[Diabetic maculopathy]. / Diabetische Makulopathie.

Diabetic maculopathy is the result of multifactorial and complex alterations of the retinal capillaries in association with diabetes mellitus and is divided into two forms, ischemic maculopathy and diabetic macular edema. Diabetic macular edema is the leading cause of blindness among people of working age. The functional and morphological results of intravitreal pharmacotherapy in cases of fovea-involving macular edema using vascular endothelial growth factor (VEGF) inhibitors such as ranibizumab and aflibercept obtained in large randomized clinical trials are excellent and are superior to results obtained with focal or grid laser coagulation alone. Steroids including dexamethasone and fluocinolone implants represent approved alternatives, although flucinolone is considered a second-line therapy in refractory and chronic cases. VEGF inhibitors can be used in different treatment strategies such as PRN and treat and extend strategies. Focal laser photocoagulation remains the gold standard for macular edema not involving the fovea (and therefore usually good visual acuity). Laser is also still indicated as a panretinal photocoagulation of peripheral retinal ischemic areas in order to prevent neovascular complications. It remains to be proven whether panretinal photocoagulation can have an effect on the treatment intervals of intravitreal pharmacotherapy, too. Surgical treatments such as vitrectomy are today limited to cases of macular edema with concomitant obvious tractional pathologies at the vitreoretinal interface.

EGFR-blockade with erlotinib reduces EGF and TGF-ß2 expression and the actin-cytoskeleton which influences different aspects of cellular migration in lens epithelial cells.

INTRODUCTION: After cataract surgery, residual lens epithelial cells migrate and proliferate within the capsular bag resulting in posterior capsule opacification (PCO). The up-regulation of TGF-ß2, EGF and FGF-2 has been identified as a key factor in PCO pathogenesis leading to actin fiber assembly and alterations in the migration pattern. In this in vitro study, the influence of Erlotinib as a selective EGFR inhibitor is investigated on the cellular features indicated, which might promote a future clinical application. METHODS: Expression of EGF, FGF-2 and TGF-ß2 was measured using RT-PCR and ELISA in human lens epithelial cells (HLEC). Computational data of an in vitro time lapse microscopy assay were used for statistical analysis of single cell migration with a particular focus on cell-cell interaction; cell velocity distribution; and displacement before, during and after mitosis. The effect of Erlotinib on the actin-cytoskeleton was evaluated using Alexa Fluor 488 Phalloidin and epifluorescence microscopy. RESULTS: EGF and TGF-ß2 mRNA expression and protein levels are reduced by Erlotinib, while FGF-2 expression remained stable. Overall fluidity of cell-cell interaction is less in the presence of Erlotinib compared to the control and the velocity distribution across all cells becomes less uniform within the cell cluster. After mitosis, HLEC move significantly faster without EGFR inhibition, which can be completely blocked by Erlotinib. Furthermore, Erlotinib diminishes the amount of actin stress fibers and the stress fiber diameter. CONCLUSION: As a novel effect of Erlotinib on HLEC, we describe the down-regulation of EGF and TGF-ß2 expression, both are crucial factors for PCO development. Cellular movement displays complex alterations under EGFR inhibition, which is partly explained by actin fiber depletion. These findings further underline the role of Erlotinib in pharmacologic PCO prophylaxis.

Attenuation of human lens epithelial cell spreading, migration and contraction via downregulation of the PI3K/Akt pathway.

BACKGROUND: Posterior capsule opacification (PCO) represents a major challenge in the postoperative management of cataract patients. Spreading, migration and contraction of residual human lens epithelial cells play a pivotal role in the pathogenesis of PCO. Therefore, we analyzed the effect of the alkylphosphocholine (APC) erufosine on these cellular features as well as on PI3K/Akt, a crucial pathway in PCO pathogenesis. METHODS: Human lens epithelial cells were cultured under standard cell culture conditions. Cell spreading was analyzed on fibronectin-coated wells and chemokinetic migration was assessed by time-lapse microscopy. For evaluation of cell-mediated collagen matrix contraction, the cells were seeded into collagen gels and incubated with an APC in different non-toxic concentrations before the surface area was measured on day 6. The activity of PI3K/Akt was assessed by an ELISA kit after incubation of the cells with different APC concentrations. RESULTS: Human lens epithelial cell spreading and migration were attenuated by APCs as follows: 7 % spreading, 48 % migration (0.1 µM APC), and 32 % spreading, 68 % migration (1.0 µM APC). APC concentrations of 0.1 µM reduced collagen gel diameter by 5 %, and 1.0 µM by less than 1 %, compared to untreated, cell-populated gels that resulted in a cell diameter contraction of 36 %. PI3K was downregulated in a concentration-dependent manner. CONCLUSIONS: The crucial cellular features of PCO pathogenesis are attenuated by the APC erufosine via downregulation of the PI3K pathway. Thus, erufosine might become a valuable tool for pharmacologic PCO prophylaxis in the future.

[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.

[Differences in the measurement results of Goldmann applanation tonometry with and without fluorescein]. / Unterschiede in den Messergebnissen nach Goldmann-Applanationstonometrie mit und ohne Fluoreszein.

BACKGROUND: Goldmann applanation tonometry (GAT) is still the gold standard for measuring the intraocular pressure (IOP). Usually fluorescein eye drops are used additional to topical anesthesia to gain the best visualization results. The present study evaluated the differences in the results of GAT with and without fluorescein. METHODS: A total of 400 eyes of 200 patients without known glaucoma were enrolled in this study and randomized to two groups: group A (first measurement without, second measurement with fluorescein) and group B (first measurement with fluorescein, second without). All measurements were performed by the same examiner with the same slit lamp. Results were analyzed by Bland-Altman plots and Spearman's correlation test. RESULTS: The examined groups showed no significant differences regarding patient age, astigmatism or reason for consulting. In both groups performing GAT without the application of fluorescein led to significantly lower measurement results. The differences were 1.5 ± 1.7 mmHg SD in group A, 1.2 ± 1.6 mmHg SD in group B and 1.4 ± 1.65 mmHg SD for all eyes. The intraocular pressure (IOP) and the differences between the groups were independent of patient age, astigmatism, reason of consulting or IOP level. Both groups showed outliers up to 10 mmHg difference because of corneal edema. CONCLUSIONS: Measurements from GAT without fluorescein differed significantly from measurements with fluorescein, independently of patient age, astigmatism, reason for consulting or IOP level. The mean difference of 1.4 mmHg may seem negligible in daily routine but can lead to serious consequences in borderline cases.

Corneal biomechanics predict the outcome of selective laser trabeculoplasty in medically uncontrolled glaucoma.

PURPOSE: To evaluate the predictive value of clinical parameters, including biomechanical properties on the outcome of selective laser trabeculoplasty (SLT) in medically uncontrolled open angle glaucoma (OAG). METHODS: Sixty-eight eyes from 68 patients with OAG and IOP insufficiently regulated by topical medications were enrolled. Patients' follow-up occurred 6 and 12 months after the procedure. The recorded parameters intraocular pressure (IOP), angle characteristics, central corneal thickness (CCT) and biomechanical properties of the eyes, including corneal hysteresis CH and corneal resistance factor CRF measured with the Ocular Responses Analyzer (ORA, Reichert Ophthalmic Instruments) were tested on their predictive value of SLT-induced IOP lowering effect using correlation analyses and regression models. RESULTS: Mean IOP reduction 12 months after SLT was 4.2 ± 5.7 mmHg (23.2%, from baseline 18.1 ± 5.2 mmHg). The preoperative IOP correlated significantly with IOP reduction (maximum Spearman's correlation r = 0.75, p < 0.001). In linear regression analysis, the corneal biomechanical properties (CH and CRF) together with the baseline IOP revealed good modelling for the IOP lowering effect of SLT (R(2) = 0.64, respectively). CONCLUSIONS: In addition to the baseline IOP biomechanical properties (CH and CRF) are significant predictors of SLT induced IOP lowering effect in medically uncontrolled OAG.

[Navigated retinal laser therapy]. / Navigierte Netzhautlasertherapie.

Navigated laser therapy introduces for the first time computerized assistance systems for retinal laser therapy. The Navilas system offers high precision and safety and provides additional benefits regarding standardization of planning, execution, documentation and quality assurance. The current focus of clinical application for navigated laser therapy besides laser treatment after retinal vein occlusion and panretinal laser photocoagulation in proliferative diabetic retinopathy (PDR) is diabetic macular edema. Recent data indicate that combined initial anti-vascular endothelial growth factor (anti-VEGF) and navigated macular laser therapy allows achievement and maintenance of treatment success with a minimum number of interventions. Despite very promising results the current assessment of navigated laser therapy is still limited by the evidence available worldwide.

Twelve-month experience with Ozurdex for the treatment of macular edema associated with retinal vein occlusion.

PURPOSE: To evaluate the efficacy and safety of a dexamethasone implant (Ozurdex) alone or in combination with bevacizumab. METHODS: Sixty-four eyes were prospectively investigated. Group 1 (22 central retinal vein occlusion (CRVO) and 16 branch retinal vein occlusion (BRVO)) was treated with Ozurdex alone, and group 2 (14 CRVO and 12 BRVO) was treated with three consecutive bevacizumab injections followed by Ozurdex. Recurrences were treated with Ozurdex only. Patients were seen preoperatively and thereafter in monthly intervals. The primary end point was best-corrected visual acuity (BCVA) at 12 months. RESULTS: In group 1, BCVA improved by 6.6 (±1.7) letters in CRVO and 7.8 (±2.9) in BRVO patients, and in group 2 by 9.8 (±1.0) vs 9.4 (±2.1) letters. A significant difference was only seen between CRVO patients in group 1 and 2 at 12 months (P<0.05). Recurrence after the first Ozurdex injection occurred after 3.8 (CRVO) and 3.5 months (BRVO) in group 1, vs 3.2 and 3.7 months in group 2. Elevated intraocular pressure (>5 mm Hg) was measured in approximately 40% cataract progression requiring surgery in about 50% of eyes after three Ozurdex injections. CONCLUSION: Combined treatment showed slightly better functional outcome for CRVO patients. Increased intraocular pressure and cataract progression was frequent and should be considered when an individual treatment is planned.

[Multikinase inhibitors as a new approach in neovascular age-related macular degeneration (AMD) treatment: in vitro safety evaluations of axitinib, pazopanib and sorafenib for intraocular use]. / Multikinase-inhibitoren als therapeutischer ansatz bei neovaskulärer AMD: in-vitro-evaluation der sicherheit von axitinib, pazopanib und sorafenib zur intraokularen anwendung.

BACKGROUND: Multikinase inhibitors (MKI) interfere effectively at different levels of the neovascularisation cascade. Early clinical and experimental data suggest that MKIs represent a promising novel approach for the treatment of neovascular age-related macular degeneration (AMD). However, so far little is known about the biocompatibility of MKIs regarding human ocular cells. This in vitro study investigates and compares the biocompatibility of three MKIs, axitinib, pazopanib, and sorafenib regarding ocular cells of the anterior and posterior segments, as well as organ-cultured donor corneas. METHODS: Primary human optic nerve head astrocytes (ONHA), trabecular meshwork cells (TMC), and retinal pigment epithelium (RPE), human corneal endothelial and lens epithelial cells (CEC and LEC) were treated with different concentrations of axitinib, pazopanib, or sorafenib (0.1 to 100 µg/mL). To simulate oxidative stress, the cells were additionally co-incubated with 400 µM hydrogen peroxide. Induction of cell death and cellular viability were examined by live-dead assay and tetrazolium dye reduction assay (MTT). In addition, the influence of the three substances on human corneal endothelium was evaluated in seropositive donor corneas in organ culture by phase contrast microscopy. RESULTS: Up to a concentration of 7.5 mg/mL of the substances tested in any cell type examined, no toxic effects were found. Even after 10 days of incubation of organ-cultured donor corneas with 7.5 µg/mL, axitinib, pazopanib, or sorafenib, no evidence for endothelial toxicity was found. CONCLUSION: All three MKIs tested, axitinib, pazopanib, and sorafenib showed a good biocompatibility on the investigated ocular cells. Even under conditions of oxidative stress, there were no toxic effects up to a concentration of 7.5 µg/mL. Only at higher concentrations, there was a dose-dependent decrease in cellular viability and pronounced induction of cell death. These effects on cellular viability and induction of cell death appeared to be stronger with pazopanib, followed by sorafenib, than with axitinib.

[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.

EGF receptor inhibitor erlotinib as a potential pharmacological prophylaxis for posterior capsule opacification.

BACKGROUND: Posterior capsule opacification (PCO) is the most frequent complication after cataract surgery, leading to a loss of sight if untreated. Erlotinib might be of therapeutic interest as an effective target agent (selective EGF-tyrosin-kinase-1 inhibitor). In this in-vitro study, erlotinib was evaluated for ocular biocompatibility and its effect on cell proliferation, migration, 3D matrix contraction and spreading of human lens epithelial cells. METHODS: To exclude toxic concentrations, erlotinib was assessed for its biocompatibility on five different human ocular cell types in vitro by the tetrazolium dye-reduction assay (MTT) and the Live-Dead assay. To determine its effect on human lens epithelial cell (HLE-B3) proliferation, the MTT test was performed after incubation with different concentrations of erlotinib. Chemotactic migration was analyzed with the Boyden chamber assay and chemokinetic migration was assessed by time lapse microscopy. Contraction was measured by a 3D collagen type 1 matrix contraction assay, and cell spreading was determined by measuring the cell diameter on a fibronectin coated surface. RESULTS: The maximum non-toxic concentration of erlotinib was determined to be 100 µM in cell culture. Erlotinib potently inhibits human lens epithelial cell proliferation, with an IC50 of about 10 µM (8.8 µM ± 0.9 µM SD; r (2) =0.94). Chemotactic migration (p=0.004) and chemokinetic migration (p=0.001) were reduced significantly in a concentration-based manner. Erlotinib prevented human lens epithelial cells from matrix contraction (p=0.001) and cell-spreading (p=0.001). CONCLUSIONS: Erlotinib might become of clinical relevance for PCO prophylaxis in the future since it displayed good biocompatibility on ocular cells and mitigated human lens epithelial cell proliferation, migration, contraction, and spreading in vitro. Further studies are warranted to evaluate its potential for clinical application.

[Improvement of fixation in diabetic macular oedema patients under intravitreal ranibizumab treatment]. / Verbesserung des Fixationsverhaltens bei Patienten mit diabetischem Makulaödem unter Therapie mit Ranibizumab.

BACKGROUND: The aim of this study was to evaluate the fixation and other functional and morphological alterations in patients with diabetic macular oedema (DMO) under intravitreal ranibizumab therapy. PATIENTS AND METHODS: Thirty patients (39 eyes) with DMO with central involvement were included in this prospective study. Morphological (fluorescein angiography, OCT) as well as functional (visual acuity, microperimetry including fixation) parameters were analysed before and after three monthly intravitreal applications of ranibizumab. RESULTS: Best-corrected mean visual acuity (BCVA) increased significantly by 6.85 + 6.45 letters from 26.15 ± 13.83 to 33.03 ± 13.31 letters. Mean central retinal thickness and mean central retinal volume decreased significantly from 503.72 ± 143.78 µm, respectively (p < 0.001) before treatment to 387.05 ± 122.02 µm after the third intravitreal injection with ranibizumab. Mean retinal sensitivity obtained with microperimetry did not change significantly over the course of treatment. Mean fixation within 2° (4°) improved from 64.15 % (85.7 %) before treatment significantly to 70.15 % (91.5 %) after three intravitreal injections with ranibizumab. Mean fixation stability within 2° improved from 43.9 % before treatment significantly to 58.5 % after three intravitreal injections. CONCLUSION: DMO improved both morphologically with a significant reduction of central retinal thickness and volume and a significantly improved BCVA as well as fixation and fixation stability over the course of three monthly intravitreal injections with ranibizumab. Retinal sensitivity obtained in microperimetry did not change significantly over the course. Based on our observations we interpret and suggest fixation and fixation stability as an early functional parameter and prior to microperimetrically detectable changes of retinal sensitivity additional to BCVA during treatment of diabetic macular edema.

[Significance of ophthalmological imaging in common hereditary retinal diseases]. / Stellenwert ophthalmologischer bildgebung bei häufigen hereditären netzhauterkrankungen.

BACKGROUND: Over the past years, a significant progress in genetic, functional and imaging diagnostics in hereditary retinal diseases has been made. Optical coherence tomography (OCT) as well as fundus autofluorescence (FAF) allow for high-resolution, non-invasive imaging - from various perspectives - of retinal and choroidal layers of the posterior fundus. Both techniques have gained more and more significance in the diagnosis of hereditary retinal diseases. PATIENTS/METHODS: Of all patients presented in this review, extensive family history was taken and a clinical ophthalmological examination performed. OCT scans as well as FAF images were acquired and compared to results of other functional and molecular genetic tests in the context of each disease. RESULTS: The presented cases in this review addressing hereditary retinal diseases (Best's disease, Stargardt's disease, cone-rod dystrophy, retinitis pigmentosa, achromatopsia, and X-linked retinoschisis) show the significance of ophthalmic imaging (OCT + FAF) for a targeted diagnosis of hereditary retinal diseases. CONCLUSION: The described imaging techniques (OCT + FAF) are becoming more and more important in the diagnosis of hereditary retinal diseases. Due to increasing availability of the devices, earlier detection of typical morphological changes not seen in clinical fundoscopy is feasible.

[Navigated focal retinal laser therapy using the NAVILAS® system for diabetic macula edema]. / Navigierte fokale retinale Lasertherapie mit dem NAVILAS®-System bei diabetischem Makulaödem.

PURPOSE: The aim of this study was to investigate the accuracy of a navigated laser photocoagulator in clinically significant macular edema (CSME). METHODS: Focal laser treatment for diabetic macular edema (DME) in 36 patients was digitally planned on fundus images and performed with navigation using NAVILAS® (OD-OS, Teltow, Germany). Treatment intensity was controlled visually during treatment so the laser spots applied were barely directly visible after treatment. Using color images (CI) and optical coherence tomography (OCT) 4,137 laser spots (mean 115 per eye) were analyzed at 1 month follow-up and accuracy of spot placement was determined. RESULTS: In total 79% of laser spots were visible on CI of which 96% were within 100 µm of the planned target position. On an intention-to-treat (ITT) basis, 76% of the laser spots were placed and visible within the 100 µm target and OCT confirmed that laser effects were limited to the outer retina. The mean time for focal treatment was < 7 min (±3 min). CONCLUSIONS: After NAVILAS treatment for DME a high percentage of laser effects could be visualized on post-treatment color images and the location showed high concordance with the preplanning target.

[Measurement of glaucoma-specific functionality with the GQL-15 and correlation with parameters of visual function]. / Messung der glaukomspezifischen Funktionsfähigkeit mit dem GQL-15 und Korrelation mit Funktionsparametern des Sehens.

INTRODUCTION: Glaucoma is one of the leading causes of irreversible blindness worldwide and can have a significant impact on patient quality of life and vision-related functioning. The Glaucoma Quality of Life 15 (GQL-15) questionnaire is a disease-specific instrument to evaluate and quantify functional impairment of patients with glaucoma. This study evaluated the German version of the GQL-15 including correlations with perimetric parameters. METHODS: A German version of the GQL-15 containing 15 items was developed and evaluated in 98 patients with glaucoma in different stages of the disease. The GQL-15 results were correlated with the perimetric parameters mean deviation (MD) and pattern standard deviation (PSD) of the better and worse eye. Classical and probabilistic test analyses (Rasch model) were performed. RESULTS: The mean GQL-15 value was 77.3 ± 21.7 (SD) and most items of the GQL-15 correlated significantly with the MD of the worse eye (r = -0.416; p = 0.0014) and the better eye (r = -0.304; p = 0.02). There was also a highly significant correlation between glaucoma-specific QoL and visual acuity. A short version containing nine items yielding a higher psychometric performance can also be used. CONCLUSIONS: The German version of the GQL-15 is a potent instrument to evaluate impairment in vision-specific functioning of patients with glaucoma. The GQL-15 values are better correlated with the sensitivity of the eye with the more severe glaucomatous damage. The data can help for a better understanding of individual patient impairment to improve medical advice and therapy of patients with glaucoma.

[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.

Intraocular caspofungin: in vitro safety profile for human ocular cells.

Endogenous Candida endophthalmitis is sight-threatening, difficult to treat and sometimes leads to loss of the eye. Only a few therapeutic agents are available for its treatment. Caspofungin is the first of a new class of antifungal drugs (echinocandins) with a high activity against Candida species, the most common pathogens found in endogenous endophthalmitis. This study investigates the safety profile of caspofungin for intraocular application in a cell-culture model. Endothelial toxicity of caspofungin was evaluated in cultured human corneas. Possible toxic effects of caspofungin (5-300 µg ml(-1)) in corneal endothelial cells (CEC), primary human trabecular meshwork cells (TMC) and primary human retinal pigment epithelium (RPE) cells were evaluated after 24 h and under conditions of inflammatory stress by treatment with tumour necrosis factor-alpha (TNF-α), lipopolysaccharides (LPS) or interleukin-6 (IL-6) and hydrogen peroxide (H(2)O(2)). Toxicity was evaluated by tetrazolium dye-reduction assay; cell viability was quantified by a microscopic live-dead assay. No corneal endothelial toxicity could be detected after 30 days of treatment with 75 µg ml(-1) of caspofungin. Concentrations up to 75 µg ml(-1) had no influence on CEC, TMC or RPE cell proliferation, or on cell viability when administered for 24 h. Exposure to H(2)O(2) did not increase cellular toxicity of caspofungin at concentrations of 5-50 µg ml(-1). After preincubation with TNF-α, LPS or IL-6 for 24 h followed by treatment with caspofungin for 24 h, no significant decrease in cell proliferation or viability was observed. This study showed no significant toxicity for caspofungin on CEC, TMC or RPE cells, or human corneal endothelium when administered in therapeutic concentrations up to 50 µg ml(-1).

[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.