[Spectrum of firework injuries at a university eye clinic after the COVID-19 lockdown]. / Spektrum von Feuerwerksverletzungen an einer Universitäts-Augenklinik nach dem COVID-19-Lockdown.

BACKGROUND: The handling of fireworks regularly leads to a variety of injuries affecting the periocular region. Due to the COVID-19 lockdown and a sales ban on consumer fireworks for the private sector the number of injuries massively decreased; however, a considerable increase was registered again at the last New Year festivities. The aim of this work was to present the extent and spectrum of such injuries in a maximum care center. METHODS: As part of the nationwide survey of firework-associated eye injuries in emergency care eye clinics and hospitals, data from the MHH Eye Hospital in Hannover were compiled over the period of 3 days (30.12.2022-01.01.2023) and evaluated with respect to gender, age, severity, injury pattern, type of fireworks and treatment. RESULTS: Of a total of n = 25 injured patients, n = 19 (76%) were male. Most patients presented on New Year's Day (n = 14, New Year's Eve: n = 9; 30.12.2022: n = 2), with the majority of cases presenting with mild injuries with irritation and erosion of the ocular surface (n = 15; 60%). Of the patients four sustained moderate to severe injuries with bulbar contusion, hyphema, and sometimes iris base tears (16%). Of the patients six suffered severe, mainly open, eye injuries (24%), two of which required primary evisceration. Ignition of fireworks batteries revealed the highest risk of serious injury, affecting mainly males 31-40 years of age. Children up to 12 years of age generally sustained only minor injuries, although there were exceptions as there were among adolescents. The person who caused the fireworks injury was affected in about 52% of the cases; in 48% the victim of the accident was a bystander. In cases of complex injuries, under certain conditions only surgical exploratory diagnostics could lead to the correct diagnosis and best possible care. CONCLUSION: The extent of firework injuries is manifold and the consequences including blindness are considerable. The burden on physicians on duty on New Year's Eve and New Year's Day was enormous, as with the permission of private fireworks a large number of patients had to be cared for via the emergency room, some of whom required complex surgical care. To prevent serious eye injuries, targeted education about the risks of private fireworks and possibilities to increase safety should be intensified.

Clinical characteristics of gyrate atrophy compared with a gyrate atrophy-like retinal phenotype.

INTRODUCTION: Gyrate atrophy (GA) is a rare retinal dystrophy due to biallelic pathogenic variants in the ornithine aminotransferase (OAT) gene, causing a 10-fold increase in plasma ornithine levels. It is characterized by circular patches of chorioretinal atrophy. However, a GA-like retinal phenotype (GALRP) without elevated ornithine levels has also been reported. The aim of this study is to compare the clinical characteristics of GA and GALRP and to identify possible discriminators. METHODS: A multicenter, retrospective chart review was performed at three German referral centres on patient records between 01/01/2009 and 31/12/2021. Records were screened for patients affected by GA or GALRP. Only patients with examination results for plasma ornithine levels and / or genetic testing of the OAT gene were included. Further clinical data was gathered where available. RESULTS: Ten patients (5 female) were included in the analysis. Three suffered from GA, while seven had a GALRP. Mean age (± SD) at onset of symptoms was 12.3 (± 3.5) years for GA compared with 46.7 (± 14.0) years for GALRP patients (p = 0.002). Mean degree of myopia was higher in GA (-8.0 dpt. ± 3.6) compared to GALRP patients (-3.8 dpt. ± 4.8, p = 0.04). Interestingly, all GA patients showed macular oedema, while only one GALRP patient did. Only one patient with GALRP had a positive family history, while two were immunosuppressed. DISCUSSION: Age of onset, refraction and presence of macular cystoid cavities appear to be discriminators between GA and GALRP. GALRP may encompass both genetic and non-genetic subtypes.

[Photodynamic therapy in Germany-Quo vadis?] / Photodynamische Therapie in Deutschland ­ Quo vadis?

BACKGROUND: Photodynamic therapy (PDT) was originally approved for the treatment of neovascular age-related macular degeneration (nAMD) and secondary choroidal neovascularization in myopia (mCNV). In addition, it is used as an off-label treatment in patients with choroidal hemangioma, polypoidal choroidal vasculopathy (PCV), and central serous chorioretinopathy (CSC). OBJECTIVE: To track the development of PDT treatment numbers in Germany between 2006 and 2021 and to investigate the composition of the therapeutic indications. METHODS: In this retrospective study the quality reports of German hospitals were evaluated in the period from 2006 to 2019 and the number of PDTs performed was recorded. In addition, the range of indications for PDT was determined exemplarily for the Eye Center at Medical Center, University of Freiburg and the Eye Center at St. Franziskus Hospital in Münster between 2006 and 2021. Finally, the estimated prevalence of CSC and an estimate of cases requiring treatment were used to calculate the number of patients in need of PDT treatment in Germany. RESULTS: The number of PDTs performed in Germany decreased from 1072 in 2006 to 202 in 2019. While PDT was used in 86% of cases in patients with nAMD and in 7% of cases with mCNV in 2006, it was mainly performed in patients with CSC (70%) and choroidal hemangiomas (21%) from 2016 to 2021. With an estimated incidence of CSC of 1:10,000 and assuming that 16% of patients develop chronic CCS requiring treatment, approximately 1330 PDTs would need to be performed per year in Germany for patients with newly diagnosed chronic CSC alone. CONCLUSION: The decreasing numbers of PDT treatment performed in Germany is mainly due to a change to intravitreal injections as the preferred treatment for nAMD and mCNV. As PDT is currently the recommended treatment of choice for chronic CSC, an underprovision of PDT in Germany can be assumed. To enable an appropriate treatment for patients, a reliable verteporfin production, a simplified approval process by health insurance companies and a close cooperation between ophthalmologists in private practice and larger centers are urgently needed.

A randomized, open-label, multicenter study of switching to brolucizumab with or without a loading dose for patients with suboptimal anatomically controlled neovascular age-related macular degeneration-the FALCON study.

BACKGROUND: Treatment initiation with brolucizumab, a new potent anti-vascular endothelial growth factor (VEGF) agent, is typically performed with three monthly injections (loading dose) and has been well studied in treatment-naïve patients. However, no clinical data are available yet on whether or not anti-VEGF pretreated patients also benefit from a loading dose. In the clinical setting, different heterogeneous treatment patterns are used as no clinical trial has addressed this so far in a head-to-head comparison. Therefore, the FALCON study is investigating whether patients with unsatisfactory response to previous anti-VEGF treatments benefit from a loading dose at the switch to brolucizumab treatment. METHODS: FALCON is a 52-week, two-arm, randomized, open-label, multicenter, multinational study in patients with residually active neovascular age-related macular degeneration (nAMD) who will be randomized 1:1 and started with brolucizumab 6 mg loading (three monthly loading doses) or brolucizumab 6 mg non-loading (one initial injection) and consecutive treatment every 12 weeks, respectively. The primary objective is to demonstrate non-inferiority of the non-loading vs. loading arm in mean change of best-corrected visual acuity (BCVA) from baseline to the mean value at week 40 to week 52. Secondary objectives include the assessment of anatomical outcomes, treatment intervals, safety and tolerability. RESULTS: FALCON will be the first study to assess treatment initiation with an anti-VEGF agent in a switch situation with or without loading dose in patients with nAMD. CONCLUSIONS: The results will support the optimization of treatment of patients with previous unsatisfactory anti-VEGF response. Therefore, we expect to see an impact on current clinical practice which has been established for more than a decade. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04679935, date of registration-22-Dec 2020; EUDRACT number: 2019-004763-53, date of registration-03 Dec 2019.

[Experienced quality assurance in the IVOM structural contract of the AOK­BW : A practical example]. / Gelebte Qualitätssicherung im IVOM-Strukturvertrag der AOK­BW : Ein Praxisbeispiel.

BACKGROUND: According to § 73c of the Social Security Codebook V (SGB V), the AOK health insurance structural contract regulates the treatment of macular diseases by intravitreal drug administration (IVOM) in Baden-Württemberg (BW). Quality assurance is a central part of the agreement in order to ensure the high quality as well as effective and sufficient care of patients. MATERIAL AND METHODS: Every year at least 2% of the cases of the 254 currently participating surgeons are evaluated in a pseudonymized procedure by a panel of experts based on the billing data. Based on quality parameters, such as accuracy of diagnosis, quality and completeness of treatment documents and adherence to treatment pathways, the Medical Advisory Board recommends sanctions or facilitation of controls. The overall assessment of an expert opinion is based on a matrix of the evaluated quality parameters. The transmission of findings and expert opinions is digital and web based. Each surgeon has access to a comparative analysis of the quality data over time (benchmarking). RESULTS: In the first 11 quality assurance rounds, a total of 3639 expert opinions were made by a total of 20 reviewers. With respect to the quality parameter "diagnosis", the surgeon and the expert opinion differed in an average 7% of cases. Sanctions or facilitation of control by changing the sample were recommended 138 times for 80 surgeons in the first 10 quality assurance rounds. Financial sanctions or exclusion from contracts were each decided four times by the steering committee. DISCUSSION: The digital, web-based quality assurance system presented here within the framework of the IOVM structural contract of the AOK-BW should be perceived as an opportunity to classify and improve one's own quality level with respect to intravitreal treatment of retinal diseases. The current focus of quality assurance is on diagnosis and adherence to the disease-specific treatment recommendations of the professional societies. If the analysis of data could be extended to individual patient histories over time, quality assurance could be better used for questions of health services research.

[Fireworks injuries of the eye: an overview of current diagnostic and treatment options]. / Diagnostik und Akuttherapie von Augenverletzungen durch Feuerwerkskörper.

Fireworks can cause very different eye injuries. The injury patterns range from spontaneously healing conjunctival and corneal lesions up to a burst eyeball with very severe injuries in the posterior ocular section and traumatic enucleation. The precise initial diagnosis in an emergency situation can be a challenge for the ophthalmologist. Children and adolescents are often affected. The patient history with respect to the circumstances of the accident is particularly important to be able to estimate the extent of the injury and to initiate a conservative or, if necessary, emergency operative treatment. This article provides an overview of typical injury patterns and advice for the diagnostics, treatment and complication management.

[3-year results of the German nationwide survey on eye injuries caused by fireworks]. / Dreijahresergebnisse der deutschlandweiten Umfrage zu Augenverletzungen durch Feuerwerkskörper.

BACKGROUND: On festive days worldwide eyes are severely injured by fireworks. The data on the number and severity are to date not registered in Germany. OBJECTIVE: How frequent are firework-induced injuries in Germany, who are the affected, how serious are the injuries, which forms of treatment are necessary and how frequent are accompanying injuries? METHOD: A German nationwide online-based survey was carried out in all inpatient eye departments and data over the last 3 consecutive years were descriptively analyzed. RESULTS: From New Years Eve 2016/2017, when 41 eye departments sent in data, the participation could be increased to 51 eye departments in 2018/2019. More than one third (33-39%) of all 1356 patients over 3 years were minors, 60% were younger than 25 years old and roughly 60% of patients were injured as bystanders or in an unclear situation. In total 25% of all eye injuries were considered severe and required inpatient treatment. Accompanying injuries of the other eye, the face and hands were more frequent in minors than in adults. Eyeball ruptures were reported in 10 minors and 38 adults over the 3 years. CONCLUSION: Particularly minors and bystanders need better protection.

[Treatment of central serous chorioretinopathy with mineralocorticoid receptor antagonists]. / Behandlung der Chorioretinopathia centralis serosa mittels Aldosteronantagonisten.

BACKGROUND: Over 3 years have passed since the last publication on the therapeutic principle "Mineralocorticoid receptor antagonists as treatment option for acute and chronic central serous chorioretinopathy" by Maier et al., and numerous new studies have been published on the topic. The aim of this work is to provide an update on the current literature and reevaluate the role of mineralocorticoid receptor antagonists in the treatment of central serous chorioretinopathy (CSC). METHODS AND RESULTS: A computer-based literature search in PubMed yielded a total of 20 relevant articles published from 2013 to 2017, which were evaluated in terms of the effect of mineralocorticoid receptor antagonists in CSC treatment. Due to study protocol variability with different primary endpoints and follow-up periods, an in-depth comparison of the selected studies could not be performed. Moreover, the small study populations further limit their validity in this per se heterogeneous disease spectrum. Despite these limitations, current data indicate that aldosterone antagonists are effective in decreasing subretinal fluid and improving visual acuity in patients with CSC. The selective aldosterone antagonist eplerenone with a low side effect profile is a treatment option in patients with non-resolving CSC. CONCLUSION: Prospective, randomized studies with uniform disease definition and study criteria are necessary to validate the therapeutic effect and to determine the ideal time of intervention and treatment duration.

Treatment of age-related neovascular macular degeneration: the patient's perspective.

OBJECTIVES: The aim of this study was to assess patients' views and expectations with regard to neovascular age-related macular degeneration (nAMD) and intravitreal anti-VEGF therapy (IVT). METHODS: We conducted a multicenter, non-interventional, prospective cohort study including nAMD patients treated with IVT in Germany. Patients with at least one IVT before study enrollment and aged ≥50 years were included. Three telephone interviews were conducted during a 12-month observational period. Here, patient's beliefs/expectations with regard to the nAMD disease and the IVT treatment were discussed. Only patients who completed all three phone interviews were included in the analyses. We used a two-step cluster analysis to identify patient clusters regarding specific patient attitudes towards nAMD and its treatment. RESULTS: Three hundred and thirty-two patients completed all interviews (mean age of 76.4 ± 7.2 years, 59.0% women). Out of these, 57.8% acknowledged that they needed general assistance in daily life, while 77.4% stated being able to attend general medical appointments on their own. However, 64.7% needed a driver or an accompanying person to attend their IVT appointments. In addition, 3.9% of the patients were afraid of IVT side effects. Also, 87.3% and 43.1% of the patients could name their disease or the anti-VEGF drug administered, respectively. More than three-quarters of the patients (83.1%) were aware of possible consequences of nAMD by stating vision loss or blindness, but only 16.6% knew that nAMD is a chronic disease. Generally, patients were optimistic: 70.2%, 5.1% and 13.0% of them expected stable visual acuity (VA), a significant improvement or expected worsening of VA in the next year, respectively. Almost two thirds of patients who provided their therapy expectations (47.0%) anticipated fewer injections/discontinuation of IVT. We identified five patient clusters differing significantly from each other with regard to four variables: being afraid of IVT, nAMD disease awareness, optimism with regard to effectiveness of IVT, and nAMD disease and treatment knowledge. CONCLUSIONS: Only a minority of patients is aware of the chronic nature of nAMD. To motivate patients to accept a life-long IVT treatment, physicians and caregivers must know that there exist different patient types with significant differences in communication needs.

[Possibilities and Limitations of OCT-Angiography in Patients with Central Serous Chorioretinopathy]. / Möglichkeiten und Grenzen der OCT-Angiografie bei Patienten mit Chorioretinopathia centralis serosa.

Purpose Central serous chorioretinopathy (CSC) is a commonly acquired maculopathy characterized by the accumulation of subretinal fluid at the posterior pole. This study aims to analyze optical coherence tomography angiography (OCTA) findings in patients with acute and chronic CSC and to compare them to conventional imaging methods. Methods A series of 43 consecutive eyes of 29 patients diagnosed with CSC and 18 eyes of 9 healthy control subjects were included in this retrospective study. The OCTA images were assessed and compared to conventional fluorescence (FAG) and indocyanine green angiography (ICG). Results All CSC patients demonstrated abnormal areas of focal hypo- and hyperperfusion in the choriocapillaris. These were particularly evident in patients with chronic atrophic CSC. FAG and ICG imaging revealed leakage points in 10 of 43 eyes and choroidal neovascularization (CNV) in 3 of 43 eyes. OCTA imaging confirmed leakage points in 4 out of 10 cases and choroidal neovascularization in 2 out of 3 cases. In one case, OCTA demonstrated a CNV which was not detectable by FAG/ICG. Conclusion OCTA reveals areas of focal hypo- and hyperperfusion in the choriocapillaris in patients with CSC. Due to the inability to detect plasma flow, OCTA is not suitable to detect leakage points in CSC with confidence. However, OCTA reliably detects CNV in CSC even in the absence of exudative activity and may, therefore, represent an important supplement in the diagnosis of CSC.

[Prognosis and treatment of macular bleeding in neovascular age-related macular degeneration]. / Prognose und Behandlung makulärer Blutungen bei neovaskulärer altersabhängiger Makuladegeneration.

Macular bleeding is associated with an acute loss of visual function and is frequently a complication of neovascular age-related macular degeneration. Blood degradation products can lead to permanent retinal neuronal damage over time. The extent of the bleeding is correlated to the coagulation status of the patient. The treatment strategy depends on the age, size and exact location of the bleeding. The spectrum of therapeutic options ranges from watchful waiting to large scale vitrectomy with removal of subretinal mass bleeding.

[Optical Coherence Tomography Angiography in Diagnosis and Post-Treatment Assessment of Hemangioblastomas in Hippel-Lindau Disease]. / Möglichkeiten der optischen Kohärenztomografie-Angiografie bei Diagnostik und postoperativer Verlaufskontrolle von Hämangioblastomen bei Von-Hippel-Lindau-Syndrom.

Background Optical coherence tomography angiography (OCTA) offers the possibility to visualize, non-invasively, blood vessels of the retina. In vascular tumors, especially hemangioblastomas in Hippel-Lindau disease, new information can be obtained with OCTA concerning structure of the tumor, tumor activity and treatment success. Patients Ten eyes of 10 patients with retinal hemangioblastoma in Hippel-Lindau disease were included. The age of the patients ranged from 19 years to 65 years (median 44 years). Results A total of 10 active and one inactive hemangioblastomas were examined with OCTA. In larger tumors, only the superficial blood flow could be visualized. Four hemangioblastomas were not treated due to their location near the optic nerve head. Six hemangioblastomas in the peripheral retina were treated with laser photocoagulation. In 4 eyes, a reduced blood flow could be shown directly after the treatment. The visualization of the perfusion was partially blocked after laser treatment. Conclusion OCTA enables innovative methods of pre- and postoperative assessment of retinal hemangioblastomas. It has the potential to give new information about the morphology, activity and effects of treatment. Prospective studies with longer follow-up are needed to evaluate the therapeutic relevance of this new imaging method.

[Intraoperative optical coherence tomography in retinal detachment]. / Intraoperative optische Kohärenztomographie bei Ablatio retinae.

BACKGROUND: Using intraoperative optical coherence tomography (iOCT) can be advantageous during macular surgery and lamellar keratoplasty. It is yet unknown if there is a distinct benefit in its application in retinal detachment surgery. OBJECTIVE: What can be shown using iOCT during retinal detachment surgery? Can therapeutically relevant decisions be made and do they have a prognostic implication on postoperative results? METHODS: Based on already published (11 patients/eyes) and our own new data (23 patients/eyes),findings by iOCT during retinal detachment surgery are presented. RESULTS: Outer retinal corrugations are a frequent feature in iOCT in retinal detachment. These corrugations persist during the application of heavy liquids. Even when the retina seems clinically reattached under the use of perfluoroctane, there is significant subfoveal fluid. Using perfluordecaline, there seems to be less subfoveal fluid. In patients with retinal detachment and macula off situation, subclinical full thickness macular holes seem to be more common than assumed. It is unclear if their incidence is influenced by the use of heavy liquids. They appear to have a negative predictive value regarding postoperative visual acuity. CONCLUSION: Even if there are no obvious benefits in using iOCT in retinal detachment surgery, this new technique offers deeper insights into the microarchitecture of the detached retina. Further investigations in more patients will show if the use of the iOCT will result in a better prognosis for our patients.

[Intraoperative real-time OCT in macular surgery]. / Intraoperative Echtzeit-OCT in der Makulachirurgie.

BACKGROUND: Spectral domain optical coherence tomography (SD-OCT) has become a standard diagnostic tool in the surgical management of vitreomacular interface disorders. The high-resolution cross-sectional information obtained from SD-OCT is a perfect complement to vitreoretinal surgery. It provides detailed intraoperative anatomical views that are not possible with a microscope. OBJECTIVE: To investigate the value of intraoperative real-time OCT with respect to improvement of surgical techniques in the management of vitreomacular disorders. METHODS: A review of the current literature was conducted and an analysis of own systematically evaluated data was included to provide a comprehensive overview of potential applications for the clinical use of intraoperative real-time OCT in macular surgery. RESULTS: Intraoperative real-time OCT can provide detailed visualization of epiretinal membranes and help to identify whether complete membrane removal has been achieved following surgery. In addition, it can provide qualitative and quantitative information that has previously not been available and assist in surgical decision-making. Intraoperative real-time OCT allows membrane peeling to be performed in selected cases without using retinal dyes, whereas it is not ideal for accurately guiding the surgeon while performing maneuvers. CONCLUSION: Intraoperative real-time OCT provides high-resolution visualization of the effects of surgical maneuvers on the microarchitecture of the retina and surrounding tissues and will fill a gap in the understanding of the pathophysiology and prognostic factors of vitreomacular disorders; however, with currently available systems, accurate intraoperative real-time guidance of surgical maneuvers is hindered by several limiting factors.

[National guidelines for treatment of diabetic retinopathy : Second edition of the national guidelines for treatment of diabetic retinopathy]. / Nationale Versorgungsleitlinie (NVL) Diabetische Retinopathie : 2. Auflage der NVL zur Therapie der diabetischen Retinopathie.

The updated German clinical practice guidelines (second edition) describe the consensus recommendations for prevention and treatment of retinal complications secondary to diabetes. According to the updated numbers on epidemiology a further increase of persons affected is expected. The prevalence of diabetic retinopathy is estimated to be 9-16 % in type 2 diabetes and 24-27 % in type 1 diabetes. A prolongation of the screening interval from 1 to 2 years is recommended for those patients with a lower risk of progression, when retinopathy has not already occurred and no increased systemic risk factors are present. Standardized documentation forms are the foundation for improved communication between the disciplines. If diabetic retinopathy is present, control examinations follow the stipulations of the ophthalmologist. The guidelines define scenarios when the use of optical coherence tomography (OCT) is necessary, e. g. diagnosis and follow-up of macular edema. Besides focal and panretinal laser therapy, the efficacy and risks of intravitreal operative pharmacotherapy are discussed. Focal laser coagulation is recommended for therapy of macular edema without foveal involvement and for macular edema with foveal involvement patients should be informed about the effective alternative forms of treatment. Panretinal laser coagulation is recommended for first line treatment of proliferative diabetic retinopathy and is optional for severe non-proliferative retinopathy.

Vitrectomy with or without encircling band for pseudophakic retinal detachment: a multi-centre, three-arm, randomised clinical trial. VIPER Study Report No. 1--design and enrolment.

PURPOSE: Scleral buckling is currently used in addition to vitrectomy for the treatment of pseudophakic retinal detachment (PRD) to better support the vitreous base and better visualisation of the periphery. AIMS: The aims of this study are to evaluate (1) whether the combination of 20 G vitrectomy and scleral buckling is superior to 20 G vitrectomy alone (control) (confirmatory), and (2) whether transconjunctival 23/25 G vitrectomy is non-inferior to 20 G vitrectomy (both without scleral buckling) regarding operation success (exploratory). METHODS: The VIPER (Vitrectomy Plus Encircling Band Vs. Vitrectomy Alone For The Treatment Of Pseudophakic Retinal Detachment) study is an unmasked, multi-centre, three-arm randomised trial. Patients with PRD were eligible, excluding complicated retinal detachment or otherwise severe ophthalmologic impairment. Patients were randomised to one of three interventions: 20 G vitrectomy alone (control C), combination of 20 G vitrectomy and circumferential scleral buckling (experimental treatment E1) or 23/25 G vitrectomy alone (experimental treatment E2). The primary endpoint is the absence of any indication for a retina re-attaching procedure during 6 months of follow-up. Secondary endpoints include best corrected visual acuity, retina re-attaching procedures, complications and adverse events. RESULTS: From June 2011 to August 2013, 257 patients were enrolled in the study. The internet randomisation service assigned 100 patients each to the treatment arms C and E1, and 57 patients to treatment E2. The imbalance is due to the fact that several retinal surgeons did not qualify for performing E2. The random assignment was stratified and balanced (ie, 1:1 or 1:1:1 ratio) by surgeon. CONCLUSIONS: The described study represents a methodologically rigorous protocol evaluating the benefits of three different vitrectomy approaches to PRD. The projected results will help to establish their overall efficacy and will permit conclusions regarding their relative value. TRIAL REGISTRATION NUMBER: DRKS00003158 (German Clinical Trials Register, DRKS).

Intestinal microbiota contributes to individual susceptibility to alcoholic liver disease.

OBJECTIVE: There is substantial inter-individual diversity in the susceptibility of alcoholics to liver injury. Alterations of intestinal microbiota (IM) have been reported in alcoholic liver disease (ALD), but the extent to which they are merely a consequence or a cause is unknown. We aimed to demonstrate that a specific dysbiosis contributes to the development of alcoholic hepatitis (AH). DESIGN: We humanised germ-free and conventional mice using human IM transplant from alcoholic patients with or without AH. The consequences on alcohol-fed recipient mice were studied. RESULTS: A specific dysbiosis was associated with ALD severity in patients. Mice harbouring the IM from a patient with severe AH (sAH) developed more severe liver inflammation with an increased number of liver T lymphocyte subsets and Natural Killer T (NKT) lymphocytes, higher liver necrosis, greater intestinal permeability and higher translocation of bacteria than mice harbouring the IM from an alcoholic patient without AH (noAH). Similarly, CD45+ lymphocyte subsets were increased in visceral adipose tissue, and CD4(+)T and NKT lymphocytes in mesenteric lymph nodes. The IM associated with sAH and noAH could be distinguished by differences in bacterial abundance and composition. Key deleterious species were associated with sAH while the Faecalibacterium genus was associated with noAH. Ursodeoxycholic acid was more abundant in faeces from noAH mice. Additionally, in conventional mice humanised with the IM from an sAH patient, a second subsequent transfer of IM from an noAH patient improved alcohol-induced liver lesions. CONCLUSIONS: Individual susceptibility to ALD is substantially driven by IM. It may, therefore, be possible to prevent and manage ALD by IM manipulation.

Switch of anti-VEGF agents is an option for nonresponders in the treatment of AMD.

BACKGROUND: Although anti-VEGF therapy of exudative AMD with bevacizumab and ranibizumab proved efficacious in the majority of patients, CNV activity does not respond to continued treatment after repeated injections in a considerable amount of patients. These are referred to as nonresponders. A change of the drug to bevacizumab or ranibizumab could possibly offer an alternative option for the treatment of nonresponding exudative AMD. METHODS AND MATERIALS: A total of 138 nonresponders who switched therapy from bevacizumab to ranibizumab (n=114) or vice versa (n=24) were included in a retrospective study. Visual acuity (VA) and foveal thickness before and after the switch of therapy were compared. By means of linear regression analysis, we analyzed possible prognostic factors associated with a favorable outcome for visual acuity. RESULTS: Linear regression analysis revealed a statistically significant benefit for nonresponders when treatment was changed to a different anti-VEGF drug (bevacizumab or ranibizumab). VA at the time of the switch was positively correlated with a beneficial development of VA after changing the drug. There was no significant correlation with age, macular thickness, number of injections before the switch, or the development of VA under treatment before the switch. Both patients switching to Avastin and Lucentis benefitted without statistically significant differences. CONCLUSIONS: An exchange of bevacizumab with ranibizumab or vice versa should be considered in nonresponders in the treatment of exudative AMD. Further prognostic factors may help to identify patients who might benefit from a switch. These factors should be investigated in further studies.

Cathepsin proteases promote angiogenic sprouting and laser-induced choroidal neovascularisation in mice.

Cysteine cathepsins are a family of proteases involved in intracellular protein turnover and extracellular matrix degradation. Cathepsin B (Ctsb) and cathepsin Z (Ctsz) promote tumorigenesis and Ctsb is a known modulator of tumor angiogenesis. We therefore investigated the angiomodulatory function of these cathepsins in vitro as well as in a mouse model of laser-induced choroidal neovascularization (laser-CNV). Ctsb(-/-), Ctsz(-/-), Ctsb/Ctsz double-knockout (Ctsb/z DKO), and wild type (WT) mice underwent argon laser treatment to induce choroidal neovascularization (CNV). The neovascularized area was quantified individually for each lesion at 14 days after laser coagulation. In vitro the effects of cathepsin inhibitors on angiogenesis were analysed by endothelial cell (EC) spheroid sprouting and EC invadosome assays. Retinas from cathepsin KO mice did not show gross morphological abnormalities. In the laser CNV model, however, Ctsb/z DKO mice displayed a significantly reduced neovascularized area compared to WT (0.027 mm(2) vs. 0.052 mm(2); p = 0.012), while single knockouts did not differ significantly from WT. In line, VEGF-induced EC spheroid sprouting and invadosome formation were not significantly altered by a specific cathepsin B inhibitor alone, but significantly suppressed when more than one cathepsin was inhibited. Our results demonstrate that laser-CNV formation is significantly reduced in Ctsb/z DKO mice. In line, EC sprouting and invadosome formation are blunted when more than one cathepsin is inhibited in vitro. These results reveal an angiomodulatory potential of cathepsins with partial functional redundancies between different cathepsin family members.

[Pathogenesis of retinopathy of prematurity]. / Pathogenese der Frühgeborenenretinopathie.

Retinopathy of prematurity (ROP) is a complex disease with a multifactorial pathogenetic cascade that is still only partially understood. Important pathogenetic factors are gestational age at birth and birth weight. Potent postnatal factors are exposure to supplemental oxygen, slow weight gain and expression of angiogenic growth factors. Some of these crucial aspects of ROP pathogenesis will be discussed in this article and put into clinical context. With the introduction of intravitreal anti-VEGF (vascular endothelial growth factor) treatment into ROP therapy, the pathomechanistic role of VEGF in ROP deserves a special focus. Apart from VEGF, other factors will be discussed that may precede VEGF upregulation and thus may represent targets for an earlier and potentially protective intervention. Among these insulin-like growth factor 1 (IGF-1) appears to be most prominent. Finally, factors such as postnatal weight gain will be discussed in light of their potential role as screening parameters and their ability to predict ROP severity.