Clinical Spectrum of Uveal Metastasis in Korean Patients Based on Primary Tumor Origin.

PURPOSE: To describe the clinical features and prognosis of patients with uveal metastasis in Korea. DESIGN: Retrospective, observational case series. PARTICIPANTS: Patients diagnosed at 2 tertiary high-volume centers between November 2005 and November 2019. METHODS: Evaluation of multimodal imaging and electronic medical records. MAIN OUTCOME MEASURES: The clinical features and outcomes were assessed based on the primary cancer site. RESULTS: A total of 134 uveal metastases (128 choroidal, 3 iris, and 3 ciliary body tumors) were diagnosed in 95 eyes of 80 patients. Mean age at diagnosis was 56 years (median, 55 years; range, 24-86 years), with a minor preponderance of women (61%). Tumors were bilateral in 15 patients (19%) and the primary origin was established in 49 patients (61%) before ocular detection. The primary tumor originated in the lung (48%), breast (24%), gastrointestinal tract (10%), liver (3%), pancreas (3%), kidney (1%), cervix (1%), and nasopharynx (1%), with some remaining unknown (10%). The overall 5-year survival rate was 21%. Kaplan-Meier analysis revealed that the worst survival was found in pancreatic cancers (mean survival, 5.9 months; P = 0.045), and the best survival was found in gastrointestinal tract cancers (mean survival, 44.5 months). CONCLUSIONS: The primary tumor origins in Korean patients with uveal metastases differed from those reported in primarily population-based studies of White patients, with a higher prevalence of lung and gastrointestinal tract cancers.

Melanoma of the eye: revealing hidden secrets, one at a time.

Melanoma of the eye can involve the uveal tract with iris, ciliary body, or choroid involvement or it can involve the conjunctiva, eyelid, or orbit. Uveal involvement with choroidal melanoma is the most common, found in light complexion Caucasians with an age-adjusted incidence of 4.3 per million persons. Early detection of uveal melanoma is critical. The ABCDEF guide helps to differentiate iris nevus from iris melanoma. The letters represent: A, age young (≤40 years); B, blood in anterior chamber; C, clock hour of mass inferiorly; D, diffuse configuration; E, ectropion; and F, feathery margins. The mnemonic of TFSOM-UHHD (To Find Small Ocular Melanoma-Using Helpful Hints Daily) helps to differentiate choroidal nevus from small melanoma and represents: T, thickness over 2 mm; F, fluid; S, symptoms; O, orange pigment; M, margin within 3 mm of the optic disc; UH, ultrasound hollow; H, halo absent; and D, drusen absent. Patients with 3 or more of these factors are likely to have melanoma. These key clinical features help to identify small melanoma at a time when therapy could be life-saving. Conjunctival melanoma usually arises from primary acquired melanosis, a flat pigmentation that can lead to melanoma. Wide excision using no touch strategy is important to tumor control. Ocular examination is advised annually for all persons for detection of refractive error, cataract, glaucoma, and other conditions, but also for the detection of asymptomatic malignancies like melanoma. One at a time, we have uncovered the secrets of ocular melanoma and we forge ahead with the goal to solve the riddle of this challenging disease.

Iris metastasis from systemic cancer in 104 patients: the 2014 Jerry A. Shields Lecture.

PURPOSE: To describe the clinical features, treatment, and outcome of patients with iris metastasis. METHODS: Retrospective case series of 160 tumors in 107 eyes of 104 patients with iris metastasis from systemic cancer. RESULTS: The median age at presentation with iris metastasis was 60 years. Iris metastasis was more common in whites (n = 93, 89%) and women (n = 65, 62%). The primary tumor was located in the breast (n = 34, 33%), lung (n = 28, 27%), skin (melanoma) (n = 13, 12%), kidney (n = 7, 7%), esophagus (n = 3, 3%), and others (n = 19, 19%). The main symptoms were pain (n = 33, 32%) or blurred vision (n = 31, 30%). The main findings were corectopia (n = 38, 37%) and secondary glaucoma (n = 38, 37%). The metastasis was unifocal (n = 84, 78%) or multifocal (n = 23, 21%) for a total of 160 tumors. The main tumor was centered at the iris root (n = 72, 69%), midzone (n = 22, 21%), or pupillary margin (n = 10, 10%), with median tumor diameter of 5 mm. Coexistent conjunctival or ciliary body/choroidal metastases were found in 39 patients. Management of iris metastasis included systemic chemotherapy (n = 18, 22%), external beam radiotherapy (n = 34, 41%), plaque radiotherapy (n = 20, 24%), surgical excision (n = 4, 5%), enucleation (n = 3, 4%), or observation (n = 4, 5%). Following treatment, tumor control without recurrence was achieved in 95% cases. In 98 cases with adequate follow-up information, death occurred in 85 (87%) at median 10 months (range, <1-239 months) from the date of iris metastasis. CONCLUSIONS: Metastatic tumors to the iris generally originate from primary malignancies in the breast, lung, or skin (melanoma). Despite successful ocular treatment, life prognosis is poor.

Eye disorders in neurofibromatosis (NF1).

Neurofibromatosis type 1 (NF 1) is an autosomal dominant disorder with high index of spontaneous mutations and extremely varied and impredictible clinical manifestations. The aim of this work was to give an account of eye disorders in NF1. 132 patients of age 0-16 years with NF1 were followed up for 15 years. They were checked repeatedly for ophthalmologic disorders. Frequent eye disorders were: Lisch nodules (Iris hamartomas, IH) 78%, hyperthelorism 19.7%, bulbomotoric disorders 15.9%, disorders of the optic disc 16.7% and optic gliomas (18.9%). The highest incidence of eye disorders by NF1 patients showed Lisch nodules (IH). Its ease of clinical recognition and if present with other diagnostic signs (for instance café au lait patches) could be deemed as reliable diagnostic criterion of NF1 in childhood.

Characteristics of Lisch nodules in patients with neurofibromatosis type 1.

PURPOSE: To assess the prevalence and location of Lisch nodules among patients with neurofibromatosis type 1. PATIENTS AND METHODS: This was a prospective observational case series in which 369 consecutive patients from a neurofibromatosis clinic participated. Predetermined inclusion and exclusion criteria were applied to these participants. The presence of Lisch nodules was determined by one of the authors (SMC). The percentage of patients with neurofibromatosis type 1 with Lisch nodules was calculated. Lisch nodules were characterized as being distributed superiorly, inferiorly, or equally in each eye. The percentage of eyes in each group was ascertained. RESULTS: Among patients of all ages with neurofibromatosis type 1, 63.2% had Lisch nodules, whereas 92% of postpubertal patients had Lisch nodules. Among eyes with Lisch nodules, 80% had an inferior distribution. CONCLUSIONS: This study corroborated previously reported data regarding the prevalence of Lisch nodules in patients with neurofibromatosis type 1 and found that Lisch nodules were predominantly located inferiorly on the iris. The authors propose that exposure to sunlight may be the mechanism for this distribution of hamartomatous nodules.

Iris melanoma in a patient with neurofibromatosis.

Neurofibromatosis type 1 (NF1) is a common autosomal dominant hamartomatous disorder, which is considered to be a neurocristopathy. Uveal melanoma, also of neural crest origin, is the most common primary malignant intraocular tumor in adults. The association of NF1 and uveal melanoma is controversial. We present a clinicopathologic report of iris melanoma in a patient with NF1 and review the literature for a possible causal association. To our knowledge, only 18 cases of uveal melanoma, including three cases of iris melanoma, have been reported in association with NF1. On the basis of the prevalence of NF1 (1 in 3000) and the prevalence of uveal melanoma (1 in 13,500), it can be estimated that approximately seven patients with NF1 in the United States would have an associated uveal melanoma by chance alone. We conclude that despite the theoretical possibility of a causal association of uveal melanoma and NF1, it may still be regarded as coincidental in the absence of any strong evidence to the contrary.

Risk of cutaneous melanoma in relation to the numbers, types and sites of naevi: a case-control study.

The atypical mole syndrome (AMS) phenotype, characterised by a large number of common naevi as well as atypical naevi, has been described in families with a genetic susceptibility to melanoma. However, the importance of this phenotype for melanoma in the general population has not been conclusively determined. This study was designed to examine the types and distribution of naevi as well as the prevalence of the AMS phenotype in melanoma patients in England compared with controls. A total of 426 cutaneous melanoma cases (61% of all incident cases) aged 16-75 years were recruited between 1989 and 1993 from the north-east Thames region of the UK and 416 controls from the same age group were recruited over the same period and from the same region. Each subject answered a questionnaire covering demographic details, sun exposure history and other risk factors and underwent a skin examination with total body naevus count performed by a dermatologist. The AMS phenotype was defined using a scoring system. Atypical naevi gave the highest relative risk for cutaneous melanoma, with an odds ratio (OR) of 28.7 (P < 0.0001) for four or more atypical naevi compared with none. Many common naevi were also an important risk factor: the OR for 100 or more naevi 2 mm or above in diameter compared with 0-4 naevi was 7.7 (P < 0.0001). Melanoma was also associated with naevi on sun-exposed sites but also with naevi on non-sun-exposed sites such as the dorsum of the feet, buttocks and anterior scalp. Sixteen per cent of the cases had the AMS phenotype compared with 2% of the controls (OR 10.4, P < 0.0001). The AMS phenotype was more common in males than females (P = 0.008). The odds ratio for the presence of the AMS phenotype was dependent on age, with an odds ratio of 16.1 (95% CI 4.6-57.5) for the presence of the AMS phenotype if aged less than 40 compared with an odds ratio of 6.9 (95% CI 2.9-16.6) if aged 40 or more. The AMS phenotype was strongly predictive of an increased risk of melanoma outside the familial context.

Risk of ocular melanoma in relation to cutaneous and iris naevi.

A case-control study was set up to assess the risk of eye melanoma in relation to the number and type of cutaneous melanocytic naevi and pigmented lesions of the iris. Cases comprised 211 unselected ocular melanoma patients attending the Ocular Oncology Clinic at Moorfields Eye Hospital, London, during November 1990 to October 1991 and diagnosed after August 1986. Hospital and general practice controls (416) were recruited in the North East Thames Region of the UK. Cutaneous naevi greater than or equal to 2 mm in diameter were counted on the skin. Clinically atypical and congenital naevi were recorded separately. Pigmented lesions of the iris were counted. The relative risk for ocular melanoma increased with numbers of atypical naevi and numbers of common naevi. Ten percent of cases but 3% of controls had at least 100 naevi of 2 mm or greater diameter. Seven percent of cases and 0.4% of controls had 4 or more atypical naevi. Pigmented lesions of the iris were significantly more common in cases than controls. Nine percent of cases had the Atypical Mole syndrome (AMS) phenotype compared with 1% of controls. Six cases had concurrent cutaneous melanoma primaries. We conclude that atypical and iris naevi are important risk factors for eye melanoma and that patients with eye melanoma are at increased risk of cutaneous melanoma. Dermatological examination for the AMS phenotype and cutaneous melanoma should be recommended in eye melanoma patients with large numbers of pigmented lesions of the skin or family history of melanoma.

Uveal metastasis from prostate carcinoma.

BACKGROUND: Although breast and lung cancers account for most metastatic tumors to the uvea, prostate carcinoma metastatic to the uvea is relatively rare. METHODS: The authors reviewed 379 consecutive patients with uveal metastasis referred to the Ocular Oncology Service at the Wills Eye Hospital to determine the frequency of prostate carcinoma as the primary neoplasm. RESULTS: Of 379 consecutive patients with uveal metastasis, the primary tumor was prostate carcinoma in 7 (2% of all patients, 5% of male patients). The mean age at ocular diagnosis was 66 years. In six patients (85%) a prior history of prostate carcinoma was known and the prior history of prostate carcinoma was known and the mean time interval between the diagnosis of the primary tumor and the uveal metastasis was 28 months. All seven patients were found to have active or regressed metastases elsewhere. The choroid was involved in six patients (85%) and the iris in one (15%). Ocular treatment included external-beam radiation therapy in five patients (70%) and episcleral radioactive plaque in two (30%). After a total mean follow-up of 84 months (range, 44-140 months) from the diagnosis of prostate carcinoma, two patients were still alive and five patients have died (mean, 6 months after diagnosis of uveal metastasis). CONCLUSIONS: Prostate carcinoma can metastasize to the uvea and the presence of uveal metastasis is associated with a shorter survival time compared with metastasis to other sites.

Images of Lisch nodules across the spectrum.

The presence of melanocytic hamartomas on the iris, known eponymously as Lisch nodules, is highly characteristic of neurofibromatosis type 1 (NF1). Early recognition of NF1 is vital for optimal detection of associated tumours and for genetic counselling of family members. Although the iris nodules are probably not visible at birth, their prevalence in patients with NF1 gradually increases from birth to about 50% of 5-year-olds, 75% of 15-year-olds and 95-100% of adults over the age of 30. Iris hamartomas in NF1 are elevated, pale brown lesions that vary in appearance depending on the underlying colour of the iris. Colour illustrations are shown in this article, enabling the clinician readily to differentiate hamartomas from other iris lesions.