[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.

Prosthetic Visual Acuity with the PRIMA System in Patients with Atrophic Age-related Macular Degeneration at 4 years follow-up.

Objective: To assess the efficacy and safety of the PRIMA subretinal neurostimulation system 48-months post-implantation for improving visual acuity (VA) in patients with geographic atrophy (GA) due to age-related macular degeneration (AMD) at 48-months post-implantation. Design: First-in-human clinical trial of the PRIMA subretinal prosthesis in patients with atrophic AMD, measuring best-corrected ETDRS VA (Clinicaltrials.gov NCT03333954). Subjects: Five patients with GA, no foveal light perception and VA of logMAR 1.3 to 1.7 in their worse-seeing "study" eye. Methods: In patients implanted with a subretinal photovoltaic neurostimulation array containing 378 pixels of 100 µm in size, the VA was measured with and without the PRIMA system using ETDRS charts at 1 meter. The system's external components: augmented reality glasses and pocket computer, provide image processing capabilities, including zoom. Main Outcome Measures: VA using ETDRS charts with and without the system. Light sensitivity in the central visual field, as measured by Octopus perimetry. Anatomical outcomes demonstrated by fundus photography and optical coherence tomography up to 48-months post-implantation. Results: All five subjects met the primary endpoint of light perception elicited by the implant in the scotoma area. In one patient the implant was incorrectly inserted into the choroid. One subject died 18-months post-implantation due to study-unrelated reason. ETDRS VA results for the remaining three subjects are reported herein. Without zoom, VA closely matched the pixel size of the implant: 1.17 ± 0.13 pixels, corresponding to mean logMAR 1.39, or Snellen 20/500, ranging from 20/438 to 20/565. Using zoom at 48 months, subjects improved their VA by 32 ETDRS letters versus baseline (SE 5.1) 95% CI[13.4,49.9], p<0.0001. Natural peripheral visual function in the treated eye did not decline after surgery compared to the fellow eye (p=0.08) during the 48 months follow-up period. Conclusions: Subretinal implantation of PRIMA in subjects with GA suffering from profound vision loss due to AMD is feasible and well tolerated, with no reduction of natural peripheral vision up to 48-months. Using prosthetic central vision through photovoltaic neurostimulation, patients reliably recognized letters and sequences of letters,and with zoom it provided a clinically meaningful improvement in VA of up to eight ETDRS lines.

[Bottlenecks in the availability of ophthalmological medications : Initiative of the Working Group on Ethics in Ophthalmology of the DOG and the University Eye Clinic Bonn]. / Engpässe bei der Verfügbarkeit von ophthalmologischen Medikamenten : Initiative der Arbeitsgemeinschaft Ethik in der Augenheilkunde der DOG und der Universitäts-Augenklinik Bonn.

BACKGROUND: Bottlenecks in drug supply in the field of ophthalmological are continuously increasing in Germany. So far, these have hardly been communicated and discussed. We see the transparent presentation of the problem as a first step in compiling concepts to counteract this development. AIM OF THE WORK: Presentation of the supply shortages in ophthalmological drugs. MATERIAL AND METHODS: A listing and discussion of the shortages in drug supply to the best of our knowledge are presented. RESULTS: We distinguish between the problems in (1) supply shortages, (2) discontinuation of production, (3) lack of availability in Germany and (4) manufacture of drugs in specialized pharmacies often lacking approval for the ophthalmological indications. DISCUSSION: The reasons for drug supply shortages in ophthalmology are complex and therefore no easy solutions can be expected; however, industrial and regulatory authorities at the national and European levels are called upon to analyze the underlying problems and to find appropriate solutions.

A randomized, open-label, multicenter study of switching to brolucizumab with or without a loading dose for patients with suboptimal anatomically controlled neovascular age-related macular degeneration-the FALCON study.

BACKGROUND: Treatment initiation with brolucizumab, a new potent anti-vascular endothelial growth factor (VEGF) agent, is typically performed with three monthly injections (loading dose) and has been well studied in treatment-naïve patients. However, no clinical data are available yet on whether or not anti-VEGF pretreated patients also benefit from a loading dose. In the clinical setting, different heterogeneous treatment patterns are used as no clinical trial has addressed this so far in a head-to-head comparison. Therefore, the FALCON study is investigating whether patients with unsatisfactory response to previous anti-VEGF treatments benefit from a loading dose at the switch to brolucizumab treatment. METHODS: FALCON is a 52-week, two-arm, randomized, open-label, multicenter, multinational study in patients with residually active neovascular age-related macular degeneration (nAMD) who will be randomized 1:1 and started with brolucizumab 6 mg loading (three monthly loading doses) or brolucizumab 6 mg non-loading (one initial injection) and consecutive treatment every 12 weeks, respectively. The primary objective is to demonstrate non-inferiority of the non-loading vs. loading arm in mean change of best-corrected visual acuity (BCVA) from baseline to the mean value at week 40 to week 52. Secondary objectives include the assessment of anatomical outcomes, treatment intervals, safety and tolerability. RESULTS: FALCON will be the first study to assess treatment initiation with an anti-VEGF agent in a switch situation with or without loading dose in patients with nAMD. CONCLUSIONS: The results will support the optimization of treatment of patients with previous unsatisfactory anti-VEGF response. Therefore, we expect to see an impact on current clinical practice which has been established for more than a decade. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04679935, date of registration-22-Dec 2020; EUDRACT number: 2019-004763-53, date of registration-03 Dec 2019.

Clinico-pathological correlation of lacrimal caruncle tumors: a retrospective analysis over 22 years at the University Eye Hospital Bonn.

PURPOSE: The lacrimal caruncle is composed of numerous structures including different glands as well as hair follicles. Accordingly, the spectrum of benign and malignant lesions is broad, and the clinical diagnosis is often challenging. Here we systematically analyzed excised caruncular tumors over the past 22 years with special emphasis on the clinico-pathological correlation to provide a guidance for clinicians. METHODS: Retrospective evaluation with clinico-pathologic correlation of surgically removed caruncular tumors between 1998 and 2020 at a tertiary referral center. RESULTS: Eighty-two caruncular tumors were identified in the respective period. The patients were between 11 and 85 years of age (mean, 46.8 years; median, 49 years). Nevi (n = 35), cystic lesions (n = 14), oncocytoma (n = 9), papilloma (n = 8), sebaceous gland hyperplasia (n = 8), and reactive lymphoid hyperplasia (n = 4) were observed most frequently. Besides, we are the first reporting herniated orbital fat accompanied by a pyogenic granuloma. 2.4% (n = 2) were malignant tumors (sebaceous gland carcinoma, conjunctival intraepithelial neoplasia with pyogenic granuloma). CONCLUSION: Caruncular tumors show a broad spectrum of mostly benign tumors. They can occur in patients of any age. However, 8/9 oncocytomas and both malignant lesions were detected in patients older than 60 years. Although the clinical diagnosis was confirmed in only 68.3% by the histopathological analysis, the two malignant lesions were identified as such already clinically. Caruncular lesions with a history of growth or other signs of malignancy should be excised followed by detailed histopathological examination to allow a final diagnosis and exclude rare malignant tumors with lethal potential.

[Intraocular inflammation with brolucizumab use : Patient management-diagnosis-therapy]. / Intraokulare Entzündungen bei Brolucizumab-Anwendung : Patientenmanagement ­ Diagnose ­ Therapie.

The anti-vascular endothelial growth factor (anti-VEGF) agent brolucizumab has been approved in the USA in October 2019 and in Europe in February 2020 for the treatment of neovascular age-related macular degeneration (nAMD). The approval was based on the randomized, double-blind phase III studies HAWK and HARRIER with a total of 1817 patients. Brolucizumab 6 mg (administered every 12 or 8 weeks depending on the activity of the disease) showed a non-inferior efficacy in terms of best-corrected visual acuity compared to aflibercept 2 mg (administered every 8 weeks). Initial reports on the use of brolucizumab after its approval in the USA indicated a safety signal of rare adverse events termed as retinal vasculitis and/or retinal vascular occlusion that may result in severe loss of vision. Typically, these events occurred in the presence of intraocular inflammation (IOI). A safety review committee (SRC) subsequently carried out an independent analysis of data from the pivotal studies. This article sets out the current state of knowledge and aims to provide users with orientation-from the authors' perspective-in treating brolucizumab-associated IOI. It appears mandatory to provide patients with information about possible symptoms of IOI. Even though the case reports and the SRC review of HAWK/HARRIER may not yet provide sufficient evidence for any final conclusions, it seems crucial to educate patients about signs and symptoms to ensure an early detection and diagnosis in cases of IOI. Once a patient is diagnosed with IOI, retinal vasculitis, and/or retinal vascular occlusive events, physicians should act promptly with an adequate and intensive anti-inflammatory treatment and brolucizumab treatment should be discontinued. It is important to note that these recommendations are primarily based on the authors' expert opinions and should be considered as guidance in managing these events rather than a formal protocol or guidelines.

[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.

Awareness of Age-Related Macular Degeneration in Community-Dwelling Elderly Persons in Germany.

Background: Due to current demographic trends age-related macular degeneration (AMD) is becoming more prevalent. When disease progresses to late-stage neovascular AMD, rapid initiation of treatment is required to achieve optimal outcomes. However, many affected individuals may be unaware of their disease impeding and delaying care seeking. Therefore, in an exploratory study we assessed whether elderly persons living independently in the community were aware of their AMD. Methods: Participants were recruited in eleven seniors' community centers. Participants underwent a standardized interview followed by non-mydriatic fundus photography of the macula and the optic disc in both eyes (Canon CR-2AF, Canon, New York, USA). The images were graded by an ophthalmologist and the data were analyzed descriptively. Results: A total of 281 participants (73.9 ± 8.1 years; 71.9% women) underwent bilateral fundus photography. The fundus photographs of 208 participants (74%; 73.6 ± 7.0 years; 73.1% women) could be graded. In a third (32.2%, n = 67) no pathological changes were detected. AMD was present in 24.5% of the examined subjects (n = 51). Half of the cases had early (47.1%), followed by intermediate (41.2%) and late (11.7%) AMD. Only one third (n = 16, 31.4%) were aware of their disease. Conclusions: A quarter of community dwelling elderly had AMD but only a third of these were aware of being affected with AMD. This confirms previous studies demonstrating low awareness for age-related eye diseases in the community. Considering the increase in population aging, awareness campaigns for AMD are needed.

[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.

[Bilateral multifocal pigment epithelial detachments associated with inhaled corticosteroids]. / Bilaterale multifokale Pigmentepithelabhebungen in Assoziation mit inhalativen Kortikosteroiden.

A 37-year-old male patient presented with metamorphopsia and unilateral visual impairment with the presence of hundreds of bilateral avascular retinal pigment epithelial detachments (PEDs). The patient suffered from allergic bronchial asthma which was treated with inhaled corticosteroids. Cessation of corticosteroid treatment resulted in flattening of larger PEDs and subsequent transition to atrophic areas over time while smaller PEDs persisted and spread peripherally over an observation period of 14½ years.

[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.

[Imaging and molecular genetic diagnostics for the characterization of retinal dystrophies]. / Bildgebung und molekulargenetische Diagnostik zur Charakterisierung von Netzhautdystrophien.

Hereditary retinal dystrophies represent a genetically and clinically heterogeneous group of diseases. A comprehensive characterization constitutes functional and high-resolution multimodal imaging. With the advent of novel treatment options the detection of the underlying gene causing the disease is becoming more important. Technical advances in molecular genetic diagnostics enable a classification of retinal dystrophies depending on the specific genetic cause of the disease, which is important particularly against the background of newly emerging therapy approaches. Targeted next generation sequencing (NGS), in particular is now an efficient method to accomplish this and can be especially helpful to identify rare and potentially new disease-causing variants. For the interpretation of the molecular genetic results a close collaboration between ophthalmologists and geneticists is essential.

[Long-term effects of anti-VEGF therapy for retinopathy of prematurity]. / Langzeiteffekte der Anti-VEGF-Therapie bei Frühgeborenenretinopathie.

BACKGROUND: Intravitreal anti-VEGF therapy is a highly efficacious new treatment option for retinopathy of prematurity (ROP) with significant advantages over conventional therapy using retinal laser coagulation in selected cases. With growing experience in the clinical application over the last years, data about the potential long-term effects of this therapeutic approach are increasingly becoming available, such as those related to ROP-associated myopia, neurodevelopment and late recurrences of ROP. Knowledge of these effects is of direct relevance for the clinical management of affected children. METHODS: The article is based on a literature review of the covered topics. RESULTS: In addition to its therapeutic effect on retinal pathology, anti-VEGF therapy in ROP can also reduce ROP-associated myopia, most likely due to a normalization of anterior segment development. As the unresolved question of potential negative effects of bevacizumab on neurodevelopment remains of concern, the use of alternative treatment options, such as ranibizumab or laser coagulation should be considered. Treatment-requiring recurrences of ROP following anti-VEGF therapy have been reported as late as 69 weeks postmenstrual age, indicating that long-term frequent ophthalmological follow-up examinations are required. CONCLUSION: Long-term effects of anti-VEGF therapy in ROP differ significantly from alternative treatment options such as laser coagulation. These differences are of relevance for the choice of treatment modality and the follow-up regimen of treated children.

[Screening for retinopathy of prematurity: Trends over the past 5 years in two German university hospitals]. / Frühgeborenenretinopathie-Screening: Trends über die vergangenen 5 Jahre an zwei deutschen Universitätskliniken.

BACKGROUND: The number of preterm births in Germany has been increasing continuously over the past decades. Retinopathy of prematurity (ROP) is a major complication of preterm birth and one of the leading causes of blindness in children. OBJECTIVES: This study analyzes the development of the incidence of ROP over the past 5 years at two German university hospitals, utilizing data from ROP screening examinations. MATERIAL AND METHODS: We assessed all children born in the years 2012-2016 who were included in the ROP screening program at two German university hospitals according to the criteria of the German ROP screening guidelines. Parameters such as gestational age, birth weight, ROP stage and zone, and need for therapeutic intervention were assessed. RESULTS: We analyzed the data of 863 children who had undergone a total of 4117 screening examinations. The number of children included in the screening program per study year increased continuously over the study period by a total of 43.1% (137 in 2012, 196 in 2016). Likewise, the number of screening examinations per year increased by 58.4% (608 in 2012, 963 in 2016). Overall, 27.5% of screened infants were diagnosed with ROP of any stage and 2.5% required treatment for ROP. The number of children diagnosed with ROP of any stage per year increased by 100.0% (32 in 2012, 64 in 2016). Mean gestational age (29.0 ± 3.0 weeks) and mean birth weight (1192 ± 513 g) remained stable over the study period. CONCLUSION: Screening data for ROP from two German university hospitals demonstrates a significant increase in both the number of screened infants and the number of infants affected by ROP over the past 5 years.