Central Serous Chorioretinopathy: Morphological and Functional Outcome after Subthreshold Thermal Laser Coagulation with a Frequency-Doubled Nd:YAG Continuous-Wave Laser.

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.

Observational outcomes in proliferative diabetic retinopathy patients following treatment with ranibizumab, panretinal laser photocoagulation or combination therapy - The non-interventional second year follow-up to the PRIDE study.

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.

Optical Coherence Tomography Angiography Findings in Proliferative Diabetic Retinopathy.

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.

Type of culture medium determines properties of cultivated retinal endothelial cells: induction of substantial phenotypic conversion by standard DMEM.

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.

[Patient's Knowledge after Informed Consent for Intravitreal Injections]. / Intravitreale Injektionen ­ welche Informationen aus dem Aufklärungsgespräch bleiben Patienten im Gedächtnis?

BACKGROUND: Intravitreal treatment (IVT) is one of the most common ophthalmological procedures. Therapeutic effectiveness is however dependent on patient compliance. Unwanted treatment cessation rates are high though. The authors therefore decided to analyse the patient's knowledge and treatment expectations, as discrepancies are known to negatively affect compliance and thus treatment outcomes. PATIENTS AND METHODS: The study was designed as an exploratory survey. In total, 100 patients presenting to an outpatient clinic of a tertiary care centre from October to December 2016 were included. A structured, anonymised questionnaire was handed out, consisting mainly of question items with closed code lists as response domains. Solely descriptive analysis of results was performed. RESULTS: The median age of patients was 73 years. 70% had received more than 3 IVTs in at least one eye. Age-related macula degeneration was the most common underlying cause (52%). 64% expected improvement of visual acuity after IVT. 42% could not name one medication used in their IVT. 55% felt that the information provided during informed consent had been adequate. 69% did not know the post-surgical occurrence of endophthalmitis. Three patients were confident of being able to drive a car directly after IVT. CONCLUSION: Patient's knowledge of their underlying disease, treatment goals and complications rates exhibited some deficiencies. Standardised patient information sheets could be of significant use and were actively suggested by patients to improve the informed consent process.

OCT Angiographic Findings in Retinal Angiomatous Proliferation. / OCT-angiografische Befunde bei retinalen angiomatösen Proliferationen.

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 (3 × 3 and 6 × 6 mm) 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, 0.5 p 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.

Bradykinin 1 Receptor Antagonist BI1026706 Does Not Reduce Central Retinal Thickness in Center-Involved Diabetic Macular Edema.

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.

Transport and fate of aflibercept in VEGF-A165-challenged retinal endothelial cells.

Retinal vessels are at least in part involved in clearing of Fc terminus-containing proteins from the vitreous. In vitro, the Fc fusion protein aflibercept is transported through a monolayer of unchallenged immortalized bovine retinal endothelial cells (iBREC), mediated by the neonatal Fc receptor (FcRn), but part of the Fc fusion protein is also degraded. Aflibercept's target VEGF-A not only enhances the permeability of REC by destabilization of tight junctions (TJs) thereby allowing for paracellular flow, it may also lower the intracellular stability of the Fc fusion protein by changing its binding properties to the FcRn. Therefore, we investigated the transport and fate of aflibercept in VEGF-A165-challenged iBREC. All cell culture media were supplemented with 5% fetal bovine serum (FBS) as its absence results in accumulation of aflibercept in iBREC due to deregulated expression of transport proteins. Early after exposure of a confluent iBREC monolayer cultivated on gold electrodes to 5% FBS, the cell index (CI) - assessed as a measure of barrier function, cell viability and cell adhesion - transiently declined but recovered again within a few hours to high values. These values remained stable for several days associated with a strong expression of the TJ-protein claudin-1, indicative of a functional barrier formed by the iBREC monolayer. Transient changes of the plasma membrane localizations of claudin-5 and vascular endothelial cadherin - both important for regulation of paracellular flow - accompanied the transient reduction of the CI not prevented by VEGF-binding proteins. Treatment of iBREC with 50 ng/ml VEGF-A165 for one day resulted in a strong and persistent decline of the CI associated with a low expression level of the TJ-protein claudin-1; reversion to normal values was complete one day after aflibercept's addition at a final concentration of 250 µg/ml. Expressions of other proteins involved in regulation of paracellular flow or transcellular transport were not significantly changed. More aflibercept passed through the monolayer of iBREC cultivated on permeable membrane inserts pretreated with VEGF-A for one day, but this was not affected by a FcRn-inhibiting antibody. Subcellular localization of aflibercept was hardly changed in VEGF-A-exposed iBREC 3 h after its addition to the cells; inhibition of (non)-lysosomal or proteasomal proteases then only weakly affected the amount of internalized aflibercept. iBREC also internalized VEGF-A which was barely detectable as early as 2 h after addition of aflibercept. In contrast, blocking the tyrosine kinase activity of VEGF receptor(s) did not prevent VEGF-A's uptake. Inhibition of cellular proteases strongly increased the amount of internalized VEGF-A in the absence and presence of the Fc fusion protein. We therefore conclude that a FcRn-mediated transport plays a minor role in aflibercept's passage through a leaky barrier of REC. Even early after addition of aflibercept to VEGF-A-exposed iBREC, the levels of free intracellular VEGF-A are low, as aflibercept likely prevents binding of VEGF-A to its receptor. Interestingly, the growth factor's detrimental effects still persist for nearly one day.

Sitagliptin and the Blood-Retina Barrier: Effects on Retinal Endothelial Cells Manifested Only after Prolonged Exposure.

Inhibitors of dipeptidyl peptidase-4 (DPP-4) are widely used to treat diabetes mellitus, but data concerning their effects on the barrier stability of retinal endothelial cells (REC) in vivo and in vitro are inconsistent. Therefore, we studied whether the barrier properties of immortalized endothelial cells of the bovine retina (iBREC) were affected by the inhibitors of DPP-4 sitagliptin (10-1000 nM) and diprotin A (1-25 µM). Their effects were also investigated in the presence of VEGF-A165 because diabetic patients often develop macular edema caused by VEGF-A-induced permeability of REC. To detect even transient or subtle changes of paracellular and transcellular flow as well as adhesion of the cells to the extracellular matrix, we continuously monitored the cell index (CI) of confluent iBREC grown on gold electrodes. Initially, the CI remained stable but started to decline significantly and persistently at 40 h or 55 h after addition of sitagliptin or diprotin A, respectively. Both inhibitors did not modulate, prevent, or revert the persistent VEGF-A165-induced reduction of the CI. Interestingly, sitagliptin and diprotin A increased the expression of the tight-junction protein claudin-1 which is an important component of a functional barrier formed by iBREC. In contrast, expressions of CD29-a subunit of the fibronectin receptor-or of the tetraspanin CD9 were lower after extended treatment with the DPP-4 inhibitors; less of the CD9 was seen at the plasma membrane after prolonged exposure to sitagliptin. Because both associated proteins are important for adhesion of iBREC to the extracellular matrix, the observed low CI might be caused by weakened attachment of the cells. From our results, we conclude that extended inhibition of DPP-4 destabilizes the barrier formed by microvascular REC and that DPP-4 inhibitors like sitagliptin do not counteract or enhance a VEGF-A165-induced barrier dysfunction as frequently observed in DME.

The Usefulness of Serum Biomarkers in the Early Stages of Diabetic Retinopathy: Results of the EUROCONDOR Clinical Trial.

The main aim of this study was to evaluate the ability of serum biomarkers to predict the worsening of retinal neurodysfunction in subjects with type 2 diabetes. For this purpose, we measured selected molecules (N-epsilon-carboxy methyl lysine (CML), laminin P1 (Lam-P1), and asymmetric dimethylarginine (ADMA)) in the serum of 341 participants of the EUROCONDOR study at baseline, 24, and 48 weeks. Retinal neurodysfunction was assessed by measuring implicit time (IT) using multifocal electroretinography, and structural changes were examined by spectral domain-optical coherence tomography. The values of IT at baseline were directly correlated with baseline serum concentrations of CML (r = 0.135, p = 0.013). Furthermore, in the placebo group, increase in CML concentration throughout follow-up correlated with the IT (r = 0.20; p = 0.03). Baseline serum levels of CML also correlated with macular retinal thickness (RT) (r = 0.231; p < 0.001). Baseline Lam-P1 levels correlated with the increase of the RT at the end of follow-up in the placebo group (r = 0.22; p = 0.016). We provide evidence that CML may be a biomarker of both retinal neurodysfunction and RT, whereas Lam-P1 was associated with RT only. Therefore, circulating levels of these molecules could provide a complementary tool for monitoring the early changes of diabetic retinopathy (DR).

VEGF receptor 2 inhibitor nintedanib completely reverts VEGF-A165-induced disturbances of barriers formed by retinal endothelial cells or long-term cultivated ARPE-19 cells.

Various severe ocular diseases are associated with an elevated intravitreal expression of VEGF-A which increases the permeability of retinal endothelial cells (REC) or retinal pigment epithelial (RPE) cells in vivo and in vitro. Inhibition of VEGF receptor 2 (VEGFR2) is sufficient to completely prevent VEGF-A165-induced dysfunctions of barriers formed by long-term cultivated, immortal human ARPE-19 cells or immortalized bovine retinal endothelial cells (iBREC). Extended exposure to VEGF-A could result in additional activation of other growth factor receptors, potentially promoting synergistic effects of corresponding factors on various cellular processes including angiogenesis. Based on these observations, we investigated whether blocking of VEGFR2 is also sufficient to revert VEGF-A-induced changes of the barriers consisting of iBREC (i.e. inner blood-retina barrier) or ARPE-19 cells (i.e. outer blood-retina barrier) in vitro. Alterations of confluent monolayers' properties induced by treatment with VEGF-A165 for one day followed by addition of small molecule inhibitors of the VEGFR2 were determined by continuous cell index (CI) measurements using the microelectronic biosensor system for cell-based assays xCELLigence. VEGF-A165 induced a long-lasting drop of the otherwise high CI of iBREC accompanied by reduced expression of the tight junction (TJ) protein claudin-1 and subtle changes of the plasma membrane localizations of TJ-protein claudin-5 and of vascular endothelial cadherin. Blocking mainly VEGFR2 with 10 nM nintedanib, 10 nM tivozanib or 500 nM ZM323881 efficiently reverted these changes within one day; higher concentrations of nintedanib or additional inhibition of neuropilin-1 were not superior. Interestingly, the CI of short-term cultivated, confluent ARPE-19 cells slightly increased in the presence of VEGF-A165, but was not changed by nintedanib. In contrast, VEGF-A165 markedly reduced the transepithelial electrical resistance of ARPE-19 cells cultivated on porous membrane inserts for three weeks, which was also accompanied by a significant loss of the then strongly plasma membrane-expressed TJ-protein ZO-1. These alterations were completely reverted within one day by 10 nM nintedanib of which higher concentrations were not superior. None of the inhibitors tested diminished the strong barrier properties of iBREC or long-term cultivated ARPE-19 cells. Taken together, inhibition of VEGFR2 efficiently reverts VEGF-A165-induced barrier disturbances of both cell types forming and regulating the inner and outer blood-retina barrier. As synergistic actions of growth factors seem to play only a minor role in inducing a barrier dysfunction, specific inhibition of VEGFR2 could be an interesting option to treat VEGF-A-induced macular edema without obvious effects on vitality and functions of REC and RPE cells.

Mutation-Dependent Pathomechanisms Determine the Phenotype in the Bestrophinopathies.

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.

[Successful Systemic Lysis Therapy in Acute Retinal Arterial Occlusions]. / Erfolgreiche systemische Lysetherapie bei akuten retinalen Arterienverschlüssen.

BACKGROUND: Retinal artery occlusion leads to dramatic and irreversible vision loss. There is currently no evidence-based standard therapy. According to the German guidelines on retinal artery occlusions, intravenous fibrinolysis therapy can be performed up to a time window of 4 h 30 min. METHODS: Two patients were treated accordingly. RESULTS: In patient 1, systemic lysis therapy was used in branch retinal artery occlusion (BRAO) of the inferior temporal retinal artery with macular involvement 4 h 15 min after symptom onset. Immediately after the therapy, the patient reported significant improvement in symptoms. Three months after therapy, retinal function was good, but with subtle atrophy of the inner neurosensory retina. Patient 2, 2 h 30 min after onset of symptoms of the inferior temporal BRAO, the patient experienced further deterioration, with clinical signs of a central retinal artery occlusion (CRAO). Visual acuity deteriorated to light perception. Emergency intravenous lysis therapy, administered 3 h later, gave an improvement in visual acuity with preservation of the inferior visual field. In both patients, a marked improvement in visual acuity was observed immediately after the lysis therapy: Patient 1: right eye, best corrected visual acuity (BCVA) initial 0.5, BCVA 3 days after lysis therapy 1.0, no defects in Goldmann visual field. Patient 2: left eye, BCVA initial 0.4, then sudden deterioration to light perception, BCVA 1 month after lysis therapy 0.6, persisting visual field defects in the superior hemisphere with preservation of the inferior visual field. CONCLUSIONS: Two patients with acute retinal artery occlusion were treated successfully with systemic intravenous fibrinolysis.

[Invasive Eyelid Infections by ß-Hemolytic Streptococci of Serogroup A]. / Invasive Lidinfektionen durch ß-hämolysierende Streptokokken der Serogruppe A.

BACKGROUND: Invasive soft tissue infections by Streptococcus pyogenes are rapidly progressive and potentially life-threatening infectious diseases. These can also affect the eyelid. Aggressive virulence factors and the synthesis of exotoxins can lead to complications, such as periorbital necrotizing fasciitis (PONF) and streptococcal toxic shock syndrome (STSS). The clinical picture is characterized by four patients with invasive eyelid infections. MATERIALS AND METHODS: Photographic documentation, radiological imaging, laboratory and smear diagnostics and intravenous antibiotic therapy were performed on all patients according to the recommendations of the German Robert Koch Institute and the local infectiology board. RESULTS: In all patients, Streptococcus pyogenes was culturally detected in a direct swab. The antibiogram showed sensitivity to the common intravenous antibiotics. The time interval between symptom onset and presentation at the clinic was between two days and one week. All patients had high systemic inflammatory parameters on admission: Pat. 1: CRP 259 mg/l, leukocytes 20.1 giga/l; Pat. 2: CRP 375 mg/l, leukocytes 15.6 giga/l; Pat. 3: CRP 378 mg/l, leukocytes 38.7 giga/l; Pat. 4: CRP 483 mg/l, leukocytes 1.7 giga/l; normal values: CRP < 5 mg/l, leucocytes 4.4 - 11.3 giga/l. In Pat. 2 and 3, a periorbital necrotizing fasciitis was diagnosed due to rapidly progressing necrosis in the area of cutis and subcutis and systemic toxicity. Pat. 3 and 4 met the diagnostic criteria of STSS. Pat. 2, 3 and 4 had to be relocated to an intermediate or intensive care unit with sepsis, despite immediate intravenous antibiotic therapy. Patient 3 underwent surgical debridement during the stay in the intensive care unit. Thanks to interdisciplinary management (ophthalmology, infectiology, ear, nose and throat medicine, internal medicine and intensive care medicine), all patients were finally discharged from our inpatient treatment in a significantly improved general condition. CONCLUSION: Invasive streptococcal infections represent a challenge in the daily routine of an ophthalmologist. Interdisciplinary management and immediate onset of high-dose intravenous antibiotic therapy are crucial for successful treatment.

[The Importance of the Preoperative Information from a Patient's Perspective - a Structured Interview of 100 Ophthalmological University-Based Outpatients]. / Die Erwartungen an das Aufklärungsgespräch aus Patientensicht ­ strukturierte Befragung von 100 Patienten einer ophthalmologischen Universitätsambulanz.

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.

Comparison between Findings in Optical Coherence Tomography Angiography and in Fluorescein Angiography in Patients with Diabetic Retinopathy.

OBJECTIVE: To compare typical findings of diabetic retinopathy in optical coherence tomography angiography (OCTA) and fluorescein angiography (FA). SUBJECTS/METHODS: 42 patients were enrolled in this study. We performed FA and obtained en face 3 × 3 mm OCTA images of the macular region. The count of microaneurysms (MAs) and the size of the foveal avascular zone (FAZ) were compared. The assessability of the imaging modalities was graded in each eye. RESULTS: 53 eyes of 42 patients with a mean age of 61 years were included. 36/53 eyes revealed nonproliferative diabetic retinopathy, 17/53 eyes had proliferative diabetic retinopathy. The mean size of the FAZ was 0.39 mm2 in FA and 0.42 mm2 in OCTA. The mean MA count was 14 in FA and 13 in OCTA. The assessability was favorable to OCTA in 38-41/53 eyes regarding the FAZ and favorable to FA in 45-49/53 eyes regarding MAs. CONCLUSION: We found a good agreement for the size of the FAZ and a weak agreement regarding the count of MAs in both imaging modalities. The readers favored OCTA for the assessment of the FAZ and FA for the assessment of MAs. Complementary use of FA and OCTA ensures the best diagnostic approach in patients with diabetic retinopathy.