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Article ; Online: Sources of Variance in Human Tear Proteomic Samples: Statistical Evaluation, Quality Control, Normalization, and Biological Insight.

Bruszel, Bella / Tóth-Molnár, Edit / Janáky, Tamás / Szabó, Zoltán

International journal of molecular sciences

2024 Volume 25, Issue 3

Abstract: Human tear fluid contains numerous compounds, which are present in highly variable amounts owing to the dynamic and multipurpose functions of tears. A better understanding of the level and sources of variance is essential for determining the functions of ...

Abstract	Human tear fluid contains numerous compounds, which are present in highly variable amounts owing to the dynamic and multipurpose functions of tears. A better understanding of the level and sources of variance is essential for determining the functions of the different tear components and the limitations of tear samples as a potential biomarker source. In this study, a quantitative proteomic method was used to analyze variations in the tear protein profiles of healthy volunteers. High day-to-day and inter-eye personal variances were observed in the tear volumes, protein content, and composition of the tear samples. Several normalization and outlier exclusion approaches were evaluated to decrease variances. Despite the intrapersonal variances, statistically significant differences and cluster analysis revealed that proteome profile and immunoglobulin composition of tear fluid present personal characteristics. Using correlation analysis, we could identify several correlating protein clusters, mainly related to the source of the proteins. Our study is the first attempt to achieve more insight into the biochemical background of human tears by statistical evaluation of the experimentally observed dynamic behavior of the tear proteome. As a pilot study for determination of personal protein profiles of the tear fluids of individual patients, it contributes to the application of this noninvasively collectible body fluid in personal medicine.
MeSH term(s)	Humans ; Proteome/metabolism ; Proteomics/methods ; Pilot Projects ; Tears/metabolism ; Eye Proteins/metabolism ; Quality Control
Chemical Substances	Proteome ; Eye Proteins
Language	English
Publishing date	2024-01-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25031559
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Article: Optical Coherence Tomography: Focus on the Pathology of Macula in Scleritis Patients.

Smeller, Lilla / Toth-Molnar, Edit / Sohar, Nicolette

Journal of clinical medicine

2023 Volume 12, Issue 14

Abstract: Optical coherence tomography (OCT) is a non-invasive imaging technique for high-resolution, cross-sectional tissue imaging of the eye. During the past two and a half decades, OCT has become an essential tool in ophthalmology. It is a painless method for ... ...

Abstract	Optical coherence tomography (OCT) is a non-invasive imaging technique for high-resolution, cross-sectional tissue imaging of the eye. During the past two and a half decades, OCT has become an essential tool in ophthalmology. It is a painless method for examining details of ocular structures in vivo with high resolution that has revolutionized patient care following and treating scleritis patients. Methods: Twenty-four patients diagnosed with scleritis were selected for this study. All of the patients went through basic ophthalmological examinations, such as visual acuity testing (VA), intraocular pressure measurement (IOP), slit lamp examination, ophthalmoscopic examination, and OCT. OCT examinations were taken by SD-OCT Spectralis OCT system (Heidelberg Engineering, Heidelberg, Germany). Results: Twenty-seven eyes of 24 patients (7 males and 17 females) were included in this study, who were diagnosed with scleritis. OCT examinations showed epiretinal membrane (ERM) in three patients (12%), cystoid macular edema (CME) (three cases, 12%), diffuse macular edema (DME) (one case, 4%), and serous retinal detachment (SRD) (one case, 4%). Conclusions: OCT proved to be a valuable, non-invasive method for detecting macular pathology in patients with scleritis. Despite the best treatment regimen applied, macular involvement resulting in reduced visual acuity (VA) can develop, which we could detect with OCT since macular edema (ME) is the leading cause of decreased vision due to the damaged outer blood-retina barrier (BRB) in inflammation. OCT investigation is a highly important method for early detection of ocular complications in scleritis in order to prevent blindness.
Language	English
Publishing date	2023-07-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm12144825
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Article: White Dot Syndrome Report in a SARS-CoV-2 Patient.

Smeller, Lilla / Toth-Molnar, Edit / Sohar, Nicolette

Case reports in ophthalmology

2022 Volume 13, Issue 3, Page(s) 744–750

Abstract: Our purpose was to report clinical features in bilateral white dot syndrome in a 47-year-old female patient who was tested positive for the SARS-CoV-2. A 47-year-old female visited our department with complaints of bilateral photophobia and blurred ... ...

Abstract	Our purpose was to report clinical features in bilateral white dot syndrome in a 47-year-old female patient who was tested positive for the SARS-CoV-2. A 47-year-old female visited our department with complaints of bilateral photophobia and blurred vision in both her eyes. She visited our department during the pandemic period after her PCR-proven SARS-CoV-2 positivity. Her symptoms were chills and fever with a temperature of 40.0°C, associated with fatigue, sweat, and complete loss of taste. Besides basic ophthalmological examinations, ocular diagnostic testing were made to differentiate between specific white dot syndromes with suggestive features of fluorescein angiography, optical coherence tomography, and fundus autofluorescence. Laboratory tests were ordered, including immunserological and haematological ones. Eye examination revealed mild bilateral vitritis and white dots in the fundus of both eyes, including the macula explaining the blurred vision. Herpes simplex virus reactivation was proved, after the SARS-CoV-2 infection. Local corticosteroids were given according to the European Reference Network's recommendations for patients with uveitis during the COVID-19 pandemic. Our report demonstrates that white dot syndrome with blurred vision could be associated with SARS-CoV-2 infection, being potentially sight-threatening because of macular involvement. Ophthalmological examinations found posterior uveitis white dot syndrome, and this should call attention to the risk of acute 2019-CoV infection or occurred 2019-CoV infection. Immunodeficiency favours the occurrence of other viral infections, such as herpes virus infections. Everybody should be aware of the risk of 2019-CoV infection, especially professionals, social workers, and those who work or live with elder people and people with immunodeficiency.
Language	English
Publishing date	2022-09-30
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2577666-6
ISSN	1663-2699
ISSN	1663-2699
DOI	10.1159/000526090
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Article ; Online: New insight into lacrimal gland function: Role of the duct epithelium in tear secretion.

Tóth-Molnár, Edit / Ding, Chuanqing

The ocular surface

2020 Volume 18, Issue 4, Page(s) 595–603

Abstract: Tear secretion is a complex process with the involvement of the main and accessory lacrimal glands, corneal and conjunctival epithelial cells and the Meibomian glands. The lacrimal gland is the main source of fluid, electrolytes and proteins in tear ... ...

Abstract	Tear secretion is a complex process with the involvement of the main and accessory lacrimal glands, corneal and conjunctival epithelial cells and the Meibomian glands. The lacrimal gland is the main source of fluid, electrolytes and proteins in tear fluid. Deficient ion and water secretion results in aqueous deficient dry eye with serious consequences on the integrity of the ocular surface. Functions of acinar cells are widely studied, whereas less information is available about the duct system of the lacrimal gland. Secretory mechanisms of duct epithelium may play an important role in tear production, but only limited studies have tried to elucidate the role of the duct system in tear secretion. Significant progress has been made in the past few years, resulting in new insight into lacrimal gland duct function. New experimental techniques were introduced, which contributed to the exploration of the role of lacrimal gland ducts in more detail. Therefore, the aim of this review is to summarize our present knowledge about the role of ducts in lacrimal gland function and tear secretion, which appears to be the first review with a focus on this topic. Short outline of pancreatic and salivary gland duct functions is also given for the purposes of comparison.
MeSH term(s)	Cornea ; Dry Eye Syndromes ; Epithelium ; Humans ; Lacrimal Apparatus ; Tears
Language	English
Publishing date	2020-07-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2208578-6
ISSN	1937-5913 ; 1542-0124
ISSN (online)	1937-5913
ISSN	1542-0124
DOI	10.1016/j.jtos.2020.07.002
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Article ; Online: A biológiai terápia helye a gyermekkori uveitis ellátásában.

Smeller, Lilla / Sümegi, Viktória / Tóth-Molnár, Edit / Sohár, Nicolette

Orvosi hetilap

2022 Volume 163, Issue 35, Page(s) 1402–1408

Abstract: Introduction: Biological therapy can be used in uveitis in children since 2016. With ophthalmological indication only adalimumab therapy can be started. Adalimumab is a monoclonal antibody that inhibits tumor necrosis factor alpha.: Objective: To ... ...

Abstract	Introduction: Biological therapy can be used in uveitis in children since 2016. With ophthalmological indication only adalimumab therapy can be started. Adalimumab is a monoclonal antibody that inhibits tumor necrosis factor alpha. Objective: To summarize our experience with patients receiving adalimumab for pediatric non-infectious uveitis. Patients and methods: We investigated our juvenile patients of non-infectious uveitis treated with adalimumab between 2017 and 2021 in a retrospective case series at the Department of Ophthalmology, Szeged University. Results: Between 01 January, 2017 and 31 May, 2021, we examined 46 children with uveitis. The mean age of these 23 girls and 23 boys was 11 years. 21 of them had juvenile idiopathic arthritis, 14 had infectious uveitis, 3 had haematological disorders, 8 had idiopathic uveitis. Adalimumab was given to 11 patients because of severe, chronic uveitis. There were 3 boys and 8 girls, their mean age was 10 years. Adalimumab was given according to the licence of the European Medicines Agency. Indication was anterior uveitis at 6 children, panuveitis at 5 children. Adalimumab can be given to children over 2 years, who have chronic, non-infectious, anterior uveitis. Children with panuveitis received the therapy by the help of a pediatric rheumatologist. Conclusion: The significance of pediatric uveitis and its therapy is emergent. Our aim was to preserve vision and decrease the possibilities of side effects and to provide a better life for these uveitic children. Early diagnosis, adequate therapy and regular ophthalmological check-ups are important. Children treated with adalimumab have good visual acuity due to the effectiveness of the therapy. No new ocular side effect was detected at the children treated with adalimumab. Orv Hetil. 2022; 163(35): 1402-1408.
MeSH term(s)	Adalimumab ; Child ; Female ; Humans ; Male ; Panuveitis ; Retrospective Studies ; Treatment Outcome ; Uveitis ; Uveitis, Anterior
Chemical Substances	Adalimumab (FYS6T7F842)
Language	English
Publishing date	2022-08-28
Publishing country	Hungary
Document type	Journal Article
ZDB-ID	123879-6
ISSN	1788-6120 ; 0030-6002
ISSN (online)	1788-6120
ISSN	0030-6002
DOI	10.1556/650.2022.32578
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Article ; Online: An Extensive Study of Phenol Red Thread as a Novel Non-Invasive Tear Sampling Technique for Proteomics Studies: Comparison with Two Commonly Used Methods.

Kecskeméti, Gábor / Tóth-Molnár, Edit / Janáky, Tamás / Szabó, Zoltán

International journal of molecular sciences

2022 Volume 23, Issue 15

Abstract: Tear samples are considered in recent publications as easily, noninvasively collectible information sources for precision medicine. Their complex composition may aid the identification of biomarkers and the monitoring of the effectiveness of treatments ... ...

Abstract	Tear samples are considered in recent publications as easily, noninvasively collectible information sources for precision medicine. Their complex composition may aid the identification of biomarkers and the monitoring of the effectiveness of treatments for the eye and systemic diseases. Sample collection and processing are key steps in any analytical method, especially if subtle personal differences need to be detected. In this work, we evaluate the usability of a novel sample collection technique for human tear samples using phenol red threads (cotton thread treated with the pH indicator phenol red), which are efficiently used to measure tear volume in clinical diagnosis. The low invasiveness and low discomfort to the patients have already been demonstrated, but their applicability for proteomic sample collection has not yet been compared to other methods. We have shown, using various statistical approaches, the qualitative and quantitative differences in proteomic samples collected with this novel and two traditional methods using either glass capillaries or Schirmer's paper strips. In all parameters studied, the phenol red threads proved to be equally or even more suitable than traditional methods. Based on detectability using different sampling methods, we have classified proteins in tear samples.
MeSH term(s)	Humans ; Phenolsulfonphthalein/analysis ; Phenolsulfonphthalein/chemistry ; Phenolsulfonphthalein/metabolism ; Proteins/metabolism ; Proteomics/methods ; Specimen Handling/methods ; Tears/metabolism
Chemical Substances	Proteins ; Phenolsulfonphthalein (I6G9Y0J1OJ)
Language	English
Publishing date	2022-08-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23158647
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Article: Minimal invasive transnasal endoscopic removal of intracranial foreign body after airbag deployment.

Kovacs, Nimrod / Zsolt, Vagi / Toth-Molnar, Edit / Foldi, Janos / Bella, Zsolt / Barzo, Pal

Ideggyogyaszati szemle

2023 Volume 76, Issue 11-12, Page(s) 427–432

Abstract: ... Airbag induced injuries such as skull and cervical spine fractures, epidural and subdural hematomas, atlantooccipital dislocations or brainstem lacerations are already documented in published literature, however, no previous case have been published ... ...

Title translation	Kinyíló légzsák okozta intracranialisan penetráló idegentest minimálinvazív transnasalis endoszkópos eltávolítása.
Abstract	Airbag induced injuries such as skull and cervical spine fractures, epidural and subdural hematomas, atlantooccipital dislocations or brainstem lacerations are already documented in published literature, however, no previous case have been published about a penetrating foreign body of the skull base following airbag deployment. Removal of an intracranial foreign body is very dangerous and difficult, or even if it possible and necessary, requires open surgery in most of the cases. In this article we present the minimal invasive, transnasal removal of a coin from the intracranial, frontobasal region using high-resolution endoscopy combined with image-guided navigation. We report the case of a 59-year-old male who was brought to the emergency department after a car accident. He suffered a penetrating injury by a coin that was placed on the car’s airbag at the moment of the accident. Upon the airbag being deployed the foreign body entered the skin through the right lower eyelid, crossing the orbital cavity, ethmoid cells, sphenoid sinus and the anterior part of the planum sphenoidale at an equal distance of 2mm from the two internal carotid arteries, extending into the intracranial space, without injuring the pituitary stalk and the chiasm. We proceeded to remove the coin endoscopically using a transnasal transseptal transsphenoidal approach under general anesthesia. The dura was closed with a multilayer skull base reconstruction technique using two layers of abdominal free fat and nasal septal mucoperiosteal flap. There were no postoperative complications, nor CSF rhinorrhea. The patient was discharged 10 days after the operation. To our knowledge, this is the first published case of a penetrating foreign body of the skull base, extending into the intracranial cavity following airbag deployment. In some dedicated cases, a minimal invasive endoscopic approach should be considered as an alternative to anterior craniotomy if access is possible when foreign bodies from the skull base area need to be removed. This procedure is efficient, safe and minimally invasive. .
MeSH term(s)	Male ; Humans ; Middle Aged ; Air Bags ; Endoscopy/methods ; Skull Base/surgery ; Foreign Bodies/diagnostic imaging ; Foreign Bodies/surgery ; Craniotomy
Language	English
Publishing date	2023-12-05
Publishing country	Hungary
Document type	Case Reports
ZDB-ID	2240317-6
ISSN	0019-1442
ISSN	0019-1442
DOI	10.18071/isz.76.0427
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Article ; Online: The Role of Aquaporin 4 in Lacrimal Gland Ductal Fluid Secretion in Mice.

Elekes, Gréta / Csapó, Virág / Szarka, Dóra / Szalay, László / Korsós, Marietta Margaréta / Tálosi, Dorottya / Török, Dénes / Tóth-Molnár, Edit

Investigative ophthalmology & visual science

2024 Volume 65, Issue 5, Page(s) 30

Abstract: Purpose: Earlier reports highlighted the predominant presence of aquaporin 4 (AQP4) in the duct cells of rabbit lacrimal glands (LGs). Whereas significant alterations in AQP4 mRNA levels have been observed in experimental dry eye and during pregnancy, ... ...

Abstract	Purpose: Earlier reports highlighted the predominant presence of aquaporin 4 (AQP4) in the duct cells of rabbit lacrimal glands (LGs). Whereas significant alterations in AQP4 mRNA levels have been observed in experimental dry eye and during pregnancy, the impact of AQP4 in LG ductal fluid production remains unclear. In our recent work, the role of AQP4 in LG ductal fluid secretion was investigated utilizing wild type (WT) and AQP4 knock out (KO) mice. Methods: Tear production was assessed in both WT and KO animals. Immunostaining was used to identify AQP4 protein. Duct segments were harvested from LGs of WT and KO mice. Fluid secretion and filtration permeability (Pf) were quantified using video-microscopy. Ductal tear production, elicited by a cell-permeable cAMP analogue (8-bromo cAMP), carbachol, vasoactive intestinal peptide (VIP), and phenylephrine (PHE), were assessed in both WT and KO ducts. Results: A higher expression of AQP4 protein was noted in the duct cells from WT mice when compared to acinar cells. Pf did not show notable alterations between WT and AQP4 KO ducts. Carbachol elicited comparable secretory responses in ducts from both WT and KO animals. However, 8-bromo cAMP, VIP, and PHE stimulation resulted in decreased secretion in ducts from AQP4 KO LGs. Conclusions: Our findings underscore the functional relevance of AQP4 in the fluid production of mouse LG ducts. AQP4 seems to play different roles in fluid secretions elicited by different secretagogues. Specifically, cAMP-mediated, and adrenergic agonist-related secretions were reduced in AQP4 KO ducts.
MeSH term(s)	Animals ; Mice ; Lacrimal Apparatus/metabolism ; Tears/metabolism ; Mice, Knockout ; Aquaporin 4/metabolism ; Aquaporin 4/genetics ; Mice, Inbred C57BL ; Female
Chemical Substances	Aqp4 protein, mouse
Language	English
Publishing date	2024-05-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.65.5.30
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Article ; Online: Szemészeti javallat alapján végzett génterápiás kezelés RPE65 biallelikus génmutáció okozta öröklődő ideghártya-dystrophiában.

Vizvári, Eszter / Smeller, Lilla / Jánossy, Ágnes / Lőrincz, Máté / Janáky, Márta / Tóth-Molnár, Edit

Orvosi hetilap

2022 Volume 163, Issue 48, Page(s) 1923–1931

Abstract: Introduction: Leber's congenital amaurosis is a genetically determined disease belonging to the group of hereditary retinal dystrophies that leads to significant visual impairment in childhood. The disease initially causes a concentric narrowing of the ... ...

Title translation	Gene therapy treatment based on an ophthalmic indication in hereditary retinal dystrophy caused by RPE65 biallelic gene mutation.
Abstract	Introduction: Leber's congenital amaurosis is a genetically determined disease belonging to the group of hereditary retinal dystrophies that leads to significant visual impairment in childhood. The disease initially causes a concentric narrowing of the visual field and, with time, loss of central vision. The RPE65 gene mutation-related retinal dystrophy is the first ophthalmic disease for which gene therapy is available using voretigene neparvovec (Luxturna®, Novartis Pharmaceuticals AG, Basel, Switzerland). Objective: To present the treatment outcomes of Hungarian patients who were the first to receive voretigene neparvovec gene therapy for the RPE65 biallelic gene mutation. Method: Two patients with RPE65 biallelic gene mutations confirmed by genetic testing received voretigene neparvovec gene therapy in one eye each. Before treatment and during the follow-up period, we assessed the best corrected visual acuity, the central retinal thickness, the degree of visual field defects and performed electrophysiological studies. Results: Both the best corrected visual acuity (+3 letters in the older sibling and +10 letters in the younger sibling) and the degree of visual field narrowing improved in both patients. The change in visual function resulted in a significant improvement in the quality of life of our patients. Conclusion: Postoperative outcomes of our patients correlate with the results of clinical trials. Orv Hetil. 2022; 163(48): 1923-1931.
MeSH term(s)	Humans ; cis-trans-Isomerases/genetics ; Quality of Life ; Retinal Dystrophies/genetics ; Retinal Dystrophies/therapy ; Genetic Therapy/methods ; Mutation
Chemical Substances	cis-trans-Isomerases (EC 5.2.-)
Language	Hungarian
Publishing date	2022-11-27
Publishing country	Hungary
Document type	English Abstract ; Journal Article
ZDB-ID	123879-6
ISSN	1788-6120 ; 0030-6002
ISSN (online)	1788-6120
ISSN	0030-6002
DOI	10.1556/650.2022.32636
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Article: Orbital Cellulitis following COVID-19 Vaccination.

Hári-Kovács, András / Vass, Attila / Lovas, Péter / Vince, Viola / Végh, Mihály / Tóth-Molnár, Edit

Case reports in ophthalmology

2022 Volume 13, Issue 1, Page(s) 210–214

Abstract: A 72-year-old male patient was referred to our outpatient clinic with a painful left eye protrusion accompanied by marked conjunctival chemosis and external ophthalmoplegia being progressed despite topical and oral antibiotic therapy. He developed ocular ...

Abstract	A 72-year-old male patient was referred to our outpatient clinic with a painful left eye protrusion accompanied by marked conjunctival chemosis and external ophthalmoplegia being progressed despite topical and oral antibiotic therapy. He developed ocular symptoms 9 days after receiving his second SARS-CoV-2 vaccine (VeroCell). Of note, in previous history, 2 weeks after the first dose of the COVID-19 vaccine, he also developed a life-threatening laryngeal oedema treated at an emergency care unit. MRI of the orbit excluded pansinusitis as possible origin of the orbital cellulitis, and repeated COVID-19 antigen and antibody PCR tests were negative during his hospitalization. On the next day after his admittance, parenteral dexamethasone 250 mg/die treatment was commenced resulting in a quick and complete resolution of the symptoms. Due to the facts regarding this case, such as the temporal coincidence and the lack of respective comorbidity, there might be a causative relationship between the vaccination and the presented orbital cellulitis. To the best of our knowledge, this is the first report on orbital cellulitis as a possible ocular adverse event following COVID-19 vaccination.
Language	English
Publishing date	2022-03-21
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2577666-6
ISSN	1663-2699
ISSN	1663-2699
DOI	10.1159/000523803
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