No differences in the long-term prognosis of iris and choroidal melanomas when adjusting for tumor thickness and diameter.

OBJECTIVE: To assess the long-term prognosis for patients with iris melanomas and compare it with the prognosis for small choroidal melanomas. DESIGN: Retrospective observational case series. METHODS: All patients treated for iris melanomas at a single referral institution between January 1st 1986 and January 1st 2016 were included. Patients treated for small choroidal melanomas during the same period were included for comparison. The cumulative incidence of melanoma-related mortality was calculated. Patient and tumor characteristics and size-adjusted hazard ratio (HR) for melanoma-related mortality were compared between iris and small choroidal melanomas. RESULTS: Forty-five iris melanomas and 268 small choroidal melanomas were included. Twenty-four iris melanomas (53%) had been treated with local resection, 12 (27%) with Ruthenium-106 brachytherapy, 7 (16%) with enucleation and 2 (4%) with proton beam irradiation. Twenty-one (68%), 7 (16%) and 2 (4%) of the iris melanomas were of the spindle, mixed and epithelioid cell types, respectively. Twenty-three patients had deceased before the end of follow-up. Median follow-up for the 22 survivors was 13.3 years (SD 9.4). Patients with iris melanomas were more often asymptomatic at presentation and had a trend towards significantly lower age (59 versus 63 years, Student's T-tests p = 0.057). Further, iris melanomas had significantly smaller basal diameter (5.8 versus 8.0 mm, p < 0.0001) and tumor volume (79 mm3 versus 93 mm mm3, p < 0.0001) but greater thickness (3.0 versus 2.5 mm, p < 0.0001). The cumulative incidence of iris melanoma-related mortality was 5% at 5 years after diagnosis, and 8% at 10, 15 and 20 years. The incidence was not significantly different to small choroidal melanomas (Wilcoxon p = 0.46). In multivariate Cox regression with tumor diameter and thickness as covariates, patients with choroidal melanomas did not have increased HR for melanoma-related mortality (HR 2.2, 95% CI 0.5-9.6, p = 0.29). Similarly, there were no significant survival differences in matched subgroups (Wilcoxon p = 0.82). CONCLUSIONS: There are no survival differences between iris and choroidal melanomas when adjusting for tumor size. The reason for the relatively favorable prognosis of iris melanomas compared to melanomas of the choroid and ciliary body is likely that they are diagnosed at a smaller size.

Uveal melanoma-associated survival in Scotland.

BACKGROUND/OBJECTIVES: The Scottish Ocular Oncology Service (SOOS) manages all patients with uveal melanoma (UM) in Scotland. Our aim was to determine the long-term all-cause and cause-specific survival of patients with UM, irrespective of treatment modality. SUBJECTS/METHODS: A retrospective single-centre cohort study including all patients diagnosed with UM by the SOOS between 1/1/1998 and 31/12/2002. Data from the SOOS database were correlated with death records held by National Records of Scotland, which provided date, and all listed causes, of death for all deceased patients. RESULTS: Two hundred and eighteen patients were newly diagnosed with UM between 1/1/1998 and 31/12/2002. One hundred and fifteen (52.8%) were female. The mean (median) age at diagnosis was 63(65) years (range: 16-89). Of 179 choroidal melanomas, melanoma-specific survival was 92.3%, 87.4% and 83.8% at 5, 10 and 15 years, respectively. Cancer-specific survival was 85.8%, 71.8% and 62.3%. All-cause survival was 81.6% (146/179), 62.0% (111/179) and 46.7% (computed, fraction inexpressible). Of 26 ciliary body melanomas, melanoma-specific survival was 87.2%, 81.3% and 81.3% at 5, 10 and 15 years. Cancer-specific survival was 62.9%, 40.6% and 40.6%. All-cause survival was 61.5% (16/26), 38.5% (10/26) and 26.9% (7/26). Of 13 iris melanomas, at all three timepoints (5/10/15 years), melanoma-specific survival was 100%, cancer-specific survival was 92.3%, and all-cause survival was 76.9% (10/13). CONCLUSIONS: Correlation of SOOS and national records survival data confirms 15-year melanoma-specific survival of 83.8%, 81.3% and 100% for choroidal, ciliary body and iris melanomas, respectively. We can now provide accurate survival data to our patients in Scotland.

Conservative management of suspicious melanocytic lesions of the iris.

PURPOSE: The diagnosis of iris melanoma can be difficult, with no established diagnostic criteria currently available. Careful monitoring of patients with suspicious iris lesions is one approach to managing these tumors. We determined the risk of malignant transformation and melanoma-related mortality in patients under observation to evaluate the validity of this management approach. METHODS: This was a retrospective chart review of patients with suspicious iris lesions diagnosed at Massachusetts Eye and Ear Infirmary (MEE) between 1975 and 2014. All patients with an initial diagnosis of suspicious iris lesion followed and/or treated after malignant transformation at the MEE in this 39-year period were included in the cohort. Rates of malignant transformation and melanoma-related mortality were calculated. Treatment outcomes after proton beam irradiation were evaluated in patients who developed iris melanomas during observation. RESULTS: Two hundred thirty-four patients had a diagnosis of suspicious iris lesion (median follow-up, 5.8 years). Malignant transformation occurred in 16 (6.8%) patients with suspicious lesions during the observation period (median follow-up, 9.9 years). All patients diagnosed with iris melanomas were treated with proton beam irradiation (PBI). Complications after treatment included cataract (18.8%), secondary glaucoma (6.3%), and neovascular glaucoma (12.5%). Two of 16 patients (12.5%) who developed iris melanomas died of metastatic melanoma 32.6 months and 10 years after treatment with PBI. Both cases had been followed regularly to monitor for malignant transformation of their suspicious lesions (8.2 years and 3.2 years before melanoma diagnosis, respectively). CONCLUSIONS: These data suggest that suspicious iris lesions have low malignant potential, and a conservative approach to the management of these lesions is appropriate. Survival does not appear to be compromised with an observational approach, and there is potential for preservation of good visual function because vision-threatening treatments can be avoided.

Use of Ruthenium-106 Brachytherapy for Iris Melanoma: The Scottish Experience.

PURPOSE: To analyse long-term outcomes of ruthenium-106 (106Ru) plaque brachytherapy for the treatment of iris melanoma. METHODS: We retrospectively reviewed medical records of 19 consecutive patients with pure iris melanoma treated with 106Ru plaque brachytherapy between 1998 and 2016 at the Scottish Ophthalmic Oncology Service, Glasgow. The iris melanoma was treated with a ruthenium plaque placed on the corneal surface to deliver a surface dose of 555 Gy. We analysed vision preservation, local tumour control, radiation-related complications, eye retention rates, symptomatic metastasis and melanoma-related mortality. RESULTS: The mean largest basal diameter of the lesions was 3.50±1.42 mm (range 1.6-6.5 mm), and the mean maximum height was 1.47±0.65 mm (range 0.7-2.8 mm). The tumour control and eye retention were 100% at a mean follow-up of 62 months (range 6-195 months). A 62% reduction in tumour height was observed on ultrasonography. Complications included cataract (68%), dry eye (47%), uveitis (37%) and scleral thinning (5%). At the final follow-up visit, the mean loss of Snellen visual acuity was 1.11±2.90 lines and vision of 6/9 or better was maintained in 53% of patients. None of the patients had evidence of symptomatic metastasis (non-imaged) or melanoma-related mortality. CONCLUSIONS: 106Ru plaque treatment for iris melanoma was highly effective a high tumour control, no tumour recurrences and a relatively a low complication rate.

[Uveal and iridociliary melanomas in young patients : A retrospective analysis of 57 cases]. / Aderhaut- und Ziliarkörpermelanome bei jungen Patienten : Eine retrospektive Analyse von 57 Fällen.

BACKGROUND: Uveal melanomas (UM) are rare malignancies in young patients. It is unknown if UM in young patients significantly differs from those in older patients concerning tumor size and localization, metastasis and genetics. The aim of this study was to evaluate the clinical course and tumor characteristics in young patients with UM. MATERIAL AND METHODS: All patients with UM below the age of 32 years who had been treated at our hospital were included in the study. Patient age and sex, duration of symptoms, visual impairment, tumor size and location, genetics, therapy, follow-up interventions and tumor-associated deaths were documented. RESULTS: A total of 57 patients (67 % male, mean age 24.7 years) were included in the study with an average symptomatic course of 5 months. Of the patients 8 (14 %) had an initial visual acuity of ≥ 0.9, 16 (28 %) 0.5-0.8, 22 (39 %) 0.05-0.4 and 9 (16 %) < 0.05 (no data for 2 patients, 4 %). After therapy visual acuity was < 0.05 in 54 % and 53 % of the tumors were choroidal UM (70 % juxtapapillary/circumpapillary), whereas 47 % were ciliochoroidal (54 % with iridociliary involvement). The average tumor size was 12.7 ± 3.6 mm with an average prominence of 6.2 ± 3.2 mm. Genetic evaluation (n = 16) revealed disomy 3 in 64 % and 54 % of the patients received radiotherapy with local application of ruthenium 106. In 46 % of cases follow-up interventions were neccessary including 70 % due to radiogenic retinopathy. CONCLUSION: In young patients UM did not show any preferred localization. The majority of genetically evaluated tumors revealed disomy 3 with no significant correlation to tumor location. Independent of tumor size, location and therapy, approximately half of the patients needed follow-up interventions, predominantly due to radiogenic retinopathy.

Iris melanoma: features and prognosis in 317 children and adults.

PURPOSE: To evaluate iris melanoma in children versus adults. METHODS: Retrospective, nonrandomized clinical case series including all patients with a clinical diagnosis of iris melanoma managed at the Ocular Oncology Service at Wills Eye Institute over 40 years. Patients were divided into three age categories based on age at presentation: children (≤ 20 years), mid-adults (21-60 years), and older adults (>60 years). The clinical features, treatments, and outcomes were statistically analyzed based on patient age at presentation. The main outcome measures were melanoma features and related metastasis and death. RESULTS: Of 8,101 eyes with uveal melanoma, there were 317 (4%) with iris melanoma, including 24 (8%) children (≤ 20 years), 187 (59%) mid-adults (21-60 years), and 106 (33%) older adults (>60 years). There was no age-related difference in race, sex, tumor quadrant, thickness, pigmentation, associated corectopia, ectropion uveae, hyphema, or extraocular extension. Significant age-related differences were found with mean tumor basal diameter, tapioca appearance, mean intraocular pressure, secondary glaucoma, tumor seeding in angle, and mean number of clock hours of angle seeding. Multivariate analysis of factors predictive of metastasis included extraocular extension and high intraocular pressure. Factors predictive of death included increased tumor thickness and high intraocular pressure. There was no difference in metastasis or death by age group. CONCLUSIONS: Iris melanoma shows significant clinical differences in children versus adults, with smaller tumor size, less tumor seeding in angle, and lower incidence of secondary glaucoma. There was no significant difference in metastasis or death by age group.

Surgical treatment of iris and ciliary body melanoma: follow-up of a 25-year series of patients.

PURPOSE: To evaluate outcome of surgical resection of iris and irido-ciliary melanomas. METHOD: Retrospective analysis of all cases treated in Denmark 1975-1999 with clinical follow-up in 2002 and death certificate analysis in 2008. A quality of life questionnaire was completed at follow-up. RESULTS: A total of 53 patients were identified. Of these, 47 were examined at follow-up. Median observation time was 7.15 years (range 0.3-27.4 years). Five patients had died of nonmelanoma causes, and one could not be reached because of immigration. None of the patient had melanoma metastases, and none had died of melanoma-related causes. Only one patient had a local recurrence, which was successfully treated by cryotherapy. The quality of life-related questions demonstrated that most patients (40) suffered from photophobia, and eight patients had changed their driving habits, not driving at night time. However, none had changed job as a consequence of the surgical treatment. Only two patients were emotionally affected by the diagnosis of iris melanoma. CONCLUSION: Resection of small iris and irido-ciliary melanomas is a safe and efficient procedure, provided that strict diagnostic and surgical procedures are followed and the preoperative intraocular pressure is normal.

[Long-term results of iridocyclectomy for iris tumours]. / Langzeitergebnisse nach Iridozyklektomie bei Iristumoren.

BACKGROUND: The aim of this study was to evaluate the long-term survival rate and functional results after iridocyclectomy. PATIENTS AND METHOD: Between 1980 and 2002 39 patients (26 female and 13 male) ranging in age from 20 to 79 years (median m = 58 years) underwent iridocyclectomy for a tumour of periphery iris by means of a lamellar technique or by trepanating. Follow-up time ranged from 3 months to 24 years (m = 11.2 years). RESULTS: In 21 cases (54 %) there was a malignant tumour including 20 melanomas (mostly spindle-cell and mixed-cell melanomas) and one filiae of a bronchial carcinoma. There was a variety of histopathological entities in the 18 benign lesions (46 %). Naevi were the most frequent. The outcome was satisfactory: 57 % of the patients kept a visual acuity of > 0.5. Three eyes had to be enucleated. The rate of recurrence was 10 % (4 cases). The Kaplan-Meyer estimate for the 10-year-survival of the patients with a malignant iris tumour was 77 %. Two patients died of metastic melanoma following spindle-cell and mixed-cell melanoma. CONCLUSION: The long-term functional results after Iridocyclectomy are good, whereas complications and recurrences are rare. The 10-year-survival is high. Over a long period iridocyclectomy is a recommendable surgical procedure for removal of progredient tumours of the anterior uvea.

Iris melanoma.

The iris is the least common site of primary uveal melanoma. The prognosis of iris melanoma is better than that of melanoma of the ciliary body and choroid, but the reason for this difference is unclear. One possible explanation is that iris melanoma is smaller than its posterior segment counterparts at the time of diagnosis. Most iris melanomas are spindle cell types, according to a modified Callender classification system. There is evidence that the proliferation of melanocytes of the anterior iris surface (iris plaque) and diffuse stromal invasion may be risk factors for local recurrence and metastasis, respectively.

Malignant melanomas of the iris.

The recognition of iris melanoma is important because a number of benign lesions clinically resemble these tumors. In this article, the epidemiological, clinical and histopathological features, treatment modalities, and prognosis of 41 iris melanoma patients, seen between 1964 and 1996 were evaluated. Of the patients, 20 were men and 21 women. Their mean age was 44.6 years. After determining the size, localization, and extension of the tumor, the management of choice was observation in 9, sector iridectomy in 15, iridocyclectomy in 6 and enucleation in 11 of the patients. During the follow-up, enucleation was also required in 6 and iridocyclectomy in 1 of the 7 patients who were in the observation or sector iridectomy group initially. Histopathologic examination revealed spindle cell in 27, mixed cell in 6 and epithelioid cell type melanomas in 2 of the 35 cases who underwent iridectomy, iridocyclectomy, and/or enucleation. The mean follow-up was 3.2 years and the mortality rate was found to be 2.4% during this period. One patient who died of metastases had epithelioid cell type melanoma.

Block excision of tumors of the anterior uvea. Report on 68 consecutive patients.

PURPOSE: This study describes the authors' surgical technique and the results in 68 consecutive patients with tumors of the iris and ciliary body involving the angle removed by block excision and tectonic corneoscleral grafting between 1980 and 1995. PATIENTS AND METHODS: There were 41 (60.3%) women and 27 (39.7%) men whose ages ranged from 14 to 85 years (median, 41 years). Follow-up ranged from 0.5 to 15.2 years (median, 6.3 years). Tumors of the iris and ciliary body with chamber angle involvement were removed with a modified block excision consisting of simultaneous en bloc removal of the tumor with adjacent iris and cornea and sclera in full-thickness. The resulting defect of 6 to 20 mm (median, 9.0 mm) diameter is covered with a tectonic corneoscleral graft. RESULTS: Forty-nine tumors (72.1%) were classified as malignant tumors of the iris and ciliary body. Twenty-one (44.7%) of 47 malignant melanomas showed histologic evidence of scleral invasion of more than one third of scleral thickness. Extrascleral extension of the tumor was present in seven (14.9%) patients with malignant melanomas and in four (21.1%) patients with benign tumors of the iris and ciliary body. The 10-year survival probability of patients with malignant melanomas was 91.4%. The main intraoperative complication was vitreous hemorrhage in 24 (35.3%) patients, and the main postoperative complication was complicated cataract, occurring in 22 (32.3%) patients. Two local tumor recurrences (2.9%) were observed. Four eyes (5.8%) had to be enucleated after block excision. Best-corrected postoperative visual acuity was better than 20/60 in 36 (52.9%) patients. CONCLUSIONS: The authors' results indicate that block excision with tectonic corneoscleral grafting may be the treatment of choice for progressive circumscribed tumors of the iris and ciliary body involving the anterior chamber angle up to 150 degrees of its circumference.

Neonatal hepatoblastoma metastatic to the choroid and iris.

A newborn boy was diagnosed with hepatoblastoma after a systemic workup was prompted because of abnormal-appearing eyes. Radiological examination revealed mass lesions involving the liver, brain, eyes, and ribs. A liver biopsy was performed before death and results showed hepatoblastoma, an unusual solid tumor of childhood. At autopsy, hepatoblastoma was also found histopathologically in the irides and choroid of both eyes. No previous report of hepatoblastoma metastatic to the eye could be found in the medical literature. In addition, we believe this is the first report in a child of a solid tumor metastatic to the choroid and iris, and of a solid tumor metastatic to the iris that is confirmed histopathologically.

Malignant melanoma of the iris. A 25-year analysis of Danish cases.

This study examined malignant melanoma of the iris in Denmark over a 25-year period on the basis of the files of the Eye Pathology Institute. From 1961 to 1985 a total of 80 cases were found (41 males, 39 females; median age 53 years, range 8-83). This means an average of 3.2 cases/year with an average population of 4.9 million. In contrast to malignant melanoma of the choroid, an increase was observed. The reason is not known, although exposure to actinic rays may be a factor. More than a third of cases were close to the pupil, a little less than a third invaded the chamber angle/ciliary body. Ten cases were ring melanomas. Half of the tumours were spindle-celled, a quarter mixed and a few epithelioid or naevoid in cell morphology. Iridectomy was performed in 28 cases, primary enucleation in 27 and secondary enucleation in ten. Iridocyclectomy was performed in 15 cases. All patients could be traced. At the date of follow-up (Dec. 1, 1991) eight had died with metastases; four of these were patients with ring melanoma and four with tumours invading the ciliary body. After iridocyclectomy, only one metastatic death was recorded--a case of incomplete resection. The grave prognosis of a ring melanoma is highlighted.

The efficacy of radiotherapy in the treatment of intraocular metastases.

From January 1980 to May 1991, 28 patients with intraocular metastases were seen at our Institute. Three presented with bilateral metastases and two developed contralateral involvement. Out of the 33 ocular metastases 27 were managed by radiotherapy. The most common primary tumour sites were breast (18/28 patients) and lung (3/28). 22 patients were treated with an 8 MV linear accelerator, using a 4 x 4 cm anterior direct field. The median dose was 40 Gy/20 fractions (range 28 Gy/14 fractions to 50 Gy/25 fractions). Of the 27 treatments reported, 16 resulted in a complete response (59%), six in a partial response (22%) and five resulted in no change (19%). Complete and partial responses lasted for a median time of 13 months (range of 3-89+ months). The median survival time from the start of ocular treatment was 13 months. The aim of radiation treatment is either to prevent or to postpone the visual loss caused by intraocular metastases.

Uveal melanoma in teenagers and children. A report of 40 cases.

A review of 3706 consecutive patients with uveal melanoma revealed that 40 patients (1.1%) were age 20 years or younger at the time of diagnosis. The youngest patient was age 6 years but the majority of patients (78%) were between 15 and 20 years old. The tumor occurred in the iris in 5 cases (12%) and in the posterior uvea in 35 cases (88%). The mean largest tumor dimension and thickness was 10 mm and 5 mm, respectively. In all cases, the diagnosis of uveal melanoma was suspected before referral, and misdirected treatment was avoided. The tumor was initially treated by enucleation in 24 cases (60%), local resection in 7 (18%), plaque radiotherapy in 3 (8%), and observation in 6 (15%). Secondary treatment was required in 7 cases in the form of enucleation (4 cases), ablative laser (1 case), plaque radiotherapy (1 case), and exenteration (1 case). The mean follow-up period was 68 months (median, 48 months) from the time of treatment, and only one patient died of metastases (from a massive ciliochoroidal melanoma 33 months after treatment). The remainder of the group of young patients are alive and healthy. Cumulative survival rates show that 96% of young patients with uveal melanoma survive at the 5-year period.

[Results of surgical treatment for anterior uveal malignant melanoma]. / Wyniki leczenia operacyjnego czerniaków przedniej jagodówki.

The authors observed for 5 to 18 years 41 patients (22 women and 19 men) with malignant iris melanoma and/or malignant melanoma of ciliary body. The age of the patients was 20 to 80 years. All patients underwent surgical treatment with preservation of the eye ball. In 21 cases iridectomy, in 18 cases iridocyclectomy, and in the remaining cases iridocyclectomy-choroidectomy was performed. In 25 eyes the tumour occupied less than 1/4, and in 16 eyes between 1/4 and 1/2 of the iris circumference. During the period of observation 7 eye balls were enucleated, and in 6 recidivation of the tumour was diagnosed. These patients belonged to the group of 18 people with the tumour occupying the iris and the ciliary body, or the ciliary body only. Mortality in this group was 28%. Among 5 patients who died, in 3 the tumour occupied more than 1/4 of the iris circumference. In 3 patients from this group recidivation was diagnosed, in 4 enucleation was necessary. In 4 eyes secondary glaucoma was diagnosed. Therefore, among risk factors one ought to list size of the tumour, recidivation, and secondary glaucoma. On the other hand infiltration of the sclera and of the optic nerve was found only in one deceased person. The authors have not been able to obtain current information about 2 patients. In the whole studied group mortality was 5 out of 39, that is 12.8%. The most common complication during the surgery was hemorrhages. Two other complications: complicated cataract, usually stationary, and secondary glaucoma occurred both before and after treatment. Despite of complications 68.3% of patients maintained good visual acuity.