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.

[Evaluation of Web-based software applications for administrating and organising an ophthalmological clinical trial site]. / Evaluation von internetbasierten Softwareanwendungen zur Verwaltung und Organisation eines klinischen Studienzentrums in der Augenheilkunde.

BACKGROUND: The importance and complexity of clinical trials is continuously increasing, especially in innovative specialties like ophthalmology. Therefore an efficient clinical trial site organisational structure is essential. In modern internet times, this can be accomplished by web-based applications. METHODS: In total, 3 software applications (Vibe on Prem, Sharepoint and open source software) were evaluated in a clinical trial site in ophthalmology. Assessment criteria were set; they were: reliability, easiness of administration, usability, scheduling, task list, knowledge management, operating costs and worldwide availability. RESULTS: Vibe on Prem customised by the local university met the assessment criteria best. Other applications were not as strong. DISCUSSION: By introducing a web-based application for administrating and organising an ophthalmological trial site, studies can be conducted in a more efficient and reliable manner.

[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.

[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.

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.

[Long-term experience of a pseudo-accommodative lens]. / Langzeiterfahrung mit einer pseudoakkommodativen Hinterkammerlinse.

BACKGROUND: The aim of this study was to investigate the clinical long-term outcome of the 1CU posterior chamber IOL. Objective accommodative dynamics as well as measured data were assessed subjectively three months and 72 months after implantation. PATIENTS AND METHODS: Retrospectively, 26 eyes after uneventful cataract surgery with 1CU IOL implantation were included. In 26 eyes (group I), the change of the anterior IOL reflex without and under stimulation with pilocarpine 1 %, and cyclopentolate (pseudophakic-accommodation), and maximum obfuscation under best corrected visual acuity (BCVA) settings (pseudo-accommodation) were examined. In 20 eyes (group II) the influence of the laser capsulotomy on the pseudophakic-accommodation was evaluated. RESULTS: Eyes, stimulated by pilocarpine 1 %, have an anterior (-) shift of the IOL reflex of -0.59 +/- 0.28 mm (pseudophakic-accommodation) after 3 months and -0.49 +/- 0.27 mm after 50.8 months (p < 0.001). The mean obfuscation under BCVA level (pseudo-accommodation) was 1.5 diopters (D). Laser capsulotomy was performed after 21 +/- 15 months in the mean. A change of the anterior reflex of the IOL of -0.5 +/- 0.3 mm before and after Nd:YAG laser treatment did not show any statistical significance. CONCLUSIONS: Under application of pilocarpine 1 % and cyclopentolate a small movement of the 1CU-IOL was examined. The amount of the anterior/posterior shift of the IOL reflex was stable over the follow-up period but is not sufficient to provide full presbyopic correction.

[Diagnostic criteria: OCT angiography for retinal angiomatous proliferation (RAP lesions, type 3 neovascularization)]. / Diagnostische Kriterien: OCT­Angiographie bei retinalen angiomatösen Proliferationen (RAP­Läsionen, Typ­3-Neovaskularisationen).

BACKGROUND: Multimodal imaging of retinal angiomatous proliferation (RAP) lesions (type 3 neovascularization) and the diagnostic significance of optical coherence tomography angiography (OCT-A). MATERIAL AND METHODS: Confirmation of the diagnosis in six case reports with fundus photography, optical coherence tomography (OCT), fluorescein angiography (FLA), indocyanine green angiography (ICGA) and optical coherence tomography angiography (OCT­A). RESULTS AND CONCLUSION: The use of OCT­A is helpful for the diagnosis and follow-up examinations of RAP lesions (type 3 neovascularization). It enables the detailed visualization of intraretinal and choroidal microcirculation. Furthermore, it is possible to evaluate the progression, classify the stages and comprehend the treatment strategy.

[A young patient with full visual acuity, small visual field defects, and normal fluorescence angiogram]. / Eine junge Patientin mit vollem Visus, kleinen Gesichtsfelddefekten und normalem Fluoreszenzangiogramm.

A 28-year-old female patient came to our clinic complaining of small central visual field defects in both eyes, without any impairments of visual acuity. She reported recent flu-like symptoms and work-related stress associated with high caffeine intake. Dark reddish cloverleaf-shaped lesions were noted in the macular region with red-free fundoscopy, and alterations of the external retinal layers were observed in spectral domain optical coherence tomography (SD-OCT). The visual field test (Octopus, program 32) revealed small central scotoma on both eyes. The fluorescein angiograms were normal. A suspected diagnosis of acute macular neuroretinopathy (AMNR) was made and the patient was scheduled for follow-up 4 weeks later. The follow-up examination showed persisting central scotoma as well as persistence of the lesions in the external retinal layers in OCT. The best-corrected visual acuity was still 20/20. In OCT angiography (OCT-A), a reduced correlation signal and therefore perfusion was detected in the outer retinal capillary plexus within the area of the fundoscopic macular lesions. Multimodal imaging, including SD-OCT and A­OCT, plays a pivotal role in the diagnosis of acute macular neuroretinopathy. Even though no serious impairments of visual acuity are reported, patients should be informed about the possibility of permanent central scotoma.

[Bartonella neuroretinitis : An atypical manifestation of cat scratch disease]. / Bartonellenneuroretinitis : Eine atypische Manifestation der Katzenkratzkrankheit.

Cat scratch disease (CSD) typically manifests as a febrile lymphadenopathy and is caused by a Bartonella henselae infection after contact with cats. This article describes the case of an atypical presentation of CSD in a 52-year-old patient with acute unilateral loss of vision and headache without fever or lymphadenopathy. Funduscopic examination showed an optic disc swelling and macular star exsudates, pathognomonic for infectious neuroretinitis. A Bartonella henselae infection was confirmed serologically. Systemic antibiotic combination therapy was initiated with doxycycline and rifampicin for 6 weeks resulting in good morphological and functional results. A Bartonella neuroretinitis should be considered in the differential diagnosis of patients with loss of vision and papilledema, even in the absence of fever or lymphadenopathy. Immediate serological testing and initiation of antibiotics are important for the outcome.

[Treatment reality with ranibizumab in clinical routine use for patients with diabetic macular edema : 1­year results of the German POLARIS cohort]. / Behandlungsrealität mit Ranibizumab in der klinischen Routineanwendung bei Patienten mit diabetischem Makulaödem : 1-Jahres-Ergebnisse der deutschen POLARIS-Kohorte.

BACKGROUND: Currently only few data are available on the treatment reality with ranibizumab in patients with diabetic macular edema (DME). MATERIAL AND METHODS: POLARIS is an international observational study which included 983 patients who were treated with ranibizumab due to DME. The primary objective of the study was to investigate the influence of treatment and control intervals as well as resource utilization on the mean change in visual acuity. Secondary endpoints included the collation of disease activity monitoring in the clinical practice. This article describes the results of the German POLARIS population. The study was conducted in 8 European countries from October 2012 to January 2015. RESULTS: In Germany 220 patients were included in the study. Visual acuity improved by 4.3 letters within the first 3 months of treatment. At 12 months, visual acuity increased on average by 4.1 (SD ± 12.4) letters (approximately 1 line) for 168 patients enrolled in the efficacy analysis. Patients received an average of 4.5 (SD ± 1.9) injections, 10.3 (SD ± 6.3) visual acuity tests and 3.3 (SD ± 3.1) optical coherence tomography (OCT) examinations during the first year. Patients with ≤3 injections showed an average improvement in visual acuity by 2.7 letters which was less improvement compared to patients with >3 injections, who achieved an average improvement of 5.4 letters. There was a correlation between the number of injections and the visual acuity achieved. DISCUSSION: For Germany, the results of the POLARIS study indicate that despite a high number of visits, patients with DME are undertreated in clinical routine practice. The injection frequency in Germany was lower than in randomized clinical trials. Almost half of the patients received less than 4 injections in the first year of treatment and thus showed an undertreatment compared to the recommendations of German and international medical societies.

[Anti-VEGF treatment for retinal angiomatous proliferation]. / Intravitreale Anti-VEGF-Behandlung retinaler angiomatöser Proliferationen.

BACKGROUND: Retinal angiomatous proliferation (RAP) is a subform of neovascular age-related macular degeneration (AMD), which is characterized by a particularly poor prognosis. The aim of this study is to describe the loading phase and maintenance phase for RAP during intravitreal anti-VEGF treatment. MATERIAL AND METHODS: A total of 82 eyes in 82 patients with RAP stages 1-3 were treated during upload therapy with repeated intravitreal injections of 1.25 mg bevacizumab at intervals of 4 weeks until the retinal edema resolved. Baseline examination included measurement of the best corrected distance visual acuity (ETDRS chart), central retinal thickness using optical coherence tomography (OCT), and fluorescein angiography (FLA). During maintenance therapy, the patients' distance visual acuity was monitored at 4- to 12-week intervals and OCT or FLA performed if needed. The average follow-up was 7.4 months (SD 4.2). Treatment with intravitreal anti-VEGF therapy was repeated if there was evidence of sub- or intraretinal fluid with a decrease in visual acuity of 5 points or more, increase of the central retinal thickness of 100 microm or more on OCT, or subjective deterioration with verifiable sub- or intraretinal fluid. RESULTS: During upload therapy an improvement in visual acuity of an average of +5.1 letters (mean, n=82 eyes) was observed. During maintenance therapy it was initially possible to sustain this treatment effect. However, 5 months after loading therapy was concluded, a deterioration of -5.5 letters (mean, n=31) was evident in comparison with the end of loading therapy. During the further course deterioration continued (12-month follow-up: -8.6 letters, n=7). Recurrence occurred in 60% of the cases, on average 8 weeks after termination of loading therapy. During an observation period of 6 months (n=66) a total of 3.6 injections were necessary. CONCLUSIONS: Therapy with intravitreal anti-VEGF medications represents a treatment option for RAP, but in the long term the disease continues to progress accompanied by functional deterioration. We thus recommend that patients with RAP be monitored at 4-week intervals to permit early treatment of recurrence.

[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.

[Multimodal imaging in Goldmann-Favre syndrome]. / Multimodale Bildgebung beim Goldmann-Favre-Syndrom.

Case report of a 23-year-old male patient suffering from Goldmann-Favre syndrome. The patient reported bilateral visual loss since 10 years of age and difficulties with dark adaptation for 2 years. Until recently a final diagnosis was not found. Multimodal imaging using multicolor fundus imaging (MCFI), optical coherence tomography (OCT), fundus autofluorescence (FAF), fluorescein angiography (FLA), electroretinography (ERG) and visual evoked potential (VEP) confirmed the diagnosis. We describe multimodal imaging of this rare hereditary retinal dystrophy. For diagnosis of Goldmann-Favre syndrome a multimodal examination is helpful. To confirm the diagnosis a genetic analysis is necessary.

[Familial exsudative vitreoretinopathy (FEVR) in childhood]. / Familiäre exsudative Vitreoretinopathie (FEVR) im Kindesalter.

A case of secondary neovascularization of the optic disc in familial exsudative vitreoretinopathy (FEVR) is reported. A 12-year-old girl presented with decreased visual acuity of the right eye to 0.05. Funduscopy showed a prominent fibrovascular neovascularization of the optic disc covering the macula. Fluorescein angiography demonstrated circular peripheral ischemia as well as vascular anomalies in both eyes. Peripheral laser coagulation of the ischemic retina of the right eye was conducted with the patient under general anesthesia. The central neovascularization regressed and visual acuity increased up to 0.4. Molecular genetic examination detected the LRP5 gene for FEVR.

[Papilledema with visual loss]. / Papillenödem mit Visusminderung.

SERIAL CASE REPORTS OF THREE MEN WITH PAPILLEDEMA AND VISUAL LOSS: The patients developed primarily visual loss on one or both sides with angiographically and clinically diagnosed papilledema. The neurological and internistic examinations were unsuspicious; however, serology ultimately confirmed the suspected papillitis in acute syphilis. CONCLUSION: Papillitis with visual loss can be a symptom of syphilis. Not only the known placoid chorioretinitis syphilis has to be considered but also a detailed medical history and diagnostic measures are essential to determine the cause. The guiding principle is usually also the relatively young age of the patients, male gender, sexual orientation and the lack of classic risk factors for anterior ischemic optic neuropathy (AION) or neurological causes of blurred edge swollen papilla as an intracranial mass lesion (papilledema).

Cost utility for penetrating keratoplasty in patients with poor binocular vision.

PURPOSE: Cost-utility and cost-effectiveness analyses are of increasing importance to clinicians and health policy experts. This study determines the costs in Germany and other countries in relation to gain of utility for patients with bilateral poor vision owing to corneal disease undergoing penetrating keratoplasty (PK) in 1 eye. DESIGN: A cost-utility analysis was performed using retrospective clinical data and high-level evidence-based data. PARTICIPANTS: Sixty patients (mean age, 46.3 years) with bilateral poor vision who underwent PK for corneal disease. METHODS: Visual acuity and utility values were obtained before and 1 year after PK and after suture removal. A 10-year graft survival rate of 80% was assumed. Expenses included costs for the corneal transplant and surgery, medication, and optical rehabilitation. A discount rate of 5% was applied for costs and quality-adjusted life years (QALYs). Cost-utility analysis encompassed a 10-year period after surgery. MAIN OUTCOME MEASURES: The number of QALYs was calculated for the study group undergoing PK. This was divided into the cost of the procedure to get the number of euros spent per QALY gained. RESULTS: Median binocular preoperative visual acuity was -log mean angle of resolution (-logMAR) 0.91+/-0.53 (Snellen equivalent 20/160) yielding a utility value of 0.67. After suture removal and optical rehabilitation, binocular visual acuity increased to median -logMAR 0.36+/-0.36 (20/46) with a utility value of 0.79. Over the 10 years after surgery and considering graft survival and discounting, a cost utility of 9551 euros per QALY was gained (equivalent to US11,557 dollars). One-way sensitivity analysis yielded a range from 7706 euros to 12874 euros per QALY, highlighting the robustness of the model. CONCLUSIONS: Although an expensive procedure, PK is cost effective in patients with bilateral poor vision.