Originalbeiträge (Originals). Altered microvascular density in patients with anorexia nervosa ­ an optical coherence tomography angiography (OCTA) pilot study.

OBJECTIVES: To investigate macular and peripapillary vascular density (VD) in patients with anorexia nervosa (AN) compared to healthy controls. Methods:Whole face scans of the superficial and deep macular layers and whole face and peripapillary scans of the radial peripapillary capillaries (RPC) were obtained using optical coherence tomography angiography (OCTA, AngioVueR, Optovue) in ten patients with AN and ten age-matched controls.The primary objective was to determine whether there was a difference between the vessel density (VD) in the above areas in AN and controls. P-values ≤ 0.0125 were considered statistically significant. Results: VD in the superficialmacular en-face OCTA image was significantly lower in the study group compared to the control group. Neither the deepmacula nor the radial peripapillary capillary (RPC) in the whole-face image nor the RPC-peripapillary imaging appeared to be significantly different. Conclusion: Patients with AN showed reduced VD in the superficialmacular layers compared to healthy controls, which can be discussed as a consequence of the malnutrition. OCTA could be a useful non- invasive tool to detect reduced peripheral blood supply to show vascular changes that occur before ocular symptoms.

Reduced Retinal Blood Vessel Densities Measured by Optical Coherence Tomography Angiography in Keratoconus Patients Are Negatively Correlated with Keratoconus Severity.

Keratoconus (KC) is the most common corneal ectasia. Optical coherence tomography angiography (OCT-A) is a relatively new non-invasive imaging technique that allows the visualization and quantification of retinal and choriocapillary blood vessels. The aim of this study is to assess retinal and choriocapillary vessel density (VD) differences between KC patients and healthy controls and to investigate correlations between VD and KC severity. Fifty-two eyes were included in this exploratory study: twenty-six eyes from 26 KC patients and twenty-six eyes from 26 age- and gender-matched healthy controls. All patients underwent Scheimpflug corneal topography with Pentacam, axis lengths measurement and optical coherence tomography angiography (OCT-A). The thinnest spot in corneal pachymetry, maximum K (Kmax) and KC severity indices from the Belin/Ambrósio enhanced ectasia display (BAD) were also assessed. There was a distinct reduction particularly in the retinal VD of the superficial capillary plexus (SCP). Correlation analyses showed strong and moderate negative correlations between the VD in the macular SCP and BAD KC scores and between the SCP VD and Kmax. There was no difference in retinal thickness between the KC and healthy controls. With this study, further evidence for altered VD measurements by OCT-A in KC patients is given. For the first time, we demonstrated negative correlations between BAD KC scores and retinal blood vessel alterations. A major limitation of the study is the relatively small sample size. Since an artefactual reduction of the quantitative OCT-A measurements due to irregular corneal topography in KC must be assumed, it remains to be investigated whether there are also actual changes in the retinal microcirculation in KC.

[Frequency and distribution of the active agent of intravitreal injections in German centers 2015-2021-An oregis study]. / Häufigkeit und Wirkstoffverteilung intravitrealer Injektionen in deutschen Zentren 2015 bis 2021 ­ eine oregis-Studie.

INTRODUCTION: Digitalization in medicine, especially the electronic documentation of patient data, is revolutionizing healthcare systems worldwide. The evaluation of real-world data collected under everyday conditions presents opportunities but also challenges. Electronic medical registries provide a means to compile extensive patient data for scientific inquiries. Oregis is the first nationwide digital registry for health services research established by the German Ophthalmological Society (DOG). Intravitreal operative medicinal injections (IVOM) are among the most frequently performed procedures in ophthalmology. Data on injection numbers and injection frequencies with anti-vascular endothelial growth factor (VEGF) are already available from other countries, whereas data at a national level are not yet available in Germany due to the lack of a nationwide register. It is known that the treatment success of anti-VEGF IVOMs depends largely on the adherence to treatment and thus on the number of injections. There are also differences in cost. In the context of this study, real-world data on the frequency and distribution of intravitreal injections in German centers from 2015 to 2021 were compiled for the first time since the introduction of oregis. The aim of this study is to collect data on the use of anti-VEGF IVOMs in Germany from oregis for the first time and to show the development of injection numbers and anti-VEGF drugs used. At the same time, the possibilities of data retrieval from oregis are demonstrated using a concrete example from daily ophthalmological practice. MATERIAL AND METHODS: An automated query of records was performed for all patients who received IVOM at oregis-affiliated healthcare facilities between 2015 and 2021. The number of treated patients and the use of anti-VEGF medications, including aflibercept, bevacizumab, brolucizumab, and ranibizumab, were determined. The data were collected in a pseudonymized and anonymized manner. RESULTS: At the time of data collection, 9 German ophthalmological healthcare facilities were affiliated with oregis. In total, 309,152 patients were registered during the observation period, with 8474 receiving IVOMs. Over the observation period, the number of participating centers, patients, and intravitreal injections increased. The proportional share of anti-VEGF agents among the total number of injections varied during the observation period. DISCUSSION: Real-world data captured in oregis offer significant potential for enhancing healthcare provision. Oregis enables the depiction of ophthalmological care conditions in Germany and contributes to research and quality assurance. The ability to query the presented data exemplifies the multitude of inquiries through which oregis can contribute to the representation of ophthalmological care in Germany.

Accuracy of Bruch's membrane opening minimum rim width and retinal nerve fiber layer thickness in glaucoma diagnosis depending on optic disc size.

BACKGROUND/AIM: The aim of this paper is to compare retinal nerve fiber layer thickness (RNFL) and Bruch's membrane opening-based minimum rim width (BMO-MRW) in terms of their performance in detecting early and moderate/advanced glaucoma using receiver operating characteristics (ROC) analysis and the classification using the 5th percentile as a cut-off. METHODS: One hundred eyes from 100 patients with early glaucoma (mean deviation (MD): < -5.0 dB) and 100 eyes from 100 patients with moderate/advanced glaucoma (MD: > -5.0 dB) were carefully matched to healthy controls based on optic disc size. Then, the dataset was divided, based on the 50th percentile of the measured Bruch's membrane opening area (BMO-A), into small (BMO-A < 1.95 mm2) and large optic discs (BMO-A > 1.95 mm2). Finally, the discriminative performance of BMO-MRW and RNFL between glaucoma and controls using ROC analysis and the manufacturer's classification based on the 5th percentile was analyzed. RESULTS: In discriminating between glaucoma and matched healthy controls, global BMO-MRW and global RNFL thickness had comparable areas under the ROC curve for eyes with early glaucoma and both small BMO-As (ROC ± confidence interval [CI] 0.91 [0.87 to 0.95] and 0.88 [0.83 to 0.93]) and large BMO-As (0.86 [0.82 to 0.92] and 0.84 [0.79 to 0.90]), as well as in moderate/advanced glaucoma with small BMO-As (0.99 [0.98 to 1.00] and 0.97 [0.95 to 1.00]) and large BMO-As (0.94 [0.91 to 0.98] and 0.97 [0.94 to 1.00]). Using the calculated 5th percentile as a threshold value, the sensitivities for the detection of early and moderate/advanced glaucoma were comparable for BMO-MRW and RNFL in eyes with small optic discs (early glaucoma: fifty-two percent and 61%; moderate/advanced glaucoma: ninety-one percent and 92%). In eyes with large optic discs, the sensitivity of BMO-MRW was inferior to that of RNFL for both early (38% versus 51%) and moderate/advanced (80% versus 91%) glaucoma. CONCLUSION: Based on an ROC analysis, the discriminative performance of BMO-MRW and RNFL between patients with early and moderate/advanced glaucoma and a healthy control group matched based on optic disc size is comparable in eyes with BMO-As smaller and larger 1.95 mm2. Using a classification based on the 5th percentile, as used in clinical practice, RNFL is shown to be superior to BMO-MRW regarding sensitivity in glaucoma detection with large optic discs. This study underscores the importance of RNFL imaging and measurement in the diagnostic evaluation of glaucoma, especially in cases of large optic discs.

FURTHER EVIDENCE AGAINST BILATERAL MANIFESTATION OF COATS DISEASE IN OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF THE MACULA.

PURPOSE: Recent studies have questioned the traditional view, which regards Coats disease as a strictly unilateral entity. Applying optical coherence tomography angiography, this prospective, monocentric study investigates quantitative capillary changes of the macula associated with Coats disease. METHODS: Twenty-four eyes (4 untreated, 8 pre-treated) of 12 patients with stage 2 Coats disease (age range: 9-61 years) and 15 eyes of healthy, age-matched controls from the University of Muenster Medical Center, Germany received macular optical coherence tomography angiography measurements of the superficial, deep, and choriocapillary capillary plexus. Flow density and parameters related to the foveal avascular zone were compared between Coats eyes and fellow eyes, and between fellow eyes and control eyes. Additional subanalyses investigated changes based on disease stage. RESULTS: Flow density did not differ between fellow eyes of Coats disease patients and control eyes in any of the parameters investigated. Comparison of Coats eyes to their respective fellow eyes revealed Coats disease to be associated with lower flow density in superficial, deep, and choriocapillary capillary plexus regions, irrespective of disease stage (all P < 0.03). There were no noticeable differences regarding the size or symmetry of the foveal avascular zone. CONCLUSION: In light of the recent discussion around the unilateral character of Coats disease, this trial provides evidence against a bilateral presentation of vascular changes in the macula.

Long-Term Outcomes of Canaliculotomy with Silicone Tube Intubation in the Management of Canaliculitis.

As a rare and often misdiagnosed disease of the lacrimal apparatus, only limited data exist on long-term outcomes of surgical methods for the treatment of primary canaliculitis. The aim of this study was to evaluate canaliculotomy with silicone tube intubation (STI) as a surgical procedure for canaliculitis in a long-term follow-up setting. A total of 25 eyes of 25 patients with canaliculitis treated with canaliculotomy and STI at the University of Muenster Medical Center, Germany, from 2015 to 2021 were included in this study. Data analysis involved clinical symptoms, complications, duration of STI and rate of recurrence. Mean patient age was 63.7 ± 17.2 years. After a follow-up time of 3.7 ± 1.5 years, 88% of cases showed no recurrence of inflammation. The mean duration of STI was 5.8 ± 3.4 months. Complications such as post-operative hemorrhage, spread of infection, obstruction of the canaliculus or migration of the STI were not observed in any of the patients. However, tube dislocation occurred in four cases, a pyogenic granuloma in two cases and a fistula formation in one case. The management of canaliculitis by canaliculotomy with STI showed very good postoperative outcomes and low complication rates in the long-term and can therefore be considered a safe and successful surgical approach.

Primary Optic Disc Tumors - Case Series and Literature Overview. / Primäre Papillentumoren ­ Fallserie und Literaturüberblick.

PURPOSE: Primary optic disc tumors are often a challenge for ophthalmologists. They have very different appearances, and many primary optic disc tumors are associated with syndromic diseases (especially phakomatoses). Because of the rarity of primary optic disc tumors, classification and assessment are often difficult. MATERIAL AND METHODS: A systematic search in the electronic patient files (period 01.01.2015 - 01.06.2022) of the Department of Ophthalmology of the University of Münster Medical Center for patients with primary optic disc tumors was performed. For each tumor entity, exemplary cases were selected, which are presented here in detail. The criteria for the exemplary case selection were a clear diagnosis, the presence of suitable image material and follow-up examinations in our clinic. RESULTS: The search yielded seven cases with three different primary tumor entities in the optic disc region (capillary hemangioblastoma, astrocytic hamartoma and melanocytoma). Four patients were selected as examples and are presented here: two cases for capillary hemangioblastoma (one isolated and the other in the context of Von-Hippel-Lindau syndrome) and one case each for astrocytic hamartoma and melanocytoma). We outline the further diagnosis and the course of the disease and we give an overview of the essential features of the underlying tumors in each case. CONCLUSION: The knowledge of the different primary tumors of the optic disc is necessary for a correct diagnosis and for the differentiation from malignant processes and optic disc anomalies. In many cases, further interdisciplinary diagnostics are necessary. Multimodal imaging is helpful and a referral to a center for ocular tumors is worth considering.

SALUS-a non-inferiority trial to compare self-tonometry in glaucoma patients with regular inpatient intraocular pressure controls: study design and set-up.

PURPOSE: The SALUS study aims to improve the healthcare situation for glaucoma patients in Germany. In order to detect diurnal intraocular pressure (IOP) fluctuations, inpatient monitoring of IOP in an eye hospital for a minimum of 24 h is the current standard. SALUS assesses the benefits of a new form of outpatient care, where IOP can be measured by the patients themselves at home using a self-tonometer. This approach should promote the patient's health competence and empowerment within the healthcare system while reducing treatment costs. METHODS: The SALUS study is a randomized controlled, open non-inferiority trial, alongside an economic analysis, determining whether outpatient monitoring of IOP with self-tonometry is at least as effective as current standard care and would reduce treatment costs. Participants (n = 1980) will be recruited by local ophthalmologists in the area of Westphalia-Lippe, Germany, and randomized to receive 7-day outpatient or 24-h inpatient monitoring. Participants in both study arms will also receive 24-h blood pressure monitoring. Furthermore, patient data from both study groups will be collected in an electronic case file (ECF), accessible to practitioners, hospitals, and the study participants. The primary endpoint is the percentage of patients with IOP peaks, defined as levels 30% above the patient-specific target pressure. Data will also be collected during initial and final examinations, and at 3, 6, and 9 months after the initial examination. RESULTS: The study implementation and trial management are represented below. CONCLUSION: SALUS is a pioneering prospective clinical trial focused on the care of glaucoma patients in Germany. If SALUS is successful, it could improve the healthcare situation and health literacy of the patients through the introduction of various telemedical components. Furthermore, the approach would almost certainly reduce the treatment costs of glaucoma care. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04698876, registration date: 11/25/2020. DRKS-ID: DRKS00023676, registration date: 11/26/2020.

[Corneal epithelial thickness in keratoconus patients compared to healthy controls]. / Hornhautepitheldicke bei Keratokonuspatienten im Vergleich zu gesunden Kontrollen.

BACKGROUND: In keratoconus (KC) a progressive deformation and thinning of the cornea occurs. In contrast to Scheimpflug-based examinations, optical coherence tomography (OCT) can precisely measure the corneal layers separately, allowing separate analyses of corneal epithelial and corneal stromal thicknesses. AIM OF THIS WORK: The aim of this work was to analyze the corneal epithelial thickness measured by optical coherence tomography (OCT) in patients with KC in comparison to the corneal epithelial thickness in healthy subjects. The diagnostic value of the observed changes was evaluated. MATERIAL AND METHODS: In a retrospective analysis 125 eyes of patients with KC and 140 eyes of healthy subjects were included. Corneal measurements were performed by OCT (Optovue, XR-Avanti, Fremont, CA, USA). Corneal stromal thicknesses and corneal epithelial thicknesses in different locations were measured and analyzed. RESULTS: There were significant differences in stromal and epithelial thickness measurements. Of the derived epithelial thickness parameters four showed a good discriminatory power between healthy controls and KC patients (area under the curve in the receiver operating characteristic analysis > 0.7). CONCLUSION: Patients with KC showed an altered epithelial thickness compared to healthy controls. The derived calculated parameters based on corneal epithelial thickness can distinguish between KC and a healthy cornea.

[Optical coherence tomography angiography (OCT-A) : Overview of the technique and the possible clinical and scientific applications]. / Optische Kohärenztomographie-Angiographie (OCT-A) : Überblick über die Technik und Anwendungsmöglichkeiten in Klinik und Wissenschaft.

Optical coherence tomography angiography (OCT-A) is a very promising noninvasive imaging modality. For the first time it enables a precise 3­dimensional depiction of the retinal microcirculation without the use of contrast medium and can be carried out rapidly and simply. This makes OCT­A interesting for both scientific and clinical applications. In many ophthalmological diseases, such as glaucoma and diabetic retinopathy, OCT­A can detect vascular alterations even in the early stages of the disease. These alterations partially correlate with functional parameters. The use of OCT­A in the clinical routine is currently still limited due to imaging artifacts, high acquisition costs and large amounts of data; however, the scientific interest in this new technology is enormous and from our point of view it will become established in the clinical routine in the future.

[Optical coherence tomography angiography and cardiovascular diseases. An overview of the current knowledge]. / Die optische Kohärenztomographie-Angiographie und Erkrankungen des kardiovaskulären Spektrums. Ein Überblick über die aktuelle Studienlage.

BACKGROUND: Cardiovascular diseases (CVD) are the leading cause of death worldwide. The observability of retinal vessel changes in the context of CVD by funduscopy has been known for a long time. Optical coherence tomography angiography (OCTA) is a novel technique for noninvasive detailed imaging and quantification of the retinal microcirculation. The OCTA enables the visualization of vascular changes in a simple and well-reproducible way. Its applications are not limited to the field of ophthalmology. In recent years, several experimental and clinical studies have been published on vascular changes detectable with OCTA in CVD. This review summarizes the most important findings of these studies. METHODS: This work is based on a comprehensive review of the literature and on the presentation of own data. RESULTS: Nowadays, OCTA studies are available for many diseases of the cardiovascular spectrum. This indicates that systemic vascular diseases are associated with changes in the retinal microcirculation. These changes can be visualized and reproducibly quantified with OCTA. In many diseases subclinical changes, which are detectable by OCTA, occur before the underlying disease causes otherwise measurable changes or noticeable symptoms for the patient. CONCLUSION: The OCTA is a promising imaging method in the context of CVD in both scientific and clinical applications. It can be used for the diagnostics and quantification of retinal vascular changes. Further studies will show whether OCTA can be of assistance in the estimation of individual systemic cardiovascular risk profiles.

[Choroidal neovascularization due to a punctate inner choroidopathy visualized by optical coherence tomography angiography]. / Choroidale Neovaskularisation infolge einer "punctate inner choroidopathy", dargestellt mittels optischer Kohärenztomographie-Angiographie.

Punctate inner choroidopathy (PIC) is often accompanied by the development of choroidal neovascularization (CNV). The identification of a fresh CNV in the context of PIC is often difficult. We present the case of a 30-year-old female patient with typical morphological features of PIC. A CNV could not be detected with certainty by optical coherence tomography (OCT) or by fluorescein angiography (FAG); however, OCT angiography (OCT-A) revealed a circumscribed CNV. The case suggests that there are a high number of undiagnosed, subclinical secondary CNVs not requiring treatment in PIC patients.

Altered microvascular density in patients with systemic lupus erythematosus treated with hydroxychloroquine-an optical coherence tomography angiography study.

PURPOSE: To evaluate the retinal microvascular density using optical coherence tomography angiography (OCTA) in patients with systemic lupus erythematosus (SLE) treated with hydroxychloroquine (HCQ). METHODS: Nineteen eyes of 19 patients with SLE (study group) without HCQ retinopathy and 19 eyes of 19 healthy subjects (control group) were included in this study. The study group was divided into patients using HCQ for > 5 years (high-risk group) and < 5 years (low-risk group). The VD data of the 3 × 3 mm OCT angiogram of the superficial capillary plexus (SCP) and the choriocapillaris (VD-CC), the foveal avascular zone (FAZ) area and the central retinal thickness (CRT) were extracted and analyzed. RESULTS: VD in the en face SCP was significantly reduced in the high-risk group and the low-risk group compared with that in the control group (p < 0.001, p = 0.001) and in the high-risk group compared with the low-risk group (p = 0.007). Correlation analysis between the cumulative dose of HCQ and the VD of the study group revealed a negative correlation, but no statistical significance (p = 0.074). However, a significant positive correlation was observed for the low-risk group (p = 0.035). In patients with SLE, VD-CC was lower (p = 0.042) and the FAZ area larger (p = 0.019). CRT showed no difference between the groups (p = 0.183). CONCLUSION: In this study, SLE patients showed a reduced VD in both groups. In patients treated with HCQ < 5 years, HCQ might have a protective effect on retinal microvasculature. Analysis of retinal microvascular density using OCTA could be useful in the diagnosis and monitoring of vascular alteration in patients with SLE.

Impact of Working Experience on Image Perception and Image Evaluation Approaches in Stroke Imaging: Results of an Eye-Tracking Study.

PURPOSE: Higher rates of missed pathologies, caused by a lack of professional experience or systematic search, suggest that a methodical approach to radiological analysis can be learned. Thus, the aim of this study is to investigate the efficiency of different principles of screening stroke CTs for cerebrovascular diseases between radiologists and neuroradiologists with different levels of experience in relation to professional experience. METHODS: A set of anonymous CT images of 20 patients, with a suspected stroke, was individually presented to 12 radiologists with different levels of professional experience. Meanwhile, their fixation position was recorded by an eye-tracking system. For statistical analysis, the interobserver variability and accuracy of lesion detection were evaluated, taking the individual level of professional experience into account. RESULTS: The sensitivity of the observer depends on the professional experience, also determined by a systematic observation sequence and knowledge of the course of the disease. The duration of eye fixation with inexperienced assessors was significantly longer for conspicuous findings, while experienced assessors were more likely to fix clinically relevant regions. The retention time of ocular fixation in important pathological findings did not differ significantly between those groups. CONCLUSION: Our results indicate that experienced radiologists are reducing the number of missed findings through a systematic approach and targeted inspection of important regions. Through raising the awareness of analyzing CT images in systematic patterns, physicians at all levels of experience seem to be able to improve their performance. KEY POINTS: · Experienced radiologists improve detection rates through targeted inspection of clinically important regions.. · Experienced radiologists reduce time spent on analysis through focused visual attention.. · All levels of experience improve their performance by analyzing CT images systematically.. CITATION FORMAT: · Kammerer S, Schülke C, Leclaire MD et al. Impact of Working Experience on Image Perception and Image Evaluation Approaches in Stroke Imaging: Results of an Eye-Tracking Study. Fortschr Röntgenstr 2019; 191: 836 - 844.

Lipofuscin-dependent stimulation of microglial cells.

PURPOSE: To examine the reaction of microglial cells (MG) when incubated with lipofuscin (LP) in vitro with emphasis on the immunological reaction of the MG toward LP and the suppression of this reaction by immunomodulatory agents. MG are involved in the pathogenesis of degenerative eye disorders such as age-related macular degeneration (AMD). LP is a heterogeneous waste material that accumulates in the retinal pigment epithelium (RPE) cells with advancing age. LP is known to have toxic effects on RPE cells and therefore an elevated LP-derived fundus autofluorescence is a risk factor for AMD development. MG in the subretinal space have been reported in eyes affected by AMD. Moreover, in senescent mice, subretinal MG were found, which display an autofluorescence that may be derived from LP uptake. METHODS: In this study, we incubated MG (BV-2 cell line and primary cells from murine brain) in vitro with LP isolated from the human RPE. We observed phagocytosis, studied cell morphologies, and analyzed the cell culture supernatants. We also investigated the effect of the immunomodulatory agents hydrocortisone (HC), minocycline, and the tripeptide TKP. RESULTS: The MG phagocytosed the LP quickly and completely. We detected highly elevated levels of pro-inflammatory cytokines (especially of IL-6, IL-23p19, TNF-α, KC, RANTES, and IL-1α) in the cell culture supernatants. Furthermore, levels of vascular endothelial growth factor (VEGF) were raised in BV-2 cells. Anti-inflammatory agents added to the cell cultures inhibited the inflammatory reaction, in particular hydrocortisone (HC). Minocycline and TKP had less impact on the cytokine release. CONCLUSION: The interaction of MG and LP could play a role in the development of retinal degeneration by triggering an inflammatory reaction and angiogenesis.

Allergies - A T cells perspective in the era beyond the TH1/TH2 paradigm.

Allergic diseases have emerged as a major health care burden, especially in the western hemisphere. They are defined by overshooting reactions of an aberrant immune system to harmless exogenous stimuli. The TH1/TH2 paradigm assumes that a dominance of TH2 cell activation and an inadequate TH1 cell response are responsible for the development of allergies. However, the characterization of additional T helper cell subpopulations such as TH9, TH17, TH22, THGM-CSF and their interplay with regulatory T cells suggest further layers of complexity. This review summarizes state-of-the-art knowledge on T cell diversity and their induction, while revisiting the TH1/TH2 paradigm. With respect to these numerous contributors, it offers a new perspective on the pathogenesis of asthma, allergic rhinitis (AR) and atopic dermatitis (AD) incorporating recent discoveries in the field of T cell plasticity.