Spironolactone in the treatment of central serous chorioretinopathy - a case series.

BACKGROUND: The pathogenesis of central serous chorioretinopathy (CSC) is still poorly understood. An animal model of CSC proved that the mineralocorticoid receptor [1] of the choroid also plays a role in CSC. Since there is still no evidence-based therapy for non-self-limiting CSC, this case series evaluates the effect of oral spironolactone in CSC patients. METHODS: In this interventional, uncontrolled, prospective case series, we present 18 consecutive CSC patients. Patients were treated with spironolactone 25 mg twice daily (Spironolacton AL® 50 mg, ALIUD PHARMA) for up to 12 weeks. Follow-up examinations with BCVA, OCT, and EDI-OCT were performed at 1, 2, and 3 months after starting the treatment. Main outcome measure was a change of subretinal fluid (SRF) (in micrometers) measured by optical coherence tomography. Secondary outcome was a change in central retinal thickness (CRT) (in micrometers) measured by OCT and a change in BCVA. RESULTS: The subretinal fluid (SRF; mean) decreased from 219 µm (baseline) to 100 µm (visit 3) (difference 119 µm). Total central retinal thickness (CRT; mean) decreased from 405 µm before treatment (baseline) to 287 µm after treatment (difference 118 µm). The BCVA (in logMAR; mean) increased from 0.32 at baseline to 0.20 at visit 3. CONCLUSION: Our case series could confirm a positive influence of spironolactone on the course CSC. Longer follow-up with a larger number of cases could provide more data about the long-term efficiency, recurrences, and safety of this well-tolerated and non-invasive treatment option of CSC.

[Wide-field fundus autofluorescence in non-infectious posterior uveitis]. / Weitwinkelfundusautofluoreszenz bei nichtinfektiöser Uveitis posterior.

BACKGROUND: Posterior uveitis comprises a heterogeneous group of diseases with inflammatory alterations of the posterior fundus and is a common cause of visual impairment and blindness. The goal of this study was to evaluate the diagnostic value of wide-field fundus autofluorescence (FAF) in patients with non-infectious posterior uveitis and chorioretinal alterations. MATERIAL AND METHODS: In this study 73 eyes from 51 patients were included. Best-corrected visual acuity, wide-field color and FAF images achieved by a wide-field scanning laser opththalmoscope (SLO, Optomap P200Tx, Optos PLC, Dunfermline UK) and a full ophthalmological examination were obtained from each patient. A systematic analysis of chorioretinal alterations detected with FAF and color images was conducted followed by the evaluation of the diagnostic information of wide-field FAF compared to the clinical finding and wide-field color images. RESULTS: Of the 73 eyes included in the study 52 showed peripheral alterations. In 32 cases wide-field FAF images revealed a greater number and more extensive chorioretinal alterations than the corresponding wide-field color images of the posterior fundus. CONCLUSIONS: In this study wide-field FAF images showed more chorioretinal alterations than seen in funduscopy or in color SLO images. Therefore, wide-field FAF images offer important additional information for detection and documentation of peripheral and central chorioretinal alterations.

[Ranibizumab in diabetic macular edema. Evaluation of functional and morphological aspects]. / Ranibizumab bei diabetischem Makulaödem. Evaluation funktioneller und morphologischer Aspekte.

BACKGROUND: Intravitreal anti-VEGF (vascular endothelial growth factor) therapy with ranibizumab has been shown to be an effective therapeutic option for foveal diabetic macular edema (DME). This prospective study evaluated the functional and morphological retinal changes after intravitreal ranibizumab treatment. MATERIAL AND METHODS: A consecutive prospective series of DME patients treated with intravitreal ranibizumab were examined before and after 3 and 6 months of intravitreal ranibizumab therapy. Best-corrected visual acuity (BCVA) according to the ETDRS protocol, retinal thickness in the macular area and central retinal thickness (CRT) measured with spectral-domain optical coherence tomography (SD-OCT) was determined. In addition, microperimetric functional macular mapping was determined before therapy and 4 weeks after the third injection. RESULTS: A total of 41 eyes from 33 patients were evaluated. During the 6-month observational period patients received a mean number of 5.2 injections. The mean BCVA increased significantly from 26 ± 14 to 33 ± 13 letters 4 weeks after the third injection and to 34 ± 14 letters 6 months after starting the treatment. The mean CRT decreased significantly from 509 ± 147 µm to 385 ± 121 µm after the third injection and to 383 ± 110 µm after 6 months. After 3 injections, the thickness of the most prominent central retinal area was less than 445 µm in 68.3% of patients and after a further 3 months of treatment in 78.0%. CONCLUSION: The presented data demonstrate that intravitreal ranibizumab is effective for DME in everyday clinical practice and results are comparable to those of registration trials. After three initial injections significant structural and functional improvements were observed in a considerable number of patients.

[The role of light in the developement of RPE degeneration in AMD and potential cytoprotection of minocycline]. / Altersbedingte Makuladegeneration: die Rolle von Licht bei der Entstehung degenerativer Veränderungen im menschlichen RPE und möglicher Zell-Schutz durch Minocyclin.

BACKGROUND: Light-induced oxidative stress is an suggested reason for retinal pigment epithelium (RPE) degeneration in age-related macular degeneration (AMD). This study investigates the influence of light on intracellular reactive oxygen species (ROS) and apoptosis in the human RPE and potential cytoprotective effects of the tetracycline antibiotic minocycline. METHODS: Primary human RPE cells were either pre- or post-incubated with minocycline and then exposed to white light or oxidative stress (600 µM, H(2)O(2)). Then viability, induction of intracellular reactive oxygen species (ROS), apoptosis and cell death was determined. Expression of apoptotic BAX and anti-apoptotic Bcl-2 protein and their mRNA were determined by RT-PCR and Western blot analysis. RESULTS: Both light exposure and oxidative stress decreased RPE cell viability and Bcl-2 expression and increased intracellular ROS, apoptotic cell death, and BAX expression. Minocycline reduced these effects under certain conditions. CONCLUSIONS: This study demonstrates that minocycline effectively protects human RPE cells against oxidative damage. However, in the light of minocycline's photosensitising properties its potential role in AMD treatment needs further evaluation.

[Cytoprotective and antiangiogenic effects of the multikinase inhibitor sorafenib on human retinal pigmentepithelium]. / Zytoprotektive und antiangiogene Wirkung des Multikinaseinhibitors Sorafenib im retinalen Pigmentepithel.

BACKGROUND: Cumulative light exposure is significantly associated with progression of age-related macular degeneration (AMD). Inhibition of vascular endothelial growth factor A (VEGF) is the main target of current antiangiogenic treatment strategies for AMD. Previous reports indicated that sorafenib, an oral multikinase inhibitor, might have beneficial effects on exudative AMD. This study investigates the effects of sorafenib on light-induced overexpression of VEGF and its receptors VEGFR1 and 2 in human retinal pigment epithelial (RPE) cells. METHODS: The effects of sorafenib on VEGFR1 and 2 expression of primary human RPE cells was investigated by reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry and western blotting. In addition, RPE cells were exposed to white light and incubated with sorafenib. Viability, expression of VEGF and its mRNA were determined by RT-PCR, immunohistochemistry, western blotting, and enzyme-linked immunosorbent assays. RESULTS: Sorafenib reduced VEGFR1 and 2 expression of RPE cells. Light exposure decreased cell viability and increased expression and secretion of VEGF. These light-induced effects were significantly reduced when cells were treated with sorafenib at a dose of 1 µg/ml. CONCLUSION: The results show that sorafenib has promising properties as a potential antiangiogenic treatment for AMD.

[Diabetic retinopathy: comparison of the diagnostic features of ultra-widefield scanning laser ophthalmoscopy Optomap with ETDRS 7-field fundus photography]. / Diabetische Retinopathie: Vergleich der diagnostischen Eigenschaften des Ultraweitwinkel-Scanning-Laser-Ophthalmoskops Optomap mit der ETDRS-7-Feld-Fundusfotografie.

OBJECTIVE: The aim of the study was to compare the diagnostic properties of a non-mydriatic 200° ultra-widefield scanning laser ophthalmoscope (SLO) with mydriatic ETDRS 7-field fundus photography for diabetic retinopathy screening. METHODS: A consecutive series of 66 eyes from 34 patients with different levels of diabetic retinopathy (DR) were examined. Grading of DR and macular edema (ME) obtained from mydriatic ETDRS 7-field fundus photography were compared with grading obtained from Optomap Panoramic 200MA SLO images. All SLOs were performed with an undilated pupil and no additional clinical information was used for evaluation of images by two independent, masked experts. RESULTS: A total of 14 eyes from ETDRS 7-field fundus photography and 11 eyes from Optomap could not be graded by at least one grader due to poor image quality, yielding 48 eyes for comparison purposes. Of the 48 ETDRS 7-field fundus photographs, 9 (11 for grader 2) eyes had no or mild DR (ETDRS levels ≤20) and 17 (23 for grader 2) eyes had no ME. Agreement of Optomap retinopathy grading with ETDRS 7-field fundus photography was good, kappa 0.70 for grader 1 and kappa 0.66 for grader 2. There was good agreement between both techniques for ME, grader 1 kappa 0.68 and grader 2 kappa 0.74. CONCLUSIONS: Grading of DR levels from Optomap Panoramic 200MA non-mydriatic images showed a good correlation with mydriatic ETDRS 7-field fundus photography. Both techniques are of sufficient quality for a valid assessment of DR. Optomap Panoramic 200MA images cover a larger retinal area and might therefore offer additional diagnostic properties.

Sorafenib prevents human retinal pigment epithelium cells from light-induced overexpression of VEGF, PDGF and PlGF.

BACKGROUND: Cumulative light exposure is significantly associated with progression of age-related macular degeneration (AMD). Inhibition of vascular endothelial growth factor is the main target of current antiangiogenic treatment strategies in AMD. However, other growth factors, such as platelet-derived growth factor (PDGF) and placenta growth factor (PlGF), have a substantial impact on development of AMD. Previous reports indicate that sorafenib, an oral multikinase inhibitor, might have beneficial effects on exudative AMD. This study investigates the effects of sorafenib on light-induced overexpression of growth factors in human retinal pigment epithelial (RPE) cells. METHODS: Primary human RPE cells were exposed to white light and incubated with sorafenib. Viability, expression, and secretion of VEGF-A, PDGF-BB, and PlGF and their mRNA were determined by reverse transcription-polymerase chain reactions, immunohistochemistry and enzyme-linked immunosorbent assays. RESULTS: Light exposure decreased cell viability and increased expression and secretion of VEGF-A, PDGF-BB and PlGF. These light-induced effects were significantly reduced when cells were treated with sorafenib at a dose of 1 µg/ml. CONCLUSION: The results show that sorafenib has promising properties as a potential antiangiogenic treatment for AMD.

Sorafenib protects human optic nerve head astrocytes from light-induced overexpression of vascular endothelial growth factor, platelet-derived growth factor, and placenta growth factor.

OBJECTIVES: Growth factors, such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and placenta growth factor (PlGF) are key players in the development of diabetic retinopathy, age-related macular degeneration, and other retinal neovascular diseases. Glial cells provide a significant source of retinal growth factor production under physiologic and pathologic conditions. Cumulative light exposure has been linked to increased retinal growth factor expression. Previous reports indicate that sorafenib, an oral multikinase inhibitor, might have a beneficial effect on retinal neovascularization. This study was designed to investigate the effects of sorafenib on light-induced overexpression of growth factors in human retinal glial cells. METHODS: Primary human optic nerve head astrocytes (ONHAs) were exposed to white light and incubated with sorafenib. Viability, expression, and secretion of VEGF-A, PDGF-BB, and PlGF and their mRNA were determined by reverse transcription-polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay. RESULTS: Light exposure decreased cell viability and increased VEGF-A, PDGF-BB, and PlGF expression and secretion. These light-induced effects were significantly reduced when cells were treated with sorafenib at a concentration of 1 microg/ml. CONCLUSION: Sorafenib significantly reduced light-induced overexpression of VEGF-A, PDGF-BB, and PlGF in primary human ONHAs. Sorafenib has promising properties as a potential supportive treatment for retinal neovascularization.

[Intracameral moxifloxacin: a safe option for endophthalmitis prophylaxis? In vitro safety profile for intraocular application]. / Moxifloxacin intrakameral: Eine sichere Option zur Endophthalmitisprophylaxe? In-vitro-Sicherheitsprofil zur intraokularen Anwendung.

BACKGROUND: Moxifloxacin (Vigamox), a 4th-generation fluoroquinolone, covers most isolates causing endophthalmitis. It is safe and effective for systemic and topical use; however, only very limited data are available on prophylactic intracameral administration to prevent endophthalmitis. This study investigated the safety of Vigamox for intracameral application in a cell-culture model. METHODS: The endothelial toxicity of moxifloxacin (Vigamox) was evaluated in cultured human corneas. Primary human retinal pigment epithelium cells (RPEs), trabecular meshwork cells (TMCs), lens epithelium cells (LECs), and corneal endothelial cells (CECs) were treated with concentrations of Vigamox. Toxic effects were evaluated after 24 h (MTT assay and live-dead assay). By treating TMC, CEC, and RPE cells either with oxidative stress or tumor necrosis factor-alpha (TNF-a), lipopolysaccharide (LPS), and interleukin-6 (IL-6), the effects of moxifloxacin on cellular viability under conditions of inflammation were investigated. RESULTS: No corneal endothelial toxicity could be detected after 30 days of treatment with moxifloxacin 500 microg/ml. Primary RPEs, TMCs, LECs, and CECs showed adverse effects on proliferation and viability only at concentrations higher than 150 microg/ml moxifloxacin. After preincubation with TNF-a, LPS, and IL-6 for 24 h and subsequent treatment with moxifloxacin at concentrations of 10-150 microg/ml for 24 h, no significant decrease in proliferation or viability was observed. H2O2 exposure did not increase cellular toxicity CONCLUSION: Vigamox did not show significant toxicity on primary RPEs, TMCs, LECs, CECs, or human corneal endothelium at concentrations up to 150 microg/ml. The MIC90 of moxifloxacin for pathogens commonly encountered in endophthalmitis is known to be in the range of 0.25-2.5 microg/ml. Therefore, intracameral use of Vigamox at concentrations up to 150 microg/ml may be safe and effective for preventing endophthalmitis after intraocular surgery.

[Laser embolectomy for central retinal artery occlusion]. / Laserembolektomie bei Zentralarterienverschluss.

We describe a case of successful Nd:YAG laser embolectomy in a patient with occlusions of the retinal artery affecting the macula and reducing visual acuity. The treatment can only be recommended in cases with a visible embolus and short duration of symptoms.

[Retinal pigment epithelial tears after intravitreal injection of bevacizumab for AMD. Frequency and progress]. / Retinale Pigmentepithelrisse nach intravitrealem Bevacizumab bei AMD. Häufigkeit und Verlauf.

PURPOSE: Intravitreal injection of the antibody bevacizumab is unofficially becoming more and more the "standard of care" in the treatment of neovascular AMD. After initial concerns about possible systemic adverse events of the drug, intravitreal injection has as yet shown a very good safety profile. Due to the common application of this VEGF inhibitor it is of great importance to report complications that may be related to the use of bevacizumab. In this scope we present a series of patients with predominantly serous detachment of the retinal pigment epithelium (PED), who developed a tear (rip) in the retinal pigment epithelium (RRPE) after intravitreal application of bevacizumab. METHODS: Our data are based on a prospective, consecutive, interventional case series of 420 patients with neovascular AMD. These patients received at least 1 intravitreal application of 1.25 mg bevacizumab within the period of 1 year. Follow-up examinations were every 4-6 weeks. Visits were documented with best corrected visual acuity according to the ETDRS standard, biomicroscopy of the retina, intraocular pressure measurement, evaluation of central retinal thickness, fluorescein angiography and fundus photography. RESULTS: Of 420 patients, 74 were classified as having predominantly serous PED. In the further course 13 out of 74 patients developed RRPE. Patients who had an intact subfoveal RPE, gained vision scores of 1.4+/-8.3 ETDRS letters (span width -15 to 14) despite RRPE or had stable Snellen vision of 0.0+/-0.1 logMar. In contrast patients with no subfoveal RPE due to RRPE showed loss of vision of -6.2+/-7.2 ETDRS letters (span width -15 to 1). CONCLUSION: This case series describes RRPE as a novel complication of intravitreal anti-VEGF therapy with bevacizumab. However, it seems that this complication is limited to the entity of predominantly serous PED. These patients should therefore be informed about the risk of RRPE before initiating anti-VEGF therapy with bevacizumab, although the reverse conclusion to generally exclude patients with PED from anti-VEGF therapy is not justifiable due to therapeutic efficiency and associated gain of vision.

[Artifacts in optical coherence tomography (OCT) imaging of the retina]. / Artefakte bei der Bildgebung der Netzhaut mittels optischer Kohärenz-Tomographie (OCT).

PURPOSE: The purpose of this study was to investigate artifacts of OCT scans and of software analysis for retinal cross-section scans in a specialised retina clinic setting. METHODS: A total of 205 vertical cross-hair OCT scans of retinal Stratus OCTs were randomly chosen from the database. All scans had been performed by one experienced technician. There were 75 (37%) normal findings, the remaining scans showed various types of retinal pathology: All scanning artifacts were analysed. Retinal thickness of all scans was measured automatically at the centre of the macula using two different software algorithms: the instrument's built-in "Stratus OCT Viewer V 4.01" and the stand-alone application "Datamedical OCTview V 3.5" (Datamedical Consulting, Hamburg). Errors of the software to correctly identify the retinal surface and the outer highly reflective layer were assigned into three categories: none, minor error (no influence on measurements) and major error. RESULTS: A total of 7.3% of all OCT scans showed scanning artifacts: 5 motion artifacts, 9 scans with low signal intensity and 1 decentred scan. Scanning artifacts significantly increased the frequency of software errors (p = 0.012). The presence of retinal pathology also increased the number of errors (p = 0.004). Software analysis yielded a total of 20 major and 2 minor errors for the Stratus OCT (overall 10.7%) and 32 major and 64 minor errors for the Datamedical Viewer (p < 0.001). Measurements by Datamedical OCTview were a mean of 57 micron higher due to a different definition of the outer retinal border. Retinal pathologies significantly increased the likelihood of software errors for both algorithms (both p < 0.01), most critical were macular holes and changes in age-related macular degeneration. CONCLUSION: Scanning artifacts were associated with a significantly higher frequency of software errors. As artifacts of scans and software occur frequently, the interpretation of OCT scans requires special attention to artifacts.