Complications After Anti-VEGF Therapy in Patients with Wet Form of AMD

Anti-VEGF therapy is the main treatment in patients with the wet form of AMD. Although successful in most cases, prolonged use of intravitreal therapy can lead to serious complications. The aim of this study is to present the possible longterm complications of anti-VEGF therapy in patients with the wet form of AMD, as well as the ways to prevent them. Methods: In our study, we included 32 patients with a wet form of AMD. They were all examined ophthalmologically in detail for VA, fundus color photography, OCT (Revue, Optovue) and OCT-A (Angiophlex, Zeiss). All patients were treated with aflibercept (Eylea) - according to the Treat and Extend scheme for a period of 2 years. They were followed for complications for a period of 2 years. Results: In the long run we observed the following complications expressed in %: tachyphylaxis to the drug substance – 20%; tears of RPE-10%; fibrosis and scarring - 45%; retinal atrophy 25%. In 20% of the observed patients we found tachyphylaxis after the first year, which led to a decrease in the effectiveness of treatment. In 10% of cases we observed rupture of RPE. This occurred mainly in patients with previous detachment of RPE with a large area and height. Retinal fibrosis developed in patients with macular hemorrhage, low VA, refractory retinal cysts, or cases of RAP. Retinal fibrosis usually appeared after 10 injections. These are patients with low initial visual acuity, thin choroid especially subfoveolar and usually occurred after a small number of intravitreal injections. Conclusion: Complications after anti-VEGF therapy are relatively rare, but always associated with very serious visual impairment. The stronger the effect of the anti-VEGF drug, the more common the complications, especially retinal fibrosis. Early detection of risk factors such as low initial vision, refractory retinal cysts, macular hemorrhage, large neovascular membrane, are a prerequisite for successful prevention and treatment of these complications

Comparative Analysis Of The Results Of Anti-VEGF Therapy In Patients With AMD

Intravitreal injections are one of the most common procedures in ophthalmology. It is connected with direct delivery of drugs in the vitreous body. The aim of our survey is to show our comparative analysis of the results in the treatment of AMD patients with Lucentis and Eylea. Material and methods: We enrolled 24 patients with wet AMD, diagnosed and treated in the ophthalmic department of MMA for a period of 2 years. In 7 of the patients we used Lucentis and in the rest 17 Eylea. All patients were examined for VA, OCT central retinal thickness and FA (Topcon 3D OCT – FA +).  The  patients  were  treated  according to  the   Treat and extend  protocol with  period of  extension of  2 weeks. Results: Our results point out that   patients treated with Lucentis had an increase of the VA with two lines. They had also a reduction of retinal thickness. In RAP patients Lucentis gave better results than other medications. The Eylea treated patients showed also improvement of the VA, which was more significant than in the previous group. The decrease in the CRT was from approximately 400±130 μm to 288±74 μm in the 6-month follow up. Conclusion: Our  survey points out that  both Lucentis and Eylea are effective in  the treatment of AMD, although aflibercept shows  slightly better results in terms of VA and CRT. The treatment of this multifactorial disease is complex and has to be individualized in order to meet the specific  needs of the patients. We have to adjust the treatment in each case to be maximum effective

Surgical management of pterygium verum-historical review, current approaches

Истинският птеригиум, традиционно описван като дегенеративна лезия на конюнктивата, представлява често срещано заболяване на очната повърхност. Представя се като криловидна по форма фиброваскуларна пролиферация на булбовата конюнктива, която инвазира роговицата в посока от корнеосклералния лимб към центъра й и предизвиква деструкция на повърхностните корнеални слоеве. Птеригиумът, подобно на други слънчево-обусловени очни заболявания (т.нар. офталмохелиози), се смята че се развива при продължително въздействие на УВ-лъчи върху очната повърхност. Основен момент в патогенезата на заболяването е локалният дефицит на лимбални стволови клетки в интерпалпебралната зона. Независимо от наличието на многобройни и разнообразни техники за хирургична лечение на птеригиума, все още сериозен проблем представлява високия процент на рецидиви, вероятно дължащ се на все още не напълно изяснената етнопатогенеза на заболяването, поради което търсенето на идеалната хирургична техника все още продължава. Целта на настоящата статия е да се направи кратък преглед на съществувалите в исторически аспект методи за лечение на птеригиума, както и на съвременните подходи за третиране на заболяването.Pterygium verum, traditionally described as a degenerative disorder of the conjunctiva, is a common disease of the ocular surface. It is a wing-shaped fibrovascular proliferation of the bulbar conjunctiva, which encroaches onto the adjacent cornea in direction from the corneoscleral limbus to the center of the cornea and leads to destruction of the surface corneal layers. Pterygium, as the other sun-related eye diseases (the ophthalmohelioses), is considered to develop after a long and intensive insolation (in? uence of sun radiation, mainly UV-B lights) into ocular surface. According to current concepts, the main cause for the development of pterygium is the local deficiency of lmbal stem cells in the interpalpebral area. Although, there are a great variety of different techniques and methods for surgical treatment, nowadays the pterygium is still a surgical problem because of the high percent of the recurrences, probably as a result of the incompletely understood ethiopathogenesis of the disease and searching for the perfect surgical procedure without recurrences continues. The aim of this article is to summarize the surgical techniques and approaches in historical plan and to reveal the current concepts and methods for surgical treatment of pterygium

Causative factors for hyperopia regression in excimer keratorefractive surgery

Регресът и хипокорекцията са специфични усложнения в кераторефрактивната хирургия, които трудно се диференцират, пряко зависят от роговичната биомеханика и обуславят икономически значима тенденция към повторна корекция. Научен интерес буди въпросът кои са и от какво естество са факторите, предразполагащи към неочаквани или нетрайни рефрактивни резултати. Не по-малко важен въпрос е дали регресът е хирургична усложнение или само проблем на селекцията на пациенти, на избора на неподходяща процедура или на лазерна платформа. Настоящото изследване предлага напълно нов подход в измерването на регpеса, както и статистически обосновани резултати по отношение на възможните причини за него.Regression and hypocorrection are specific complications in refractive surgery that frequently lead to unexpected or perishable refractive results. They develop due to unforeseen alteration in corneal biomechanics and are hard to differentiate and presume. Their ethiology and pathogenesis are still vague and no statistical evidence on predisposing factors is present. Once more familiar, the regression might be controlled by patient selection, procedure planning or laser platform opting. This study offers a completely new approach to the measurement of regression and statistically sound results in terms of the possible reasons and biomarkers

Radiotherapeutic alternatives for previously irradiated recurrent gliomas

Re-irradiation for recurrent gliomas has been discussed controversially in the past. This was mainly due to only marginal palliation while being associated with a high risk for side effects using conventional radiotherapy

Tailor-Made Zinc-Finger Transcription Factors Activate FLO11 Gene Expression with Phenotypic Consequences in the Yeast Saccharomyces cerevisiae

Cys2His2 zinc fingers are eukaryotic DNA-binding motifs, capable of distinguishing different DNA sequences, and are suitable for engineering artificial transcription factors. In this work, we used the budding yeast Saccharomyces cerevisiae to study the ability of tailor-made zinc finger proteins to activate the expression of the FLO11 gene, with phenotypic consequences. Two three-finger peptides were identified, recognizing sites from the 5′ UTR of the FLO11 gene with nanomolar DNA-binding affinity. The three-finger domains and their combined six-finger motif, recognizing an 18-bp site, were fused to the activation domain of VP16 or VP64. These transcription factor constructs retained their DNA-binding ability, with the six-finger ones being the highest in affinity. However, when expressed in haploid yeast cells, only one three-finger recombinant transcription factor was able to activate the expression of FLO11 efficiently. Unlike in the wild-type, cells with such transcriptional activation displayed invasive growth and biofilm formation, without any requirement for glucose depletion. The VP16 and VP64 domains appeared to act equally well in the activation of FLO11 expression, with comparable effects in phenotypic alteration. We conclude that the functional activity of tailor-made transcription factors in cells is not easily predicted by the in vitro DNA-binding activity

Multiple Signals Converge on a Differentiation MAPK Pathway

An important emerging question in the area of signal transduction is how information from different pathways becomes integrated into a highly coordinated response. In budding yeast, multiple pathways regulate filamentous growth, a complex differentiation response that occurs under specific environmental conditions. To identify new aspects of filamentous growth regulation, we used a novel screening approach (called secretion profiling) that measures release of the extracellular domain of Msb2p, the signaling mucin which functions at the head of the filamentous growth (FG) MAPK pathway. Secretion profiling of complementary genomic collections showed that many of the pathways that regulate filamentous growth (RAS, RIM101, OPI1, and RTG) were also required for FG pathway activation. This regulation sensitized the FG pathway to multiple stimuli and synchronized it to the global signaling network. Several of the regulators were required for MSB2 expression, which identifies the MSB2 promoter as a target “hub” where multiple signals converge. Accessibility to the MSB2 promoter was further regulated by the histone deacetylase (HDAC) Rpd3p(L), which positively regulated FG pathway activity and filamentous growth. Our findings provide the first glimpse of a global regulatory hierarchy among the pathways that control filamentous growth. Systems-level integration of signaling circuitry is likely to coordinate other regulatory networks that control complex behaviors

Variation in the provision and practice of implant-based breast reconstruction in the UK: Results from the iBRA national practice questionnaire

Introduction The introduction of biological and synthetic meshes has revolutionised the practice of implant-based breast reconstruction (IBBR) but evidence for effectiveness is lacking. The iBRA (implant Breast Reconstruction evAluation) study is a national trainee-led project that aims to explore the practice and outcomes of IBBR to inform the design of a future trial. We report the results of the iBRA National Practice Questionnaire (NPQ) which aimed to comprehensively describe the provision and practice of IBBR across the UK. Methods A questionnaire investigating local practice and service provision of IBBR developed by the iBRA Steering Group was completed by trainee and consultant leads at breast and plastic surgical units across the UK. Summary data for each survey item were calculated and variation between centres and overall provision of care examined. Results 81 units within 79 NHS-hospitals completed the questionnaire. Units offered a range of reconstructive techniques, with IBBR accounting for 70% (IQR:50–80%) of participating units' immediate procedures. Units on average were staffed by 2.5 breast surgeons (IQR:2.0–3.0) and 2.0 plastic surgeons (IQR:1.0–3.0) performing 35 IBBR cases per year (IQR:20-50). Variation was demonstrated in the provision of novel different techniques for IBBR especially the use of biological (n = 62) and synthetic (n = 25) meshes and in patient selection for these procedures. Conclusions The iBRA-NPQ has demonstrated marked variation in the provision and practice of IBBR in the UK. The prospective audit phase of the iBRA study will determine the safety and effectiveness of different approaches to IBBR and allow evidence-based best practice to be explored

Design of therapeutic proteins with enhanced stability

Therapeutic proteins such as antibodies constitute the most rapidly growing class of pharmaceuticals for use in diverse clinical settings including cancer, chronic inflammatory diseases, kidney transplantation, cardiovascular medicine, and infectious diseases. Unfortunately, they tend to aggregate when stored under the concentrated conditions required in their usage. Aggregation leads to a decrease in antibody activity and could elicit an immunological response. Using full antibody atomistic molecular dynamics simulations, we identify the antibody regions prone to aggregation by using a technology that we developed called spatial aggregation propensity (SAP). SAP identifies the location and size of these aggregation prone regions, and allows us to perform target mutations of those regions to engineer antibodies for stability. We apply this method to therapeutic antibodies and demonstrate the significantly enhanced stability of our mutants compared with the wild type. The technology described here could be used to incorporate developability in a rational way during the screening of antibodies in the discovery phase for several diseases.National Center for Supercomputing ApplicationsNovartis Pharma AGNational Science Foundation (Grant MCB060103