[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.

Human Platelets Take up Anti-VEGF Agents.

PURPOSE: Growing evidence suggests different systemic exposure of anti-vascular endothelial growth factor (anti-VEGF) agents with repeated intravitreal application. Since the penetration of anti-VEGF agents through vascular barrier was reported, the interaction of anti-VEGF with nonresident platelets has become a topic of interest. The purpose of this study was to evaluate, with the help of visualization techniques, whether platelets take up the anti-VEGF agents ranibizumab, aflibercept, and bevacizumab. METHODS: The uptake of anti-VEGF agents with or without VEGF treatment was investigated using immunofluorescence and immunogold staining in human platelets. The role of actin filaments and clathrin-coated vesicles in the transport of ranibizumab, aflibercept, and bevacizumab was evaluated by two pharmacologic inhibitors: staurosporine (protein kinase C inhibitor) and cytochalasin D. RESULTS: All three anti-VEGF agents were taken up by platelets and colocalized with VEGF. Ranibizumab and aflibercept were mainly detected in alpha-granules; however, bevacizumab was equally localized in alpha-granules and in platelet vesicles. Both staurosporine and cytochalasin D completely inhibited the uptake of aflibercept into platelets. Both pharmacological inhibitors also decreased the transport of ranibizumab and bevacizumab into platelets. Bevacizumab was significantly more frequently colocalized within clathrin-coated vesicles than ranibizumab and aflibercept. CONCLUSION: All three anti-VEGF agents are taken up by platelets and internalized in alpha-granules, which may result in a higher local exposure of anti-VEGF after the activation of platelets, potentially contributing to arterial thromboembolic events. Clathrin-coated vesicles seem to be more prominent in the transport of bevacizumab than ranibizumab and aflibercept. Nevertheless, whether the different localization and transport of bevacizumab are truly related to specific differences of receptor-mediated endocytosis has to be revealed by further research.

[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.

Influence of aflibercept on platelet activation profile.

Aflibercept appears to accumulate in systemic circulation following intravitreal injections in therapy of neovascular age-related macular degeneration. This gives raise to the question of whether aflibercept affects platelets and their function such as activation and aggregation, which are substantial in the pathogenesis of an arterial thromboembolic event (ATE). In order to determine the effect of aflibercept in platelet activation, platelets from healthy volunteers were treated with aflibercept and its solvents at equal concentrations (0.04 µg/mL - 4 µg/mL - 40 µg/mL - 400 µg/mL - 4 mg/mL) for 10 and 30 min before addition of agonists. IgG1 antibody was used as a control. The surface expression of GPIIb/IIIa, P-selectin, and platelet-bound stromal-cell-derived factor-1, which are potential blood biomarkers for ATEs, was determined on resting and activated platelets by the multispectral imaging flow cytometry, combining the features of flow cytometry with fluorescence microscopy. Platelet aggregation was assessed with light transmission aggregometry. To determine whether aflibercept directly interacts with platelets, aflibercept was labeled with the fluorescence FITC. Co-treatment of platelets with thrombin or PAR-4-AP and aflibercept resulted in increased activation of the fibrinogen receptor GPIIb/IIIa in comparison to controls (P < 0.05). Interestingly, the expression of platelet-derived P-selectin and SDF-1 was not affected by aflibercept, except thrombin-activated CD62P with 0.04 µg/mL aflibercept (aflibercept vs. its solvent: MSI = 1.54, IC = 1.201-1.879 vs. MSI = 1.37, IC = 1.136-1.604 [P = 0.031]) and SDF-1 with 4 mg/mL aflibercept (aflibercept vs. its solvent: MSI = 1.971, IC = 1.206-2.737 vs. MSI = 1.200, IC = 0.738-1.662 [P = 0.041]). Although the levels of platelet-bound aflibercept-FITC were significantly increased in all activated platelets, no effect was observed in platelet aggregation. Albeit no impact of aflibercept was found on platelet aggregation under the studied experimental conditions, the increased activation of the fibrinogen receptor GPIIb/IIIa and the presence of a direct interaction between aflibercept and platelets may partially explain the risk of ATE in patients under aflibercept treatment due to FcγRIIa mediated αIIbß3 outside-in integrin signaling and transport of aflibercept into platelets. Therefore, the Fc domain seems to be involved in interactions between aflibercept and platelets. Further research is needed to explain the role of Fc containing aflibercept in the pathogenesis of drug-associated vascular events involving platelets, coagulation cascade, extracellular matrix proteins and other cells.

[Ophthalmological health care of the institutionalized elderly : The OVIS study]. / Ophthalmologische Versorgung in Seniorenheimen : Die OVIS-Studie.

BACKGROUND: Due to demographic change and societal transformation the number of elderly persons living in retirement homes is growing in Germany. Access to health care is more complicated in the setting of nursing homes. Different regional studies suggest unmet ophthalmological health care needs in institutionalized elderly people. This study assessed the current ophthalmological health care structure and supply status in nursing homes in Germany. METHODS: This prospective, multicenter cross-sectional study was conducted by 14 study centers in Germany. Elderly people living in 32 nursing homes were included after approval by the local institutional review boards. A standardized examination was performed which included a detailed medical and ocular history, refraction, visual acuity testing, tonometry, biomicroscopy and dilated funduscopy. Unmet ophthalmological health care needs were documented and the data were analyzed descriptively and via logistic regression modelling. RESULTS: A total of 600 participants (434 women and 166 men) aged 50-104 years were examined of which 368 (61%) had ophthalmological conditions requiring treatment. The most prevalent findings were cataracts (315; 53%), disorders of the eyelids (127; 21%), dry eye disease (57; 10%) and posterior capsule opacification (43; 7%). In 63 (11%) of the participants glaucoma was suspected and 55 (9%) of the examined population had a known diagnosis of glaucoma, of whom one third was not on any or on insufficient anti-glaucomatous therapy. 236 (39%) showed signs of age-related macular degeneration (AMD). Only 52% of the examined cohort had been examined by an ophthalmologist within the last 5 years and 39% stated that they would currently not be able to consult an ophthalmologist. Reported barriers were mainly transport and lack of support. CONCLUSION: This study demonstrates considerable unmet ophthalmological health care needs of the institutionalized elderly in Germany. Novel and reformed models of specialist care provision have to be developed.

Establishment of a retinal hypoxia organ culture model.

Hypoxia plays an important role in several retinal diseases, especially in central retinal artery occlusion (CRAO). Although CRAO has been known for over a hundred years, no cure or sufficient treatment is available. Potential therapies are being evaluated in several in vivo models or primary cultures. However, in vivo models or primary cultures are very time-consuming, expensive, and furthermore several therapies or agents cannot be tested. Therefore, we aimed to develop a standardized organotypic ex vivo retinal hypoxia model. A chamber was developed in which rat retinal explants were incubated for different hypoxia durations. Afterwards, the retinas were adjusted to normal air and incubated for 24, 48 or 72 h under standard conditions. To analyze the retinal explants, and in particular the retinal ganglion cells (RGC) immunohistology, western blot and optical coherence tomography (OCT) measurements were performed. To compare our model to a standardized degeneration model, additional retinal explants were treated with 0.5 and 1 mM glutamate. Depending on hypoxia duration and incubation time, the amount of RGCs decreased and accordingly, the amount of TUNEL-positive RGCs increased. Furthermore, ß-III-tubulin expression and retinal thickness significantly decreased with longer-lasting hypoxia. The reduction of RGCs induced by 75 min of hypoxia was comparable to the one of 1 mM glutamate treatment after 24 h (20.27% versus 19.69%) and 48 h (13.41% versus 14.41%) of incubation. We successfully established a cheap, standardized, easy-to-use organotypic culture model for retinal hypoxia. We selected 75 min of hypoxia for further studies, as approximately 50% of the RGC died compared to the control group after 48 h.

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 ).

[Secondary diseases in high myopia]. / Sekundärerkrankungen bei hoher Myopie.

BACKGROUND: Eyes with high myopia (axial length ≥ 26.5 mm) do not just have a different size. Due to morphological and structural changes there is a considerably increased risk for many different secondary diseases. OBJECTIVE: Determination of the incidence and mortality in high myopia, discussion of effects and clinical signs, presentation of treatment recommendations and counselling. MATERIAL AND METHODS: A systematic search of the literature was carried out and a discussion on basic principles and epidemiological investigations is presented. RESULTS: Findings due to high myopia are not in a closed state but undergo continuous changes. Choroidal neovascularization (adjusted prevalence 2.5-5%), staphyloma, foveoschisis and peripheral retinal degeneration are examples of problems contributing to the increased rate of visual impairment and blindness related to myopia. High myopia is associated with a clearly increased risk of retinal detachment after lens surgery (hazard ratio 6.1) and particularly more frequently in younger people. The associated primary open-angle glaucoma (odds ratio 2.46) is often recognized too late due to relatively low values of intraocular pressure. CONCLUSION: Understanding of atrophic areas and staphyloma has benefited from recent advances in imaging (e.g. magnetic resonance imaging, optical coherence tomography and wide-field imaging) that complement and explain histological findings. Knowledge of the associated risk profile is of major clinical relevance.

[Regional Differences in the Care of Patients with Neovascular Age-Related Macular Degeneration, Based on the Non-Interventional OCEAN Study]. / Regionale Unterschiede in der Versorgung von Patienten mit neovaskulärer  altersabhängiger Makuladegeneration in einer nicht interventionellen Beobachtungsstudie (OCEAN).

Background: The main cause of blindness in the elderly in Germany is neovascular age-related macular degeneration (nAMD). In the non-interventional OCEAN study, data were prospectively collected on the routine clinical care of patients treated with the drug ranibizumab. Patients: As part of an interim analysis within the ongoing study (NCT02194803), stratification was performed by the 17 regions of the German associations of panel physicians and by areas of different population density. Only data were analysed for patients for whom the first treatment with ranibizumab was documented. Results: A total of 5,606 patients were documented. The present manuscript reviews 2,658 treatment-naive patients with nAMD, documented by 324 ophthalmologists. Most patients receiving an intravitreal injection were female (60 %). The average patient was aged 77.7 ± 8.2 years at study start. The great majority of patients had statutory health insurance (91 %). At baseline, fluorescein angiography (FLA) was performed for 72 % of patients, while optical coherence tomography (OCT) was carried out for 76 %. A combination of both was performed for 54 % of patients, varying regionally from 26 % (Saxony-Anhalt) to 100 % (Berlin). The average waiting time between the first examination and the first injection was 20.0 ± 18.5 days. With different statistical models (ANOVA adjusted, with/without interactions), significant effects on treatment delay were found for district type (population density), federal state and type of specialist. Conclusion: No major regional differences were observed in the demographic characteristics of the patient population. The main regional disparities in the care of nAMD patients were in the application of diagnostic methods and the waiting times between the first examination and the first drug administration. The regional variations in treatment delays could clearly influence the risk of worse functional outcome.

[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.

[Economic Short-Term Cost Model for Stereotactic Radiotherapy of Neovascular AMD]. / Ökonomisches Kostenmodell zur Radiotherapie der neovaskulären AMD.

OBJECTIVES: Stereotactic radiation therapy (Oraya, OT) is available as a second line therapy for patients who, despite intensive anti-VEGF therapy for neovascular AMD, do not show an improvement in CNV. As OT is expensive (5,308 €), the short term economics for starting this therapy were investigated. METHODS: A short-term cost model was set up in MS Excel with a two year time horizon. On the basis of the data of the randomised, controlled INTREPID pivotal trial and current treatment practice in Germany, the costs were compared of conventional anti-VEGF therapy, with or without a single OT treatment. Patients with an active lesion after initial anti-VEGF therapy and a maximum lesion diameter ≤ 4 mm were included. Modeled cost components/aspects were direct savings from injection number, control follow-up examinations and aids, as well as anti-VEGF switches. Costs for Germany were employed and a univariate sensitivity analysis was performed to address the existing uncertainty. RESULTS: For the patients with a maximum AMD lesion diameter ≤ 4 mm and a macula volume > 7.4 mm(3), the INTREPID trial showed a mean reduction of 3.68 intravitreal injections for 16 Gy radiation versus sham over a time period of 2 years. These 3.68 IVM result in ~ 4,500 € direct cost savings. Moreover, due to the higher response rate with 16 Gy radiation, the number of follow-up visits and aids can be reduced, which results in savings between 207 € and 1,224 € over 2 years. After radiation, fewer anti-VEGF switches for low or non-responders are expected, which is modeled to result in ~ 1.7 fewer injections over 2 years. Due to overall fewer injections, fewer endophthalmitis cases would be expected. However, endophthalmitis and microvascular abnormalities, which can be observed in a few cases, are associated with low or non-quantifiable costs in this cost-cost comparison model. In summary, cost reductions of between 6,400 and 8,500 € are predicted in the model over two years, which have to be compared to the costs of a single application of OT. CONCLUSIONS: The short-term economic analysis shows that anti-VEGF therapy combined with OT results in savings above the costs for OT itself over a 2 year time horizon. Overall, the approach gives potential cost reductions, if the appropriate indication is followed.

[Design of the ORCA module in the OCEAN study : Evaluation of SD-OCT results in daily routine practice]. / Design des ORCA-Moduls der OCEAN-Studie : Evaluierung der SD-OCT-Befunderhebung in der täglichen Praxisroutine.

BACKGROUND: The prevalence of blindness as defined by law could be reduced by the introduction of anti-vascular endothelial growth factor (VEGF) therapy. Because the treatment is governed by patient needs, mostly using morphological criteria, imaging diagnostics are of particular importance. The non-interventional OCEAN study investigates the treatment with ranibizumab in the clinical routine practice. In a subgroup of patients the interpretation of spectral domain optical coherence tomography (SD-OCT) scans by the treating physicians will be analyzed (ORCA module). METHODS: Over a period of 24 months data from patients with exudative age-related macular degeneration (AMD), macular edema due to retinal vein occlusion or diabetes mellitus, who are receiving intravitreal injections of ranibizumab, will be assessed. Information on examinations, visual acuity, treatment and recordings from imaging techniques will be documented using a questionnaire. The SD-OCT scans, fluorescence angiography and fundus photography will be independently analyzed by the ophthalmologist of the study center and by three reading centers (CIRCL Cologne, GRADE Bonn and M3 Münster). Automated measurements of retinal thickness by the manufacturers' software will be checked and if necessary manually corrected. A qualitative interpretation in terms of morphological criteria for (further) treatment will be performed. CONCLUSION: A thorough assessment of SD-OCT images during anti-VEGF therapy provides the basis for the best possible needs-oriented treatment regimen. The control of the quality of data from daily routine practice may indicate possible weaknesses allowing explicit training and therefore optimization of patient treatment.

[Delayed treatment initiation of more than 2 weeks. Relevance for possible gain of visual acuity after anti-VEGF therapy under real life conditions (interim analysis of the prospective OCEAN study)]. / Verzögerung des Behandlungsbeginns um mehr als 2 Wochen. Relevanz für möglichen Visusgewinn nach Anti-VEGF-Therapie unter Real-Life-Bedingungen (Interimanalyse der prospektiven OCEAN-Studie).

BACKGROUND: The largest German prospective non-interventional ophthalmological study OCEAN (NCT02194803) investigates the treatment of retinal diseases with ranibizumab in routine patient care. A feature of this study is the participation of ophthalmic surgeons in surgical centers as well as general ophthalmologists who do not perform intravitreal injections themselves. OBJECTIVES: The functional outcome following administration of three intravitreal injections was analyzed with respect to the time from initial examination to the first injection (defined as treatment delay) as well as potentially confounding factors. MATERIAL AND METHODS: This interim analysis included only data from therapy naïve patients participating in the OCEAN study, who received at least three ranibizumab injections. The potential impact of various factors on treatment delay was analyzed by the χ(2)-test. RESULTS: Data of 1333 patients were analyzed. The median delay before treatment was 15 days (range 0-90 days). Patients with a delay of more than 28 days showed a significantly lower gain in visual acuity than patients with a delay of less than 14 days. Age, gender and baseline visual acuity did not show an association with the treatment delay; however, referral from a primary care ophthalmologist, undertaking fluorescein angiography in an external practice and the underlying indications did affect the observed treatment delays. CONCLUSION: Every patient should be treated within 14 days, following recent recommendations of the ophthalmological societies. Liability issues have to be considered as the statistical evaluation of real life data showed unambiguous results.

[Retrospective investigation of anti-VEGF treatment reality and effectiveness in patients with neovascular age-related macular degeneration (AMD) in Germany: treatment reality of ranibizumab for neovascular AMD in Germany]. / Retrospektive Untersuchung der Anti-VEGF-Behandlungsrealität und Wirksamkeit bei Patienten mit neovaskulärer altersabhängiger Makuladegeneration (nAMD) in Deutschland : Behandlungsrealität von Ranibizumab bei nAMD in Deutschland.

BACKGROUND: Neovascular (wet) age-related macular degeneration (wAMD) is a progressive and degenerative retinal disease. This study reports the real-life use in Germany of the standard anti-vascular endothelial growth factor (VEGF) therapy for wAMD as an intravitreal operative drug application. PATIENTS AND METHODS: Within the framework of an international retrospective study the medical records of patients with wAMD who were first treated with ranibizumab between 1 January and 31 August 2009 were evaluated. Data were collected until the end of treatment and/or monitoring or until 31 August 2011. The primary objective was to evaluate changes in visual acuity after the start of anti-VEGF therapy. Secondary outcomes included determining real-life anti-VEGF treatment regimens and disease-monitoring practices. RESULTS: Out of 2227 patients who received ≥ 1 anti-VEGF injection with a baseline visual acuity assessment and ≥ 1 post-baseline visual acuity assessment for the treated eye, 420 were included in the German cohort. Visual acuity improved until about day 90 but these gains in visual acuity were not maintained. The mean changes in visual acuity scores from baseline to years 1 and 2 were 1.1 ± 15.7 and - 0.8 ± 17.2 letters, respectively. Patients received a mean of 4.3 ± 1.9 and 1.3 ± 2.2 injections in years 1 and 2, respectively. The majority of visits ( 98.6 %) were conducted irregularly and outside the time frame recommended at the time of the study, with an average of 47.7 ± 36.7 days between visits. More frequent visits and injections were associated with greater improvements in visual acuity. CONCLUSION: Treatment intensity was not sufficient to maintain the initial improvement in visual acuity by ranibizumab treatment. Real-life results for visual acuity and injection frequency in the German cohort were worse at that time than in other countries. Regular follow-up visits as well as timely retreatment in the presence of signs of disease activity are required to achieve optimal results in wAMD when applying a pro re nata-based strategy.

Conjunctival amyloidosis -- clinical and histopathologic features.

PURPOSE: Conjunctival amyloidosis is a rare disorder. It is often clinically not suspected or diagnosed. This study intended to demonstrate the clinical and histopathologic features of this infrequent disease, including an immunohistochemical search for amyloidotic proteins. METHODS: Retrospective case series of the clinical and histopathologic characteristics of six patients with conjunctival amyloidosis. Immunohistochemical analysis with respect to possible amyloidotic components of the conjunctival deposits was performed. RESULTS: The diagnosis of amyloidosis was not suspected in all six cases presenting with an amelanotic conjunctival lesion. In three patients a conjunctival tumor of unknown origin, in one case each a papillomatous alteration of the conjunctiva, a conjunctival granulomatous inflammation, and a lymphoma were assumed respectively. The diagnosis of amyloidosis was made by histopathology. Immunohistochemical examination found lambda and kappa light chains as well as prealbumin within the amyloid deposits in one of the six specimens. CONCLUSIONS: The diagnosis of amyloidosis has to be kept in mind in cases with an unclear conjunctival mass or inflammatory process. Only a tissue biopsy is able to prove the diagnosis. A possible underlying systemic disease has to be ruled out.

[Original preparations versus generics--latanoprost: how similar is different?]. / Originalpräparat versus Generika--Latanoprost : Wie gleich ist unterschiedlich?

BACKGROUND: To test the interchangeability of the commercially available (in Germany) latanoprost drugs and their generics respectively, the concentration of the active substance was tested. Guidelines of the European Medicines Agency postulate a sufficient bioequivalence, if the range of the agent is within 80-125% of the original drug. METHODS: All compounds of latanoprost were procured registered. The concentration of latanoprost and benzalkoniumchloride was measured by high-performance liquid chromatography (HPLC) in a validated reference labroratory for 23 generics. In addition, the mean volume of drops and the pH of the formulation were measured. The packaging label and the readability of the enclosed information leaflet were checked. RESULTS: All products contained less than 50 µg/ml latanoprost. The deviating reduction of the active substance (mean: - 7.39%, ± 2.8%) was accompanied by fluctions of the eyedrops' mass (mean: 0.03 g, ± 0.002 g). The concentration of benzalkonium chloride was mostly increased (median: 5.45%, min: - 2.5%, max: 11.5%). The pH of the original drug and the generics (median 6.78, min: 6.62, max: 6.81) was similar to the original drug, but was significantly different from an unpreserved formulation (pH 7.18). Due to type size, the packaging leaflet was illegible for humans with impaired vision. CONCLUSIONS: Before prescribing generics in ophthalmology, different factors have to be considered, which might influence the amount of IOP lowering in effect. In the absence of healthcare research it is still unclear, how different bottle forms of eyedrops--such as appearance (e.g. Cyrillic characters) or pressure point (administration)--reduce the adherence of glaucoma patients.

[Chronic central serous chorioretinopathy (cCSC): differential diagnosis to choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD)]. / Chronische RCS (chronic Central Serous Chorioretinopathy cCSC) als Differenzialdiagnose der feuchten, altersbedingten Makuladegeneration (AMD).

Central neurosensory detachments (NSD) with time-dependent height constitute a disease called central serous chorioretinopathy (CSC), if not arising from uveitis, choroidal neovascularisations (CNV) or leaking retinal vessels. In 10 % of these patients, CSC develops into a chronic disease with recurrent NSD, atrophy of photoreceptors and severe drop in visual acuity. This review article summarises recent progress in understanding this disease and its appearance in funduscopy, FLA, ICG, OCT, autofluorescence as well as its progress, therapy and possible development into secondary CNV. The provided examples illustrate the progression of acute CSC into chronic CSC and with CNV over years. The different appearance of polypoidal choroidal vasculopathy (PCV) in ICG and some of the signs of atypical chronic CSC are discussed. To distinguish between cCSC and wet AMD--both exhibiting leakage in FLA--typical signs are helpful, e.g., "gravitational tracks", retinal precipitates and missing drusen. However, in small lesions, it may be difficult or almost impossible to ensure the correct diagnosis of the underlying disease. The same holds for occult and classic secondary CNV in cCSC vs. CNV in AMD, where photodynamic therapy (PDT) can be successful only in cCSC-CNV and in cCSC without CNV. Corticosteroids often lead to further impairment, even in cases of atypical cCSC, when frequently misdiagnosed as uveitis. As a duration of NSD of more than 4 months is suspected to induce an impairment of photoreceptors, regular examinations are necessary not only in chronic CSC but also after acute CSC (as this form can develop into chronic CSC), while effective therapies are available to resolve the NSD (PDT, anti-VEGF).

[Morphological features of myopic choroidal neovascularization: differences to neovascular age-related macular degeneration]. / Morphologische Charakteristika der myopen choroidalen Neovaskularisation: Unterschiede zur neovaskulären altersabhängigen Makuladegeneration.

Choroidal neovascularization due to pathological myopia (mCNV) differs in important characteristics from lesions seen in age-related macular degeneration (ARMD). Myopic CNV is associated with typical phenomena, such as lacquer cracks or patchy atrophy drusen or pigment epithelium detachment are rare occurrences. The dimensions of mCNV and the extent of leakage are substantially smaller. The heterogeneous combination of thinning and concomitant staphyloma often complicates the early detection of neovascular lesions. Diagnosis and evaluation of the clinical progress are only possible using the combination of different imaging modalities, e.g. funduscopy, fluorescein angiography (FLA) and spectral domain optical coherence tomography (SD-OCT). Special forms, such as periconal mCNV or dome-shaped variants exhibit a typical progression and response to therapy. In the course of the disease a progressive pigmentation and secondary atrophy occur and later, depigmentation of the mCNV complicates the demarcation of the original mCNV within the zone of atrophy. Extensive information and counselling seem to be mandatory in order to allow a better self-assessment. Sometimes, patients notice the first symptoms of recurrent mCNV activity before confirmation is possible by objective diagnostics.