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Browsing by Author "Borroni, Davide"

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    Assessing the Effects of 0.3% Carboxymethylcellulose Tear Substitute Treatment on Symptoms and Signs of Dry Eye Disease in Elderly Population : A Prospective Longitudinal Study
    (2023-12) Ballesteros-Sánchez, Antonio; Sánchez-González, José María; Tedesco, Giovanni Roberto; Rocha-De-Lossada, Carlos; Murano, Gianluca; Spinelli, Antonio; Borroni, Davide; Department of Ophthalmology
    Background: We aimed to evaluate the effects of 0.3% carboxymethylcellulose (CMC) tear substitute treatment in dry eye disease (DED), as well as treatment compliance and adverse events (AEs). Methods: In this prospective, longitudinal study, a total of 30 eyes receiving 0.3% CMC tear substitute four times daily for DED were evaluated. Clinical endpoints included an ocular surface disease index (OSDI) questionnaire, average non-invasive tear film break-up time (A-NIBUT), lipid layer thickness (LLT), and a Schirmer test with anesthesia (ST). Treatment compliance and AEs were also assessed. All evaluations were performed at 2, 4, and 12 weeks of follow-up. Results: At the end of the follow-up, significant improvement was observed in all clinical endpoints with the following mean values: ΔOSDI questionnaire of −22.53 ± 14.68 points, ΔA-NIBUT of 4.81 ± 2.88 s, ΔLLT of 5.63 ± 6.53 nm, and ΔST of 2.8 ± 2.1 mm (p < 0.001 for all comparisons). Although repeated measures analysis showed that all clinical endpoints presented statistically significant differences (p < 0.001 for all comparisons LLTBaseline–LLT2-weeks (p = 0.460) and LLT4-weeks–LLT12-weeks (p = 0.071) were the only pairs of measures that reported non-statistically significant differences). In addition, treatment compliance was 94.3 ± 5.2% and transient AEs related to the use of 0.3% CMC tear substitute were reported. Conclusions: 0.3% CMC tear substitute treatment seems to achieve beneficial effects on the OSDI questionnaire, A-NIBUT, LLT, and ST. However, further studies at this concentration are needed to confirm these results.
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    Assessment of visual morbidity amongst diabetic retinopathy at tertiary eye care center, Nepal : A cross-sectional descriptive study
    (2017-12-28) Pandey, Araniko; Lamichhane, Gyanendra; Khanal, Roshija; Rai, Salma K.C.; Bhari, Arjun Malla; Borroni, Davide; Gautam, Narayan; Rīga Stradiņš University
    Background: Diabetic retinopathy (DR) is one of the leading causes of preventable blindness in low and middle income countries. In Nepal, there are less studies regarding DR and they too are limited around Kathmandu valley. This study was done to assess visual morbidity in patients with DR at a peripheral tertiary eye care center of Nepal. Methods: This was a prospective, hospital based, cross-sectional study in which all consecutive cases of DR were evaluated. DR was classified according to Early Treatment Diabetic Retinopathy Study Research Group - report no. 10 Table A5-1 (Modified Airlie House Classification). Data entry and analysis was done in an SPSS unit version 20. Wherever applicable, variables were set as 100 eyes. Results: Total number of patients included in this study was 50. Commonest age group was 50-69 yrs. (43/77 yrs.; min/max) comprising 80% of the total population (n = 50) and the predominant population was male (76%). Non proliferative diabetic retinopathy (NPDR) was found in 69%, proliferative diabetic retinopathy (PDR) in 31% and advanced diabetic eye disease (ADED) in 3% (n = 100). Conclusions: All the stages of DR were present at significant proportions in this study, noteworthy was the percentage of PDR. This study shows an urgency to gather a national data on DR, raise awareness among diabetics and train effective man power at a local level to diagnose DR at an early stage.
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    Autologous versus allogeneic versus umbilical cord sera for the treatment of severe dry eye disease : a double-blind randomized clinical trial
    (2022-03) Rodríguez Calvo-de-Mora, Marina; Domínguez-Ruiz, Cayetano; Barrero-Sojo, Francisco; Rodríguez-Moreno, Gustavo; Antúnez Rodríguez, Cristina; Ponce Verdugo, Laura; Hernández Lamas, María del Carmen; Hernández-Guijarro, Luisa; Villalvilla Castillo, Jacinto; Fernández-Baca Casares, Idefonso; Prat Arrojo, Isidro; Borroni, Davide; Alba-Linero, Carmen; Zamorano-Martín, Francisco; Moreno-Guerrero, Antonio; Rocha-de-Lossada, Carlos; Department of Doctoral Studies
    Purpose: To measure the effects of Autologous serum (AS), Allogeneic Serum (HS) and Umbilical Cord serum (CS) eye drops in severe dry eye disease (DES), as well as to characterize and quantify several molecules in the three sera (albumin, fibronectin; Vitamin A and E; IgG, IgA and IgM; Transforming growth factor β; Epithelial growth factor). Methods: Randomized, double-blind, single-centre, three-arm (AS, HS and CS) clinical trial. Sixty-three subjects were included with severe DES, 21 in each arm of the study. Visual acuity, Schirmer test, Breakup time (BUT), lissamine green, fluorescein staining measurements and a questionnaire were performed prior to treatment, and after one-month and three-month follow-up. Results: There was a significant main effect of time on visual acuities, Schirmer and BUT tests and fluorescein and lissamine green staining measurements and questionnaire scores (p = 0.015, p = 0.002, p < 0.001, p < 0.001, p = 0.031 and p < 0.001, respectively), although there was no significant interaction between time and serum type, nor between serum type and the test performed. Regarding the concentration of molecules, in our study AS contained significantly higher concentrations of IgA, IgG and fibronectin whereas HS contained significantly higher concentration of IgM, vitamins A and E, TGF and albumin. Contrary to previous reports, CS did not show higher concentration of any of the molecules analysed. Conclusions and relevance: The three sera were effective in the treatment of severe DES. CS did not contain a higher proportion of molecules compared to AS/HS. More research is needed to assess the effect of AS in patients with DES and autoimmune diseases.
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    Chord Mu (µ) and Chord Alpha (α) Length Changes in Fuchs Endothelial Corneal Dystrophy before and after Descemet Membrane Endothelial Keratoplasty (DMEK) Surgery
    (2021-11-01) Rocha-De-lossada, Carlos; Sánchez-González, José María; Borroni, Davide; Llorens-Bellés, Víctor; Rachwani-Anil, Rahul; Torras-Sanvicens, Josep; Romano, Vito; Peraza-Nieves, Jorge; Department of Doctoral Studies
    This paper will evaluate chord mu and alpha length in patients with Fuchs endothelial corneal dystrophy (FECD) and its changes following Descemet membrane endothelial keratoplasty (DMEK). Patients with FECD that underwent DMEK surgery were included in this retrospective study. Scheimpflug Tomography was carried out in order to calculate chord mu and chord alpha lengths prior to surgery and at 3 and 12 months postoperative. This study included 27 eyes from 27 patients. Significant changes in chord mu were observed within the first three months (from 0.47 ± 0.32 to 0.29 ± 0.21 mm, p < 0.01) and remained stable 12 months postoperative (0.30 ± 0.21 mm, p > 0.05). However, chord alpha remained stable throughout the 12 months post surgery (from 0.53 ± 0.19 to 0.49 ± 0.14 mm, p > 0.05). In addition to the pupillary center distance from the corneal apex (from 0.35 ± 0.25 to 0.34 ± 0.20 mm, p > 0.05) also remain stable. In FECD patients undergoing DMEK surgery, chord mu length decreased, and chord alpha length remained stable after 12 months of follow-up.
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    A Comparative Analysis of the Ocular Microbiome : Insights into Healthy Eyes and Anophthalmic Sockets
    (2024-11) Zamorano-Martín, Francisco; Chumaceiro, Guillermo; Navarro-Torres, Pablo; Borroni, Davide; Urbinati, Facundo; Molina, Ángel; Paytuví-Gallart, Andreu; Rocha-de-Lossada, Carlos; Department of Ophthalmology
    The purpose of this study is to characterize the ocular surface microbiota of patients with an anophthalmic cavity. An eNAT with 1 mL of Liquid Amies Medium was used to collect samples. Microbial DNA from anophthalmic socket and healthy fellow control eye samples was isolated and sequenced. Raw reads were analyzed with GAIA (v 2.02). The richness and Shannon alpha diversity metrics, as well as Bray–Curtis beta diversity and Wilcoxon signed-rank test values, were computed with R packages such as phyloseq, mia, or DESeq2 to allow for microbiome analysis. Principal coordinate analysis (PCoA) was performed using the function plotReducedDim from the R package scater. The different taxonomic profiles were described under the concept of eye community state type (ECST). The microbiomes of both eyes from 25 patients with an anophthalmic cavity were analyzed in this study. While the microbial communities of paired eyes from the same patients showed notable dissimilarity, no consistent patterns emerged when comparing healthy eyes to anophthalmic sockets. Alpha diversity values did not significantly differ between healthy eyes and anophthalmic socket samples, though there was considerable variability within each group. Notably, anophthalmic socket samples generally exhibited lower abundances of genera such as Staphylococcus, Enterococcus, Paenibacillus, and Sediminibacterium compared to their healthy counterparts. Microbial variability between healthy eyes and anophthalmic sockets may be due to anatomical differences. Further research is needed to determine whether patients without anophthalmic sockets exhibit similar microbiome patterns in both eyes.
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    Corneal Endothelial Cell Loss in Glaucoma and Glaucoma Surgery and the Utility of Management with Descemet Membrane Endothelial Keratoplasty (DMEK)
    (2022) Vallabh, Neeru A.; Kennedy, Stephnie; Vinciguerra, Riccardo; McLean, Keri; Levis, Hannah; Borroni, Davide; Romano, Vito; Willoughby, Colin E.; Department of Doctoral Studies
    The corneal endothelium has a crucial role in maintaining a clear and healthy cornea. Corneal endothelial cell loss occurs naturally with age; however, a diagnosis of glaucoma and surgical intervention for glaucoma can exacerbate a decline in cell number and impairment in morphology. In glaucoma, the mechanisms for this are not well understood and this accelerated cell loss can result in corneal decompensation. Given the high prevalence of glaucoma worldwide, this review aims to explore the abnormalities observed in the corneal endothelium in differing glaucoma phenotypes and glaucoma therapies (medical or surgical including with new generation microinvasive glaucoma surgeries). Descemet membrane endothelial keratoplasty (DMEK) is increasingly being used to manage corneal endothelial failure for glaucoma patients and we aim to review the recent literature evaluating the use of this technique in this clinical scenario.
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    Covid-19 : The need of non-traditional techniques to screen for the virus
    (2020) Borroni, Davide; Gadhvi, Kunal
    BACKGROUND: At the present moment, the etiological diagnosis of SARS-CoV-2 is based on the polymerase chain reaction (PCR). False negative cases are increasingly reported in several studies using reverse transcription-PCR (RT-PCR). For example, the positive rate of RT-PCR for throat swabs was reported to be about 60% in early stage of COVID-19. AIM: We aimed to present metagenomic next-generation sequencing (mNGS) as a potential tool to detect pathogens. METHODS: In the recent year, mNGS is shown the potential to detect pathogens without the need of hypothesis guided approach and is proven to be highly effective. RESULTS: A recent prospective study in the United States compared the diagnostic performance of routine diagnostic tests with mNGS and showed that mNGS detected a bacteria or virus in the CSF of 13 of 58 patients presenting with meningoencephalitis who were negative for or not assessed with routine diagnostic test including PCR. NGS also has the advantage to cover entire viral genomes. CONCLUSION: As viral metagenomics has significantly improved in recent years and become more cost effective, we think that a change in the approach toward a shot-gun metagenomic testing should be explored and could potentially aid the diagnosis of COVID-19 cases and the management of this pandemic.
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    Descemet membrane endothelial keratoplasty in pseudophakic bullous keratopathy : Outcomes and evidence-based suggestions
    (2018) Borroni, Davide; Ferronato, Melanie; Orube, Ineta; Erts, Renars; Sepetiene, Svetlana; Drucka, Eva; Krumina, Zita; Rīga Stradiņš University; Department of Ophthalmology; Department of Biology and Microbiology
    The purpose of the study was to determine clinical outcomes of Descemet Membrane Endothelial Keratoplasty (DMEK) in patients with Pseudophakic Bullous Keratopathy (PBK). The study was conducted at a tertiary referral center. This was a retrospective case series. Pseudophakic eyes having undergone DMEK surgery for Pseudophakic Bullous Keratopathy was considered the object of study. The examination implied the analysis of best corrected visual acuity (BCVA or CDVA), endothelial cell density (ECD), intraocular pressure (IOP), intraoperative and postoperative complications and a follow-up in 1, 3, and 6 months. For the purposes of the study, 25 pseudophakic eyes with PBK were examined. One month after the surgery patients reached a BCVA of 0.49±0.08(M±SD), after 3 months - BCVA of 0.65±0.12(M±SD), and a BCVA of 0.78±0.17 (M±SD) in the last follow-up in 6 months after the surgery (P<0,001). The mean ECD after one month was 1661±133 (M±SD) cells/mm2, after 3 months - 1591±124 (M±SD) cells/mm2, and during the last control in 6 months -1579±128 (M±SD) cells/mm2. The graft detachment rate was 12% (3 cases). Hypertension was observed in one eye (4%), necessitating partial air elimination through a corneal wound within the first hours after the surgery. DMEK may give excellent visual results in Pseudophakic eyes without increasing the risk of complications when compared to Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) and Penetrating Keratoplasty (PKP). Anatomic repair after DMEK is associated with improved corneal clarity and BCVA.
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    Descemet Membrane Endothelial Keratoplasty: NGS Metagenomics-Optimized Tissue Preparation and Surgical Technique. Doctoral Thesis
    (Rīga Stradiņš University, 2021) Borroni, Davide; Krūmiņa, Zita; Giovanni, Porta
    Title: Next-generation sequencing for the detection of microorganisms present in human donor corneal preservation medium. Aim: To detect the presence of microorganisms in the storage media of human donor corneas using next-generation sequencing method. Methods: Seven samples from organ culture (OC) group (Cornea Max, Eurobio, Les Ulis, France) with one control (sterile media without any cornea) and seven samples from hypothermic storage group (Cornea Cold, Eurobio) with one control were used for this study. The corneas were placed in the respective storage media for 14 days before collecting the samples. Storage media (2 mL) from each sample were collected in RNAase-free tubes and shipped for ribosomal RNA sequencing of 16S and 18S. Simultaneously, another 1 mL of media sample was used for conventional diagnostic method (CDM) using Bactec instruments. Results: In both, OC and hypothermic storage and control samples, the most abundant genera were Pseudomonas, Comamonas, Stenotrophomonas, Alcanivorax, Brevundimonas and Nitrobacter. Acidovorax, Acetobacter and Hydrogenophilus were detected mostly in the hypothermic storage group. The most abundant fungal pathogen detected belonged to the genus Malassezia, which was found in both the storage conditions. CDM was negative for microorganisms in all the samples. Conclusion: Metagenomics provides full taxonomic profiling of the detected genomic material of the organisms and thus has the potential to deliver a much wider microbiological diagnostic approach than CDM. The costs and turnaround time need to be reduced, and; the detection of viable organisms would help this technology to be introduced into routine clinical practice.
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    Descemet Membrane Endothelial Keratoplasty: NGS Metagenomics-Optimized Tissue Preparation and Surgical Technique. Summary of the Doctoral Thesis
    (Rīga Stradiņš University, 2021) Borroni, Davide; Krūmiņa, Zita; Giovanni, Porta
    Title: Next-generation sequencing for the detection of microorganisms present in human donor corneal preservation medium. Aim: To detect the presence of microorganisms in the storage media of human donor corneas using next-generation sequencing method. Methods: Seven samples from organ culture (OC) group (Cornea Max, Eurobio, Les Ulis, France) with one control (sterile media without any cornea) and seven samples from hypothermic storage group (Cornea Cold, Eurobio) with one control were used for this study. The corneas were placed in the respective storage media for 14 days before collecting the samples. Storage media (2 mL) from each sample were collected in RNAase-free tubes and shipped for ribosomal RNA sequencing of 16S and 18S. Simultaneously, another 1 mL of media sample was used for conventional diagnostic method (CDM) using Bactec instruments. Results: In both, OC and hypothermic storage and control samples, the most abundant genera were Pseudomonas, Comamonas, Stenotrophomonas, Alcanivorax, Brevundimonas and Nitrobacter. Acidovorax, Acetobacter and Hydrogenophilus were detected mostly in the hypothermic storage group. The most abundant fungal pathogen detected belonged to the genus Malassezia, which was found in both the storage conditions. CDM was negative for microorganisms in all the samples. Conclusion: Metagenomics provides full taxonomic profiling of the detected genomic material of the organisms and thus has the potential to deliver a much wider microbiological diagnostic approach than CDM. The costs and turnaround time need to be reduced, and; the detection of viable organisms would help this technology to be introduced into routine clinical practice.
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    Descemeta membrānas endotēlija keratoplastika: nākamās paaudzes sekvenēšanas metagenomiski optimizētu audu sagatavošana un ķirurģijas tehnika. Promocijas darba kopsavilkums
    (Rīgas Stradiņa universitāte, 2021) Borroni, Davide; Krūmiņa, Zita; Giovanni, Porta
    Pētījumā tika analizēta optimizācija, pielietojot metagenomiku radzenes audu saglabāšanā. Nosaukums: Nākamās paaudzes sekvencēšana mikroorganismu noteikšanai cilvēka donora radzenes audu saglabāšanas vidē. Mērķis: Ar nākamās paaudzes sekvencēšanas metodi noteikt mikroorganismu klātbūtni cilvēka donora radzenes audu uzglabāšanas vidē. Materiāli un metodes: Kopā tika izmantoti septiņi paraugi no orgānu kultūras (no angļu val. – organ culture (OC)) grupas (Cornea Max, Eurobio, Les Ulis, Francija) ar vienu kontroli (sterila barotne bez radzenes audiem) un septiņi paraugi no hipotermiskās uzglabāšanas grupas (Cornea Cold, Eurobio) ar vienu kontroli. Pirms paraugu savākšanas radzenes audus ievietoja attiecīgajās uzglabāšanas vietās uz 14 dienām. Uzglabāšanas vide (2 ml) no katra parauga tika ievietota mēģenēs, kas nesatur RNS-āzi, un tika nosūtīta 16S un 18S ribosomu RNS sekvencēšanai. Vienlaikus 1 ml barotnes parauga tika izmantots konvencionālajai diagnostikas metodei (no angļu val. – conventional diagnostic method (CDM)), izmantojot Bactec instrumentus. Rezultāti: Gan OC, gan hipotermiskās uzglabāšanas un kontroles paraugos visbiežāk novēroja Pseudomonas, Comamonas, Stenotrophomonas, Alcanivorax, Brevundimonas un Nitrobacter ģintis. Acidovorax, Acetobacter un Hydrogenophilus ģintis tika atklātas galvenokārt hipotermiskās uzglabāšanas grupā. Visbiežāk konstatētais sēņu patogēns piederēja Malassezia ģintij, kas tika atrasts abās uzglabāšanas vidēs. Ar CDM visi paraugi bija negatīvi attiecībā uz mikroorganismiem. Secinājumi: Metagenomika nodrošina pilnīgu taksonomisko profilu noteikto organismu genomiskajam materiālam, tādējādi sniedzot daudz plašāku mikrobioloģiskās diagnostikas pieeju nekā CDM. Metodes izmaksu un apgrozījuma laika dzīvotspējīgu organismu noteikšanai samazināšana palīdzētu šo tehnoloģiju ieviest ikdienas klīniskajā praksē.
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    Doxycycline : From Ocular Rosacea to COVID-19 Anosmia. New Insight Into the Coronavirus Outbreak
    (2020-05-08) Bonzano, Chiara; Borroni, Davide; Lancia, Andrea; Bonzano, Elisabetta
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    Dry Eye Para-Inflammation Treatment : Evaluation of a Novel Tear Substitute Containing Hyaluronic Acid and Low-Dose Hydrocortisone
    (2023-12) Borroni, Davide; Mazzotta, Cosimo; Rocha-de-Lossada, Carlos; Sánchez-González, José María; Ballesteros-Sanchez, Antonio; García-Lorente, María; Zamorano-Martín, Francisco; Spinelli, Antonio; Schiano-Lomoriello, Domenico; Tedesco, Giovanni Roberto
    Purpose: The purpose of this study was to check the efficacy and safety of a novel tear substitute containing hyaluronic acid and low-dose hydrocortisone in the treatment of moderate dry eye disease. Methods: In this prospective randomized study, 38 patients with moderate dry eye disease were divided into two treatment groups: Group 1 received one drop of 0.2% sodium hyaluronate and 0.001% hydrocortisone four times daily for 3 months, while Group 2 received 0.15% sodium hyaluronate and 3% trehalose at the same dosage. OSDI and SANDE questionnaires, Non-Invasive Break-Up time (NIBUT), Tear Meniscus Height (TMH), meibography, Lipid Layer Thickness (LLT), Tear Break-Up Time (TBUT), Corneal Staining Score (CFS), and Intraocular Pressure (IOP) were evaluated at baseline and after 1, 2, and 3 months of treatment. Results: During the treatment period, Group 1 showed statistically significant improvement in OSDI score (p = 0.002), SANDE score (p = 0.01), NIBUT (p < 0.0001), LLT (p < 0.0001), TBUT (p = 0.01), and CFS (p = 0.02). In Group 2, significant improvement was observed only in the TBUT score (p < 0.05). Comparison of the two groups showed that NIBUT and LLT were significantly different at the end of treatment (p = 0.001 for both comparisons), with more favorable results for sodium hyaluronate and hydrocortisone than for sodium hyaluronate and trehalose. No significant variations in intraocular pressure were observed in either group during the treatment period (p > 0.05). Conclusions: The study confirms that a 3-months treatment with hyaluronic acid 0.2% in combination with low-dose hydrocortisone 0.001% improves the signs and symptoms of moderate DED and that a low-dosage 0.001% hydrocortisone can be helpful in preventing the progression to chronic stages of DED.
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    Efficacy and Safety of Quantum Molecular Resonance Electrotherapy in Patients with Aqueous-Deficient, Evaporative and Mixed-Type Dry Eye : A Randomized Interventional Study
    (2024-02) Ballesteros-Sánchez, Antonio; Sánchez-González, José María; Tedesco, Giovanni Roberto; Rocha-De-Lossada, Carlos; Russo, Fedele; Spinelli, Antonio; Ingrande, Irene; Borroni, Davide; Rīga Stradiņš University
    Introduction: To evaluate the efficacy and safety of Quantum Molecular Resonance (QMR) treatment in patients with severe dry eye disease (DED), as well as its effects on aqueous-deficient (ADDE), evaporative (EDE), and mixed (MDE) dry eye. Methods: In this prospective, interventional study, 81 patients were randomly allocated to received four treatment sessions of QMR at 1-week intervals (Rexon-Eye®, Resono Ophthalmic, Trieste, Italy) (QRM group) or tear substitute four times daily, containing 0.15% sodium hyaluronate and 3% trehalose (Thealoz Duo®, Thea Pharma, France) (SH-TH group). Outcome measures included ocular surface disease index (OSDI) questionnaire, tear meniscus height (TMH), tear breakup time (TBUT), non-invasive breakup time (NIBUT), corneal fluorescein staining (CFS), lipid layer thickness (LLT), tear film osmolarity (OSM), and meibomian gland dysfunction (MGD) grade, which were assessed at baseline and 1-month and 3-month follow-up. Results: The QMR group achieved better improvements than the SH-TH group in OSDI and SANDE questionnaires, NIBUT, LLT, and CFS. The mean differences between the groups were as follows: OSDI (− 12.4 ± 0.25 points, P = 0.01), SANDE (10.6 ± 1.7 points, P = 0.01), NIBUT (2 ± 0.25 s, P = 0.01), LLT (18.7 ± 0.7 nm, P = 0.01), and CFS (1.2 ± 0.1 points, P = 0.02). In subgroups analysis, QMR treatment demonstrated a beneficial role to improve DED symptoms and signs in ADDE, EDE, and MDE. Conclusion: QMR is an effective and well-tolerated treatment that seems to improve DED symptoms and signs in patients with severe DED. However, further studies are needed to confirm this. Trial Registration: ClinicalTrials.gov identifier NCT06119386.
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    Efficacy of bilateral OC-01 (varenicline solution) nasal spray in alleviating signs and symptoms of dry eye disease : A systematic review
    (2024-02) Ballesteros-Sánchez, Antonio; Borroni, Davide; De-Hita-Cantalejo, Concepción; Sánchez-González, María Carmen; Sanchez-Gomez, Serafin; Rocha-de-Lossada, Carlos; Sánchez-González, José María; Department of Doctoral Studies
    Purpose: To comprehensively review the efficacy and safety of OC-01 varenicline nasal spray versus vehicle nasal spray (VNS) in the treatment in dry eye disease (DED). Methods: A systematic review that included full-length randomized controlled studies (RCTs), as well as post hoc analyses of RCTs reporting new findings on OC-01 VNS treatment in three databases, PubMed, Scopus and Web of Science, was performed according to the PRISMA statement. The search period included studies published between December 2021 and September 2023. The Cochrane risk of bias tool was used to analyze the quality of the studies selected. Results: A total of 8 studies were included in this systematic review. OC-01 VNS treatment achieved higher improvement than vehicle in all reported variables. The mean differences between both groups were in favor of OC-01 VNS treatment and were as follow: eye dryness score base on a visual analogue scale (EDS-VAS) of −7.5 ± 2.2 points [-11.6 to −5.6], Schirmer test (ST) with anesthesia of 6.6 ± 2.3 mm [4.9 to 11.8] and total corneal fluorescein staining (tCFS) of −1.2 ± 0.01 points [-1.2 to −1.1]. Similar improvements were reported with OC-01 VNS 0.03 mg and 0.06 mg. Adverse events (AEs) were 15.5 ± 19.4 % [-13 to 80.5] higher in the OC-01 VNS group with an overall adherence > 93 %. Conclusions: OC-01 VNS improves dry eye symptoms and signs with a satisfactory tolerability. Therefore, OC-01 VNS seems to be a safe and effective treatment that could be recommended in patients with DED. This new treatment could be particularly useful in those patients who have difficulties with the administration of traditional topical therapies.
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    Epithelial downgrowth leading to graft rejection after penetrating keratoplasty
    (2023-07) Godin, Fernando; Mercado, Carolina; Larco, Pablo; Pacheco L, Maria A.; Borroni, Davide; Chacon Aponte, Alberto; Rīga Stradiņš University
    Purpose: To report a case of epithelial downgrowth after penetrating keratoplasty. Case description: A 58-year-old man presented with graft rejection in his three-month-old, repeat penetrating keratoplasty. Examination revealed centripetal opacification of the posterior cornea due to deep epithelization. He had new retro-corneal membranes and anterior uveitis. Specular microscopy and anterior segment optical coherence tomography were performed, and a clinical diagnosis of epithelial downgrowth was made. The patient had intracameral injections with 5-fluorouracil (5FU) and achieved resolution of intraocular findings after treatment. Conclusions: Epithelial downgrowth is an uncommon complication of penetrating keratoplasty. It affects the patients’ visual acuity and graft survival. Clinical observation is preferred in severe cases due to the high risk of intraocular damage; intracameral 5FU promises to be a good option in these cases.
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    Evaluating GlicoPro Tear Substitute Derived from Helix aspersa Snail Mucus in Alleviating Severe Dry Eye Disease : A First-in-Human Study on Corneal Esthesiometry Recovery and Ocular Pain Relief
    (2024-03) Ballesteros-Sánchez, Antonio; Sánchez-González, José María; Tedesco, Giovanni Roberto; Rocha-de-Lossada, Carlos; Murano, Gianluca; Spinelli, Antonio; Mazzotta, Cosimo; Borroni, Davide; Department of Ophthalmology
    Background: To evaluate the effects of 10% GlicoPro tear substitute therapy in patients with severe dry eye disease (DED). Methods: In this prospective longitudinal study, 30 individuals receiving 10% GlicoPro four times daily for DED were evaluated. The ocular surface disease index (OSDI) questionnaire, average non-invasive break-up time (A-NIBUT), non-anesthetic and anesthetic corneal esthesiometry (CE), ocular pain, and the presence of conjunctivochalasis (CCH) were used as clinical endpoints. Treatment compliance using dosing diaries and AEs was assessed. Results: A significant improvement was observed in the clinical endpoints: the ΔOSDI questionnaire was −39.27 ± 13.22 [−65 to −15] points, ΔA-NIBUT was 3.10 ± 1.31 [1 to 5] s, Δnon-anesthetic CE was 14 ± 6.35 [5 to 25] mm, and Δanesthetic CE was 13 ± 5.35 [5 to 20] mm (p < 0.001 for all comparisons). Ocular pain was reduced in 92.5% of the patients at the end of the follow-up. However, there was no change in the presence of CCH. In addition, all the patients were fully compliant with the dosing and no AEs related to the use of the 10% GlicoPro tear substitute were reported. Conclusions: The 10% GlicoPro tear substitute has the potential to achieve beneficial effects in ocular surface treatments.
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    Expression of Otx Genes in Müller Cells Using an In Vitro Experimental Model of Retinal Hypoxia
    (2021) Azzolini, Claudio; Donati, Simone; Micheloni, Giovanni; Moretti, Vittoria; Valli, Roberto; Acquati, Francesco; Costantino, Lucy; Ferrara, Fulvio; Borroni, Davide; Premi, Elias; Testa, Francesco; Simonelli, Francesca; Porta, Giovanni; Department of Doctoral Studies
    Introduction. Müller glial cells typically activate to react to hypoxic tissue damage in several retinal diseases. We evaluated the in vitro response to a hypoxia-mimicking stimulus on the expression of a set of genes, known to contribute to eye morphogenesis and cell differentiation. Materials and Methods. A MIO-M1 Müller cell line was cultured in a hypoxia-mimicking environment by the addition of cobalt chloride to the culture medium, followed by a recovery time in which we mimic restoration from the hypoxic insult. The HIF-1α protein and VEGF-A gene expression were quantified to verify the induction of a hypoxia-like state. Results. Among the genes under study, we did not observe any difference in the expression levels of Otx1 and Otx2 during treatment; conversely, Otx1 was overexpressed during recovery steps. The VEGF-A gene was strongly upregulated at both the CoCl2 and recovery time points. The transactivated isoform (TA) of the TP73 gene showed an overexpression in long-term exposure to the hypoxic stimulus with a further increase after recovery. Discussion. Our molecular analysis is able to describe the activation of a set of genes, never before described, that can drive the response to a hypoxia-like status. The improved comprehension of these cellular events will be useful for designing new therapeutical approaches for retinal pathologies.
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    Expression of VEGF-A, otx homeobox and p53 family genes in proliferative vitreoretinopathy
    (2013) Azzolini, Claudio; Pagani, Ilaria Stefania; Pirrone, Cristina; Borroni, Davide; Donati, Simone; Al Oum, Muna; Pigni, Diana; Chiaravalli, Anna Maria; Vinciguerra, Riccardo; Simonelli, Francesca; Porta, Giovanni
    Introduction. Proliferative vitreoretinopathy (PVR) is a severe inflammatory complication of retinal detachment. Pathological epiretinal membranes grow on the retina surface leading to contraction, and surgery fails in 5% to 10% of the cases. We evaluated the expression of VEGF-A, Otx1, Otx2, Otx3, and p53 family members from PVR specimens to correlate their role in inducing or preventing the pathology. Methods. Twelve retinal samples were taken from patients affected by PVR during therapeutic retinectomies in vitreoretinal surgery. Gene expression was evaluated using quantitative real-time reverse transcriptase PCR analysis and immunohistochemistry, using four healthy human retinae as control. Result. Controls showed basal expression of all genes. PVR samples showed little or no expression of Otx1 and variable expression of VEGF-A, Otx2, Otx3, p53, and p63 genes. Significant correlation was found among VEGF-A, Otx2, p53, and p63 and between Otx1 and Otx3. Conclusions. Otx homeobox, p53 family, and VEGF-A genes are expressed in PVR human retina. We individuated two possible pathways (VEGF-A, Otx2, p53, p63 and Otx1 and Otx3) involved in PVR progression that could influence in different manners the course of the pathology. Individuating the genetic pathways of PVR represents a novel approach to PVR therapies.
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    Infectious Keratitis : Characterization of Microbial Diversity through Species Richness and Shannon Diversity Index
    (2024-04) Schiano-Lomoriello, Domenico; Abicca, Irene; Contento, Laura; Gabrielli, Federico; Alfonsi, Cinzia; Di Pietro, Fabio; Papa, Filomena Tiziana; Ballesteros-Sánchez, Antonio; Sánchez-González, José María; Rocha-De-Lossada, Carlos; Mazzotta, Cosimo; Giannaccare, Giuseppe; Bonzano, Chiara; Borroni, Davide; Department of Ophthalmology
    Purpose: To characterize microbial keratitis diversity utilizing species richness and Shannon Diversity Index. Methods: Corneal impression membrane was used to collect samples. All swabs were processed and analyzed by Biolab Laboratory (level V—SSN Excellence: ISO 9001:2015), Biolab Srl (Ascoli Piceno, Italy). DNA extraction, library preparation, and sequencing were performed in all samples. After sequencing, low-quality and polyclonal sequences were filtered out by the Ion software. At this point, we employed Kraken2 for microbial community analysis in keratitis samples. Nuclease-free water and all the reagents included in the experiment were used as a negative control. The primary outcome was the reduction in bacterial DNA (microbial load) at T1, expressed as a percentage of the baseline value (T0). Richness and Shannon alpha diversity metrics, along with Bray–Curtis beta diversity values, were calculated using the phyloseq package in R. Principal coordinate analysis was also conducted to interpret these metrics. Results: 19 samples were included in the study. The results exhibited a motley species richness, with the highest recorded value surpassing 800 species. Most of the samples displayed richness values ranging broadly from under 200 to around 600, indicating considerable variability in species count among the keratitis samples. Conclusions: A significant presence of both typical and atypical bacterial phyla in keratitis infections, underlining the complexity of the disease’s microbial etiology.
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