bluuebunny/crossref_metadata_2025_split huggingface dataset:
Orbital abscess surgery in a patient with odontogenic pansinusitis
Authors: Carsi Marta Comes , Tepper Sergio Maugard , García Maria Amparo Lanuza , Duch Samper Antonio M. 
Published: December 2022

AbstractPurpose: In orbital abscesses with sinus origin, the most frequent treatment is a endoscopic sinus surgery (ENSS), if there is a subperiosteal abscess that may compromise the vision, an external drainage should be performed, depending on the location of the abscess. We present an orbital abscess of odontogenic cause that required an orbital approach.Methods: We present an orbital abscess in a 44‐year‐old man with no relevant medical or ophthalmological history, who, after complicated dental extraction, suffered a left orbital cellulitis.Surgical technique: Ethmoidectomy was performed by endoscopic sinus surgery (ENSS), without resolution of the infection, requiring drainage of the abscess through an external orbital superomedial approach.Results: This abscess was located between the middle and superior rectus muscles. A superomedial incision was made, dissecting up to the periosteum and incising the periorbita, observing the exit of purulent material. A drainage was left in place. At the same time, ENSS was performed with exeresis of the lamina papyracea. The patient evolved torpidly, with productive drainage. Computed tomography (CT) shows two collections adjacent to the drainage and the thickening of the lateral rectus muscle. Reoperation was performed, draining the abscesses visualized and washing the area with hydrogen peroxide and metronidazole. New drainage was placed. The evolution was favourable.Conclusions: In orbital abscesses, antibiotic therapy is usually not sufficient, and surgical intervention is indicated. There are various types of procedures and surgical approaches for the drainage of orbital abscesses, the most common is ENSS, but in complex abscesses an external approach may be necessary. Imaging tests facilitate the location of the abscess, serving as a guide for surgery.
Repurposing dimethyl fumarate? In vitro evidence of Nrf2‐pathway activation and cytoprotective effects in human retinal endothelial cells
Authors: Amadio Marialaura , Manai Federico 
Published: December 2022

AbstractReferences: Nrf2 (NF‐E2‐related factor 2) pathway is a major defensive system orchestrating cellular response to pro‐oxidant and pro‐inflammatory stress and regulating the expression of many cytoprotective genes. Pharmacologic activation of Nrf2 has emerged as an attractive strategy for many pathologic conditions. The best‐known Nrf2 activator is dimethyl fumarate (DMF), currently used for the treatment of relapsing–remitting multiple sclerosis and psoriasis. However, literature evidence in animal models of eye diseases reports that DMF displays beneficial effects also at ocular level, suggesting its potential therapeutic use also in retinal pathologies.Purpose: The aim of this study was to evaluate in vitro whether DMF activates Nrf2‐pathway and exerts beneficial effects in human retinal endothelial cells, and to test its possible cytoprotection against a diabetic retinopathy‐related insult.Methods: Human Retinal Endothelial Cells (HREC) were exposed to increasing concentrations of DMF and tested for viability and Nrf2‐pathway activation. Expression of Nrf2 and its target HO‐1 (Heme Oxygenase‐1) coding an antioxidant and detoxifying enzyme relevant for vascular endothelium, were evaluated by Western blotting and real‐time quantitative PCR. Intracellular levels of reactive oxygen species (ROS) were investigated after DMF treatment through flow cytometry. DMF‐mediated pro‐survival effects were also tested in HREC under hyper‐glucose conditions.Results: In basal conditions, DMF is optimally tolerated and activates Nrf2/HO‐1 pathway, decreasing intracellular ROS levels in HREC. DMF protects HREC under high glucose conditions.Conclusions: Together with the most recent evidence of DMF effects at ocular level, our findings open a new perspective for the repositioning of DMF in eye pathologies involving alterations of the endothelium and, more extensively, for ocular diseases characterized by oxidative stress and inflammation.
A CYP1B1 associated irido‐trabeculodysgenesis
Authors: Gupta Shikha , Panigrahi Arnav , Mahalingam Karthikeyan , Singh Abhishek , Gupta Viney 
Published: December 2022

AbstractPurpose: CYP1B1 mutations are commonly associated with primary congenital glaucoma (PCG). PCG is due to an isolated trabeculodysgenesis and classically does not involve iris dysgenesis. We describe a cohort of atypical PCG phenotype showing iris atrophy.Methods: In this study, exome sequencing was carried out in five patients with neonatal onset congenital glaucoma who also had features of iris atrophy that were detected once the children were old enough for slit lamp examination.Results: The five patients identified had presented with bilateral neonatal onset glaucoma with iris abnormalities like iris atrophy, corectopia and polycoria detected when they were older. All patients had undergone bilateral trabecutectomy with ab externo trabeculotomy during early childhood. The mean age of these children at the time of this study was 14.4 years (range: 8–25 years). The iris atrophy was characteristically peripheral and circumferential. However, none of these patients had evidence of a posterior embryotoxon or peripheral anterior synechiae in the angle (PAS), typical of Axenfeld Rieger Syndrome (ARS). Whole exome sequencing identified biallelic CYP1B1 mutations in all of these five patients as pathogenic variants.Conclusion: This variant of neonatal onset PCG associated with biallelic CYP1B1 mutations may have associated iridodysgenesis and may resemble the ARS phenotype.
Biological processes and clinical variables affecting trabeculectomy surgery outcome
Authors: Nättinen Janika , Aapola Ulla , Nukareddy Praveena , Gielen Fabian , Vaajanen Anu , Uusitalo Hannu 
Published: December 2022

AbstractPurpose: To establish what preoperative clinical factors and tear protein levels influence the trabeculectomy outcome.Methods: In this prospective study, we followed 80 glaucomatous eyes for 5 years after trabeculectomy. Preoperatively, tear fluid samples and clinical data were collected from all patients. Postoperative statuses, i.e., qualified success (QS) in case of 5‐fluorouracil (5FU), needling or restart of glaucoma medication and failure (F) in case of reoperation, were recorded. The patients' postoperative statuses were then compared against the preoperative tear proteomics and clinical variables with Wilcoxon rank sum test. Proteomic pathway analyses were performed using Ingenuity Pathway Analysis (IPA) software.Results: Within 1 year of the surgery, 15 (19%) QS + F patients were detected. Patients with early failure were younger than those with a successful early outcome (64.7 ± 9.5 vs 70.1 ± 7.6 years, respectively, p = 0.04) and according to pathway analysis results, had increased activation of immune responses prior to surgery (all p‐values <0.05). Overall, 24 (31%) QS + F cases occurred during the 5‐year follow‐up. Pathway analysis revealed that these patients had increased levels of apoptosis prior to surgery (activation z‐score = 2.2, p‐value = 0.02).Conclusions: These results further emphasize the importance of observing the preoperative state of the ocular surface. The tear proteomic profiles reveal biological functions that are associated with the trabeculectomy outcome.
Development of a biocompatible allogenic extra cellular matrix (MEC) for gradual dispensation of active substances
Authors: Barnouin Laurence , Grossetete Florine 
Published: December 2022

AbstractPurpose: TBF aims to design an allogeneic extra cellular matrix that can be loaded with a large range of active substances: antibiotic, anti‐inflammatory or biological components and able to provide a gradual dispensation of these substances.Methods: TBF developed an amniotic membrane of umbilical cord (AM‐UC). The product is a moulded foam or fibres to be reconstituted in dry eyes or gel. The product is virally inactivated, freeze‐dried and sterilized. Products are safe and biocompatible. The testing product consists in a moulded small strip that can be inserted behind the lower eyelid. These products contain hyaluronic acid, growth factors and proteoglycans. They have been impregnated after gamma irradiation with a known quantity of gentamycin, dexamethasone or extracellular micro‐vesicles extracted from mesenchymal stem cells cultures. Impregnated products have been placed in an extraction medium, which has been removed and replaced at defined times. Actives substances have then been quantified in the different extracts according to appropriate methods. Gentamycin has been quantified according to the Method A from the Eur. Ph., dexamethasone by an ELISA detection kit then supported by HPLC‐MS/MS method (after a bioreactor study) and exosomes using an ELISA detection kit based on CD63 protein binding.Results: For gentamycin and dexamethasone, quantifications have shown that the products enable a progressive release during the first 6 h of extraction of 40%–60% of the active substance with still extraction after 24 h. Then a threshold is reached, and the release is stabilized over the remaining time of extraction until reaching 55%–70% of extraction. Exosomes are constantly released in extraction medium; all observation points are similar.Conclusions: The results obtained tend to show that the product developed can be impregnated with different type of active substances and allow a gradual dispensation. It could be used in ophthalmological pathologies in order to increase contact duration between the eye and the active substance.
Analysis of glaucoma genes in Finnish patients with juvenile open‐angle glaucoma
Authors: Liuska Perttu , Tadji Abdesallam , Repo Pauliina , Hiltunen Juho , Backlund Michael , Järvinen Reetta‐Stiina , Ojanen Eeva , Majander Anna , Kivelä Tero , Harju Mika , Turunen Joni 
Published: December 2022

AbstractPurpose: Juvenile open‐angle glaucoma (JOAG) is a rare type of glaucoma diagnosed between the age of 4 and 40 years. Predisposition to JOAG is often inherited as a Mendelian autosomal dominant pattern. Pathogenic myocilin (MYOC) variants are reported in 8%–36% of patients but rarer variants in other genes could also predispose to JOAG. We investigated germline variants in known glaucoma genes in Finnish patients with JOAG.Methods: Finnish patients with JOAG treated between 2010 and 2018 at the Department of Ophthalmology, Helsinki University Hospital, Finland, were enrolled in the study. We sequenced all exonic regions and flanking splice sites of MYOC for six patients and one healthy relative using Sanger sequencing. In 55 patients, we performed exome sequencing to investigate variants also in 26 other glaucoma genes.Results: A total of 61 patients with JOAG from 58 pedigrees, and one healthy relative, were included. The mean [SD; range] age at diagnosis was 31.9 [7.5; 11–39]. Eight subjects (13.8%) had a normal‐tension disease, while 50 individuals (86.2%) had a disease with elevated intraocular pressure. Five probands had probable pathogenic variants in MYOC: c.1102C > T p.(Gln368Ter), c.1109C > T p.(Pro370Leu), c.1130C > T p.(Thr377Met), c.1132G > A p.(Asp378Asn), and c.1456C > T p.(Leu486Phe). Four of these patients had a family history of dominantly inherited JOAG. One patient and his mother with JOAG had a novel loss‐of‐function variant in the FOXC1 gene, c.366G > A p.(Trp122Ter). A patient with sporadic JOAG had a homozygous likely pathogenic variant in the LTBP2 gene, c.3938G > A p.(Cys1313Tyr). The frequency of MYOC variants was 8.6% (5/58). The genetic variants explained 12.1% (7 out of 58; 95% CI, 6.0%–22.8%) of JOAG in our cohort.Conclusions: The prevalence of pathogenic variants in known glaucoma genes is low in Finnish patients with JOAG. Due to the specific population history of Finland, it might be possible to identify novel glaucoma genes in the future.
Nerve regeneration and corneal wound healing by ophthalmic formulations based on sodium hyaluronate, taurine, vitamin B6 and vitamin B12
Authors: Bucolo Claudio , Maugeri Grazia , Giunta Salvatore , Romano Giovanni Luca 
Published: December 2022

AbstractPurpose: To evaluate the pharmacological profile of ocular formulations based on cross‐linked sodium hyaluronate (CL‐SH), taurine (Tau), Vit B6 and Vit B12 using in vitro and in vivo paradigms.Methods: Rabbit corneal epithelial cells (SIRC) were used to assess wound healing and ROS formation by scratch assay and oxidative stress (0.3 mM H2O2; 30 min), respectively w/ or w/o ocular formulations exposure. In vivo studies were carried out on albino rabbits to evaluate corneal nerve regeneration and corneal wound healing with or without treatment with six different formulations. Animals were anaesthetised, the corneal epithelium was removed, and formulations were topically administered (30 μl/eye; 3 times/day for 6 days). Slit‐lamp observation was carried out at the following day: T0, T2 and T5. After 6 days the animals were killed, and corneas were collected to evaluate corneal re‐innervation by immunohistochemistry of selective neuronal marker β‐III tubulin.Results: Formulations containing the concentrations 0.16% or 0.32% of CL‐SH, Tau, Vit B6 and B12 accelerated corneal wound healing. Cells exposed to H2O2 led to significant (p < 0.001) increase of ROS concentration that was significantly (p < 0.001) counteract by formulations containing CL‐SH (0.32%) and Tau w/ or w/o Vit B6 and B12. The extent of re‐innervation, in terms of β‐III tubulin staining, was 5‐fold greater (p < 0.01) in the eye of rabbits treated with formulation containing 0.32% CL‐SH, Tau, Vit B6 and Vit B12 (RenerviX®) compared with the control group (no treatment). Furthermore, re‐innervation with RenerviX® group was significantly greater (p < 0.01) also compared with the groups treated with the formulation containing 0.32% CL‐SH and Tau w/o vitamins and with the formulation containing 0.5% linear SH, Tau, and Vit B12.Conclusions: Among all formulations tested, the new ophthalmic gel RenerviX® was able to contrast oxidative stress, to accelerate corneal re‐epithelization and to promote nerve regeneration.
Ambra1 haploinsufficiency results in metabolic alterations and exacerbates age‐associated retinal degeneration
Authors: Villarejo‐Zori Beatriz , Ramírez‐Pardo Ignacio , Jiménez‐Loygorri Juan Ignacio , Sierra‐Filardi Elena , Alonso‐Gil Sandra , Gómez‐Sintes Raquel , Boya Patricia 
Published: December 2022

AbstractPurpose: Retina is a highly complex and metabolically active tissue that sense the light. Persistent light‐induced stimuli lead to constant turnover of the damaged cellular structures by proteostatic mechanisms such as autophagy. During aging there is a gradual decrease of autophagy which compromises retinal homeostasis and visual function. AMBRA1 (autophagy and beclin‐1 regulator 1) is a key protein involved in the initiation phase of autophagy pathway. To further determine the importance of autophagy along aging, we will use Ambra1+/gt heterozygous mice, mimicking the decrease of autophagy during the aging process.Methods: We have used young (3 months), middle‐aged (12 months) and old (25 months) Ambra1+/+ and Ambra1+/gt mice for this study. Visual function was determined by electroretinographic recordings (ERGs) along aging. Eyes were enucleated for histological porpoises or retinas were isolated for biochemical procedures. Retinal morphology and cellular components were assessed by immunofluorescence techniques on retinal cryosections or flatmounts. mRNA and protein lysates were obtained from isolated retinas. Metabolomic analyses were conducted using mass spectrometry and bioinformatic analysis was performed.Results: Ambra1+/gt retinas display a reduced autophagic flux at young without changes in the retinal integrity and function. However, aged Ambra1+/gt animals show an exacerbated loss of visual function also evidenced by morphological changes as increased gliosis, reduced nuclear density and cone number. Interestingly, we observed increased bipolar cell protrusions that might indicate the loss of synapsis between retinal layers. Partial loss of autophagy results in increased damaged mitochondria evidenced by a reduction in the mitochondrial membrane potential (MMP) in young age, higher oxidative stress at middle‐aged and accumulation of mitochondrial mass in old Ambra1+/gt retinas. Finally, by metabolomics, we demonstrate marked metabolic alterations suggestive of defective oxidative metabolism in Ambra1+/gt animals at 1 year of age.Conclusions: Reduced autophagic response in Ambra1 haploinsufficient retinas leads to an exacerbated age‐associated declines in retinal function, metabolic alterations and accumulation of damaged mitochondria.
Preliminary results obtained by a new intraocular lens based on accommodative technology for the treatment of cataract and presbyopia
Authors: Martínez‐Abad Antonio , Alio Jorge , Yebana Pilar , Puche Ana Belen Plaza 
Published: December 2022

AbstractPurpose: The aim of this study was to report the clinical results obtained by a new accommodative intraocular lens (AIOL) in terms of visual acuity, refraction, defocus curve, contrast sensitivity and complications incidence for multiple follow‐up phases.Methods: This is a prospective and experimental study composed by patients interested in an AIOL implantation (Lumina, Akkolens) to improve their visual performance. An exhaustive postoperative follow‐up (1 week, 1 month, 3 months, 6 months, 1 year) was performed including the measurements of visual acuity for multiple distances in decimal notation, subjective refraction, accommodative evaluation by defocus curve, contrast sensitivity and a slit lamp and fundus exploration.Results: The study included 42 eyes of 21 patients (mean age of 61.4 ± 10.9 years; 52% females, 48% males). The mean uncorrected distance visual acuity at week was 0.71 ± 0.28, but it improved to 0.85 ± 0.27 a year after the surgery. Similarly, the mean uncorrected near visual acuity improved for 0.48 ± 0.23 at 1 week to 0.60 ± 0.17 at 1 year. The mean equivalent sphere was −0.39 ± 0.60 diopters and the mean corrected distance visual acuity was 1.04 ± 0.16 at 1 year. For a defocus range comprised between 0.00 and −2.00 diopters the mean visual acuity was better than 0.50. The contrast sensitivity assessment showed values higher than 1.10 log units for all frequencies. Capsule opacification with YAG laser requirement was present in 21% of cases (N = 9). At the end of the follow‐up all minimal complications were resolved.Conclusions: The AIOL Lumina Akkolens provided suitable distance vision and functional near vision improving its performance over time. Contrast sensitivity was good being comparable with a monofocal design, but the Lumina IOL shows better near visual performance as revealed in the defocus curve. Significant persistent complications were not observed. These results will be updated with more patients and will be compared with a control group.
Exacerbated mitochondrial fusion abrogates mitophagy and leads to pro‐inflammatory signalling in Müller glia during diabetic retinopathy
Authors: Anderson Aidan , Alfahad Nada , Ganley Ian G. , Rauz Saaeha , Wallace Graham , Curtis Tim M. , Romero Jose M. 
Published: December 2022

AbstractPurpose: To determine how the dysregulated interplay between mitochondrial dynamics and mitophagy contribute to the progression of diabetic retinopathy [DR].Methods: 3‐months and 9‐month‐old diabetic mitophagy reporter (MitoQC‐Ins2Akita) mice and their non‐diabetic siblings, were used to evaluate the interplay between mitochondrial dynamics and mitophagy by confocal morphometry. To model the dysregulation of mitochondrial quality control processes in vitro, mitochondrial fission was antagonized in retinal Müller cells (mouse primary and MIO‐M1 cell‐line) using a Drp1 inhibitor peptide (P110), under physiological (5.5 mM) and elevated glucose (30.5 mM) conditions. Mitochondrial fitness was assessed via metabolic flux (Seahorse) along with mitochondrial membrane potential (JC‐1), while the Müller glia inflammatory secretome was determined using Luminex.Results: In contrast to younger ages, 9‐month‐old diabetic mice displayed exacerbated mitochondrial fusion at the outer retina (e.g., increased interconnectivity and mitochondrial aspect ratios), which was strongly associated with impaired mitophagy levels (r2 = 0.7, p < 0.001). P110 peptide inhibited mitochondrial fission/exacerbated fusion in retinal Müller cells, and abrogated mitophagy similarly to that found at advanced DR stages. Importantly, exacerbated mitochondrial fusion under hyperglycaemia (but not normoglycaemia) disrupted mitochondrial membrane potential (p < 0.05) in Müller cell cultures, further compromising mitochondrial fitness, as shown by decreased spare respiratory capacity and bioenergetic health index (p < 0.001 both). This was accompanied by significantly elevated secretion of key DR pro‐inflammatory factors, particularly CCL2 and VEGF‐A (p < 0.05 both).Conclusions: Exacerbated mitochondrial fusion contributes to DR pathology by inhibiting mitophagy in Müller glia. Therapies aimed at facilitating mitochondrial fission/mitophagy in a controlled fashion may hold therapeutic potential for managing DR.
Orbital sarcoidosis. Case report
Authors: Martínez Julia Pérez , Prades Gemma Ortega , García Amparo Lanuza , Ibor Francisca García , Samper Antonio Miguel Duch 
Published: December 2022

AbstractPurpose: Sarcoidosis is an autoimmune granulomatous disease that can affect any organ system in the body. Orbital manifestations are relatively uncommon. We present the clinical features and management in a case report with orbital sarcoidosis.Methods: This case report study a 51 year‐old female patient being investigated for headache, blurred vision and diplopia of 7 days onset. She had proptosis of the left eye, diplopia and complete ophthalmoparesis on supraversion and abduction and partial on adduction. The magnetic resonance showed probable orbital inflammation (inflammatory pseudotumor)/Tolosa Hunt syndrome with predominant involvement of the left superior rectus muscle, cavernous sinus, and pachymeninges. Chest X‐ray showed no pathological findings and laboratory tests, thyroid profile, serology, IgG subclasses, angiotensin converting enzyme and autoantibodies were negative. The computed tomography (CT) showed pulmonary lesions compatible with stage III sarcoidosis. After the results of the imaging tests, it was decided to start treatment with a bolus of methylprednisolone for 5 days and then oral prednisone was started with clear clinical and radiological improvement. The mediastinal lymph node biopsy could not be performed due to the decrease in its size.Results: The patient was treated with decreasing doses of corticosteroids until the disappearance of the orbital and pulmonary radiological symptoms. It has been followed for 2 years without recurrence.Conclusions: The presentation of sarcoidosis simulating a pseudotumor is uncommon. Despite this, we must take it into account in the differential diagnosis. In our case, the presentation of CT showing a pulmonary lesion compatible with sarcoidosis and the improvement with corticoid treatment made us reinforce the suspicion of a diagnosis of sarcoidosis. In any case, the definitive diagnosis of this pathology is biopsy and pathological analysis.