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Table of Contents
Year : 2019  |  Volume : 2  |  Issue : 2  |  Page : 241-243

The story of two eyes- What to look for in the patient's eyes?

1 Department of Medical Oncology, Tata Memorial Hospital; Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
2 Homi Bhabha National Institute HBNI); Department of Radiodiagnosis, Tata Memorial Hospital, Mumbai, Maharashtra, India

Date of Web Publication20-Dec-2019

Correspondence Address:
Vanita Noronha
HBB 304 3rd Floor, Tata Memorial Hospital, Mumbai - 400 012, Maharashtra; Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/CRST.CRST_57_19

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How to cite this article:
Talreja VT, Noronha V, Joshi A, Patil V, Mahajan A, Prabhash K. The story of two eyes- What to look for in the patient's eyes?. Cancer Res Stat Treat 2019;2:241-3

How to cite this URL:
Talreja VT, Noronha V, Joshi A, Patil V, Mahajan A, Prabhash K. The story of two eyes- What to look for in the patient's eyes?. Cancer Res Stat Treat [serial online] 2019 [cited 2020 Oct 26];2:241-3. Available from: https://www.crstonline.com/text.asp?2019/2/2/241/273676

  Case History and Approach Top

A 65-year-old female patient with no comorbidities presented with a 4-month history of low backache and shortness of breath. She was diagnosed with metastatic anaplastic lymphoma kinase (ALK)-positive (on immunohistochemistry by D5F3 Ventana antibody clone) adenocarcinoma of the lung with pleural effusion, skeletal and bilateral lung metastases. She was started on crizotinib 250 mg orally twice daily and zoledronic acid and had a sustained partial response for 7 months. She then complained of right-sided periorbital pain and blurring of vision. Fundus examination was performed [Figure 1]. What is the diagnosis? What investigations should be done to confirm your diagnosis and how should the patient be treated? Once you have finalized your answer, please turn to page 242.
Figure 1: Fundus photograph of the right eye

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The pretreatment fundus photograph of the right eye [Figure 1] showed a severe elevated subretinal lesion. Magnetic resonance imaging (MRI) orbit [Figure 2] showed a 6-mm sized plaque-like T2 and T1 hypointense lesion showing postcontrast enhancement in the posterior segment of the right eye, just superior to the optic disc. The diagnosis was choroidal metastasis for which she received choroidal radiation, dosed at 20 Gy in 5 fractions using 6 MV photons in Trilogy. She had systemic clinical and radiological progression on response assessment in the lung and the mediastinal lymph nodes for which systemic therapy was changed to ceritinib 450 mg once daily with meals and the patient sustained a clinical and radiological response [Figure 3] with improvement in blurring of visual acuity till the last follow-up at 1 year.
Figure 2: Magnetic resonance imaging of the orbit

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Figure 3: Fundus photograph of the right eye 2 months after starting ceritinib treatment showing the subretinal lesion to have significantly decreased in size

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  Case Discussion Top

Lung cancer has been reported to metastasize to the eye in 0.2% to 7% of patients based on clinical studies. The choroid is the most common ocular tissue affected by metastatic disease. Choroidal metastasis represents the most common form of intraocular malignancies. While symptomatic ocular metastatic disease contributes to <3% of orbital tumors,[1] asymptomatic metastases are likely to be more common as the orbit is not a routinely evaluated site as part of the metastatic workup. The standard treatment for choroidal metastases is ocular radiotherapy or photocoagulation intended to preserve vision; however, it is associated with various complications, such as cataracts (0.04%), retinopathy, and glaucoma (0.01%).[2],[3],[4],[5],[6] The differential diagnosis of choroidal metastases includes choroidal melanoma, hemangioma, granuloma, osteoma, and sclerochoroidal calcification.[4] The treatment of choroidal metastasis depends on the status of the systemic disease, the number of choroidal tumors, location, and laterality. Observation is preferred in patients with poorly controlled systemic disease; systemic therapy including chemotherapy, immunotherapy, or hormone therapy, or whole eye radiotherapy if the metastases are multifocal and bilateral; plaque radiotherapy, transpupillary radiotherapy, or photodynamic therapy for solitary metastasis; and enucleation for blind painful eyes. There are few case reports of patients with choroidal metastasis of ALK-rearranged non-small cell lung cancer.[7],[8],[9],[10],[11],[12],[13] Four patients were treated with crizotinib therapy, and one patient was on alectinib therapy for a crizotinib-resistant disease. These cases had been pretreated with radiotherapy. This could explain the increase in blood–brain barrier permeability, thus justifying the response, or it is possible that there might be a different benefit of crizotinib in the central nervous system postirradiation as for other inhibitors.[10],[11] 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%. However, the extended treatment period of EBRT makes the treatment inconvenient and impractical in critically ill-patients with poor life expectancy. Radiation-related complications include cataract (7%), radiation retinopathy (3%), exposure keratopathy (3%), optic neuropathy (2%), and neovascularization of the iris (2%).[14] Distinct features on ophthalmoscopy and various imaging modalities distinguish choroidal metastases from other choroidal tumors. On ophthalmoscopic examination, choroidal metastases often have overlying subretinal fluid and lipofuscin that typically appear as scattered clumps of brown pigment.[15] MRI often shows a well-demarcated choroidal mass that appears isointense on T1-weighted images and hypointense on T2-weighted images.[16]

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Kreusel KM, Bechrakis NE, Wiegel T, Krause L, Foerster MH. Incidence and clinical characteristics of symptomatic choroidal metastasis from lung cancer. Acta Ophthalmol 2008;86:515-9.  Back to cited text no. 1
Jardel P, Sauerwein W, Olivier T, Bensoussan E, Maschi C, Lanza F, et al. Management of choroidal metastases. Cancer Treat Rev 2014;40:1119-28.  Back to cited text no. 2
Kanthan GL, Jayamohan J, Yip D, Conway RM. Management of metastatic carcinoma of the uveal tract: An evidence-based analysis. Clin Exp Ophthalmol 2007;35:553-65.  Back to cited text no. 3
Mauget-Faÿsse M, Gambrelle J, Quaranta-El Maftouhi M, Moullet I. Photodynamic therapy for choroidal metastasis from lung adenocarcinoma. Acta Ophthalmol Scand 2006;84:552-4.  Back to cited text no. 4
Wiegel T, Bottke D, Kreusel KM, Schmidt S, Bornfeld N, Foerster MH, et al. External beam radiotherapy of choroidal metastases – Final results of a prospective study of the German Cancer Society (ARO 95-08). Radiother Oncol 2002;64:13-8.  Back to cited text no. 5
Shields CL, Shields JA, Gross NE, Schwartz GP, Lally SE. Survey of 520 eyes with uveal metastases. Ophthalmology 1997;104:1265-76.  Back to cited text no. 6
Jiang K, Brownstein S, Sekhon HS, Laurie SA, Lam K, Gilberg S, et al. Ocular metastasis of lung adenocarcinoma with ELM4-ALK translocation: A case report with a review of the literature. Saudi J Ophthalmol 2013;27:187-92.  Back to cited text no. 7
Kinoshita Y, Koga Y, Sakamoto A, Hidaka K. Long-lasting response to crizotinib in brain metastases due to EML4-ALK-rearranged non-small-cell lung cancer. BMJ Case Rep 2013;2013. pii: bcr-2013- 200867.  Back to cited text no. 8
Kaneda H, Okamoto I, Nakagawa K. Rapid response of brain metastasis to crizotinib in a patient with ALK rearrangement-positive non-small-cell lung cancer. J Thorac Oncol 2013;8:e32-3.  Back to cited text no. 9
Stemmler HJ, Schmitt M, Willems A, Bernhard H, Harbeck N, Heinemann V. Ratio of trastuzumab levels in serum and cerebrospinal fluid is altered in HER2-positive breast cancer patients with brain metastases and impairment of blood-brain barrier. Anticancer Drugs 2007;18:23-8.  Back to cited text no. 10
Feng Y, Singh AD, Lanigan C, Tubbs RR, Ma PC. Choroidal metastases responsive to crizotinib therapy in a lung adenocarcinoma patient with ALK 2p23 fusion identifi ed by ALK immunohistochemistry. J Thorac Oncol 2013;8:e109-11.  Back to cited text no. 11
Rao RC, Gragoudas ES. Choroidal metastases from EML4-ALK-positive non-small-cell lung adenocarcinoma. J Clin Oncol 2015;33:e112-4.  Back to cited text no. 12
Bearz A, Santarossa S, Manfrè A, Beltrame G, Urbani M, Sartor I, et al. Activity of crizotinib over choroidal metastases in non-small-cell lung cancer (NSCLC)-ALK rearranged: A case report. BMC Res Notes 2014;7:589.  Back to cited text no. 13
Okuma Y, Tanaka Y, Kamei T, Hosomi Y, Okamura T. Alectinib for choroidal metastasis in a patient with crizotinib-resistant ALK rearranged positive non-small cell lung cancer. Onco Targets Ther 2015;8:1321-5.  Back to cited text no. 14
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.  Back to cited text no. 15
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.  Back to cited text no. 16


  [Figure 1], [Figure 2], [Figure 3]


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