Hong Kong Med J 2023 Dec;29(6):506–13 | Epub 4 Dec 2023
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
Uveal and conjunctival melanomas: disease course and outcomes in Chinese patients
Julia YY Chan, FCOphthHK, FHKAM (Ophthalmology)1,2; Stacey Carolyn Lam, FCOphthHK, FHKAM (Ophthalmology)1,2; Hunter KL Yuen, FRCOphth, FRCSEd1,2
1 Hong Kong Eye Hospital, Hong Kong SAR, China
2 Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
Corresponding author: Dr Julia YY Chan (yy.chan@link.cuhk.edu.hk)
 Full paper in PDF
Introduction: Epidemiological studies of ocular melanomas have largely focused on Caucasian populations. This study reviewed the course and outcomes of uveal melanoma (UM) and conjunctival melanoma (CM) in Chinese patients.
Methods: This retrospective study included patients with UM and CM who received treatment in a tertiary eye centre in Hong Kong from January 1994 to December 2019. Data were recorded concerning patient demographics, tumour laterality, tumour characteristics, investigations performed, treatment regimen, and final outcomes.
Results: During the 25-year study period, there were 13 patients with UM and 11 patients with CM who did not display nodal or systemic involvement at diagnosis. The mean ± standard deviation ages at diagnosis of UM and CM were 59 ± 15.8 and 57 ± 13.9 years, respectively. There were more men among patients with UM than among those with CM (P=0.042). Most patients with UM underwent primary enucleation (n=12; 92.3%), whereas most patients with CM underwent orbital exenteration (n=9; 81.8%). The prognosis was significantly worse for CM than for UM. The median disease-free survival were 5.2 years (range, 0.7-20.5) and 2.1 years (range, 0.1-24.9) for UM and CM, respectively. Melanoma-related mortality was significantly higher among patients with CM than among those with UM (P=0.006).
Conclusion: Compared with UM, CM has higher rates of systemic metastasis and tumour-related mortality in Hong Kong Chinese patients, regardless of prior definitive treatment.
New knowledge added by this study
  • Among Chinese patients, conjunctival melanoma constituted a larger proportion of ocular melanoma cases than previously identified in Caucasian populations, similar to the findings in a Korean study.
  • Compared with uveal melanoma, conjunctival melanoma has a worse prognosis with a higher rate of metastasis, shorter disease-free survival, and shorter overall survival.
Implications for clinical practice or policy
  • Primary enucleation is an effective treatment for patients with uveal melanoma, but patients with conjunctival melanoma may experience systemic metastasis despite radical treatment with wide excisional biopsy or primary orbital exenteration.
  • Ophthalmologists and oncologists should offer long-term follow-up with regular systemic surveillance to patients with conjunctival melanoma who have received definitive treatment.
Primary ocular melanoma from melanocytes within the eye constitutes uveal melanoma (UM), whereas ocular melanoma from melanocytes on the globe surface is considered conjunctival melanoma (CM). Although both UM and CM develop from similar neural crest lineages and are classified as ocular melanomas, they have distinct clinical behaviours, management, prognosis, cancer staging features, and molecular characteristics. Overall, 85% of melanomas in ocular regions arise from the uvea (iris, choroidal, and ciliary body), 5% arise from the conjunctiva, and 10% occur in other sites.1 The most common site of UM is the choroid, which is involved in 90% of cases.2
For most cases of UM, the primary treatment is enucleation. Alternative options include plaque brachytherapy and proton beam radiation; these options are currently unavailable in Hong Kong and similar Asian countries (eg, Singapore). Systemic metastases of UM most commonly affect the liver, followed by lung and bone. Conjunctival melanoma is usually managed by complete excisional biopsy with wide surgical margins, using a ‘no-touch’ technique. Adjuvant therapies such as cryotherapy or topical mitomycin C are offered, followed by reconstruction with an amniotic membrane graft. Orbital exenteration may be necessary for advanced tumours where local resection is not feasible. Metastatic disease, often to regional lymph nodes and the brain, occurs in 20% to 30% of patients with CM.3
Melanomas are generally rare tumours and their incidences are particularly low in Asian populations. The annual incidence of UM in Caucasian populations is 5.1 cases per million,2 whereas the respective incidences in Japanese4 and Korean5 populations are 0.2 and 0.6 cases per million. The incidences of CM are similar: 0.2 to 0.5 cases per million in Caucasian populations3 and 0.15 cases per million in Asian populations.6 Because of this rarity among Asian populations, very few studies have focused on Chinese patients. Epidemiological studies have largely involved Caucasian populations. Clinical characteristics may differ in Asian populations; for example, Asian patients are initially diagnosed with UM5 and CM6 at younger ages.
Known risk factors for UM include fair skin, light-coloured eyes, congenital ocular melanocytosis, ocular melanocytoma, and BAP1 tumour predisposition syndrome.7 In contrast, risk factors for CM include increased conjunctival pigmentation and a history of primary acquired melanosis. Predictors of recurrence or new tumour formation after CM treatment are older age, a history of prior conjunctival surgery, and advanced T subclassification in the American Joint Committee on Cancer (AJCC) staging system.8
This study explored the disease course and outcomes of UM and CM in Chinese patients without nodal metastasis on presentation.
This retrospective study included patients who received treatment for UM or CM in a single tertiary ophthalmic centre in Hong Kong between January 1994 and December 2019. Inclusion criteria included Chinese ethnicity and imaging-confirmed lack of tumour dissemination at diagnosis. Exclusion criteria were <6 months of follow-up, insufficient available information, loss to follow-up, or presence of any precursor lesions (eg, atypical primary acquired melanosis). The following data were recorded: patient demographics, tumour laterality, tumour characteristics (eg, presentation and staging according to the AJCC Cancer Staging Manual [8th Edition]9 10), investigations performed, treatment regimen, and final outcomes. The study adhered to the principles outlined in the Declaration of Helsinki.
Provisional clinical diagnoses of UM and CM were made based on each patient’s medical history, primary acquired melanosis status, and clinical presentation. Final diagnoses of UM and CM were confirmed by excisional biopsy or analysis of a specimen collected during definitive surgical treatment. Unless refused by the patient, positron emission tomography–computed tomography (PET-CT) scans of UM and CM were performed after 2001 (when such scans became commercially available). Magnetic resonance imaging scans of the brain and orbit, as well as fundus fluorescein angiography and indocyanine green angiography, were conducted to investigate suspected UM. All patients with pathologically confirmed UM or CM underwent definitive surgical treatment. The specific surgical treatment was selected according to melanoma location and size, depth of invasion, systemic metastasis status, and the patient’s physical condition.
SPSS software (Windows version 20; IBM Corp, Armonk [NY], US) was utilised for statistical analysis. Differences between patient groups were calculated using the Chi squared and Mann-Whitney U tests. P values <0.05 were considered statistically significant. Kaplan-Meier survival analysis was performed to estimate disease-free survival and overall survival in patients who had received definitive treatment. Continuous data were reported as mean ± standard deviation.
In this 25-year retrospective study, there were 13 and 11 patients with pathologically confirmed UM and CM, respectively. Two other patients were excluded: both displayed ocular symptoms (upper eyelid mass and bloody discharge) but were subsequently diagnosed with ocular metastases of primary nasal melanoma. The mean follow-up durations for UM and CM were 67 ± 53.2 and 74 ± 83.3 months, respectively. There were more men among patients with UM than among those with CM (P=0.042). The incidence of pre-existing conjunctival nevus was higher among patients with CM than among those with UM (P=0.049). There were no other significant differences in terms of age at diagnosis, tumour laterality, duration of symptoms, history of ocular nevi, or pathologically determined lesion diameter (Table 1).

Table 1. Patient demographics and tumour characteristics
Twenty-three of the 24 included patients had visual symptoms on presentation. Among patients with UM, 84.6% (n=11) reported blurring of vision and 7.7% (n=1) presented with photopsia. In one male patient (7.7%), the tumour was discovered during a routine ophthalmological examination. Patients with CM had more diverse visual symptoms: 63.6% (n=7) exhibited conjunctival pigmentation, 18.2% (n=2) had either an upper or lower eyelid mass, 9.1% (n=1) displayed bloody ocular discharge, and 9.1% (n=1) had experienced bleeding from the mass.
Tumour staging
Retrospective melanoma staging of UM9 and CM10 was conducted in accordance with the AJCC Cancer Staging Manual (8th Edition). Uveal melanoma stages varied from T1a to T4a and from stage I to IIIa. Most UM cases were clinical stage II: 38.5% (n=5), 38.5% (n=5), 7.7% (n=1), and 15.3% (n=2) of patients with UM had clinical stage I, IIA, IIB, and IIIA tumours, respectively. Pathological staging of the tumours revealed that 46.2% (n=6) were spindle cell type, 38.5% (n=5) were epithelioid cell type, and the remaining 15.3% (n=2) were mixed cell type (ie, >10% epithelioid cells and <90% spindle cells). Pathological staging tended to be equivalent to or higher than the initial clinical staging: two patients with pathological stage IIB disease were initially diagnosed with clinical stage I disease, and three patients with pathological stage IIB disease were initially diagnosed with clinical stage IIA disease. For the remaining eight patients, the clinical and pathological stages were identical. Overall, 23.1% (n=3), 15.4% (n=2), 46.2% (n=6), and 15.3% (n=2) of patients with UM had pathological stage I, IIA, IIB and III tumours, respectively.
At diagnosis of CM, the clinical T (cT) stage was cT2 in 72.7% (n=8) of patients and cT3 in 27.3% (n=3) of patients. There were no cT1 or cT4 tumours in our cohort. The pathological T (pT) stage was pT2 in 54.5% (n=6) of patients and pT3 in 45.5% (n=5) of patients. No patients were diagnosed with pT1 or pT4 disease. Unlike the approach or UM, the AJCC staging system for CM does not include guidance regarding overall stage; there is only clinical and pathological staging for the T (tumour) component. One patient had a lower clinical stage (T2b) than pathological stage (T3b); all other patients had identical clinical and pathological stages.
Disease management
In terms of disease management, biopsies were more frequently performed before definitive treatment in patients with CM than in those with UM (P=0.003). Enucleation was performed in 92.3% (n=12) of patients with UM, whereas orbital exenteration was performed in 81.8% (n=9) of patients with CM. The interventions and treatments performed are shown in Table 2.

Table 2. Interventions for uveal and conjunctival melanomas
After definitive treatment, all patients initially attended weekly follow-up visits; they gradually transitioned to follow-up at 6-month intervals. Clinical examinations were performed for any surgical complications or disease recurrence. In cases of suspected disease recurrence or metastasis, contrast CT scans of the brain and orbit were performed. No patients with UM or CM had short-term or long-term wound complications. There were no instances of local recurrence during follow-up.
One patient with UM (7.7%) had metastasis to bone, lung, and breast tissue, as determined by high-resolution CT at 105 months of follow-up. The patient died 117 months after initial diagnosis. Two patients (15.3%) died of causes unrelated to melanoma, such as hepatocellular carcinoma or squamous cell carcinoma of the lung.
Patients with CM had worse outcomes than those with had UM, in terms of systemic metastasis (P=0.031) and tumour-related mortality rates (P=0.006). Overall, 45.5% (n=4) of patients with CM developed systemic metastasis during follow-up; the mean time from definitive treatment to systemic metastasis was 55.8 ± 66 months (range, 14-168). Cases were detected when patients were symptomatic and admitted to an acute care hospital for whole-body PET-CT or brain magnetic resonance imaging. Lymph node metastasis in two patients and liver metastasis in one patient were confirmed by fine needle aspiration cytology. Brain metastasis was identified by brain CT in two patients, one of whom had simultaneous bone and lung metastases confirmed by PET-CT. Overall, 18.2% (n=2) of patients died of causes unrelated to melanoma. The mean time from definitive treatment to death was 39 ± 26 months (range, 1-64). Patients with CM had shorter median disease-free survival (P=0.004) and overall survival (P=0.006). Detailed results are presented in Table 3.

Table 3. Outcomes of primary uveal and conjunctival melanomas
At 2 years after definitive treatment, the probabilities of disease-free survival were approximately 0.55 for CM and 1.0 for UM. At 10 years, these probabilities decreased to 0.4 for CM and 0.7 for UM. Overall survival was 100% among patients with UM at 10 years after definitive treatment. In contrast, patients with CM displayed a progressive decrease in overall survival, reaching 35% at 5 years after definitive treatment. Survival curves are depicted in Figures 1 and 2.

Figure 1. Disease-free survival (DFS) curves for uveal and conjunctival melanomas. Blue line represents conjunctival melanoma and green line represents uveal melanoma; hash marks indicate censoring

Figure 2. Overall survival (OS) curves for uveal and conjunctival melanomas. Blue line represents conjunctival melanoma and green line represents uveal melanoma; hash marks indicate censoring
To our knowledge, this is the first retrospective study of disease course and outcomes among patients with UM and CM in southern China.
In the present study, the mean ages at diagnosis of UM and CM were 59 and 57 years, respectively. These findings are similar to the ages at diagnosis of UM in Taiwan (55 years)11 and the US (58 years),12 but slightly older than the ages in Singapore (52 years)13 and South Korea (53 years).14 The findings are also similar to the ages at diagnosis of CM in the US and mainland China (61 years15 and 54 years,16 respectively). It is clear that UM and CM both affect patients in their late 50s to early 60s, regardless of ethnicity.
Uveal melanoma primarily affected men in the present study, consistent with findings in Australian17 and European18 Caucasian populations. No previous studies have identified oestrogen receptors in normal uveal tissue or UM tumours,19 and there is no evidence that oral contraceptives or postmenopausal oestrogens participate in UM aetiology.20 Because female hormones do not have protective or exacerbating roles in UM, there is speculation that testosterone receptors are present on UM tumours, leading to a higher incidence in men.21 The present study revealed that CM primarily affected women, but previous studies have not found a relationship between sex and CM incidence.22 23 In contrast to our results, a study in mainland China showed that CM primarily affected men.15 Further studies are needed regarding the relationship between sex and CM.
Studies in Caucasian populations have demonstrated that the incidence of UM is much higher than that of CM, with a ratio of approximately 3 to 1.21 24 In the present study, CM constituted a larger proportion of ocular melanoma cases than previously identified in Caucasian populations, with results similar to epidemiological findings from Korea.5 Asian populations may have a lower risk of UM, but further research is warranted to confirm this speculation.
Clinical presentation
Zloto et al21 described an intriguing phenomenon whereby men were less likely than women to report symptoms of UM. Among our patients with UM, nearly all reported symptoms; one male patient did not report symptoms and had a tumour identified during a routine examination. Although this finding was not statistically significant, it is consistent with the previous results in a Caucasian population.2
In the present study, more patients with CM had pre-existing conjunctival pigmented lesions, compared with those who had UM. Somatic mutations in the BRAF gene frequently occur in human melanomas, including CM; such mutations are strongly associated with ultraviolent light exposure.25 In subtropical regions such as Hong Kong where there is abundant sunlight, analyses of underlying BRAF gene mutations could be insightful.
Tumour staging
Among 10 ophthalmology centres on four continents (North and South America, Europe, and Asia), the proportions of UM stages I, IIA, IIB, and IIIA were 32%, 34%, 22.1%, and 8.8%, respectively10; the present study demonstrated a comparatively greater proportion of cases with stage IIB or higher.
Comparative analysis of CM data revealed similar results: patients in the present study had higher clinical stages relative to patients in the US, where three-quarters and more than half of the patients had clinical and pathological stage I disease. This discrepancy could be explained by the rare nature of CM, particularly in Asian populations, leading to lower disease awareness and delayed referral to an ophthalmologist.
Primary enucleation was an effective treatment for patients with UM in the present study; only one patient (7.7%) had systemic metastasis. In that patient, although no systemic metastasis was detected on PET-CT at diagnosis, the maximum standardised uptake value of the UM tumour was particularly high (9.4); UM tumours in other patients had maximum standardised uptake values of 0 to 3.9. Considering the exceptionally high metabolic rate in the UM tumour of the patient with systemic metastasis, microscopic metastasis may have been present before enucleation.
Despite radical treatment with wide excisional biopsy or primary orbital exenteration, systemic metastasis occurred in nearly half of the patients with CM. Regular imaging surveillance by PET-CT may be beneficial for patients with CM after orbital exenteration.
Among patients with UM, we observed a much lower rate of systemic metastasis than reported in Singapore (7.7% vs 45.5%26). This difference could be attributed to the performance of early radical treatment (ie, enucleation) before detection of systemic metastasis. Notably, the disease-free survival rate was better in our cohort of patients with UM than in another study of Chinese patients with UM (5- and 10-year disease-free survival rates of 80% and 70%, respectively)27 and better than in a study of Singaporean patients with UM (5-year disease-free survival rate of 56.8%).13 For comparison, in Caucasian populations, the 5-year and 10-year disease-free survival rates were 81.6%17 and 50%,28 respectively.
The rates of systemic metastasis and tumour-related mortality are consistently higher in patients with CM than in those with UM. In the present study, tumour-related mortality at 5 years was similar to the rate in Chinese patients (30.5%)16 but higher than that among patients in the US (7%).29 In five large studies (n=734 cases overall) of CM after surgical resection with tumour-free margins, the 5-year overall survival rates ranged from 74% to 86%.30 31 32 33 34 A recent Singaporean study revealed a slightly lower 5-year overall survival rate (68.8%).13 In the present study, the 5-year overall survival rate was substantially lower than the rates in other countries. Shields et al29 reported that a pathologically confirmed positive tumour margin and the absence of limbal involvement were risk factors for CM metastasis. Although all patients with CM in our cohort had pathologically confirmed clear margins, most patients with metastasis (n=6) had palpebral CM (83.3%, n=5) in which the melanoma did not reach the limbus. Thus, tumour location and ethnicity may explain the poor overall survival among patients with CM in the present study.
The higher risk of metastasis and lower rates of 5- and 10-year overall survival in CM, compared with UM, could be attributed to multiple factors. We did not find significant differences between UM and CM in terms of tumour stage or delays in diagnosis/treatment. We suspect that the differences between tumours are related to the nature of the disease, the primary mode of metastasis (UM spreads through the vasculature, whereas CM spreads through the lymphatic system), and genetic alterations (UM is associated with chromosomal abnormalities and CM is associated with mutations in specific genes). In terms of monitoring UM recurrence, the use of single-cell technologies to identify circulating tumour cells has implications for clinical stratification, particularly in cases of UM where specific genetic mutations have been identified.35 Because circulating tumour cell tests have received US Food and Drug Administration’s approval for clinical use in the management of various tumours (eg, metastatic breast and prostate cancers), they may be utilised in future efforts to detect circulating UM tumour cells.
In our centre, sentinel lymph node biopsy (SLNB) is not performed as a component of CM management. Mor et al36 recommend SLNB for patients with CM because false-negative findings are rare and 5-year survival can reach 79%. Therefore, early diagnosis of CM, including SLNB in cases with poor prognosticating factors (lack of limbal involvement and positive biopsy margin), and radical neck dissection as appropriate (with support from head and neck surgeons) should be considered before systemic treatment is offered.
This retrospective study included a low number of patients. Additionally, genetic testing was not performed on tissue samples from patients with pathologically confirmed tumours. Chromosomal abnormalities (monosomy 3, gain of chromosome 8q, and monosomy 3 combined with loss of 1p36) have been associated with decreased survival in UM,37 whereas mutations in the BRAF, RAS, cKIT, and NF1 genes have been associated with CM38; thus, survival could be more closely related to specific genetic features, and it may be inappropriate to consider these tumours as single entities.
Because UM and CM are rare conditions, they represent challenges for primary physicians (ie, timely referral) and ophthalmologists (ie, appropriate treatment and adequate long-term follow-up). Currently, there is limited information regarding the roles of newer targeted therapies for UM and CM, compared with the application of such therapies to cutaneous melanoma. Among patients with CM, long-term mortality remains high despite definitive radical treatment. This study explored the disease course and outcomes in Hong Kong Chinese patients, then compared the findings with data from patients in other countries. For patients with UM and CM, we recommend long-term follow-up with close monitoring, a detailed medical history, holistic assessment involving cervical and head lymph node palpation, and ophthalmological examination. Collaborations with oncologists to provide regular systemic evaluation during long-term followup, with the goal of early detection for distant metastases, are also important. Chest X-ray, brain magnetic resonance imaging, and cytology with SLNB should be performed regularly (annually if possible) to improve survival, particularly in patients with CM.
Author contributions
Concept or design: HKL Yuen.
Acquisition of data: JYY Chan.
Analysis or interpretation of data: SC Lam, JYY Chan.
Drafting of the manuscript: JYY Chan.
Critical revision of the manuscript for important intellectual content: SC Lam, HKL Yuen.
All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
Conflicts of interest
All authors have disclosed no conflicts of interest.
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Ethics approval
The study protocol was approved by the Research Ethics Committee (Kowloon Central/Kowloon East) of Hospital Authority, Hong Kong (Ref No.: KC/KE-21-0129/ER-1). Patients were treated in accordance with the tenets of the Declaration of Helsinki, provided written informed consent for all treatments and procedures, and consented to publication of this report.
1. Chang AE, Karnell LH, Menck HR. The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer 1998;83:1664-78. Crossref
2. Kaliki S, Shields CL. Uveal melanoma: relatively rare but deadly cancer. Eye (Lond) 2017;31:241-57. Crossref
3. Vora GK, Demirci H, Marr B, Mruthyunjaya P. Advances in the management of conjunctival melanoma. Surv Ophthalmol 2017;62:26-42. Crossref
4. Stang A, Parkin DM, Ferlay J, Jöckel KH. International uveal melanoma incidence trends in view of a decreasing proportion of morphological verification. Int J Cancer 2005;114:114-23. Crossref
5. Park SJ, Oh CM, Kim BW, Woo SJ, Cho H, Park KH. Nationwide incidence of ocular melanoma in South Korea by using the national cancer registry database (1999-2011). Invest Ophthalmol Vis Sci 2015;56:4719-24. Crossref
6. Hu DN, Yu G, McCormick SA, Finger PT. Population-based incidence of conjunctival melanoma in various races and ethnic groups and comparison with other melanomas. Am J Ophthalmol 2008;145:418-23. Crossref
7. Jager MJ, Shields CL, Cebulla CM, et al. Uveal melanoma. Nat Rev Dis Primers 2020;6:24. Crossref
8. Vaidya S, Dalvin LA, Yaghy A, et al. Conjunctival melanoma: risk factors for recurrent or new tumor in 540 patients at a single ocular oncology center. Eur J Ophthalmol 2021;31:2675-85. Crossref
9. Baron ED, Di Nicola M, Shields CL. Updated AJCC classification for posterior uveal melanoma. Available from: https://retinatoday.com/pdfs/0518RT_Oncology.pdf. Accessed 1 Mar 2021.
10. Jain P, Finger PT, Damato B, et al. Multicenter, international assessment of the Eighth Edition of the American Joint Committee on Cancer Cancer Staging Manual for conjunctival melanoma. JAMA Ophthalmol 2019;137:905-11. Crossref
11. Ma ST, Hsieh YT, Wei YH, Liao SL. A 45-year experience of uveal melanoma in Taiwan: verification of American Joint Committee on Cancer staging system and prognostic factors. J Formos Med Assoc 2021;120:1361-8. Crossref
12. Shields CL, Furuta M, Thangappan A, et al. Metastasis of uveal melanoma millimeter-by-millimeter in 8033 consecutive eyes. Arch Ophthalmol 2009;127:989-98. Crossref
13. Tan LL, Hong J, Goh WL, et al. Clinical features and survival outcomes of ocular melanoma in a multi-ethnic Asian cohort. Sci Rep 2020;10:16367. Crossref
14. Lee CS, Lee J, Choi JJ, et al. Cytogenetics and prognosis for uveal melanoma in Korean patients. Acta Ophthalmol 2011;89:e310-4. Crossref
15. Yousef YA, Finger PT. Predictive value of the seventh edition American Joint Committee on Cancer staging system for conjunctival melanoma. Arch Ophthalmol 2012;130:599-606. Crossref
16. Zhou C, Wang Y, Jia R, Fan X. Conjunctival melanoma in Chinese patients: local recurrence, metastasis, mortality, and comparisons with Caucasian patients. Invest Ophthalmol Vis Sci 2017;58:5452-9. Crossref
17. Vajdic CM, Kricker A, Giblin M, et al. Incidence of ocular melanoma in Australia from 1990 to 1998. Int J Cancer 2003;105:117-22. Crossref
18. Singh AD, Turell ME, Topham AK. Uveal melanoma: trends in incidence, treatment, and survival. Ophthalmology 2011;118:1881-5. Crossref
19. Mäkitie T, Tarkkanen A, Kivelä T. Comparative immunohistochemical oestrogen receptor analysis in primary and metastatic uveal melanoma. Graefes Arch Clin Exp Ophthalmol 1998;236:415-9. Crossref
20. Holly EA, Aston DA, Ahn DK, Kristiansen JJ, Char DH. Uveal melanoma, hormonal and reproductive factors in women. Cancer Res 1991;51:1370-2.
21. Zloto O, Pe’er J, Frenkel S. Gender differences in clinical presentation and prognosis of uveal melanoma. Invest Ophthalmol Vis Sci 2013;54:652-6. Crossref
22. McLaughlin CC, Wu XC, Jemal A, Martin HJ, Roche LM, Chen VW. Incidence of noncutaneous melanomas in the U.S. Cancer 2005;103:1000-7. Crossref
23. Wong JR, Nanji AA, Galor A, Karp CL. Management of conjunctival malignant melanoma: a review and update. Expert Rev Ophthalmol 2014;9:185-204. Crossref
24. Hu DN, Yu GP, McCormick SA, Schneider S, Finger PT. Population-based incidence of uveal melanoma in various races and ethnic groups. Am J Ophthalmol 2005;140:612-7. Crossref
25. Besaratinia A, Pfeifer GP. Sunlight ultraviolet irradiation and BRAF V600 mutagenesis in human melanoma. Hum Mutat 2008;29:983-91. Crossref
26. Wong W, Sundar G, Chee C, Zhao PS, Rajagopalan R, Gopal L. Clinical spectrum, treatment and outcomes of uveal melanoma in a tertiary centre. Singapore Med J 2019;60:474-8. Crossref
27. Yue H, Qian J, Yuan Y, et al. Clinicopathological characteristics and prognosis for survival after enucleation of uveal melanoma in Chinese patients: long-term follow-up. Curr Eye Res 2017;42:759-65. Crossref
28. Virgili G, Gatta G, Ciccolallo L, et al. Survival in patients with uveal melanoma in Europe. Arch Ophthalmol 2008;126:1413-8. Crossref
29. Shields CL, Shields JA, Gündüz K, et al. Conjunctival melanoma: risk factors for recurrence, exenteration, metastasis, and death in 150 consecutive patients. Arch Ophthalmol 2000;118:1497-507. Crossref
30. Tuomaala S, Eskelin S, Tarkkanen A, Kivelä T. Population-based assessment of clinical characteristics predicting outcome of conjunctival melanoma in whites. Invest Ophthalmol Vis Sci 2002;43:3399-408.
31. Missotten GS, Keijser S, De Keizer RJ, De Wolff-Rouendaal D. Conjunctival melanoma in the Netherlands: a nationwide study. Invest Ophthalmol Vis Sci 2005;46:75-82. Crossref
32. Shields CL, Kaliki S, Al-Dahmash SA, Lally SE, Shields JA. American Joint Committee on Cancer (AJCC) clinical classification predicts conjunctival melanoma outcomes. Ophthal Plast Reconstr Surg 2012;28:313-23. Crossref
33. Esmaeli B, Wang X, Youssef A, Gershenwald JE. Patterns of regional and distant metastasis in patients with conjunctival melanoma: experience at a cancer center over four decades. Ophthalmology 2001;108:2101-5. Crossref
34. Werschnik C, Lommatzsch PK. Long-term follow-up of patients with conjunctival melanoma. Am J Clin Oncol 2002;25:248-55. Crossref
35. Wang MM, Chen C, Lynn MN, et al. Applying single-cell technology in uveal melanomas: current trends and perspectives for improving uveal melanoma metastasis surveillance and tumor profiling. Front Mol Biosci 2021;7:611584. Crossref
36. Mor JM, Rokohl AC, Koch KR, Heindl LM. Sentinel lymph node biopsy in the management of conjunctival melanoma: current insights. Clin Ophthalmol 2019;13:1297-302. Crossref
37. van den Bosch T, Kilic E, Paridaens D, de Klein A. Genetics of uveal melanoma and cutaneous melanoma: two of a kind? Dermatol Res Pract 2010;2010:360136. Crossref
38. Gkiala A, Palioura S. Conjunctival melanoma: update on genetics, epigenetics and targeted molecular and immune-based therapies. Clin Ophthalmol 2020;14:3137-52. Crossref