The effect of cumulative energy in repeated subliminal transscleral cyclophotocoagulation: a retrospective study.

BACKGROUND: The long-term safety and efficacy of repeated applications of subliminal transscleral cyclophotocoagulation (SL-TSCPC) with a focus on cumulative energy was evaluated in glaucoma patients. METHODS: In this retrospective, multicentric study the data of a total of 82 eyes with various causes of glaucoma that were treated with a single or multiple applications of SL-TSCPC were collected. Treatments were performed under general or local anesthesia with an 810 nm diode laser. Power was 2000 mW; duty cycle, 31.3%; total treatment duration, 80-320 s; equaling a total energy of 50-200 J per treatment session. Fifty-five eyes (55 patients) presented for all follow-ups, and these eyes were selected for further statistical analysis. The mean age was 60.0 ± 17.1 years, and 22 (40%) of the patients were female. Intraocular pressure (IOP) and dependence on further glaucoma medication were evaluated at 12 months following the initial treatment. RESULTS: Eyes underwent 1 or 2 consecutive SL-TSCPC treatments. Median (min-max) baseline IOP of 34 (13-69) decreased to 21.5 (7-61), 22 (8-68), 20 (9-68), and 19.5 (3-60) mmHg at the 1, 3, 6, and 12-month postoperative timepoints respectively. The mean (± SD) IOP decrease at 12 months was 26 ± 27%, 39 ± 32%, and 49 ± 33% in the low (below 120 J, n = 18), medium (120-200 J, n = 24), and high (above 200 J, n = 13) cumulative energy groups respectively. At the 12-month timepoint, oral carbonic anhydrase use was discontinued in ¾ of the cases. CONCLUSIONS: It was found that the repeated application of SL-TSCPC safely and efficiently decreases IOP in a Caucasian population with heterogenous causes of glaucoma, eyes with silicone oil responded to a greater extent. Inclusion of cumulative energy scales may contribute to better addressing repeated procedures in a standardized fashion.

Carnosic Acid Inhibits Herpes Simplex Virus Replication by Suppressing Cellular ATP Synthesis.

Acquiring resistance against antiviral drugs is a significant problem in antimicrobial therapy. In order to identify novel antiviral compounds, the antiviral activity of eight plants indigenous to the southern region of Hungary against herpes simplex virus-2 (HSV-2) was investigated. The plant extracts and the plant compound carnosic acid were tested for their effectiveness on both the extracellular and intracellular forms of HSV-2 on Vero and HeLa cells. HSV-2 replication was measured by a direct quantitative PCR (qPCR). Among the tested plant extracts, Salvia rosmarinus (S. rosmarinus) exhibited a 90.46% reduction in HSV-2 replication at the 0.47 µg/mL concentration. Carnosic acid, a major antimicrobial compound found in rosemary, also demonstrated a significant dose-dependent inhibition of both extracellular and intracellular forms of HSV-2. The 90% inhibitory concentration (IC90) of carnosic acid was between 25 and 6.25 µg/mL. Proteomics and high-resolution respirometry showed that carnosic acid suppressed key ATP synthesis pathways such as glycolysis, citrate cycle, and oxidative phosphorylation. Inhibition of oxidative phosphorylation also suppressed HSV-2 replication up to 39.94-fold. These results indicate that the antiviral action of carnosic acid includes the inhibition of ATP generation by suppressing key energy production pathways. Carnosic acid holds promise as a potential novel antiviral agent against HSV-2.

The Role of Aquaporin 4 in Lacrimal Gland Ductal Fluid Secretion in Mice.

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.

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

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.

Minimal invasive transnasal endoscopic removal of intracranial foreign body after airbag deployment.

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. 

Biosimilar SB15 versus reference aflibercept in neovascular age-related macular degeneration: 1-year and switching results of a phase 3 clinical trial.

BACKGROUND/AIMS: To evaluate efficacy, safety, pharmacokinetics (PK) and immunogenicity of SB15 versus reference aflibercept (AFL), and switching from AFL to SB15 in neovascular age-related macular degeneration (nAMD). DESIGN: Prospective, double-masked, randomised, phase 3 trial. METHODS: Participants with nAMD were randomised 1:1 to receive SB15 (N=224 participants) or AFL (N=225). At week 32, participants either continued on SB15 (SB15/SB15, N=219) or AFL (AFL/AFL, N=108), or switched from AFL to SB15 (AFL/SB15, N=111). This manuscript reports 1-year and switching results of secondary efficacy endpoints such as changes from baseline to week 56 in best-corrected visual acuity (BCVA), central subfield thickness (CST, from internal limiting membrane (ILM) to retinal pigment epithelium), and total retinal thickness (TRT, from ILM to Bruch's membrane). Additional endpoints included safety, PK and immunogenicity. RESULTS: Efficacy results were comparable between groups. The least squares mean (LSmean) change in BCVA from baseline to week 56 was 7.4 letters for SB15/SB15 and 7.0 letters for AFL/AFL (difference (95% CI)=0.4 (-2.5 to 3.2)). The LSmean changes from baseline to week 56 in CST and TRT were -119.2 µm and -132.4 µm for SB15/SB15 and -126.6 µm and -136.3 µm for AFL/AFL, respectively (CST: difference (95% CI)=7.4 µm (-6.11 to 20.96); TRT: difference (95% CI)=3.9 µm (-18.35 to 26.10)). Switched and non-switched participants showed similar LSmean changes in BCVA from baseline to week 56 (AFL/SB15, 7.9 letters vs AFL/AFL, 7.8 letters; difference (95% CI)=0.0 (-2.8 to 2.8)). Safety, PK and immunogenicity were comparable between groups. CONCLUSIONS: Efficacy, safety, PK and immunogenicity were comparable between SB15 and AFL and between switched and non-switched participants.

Long-Term Follow-Up of a Family with Retinal Dystrophy Caused by RPE65 Mutation.

We present here the case histories of two siblings, a boy and a girl, with Leber's congenital amaurosis (LCA). The diagnosis was based on non-recordable full-field electroretinogram (ffERG). The long-term ophthalmologic follow-up included kinetic perimetry (Goldmann), visual evoked potentials with flash stimulation, optical coherence tomography (OCT: B-scan images at the area of fovea), and multifocal ERG. The boy (sibling 1, born in 1986) was sent for electrophysiological examination at the age of four because he had nystagmus from birth. The diagnosis would be LCA based on non-recordable ffERG. Four years later, his visual acuity decreased rapidly due to vitreous opacification, caused by the autoimmune reaction of the retinal pigment epithelial cells. This was treated successfully with steroid injections, administered parabulbarly. Retinal autoimmune panel was not performed. Genetic testing became available only in 2019, and it revealed a RPE65 gene mutation: (NM_000329.2) c.{442G>A};{442G>A} (p.{Glu148Lys}; {Glu148Lys}). His sister (sibling 2, born in 1993) showed similar symptoms, caused by the same genetic mutation. Even though their parents were free of symptoms, it appeared that they were heterozygous carriers of the same mutation. Research of the family tree revealed a consanguineous marriage four generations before. Both siblings received successful gene therapy relatively late in their age: sibling 1 was 35 and sibling 2 was 28 years old, meaning that they were at an advanced stage of the disease. Nevertheless, follow-up examinations showed measurable improvements in their retinal function. The study shows that electrophysiological examinations, including flash-evoked responses, are useful in the objective evaluation of the progression in the central photoreceptor loss during the follow-up of LCA. The results also show that gene therapy can have beneficial effects even at an advanced stage of the disease.

Optical Coherence Tomography: Focus on the Pathology of Macula in Scleritis Patients.

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.

Efficacy and Safety of the Aflibercept Biosimilar SB15 in Neovascular Age-Related Macular Degeneration: A Phase 3 Randomized Clinical Trial.

Importance: Aflibercept biosimilars can expand available treatment options in retinal diseases and have the potential to improve patient access to safe and effective therapy. Objective: To establish equivalence in efficacy and similarity in safety, pharmacokinetics, and immunogenicity of SB15 and reference aflibercept (AFL) in neovascular age-related macular degeneration (nAMD). Design, Setting, and Participants: This was a randomized double-masked parallel group phase 3 trial conducted at 56 centers in 10 countries from June 2020 to March 2022, including follow-up through 56 weeks. Of 549 screened participants, 449 participants 50 years and older with treatment-naive nAMD were included and randomly assigned to SB15 (n = 224) or AFL (n = 225). Key exclusion criteria included considerable scarring, fibrosis, atrophy, and hemorrhage. This report includes results up to the end of the parallel group period at week 32. Of the 449 randomized participants, 438 (97.6%) completed week 32 follow-up. Intervention: Participants were randomized 1:1 to receive 2 mg of SB15 or AFL every 4 weeks for the first 12 weeks (3 injections), followed by dosing every 8 weeks up to week 48, with final assessments at week 56. Main Outcomes and Measures: The primary end point was the change in best-corrected visual acuity (BCVA) from baseline to week 8 with predefined equivalence margins of -3 letters to 3 letters. Other key end points were changes in BCVA and central subfield thickness up to week 32, safety, pharmacokinetics, and immunogenicity. Results: The mean (SD) age among the 449 included participants was 74.0 (8.1) years, and 250 participants (55.7%) were female. Baseline demographic characteristics and most disease characteristics were comparable between treatment groups. The least squares mean change in BCVA from baseline to week 8 in the SB15 group was equivalent to that in the AFL group (6.7 letters vs 6.6 letters, respectively; difference, 0.1 letters; 95% CI, -1.3 to 1.4). Comparable efficacy between treatment groups was maintained up to week 32 (least squares mean change from baseline in BCVA: SB15, 7.6 letters vs AFL, 6.5 letters; least squares mean change from baseline in central subfield thickness: SB15, -110.4 µm vs AFL, -115.7 µm). No clinically relevant differences were observed in the incidence of treatment-emergent adverse events (TEAEs) (SB15, 107/224 [47.8%] vs AFL, 98/224 [43.8%]) and ocular TEAEs in the study eye (SB15, 41/224 [18.3%] vs AFL, 28/224 [12.5%]). The serum concentration profiles and cumulative incidences of overall antidrug antibody positive participants were comparable. Conclusions and Relevance: In this phase 3 randomized clinical trial, SB15 and AFL showed equivalent efficacy and comparable safety, pharmacokinetics, and immunogenicity in participants with nAMD. Trial Registration: ClinicalTrials.gov Identifier: NCT04450329.

Cognitive functioning and clinical characteristics of children with non-syndromic orofacial clefts: A case-control study.

Introduction: The higher rate of neuropsychiatric disorders in individuals with non-syndromic orofacial clefts has been well documented by previous studies. Our goal was to identify children with non-syndromic orofacial clefts that are at risk for abnormal neurodevelopment by assessing their developmental history and present cognitive functioning. Materials and methods: A single-center, case-controlled study was carried out at the Department of Pediatrics of the University of Pécs in Hungary. The study consisted of three phases including questionnaires to collect retrospective clinical data and psychometric tools to assess IQ and executive functioning. Results: Forty children with non-syndromic oral clefts and 44 age-matched controls participated in the study. Apgar score at 5 min was lower for the cleft group, in addition to delays observed for potty-training and speech development. Psychiatric disorders were more common in the cleft group (15%) than in controls (4.5%), although not statistically significant with small effect size. The cleft group scored lower on the Continuous Performance Test. Subgroup analysis revealed significant associations between higher parental socio-economic status, academic, and cognitive performance in children with non-syndromic orofacial clefts. Analyzes additionally revealed significant associations between early speech and language interventions and higher scores on the Verbal Comprehension Index of the WISC-IV in these children. Discussion: Children with non-syndromic orofacial clefts seem to be at risk for deficits involving the attention domain of the executive system. These children additionally present with difficulties that affect cognitive and speech development. Children with non-syndromic orofacial clefts show significant skill development and present with similar cognitive strengths as their peers. Longitudinal studies with larger sample sizes are needed to provide more conclusive evidence on cognitive deficits in children with non-syndromic orofacial clefts at risk for neurodevelopmental difficulties.

Challenges in the Complex Management of Neglected Cutaneous Melanomas in the Head and Neck Area: A Single Center Experience.

Familiar controversies in the management of head and neck melanomas are more remarkable in locally advanced cases, and they represent a treatment challenge both surgically and oncologically. In our retrospective study, patients with surgically treated primary malignant melanoma of the head and neck region larger than 3 cm in diameter were included. Five patients met our inclusion criteria. In all cases, wide excision and immediate reconstruction were performed without sentinel lymph node biopsy. The defect on the scalp was covered by a split skin graft, with local flaps chosen for reconstruction on the face on an individual basis. After a 2-6 year follow-up, a good oncological, functional, and esthetic result was achieved. Our results show that in the case of large, locally advanced melanomas, surgical treatment still plays a crucial role that can provide long-term local control and support the effect of systemic treatment.

[Gene therapy treatment based on an ophthalmic indication in hereditary retinal dystrophy caused by RPE65 biallelic gene mutation.] / Szemészeti javallat alapján végzett génterápiás kezelés RPE65 biallelikus génmutáció okozta öröklodo ideghártya-dystrophiában.

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.

Human Thelaziosis Caused by Thelazia callipaeda Eyeworm, Hungary.

Ocular infections with Thelazia callipaeda eyeworms in Europe have become more common. We report a case in Hungary caused by T. callipaeda eyeworms in a 45-year-old woman who had no travel history abroad.

Biological therapy of uveitis in children / A biológiai terápia helye a gyermekkori uveitis ellátásában

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 be-tween 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 hae-matological 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. Adali-mumab 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 de-crease 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.

An Extensive Study of Phenol Red Thread as a Novel Non-Invasive Tear Sampling Technique for Proteomics Studies: Comparison with Two Commonly Used Methods.

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.

Orbital Cellulitis following COVID-19 Vaccination.

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.

White Dot Syndrome Report in a SARS-CoV-2 Patient.

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.

TRPM4 links calcium signaling to membrane potential in pancreatic acinar cells.

Transient receptor potential cation channel subfamily M member 4 (TRPM4) is a Ca2+-activated nonselective cation channel that mediates membrane depolarization. Although, a current with the hallmarks of a TRPM4-mediated current has been previously reported in pancreatic acinar cells (PACs), the role of TRPM4 in the regulation of acinar cell function has not yet been explored. In the present study, we identify this TRPM4 current and describe its role in context of Ca2+ signaling of PACs using pharmacological tools and TRPM4-deficient mice. We found a significant Ca2+-activated cation current in PACs that was sensitive to the TRPM4 inhibitors 9-phenanthrol and 4-chloro-2-[[2-(2-chlorophenoxy)acetyl]amino]benzoic acid (CBA). We demonstrated that the CBA-sensitive current was responsible for a Ca2+-dependent depolarization of PACs from a resting membrane potential of -44.4 ± 2.9 to -27.7 ± 3 mV. Furthermore, we showed that Ca2+ influx was higher in the TRPM4 KO- and CBA-treated PACs than in control cells. As hormone-induced repetitive Ca2+ transients partially rely on Ca2+ influx in PACs, the role of TRPM4 was also assessed on Ca2+ oscillations elicited by physiologically relevant concentrations of the cholecystokinin analog cerulein. These data show that the amplitude of Ca2+ signals was significantly higher in TRPM4 KO than in control PACs. Our results suggest that PACs are depolarized by TRPM4 currents to an extent that results in a significant reduction of the inward driving force for Ca2+. In conclusion, TRPM4 links intracellular Ca2+ signaling to membrane potential as a negative feedback regulator of Ca2+ entry in PACs.

The regulatory role of vasoactive intestinal peptide in lacrimal gland ductal fluid secretion: A new piece of the puzzle in tear production.

Purpose: Vasoactive intestinal peptide (VIP) is an important regulator of lacrimal gland (LG) function although the effect of VIP on ductal fluid secretion is unknown. Therefore, the aim of the present study was to investigate the role of VIP in the regulation of fluid secretion of isolated LG ducts and to analyze the underlying intracellular mechanisms. Methods: LGs from wild-type (WT) and cystic fibrosis transmembrane conductance regulator (CFTR) knockout (KO) mice were used. Immunofluorescence was applied to confirm the presence of VIP receptors termed VPAC1 and VPAC2 in LG duct cells. Ductal fluid secretion evoked by VIP (100 nM) was measured in isolated ducts using videomicroscopy. Intracellular Ca2+ signaling underlying VIP stimulation was investigated with microfluorometry. Results: VIP stimulation resulted in a robust and continuous fluid secretory response in isolated duct segments originated from WT mice. In contrast, CFTR KO ducts exhibited only a weak pulse-like secretion. A small but statistically significant increase was detected in the intracellular Ca2+ level [Ca2+]i during VIP stimulation in the WT and in CFTR KO ducts. VIP-evoked changes in [Ca2+]i did not differ considerably between the WT and CFTR KO ducts. Conclusions: These results suggest the importance of VIP in the regulation of ductal fluid secretion and the determining role of the adenylyl cyclase-cAMP-CFTR route in this process.

Alpha-Adrenergic Agonists Stimulate Fluid Secretion in Lacrimal Gland Ducts.

Purpose: The role of adrenergic innervation in the regulation of lacrimal gland (LG) ductal fluid secretion is unknown. The Aim of the present study was to investigate the effect of adrenergic stimulation on fluid secretion in isolated LG duct segments and to study the underlying intracellular mechanisms. Methods: Fluid secretion of isolated mouse LG ducts was measured using video-microscopy. Effect of various adrenergic agonists (norepinephrine, phenylephrine, and isoproterenol) on fluid secretion as well as inhibitory effects of specific antagonists on adrenergic agonist-stimulated secretory response were analyzed. Changes in intracellular Ca2+ level [Ca2+i] were investigated with microfluorometry. Results: Both norepinephrine and phenylephrine initiated a rapid and robust fluid secretory response, whereas isoproterenol did not cause any secretion. Phenylephrine-induced secretion was completely blocked by α1D-adrenergic receptor blocker BMY-7378. The endothelial nitric oxide synthase (eNOS) inhibitor L-NAME or guanylyl cyclase inhibitor ODQ reduced but not completely abolished the phenylephrine-induced fluid secretion, whereas co-administration of Ca2+-chelator BAPTA-AM resulted in a complete blockade. Phenylephrine stimulation induced a small, but statistically significant elevation in [\(Ca_i^{2 + }\)]. Conclusions: Our results prove the direct role of α1-adrenergic stimulation on LG ductal fluid secretion. Lack of isoproterenol-induced fluid secretory response suggests the absence of ß-receptor mediated pathway in mouse LG ducts. Complete blockade of phenylephrine-induced fluid secretion by BMY-7378 and predominant inhibition of the secretory response either by L-NAME or ODQ suggest that α-adrenergic agonists use the NO/cGMP pathway through α1D receptor. Ca2+ signaling independent from NO/cGMP pathway may also play an at least partial role in α-adrenergic induced ductal fluid secretion.