Iris and Ciliary Body Metastasis

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Article initiated by:
Hashem Abu Serhan
All contributors:
Oase Sbei, Savannah Hensley, Abdullah Ahmed, Cameron Reinisch, Zamzam M Al-Baker, MD, Hashem Abu Serhan
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Uveal metastasis is the most common intraocular malignancy in adults, with the choroid affected in 90% of cases, followed by the iris and ciliary body. Iris and ciliary body metastases typically arise from advanced breast, lung, or melanoma primaries and are often associated with poor prognosis. Diagnosis relies on slit-lamp exam, imaging, and histopathology, while treatment involves systemic therapy and local ocular management.

Disease Entity

Uveal metastasis is the most common form of intraocular malignancy in adults. Among patients with advanced carcinoma, the prevalence of uveal metastases ranges from 2–9%. The choroid is involved in approximately 90% of cases, followed by the iris (8%) and the ciliary body (2%) [1][2]. Both iris and ciliary body metastases are typically associated with advanced systemic disease and a poor overall prognosis [3]. Iris metastases most commonly originate from primary breast and lung carcinomas or cutaneous melanoma. Less frequently, metastases may arise from renal or gastrointestinal primaries [1]. Ciliary body metastases are rare and challenging to characterize due to limited direct visualization. When present, they most often originate from breast or lung cancers.

Etiology

Iris and ciliary body metastases result from hematogenous spread of systemic malignancies, most commonly breast or lung carcinomas and cutaneous melanoma. Risk factors for intraocular metastasis, including to the iris and ciliary body, include advanced-stage disease with evidence of hematogenous dissemination and widespread metastatic involvement.

Risk Factors

Breast Cancer

Ocular metastasis can occur at any stage of breast cancer, though the risk is greatest in the setting of advanced metastatic disease. Risk factors for disseminated breast cancer—such as high stage at diagnosis, axial lymph node involvement, and unfavorable tumor biology, including triple-negative or HER2-positive subtypes, as well as invasive ductal carcinoma—are similarly associated with an increased likelihood of intraocular metastasis [4] [5]. Compared to invasive ductal carcinoma, invasive lobular carcinoma carries a significantly higher risk of metastasis to the ciliary body or iris [4][6]. The presence of brain metastases is also strongly linked to ocular involvement, particularly affecting the uvea and optic disc [6]. Elevated tumor markers CA-125 and CA15-3 are independent predictors of intraocular metastasis. Serum biomarkers associated with increased risk also include decreased levels of LDL cholesterol, apolipoprotein A1 (ApoA1), and hemoglobin [4][5][6].

Lung Cancer

Risk factors for disseminated lung cancer include advanced stage at diagnosis, aggressive histologic subtypes such as poorly differentiated non-small cell lung cancer, small cell lung cancer, and mucinous adenocarcinoma, as well as lymph node involvement, vascular invasion, and elevated carcinoembryonic antigen (CEA) [7][8]. Patients with underlying chronic lung diseases—including COPD, emphysema, interstitial lung disease, or a history of pulmonary tuberculosis—are more likely to present with advanced disease due to delayed diagnosis caused by overlapping respiratory symptoms [9]. Risk factors for metastasis to the iris and ciliary body reflect those for metastatic disease. Notably, a substantial proportion of patients with uveal metastases from lung cancer may not have a known diagnosis of primary lung cancer at the time of ocular presentation. In one retrospective review of 194 patients with confirmed uveal metastases, 44% were undiagnosed with lung cancer at the time of metastasis detection [10]. Serum biomarkers associated with intraocular metastasis include elevated CA15-3, CA-125, CEA, and CYFRA 21-1; however, no individual marker has demonstrated predictive value for risk of intraocular involvement, including to the iris or ciliary body [11][12].

Cutaneous Melanoma

Metastasis to the iris and ciliary body is typically associated with widely disseminated disease and is considered a late manifestation in the course of melanoma. Risk factors for metastatic spread include advanced stage at diagnosis, lymph node involvement, and aggressive histologic features of the primary melanoma [13]. High-grade epithelioid cytology has been linked to an increased risk of distant metastasis, including to the iris and ciliary body via hematogenous dissemination [13]. These lesions often exhibit immunopositivity for BRAF mutations, which can aid in distinguishing metastatic melanoma from primary uveal melanoma [14][15]. However, while helpful for diagnostic confirmation, the presence of BRAF mutations in the primary tumor does not confer an increased risk of metastasis to uveal structures such as the iris or ciliary body [14].

General Pathology

Uveal metastases occur through hematogenous spread from distant primary malignancies. The choroid, supplied by the posterior ciliary arteries, has the richest vascularity within the uveal tract, making it the most susceptible to metastatic seeding. In contrast, the iris and ciliary body have a comparatively less extensive blood supply, contributing to the rarity of metastases in these structures. Additionally, the blood-aqueous barrier in the anterior segment further reduces the likelihood of metastatic infiltration in the iris and ciliary body [16] [2] .

Pathophysiology

Iris Metastasis

Metastatic cells reach the vascular stroma of the iris via the bloodstream. These lesions typically present as solitary or multifocal yellow-white nodules, which may extend into the anterior chamber angle. They are most commonly located at the iris root, midzone, or pupillary margin [16][17].

Ciliary Body Metastasis

Metastatic seeding occurs in the vascular stroma of the ciliary body, often in the inferior quadrant. Due to their position posterior to the iris, these lesions are challenging to visualize on exam and are frequently occult. As a result, they are more likely to present with secondary angle closure, lens displacement, or elevated intraocular pressure rather than visible nodules [16].

Histology

On histology, both ciliary and iris metastases generally mirror the characteristics of the primary tumor. Metastases from lung or breast carcinoma typically display epithelial features, while those from melanoma may consist of pigmented or amelanotic spindle-shaped or epithelioid cells [2][18].

Primary Prevention

Primary prevention for iris and ciliary body metastases is indirectly achieved by preventing systemic malignancies, particularly breast cancer, lung cancer, and cutaneous melanoma, as these cancers frequently metastasize to ocular structures [17]. Effective primary prevention strategies for these cancers include lifestyle modifications (smoking cessation, maintaining a healthy weight, avoiding UV radiation exposure), routine screenings (mammograms for breast cancer, chest imaging for lung cancer), and early management of precancerous lesions [10]. Early-stage detection and timely intervention significantly reduce the risk of metastatic spread, thereby decreasing the likelihood of iris and ciliary body involvement [19].

Diagnosis

Diagnosis of iris and ciliary body metastases demands clinical vigilance, especially in patients with known malignancies presenting new ocular symptoms or unexplained visual disturbances. Definitive diagnosis relies on detailed clinical evaluation, advanced imaging techniques, and histopathological or cytological confirmation [18]. In addition, an assessment of tumor markers in the aqueous humor, combined with fine needle aspiration cytology, aids in the diagnosis of metastatic tumors of the iris [20].

History

A thorough medical history is vital in evaluating iris and ciliary body metastases. Patients commonly have an established diagnosis of malignancies like breast carcinoma, lung cancer, or melanoma. However, ocular metastasis may sometimes represent the initial clinical presentation of an undiagnosed primary tumor, notably lung cancer [19].

Physical Examination

Physical examination begins with detailed slit-lamp evaluation, crucial in visualizing iris lesions. Iris metastases typically appear as yellow-white, nodular lesions located at the iris root, midzone, or pupillary margin [10]. These lesions might extend into the anterior chamber angle, resulting in secondary complications. Ciliary body metastases, due to their posterior positioning, are often difficult to visualize directly and may manifest indirectly as lens displacement, shallowing of the anterior chamber, or raised intraocular pressure from secondary angle-closure glaucoma [21].

Signs

Characteristic signs of iris metastases include single or multiple nodular iris lesions, pupil irregularities due to mass effect or posterior synechiae, localized neovascularization, anterior chamber cells, and occasional hyphema [22]. In ciliary body metastasis, clinical signs are usually subtle and include anterior chamber shallowing, elevated intraocular pressure, secondary glaucoma, and lens displacement without direct visualization of a mass [23].

Symptoms

Patients with iris or ciliary body metastases commonly present with progressive visual disturbances such as blurred vision, photophobia, visual field defects, and ocular discomfort or pain, especially if intraocular pressure elevation occurs. However, early metastases can remain asymptomatic until secondary complications emerge, highlighting the importance of routine ophthalmologic surveillance in high-risk populations [19].

Clinical Diagnosis

The clinical diagnosis of iris and ciliary body metastasis integrates ophthalmologic findings with known systemic cancer status. Patients with iris tumors require comprehensive slit-lamp biomicroscopy, intraocular pressure measurement to assess glaucoma risk, gonioscopy, transillumination, and imaging via B-scan ultrasound or ultrasound biomicroscopy (UBM) [24][25]. For patients without known malignancy, ophthalmologic signs may prompt systemic investigation through imaging and biopsy to identify the primary cancer site. Imaging modalities such as ultrasound biomicroscopy (UBM) and anterior segment optical coherence tomography (AS-OCT) enhance visualization, particularly for ciliary body metastases [16].

Diagnostic Procedures

Essential diagnostic procedures include comprehensive slit-lamp evaluation, ultrasound biomicroscopy for deeper or obscured ciliary body lesions, anterior segment OCT for detailed lesion characterization, and fine-needle aspiration biopsy (FNAB) for cytological confirmation [25]. Systemic evaluation using orbital MRI, cranial CT, and whole-body PET/CT scanning is crucial for determining the extent of metastatic disease and guiding systemic management [19].

Laboratory Test

Laboratory investigations contribute significantly to diagnostic accuracy and systemic evaluation. Elevated serum tumor markers such as CA-125, CA15-3, carcinoembryonic antigen (CEA), and CYFRA 21-1 are associated with metastatic intraocular involvement, particularly from breast and lung cancers [19]. Furthermore, decreased serum levels of LDL cholesterol, apolipoprotein A1 (ApoA1), and hemoglobin may suggest a higher risk of metastasis in breast cancer patients [10]. BRAF mutation testing can distinguish primary uveal melanoma from metastatic melanoma, further aiding the diagnostic process [19].

Differential Diagnosis

Differentiating iris and ciliary body metastases from other lesions with overlapping features is crucial. Primary iris or ciliary body melanoma is the primary concern, typically presenting as a solitary pigmented lesion with slow, progressive enlargement and distinctive imaging characteristics [16]. Benign iris cysts, usually stationary, translucent structures, differ significantly from metastatic lesions, as do granulomas associated with inflammatory conditions such as sarcoidosis or tuberculosis, which present with nodular iris lesions accompanied by inflammation [16]. Juvenile xanthogranuloma, primarily affecting young patients, appears as characteristic yellow-orange iris nodules, contrasting clinically with metastatic lesions typically seen in older adults [2]. Fuchs’ heterochromic iridocyclitis is recognized by chronic unilateral inflammation, iris heterochromia, and cataract formation rather than discrete metastatic nodules. Additionally, metastatic uveal melanoma originating in the choroid can resemble iris and ciliary body metastases, necessitating systemic investigation and detailed ocular imaging [19].

Management

Effective management of iris and ciliary body metastases involves local ocular tumor control and systemic oncologic treatment tailored to individual patient needs, lesion characteristics, and overall disease status.

General Treatment

Local radiation therapy, including plaque brachytherapy or external beam radiotherapy, is the cornerstone of ocular lesion control, providing effective tumor stabilization and preserving visual function [16]. Systemic chemotherapy or targeted therapy is dictated by the histology of the primary malignancy, helping reduce further metastatic dissemination and control systemic disease. Intravitreal anti-VEGF injections can address complications such as neovascular glaucoma or retinal hemorrhages associated with metastatic disease [19].

Medical Therapy

Systemic therapy selection depends on primary tumor histology: hormonal therapies like tamoxifen or aromatase inhibitors for breast cancer, immunotherapy agents (checkpoint inhibitors) for melanoma, or chemotherapy and targeted agents for lung cancer metastases [26]. Topical corticosteroids reduce associated inflammation, and topical intraocular pressure-lowering medications manage secondary glaucoma [27].

Medical Follow-up

Regular ophthalmologic evaluations are vital for monitoring lesion regression, intraocular pressure, and potential complications such as cataract and radiation-induced retinopathy. Close collaboration with oncology teams is essential to comprehensively manage systemic disease progression [10].

Surgery

Surgery is rare and typically reserved for diagnostic biopsies or management of secondary complications like cataract or glaucoma. Enucleation is considered for extensive disease, uncontrolled glaucoma, or painful blind eyes [16].

Surgical Follow-up

Postoperative follow-up includes regular assessments for healing, intraocular pressure stability, recurrence monitoring, and visual rehabilitation. Coordination with oncology ensures overall patient care continuity.

Complications

Potential complications include secondary glaucoma, cataract, intraocular hemorrhage, painful blind eye, radiation-induced retinopathy or optic neuropathy, and tumor recurrence or systemic progression [16].

Prognosis

Iris and ciliary body metastases typically signify advanced systemic malignancy with a generally poor prognosis. Median survival post-diagnosis varies according to primary cancer type, typically ranging from months to several years. Breast cancer metastases generally confer a better prognosis, whereas melanoma and lung cancer metastases predictably have shorter survival outcomes [2][16].

References

  1. ↑ 1.0 1.1 Kanthan GL, Jayamohan J, Yip D, Conway RM. Management of metastatic carcinoma of the uveal tract: an evidence-based analysis. Clin Exp Ophthalmol. 2007;35(6):553-565. doi:10.1111/j.1442-9071.2007.01550.x
  2. ↑ 2.0 2.1 2.2 2.3 2.4 Shields CL, Shields JA, Gross NE, Schwartz GP, Lally SE. Survey of 520 eyes with uveal metastases. Ophthalmology. 1997;104(8):1265-1276. doi:10.1016/s0161-6420(97)30148-1
  3. ↑ Demirci H, Shields CL, Chao AN, Shields JA. Uveal metastasis from breast cancer in 264 patients. Am J Ophthalmol. 2003;136(2):264-271. doi:10.1016/s0002-9394(03)00192-2
  4. ↑ 4.0 4.1 4.2 Tang J, Yan B, Li GF, et al. Carbohydrate antigen 125, carbohydrate antigen 15-3 and low-density lipoprotein as risk factors for intraocular metastases in postmenopausal breast cancer. Medicine (Baltimore). 2021;100(43):e27693. doi:10.1097/MD.0000000000027693
  5. ↑ 5.0 5.1 Liang RB, Yu K, Wu JL, et al. Risk factors and their diagnostic values for ocular metastases in invasive ductal carcinoma. Cancer Med. 2021;10(3):824-832. doi:10.1002/cam4.3656
  6. ↑ 6.0 6.1 6.2 Yousef YA, Mohammad M, Khalil H, et al. Ocular and Periocular Metastasis in Breast Cancer: Clinical Characteristics, Prognostic Factors and Treatment Outcome. Cancers (Basel). 2024;16(8):1518. Published 2024 Apr 16. doi:10.3390/cancers16081518
  7. ↑ Wang J, Chu Y, Li J, et al. The clinical value of carcinoembryonic antigen for tumor metastasis assessment in lung cancer. PeerJ. 2019;7:e7433. Published 2019 Aug 7. doi:10.7717/peerj.7433
  8. ↑ Xu L, Tavora F, Burke A. Histologic features associated with metastatic potential in invasive adenocarcinomas of the lung. Am J Surg Pathol. 2013;37(7):1100-1108. doi:10.1097/PAS.0b013e31827fcf04
  9. ↑ Ang L, Ghosh P, Seow WJ. Association between previous lung diseases and lung cancer risk: a systematic review and meta-analysis. Carcinogenesis. 2021;42(12):1461-1474. doi:10.1093/carcin/bgab082
  10. ↑ 10.0 10.1 10.2 10.3 10.4 Shah SU, Mashayekhi A, Shields CL, et al. Uveal metastasis from lung cancer: clinical features, treatment, and outcome in 194 patients. Ophthalmology. 2014;121(1):352-357. doi:10.1016/j.ophtha.2013.07.014
  11. ↑ Shi WQ, Liu WF, Li B, et al. Assessment of Serum Tumor Markers for Predicting Ocular Metastasis in Lung Adenocarcinoma: A Retrospective Study. Dis Markers. 2020;2020:2102158. Published 2020 Jun 25. doi:10.1155/2020/2102158
  12. ↑ Lin Q, Chen XY, Liu WF, et al. Diagnostic value of CA-153 and CYFRA 21-1 in predicting intraocular metastasis in patients with metastatic lung cancer. Cancer Med. 2020;9(4):1279-1286. doi:10.1002/cam4.2354
  13. ↑ 13.0 13.1 Rosenberg C, Finger PT. Cutaneous malignant melanoma metastatic to the eye, lids, and orbit. Surv Ophthalmol. 2008;53(3):187-202. doi:10.1016/j.survophthal.2008.02.003
  14. ↑ 14.0 14.1 Neerukonda VK, Kim IK, Stagner AM. Primary vitreoretinal involvement and immunopositivity for BRAFV600E help distinguish metastatic from primary intraocular melanoma: a detailed histopathologic study of metastatic cutaneous melanoma to the eye. Histopathology. 2022;80(7):1061-1070. doi:10.1111/his.14640
  15. ↑ Adler NR, Wolfe R, Kelly JW, et al. Tumour mutation status and sites of metastasis in patients with cutaneous melanoma. Br J Cancer. 2017;117(7):1026-1035. doi:10.1038/bjc.2017.254
  16. ↑ 16.0 16.1 16.2 16.3 16.4 16.5 16.6 16.7 16.8 16.9 Shields CL, Kalafatis NE, Gad M, et al. Metastatic tumours to the eye. Review of metastasis to the iris, ciliary body, choroid, retina, optic disc, vitreous, and/or lens capsule. Eye (Lond). 2023;37(5):809-814. doi:10.1038/s41433-022-02015-4
  17. ↑ 17.0 17.1 Shields CL, Kaliki S, Crabtree GS, et al. Iris metastasis from systemic cancer in 104 patients: the 2014 Jerry A. Shields Lecture. Cornea. 2015;34(1):42-48. doi:10.1097/ICO.0000000000000285
  18. ↑ 18.0 18.1 Shields CL, Shields JA, Gross NE, Schwartz GP, Lally SE. Survey of 520 eyes with uveal metastases. Ophthalmology. 1997;104(8):1265-1276. doi:10.1016/s0161-6420(97)30148-1
  19. ↑ 19.0 19.1 19.2 19.3 19.4 19.5 19.6 19.7 Mathis T, Jardel P, Loria O, Delaunay B, Nguyen AM, Lanza F, Mosci C, Caujolle JP, Kodjikian L, Thariat J. New concepts in the diagnosis and management of choroidal metastases. Prog Retin Eye Res. 2019 Jan;68:144-176. doi: 10.1016/j.preteyeres.2018.09.003. Epub 2018 Sep 19. PMID: 30240895.
  20. ↑ Mitamura M, Kase S, Suimon Y, et al. A case of metastatic iris tumor from adenocarcinoma of the cecum diagnosed by combined tumor markers in aqueous humor and fine needle aspiration cytology. Case Rep Oncol. 2025;18(1):29-34. doi:10.1159/000542905. PubMed PMID: 39980514.
  21. ↑ Zhumageldiyeva F, Teleuova T. Metastatic tumor of the ciliary body manifesting as phacomorphic glaucoma: A clinical case. J Clin Med Kaz. 2022;19(3):69-72. doi: 10.23950/jcmk/11967.
  22. ↑ Shields JA, Shields CL, Kiratli H, De Potter P. Metastatic tumors to the iris in 40 patients. Am J Ophthalmol. 1995;119:422–30. doi: 10.1016/S0002-9394(14)71227-9.
  23. ↑ T. Alasil, B. Khazai, L. Loredo, M.E. Rauser. Renal cell carcinoma metastasis to the ciliary body responds to proton bean radiotherapy: a case report J Med Case Rep, 5 (2011), p. 345
  24. ↑ Conway RM, Chew T, Golchet P, Desai K, Lin S, O'Brien J. Ultrasound biomicroscopy: role in diagnosis and management in 130 consecutive patients evaluated for anterior segment tumours. Br J Ophthalmol. 2005 Aug;89(8):950-5.
  25. ↑ 25.0 25.1 Pilling RF, Khan A, Ball JL. The utility of anterior segment optical coherence tomography in monitoring intraocular epithelial cysts in children: a mini case series. Br J Ophthalmol. 2010 Sep;94(9):1265.
  26. ↑ Chen KJ, Chao AN, Wang CL. Iris metastasis regression following Osimertinib treatment. JAMA Ophthalmol. 2020;138:e202095. doi: 10.1001/jamaophthalmol.2020.2095.
  27. ↑ Goduni L, Ashkenazy N, Hansen E, Soyano-Muller A, Correa ZM, Harbour JW. Iris metastasis from breast cancer successfully treated with Abemaciclib and Letrozole. Retin Cases Brief Rep. 2022. 10.1097/ICB.0000000000001176.
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