[Prospective noninterventional BLUE SKY study evaluating the efficacy of brolucizumab in treatment-naïve and previously treated patients with neovascular AMD]. / Prospektive nichtinterventionelle BLUE SKY-Studie zur Beurteilung der Wirksamkeit von Brolucizumab bei unbehandelten und vorbehandelten Patienten mit neovaskulärer AMD.

Intravitreal injection of anti-vascular endothelial growth factor (VEGF) is the standard treatment for patients with neovascular age-related macular degeneration (nAMD). In addition to the approved substances ranibizumab (Lucentis®, Novartis) and aflibercept (Eylea®, Bayer), bevacizumab (Avastin®, Roche) is also available. Furthermore, brolucizumab (Beovu®, Novartis) has been approved and has been available in Germany since April 2020. The multicenter, noninterventional prospective BLUE SKY study investigates brolucizumab treatment with different schemes in 600 treatment-naive and pretreated nAMD patients in routine clinical practice over a 24-month period. Besides general patient data, visual acuity and treatment data will be documented. Fluorescein angiography, fundus photography, spectral domain optical coherence tomography and swept-source optical coherence tomography angiography will be performed and analyzed by reading centers. The focus of the analysis will be on the intraretinal and subretinal fluid distribution as well as morphological MNV changes and injection frequency. Also, safety and adverse drug effects of brolucizumab, with a specific focus on inflammatory complications, particularly retinal (occlusive) vasculitis will be evaluated.

[Retinal manifestation in hematological diseases]. / Retinabeteiligung bei hämatologischen Erkrankungen.

Hematological diseases can lead to ocular manifestations. Retinal manifestation occurs in patients with anemia, leukemia, lymphoma, myeloproliferative and myelodysplastic syndromes. It is not uncommon for the ocular findings to be the first manifestation of the systemic disease. In these patients the correct diagnosis can be difficult because as a rule the retinal involvement is unspecific. In cases of unexplained retinal changes with hemorrhage and cotton wool spots, an underlying hematological disease should be suspected and the appropriate diagnostics should be recommended.

[Ultra-widefield angiography for retinal vein occlusion : How large is large enough?] / Ultraweitwinkelangiographie beim retinalen Venenverschluss : Wie groß ist groß genug?

BACKGROUND: The introduction of full fundus angiography (FAG) for retinal vein occlusion (RVO) has enriched diagnostic imaging; however, it is unclear how much of the retina has to be visualized to evaluate the risk of neovascularization. We investigated the 102° Spectralis camera to assess if imaging beyond the central 102° is necessary. METHODS: In this retrospective study we assessed 80 eyes of 80 patients with RVO to analyze central and peripheral ischemia using the ultra-widefield 102° Spectralis camera. The standard viewer software was used to delineate ischemic areas (IA) and to measure the amount of pixels of IA in correlation to the total amount of pixels in the peripheral image. RESULTS: Among the 80 eyes with RVO there were 51 eyes with ischemic areas (central and/or peripheral), of which IA could be detected in 49 eyes by analyzing a fovea-centered FAG image. The average IA in these 51 eyes was 23.5% of the total image area and 53.7% of disc areas, respectively. DISCUSSION: A fovea-centered FAG image with a 102° angle appears to be sufficient to determine the clinically relevant extent of IA. Old recommendations and imaging methods should be rethought. The 102° Spectralis camera provides a clinically suitable, fast and exact method which might replace old methods to describe and document the extent of ischemia by disc areas.

[Diagnostic Approaches to Suspected Choroidal Melanoma]. / Diagnostisches Vorgehen bei Verdacht auf Aderhautmelanom.

Whenever funduscopy reveals possible choroidal melanoma, all available information must be gathered to either confirm or exclude the diagnosis. Well-defined funduscopic criteria are available, which can already lead to a high degree of diagnostic certainty. Additional technical examinations can be used to exclude possible differential diagnoses. In cases where no clear diagnosis can be established, it is possible to take a biopsy or to watch and wait in order to observe possible growth. Whenever the diagnosis of a choroidal melanoma is established, cancer staging has to be performed in order to search for possible metastases.

High-throughput screening of antibiotic-resistant bacteria in picodroplets.

The prevalence of clinically-relevant bacterial strains resistant to current antibiotic therapies is increasing and has been recognized as a major health threat. For example, multidrug-resistant tuberculosis and methicillin-resistant Staphylococcus aureus are of global concern. Novel methodologies are needed to identify new targets or novel compounds unaffected by pre-existing resistance mechanisms. Recently, water-in-oil picodroplets have been used as an alternative to conventional high-throughput methods, especially for phenotypic screening. Here we demonstrate a novel microfluidic-based picodroplet platform which enables high-throughput assessment and isolation of antibiotic-resistant bacteria in a label-free manner. As a proof-of-concept, the system was used to isolate fusidic acid-resistant mutants and estimate the frequency of resistance among a population of Escherichia coli (strain HS151). This approach can be used for rapid screening of rare antibiotic-resistant mutants to help identify novel compound/target pairs.

Experimental system design for the integration of trapped-ion and superconducting qubit systems.

We present a design for the experimental integration of ion trapping and superconducting qubit systems as a step towards the realization of a quantum hybrid system. The scheme addresses two key difficulties in realizing such a system: a combined microfabricated ion trap and superconducting qubit architecture, and the experimental infrastructure to facilitate both technologies. Developing upon work by Kielpinski et al. (Phys Rev Lett 108(13):130504, 2012. doi:10.1103/PhysRevLett.108.130504), we describe the design, simulation and fabrication process for a microfabricated ion trap capable of coupling an ion to a superconducting microwave LC circuit with a coupling strength in the tens of kHz. We also describe existing difficulties in combining the experimental infrastructure of an ion trapping set-up into a dilution refrigerator with superconducting qubits and present solutions that can be immediately implemented using current technology.

Does ocriplasmin affect the RPE-photoreceptor adhesion in macular holes?

BACKGROUND: To evaluate the anatomical outcome of patients after vitrectomy due to persisting symptomatic vitreomacular traction (VMT), including full-thickness macular holes (FTMHs) of less than 400 µm, after ocriplasmin treatment. METHODS: Retrospective, single centre, consecutive interventional case series. Patients were treated with a single intravitreal injection of ocriplasmin (Jetrea, Thrombogenics Inc, USA, Alcon/Novartis EU). MAIN OUTCOME MEASURES: resolution of VMT, closure of FTMH and anatomical outcome of vitrectomy after unsuccessful treatment with ocriplasmin. RESULTS: Five patients were treated with ocriplasmin injection. VMT persisted in all but one case. Four patients underwent pars-plana vitrectomy (PPV) for treatment of persistent VMT and FTMH (n=2, size of macular hole <400 µm) in spectral-domain optical coherence tomography (SD-OCT). FTMHs were closed in both cases within the first week postoperatively. After PPV, in three eyes newly developed subretinal fluid was detected, which persisted up to several months postoperatively. CONCLUSIONS: Data on ocriplasmin remain controversial. We report on four cases with resolution of VMT following PPV after unsuccessful ocriplasmin treatment. Newly developed subretinal fluid has been described after ocriplasmin treatment, predominantly in cases with resolution of VMT. We also detected this newly developed subretinal fluid after vitrectomy, which persisted for several weeks up to 7 months in two cases with FTMHs. This may be attributable to loosening of the photoreceptor complex due to enzyme activity of ocriplasmin. Long-term effects of ocriplasmin are still to be evaluated using SD-OCT.

[Intravitreal treatment of patients with branch retinal vein occlusion depending on the duration of macular edema]. / Behandlung der Patienten mit einem Venenastverschluss in Abhängigkeit von der Verschlussdauer.

PURPOSE: The aim of this study was to evaluate the effects of intravitreal treatment with bevacizumab (IVB) compared with triamcinolone (IVT) in patients with macular edema due to branch retinal vein occlusion (BRVO) depending on the duration of BRVO. METHODS: A total of 65 BRVO patients were divided into 2 subgroups: group 1 with early treatment (≤ 3 months since onset of BRVO) and group 2 with late treatment (> 3 months since onset). For the two groups IVB was injected into 17 eyes as early (IVB1) and into 18 eyes as late (IVB2) treatment. For comparison IVT was injected into 14 eyes as early (IVT1) and into 16 eyes as late (IVT2) treatment. Best corrected visual acuity (BCVA) and central retinal thickness (CRT) were analyzed at baseline, 1, 3 and 6 months after treatment. RESULTS: In both subgroups a significant improvement of BCVA and CRwas observed. After 6 months, for patients with early treatment, IVB1 showed better results than IVT1 (BCVA: p = 0.008, CRT: p = 0.021). In the late treatment no significant differences between IVT2 and IVB2 were found. CONCLUSIONS: Bevacizumab and triamcinolone significantly improved BCVA and CRT in patients with BRVO. The best BCVA was found if bevacizumab was used as early treatment. In the late treatment no significant differences between bevacizumab and triamcinolone were observed.

[Contemporary possibilities of artificial vision in blind patients using artificial neuro-prosthesis--review]. / Soucasné moznosti náhrady vid6ení nevidomých pacientü pomocí arteficiálních neuroprotéz.

The authors present the knowledge summarization of vision substitute using artificial retinal neuroprostheses. The overview was compiled from available literature found in the Medline and Embase databases. The text focuses on global summarizing of the whole issue since the beginning of the development to the state up to date. In individual types of neuroprostheses, the advantages, disadvantages, and possible obstacles to their use in clinical practice are discussed. Furthermore, the brain plasticity and functional changes of the brain in blinds are considered. The aim of the review is not to present all information in detail, but complex overview with relevant literature sources.

Retinal vein thrombosis: pathogenesis and management.

Retinal vein occlusion (RVO) is the most common retinal vascular disease after diabetic retinopathy. Owing to its multifactorial nature, however, management of this condition remains a challenge. Of the two main types of RVO, branch retinal vein occlusion (BRVO) is more prevalent than central retinal vein occlusion (CRVO). Most patients develop the disease at an elderly age, and more than half of them have associated systemic disorders (e.g. hypertension, hyperlipidemia and/or diabetes mellitus). There is no evidence to suggest routine testing for heritable thrombophilias in patients with RVO. The main cause of the visual impairment is macular edema, while neovascularization of the retina and optic disc are the most serious complications leading to vitreous hemorrhage, retinal detachment and neovascular glaucoma. Macular grid laser photocoagulation is an effective treatment for macular edema in patients with BRVO and a visual acuity of 20/40 or less. Other treatment options for reducing the edema are intravitreal steroids, anti-VEGF drugs and vitrectomy. The recently introduced intravitreal application of steroids and anti-VEGF drugs may prove to be a better approach for improving visual acuity. Finally, scatter panretinal laserphotocoagulation can effectively treat neovascularization and its secondary complications.

[Antiphospholipid syndrome and retinal vein occlusion. Meta-analysis of Published Studies]. / Antiphospholipidsyndrom und retinale venöse Verschlüsse. Metaanalyse publizierter Studien.

The role of antiphospholipid syndrome (APS) in the pathogenesis of retinal vein occlusion has been discussed for several years. Conflicting results of the published studies are caused by small numbers of investigated patients and lack of control groups. We performed a meta-analysis of all case-control studies published up to July 2007 that investigated the prevalence of APS according to current diagnostic criteria for this syndrome.The results of meta-analysis show a significantly higher prevalence of APS in patients with retinal vein occlusion compared with controls. Patients with APS are treated with anticoagulants to reduce the risk of recurrence of thrombosis. Therefore, screening for APS seems to be indicated in all patients with retinal vein occlusion, and, in the case of a positive result, initiation of anticoagulation. For patients with retinal vein occlusion with APS, no data are currently available regarding the recurrence of thrombosis. To give a clear recommendation, a prospective randomized study is required to investigate the benefit of anticoagulation.

[The intravitreal application of the tissue plasminogen activator in the treatment of submacular hemorrhage--a case report]. / Intravitreální aplikace tkánového aktivátoru plazminogenu v lécbe submakulární hemoragie--kazuistika.

The authors present the possibility to influence therapeutically the submacular hemorrhage caused by age-related macular degeneration in the presence of choroidal neovascular membrane by means of recombinant plasminogen tissue activator (rt-PA) and expansive gas intravitreal injection followed by pneumatic relocation of the hemorrhage out of the foveolar region. The therapy is presented in a case report. The submacular hemorrhage without treatment causes serious decrease of visual functions. The human recombinant plasminogen tissue activator that is a glycoprotein, activating the transformation of plasminogen directly to plasmin has a trombolytic effect. Rt-PA is activated by binding to fibrin with high affinity. This minimally invasive procedure gives the possibility to treat this prognostic unfavorable finding, so after the lysis and pneumorelocation of the hemorrhage from the macular region we can treat the choroidal neovascular membrane.

[Disturbances of the plasma coagulation defects in retinal venous occlusions]. / Poruchy hemokoagulacní kaskády u retinálních venózních okluzí.

Occlusions of retinal veins (central and branch) represent multifactorialy-conditioned disease involving presumably older patients, in whom the changes of retinal vessels caused by hypertension and atherosclerosis present the most important pathophysiological factors for development of this disease. In last years, the intensive scientific research is focused to the explanation of the role of the defects of the coagulations cascade. Especially in younger patients, the most often mentioned defect of the coagulations cascade is called as APC-resistance. Up to 95% of all patients with APC-resistance are carriers of so called Leiden mutation. The aim of our study was to establish the prevalence of the ACP-resistance in 92 patients with central or branch occlusion of the retinal vein verified by means of angiography treated at the Department of Ophthalmology, Faculty Hospital, Olomouc, Czech Republic, EU, during the period 1999-2005. The control group consisted of 40 patients without any vascular, eye-related disease. In the group of patients with occlusion of the retinal vein, the prevalence of the APC-resistance was 10.9% and in the control group 5%. In the group of patients 55 years old and younger the prevalence of the ACP-resistance was 14.3%, in patients older than 55 years it was 5.6%. According to the relatively small groups of patients, the established difference did not reach the level of statistical evidence. Results of our study confirmed the conclusions of previously published papers that the prevalence of the APC-resistance is not significantly higher in patients with retinal vein occlusion according to the prevalence in controls.

[Primary vitrectomy with intravitreal antibiotic application in postoperative and posttraumatic endophthalmitis]. / Primární vitrektomie s intravitreální aplikací antibiotik u pooperacních a posttraumatických endoftalmitid.

AIM: The aim of our study was to evaluate the results of the treatment of postoperative and posttraumatic endophthalmitis by means of primary vitrectomy with intravitreal antibiotic application. METHODS: In 42 patients treated for postoperative and posttraumatic endophthalmitis during the period January 2000-March 2006 at the University Department of Ophthalmology in Leipzig, Germany, EU, the postoperative visual acuity was followed-up. Furthermore, the results of microbial cultivation of the vitreous sample and the correlation between the final visual acuity and the causing etiological agent were evaluated. The treatment of endophthalmitis in 39 patients consisted of the primary vitrectomy with intravitreal antibiotics application; in three patients, solely the intravitreal injection of antibiotics was performed. In all patients, the antibiotics were administered locally and intravenously as well. The postoperative follow-up period lasted between 2 weeks to 24 months (median, 4.5 months). RESULTS: The cause of endophthalmitis was in 31 (73%) patients the cataract surgery or secondary implantation of the intraocular lens; and in 4 (10%) patients the previous pars plana vitrectomy was performed. In 2 patients (5%) the endophthalmitis developed after trabeculectomy and in 5 (21%) patients, the endophthalmitis followed after perforating eye trauma. By means of microbiological cultivation, the agent was proved in 20 patients. The most common cause of endophthalmitis was Staphylococcus epidermidis. The postoperative improvement of the visual acuity we noticed in 39 patients. The final visual acuity better than 1/50 was reached by 88% of patients, thereof in 52% we proved at the end of the follow-up period the visual acuity better than 0.5. CONCLUSION: The primary vitrectomy with intravitreal application of antibiotics combining with local as well as intravenous applications of antibiotics is a successful method of endophthalmitis treatment; in our study, in 88% of patients, the partial (orientational) vision was maintained.

[Lutein and antioxidants in the prevention of age-related macular degeneration]. / Lutein und Antioxidantien zur Prävention der AMD.

Demographic developments in Europe and North America are causing an increase of age-related diseases. Age-related macular degeneration (AMD) is one of the leading causes of severe central visual acuity loss in elderly people and seems to be an economic problem, too. There is evidence that oxidative damage is an important factor for exacerbation of AMD. Macular pigment with its antioxidative effect may serve as"natural sunglasses" filtering the blue light acting as a possible source of photooxidative damage to the neurosensory retina. The macular pigment consists mostly of lutein and zeaxanthin. These micronutrients from the group of carotenoids, as is the case for vitamins (vitamins C, E, and beta-carotene), cannot be synthesized in mammals and that is the reason why the role of micronutrition or its supplementation and its correlation to AMD progression has been discussed for years. The results of currently published studies are often contradictory. At present there are no results from randomized controlled studies confirming that supplementation of lutein and zeaxanthin can reduce the risk for AMD. Several epidemiological studies investigating the impact of antioxidants and omega-3 fatty acids on the incidence of AMD provided conflicting results.Up to now, AREDS is the largest randomized controlled study investigating the effect of supplementation of antioxidants, zinc, and copper on the progression of AMD. AREDS showed a significant effect of this supplementation in some particular groups of patients with AMD. The supplementation of lutein and omega-3 fatty acids is not toxic but a positive effect has not been proven by randomized studies.

[Transcorneal and transscleral iontophoresis of the dexamethasone phosphate into the rabbit eye]. / Transkorneá1na a transsklerálna ionoforéza dexametazón fosfátu do oka králika.

PURPOSE: To evaluate the efficiency of the dexamethasone phosphate penetration into the rabbit eye after transcorneal and transscleral iontophoresis using a drug loaded hydrogel assembled on a portable iontophoretic Mini Ion device. METHODS: lontophoresis of dexamethasone phosphate was studied in healthy rabbits using drug-loaded disposable HEMA hydrogel sponges and portable iontophoretic device. Corneal iontophoretic administration was performed with electric current of 1 mAmp for 1, 2, and 4 min. In the control group, the dexamethasone was applied in drops into the conjunctival sac. Transconjunctival and transscleral iontophoresis were performed in the pars plana area, through the conjunctiva or directly on the sclera. Dexamethasone concentrations were assayed using HPLC method. To study the anatomical changes after iontophoresis application, histological examinations of corneas excised 5 minutes and 8 hours after the procedure were performed. RESULTS: Dexamethasone levels in the rabbits' corneas after a single transcorneal iontophoresis were up to 38 times higher compared to those obtained after topical eye drops instillation. High drug concentrations were obtained in the retina and sclera 4 hours after transscleral iontophoresis as well. There were no statistically significant differences in the drug concentration after transscleral and tranconjunctival iontophoresis. Histological examination of the corneas after the iontophoresis showed only discrete reversible changes of the epithelium and the stroma. CONCLUSION: A short, low-current, non-invasive iontophoretic treatment using the dexamethasone-loaded hydrogels has a potential clinical value in increasing the drug's penetration into the anterior and posterior segment of the eye.

[Primary vitrectomy with intraocular antibiotic application in postoperative endophthalmitis]. / Primäre vitrektomie mit intraokularer antibiotikaapplikation bei akuter postoperativer endophthalmitis.

PURPOSE: Pars plana vitrectomy with intravitreal antibiotic application is an established procedure for treating postoperative endophthalmitis. The presented study analyzes our own results with this treatment as well as the role of adjuvant systemic steroid treatment. METHOD: We analyzed the data of 34 consecutive patients with postoperative endophthalmitis from January 2000 to March 2006. Thirty-two patients underwent vitrectomy and intravitreal application of antibiotics, and two patients received intravitreal antibiotics only. All patients received intravitreal dexamethasone and systemic antibiotics, and 12 patients received the systemic treatment with prednisolone. The effect of vitrectomy with respect to final visual acuity and the rate of postoperative complications were analyzed. The vitreous was microbiologically examined. Postoperative follow-up time ranged from 2 weeks to 24 months. RESULTS: Endophthalmitis followed cataract surgery with intraocular lens implantation in 30 patients (89%) and followed pars plana vitrectomy in four patients (11%). Positive cultures were obtained in 19 (56%) patients. Visual acuity improved in 31 (91%) patients. At their final examinations, 27 (79%) patients had gained visual acuity of 0.05 or better. CONCLUSION: Immediate vitrectomy in combination with intraocular antibiotics and steroid administration resulted in preservation of ambulatory vision in most of the patients. Systemic postoperative therapy with steroids seems to be associated with better final visual acuity.

[Functional examination of retinal vessels in patients with central retinal vein occlusion]. / Funkcní vysetrení retinálních cév u pacientu s okluzí centrální sítnicové zíly.

Retina vessel analyzer (RVA) provides the functional examination of retinal vessels based on the analysis of the extent (size) of their dilation and constriction. The RVA measures continuously on-line the diameter of retinal arteries and veins after different kind of stimulation. Beyond dynamic vessel analysis, another possibility of the RVA's utilization is a static vessel assessment, measuring the arterial and venous diameter ratio (A/V ratio), which provides the information about the rate of arterial vasoconstriction. The aim of the presented study was to investigate static and dynamic retinal vessel changes in patients with central retinal vein occlusion (Group 1). The second investigated group consists of patients with arterial hypertension; as a control group, healthy persons without any vascular disease were examined. Altogether 40 eyes were examined. Statistically significant differences of A/V ratio were observed in the static vessel analysis in all three investigated groups. The dynamic analysis showed statistically significant differences in arterial dilatation and constriction between all investigated groups as well. The presented results confirm that the degree of retinal vessels endothelial dysfunction is one of the determinating ethiopathological factors of central retinal vein occlusion.

[Orbital apex syndrome of the aspergillus etiology--a case report]. / Syndrom orbitálního hrotu aspergilové etiologie--kazuistika.

The authors present a case report of a patient, in whom after a head injury the monolateral blindness occurred. Because of autoimmune thrombocytopeny the patient was treated with long-term corticosteroids. The clinical findings corresponded with the orbital apex syndrome. According to the results of the CT and MRI examinations, the sphenoidotomy was indicated, and the histological findings verified fragments of paranasal sinuses' aspergiloma. During the next course of the disease, despite antimycotic therapy, the progression of the aspergiloma in to the anterior cranial fossa occurred. Invasive sino-orbital aspergilosis, after the penetration of the infectious agent across the wall of the sinus, may cause the orbital apex syndrome with paralysis of all three cranial nerves innervating the extraocular muscles, sensoric defect in the area of the ophthalmic nerve and the involvement of the optic nerve.