\r\n\tIn recent decades, numerous studies have been carried out on eukaryotic microorganisms viz., fungi, protozoa and algae to unravel the disease mechanisms caused by them and also their potential use in genetic engineering. The current book will accumulate the latest findings related to eukaryotic microorganisms in order to guide the future research and to uplift this area of microbiology for potential applications in medical and agricultural sciences.
",isbn:null,printIsbn:"979-953-307-X-X",pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"111dd972fdc98d1968c9f854910f7188",bookSignature:"Dr. Asghar Ali Kamboh",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/8963.jpg",keywords:"Mycology, Protozoology, Phycology, Gut eukaryotic microbiota, Antifungal / Antiprotozoal agents, Manipulating the Genes of Eukaryotes, Use of Eukaryotes in genetic engineering",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"August 27th 2019",dateEndSecondStepPublish:"September 17th 2019",dateEndThirdStepPublish:"November 16th 2019",dateEndFourthStepPublish:"February 4th 2020",dateEndFifthStepPublish:"April 4th 2020",remainingDaysToSecondStep:"a year",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"225390",title:"Dr.",name:"Asghar Ali",middleName:null,surname:"Kamboh",slug:"asghar-ali-kamboh",fullName:"Asghar Ali Kamboh",profilePictureURL:"https://mts.intechopen.com/storage/users/225390/images/system/225390.jpeg",biography:"Dr. Asghar Ali Kamboh was born in Mehrabpur, Sindh, Pakistan in 1979. He completed his studies in Veterinary Medicine and Masters in Veterinary Microbiology in 2003 and 2007 respectively, with distinguished grades. In 2009, he was awarded an oversees scholarship by the Government of Pakistan and proceeded to China for doctoral studies. Currently, he is working as an Associate Professor and Chairperson of the Department of Veterinary Microbiology, Sindh Agriculture University, Tandojam. He has published more than 80 research and review articles in national and international peer reviewed journals. He has supervised/co-supervised more than 30 M.Phil students. He is also the author of many books and book chapters. In addition, he is an editor/editorial board member of many scholarly journals in the area of animal health and production.",institutionString:"Sindh Agriculture University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Sindh Agriculture University",institutionURL:null,country:{name:"Pakistan"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"13",title:"Immunology and Microbiology",slug:"immunology-and-microbiology"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"305835",firstName:"Ketrin",lastName:"Polesak",middleName:null,title:"Mrs.",imageUrl:"https://mts.intechopen.com/storage/users/305835/images/9351_n.png",email:"ketrin@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"8470",title:"Poultry",subtitle:"An Advanced Learning",isOpenForSubmission:!1,hash:"88f09746e2b424573c8dc0bd927e9dbb",slug:"poultry-an-advanced-learning",bookSignature:"Asghar Ali Kamboh",coverURL:"https://cdn.intechopen.com/books/images_new/8470.jpg",editedByType:"Edited by",editors:[{id:"225390",title:"Dr.",name:"Asghar Ali",surname:"Kamboh",slug:"asghar-ali-kamboh",fullName:"Asghar Ali Kamboh"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4816",title:"Face Recognition",subtitle:null,isOpenForSubmission:!1,hash:"146063b5359146b7718ea86bad47c8eb",slug:"face_recognition",bookSignature:"Kresimir Delac and Mislav Grgic",coverURL:"https://cdn.intechopen.com/books/images_new/4816.jpg",editedByType:"Edited by",editors:[{id:"528",title:"Dr.",name:"Kresimir",surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"40006",title:"Phase Transitions, Dielectric and Ferroelectric Properties of Lead-free NBT-BT Thin Films",doi:"10.5772/52395",slug:"phase-transitions-dielectric-and-ferroelectric-properties-of-lead-free-ferroelectric-nbt-bt-thin-fil",body:'\n\t\tFerroelectric perovskites based on Na0.5Bi0.5TiO3 (NBT) are considered among the most promising lead-free candidate materials to substitute Pb(Zr\n\t\t\t\t\t1-x\n\t\t\t\tTi\n\t\t\t\t\tx\n\t\t\t\t)O3 (PZT) in devices designed to respect standards and environmental laws. Taking into account the toxicity of lead-based systems, there are numerous lead-free piezoelectric materials under investigation in worldwide spread laboratories for replacing PZT in future devices. Constant efforts are made to find viable replacements for all these materials containing harmful elements.
\n\t\t\tSolid-solution systems based on lead-free perovskites like Na0.5K0.5NbO3 (NKN), BaTiO3 (BT), Na0.5Bi0.5TiO3 (NBT) or bismuth layered-structured SrBi2Ta2O9 (SBT), and SrBi2Nb2O9 (SBN) are considered as viable alternatives for replacing lead-based materials. For example, (K,Na)NbO3–LiTaO3–LiSbO3 alkaline niobate ceramics exhibit a d\n\t\t\t\t\n\t\t\t\t\t33\n\t\t\t\t piezoelectric coefficient up to 416 pC/N together with Curie temperature Tc around 526 K, as reported by Saito et al [1]. Sodium/bismuth titanate (NBT) belongs to the bismuth-based perovskites in which the A-site atom is replaced. The crystalline structure, phase transitions and physical properties have been intensively studied since the discovery of the material in 1960 by Smolensky et al [2]. NBT has a relatively high depolarization temperature, Td = 470 K, high remanent polarization, 38 μC/cm2 and piezoelectric coefficient d33 = 125 pC/N [3]. However, owing to the high value of the coercive field and high electrical conductivity, NBT cannot be easily polarized, therefore different A-site substitutions have been attempted to avoid this drawback.
\n\t\t\tThe end-members of perovskite NBT-BT: rhombohedral NBT and tetragonal BT. Cations Na+/Bi3+ and Ba2+ occupy the A-sites while Ti4+ occupies B-sites (oxygen octahedra centers).
The solid solution with BaTiO3, (1-x) NBT-x BT shows a morphotropic phase boundary (MPB) between the rhombohedral and the tetragonal phase, at x between 0.06 and 0.07 for which the material properties are considerably improved. Indeed d33 values up to 450 pC/N, and huge electric field-induced strain have been reported [4, 5]. Figure 1 shows the crystalline structures of the NBT and BT end members at room temperature. Perovskite structure deformations include oxygen octahedral rotations around different axis and cation shifts, therefore giving rise to a complex succession of ferroelastic and ferroelectric phase transformations with temperature variation.
\n\t\t\tDue to this polymorphic structure, NBT and NBT-BT have been also intensively studied in order to clarify their complicated phase transitions, which still pose questions [6].Structural and polar transformations in NBT-BT are more complicated than in other perovskite solid solutions, also due to the strong disorder of the A-sites occupied by Na+, Bi3+ or Ba2+ ions, with different valence, mass and ionic radius. NBT transforms successively, from the high temperature cubic paraelectric into tetragonal antiferroelectric (or ferrielectric) and further into a rhombohedral ferroelectric phase [6]. In solid solution with BT, the ground ferroelectric phase changes from rhombohedral R3c to tetragonal ferroelectric P4mm, at the so-called morphotropic phase boundary (MPB) (x ≈ 0.06-0.07) [5, 7, 8]. The phase diagram of NBT-BT bulk material, mainly based on dielectric measurements, was completed by Cordero et al by performing direct anelastic measurements, the border between tetragonal and cubic phases being evidenced [9, 10, 11].
\n\t\t\tFor NBT-BT thin films growth many techniques have been used. Guo et al. have investigated NBT-BT-based tri-layered films prepared by chemical solution deposition as a possible solution to the problem of avoiding leakage currents under high electric fields [12, 13]. Using pulsed laser deposition (PLD), Duclère et al. have reported the heteroepitaxial growth of NBT thin films on epitaxial platinum electrodes supported on a sapphire substrate [14]. More recently, M.Bousquet et al have described the electrical properties of (110)- oriented NBT thin films deposited by laser ablation on (110)Pt/(110) SrTiO3 substrates [15]. They reported the coexistence of two kinds of grains with different shapes in the films, flat and elongated grains corresponding to (100) and (110) oriented NBT crystallites. The effects of Bi- excess in target on the dielectric and ferroelectric properties of the films have been also presented; the reported values for relative permittivity and remnant polarization were εr≈225-410 and 14 μC/cm2, respectively. Furthermore, very recently, the electrical properties of (100)-oriented Na0.5Bi0.5TiO3-BiFeO3 thin films deposited by sol-gel have been reported by Qin et al, aiming to important applications such as photovoltaic devices [16].
\n\t\t\tHowever, despite the fact that ferroelectric materials with MPB have enhanced ferroelectric and piezoelectric properties, it is difficult to transpose them in thin films since MPB is limited to a small composition range. Almost all the physical parameters involved in thin films deposition like the substrate type, the microstructure and stress have strong impact on their physical properties [17]. In some previous papers we have investigated the role of different deposition parameters on NBT-BT film growth and properties [18, 19]. In this chapter, we discuss the role of certain experimental conditions like deposition temperature and substrate type, as well as of the amount of BT present in the target on crystalline structure, microstructure, dielectric properties, phase transition temperatures and stability limits of ferroelectric phases in NBT-BT thin films produced by PLD.
\n\t\tPulsed laser deposition (PLD) was used for the film growth. The targets with composition (NBT)1-x\n\t\t\t\t(BT)\n\t\t\t\t\tx\n\t\t\t\t (x = 0.06-0.08), further called NBT-BT6 and NBT-BT8, have been prepared following the mixed oxide route and sintered at 1150 oC for 2 h. The sintering was performed in crucibles with the sample surrounded with NBT pack, in order to avoid the loss of Na and Bi, which occurs at temperatures over 1000 oC; more details can be found in Ref.11. X-ray diffraction analysis evidenced the obtaining of pure perovskite phase. The microstructure of the sintered targets was investigated on polished and etched surfaces by scanning electron microscopy. The observed grain sizes were 2-10 μm.
\n\t\t\tFor the film deposition, a Surelite II Nd:YAG pulsed laser with wavelength of 265 nm, pulse duration of 5 ns and frequency 10 Hz, has been employed. The laser fluence was set at 1.6 J/cm2. The films were grown on Nb:STO and Pt/TiO2/SiO2/Si substrates, placed at a distance of about 4.3 cm from the target. Different sets of films have been grown at different substrate temperatures, ranging between 650-730 oC. Deposition and after-deposition cooling were performed in flowing oxygen atmosphere (0.3-0.6 mbar) to favour the formation of perovskite phase without oxygen vacancies. Chemical composition was checked via SIMS technique using a Hiden SIMS/SNMS system. The thickness of the thin films, evaluated by spectroellipsometry, was between 300-500 nm.
\n\t\t\tFor the investigation of the crystalline structure of the targets and films, a PANalytical X’pert MRD diffractometer in Bragg-Brentano geometry was used. The measurements were performed with a step size of 0.020 and with a scanning time on step of 25 s or 250 s, depending on the angular range.
\n\t\t\tThe film surface morphology was examined by AFM (model XE100, Park Systems). Piezoelectric force microscopy measurements were performed with a PFM system which includes a lock-in amplifier SR-830 and a dc- high voltage amplifier WMA-280. Conductive all-metal Pt tips were employed for these measurements were the switching characteristcs of the films have been tested.
\n\t\t\tSeveral Au electrode dots with an area of about 0.22 mm2 have been evaporated through a mask on the films for electrical characterization. Polarization hysteresis was measured by using a Radiant Technology RT66A ferroelectric test system, in the virtual ground mode. The dielectric measurements were carried out in a frequency range between 200 Hz and 1 MHz using an HP 4194A impedance analyzer and an HP 4284A LCR meter with a four wire probe. The measurements were performed at 1.5 K/min between 300 and 570 K in a Delta Design climatic chamber model 9023 A (on targets) and in a Linkam variable-temperature stage (model HFS 600E) on films.
\n\t\tThe microstructure of ceramic thin films is one of the most important factors that influence their physical properties. Since the growth mode of thin films is strongly dependent on the substrate type, we investigated the deposition of NBT-BT thin films on two different types of substrates:
\n\t\t\t\tsingle crystal SrTiO3: Nb (Nb:STO) and
Pt/TiO2/SiO2/Si.
The AFM pictures obtained on the two sets of films show important microstructural differences, mainly due to different growth mechanisms. In Figure 2 we show AFM images taken on a NBT-BT6 film deposited on Nb: STO monocrystalline substrate at 650 0C. It can be observed that a first stage of growth resulting into a continuous layer stops when the critical thickness for misfit dislocations (probably a few tens of nm) is reached. After that, the growth continues in platelet-like form (see details in Fig. 2 b). If the deposition temperature is not sufficiently high to favor material exchange between platelets via surface migration, successive layers will grow on the top of the first islands and the growth will result into a discontinuous layer. This explains the platelet-like aspect of the film shown in Figure 2.
\n\t\t\t\tAFM images of NBT-BT6% films deposited on Nb:STO substrates at temperature of 650 oC. The displayed surfaces are 20x20 μm2 (a) and 5x5 μm2 (b).
AFM images of NBT-BT6% films deposited on Nb:STO substrates at 700oC. The displayed surfaces are 20x20 μm2 (a) and 5x5 μm2 (b).
However, raising the substrate temperature to 700 0C during the deposition of a second set of films while keeping constant all the other parameters, including the number of laser pulses, produces a uniform layer of continuous platelets, on top of which new islands nucleate (Figure. 3).
\n\t\t\t\tA rather different morphology is displayed by NBT-BT films grown on Pt/TiO2/SiO2/Si (Fig. 4 and 5). In this case, the growth progresses from the beginning in island-like form since the polycrystalline Pt layer provide the nucleation sites for their formation. Moreover, these NBT-BT islands grow on the Pt layer without preserving a unique orientation, due to the same reason. Instead films grown on Nb:STO monocrystalline structures are uniaxially (001)-oriented, as it will be shown in the next section.
\n\t\t\t\tAFM images of NBT-BT6% films deposited on Pt/TiO2/SiO2/Si substrate at a temperature of 700 oC. The displayed surfaces are 20x20 μm2 (a) and 5x5 μm2 (b).
A fine microstructure with grain size ranging from a few tens of nm up to a few hundred of nm is displayed by NBT-BT6 films (Fig. 4). We note the striking difference with bulk samples microstructures (not shown here), which consists of crystallites of 1-10 μm size.
\n\t\t\t\tA similar fine microstructure is displayed by NBT-BT8% films grown on Pt/TiO2/SiO2/Si (Fig. 5 a). However, the enlarged AFM image displayed in Fig 5 b) reveales a somewhat different aspect with triangular nanograins lying in plane.
\n\t\t\tAFM images of NBT-BT8% films deposited on Pt/TiO2/SiO2/Si substrate at a temperature of 700 o C. The displayed surfaces are 20x20 μm2 (a) and 5x5 μm2 (b).
The XRD spectrum of NBT-BT6 target corresponds to a mixture of rhombohedral R3c and tetragonal P4mm phases, as shown by the splitting of (111) and (200), (012) and (024) rhombohedral peaks in the bottom pattern in Fig. 6 [20]. The main Miller index of the rhombohedral phase are depicted horizontally on the bottom of the figures while those of the tetragonal phase vertically above. On the same graph, the pattern corresponding to the NBT-BT6 film grown on Pt/TiO2/SiO2/Si at 700 0C is given. The curve corresponding to NBT-BT6/Pt/TiO2/SiO2/Si film deposited in the same conditions but at a substrate temperature of 6500 exhibits similar features as we had reported and is not presented here [18].The as deposited thin films exhibit pure perovskite phase with symmetry congruent with that of the target. The reflection peaks indicate a randomly oriented structure, consistent with the polycrystalline nature of the films.
\n\t\t\t\tXRD spectra of NBT-BT6% deposited on Pt/TiO2/SiO2/Si substrate. The bottom pattern corresponds to the target
\n\t\t\t\t\tFigure 7 displays the XRD patterns of NBT-BT6 films deposited at two temperatures, 650 0C and 700 0C, around the (100)/(001) and (200)/(002) reflections of the Nb:STO substrate. The spectra indicate the epitaxial growth of NBT-BT6% films on the Nb:STO substrate at the two temperatures. This feature is congruent with the microstructure shown in the previous section (Fig. 2 and Fig. 3), consisting of large platelet-like crystallites which preserve the same axis of orientation with the monocrystalline substrate.
\n\t\t\t\tXRD spectra of NBT-BT6% /Nb:STONb:STO films deposited at 650 oC and 700 oC. The grey pattern represents the Nb:STONb:STO target reflection peaks.
\n\t\t\t\t\tFigure 8 shows the XRD patterns of NBT-BT8 films grown on Pt/TiO2/SiO2/Si and Nb:STO substrates at 700 0C. The grey pattern represents the NBT-BT8 target spectrum, which corresponds to the tetragonal P4mm symmetry. It can be observed that, similar to the previous composition, the growth on single crystal Nb:STO substrate produces an epitaxial film, while the growth on Pt/TiO2/SiO2/Si substrate results into a polycrystalline randomly oriented film.
\n\t\t\t\tXRD spectra of NBT-BT8% deposited on Pt/TiO2/SiO2/Si and on Nb:STONb:STO substrates
The dielectric and ferroelectric properties of NBT-BT thin films have been evaluated on capacitors formed by evaporating through a mask an array of gold electrode dots with an area of about 0.22 mm2 on the surface of films grown on Pt/TiO2/SiO2/Si and Nb:STO substrates. The bottom electrode was formed by the Pt layer in the first case or by the Nb:STO substrate itself in the second case.
\n\t\t\t\tThe piezoresponce force microscopy results are presented in Figure 9. The full-Pt tips were brought in contact with the surface of the sample and then a dc bias and test ac bias were applied between the tip and the bottom electrode of the samples. The dc bias was generated by a high voltage amplifier and the ac bias was generated by a lock-in amplifier. The same lock-in amplifier was used to analyse the vertical deflection signal from the PSPD, in order to extract the amplitude and the phase of the cantilever oscillations induced by the local deformation of the sample due to the applied dc bias. The NBT-BT6/Pt/Si thin films show good switching behavior, the piezoelectric hysteresis and pronounced imprint (not showed here) confirming the piezoelectric and ferroelectric characteristics. The dependence of effective piezoelectric coefficient d33\n\t\t\t\t\teff on the applied electric field is given in Figure 9. The locally measured values with the highest being around d33\n\t\t\t\t\teff≈ 83 pm/V, are even higher then for previouslly reported values for pure NBT or lead-based thin films, such as Pb(ZrTi)O3 or PbTiO3 [21, 22]. However, these d33\n\t\t\t\t\teff are a bit smaller then NBT-BT6 ceramics which are reported to be more than 100 pm/V [21]. The reasons for these smaller values are related with the film’s porosity, but also with the clamping effect which occurs because the PFM tip- applied electric field will piezoelectrically deform only a small fraction of the film. The rest of the sample will restrict the relative deformation of this small fraction, resulting a lower value for d33\n\t\t\t\t\teff [5, 22].
\n\t\t\t\tThe piezoresponse measurements performed on NBT-BT6 thin films.
In Fig. 10 the room temperature dielectric properties of NBT-BT6 films deposited on Pt/TiO2/SiO2/Si at different substrate temperatures, 650 0C and 730 0C, have been compared in the frequency range 100 Hz-1 MHz. Films grown at 650 0C show a higher dielectric constant (ε’ ~ 1000), in the order of magnitude of the bulk values (ε’bulk ~ 1900), while films grown at 730 0C show lower values (ε’ ~ 700). The dielectric loss values are instead comparable in the two samples, and similar to bulk values.
\n\t\t\t\tRoom temperature dielectric constant ε’ and loss tanδ variation with frequency for NBT-BT6% films deposited at different temperatures on Pt/TiO2/SiO2/Si.
\n\t\t\t\t\tFigure 11 displays the room temperature dielectric constant and dielectric loss in the frequency range 100 Hz-1 MHz for NBT-BT8 films grown on Pt/TiO2/SiO2/Si at different temperatures: 650, 700 and 730 0C. Unlike the previous composition, in this case growth at higher substrate temperatures was beneficial for the improvement of dielectric properties, at least in the frequency domain up to a few hundred kHz. Above this frequency there is a strong increase of dielectric loss. Since an increase is registered also in the dielectric constant, this could be caused by a relaxation mechanism which is active at room temperature at these frequencies, like e.g. free charge relaxation.
\n\t\t\t\tRoom temperature dielectric constant and loss variation with frequency for NBT-BT8% films deposited at different temperatures on Pt/TiO2/SiO2/Si
Polarization hysteresis measurements on NBT-BT6 films grown on Pt/TiO2/SiO2/Si are shown in Fig. 12. Spontaneous polarization was about 30 μC/cm2 and the remnant polarization was about 10 μC/cm2. The rather high value of coercive field (100 kV/cm) could be explained by the presence of intrinsic strain and pinning defects.
\n\t\t\t\t\n\t\t\t\tDielectric and ferroelectric properties measurements on films deposited on Nb:STO substrates have been less reliable, probably due to the presence of a non-ohmic contact at the NBT-BT film – semiconductor Nb:STO interface. However PFM measurements (not shown here) evidenced good piezoelectric response, which indicates good intrinsic dielectric and ferroelectric properties, although quantitative values are difficult to extract.
\n\t\t\tPolarization-electric field hysteresis loop measured on a NBT-BT6% film deposited on Pt/TiO2/SiO2/Si
Phase transitions in ferroelectric materials are accompanied by anomalies of complex dielectric permittivity variation with temperature, generally narrow peaks or steps, depending on the type of phase transformation. However NBT-BT compositions near the morphotropic phase boundary behave as relaxors, due to the cation disorder. This is evidenced in Fig. 13 for NBT-BT8 bulk material. The main characteristic of a relaxor ferroelectric is a broad dielectric peak at a temperature Tm which is not related to a structural transformation. This is due to a wide distribution of relaxation times which characterizes the dielectric response of polar nanoregions. This peak shifts with the increasing of the measurement frequency toward higher temperatures. Thus the dielectric maximum of NBT-BT8 shifts from about 497 K at 200 Hz to about 512 K at 100 kHz. A similar dependence is obeyed also by the dielectric loss.
\n\t\t\t\t\n\t\t\t\tIn Fig. 14 the variation of dielectric constant and loss with temperature for a NBT-BT8 film deposited on Pt/TiO2/SiO2/Si is shown. The maximum of the dielectric constant occurs at about 485 K, not far from bulk Tm. However the anomaly is characteristic of a well-behaved phase transition, since the peak temperature Tm does not shift with frequency. A similar qualitative behavior was observed also on the dielectric permittivity variation with temperature for NBT-BT6 films (not shown here).
\n\t\t\t\tThe dielectric permittivity and loss variation with temperature measured on a NBT-BT8% bulk sample at different frequencies. The long arrows mark the increasing of frequency.
While the dielectric permittivity peak position Tm ~ 485 K does not shift with measuring frequency, peak height is strongly dependent on it, decreasing for higher frequencies. This can be attributed to the possible presence of a non-polar dielectric layer, which does not influence the general behavior at phase transition, but can modify the value of the dielectric constant [23]. Generally these interface layers can have strong frequency-dependent dielectric properties which influence the overall properties of the heterostructures. However we stress again that the dependence on temperature and phase transition temperatures can be influenced only in the limits of a monotonous contribution, since the dielectric behaviour of non-polar layers is free of temperature anomalies. Indeed the stronger variation with temperature of the peak intensity at Tm could be attributed to the non-polar layer contribution at higher temperatures due to conductivity variation.
\n\t\t\t\tThe temperature Td where a strong increase of dielectric loss and dielectric constant occurs marks the ferroelectric – antiferroelectric phase transition which, in bulk samples with the same composition is visible only in the poled state. It is called also depolarization temperature.
\n\t\t\t\tThe dielectric permittivity and loss variation with temperature measured on a NBT-BT8% thin film at different frequencies. The long arrows mark the increasing of frequency.
An apparent frequency dependence of the step increase in tanδ which marks Td is visible on the lower curves in Fig. 14. This could be attributed to a partial relaxor behavior due to mixed nanodomains-normal ferroelectric domains, which can be find also, but in proportion displaced to the nanodomain limit, in bulk samples. We must remark that the films were not poled, since no bias electric field was applied. Therefore the occurrence of a ferroelectric ground state in the NBT-BT films, in striking contrast with relaxor bulk samples with the same composition, must be generated by some intrinsic differences between ceramic bulk samples and ceramic thin films. The first and most obvious reason could be related to the constraining stress of the substrate on the thin films. This is strong in epitaxially grown thin films with a thickness generally below 100 nm, but it should be almost absent in polycrystalline films, randomly oriented and with a thickness of several hundreds of nm. This last one is the case for NBT-BT thin films deposited on Pt/TiO2/SiO2/Si substrates. The second reason could be related to the strong differences in the microstructures of ceramic thin films and bulk materials with the same composition. Therefore the occurrence of a ferroelectric ground state instead of a relaxor state in NBT-BT films, as well as the occurrence of a true ferroelectric phase transition could be due to the constrainig imposed by the nanograin boundaries on the ensemble of polar nanoregions.
\n\t\t\tIn summary, we have investigated the role of deposition temperature and substrate type as well as the amount of BT present in the target on crystalline structure, microstructure, dielectric properties, phase transition temperatures and stability limits of ferroelectric phases in NBT-BT thin films grown by pulsed laser deposition. We have successfully deposited pure perovskite epitaxial films on single-crystal Nb:STO substrates. Successful growth of NBT-BT films on platinized silicon substrates has been achieved. Good dielectric and ferroelectric properties, comparable with bulk values, have been obtained. The NBT-BT6/Pt/Si thin films show a classic switching behavior, the piezoelectric hysteresis and pronounced imprint confirming the piezoelectric and ferroelectric characteristics. The locally measured value of effective piezoeletric coefficient d33\n\t\t\t\teff was around 83 pm/V, higher to the previouslly reported values for pure NBT or lead-based thin films. An enhanced stability of ferroelectric phase in thin films with respect to bulk has been observed and explained by their peculiar nanocrystalline microstructure.
\n\t\tMalignant melanoma of uvea (iris, ciliary body, and choroid), is the most widely recognized essential intraocular danger in grown-ups. Uveal melanoma (UM) is analyzed generally in more established age, with a dynamically increasing age-explicit frequency rate that tops close to the age of seventy. Ocular melanoma is probably going to metastasize in different lregions of the body, for example, breast, lung, kidney or liver.
\nThere are many factors associated with the development of uveal melanoma. The most important include genetic factors, race, color of the eyes, fair coloring of the skin and the ability to tan. Many observational studies up to date have attempted to explore the relationship between sunlight exposure and risk of uveal melanoma development [1].
\nUsually, uveal melanomas are in early stages of their development completely asymptomatic. The comparatively low incidence of iris melanomas (anterior segment melanoma) has been attributed to the characteristic features of these tumors. Iris melanomas also rarely metastasize. Posterior melanoma - choroidal melanoma is the most common ocular melanoma type. This type is involved in over 75% of all intraocular melanomas. Iris melanoma wchis is in anterior segment is cytologically less malignant and metastatize less frequently tnak posterios uveal melanomas.
\nOrdinarily, choroidal melanoma is brown colored, raised mass, and the level of its pigmentation can go from dim earthy colored to thoroughly white, amelanotic.
\nIn advanced stages the symptoms are dependent on tumor location. The most important test to establish the presence of intraocular melanoma, is the examination by an experienced clinician at specialized Ophthalmology Department. Diagnostic testing can be extremely valuable in establishing and confirming the diagnosis.
\nPrognosis can be influenced by number of factors. The most important are the histopathologic type of cells, the size of tumor, tumor volume, the margins of the tumor, karyotype and grading and staging by TNM Classification (e.g. extraocular extension). Cell type, however, remains the most often used predictor of outcome with genetic results.
\nThe treatment relies upon the site of birthplace (choroid, ciliary body or iris), the size, volume and area of the injury, the general statis of the patient, age of the patient and whether extraocular attack, repeat or metastasis has happened. Extraocular augmentation, repeat, and metastasis are related with a very helpless guess and long - term endurance cannot be normal [2].
\nElective therapy modalities have been proposed as of late including extremist careful evacuation of the eye globe (enucleation), nearby resection, light procedures: plaque brachytherapy, charged-molecule radiotherapy, stereotactic photon bar illumination treatment or in start of the tumor transpupillary thermotherapy and photodynamic treatment.
\nOver the past 3–4 decades diagnostic methods have improved and radiotherapy (external beam, charged particle or brachytherapy) has become the preferred treatment for most of the patients with uveal melanoma. The aim of the treatment is to improve survival and preserve eye globe anatomically with aim to preserve the best vision in patients with uveal melanoma. Different radiation modalities are currently in use in treatment of posterior uveal melanoma in many Ophthalmology Centers. One of the methods of “conservative” approach is the stereotactic radiosurgery (SRS) by linear accelerator [2, 3, 4, 5].
\nThe uveal parcel frames the center layer (or „vasculo-strong” coat) mass of the eyeball. Uvea layer is a combination of veins, pigmented cells and muscles, woven together by connective tissue. It has a nutritive capacity of the eye globe. The uveal parcel comprises of three anatomical parts, all profoundly vascular and pigmented. The noticeable part in front is the iris (part of the foremost portion of the eye) and it makes the shade of the eye globe. The iris consolidates in reverse into the ciliary body, and the ciliary body offers path to the choroid, to the back fragment of the eye globe, which is such a vascular undercoat between the sclera and the shade retina. It is substantial pigmented, along these lines engrossing light which has gone through the retina.
\nThe pigmented cells (the melanocytes) - are derived from the neural crests which have migrated to the skin and mucous membranes. Melanocytes synthesize a special organelle called a melanosome – this is responsible for the characteristic color of the skin in different races. Melanosis (melanocytosis) refers to increased pigmentation caused by hyperplasia or hypertrophy of melanocytes.
\nChanges in melanocytes usually cause melanomas. Melanocytes produce melanin, which is responsible for skin and hair tone. It can show up on ordinary skin or it might start as a mole or other territory that has changed in appearance. A few moles that are available upon entering the world may form into melanomas during the adulthood.
\nBenign tumor composed of nevus cells or melanocytes is nevus. In nevi cells contain melanosomes and are therefore capable of producing pigment melanin [1].
\nMelanoma is a malignant tumor resulting from a transformation of melanocytes or nevus cells. It may be pigmented or non-pigmented. Melanoma is caused mainly by intense, occasional UV exposure (frequently leading to sunburn), especially in those who are genetically predisposed to the disease. Most melanomas are dark or earthy colored, however they can likewise be skin-shaded, pink, red, purple, blue or white. In the event that melanoma is perceived and treated early, it is quite often reparable, however on the off chance that it is not, the tumor can progress and spread to different pieces of the body, particularly liver, where it turns out to be difficult to treat and can be deadly. Melanomas frequently metastasize widely and the regional lymph nodes, liver, lungs and brain are likely to be involved.
\nIntraocular melanoma is the most common primary ocular malignant tumor in adults and develops from uvea. Intraocular tumors might be benign or malignant.
\nIntraocular melanoma is a quite rare type of tumor and it occurs most often in elderly people. There is lot of cases when ophthalmologists detected intraocular melanoma during a routine eye examination. The chance of recovery is depending on factors such as the size, localization and cell type of the tumor. Extraocular extension is the term used to describe the intraocular melanoma which spreads to the optic nerve or nearby tissue of the eye socket and is the sign of the advanced stage of the tumor [6].
\nIntraocular melanoma of the ciliary body and choroid (structures together called the posterior uvea), is the most common primary ocular malignant tumor in adults. Iris melanomas are a subset of uveal melanomas that tend to have a more benign course, in comparison with posterior uveal melanomas. Anterior segment melanomas have a lower incidence of metastases when compared to ciliary body and choroidal melanomas. Anterior segment melanomas account for about 15% of all uveal melanomas. The incidence of uveal melanoma increases with age and reaches a maximum between the 6th and 7th decade of life. It is more common in males and is uncommon or rare in kids and darker looking people. Uveal melanomas are infrequently two-sided. Be that as it may, the quantity of patients with two-sided inclusion is more noteworthy than would be anticipated by chance alone, subsequently inferring a potential hereditary inclination.
\nAs mentioned before, choroidal melanoma represents the most common primary intraocular tumor in adults. Peak incidence is in the early 60s representing about 7.5 cases per one million populations. Incidence is rare in younger adults under 30 years of age with an estimated peak incidence of about six cases per one hundred million. Caucasians are 8 times more likely to develop the melanoma than Africans or Afro-Americans and 3 times more likely than Asians. Intraocular melanoma is arising from choroid in more than 75% of all the cases. Whether some environmental exposure triggers the development of uveal melanoma remains an open question. Sunlight has been proposed as an environmental risk factor for melanoma generally. Unlike cutaneous melanoma, incidence rates for uveal melanoma have not increased over time and last decades and it does not vary by latitude [7, 8].
\nThe first step to diagnose uveal melanoma is patient’s history. Patients with uveal melanoma may present with complaints of visual acuity reduction, but many can be without symptoms and the condition is discovered on routine ocular examination or by glasses prescription. In eyes with clear optic media, the diagnosis of posterior uveal melanoma can be made by indirect ophthalmoscopy.
ophthalmoscopy, fundus photography,
transillumination,
perimetry,
fluorescein angiography, indocyanine green angiography,
ultrasonography (A and B modes),
ultrasound biomicroscopy - UBM,
optical coherence tomography - OCT,
computed tomography - CT,
magnetic resonance imaging - MRI,
fine-needle biopsy
whole body PET/CT to distinguish metastasis.
Depending on their site of growth, posterior uveal melanomas differ in their symptoms, clinical presentation and appearance. A ciliary body melanoma can attain a large size, volume, before it is clinically recognized. It can be seen in association with one or more dilated episcleral blood vessels, it can present itself as an epibulbar pigmented lesion if there is transscleral extension of the tumor. Also, cataract, and/or lens subluxation or secondary glaucoma due to infiltration of the trabecular meshwork in the angle of the eye can be present. The tumor can be envisioned clinically through a broadly enlarged understudy by cut light assessment as an arch formed collection in the area or it can have a diffuse circumferential development design known as “ring melanoma”. It can develop anteriorly into the front chamber – iridocorneal point and iris (iridociliary melanoma) or back into the choroid (ciliochoroidal melanoma).
\nA melanoma of choroid ordinarily presents as a sessile or curve formed collection arranged under the retina. Initial step analytic techniques can be aberrant ophthalmoscopy, ultrasound and fluorescein angiography. Surface orange color at the degree of the retinal shade epithelium can be imagined clinically, particularly in more modest back melanomas. Retinal separations can be seen auxiliary to the tumor development just as Bruch membrane rupture (cellar layer bellow the retinal shade epithelium). We can divide melanoma of chodoid into two groups the first is melanoma with pigment and the second one is melanoma withou pigment and can likewise accept a spread development design with just negligible tumor diameter under 3 mm.
\nMelanoma of ciliary body and melanomas of choroidea may develop cataracts, extraocular extension, secondary glaucoma. Orbital infiltration can be seen usually when the tumor has large volume, higher stage and they therefore have a worse prognosis [9].
\nDue to the huge range of clinical, morphologic and cytological changes and an absence of discrete stages it is hard to foresee clinical result in singular instances of uveal melanoma based on intraocular tumor size. His size and volume is perhaps the best boundary used to foresee metastatic infection.
\nA little tumor - melanoma - is characterized as estimating 3 mm or less in thickness and under 10 mm in breadth because of TNM plot. A tumor is delegated medium-sized in the event that it measures between 3 to 5 mm in thickness and between 10 to 15 mm in width. A huge tumor is more prominent than 5 mm in thickness and in excess of 15 mm in breadth.
\nPatients, who are diagnosed with a primary choroidal “intraocular” melanoma, have usually no signs or symptoms of metastatic tumor. Even with total body positron emission tomography/computed tomography (PET/CT) imaging, very few patients are found to have their melanomas spread to other parts of their body. Others may be found to have metastasis over the following years. The overall percentage of the patients diagnosed for choroidal melanoma does not develop metastatic melanoma. The size of the tumor is one of the very important factors to predict the risk for metastatic spreading. Treatments that limit tumors ability to enlarge will decrease the chance of metastasis because removing the eye tumor is the best method to prevent future spread from that tumor. It is very important for the patients to have periodic general medical examinations because the treatment itself does not affect micrometastasis that can be already present at the time the treatment occurs.
\nPatients who have metastatic choroidal melanoma, as mentioned above, seem to have no symptoms. For this reason, they should have periodic medical examinations, physical examinations, blood tests and radiographic imaging tests as X-ray, MRI, CT or PET/CT. Later on, patients may have symptoms like loss of their appetite, difficulty with breathing or fatigue.
\nThe highest percentage of metastatic choroidal melanoma is likely to be found in the liver. Metastases in this area of the body can be discovered by blood tests or abdominal imaging studies even in cases when patients are asymptomatic. Besides this, other organs also can be affected, e.g. subcutaneous lymph nodes, lung, bone and brain. A needle biopsy can be used to aspirate tumor cells for cytopathologic examination, when a liver or skin metastasis is suspected.
\nThe liver is the known site of metastasing of choroidal melanoma. Hepatic enzyme levels are tested in all patients with melanoma of uvea. The most sensitive tests of liver capacity are serum antacid phosphate levels, glutamate oxaloacetic transaminase, lactate dehydrogenase and gamma-glutamyl transpeptidase. These test results are negative at closure hour in the majority of patients with choroidal melanoma. If any of the results of these research devices is anomalous, ultrasonography and CT of the liver are displayed. Both imaging modalities have low susceptibility to metastases with a diameter of less than 10–20 mm. [10, 11, 12, 13].
\nEndurance displaying gives a sign of guess. Likewise, it empowers exceptional measures to be focused just as it improves the assessment of clinical methodology.
\nEndurance rates give a more precise system so as to depict the visualization for patients with a specific stage and type of disease. These rates are frequently founded on past results of huge quantities of individuals who had the sickness, however they cannot anticipate what will occur in a specific patient’s case. In patients whose malignancy is bound to the eye, the five-year endurance rate is about 80%. This is as opposed to melanomas that have spread to inaccessible pieces of the body, where the five-year endurance rate is about 15%.
\nPigmented choroidal lessions that are somewhat raised might be called vague sores and present a test concerning determination and the board. Given the dangers and restrictions regarding getting histological affirmation of harm, ophthalmologists need to depend on clinical qualities recognized as prescient of development and metastasis so as to separate little melanomas from raised choroidal melanocytic tumors that are likely kindhearted. Shields et al. distinguished five components related with danger of development of little choroidal melanocytic lessions under 3 mm in diameter using examinations retrospectively of around 1300 patients [14].
\nThese factors were:
posterior tumor margin touching the disc;
visual symptoms;
tumor thickness bigger than 2.0 mm;
subretinal fluid;
orange pigment.
In 4 percent of patients was observed growth of lesion with none of risk factor, in 36 percent of patients was present one risk factor, and three or more factors were present in more than 50 percent of patients.
\nClinical factors associated with an increased risk of metastasis included:
growth documentation;
increased tumor diameter (bigger than/equal to 1.1 mm);
posterior margin touching the disc.
The small-tumor observational study conducted by the COMS Group identified similar risk factors associated with tumor growth; namely
apical tumor thickness was greater,
initial basal diameter was larger,
orange pigment was present,
there were no drusen,
retinal pigment epithelial change adjacent to the tumor was absent.
Prognostic factors for uveal melanoma can be subdivided into three categories: clinical, histopathological and genetical. Clinical predictive factors have been extensively described. Location of the tumor, its thickness and diameter are clinical factors predicting tumor growth. In addition, age at time of treatment, male gender and secondary glaucoma were prognostic relevant. Shields constructed a mnemonic” TFSOM” “to find small ocular melanoma” (thickness greater than 2 mm, subretinal fluid, symptoms, orange pigment and margin at the disc) to assist in identifying small choroidal melanoma at risk for growth. The most important histopathological markers predicting clinical behavior are the presence of epithelioid cells, largest tumor diameter, sclera invasion, and presence of vascular loops. Other valuable prognostic factors are the presence of mitotic figures and tumor-infiltrating lymphocytes. The cell sort of uveal melanoma is identified with guess. Patients with tumors made out of unadulterated axle cells have a more ideal guess, and those with a part of epithelioid cells (blended or epithelioid-cell types) have a more awful visualization. Melanomas with a low mitotic movement show a superior anticipation. Tumor invasion by lymphocytes has been related with diminished endurance [15].
\nThese days there are a lot greater treatment choices other than enucleation, which was the main alternative for a large portion of a century ago. The more moderate treatment choices mean to save the influenced eye and hold vision. Treatment of uveal melanoma relies upon different variables including age of the patients, foundational strength of the patient, state of the contrary eye, tumor size and area.
\nNeverthesess, metastases cannot be prevented. Based on the theoretical models, clinically manifest metastases are likely to occour 5 or 6 years onset of the systemic dissemination. By the time we diagnosis uveal melanoma, micrometastases may have been spread as of now. Along these lines, metastatic sickness happening after therapy is not unprecedented. Roughly 50% of the patients will kick the bucket from the sickness inside 10 to 15 years of enucleation. When a metastasis is found the endurance is under 7 months. In the event that a metastasis emerges as a lone injury in the liver, expanded endurance might be acquired by nearby resection of the tumor mass.
\nTumor area and size are considered to be two of the primary factors in deciding on the treatment of ocular melanoma. There is no reason to save the eye if a small melanoma in a necessary place completely destroyed vision. It is important to remember this - patients who have undergone enucleation and individuals who have undergone radiation treatment respond appropriately when they receive information about the nature of their patients after treatment. The most important for them was tumor endurance.
\nTreatment using radiation is a typical therapy for intraocular melanoma that utilizes high energy radiation to kill tumor cells. Radiation treatment can regularly safeguard some vision, albeit once in a while this is lost at any rate since radiation harms different pieces of the eye. The structure of the eye is saved and this is mainly the advantage of this sort of treatment.
\nRadiation treetment can be divided into two categories. External radiation treatment that utilizes a machine outside the body to send radiation toward the tumor, and the second type is inside radiation treatment that utilizes a radioactive substance fixed in needles, seeds, wires, or catheters that are set legitimately into or close to the tumor. The manner in which the radiation treatment is given relies upon the sort and phase of the tumor being dealt with. In ophthalmooncology field we utilize both photon pillar light and furthermore proton beam irradiation.
\nThe metastatic free survival rate, the local control and the late toxicity were studied in patients that underwent fractionated Stereotactic Radiation Therapy (fSRT) for uveal melanoma. These patients had a median follow-up 32 months and were given five fractions of 10 Gy. The results showed that fSRT is an effective treatment for uveal melanoma with a good local control. There were performed 15 enucleations after irradiation mainly because of neurovascular glaucoma [16].
\nPlaque therapy is the most often utilized framework for delivering radiation The other methods are Gamma Knife or methods that include proton beam. Radiation plaque treatment which offers great tumor control, can frequently safeguard helpful vision, and has a fundamental visualization that is practically identical to that of enucleation. Enucleation remains the standard strategy for the board of the biggest melanomas of the choroid and ciliary body. The Collaborative Ocular Melanoma Study (COMS) is randomized clinical trial assessing essential enucleation versus beam radiation done externaly followed by enucleation in the management of patients with choroidal melanomas. The study demonstrated that the two options to be used in same medium sized tumors. COMS studied also treatment of large tumors and found out that combined external radiotherapy followd by enucleation shown that there is no limit in orbital recurrence of the tumor mass. [10, 11, 12, 13].
\nStereotactic radiosurgery (SRS) is technically challenging therapeutic irradiating method. SRS complements or supplies (replaces) classic surgical intervention. The purpose of using SRS is single, because high therapeutic irradiation dosage is to involve only an exact specified tumor structure, while the other organs and structures are contemporary protected. We use special hardware equipment of workstation and software. Professional experiences of specialists of various fields (neurosurgeon trained in stereotactic radiosurgery, radiation oncologist, ophthalmologist, radiologist, clinical physicist and registered nurse trained for radiosurgery) are needed.
\nThe surgery is determined by patient preparation before surgery intervention. This consists of processing of health of the patient and whole patients imaging documentation. It is important to analyze the patient’s illnesses and the patient’s indication by the Indicating Commission (BTB). The Commission consists of the members as a neurosurgeon trained in radiosurgery, radiation oncologists, ophthalmologists, radiologists and clinical physicists. Just after the see the records and imaging of the patients they decides whether to do SRS or not. The Progress Committee selects, on the basis of a recommendation on the suitability of ophthalmic oncological surgery, which evaluates the suitability of conventional surgery, stereotactic radiosurgery, fractional stereotactic radiosurgery, intensity modulated radiotherapy (IMRT) or three-dimensional comfort radiotherapy (3 D-CRT).
\nIndicated patients for stereotactic radiosurgical intervention are concerned for inpatient care Ophthalmology Department of Faculty of Medicine, Comenius University in Bratislava. The whole hospitalization lasts most often three days. The patient admission includes interview with the patient with detailed information about the course of operation, performance benefits as well as acquaintance with potential acute and late postoperative complications (adverse effects), after the informed consent is signed by the patient.
\nPatient’s affirmation in hospital bed department (clinical care) is carried two days before the surgery. Clinical examination will be done in detail. The documentation patient brought is studied, in case there are some missing examinations they are done and completed by the time of the surgery and a preoperative pharmacotherapy treatment in hospital bed department is placed on. One day before the stereotactic radiosurgery (SRS) patient has to use premedication. Within the preoperative premedication the patient is using the antiedema therapy, which intensity depends on the size, location of the lesion and the presence of edema. The presented therapy continues at the day of surgery and also the following day.
\nThe patient’s record must incorporate the age at treatment, volume and size of tumor, the most extreme stature of the tumor estimated by A, B scan ultrasound. The presence and the degree of secondary retinal detachment, and note if there is an extrascleral expansion must be recorded in patients file. Tumor volume, in every patient straightforwardly after computer CT and MRI assessment is determined as the progression of SRS strategy and is included to the scheme of stereotactic planning.
\nMechanical fixation to the stereotactic (Leibinger) frame is done before stereotactic irradiation immobilization of the affected eye. Stiches are put under 4 direct extraocular muscles through conjunctiva and through the upper and lower lid. The stereotactic frame is fixed to the head and the stiches are attached to the stereotactic frame on the side of affected eye. The patient undergoes a CT examination with the eye tied to the patient’s frame. After fixation and administration of the drug contrast agent, the examination is performed on one-millimeter scans. After completing the CT examination, the patient is transferred to an MRI examination. The patient undergoes an MRI examination with the eye still fixed on a stereotactic frame. After placement in the MRI, a contrast agent is administered. MRI and CT imaging records are sent to a computer console in the computer room.
\nAt that point after the CT and MRI examinations patient is transported to the resting room of Department of radiotherapy of St. Elizabeth Oncological Institute and is waiting for exposure in the linear accelerator.
\nClinical physicist processes imaging records for the purpose of fusion and subsequent planning of stereotactic radiosurgery irradiation. By the fusion of images obtained from the CT and MRI it is obtained an accurate image and the structure-relationship of operated patient. CT examination does not always perfect morphology image of targeting and risk structures, but it is an accurate and does not distort the displaying structures. MRI can distort displaying targeted and risk structures, particularly in the area of bone structures arises the distortion. Neural structures are showed in three dimensions, which allows a reconstruction and good distinctiveness of targeted and risk neural structures. Planning system communicates only with the CT imaging, in which information is transmitted from other investigating modalities. Clinical physicist makes by the fusion the correction of the treating volume of a focus and risk structures from the MRI records to CT imaging.
\nAfter imaging the target and risk structures, the neurosurgeon draws the target volumes and risk structures in sections of one millimeter in a CT record and consults them with an ophthalmologist and radiologist. The planning of stereotactic treatment after the fusion of CT and MR is optimized according to the critical structures, which are the lens, the optic nerve on both sides, and chiasma is also marked as the critical structure.
\nThe best plan is after applied for therapy at linear accelerator. Calculation of tumor volume depends on the ROI (region of interest) of the tumor and 3D reconstruction is done. The planned therapeutic dose is 35.0 Gy by 99% of DVH (dose volume histogram). Model LINAC C 600 C/D Varian with 6 MeV X is utilized.
\nThe stereotactic treatment arranging after combination of CT and MRI pictures is streamlined by the basic structures - focal point, optic nerve, and furthermore focal point and optic nerve at the contralateral side, chiasm.
\nThe planned therapeutic dose in SRS is 35.0 Gy, TDmin. The dose varies from 35.0 to 38.0 Gy, TDmax 37.0–50.0 Gy to the margin of the lesion. We use PTV (treatment volume planning) at least 95% isodose planning. Doses for critical structures such as the optic nerve and optic disc are less than 8.0 Gy and 10.0 Gy for the anterior segment of the eye (Figures 1 and 2).
\nStereotactic planning scheme for patient with uveal melanoma on linear accelerator (TD – 35.0 Gy) – Part a. origin: Dept. of stereotactic radiosurgery, Bratislava.
Stereotactic planning scheme for patient with uveal melanoma on linear accelerator (TD – 35.0 Gy) – Part B. origin: Dept. of stereotactic radiosurgery, Bratislava.
The clinical physicist embeds the plan into the verification system after printing the radiation parameters and documentation. At the same day after the planning is finished the patient undergoes irradiation at linear accelerator in the afternoon.
\nMechanical fixation to the stereotactic frame ensures that the head while the examination and treatment is in the same, right position. Along with the merger of images from CT and MRI is guaranteed the accuracy of the method in the order of tenths of a millimeter.
\nWhen the exposure id completed the patient is unfixed from the operating table and moved into the operating room. According to volume and collimators the whole procedure lasts from 15 to 50 minutes.
\nIn the case of application of stereotactic radiosurgery using micro-multileaf collimator makes clinical physicist verification plan using the verification phantom. He inserts the irradiation plan of patient into verification system of linear accelerator and verifies the accuracy of irradiation plan applications into verification phantom by irradiation of verification phantom by the dosimetric system.
\nTreatment of uveal melanoma in Slovakia is performed on direct quickening agent LINAC. One-fraction LINAC radiotherapy/radiosurgery is an unusual approach to treatment of choroidal melanoma. Hypofractionation with a broad shoulder in linear-quadratic model for radioresistant tumors like choroidal melanoma is still in discussion.
\nWe evaluated in our study local failure which leads into enucleation as an end point in patients treated by SRS with long-term follow-up having accrued at the time of analysis. We evaluate in our study the treatment of posterior uveal melanoma by one-day session of LINAC stereotactic radiosurgery.
\nThe first goal of our study was to evaluate treatment BCVA decline in patients who has posterior uveal melanoma treated with SRS in 6 months interval 24 months after SRS.
\nThe second goal was to find out whether the group of patients with better initial visual acuity on the beginning of treatment would have also a better chance to preserve vision. The observed after-treatment decline in BCVA was 24 months interval after the treatment.
\nThe third goal was observation of the tumor regression by the maximum elevation measurement using B-scan ultrasound in the group of patients with single irradiation (SRS) in interval 1 and 2 years after the treatment.
\nFor patients treated by SRS in the period 2001–2008 was a retrospective analysis was undertaken. At the Department of Ophthalmology, Comenius University in Bratislava we reviewed 84 patients records with choroidal melanoma or with ciliary body melanoma treated in this period. 44 patients underwent primary enucleation (52.4%) out of 84 patients and 40 patients underwent SRS as an initial treatment (47.6%). The diagnosis was established on the basic of ophthalmological examination, ultrasound, CT or MRI examination. Excluded from analyzed cohort were metastatic intraocular tumors, juxtapapillary localized tumors and melanocytomas.
\nEach patient record must have details such as the age at treatment, tumor size, tumor volume, the maximum height of the tumor by A, B scan ultrasound, the presence and the extent of secondary retinal detachment, and if there are signs of extrascleral spread.
\nThe tumors were divided into 3 groups as follows: small up to 4 or 5 mm of maximal elevation, middle 4–8 mm, and large over 8 mm.
\nIn the group of one stereotactic irradiation, an increase in the tumor was observed in a 6-month interval by ultrasound with a B-scan ophthalmologist. We compared tumor regression by measuring maximal elevation using B-scan ultrasound in a group of 25 patients with single irradiation (SRS) at 12 and 24 months post-treatment.
\nWe analyzed the treatment outcome and possible survival difference between radical surgical treatment (primary enucleation) and stereotactic radiosurgery (SRS) at the Department of Ophthalmology, Comenius University in Bratislava, in patients with posterior uveal melanoma.
\nPatients treated for uveal melanoma in posterior during the period 2001–2008 are analyzed in the study. The goal of the study was to compare the relapse-free survival in the cohort of patients initially treated by SRS or they primary underwent enucleation. Together we included 84 patients. Treatment was determined on a case-by-case basis.
\nWe analyzed each patient’s record with ciliary body or choroidal melanoma treated by enucleation. We divided them into two groups: first group had 44 patients (52%) using surgical treatment and the second group had 40 patients (48%) using SRS treatment. The therapeutic attitude was set up based on ophthalmoscopy, ultrasound (A, B mode), other ophthalmological findings, visual acuity, and general status of each patient and MRI examination. Volume of the tumor was determined by using the formula:
\nThe disease-free interval was defined as the period from treatment (either enucleation or SRS) until the development of metastasis, or the death of the patient. The patients after enucleation were examined by ophthalmologist every six months, with a monthly interval in the first six months, dependent on problems with using individual prosthesis. The patients after stereotactic radiosurgery were examined by an ophthalmologist every three months: visual acuity, biomicroscopy (slit lamp), intraocular pressure, ultrasound in A and B mode, fundus photography and since the year 2007 also OCT (optical coherence tomography) was routinely done. Post radiation complications and tumor dimension and extent of secondary retinal detachment were observed. The patients were observed in the period from 2001 (01/01) to 2008 (31/12) and the data were analyzed.
\nThe disease-free interval was defined as the time from treatment until the development of metastases. Patients were seen in three months interval in the first year after the SRS, later in six months interval following SRS. Patients in both groups were regularly in six months interval recommended to their oncologist to a liver ultrasound, abdominal ultrasound, liver function test, brain CT, chest X-ray to confirm or exclude the presence of metastases. In individual cases they were recommended to brain CT or PET/CT.
\nIn the period 2001–2008 a total number of 84 patients with intermediate or large uveal melanoma were treated with either radical surgical removal of the whole eyeball (enucleation), or SRS. In a group of 40 patients who underwent SRS there were 22 male and 18 female - the total median age was 55 years; the median age of female was 54 years and 58 years of male. In a group of 44 patients with enucleated eyes the median age was 68.5 year. In the group there were 21 males (median age 64), and 23 females (median age 73). The median tumor volume in group of stereotactic patients was 0,65 cm3 (0,4 - 0,8), in group of enucleated patients 1,1 cm3 (0,8 - 1,25).
\nFive patients treated in the first step with SRS required subsequent enucleation due to the complications - secondary neovascular glaucoma. Three patients of this subgroup underwent pars plana vitrectomy with endoresection of the tumors plus silicon oil, but the enucleation was necessary due to the complication - relapse of the tumor.
\nHistopathologically in the group of enucleated eyes after SRS due to complications in four patients with malignant melanoma of the mixed cell type, in two cases an epithelioid type, and in one case a spindle-cell type A was confirmed.
\nIn the group of primary enucleated eyes, there were four findings of an epithelioid-cell type, one case of a nodular type, as well as 10 cases of both, a mixed-cell type and 29 cases of a spindle-cell type (A or B) melanoma.
\nThe age and tumor volume are important explanatory variables (termed covariates) that are assumed to be associated with survival and need to be incorporated in the model. Results on logistic regression confirmed significance of the model with the predictors age and tumor volume (P = 0.01). The tumor volume was a significant unique predictor (P = 0.035); age with its borderline probability value of 0.1 could be assumed as possibly associated with the outcome. The estimator of survival rates adjusted for these predictors was constructed based on Cox’s regression model which examines the relationship between survival and both predictors.
\nThe fundamental objective of radioactive therapy is to control malignancy while maintaining useful vision. Present techniques result in a high incidence of tumor control for intermediate and small lesions (< 8 mm in height). Tumor control for enormous sores is not ideal, also, here is a higher frequency of late complexities bringing about hindered vision in huge sores. All things considered, radiation portion decrease to the uninvolved piece of the eye will lessen the rate of late difficulties while keeping up a high occurrence of tumor control for more modest tumors.
\nUtilizing of 3-D radiation dosimetry is accepted that will have significant advantage as far as therapy enhancement and lower frequency of late inconveniences. Such a 3-D framework grants exact pre-treatment arranging and adjustments of the arrangement at short notification, for example, on account of new intraoperative discoveries. There is overpowering proof that threatening melanoma of the uveal plot can be dealt with securely with radioactive plaques with long haul endurance rates equivalent to those of enucleation. We think, that the vessels around the optic plate are harmed by full portion light, prompting retinal ischemia, and this courtesies the presence of neovascular glaucoma. Safeguarding of the eye work is normal in most of radioactive-plaque treatment treated patients. Utilization of low energy isotopes, collimation of individual seeds, and routine utilization of 3-D imaging and 3-D dosimetry should assist with promoting improve episcleral plaque treatment. In writing the rate of post-radiotherapy enucleation from all causes is about 20%. The diminishing of the occurrence of intricacies as waterfall, radiation papillitis, radiation maculopathy, optional glaucoma is because of extremely exacting signs of back uveal melanoma. Today, no randomized planned investigation of the impact of the elective moderate medicines for choroidal melanoma on visual result have been performed.
\nIn our group of patients after Ru106/Rh106 plaque treatment the accompanying late intricacies prompted crumbling of visual keenness and were seen at the last subsequent assessment:
macular pulverization due to scarring around the tumor, optic nerve decay,
macular degeneration, retinopathy, fractional focal point haziness, complete waterfall, glassy discharge, optional glaucoma, apoplexy of the focal retinal vein.
The patient will develop radiation cataract if more than 30% of the periphery of the lens is irradiated. If the diameter of the tumor is large, invasion of the iris may occur, or if the anterior margin of the tumor is well in front of the equator, the lens may be more sensitive to irradiation. Post-radiation cataracts can occur even if less than 30% of its periphery is irradiated.
\nOur clinical experience shows that auxiliary enucleation after stereotactic radiosurgery because of light neuropathy and optional glaucoma was essential just in 11.5% in 3 to 5 years stretch after illumination.
\nThe patient after SRS is controlled regularly ambulatory, the clinical and MRI examinations are carried out, which are made ambulatory, initially and MRI is controlled after 3 months after SRS, first year, next two years in half yearly intervals, then 1 time a year in a following 5 years. Patient is monitored by an ophthalmologist in 2 weeks, later 6 weeks and 3 months interval - visual acuity, intraocular pressure, slit lamp examination, fundus photo, ultrasound – B-scan, OCT, perimetry. In 3-months’ interval patient is send to MRI control [2, 17, 18].
\nFifty years back, enucleation was the main acknowledged choice of treatment for melanoma, perception until recorded development was supported for little tumors that could not be unquestionably analyzed as melanomas on beginning introduction. These days with the openness and showed sufficiency of eyeball-sparing medicines, a conflict can be made for before treatment of these vague lessions. Data from the COMS primers reveals that melanoma-related mortality varies with tumor size at period of treatment. For medium estimated tumors (portrayed as tumors 2.5 to 10 mm in apical height and up to 16 mm in greatest basal width), melanoma-express mortality was 10% at five years, and 18% at 10 years. For huge tumors (those astounding the size models for medium tumors in either apical height or greatest basal expansiveness; or peripapillary tumors with an apical height more conspicuous than 8 mm), the rates extended to generally 27% at five years and 40% at 10 years. Also, as referenced above, archived development before treatment has been demonstrated to be a danger factor for metastasis. In any case, development might be a marker for more forceful tumors, and it has not been demonstrated that treating these tumors prior diminishes mortality [7].
\nOur present strategies for radiotherapy consider powerful nearby tumor control with eyeball preservation, yet visual morbidity is still high. In this manner, it is important to gauge the mortality hazard caused via cautious perception before treatment of uncertain sores against the outcomes of visual misfortune actuated by treatment.
\nIn a small COMS tumor observation study, there were six melanoma-related transitions from a cohort of 67 tumor patients treated after baseline perception. Only two of these transitions occurred within five years of enrollment, resulting in an inaccurate five-year death rate with an explicit melanoma of 3% [11].
\nOne-portion LINAC radiotherapy/radiosurgery is an abnormal way to deal with treatment of choroidal melanoma. Hypofractionation with a wide shoulder in straight quadratic model is still in conversation for radioresistant tumors like choroidal melanoma. In this examination we assessed nearby disappointment prompting enucleation as an end point in patients treated by SRS with long haul development having accumulated at the hour of investigation [19].
\nPicture combination of a differentiation improved attractive reverberation imaging (MRI) and figured tomography (CT) is utilized for treatment arranging co-ordinates. A few creators incline toward light before enucleation for huge uveal melanoma. This treatment is utilized in a method of SRS with a solitary division managed with a valuable spatial exactness utilizing a collimating framework.
\nBecause of our outcomes the saw after-treatment decrease in BCVA was not emphatically connected with higher pervasiveness of better BCVA before SRS, however the anatomical outcome after the treatment was at any rate anatomically saved eyeball [17].
\nEmpowering our outcomes legitimize further examinations to assess one day meeting method and its viability as an option in contrast to other light helpful methodologies. On the off chance that we utilized single SRS treatment just, in patients with tumor volume over 0.6 cm3 the danger of relapse was high, over half and extra treatment was essential. As per our experience the portion of 35.0 Gy is not adequate light and may cause backslide just in patients with high volume tumors, over 0.6 cm3. By breaking down individual patient’s consequences of this examination, we presume that this treatment is adequate for little and middle of the road tumors with the rise not more than 6 mm, resp. volume up to 0.4 cm3 as per individual stereotactic arranging plan of every patient as a solitary treatment system. Auxiliary enucleation after stereotactic radiosurgery due to mild neuropathy and secondary glaucoma was vital in only 11.5% at 3 to 5 years after illumination. In our examination, proximal tumor control was effective in 95% of patients at 3 years after stereotactic radiosurgery and in 85% of patients at 5 years after stereotactic radiosurgery [20].
\nAs indicated by our outcomes one-day session SRS with 35.0 Gy is adequate to treat little and center stage melanoma. No endurance distinction inferable from stereotactic light or consolidated and surgical attitude - enucleation of uveal melanoma has been exhibited in the review concentrate in Slovak Republic. Enucleation after SRS in 7 patients was in stretch 6 months to two years after SRS. A little distinction is conceivable, yet a clinically significant contrast in death rates, regardless of whether from all causes or from metastatic melanoma, is improbable.
\nA high degree of local control can be achieved with a five-year control rate exceeding 95% in patients treated with charged particles. Radiotherapy with a 62 MeV proton rod with a cyclotron achieves a high rate of close tumor control and visual protection, with the visual outcome depending on the size and area of the tumor.
\nHuge, imminent, randomized preliminaries were intended to look at mortality figures for medium-sized melanomas treated by brachytherapy or enucleation. The outcomes could not show the distinction in death rates between the two treatment bunches following a limit of 12 years of development.
\nIn the most recent years, the administration of patients with uveal melanoma has changed toward eyeball saving strategies. Options other than extreme enucleation range from perception to perception to transpupillary thermotherapy, block-extraction, endoresection with standards plana vitrectomy, brachytherapy utilizing an assortment of radioisotopes, outside bar radiotherapy, charged particles and stereotactic radiosurgery or strategies can be approached. SRS has recently been proposed as an optional treatment for posterior uveal melanoma. Treatment for each patient should be selected according to the patient’s general condition, stage and nature of the tumor. COMS is planned to provide remote information on regular history as well as a useful speech.
\nSingle-division stereotactic radiosurgery is normally finished with a Gamma Knife just as more as of late with a CyberKnife. The remedial single portion has been diminished to as low as 35.0 Gy in the course of recent years without decrease in tumor control. Dosages of 40.0 Gy conveyed at the half isodose bring about great nearby tumor control and satisfactory harmfulness. Since radiobiological contemplates show a potential favorable position of hypo fractionated treatment over a solitary huge portion to clean uveal melanoma cell lines, fractionated stereotactic radiotherapy (SRT) has increased extra interest. Other than expanded tumor control, poisonousness ought to hypothetically be diminished by fractionation. Direct quickening agents (LINAC) have the upside of an attainable fractionation. Most LINAC contemplates utilize a hypo fractionated plan of 4–5 portions and complete dosages somewhere in the range of 50.0 and 70.0 Gy. The viability of SRT for uveal melanoma has been demonstrated in various investigations with neighborhood tumor control rates announced over 90%, 5 and 10 years after treatment. Radiogenic results after SRT are accounted for also to different types of radiotherapy, with waterfall advancement, radiation retinopathy, opticopathy and neovascular glaucoma being liable for most of optional vision misfortunes and auxiliary enucleations. Generally speaking, stereotactic photon bar radiotherapies (SRS and SRT) are viewed as compelling treatment modalities for uveal melanoma, with promising late tumor control and poisonousness rates. SRS is a generally new strategy, so there is a requirement for multi-focus preliminary to contrast the results following stereotactic radiosurgery and different techniques. Nonetheless, as of recently, no investigation has been acted in this point. Studies contrasting endurance rates following enucleation versus more current treatment modalities, including SRS, recommended comparative rates for tantamount sores and in light of the fact that revealed nearby tumor control rate following SRS seem similar, we offer SRS to patients who might somehow or another require enucleation [1].
\nStereotactic photon treatment of uveal melanoma, in light of CT and MRI pictures, is a protected and exact treatment choice. Neighborhood control was discovered to be superb. Due to choice models, the quantity of patients in the investigation with decreased visual sharpness will likely expansion later on.
\nNeighborhood power over 95% shows up in certain investigations: in the investigation of Dieckmann nearby control is 98% after a middle perception time 33 months follow up. The perception time is still too short to even consider allowing complete ends, yet their outcomes are tantamount with the 82–98% nearby control rate detailed by different gatherings after a middle perception season of as long as 15 years [21].
\nVisual misfortune after proton pillar light was depicted in 33–47% following 1 and 2 years, individually, for tumors situated close to the optic plate and fovea.
\nDifferent creators announced in a review study that light of 30.0 Gy of in excess of 2 mm of the optic nerve head started an optic neuropathy.
\nIn the investigation of Dieckmann because of troublesome tumor size and area in the region of basic structures, for example optic nerve and macula, visual decrease was seen in a high number of the patients. After a perception season of beyond what a half year visual sharpness can be assessed in 79 patients. In the gathering of 77 patients 85.5% gave visual sharpness of 0.1 or better before radiotherapy. LINAC based stereotactic light for melanoma of uvea is plausible and all around endured. Can be offered to patients with medium measured and horribly found melanoma of uvea who are looking for an eye-protecting therapy [22].
\nTo accomplish great visual keenness result it is significant right limitation of the tumor. Brachytherapy Ru106 of back choroidal melanoma accomplishes great preservation of vision if the tumor does not stretch out near the optic nerve or fovea. Realize that the intensity of a test to look at endurance in at least two gatherings is connected not to the all out example size but rather to the quantity of functions of interest, (for example, passing for this situation). At the end of the day, the endurance tests perform better when the editing is not excessively substantial, and, specifically, when the example of controlling is comparable over the various gatherings. High number of right-blue-penciled information (from those patients who actually were alive toward the finish of perception, or exited the investigation for different reasons other than death before its end) could influence the unwavering quality of the outcomes. Subsequently, the substantial controlling may confuse the assessment of the endurance model, since it diminishes the comparable number of subjects uncovered (in danger) at later occasions, decreasing the successful example sizes. Also, little example sizes may additionally expand the impact of the presumption infringement. It is not sensible, notwithstanding, to drop the chose informative variable(s) from the model, since there are “genuine world” reasons why these specific factors ought to stay in the last model [23].
\nTo this date, no preliminary examination of the dosimetry, safety and viability of SRS or evaluation of gamma knife radiosurgery results for melanoma has been performed. So far information from several reported cases recommends that SRS can have comparable close tumor control rates, metastases, death rates and involvement rates brachytherapy. Late examinations recommend that gamma knife radiosurgery and SRS may be an appropriate choice for the treatment of uveal melanoma in those patients in whom ulcers are not suitable for conventional brachytherapy. The findings in the setting recommend a part of SRS in the treatment of selected cases of uveal melanoma [24].
\nEntanglements after specific techniques can prompt auxiliary neovascular glaucoma and may result to the enucleation, that is the reason the eye maintenance is one of the fundamental objectives of the moderate treatment. A multivariate information investigation by utilizing the directed learning methods, specifically the calculation known as Regularized Least Squares (RLS) was utilized in investigation of Mosci. Their examination was the biggest one in Italy and they exhibited the brilliant neighborhood tumor control, endurance and eye consistency standard after the proton shaft light treatment. As their results suggest, further improvements in treatment delivery may be important in determining visual outcomes and complexities after proton shaft therapy in visual melanoma dosing and delivery [25].
\nThe basic problems of radiotherapy in one meeting are the effects of propagation and hypofractionation of the part. The size and area of the tumor, for example closer than 2 mm from the optical plate, are the main components for determining the clinical evaluation of the visual acuity result.
\nDistinguishing proof of danger variables may lessen the paces of repeat and lead to less inconveniences, safeguarding of the eye, improved visual capacity and, conceivably, better endurance result. Repeat of optic neuropathy after stereotactic radiosurgery is an issue by intraocular tumors as well as for example by perichiasmal tumors stereotactic illumination. Albeit uncommon, optic neuropathy may follow radiosurgery to injuries close to the visual pathways. Cautious portion arranging guided by MRI with limitation of the maximal portion to the visual pathways to under 8.0 Gy will probably diminish the frequency of this entanglement.
\nSimilar issues with visual sharpness misfortune as in stereotactic radiosurgery are found in patients after other radiotherapy methods, for example brachytherapy. In the sequential arrangement of patients after Ru106 brachytherapy, patients held some helpful vision in the principal postoperative years and a couple even improved visual sharpness, notwithstanding, the drawn out visual result is poor with a proceeding with visual keenness misfortune over the long run. Countless patients became visually impaired or lost perusing capacity following 5 years, either due to radiation confusions or auxiliary enucleation.
\nStereotactic radiosurgery and fractionated stereotactic radiotherapy have developed as promising, non-intrusive medicines for uveal melanoma [26]. Albeit, verifiably, melanoma has been viewed as a moderately radioresistant tumor, fresher information have tested this perspective, and radiation treatment is currently viewed as a helpful segment of the restorative armamentarium for harmful melanoma. As indicated by our outcomes a solitary one-day meetings SRS with 35.0 Gy is adequate to treat little and center stage melanoma. No endurance distinction inferable from stereotactic light or joined and careful mentality - enucleation of uveal melanoma has been exhibited in the review concentrate in Slovakia.
\nIn our examination bunches researched, endurance investigation changed for indicators demonstrated that the gathering of patients after stereotactic radiosurgery had similar result as the gathering of patients treated with extremist medical procedure. In light of our examination, we expect that the endurance guess is basically dictated by the personality of the tumor in relationship to the status of the patient. Clinically, the main factors that influence the metastatic cycle are the limitation and size (volume) of the sore.
\nThere has been played out no multicenter preliminary to survey dosimetry, wellbeing and adequacy of SRS, or to assess results of gamma knight radiosurgery for melanoma yet, yet information from a few announced case arrangement recommend that SRS could have comparative nearby tumor control rate, metastasis rate, death rate and intricacies rate when contrasted with brachytherapy. Late investigations have proposed that gamma knight radiosurgery and SRS might be a fitting option for treating uveal melanoma in those patients, in whom sores are ineligible for customary brachytherapy. The discoveries in the arrangement propose a part of SRS in the treatment of chose instances of uveal melanoma. Treatment by either essential enucleation or SRS as per our outcomes does not seem to impact the improvement of metastases in patients with uveal melanoma; the endurance anticipation is basically controlled by the stage and character of the tumor.
\nNo endurance contrast inferable from stereotactic light or extremist careful disposition - enucleation of uveal melanoma has been shown in this review study. A little contrast is conceivable, yet a clinically significant distinction in death rates, regardless of whether from all causes or from metastatic melanoma, is far-fetched. SRS is a non-intrusive option in contrast to enucleation in the treatment of uveal melanoma with a high tumor control. There is a requirement for multi-focus preliminaries to think about the results following stereotactic radiosurgery in treatment of uveal melanoma.
\nThe single light of the tumor itself is another methodology – it has been appeared to accomplish ultrasonic tumor relapse along these lines to brachytherapy. SRS of extracerebral sores like uveal melanoma has been developed over the most recent twenty years and is an elective treatment for center and enormous back choroidal melanoma. With plaque radiotherapy, eye rescue is accomplished, and especially for cases in which the tumor is found away from the optic circle or macula, helpful vision can be held after treatment.
\nAs indicated by the creators experience dependent on consequences of their exploration aftereffects of the adequacy of LINAC-based stereotactic radiosurgery treatment in addition to joined strategies in patients with back uveal melanoma in stage T2/T3, the stereotactic radiosurgery is a successful strategy to treat middle of the road phase of uveal melanoma. At last, one-venture LINAC-based SRS with a solitary portion 35.0 Gy can treat patients with center back uveal melanoma and save the eyeball or be the initial step of consolidated strategies: illumination before endoresection or cyclectomy.
\nNone of the authors has conflict of interest with this submission.
Printed form supported by KEGA 023 STU-4/2020, VEGA 1/0395/21, APVV - 17 – 0369.
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