Edit Tóth-Molnár

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.

Dysplastic nevi are a risk factor for uveal melanoma

Many studies have characterized the phenotypic features of individuals who are likely to develop cutaneous melanoma. One of the major items included in melanoma risk assessment has been the presence of clinically atypical nevi (dysplastic nevi). This study assessed the number of subjects with dysplastic nevi in groups of patients with uveal melanoma or cutaneous melanoma and in a group of volunteer controls. The SPSS program was used to calculate the odds ratios (hereafter called relative risks; RR) and 95% confidence intervals (CI) in melanoma patients and controls. The RR was 4.36 for uveal melanoma (95% CI 1.84–10.36) and 4.22 for cutaneous melanoma (95% CI 1.81–9.84). These results suggest that cutaneous dysplastic nevi are a significant risk factor for uveal melanoma.

Ocular pigmented findings in patients with dysplastic naevus syndrome

There is a growing body of evidence supporting the theory that cutaneous dysplastic naevus syndrome patients are at increased risk of developing not only skin but also uveal melanoma. The relationship between dysplastic naevus syndrome and ocular naevi needs to be clarified. In this study we investigated the ocular pigmented findings in patients with dysplastic naevus syndrome and compared the results with a control group (subjects without atypical moles) in order to investigate the frequency of ocular naevi among dysplastic naevi-bearing patients. A total of 152 dysplastic naevus syndrome patients were enrolled in our investigation. The control group consisted of 142 sex-, age- and skin type-matched healthy volunteers without cutaneous dysplastic naevi or skin melanoma. Conjunctival and uveal pigmented findings and iris colour were recorded during a detailed ophthalmic examination. A greater number of conjunctival naevi (3.2% versus 0%), iris naevi (5.2% versus 1.4%), iris freckles (17% versus 5.6%) and choroidal naevi (5.2% versus 0.7%) were detected in the dysplastic naevus syndrome group compared with the controls. The difference reached statistical significance in the case of conjunctival naevi, choroidal naevi and iris freckles. Our results confirm the hypothesis that dysplastic naevus syndrome patients might have overstimulation of their melanocytic system not only in the skin but also in the uvea, leading to increased benign (as well as rarely malignant) melanocytic proliferation. Dysplastic naevus syndrome patients should be screened by ophthalmologists because of the increased frequency of different ocular pigmented alterations.

Long‐term hazards of neonatal blue‐light phototherapy

Blue‐light phototherapy has been an essential therapeutic tool in the management of neonatal jaundice for decades. Rarely, it is accompanied by acute dermatological and systemic side‐effects, but fortunately these are reversible and can be adequately and promptly treated in routine neonatal practice. In contrast, much less is known about the potential long‐term side‐effects of neonatal blue‐light phototherapy (NBLP). Many of the data that are currently available on how NBLP influences melanocytic naevus (MN) development are controversial. The results of recent well‐designed epidemiological surveys suggest that NBLP could well be a risk factor for MN formation, and highlight the need for additional in vivo and in vitro studies. NBLP is at present the mainstay of treatment for neonatal jaundice, but in the future greater consideration should be given to its long‐term side‐effects when phototherapy is indicated. It is relevant to emphasize the importance of appropriately restricted and adequate clinical guidelines, and strict monitoring of the management of hyperbilirubinaemia, in order to avoid the unnecessary overtreatment of newborn infants.

Cutaneous dysplastic naevi in uveal melanoma patients: markers for prognosis?

&NA; We have previously reported that the presence of cutaneous dysplastic naevi is a risk factor for uveal melanoma. In the present study our goal was to determine the incidence of different histopathological features of uveal melanoma among 91 patients with or without cutaneous dysplastic naevi. Statistical analysis revealed that the presence of cutaneous dysplastic naevi in uveal melanoma patients is associated with an increased incidence of the prognostically worst forms of uveal melanoma (epithelioid or mixed cell type melanomas). The relative risk was 5.97 (95% confidence interval 1.61‐22.14). Our results suggest that the presence of cutaneous dysplastic naevi is not only a risk factor but also a prognostic factor for uveal melanoma.

Experimental Evidence of Fluid Secretion of Rabbit Lacrimal Gland Duct Epithelium

PURPOSE To investigate the osmotic water permeability of lacrimal gland (LG) duct epithelium by means of calculation of filtration permeability and to investigate LG ductal fluid secretion. METHODS Experiments were performed on isolated rabbit LG duct segments maintained in short-term culture. Osmotically determined fluid movement or fluid secretion into the closed intraluminal space of cultured LG interlobular ducts was analyzed using video microscopic technique. RESULTS The end of the LG ducts sealed after overnight incubation forming a closed luminal space. For the calculation of osmotic water permeability, ducts were initially perfused with isotonic HEPES buffered solution, and then with hypotonic HEPES buffered solution. Filtration permeability was calculated from the initial slope of the relative volume increase. Secretory responses to carbachol or to forskolin stimulation were also investigated. Forskolin stimulation resulted in a rapid and sustained secretory response in both solutions. Forskolin-stimulated fluid secretion was completely inhibited by bumetanide both in HEPES buffered and in HCO3 (-)/CO2 buffered solutions, suggesting the central role of Na(+)-K(+)-2Cl(-) cotransporter type 1 (NKCC1). Administration of carbachol initiated a rapid but short secretory response in both HEPES buffered and in HCO3 (-)/CO2 buffered solutions. Atropine completely abolished the carbachol-evoked fluid secretion. CONCLUSIONS A new method was introduced to investigate LG duct function. Water permeability of rabbit LG duct epithelium was measured by calculating filtration permeability. Fluid secretion of LG duct cells induced by carbachol or forskolin was also demonstrated. These results provide calculated values of lacrimal duct osmotic permeability and direct experimental evidence of LG duct fluid secretion.

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.

HPLC analysis of blood-brain barrier penetration of 4-fluorodeprenyl

Validated HPLC analysis was developed in order to monitor the level of 4-fluorodeprenyl in rats. Male Wistar rats were intraperitoneally treated with 30 mg/kg of (-)-4-fluorodeprenyl. The rats were sacrificed after 5, 15, 30 and 60 min of treatment, and various tissues were isolated, such as serum, brain, CSF, liver, testis and lacrimal gland. Perchloric acid was given to aliquots, which were then homogenized, centrifuged and the supernatants were taken. The 4-fluorodeprenyl content was determined using reversed-phase HPLC, based on the comparison of the calibration line of the spiked samples. The level of 4-fluorodeprenyl was between 0.5 and 24 μg/g, showing maximum concentration in the brain and the liver after 5 min following its administration and in serum, CSF, testis, eyes and lacrimal gland after 15 min following its administration, while a relatively high concentration was found in the liver and the lacrimal gland.

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.

Új nemzetközi konszenzusnyilatkozat a száraz szem definíciójáról, felosztásáról, etiológiájáról, diagnosztikájáról és terápiájáról

Ten years have passed since the publication of the DEWS Report that summarized the information based on scientific literature concerning dry eye disease. Hundreds of papers have been published since then and time has come for a new summary. Organized by the Tear Film & Ocular Surface Society, 12 working groups summerized former and recent data. The DEWS II Report was created. The authors of the present publication summarize the most important changes in definition, classification, diagnostics, and therapy concerning dry eye disease. They also disclose the relevant changes on which the non-ophthalmologist specialists have to be informed. The DEWS II Report published by TFOS consists of 11 chapters. Completely new chapters deal with the role of sensation/pain and iatrogenic dry eyes. Orv Hetil. 2018; 159(20): 775-785.Ten years have passed since the publication of the DEWS Report that summarized the information based on scientific literature concerning dry eye disease. Hundreds of papers have been published since then and time has come for a new summary. Organized by the Tear Film & Ocular Surface Society, 12 working groups summerized former and recent data. The DEWS II Report was created. The authors of the present publication summarize the most important changes in definition, classification, diagnostics, and therapy concerning dry eye disease. They also disclose the relevant changes on which the non-ophthalmologist specialists have to be informed. The DEWS II Report published by TFOS consists of 11 chapters. Completely new chapters deal with the role of sensation/pain and iatrogenic dry eyes. Orv Hetil. 2018; 159(20): 775-785.