Unilateral Glaucoma as a Clinical Indicator of Iris and Ciliary Body Melanoma

The most common malignant intraocular tumors with a high mortality in adults are uveal melanomas. Uveal melanomas arise most frequently in the choroid or ciliary body (97%) and rarely in the iris (3%). Whereas conjunctival and posterior uveal (ciliary body and choroidal) melanomas have been studied in more detail genetically, little data exist regarding iris melanomas. In our study, we genetically analyzed 19 iris melanomas, 8 ciliary body melanomas, 3 ring melanomas, and 4 iris nevi. A targeted next-generation sequencing approach was applied, covering the mutational hotspot regions of nine genes known to be mutated in conjunctival and uveal melanoma (BRAF, NRAS, KIT, GNAQ, GNA11, CYSLTR2, SF3B1, EIF1AX, and BAP1). Activating GNAQ or GNA11 hotspot mutations were detected in a mutually exclusive fashion in 84% (16/19) of iris melanomas. EIF1AX gene mutations also were frequent, detected in 42% (8/19) of iris melanomas. In 4 iris nevi, one GNAQ mutation was identified. GNAQ, GNA11, EIF1AX, and BAP1 mutations were identified at varying frequencies in ciliary body and ring melanomas. In this most comprehensive genetic analysis of iris melanomas published to date, we find iris melanomas to be related genetically to choroidal and ciliary body melanomas, frequently harboring GNAQ, GNA11, and EIF1AX mutations. Future studies will need to assess if screening mutation profiles in iris melanomas may be of diagnostic or prognostic value.

Cysts of the Iris Pigment Epithelium. What Is New and Interesting? The 2016 Jose Rizal International Medal Lecture.

Genetic Background of Iris Melanomas and Iris Melanocytic Tumors of Uncertain Malignant Potential

Management of iris melanoma with secondary glaucoma.

Purpose: To report the ultrasound biomicroscopy (UBM) findings of anterior segment tumors and simulating conditions. Methods: Thirty-five patients underwent UBM. Of those, 16 had histopathologically or cytopathologically diagnosed tumors, and 19 had clinically diagnosed lesions. Results: The study material comprised 13 iris pigment epithelial (IPE) cysts, 7 ciliary body melanomas, 4 iris melanomas, 4 iris nevi, 3 intraocular invasions of conjunctival squamous cell carcinoma, 2 ring melanomas of the anterior chamber angle, 1 medulloepithelioma and 1 pars plana cyst. On UBM, all IPE cysts presented as cystic lesions with a thin cyst wall and no solid components. All ciliary body melanomas showed low to medium reflectivity, with cavitation in one case and extraocular extension in another. Iris melanomas presented as anterior (stromal) iris lesions with medium to high internal reflectivity. There was irregularity and convex bowing of the posterior iris plane in iris melanomas, a feature not seen in iris nevi. Intraocular invasion of conjunctival squamous cell carcinoma was evidenced as areas of medium to high reflectivity in the ciliary body and iris, loss of the acute angle shape and highly reflective spots in the anterior chamber. Conclusions: UBM was particularly useful in the diagnosis of IPE cysts, in the visualization of small ciliary body melanomas, in the differentiation of iris melanomas from iris nevi and in the demonstration of intraocular invasion from conjunctival squamous cell carcinoma.

Background: While traditional eye plaque brachytherapy can be used for the treatment of iris melanoma, it faces challenges of poor patient tolerability due to cornea-plaque touch caused by radius of curvature mismatch and potential dosimetric inaccuracy from incomplete coverage. We present novel plaque designs and the first clinical application of the plaques for iris melanoma. Methods: Two dome-shaped plaques (EP2132 and EP1930) were designed to vault above the cornea to treat tumors of the iris and ciliary body. Image-based treatment planning of the first 2 clinical cases using the EP2132 plaque covered the tumor base plus a 2 mm margin and the involved ciliary body with at least 75 Gy to the tumor apex. Results: The tumors decreased in size following treatment. The patients tolerated the treatment well. There was no adverse event associated with the traditional iris plaques, such as decreased vision, pain, corneal edema, glaucoma, or cataract. Conclusion: The novel dome-shaped plaques for the treatment of iris melanoma provide effective dose distribution, improved surgical maneuverability, and increased tolerability for the patient. This plaque model can be used to treat iris melanoma of various sizes, configurations, and locations, including the ciliary body. The need for a customized plaque platform for each patient is minimized.

Distinguishing an iris melanoma from an iris nevus can be challenging as few clinical features other than documented growth are helpful in making the diagnosis. In this study, we compared the presenting intraocular pressure (IOP) and cup-to-disc ratio (CDR) between affected and unaffected eyes in patients with iris melanoma and iris nevus. This was a single-institution retrospective case series of patients treated for iris melanoma and iris nevus from January 2013 to October 2022. Thirty-nine subjects with iris melanoma and forty age-matched patients with iris nevus were included. We analyzed the difference in IOP, CDR, and diagnosis of glaucoma between affected and unaffected eyes in patients with iris melanoma and control iris nevus cohort. The average IOP for eyes with iris melanoma and iris nevus was 18.8±6.1 mmHg and 14.6±3.5 mmHg (P<0.001), respectively. The average CDR was 0.36±0.27 and 0.24±0.14 (P=0.02), respectively. The average IOP of the contralateral unaffected eye in iris melanoma patients was 16.3±3.5 mmHg, significantly less than the affected eye (P=0.03). The average CDR of the contralateral unaffected eye in iris melanoma was 0.25±0.15, which was trending towards being less than the affected eye (P=0.05). There was no difference in the average IOP (P=0.89) or average CDR (P=0.49) between the affected and unaffected eye in patients with iris nevus. We demonstrate that patients with iris melanoma are more likely to have greater IOP and CDR in the affected eye compared to the unaffected eye, and a diagnosis of unilateral glaucoma than eyes with iris nevus. Patients with iris melanoma had greater IOP asymmetry between the affected and unaffected eye. Therefore, IOP and CDR asymmetry may suggest a diagnosis of iris melanoma.

Adenoma of the iris pigment epithelium (IPE) is an uncommon lesion that can simulate iris or ciliary body melanoma, melanocytoma, and pigment epithelial cyst. To evaluate the clinical and pathological features and prognosis of adenoma of the IPE in patients managed by us and to elucidate the features that help to differentiate this tumor from iris melanoma and other similar conditions. The medical records of 20 patients with adenoma of the IPE were reviewed, and the clinical and histopathologic features were tabulated. Ten patients were male and 10 were female, with a mean age of 60.0 years (range, 11-85 years). All patients were referred because of suspected iris or ciliary body melanoma. All lesions were solitary and unilateral. Sixteen were located in the peripheral iris; 2, in the midzone; and 2, near the pupillary margin. Clinically, all tumors were abruptly elevated, all but 1 were dark gray to black, and all had a smooth, but sometimes multinodular, surface. The tumors caused thinning or complete effacement of the overlying iris stroma, but they did not directly involve the stroma. They typically blocked light with transillumination. On ultrasound biomicroscopy findings, adenoma of the IPE shows a solid tumor pattern, sometimes with small cystoid spaces. The tumor was managed by local resection in 2 patients and observation in 18, all of whom have been stable, with follow-up ranging from 6 months to 9 years. Histopathologic examination revealed a tumor originating in the IPE consisting of cords of pigment epithelial cells separated by septae of connective tissue. Adenoma of the IPE usually has characteristic features that should differentiate it from iris melanoma, ciliary body melanoma, iris melanocytoma, and iris cyst. Adenoma of the IPE is a benign tumor that may remain relatively stable for years.

To report clinical outcomes of modified Collaborative Ocular Melanoma Study IRIS (COMS IRIS) plaques for treatment of iris, iridociliary, and ciliary body melanoma. Retrospective, single-centre cohort study of iris melanoma treated with COMS IRIS plaque radiotherapy from July 26, 2010 to October 15, 2018. Medical records were reviewed for demographics, tumour features, treatment parameters, and clinical outcomes. There were 22 cases, diagnosed at mean age of 59 years (median 65, range 21-85 years) with female sex in 14 (64%). Presenting tumour features included Snellen visual acuity (VA) ≥ 20/40 in 18 (82%) cases, mean largest tumour basal diameter 4.7 mm (median 3.9, range 2.3-13.8 mm) and thickness 1.7 mm (median 1.6 mm, range 0.8-3.9 mm), iris stromal seeding in 3 (14%) cases, angle seeding in 16 (73%), and ciliary body involvement in 13 (59%). After mean follow-up of 51 months (median 44, range 4-113 months), Snellen VA was ≥20/40 in 14 (64%) cases, with local tumour recurrence in 2 (9%), and enucleation in 2 (9%). The 3-year Kaplan-Meier estimated risk of local tumour recurrence was 7%. The most common radiation side effects were cataract in 17 (77%) patients and dry eye in 5 (23%). Systemic metastasis occurred in no cases, and 1 (5%) non-melanoma-related death due to natural causes was observed at last follow-up. COMS IRIS plaques are effective for treatment of iris, iridociliary, and ciliary body melanoma with modest VA outcomes and low frequency of local tumour recurrence, enucleation, radiation side effects, and systemic metastasis.

Comparison of microcirculation patterns and MIB-1 immunoreactivity in iris and posterior uveal melanoma

To determine the frequency of optic nerve invasion in uveal melanoma, to identify clinical factors associated with optic nerve invasion, and to analyze the metastatic pattern and the association with survival. All iris, ciliary body, and choroidal melanomas (N = 2758) examined between 1942 and 2001 at the Eye Pathology Institute, University of Copenhagen, Denmark, and the Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark, were reviewed. Cases with optic nerve invasion were identified and subdivided into prelaminar or laminar invasion and postlaminar invasion. Clinical characteristics were compared with those from 85 cases randomly drawn from all ciliary body and choroidal melanomas without optic nerve invasion from the same period. Survival data were obtained by the Kaplan-Meier method, and the Mantel-Cox log-rank test was used to test differences in survival among the three patient groups. Optic nerve invasion was found in 157 uveal melanomas (5.7%; 95% confidence interval [CI], 4.8%-6.6%). Frequency varied during the observation period between 5% and 7%. Only choroidal and ciliary body melanomas were found to invade the optic nerve. Eighty-five (54%) were confined to the prelaminar or laminar part, and 72 (46%) were confined to the postlaminar part. Increased intraocular pressure (IOP) and juxtapapillary location were associated with prelaminar or laminar invasion and postlaminar invasion. Age older than 70 years, reduced vision to light perception or worse, nonvisible fundus, and large (>15 mm) tumor size were associated with postlaminar spread. In univariate analysis, patients with postlaminar invasion had significantly higher all-cause and melanoma-related mortality than the other patients. Optic nerve invasion in uveal melanoma is found in 1 in 20 patients. Visible juxtapapillary melanoma or loss of light perception should make the clinician suspicious of melanoma with optic nerve invasion, and special awareness of postlaminar spread should be addressed when increased IOP is present independently of decreased visual acuity and tumor location.

Introduction Iris/ciliary body tumors can broadly be classified as benign or malignant, cystic or solid, and melanocytic or non-melanocytic. This study aims to provide a systematic review of anterior segment optical coherence tomography (AS-OCT) findings in iris and ciliary body tumors. Methods We conducted a search of published articles related to the use of AS-OCT in iris/ciliary body tumors as of December 2022. Databases that were searched included PubMed, Scopus, and Web of Science. The following search terms in various combinations were used: ‘anterior segment optical coherence tomography,’ ‘ciliary body melanoma,’ ‘ciliary body nevus,’ ‘ciliary body tumor,’ ‘iris cyst,’ ‘iris melanoma,’ ‘iris nevus,’ ‘iris tumor,’ and ‘metastasis.’ Results A total of 41 studies (10 original articles and 31 case reports) met the inclusion criteria. AS-OCT data pertaining to 545 iris/ciliary body lesions could be retrieved. Conclusion AS-OCT has proved to be useful as a noninvasive tool for the diagnosis of solid tumors involving the iris/angle with no marked ciliary body involvement, iris pigment epithelial, and iris stromal cysts. To the best of our knowledge, this is the first systematic review in the literature evaluating the utility of AS-OCT in iris/ciliary body tumors.

Intraocular eye cancer diagnosis is based on ophthalmic examination, patient history, A/B scan ultrasonography, fluorescein and indocyanine green angiography, and optical coherence tomography. Ocular tumors can be generally divided into the categories that appear below. These cancers can arise in children or adults. I. Intraocular tumors of childhood A. Retinal tumors -1. Retinoblastoma B. Iris and ciliary body lesions -1. Medulloepithelioma C. Choroidal and RPE lesions -1. Congenital hypertrophy of the retinal pigment epithelium -2. Combined hamartoma of the retina and retinal pigment epithelium -3. Congenital melanocytosis D. Other benign tumors II. Intraocular tumors in adults A. Choroidal and RPE lesions -1. Choroidal nevus -2. Choroidal melanoma B. Iris and ciliary body lesions -1. Fuchs adenoma -2. Iris nevus -3. Ciliary body nevus -4. Iris melanoma -5. Ciliary body melanoma C. Metastatic disease to the choroid III. Vascular tumors A. Retinal capillary hemangioma B. Retinal cavernous hemangioma C. Choroidal hemangioma Clinics and pathology

BackgroundUveal melanomas can develop in the choroid, ciliary body and iris. In choroidal and ciliary body melanomas, specific chromosomal changes correlate with metastatic disease. Iris melanomas have a better prognosis...

Chapter 7 - Iris melanoma