Iris melanoma: Review of clinical features, risks, management, and outcomes.

Primary uveal melanoma is rare and affects approximately 8,000 persons per year worldwide. This malignancy can involve the iris, ciliary body, and choroid. Of these three structures, the iris is the least commonly affected site, representing only 4% of all uveal melanomas. Iris melanoma can arise from iris melanocytic nevus, iris melanocytosis, or de novo. In a longitudinal study of 1,611 patients with iris nevus, transformation into melanoma, using Kaplan-Meier estimates, was found in 2.6% by five years and in 4.1% by 10 years. The factors that predicted growth of iris melanocytic nevus into melanoma are denoted by a letter (ABCDEF) guide: A for age ≤40 years old at presentation (hazard ratio [HR] = 3, P = .01), B for blood (hyphema) (HR = 9, P < .0004), C for clock hour of tumor inferiorly (tumor location) (HR = 9, P = .03), D for diffuse flat tumor configuration (HR = 14, P = .02), E for ectropion uveae (HR = 4, P = .002), and F for feathery ill-defined margins (HR = 3, P = .02). At diagnosis, iris melanoma has a mean cross-sectional diameter of 5.5 mm and thickness of 2.1 mm, often with tumor seeding (28%) and secondary glaucoma (35%). We provide a comprehensive review of iris nevus and melanoma to explore relevant demographic and clinical data, risk factors for tumor growth, management, and prognosis, with the hope that clinicians will be more comfortable in understanding this rare malignant condition.

Side Effects of Proton Beam Radiotherapy Treatment on Iris Melanoma.

PURPOSE: This study evaluated the functional outcome and ocular side effects of patients receiving proton beam radiotherapy (PBR) for the treatment of iris melanoma (IM). DESIGN: This retrospective study analyzed prospectively collected data. PARTICIPANTS: Patients with IM who underwent PBR as a primary treatment. METHODS: Treatment was given in the form of whole PBR (wPBR: n = 51) or segmental PBR (sPBR: n = 98). MAIN OUTCOME MEASURES: Visual acuity (VA) and side effects were divided into ocular surface disease (OSD), secondary glaucoma, or cataract development. RESULTS: A total of 149 eyes of 149 patients with a mean age of 53.9 ± 16.0 years were included. Tumor recurrence developed in 3 patients (wPBR: 1/51; sPBR: 2/98). Ocular surface disease was observed in 78.4% of the wPBR group (40/51) and 25.5% of the sPBR group (25/98) (P < 0.001) after 0.7 ± 1.2 years and 1.1 ± 0.9 years, respectively. The main side effect was dry eye syndrome in both groups, but severe side effects such as limbal stem cell failure were found only in the wPBR group (4/51; 7.8%). Secondary glaucoma developed in 31.4% of the wPBR group (16/51) compared with 1.0% in the sPBR group (1/98; P < 0.001). Glaucoma control was generally achieved with eye drops, whereas surgery was necessary in 5 patients (wPBR: 4/51, 7.8%; sPBR: 1/98, 1%). Cataract surgery was performed in 47.9% of the wPBR group (23/48) and 19.8% of the sPBR group (19/96) (P < 0.001). Before treatment, VA was 0.14 ± 0.27 logarithm of the minimum angle of resolution (logMAR) in the wPBR group and 0.04 ± 0.19 logMAR in the sPBR group. A worsening was seen in the wPBR group (0.55 ± 0.16 logMAR; P < 0.001) 6 months after radiotherapy, which normalized after 12 months (0.15 ± 0.30 logMAR; P = 0.17). In the sPBR group, no such decrease in VA was observed (6 months: 0.03 ± 0.22 logMAR, P = 0.54; 12 months: 0.04 ± 0.21 logMAR, P = 0.98). CONCLUSIONS: Our results demonstrate that PBR is a very successful treatment option for patients with IM, showing a high tumor control rate and relatively low complication profile. Tumor recurrence was a rare event, and secondary enucleation was not necessary in any patient. Side effects are commonly seen, but severe side effects such as limbal stem cell failure or secondary glaucoma mainly developed after wPBR. These results are important for clinical decision making and discussion with the patient regarding this form of radiotherapy. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

A distorted pupil could be caused by an iris melanoma.

Melanoma isolated to the iris is rare and can present with a distorted pupil. This is a case report of an 81-year-old asymptomatic man, who had a large pigmented element in his left iris through 30 years. Because of involvement of the angle the tumour was excised with the ciliary body, and histopathologic examination revealed an iris melanoma. The aim of this report is to underscore the clinical signs of an iris melanoma and when surgery is needed.

Iris melanoma: Prognostication for metastasis.

Uveal melanoma prognostication studies have mainly included posterior uveal melanomas located in the ciliary body and choroid, often excluding iris melanoma. In this study, we report prognostic status and survival outcomes in a series of 35 patients with biopsy-proven iris melanoma. Fluorescence in situ hybridization was performed in 10 (29%) cases and 2 (5%) underwent multiplex ligation-dependent probe amplification. In total, 9 cases demonstrated disomy 3, 2 cases with monosomy 3 (fluorescence in situ hybridization), and 1 had a technical failure. On gene expression profile testing, 20 of the 23 cases (90%) were gene expression profile class 1A, and the remaining 3 (10%) were class 1B. No patient had a Class 2 status. The median follow-up period was 49 months (mean 59, range 2-156 months). No metastasis was reported during follow-up, and metastasis-free survival was 100%. A review of the published literature revealed 47 cases with high-risk status on molecular prediction, of which only 6 (13%) developed metastasis. Ciliary body involvement was reported in 5 cases and was unknown in 2 cases. We conclude that molecular prognostication of iris melanoma demonstrates low-risk prognostic status in the majority of cases irrespective of the technique used. Even those with high-risk status do not develop metastasis unless the tumor involves the ciliary body.

Proton Therapy for 166 Patients with Iris Melanoma: Side Effects and Oncologic Outcomes.

OBJECTIVE: To investigate the oncologic and functional outcomes of a large cohort of patients with a favorable stage of circumscribed and diffuse iris melanoma who underwent primary proton treatment and the risk factors related to initial tumor characteristics and the treatment field architecture. DESIGN: Retrospective, single-center, case study. PARTICIPANTS: We reviewed 225 patients with iris melanoma who were consecutively treated with proton beam therapy at our institution between 1998 and 2020. METHODS: We performed Kaplan-Meier time-to-event analyses and multivariate Cox proportional hazard analyses to identify the impacts of tumor characteristics and target volumes on oncologic and functional outcomes. MAIN OUTCOME MEASURES: We measured local tumor control, eye preservation rates, metastasis-free survival, cataract and glaucoma-directed surgery, intraocular pressure, and changes in visual acuity. RESULTS: Of the 192 patients with tumors confined to the iris (T1a-c) who underwent proton therapy as primary treatment, a total of 166 patients (mean age, 58.4 years; 88 women) with a minimum follow-up of 6 months were included. Multifocal or diffuse tumor spread was present in 77 (46.4%) patients. The median follow-up time was 54.0 (interquartile range, 27.4-91.8 months) months. Local recurrence occurred in 2 patients (1.2%) with circumscribed iris melanoma. Enucleation was a rare event (n = 5, 3%) and no patient developed metastatic disease. A large-treatment field (full aperture, involving > 10 clock hours) was identified as a risk factor for the development of secondary glaucoma (hazard ratio [HR], 6.3; P < 0.001) and subsequent surgical interventions (HR, 10.85; P < 0.001). The large-treatment field group showed a significant decline in visual acuity (logarithm of the minimum angle of resolution > 0.3; log-rank P < 0.0001), which was associated with secondary glaucoma (HR, 3.40; P = 0.002). CONCLUSIONS: Proton therapy provides an effective, noninvasive treatment option for patients with a favorable stage of iris melanoma. Irradiation of the anterior segment for up to 10 clock hours is associated with a low risk of the development of secondary glaucoma and vision loss. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Population-based incidence of intraocular tumours in Olmsted County, Minnesota.

BACKGROUND/AIMS: To determine population-based incidence of intraocular tumours in Olmsted County, Minnesota. METHODS: Record review of the Rochester Epidemiology Project medical record linkage system from 1 January 2006 to 31 December 2015 for patient demographics, tumour type by clinical diagnosis and presence or absence of confirmation by histopathology. The incidence rate of any intraocular tumour and of each tumour type was calculated per million person-years. Poisson regression analysis was used to analyse changes in incidence over time. RESULTS: There were 948 patients diagnosed with intraocular tumours resulting in an age-adjusted and sex-adjusted incidence rate of 727.5 per million (95% CI: 680.8 to 774.2, p<0.05). Most tumours were benign (953, 98%). Of the benign lesions, melanocytic lesions were the majority (942, 97%), with adjusted incidence rates of 646.9 (95% CI: 602.8 to 691.1) for choroidal nevus and 55.8 (95% CI: 43.2 to 64.8) for iris nevus. Malignant lesions were rare (16, 2%) with 13 cases of choroidal melanoma and 1 case each of iris melanoma, retinal leukaemic infiltration and metastasis. The adjusted incidence rate for choroidal melanoma was 7.1 (95% CI: 2.5 to 11.8). CONCLUSION: In a population-based setting, most intraocular tumours are benign and melanocytic. Although malignant lesions are less common, it is important to remain vigilant with appropriate monitoring given the potential for vision loss and life-threatening malignancy.

Focal choroidal excavation associated with nonmelanocytic iris tumor.

PURPOSE: To describe a unique unilateral association between an iris stromal tumor and a macular focal choroidal excavation. CASE DESCRIPTION: A 40-year old patient presented with a small iris tumor associated with a unilateral macular lesion disclosed during a routine ophthalmologic examination. The patient was asymptomatic and visual function was not affected. After clinical and instrumental evaluation, a diagnosis of nonmelanocytic undefined stromal tumor of the iris associated with macular focal choroidal excavation was made. The size and shape of the two lesions remained stable during a 7-year follow-up and the patient did not develop other signs. CONCLUSION: The concurrent presence of a stromal iris tumor associated with focal choroidal excavation has never been reported. Further reports of this association are required in order to understand its exact pathogenesis.

Iris melanocytic tumours in New Zealand/Aotearoa: presentation, management and outcome in a high UV exposure environment.

BACKGROUND/OBJECTIVES: Iris melanoma, a rare intraocular malignancy, represents the smallest subgroup of uveal melanoma. This first, comprehensive study of iris melanocytic lesions in the high ultraviolet environment in New Zealand/ Aotearoa (NZ) examines diagnosis, management and outcomes. SUBJECTS/METHODS: Retrospective study of iris melanocytic tumours referred to tertiary referral centres in Auckland, NZ, over 20 years (1999-2018). Data analysed include demographics, tumour characteristics, histology, genetic analyses, treatment modalities, recurrence, metastasis, 5-year and overall survival. RESULTS: Cohort (N = 51) was predominantly NZ European (98.0%) with no indigenous Maori, or Pasifika. Median age at presentation was 58 years. Tumours involved a median of two clock hours of iris. The posterior tumour margin extended to the anterior chamber angle in 22 patients (45.8%). Management included initial observation 54.9%, iridectomy/excision biopsy 29.4%, irido-cyclectomy 7.8%, plaque radiotherapy 7.8%, proton beam radiotherapy 7.8%, and ultimately enucleation 17.6%. Histology was performed in 19 cases (37%) with 16 confirmed melanomas (84%). Mean follow-up 4.2 years with median visual acuity of 6/7.5 two years post intervention. Melanoma-related metastasis and mortality occurred in two cases with five-year melanoma-related mortality of 2.0%. CONCLUSION: In a climate with high ultraviolet exposure iris melanocytic tumours occurred almost exclusively in NZ Europeans, however, the majority of cases were category T1, possibly reflecting early diagnosis in the NZ health system. Nonetheless, >50% underwent surgery or radiotherapy, often utilising more than one modality. A high index of suspicion and early referral of iris melanocytic lesions should be considered in regions with high UV exposure.

Iris melanoma: factors predictive of post-management secondary glaucoma in 271 cases at a Single Ocular Oncology Centre.

BACKGROUND/AIMS: To identify factors predictive of post-management secondary glaucoma in eyes with iris melanoma. METHODS: Patients with iris melanoma who were conservatively managed on the Ocular Oncology Service, Wills Eye Hospital from 1970 to 2016 were included. Charts were retrospectively reviewed, and binary logistic regression analysis was performed. Main outcome measures were factors predictive of post-management glaucoma, defined as intraocular pressure (IOP) > 22 mmHg following melanoma treatment. RESULTS: Of 271 patients with iris melanoma, melanoma-related glaucoma was identified in 40 (15%) at presentation and post-management glaucoma developed in 75 (28%) at a mean of 103.7 months (range:1.0-120.0). Comparison (post-management glaucoma vs. no glaucoma) revealed patients with post-management glaucoma presented with worse visual acuity (20/50-20/150) (17% vs. 5%, p = 0.001), increased mean tumour basal diameter (5.1 mm vs. 4.3 mm, p = 0.004), greater melanoma-related increased IOP on presentation (24.1 mmHg vs. 16.2 mmHg, p < 0.001), diffuse tumour shape (9% vs. 4%, p = 0.01), American Joint Committee on Cancer (AJCC) T4 category (7% vs. 2%, p = 0.03), and extraocular tumour extension (7% vs. 2%, p = 0.03). Risk factors for post-management glaucoma identified by multivariate analysis included melanoma-related increased IOP at presentation (OR:1.1, [1.08-1.22] per 1-mmHg increase, p < 0.001), increased mean tumour basal diameter (OR:1.17, [1.02-1.33] per 1-millimetre increments, p = 0.03), advanced AJCC clinical T subcategory (OR:1.23, [1.04-1.46] per 1-subcategory increments, p = 0.02) and plaque radiotherapy treatment (OR:2.32, [1.13-4.75], p = 0.02). CONCLUSION: Features of iris melanoma that predicted post-management glaucoma included melanoma-related increased IOP on presentation, advanced AJCC clinical T subcategory, increased mean tumour basal diameter, and plaque radiotherapy treatment.

IRIS METASTASIS FROM BREAST CANCER SUCCESSFULLY TREATED WITH ABEMACICLIB AND LETROZOLE.

PURPOSE: To describe a patient with an unusual presentation of iris metastasis from breast cancer and her response to systemic therapy. METHODS: Retrospective chart review of one patient. RESULTS: A 57-year-old woman presented with a superonasal translucent vascularized iris stromal mass with fish egg-like structures budding from the surface. High-frequency anterior segment ultrasonography demonstrated a solid iris stromal mass measuring 6.0 mm × 3.3 mm × 1.9 mm. On optical coherence tomography, the egglike structures appeared as hyperreflective spheres, some of which were detached from the main iris stromal tumor. Oncologic evaluation revealed metastatic breast cancer involving the brain and lung. She was treated with oral abemaciclib and letrozole, as well as external beam radiotherapy to the brain. The iris mass had completely regressed within 4 months and remained undetectable through the 8-month follow-up. The other metastatic lesions responded well to therapy. CONCLUSION: A case of iris metastasis was reported as the presenting sign of cancer dissemination that was successfully treated with targeted systemic therapy without ocular radiotherapy.

Iris melanoma outcomes based on the Cancer Genome Atlas (TCGA) classification in 78 consecutive patients.

BACKGROUND: The Cancer Genome Atlas (TCGA) classification of genetic alterations in uveal melanoma is widely used for prognostication. We present novel observations on the impact of TCGA Group specifically for iris melanoma. METHODS: This was a retrospective cohort study at a tertiary referral ocular oncology center. All patients with a diagnosis of iris melanoma who underwent genetic evaluation and assessment for TCGA classification between 20 November 1995 and 5 April 2021 were included. The main outcome measures were visual acuity, secondary glaucoma, tumor recurrence, melanoma-related metastasis and death per TCGA group. RESULTS: There were a total of 78 patients included. The mean patient age was 49.6 years (median 53.0, range 3.0-85.0), mean tumor basal diameter was 6.7 mm (median 6.0, range 1.5-22.0), and mean tumor thickness was 2.6 mm (median 2.5, range 0.5-8.5). Cytology results confirmed iris melanoma (93%) or were inconclusive (7%). The TCGA groups included Group A (n = 36, 46%), Group B (n = 7, 9%), Group C (n = 34, 44%), and Group D (n = 1, 1%). There was no statistically significant difference in outcomes of visual acuity, tumor thickness reduction, secondary glaucoma, tumor recurrence, melanoma-related metastasis or death per individual TCGA group (A vs. B vs. C vs. D) and per bimodal comparison (A/B vs. C/D). CONCLUSIONS: In this analysis, iris melanoma was classified as TCGA group A or B in 55% and as C or D in 45%. The TCGA classification was not predictive of melanoma-related metastasis or death.

[Lisch nodules: an ophthalmic marker of neurofibromatosis type 1]. / Nodules de Lisch: marqueur ophtalmologique de la neurofibromatose de type 1.

Von Recklinghausen disease or neurofibromatosis type I (NF1) is the most common phacomatosis. It is inherited in an autosomal dominant manner. Lisch nodules are the most common ophthalmic manifestation of NF1. They are reported in 73-95% of cases. We here report the case of a 49-year-old female patient referred for a consultation with an ophthalmologist for routine eye check-up after the onset of the following symptoms: coffee-with-milk colored spots and multiple neurofibromas (A). She reported similar family history. Visual acuity was 10/10 P2 in both eyes. Examination of the anterior segment showed several Lisch nodules in both irises. They were scattered over the entire iris surface and varied in size (B). Fundus examination was unremarkable. CT scan of the brain and the orbit as well as thoracoabdominal CT scan showed no associated lesion. The patient met NIH diagnostic criteria for NF1. Lisch nodules are small brown dome-shaped lesions developing on the surface of the iris, with well-defined edges, embedded in the stroma and lighter than iris pigmentation. Differential diagnosis includes iris mammillations, iris naevi, iris melanoma, iris granulomatous nodules. Unlike skin signs, the presence of multiple Lisch nodules are considered a specific indication of NF1. These nodules may occur in childhood and their prevalence and number increase with age. Thus, periodic eye examinations in subjects with suspected neurofibromatosis type I may help to improve early diagnosis.