\r\n\t
\r\n\tThe authors are cordially invited to express their knowledge and awareness in this domain, to share their unpublished clinical trials pertaining to any type of STT, to analyse any new data emerged from their studies and to display their information in a methodical way, so that we may present an original book with novel and useful medical material.
Temporal and spatial biogeographical patterns change in space and time. Historical biogeographical boundaries usually mark great mass extinction events. The role of spatial boundaries is controversial in recent global changes. Some suggest that species at sharp biogeographical boundaries are at the edge of their existence and doomed to extinction, others allege that transition zones can serve as biodiversity hot spots. They harbor either wide-ranging species adapted to broad environmental circumstances or narrow-ranging species occurring in unique environments. Researchers assuming specialized species in boundary regions imply that biogeographical boundaries are suitable for climate change detection and specialists can be used as early warning signals. Several studies suggest that specialization is the greatest extinction risk [1]. However, mass extinction events affect both specialized and generalized species. Studies show that both groups are declining under global changes. Interactions between specialists and generalists are not exactly clear. It is urgent to detect their locations globally and clarify their roles. It is also an alarming trend that not only boundaries but also core regions are weakening, which leads to homogenization, the abundance of generalized species, and biodiversity loss. Recent anthropogenic changes are complex including not only climatic changes but also habitat destruction, fragmentation, and pollution which act synergistically.
\nThis chapter addresses the following issues: (1) Are biogeographical boundaries the scenes of extinction? (2) Which factors weaken spatial boundaries and core regions? (3) Are core areas threatened by climate change? (4) Are biogeographical boundaries unique regions? (5) Do they harbor generalized or specialized species? (6) What are the roles of specialists and generalists in extinction processes?
\nTemporal and biogeographical boundaries cannot be separated from each other. Temporal boundaries eliminate old spatial boundaries and create new ones. Temporal boundaries are usually associated with extinction processes. It is suggested that mass extinctions start at local scales and spill over to higher scales in time [2].
\nLocal species and communities replace each other in time. At ecological time scale, this process is induced by repeated disturbances, and it is called succession. The Clementsian school considers succession as a deterministic process that culminates in a predictable stable, “climax” community [3]. Succession is not random, because it is determined by climatic and soil conditions. In contrast, the stochastic Gleasonian school suggests that a single region can have several successional stages at the same time and more than one stable stages or climaxes [1].
\nMajor extinction events indicate boundaries in geological time. Approaching an extinction event, ecosystems display specific traits serving as warning signals of a catastrophic shift. (Post-extinction periods also show distinctive pattern of biotic restructuring.) Extinction events as temporal boundaries eliminate old spatial boundaries and create new ones. Non-catastrophic extinctions affect biological systems at different spatial scales and different trophic levels in a selective way. The inherent extinction proneness of taxa also contributes to the selective nature of extinctions. In contrast, catastrophic extinction events or, in other words, mass extinctions affect the whole global ecosystem in a non-selective way wiping out most living creatures. Several studies suggest that we are undergoing the sixth mass extinction.
\nNon-selectivity is the main characteristic that makes a difference between background and mass extinction. During mass extinction events, widespread and abundant species also extinct [4, 5]. The disappearance of generalists is a sign of shifting toward nonselectivity [6, 7]. (Large body as a main extinction trait is often mentioned in literature; therefore, losing large-body mammals [8] is an early indicator.)
\nAt global spatial scale and at longer time period (historical time scale), sudden and large environmental perturbations wipe out whole biotas causing mass extinction. This large-scale, repeated replacement is similar to local succession. Apart from mass extinctions, changes in biotas are of smaller magnitude and rather gradual. That is why an increase in frequency and magnitude of changes in communities or biotas is an early signal of a regime shift. At geological time scale, mass extinctions usually mark a boundary between time units (e.g., eras, period, epochs), the tipping point of a biotic shift. They are associated with drastic environmental perturbations (sudden climate change, volcanism, sea-level changes, meteor impact events). Referring back to recent climatic changes, historical mass extinctions accompanied with global warming can provide valuable information for us to be able to presage future trends.
\nThe geographic ranges of species evolve under limited environmental conditions creating a spatial pattern. Broad-ranging species perceive fewer boundaries than species with restricted geographic ranges, and they can shift their ranges relatively more easily under changing environmental conditions.
\nSpatial boundaries are affected by natural biotic and abiotic factors and anthropogenic disturbation which enhance each other’s effect through interactions. Extreme changes in these factors and in the inherent traits of boundaries can lead to extinctions.
\nThe abundance and the distribution of species are usually affected by the synergy of multiple environmental factors, such as temperature, water availability, soil and water chemistry, etc. For example, the tolerance of high temperature is typically lower in plants, which don’t tolerate decreased soil moisture. Local extinctions at the boundaries of species ranges are common during droughts [1, 9, 10].
\nDisturbances such as fires, storms, and volcanic eruptions either destroy or maintain boundaries, depending on their magnitude and frequency. Natural ignition (lightning), for example, prevents woody encroachment and exotic species invasion at forest and shrub/grassland boundaries; therefore, artificial fire suppression leads to forest expansion. In arid regions, the decrease in natural fires coupled with livestock grazing often results in desertification. Desert shrublands expand at the expense of grasslands [1, 11, 12]. Synergistic processes have an important role in this case as well. Fragmentation lowers the probability of lightning-ignited fires. Increased fragmentation along with the disappearance of an important boundary regulator leads to the local extinctions of native grassland species which can spill over to higher spatial levels supporting the homogenization processes.
\nThe investigations conducted by du Toit et al. [13] in the South African Nama Karoo transition zone confirmed that more frequent and/or more intensive fires can lead to a biome shift if the most abundant species fails to recover after an extreme disturbance in a transition zone. The dominant vegetation of Nama Karoo is grass, and shrub and fires are rare. They monitored the recovery of the vegetation after a natural ignition. Most of the species managed to recover except the most abundant Karoo shrub species seven months after the fire. This might suggest a biome shift from shrubland to grassland.
\nClimate change enhances the magnitude and the frequency of extreme events [14]. Frequent extreme climatic events, e.g., extreme droughts, weaken both core areas and boundary regions by altering species composition, diversity, and functional and structural attributes. Native species being less adaptive to extreme events may be displaced by non-native generalist invaders [15].
\nBoundaries are more exposed to extreme events than core regions; therefore, even the events of low magnitude can degrade their structure. Several studies confirm that relatively weak winds can contribute to the invasion of weedy species by dropping wind-transported seeds at the edges [16, 17].
\nRecent droughts have induced forest canopy thinning in the core areas of tropical forests. In some high-rainfall places, forests have disappeared probably because of the relatively long dry season in Australia [18, 19]. Longer dry periods have also been experienced in tropical montane forests in Costa Rica with severe consequences [20]. Drier climatic conditions opened a path for pathogenic invaders from lower altitudes [21] resulted in the die-off of most endemic frog and toad species during the 1980s [22]. This example illustrates the devastating effects of synergistic extinction drivers on endemic species. According to Fjeldså [23], the lack of endemic species in a tropical montane forest indicates that the local biotic community cannot maintain a hydrological balance anymore and withstand global changes.
\nHabitat destruction and fragmentation can be considered as extreme anthropogenic perturbation. Fragmentation is detrimental for specialized species. It eliminates intact core zones and reduces the imperviousness of edges providing open space for non-native, wide-ranging species. The higher trophic level and large body size make terrestrial species sensitive to fragmentation. This can further enhance the extinction proneness of African megaherbivores maintaining biome boundaries.
\nJanzen [24] confirmed that fragmentation leads to weed expansion in habitat patches. Forest fragmentation results in smaller patches which probably become more and more distinct from the intact forest, because the mortality of native tree species along the edges is higher than that of environmentally more tolerant weedy species [24]. The success of weed invasion depends on the width and the imperviousness of buffer zones as well as their relative dispersal abilities [25]. Buffer zones are the zones between the core areas and edges, or, in another point of view, they can be considered as wider edge zones. If they are occupied by weedy species, native interior tree species cannot reestablish [26]. In small patches, forest specialists can be completely replaced by generalists after perturbation [27]. Conservationists emphasize that it is important to preserve larger habitat patches which presumably contain more specialist species. Nevertheless, Beier et al. [28] pointed out that the generalists inhabiting small habitat patches provide important ecosystem services; therefore, they can be the centers for future ecosystem recovery [28].
\nIn general, higher trophic levels give stronger responses to fragmentation and habitat loss than lower trophic levels [29, 30, 31]. Krauss et al. [32] assume that lower population sizes, higher population variability, and dependence on lower trophic levels are the main reasons for fragmentation susceptibility of higher trophic levels. Large body size can also enhance the sensitivity to fragmentation and increase the extinction risk of terrestrial species according to several sources [33].
\nThe main biotic factors forming boundaries are competition, predation, and mutualism.
\nSpecies limit each other’s distribution by competition. Strong competition can result in non-overlapping range boundaries [1]. Non-overlapping boundaries display sudden regime shifts under environmental changes. The current shifting of species ranges is also influenced by competition, which affects both the generalized and specialized species.
\nIn the last decades, woody encroachment has been experienced globally under the effects of global warming [34, 35, 36] mainly because of CO2 enrichment. Woody species which are generally superior competitors [1, 37] tend to be sensitive to abiotic stress (fire, drought). However, they experienced fewer detrimental perturbations recently, which also helped their expansion.
\nThe relationship between species diversity and geographic range limitation affects spatial patterns [1]. Abiotic and biotic factors vary along range boundaries. Under unfavorable environmental conditions, species diversity and hence competition are lower. When environmental conditions are beneficial for most species, diversity increases and biotic interactions (e.g., competition, predation) will become the limiting factors. This might be the reason why many biodiversity hot spots are located along the tropical biome boundaries.
\nThe global spatial pattern of generalist and specialist species reflects the changing abiotic conditions in a similar way. In the tropical zone where the environmental conditions are favorable, the diversity and the biotic interactions are high, many species tend to be specialized, and the ecosystems are productive. Proceeding to the poles, environmental conditions become more unfavorable, diversity and productivity decrease, and the species become more generalized. Isolated and small geographic ranges (small islands and forest fragments) are also homogenized and dominated by a few generalized species because of the unfavorable conditions. Decreasing geographic ranges and increasing disturbance jeopardize both specialized and generalized species.
\nThe tropical region provides interesting examples for diffuse competition which also modifies species ranges under recent climate change. Proceeding to the equator, the southern limits of the geographical ranges become less climate dependent and more effective by competition in the Northern Hemisphere. MacArthur et al. [38] suggest that strong biotic competition restricts some tropical species to habitats with less favorable environmental conditions. The same species can turn into widespread and abundant species in subtropical and temperate zones by diffuse competition. Yellow warbler (Dendroica petechia) is a good example for that. Its geographic range is widely expanded in the temperate zone, while under tropic conditions, it is strongly restricted [38]. According to MacArthur et al. [38], diffuse competition of tropical species is on increase.
\nBennett et al. [37] also observed strong tropical competitors in the temperate zone. Tropical herbivorous fish shifted northward at the expense of seaweeds. Seaweeds are dominant, wide-spreading taxa in subtropical and temperate coastal zones. The poleward shift of tropical herbivorous fish prevents the recovery of seaweeds and maintains a canopy-free alternative state after the extreme disturbances (overgrazing).
\nIn some cold regions, specialists are displacing generalized species. Directional taxonomic shifts of the algal communities in the Northern Hemisphere have been observed by Ruhland et al. [39], especially in the alpine regions and arctic zones with a tendency of an increase in specialized taxa which are replacing generalized species [40].
\n\nPredation can limit the distribution of both predators and preys. Specialization or overhunting can lead to a drop in prey abundance, and this way both groups suffer. The geographical ranges of highly specialized predators are usually further constricted by other limiting factors; hence, they are especially prone to extinction.
\n\nMutualism results in the identical ranges of parasites and hosts; therefore, coevolved species at boundaries and in core regions are prone to co-extinction. Mutualism-related co-extinction is strongly enhanced by fragmentation. Co-extinction affects both specialist and generalists, which can lead to wider extinction.
\nGrasslands are endangered globally. Grassland specialists can expect a long-term decline because of the drastic loss of their habitats [32]. Time-delayed extinction of long-lived vascular plants may bring about the co-extinction of short-lived specialized herbivores, e.g., butterflies [32].
\nRainforests are also jeopardized by habitat destruction. The decline of old native trees in rainforests because of fragmentation may cause the co-extinction of specialized mutualists and herbivores [41].
\nInvasion can replace core super-generalists in the mutual networks, as well. Giannini et al. [42] observed invasive super-generalist bee species in Brazil replacing native super-generalist species which can modify the interactions in networks. The non-native, super-generalist bee species invaded into the core of the networks rapidly. Romanuk et al. [43] and Lurgi et al. [44] suggest that large and more generalist species are the best invaders.
\nDario Palacio et al. [45] studied a highly diverse network of plant and fruit-eating birds in a cloud forest in the Colombian Andes. They found that the elimination of super-generalists which are the connectors of disconnected subsets of species makes the mutualistic network prone to collapse despite its high diversity. They experienced the early decline of large frugivores forming the core of the network because of their high vulnerability to fragmentation. They also noted that the early loss of endemic and specialized species may precede the decline of central super-generalists. However, the extinction of less-connected specialized species presumably does not lead to the collapse of the whole network in contrast with the decline of the central super-generalist species. Similar networks are located in the Atlantic Forest in Brazil as well which are also threatened by extinction [46]. The authors’ results suggest that generalist species play an important role in the ecosystem functions.
\nBoth active- and passive-dispersing specialist species are declining. Specialist species are at great risk even if they are active dispersal.
\nGood dispersals are able to shift their ranges and avoid abiotic stress. For this reason, the natural range boundaries of plants and sessile animals change relatively slowly. For instance, the contemporary biome distribution pattern in Africa does not reflect the actual current climate but historical conditions [47].
\nAccording to Terborgh [48], mainly specialization, high trophic level, and poor dispersal ability promote extinction. Laurance [49] and Turner et al. [50] suggest that mammals and plants with poor dispersing abilities are more prone to extinction than active dispersers, which leads to a higher abundance of generalist species [51]. Wilson and Willis [51] highlight the early loss of specialists during extinction events. Short-lived pollinators with good dispersal abilities shifted their ranges in North America and Europe under climate change [52]. Short-lived specialists are sensitive to environmental changes [53], which makes them good early warning indicators of perturbation. Bartomeus et al. [54] described a decline in plant-pollinator networks throughout the US over the last 120 years. Scheffers et al. [55] suggest that specialized pollination systems are expected to be more vulnerable and hence more sensitive indicators of global warming. Krauss et al. [32] found that short-lived specialist butterflies experienced severe decline after perturbation despite the fact that they are active dispersers.
\nRare species are usually more localized, sparse, and relatively more specialized [33]. Their geographic ranges are more fragmented; hence, metapopulation and edge effects can be significant contributors of their decline [56]. Specialized taxa tend to be rare, which increases the extinction likelihood [33]. Rarity and specialization are two different traits, but they often act synergistically. However, Didham et al. [57] pointed out that range-restricted species may be more disperse and persistent than common, sessile species in small fragments. Didham et al. [57] investigated the effects of forest fragmentation on beetle species in central Amazonia. They found that rare species were better survivor in small fragments than “common” species. They concluded that rare species are more mobile and more persistent in contrast with competitively dominant but more sessile species which are more prone to extinction under forest fragmentation. Hanski and Ovaskainen [58] argue that the transient abundance of rare species can be experienced after excessive habitat loss and fragmentation.
\nSpecies at different development stages show different tolerance of environmental conditions, which affects their range sizes, their boundary types, and boundary perception. For example, the life cycle of a frog or a dragonfly includes very different ranges and boundaries because of the varied niches of stages.
\nHiggins et al. [59] emphasize that the growth rate of Savanna tree seedling and saplings affects their survival during fire events. Fire suppression, especially during the sensitive development stages of trees, favors woody encroachment.
\nThe theory of continental drift was formed during the last century. It was a revolutionary step, and it revealed the secret of several vague biogeographical issues, for example, the omnipresence of sessile animals, which are not able to cross oceans. Plate tectonics is responsible for the birth and the destruction of continents. The assemblage and the positions of continents are changing. Their union creates bridges between terrestrial biotas providing free gene flow, and their separation may lead to their isolation. These processes are selective as species are sensitive to boundaries to different degrees especially considering their dispersal abilities, but it can be stated that global changes of large magnitude affect most species uniformly in many cases.
\nAccording to Lyell’s geoclimatic theory, the concentration of continents near the equator triggers global warming, while the juxtaposition of landmasses close to the poles evokes global cooling. Hence, continental drift can be considered as a climate regulator and thus a temporal boundary “creator.”
\nThe collision of continental plates can establish a connection between biotas, but paradoxically it can create a spatial boundary as well, since continental collisions produce towering mountain ranges which are restrictive to lowland species. The union of landmasses is a violent event erasing and reshaping boundaries. The Great Permian Extinction may have also been associated with the formation of the Pangea supercontinent which brought about a significant drop in the sea level and the drying of the continental shelves [1]. However, Pangea also served as a cradle for many survivors and novel species which expanded their range boundaries over the continent. When the continents separated, global climatic conditions changed dramatically again. The species survived this event radiated and diversified under new environmental circumstances.
\nBiogeographical boundaries can be categorized in many ways [60, 61]. Here, mainly sharp boundaries are discussed in relation to global changes.
\nControversial views on boundaries are partly generated by incoherent spatial scales applied in studies.
\nClimate has a great effect on the biogeographical pattern. Geography and meteorology apply similar spatial scales which makes the scientific investigations more consistent. Saunders and Briggs [62] emphasize the importance of proper scale. If biogeographical problems are not managed at the proper scale, it can lead to the loss of biota. The mismatches of human-related and natural boundaries can deteriorate the environment. Improper scale also brings about biased and controversial data.
\nSub-local spatial scale (< a few meters) includes microhabitats and small boundaries. For example, the boundaries between surfaces of different exposures on a boulder also mark the borders between the patches of different lichens. Local spatial scale (a few meters to 1 km) deals with the level of communities. Regional spatial scale (1–100 km) can be related to landscape boundaries, and continental spatial scale (>100 km) is appropriate for researches on landmass boundaries. Increasing spatial scale is usually associated with increasing temporal scale, from a couple of hours or days to millions of years.
\nNatural boundaries are the formations of the nature which divide two or more different units of natural origin, like timberlines, mountain chains, and watercourses. Anthropogenic boundaries are usually man-made objects (transportation, industrial, residential elements) and the boundaries of anthropogenic plant communities (croplands and plantations). Anthropogenic boundaries are always sharp representing an obstacle or filter to migration and gene flow. They can be either physical objects or boundaries of high contrast between the adjacent units, for instance, edges between forests and croplands where different microclimatic and ecological conditions meet.
\nNature can produce relatively quick changes at boundaries as well; however, along environmental gradients, abiotic and biotic changes are gradual. This leads to an important difference between sharp and gradual biogeographical boundaries. They are usually referred to as “ecotones” and “ecoclines” in ecology.
\nStarting with the latter one, ecoclines are ecosystems in which the associated communities show a gradual change along an environmental gradient. The environmental heterogeneity results in gradual phenotypic and/or genetic differences of species which are also called ecotypes. This gradual variation reflects an adaption to the changing environment. In an ecocline the physiological characteristics of plants and animals change gradually proceeding to higher latitudes (e.g., the skin color in human populations). This phenomenon can lead to speciation only if the environmental conditions change dramatically.
\nResearchers usually show more interest in ecotones which represent sharp biogeographical boundaries between ecosystems.
\nSharp boundaries are usually referred to as ecotones in literature. It is suggested that sharp boundaries (hereinafter ecotones) might be unique environments.
\nEcotones have been studied for more than a century [63, 64, 65]; however, researchers have devoted more attention to the investigation of distinct, relatively homogeneous ecological units until recently. Various authors suggest that understanding boundaries may have an important role in the early detection of global climate change [66, 67, 68, 69, 70] and in conservation works [71, 72, 73, 74].
\nEcotones are also referred to as transition zones, junction zones, tension belts, edges, borders, etc. Ecotones can be considered as the edge or the periphery of an ecological system or as a transient zone between two or more adjoining ecological units. Ecological boundaries which have sharp environmental and ecological gradients are usually unstable [75]. They share common traits with the adjoining regions but also hold unique features [76]. Ecotones promote high biodiversity and unique, rare, specialized, vulnerable species, which make them biodiversity hot spots [74] and may be central regions for future conservation efforts.
\nEcotones harbor range-restricted species which are mostly considered to be vulnerable to climatic changes and fragmentation and thus prone to extinction. According to researchers, specialists will be the first to extinct under the sixth mass extinction. The role of specialists prior to extinction processes has a main priority in most studies as they can be used as early warning signals. Generalists as the main survivors of environmental changes are usually disregarded in approaching havocs, though they maintain the communities as well. Kark and van Rensburg [74] argue that not only ecotones but also core regions are threatened by global changes.
\nKark and van Rensburg [74] raised an important research question related to ecotonal species assemblage: “Are they young species currently diverging in the ecotone region via parapatric speciation or rather wide-ranging species that have expanded their ranges to ecotonal environments?” Studies are controversial in this respect, and they emphasize the importance of both generalist and specialist species in core regions and in boundary regions as well.
\nIn literature, wide-ranging species are implied to in many ways, such as generalist, generalized, widespread, abundant, r-strategist, weed, ruderal, tolerant, invasive, opportunistic, pioneer, and widely dispersing. Narrow-ranging species are referred to as range restricted, narrowly adapted, specialist, k-strategist, competitive, endemic, rare, unique, vulnerable, sensitive, etc. Generalized species are able to adapt to a broad variety of environmental conditions, and they can shift their diet. Specialists are less flexible in adaptation, and they occupy only a narrow range of niche.
\nGosz [77] suggests that edge species are likely to be generalist, wide-ranging, and dominant. Generalists are able to cross boundaries. Wide-ranging, generalist taxa are more mobile than sensitive, vulnerable taxa which tend to be sessile; that’s why generalists perceive fewer boundaries and detect the landscape more homogenous [78, 79]. Generalist can be forced to leave their habitat and cross boundaries by habitat destruction or overpopulation. For instance, wide-ranging predators leave overpopulated habitat patches and cross the boundaries in cross-edge spillover predation [80, 81, 82].
\nSome studies suggest that generalists might have an important role both in core regions and at boundaries by maintaining communities. For example, krill have an important role in connecting different trophic levels in oceans. They are widespread globally; however, Antarctic krill occur only along the boundary between sea ice and ocean water, because they can find both rich food and shelter from predators there [83].
\nAccording to traditional textbooks, specialized species tend to become rare or even lost in a deteriorated environment. In contrast, generalist species prefer impaired habitats where they are found in great number. Disturbed and damaged sites are occupied by generalist species adopting disturbance strategy. However, ecotones can be under disturbance, still having lots of specialized species, and damaged tropical grasslands are rich in specialists as well.
\nOthers studies suggest that the unique environmental conditions favor specialized and endemic species in ecotones [71, 84].
\nAccording to Morelli [85], both specialists and generalists should be applied as bioindicators in disturbed landscapes because of the homogenization of communities. He used bird observation data to identify avian hot spots. He selected specialized species in natural environments and both generalized and specialized species in disturbed environments. The selected species varied in different environments. He found that only a few common species are enough to detect high species richness hot spots. He also observed that two specialized bioindicators occurred both in cultivated and natural landscapes (in forest and in grassland, respectively).
\nMcKinney [33] points out that extinction promoting traits tend to covary. According to Brown’s hypothesis [86], species having narrow niche are adapted narrowly in several parameters, whereas species with broader niche are broadly adapted in not only one but several parameters. Furthermore, narrow niche is characterized by low local abundance and small geographical range [87, 88]. Considering the synergistic combination of traits related to narrow niche, the fate of specialist species is sealed under anthropogenic threats [87, 88].
\nGeneralists are usually broadly adapted in not only one but several parameters, while specialists are narrowly adapted in many respects [87, 88] so they represent two extremes of adaptation and thus two extremes of extinction proneness. However, it is important to note that the degree of specialization and generalization can urge or delay extinction processes in the transition zones and in the core regions as well.
\nBroadly adapted biotas are able to shift their ranges in response to climatic changes [89]. Biotas which are broadly adapted can keep pace with global warming more easily and may experience lower rate of extinction. Several paleontological records confirm the extinction resistance traits of generalist species [90, 91, 92]. Generalist species are more resistant to background and mass extinction than specialist ones. Mammals are more specialized than insects, and small mammals are more generalized than large mammals [93]. Scheffers et al. [55] evaluated literature on climate change impacts. They concluded that warming climate may result in a decreased body size in most cases as a large surface-to-volume ratio is more favorable under warm climate [94].
\nDespite the long history of ecotone investigations [63, 65], studies show mixed results on the role of transition zones in maintaining high diversity [95]. Odum [76] suggested among the first ones that ecotones may have high species richness and unique, endemic species. Since then, several studies seem to have confirmed that near ecotones, species richness and rarity are increased. Kark and van Rensburg [74] claim that boundary regions sustain high diversity because of the adjoinings and overlapping ecoregions (mass effect), but they are also locations for speciation and hence rare and unique species. Kark et al. [95] found that passerine birds, including rare species, occur in higher number in transition zones than in the adjacent ecoregions in the New World. van Rensburg et al. [96] concluded that range-restricted birds and frogs are frequently located closer to ecotones in South Africa. Kark [95] pointed out that rainforest ecotones in Central Africa may be the centers of speciation as a result of evolutionary and ecological processes, hence supporting the biodiversity of the whole biome. Kark et al. [97, 98] observed a biodiversity hot spot at a sharp ecotone between the Mediterranean and semi-arid regions in southern Israel. It is important to note that rarity is one of the best predictors of extinction [33, 91, 99].
\nBiogeographic regions with the significant level of biodiversity and high rate of endangered species are considered as biodiversity hot spots. It is an interesting question if biodiversity hot spots are ecotonal or rather core regions. The tropical zone is the most abundant of biodiversity hot spots. It has approximately ten times more biodiversity hot spots than the non-tropical zones do [100]. Stevens [101] claims that tropical species are generally more endemic and smaller and they have narrower ranges than temperate species, which make them extinction prone. This might suggest that in the tropical zone both core areas and ecotones have an important role in maintaining biodiversity. Several studies suggest that future extinction will affect the humid tropics the most severely [102, 103].
\nTropical grasslands are also diverse and rich in endemic species, and they are as endangered as forests. Grassy biomes include biodiversity hot spots with lots of endemic species. Non-forest habitats are rich in endemic vertebrates and invertebrates. Non-forests hold 30–50% of plant diversity [104]. Ancient grasslands which are alternative stable states of forests are probably rich in endemic species. For example, Cerrado tropical grassy biome in Brazil is a threatened biodiversity hot spot [105].
\nHigh rainfall grasslands in Brazil [106], Africa [107], Thailand [108], etc. have a particularly high level of plant diversity and many endemic species. The Indian montane grasslands have many endemic species [109]. Madagascan grasslands are also rich in endemics [110, 111].
\nGrassy biomes have high light requirements and disturbance tolerance. The similar may be true for sharp boundaries between tropical grasslands and forests. These boundaries are maintained by megaherbivores and fires. High diversity and high number of specialized (and endemic) species are typical for grasslands. Open savannas labeled as “disturbed” or “degraded” harbor many specialists and maintain high diversity in Madagascar and Indonesia [104]. Grassland fauna resists to fire and has great resilience. Savanna species are usually competitive, are mobile, and have a wide range of diet, which means that they can shift their diet, and they prefer open environments [112]. Bond and Parr [104] allege that the loss of grassland specialist birds can be used as early warning signals of shifts to forest at landscape scale considering their large habitat requirements. According to Skowno and Bond [113], specialized bird species of different levels of forest already appeared in significant number in grassy ecosystems.
\nAccording to Strayer et al. [114], species assemblage and interactions along boundaries may be unique, or they may represent the average of the adjacent patches. They refer to these two types as “interactive and noninteractive boundaries.” Under certain circumstances, ecotones may be unique environments separately from the adjoining communities and not the mix of the adjacent environments.
\nThe Earth’s climate can be characterized by natural cycles of cooling and warming phases. Cooling usually results in less diverse and broadly adapted biotas with selectively eliminated tropical biotas. Warming is beneficial for the development of more complex and specialized biotas [91]. Currently, we are in a controversial situation. Despite the fact that we are undergoing a natural cooling process lowering the diversity level, we are experiencing anthropogenic global warming, which also contributes to extinctions because of its high rate.
\nThe role of ecotones in climate change processes is unclear. Gaston et al. [115] suggest that ecotones are sensitive to global warming as ecotonal species are already at the edge of their ranges, which make them prone to extinctions. Others argue that ecotones are places of temporal and spatial fluctuations; hence, ecotonal communities should be more resistant to global warming [74]. Some also suggest that changes in ecotones might serve as early warning signals of ecosystem shifts [50, 51]. Ecotones may be viable areas that sustain themselves over time, or they are temporary product of constant flow from the adjacent communities [116]. This might have an effect on their persistence to future global changes.
\nConservation works have shifted from protecting of individuals to identifying regions with high diversity [117]: botanical hot spots [118] and hot spots of endemic birds [119], which are targets of mass extinction as rare species are concentrated in small areas. We can assume that a part of the biodiversity hot spots might be transition zones, some of which are rich in young and novel species. Brooks and McLennan [120] and Erwin [121] propose that these regions will be the first victims of mass extinction as they contain restricted-range species in small place so they can be wiped out completely. On the other hand, they might be also the centers of repopulation after mass extinction.
\nHampe and Petit [122] suggest that southern (rear) edge of species ranges should deserve greater attention or at least should not be neglected compared to the more studied northern (poleward) expanding edge, as the rear-edge populations store the species’ genetic diversity. This might be applied as analogue in case of greater transition zones serving as biodiversity hot spots. It is an interesting question whether low latitude transitional zones are the most important biodiversity hot spots serving as a refugium in future mass extinction.
\nBased on the estimation of the Late Quaternary glacial-interglacial climate displacement rate, Sandel et al. [123] concluded that high-velocity and unstable regions tend to have mainly widespread species which are resilient to climatic oscillations and have strong dispersal abilities. Their results show that during the Late Quaternary the northeastern part of North America and the north-central Eurasia had the highest velocity and the weakly dispersing amphibians were affected the most. They pointed out that low-velocity regions can be refuges for sessile and small-ranged species [123]. Many bird and mammal endemic species are concentrated in the Southern Hemisphere where a higher velocity of changes can be expected according to predictions [123].
\nBiogeographical boundaries are shifting globally. Late Quaternary glacial-interglacial climate change proves that climate displacement rate tends to vary regionally [123]. Sandel et al. [123] argues that high-velocity and unstable regions have mainly widespread species which are resilient to climatic oscillations and have strong dispersal abilities. However, the rapid expansion of specialized species has been observed in the tropical, temperate, and arctic zone as well as in the mountains [1, 55]. Warming climate seems to favor species with strong competitive and dispersal abilities. Recent studies [55] suggest that non-sessile specialized species which are strong competitors thrive in high-velocity, shifting boundary regions and as Brown and Lomolino [1] conclude that they start to behave as generalists. Other studies describe the extinction of both active- and passive-dispersing specialized species [32]. Short-lived pollinators and birds, for instance, are at great risk.
\nAccording to Sandel et al. [123], low latitude transitional zones harbor sessile, small-ranged species and can be characterized by low climate displacement rate. He suggests that low-velocity regions might serve as refuges under anthropogenic extinction processes. Sandel et al. [123] predict that the climate displacement rate will be higher in the Southern Hemisphere than it was during the Late Quaternary climate change. The Southern Hemisphere is rich in endemic hot spots, which suggests a higher rate of endangerment and biodiversity loss. It can also mean that regions which could serve as refugia might be exterminated. Tropical grassland and forest biomes and their boundary regions maintain high diversity and rich in endemic species; therefore, they are jeopardized by global warming.
\nSeveral studies pointed out that some ecotones are biodiversity hot spots and they are places for speciation. These observations originate mainly from the tropical and subtropical zones [72, 95]. The core regions harbor specialized species as well. This raises important questions. What are the roles of core region and boundary specialists in extinctions and how much they differ (if they differ) in extinction proneness? Many studies claim that specialization is one of the greatest extinction risks [33], which makes specialized species good bioindicators. Can core region specialists expand their ranges under global warming or they are among the first victims because of the weakening core regions? As nothing is black and white, maybe no obvious answer exists. Local and regional divergences as well as the synergy of many factors suggest several outcomes. For example, African megaherbivores are considered to be specialized in diet. However, recent studies [124] show that they can shift their diet, which makes them more generalized than previously thought. Still, they are endangered boundary species mainly because of overhunting and habitat destruction. Their large body size and higher tropic level also contribute to extinction proneness.
\nSome studies [77] claim that generalized species might be the beneficiaries of climate change as they are more adaptive than specialized species. However, specialists are displacing generalized species which are supposed to be weaker competitors in many places. Native super-generalists are being expelled by invasive super-generalists in mutualist networks. The decay of generalized species is a threatening issue, because they maintain communities. Fragmentation is a key contributor of their decline in many cases. The increasing number of perishing specialized and generalized species probably refers to a post-initial phase of mass extinction. Morelli [85] suggests the use of both specialists and generalists as bioindicators in deteriorated regions.
\nZhu et al. [34] and others observed woody encroachment in many regions all over the world, which might suggest that it helps maintain biodiversity. However, it jeopardizes grassland biodiversity hot spots. Even degraded tropical grasslands harbor several rare, endemic, specialized species. Fragmentation and fewer numbers of natural fires also contribute to the decay of grasslands. At the same time, tropical forests, paradoxically, are also suffering. Extreme perturbations affect not only boundary but also core regions, which can trigger the invasion of exotic species and the extinction of native species. Climate change–induced woody encroachment is not necessarily accompanied by an increase in biodiversity. On the contrary, biodiversity loss is detected worldwide.
\nIn summary, climate change affects most levels of the global ecosystem. Both core regions and boundaries are eroding which leads to biodiversity loss and homogenization. Decaying generalized species probably refer to a post-initial stage of mass extinction.
\nMalignant 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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