Background and Objective Central serous chorioretinopathy (CSCR) is characterized by serous detachments of the central neurosensory retina. Besides, other alterations of the retinal pigment epithelium (RPE) of the focal detachment of the RPE can occur. We explored the frequency of RPE detachment and double layer sign in OCT in our patient population, the influence of subthreshold photocoagulation (ST-LP) on these parameters and the possibility of correlations with visual acuity. Materials and Methods We conducted a retrospective analysis of all patients who underwent ST-LP based on the diagnosis of CSCR in a German university eye clinic from 2009 to 2014. Measurements in OCT were performed regarding pigment epithelial detachment (PED) and double layer sign (DLS). Results 54 eyes of 49 patients were included in the study. The frequency of PEDs dropped from 66% of cases at baseline to 50% after 3 months. No significant differences in calculated areas of lift-off volume of PED were identified. The frequency of a DLS was significantly lower 8 weeks after ST-LP compared to baseline (63%, p<0.05), but not after 12 weeks. Conclusion We conclude that PEDs and DLS are common in CSCR. In this study, no convincing correlation can be identified between BCVA before ST-LP or at the last visit and different characteristics of PED as well as DLS. While the area of PED becomes smaller after ST-LP, the extent of the DLS seems to increase. Further prospective studies are required, and DLS with respect to the occurrence of CNV should also be given attention.

Purpose: Central serous chorioretinopathy (CSCR) presents itself as a serous detachment of the central neurosensory retina (NR), which may be accompanied by focal detachment of the retinal pigment epithelium (RPE) and changes in the RPE itself. It is often self-limiting; however, if the macular region is affected, visual impairment can be serious. If spontaneous remission does not occur, data on the effectiveness of further treatment options are sparse. We therefore decided to examine the effectiveness of subthreshold laser photocoagulation (ST-LP) on best-corrected visual acuity (BCVA) and subretinal fluid (SRF) resorption. We conducted a retrospective analysis of all patients who underwent ST-LP based on the diagnosis of CSCR in a German university eye hospital from 2009 to 2014. Methods: The diagnosis of CSCR was based on the following criteria: detachment of the NR and possibly the RPE visible on ophthalmoscopy, evidence of SRF on optical coherence tomography (OCT), visualization of one or more source points typical for CSCR in fluorescein angiography, and exclusion of differential diagnoses. The time between the anamnestic onset of symptomatic complaints and ST-LP was determined as well as BCVA and OCT before ST-LP. ST-LP was performed as a subthreshold thermal laser coagulation with a frequency-doubled Nd:YAG continuous-wave laser. Follow-up examinations were scheduled at 4, 8, and 12 weeks after ST-LP. Results: Fifty-four eyes of 49 patients were included in the study. The median age of patients was 47 years. Eighty-nine percent of the included patients were male. Twenty percent of patients had a first manifestation of CSCR, 69% had a recurrence, and 11% had persistent SRF for >6 months. The median visual acuity rose from 0.30 at baseline (BL) to 0.10 at 4 weeks and 0.00 at 8 weeks, before dropping slightly to 0.05 at 12 weeks. Changes of visual acuity in comparison to BL were statistically significant (p < 0.05). The initial median retinal thickness of 397 μm at BL decreased to 264 μm at 4 weeks, to 236 μm at 8 weeks, and to 239 μm at 12 weeks (decreases to BL all statistically significant p < 0.05). Conclusion: In our cohort, we were able to achieve substantial and significant clinical benefit through ST-LP measured by improvement in BCVA. Furthermore, we were also able to demonstrate measurable, significant morphological improvements as decreased retinal thickness and increased resorption of SRF as probable mechanisms explaining clinical improvement of CSCR with ST-LP. The advantage of ST-LP over other methods is the low risk of adverse events and its high availability. Controlled, randomized studies are necessary to confirm the data and demonstrate the effect over a longer period of time.

PURPOSE:Ranibizumab monotherapy showed stronger effects on area of retinal neovascularization (NV) reduction while offering better visual acuity (VA) results than panretinal laser photocoagulation (PRP) monotherapy during the first 12 months of the PRIDE study. The second year of PRIDE was an observational, non-interventional follow-up, performed to evaluate long-term anatomical and functional outcomes in proliferative diabetic retinopathy (PDR) patients under real-life conditions, prior to the approval of ranibizumab for PDR.METHODS:Seventy-three PDR patients (28 from the ranibizumab group; 20 from the PRP group; 25 from the combination group) were included in the observational follow-up phase and treated at the investigators discretion. Visual acuity (VA) measurements and retinal imaging were performed at Months 12, 18 and 24.RESULTS:Mean (± SD) NV area in the ranibizumab monotherapy and combination follow-up groups increased from 3.16 ± 4.30 mm2 and 1.13 ± 2.78 mm2 at Month 12 to 6.09 ± 10.79 mm2 and 2.14 ± 4.41 mm2 at Month 18 and 10.00 ± 17.63 mm2 and 3.26 ± 7.05 mm2 at Month 24, respectively. In the PRP follow-up group, NV area declined from 5.44 ± 14.55 mm2 at Month 12 to 1.22 ± 1.67 mm2 at Month 18, but increased again to 4.05 ± 11.66 mm2 at Month 24. During the observational phase, only 2 (6;8) patients in the ranibizumab (PRP;combination) follow-up group were treated with anti-VEGF medications, while 17 (6;10) patients received PRP laser therapy.CONCLUSION:Discontinuation of ranibizumab treatment in PDR patients may result in an increase of NV area and VA loss. Tight monitoring of disease activity and continued treatment beyond the first year is needed to maintain disease control.

PURPOSE:To characterize preretinal neovascularizations (NV) and their corresponding branching routes in proliferative diabetic retinopathy (PDR) with optical coherence tomography angiography (OCTA) and compare the findings with fluorescein angiography (FA).METHODS:In patients with PDR, angiograms were acquired with spectral-domain OCTA (CIRRUS 5000, OCTA AngioPlexTMCarl Zeiss Meditec, Inc.) and FA (Zeiss FF450PlusIR fundus camera or Spectralis HRA-OCT SLO, Heidelberg Engineering Inc.) and were consecutively evaluated. Neovascularization of the disc (NVD) and neovascularization elsewhere (NVE) were analyzed with 6 × 6 and 8 × 8 mm OCTA flow images and B-scans with flow registration. Segmentations of the vitreoretinal interface (VRI) and superficial retina were performed for analysis. Two independent investigators examined OCTA findings and compared them to corresponding FA.RESULTS:Forty-two eyes of 30 patients with PDR were analyzed. A total of 76 NV with their corresponding proliferation routes were visualized and characterized, with 55 (72.4%) proliferating along the posterior hyaloid membrane (PHM), 14 (18.4%) along the epiretinal membrane, and 7 (9.2%) along the fibrovascular membrane. The posterior vitreous was partially detached in 37 of 42 eyes (88.1%), completely detached in 1 of 42 eyes (2.4%), and adherent in 1 of 42 eyes (2.4%). In 38 of 42 cases, OCTA was superior (n = 23) or equivalent (n = 15) to FA in detecting NV and provided a more detailed information of the neovascular vessels. In 4 of 42 study eyes, OCTA was inferior to FA.CONCLUSIONS:OCTA is a useful tool to detect NV in PDR. In comparison to FA, OCTA has the advantages that it is noninvasive and the image capture takes only seconds. We were able to identify all NV and characterize their corresponding proliferation routes in the VRI, the superficial retina slab, or the B-scan with flow registration. Through evading the masking effect of dye leakage in FA, OCTA is capable of better visualization of NV. FA, however, remains essential for the detection of all NV, since OCTA supplies a smaller detection field. Additionally, we identified the PHM as the main proliferating route of diabetic NV (72.4%), marking it as an important structure for sprouting vessels in neoangiogenesis in PDR.

Contradictory behavior of microvascular retinal endothelial cells (REC) - a reliable in vitro model to study retinal diseases - have recently been reported which might result from cultivating the cells in standard DMEM not optimized for this cell type. Therefore, we studied DMEM's effects on phenotype and behavior of immortalized bovine REC. Cells were cultivated in endothelial cell growth medium (ECGM) until a confluent monolayer was reached and then further kept for 1–4 days in ECGM, DMEM, or mixes thereof all supplemented with 5% fetal bovine serum, endothelial cell growth supplement, 90 μg/ml heparin, and 100 nM hydrocortisone. Within hours of cultivation in DMEM, the cell index – measured to assess the cell layer's barrier function - dropped to ~5% of the initial value and only slowly recovered, not only accompanied by stronger expression of HSP70 mRNA and secretion of interleukin-6, but also by lower expressions of tight junction proteins claudin-5, claudin-1 or of the marker of cell type conversion caveolin-1. Altered subcellular localizations of EC-typic claudin-5, vascular endothelial cadherin and von Willebrand factor were also observed. Taken together, all experiments with (retinal) EC cultivated in common DMEM need to be interpreted very cautiously and should at least include phenotypic validation.

Ein 78-jähriger Patient stellte sich mit einer seit 3 Wochen bestehenden, beidseitigen Visusminderung mit nebligem und unscharfem Sehen sowie einer reduzierten Farbwahrnehmung vor. Weiter klagte der Patient über ebenfalls seit 3 Wochen vorhandene Kopfschmerzen. An Vorerkrankungen waren ein Diabetes mellitus Typ II (HbA1c = 6,7%), eine arterielle Hypertonie, Vorhofflimmern, ein Z. n. Apoplex im Mediastromgebiet links 2015 mit Lysetherapie sowie Z. n. beidseitigen, asymptomatischen Lungenarterienembolien und eine chronische Sinusvenenthrombose im Sinus transversus links bekannt. Eine orale Antikoagulation mit Pradaxa wurde aufgrund der genannten Vorerkrankungen eingenommen. Die ophthalmologische Anamnese war bis auf eine beidseitige Kataraktoperation leer.

Ein gigantischer Stern am deutschen und globalen Ophthalmologen-Himmel hat aufgehört zu leuchten – Gottfried Otto Helmut Naumann ist tot. Wer war dieser schon zu Lebzeiten legendäre deutsche Augenarzt, dessen Person und Wirken weit über die Grenzen unseres Landes hinaus strahlte?

Vor 10 Jahren hat die Schriftleitung der Klinischen Monatsblätter für Augenheilkunde das Format von 12 Schwerpunktthemen (Onkologie und Pathologie/Entzündliche Erkrankungen/Hornhaut, Sklera und Bindehaut/Ophthalmoplastische Chirurgie/Glaukom/Strabologie und Kinderophthalmologie/Neue Technologien/Retina und Glaskörper/Linse, Katarakt und refraktive Chirurgie/Genetik/Neuroophthalmologie/Handlungspfade und Schritt für Schritt) ins Leben gerufen.

Background The patient's knowledge about their illness, as well as their expectations regarding pre-intervention, consultation and treatment, may differ from the physician's assumptions. Therefore, it is of great importance that the physician can identify misconceptions and missing knowledge and to focus on those points in the preoperative consultation, as well as meeting patient expectations as to the consultation itself. The aim of this study was to identify such expectations and the knowledge gaps of patients scheduled for ophthalmologic treatment.Method An anonymous questionnaire containing predominantly closed questions was handed out to 100 patients in an ophthalmological outpatient clinic of a tertiary care center. Answers were mostly single choice items on a rating scale.Results 55% of patients had received ophthalmological interventions prior to receiving the questionnaire; 36% received more than two. More than half had not informed themselves about the planned procedure prior to their appointment. They were worried the most about complications (59%) and least about the anaesthesia (29%). When asked, patients attributed the highest priority to provision of information regarding complications and most often requested information on implications of the planned surgery on daily activities.Conclusion Roughly half of the patients came without having informed themselves prior to the consultation. A comprehensive explanation with regard to success rates and possible post-surgical impairments appears to be essential. Possibilities of new media, such as the internet, surprisingly do not seem to be of importance to patients in this context.

Background OCT angiography (OCT-A) allows non-invasive blood flow registration of the retina and choroid. In contrast to fluorescein angiography (FA), no dye has to be administered. The OCT-A also provides depth-selective information. OCT-A and FA were compared in patients with neovascular age-related macular degeneration (AMD) with retinal angiomatous proliferation (RAP) stage 1. In stage 1, the neovascularizations are intraretinal. In contrast to the two-dimensional total image of the FA, the OCT-A allows a depth-selective display of the individual retinal layers. In this way, a conclusion can be drawn about the place of origin of the RAP. Patients and Methods Three patients with neovascular AMD and RAP stage 1 were included. They were examined with OCT (ZEISS CIRRUS HD-OCT 5000, Carl Zeiss Meditec, Inc., Dublin, USA), OCT-A (ZEISS AngioPlex OCT-Angiography) as well as FA (HRA2, Heidelberg Engineering) between January 2016 and March 2019. A complete ophthalmological examination was performed. A qualitative analysis of the OCT-A images (3x3 and 6x6mm) and the FA images was carried out. Leaks in the FA were compared with the en-face images of the OCT-A followed by a depth-selective assignment using the corresponding B-scans of the OCT-A. Results It was one woman and two men aged 66-89 years. The visual acuity was 0.4 in the first, 0.5p in the second and 0.8 in the third patient. The diagnosis of RAP stage 1 could be made both in the OCT, the FA and the OCT-A. All patients showed macular edema in the OCT. The FA showed selective hyperfluorescence in the early phase and fluorescein extravasation in the late phase. In OCT-A, the blood flow in all patients could be shown in the hyperreflective structure of the RAP in the B-scan. The first patient showed two RAP lesions in the FA, which were in the deep vascular plexus in the OCT-A. In the second patient, three RAP lesions were found in the FA, and a total of five RAP lesions in the OCT-A. One could be located in the superficial and deep vascular plexus, four in the deep vascular plexus. The third patient showed one RAP lesion in the FA as well as in the OCT-A, which could be assigned to the superficial vascular plexus. Conclusion The OCT-A is well suited for the diagnosis of RAP stage 1. In the present cases, the diagnosis in the OCT-A could be made as clearly as by FA. A major advantage of the OCT-A results from the non-invasive character and the depth selectivity. The RAP 1 lesions could be assigned to both the superficial and the deep vascular plexus. Depth selection is not possible with the FA due to the summary picture. Zusammenfassung Hintergrund Die optische Koharenztomografie-Angiografie (OCT-A) ermoglicht eine nicht invasive Blutflussregistrierung der Netzhaut und Aderhaut. Im Gegensatz zur Fluoresceinangiografie (FA) wird kein Farbstoff verabreicht. Die OCT-A liefert zusatzlich tiefenselektive Informationen. Bei Patienten mit neovaskularer altersbezogener Makuladegeneration (AMD) mit retinalen angiomatosen Proliferationen (RAP) Stadium 1 wurden OCT-A und FA verglichen. Im Stadium 1 befinden sich die Neovaskularisationen intraretinal. Im Gegensatz zum 2-dimensionalen Summenbild der FA kann mithilfe der OCT-A eine tiefenselektive Darstellung der einzelnen Netzhautschichten erfolgen. Hierdurch kann ein Ruckschluss auf den Entstehungsort der RAP gezogen werden. Patienten und Methoden Es wurden 3 Patienten mit neovaskularer AMD und RAP Stadium 1 eingeschlossen, die zwischen Januar 2016 und Marz 2019 sowohl mit OCT (ZEISS CIRRUS HD-OCT 5000, Carl Zeiss Meditec, Inc., Dublin, USA), OCT-A (ZEISS AngioPlex OCT-Angiografie) als auch FA (HRA2, Heidelberg Engineering) untersucht wurden. Es erfolgte eine komplette augenarztliche Untersuchung. Es wurde eine qualitative Analyse der OCT-A-Bilder (3x3 und 6x6mm) und der FA-Bilder durchgefuhrt. Leckagen in der FA wurden mit den En-face-Aufnahmen der OCT-A verglichen. Anschlie ss end erfolgte eine tiefenselektive Zuordnung anhand der entsprechenden B-Scans der OCT-A. Ergebnisse Es handelte sich um eine Frau und 2 Manner im Alter zwischen 66 und 89 Jahren. Der Visus betrug 0,4 beim 1., 0,5p beim 2. und 0,8 beim 3. Patienten. Die Diagnose einer RAP Stadium 1 konnte sowohl im OCT, mit der FA als auch mit der OCT-A gestellt werden. Bei allen Patienten zeigte sich in der OCT ein Makulaodem. In der FA zeigten sich punktuelle Hyperfluoreszenzen in der Fruhphase und eine Fluoresceinextravasation in der Spatphase. In der OCT-A konnte im B-Scan der Blutfluss bei allen Patienten in der hyperreflektiven Struktur der RAP dargestellt werden. Bei dem 1. Patienten zeigten sich 2 RAP-Lasionen in der FA, die in der OCT-A im tiefen vaskularen Plexus lagen. Beim 2. Patienten fanden sich 3 RAP in der FA, in der OCT-A insgesamt 5 RAP-Lasionen. Eine konnte im oberflachlichen und tiefen vaskularen Plexus, 4 im tiefen vaskularen Plexus lokalisiert werden. Bei dem 3. Patienten zeigte sich eine RAP in der FA, ebenso wie in der OCT-A, die sich dem oberflachlichen vaskularen Plexus zuordnen lie ss. Schlussfolgerung Die OCT-A eignet sich gut zur Diagnostik einer RAP Stadium 1. In den vorliegenden Fallen konnte die Diagnose in der OCT-A ebenso eindeutig wie durch eine FA gestellt werden. Ein gro ss er Vorteil der OCT-A ergibt sich durch den nicht invasiven Charakter und die Tiefenselektivitat. Die RAP-1-Lasionen konnten sowohl dem superfiziellen als auch dem tiefen vaskularen Plexus zugeordnet werden. Eine Tiefenselektion ist mit der FA aufgrund des Summenbildes nicht moglich.

Best vitelliform macular dystrophy (BD), autosomal dominant vitreoretinochoroidopathy (ADVIRC), and the autosomal recessive bestrophinopathy (ARB), together known as the bestrophinopathies, are caused by mutations in the bestrophin-1 (BEST1) gene affecting anion transport through the plasma membrane of the retinal pigment epithelium (RPE). To date, while no treatment exists a better understanding of BEST1-related pathogenesis may help to define therapeutic targets. Here, we systematically characterize functional consequences of mutant BEST1 in thirteen RPE patient cell lines differentiated from human induced pluripotent stem cells (hiPSCs). Both BD and ARB hiPSC-RPEs display a strong reduction of BEST1-mediated anion transport function compared to control, while ADVIRC mutations trigger an increased anion permeability suggesting a stabilized open state condition of channel gating. Furthermore, BD and ARB hiPSC-RPEs differ by the degree of mutant protein turnover and by the site of subcellular protein quality control with adverse effects on lysosomal pH only in the BD-related cell lines. The latter finding is consistent with an altered processing of catalytic enzymes in the lysosomes. The present study provides a deeper insight into distinct molecular mechanisms of the three bestrophinopathies facilitating functional categorization of the more than 300 known BEST1 mutations that result into the distinct retinal phenotypes.

Purpose:The bradykinin 1 receptor may be important in inflammatory retinal vascular leakage in diabetic macular edema. BI 1026706 is an antagonist of bradykinin 1 receptor that has demonstrated efficacy in preclinical studies. Boehringer Ingelheim trial 1320.22 (NCT02732951) was a randomized, double-blind, placebo-controlled study. The pharmacodynamics, safety, and tolerability of oral BI 1026706 for 12 weeks were evaluated in patients with type 1 or type 2 diabetes mellitus and mild visual impairment owing to center-involved diabetic macular edema. Methods:Patients (n = 105) were randomized to receive either oral BI 1026706 100 mg twice daily (morning and evening) or placebo for 12 weeks. The primary end point of the study was week 12 change from baseline in central subfield foveal thickness (CSFT) by spectral domain optical coherence tomography. Additional end points included absolute CSFT values, safety, and pharmacokinetics. Results:After 12 weeks of treatment, there was no meaningful change from baseline in the adjusted mean CSFT in either treatment group (BI 1026706, 10.3 µm; placebo, -6.2 µm; adjusted mean treatment difference, 16.5 µm [95% confidence interval, -16.2 to 49.1]). There were also no differences in best-corrected visual acuity outcomes between treatment groups. Most reported adverse events were of mild or moderate intensity, and were balanced between treatment groups. Conclusions:BI 1026706 was not superior to placebo in CSFT week-12 change from baseline. Therefore, BI 1026706 does not reduce CSFT, a morphologic sign of diabetic macular edema. Translational Relevance:Kinin-kallikrein inhibition effects may not be apparent over 12 weeks for bradykinin 1 receptor inhibition alone.