The role of electrochemotherapy in the treatment of locally advanced or recurrent eyelid-periocular basal cell carcinoma: long-term results.

BACKGROUND: While electrochemotherapy (ECT) is increasingly utilized as a highly effective method in the treatment of tumors in the head and neck region, there is significantly less data available for eyelid-periocular skin tumors. Our group reported the first extensive case series of eyelid-periocular basal cell carcinoma (BCC) patients with short-term follow-up treatment with ECT. The present study aims to report our long-term results of eyelid-periocular BCC cases treated with ECT. METHODS: The treatments were performed according to the ESOPE (European Standard Operating Procedures on Electrochemotherapy) guidelines using the Cliniporator™ device. All patients received bleomycin-based ECT, administered intratumorally or intravenously. Tumor response was evaluated using the RECIST 1.1 criteria. RESULTS: The results of 19 patients treated with ECT are presented. Four patients had locally advanced primary tumors, while 15 patients had recurrent tumors. Bleomycin was administered intratumorally in four patients and intravenously in 15 patients. The overall response was 100%, while the complete response rate proved to be 95%. In three cases (15.8%), recurrence was observed during the mean follow-up period of 78.9 months. CONCLUSIONS: ECT can effectively treat locally advanced or recurrent BCC in the eyelid-periocular skin region. Excellent tumor control can be achieved with good functional and cosmetic results without systemic adverse events with long interval follow-up.

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.

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.

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.

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.

The electrophysiological effect of cannabidiol on hERG current and in guinea-pig and rabbit cardiac preparations.

Cannabis use is associated with cardiovascular adverse effects ranging from arrhythmias to sudden cardiac death. The exact mechanism of action behind these activities is unknown. The aim of our work was to study the effect of cannabidiol (CBD), tetrahydrocannabinol and 11-nor-9-carboxy-tetrahydrocannabinol on cellular cardiac electrophysiological properties including ECG parameters, action potentials, hERG and IKr ion channels in HEK cell line and in rabbit and guinea pig cardiac preparations. CBD increased action potential duration in rabbit and guinea pig right ventricular papillary muscle at lower concentrations (1 µM, 2.5 µM and 5 µM) but did not significantly change it at 10 µM. CBD at high concentration (10 µM) decreased inward late sodium and L-type calcium currents as well. CBD inhibited hERG potassium channels with an IC50 value of 2.07 µM at room temperature and delayed rectifier potassium current with 6.5 µM at 37 °C, respectively. The frequency corrected QT interval (QTc) was significantly lengthened in anaesthetized guinea pig without significantly changing other ECG parameters. Although the IC50 value of CBD was higher than literary Cmax values after CBD smoking and oral intake, our results raise the possibility that hERG and potassium channel inhibition might have a role in the possible proarrhythmic adverse effects of cannabinoids in situations where metabolism of CBD impaired and/or the repolarization reserve is weakened.

Retinal Nerve Fibre Layer Thickness Change After CO2 Laser-Assisted Deep Sclerectomy Surgery.

PURPOSE: The goal of our study was to investigate changes in intraocular pressure (IOP), best-corrected visual acuity (BCVA), and retinal nerve fibre layer thickness (RNFLT) after CO2 laser-assisted deep sclerectomy (CLASS). METHODS: We carried out uncomplicated CLASS surgeries and a 12-month follow-up on 22 open-angle glaucomatous (OAG) eyes of 22 patients. IOP, BCVA, and RNFLT with spectral-domain optical coherence tomography (SD OCT) were recorded before and 1, 3, 6, 12 months after surgery. RESULTS: Mean age of patients was 68.1 years. IOP decreased from preoperative 28.45±5.99 SD mmHg (mean±standard deviation) to 15.09±2.40 mmHg (p=0.00039) at 12 months after surgery. BCVA-change from preoperative 0.34±0.38 SD (LogMAR) to 0.37±0.41 SD (LogMAR) was not significant (p=0.2456). RNFLT-change from preoperative 60.50±18.15µm to 59.63±17.52 µm at 12 months postoperatively was not significant (p=0.056). Qualified success rate of CLASS surgery was 72.7%, whereas complete success rate was 64% at 1 year postoperatively. CONCLUSION: Successful CLASS surgery efficiently reduced IOP. At postoperative 12 months, RNFLT and BCVA were not reduced significantly. There was no significant glaucomatous progression after surgery encountered in respect of investigated parameters.

Predominant neurological phenotype in a Hungarian family with two novel mutations in the XPA gene-case series.

OBJECTIVE: The prevalence of xeroderma pigmentosum (XP) is quite low in Europe, which may result in a delay in determining the appropriate diagnosis. Furthermore, some subtypes of XP, including XPA, may manifest themselves with quite severe neurological symptoms in addition to the characteristic dermatological lesions. Accordingly, the aim of the current study is to highlight the predominant neurological aspects of XPA, as well as mild-to-moderate dermatological signs in a Hungarian family with 5 affected siblings. CASE REPORTS: The symptoms of the Caucasian male proband started to develop at 13-14 years of age with predominantly cerebellar, hippocampal, and brainstem alterations. His elder sister and three younger brothers all presented similar, but less expressed neurological signs. The diagnostic work-up, including clinical exome sequencing, revealed 2 novel compound heterozygous mutations (p.Gln146_Tyr148delinsHis, p.Arg258TyrfsTer5) in the XPA gene. Surprisingly, only mild-to-moderate dermatological alterations were observed, and less severe characteristic ophthalmological and auditory signs were detected. CONCLUSIONS: In summary, we present the first family with genetically confirmed XPA in the Central-Eastern region of Europe, clearly supporting the notion that disturbed function of the C-terminal region of the XPA protein contributes to the development of age-dependent neurologically predominant signs. This case series may help clinicians recognize this rare disorder.

Giant Squamous Cell Papilloma of the Eyelid-Diagnostic and Therapeutic Challenges.

Squamous cell papilloma (SCP) is generally a human papillomavirus (HPV) induced exophytic or endophytic proliferation on the surface of the skin, oral cavity, larynx, esophagus, cervix, vagina, and anal canal. The endophytic type SCP can cause differential diagnostic difficulties with keratoacanthoma, inverted follicular keratosis, and squamous cell carcinoma; however, these lesions are not associated with HPV infection. The authors present a female patient who noticed an extremely rapidly growing tumor destructing the left lower eyelid. The histological analysis of the biopsy sample revealed a virus-induced squamoproliferative lesion. The eyelid affected was completely removed, and the histological examination resulted in a HPV induced endophytic squamous cell papilloma. The tarsus and the conjunctiva were replaced by a chondromucosal graft harvested from the nasal septum, while the skin defect could be closed directly. Restoration of the eyelid function has been achieved with satisfying functional and cosmetic results.

Electrochemotherapy in the treatment of locally advanced or recurrent eyelid-periocular basal cell carcinomas.

There is increasing evidence about the effectiveness of electrochemotherapy (ECT) in the treatment of basal cell carcinomas in the head and neck region, although its role in the management of eyelid-periocular skin tumors has to be clarified. The aim of the present study is to evaluate the results of ECT in the treatment of locally advanced primary and recurrent eyelid-periocular skin basal cell carcinomas. Twelve patients with basal cell carcinoma involving the eyelid-periocular skin region were treated with ECT. Three patients had locally advanced primary tumors, while 9 patients had recurrent tumors. All treatments were performed according to the ESOPE guidelines, using Cliniporator TM device. All patients received bleomycin based ECT. The route of administration was intratumoral in 3 patients and intravenous in 9 patients. Tumor response was evaluated using the RECIST 1.1. criteria. ECT resulted in complete response of the periocular skin tumors in all patients. Lower eyelid ectropion was developed in 3 patients which had to be corrected surgically. ECT can be used effectively in the treatment of locally advanced or recurrent basal cell carcinomas in the eyelid-periocular skin region. Excellent tumor control can be achieved with good functional and cosmetic results without systemic adverse events with short interval follow-up.

Conjunctival melanocytic naevus: Diagnostic value of anterior segment optical coherence tomography and ultrasound biomicroscopy.

PURPOSE: Conjunctival naevi are the most frequently diagnosed primary melanocytic lesions of the conjunctiva. The clinical manifestations are greatly variable which may result in diagnostic difficulties and differential diagnostic confusions. Therefore aims of the present study were: 1) to assess the morphologic features of conjunctival naevi; 2) to delineate the anterior segment optical coherence tomography (AS-OCT) characteristics of these lesions; 3) to compare AS-OCT and ultrasound biomicroscopy (UBM) as diagnostic tools in these alterations and 4) to correlate histological results with the AS-OCT pictures in case of surgically excised naevi. METHODS: All lesions were photo-documented. AS-OCT and UBM (over the age of 18 years) were performed. Surgically excised lesions were admitted to histological examinations. RESULTS: In our series of 57 conjunctival naevi, 54.4% were highly pigmented, 15.8% proved to be amelanotic. AS-OCT could detect intralesional cysts in 61.4% of the naevi, while slit-lamp and UBM proved to be less sensitive (40.3% vs. 28.5%). UBM could visualize the posterior margins of all naevi, while AS-OCT proved to be less sensitive with the detection of 89.4% of posterior naevus margins. Thickness of the conjunctival epithelial layer could be measured with AS-OCT in case of subepithelial naevi, while no distinct epithelial layer could be detected in compound and junctional naevi. CONCLUSIONS: Superiority of AS-OCT over UBM was demonstrated in visualizing internal structures of conjunctival naevi. UBM proved to be a better tool in highly pigmented and remarkably elevated naevi. Correlation was found between the histological type of the naevus and the thickness of the epithelial layer covering the lesion.

Novel Insight Into the Role of CFTR in Lacrimal Gland Duct Function in Mice.

Purpose: The role of cystic fibrosis transmembrane conductance regulator (CFTR) in lacrimal gland (LG) function has only recently received some attention, mainly from our group. In the present study, we investigated the potential changes of LG pathology, tear secretion, ocular surface integrity, and fluid secretion in isolated LG ducts from CFTR knockout (KO) mice. Methods: Tear production and ocular surface integrity were investigated in anesthetized wild-type (WT) and KO mice using cotton threads and fluorescein staining, respectively. Immunofluorescence was used to localize CFTR protein in the LGs. Ductal fluid secretions evoked by forskolin (10 µM); cell-permeable cAMP analogue (8-bromo cAMP, 100 µM); or carbachol (100 µM) were measured in isolated LG ducts using video-microscopy. Intracellular Ca2+ homeostasis underlying carbachol stimulation was investigated with microfluorometry. Results: Significant decrease in tear secretion and impaired ocular surface integrity were observed in KO mice. Immunofluorescence demonstrated the predominant presence of CFTR protein in the apical membranes of the duct cells from WT mice. Continuous fluid secretion was evoked by forskolin and 8-bromo cAMP in LG ducts from WT mice, while no secretory response was observed in ducts from KO mice. Carbachol caused similar secretory responses in ducts from WT and KO animals without significant differences in cytosolic Ca2+ signaling. Conclusions: Our results suggest the important role of CFTR in LG ductal secretion and in the maintenance of ocular surface integrity, suggesting that CFTR may be a promising target of novel therapeutic approaches in the treatment of dry eye.

Giant Conjunctival Nevus in a 12-Year-Old Child.

We describe a case of a giant conjunctival nevus presented in a 12-year-old girl with suspicious clinicomorphological appearance. The lesion was noticed by the parents at the age of 3 years as a "fleshy spot" on the bulbar conjunctiva. The lesion remained unchanged until approx. 6 months before recent admission. On slit-lamp examination, a large conjunctival lesion with variegate pigmentation and indistinct margins was detected on the superonasal part of the bulbar conjunctiva of the left eye. Intralesional cysts and vessels were detected with AS-OCT examination. Wide excision and cryotherapy to the scleral bed were performed and amniotic membrane graft was used to restore the ocular surface. Histopathological examination revealed compound type conjunctival nevus and disclosed any sign of malignancy. Although giant conjunctival nevus is a rare entity, precise diagnosis and adequate management are very important as it can be confused with malignant melanoma.

Risk Factors and Relationship of Cutaneous and Uveal Melanocytic Lesions in Monozygotic and Dizygotic Twin Pairs.

BACKGROUND: The similar genetic background of a pair of twins, and the similar environmental impacts to which they are exposed allow an exact and objective investigation of various constitutional and environmental factors in naevus development. As far as we are aware, this is the first published survey that simultaneously examines cutaneous and ocular pigmented lesions in an appreciable sample of identical and non-identical twins. METHODS: 172 pairs of twins of Caucasian origin were included in this study. A whole-body skin examination and a detailed ophthalmological examination were performed to determine the density of melanocytic lesions. A standardized questionnaire was used to assess the data relating to constitutional, sun exposure and other variables. RESULTS: A notably high proportion of the subjects (36.78%) manifested one or more clinically atypical melanocytic naevi (CAMNs), and approximately one-third (31.4%) of them at least one benign uveal pigmented lesion (BUPL). The incidence of iris freckles (IFs), iris naevi (INs) and choroidal naevi (CHNs) proved to be 25.35%, 5.98% and 3.52%, respectively. The interclass correlation coefficients for common melanocytic naevi (CMNs), CAMNs, and INs were 0.77, 0.76 and 0.86 in monozygotic twins, as compared with 0.5, 0.27 and 0.25 in dizygotic twin pairs, respectively. A statistically significant correlation was found between the prevalence of CAMNs and that of INs. CONCLUSIONS: This significant correlation suggests the existence of a subgroup of Caucasian people with an increased susceptibility to both cutaneous and ocular naevus formation. There is accumulating evidence that, besides the presence of cutaneous atypical naevi, INs can serve as a marker of a predisposed phenotype at risk of uveal melanoma. The correlation between cutaneous and ocular pigmented lesions underlines the need for the adequate ophthalmological screening of subjects with CAMNs and INs.

Characterization of Na+-K+-2Cl- Cotransporter Activity in Rabbit Lacrimal Gland Duct Cells.

PURPOSE: We recently reported that isolated duct segments from rabbit lacrimal gland (LG) were able to secrete fluid in response to secretagogues, which were blocked completely by bumetanide. This suggests the functional involvement of Na+-K+-2Cl- cotransporter (NKCC1) in ductal fluid secretion. Therefore, the aim of this study was to investigate the activity profile of NKCC1 in isolated rabbit LG duct segments. METHODS: Interlobular ducts were isolated from fresh rabbit LG tissue. Microfluorometry with the ammonium (NH4+)-pulse technique was used to elicit pH changes in duct cells, and the rate of bumetanide-sensitive cytosolic acidification after addition of NH4+ was used to quantify the activity of NKCC1. RESULTS: While basal activity of NKCC1 was undetectable, low cytosolic chloride (Cl-) level and hyperosmotic challenge (390 mOsm) were able to increase the activity of NKCC1. Carbachol (100 µM) had no significant effect on NKCC1 activity. Elevation of cytosolic calcium (Ca2+) level with Ca2+-ionophore (A 23187, 1 µM) did not cause any alteration in the activity of the cotransporter while direct activation of protein kinase C (phorbol myristate acetate, 100 nM) increased its activity slightly but in a significant manner. Addition of either forskolin (10 µM), cell-permeable cAMP analogue (8-bromo cAMP, 100 µM) or vasoactive intestinal peptide (200 nM) resulted in a significant increase in the activity of NKCC1. CONCLUSIONS: These results highlight the functional involvement of NKCC1 in LG duct secretion. These findings may facilitate our understanding of LG function and may contribute to the development of targeted pharmacologic interventions in case of dry eye disease.

Neonatal blue light phototherapy and melanocytic nevi: a twin study.

BACKGROUND: Neonatal blue light phototherapy (NBLP) has been widely and successfully used for the treatment of neonatal jaundice to reduce the plasma concentration of bilirubin and, hence, to prevent kernicterus. Only a few and controversial data are available in the literature as to how NBLP influences melanocytic nevus development. OBJECTIVE: Our goal was to conduct a twin study with the aim of better understanding the role of NBLP in melanocytic nevus development. We also investigated the roles of other environmental and constitutional factors in nevus formation. METHODS: Fifty-nine monozygotic and dizygotic twins were included in this cross-sectional study. One of the twin members received NBLP, and the other did not. A whole-body skin examination was performed to determine the density of melanocytic skin lesions. The prevalence of benign pigmented uveal lesions was evaluated during a detailed ophthalmologic examination. A standardized questionnaire was used to assess data relating to constitutional, sun-exposure, and other variables. To search for possible gene-environmental interactions involved in the appearance of pigmented lesions, the melanocortin 1 receptor variants and the I439V polymorphism of histidine ammonia-lyase genes were also determined in the enrolled twins. RESULTS: NBLP was associated with a significantly higher prevalence of both cutaneous and uveal melanocytic lesions. No association was found between the examined gene polymorphisms and the number of pigmented alterations in the examined study group. CONCLUSIONS: Our data suggest that NBLP could well be a risk factor for melanocytic nevus development. Phototherapy with blue-light lamps is a standard and essential therapeutic modality in neonatal care; therefore, additional in vivo and in vitro studies are necessary to establish its potential long-term adverse effects.

[Connection between uveal melanoma and dysplastic naevus syndrome]. / Az uvealis melanoma és a dysplasticus naevus-syndroma kapcsolata.

The dysplastic naevus syndrome increases the risk of cutaneous (RR: 4.36; CI: 1.84-10.36) as well as uveal melanoma (RR: 4.22; CI: 1.81-9.84). A significantly higher occurrence rate of conjunctival naevi (3.2% vs. 0%; p=0.029), choroidal naevi (5.2% vs. 0.7%; p=0.023) and iris freckles (17.1% vs. 5.6%; p=0.002) could be detected in the dysplastic naevus syndrome patients compared to subjects in the control group. The presence of cutaneous dysplastic naevi in uveal melanoma patients increases the risk of the prognostically worse--epitheloid or mixed--forms of uveal melanoma (RR: 5.97%; CI: 1.61-22.14), compared to patients without cutaneous atypical naevi.

[Second primary malignant tumors in patients with ocular melanoma]. / Második primer malignus daganat elôfordulása ocularis melanomás betegek között.

Multiple primary malignant tumors have been documented with increased frequency over the last two decades. Continuously increasing success of modern oncotherapy has led to long-term remissions in many cases, but this success rate poses a growing risk for the development of second primary malignancies. The incidence of those involving an intraocular tumor is relatively rare. In the present study we report five ocular melanoma patients with second primary malignant tumors diagnosed during a fourteen-year period in our department. We wish to emphasize that an intraocular mass lesion in a patient with a history of a previous malignancy should not be dismissed as a metastatic lesion. The diagnosis of an intraocular lesion as a separate primary tumor drastically changes the prognosis and the therapeutic approach.