An optimized 3T MRI scan protocol to assess iris melanoma with subsequent histopathological verification - A prospective study.

INTRODUCTION: Magnetic resonance imaging (MRI) has demonstrated high levels of tissue contrast, accuracy and reproducibility in evaluating posterior uveal melanoma. Owing to smaller size, the role of MRI in detecting and characterising iris melanoma has not yet been explored. AIMS: To develop a protocol to image iris melanoma and describe the MRI characteristics of histopathological-confirmed iris melanoma. MATERIALS AND METHODS: An optimised MRI protocol, using a 3T MRI scanner and a 32-channel head coil, was developed to image iris tumours. A prospective, single-centre, 12-month study was conducted on all patients with lesions suspicious for iris melanoma. All patients were offered an MRI scan in addition to the standardised clinical procedures. Image quality comparison was made with existing clinical investigations. Iris melanoma characteristics on MRI are described. RESULTS: A successful optimised MRI scan protocol was developed that was able to detect and characterise iris melanoma. One normal participant and five patients with subsequent histopathological-confirmed iris melanoma (n = 6) were recruited. Four patients completed the full MRI sequence. All iris melanoma were detected on at least one T1- or T2-weighted images. When compared to the vitreous, all iris melanomas demonstrated hyper-intensity on T1-weighted images and hypo-intensity on T2-weighted images. On T1-mapping, T1-values of iris melanoma demonstrated an inverse relationship with the degree of tumour pigmentation. CONCLUSIONS: This study highlights an optimised, easily reproducible MRI scan protocol to image iris melanoma. Numerous MR imaging characteristics of iris melanoma are reported for the first time and a potential non-invasive tumour biomarker is described.

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.

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 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.

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.

Iris melanocytoma and secondary glaucoma.

Iris melanocytoma (IM) is a rare variant of iris nevus with distinctive clinical and histopathological features. A 66-year-old woman, with a history of right eye pigmented iris nevus, presented to us with a recent onset of visual acuity decrease in that eye. She had a melanocytic iris lesion with iridocorneal angle invasion, peripheral corneal adhesion, pupil corectopia, sectorial cataract and high intraocular pressure. Ultrasound biomicroscopy did not exclude malignant transformation, so excisional biopsy was performed revealing the presence of IM without signs of atypia. Subsequently, the patient underwent cataract surgery combined with iridoplasty and later an ab externo trabeculectomy. Most cases of IM remain stable and require no intervention, but in cases of unusual clinical course, with rapid growth or secondary glaucoma, surgical treatment is indicated as a diagnostic and therapeutic measure. This case report highlights the importance of a timely and multidisciplinary ophthalmological approach for a better visual outcome.

Molecular profiling of vitreous fluid by massively parallel sequencing: a case series.

INTRODUCTION: In cases of suspected intraocular malignancy, vitreous may be the preferred pathologic sample; however, cellularity may be insufficient for definitive cytopathological diagnosis. Ancillary methodology to study vitreous fluid aspiration for mutational analysis may assist in treatment decisions. MATERIALS AND METHODS: Three individual patient vitreous humor samples were received in the laboratory for mutation testing. The samples were collected during standard of care and analyzed for routine cytopathology. In each case, cytopathology was inconclusive and mutational analyses to support diagnostic suspicions were clinically requested. Based on the clinically and pathologically suspected diagnoses, an appropriate massively parallel sequencing assay previously validated for clinical use was performed using DNA extracted from vitreous samples that had previously undergone various processing. Nucleic acid yield was assessed by fluorometric or spectrophotometric methods, with yield ranging from 2.7 to 86.5 ng. Library preparations were performed using standard laboratory protocols. RESULTS: Two of the cases were suspicious for melanoma and a 50-gene solid tumor panel was performed. The third case was worrisome for vitreoretinal lymphoma and a 49-gene myeloid panel was performed. CONCLUSIONS: In all cases, the molecular profiling assisted with the clinical assessment and/or management of each patient.

Whole genome landscapes of uveal melanoma show an ultraviolet radiation signature in iris tumours.

Uveal melanoma (UM) is the most common intraocular tumour in adults and despite surgical or radiation treatment of primary tumours, ~50% of patients progress to metastatic disease. Therapeutic options for metastatic UM are limited, with clinical trials having little impact. Here we perform whole-genome sequencing (WGS) of 103 UM from all sites of the uveal tract (choroid, ciliary body, iris). While most UM have low tumour mutation burden (TMB), two subsets with high TMB are seen; one driven by germline MBD4 mutation, and another by ultraviolet radiation (UVR) exposure, which is restricted to iris UM. All but one tumour have a known UM driver gene mutation (GNAQ, GNA11, BAP1, PLCB4, CYSLTR2, SF3B1, EIF1AX). We identify three other significantly mutated genes (TP53, RPL5 and CENPE).

Iris biopsy to investigate feline iris hyperpigmentation.

OBJECTIVE: To evaluate the benefit of iris biopsy in cats with iris hyperpigmentation to differentiate melanosis from early feline diffuse iris melanoma (FDIM). METHODS: The medical records of cats with unilateral iris hyperpigmentation that had undergone iris biopsy between February 2013 and September 2016 at Willows Veterinary Centre & Referral Service were reviewed. RESULTS: Seven cats with unilateral iris hyperpigmentation were included in this retrospective study. The biopsy procedure was performed under general anesthesia (n = 7) with neuromuscular blockade (n = 6) following pre-operative topical miotic therapy (n = 5). One to six biopsy samples per eye were harvested from areas of hyperpigmentation. The samples were partial thickness (n = 4 eyes) and full thickness (n = 3 eyes). Complications were minor: mild intra-operative hemorrhage (n = 4), fibrin clot (n = 2), corneal ulcer (n = 1), post-operative ocular hypertension (n = 1), dyscoria (n = 1), and pseudopolycoria (n = 2). The first biopsy was diagnostic in six cats; a repeat biopsy was necessary in one cat. Histopathology was consistent with melanosis in five cats and with early FDIM in two cats. Screening for signs of metastatic disease (thoracic computed tomography and abdominal ultrasonography) was negative in the two cats with a preliminary diagnosis of early FDIM. Subsequent enucleation and histopathology confirmed the initial diagnosis in both cases. CONCLUSIONS: Iris biopsy in cats with iris hyperpigmentation can be beneficial to differentiate melanosis from early FDIM and thereby help to justify the decision for early enucleation.

Intravitreal air bubble during exoresection of an iris-ciliary body melanoma.

In this manuscript, as members of a National Reference Unit in Ocular Oncology, we present succinctly our preferred surgical technique for iris-ciliary body melanomas. We attach a video describing the steps we usually follow [Video Clip 1], in which an impressive image of an intravitreal air bubble through the hyaloid membrane can be observed [Fig. 1].

Neuroblastoma of the Iris in Children.

Neuroblastoma of the iris is an extremely rare clinical entity. An otherwise healthy 2-month-old male infant presented to the oncology clinic with a nodular whitish iris lesion in his right eye. The excisional tumor biopsy was consistent with a pathological diagnosis of neuroblastoma with differentiation and negative MYCN gene mutation. Further systemic evaluation revealed a right adrenal mass with no metastatic lesion. The biopsy of the adrenal lesion was also consistent with neuroblastoma. After four courses of chemotherapy, the adrenal mass was completely resected. The patient underwent two additional courses of postoperative chemotherapy and continued retinoic acid treatment. The patient is under regular follow-up with no evidence of recurrence 36 months after the initial diagnosis. This is the first case report to present a histopathological verification of neuroblastoma of the iris. The authors suggest that neonates and infants who are diagnosed as having neuroblastoma undergo an ophthalmologic examination after the initial diagnosis to investigate the true incidence of small iris lesions in neuroblastoma that may have been unrecognized. Neuroblastoma should be included in the differential diagnosis of amelanotic iris lesions in infants and young children. [J Pediatr Ophthalmol Strabismus. 2019;56:e12-e16.].