Outcome of brain metastases from adrenocortical carcinoma: a pooled analysis.

PURPOSE: Brain metastases rarely complicate the natural history of patients with adrenocortical carcinoma (ACC). No information is available regarding the life expectancy and efficacy of treatments in ACC patients with brain involvement. METHODS: A pooled analysis was performed by searching on PubMed and using the keywords: "brain metastases in adrenocortical carcinoma", and "leptomeningeal metastases in adrenocortical carcinoma". Four patients diagnosed at Spedali Civili Hospital in Brescia were added to the analysis. Data concerning demographic, disease characteristics, adopted treatments and patient prognosis were collected. RESULTS: A total of 27 patients (18 adults and 9 children) were included in this study, 22 of them had an adequate follow-up. Brain metastases occurred late in the natural history of adult patients but not in that of children. Surgery plus/minus radiation therapy was the treatment of choice. Adult patients with brain metastases had a poor prognosis with a median progression-free survival (PFS) and overall survival (OS) of 2 and 7 months, respectively. Median PFS and OS were not attained in children. CONCLUSION: Brain metastases in ACC patients are rare and are associated with poor prognosis, particularly in adults. Surgery plus/minus radiotherapy is the only therapeutic approach that can offer patients a chance to obtain durable local disease control.

Evaluation of choroidal substructure perfusion in patients affected by systemic sclerosis: an optical coherence tomography angiography study.

Objective: Vasculopathy in systemic sclerosis (SSc) is characterized by the obliteration of arterioles and a reduced capillary density in various tissues. In SSc, atrophic alterations of the choroid have been suggested based on morphological data acquired by optical coherence tomography (OCT). In this study, we aimed to assess the choroid in eyes of patients with SSc from a microcirculatory, dynamic point of view by adding optical coherence tomography angiography (OCTA) to the diagnostic spectrum.Method: SSc patients were enrolled, and age- and gender-matched healthy subjects were used as controls. In addition to basic ophthalmological and rheumatological examinations, individuals underwent enhanced-depth imaging OCT and OCTA. Subfoveal thicknesses of the choroid as well as all three choroidal vascular sublayers were measured and submacular perfusion values were evaluated.Results: In total, 12 patients with SSc and 12 matched controls were included. The median age of participants was 64 years. Submacular perfusion was significantly lower in the choriocapillaris (Δ = 0.72%; p = 0.045), Sattler's layer (Δ = 2.87%; p = 0.001), and Haller's layer (Δ = 2.69%; p = 0.018) of SSc patients compared to controls. Subfoveal thicknesses of Sattler's layer (Δ = 15 µm; p = 0.026) and Haller's layer (Δ = 41 µm; p = 0.045) were also significantly smaller in the SSc group.Conclusion: Choroidal microcirculation is impaired in SSc, even in patients without ophthalmological symptoms. Choroidal OCT and OCTA may offer additional biomarkers for SSc activity.

Retinal perfusion 6 months after trabeculectomy as measured by optical coherence tomography angiography.

PURPOSE: To investigate potential changes of vessel density (VD) at the optic nerve head (ONH) and the macula 6 months after trabeculectomy (TE). METHODS: In a prospective monocentric study, 19 eyes with open-angle glaucoma were treated with TE + MMC (mitomycin C). At four different time points multiple morphological papillary parameters were measured by OCT, and the ONH VD in the radial peripapillary capillary layer and the superficial and deep plexuses of the macula was determined by OCTA (optical coherence tomography angiography, RTVue-XR, Optovue). The mean defect was determined by visual field examination (mode 30-2, Humphrey Field Analyzer). The duration of follow-up was 6 months. RESULTS: Nineteen eyes, one each from 19 patients (11 females; 8 males) with a mean age of 66.0 (58.07, 70.94) years and a mean intraocular pressure (IOP) of 21.0 mmHg (17.07, 23.87), were included in the study. All showed a significant reduction in IOP at each follow-up after TE (p < 0.0001). There was no significant change in the peripapillary retinal nerve fiber layer thickness (p = 0.88), the ganglion cell complex (p = 0.97), the cup-disk ratio (p = 0.63), the rim area (p = 0.78), or the mean visual field defect (p = 0.82). With regard to VD, no significant difference could be determined in either the ONH or the macular area. CONCLUSIONS: After significant surgical reduction of IOP by TE, there are no significant detectable morphological changes in the ONH or the ganglion cell complex as measured by OCT, nor does the papillary or macular OCTA-determined VD change significantly. Trial registration 2016-409-f-S Avanti-OCT-A. Registered December 1, 2016.

Cognitive reserve maps the core loci of neurodegeneration in corticobasal degeneration.

BACKGROUND AND PURPOSE: Cognitively stimulating life experiences and activities are deemed to moderate the clinical impact of brain damage progressively building a neural and cognitive reserve (CR). CR has been studied extensively in various neurodegenerative disorders, but not in corticobasal degeneration (CBD). METHODS: Using Statistical Parametric Mapping 8, years of education, as a determinant of CR, was correlated with tracer uptake on positron emission tomography with 18 F-fluorodeoxyglucose, as a marker of neurodegeneration, in 35 patients with various phenotypes of CBD, including a cognitive-motor composite score or symptoms duration as covariates for controlling disease stage. RESULTS: A cluster of relative hypometabolism was found associated with higher education in the left inferior regions of pre- and post-rolandic gyri and insula, which represent typical loci of neurodegeneration in CBD regardless of clinical presentation. CONCLUSIONS: The present findings extend to CBD the evidence gathered in other neurodegenerative disorders that a higher CR has a protective effect against the clinical manifestations of brain degeneration.

OCTA vessel density changes in the macular zone in glaucomatous eyes.

PURPOSE: To evaluate whether macular optical coherence tomography angiography (OCTA) can detect altered vessel density (VD) in the superficial and deep vascular plexus in glaucomatous eyes and to compare the diagnostic utility of the individual VD parameters. METHODS: The macular VD of 135 eyes, comprising 85 eyes diagnosed with glaucoma and 50 healthy control eyes, was examined using two OCTA devices (AngioPlex-Zeiss Meditec, Inc., Dublin, CA, USA, and AngioVue-OptoVue, Inc., Fremont, CA, USA). All study participants had neither vascular pathology, diabetes, nor vasoactive medication. The macular VD was measured at two different levels of segmentation (superficial [SL] and deep [DL] retinal vascular plexus) with a 6 × 6-mm macula scan, and VD was correlated with various structural and functional measurements. In order to test the accuracy of differentiation between eyes with and without glaucoma, we calculated the receiver operating characteristic (ROC) curve and the area under the curve (AUC). RESULTS: Macular VD was significantly lower in both SL and DL in glaucomatous eyes than in healthy eyes (p = SL < 0.0001; DL = 0.009). There was no significant difference in VD between the SL and the DL (p = 6.60 · 10-18). The greatest reduction of VD in glaucomatous eyes was found in the inferior macular sector. There was no correlation of VD with age or refractive error but moderate to high correlation with intraocular pressure, time of initial diagnosis, mean deviation, ganglion cell complex, peripapillary retinal nerve fiber layer thickness, cup to disc ratio, and rim area. Among the 14 individual features of macular VD, whole VD in the SL had the best diagnostic accuracy (77.6%) as measured by the area under the ROC. CONCLUSION: OCTA detects glaucomatous damage by measuring the macular vessel density in the superficial and deep retinal vascular plexus. It can be an additional diagnostic tool to detect glaucoma independently of the optic nerve.

[Current Diagnosis of Choroidal Nevi]. / Aktuelle Diagnostik bei choroidalen Nävi.

Despite the diversity of techniques for documentation and diagnostics of choroidal nevi, the differential diagnosis, especially regarding small uveal melanomas, remains difficult. In many cases, frequent controls to exclude growth or for the detection of an unchanged appearance are recommended. This article reviews-under consideration of the actual literature-different diagnostic techniques for documentation and differentiation of choroidal nevi.

[Potentials and Limitations of the Detection of Circulating Melanoma Cells]. / Potenziale und Limitationen der Detektion von zirkulierenden Melanomzellen.

The detection and characterisation of circulating melanoma cells (CMC) is a non-invasive procedure with a low complication rate and can potentially distinguish choroidal nevi from uveal melanomas and help to initiate early adequate therapy. It has the perspective to select and monitor treatment. This technique may lead to new insights into the metastasis process itself and help to detect specific targets for future therapies. This article introduces the different techniques for CMC detection; their potentials and limitations are discussed.

[Expression of EphA2 in Metastatic and Non-Metastatic Primary Uveal Melanoma]. / Expression von EphA2 in metastasierten und nicht metastasierten primären uvealen Melanomen.

BACKGROUND: Little is known about how the expression of Ephrin type-A receptor 2 (EphA2) influences cell-cell adhesion, migration, angiogenesis, and the formation of vasculogenic mimicry (VM) channels in uveal melanomas or how this may be related to the rate of metastasis. MATERIAL AND METHODS: Paraffin embedded sections of 50 histopathologically well characterised primary uveal melanomas (mean largest tumour diameter: 16.3 mm) were evaluated with respect to the expression of EphA2. Systemic metastasis was detected in 29 patients. The remaining 21 patients were followed for a mean of 10 years. Tumour angiogensis was analysed by endoglin expression (CD105), the activity of the mature vascular system (von Willebrand factor) and the presence of VM (CD31/PAS staining). RESULTS: All uveal melanomas expressed EphA2, with a mean of 95.93 % positive cells ± SD: 6.3 %. There was no significant association between EphA2 and the rate of metastases (p = 0.196), endoglin expression (p = 0.652), VM (p = 0.267) or with any other clinical or histopathological factors (p < 0.05). However, there was significant up-regulation of EphA2 in the nucleus of the metastatic uveal melanoma subgroup, while cytoplasmatic localisation in the subgroup was associated with better prognosis (p = 0.006). There were low levels of EphA2 expression in the specific retinal layers, the ciliary and corneal epithelium, and the choroidal and corneal endothelium. CONCLUSION: Nuclear expression of EphA2 in this series of large tumours was significantly associated with an increased rate of metastasis. On the other hand, cytoplasmic localisation was associated with a better prognosis. As there was no correlation between EphA2 expression and angiogenesis, the mature vasculature or VM, EphA2 appears to become less important in the advanced stages of the disease.

Two-year clinical experience with the CyPass micro-stent: safety and surgical outcomes of a novel supraciliary micro-stent.

PURPOSE: The aim of this study was to evaluate through 2 postoperative years the clinical outcomes associated with a novel supraciliary micro-stent for the surgical treatment of open-angle glaucoma (OAG) when implanted in conjunction with cataract surgery. PATIENTS AND METHOD: In a multicenter, prospective, consecutive case series, 136 subjects (136 eyes) with OAG and requiring cataract surgery with 24-month postoperative data were included. A combined phacoemulsification procedure, with intraocular lens insertion and CyPass Micro-Stent implantation into the supraciliary space of the study eye, was performed. At baseline, all subjects were on glaucoma medication with either uncontrolled intraocular pressure (IOP; ≥ 21 mmHg, Cohort 1, n=51) or controlled IOP (<21 mmHg, Cohort 2, n=85). Glaucoma medications were stopped postoperatively, but could be restarted if needed, at the investigator's discretion. Device-related adverse events, postoperative IOP, best corrected distance visual acuity (BCDVA), and number of IOP-lowering medications were recorded. RESULTS: The micro-stent was successfully implanted in all eyes. At 24 months, 82 subjects remained in the study. No sight-threatening adverse events occurred. The most common adverse events were transient hypotony (15.4%) and micro-stent obstruction (8.8%), typically due to iris tissue overgrowth. Fifteen subjects (11%) required secondary incisional glaucoma surgery. For Cohort 1 (n=23), mean ± SD IOP was 15.8 ± 3.8 mmHg after 24 months (change, -37% ± 19%). Mean IOP decrease from baseline was statistically significant (p<0.0001) at months 6, 12, and 24. For Cohort 2 (n=59), mean ± SD IOP at 24 months was 16.1 ± 3.2 mmHg (change, 0% ± 28%). Mean decrease from baseline was statistically significant at months 6 (p=0.0188) and 12 (p=0.0356). At 24 months, the mean ± SD number of medications was 1.0 ± 1.1 in Cohort 1 and 1.1 ± 1.1 in Cohort 2. Mean decrease from baseline medication use was statistically significant at months 6 (p<0.001), 12 (p<0.001), and 24 (p=0.0265) in Cohort 1, and at months 6, 12, and 24 (all p<0.0001) in Cohort 2. CONCLUSIONS: CyPass Micro-Stent implantation, in combination with cataract surgery, was associated with minimal complications while substantially lowering IOP and/or use of IOP-lowering medications.

Diagnosis and treatment of malignant eyelid tumors.

BACKGROUND: Malignant tumors of the eyelid are much less frequent than benign eyelid alterations. These are frequently incidental findings without symptoms which are often overlooked or misinterpreted by patients. OBJECTIVE: This article gives an overview of clinical aspects, diagnostics and treatment of the five most common malignant eyelid tumors and exemplarily explains the essential principles of evidence-based treatment of malignant eyelid tumors. METHODS: This narrative review was prepared based on a selective literature search. The depiction of the treatment of eyelid tumors is supported by illustrations of clinical cases. RESULTS: The medical history and inspection provide initial indications of malignancy. Every eyelid change suspected of being malignant should be examined histologically to confirm a diagnosis. By far the most common malignant eyelid tumor in Europe is basal cell carcinoma, which metastasizes only in exceptional cases. Squamous cell carcinomas, sebaceous adenocarcinomas, melanomas and Merkel cell carcinomas occur much less frequently. In these cases, potential metastasis in particular must be considered when making the diagnosis and staging has to be initiated. Surgical excision into healthy tissue with tumor-free margins is the gold standard for malignant eyelid tumors. Non-surgical adjuvant or neoadjuvant forms of evidence-based treatment can be initiated based on the individual case to minimize the risk of recurrence and metastasis. CONCLUSION: It is essential to recognize eyelid changes at an early stage, to classify them correctly and to initiate the appropriate treatment. The interaction between the general condition and the personal needs of a patient as well as state of the art medicine are the keys to a good personalized treatment.

[Diagnosis and treatment of malignant eyelid tumors]. / Diagnose und Therapie der malignen Lidtumoren.

BACKGROUND: Malignant tumors of the eyelid are much less frequent than benign eyelid alterations. These are frequently incidental findings without symptoms which are often overlooked or misinterpreted by patients. OBJECTIVE: This article gives an overview of clinical aspects, diagnostics and treatment of the five most common malignant eyelid tumors and exemplarily explains the essential principles of evidence-based treatment of malignant eyelid tumors. METHODS: This narrative review was prepared based on a selective literature search. The depiction of the treatment of eyelid tumors is supported by illustrations of clinical cases. RESULTS: The medical history and inspection provide initial indications of malignancy. Every eyelid change suspected of being malignant should be examined histologically to confirm a diagnosis. By far the most common malignant eyelid tumor in Europe is basal cell carcinoma, which metastasizes only in exceptional cases. Squamous cell carcinomas, sebaceous adenocarcinomas, melanomas and Merkel cell carcinomas occur much less frequently. In these cases, potential metastasis in particular must be considered when making the diagnosis and staging has to be initiated. Surgical excision into healthy tissue with tumor-free margins is the gold standard for malignant eyelid tumors. Non-surgical adjuvant or neoadjuvant forms of evidence-based treatment can be initiated based on the individual case to minimize the risk of recurrence and metastasis. CONCLUSION: It is essential to recognize eyelid changes at an early stage, to classify them correctly and to initiate the appropriate treatment. The interaction between the general condition and the personal needs of a patient as well as state of the art medicine are the keys to a good personalized treatment.

Immune-related adverse events as potential surrogates of immune checkpoint inhibitors' efficacy: a systematic review and meta-analysis of randomized studies.

BACKGROUND: Immune-related adverse events (irAEs) are frequently reported during immune checkpoint inhibitor (ICI) therapy and are associated with long-term outcomes. It is unknown if the irAE occurrence is a valid surrogate of ICIs' efficacy. METHODS: We identified articles reporting the results of randomized trials of experimental ICI therapy in solid tumors with a systematic search. The control arms could be placebo, cytotoxic/targeted therapy, or ICI therapy. We extracted the hazard ratios for overall survival (OS) with the number of OS events per arm and the number and percentages of overall and specific irAEs of grade 1-2 and grade 3-4 per arm. We estimated the treatment effect on the potential surrogate outcome with the odds ratio of the irAE rate between the experimental and the control arm. The statistical analysis consisted of weighted linear regression on a logarithmic scale between treatment effects on irAE rate and treatment effects on OS. RESULTS: Sixty-two randomized trials were included for a total of 79 contrasts and 42 247 patients. The analyses found no significant association between the treatment effects for overall grade 1-2 or grade 3-4 irAE rates or specific (skin, gastrointestinal, endocrine) irAE rates. In the non-small-cell lung cancer (NSCLC) trial subset, we observed a negative association between treatment effects on overall grade 1-2 irAEs and treatment effects on OS in studies with patients selected for programmed death-ligand 1 expression (R2 = 0.55; 95% confidence interval 0.20-0.95; R = -0.69). In the melanoma trial subset, a negative association was shown between treatment effects on gastrointestinal grade 3-4 irAEs and treatment effects on OS in trials without an ICI-based control arm (R2 = 0.77; 95% confidence interval 0.24-0.99; R = -0.89). CONCLUSIONS: We found low-strength correlations between the ICI therapy effects on overall or specific irAE rates and the treatment effects on OS in several cancer types.

The impact of tumour histology and recursive partitioning analysis classification on the prognosis of patients treated with whole-brain hypofractionated radiotherapy for brain metastases: analysis of 382 patients.

PURPOSE: Recursive partitioning analysis (RPA) is a prognostic index capable of predicting survival in patients with brain metastases. Histology of the primary tumour has only recently been introduced among the factors that could potentially affect the prognosis of these patients. The main purpose of this study was to analyse the impact of RPA in correlation with histology of the primary tumour in patients with brain metastases treated with hypofractionated radiotherapy. MATERIALS AND METHODS: A total of 382 patients were treated at the Department of Radiotherapy of Brescia University, and RPA classes were retrospectively assigned to all patients. Univariate and multivariate analyses were then performed to verify the role of the single prognostic variables, for the entire group and for each prognostic class, as well as in correlation with histology of the primary tumour. RESULTS: Most patients were classified as RPA prognostic class 2 (48%). The majority of patients was treated with a total dose of 30 Gy delivered in ten fractions, whereas the dose of 20 Gy in four or five fractions was primarily used in patients classified as RPA class 3. At univariate analysis, the main variable correlating with overall survival (OS) was RPA class (p=0.000). Uni- and multivariate analysis performed on RPA class 1 patients only confirmed the role of general performance status, number of metastases and total radiotherapy dose for predicting OS. In the group with the worst prognosis (RPA class 3), none of the variables had a statistically significant role in improving OS. Tumour histology and radiotherapy dose influence OS, even in RPA class 1 and 2 patients. CONCLUSIONS: This analysis confirms that RPA prognostic class is the factor that most predicts survival. Primary tumour histology helps determine prognosis, especially in RPA prognostic classes 1 and 2. As regards RPA class 3, no factor influences survival prognosis.

[Clinical procedures for intraocular lymphomas]. / Klinisches Vorgehen bei intraokulären Lymphomen.

BACKGROUND: The classification of intraocular lymphomas is based on their anatomical location. They are divided into uveal lymphomas with involvement of the choroid, ciliary body or iris and vitreoretinal lymphomas with isolated or combined involvement of the vitreous body and/or retina. Over the last decades it has become increasingly possible to work out the clinical and pathobiological features of the various subtypes, thereby reducing the diagnostic hurdles and creating improved treatment options. OBJECTIVE: A summary of the various types of intraocular lymphoma in terms of clinical features, diagnostics, treatment and prognosis is given as well as recommendations for follow-up care. METHODS: A selective literature search was carried out on the subject of intraocular lymphomas using PubMed and Google Scholar. RESULTS: Intraocular lymphomas affect different structures, so that the symptoms can also be very different. The diagnostic spectrum ranges from typical ocular examination methods to sample biopsies with subsequent cytological, histological and molecular pathological processing. The treatment pillars available are percutaneous irradiation and intravitreal drug administration as local treatment and systemic treatment or a combination of systemic and local treatment. The prognosis depends mainly on the subtype of the lymphoma and the extent of the infestation when the diagnosis is confirmed. Even though some effective treatment options are now available, it has not yet been possible to significantly reduce the mortality rate. CONCLUSION: Many different options are available for the diagnostics and treatment of intraocular lymphomas, which require close interdisciplinary cooperation. The further developments in the field of molecular pathology allow a faster and more accurate diagnosis and could open up new treatment options in the future.

Phase II study of cabazitaxel as second-third line treatment in patients with metastatic adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a poor prognosis. No efficacious treatment options are currently available for patients with advanced metastatic disease with disease progression to standard etoposide, doxorubicin, cisplatin and mitotane (EDP-M) therapy. We assessed the activity and tolerability of cabazitaxel as a second/third-line approach in metastatic ACC. PATIENTS AND METHODS: Patients included in this single-center, phase II study (ClinicalTrials.gov identifier NCT03257891) had disease progression to a cisplatin-containing regimen (such as EDP) plus mitotane, plus/minus a further chemotherapy line. Cabazitaxel was administered intravenously at 25 mg/m2 on day 1 of a 21-day cycle, for a maximum of six cycles. The primary endpoint was a disease control rate after 4 months. RESULTS: From March 2018 to September 2019, 25 eligible patients were enrolled. A disease control rate after 4 months was obtained in six patients (24%). No patients attained a disease response according to RECIST 1.1, 9 patients (36%) had stable disease and 16 patients (64%) progressive disease. Median progression-free survival and overall survival were 1.5 months (range 0.3-7 months) and 6 months (range 1-22.2 months), respectively. Cabazitaxel therapy was well tolerated and only three (12%) patients developed grade 3 toxicity which were nausea in one patient (4%) and anemia in two patients (8%). CONCLUSIONS: Cabazitaxel has a manageable toxicity profile but is poorly active as second/third-line treatment in advanced ACC patients. These results do not support further evaluation of cabazitaxel in this setting.

[Proliferative vitreoretinopathy process-To heal or not to heal]. / Proliferative Vitreoretinopathie-Prozess ­ "To heal or not to heal".

BACKGROUND: Proliferative vitreoretinopathy (PVR) is still an unsolved problem after half a century of research. METHODS: This article provides a review of mechanisms leading to PVR in the context of wound healing research. RESULTS: Wound healing is a physiological repair process that occurs in a similar way in all organs and may end in scar formation. The development of PVR is based on this wound healing mechanism. The localization and structures involved lead to specific characteristics and consequences. Up to now the pharmacotherapeutic strategies were not sufficiently effective. The growing understanding of the mechanisms of scar-free fetal wound healing, could however lead to a solution of the PVR problem. CONCLUSION: The PVR is a physiological process with a pathological result. The complex steps involved in vitreoretinal wound healing are well understood. There is currently no therapeutic approach neither in ophthalmology nor in other medical disciplines that is able to restore the original function and structure of the involved tissue or organ but there is hope that this can succeed in the future.

[Proliferative vitreoretinopathy (PVR) minimal: same, same but different. Characteristics and surgical treatment of PVR-associated macular pucker]. / Proliferative Vitreoretinopathie (PVR) minimal: "Same same, but different". Besonderheiten und chirurgische Therapie des PVR-assoziierten Makula-Puckers.

BACKGROUND: Epiretinal membrane formation resulting in a macular pucker is among the typical complications associated with proliferative vitreoretinopathy (PVR) in retinal detachment and has a major impact on the functional outcome after surgical treatment. METHODS: A literature search was carried out in PubMed. RESULTS: Approaches to the surgical treatment of PVR-associated macular pucker include complete membrane removal within the vascular arcades aimed at relieving retinal traction at the posterior pole and peeling of the internal limiting membrane (ILM). As a further option it has been suggested that primary ILM peeling in rhegmatogenous retinal detachment repair may reduce or even prevent postoperative epiretinal membrane formation. In addition, correct timing of surgery is a factor that may contribute to successful treatment. DISCUSSION: Due to the particularly strong adhesion and the frequent occurrence of concurrent retinal detachment, the surgical approach to PVR-associated macular pucker is particularly challenging. As with idiopathic epiretinal membranes, surgical removal has the potential to improve functional outcomes; however, visual improvement depends largely on whether the macula was involved in the original retinal detachment.

[Proliferative vitreoretinopathy (PVR) surgery: Scar Wars : Five steps to successful treatment of PVR detachment]. / Proliferative Vitreoretinopathie(PVR)-Chirurgie: "Scar Wars" : Fünf Schritte zur erfolgreichen Therapie der PVR-Amotio.

BACKGROUND: After initially successful surgery of retinal detachment, proliferative vitreoretinopathy (PVR) is the most common cause of renewed retinal detachment. With an incidence of 5-20% it represents a frequent surgical challenge based on a pronounced epiretinal, subretinal and intraretinal scar formation. MATERIAL AND METHODS: The five most important steps leading to a successful repair of a PVR retinal detachment are described. RESULTS: 1. The basic prerequisite is the complete removal of the vitreous body in order to remove the substrate for proliferation of pathological cells. 2. Furthermore, the complete removal of all tractional PVR membranes is necessary. Subretinal PVR membranes that show no traction can be left in place. 3. The professional care of the macular is still important. As approximately 12% of all patients who undergo surgery for retinal detachment develop an epiretinal gliosis/macular pucker, peeling of the internal limiting membrane (ILM) is obligatory in cases of PVR. 4. Particularly in PVR detachment the mentioned surgical procedure is facilitated by the selection of suitable modern instruments, including wide-angle optics, such as the binocular indirect ophthalmomicroscope (BIOM), chandelier lights, perfluorocarbons (PFCL) and silicone oil. 5. Last but not least, the credo as much as necessary, as little as possible is of essential importance, as PVR eyes have usually been previously operated on and any further surgical intervention leads to subsequent inflammation and a persisting stimulation of the PVR reaction and further damage. CONCLUSION: Following a few decisive rules and tips is a prerequisite for a successful reattachment in cases of PVR retinal detachment.

[Glaucoma drainage implants]. / Glaukom-Drainagechirurgie.

INTRODUCTION: The number of available glaucoma drainage implants has increased in recent years and now offers additional therapeutic opportunities in refractory glaucoma patients. METHODS: In drainage surgery two different functional principles are practised. The most commonly used implants (Ahmed, Krupin, Schocket, Molteno, Baerveldt) drain ocular fluid via a silicone tube into an episcleral reservoir. Multiple studies have compared the operative results of tubes, which differ in insertion, valve, material and surface characterstics. In analogy a miniature stainless steel implant (Ex-PRESS) is implanted at the limbus into the anterior chamber and drains subconjunctivally. These implants shunt ocular fluid under a scleral flap or directly under the conjunctiva. Intrascleral systems (Seton, SLOX, Silicone tubes) drain ocular fluid from the anterior chamber into the suprachoroidal space to regulate intraocular pressure (IOP). RESULTS: In the literature the postoperative success rates in tube shunts range between 22 % and 100 % depending on glaucoma form and implant. Most of the studies were retrospective. Miniature stainless steel devices (Ex-PRESS) placed directly under the conjunctiva may cause erosion of the conjunctiva and hypotony. Implantation under a scleral flap decreases these complications. Compared with trabeculectomy the implantation of this shunt under a scleral flap reduces the early postoperative rate of hypotony and choroidal effusion. Microimplants of Schlemm's canal ab externo or interno should reduce the intraocular pressure by connecting the anterior chamber and Schlemm's canal. Suprachoroidal shunts are an option in patients with scarred conjunctiva. Though, complications of fibrous encapsulation and dislocation are described. DISCUSSION: The development of drainage implants allows the reduction or avoidance of complications which are typical of traditional glaucoma filtering surgery. However, in the absence of long-term follow-ups, the procedures with their new side effects have to be further evaluated.

Network indirect comparison of 3 BRAF + MEK inhibitors for the treatment of advanced BRAF mutated melanoma.

BACKGROUD: Synergistic combinations between BRAF and MEK inhibitors, such as dabrafenib plus trametinib, vemurafenib plus cobimetinib or encorafenib plus binimetinib, represent the current standard of care in metastatic or locally advanced BRAF V600 mutated malignant melanomas (MM). However, no studies explored the direct head-to-head comparison between the three different combinations. In this paper, we performed a network meta-analysis to evaluate their efficacy in terms of overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and safety profile. METHOD: We performed a systematic review of the literature about published first line trials of BRAF and MEK inhibitors doublets in advanced mutated malignant melanoma. We compared then the results with an adjusted indirect analysis of randomized-controlled trials. Our primary survival outcome was OS. Secondary endpoints were PFS, ORR, G3-4 toxicities described in at least 5% of patients in experimental arms. RESULTS: We identified three phase-3 trials: coBRIM (vemurafenib and cobimetinib), COMBI-v (dabrafenib and trametinib) and Columbus study (encorafenib and binimetinib) for a total of 1230 included patients. The control arm was vemurafenib in all studies. The indirect comparison revealed no statistically differences for OS, PFS and ORR across trials, while safety profile differed between the three couples of agents. CONCLUSION: This indirect adjusted meta-analysis suggests a similar efficacy and a slightly different safety profile, related to specific molecular properties of the three different BRAF and MEK inhibitors currently approved in the management of advanced MM.