Intraocular Tumors: Diagnosis and Management

Educational Objectives

The goal of this program is to improve the management of intraocular tumors. After hearing and assimilating this program, the clinician will be better able to:

1. Outline the diagnosis and management of common intraocular tumors.
2. Analyze the outcomes of the Collaborative Ocular Melanoma Study.
3. Use gene expression profile testing to stratify risk for metastasis in choroidal melanoma.

Summary

Choroidal Nevus

Presentation: patients may present with a spot in the eye without any symptoms; the pigmented choroidal lesion may be flat, with drusen on the surface and no autofluorescence; A-scan ultrasonography (USG) may show high internal reflectivity; the lesion may be relatively flat on B-scan USG

Choroidal nevi: flat or minimally elevated pigmented or nonpigmented choroidal lesions; common (≈1 in 20 individuals); visible on indirect ophthalmoscopy after dilating the pupil; patients with asymptomatic nevi are increasingly referred by optometrists (perform routine wide-angle imaging of the fundus [not advised]) and ophthalmologists; usually asymptomatic and found incidentally; symptoms are associated with subretinal fluid (does not always indicate malignancy); the annual rate of malignant transformation is 1 in ≈9000; annual monitoring is advisable

Risk factors for growth: include height >2 mm on USG, presence of subretinal fluid, orange pigmentation (indicates activity), juxtapapillary location, presence of symptoms, acoustic hollowness on B-scan USG, and absence of drusen and halo; the presence of drusen suggests a nevus (and chronicity and inactivity)

Management: does not require referral unless changes are observed

Choroidal Metastases (CM)

Presentation: patients may present with a lesion in the eye with a history of breast cancer; on B-scan USG, an acoustically fairly dense thick lesion may be observed; on A-scan USG, the lesion may display irregular acoustic challenge; the lesion may exhibit autofluorescence; although a biopsy can confirm malignancy, obtaining a tissue diagnosis can sometimes be difficult

Choroidal metastases: not uncommon; metastases are more likely in the choroid (followed by iris and ciliary body); occurs in the fifth or sixth decade; the most common primary site is lung cancer in men and breast cancer in women; in ≈15% of patients, the primary site remains unknown; characteristic metastatic lesion in the eye in the absence of a primary lesion warrants referral to oncology

Clinical features: blurred vision; an amelanotic yellow plateau-shaped lesion often with subretinal fluid is a characteristic feature of CM; amelanotic lesions with subretinal fluid are metastatic lesions until proven otherwise; internal reflectivity is variable

Management: requires multidisciplinary collaboration; treatment involves chemotherapy or external beam radiotherapy (EBRT); plaque brachytherapy (PB) may not be appropriate for multiple lesions; EBRT is highly effective without loss of visual acuity

Choroidal Hemangiomas (CHs)

Presentation: presents as choroidal mass; on fundal imaging, may present as a hypopigmented lesion (slight yellow or orange coloration); on USG, internal reflectivity is high; guttering effect may be seen with autofluorescence in the presence of serous fluid; subretinal fluid can be seen on optical coherence tomography (OCT); guttering may be observed on fluorescein angiography (FA) and indocyanine green angiography (ICG)

Choroidal hemangioma: commonly misdiagnosed (as amelanotic melanoma); CHs are benign congenital vascular tumors; asymptomatic; visual symptoms develop from subretinal fluid accumulation

Clinical features: well-circumscribed lesions with red-orange appearance; usually occur posteriorly; high internal reflectivity; progressive hyperfluorescence and diffuse late staining on FA; ICG shows rapid filling with late hyperfluorescence

Management: if the lesion is peripheral and does not affect vision, observation is advisable; for symptomatic patients, photodynamic therapy (PDT) is very effective; PB or EBRT may result in destruction of the retina, scarring, and vision loss; the speaker prefers PDT

Choroidal Melanoma

Presentation: patients may present with pigmented elevated mass (may be associated with fluid); on B-scan USG, a characteristic deep drop (from the front to the back of the tumor) with intermediate to low reflectivity and acoustic hollowness may be observed

Choroidal melanoma: the most common primary intraocular malignancy in adults; not common; light skin color is a risk factor; appears as a dome-shaped mass (melanotic [common] or amelanotic); fundus imaging helps monitor growth; multimodal imaging — A-scan USG shows high initial amplitude with rapid drop to low internal reflectivity; OCT can detect subretinal fluid; fundus autofluorescence highlights lipofuscin; FA is not helpful

Collaborative Ocular Melanoma Study (COMS): consisted of small-, medium-, and large-sized arms

Small-sized melanoma arm: tumors <3 mm were observed; ≈20% of tumors grew at 2 yr and ≈30% at 5 yr; mortality was relatively low; metastasis was confirmed in 20% of tumors; no difference in outcome with or without treatment; the study offered no recommendations for treatment; treatment is advisable for documented growth

Medium-sized melanoma arm: Diener-West et al (2001) randomized patients to enucleation or PB; no difference in mortality between enucleation vs PB (12-yr cumulative mortality rate, 43% vs 41%; 5-yr mortality rate, 19% vs 18%); complications of PB — include dry eyes and cataract; radiation retinopathy and radiation optic neuropathy pose big challenges; neovascular glaucoma may occur in large tumors; frequency of vision loss is related to the tumor location (eg, proximity to macula, radiation dose)

Large-sized melanoma arm: Hawkins et al (2004) randomized patients to preenucleation RT plus enucleation or enucleation alone; as enucleation was thought to enhance the dissemination of melanoma cells, enucleation was performed with as little manipulation of the tissue as possible; no difference between the groups; the 5-yr mortality rate was higher compared with that of the medium-sized arm; however, mortality rate did not increase significantly over the next 5 yr, as metastases and death occurred earlier in larger tumors

Management: depends on the size of the lesion (based on the COMS); enucleation is recommended for large tumors; stereotactic radiosurgery may not be effective; PB is limited by the size of the plaque (≤22 mm); for medium-sized tumors, PB or proton beam therapy (PBT) is advised; small tumors are observed until documented growth; globe-sparing therapy (eg, photocoagulation, transpupillary thermotherapy) may be considered for smaller lesions; PBT — alternative to PB, with comparable outcomes; PBT involves a single surgical procedure; although some studies suggest fewer complications than PB, strong evidence is lacking; expensive; may not be covered by insurance; genetic testing — intravitreal or transscleral biopsies can be potentially prognostic

Metastatic evaluation: consult oncology, as many patients develop metastatic disease; tumor biopsy is difficult, and treatment is initiated in the absence of a tissue diagnosis; transscleral or transvitreal fine-needle aspiration biopsy can be performed; genetic profiling can identify key genomic mutations with variable risks for metastasis; gene expression profile testing can identify 15 genes and stratify patients into low, intermediate, or high risk for metastasis (class 1A, 2% risk for metastasis at 5-yr; class 1B, 21% risk; class 2, 72% risk); the Collaborative Ocular Oncology Group demonstrated that PRAME is an adjunct biomarker and provides a prognostic value; however, that survival improves with early detection of metastatic disease has not been rigorously documented; genetic profiling may not be useful in practice

Newer options: Diabetic Retinopathy Clinical Research Retina Network Protocol for radiation retinopathy randomizes patients to monitoring or early treatment with antivascular endothelial growth factor therapy or steroids; belzupacap sarotalocan (a virus-like drug conjugate) may be beneficial for early melanoma; in a phase 3 trial, Hassel et al (2023) randomized patients with a specific mutation to tebentafusp (eg, KIMMTRAK) vs investigator’s choice; tebentafusp extended the overall survival by 5 mo in patients with documented metastatic melanoma

Readings

Collaborative Ocular Melanoma Study Group. The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma: V. Twelve-year mortality rates and prognostic factors: COMS report No. 28. Arch Ophthalmol. 2006;124(12):1684-1693. doi:10.1001/archopht.124.12.1684; Diener-West M, Earle JD, Fine SL, et al. The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma, III: initial mortality findings. COMS Report No. 18. Arch Ophthalmol. 2001;119(7):969-982. doi:10.1001/archopht.119.7.969; Field MG, Harbour JW. Recent developments in prognostic and predictive testing in uveal melanoma. Curr Opin Ophthalmol. 2014;25(3):234-239. doi:10.1097/ICU.0000000000000051; Gezgin G, Luk SJ, Cao J, et al. PRAME as a potential target for immunotherapy in metastatic uveal melanoma. JAMA Ophthalmol. 2017;135(6):541-549. doi:10.1001/jamaophthalmol.2017.0729; Hassel JC, Piperno-Neumann S, Rutkowski P, et al. Three-year overall survival with tebentafusp in metastatic uveal melanoma. N Engl J Med. 2023;389(24):2256-2266. doi:10.1056/NEJMoa2304753; Hawkins BS, Collaborative Ocular Melanoma Study Group. The Collaborative Ocular Melanoma Study (COMS) randomized trial of pre-enucleation radiation of large choroidal melanoma: IV. Ten-year mortality findings and prognostic factors. COMS report number 24. Am J Ophthalmol. 2004;138(6):936-951. doi:10.1016/j.ajo.2004.07.006; Margo CE. The Collaborative Ocular Melanoma Study: an overview. Cancer Control. 2004;11(5):304-309. doi:10.1177/107327480401100504; Shields CL, Shields JA, Gross NE, et al. Survey of 520 eyes with uveal metastases. Ophthalmology. 1997;104(8):1265-1276. doi:10.1016/s0161-6420(97)30148-1; Shields CL, Welch RJ, Malik K, et al. Uveal metastasis: clinical features and survival outcome of 2214 tumors in 1111 patients based on primary tumor origin. Middle East Afr J Ophthalmol. 2018;25(2):81-90. doi:10.4103/meajo.MEAJO_6_18; Singh AD, Kalyani P, Topham A. Estimating the risk of malignant transformation of a choroidal nevus. Ophthalmology. 2005;112(10):1784-1789. doi:10.1016/j.ophtha.2005.06.011; Mortality in patients with small choroidal melanoma. COMS report no. 4. The Collaborative Ocular Melanoma Study Group. Arch Ophthalmol. 1997;115(7):886-893.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose. Dr. Sternberg's lecture includes information related to the off-label or investigational use of a product, therapy, or device.

Acknowledgements

Dr. Sternberg was recorded at the 23rd Annual Downeast Ophthalmology Symposium, held September 27-29, 2024, in Bar Harbor, Maine, and presented by the Maine Society of Eye Physicians & Surgeons. For more information about upcoming CME activities from this presenter, please visit https://maineeyemds.com. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.25 CE contact hours.

Lecture ID:

OP630201

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.