Year : 2017 | Volume
: 20 | Issue : 2 | Page : 122--126
Choroidal metastasis: A review of literature
Department of Radiation Oncology, VMMC and Safdarjung Hospital, New Delhi, India
Room No. 271, 2nd Floor, New OPD Block, VMMC and Safdarjung Hospital, New Delhi - 110 029
Choroidal metastasis is a significant clinical problem in patients with metastatic cancer owing to abundant vascular supply. The two most common cancers leading to choroidal metastases are breast cancer followed by lung cancer. The treatment of choroidal metastasis depends on the status of primary disease, number, and location of choroidal metastasis, symptomatology and the general condition of the patient. A number of options are available for the therapy of ocular metastasis, including observation, chemotherapy, photocoagulation, cryosurgery, surgical resection, or radiotherapy. A database search was conducted on Google scholar and PubMed using phrase words, using the terms “choroidal metastasis,” in combination with terms such as “treatment,” “features,” or “diagnosis.” References of all publication were also searched. All relevant publications were collected, reviewed, and analyzed.
|How to cite this article:|
Sharma D. Choroidal metastasis: A review of literature.Trop J Med Res 2017;20:122-126
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Sharma D. Choroidal metastasis: A review of literature. Trop J Med Res [serial online] 2017 [cited 2019 Mar 20 ];20:122-126
Available from: http://www.tjmrjournal.org/text.asp?2017/20/2/122/218213
Earlier, metastatic cancer to the eye, especially choroidal metastasis was considered a rare phenomenon. The first case of choroidal metastasis was reported by Perls in 1872. In a study by Godtfredsen, only 0.07% of patients were reported with choroidal metastasis. Choroidal metastases are now considered the most common intraocular malignancy in the adult population. In a review of patients dying from the malignancy, 8% displayed choroidal metastases on autopsy. Choroidal metastases tend to become apparent late in the course of malignancy and are associated with disseminated disease and poor prognosis.,,, and therefore, choroidal metastasis should be suspected in a patient complaining of decrease or loss of vision. In this article, we will review the common primary tumor origins, the salient features of metastases, and treatment options available for these lesions.
A database search was conducted on Google scholar and PubMed using phrase words, using the terms “choroidal metastasis,” in combination with terms such as “treatment,” “features,” or “diagnosis.” References of all publication were also searched. All relevant publications were collected, reviewed, and analyzed in detail to summarized in this paper.
Epidemiology and Etiopathogenesis
The most common site for intraocular metastasis is uveal tract (choroidal metastasis accounts for 88% of cases followed by iris and ciliary body). The potential reason for such metastasis is the high vascular supply of the uveal tract.,,, The choroid provides a vascular avenue for tumor emboli to sequester and allows an environment receptive to growth.
The first two most common causes of choroidal metastasis are breast carcinoma followed by lung cancer.,,, Other less common primary tumors causing choroidal metastases are carcinoma of the gastrointestinal tract (4%), prostate (2%), kidney (2%–4%), and skin (2%).,, Tumors arising from the submandibular gland, thyroid, contralateral choroid, testes, ovaries, urothelial tract, neuroendocrine tumor, and sarcoma are few rare causes for choroidal metastasis.,,,,,,,, Studies had shown that in about 34% of cases, choroidal metastasis appear before the diagnosis of systemic cancer. Of those without known cancer, the primary tumor sites included lung cancer (7%), breast cancer (35%), and about 50% of patients with the primary site not found.
Presentation and Diagnosis
The majority of symptomatic patients note a decreased visual acuity at the time of presentation. Other presenting signs or symptoms include diplopia, photophobia, ptosis, blepharitis, metamorphopsia, pain, flashes and floaters, mass lesion, uveitis, exophthalmos, secondary glaucoma, and detached retina.,, Bilateral choroidal metastasis is also common. It varies from 19% to 31% in different studies.,,
The presence of metastatic disease to the eye is obviously high in the differential diagnosis of ocular lesions when a primary cancer is present elsewhere. Other conditions can be mistaken for metastatic disease; therefore, a careful evaluation is necessary for a correct diagnosis. The differential diagnosis includes amelanotic nevus, amelanotic melanoma, choroidal hemangioma, posterior scleritis, choroidal osteoma, retinitis, hemorrhage, choroiditis, rhegmatogenous retinal detachment, reactive lymphoid hyperplasia, lymphoma, Harada's disease, uveal effusion syndrome, and central serous chorioretinopathy.
The diagnosis of ocular metastases is based primarily on clinical findings supplemented by imaging studies. The choroidal metastases usually appear as solid, flat, plaque-like, mottled, and yellow-brown lesions. A number of ancillary ophthalmologic procedures can assist in the diagnosis of metastatic tumors. These procedures include autofluorescence (AF), ultrasonography, fluorescein angiography (FA), tomography/magnetic resonance imaging (MRI), fine-needle aspiration biopsy.
AF is a noninvasive imaging technique, used to define tumor surface characteristics and to delineate progressing tumor margins., Fundus autofluorescence photography relies on the stimulated emission of light from naturally occurring fluorophores, the most significant being lipofuscin. On ophthalmoscopic examination, choroidal metastases often have overlying subretinal fluid and lipofuscin that typically appear as scattered clumps of brown pigment.,
Ultrasonography determines tumor dimensions and echogenicity and allows differentiation of metastases from other intraocular neoplasms, particularly melanomas. On B-scan ultrasound, metastatic tumors tend to be acoustically solid convex masses with a lower silhouette, that is, lower height-to-base ratios than malignant melanoma. A-scan ultrasound shows moderate internal reflectivity compared with melanoma, which is usually low.
Shields et al. also demonstrated that thickness tends to correlate to origin of metastases, example a mean thickness of metastases secondary to melanoma measuring 1 mm, breast 2 mm, lung and prostate 3 mm, and gastrointestinal and kidney measuring 4 mm.
Optical Coherence Tomography
Optical coherence tomography (OCT) is analogous to ultrasound imaging, except that it uses light instead of sound allows evaluation of secondary retinal-retinal pigment epithelial changes. In addition, the technique is useful in the follow-up of lesions after treatment. Enhanced depth imaging OCT also allows detection of micrometastases often inapparent with fundoscopy.
FA can provide ancillary data necessary to differentiate choroidal metastases from choroidal melanomas. FA typically displays a hypofluorescent pattern in early arterial phases, with hyperfluoresence in the late venous phases, later than most choroidal melanomas., Choroidal metastases also contain dilated retinal capillaries with a pinpoint leakage at the tumor border in 73% of cases as compared to melanoma in 16% of cases.
Magnetic Resonance Imaging
Computed tomography and MRI have a limited role in the diagnosis of ocular metastasis. Nevertheless, brain imaging is useful before initiation of radiotherapy to rule out metastasis or extension to central nervous system (CNS). Mewis and Young reported that 22% of patients diagnosed with choroidal metastasis had a concurrent diagnosis of CNS metastasis. An additional 19% of patients had a subsequent diagnosis. MRI often shows a well-demarcated choroidal mass that appears isointense on T1-weighted images and hypointense on T2-weighted images.,
Fine Needle Aspiration Biopsy
In cases of unidentified primary source and indeterminate diagnostic findings, fine-needle aspiration biopsy can provide cytological evidence of metastasis versus primary occurrence.
The treatment of choroidal metastasis depends on the status of primary disease, number and location of choroidal metastasis, symptomatology and the general condition of the patient. A patient with an asymptomatic metastasis with poor general condition does not require therapy. On the other hand, a symptomatic patient with controlled systemic disease should receive therapy to prevent further deterioration in vision. A number of options are available depending on disease status such as chemotherapy, photocoagulation, cryosurgery, surgical resection, or radiotherapy.
Systemic treatment depends on the type of primary cancer. Fenestrated endothelium in the choriocapillaris allows entry of medications into the choroidal tumors to provide effective tumor control. Studies have shown the expression of estrogen and progesterone receptors in choroidal metastasis making therapy with tamoxifen and aromatase inhibitors effective., Regression of choroidal metastasis from breast and lung carcinoma after systemic chemotherapy has been noted.,
External Beam Radiotherapy
External beam radiotherapy (EBRT) at a dosage of 40–60 Gy causes tumor regression in 85%–93% of patients with vision improvement or stabilization in 56% of eyes.,, However, no consensus about the adequate dose and technique of radiation therapy has been reached yet. In patients with uncontrolled primary, the approach is usually palliative. Rudoler et al. reported a multivariate analysis of 188 patients treated with EBRT for choroidal metastasis. The median total dose of radiotherapy was 36 Gy with a range of 30–40 Gy in 2–3 Gy fractions. Ninety-three percent of patients remained free of clinically evident recurrent disease at last follow-up, with a 98% rate of globe preservation. In another study by Roy et al. short course palliative radiation therapy of 30 Gy in 10 # is an effective modality for the management of choroidal metastasis in patients of carcinoma breast.
Gamma knife radiosurgery (GKR) and cyberknife radiosurgery both have been used in the treatment of uveal melanomas as well as choroidal metastases.,, Two reports have documented the success of GKR with choroidal metastases, with the larger study comprised 57 eyes, documenting 100% control in Grade 1 lesions and 63% response in all choroidal metastases overall, over a mean follow-up of 7 months.,
Proton Beam Radiotherapy
Proton beam radiotherapy (PBT) allows for more focused irradiation, as compared to GKR, PBT, used for the treatment of uveal melanomas has recently been applied to choroidal metastases as well., In a retrospective study of 76 eyes treated with PBT, complete regression was observed in 84% within 5 months with no recurrence after a mean follow-up of 10 months. Associated serous retinal detachments resolved in 82% of patients within 3.8 months.
Plaque brachytherapy permits radiation to be delivered directly to the choroidal lesion and has been used successfully for choroidal melanomas and more recently, for solitary choroidal metastasis. In one retrospective study of 36 patients, lesion regression was noted in 94% of patients at a mean follow-up of 11 months. Complications were seen in 8% of patients and included radiation retinopathy, papillopathy, and cataract in anteriorly placed plaques.
Transpupillary thermotherapy (TTT) uses diode laser to administer heat to the choroid and retinal pigment epithelium, inducing tumor necrosis. The technique was first used as an adjuvant therapy for choroidal melanoma incompletely responsive to plaque radiotherapy. Expansion of the technique into other intraocular tumors has led to the treatment of choroidal metastases., In a study of 59 eyes with choroidal metastasis managed with TTT as the primary treatment, 71% of eyes showed regression or inhibition of growth, whereas 7% showed progression over a follow-up of 15 months.
Photodynamic therapy causes tumor necrosis through the production of reactive singlet oxygen, as well intravascular thrombosis and subsequent tumor infarction through verteporfin. Kaliki et al. documented tumor regression in 7 of 9 patients, with stable or improved vision in all but one case over an average follow-up of 17 months.
Intravitreal Anti-Vascular Endothelial Growth Factor Injection
Intravitreal anti-vascular endothelial growth factor injections have redirected the management of neovascular ocular conditions. With the dependence of metastases on neovascularization for growth, the use of intravitreal bevacizumab and ranibizumab to prevent angiogenesis is an effective modality of treatment.,,
Survival and Follow-Up
In general, survival is limited after the diagnosis of ocular metastasis. Ferry and Font noted a median survival of 7.4 months. Other authors have noted similar median survival rates of 5–32 months.,,,
Choroidal metastasis is a significant but under-recognized clinical problem, frequently occurring in the later stages of disseminated disease and is considered a poor prognostic sign. Effective control of these lesions is imperative. Systemic chemotherapy allows tumor control in some cases, whereas focal therapy is advised in tumors causing visual loss or is unresponsive to systemic treatment.
I acknowledge the help of my family, especially my angel Avishi for providing time and support.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
|1||Perls M. Contributions to pathology of tumors. Virchows Arch Pathol Anat 1872;56:437.|
|2||Godtfredsen E. On the frequency of secondary carcinomas in the choroid. Acta Ophthalmol 1944;22:394-400.|
|3||Bloch RS, Gartner S. The incidence of ocular metastatic carcinoma. Arch Ophthalmol 1971;85:673-5.|
|4||Ferry AP, Font RL. Carcinoma metastatic to the eye and orbit. I. A clinicopathologic study of 227 cases. Arch Ophthalmol 1974;92:276-86.|
|5||Shields CL, Shields JA, Gross NE, Schwartz GP, Lally SE. Survey of 520 eyes with uveal metastases. Ophthalmology 1997;104:1265-76.|
|6||Eliassi-Rad B, Albert DM, Green WR. Frequency of ocular metastases in patients dying of cancer in eye bank populations. Br J Ophthalmol 1996;80:125-8.|
|7||Avram AM, Gielczyk R, Su L, Vine AK, Sisson JC. Choroidal and skin metastases from papillary thyroid cancer: Case and a review of the literature. J Clin Endocrinol Metab 2004;89:5303-7.|
|8||Emirci H, Shields CL, Chao AN, Shields JA. Uveal metastasis from breast cancer in 264 patients. Am J Ophthalmol 2003;136:264-71.|
|9||Shah SU, Mashayekhi A, Shields CL, Walia HS, Hubbard GB 3rd, Zhang J, et al. Uveal metastasis from lung cancer: Clinical features, treatment, and outcome in 194 patients. Ophthalmology 2014;121:352-7.|
|10||Harbour JW, De Potter P, Shields CL, Shields JA. Uveal metastasis from carcinoid tumor. Clinical observations in nine cases. Ophthalmology 1994;101:1084-90.|
|11||Nabi G, Dadeya S, Dogra PN, Lal H. Eye metastasis form urothelial tumours. Int Urol Nephrol 2002;34:51-4.|
|12||Besic N, Luznik Z. Choroidal and orbital metastases from thyroid cancer. Thyroid 2013;23:543-51.|
|13||De Potter P, Shields CL, Shields JA, Tardio DJ. Uveal metastasis from prostate carcinoma. Cancer 1993;71:2791-6.|
|14||Fernandez-Perez S, Ruiz-Moreno O, Pueyo V, de la Mata G, Pablo L. Bilateral choroidal metastases as presentation of dissemination of cutaneous malignant melanoma. Case Rep Ophthalmol Med 2012;2012:486167.|
|15||Shields JA, Carvalho C, Shields CL, Singh AD, Wagner D. Bilateral choroidal metastasis from adenoid cystic carcinoma of the submandibular gland. Retina 2000;20:406-7.|
|16||Eagle RC Jr, Ehya H, Shields JA, Shields CL. Choroidal metastasis as the initial manifestation of a pigmented neuroendocrine tumor. Arch Ophthalmol 2000;118:841-5.|
|17||Freedman MI, Folk JC. Metastatic tumors to the eye and orbit: Patient survival and clinical characteristics. Arch Ophthalmol 1987;105:1215-9.|
|18||Mewis L, Young SE. Breast carcinoma metastatic to the choroid: Analysis of 67 patients. Ophthalmology 1982;89:147-51.|
|19||Michelson JB, Stephens RF, Shields JA. Clinical conditions mistaken for metastatic cancer to the choroid. Ann Ophthalmol 1979;11:149-53.|
|20||Merrill CF, Kaufman DI, Dimitrov NV. Breast cancer metastatic to the eye is a common entity. Cancer 1991;68:623-7.|
|21||Shields JA, Shields CL. Intraocular Tumors: A Text and Atlas. 4th ed. Philadelphia, PA: W.B. Saunders Co.; 1992. p. 208-38.|
|22||Ishida T, Ohno-Matsui K, Kaneko Y, Tobita H, Hayashi K, Shimada N, et al. Autofluorescence of metastatic choroidal tumor. Int Ophthalmol 2009;29:309-13.|
|23||Natesh S, Chin KJ, Finger PT. Choroidal metastases fundus autofluorescence imaging: Correlation to clinical, OCT, and fluorescein angiographic findings. Ophthalmic Surg LasersImaging 2010;41:406-12.|
|24||Rovati L, Docchio F. Autofluorescence methods in ophthalmology. J Biomed Optics 2004;9:9-21.|
|25||Coleman DJ, Abramson DH, Jack RL, Franzen LA. Ultrasonic diagnosis of tumors of the choroid. Arch Ophthalmol 1974;91:344-54.|
|26||Arevalo JF, Fernandez CF, Garcia RA. Optical coherence tomography characteristics of choroidal metastasis. Ophthalmology 2005;112:1612-9.|
|27||Al-Dahmash SA, Shields CL, Kaliki S, Johnson T, Shields JA. Enhanced depth imaging optical coherence tomography of choroidal metastasis in 14 eyes. Retina 2014;34:1588-93.|
|28||Almeida A, Kaliki S, Shields CL. Autofluorescence of intraocular tumours. Curr Opin Ophthalmol 2013;24:222-32.|
|29||Li L, Wang WJ, Chen RJ, Qian J, Luo CQ, Zhang YJ, et al. Fundus fluorescein angiography in metastatic choroidal carcinomas and differentiating metastatic choroidal carcinomas from primary choroidal melanomas. Zhonghua Yan Ke Za Zhi 2011;47:27-34.|
|30||Shields CL, Say EA, Stanciu NA, Bianciotto C, Danzig CJ, Shields JA. Cavitary choroidal metastasis from lung neuroendocrine tumor: Report of 3 cases. Arch Ophthalmol 2011;129:102-4.|
|31||Peyster RG, Augsburger JJ, Shields JA, Hershey BL, Eagle R Jr, Haskin ME. Intraocular tumors: Evaluation with MR imaging. Radiology 1988;168:773-9.|
|32||Shields JA, Shields CL, Ehya H, Eagle RC Jr, De Potter P. Fine-needle aspiration biopsy of suspected intraocular tumors. The 1992 Urwick Lecture. Ophthalmology 1993;100:1677-84.|
|33||Logani S, Gomez H, Jampol LM. Resolution of choroidal metastasis in breast cancer with high estrogen receptors. Arch Ophthalmol 1992;110:451-2.|
|34||Manquez ME, Brown MM, Shields CL, Shields JA. Management of choroidal metastases from breast carcinomas using aromatase inhibitors. Curr Opin Ophthalmol 2006;17:251-6.|
|35||George B, Wirostko WJ, Connor TB, Choong NW. Complete and durable response of choroid metastasis from nonsmall cell lung cancer with systemic bevacizumab and chemotherapy. J Thorac Oncol 2009;4:661-2.|
|36||Kosmas C, Malamos NA, Antonopoulos M. Complete regression of choroidal metastases from breast cancer after docetaxel-based systemic chemotherapy. Med Pediatr Oncol 2000;34:229-30.|
|37||Ratanatharathorn V, Powers WE, Grimm J, Steverson N, Han I, Ahmad K, et al. Eye metastasis from carcinoma of the breast: Diagnosis, radiation treatment and results. Cancer Treat Rev 1991;18:261-76.|
|38||Chu FC, Huh SH, Nisce LZ, Simpson LD. Radiation therapy of choroid metastasis from breast cancer. Int J Radiat Oncol Biol Phys 1977;2:273-9.|
|39||Marchini G, Babighian S, Tomazzoli L, Gerosa MA, Nicolato A, Bricolo A, et al. Gamma Knife stereotactic radiosurgery of ocular metastases: A case report. Stereotact Funct Neurosurg 1995;64 Suppl 1:67-71.|
|40||Rudoler SB, Shields CL, Corn BW, De Potter P, Hyslop T, Curran WJ Jr, et al. Functional vision is improved in the majority of patients treatment with external-beam radiotherapy for choroidmetastases: A multivariate analysis of 188 patients. J Clin Oncol 1997;15:1244-51.|
|41||Roy S, Madan R, Gogia A, Tripathy K, Sharma D, Julka PK, et al. Short course palliative radiotherapy in the management of choroidal metastasis: An effective technique since ages. J Egypt Natl Cancer Inst 2016;28:49-53.|
|42||Daftari IK, Petti PL, Larson DA, O'Brien JM, Phillips TL. A noninvasive eye fixation monitoring system for CyberKnife radiotherapy of choroidal and orbital tumors. Med Phys 2009;36:719-24.|
|43||Haas A, Pinter O, Papaefthymiou G, Weger M, Berghold A, Schröttner O, et al. Incidence of radiation retinopathy after high-dosage single-fraction gamma knife radiosurgery for choroidal melanoma. Ophthalmology 2002;109:909-13.|
|44||Bellmann C, Fuss M, Holz FG, Debus J, Rohrschneider K, Völcker HE, et al. Stereotactic radiation therapy for malignant choroidal tumors: Preliminary, short-term results. Ophthalmology 2000;107:358-65.|
|45||Gragoudas ES, Goitein M, Verhey L, Munzenreider J, Suit HD, Koehler A. Proton beam irradiation. An alternative to enucleation for intraocular melanomas. Ophthalmology 1980;87:571-81.|
|46||Gragoudas ES, Goitein M, Koehler AM, Verhey L, Tepper J, Suit HD, et al. Proton irradiation of small choroidal malignant melanomas. Am J Ophthalmol 1977;83:665-73.|
|47||Tsina EK, Lane AM, Zacks DN, Munzenrider JE, Collier JM, Gragoudas ES. Treatment of metastatic tumors of the choroid with proton beam irradiation. Ophthalmology 2005;112:337-43.|
|48||Shields CL, Shields JA, De Potter P, Quaranta M, Freire J, Brady LW, et al. Plaque radiotherapy for the management of uveal metastasis. Arch Ophthalmol 1997;115:203-9.|
|49||Oosterhuis JA, Journee-de Korver HG, Kakebeeke-Kemme HM, Bleeker JC. Transpupillary thermotherapy in choroidal melanomas. Arch Ophthalmol 1995;113:315-21.|
|50||Romanowska-Dixon B, Kowal J, Pogrzebielski A, Markiewicz A. Transpupillary thermotherapy (TTT) for intraocular metastases in choroid. Klin Oczna 2011;113:132-5.|
|51||Ardjomand N, Kucharczyk M, Langmann G. Transpupillary thermotherapy for choroidal metastases. Ophthalmologica 2001;215:241-4.|
|52||Kaliki S, Shields CL, Al-Dahmash SA, Mashayekhi A, Shields JA. Photodynamic therapy for choroidal metastasis in 8 cases. Ophthalmology 2012;119:1218-22.|
|53||Detorakis ET, Agorogiannis G, Drakonaki EE, Tsilimbaris MK, Pallikaris IG. Successful management of choroidal metastasis with intravitreal ranibizumab injections. Ophthalmic Surg Lasers Imaging 2012;43:e47-51.|
|54||Kuo IC, Haller JA, Maffrand R, Sambuelli RH, Reviglio VE. Regression of a subfoveal choroidal metastasis of colorectal carcinoma after intravitreous bevacizumab treatment. Arch Ophthalmol 2008;126:1311-3.|
|55||Mansour AM, Alameddine R. Intravitreal bevacizumab for consecutive multiple choroidal breast metastatic lesions. BMJ Case Rep 2012;2012. pii: bcr0320126124.|