHg at Month 6 (reduction of 5.1 ± 3.7 mmHg; 24.1%; p < 0.0001). IOP reduction was also statistically significant at Week 4 (23.1%; p < 0.0001) and Week 12 (24.7%; p < 0.0001). Based on data cutoff values for mean IOP change of ≥ 20%, ≥ 25%, ≥ 30% and ≥ 35%, respective Month 6 responder rates were 68.1%, 48.7%, 36.2% and 26.9%. Most ocular signs and symptoms were significantly reduced in severity from baseline at Month 6. Two non-serious and mild AEs were reported during the study period, among which, one AE was treatment-related (eyelash growth). &#x2003Conclusion: Italian OAG and OHT patients demonstrated a significant IOP reduction from baseline at Week 4 that was maintained over a 6-month period following a switch from topical PGA or beta-blocker monotherapy to PF tafluprost/timolol FC therapy. Severity of most ocular signs and symptoms was significantly reduced during the study period, and PF tafluprost/timolol FC was generally well tolerated.Keywords: fixed-dose combination therapy, intraocular pressure, ocular hypertension, PF tafluprost/timolol FC, preservative-free topical medication, primary open-angle glaucoma

Introduction: Despite an improved understanding of its pathogenesis, dry eye disease (DED) remains relatively underestimated and its treatment challenging. A better alignment between the clinical evaluation and the patient self-assessment also requires capturing the whole patient experience of DED. This project aimed to unveil this experience through narrative medicine (NM)., Methods: The project involved 38 expert centres in Italy and one in San Marino, targeting adult patients with DED, their informal caregivers and their treating ophthalmologists. Written narratives and sociodemographic and quality of life (QoL)-related data were anonymously collected through the project's webpage. Narratives were analysed through MAXQDA (VERBI Software, Berlin, Germany), NM classifications and content analysis., Results: A total of 171 patients with DED, 37 informal caregivers and 81 ophthalmologists participated in the research. DED was defined as a disabling condition by 19% of patients and 35% of caregivers; 70% of patients reported that a therapeutic alliance is an integral part of DED treatment and 32% hope for more effective therapies. Forty-four per cent of patients assessed their own QoL as good; however, DED emerged as importantly impacting work performance and social events. DED physical, emotional and economic burden and the cruciality of a trusting care relationship represent the main themes that emerged across all narratives, while empathy and effective treatment are among the factors favouring coping with DED., Conclusion: This project marked a pioneering initiative investigating the lived experience of patients with DED through NM, simultaneously involving all viewpoints involved in the care pathway. NM enabled the unveiling of factors favouring the ability to cope with DED and its associated QoL implications and provided valuable insights to improve the therapeutic alliance., (© 2024. The Author(s).)

Purpose: To compare the Comprehensive Complication Index (CCI) to the Clavien-Dindo classification (CDC) in an elderly population who underwent percutaneous nephrolithotomy (PCNL) and to identify predictors of postoperative complications in this population., Methods: We conducted a retrospective cohort study involving patients 60 years and older who underwent PCNL at our Institution between 2009 and 2020. Postoperative complications were considered up to 30 days after surgery. Both CDC and CCI were calculated to assess patient outcomes. Length of stay (LOS) and admission to the emergency room (ER) were used as surrogates of postoperative complications., Results: We included 244 patients with a median age of 65 [63-69] years. 15.6% presented postoperative complications, and 2.5% multiple complications. LOS had a correlation coefficient of 0.29 (p < 0.001) and ER admissions had a coefficient of 0.27 (p < 0.001) with both CDC and CCI. Cost of hospitalization based on CDC underestimated CCI-based cost of hospitalization in 0.8% (p = 0.049). Higher American Society of Anesthesiology (ASA) physical status (p = 0.02), Charlson Comorbidity Index (p = 0.008), Guy's classification (p = 0.005), and history of urinary tract infection (UTI, p = 0.047) exhibited significant correlations with postoperative complications., Conclusion: Both CDC and CCI equally correlate with LOS and ER admissions following PCNL in elderly patients. However, CDC underestimates cost of hospitalization in comparison to CCI. We found higher ASA physical status, Charlson Comorbidity Index, Guy's classification, and history of UTI as predictors of postoperative complications after this procedure in this population., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To protect the corneal endothelium, various ophthalmical viscoelastic devices (OVDs) are used during cataract surgery. In this study, we compared two sodium hyaluronate-based OVD, the bacteria-derived FIDIAL PLUS OVD (test) with the animal-derived IAL ® -F OVD (reference) during the surgical procedure. Methods: Fifty patients with bilateral cataract participated in the study: 50 eyes randomly received FIDIAL PLUS and 50 eyes received IAL ® -F (ratio 1:1). Noninferior efficacy of FIDIAL PLUS compared with reference OVD (first objective) was evaluated using a paired t -test comparing the mean percent loss of corneal endothelial cells (CECs) with FIDIAL PLUS against the mean percent loss with IAL ® -F. Corneal endothelial protection during cataract surgery with FIDIAL PLUS without significant (≥30 mmHg) postoperative intraocular pressure (IOP) increase (main secondary objective) was assessed using a repeated measures logistic model comparing the incidence of significant postoperative IOP elevation between the two groups. Safety, tolerability, and efficacy were also evaluated by assessing secondary endpoints before and after surgery. Results: FIDIAL PLUS showed a statistically noninferior efficacy compared with IAL ® -F; there was no significant increase in IOP in either group or different trends of the secondary endpoints were observed between the OVD groups. The safety profile was similar in both OVD groups and no adverse device effects were reported. Conclusions: This study demonstrates the equivalent efficacy, tolerability, and safety of the bacteria-derived FIDIAL PLUS compared with the animal-derived IAL ® -F, confirming the clinical value of this product.

Purpose: To review the literature focusing on the clinical outcomes of KeraKlear (KK) (KeraMed), a foldable intrastromal keratoprosthesis., Methods: We searched 6 databases using 4 keywords: KeraKlear, Foldable Keratoprosthesis, Intrastromal Keratoprosthesis, and Non-penetrating Keratoprosthesis. Included studies had to be conducted in vivo on humans, published until January 3, 2023, and had to investigate the implantation of the KK. Eyes were considered at high risk of keratoprosthesis retention failure whenever there was an active inflammatory ocular surface disorder or in case of previous KK failure. We aimed at recording the postoperative complications, rate of prosthesis retention, and mean improvements in visual acuity., Results: We identified 144 publications, 6 of which (38 eyes) met the inclusion criteria. No randomized controlled trials were found, and some studies had significant limitations regarding sample size and follow-up duration. With a mean follow-up of 28 ± 18.8 months, postoperative complications of any kind occurred between 0% and 50% and 24% had an implant extrusion/needed a reoperation. The mean postoperative visual acuity improvement on the last follow-up was -0.83 ± 0.27 LogMAR, that is, -0.57 ± 0.3 for high-risk and -1.03 ± 0.25 for low-risk eyes, whereas 1 year after implantation, 50% of the prostheses were retained in the former and 81% in the latter group. None of the eyes developed glaucoma, endophthalmitis, or expulsive hemorrhages; none had to be eviscerated/enucleated., Conclusions: Despite the limited quality and quantity of evidence, the available literature seems to suggest the KK to be a valuable tool in the treatment of complicated corneal disorders. Because in many parts of the world, the access to corneal transplantation is limited, this prosthesis could represent a valid alternative., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The PRESERFLO™ MicroShunt (PMS) has been proven to significantly lower intraocular pressure (IOP) in patients with glaucoma and has been available for use since 2019. With increasing published evidence and growing experience of glaucoma surgeons, the aim of this modified Delphi panel was to build on the findings of a previous Delphi panel conducted in 2021 and provide further guidance on the role of the PMS to treat patients with glaucoma in Europe., Methods: Thirteen European glaucoma surgeons experienced in the PMS procedure participated in a 3-round modified Delphi panel. A targeted literature review and expert steering committee guided Round 1 questionnaire development. Consensus was pre-defined at a threshold of ≥ 70% of panellists selecting 'strongly agree'/'agree' or 'strongly disagree'/'disagree' for 6-point Likert scale questions or ≥ 70% selecting the same option for multiple or single-choice questions. Questions not reaching consensus were restated/revised for the next round, following guidance from free-text responses/scoping questions., Results: In total, 28% (n = 9/32), 52% (n = 16/31) and 91% (n = 10/11) of statements reached consensus in Rounds 1, 2 and 3, respectively. There was agreement that the PMS may be used in patients with pigmentary, post-trauma or post-vitrectomy glaucoma and for patients with uveitic glaucoma without active inflammation. The PMS may be more suitable for patients with contact lenses than other subconjunctival filtering surgeries, without eliminating bleb-associated risks. Consensus was reached that combining PMS implantation and phacoemulsification may be as safe as standalone PMS surgery, but further efficacy data are required. Following a late rise in IOP ≥ 4 months post-surgery, topical aqueous suppressant drops or bleb revision may be suitable management options., Conclusions: This Delphi panel builds on the considerations explored in the 2021 Delphi panel and provides further detailed guidance for glaucoma surgeons on the use of the PMS, reflecting the availability of novel evidence and surgical experience. Videos are available for this article., (© 2024. The Author(s).)

Background: The prevalence of obesity, a chronic disease, is increasing, and obesity is now considered a global epidemic. Eye diseases are also increasing worldwide and have serious repercussions on quality of life as well as increasingly high costs for the community. The relationships between obesity and ocular pathologies are not yet well clarified and are not pathologically homogeneous: they seem to be somehow linked to excess body fat, especially to the distribution of adipose tissue and its ectopic deposits., Purpose: Our objective was to examine the associations between obesity and anthropometric indices, including body mass index (BMI), waist circumference (WC), and the waist/hip ratio (WHR), and the risk of most widespread eye diseases, with particular attention given to the most significant metabolic mechanisms., Methods: This article provides a narrative overview of the effect of obesity and anthropometric measurements of body fat on prevalent eye diseases. We used the MEDLINE/PubMed, CINAHL, EMBASE, and Cochrane Library databases from 1984 to 2024. In addition, we hand-searched references from the retrieved articles and explored a number of related websites. A total of 153 publications were considered., Results: There is significant evidence that obesity is associated with several eye diseases. Waist circumference (WC) and the waist/hip ratio (WHR) have been observed to have stronger positive associations with eye diseases than BMI., Conclusions: Obesity must be considered a significant risk factor for eye diseases; hence, a multidisciplinary and multidimensional approach to treating obesity, which also affects ocular health, is important. In the prevention and treatment of eye diseases related to obesity, lifestyle factors, especially diet and physical activity, as well as weight changes, both weight loss and weight gain, should not be overlooked., Level of Evidence: Level V narrative review., (© 2024. The Author(s).)

Quantitative measurement of physical activity may complement neurological evaluation and provide valuable information on patients' daily life. We evaluated longitudinal changes of physical activity in patients with Friedreich ataxia (FRDA) using remote monitoring with wearable sensors. We performed an observational study in 26 adult patients with FRDA and 13 age-sex matched healthy controls (CTR). Participants were asked to wear two wearable sensors, at non-dominant wrist and at waist, for 7 days during waking hours. Evaluations were performed at baseline and at 1-year follow-up. We analysed the percentage of time spent in sedentary or physical activities, the Vector Magnitude on the 3 axes (VM3), and average number of steps/min. Study participants were also evaluated with ataxia clinical scales and functional tests for upper limbs dexterity and walking capability. Baseline data showed that patients had an overall reduced level of physical activity as compared to CTR. Accelerometer-based measures were highly correlated with clinical scales and disease duration in FRDA. Significantly changes from baseline to l-year follow-up were observed in patients for the following measures: (i) VM3; (ii) percentage of sedentary and light activity, and (iii) percentage of Moderate-Vigorous Physical Activity (MVPA). Reduction in physical activity corresponded to worsening in gait score of the Scale for Assessment and Rating of Ataxia. Real-life activity monitoring is feasible and well tolerated by patients. Accelerometer-based measures can quantify disease progression in FRDA over 1 year, providing objective information about patient's motor activities and supporting the usefulness of these data as complementary outcome measure in interventional trials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Fichera, Nanetti, Monelli, Castaldo, Marchini, Neri, Vukaj, Marzorati, Porcelli and Mariotti.)

Objective: The objective of this narrative review is to discuss the current state of research funding in Brazil., Materials and Methods: This study is based on the most recent edition of the course Funding for Research and Innovation in the University of Sao Paulo School of Medicine which was a three-day course with 12 hours of instruction. The course brought together leading experts in the field to comprehensively discuss the current state of research funding in Brazil. Each speaker provided a presentation on a specific topic related to research funding. After the workshop, speakers assembled relevant topics in this manuscript., Results: collaborative research is critical for securing research funding. It optimizes proposal competitiveness, amplifies societal impact, and manages risks effectively. As such, fostering and supporting these collaborations is paramount for both researchers and funding agencies. To maintain the highest integrity in research, investigators involved in these collaborations must disclose any relationships that could potentially influence the outcomes or interpretation of their projects., Conclusions: In Brazil, the mainstay of research funding stems from public entities, with agencies such as CNPq, CAPES, and state bodies like FAPESP, FAPERJ, FAPEMIG and others at the forefront. Concurrently, industry funding offers viable pathways, especially through industry-sponsored studies, investigator-led projects, and collaborative initiatives. The Brazilian funding landscape is further enriched by innovative platforms, including crowdfunding and the contributions of institutions like the Serrapilheira Institute. Internationally, esteemed organizations such as the National Institutes of Health (NIH) and the Bill & Melinda Gates Foundation stand out as potential funders., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Aiming at the inhaled treatment of pulmonary diseases, the optimization process of the previously reported MAPI compound 92a is herein described. The project was focused on overcoming the chemical stability issue and achieving a balanced bronchodilator/anti-inflammatory profile in rats in order to be confident in a clinical effect without having to overdose at one of the biological targets. The chemical strategy was based on fine-tuning of the substitution pattern in the muscarinic and PDE4 structural portions of the dual pharmacology compounds, also making use of the analysis of a proprietary crystal structure in the PDE4 catalytic site. Compound 10f was identified as a chemically stable, potent, and in vivo balanced MAPI lead compound, as assessed in bronchoconstriction and inflammation assays in rats after intratracheal administration. After the in-depth investigation of the pharmacological and solid-state profile, 10f proved to be safe and suitable for development.

Purpose: To evaluate corneal biomechanical changes after meniscus-shaped stromal lenticule addition keratoplasty (MS-SLAK) performed for the treatment of keratoconus., Methods: This interventional study included patients affected by advanced keratoconus (stage III and IV) who underwent examination with a dynamic Scheimpflug analyzer and non-contact tonometer (Corvis ST; Oculus Optikgeräte GmbH) at baseline and 12 months after MS-SLAK. The biomechanical parameters evaluated in this study were integrated inverse radius (1/R), deformation amplitude ratio (DA ratio), stiffness parameter at first applanation (SP-A1), biomechanical intraocular pressure (bIOP), central corneal thickness (CCT), and stress-strain index (SSI)., Results: Sixteen patients were enrolled in the study. The analysis was ultimately conducted on 15 patients. Comparative analyses showed an increase in corneal stiffness as demonstrated by a rise in SSI ( P < .0001) and SP-A1 ( P < .0001) and a decrease in DA ratio ( P < .0001) and 1/R ( P = .01). A significant increase in CCT was found ( P < .0001). No statistically significant modification was found for bIOP ( P = .43)., Conclusions: The corneal biomechanical analyses evaluated by the Corvis ST showed that MS-SLAK for advanced keratoconus is able to increase corneal overall stiffness. This result is explained by the significant increase in thickness induced by MS-SLAK. [ J Refract Surg . 2023;39(7):499-504.] .

Purpose: To evaluate visual performance and quality of life after bilateral implantation of 2 extended depth-of-focus intraocular lenses (EDOF IOLs)., Setting: Ophthalmology Clinic, Department of Medicine and Science of Ageing, University "G. d'Annunzio" Chieti-Pescara, Italy, and Ophthalmic Unit, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Italy., Design: Prospective clinical study., Methods: 60 eyes of 30 patients with senile cataract were enrolled in this study. Patients underwent phacoemulsification and bilateral implantation of the Mini WELL IOL in the dominant eye and the Mini WELL PROXA IOL in the nondominant eye within a month. The main outcome measures over a 3-month follow-up period were uncorrected and corrected visual acuity at different distances (33 cm, 60 cm, and 4 m), defocus curve, contrast sensitivity, and patient satisfaction (evaluated by mean of the National Eye Institute Refractive Error Quality-of-Life instrument-42 questionnaire)., Results: Binocular uncorrected visual acuity at 90 days was 0.03 ± 0.11 logMAR for long distance, 0.05 ± 0.10 logMAR for intermediate distance, 0.03 ± 0.08 logMAR at 40 cm, and 0.06 ± 0.08 logMAR at 33 cm. Statistically significant differences between the 2 EDOF IOLs in favor of Mini WELL PROXA IOL were observed for uncorrected near visual acuity at 40 and 33 cm ( P < .001 and P < .001, respectively) and for distance-corrected near visual acuity at 40 cm ( P < .001). Significant differences between the 2 IOLs in the defocus curves were reported., Conclusions: In this small pilot study, bilateral implantation of Mini WELL IOL and Mini WELL PROXA IOL achieved good quantity and quality of vision., (Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease characterized by lung fibrosis leading to an irreversible decline of lung function. Current antifibrotic drugs on the market slow down but do not prevent the progression of the disease and are associated with tolerability issues. The involvement of lysophosphatidic acid receptor 2 (LPA 2 ) in IPF is supported by LPA 2 knockdown studies. To further validate the role of LPA 2 receptors in modulating IPF and potentially other fibrotic processes, a potent and selective LPA 2 receptor antagonist with a good pharmacokinetic (PK) profile is needed. Herein, we report the medicinal chemistry exploration that led to the discovery of a new class of highly potent and selective LPA 2 antagonists. Among them, compound 58 exhibits excellent potency, selectivity, and oral PK profile, making it a suitable tool for probing the involvement of LPA 2 receptors in IPF and other fibrotic processes.

Purpose: To analyze the objective and subjective visual performances of a new hybrid refractive/aspheric extended depth of focus (EDOF) intraocular lens (IOL)., Methods: In this monocentric prospective study patients with bilateral cataracts underwent cataract surgery and were implanted with a Lucidis IOL (SAV-IOL SA, Neuchâtel, Switzerland) in both eyes, 1 week apart from each other. At 3 months from implantation postoperative evaluations included monocular and binocular uncorrected and distance-corrected distant (4 m), intermediate (80 cm, 67 cm) and near (40 cm) visual acuities (UDVA/DCVA, UI80-67VA/DCI80-67VA, UNVA/DCNVA), binocular defocus curves, halometry, contrast sensitivity and objective quality-of-vision measurements. Also, patients were also asked to complete the national eye institute refractive error quality of life (NEI-RQL-42) questionnaire., Results: Twenty-five patients (50 eyes) were included. The mean postoperative binocular UDVA, UI80VA, UI67VA and UNVA were-0.02 ± 0.13, 0.05 ± 0.09, 0.05 ± 0.08 and 0.03 ± 0.1 LogMar, and did not significantly differ from their corrected counterparts. On binocular defocus curves a VA ≥0.05LogMar was found between +0.50 and - 2.50 D of vergence, whereas the mean distance from the central stimulus on halometry was 1.23 ± 0.01. Mean ocular and corneal radical mean square at 4 mm were 0.31 ± 0.28 and 0.19 ± 0.07, respectively; whereas the mean Strehl ratio was 0.2 ± 0.09., Conclusion: Lucidis IOLs demonstrated excellent visual performances, especially at close distances while maintain good quality of vision, contrast sensitivity, and overall patient-satisfaction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pedrotti, Bonacci, Kilian, Pagnacco, Anastasi, Ventura and Marchini.)

Purpose: To evaluate the astigmatism tolerance and the visual outcomes after implantation of a premium intraocular lens (IOL) with a continuous transitional focus (Precizon Presbyopic; Ophtec BV) in pseudophakic presbyopia correction., Methods: This prospective study enrolled 20 patients (40 eyes) after bilateral phacoemulsification and IOL implantation. Corrected and uncorrected visual acuities at 4 m and 80, 67, and 40 cm (CDVA, UDVA, DCI80VA, UI80VA, DCI67VA, UI67VA, DCNVA, and UNVA), astigmatic and spheric defocus curve, mean reading speed (MRS), critical print size (CPS), contrast sensitivity, optical aberrations (modulation transfer function [MTF] cut-off, Strehl ratio, and higher order aberration root mean square [HOA RMS]), objective halometry, and National Eye Institute Refractive Error Quality of Life Instrument 42 [NEI RQL-42] questionnaire were evaluated 3 months after surgery., Results: Astigmatic defocus curves revealed a tolerance up to -1.00 and +0.75 diopters (D) for with-the-rule astigmatism, and up to -1.00 and +1.00 D for against-the-rule astigmatism. Binocular spheric defocus curve showed that the mean visual acuity was greater than 0.15 logMAR from 1.00 to -1.00 D. MRS, CPS, MTF cut-off, Strehl ratio, and HOA RMS were 116.97 ± 21.94 words/min, 0.45 ± 0.06 logRDA, 20.03 ± 4.86 cycles/degree, 0.11 ± 0.07, and 0.28 ± 0.09, respectively. Contrast sensitivity was within the normal range for all tested light conditions. The NEI RQL-42 evidenced high subjective satisfaction for all subscales, especially for far vision, activity limitations, dependence on correction, suboptimal correction, appearance, and satisfaction with correction., Conclusions: The Precizon Presbyopic IOL allows good astigmatism tolerance and both objective and subjective high quality of vision. [ J Refract Surg . 2023;39(1):33-39.] .

The development of nanoparticles (NPs) to enable the passage of drugs across blood-brain barrier (BBB) represents one of the main challenges in neuropharmacology. In recent years, NPs that are able to transport drugs and interact with brain endothelial cells have been tested. Here, we investigated whether the functionalization of avidin-nucleic-acid-nanoassembly (ANANAS) with apolipoprotein E (ApoE) would allow BBB passage in the SOD1 G93A mouse model of amyotrophic lateral sclerosis. Our results demonstrated that ANANAS was able to transiently cross BBB to reach the central nervous system (CNS), and ApoE did not enhance this property. Next, we investigated if ANANAS could improve CNS drug delivery. To this aim, the steroid dexamethasone was covalently linked to ANANAS through an acid-reversible hydrazone bond. Our data showed that the steroid levels in CNS tissues of SOD1 G93A mice treated with nanoformulation were below the detection limit. This result demonstrates that the passage of BBB is not sufficient to guarantee the release of the cargo in CNS and that a different strategy for drug tethering should be devised. The present study furthermore highlights that NPs can be useful in improving the passage through biological barriers but may limit the interaction of the therapeutic compound with the specific target.

Objectives: Friedreich's ataxia (FA) is the most common hereditary ataxia, characterized by multisystemic manifestations including neurological, cardiological, and skeletal abnormalities. In this study, we aimed to analyze the incidences of disease-related and unrelated comorbidities occurring in different stages of the disease progression., Methods: We analyzed longitudinal data from a 10-year prospective observational study in a cohort of 175 FA patients with disease onset < 25 years. We analyzed the time of diagnosis for the most frequently reported medical conditions, with respect to age and disease duration of each patient., Results: In the early stage of the disease, scoliosis (53.3%), hypertrophic cardiomyopathy (46.7%), and pes cavus (33.3%) were the most frequently diagnosed conditions, sometimes occurring even before the onset of ataxia. Diabetes, bone fractures, and depression have the same incidence at all disease stages. In patients with > 20 years of disease duration, the most frequent complications were hearing and visual loss (20% and 26%), arrhythmias (16%), and psychosis (18%). Thirteen patients presented hallucinations/delusions in the absence of neurological acute events or mental illness predisposing to psychotic manifestations. Six of these patients fulfill the diagnostic criteria for Charles Bonnet syndrome., Conclusions: Incidence of FA-related medical conditions varies according to disease duration. In patients with very long disease duration, we observed an unexpectedly high incidence of visual and auditory pseudo-hallucinations that were not previously reported in FA patients. We hypothesized that these late complications may be possibly related to the severe sensory deafferentation syndrome observed in the advanced stages of FA disease., (© 2022. Fondazione Società Italiana di Neurologia.)

Purpose: To evaluate the feasibility of a new method of conjunctival transplantation to achieve recovery of the normal conjunctival epithelium over the bare sclera after pterygium excision and prevent its recurrence., Methods: After excision of the primary pterygium, we performed simple conjunctival epithelial transplantation (SCET) in which we glued an amniotic membrane patch pre-loaded with tiny autologous conjunctival tissue fragments over the scleral defect. Slit-lamp evaluation was performed at 2 and 7-10 days, and then at 1, 3, 6, and 12 months after surgery, together with confocal microscopy at 3, 6, and 12 months., Results: Surgical excision and SCET for nasal primary pterygium were performed in 6 eyes (6 patients). No graft detachment occurred. An inflammatory granuloma was excised without sequelae in one patient 2 months after surgery. No signs of recurrence or sight-threatening complications were recorded at 12 months, and in vivo confocal microscopy showed progressive expansion of the conjunctival cell population and formation of a clear corneal-conjunctival transition., Conclusions: SCET takes advantage of the ability of the amniotic membrane and conjunctival cells to renew. Outcomes after SCET are comparable to conventional conjunctival flap surgery and can be achieved in less surgical time and with less donor tissue to be removed., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Subclinical mastitis (SCM) is an inflammatory state of the lactating mammary gland, which is asymptomatic and may have negative consequences for child growth. The objectives of this study were to: (1) test the association between the dietary inflammatory index (DII®) and SCM and (2) assess the differences in nutrient intakes between women without SCM and those with SCM. One hundred and seventy-seven women with available data on human milk (HM) sodium potassium ratio (Na:K) and dietary intake data were included for analysis. Multivariable logistic regression was used to examine the association between nutrient intake and the DII score in relation to SCM. Women without SCM had a lower median DII score (0.60) than women with moderate (1.12) or severe (1.74) SCM (p < 0.01). A one-unit increase in DII was associated with about 41% increased odds of having SCM, adjusting for country and mode of delivery, p = 0.001. Women with SCM had lower mean intakes of several anti-inflammatory nutrients. We show for the first time exploratory evidence that SCM may be associated with a pro-inflammatory diet and women with SCM have lower intakes of several antioxidant and anti-inflammatory nutrients.

Background: Transplantation of ex vivo cultured conjunctival cell layers, generated on amniotic membrane or other scaffolds, provides a viable option in treating heterogeneous ocular surface conditions. By comparison, cell therapy is costly, labour-intensive and subject to good manufacturing practice requirements and regulatory approval; no conjunctival cell-based therapy is currently available. Several techniques are available after primary pterygium excision to recover the ocular surface anatomy by restoring healthy conjunctival epithelium and preventing recurrence and complications. However, application of conjunctival free autograft or transpositional flap to cover the bared scleral area is limited when the conjunctiva are to be spared for future glaucoma filtering surgery, in patients with large or double-headed pterygia, in recurrent pterygia, or when the harvesting of donor conjunctival is precluded by scarring., Aim: To develop a simple technique to obtain expansion of the conjunctival epithelium when applied in vivo in diseased eyes., Methods: We evaluated in vitro the best way of gluing conjunctival fragments over the AM, the efficiency of the fragments to generate conjunctival cell outgrowths, the molecular marker expression, and the feasibility of shipping preloaded AM.We performed simple conjunctival epithelial transplantation (SCET) in which we glued an amniotic membrane patch pre-loaded with autologous conjunctival tissue fragments over the scleral defect after pterygium excision and evaluated the recovery of the normal conjunctival epithelium and the disease recurrence up to 12 months after surgery., Results: 65-80% of fragments generated outgrowth 48-72h after gluing, without differences between type of AM preparation and fragment size. Within 6-13 days, a full epithelium covered the surface of the amniotic membrane. Specific marker expression (Muc1, K19, K13, p63, ZO-1) was detected. The shipping test showed after 24h the 31% of the fragments glued over the AM epithelial side, compared to more than 90% of fragments stayed attached in the remaining conditions (stromal side, stromal without spongy layer, epithelial side without epithelium).Surgical excision and SCET for nasal primary pterygium were performed in 6 eyes/patients. No graft detachment and recurrence occurred within 12 months. In vivo confocal microscopy showed progressive expansion of the conjunctival cell population and formation of a clear cornea-conjunctiva transition., Conclusions: We established the most suitable conditions for a novel strategy based on in vivo expansion of conjunctival cells from conjunctival fragments glued over the AM. The application of SCET seems to be effective and replicable for the renewal of conjunctiva in patients requiring ocular surface reconstruction., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The implantation of the PRESERFLO™ MicroShunt (PMS) device has been shown to significantly lower increased intraocular pressure (IOP) in patients with primary open-angle glaucoma (POAG). However, guidelines on best practice for patient selection and pre-/peri-/postoperative care management are lacking. The aim of this modified Delphi panel was to achieve expert consensus on the role of the PMS to treat patients with glaucoma in Europe., Methods: Twelve European glaucoma surgeons experienced with the PMS procedure participated in a three-round modified Delphi panel. A targeted literature review and expert steering committee guided round 1 questionnaire development. Consensus was set at a pre-defined threshold of at least 70% of panellists selecting 'Strongly disagree'/'Disagree' or 'Strongly agree'/'Agree' for six-point Likert scale questions, or at least 70% selecting the same option for multiple-choice questions. Questions not reaching consensus were restated/revised for the next round, following guidance from free-text responses/scoping questions., Results: Consensus was achieved for 60.3% (n = 38/63), 60.0% (n = 18/30), and 100.0% (n = 11/11) of Likert/multiple-choice questions in rounds 1, 2, and 3, respectively. There was agreement that the PMS procedure is effective at reducing IOP in patients with high-tension POAG (greater than 21 mmHg). Although surgical techniques may vary slightly, consensus was reached on several points, including the importance of posterior application of mitomycin C (MMC). Panellists agreed that the PMS postoperative follow-up appointment schedule is reasonably predictable and mostly characterised by fewer visits than with trabeculectomy, particularly in the early phase. Although panellists agreed that combined cataract/PMS surgery and the use of non-MMC wound-healing modulators/antifibrotics during the procedure are possible, further data are needed to determine efficacy., Conclusion: The expert consensus reached in this panel will help inform best practice guidelines in the treatment of patients with glaucoma in Europe. Panellists also highlighted key areas for future research to improve understanding of the PMS in the treatment algorithm of glaucoma., (© 2022. The Author(s).)

Purpose: To summarize the actions taken to give continuity to the surgical treatment of glaucoma patients and to present the volume and characteristics of glaucoma surgery in the first year of pandemic at the Tertiary Glaucoma Center of the University Hospital of Verona (Veneto, Italy)., Methods: Demographical and surgical features of patients who underwent glaucoma surgery from March 9th, 2020 to March 8th, 2021 have been collected and compared to the same date range of the previous year. The analyzed data included age, gender, region of origin, glaucoma staging, type of anesthesia and surgical procedure., Results: The surgical volume of glaucoma has dropped by 30.1%. In comparison with the previous year, we found a significant variation in the overall distribution of the performed surgical procedures (p < 0.001). There was a decline in Baerveldt tube implants (- 4.9%), and an increase of non-penetrating surgery (+ 2.6%), cyclo-photo ablative procedures (+ 4.2%) and MIGS (+ 5.7%). Only 24.3% of the procedures were performed under general anesthesia compared to 41.5% in the pre-pandemic period (p < 0.001). The number of procedures performed on eyes affected by advanced or end-stage glaucoma is doubled (p < 0.001)., Conclusions: To give continuity to glaucoma surgery, we prioritized interventions on patients with poorer visual fields, rapidly progressing visual field deficit and elevated IOP uncontrolled by maximal medical therapy. Secondly, we have rescheduled the other interventions following the same priority criteria. Finally, we managed some lower priority cases with MIGS, minimizing the need for close post-intervention follow-up. Considering the negative consequences that a delay in the management of glaucoma can have in terms of visual loss, the closure of the operating rooms in the first quarter of the pandemic was detrimental. It appears that glaucoma surgery deserves urgencies that cannot be overshadowed and the greatest effort must be to give continuity to this type of eye surgery., (© 2022. The Author(s).)

Background: The prospective DIabetes and CATaract Study II (DICAT II) was performed to characterise the risks of cataract surgery to the retinae of patients with early diabetic macular oedema (E-DMO)., Methods: DICAT II was a prospective, comparative, multicentre, observational study involving six Italian clinics. Patients were aged ≥55 years, had type 1 or 2 diabetes with spectral-domain optical coherence tomography evidence of ESASO classification Early DMO. Group 1 eyes (78 eyes, 78 patients) underwent phacoemulsification-based cataract surgery. Group 2 eyes (65 eyes, 65 patients) had E-DMO and either clear media or had undergone uncomplicated cataract surgery ≥1 year previously. Central subfield thickness (CST) and best-corrected visual acuity (BCVA) were assessed in both groups., Results: The negative impact of surgery on CST was evident after the first postoperative week; CST peaked during the first month, then rapidly decreased. CST worsening ≥10 µm was observed in 63/78 eyes (80.7%) and 29/65 eyes (44.6%) in Groups 1 and 2, respectively (p < 0.0001). CST worsening of ≥50 µm was observed in 51 eyes (65.4%) and 10 eyes (15.4%) in Groups 1 and 2, respectively (p < 0.0001). Mean CST worsening was lower in Group 2 than in Group 1 (38.6 ± 30.4 µm vs 85.5 ± 55.3 µm, p < 0.0001) with a lower BCVA loss (-2.6 ± 3.5 letters vs -8.2 ± 6.2 letters, p < 0.0001). Higher glycaemic levels and HBA1c levels were significantly associated with the risk of >50 μm CST worsening in eyes from both groups., Conclusion: Early DMO is associated with poorer outcomes after cataract surgery and requires close pre- and postoperative monitoring., (© 2021. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

This study investigates the impact of antenatal and postnatal infection or inflammation on the onset and progression of Retinopathy of Prematurity (ROP). We retrospectively collected clinical and demographic data of preterm infants with birth weight ≤ 1500 g or gestational age < 30 weeks admitted to the neonatal intensive care unit of Verona from 2015 to 2019. Uni- and multivariable analysis was performed to evaluate the potential effect of selected variables on the occurrence of any stage ROP and its progression to severe ROP, defined as ROP requiring treatment. Two hundred and eighty neonates were enrolled and 60 of them developed ROP (21.4%). Oxygen need for 28 days and late-onset sepsis (LOS) increased the risk of any grade ROP after adjusting for birth weight and gestational age (OR 6.35, 95% CI 2.14-18.85 and OR 2.49, 95% CI 1.04-5.94, respectively). Days of mechanical ventilation and of non-invasive ventilation increased the risk of progression to severe ROP after adjusting for birth weight and gestational age (OR 1.08, CI 1.02-1.14 and OR 1.06, CI 1.01-1.11, respectively). Exposure to infection with production of inflammatory mediators may contribute to increase the risk of ROP occurrence in very preterm neonates., (© 2022. The Author(s).)

Purpose: To describe posterior ocular involvement features of Whipple's disease (WD) in a patient with no gastrointestinal symptoms., Methods: Retrospective case report., Observation: A 53-year-old man with a 2-year history of seronegative arthritis presented with bilateral intraocular inflammation, optic disc edema, and cystoid macular edema (CME) in the left eye. A diagnosis of noninfectious uveitis was made and oral prednisolone was started. Despite initial improvement, after 6 weeks, CME was found in both eyes. Because of the initial response, the anti-tumor necrosis factor agent Adalimumab was started. Twelve weeks after initiation of adalimumab, fundus examination revealed widespread dot-blot retinal hemorrhages and multifocal chorioretinal lesions at the posterior pole and mid-periphery. The chorioretinal lesions appeared as hyperreflective drusen-like deposits located in the sub-retinal pigment epithelium (RPE) space on the tomographic scan. WD was considered and confirmed by polymerase chain reaction test and duodenal biopsy., Conclusion: Posterior ocular involvement in WD may present with a wide clinical spectrum including intraocular inflammation and unique features of sub-RPE deposits, widespread retinal hemorrhages, and optic disc edema.

The human brain is the most complex organ in biology. This complexity is due to the number and the intricate connections of brain cells and has so far limited the development of in vitro models for basic and applied brain research. We decided to create a new, reliable, and cost-effective in vitro system based on the Nichoid, a 3D microscaffold microfabricated by two-photon laser polymerization technology. We investigated whether these 3D microscaffold devices can create an environment allowing the manipulation, monitoring, and functional assessment of a mixed population of brain cells in vitro. With this aim, we set up a new model of hippocampal neurons and astrocytes co-cultured in the Nichoid microscaffold to generate brain micro-tissues of 30 μm thickness. After 21 days in culture, we morphologically characterized the 3D spatial organization of the hippocampal astrocytes and neurons within the microscaffold, and we compared our observations to those made using the classical 2D co-culture system. We found that the co-cultured cells colonized the entire volume of the 3D devices. Using confocal microscopy, we observed that within this period the different cell types had become well-differentiated. This was further elaborated with the use of drebrin, PSD-95, and synaptophysin antibodies that labeled the majority of neurons, both in the 2D as well as in the 3D co-cultures. Using scanning electron microscopy, we found that neurons in the 3D co-culture displayed a significantly larger amount of dendritic protrusions compared to neurons in the 2D co-culture. This latter observation indicates that neurons growing in a 3D environment may be more prone to form connections than those co-cultured in a 2D condition. Our results show that the Nichoid can be used as a 3D device to investigate the structure and morphology of neurons and astrocytes in vitro. In the future, this model can be used as a tool to study brain cell interactions in the discovery of important mechanisms governing neuronal plasticity and to determine the factors that form the basis of different human brain diseases. This system may potentially be further used for drug screening in the context of various brain diseases.

Purpose: Human milk (HM) composition is influenced by factors, like maternal diet and body stores, among other factors. For evaluating the influence of maternal fatty acid (FA) status on milk FA composition, the correlation between FA content in HM and in maternal plasma, erythrocytes, and adipose tissue was investigated., Methods: 223 European women who delivered at term, provided HM samples over first four months of lactation. Venous blood and adipose tissue (only from mothers who consented and underwent a C-section delivery) were sampled at delivery. FAs were assessed in plasma, erythrocytes, adipose tissue, and HM. Evolution of HM FAs over lactation and correlations between FA content in milk and tissues and between mother's blood and cord blood were established., Results: During lactation, arachidonic acid (ARA) and docosahexaenoic acid (DHA) significantly decreased, while linoleic acid (LA), alpha-linolenic acid (ALA), and eicosapentaenoic acid (EPA) remained stable. Positive correlations were observed between HM and adipose tissue for palmitic, stearic, oleic, and polyunsaturated fatty acids (PUFAs). Correlations were found between milk and plasma for oleic, LA, ARA, ALA, DHA, monounsaturated fatty acids (MUFAs), and PUFAs. No correlation was observed between erythrocytes and HM FAs. LA and ALA were more concentrated in maternal blood than in infant blood, contrary to ARA and DHA, supporting that biomagnification of LCPUFAs may have occurred during pregnancy., Conclusions: These data show that maternal adipose tissue rather than erythrocytes may serve as reservoir of PUFAs and LCPUFAs for human milk. Plasma also supplies PUFAs and LCPUFAs to maternal milk. If both, adipose tissue and plasma PUFAs, are reflection of dietary intake, it is necessary to provide PUFAs and LCPUFAs during pregnancy or even before conception and lactation to ensure availability for mothers and enough supply for the infant via HM., (© 2022. The Author(s).)

Purpose: This report describes a case of bilateral primary angle closure (PAC) progressing to unilateral end-stage primary angle closure glaucoma (PACG) associated with treatment for coronavirus disease-19 (COVID-19) infection., Methods: A 64-year-old man came to our attention because of blurred vision after a 2-month hospital stay for treatment of COVID-19 infection. Examination findings revealed PACG, with severe visual impairment in the right eye and PAC in the left eye due to plateau iris syndrome. The patient's severe clinical condition and prolonged systemic therapy masked the symptoms and delayed the diagnosis. Medical chart review disclosed the multifactorial causes of the visual impairment. Ultrasound biomicroscopy (UBM) aided in diagnosis and subsequent therapy., Results: The cause behind the primary angle closure and the iridotrabecular contact was eliminated by bilateral cataract extraction, goniosynechialysis, and myotic therapy., Conclusions: COVID-19 treatment may pose an increased risk for PAC. Accurate recording of patient and family ophthalmic history is essential to prevent its onset. Recognition of early signs of PAC is key to averting its progression to PACG.

The aim of this trial was to evaluate the effect of progesterone gel compared to placebo in prolonging pregnancy among women with preterm labor. Methods: A randomized controlled trial in Sweden in 2009−18. Women with early preterm labor were randomized to daily doses of progesterone gel 90 mg (n = 28) or placebo (n = 30) after standard intravenous tocolytics. Women with intravenous tocolytics alone (n = 29) served as controls. Results: The median latency to delivery was 68 (range 28−88) days with progesterone and 72 (range 9−90) days with placebo (p = 0.84), compared to 1 (range 1−2) day in the control group (progesterone and placebo vs. control p < 0.001). The rate of preterm birth before 34 weeks was 32% after progesterone and 37 % after placebo (p = 0.32) compared to 100 % in the control group (p < 0.001, respectively). The composite neonatal morbidity (p = 0.65) and neonatal intensive care unit admission (p = 0.12) were comparable between the progesterone and placebo groups and lower in these groups compared with neonates in the control group (p < 0.001, respectively). Conclusions: Progesterone gel and placebo were equally effective in prolonging pregnancy among women with early preterm labor, and both treatments were more effective than standard intravenous tocolysis alone. We hypothesize that the acidic placebo gel reinforced the biochemical barrier at the uterine cervix, which counteracts ascending pathogen invasion and subsequent inflammation, and thereby prevented preterm labor.

Ocular surgery encompasses a wide range of procedures, including surgery of the tear ducts, eyelid, cornea and conjunctiva, lens, ocular muscle, and vitreoretinal and iris surgery. Operations are also performed for the removal of tumors, repairs of ocular trauma and, finally, corneal transplantation. Antibiotic prophylaxis for the prevention of surgical site infections (SSIs) in ocular surgery is a complex field in which shared lines of action are absent. In light of the scarcity of shared evidence in the use of ocular antimicrobial prophylaxis for the pediatric population, this consensus document aims to provide clinicians with a series of recommendations on antimicrobial prophylaxis for patients of neonatal and pediatric age undergoing eye surgery. The following scenarios are considered: (1) intraocular surgery; (2) extraocular surgery; (3) ocular trauma; (4) ocular neoplasm; (5) ocular surface transplantations; (6) corneal grafts. This work has been made possible by the multidisciplinary contribution of experts belonging to the most important Italian scientific societies and represents, in our opinion, the most complete and up-to-date collection of recommendations regarding clinical actions in the peri-operative environment in eye surgery. The application of uniform and shared protocols aims to improve surgical practice, through the standardization of procedures, with a consequent reduction of SSIs, also limiting the phenomenon of antimicrobial resistance.

c-Jun N-terminal kinases (JNKs) are stress-activated serine/threonine protein kinases belonging to the mitogen-activated protein kinase (MAPK) family. Among them, JNK3 is selectively expressed in the central nervous system, cardiac smooth muscle, and testis. In addition, it is the most responsive JNK isoform to stress stimuli in the brain, and it is involved in synaptic dysfunction, an essential step in neurodegenerative processes. JNK3 pathway is organized in a cascade of amplification in which signal transduction occurs by stepwise, highly controlled phosphorylation. Since different MAPKs share common upstream activators, pathway specificity is guaranteed by scaffold proteins such as JIP1 and β-arrestin2. To better elucidate the physiological mechanisms regulating JNK3 in neurons, and how these interactions may be involved in synaptic (dys)function, we used (i) super-resolution microscopy to demonstrate the colocalization among JNK3-PSD95-JIP1 and JNK3-PSD95-β-arrestin2 in cultured hippocampal neurons, and (ii) co-immunoprecipitation techniques to show that the two scaffold proteins and JNK3 can be found interacting together with PSD95. The protein-protein interactions that govern the formation of these two complexes, JNK3-PSD95-JIP1 and JNK3-PSD95-β-arrestin2, may be used as targets to interfere with their downstream synaptic events.

Background: The effect of the mode of neonatal delivery (cesarean or vaginal) on the nutrient composition of human milk (HM) has rarely been studied. Given the increasing prevalence of cesarean section (C-section) globally, understanding the impact of C-section vs. vaginal delivery on the nutrient composition of HM is fundamental when HM is the preferred source of infant food during the first 4 postnatal months., Objective: This study aimed to evaluate the association between mode of delivery and nutrient composition of HM in the first 4 months of life., Design: Milk samples were obtained from 317 healthy lactating mothers as part of an exploratory analyses within a multicenter European longitudinal cohort (ATLAS cohort) to study the HM composition, and its potential association with the mode of delivery. We employed traditional mixed models to study individual nutrient associations adjusted for mother's country, infant birth weight, parity, and gestational age, and complemented it, for the first time, with a multidimensional data analyses approach (non-negative tensor factorization, NTF) to examine holistically how patterns of multiple nutrients and changes over time are associated with the delivery mode., Results: Over the first 4 months, nutrient profiles in the milk of mothers who delivered vaginally ( n = 237) showed significantly higher levels of palmitoleic acid (16:1n-7), stearic acid (18:0), oleic acid (18:1n-9), arachidic acid (20:0), alpha-linolenic acid (18:3n-3), eicosapentaenoic acid (20:5n-3), docosahexenoic acid (22:6n-3), erucic acid (22:1n-9), monounsaturated fatty acids (MUFA)%, calcium, and phosphorus, whereas the ratios of arachidonic acid/docosahexaenoic acid (ARA/DHA) and n-6/n-3, as well as polyunsaturated fatty acids (PUFA)% were higher in milk from women who had C-sections, in the unadjusted analyses ( p < 0.05 for all), but did not retain significance when adjusted for confounders in the mixed models. Using a complementary multidimension data analyses approach (NTF), we show few similar patterns wherein a group of mothers with a high density of C-sections showed increased values for PUFA%, n-6/n-3, and ARA/DHA ratios, but decreased values of MUFA%, 20:1n-9, iodine, and fucosyl-sialyl-lacto-N-tetraose 2 during the first 4 months of lactation., Conclusion: Our data provide preliminary insights on differences in concentrations of several HM nutrients (predominantly fatty acids) among women who delivered via C-section. Although these effects tend to disappear after adjustment for confounders, given the similar patterns observed using two different data analytical approaches, these preliminary findings warrant further confirmation and additional insight on the biological and clinical effects related to such differences early in life., Competing Interests: ’This study received funding from Société des Produits Nestlé S.A. The funder had the following involvement with the study: study design, data analysis, interpretation of the results, and reporting in scientific journal. TS, LL, CC, FG, SD, and ST are currently employees of Société des Produits Nestlé S.A. PF and FT are consultants to Société des Produits Nestlé S.A. CM-C, KH, GM, MA, TR, MC, J-CP, and CB received funding from Société des Produits Nestlé S.A. to conduct the study. FT received funding for the research and drafting the manuscript., (Copyright © 2022 Samuel, Thielecke, Lavalle, Chen, Fogel, Giuffrida, Dubascoux, Martínez-Costa, Haaland, Marchini, Agosti, Rakza, Costeira, Picaud, Billeaud and Thakkar.)

Purpose: The relation between OSAS and eye diseases is well known in adults, while very few and contradictory data can be found regarding paediatric ages. The aim of this study is to explore the early corneal, macular and optic nerve changes in paediatric patients with OSAS., Methods: Prospective study that enrolled children aged ≥ 4 years referred to the Paediatric Pneumology Clinic in Verona for suspected obstructive sleep apnoea syndrome (OSAS) and investigated with the overnight respiratory polygraphy. Patients with apnoea-hypopnea index (AHI) > 1 were classified as OSAS, while those with AHI < 1 were classified non-OSAS. All patients underwent comprehensive eye examination including slit lamp, refraction, intraocular pression (Goldman applanation tonometry), corneal tomography (corneal astigmatism, corneal keratometry at the apex, surface asymmetry index, central corneal thickness and thinnest corneal thickness) and optical coherence tomography (central macular thickness, macular volume and retinal nerve fibre layer)., Results: Seventy-two children were enrolled in the study. The overall prevalence of OSAS was 48.6%. Statistically significant differences were found between OSAS and non-OSAS group for corneal asymmetry (0.9 ± 0.5 and 0.6 ± 0.3, respectively; p = 0.02), thinnest corneal thickness (551.8 ± 33.9 and 563.7 ± 32.5; p = 0.04), average retinal nerve fibre layer (102.8 ± 10.5 µm and 98.1 ± 12.3 µm; p = 0.012) and in nasal quadrant (76.2 ± 15.4 µm and 66.5 ± 12.6 µm; p = 0.0002)., Conclusions: A comprehensive eye examination with corneal and optic nerve imaging showed early corneal and optic nerve changes in children newly diagnosed with OSAS. These could be prelude of the known ocular manifestations associated with OSAS in adult patients., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)