[Retinal optical coherence tomography biomarkers in dementia]. / Retinale optische Kohärenztomographie-Biomarker bei demenziellen Erkrankungen.

BACKGROUND: Due to the general aging of society, the prevalence and incidence of dementia are expected to increase considerably. In order to timely identify patients and assess their need for treatment and/or supportive measures, comprehensive and easy access screening methods are required, which, however, are yet to be developed. To date, several biomarkers for the presence of dementia on high-resolution spectral domain optical coherence tomography (OCT) and OCT angiography (OCT-A) images were identified. AIM: To summarize previously identified OCT biomarkers in dementia and to assess their suitability for comprehensive screening examinations. MATERIAL AND METHODS: A literature search was conducted on PubMed until March 2023 for the keywords "dementia", "mild cognitive impairment", "OCT", "OCT angiography" and "retinal biomarkers". Relevant publications were identified and summarized. RESULTS: Numerous unspecific alterations on OCT imaging and OCT­A were identified in patients with (predementia) dementia according to many population and clinical studies. These include a reduced thickness of the peripapillary retinal nerve fiber layer, the ganglion cell complex and the central retinal region. Additionally, a reduced vascular density and an enlarged foveal avascular zone (FAZ) were identified on OCT­A imaging. CONCLUSION: The currently known OCT biomarkers are too unspecific, and there is to date no OCT or OCT-A-based signature distinguishing between different types of dementia. Further longitudinal studies with larger sample sizes are warranted to develop and evaluate such distinct OCT signatures for different types of dementia and their respective early disease stages and to assess their prognostic value. Only then is the inclusion in comprehensive screening investigations feasible.

[Status and perspectives of registry-based studies in German ophthalmology]. / Stand und Perspektiven registerbasierter Studien in der deutschen Augenheilkunde.

BACKGROUND AND OBJECTIVE: Registry studies provide insights into real-life diagnostic and treatment data outside of clinical trials. Registry studies are interesting for quality management and explorative analyses can lead to the identification of possible risk or prognostically relevant factors and generate hypotheses. There are currently relatively few active registry studies in German ophthalmology. The aim of this survey was to collate the different infrastructure and in particular the potential hurdles in the establishment and performance of registry studies in German ophthalmology departments. METHODS: An online questionnaire collected data on participation in registry studies in German ophthalmology departments between September and December 2018. The survey was addressed to all hospital management and medical staff involved in registry studies in German ophthalmology. RESULTS: Out of 45 participants 18 were head of the department, the remaining 27 were consultants (15), medical specialists (2) and residents (10). According to the department head an average of 2.5 (2.0-3.5) employees per clinic participate in 2.0 (1.7-3.0) registry studies. The amount of reimbursement recommended by the hospital management differed significantly from the amount suggested by the staff (0.0 (0; 75) € (0-100) vs. 100.0 (50.0; 150.0) €; p = 0.0012). The most frequent hurdles to conducting a registry study were bureaucracy and limited human resources. Half of the surveyed centers profited from a separate study center and good clinical practice (GCP) courses for employees involved in studies were mandatory. A quarter of these centers received support from an IT department and/or a statistician. CONCLUSION: Registry studies are an important instrument in ophthalmology research and their importance is increasing in Germany. An agreement on national standards would make the establishment of further registry studies easier.

[ANDROMEDA-an investigation of factors influencing the adherence of patients with neovascular age-related macular degeneration using the newly developed patient questionnaire LAF-IVT]. / ANDROMEDA ­ Eine Untersuchung von Einflussfaktoren auf die Adhärenz von Patienten mit neovaskulärer altersabhängiger Makuladegeneration mithilfe des neu konzipierten Patientenfragebogens LAF-IVT.

BACKGROUND: Lack of adherence to treatment is a widespread problem in the anti-VEGF (Vascular Endothelial Growth Factor) treatment of patients with neovascular age-related macular degeneration (nAMD). In contrast to the extent of the lack of treatment adherence, there is so far insufficient evidence for elucidating the causes of nonadherence. The ANDROMEDA study was initiated to investigate the influencing factors on the adherence of nAMD patients to treatment. The focus of the study was on patient reported endpoints, as the perceptions and experiences of the patients are of enormous importance for the investigation of the various aspects of adherence to treatment. OBJECTIVE: This publication presents the design of the ANDROMEDA study as well as the development of a new patient questionnaire for the assessment of barriers to treatment within the design of the study. MATERIAL AND METHODS: This prospective noninterventional observational study to assess the compliance of patients with nAMD and anti-VEGF treatment was started at the end of January 2019. It is planned to include 1000 patients in 120 study centers throughout Germany with an observational period of 24 months. Patient interviews on general and vision-related quality of life, treatment satisfaction and possible barriers to treatment will be conducted at the beginning and after 4, 12 and 24 months. All patient visits will be documented by the study centers as part of the clinical routine. To date, there has been no suitable instrument for recording patient-related circumstances and potential barriers to anti-VEGF treatment. Therefore, a specific patient questionnaire for longitudinal assessment of adherence factors to intravitreal (anti-VEGF) therapy (LAF-IVT) was developed as part of the study concept. The questionnaire, developed by an expert panel, was tested via qualitative interviews for its cognitive characteristics ahead of its use. RESULTS: The results of the study are expected in early 2023. The cognitive examination of the LAF-IVT confirmed the feasibility of the new questionnaire. The practicability and significance of the new instrument can be assessed after completion of the quantitative data collection. CONCLUSION: The symptoms, barriers, burdens and quality of life effects experienced by patients influence the adherence to treatment and thus the outcome. A better understanding of the patient's views and experiences is the basis for long-term optimization of care.

[Epidemiology of severe visual impairment and blindness of old people in Germany]. / Epidemiologie hochgradiger Sehbehinderungen und Blindheit älterer Menschen in Deutschland.

Approximately 500,000 blind and 1 million visually impaired persons live in Germany, which lacks a national blind registry. Therefore data from social welfare agencies and population-based studies are used to estimate prevalence and incidence. Main causes for severe visual impairment and blindness are age-related macular degeneration, glaucoma and diabetic eye diseases. We observed a relative decline of the incidence of severe visual impairment and blindness over the last decades, which is primarily due to improved ophthalmic care and better treatment options. However, the absolute number of subjects with severe visual impairment and blindness increases due to population ageing. This will cause significant social and economic challenges in the future.

[Physical activity in older persons with eye diseases : Applicability of wrist-worn accelerometer]. / Physische Aktivität bei älteren Menschen mit Augenerkrankungen : Anwendbarkeit von Armbandakzelerometern.

BACKGROUND AND OBJECTIVES: Physical activity (PA) impacts age-related diseases but its measurement is difficult. The acceptance of wrist-worn accelerometers (ACC) in older patients with eye diseases was evaluated and the results were compared with a validated activity questionnaire. MATERIALS AND METHODS: In this study 50 patients underwent a clinical examination and were interviewed with the International Physical Activity Questionnaire (IPAQ). They then wore an ACC for 7 days and then for 30 days. After descriptive analysis of the data, influencing factors on the PA were assessed using multiple, linear models. RESULTS: A total of 94% of participants wore the ACC for 7 days and 74% for 30 days. For 36 patients complete data were available. In comparison, IPAQ (e. g. moderate PA: 1183.4 ± 864.3 min/week) vs. ACC across 7 and 30 days (248.5 ± 266.0 min/week and 248.8 ± 190.6 min/week, respectively) showed substantially higher results (p < 0.05 for both intervals). The ACC data across 7 and 30 days were comparable (e. g. high PA: 25.4 ± 33.7 min/week and 22.5 ± 29.0 min/week). In multiple, linear models body mass index (BMI) was associated with 7 days moderate activity (ß = -0.22 [95% confidence intervals CI: -21.7; -1.9]; p = 0.021) and vigorous activity (ß = -0.35 [95% CI: -4.3; -0.5]; p = 0.033) as well as 30 days vigorous activity (ß = -0.45 [95% CI: -5.9; -0.1]; p = 0.044). Other factors such as better visual acuity, age and gender were not associated. CONCLUSION: The use of ACCs are acceptable to the majority of older patients with eye diseases. The results of ACC are more precise with lower variation, and much lower PA than those of a comparable activity questionnaire. Measurement over 7 days is sufficient for capturing the average PA in older patients and can be easily applied in clinical trials.

[Pro re nata anti-VEGF treatment results for neovascular age-related macular degeneration in routine clinical treatment: comparison of single with triple injections]. / Pro-re-nata-anti-VEGF-Behandlungsergebnisse bei neovaskulärer altersabhängiger Makuladegeneration in der klinischen Routineversorgung: Vergleich von Einzel- mit 3er-Injektionen.

BACKGROUND: Different injection regimens from continuous to pro re nata (PRN) have been proposed for treatment of neovascular age-related macular degeneration (nAMD). So far the PRN single injection on reactivation regimen has not been compared to the PRN triple injection on reactivation regimen (IVAN scheme). OBJECTIVE: Comparison of the two nAMD PRN injection regimens with single and triple injections on reactivation in a real-world setting in a retrospective case series in two German treatment centers. MATERIAL AND METHODS: Naïve nAMD patients, who started treatment according to either the single or triple injection regimen were included. Endpoints were best corrected visual acuity (LogMAR), central retinal thickness on optical coherence tomography (µm) and number of injections, all at 3, 6, 12, 18 and 24 months after treatment initiation. RESULTS: A total of 146 patients with single injection and 148 patients with triple injection regimens were included. There were no significant differences between the two treatment regimens in best corrected visual acuity (single vs. triple injection scheme: 0.50 ± 0.42 vs. 0.56 ± 0.42, p = 0.14), central retinal thickness (303 ± 76.2 vs. 306 ± 110, p = 0.79) and number of injections (13 ± 4.4 vs. 12 ± 5.4, p = 0.31). This was the case for all analyzed time points. CONCLUSION: There were no significant functional or morphological differences between the two PRN injection regimens with single and triple injections on reactivation after 24 months. For evaluation of long-term therapy results further studies are warranted.

[Registry-based research in ophthalmology]. / Registerstudien in der Ophthalmologie.

Medical registries and registry studies are frequently used for health services research as they represent a valuable means of capturing real-life data. Registry studies are particularly suitable for rare diseases for which epidemiological population-based or randomized controlled clinical studies are difficult. The are many examples of successful medical registries that have not only contributed to both epidemiological and clinical research, but which have also improved health service delivery. Only few ophthalmological medical registries are currently available. For non-infectious uveitis in children and adolescents with juvenile idiopathic arthritis (JIA), a rare disease entity, there is a need for data on, e.g., treatment, long-term outcomes, and risk factors for progression. The advantages for this disease of a registry with uveitis module from which numerous scientific publications and guidelines have been derived has been proven. Thus, we use the example of non-infectious uveitis to discuss the benefits of registries for other areas of ophthalmology.

[Reasons for delayed and discontinued therapy in age-related macular degeneration]. / Gründe für Therapieverzögerung und -abbruch bei altersabhängiger Makuladegeneration.

BACKGROUND: Critical prerequisites for successful therapy of neovascular age-related macular degeneration (nvAMD) are an early initiation and continuous monitoring; however, delays in starting therapy and non-medically indicated discontinuation of therapy are frequent, which limits therapy efficacy and, thus, visual outcomes. OBJECTIVE: To identify the reasons for delay in therapy and non-medically indicated termination of therapy. MATERIAL AND METHODS: Patients who had started a new therapy (starters) and those who independently terminated therapy (dropouts) were interviewed by telephone with a specific, standardized questionnaire. Results were summarized descriptively. RESULTS: A total of 100 starters and 55 dropouts were interviewed. The mean therapy delay was 22 (±28 SD) days. This was mainly due to the time until the decision to see an ophthalmologist was made. Main reasons for dropping out were: transportation issues (27%), poor general health (25%) and the assumption that there is no benefit from therapy (11%). Of the patients who dropped out 63% would have liked to continue therapy. CONCLUSION: There is potential for improvement in nvAMD management regarding therapy start as well as therapy maintenance. Sensitizing for initial nvAMD symptoms is important as is reduction of barriers to therapy maintenance, since most therapy dropouts would like to continue the therapy.

[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.

Age-related macular degeneration and mortality: the Melbourne Collaborative Cohort Study.

AimsTo assess associations between features of age-related macular degeneration (AMD) and mortality.MethodsA total of 21 129 participants from the Melbourne Collaborative Cohort Study aged 47-85 years (60% female) were assessed for AMD (2003-2007). Mortality data to December 31, 2012 were obtained through linkage with the National Death Index. Associations were assessed using Cox regression, adjusting for age, sex, smoking, region of birth, education, physical activity, diet and alcohol.ResultsLate AMD was identified in 122 (0.6%) participants, including those with choroidal neovascularisation (n=55, 0.3%), geographic atrophy (n=87, 0.4%) and reticular pseudodrusen (n=87, 0.4%). After a median follow-up period of 8.1 years, 1669 (8%) participants had died, including those from cardiovascular diseases (386), tobacco-related cancers (179), and neurodegenerative disease (157). There was evidence of an increased rate of all-cause mortality for those with choroidal neovascularisation (Hazard Ratio (HR) 1.71 95% CI 1.06-2.76) and geographic atrophy (HR 1.46 95% CI 0.99-2.16). Choroidal neovascularisation was also associated with an increased rate of cardiovascular mortality (HR 3.16 95% CI 1.62-6.15) and geographic atrophy was associated with an increased rate of death from tobacco-related cancer (HR 2.86 95% CI 1.15-7.09). Weak evidence was also present for an association between choroidal neovascularisation and death from neurodegenerative disease (HR 2.49 95% CI 0.79-7.85). Neither reticular pseudodrusen nor the earlier stages of AMD were associated with mortality.ConclusionsLate AMD is associated with an increased rate of all-cause mortality. Choroidal neovascularisation and geographic atrophy were associated with death from cardiovascular disease and tobacco-related cancer, respectively.

[Retinal imaging of the macula and optic disc in neurodegenerative diseases]. / Retinale Bildgebung von Makula und Papille bei neurodegenerativen Erkrankungen.

BACKGROUND: Due to current demographic trends, the prevalence of mild cognitive impairment and dementia is expected to increase considerably. For potential new therapies it is important to identify patients at risk as early as possible. Currently, there is no population-based screening. Therefore, identification of biomarkers that will help screen the population at risk is urgently needed. Thus, a literature review on retinal pathology in neurodegenerative diseases was performed. METHODS: PubMed was searched for studies published up to August 2016 using the following keywords: "mild cognitive impairment", "dementia", "eye", "ocular biomarkers", "OCT" and "OCT angiography". Relevant publications were selected and summarized qualitatively. RESULTS: Multiple studies using noninvasive in vivo optical coherence tomography (OCT) imaging showed nonspecific retinal pathological changes in patients with neurodegenerative diseases such as mild cognitive impairment, Alzheimer's and Parkinson's disease. Pathological changes in macular volume, optic nerve fiber layer thickness and the ganglion cell complex were observed. However, based on available evidence, no ocular biomarkers for neurodegeneration which could be integrated in routine clinical diagnostics have been identified. CONCLUSION: The potential use of OCT in the early diagnostic workup and monitoring of progression of neurodegenerative diseases needs to be further explored in longitudinal studies with large cohorts.

[Epidemiology of age-related macular degeneration]. / Epidemiologie der altersbedingten Makuladegeneration.

Age-related macular degeneration (AMD) is the main cause of blindness in industrialized societies. Population-based epidemiological investigations generate important data on prevalence, incidence, risk factors, and future trends. This review summarizes the most important epidemiological studies on AMD with a focus on their transferability to Germany including existing evidence for the main risk factors for AMD development and progression. Future tasks, such as the standardization of grading systems and the use of recent retinal imaging technology in epidemiological studies are discussed. In Germany, epidemiological data on AMD are scarce. However, the need for epidemiological research in ophthalmology is currently being addressed by several recently started population-based studies.

[Health services for patients with neovascular age-related macular degeneration in Germany]. / Versorgung von Patienten mit neovaskulärer altersabhängiger Makuladegeneration in Deutschland.

In neovascular age-related macular degeneration (NVAMD) successful treatment outcome depends on regular intravitreal injections of vascular endothelial growth factor inhibitors (anti-VEGF). Several observational trials on the use of ranibizumab in the clinical routine demonstrated a low injection frequency, a low number of ophthalmic reviews which included optical coherence tomography, and suboptimal treatment outcomes in Germany. To date it remains unclear whether the use of ranibizumab reflects the use of all anti-VEGF agents including aflibercept and bevacizumab in the clinical routine in Germany. However, based on available data, treatment provision and outcomes seem to be suboptimal, in particular for elderly patients with NVAMD. As poorly treated NVAMD carries a high risk of loss of vision and ultimately blindness, service provision and treatment outcomes need to be improved.

[Trends in inpatient treatment in ophthalmology in Germany]. / Entwicklung der stationären augenärztlichen Versorgung in Deutschland.

BACKGROUND: Over the last decade inpatient treatment has been reduced in favor of outpatient care or markedly shortened inpatient stays in most organ-specific surgical specialties such as ophthalmology in Germany. METHODS: Data from the federal statistics agency on the international classification of disease (ICD), diagnosis-related groups (DRG) and performed operations and procedures from 2000 to 2010 as well as data from the Institute for Reimbursements of Hospitals (InEK) on average costs per DRG in every German DRG (G-DRG) version from 2004 to 2010 were analyzed for ophthalmology. RESULTS: From 2000 to 2010, the number of cases with a main ophthalmological diagnosis decreased (-19 %), which was mostly due to a reduction in the number of cataract inpatients (-56 %). All subspecialties such as glaucoma (+82 %) and retina (+68 %) with the exception of primary strabismus diagnoses (-15 %) gained in number of cases. Inpatient cataract surgery was the most common surgery in 2004 but numbers decreased to 2010 (-9 %). The most often performed inpatient procedure was vitreoretinal surgery in 2007 and 2010 (increase 2004-2010 + 46 %). Average hospital stay decreased between 2005 and 2010 from 3.9 to 3.4 days and the average cost per case increased by 3.6 % overall and by 13.4 % for surgical cases. CONCLUSION: Ophthalmic healthcare provided as inpatient services decreased with a trend towards more complex cases being treated as inpatients from 2000 to 2010.

[Access to healthcare services for elderly patients with neovascular age-related macular degeneration]. / Versorgung von älteren Menschen mit neovaskulärer altersabhängiger Makuladegeneration.

BACKGROUND: Neovascular (nv) age-related macular degeneration (AMD) is the leading cause of blindness in Germany and is usually treated with monthly injections of anti-VEGF agents. The current level and the estimated need of service provision for nv-AMD were assessed. METHODS: Current levels of service provision with ranibizumab (Lucentis) were documented in 3,633 patients in the WAVE study, the currently largest observational study in Germany on the use of anti-VEGF agents. The expected need was calculated using German population figures for 2010 and available prevalence data. Both were stratified by age and gender and descriptively analyzed. RESULTS: A larger number of younger patients with nv-AMD (< 75 years) than expected were treated in the WAVE study. Expected need in the age groups 75-84 years and 84 years and older was much higher than the proportion of patients actually treated in these age groups (up to 3 times). Based on expected need, women accessed treatment less often than men. CONCLUSION: In the WAVE study, less elderly persons and in particular elderly women seemed to access treatment for nv-AMD than expected. Future studies should investigate barriers in accessing treatment for nv-AMD and how to address these problems.

[Basic principles, planning and implementation of non-commercial clinical trials]. / Grundlagen, Planung und Durchführung nichtkommerzieller klinischer Studien.

The proof of a drug's efficacy in randomized controlled trials is fundamental to therapeutic concepts determined by evidence-based medicine. Clinical trials according to the German Medicinal Products Act are performed by the pharmaceutical industry as company-sponsored trials (CST) driven by commercial interests or by non-commercial facilities as investigator-initiated trials (IIT), typically implemented by University Hospitals. In areas with no commercial interest, IITs are the driving force that generate scientific progress leading to treatment optimization. Therefore, non-commercial or investigator-initiated clinical trials are indispensable for improving medical care. To ensure the safety of trial participants and the quality of the data obtained, clinical trials are controlled by many legal regulations and internationally accepted quality standards. Therefore implementation of a clinical trial requires profound knowledge, qualified personnel, appropriate infrastructure, and substantial financial resources. In IITs unlike CSTs this has to be accomplished by the University without the assistance of the pharmaceutical industry. Since teaching of skills needed to perform clinical trials is still largely neglected in medical school and during residency this review addresses the (in clinical trials) inexperienced physician and outlines the characterization of a clinical trial, the range and division of responsibilities and the performance of clinical trials according to the German Medicinal Products Act.

[Methods for estimating personal costs of disease using retinal diseases as an example]. / Methoden zur Ermittlung persönlicher Krankheitskosten am Beispiel retinaler Erkrankungen.

PURPOSE: Age-related macular degeneration (AMD) and other retinal diseases, such as diabetic retinopathy (DRP) and hereditary retinal dystrophy can not only lead to a loss of visual function but also to a higher psychological and financial burden for the affected persons. Against this background a quantification of personal cost and vision-related quality of life was performed. METHODS: A total of 66 patients (mean age 69 years, SD 13 years) with clinically confirmed diagnoses of AMD, DRP or retinal dystrophy were interviewed regarding costs for medicines, aids and equipment, support in everyday life and social benefits. Vision-related quality of life was recorded using the Impact of Vision Impairment profile (IVI). RESULTS: The average total annual cost was 751 per patient, out of which the largest amount was cost of support in everyday life (506). Costs as well as dependence on other persons or social services increased with decreasing visual acuity (p=0.013). Vision-related quality of life decreased with increasing visual disability especially in the IVI subscales mobility and independence as well as reading and accessing information (p=0.002). CONCLUSIONS: Prevention or delay of visual disability and blindness caused by AMD or other retinal diseases and thus ensuring independence is not only relevant from a medical perspective but also from a health economic perspective. Against the background of a relative shortage of resources, costs should be reduced regardless of whether they are personal or societal costs.

[Patient-reported and patient-weighted outcomes in ophthalmology]. / Patientenberichtete und patientengewichtete Endpunkte in der Augenheilkunde.

Considering patients' values and preferences in comparative effectiveness research (CER) is one of the main challenges in ophthalmology (value-based medicine). This article defines core terms in CER. The concept of patient-relevant (or patient-important) outcomes is distinguished from patient-reported outcomes (PRO) by means of examples in the field of ophthalmology. In order to be able to give a consistant recommendation if an intervention leads to conflicting results for different outcomes (trade-off), a ranking of outcomes will be necessary. Examples of studies in glaucoma patients are provided that demonstrate the possibilities of ranking of outcomes based on patient preferences.