**2. Pathogenesis of UM**

The occurrence and development of UM involve multi-factors, multi-stages, and multi-gene variation accumulation.


BAP1 (BRCA1-Associated Protein 1) is an important tumor suppressor gene. Wiesner et al. [22] found that the patients suffering from uveal and skin melanoma are related to the abnormal expression of the BAP1 family. BAP1 can regulate the cell cycle, cell differentiation, apoptosis, DNA damage response, and gene expression [23]. Due to the key regulatory role of BAP1 on cells, the decreased gene expression or gene mutation is related to the occurrence and development of various malignant tumors, but its specific mechanism has not yet been elucidated [24]. The loss of BAP1 is associated with the loss of chromosome 3 in UM cells, and the loss of chromosome 3 in UM cells is a risky prognostic factor for the occurrence of metastasis in

*Basis, Diagnosis, and Treatment of Uveal Melanoma DOI: http://dx.doi.org/10.5772/intechopen.110329*

UM [25–29]. SF3B1 mutation exists in 19% of UM, which suggests that UM has a better prognosis [30]. Mutations in SF3B1 cause a large amount of mRNA alternative splicing, but how it promotes UM remains unclear. Martin et al. [31] found that 24% of UM had mutations in EIFIAX, which had a good prognosis. The protein encoded by EIF1AX is involved in protein translation, but the specific mechanism between its mutation and the development of UM is still unclear.

4.**Non-coding RNA:** Both miRNA and long non-coding RNA (lncRNA) belong to non-coding RNA, and both play a regulatory role in the occurrence and development of UM.

miRNAs are a group of endogenous RNAs that can directly bind to mRNA and regulate gene expression after transcription. miRNAs are involved in the development process of almost all malignant tumors, including cell proliferation, differentiation, apoptosis, and metastasis mechanisms. In recent years, miRNA has attracted much attention in the field of tumor research. Scientists have analyzed the miRNA expression profile of UM, and a variety of miRNAs have been found to be associated with the prognosis of UM. The genes encoding these miRNAs are considered novel oncogenes and tumor suppressors. For example, both miRNA-130a and miRNA26a exhibit tumor suppressor properties when overexpressed [32, 33].

lncRNAs play a crucial role in the maintenance of cellular homeostasis and participate in many key cellular pathways. In cancer, lncRNAs are associated with apoptosis evasion, proliferation, invasion, and drug resistance. Among them, autophagyrelated lncRNA plays an important role in predicting the prognosis of UM patients. The lncRNA RHPN1-AS1 is oncogenic and can suppress UM cell proliferation by silencing its expression [34].

## **3. Diagnosis**

#### **3.1 Symptoms and signs**

UM includes melanoma that occurs in the iris, ciliary body, and choroid, and can spread outside the eye, with various clinical symptoms and many complications. Various symptoms and signs appear depending on the site of occurrence. UM can be divided into four stages according to clinical manifestations: intraocular stage, glaucoma stage, extraocular extension stage, and systemic metastasis stage.

The clinical symptoms of choroidal melanoma are diverse, and the ocular symptoms are the most prominent. Symptoms such as vision loss, visual obstruction, metamorphopsia, or discoloration often appear, and the symptoms vary with the location of the tumor. If the tumor is located in the macular area, the early subjective symptoms are metamorphopsia, microopia or macroopia, changes in color vision. Visual field defects may have relative or absolute scotoma, or persistent hypermetropia, or floating in front of the eyes. When the tumor is located in the peripheral part of the fundus, there may be no symptoms. The morphology of choroidal melanoma is divided into three types, namely dome-shaped, mushroom-shaped, and flat diffuse. The melanoma in the choroid often causes exudative retinal detachment, sometimes with vitreous hemorrhage, causing blurred vision.

In iris melanoma, raised lesions in dark brown with clear edges can be seen on the surface of the iris, and dilated "sentinel vessels" can be seen on the surface of the sclera. The OCT examination of the anterior segment showed that there was a circular raised lesion on the surface of the iris, and the anterior surface of the tumor was echogenic; the internal echo of the tumor was attenuated, and imaging could not be performed on the posterior surface.

The location of the ciliary body is hidden and difficult to observe. It is difficult to detect tumors in its location early, because ciliary body melanoma may not have any specific clinical manifestations in the early stage. Ciliary body melanoma can grow forward, backward, and toward the vitreous cavity and sclera, and the clinical manifestations of ciliary body tumors can be different depending on the extent of ciliary body tumor invasion. Ciliary body melanoma can lead to clinical manifestations such as glaucoma, uveitis, lens displacement to varying degrees, diopter changes, vitreous hemorrhage, retinal detachment, and macular edema.

Intraorbital spread of UM: (1) spread along the scleral duct and scleral vortex vein; (2) directly invade the sclera and spread to the outside of the eyeball; (3) directly spread along the cribriform plate; (4) invade the retina, ciliary body, and iris, conjunctiva. The way of extraocular extension of UM is related to the growth location of the tumor. Extraocular extension occurred in the front of the equator, and black nodules can be seen in the conjunctiva, which can be misdiagnosed as scleral staphyloma. The posterior part of the globe spreads, with exophthalmos, eyelid edema, and ocular motility disturbances. Although no tumor was palpable on the orbital rim, the orbital pressure was high and the eyeball could not move back. In severe cases, the eyeball protrudes outside the palpebral fissure, and the surface structure of the eyeball is damaged and uneven. Due to massive necrosis of tumor tissue, panophthalmitis, hypopyon, and orbital cellulitis may occur.

#### **3.2 Eye examination**

A comprehensive examination should be performed including vision, intraocular pressure, anterior segment, and fundus. Slit-lamp microscopy and indirect ophthalmoscopy are the main examination methods in ophthalmology, and sometimes gonioscopy or transillumination examination is also required. All patients underwent evaluation of the anterior segment using slit-lamp microscopy and the posterior segment using indirect ophthalmoscopy to determine tumor location, shape, pigmentation, vascularity, tumor margin morphology, distance from the macula, optic disc, and ciliary body and corneal involvement, anterior scleral extension. The evaluation is required to determine whether there are secondary lesions such as malignant transformation of choroidal nevi, such as sentinel vessels on the surface of the sclera, cataracts, subretinal fluid, or orange pigment in the tumor. Gonioscopy can identify involvement of the anterior chamber angle by iris or ciliary body melanoma. Transillumination is performed by transscleral or pupillary illumination to determine the degree of ciliary body involvement.

#### **3.3 Auxiliary inspection**

In recent years, with the development of imaging technology, especially the application of ocular ultrasound, CT, MRI, and fundus angiography, the diagnostic accuracy of UM has been greatly improved.

*Basis, Diagnosis, and Treatment of Uveal Melanoma DOI: http://dx.doi.org/10.5772/intechopen.110329*


or fusion fluorescence in the late phase. In some patients, large blood vessels can be seen during angiography, and in the late phase, fluorescence leakage occurs in tumors. Advanced tumors have emptying phenomenon or three-ring images in some patients. ICGA and FFA are the effective diagnostic and differential means for diagnosing UM. FFA can show the double circulation of the tumor and retinal telangiectasia, and ICGA is used as a supplementary inspection method of FFA. Both of them have important clinical value.

