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.

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 ).

[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.

[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.

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.

[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.

[Research funding in German ophthalmology]. / Möglichkeiten der Forschungsförderung--die Ophthalmologie in der DFG.

Since 2004 applications for research funding in ophthalmology have been evaluated together with those from neurosurgery, neuropathology, psychiatry, psychotherapy, psychosomatics, otolaryngology and neurology by a joint review board of the German Research Council (DFG). Facing a decreasing number of applications--in contrast to the need and importance of widespread ocular diseases--the working group "young academics" of the Deutsche Ophthalmologische Gesellschaft (DOG) assessed the perception of funding programmes and grants available. Young ophthalmologists think that they have poor prospects to receive funding by a DFG proposal. In comparison, specialist funding quotas show a stable development within the neurosciences over the last years. The sum of requested funding has a strong correlation with the total amount actually paid. By clarifying the number of funded proposals, the better transparency and communication for the existing programmes should improve the cooperativeness, the funding rate and number of applications in future. This inventory explicitly includes a motivational guidance for young researchers to take the initiative to do more proposals.

[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).

[Myopic CNV]. / Myope CNV.

Choroidal neovascularisation secondary to pathological myopia is the most common cause of severe visual impairment in myopic patients younger than 50 years old. The typical features of myopic CNV in contrast to age-related macular degeneration as well as the anatomic characteristics have an impact on the parameters of the baseline and follow-up examinations. As the usually small fibrovascular lesions show a rapid progression in the spontaneous course of the disease and lead to irreversible damage to the photoreceptors, prompt initiation of treatment is mandatory. The superior functional results of anti-VEGF drugs provide the reason for the first-line status of this treatment modality. Increasing safety data and consistent results of prospective pilot trials have proved photodynamic therapy to be inferior. There are signs that PRN-based treatment algorithms may allow for less frequent dosing than in other retinal diseases.

[Preservative-free triamcinolone versus purified triamcinolone preparations]. / Primär konservierungsmittelfreies Triamcinolon im Vergleich zu aufgereinigten Triamcinolonpräparaten.

BACKGROUND: Intravitreal injections of triamcinolone are not only an important therapeutic tool for a variety of vitreo-retinal disorders, but can also be employed for visualisation of the vitreous during pars plana vitrectomy. Triesence® is a preservative-free triamcinolone suspension that has been approved for visualisation during vitrectomy via intravitreal administration and as intravitreal therapy for certain rare ocular diseases. However, the differences between Triesence® and purified (and thus also preservative-free) triamcinolones such as Volon A® or Kenalog® are not well specified, although the manufacturer of Triesence® advertises the product as "specifically formulated for the eye". METHODS: The publicly available FDA application material and information provided by the manufacturer for Triesence®, Kenalog® and Volon A® were analysed with respect to the differences between Triesence® and older triamcinolone preparations. RESULTS: According to the publicly available FDA documents the approval of Triesence mainly was based on studies that have been conducted with the older triamcinolone preparations Kenalog® or purified Volon A®. Apart from the absence of preservative the differences between Triesence® and the "older" triamcinolone preparation seem marginal. Published experimental or clinical studies in respect to the possible advantages of Triesence® compared to Kenalog® or Volon A® are lacking. Triesence® has been approved for sympathetic ophthalmia, temporal arteriitis, uveitis unresponsive to topical corticosteroids and for enhancing tissue visualisation during vitrectomy. Recently, the manufacturer of Kenalog® added a warning label ("not for intraocular use") on each vial of Kenalog®. The motifs for this re-labelling of Kenalog® remain unclear. CONCLUSION: Apart from the intraoperative use during vitrectomy Triesence® has only been approved for sympathetic ophthalmia, temporal arteriitis, and ocular conditions unresponsive to topical steroids. Consequently, the use of Triesence® like the older triamcinolone preparations (Kenalog® or Volon A®) for diabetic macular oedema, for Irivine-Gass syndrome, for neovascular AMD or after retinal vein occlusion is off-label.

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.

[Macular translocation - a therapeutic approach for neovascular macular degeneration in the era of anti-VEGF therapy?]. / Makulatranslokation - eine Therapie der neovaskuläre Makuladegeneration im Zeitalter der Anti-VEGF-Therapie?

Since anti-VEGF treatment has been proven to achieve a significant improvement of visual acuity in a cohort of patients with neovascular age-related macular degeneration (AMD), macular surgery and particularly the macular translocation with 360 degrees retinotomy (FMT: full macular translocation) have lost their former popularity. However, the approach of macular surgery still remains a promising therapy in selected cases. A prospective randomised study, comparing FMT and photodynamic therapy in subfoveal classic choroidal neovascularisation (CNV), recently showed the superiority of FMT in terms of visual gain. In spite of the postoperative complications and the disturbed binocular vision, the reading acuity and the life quality of many patients improved. Therefore, it is justified to discuss the chances and advantages of the FMT at least in selected cases. After all, case selection was an important determinant also in the phase III studies of ranibizumab; many patients seen during the routine consulting hours were excluded as a consequence of the study criteria. Most of them were suspected to achieve a less favourable outcome of the anti-VEGF regimen. Thus, patients who did not meet the inclusion criteria of recent studies or showed no response to the anti-VEGF therapy, as well as patients with extensive submacular bleeding or ruptures of the pigment epithelium can also be considered as candidates of FMT. Generally, in the presence of highly effective anti-VEGF drugs, FMT can be discussed for second-line treatment, if the fellow eye has poor function and no additional risk factors of the affected eye are known (e. g., hyperopia, large lesion size, etc). Detailed information relating to the potential adverse events have to be mentioned. Although the indication is restricted, surgeons should have the continuing ability to perform the challenging surgical procedure.

[Intravitreal injection. Monitoring to avoid postoperative complications]. / Intravitreale Injektion. Kontrollen zur Vermeidung von postoperativen Komplikationen.

Intravitreal injection is generally regarded as safe. Many of the potential complications caused by this procedure are extremely rare and can be avoided by careful inspection beforehand and proper performance of the injection. In rare cases, however, the administered drugs may cause various pharmacological side effects. This article summarizes the safety profiles of Macugen and Lucentis from the drug approval studies and describes initial findings on possible or observed side effects after intravitreal administration of Avastin. In addition, important points to observe in order to avoid intra- and postoperative complications are provided.

[Chances and risks of anti-VEGF therapy]. / Chancen und Risiken der Anti-VEGF-Therapie.

Vascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis. Through regulation of haemodynamics, haematopoesis and the immune system, endocrinology and reparative processes, inhibition of VEGF can cause multiple adverse events. Previous data suggest that--even after intravitreal injection--systemic exposure might occur, thus bearing the risk of manifestation of side effects. Experience with intravenous administration of the antibody bevacizumab (Avastin) pointed to the potential consequences of a pan-VEGF blockade. The change of haemodynamic parameters implies a potential influence on the patient's morbidity. Studies already conducted during the approval process do not provide sufficient statistical power when evaluating whether systemic events significantly differ between the treatment and control groups. Retinal perfusion showed an altered vascular tone (change in vessel diameter) following anti-VEGF treatment. Physiological fenestration of the choroicapillaris is significantly reduced. Possible effects on the local oxygen supply in ischaemic tissue have to be considered. In contrast to destructive treatment modalities (laser, cryo), VEGF inhibitors promise the prompt and efficient response of retinal neovascularisation and the preservation of a better function (visual fields). The maturation of growing vessels (pericytes) and the secondary formation of membranes are limiting factors with regard to the time-point at which anti-VEGF therapy is most effective. A diligent use of the available drugs has to take into account which types of exudative retinopathy are showing no or only very limited response to the treatment.

[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.

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.

[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.