[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.

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.

[Regression of idiopathic epiretinal membrane-Case report and consideration of the possible mechanism]. / Regression einer idiopathischen epiretinalen Gliose ­ Kasuistik und Überlegungen zum Mechanismus.

In the presence of a symptomatic epiretinal gliosis, pars plana vitrectomy with membrane peeling to remove the membrane is usually indicated in clinical practice. According to common clinical experience, almost no independent regression of such an epiretinal membrane and thus healing of the pathology alone exists. Therefore, the unusual case of bilateral independent regression of idiopathic epiretinal gliosis and formation of a lamellar macular hole in a 73-year-old male patient is described. Considerations of the possible mechanism are presented based on the existing literature. These include separation of inflammatory versus noninflammatory membranes, possible separation of individual layers depending on the status of the posterior vitreous limiting membrane and also the possible action of proteolytic systems in the posterior vitreous region. Finally, the question arises, whether patients have to be informed about this fact before possible surgery.

[Work sampling in ophthalmological clinical studies. A multicenter field study]. / Zeiterfassung in ophthalmologischen klinischen Studien. Eine multizentrische Feldstudie.

BACKGROUND: Work in clinical studies is generally more elaborate and therefore more time-consuming in comparison to the clinical routine. The purpose of this study was to systematically investigate the time consumption in the German ophthalmological clinical trial centers. METHODS: The members of the working group of the German Ophthalmology Society clinical study centers (Arbeitsgemeinschaft DOG Klinische Studienzentren) were asked to fill in three questionnaires about best estimations for the time spent on study-related procedures and administration. Additionally, work sampling was performed for each employee at each study center over a period of 3 weeks. RESULTS: The questionnaires were completed by 9 of the 11 centers. Overall, 5504 working hours were recorded. On an average working day, the time spent for both documentation and administration averaged 4 h each. Operative interventions consumed a significant amount of time (2.8 h), as did ophthalmological examinations (2.5 h) and obtaining informed consent (1.5 h). The recorded time consumption for visual acuity testing, informed consent and documentation was well aligned with the best estimates of the three questionnaires. By contrast, interventions, ophthalmological examinations and biomaterial sample handling were underrated in the best estimations. DISCUSSION: A considerable amount of time in clinical studies is spent on documentation and administration. From work sampling, ophthalmological examinations and biomaterial sampling turned out to be surprisingly time consuming. This is probably due to preparation and postprocessing tasks. It is important to consider this when calculating the overall costs of a clinical study. In addition, many administrative activities cannot be attributed to specific patients and can therefore not be compensated on the basis of case payments alone. Additional remuneration is required to fully cover the costs in an ophthalmological study center.

[Oral anticoagulation : Current overview and perioperative management in ophthalmic surgery]. / Orale Antikoagulation : Aktuelle Übersicht und perioperatives Management in der Ophthalmochirurgie.

Antithrombotic treatment with oral anticoagulants and antiplatelet agents can increase the risk for perioperative bleeding. In contrast to other surgical fields, the optimal perioperative management in ophthalmic surgery has not yet been exactly defined and, thus, is not standardized. In this contribution, we provide an overview of currently available oral anticoagulants and discuss potential strategies for the management of these agents in different ophthalmic surgical procedures.

[Does the micropulse laser have an effect on chronic CSC?] / Hat der Mikropulslaser bei chronischer CCS einen Effekt?

INTRODUCTION: Central serous chorioretinopathy (CSC) is the fourth most common cause of vision loss without an evidence-based treatment recommendation. A positive effect of micropulse laser (MPL) treatment has been described in the literature in recent years. This study aimed to reappraise these results in a patient population with chronic CSC. METHODS: Patients suffering from chronic CSC with a source point detectable in fluorescein angiography (longer than 3 months duration and unresponsive to treatment with eplerenone and carbonic anhydrase inhibitors) were identified and included in this prospective and consecutive case study. Patients were controlled with a yellow laser (577 nm) after 6 weeks, 12 weeks and then every 3 months. RESULTS: A total of 28 patients were included (28 eyes). The mean duration of anamnesis was 444 days (90-1412 days) and the mean duration of the observation period after MPL was 257 days (42-909 days). The foveal retinal thickness measured 351.7 ± 82.4 µm before, compared to 253.6 ± 86.48 µm after MPL (mean of all patients over the whole observation period). Visual acuity was 0.33 ± 0.21 logMAR prior to MPL and 0.30 ± 0.22 logMAR posttreatment. Of the patients two underwent a second MPL and three patients underwent photodynamic treatment (PDT) after insufficient clinical improvement and were consequently excluded from the study. CONCLUSION: Retinal thickness in this patient population with chronic CSC was significantly reduced after MPL treatment with no significant changes of visual acuity. No side effects of MPL were observed. Larger studies including control groups are warranted to quantify the effects of MPL further.

[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.

[Management of anticoagulants in ophthalmic surgery-a survey among ophthalmic surgeons in Germany]. / Umgang mit gerinnungshemmenden Substanzen in der Ophthalmochirurgie ­ eine Umfrage unter Ophthalmochirurgen in Deutschland.

INTRODUCTION: As our population ages and comorbidities rise, ophthalmic surgeons are increasingly faced with patients on anticoagulant therapy or with clotting disorders. The ophthalmic surgeon has to weigh the perioperative risk of haemorrhage when anticoagulation continues against the risk of thromboembolism caused by discontinuation or changing the patient's medication (bridging, switching, cessation). There are currently no guidelines or recommendations. METHODS: A survey was sent to the DOG (German Ophthalmologic Society) divisions and associated surgical organizations to determine the status quo. A questionnaire was sent out and filled out by the different groups of specialists. RESULTS: All four divisions of the DOG and four associated organizations returned completed questionnaires. Surgical interventions were listed that are carried out during anticoagulant therapy without exceptions, as well as interventions that were classified to require medical adjustment. Although the assessments varied, general consensus was achieved regarding interventions not requiring adjustments due to anticoagulants (i. e., intravitreal injection, cataract surgery, laser and corneal operations, simple muscle surgery), and those interventions requiring adjustments in medications (glaucoma operations, complex retina surgery, eye socket surgery, complex surgery of the lid). CONCLUSION: Main result of this survey was the specification of serious bleeding complications which are permanent vision loss and re-operation. They could serve as endpoint parameters for essential future investigations. Nevertheless, this survey makes clear that the decision about an adjustment of anticoagulant medication in ophthalmic surgery is currently made individually and not based on established standards.

[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.

[Buckling Surgery: Old Fashioned or Cutting Edge?] / Buckelchirurgie: Old Fashion oder Cutting Edge?

For many decades, scleral buckling surgery was the only reasonable surgical procedure in eyes with primary rhegmatogenous retinal detachment. In recent years, primary vitrectomy has apparently become the treatment of choice, although evidence from comparative clinical trials is missing. In this article, data from clinical trials and indications for buckling surgery are presented.

[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.

[Retinal artery occlusion]. / Retinaler Arterienverschluss.

Retinal artery occlusion leads to profound visual impairment in the affected eye. It is rarely caused by local ophthalmic pathologies. Most patients present with a large number of cardio- and cerebrovascular risk factors. Visual loss is the leading symptom in central retinal artery occlusion (CRAO), whereas a circumscribed visual field defect is claimed in branch retinal artery occlusion (BRAO). Although many attempts have been made to improve the course of the disease, no effective therapy is available. There is some hope that intravenous fibrinolysis could influence the natural course but the therapeutic window is small (ca. 4.5 h), and treatment efficacy is still not proven. It is important for ophthalmologists to guide the patients to a comprehensive and prompt neurological and cardiological diagnostic work-up.

Demographics of patients receiving Intravitreal anti-VEGF treatment in real-world practice: healthcare research data versus randomized controlled trials.

BACKGROUND: While randomized controlled trials (RCTs) are based on strict inclusion/exclusion criteria, non-interventional studies (NISs) might provide additional information to guide management in patients more representative to the real-world setting. The aim of this study was to compare baseline characteristics of patients receiving intravitreal treatment in the NIS OCEAN with those from published RCTs. METHODS: The ongoing OCEAN study enrolled patients treated with ranibizumab for neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DME) or branch/central retinal vein occlusion (B/CRVO). Baseline patient characteristics were compared by indication within the OCEAN cohort. Furthermore, the characteristics were set in reference to those of published RCTs in the same indications. Confidence intervals (CIs) were calculated and assessed for statistically significant differences as indicated by non-overlapping CIs. RESULTS: Patient characteristics in the NIS OCEAN were evaluated for 3,614 patients with nAMD, 1,211 with DME, 204 with BRVO and 121 with CRVO. Between these groups, significant differences in mean age, gender distributions, and mean baseline VA were seen, reflecting known differences between the indications. Compared to the patient characteristics of published RCTs (trials selected by literature search: nAMD: 13 RCTs, DME: 9, RVO: 5), the OCEAN patients' mean age was significantly higher in every indication. The gender distributions across the trials were comparable, with only few differences between OCEAN and the RCTs. Regarding the mean baseline VA, notable differences were found in nAMD and in DME, with VA significantly higher in some RCTs and lower in others. CONCLUSIONS: The described differences underline the complementarity of NISs and RCTs. OCEAN covers a broader spectrum and more variability of patients than do RCTs. As baseline values may have impact on the treatment response (ceiling effect), there is an ongoing need for research in all patient subgroups. Country-specific assessments of patient populations can better reflect the real-world situation. NISs can deliver insights that RCTs may not, as NISs can include non-typical patients, patients with comorbidities, a broader age spectrum and patients of various disease stages. TRIAL REGISTRATION: The NIS OCEAN was registered on www.clinicaltrials.gov (identifier: NCT02194803 ).

[Optic disc pit-associated maculopathy and iris-retinochoroidal-coloboma - a rare combination]. / Kranenburg-Syndrom und Iris-Netzhaut-Aderhaut-Kolobom ­ eine seltene Kombination.

Kranenburg's syndrome is defined as central serous detachment associated with an optic disc pit. We report the interesting and very seldom combination of Kranenburg's syndrome and iris-retinochoroidal-coloboma. Reattachment was achieved after vitrectomy, peeling of epiretinal membranes, laser coagulation adjacent and temporal to the optic disc and gas endotamponade. Coincidence of this syndrome with an iris-retinochoroidal-coloboma is extremely rare. Both coloboma and optic disc pit are based on closure defects during week 6 of embryogenesis.

[Platelet aggregation inhibitors and anticoagulants during ophthalmic interventions]. / Thrombozytenaggregationshemmer und Antikoagulantien bei augenchirurgischen Eingriffen.

In ophthalmology many patients undergo surgical treatment who need to take anticoagulant medication due to cardiovascular diseases. The proper handling of these drugs requires both correct assessment of the risk of thromboembolism as well as the rating of the risk of surgery-related hemorrhages. While there are established recommendations for estimation of the risk of thromboembolism based on a large body of prospective randomized trials, data regarding the evaluation of the related complications secondary to ophthalmic surgery are limited. In comparison to other surgical procedures, most interventions in ophthalmic surgery tend to have a relatively low risk of bleeding; therefore, in general there is no need to convert or discontinue anticoagulant drugs in patients undergoing opthalmic surgery. The sparse data available justifying the abrupt termination of anticoagulation are contrary to the approach currently widely distributed in clinical practice. This overview covers the relevant knowledge of the perioperative use of anticoagulant drugs. In addition, the data on the risk of hemorrhage in ophthalmological procedures are presented and discussed.