[Periocular Merkel Cell Carcinoma - an overview of clinical aspects and current therapeutic options]. / Das periokuläre Merkelzellkarzinom ­ eine Übersicht klinischer Aspekte und aktueller Therapieoptionen.

Merkel cell carcinoma (MCC) is a rare but highly aggressive and rapidly expanding malignant skin tumor. It affects the periocular region in approximately 10% of cases. The current treatment recommendation for resectable non-metastatic MCC comprises total surgical excision; however, lymph node or distant metastases are often already present by the time of the diagnosis. Since an immune checkpoint inhibitor therapy with avelumab was first approved for MCC in 2016, there has been considerable improvement in mean survival compared to cytostatic therapy; at the same time, there has been a reduction in serious treatment-associated adverse events. Other immune checkpoint inhibitors are currently still in clinical trials, with very promising initial results. Because of the complexity of the diagnosis, treatment, and prognosis, it is essential that MCC patients receive interdisciplinary care in a specialized center including consultation with a tumor review board.

Retinal microvascular density analysis in patients with rheumatoid arthritis treated with hydroxychloroquine.

PURPOSE: Rheumatoid arthritis (RA) is the most common inflammatory joint disease, and hydroxychloroquine (HCQ) is an established treatment. The extent to which HCQ impacts ocular microvascular vessel density (VD) in patients with RA without evidence of HCQ retinopathy has not yet been conclusively clarified. The main aim of this study was to evaluate VD measured by optical coherence tomography angiography (OCTA) in patients with RA treated with HCQ. METHODS: The VD data of the 3 × 3 mm OCT angiogram (RTVue XR Avanti, Optovue Inc., Fremont, California, USA) as well as the retinal thickness (RT) data of patients with RA (n = 30) and healthy controls (n = 30) were extracted and analyzed. The study group was further divided into patients undergoing HCQ treatment for > 5 years (high-risk-group) and < 5 years (low-risk group). RESULTS: Patients with RA showed no evidence of VD reduction compared to the control group in all obtained regions (p > 0.05). Correlation analysis revealed no dependency between VD, RT, and HCQ therapy duration or cumulative HCQ dose (p > 0.05). High-risk patients showed a decreased VD in the superficial quadrant of the superficial capillary plexus compared to low-risk-patients (p = 0.022). Whole-en-face RT was reduced in the high-risk group compared to the control group (p = 0.019). CONCLUSION: Our study showed no evidence that HCQ diminishes VD in patients with RA without HCQ retinopathy measured by OCTA. However, RA patients with a long duration of therapy showed a significantly reduced RT. Our results suggest that quantitative VD analysis by OCTA may not be suitable for early detection of HCQ retinopathy and that the focus on detecting early HCQ retinopathy should be on intensive and sequential OCT diagnostics.

Periocular Merkel Cell Carcinoma - An Overview of Clinical Aspects and Current Treatment Options. / Das periokuläre Merkel-Zell-Karzinom ­ eine Übersicht klinischer Aspekte und aktueller Therapieoptionen.

Merkel cell carcinoma (MCC) is a rare but highly aggressive and rapidly expanding malignant skin tumor. It affects the periocular region in approximately 10% of cases. The current treatment recommendation for resectable non-metastatic MCC comprises total surgical excision; however, lymph node or distant metastases are often already present by the time of the diagnosis. Since an immune checkpoint inhibitor therapy with avelumab was first approved for MCC in 2016, there has been considerable improvement in mean survival compared to cytostatic therapy; at the same time, there has been a reduction in serious treatment-associated adverse events. Other immune checkpoint inhibitors are currently still in clinical trials, with very promising initial results. Because of the complexity of the diagnosis, treatment, and prognosis, it is essential that MCC patients receive interdisciplinary care in a specialized center including consultation with a tumor review board.

Bilateral Upper Eyelid Swelling with Abscess under Treatment with Etanercept. / Bilaterale Oberlidschwellung mit Abszedierung unter Etanercept-Therapie.

We report the case of a 66-year-old female patient with rheumatoid arthritis and bilateral upper eyelid abscess under treatment with etanercept. Because bilateral upper lid abscesses due to a systemic cause are rare and cases of abscess formation under treatment with etanercept have been described in the literature, we discuss a possible connection between the bilateral upper lid abscess and the existing immunosuppressive medication.

Social participation and depressive symptoms among older adults during the Covid-19 pandemic in Serbia: A cross-sectional study.

OBJECTIVES: To determine the predictors and level of social participation and depressive symptoms within the context of isolation during the COVID-19 pandemic and investigate if the residence and type of housing had a moderating role in the relationship between social participation and depressive symptoms. METHODS: This cross-sectional, comparative, and correlational study was conducted on a sample of 299 participants. Research instruments used in this study included: socio-demographic questionnaire, the Geriatric Depression Scale, the Maastricht Social Participation Profile, and Mini-Mental State Exam. RESULTS: Social participation was found to contribute negatively to symptoms of depression (ß = -0.245, p < .01), with a higher level of depression being found in older adults living in nursing homes (ß = -0.152, p < .05). CONCLUSIONS: The study confirmed a strong relationship between social participation and depressive symptoms in the COVID-19 pandemic.

Ocular perfusion in patients with reduced left ventricular ejection fraction measured by optical coherence tomography angiography.

AIMS: The aim of this study is to evaluate retinal and optic nerve head (ONH) perfusion in patients with systolic chronic heart failure (CHF) compared to healthy control subjects. METHODS: Twenty-seven eyes of 27 patients with CHF (study group) and 31 eyes of 31 healthy subjects (control group) were prospectively included in this study. CHF Patients had a left ventricular ejection fraction (LVEF) < 50% and were classified by New York Heart Association (NYHA) class. OCT-A was performed using RTVue XR Avanti with AngioVue (Optovue, Inc, Fremont, CA, USA). The area of the foveal avascular zone (FAZ) and flow density (FD) data were extracted and analyzed. RESULTS: There was no significant difference in the signal strength index between the study group (group 1) and the control group (group 2) (ONH: p = 0.015; macula: p = 0.703). The difference in the area of the foveal avascular zone between the two groups was also not significant (p = 0.726). The flow density (whole en face) in the ONH (RPC) in group 1 was significantly lower compared to control (group 1 = 48.40 ± 2.48 (49.0 [46.7, 50.3]); group 2 = 50.15 ± 1.85 (50.6 [48.5, 51.70]); p = 0.008). There was a significant and strong correlation between LVEF and the macular flow density (whole en face) (superficial: rs = 0.605 deep: rs = 0.425, p < 0.01). CONCLUSIONS: Patients with CHF showed reduced flow density compared with healthy controls. The reduced FD correlated with the LVEF and the functional (NYHA) class. Retinal perfusion as measured using OCTA might provide an insight into the global microperfusion and hemodynamic state of heart failure patients.

Application Possibilities of a New Preloaded Nasolacrimal Duct Intubation System. / Anwendungsmöglichkeiten eines neuartigen vorgeladenen Intubationssystems für Tränenwege.

INTRODUCTION: The LacriJet (FCI S. A. S. - France Chirurgie Instrumentation, Paris, France) represents a novel, simplified and preloaded system for monocanalicular or monocanaliculonasal nasolacrimal duct intubation. It is a further development of the Masterka and shall reduce the intubation time during the surgical procedure. The aim of the present study was to present first experiences with this system for different indications. MATERIAL AND METHODS: All patients who underwent nasolacrimal duct intubation with the LacriJet at the University of Muenster Medical Center in the period from March to November 2019 were included. The postoperative outcome was evaluated 3 to 6 months later. RESULTS: In total, 12 nasolacrimal duct intubations with the LacriJet were performed at our center in the above-mentioned period. The main indication for intubation was congenital nasolacrimal duct obstruction (CNLDO). In addition, intubation was performed in cases with eye lid tumors involving the nasolacrimal duct, in a case of canalicular laceration and in a case of canaliculitis. In 3 cases, there was an early dislocation or a complete loss of intubation. Of these, 2 were cases with CNLDO and the third dislocation was due to manipulation by the patient. All in all, the functional results were satisfying. SUMMARY: The use of the LacriJet is highly suitable for the treatment of CNLDO, stenting in canalicular laceration or lid tumours involving the lacrimal drainage system. However, the known disadvantages of monocanalicular intubation (dislocation, early loss of intubation) also occur with this type of system and a system briefing seems useful. The LacriJet therefore represents a modern and simple method for nasolacrimal duct intubation and can be used for various indications.

ALTERED RETINAL PERFUSION IN PATIENTS WITH INACTIVE GRAVES OPHTHALMOPATHY USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

Objective: The aim of this study was to evaluate retinal and optic nerve head (ONH) perfusion in patients with inactive Graves ophthalmopathy (GO) and compare it to healthy controls using optical coherence tomography angiography (OCTA). Methods: Twenty-nine eyes of 29 patients with inactive GO (study group) and 29 eyes of 29 healthy subjects (control group) were included in this study. The vessel density (VD) data in the superficial and deep retinal OCT angiogram of the macula and the radial peripapillary capillary network (RPC) were extracted and analyzed. OCTA was performed using RTVue XR Avanti with AngioVue (Optovue Inc, Fremont, CA). Clinical activity was evaluated using the clinical activity score, the severity assessment using the NOSPECS classification. Results: The VD in the superficial OCT angiogram and in the OCT angiogram of the ONH was significantly lower in the GO group when compared to the control group (whole en face, P = .016; parafovea, P = .026; RPC peripapillary, P = .027). There was no significant correlation between VD and functional parameters or the NOSPECS classification. Conclusion: Macular VD and ONH capillary density measured using OCTA were significantly lower in the study group compared to healthy controls. Noninvasive quantitative analysis of retinal perfusion using OCTA could be useful in monitoring patients with GO. Abbreviations: CAS = clinical activity score; GO = Graves ophthalmopathy; OCTA = optical coherence tomography angiography; ONH = optic nerve head; RPC = radial peripapillary capillary; rSp = Spearman's correlation coefficient; VD = vessel density.

Altered microvascular density in patients with systemic lupus erythematosus treated with hydroxychloroquine-an optical coherence tomography angiography study.

PURPOSE: To evaluate the retinal microvascular density using optical coherence tomography angiography (OCTA) in patients with systemic lupus erythematosus (SLE) treated with hydroxychloroquine (HCQ). METHODS: Nineteen eyes of 19 patients with SLE (study group) without HCQ retinopathy and 19 eyes of 19 healthy subjects (control group) were included in this study. The study group was divided into patients using HCQ for > 5 years (high-risk group) and < 5 years (low-risk group). The VD data of the 3 × 3 mm OCT angiogram of the superficial capillary plexus (SCP) and the choriocapillaris (VD-CC), the foveal avascular zone (FAZ) area and the central retinal thickness (CRT) were extracted and analyzed. RESULTS: VD in the en face SCP was significantly reduced in the high-risk group and the low-risk group compared with that in the control group (p < 0.001, p = 0.001) and in the high-risk group compared with the low-risk group (p = 0.007). Correlation analysis between the cumulative dose of HCQ and the VD of the study group revealed a negative correlation, but no statistical significance (p = 0.074). However, a significant positive correlation was observed for the low-risk group (p = 0.035). In patients with SLE, VD-CC was lower (p = 0.042) and the FAZ area larger (p = 0.019). CRT showed no difference between the groups (p = 0.183). CONCLUSION: In this study, SLE patients showed a reduced VD in both groups. In patients treated with HCQ < 5 years, HCQ might have a protective effect on retinal microvasculature. Analysis of retinal microvascular density using OCTA could be useful in the diagnosis and monitoring of vascular alteration in patients with SLE.

Cytomegalovirus retinitis in children and adolescents with acute leukemia following allogeneic hematopoietic stem cell transplantation.

Cytomegalovirus retinitis (CMVR) may occur after allogeneic hematopoietic stem cell transplantation (HSCT). However, little is known about its incidence, strategies for ophthalmic surveillance, and timely implementation of adequate antiviral treatment in pediatric allogeneic HSCT recipients. We provide a retrospective analysis of the epidemiology and clinical features of CMVR in pediatric allogeneic HSCT patients transplanted at our center over a 16-year period. Two patients of this cohort with leukemia are presented. Our analysis is supplemented by a systematic review on pediatric patients with leukemia and CMVR in the setting of allogeneic HSCT. The overall incidence of CMVR in our cohort was 1% (4/338) and 14.2% (3/21) in leukemic patients. In published cases, CMVR occurred at a median of 143 days after transplantation, and, in the majority of patients, was preceded by CMV detection in blood by a median of 93 days. Continued immune suppression following engraftment likely triggers CMVR. Preemptive treatment with ganciclovir as standard is usually successful. Foscarnet is used in case of resistance to ganciclovir or drug-induced granulocytopenia. Overall, CMVR after HSCT in pediatric leukemic patients is rare, but a potentially higher vulnerability of this population for involvement of the eye warrants a standardized ophthalmological examination plan.

Attitudes and Knowledge Regarding Postmortem Cornea Donation among Young and Elderly People in Germany: Sufficient for Decision Making?

OBJECTIVES: To evaluate the knowledge of and attitudes toward postmortem cornea donation in living young and elderly potential donors in a German city. METHOD: High-school students and seniors participated in a nonrandomized prospective survey focusing on willingness to donate corneas postmortem and factors that might influence underlying specific attitudes. Statistical analysis was descriptive and included logistic regression. RESULTS: The survey showed that 73.3% of the high-school students and 41.6% of the seniors, 53.2% of whom had already signed an advanced medical directive, felt insufficiently informed about donation. High-school students were significantly less willing to donate their corneas postmortem (p < 0.001), and fewer of them possessed a donor card (p < 0.001). High-school students specified the internet as their favored source of information about donation in 82.7% of cases, while the family physician was the first preference for 47.8% of the seniors. CONCLUSIONS: The willingness to donate and the proportion of donor card ownership were significantly lower in the high-school students than among the seniors, corresponding to their respective knowledge in matters of donation. Young people should be systematically informed about cornea donation at school, as soon as they reach the legal minimum age for donation, and primary-care physicians should provide relevant information to every new patient to aid their decision making concerning postmortem cornea donation.

[Expression of Motion Artifacts in OCT-Angiography Imaging in Healthy Subjects Using Two Different Devices]. / Vergleich der Bildqualität zweier unterschiedlicher OCT-Angiografie-Systeme mit Fokus auf Bewegungsartefakten bei gesunden Probanden.

BACKGROUND: To compare the expression of motion artifacts in optical coherence tomography angiography (OCT-A) in healthy subjects using two different devices. METHODS: In this study, 25 eyes of 25 healthy volunteers with no history of any ocular disease or ocular surgery were included. OCT-A imaging was performed using the RTVue XR Avanti (Optovue Inc., Fremont, California, USA) and the Spectralis OCT-A (Heidelberg Engineering, Heidelberg, Deutschland). The macula was imaged twice in each proband with active eye tracking (ET) using a 3 × 3 mm2 or a 10 × 10° scan, respectively. The expression of motion artifact was analyzed by two independent readers in the superficial OCT-angiogram using the Motion Artifact Score (MAS). RESULTS: The signal strength index (SSI) was 73.0 ± 7.8 (Optovue) and 39.6 ± 3.6 (Heidelberg), which is equivalent to 73.0% (Optovue SSImax = 100 = 100%) and 79.2% (SSImax = 50 = 100%) of the maximum quality score. Both devices showed a very good image quality (mean MAS Optovue: 1.32 ± 0.551, mean MAS Heidelberg: 1.7 ± 0.789, p = 0.006). Of all measurements, quilting/banding was found in 20% of Optovue patients (10/50) and 6% of Heidelberg patients (3/50). Stretching was found in 4% of Optovue patients (2/50) and in 6% of Heidelberg patients (3/50). Vessel doubling was only seen in one Optovue angiogram (2%) as well as a displacement (2%). Blink lines only existed in three Heidelberg angiograms (6%). CONCLUSION: Despite different software and hardware approaches, both devices were able to take high-quality images with a very low prevalence of motion artifacts. Nevertheless, these artifacts still also occur in healthy subjects with good fixation. With regards to MAS, there was a high agreement between the two readers. However, the analysis of artifacts remains complex and requires experience as well as a precise assessment in evaluating OCT-A images.

[Treatment Options for Adenoid Cystic Lacrimal Gland Carcinoma - A Case Series and Literature Review]. / Therapieoptionen bei adenoidzystischem Tränendrüsenkarzinom ­ Fallserie und aktueller Literaturüberblick.

Adenoid cystic carcinoma of the lacrimal gland (ACC) is a rare malignant orbital tumour with a poor overall prognosis. Current therapeutic approaches like radical and local surgery, adjuvant radiation and neoadjuvant intra-arterial chemotherapy are controversial. We present three cases of patients with ACC with different therapy concepts and discuss these with current recommendations from the literature.

Serum Clara cell protein and atopic phenotype in children up to 2 years of age.

BACKGROUND: Low value of serum Clara cell protein (CC16) is associated with bronchial hyperreactivity in children. OBJECTIVE: To evaluate the serum CC16 in relation to atopy and previously manifested LRTD. METHODS: In the population of 163 healthy 5- to 24-month-old children, atopy was determined by Phadiatop-infant (serum-specific IgE≥0.35 kUA/L), serum CC16 by ELISA, while data on previously manifested low respiratory tract diseases (LRTD) were collected from the Health Care Center database. RESULTS: In atopic children, serum CC16 negatively correlated with age (r -.281, P=.041, n=53), while in nonatopic children, this correlation was positive (r .200, P=.036, n=110). Atopic ≥8-month-old children with previously manifested LRTD had lower level of CC16 (3.07 ng/mL) in relation to atopic children without LRTD at the same age (6.51 ng/mL), P=.029 (value of serum CC16≥4.8 ng/mL indicates atopic phenotype without LRTD 75% sensitivity, 87.5% specificity). In 8- to 24-month-old children with previously manifested pneumonia, serum CC16 was lower in atopic (2.9 ng/mL) in relation to nonatopic children (3.7 ng/mL), P=.029 (serum CC16 ≤3.4 ng/mL indicating atopy in the group of children with pneumonia, sensitivity 100%, and specificity 77%). Atopic 8- to 24-month-old children with previously manifested pneumonia had lower CC16 in relation to other atopic children in this age (P=.021) (for cutoff CC16≤3.4 ng/mL sensitivity 100%, specificity 77%), and also often chronic wheezing (atopic with pneumonia 83.3%, n=5/6 vs atopic without pneumonia 21.4%, n=3/14), P=.018. CONCLUSION: Low serum CC16 is associated with previously expressed pneumonia and chronic wheezing in atopic children.

Epidemiology of Suicidal Behaviour in Shumadia District, Serbia: a Fifteen-year Retrospective Study.

OBJECTIVE: The purpose of this study is to analyze epidemiological characteristics of suicide, as well as to emphasize possible risk factors. METHODS: This is a retrospective study, covering the period of fifteen years (1996-2010), which aims at discovering the relevant factors which have an influence on suicidal behaviour. This research uses the data from the documentation of the Ministry of Internal Affairs of Serbia and Police Department in Kragujevac, hospitalization reports of patients treated at Psychiatric Clinic of the Clinical Centre Kragujevac, as well as the medical records of patients treated at the Health Centre Kragujevac. χ2 test was applied to examine the influence of all selected factors on incidence of suicide and for this purpose SPSS statistical software package was used. RESULTS: The analysis has shown that during the given period average suicide rate reached 11.8 per population of 100,000. The male to female suicide ratio of 3.6:1 obtained through this study suggests that men (78.4%) are more prone to suicide than women (21.6%). The highest number of suicides has been found within the age group of 65-year-olds (31.2%), while for the youngest age group (15-24 years) the lowest prevalence of 8.8% has been determined. In other words, the youngest subjects are 3.5 times less likely to commit suicide than the participants of the oldest age group. During the given period suicide was most often committed by married males and females with primary school education than by employed and retired people. The research has also revealed that most suicides came from urban areas (52.0%) and that the most common method of suicide is hanging (60.8%), followed by suicide by firearms, jumping from height, poisoning, and drowning. CONCLUSION: In order to prevent suicide, it is essential to collect and analyze all information concerning suicide victims.

Microvascular Density Analysis of Patients with Inactive Systemic Lupus Erythematosus-A Two-Year Follow-Up Optical Coherence Tomography Angiography Study.

Background/Objectives: This study aims to investigate the long-term effect of inactive systemic lupus erythematosus (SLE) on the retinal microcirculation measured via optical coherence tomography angiography (OCT-A). Methods: Twenty-four eyes of 24 patients with inactive SLE under hydroxychloroquine (HCQ) therapy were included. The OCT-A data (mainly vessel density (VD) and foveal avascular zone (FAZ) data of the superficial and of the deep capillary plexus (SCP, DCP) and the choriocapillaris (CC)) were analyzed and compared between the baseline examination (t0) and 2 years later (t1). Results: At t1, VD in the whole en face SCP and in the CC was notably reduced compared to t0 (SCP: p = 0.001, CC: p = 0.013). VD in the DCP, CRT and FAZ area showed no difference at t1 compared to t0 (DCP: p = 0.128, FAZ: p = 0.332, CRT fovea: p = 0.296). Correlation analysis between the increase in cumulative doses of HCQ between t0 and t1 and the VD of the whole en face SCP did not show any correlation (Spearman r = 0.062 (95% CI -0.367; 0.477). Conclusions: SLE patients demonstrated a decrease in the retinal VD of the SCP and CC over a 2-year period. There was no correlation with the change in cumulative doses of HCQ. These results suggest an ongoing effect of the disease on the retinal and choriocapillary microcirculation.

Evaluation of Ocular Perfusion in Patients with End-Stage Renal Disease Receiving Hemodialysis Using Optical Coherence Tomography Angiography.

Hemodialysis (HD) is known to affect ocular blood flow. This case-control study aims to evaluate macular and peripapillary vasculature in patients with end-stage renal disease (ESRD) receiving HD in comparison to matched controls. A total of 24 eyes of 24 ESRD patients receiving HD and 24 eyes of 24 healthy, age- and gender-matched control subjects were prospectively included in this study. Optical coherence tomography angiography was used to image the superficial (SCP), deep (DCP), and choriocapillary (CC) macular vascular plexus, as well as the radial peripapillary capillaries (RPC) of the optic disc. In addition, retinal thickness (RT) and retinal volume (RV) were compared between both groups. Flow density (FD) values of each retinal layer and data of parameters related to the foveal avascular zone (FAZ), as well as RT and RV, were analyzed using Mann-Whitney U tests. There was no significant difference in FAZ parameters between the two groups. Whole en face FD of the SCP and CC was noticeably reduced in the HD group in comparison to the control group. FD was negatively correlated with the duration of HD treatment. RT and RV were significantly smaller in the study group than in controls. Retinal microcirculation appears altered in patients with ESRD undergoing HD. Concurrently, the DCP appears more resilient towards hemodynamic changes in comparison to the other microvascular retinal layers. OCTA is a useful, non-invasive tool to investigate retinal microcirculation in ESRD patients.

Nasolacrimal intubation in transcanalicular endoscopic dacryoplasty: a long-term follow-up study.

Nowadays, transcanalicular endoscopic dacryoplasty represents the majority of lacrimal duct surgery procedures performed in adults in specialised centers. However, there are still hardly any data available regarding the intra- and postoperative care, particularly regarding the duration of silicone tube intubation (STI). Our aim was to evaluate the relation between tube duration and recurrence of symptoms in patients who underwent transcanalicular microdrill dacryoplasty (MDP) in a long-term setting. Medical records of 576 adult patients after MDP were retrospectively reviewed. A total of 256 eyes of 191 patients could be included. The median follow-up time was 7.83 [7.08; 9.25] years. In 57.0% of the cases there was still full resolution of symptoms at the time of the survey. The median duration of the STI was 6 [3.00; 6:00] months. When distinguishing between a tube duration < 3 months and ≥ 3 months there was a significant difference in the long-term success rate (< 3 months: 38%; ≥ 3 months: 61%; p = 0.011). In conclusion, an early removal of the STI (< 3 months) after transcanalicular MDP seems to be associated with a higher incidence of recurrence of symptoms. This should be considered in the intra- and postoperative care of patients following this minimally invasive first-step procedure.

The first reported case of a deletion of the entire RPGR gene in a family with X-linked retinitis pigmentosa.

Clinical phenotypes of a patient with a deletion of the entire RPGR gene have not been described in the literature yet. We hereby report a new mutation in a family of X-linked retinitis pigmentosa (×lRP), showing the deletion of the entire RPGR gene. Gene therapy for inherited retinal diseases holds great promise; however, so far there has been no approved treatment of RPGR-mediated retinitis pigmentosa. The presented evidence of genotype-phenotype correlation may be useful for genetic diagnosis or even genetic treatment in the near future.