[Efficiency and Therapy Safety of Fractionated Cyclophotocoagulation with up to Ten Laser Spots for Advanced Primary Open-Angle and Pseudoexfoliation Glaucoma]. / Effektivität und Therapiesicherheit der fraktionierten Zyklophotokoagulation mit bis zu 10 Herden für fortgeschrittene primäre Offenwinkel- und Pseudoexfoliationsglaukome.

BACKGROUND: Various procedures are available for the treatment of advanced glaucoma. We examined the efficacy and safety of fractionated cyclophotocoagulation (CPC) with up to ten laser spots for advanced primary open-angle glaucoma (POAG) and pseudoexfoliation (PEX) glaucoma treated with maximal topical therapy or eye-drop intolerance. MATERIAL UND METHODS: This retrospective study evaluated data from 297 eyes with advanced POAG and PEX glaucoma which received 10 applications of CPC between February 2012 and June 2017. Intraocular pressure (IOP), number of topical eye drops and postoperative complications were evaluated. Data were collected preoperatively, four weeks postoperatively, and at the last documented contact (six months postoperative visit). The paired Wilcoxon rank sum test was used to analyse the changes. RESULTS: The IOP for open-angle glaucoma decreased from 16.66 ± 4.36 mmHg preoperatively to 13.87 ± 3.59 mmHg at the last visit (6 months postoperative visit; p < 0.05). The IOP for the PEX glaucoma decreased significantly from 20.76 ± 9.55 mmHg preoperatively to 15.50 ± 5.93 mmHg at the last visit (p < 0.003). The number of hypotensive agents in the POAG was 2.51 ± 1.00 preoperatively and at the last visit 2.27 ± 1.03. In PEX glaucoma, the number of hypotensive agents was 2.46 ± 1.07 preoperatively and at the last visit 1.88 ± 0.97. Treatment-related complications occurred in three eyes - two cases of postoperative macular oedema, which were treated well with systemic steroids, and one case of pretreated anterior chamber irritation with hyphema, which was also treated with topical steroids. CONCLUSION: In our group of patients, the mild CPC performed by us with a maximum of 10 applications (vs. the conventional 20 - 30 applications) produced a good reduction of intraocular pressure, as well as a reduction in topical medication, with a low complication rate.

Early REperfusion therapy with intravenous alteplase for recovery of VISION in acute central retinal artery occlusion (REVISION): Study protocol of a phase III trial.

RATIONALE: Meta-analyses of case series of non-arteritic central retinal artery occlusion (CRAO) indicate beneficial effects of intravenous thrombolysis when initiated early after symptom onset. Randomized data are lacking to address this question. AIMS: The REperfusion therapy with intravenous alteplase for recovery of VISION in acute central retinal artery occlusion (REVISION) investigates intravenous alteplase within 4.5 h of monocular vision loss due to acute CRAO. METHODS: This study is the randomized (1:1), double-blind, placebo-controlled, multicenter adaptive phase III trial. STUDY OUTCOMES: Primary outcome is functional recovery to normal or mildly impaired vision in the affected eye defined as best-corrected visual acuity of the Logarithm of the Minimum Angle of Resolution of 0.5 or less at 30 days (intention-to-treat analysis). Secondary efficacy outcomes include modified Rankin Score at 90 days and quality of life. Safety outcomes include symptomatic intracranial hemorrhage, major bleeding (International Society on Thrombosis and Haemostasis definition) and mortality. Exploratory analyses of optical coherence tomography/angiography, ultrasound and magnetic resonance imaging (MRI) biomarkers will be conducted. SAMPLE SIZE: Using an adaptive design with interim analysis at 120 patients, up to 422 participants (211 per arm) would be needed for 80% power (one-sided alpha = 0.025) to detect a difference of 15%, assuming functional recovery rates of 10% in the placebo arm and 25% in the alteplase arm. DISCUSSION: By enrolling patients within 4.5 h of CRAO onset, REVISION uses insights from meta-analyses of CRAO case series and randomized thrombolysis trials in acute ischemic stroke. Increased rates of early reperfusion and good neurological outcomes in stroke may translate to CRAO with its similar pathophysiology. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04965038; EU Trial Number: 2023-507388-21-00.

[Use of antiglaucomatous drugs in the urban adult population : New Insights into the prevalence of glaucoma from the Hamburg City Health Study]. / Anwendung von Antiglaukomatosa in der urbanen erwachsenen Bevölkerung : Erkenntnisse zur Glaukomprävalenz aus der Hamburg City Health Study.

BACKGROUND: Glaucoma is a widespread ophthalmological disease. Knowledge about the spread of the disease in the population is necessary with respect to further questions on comorbidities, risk factors and the provision of care. OBJECTIVE: An analysis of the use of glaucoma medications and the prevalence of glaucoma in an urban adult population was carried out. MATERIAL AND METHODS: The Hamburg City Health Study (HCHS) is a prospective, long-term, population-based cohort study that includes a random sample of 45,000 participants aged between 45 and 79 years from the general population of Hamburg, Germany. Apart from various medical parameters, data include premedication and the medical history of the participants. The use of antiglaucomatous medication among the first 10,000 study participants was analyzed and the prevalence of glaucoma was estimated according to the use of medications as well as by the self-reported history of glaucoma. Descriptive analysis and logistic regression analysis were performed to analyze the data and to calculate correlations by age and gender. RESULTS: In the study population 319 persons were on medication to lower the intraocular pressure (IOP, mean age 67.1 years, SD = 7.57 years), which is equivalent to an estimated prevalence of 3.35% (95% confidence interval, CI 3.00-3.70%). A positive correlation was observed between age and the use of IOP-lowering medication, which is statistically highly significant (p = < 0.001). The analysis by gender showed a slightly higher prevalence among women, which was not statistically significant. The estimated prevalence according to glaucoma medication and history were only partly congruent. DISCUSSION: This estimated prevalence of glaucoma is comparable to other epidemiological studies. The study results cover not only patients with manifest glaucoma but also persons who were treated for ocular hypertension. The inconsistency between the prevalence of glaucoma medication and the diagnosis of glaucoma can be explained by different treatment strategies and also by information deficits.

Central retinal artery occlusion - detection score.

Purpose: To investigate the sensitivity and specificity of central retinal artery occlusion (CRAO)-Detection Score in diagnosing CRAO via questionnaire and without fundoscopy. Methods: This prospective study enrolled 176 emergency patients suffering from acute visual loss, of whom 38 were suffering from CRAO. Before conducting any examination, we administered our questionnaire containing six questions, followed by a thorough ophthalmologic examination to make the diagnosis. Statistical analysis involved a LASSO penalised multivariate logistic regression model. Results: Our receiver operating characteristic (ROC) analysis based on a LASSO penalised multivariate logistic regression model showed an area under the curve (AUC) of 0.9 - three out of six questions were selected by LASSO. Interestingly, the unweighted ROC analysis of only two questions (Short CRAO-Detection Score) yielded similar results with an AUC of 0.88. The short CRAO-Detection Score of 2 yielded 14% (4/28) false positive patients. Conclusion: This prospective study demonstrates that a high percentage of CRAO patients are detectable with a questionnaire. The CRAO-Detection Score might be used to triage patients suffering acute visual loss, which is important as intravenous fibrinolysis seem to be time-dependent to be effective.

Inner Retinal Layer Hyperreflectivity Is an Early Biomarker for Acute Central Retinal Artery Occlusion.

Purpose: To investigate inner retinal hyperreflectivity on optical coherence tomography (OCT) as a potential biomarker indicating acute central retinal artery occlusion (CRAO). Methods: A total of 56 patients at two university hospitals with acute CRAO (symptom onset ≤48 h) were included in this retrospective study. The optical intensity of the inner retinal layers was determined in both eyes and the relationship between symptom onset and inner retinal layer optical intensity in OCT scans compared to the unaffected fellow eye was analyzed. Several differential diagnoses [central retinal vein occlusion, anterior ischemic optic neuropathy, diabetic macular edema, and subretinal fibrosis/disciform scar (Junius-Kuhnt)] served as controls to validate optical intensity-based diagnosis of CRAO. Results: CRAO strongly correlated with an increased inner retinal layer hyperreflectivity in this cohort with acute CRAO with a time since symptom onset ranging from 1.1 to 48.0 h. Receiver operating characteristic (ROC) analysis showed an area under the curve of 0.99 to confirm CRAO with a true positive rate of 0.93 and a false positive rate of 0.02. No correlation between optical intensity and time since symptom onset was noticeable. None of the differential diagnoses did show an elevated optical intensity of the inner retinal layers as it was detectable in CRAO. Conclusion: OCT-based determination of inner retinal layer hyperreflectivity is a very promising biomarker for a prompt diagnosis of CRAO in an emergency setting. This may be of major interest to speed up the administration of a possible thrombolytic treatment.

Surgical management of submacular hemorrhage due to n-AMD: a comparison of three surgical methods.

BACKGROUND: To compare and assess the efficacy of three surgical methods for the treatment of acute submacular hemorrhage (ASH): pneumatic displacement with C2F6, in combination with intravitreal injection of bevacizumab and rtPA, pars plana vitrectomy (PPV) with intravitreal injection of gas (C2F6), bevacizumab and subretinal injection of recombinant tissue plasminogen activator (rtPA), pars plana vitrectomy (PPV) with intravitreal injection of gas (C2F6), bevacizumab and intravitreal injection of recombinant tissue plasminogen activator (rtPA). METHODS: The study included 85 patients with ASH. In the group without PPV (A), patients were treated with intravitreal injection of C2F6, bevacizumab and rtPA. In the second and third group, patients underwent a PPV, intravitreal injection of bevacizumab, pneumatic displacement with C2F6 and a subretinal (B) or intravitreal (C) injection of recombinant tissue plasminogen activator (rt PA). RESULTS: In group A, mean BCVA increased from preop logMAR 1.41 to 1.05, in group B from 1.46 to 1.28 and in group C from 1.63 to 1.33. In group A, CFT changed from 764 ± 340 µm at time point 0 to 246 ± 153 µm at time point 1, in group B from 987 ± 441 µm to 294 ± 166 µm and in group C from 642 ± 322 µm to 418 ± 364 µm. Patients had an average of 5 injections after surgery. CONCLUSION: Our study demonstrates that the three methods are equally effective in improving the morphology and the BCVA of patients with ASH.

Locally Ablative Radiation Therapy of a Primary Human Small Cell Lung Cancer Tumor Decreases the Number of Spontaneous Metastases in Two Xenograft Models.

PURPOSE: To investigated the influence of radiation therapy (RT), surgery (OP), radio-chemotherapy (RChT), or chemotherapy (ChT) on small cell lung cancer metastases in 2 xenograft models. METHODS AND MATERIALS: A total of 1 × 106 human small cell lung cancer cells (OH1, H69) were subcutaneously injected into severe combined immunodeficiency mice to form a local primary tumor node at the lower trunk. Radiation therapy, OP, RChT, or ChT were started after development of palpable tumors. Chemotherapy was given as a single intraperitoneal injection of cisplatin. Radiation therapy was 5 × 10 Gy on the local tumor node. Two additional groups were implemented to assess primary tumors and distant metastases in untreated mice at the beginning (control group A) and at the end of the experiment (control group B). Proapoptotic, antiproliferative, antiangiogenic, and hypoxic effects were assessed by Feulgen, Ki67, S1P1 receptor, and hypoxia-inducible factor 1α staining, respectively. Quantitative Alu-polymerase chain reaction was used to determine circulating tumor cells in the blood, and disseminated tumor cells in the lungs, bone marrow, liver, and brain. RESULTS: In both xenograft models, RT and RChT abrogated local tumor growth, indicated by increased apoptosis, decreased cell proliferation, and reduced microvessel density (equally affecting vessels of all diameters). Regarding metastases, RT and RChT not only counteracted the time-dependent increase of dissemination but also decreased the metastatic load pre-existing at therapy induction in the blood, lungs, and liver. Only in the case of relapse-free surgery could similar effects be achieved by OP. CONCLUSIONS: Our models provide evidence that RT and RChT ablate the primary tumor and inhibit metastasis development over time. Upon local recurrence, RT showed beneficial effects compared with OP with regard to suppression of circulating tumor cells and disseminated tumor cells.

Design, performance characteristics and application examples of a new 4D motion platform.

In this publication, a three-dimensionally movable motion phantom is described and its performance characteristics are evaluated. The intended primary fields of application for the phantom are the quality assurance (QA) of respiratory motion management devices in radiation therapy (RT) like gating or tumour tracking systems, training for clinical use of these techniques, and related 4DRT research. Considering especially the QA aspect, the phantom was designed as a motion platform that can be equipped with an appropriate add-on like standard QA phantoms for dosimetric measurements. The platform is driven by three computer-controlled independent linear motors (motion range: 40 × 50 × 50 mm in anterior-posterior/superior-inferior/lateral direction; max. velocity: 3.9 m/s; max. acceleration: 10 m/s(2)), which allow the simulation of normal breathing patterns as well as arbitrary trajectories and anomalous events like coughing or baseline drift. For normal breathing patterns (here: sinusoidal curves with an amplitude of 20mm and a period of 3 s/6 s), the accuracy of the simulated motion paths was measured to be within 0,521 mm even for the ArcCHECK (weight: 20 kg) as a platform load - values that we consider to be sufficient for the intended fields of application. The respective use of the motion phantom is illustrated.

Partial body irradiation of small laboratory animals with an industrial X-ray tube.

AIMS: Dedicated precise small laboratory animal irradiation sources are needed for basic cancer research and to meet this need expensive high precision radiation devices have been developed. To avoid such expenses a cost efficient way is presented to construct a device for partial body irradiation of small laboratory animals by adding specific components to an industrial X-ray tube. METHODS AND MATERIALS: A custom made radiation field tube was added to an industrial 200 kV X-ray tube. A light field display as well as a monitor ionization chamber were implemented. The field size can rapidly be changed by individual inserts of MCP96 that are used for secondary collimation of the beam. Depth dose curves and cross sectional profiles were determined with the use of a custom made water phantom. More components like positioning lasers, a custom made treatment couch, and a commercial isoflurane anesthesia unit were added to complete the system. RESULTS: With the accessories described secondary small field sizes down to 10 by 10 mm2 (secondary collimator size) could be achieved. The dosimetry of the beam was constructed like those for conventional stereotactical clinical linear accelerators. The water phantom created showed an accuracy of 1 mm and was well suited for all measurements. With the anesthesia unit attached to the custom made treatment couch the system is ideal for the radiation treatment of small laboratory animals like mice. CONCLUSION: It was feasible to shrink the field size of an industrial X-ray tube from whole animal irradiation to precise partial body irradiation of small laboratory animals. Even smaller secondary collimator sizes than 10 by 10 mm2 are feasible with adequate secondary collimator inserts. Our custom made water phantom was well suited for the basic dosimetry of the X-ray tube.