Optometry: Open Access
Open Access

Uveal malignant melanoma (UM) is that the second most typical primary malignancy of the attention worldwide when childhood malignant tumor and is that the principal fatal intraocular sickness in adults. The according incidence ranges from four to eleven cases per million/year, variable by country and quality, with a considerably higher incidence in Caucasians than in African and Asian populations. UM arises in melanocytes placed among the 3 totally different regions of the body structure tract: the iris, tissue layer, and tissue layer [1].

UM is diagnosed at any age however it's additional common in middle to later life, with a median age of onset of 55–60 years. Though it's a comparatively rare tumor, UM is related to significantly high mortality, primarily because of a high level of pathologic process disease that develops in nearly 1/2 patients among fifteen years of identification. Once liver metastasis is detected, prognosis is poor, with a according median survival length starting from two.2 to 12.5 months [2]. A poor clinical outcome, plus restricted treatment choices (there are not any specific therapeutic modalities presently accessible for pathologic process UM), underscores the necessity to outline exactly the underlying risk/predisposing factors that cause body structure epidermal cell transformation and ulterior metastasis, with the main target the maximum amount on interference as on early identification.

Various risk factors related to UM are known. A correlation between UM incidence and latitude in European populations suggests that lack of ocular pigmentation may be a risk issue for UM, and lightweight iris color has conjointly been connected to poor prognosis in patients with UM. Among populations with lightweight irises, however, elevated levels of choroidal pigmentation are connected to associate accumulated incidence of UM. Alternative recognized risk factors embrace Caucasian quality, preexistent choroidal nevi, and genetic factors like specific body abnormalities and GNAQ/11 mutations [3]. Moreover, some familial factors are related to associate accumulated risk of UM and therefore the prevalence is higher in men than girls.

A link between ultraviolet exposures and UM, as discovered with body covering malignant melanoma, has been prompt; however the proof for this is often inconclusive. It’s been legendary for several years that ultraviolet exposure, plus specific skin pigment cistron polymorphisms, could be a distinguished considers the event of body covering malignant melanoma. This sturdy link has successively driven efforts to determine whether or not there's an identical link in patients with UM; but, medicine and genetic studies have usually didn't show such a association [4].

Genetic studies conjointly counsel that ultraviolet doesn't considerably contribute to UM. for instance, the oncogenic V600E bRAF mutation, expressed within the majority of patients with body covering malignant melanoma, is believed to be the results of star ultraviolet exposure and is absent from melanomas occurring in body locations that square measure naturally shielded from ultraviolet. This link provides a helpful molecular tool that permits direct insight into the contribution of star ultraviolet to UM incidence. Genetic analysis of V600E bRAF expression in patients with UM has uncovered a relationship between the frequency of this mutation and therefore the ocular location of the malignant melanoma [5]. V600E mutations are detected in patients with anterior UM, like those of the iris, in keeping with ultraviolet exposure; but, most UM cases arise within the posterior body structure tract and V600E mutation rates here square measure negligible. This knowledge imply that whereas ultraviolet might play a job in some cases of anterior UM, it doesn't considerably contribute to the oncogenic changes driving the bulk of UM arising within the posterior body structure tract.

The combined epidemiological/genetic case against a major role for ultraviolet within the etiology of this sickness is in keeping with the established properties of the adult lens and tissue layer that together separate out all wavelengths below four hundred nm. Maybe the key to understanding the link between UM and activities that generate high amounts of electromagnetic wave doesn't dwell what's filtered out however in what will submit to the lens and tissue layer. For example, arc fastening produces vital amounts of intense short-wave lightweight.

not like ultraviolet, shortwave (perceived as blue) lightweight (400–500 nm) will reach the posterior body structure tract whereas retentive ample energy to be harmful to biological structures. In fact, though actinic radiation reaching the tissue layer could be a requirement for sight [6], phototoxic injury caused by its higher energy blue element isn't associate uncommon feature of the class eye. a major variety of articles have documented blue-light-mediated injury to cells derived from the retinal pigment animal tissue, retinal neural structure cell layer, and alternative epithelia, particularly blue lightweight within the 425– 475 nm vary. This cellular injury is believed to be primarily chemical science and arises from chromophores, like animal pigment, retinoid, and lipofuscin. Blue lightweight may also generate reactive chemical element species (ROS) in mitochondria. This injury sometimes leads to cell pathology or death, the most causes of cellular aging and agerelated degeneration (AMD), however can also contribute to growth genesis. During this paper, we tend to review the accessible proof for a causative link between blue lightweight and UM [7].

Role of Blue Light-Weight in Bodily Structure Malignant Melanoma

Systematic literature searches conducted through Ovid showed that the earliest reports of associate degree association between exposures to blue light-weight and also the development of UM have come back from in vitro and animal work. Many studies have shown that blue light-weight encompasses a mitotic impact on human UM cell lines. Cultivated human UM cells exposed to blue light-weight considerably accumulated their mitotic division rate relative to bluelight protected controls, a control that was blocked employing a blue light-filtering lens. Though the precise mechanism underlying the link between blue light-weight and accumulated proliferation of bodily structure malignant melanoma cells is unknown, it's been shown that shorter wavelengths of sunshine will induce retinal pigment vegetative cell death by mitochondrial-derived ROS production [8]. Thus, though specific studies square measure needed, investigation ROS production following blue light-weight exposure in bodily structure malignant melanoma cells would be an honest place to begin for elucidating the said relationship.

This fascinating observation was followed up by a study that sought-after to mimic the impact of blue light-weight on UM cells among the context of the class eye. Human UM cells xenografted into the attention of associate degree unusual person rabbit model of ocular malignant melanoma and after exposed to blue light-weight showed increased proliferation upon removal and reculture, compared with management samples shielded from blue light-weight [9]. the importance of this finding is that the UM cells were exposed to blue light-weight whereas residing among the choroid coat, effectively demonstrating that blue light-weight affects bodily structure cells and might enhance their mitotic ability, a vital step in linking blue lightweight to malignant changes among bodily structure melanocytes in vivo. A final confirmation of the link between blue light-weight and UM in vivo comes from a study in Long Evans rats, a strain with pigmented eyes during which there are no rumored cases of intraocular malignant melanoma. This study represented the event of associate degree ocular neoplasm in one associate degreeimal following blue light-weight exposure (434–475 nm) let alone the administration of an antiapoptotic agent. The neoplasm concerned the iris, tissue layer, choroid, and sclera, and contained massive amounts of animal pigment.

Paradoxically, however, 450 nm blue light-weights seem to be phototoxic to mouse connective tissue malignant melanoma cells. Initial work rumored that 450 nm light-weights from a diode was cytostatic to B16 cells, further as inhibiting the power of those cells to distribute to the respiratory organ once injected intravenously into mice. More work has extended these early observations to point out that 450 nm light-weights is each cytostatic and cytocidal to B16 cells [10]. It’s conjointly been advised that blue light-weight medical care could also be of clinical profit in cases of harm pathological process malignant melanoma, supported knowledge from one patient receiving aggressive therapy for a malignant melanoma on the anterior forearm. It ought to be noted that these phototoxic knowledge square measure all supported connective tissue malignant melanoma and for the foremost half the behavior of one mouse cell line.

Further proof underpinning a link between blue light-weight and UM comes from babe blue light-weight medical care studies. Blue ligh tweight medical care is a vital tool in treating babe jaundice as a result of dermal/subcutaneous hematoidin absorbs light-weight maximally at 425–475 nm, resulting in its conversion to a less harmful soluble kind [11]. A rumored long-run facet impact of this therapy is that the accumulated risk of abnormal condition birthmark development in each the skin and eye (clinically, atypical nevi, or abnormal condition nevi, square measure usually accepted to extend associate degree individual’s risk of melanoma). Associate degree initial report represented the next prevalence of atypical however not common melanocytic nevi within the skin of college youngsters World Health Organization had antecedently received babe blue light-weight medical care. though broad-spectral emission bulbs square measure overtimes employed in this medical care (370–600 nm, outside emission 450 nm), ultraviolet A contamination remains negligible at more or less zero.3% of output. A follow-up study of monozygotic and heterozygotic twins, during which one in all every try had received and one had not received babe blue light-weight medical care, not solely reproduced these findings; however conjointly found a rise in benign ocular pigmented lesions of the iris within the cohort World Health Organization had received blue light-weight medical care. The latter finding is stunning as a result of eye protection is worn in babe blue light-weight medical care [12]; but, accidental removal of eye coverings could occur and also the babe eye permits bigger transmission of lower frequency blue lightweight relative to the adult eye.

Blue light-weight has been shown to induce nuclear desoxyribonucleic acid lesions, suggesting a potential mechanism for neoplasm genesis. Specific nuclear desoxyribonucleic acid lesions ensuing from blue light-weight are recorded within the presence of lipofuscin, a photograph iatrogenic intracellular generator of ROS. Moreover, though no study has shown desoxyribonucleic acid mutations in bodily structure melanocytes within the presence of blue light-weight, the malignant neoplastic disease potential of radiation within the 365–436 nm ultraviolet A/blue light-weight crossover region has been incontestible. In animal models of malignant melanoma, ultraviolet A/blue light-weight isn't directly absorbed by desoxyribonucleic acid however rather exerts its impact through a chemical science interaction with animal pigment. Given the filtering power of the lens and tissue layer, there's a big window of agent chance for blue light-weight of 400–436 nm, and possibly higher, as a result of 365–436 nm portrayed the height of activity [13]. Curiously, it's been shown that ultraviolet B and ultraviolet A differentially induce connective tissue malignant melanoma through direct desoxyribonucleic acid injury and indirect melanin-derived ROS-mediated injury, severally. The wavelengths of ultraviolet A and blue light-weight square measure adjacent and their biological effects in all probability overlap, as their shared ability to come up with ROS demonstrates. Though the link between epidermal cell animal pigment, ROS generation, and desoxyribonucleic acid injury is complicated, a plausible situation involving blue-light-triggered ROS iatrogenic epidermal cell mutation may be hypothesized as a causative issue resulting in UM.

Clinical Implications

If blue light is a known risk factor for AMD and, at the very least, a suspect in UM development, can this knowledge be translated into some form of meaningful preventive measure? One area of immediate relevance is the current debate surrounding intraocular lens (IOL) implants used after cataract surgery. The replacement of the crystalline lens by an IOL is a central component of this procedure. IOLs are designed to filter out ultraviolet radiation to protect the eye from damage. Early IOL models filtered out ultraviolet radiation, but more recently developed IOLs filter out a wider spectral range, including at least the more energetic parts of blue light because, ideally, the spectral emission characteristics of an IOL should mimic those of the lens that was removed. As the crystalline lens ages, it yellows and filters out significantly more blue light above 400 nm [14]. This process appears to be caused by the progressive accumulation of yellow chromophore deposits, primarily 3- hydroxykynurenine glucoside derivatives, estimated to reduce the blue light transmission capacity of the crystalline lens by around 0.7–0.8%/year. Consequently, the 400– 500 nm transmission capacity of 80–90% associated with the lens of a healthy child or young adult is cumulatively reduced in later life, dropping to around 50% by the fifth decade and to as little as 25% or less at 70 years and over [15]. There is also evidence to suggest that retinal tissue becomes more sensitive to phototoxicity, possibly owing to increased lipofuscin concentration and impaired antioxidant activity, concomitant with altered lens function. Therefore, there is a clinical rationale for considering the use of blue-filtering IOLs, and this is further supported by the evidence presented in this paper (Figure 1).

Figure 1: (a) The young crystalline lens and cornea together filter UVA and UVB while allowing transmission of most blue light (defined as 400-500 nm) to the retina.Around 80-90% of blue light at 450 nm can pass through the young lens. (b) As the crystalline lens ages it yellows and progressively filters more blue light until, by the sixth or seventh decade, blue light transmission can be as low as 20% of that transmitted by the young lens. (c) Early types of IOLs used to replace the crystalline lens during cataract surgery effectively filter UV but do not block blue light. It is hypothesized that blue light reaching the retina increases the risk of preexisting dysplastic nevi (indicated as CN, choroid nevus) progressing to UM. A typical CN is shown in the small retinal photograph, while a UM is shown in the magnified retinal photograph. (d) Blue-light-filtering IOLs are designed to filter up to 50% of blue light. This models the natural filtering ability of the middle-aged eye, reducing potentially damaging radiation while not impacting on vision. We argue that preexisting CNs (shown in the small retinal photograph) are less likely to progress to UMs in this environment. CN, choroidal nevus; IOL, intraocular lens; UM, uveal melanoma; UV, ultraviolet; UVA, ultraviolet A; UVB, ultraviolet B.

Conclusion

In summary, cumulative epidemiological and experimental evidence indicates that blue light is a credible risk factor for the development of UM. Additional studies are required to clarify the risk associated with blue light and the protective potential of blue-filtering IOLs following cataract surgery. As life expectancy continues to increase, individuals are expected to live longer after cataract surgery. Shielding individuals from the known harmful effects of blue light, a role normally performed by the aging crystalline lens, through the use of blue-filtering IOLs is of clinical benefit as a preventive measure against UM.

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