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Year : 2022  |  Volume : 4  |  Issue : 1  |  Page : 7

Paraneoplastic optic neuropathy with simultaneous retinal and choroidal metastasis in metastatic lung carcinoma: A rare entity

Department of Ophthalmology, Hospital Sultanah Aminah, Johor Bahru, Malaysia

Date of Submission05-Jun-2021
Date of Decision03-Jul-2021
Date of Acceptance03-Jan-2022
Date of Web Publication09-Feb-2022

Correspondence Address:
Dr. Cheau Wei Chin
Department of Ophthalmology, Hospital Sultanah Aminah, Jalan Mahmoodiah, 80100 Johor Bahru, Johor
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/pajo.pajo_97_21

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Paraneoplastic optic neuropathy (PON) is a rare phenomenon that is associated with lung carcinoma. In addition, retinal metastasis is extremely rare, accounting for <1% of intraocular metastasis. We hereby report a rare case of synchronous metastases from lung carcinoma to the choroid of the right eye and the retina of the left eye complicated with presumed PON. The presence of intraocular mass and optic disc swelling should prompt investigations for systemic malignancies.

Keywords: Choroidal metastasis, lung carcinoma, paraneoplastic optic neuropathy, retinal metastasis

How to cite this article:
Chin CW, Ling KP, Vendargon FM. Paraneoplastic optic neuropathy with simultaneous retinal and choroidal metastasis in metastatic lung carcinoma: A rare entity. Pan Am J Ophthalmol 2022;4:7

How to cite this URL:
Chin CW, Ling KP, Vendargon FM. Paraneoplastic optic neuropathy with simultaneous retinal and choroidal metastasis in metastatic lung carcinoma: A rare entity. Pan Am J Ophthalmol [serial online] 2022 [cited 2023 Sep 29];4:7. Available from: https://www.thepajo.org/text.asp?2022/4/1/7/337480

  Introduction Top

Paraneoplastic syndromes affect less than 10% of patients with malignancies, with less than 0.1% involving the visual system. Paraneoplastic neurological syndrome (PNS) rarely manifests as paraneoplastic optic neuropathy (PON), which is usually activated by the autoantibodies produced in patients with malignancies, commonly associated with lung carcinoma.[1]

Furthermore, intraocular metastasis is often associated with advanced malignancies and is suggestive of poor survival prognosis. The most common site of primary malignancy of intraocular metastases is breast, followed by lung and gastrointestinal tract.[2] The most common site of intraocular metastasis remains to be the choroid (88%), owing to its intense vascular supply.[2] On the other hand, retinal metastasis is extremely rare, accounting for less than 1% of all intraocular metastasis. Therefore, retinal metastasis may pose a diagnostic challenge as only limited reports are available in the literature.[3]

We hereby report an exceptionally rare coexistence of PON and simultaneous choroidal and retinal metastasis in a patient with metastatic lung carcinoma.

  Case Report Top

A 39-year-old Nepalese gentleman who is a nonsmoker with no prior history of cancer was referred to us for progressive painless blurring of vision in his left eye for 2 months. There was no preceding trauma, flash, or floaters. At that point, he was investigated under the medical team for fever, shortness of breath, vomiting, and loss of weight.

On examination, his best-corrected visual acuity was 6/9 and 6/45 in the right and left eye, respectively. The relative afferent pupillary defect was grade I positive on the left eye, with light brightness of 50% and red desaturation of 100%. The anterior segment examination and intraocular pressure were normal. Fundus examination revealed a choroidal lesion in the right eye and a retinal lesion with swollen optic disc and blurred disc margin in the left eye, accompanied by bilateral exudative retinal detachment inferiorly [Figure 1]. No obvious vitritis was noted in the posterior pole. The extraocular muscle movements were intact, and no other cranial nerves affected. The rest of his neurological examination was unremarkable.
Figure 1: Fundus photograph of (a) the right eye showing choroidal mass and (b) the left eye showing swollen optic disc with blurred margin and retinal mass

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Spectral-domain optical coherence tomography demonstrated a dome-shaped choroidal mass with subretinal fluid in the right eye and a dome-shaped full-thickness retinal mass in the left eye [Figure 2]. Contrast-enhanced computed tomography (CECT) brain and orbit ruled out the presence of space-occupying lesion, intracranial bleed, and optic nerve infiltration [Figure 3].
Figure 2: Spectral-domain optical coherence tomography showing (a) choroidal mass with subretinal fluid in the right eye and (b) a large dome-shaped retinal mass with subretinal fluid in the left eye

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Figure 3: (a) Contrast-enhanced computed tomography brain showing normal optic nerves with no compression or space-occupying lesion; (b) contrast-enhanced computed tomography thorax showing ill-defined hypodense lesion in the left upper lobe suggestive of lung carcinoma; (c) contrast-enhanced computed tomography abdomen showing multiple enlarged hypodense lesions in the liver suggestive of liver metastasis and (d) filling defect within the inferior vena cava indicating inferior vena cava thrombosis and lytic lesion in the spine suggestive of bone metastasis

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His full blood count revealed normochromic normocytic anemia with leukocytosis. His renal showed hyponatremia with normal renal function. In addition, the presence of low serum osmolality was suggestive of syndrome of inappropriate antidiuretic hormone secretion (SIADH). His liver profile also showed transaminitis picture. The serum C-reactive protein and lactate dehydrogenase (LDH) were significantly elevated. Tumor markers revealed raised CA19-9 and CA125 levels. Otherwise, the autoimmune and infective screening for leptospirosis, tuberculosis, VDRL, HIV, and hepatitis B and C were unremarkable.

Ultrasound of the abdomen revealed multiple hyperechoic target nodules scattered in both liver lobes, suggestive of liver metastasis. CECT of the neck, thorax, abdomen, and pelvis was then proceeded urgently, which demonstrated left vocal cord palsy and ill-defined hypodense lesion with surrounding ground-glass changes in the left upper lobe and left major fissure suggestive of lung carcinoma [Figure 3], accompanied by multiple enlarged necrotic mediastinal, left supraclavicular, bilateral hilar, mesenteric, and para-aortic lymph nodes. There were enlarged hypodense lesions in his liver, adrenal glands, and kidneys consistent with metastasis. Multiple ill-defined mixed lytic sclerotic lesions distributed throughout the entire spine were consistent with bone metastasis as well. Furthermore, a long-segment filling defect within the inferior vena cava indicated inferior vena cava thrombosis. Unfortunately, no biopsy was performed to determine the type of lung carcinoma in view of financial constraint.

Based on his clinical symptoms, he was suspected to have paraneoplastic syndrome secondary to advanced metastatic lung carcinoma as evidenced by a combination of anemia, SIADH, raised LDH, and hypercoagulable status, resulting in inferior vena cava thrombosis. His left optic disc swelling was likely attributed to PON as his brain imaging ruled out the presence of space-occupying lesion and optic nerve infiltrations. However, no paraneoplastic onconeural antibody testing was performed in view of cost and logistic issues. The patient requested to be transferred back to Nepal for continuation of care in view of financial constraints.

  Discussion Top

PON is a rare and diverse subtype of PNS that results in irreversible damage and glial filling of the optic nerve secondary to an onconeural antigen-specific antibody autoimmune response, activated by the underlying systemic cancer affecting the central or peripheral nervous system.[1],[4] Collapsin response-mediator protein-5 (CRMP-5 IgG) is one of the well-characterized onconeural antibodies for PNS which is strongly associated with small cell lung carcinoma.[4] It is expressed in glial cells, retinal nerves, optic nerves, as well as central and peripheral neurons and is associated with the development of neuronal plasticity.[5]

Typical clinical presentation of PON is painless, subacute severe vision loss accompanied with optic disc swelling.[1] Some patients also experienced neurological sequelae such as ataxia, neuropathy, myelopathy, opsoclonus, and internuclear ophthalmoplegia.[6] Our case is distinctive as our patient did not experience any neurological deficits. Optic nerve metastasis was unlikely as the CECT imaging showed no optic nerve compression or infiltration. Furthermore, the presence of paraneoplastic syndrome in our patient pointed the diagnosis toward PON. Ideally, CRMP-5 IgG should be tested in a suspected case of PON. However, in this case, we could not do so due to patient's financial constraint and logistic difficulties. As per the consensus of the experts from the PNS EuroNetwork,[7] our patient's presentation is consistent with possible PNS as he has optic neuritis which fits in one of the nonclassical syndromes of PNS and malignancy that is present within 2 years of diagnosis but has no confirmatory onconeural antibodies.

There is no consensus on the treatment for PON as it is an exceedingly rare entity. The two principles of treatment are oncologic and immunosuppressive therapy to reduce the systemic titers of autoantibody and to prevent irreversible neuronal loss.[4] However, Xu et al. reported that patients with PON are generally insensitive to steroid therapy.[1] Other immunosuppressive therapies such as intravenous immunoglobulin or plasma exchange plus cyclophosphamide were also reported in the literature.[5] Nonetheless, the primary management should be early detection of the underlying malignancy and early commencement of anticancer therapy as it is shown to improve patient's vision significantly.[5] In this case, despite we managed to determine the underlying malignancy, our patient refused further treatment due to financial and logistic issue.

In addition, our patient also has synchronous retinal and choroidal metastasis. Choroidal metastasis may mimic choroidal melanoma, osteoma, hemangioma, granuloma, and choroiditis.[2],[8] Choroidal metastasis generally presents as a pale-yellowish mass associated with subretinal fluid and is often dome shaped,[2],[8] which is consistent with our patient's findings. On the other hand, retinal metastases have been a diagnostic challenge as they generally present as a unilateral yellowish retinal mass accompanied with vitreous seed or subretinal fluid and are often misdiagnosed as infection or inflammation.[3] However, vitreous seeding was not observed in our patient and the presence of lung malignancy with multiple metastasis sites points more toward the diagnosis of retinal metastasis.

Management of intraocular metastasis varies from observation to enucleation. Utilization of photodynamic therapy, radiation therapy, intravitreal anti-vascular endothelial growth factor, vitrectomy, and retinectomy has been reported in some cases, but there were a lack in data and inconsistent outcomes.[8] Overall, patients with intraocular metastases have poor life expectancy. The median survival time between diagnosis of intraocular metastases and death was 6 months. Retinal metastases are associated with an exceptionally poor prognosis as they usually enter the eye via the hematogenous route at the end stage of malignancy with diffuse dissemination to all organs,[3] as in our patient's case. Therefore, Shields et al. suggested conservative management with observation or globe conservation with radiotherapy methods in these cases.[3] However, enucleation may be necessary in cases of blind and painful eye associated with persistent tumor growth and neovascular glaucoma.[8]

  Conclusion Top

This is probably the first report that describes the co-existence of PON with synchronous choroidal and retinal metastasis as both are exceptionally rare conditions. The presence of intraocular mass and optic disc swelling should prompt investigations for systemic malignancies. Early commencement of anticancer therapy in patients with PON is crucial to improve patient's vision, but conservative management is preferred in patients with retinal metastasis due to its particularly poor systemic prognosis.

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

Xu Q, Du W, Zhou H, Zhang X, Liu H, Song H, et al. Distinct clinical characteristics of paraneoplastic optic neuropathy. Br J Ophthalmol 2019;103:797-801.  Back to cited text no. 1
Jorge DM, Labarrere M, Rodrigues MW, Shields CL, Jorge R. Simultaneous choroidal and retinal metastases from lung carcinoma. Retin Cases Brief Rep 2020;14:90-5.  Back to cited text no. 2
Shields CL, McMahon JF, Atalay HT, Hasanreisoglu M, Shields JA. Retinal metastasis from systemic cancer in 8 cases. JAMA Ophthalmol 2014;132:1303-8.  Back to cited text no. 3
vine MF, Kothapalli N, Elkhooly M, Dubey D. Paraneoplastic neurological syndromes: clinical presentations and management. Ther Adv Neurol Disord. 2021 Feb 1;14:1756286420985323. doi: 10.1177/1756286420985323. PMID: 33796141; PMCID: PMC7970694.  Back to cited text no. 4
Nakajima M, Uchibori A, Ogawa Y, Miyazaki T, Ichikawa Y, Kaneko K, et al. CV2/CRMP5-antibody-related paraneoplastic optic neuropathy associated with small-cell lung cancer. Intern Med 2018;57:1645-9.  Back to cited text no. 5
Ko MW, Dalmau J, Galetta SL. Neuro-ophthalmologic manifestations of paraneoplastic syndromes. J Neuroophthalmol 2008;28:58-68.  Back to cited text no. 6
Graus F, Delattre JY, Antoine JC, Dalmau J, Giometto B, Grisold W, et al. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry 2004;75:1135-40.  Back to cited text no. 7
Konstantinidis L, Damato B. Intraocular metastases – A review. Asia Pac J Ophthalmol (Phila) 2017;6:208-14.  Back to cited text no. 8


  [Figure 1], [Figure 2], [Figure 3]


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