History of present illness
A 65-year-old woman with a history of non–small cell lung cancer (NSCLS) with metastasis to the brain presented with visual disturbances in both eyes. She describes the vision changes as “television static or sparkles” that had been present for the past 5 years with recent improvement. She denies any loss of vision, trauma, or history of eye surgery/procedures. She does confirm mild nyctalopia, although she denies any family history of retinal degeneration or macular degeneration.
Ocular examination findings
At her initial presentation, best corrected visual acuities were 20/20 in each eye, intraocular pressures were normal (13 right eye and 15 left eye), and trace nuclear sclerosis was present. Dilated fundus examination of each eye showed a clear vitreous, healthy optic nerve, sharp foveal reflex, and absence of retinal hemorrhage, cotton wool spots, macular edema, drusen, or retinal or choroidal metastases ( Fig. 57.1 ).
Imaging
A spectral domain optical coherence tomography (OCT) scan ( Fig. 57.2 ) demonstrated parafoveal outer retinal attenuation in both eyes. A concurrent OCT angiogram (OCTA) ( Fig. 57.3 ) showed no abnormalities.
Questions to ask
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Does the patient have a family history of ocular conditions or consanguinity? A family history would be important to ascertain etiologies for retinal dystrophies such as cone dystrophy and rod-cone dystrophy, as well as macular degeneration.
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No.
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What is the current status of the patient’s cancer? Is it in remission? Does the patient have recent neurological imaging and up-to-date systemic screening? Given her history of systemic/metastatic cancer, it is important to understand the patient’s current medical status and to have documentation of neuroimaging.
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The patient’s cancer was in remission. Recent screening magnetic resonance imaging, positron emission tomography, and computed tomography scans showed no evidence of recurrence in the lung.
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What past or current cancer treatment is the patient undergoing? What medications does the patient take? There are multiple different chemotherapeutic regiments that are associated with retinal toxicity, such as mitogen-activated protein kinase (MEK) inhibitors, alkylating agents, checkpoint inhibitors, and anaplastic lymphoma kinase (ALK) inhibitors.
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She had been taking multiple different chemotherapeutic regiments with ALK inhibitors. The patient was currently taking crizotinib for 4 years, followed by ceritinib for 3 years and most recently switched to alectinib. She noted that once she had switched to alectinib, her visual disturbances improved.
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Assessment
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This is a case of a 65-year-old woman with a history of metastatic NSCLC on multiple chemotherapeutic agents demonstrating chronic photopsias and parafoveal outer retinal attenuation on OCT.
Differential diagnosis
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Medication-induced retinal toxicity
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Cancer-associated retinopathy
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Cone dystrophy
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Rod and cone dystrophy
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Central areolar choroidal dystrophy
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Age-related macular degeneration
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Retinal metastasis
Working diagnosis
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Retinal toxicity associated with ALK inhibitor use
Multimodal testing and results
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Fundus photographs
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Fundus examination was normal in our patient. There is no documented standard presentation for ALK inhibitor retinal toxicity.
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OCT
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This patient’s OCT demonstrated parafoveal outer retinal attenuation specific to the ellipsoid zone in both eyes. There is limited data on ALK inhibitor retinal toxicity. Outer retinal attenuation is a common nonspecific finding in medication-induced retinal toxicity and retinal dystrophies.
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Electroretinogram (ERG)
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An ERG was obtained given the patient’s history of metastatic lung cancer and target anticancer agents. The ERG showed a mixed rod/cone diminished response, specifically a diminished b-wave in dark-adapted state ( Fig. 57.4 ). ALK inhibitors have been shown to affect the signaling process of retinal ganglion cells creating a functional disturbance possibly leading to visual disorders. Furthermore, a study found crizotinib decreased the b-wave amplitude during dark adaption.
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