Docetaxel Chemotherapy-Associated Central Retinal Artery Occlusion in Metastatic Prostate Cancer

Clinical Correspondence Docetaxel Chemotherapy–Associated Central Retinal Artery Occlusion in Metastatic Prostate Cancer May Ameri, BS, Saif A. Alryalat, MD, Osama Al Deyabat, MD, Noor Laylani, MD, Andrew G. Lee, MD C entral retinal artery occlusion (CRAO) is an acute ischemic stroke of the eye that leads to acute painless unilateral vision loss and may be vasculitic (e.g., giant cell arteritis), embolic (e.g., cholesterol or platelet-fibrin carotid artery plaques or calcium from cardiac valves), or thrombotic (e.g., inflammatory or hypercoagulable disorder). Cancer is an important risk factor for venous and arterial thromboembolic events like CRAO because of the hypercoagulable state of malignancy but ischemic events can also be a result of the treatment of cancer (e.g., chemotherapy or radiation side effects). CRAO has been reported after chemotherapy in the setting of cisplatin therapy (one in cervical carcinoma and one gestational trophoblastic neoplasia).1 Docetaxel is an anticancer cytotoxic drug in the taxane family that binds b-tubulin to inhibit the disassembly of microtubule preventing cell replication and inducing apoptosis. Commonly reported adverse ocular side effect of docetaxel include epiphora, punctual stenosis, conjunctivitis, and cystic maculopathy. We describe a patient who developed acute CRAO while undergoing treatment for metastatic prostate cancer with docetaxel. Although prior reports of taxanerelated ophthalmic complications have included CRAO, based on our review of the English language ophthalmic literature, we believe that our case is novel. An 85-year-old man presented with acute, painless visual loss because of a CRAO. Medical history included hypertension and aortic valve stenosis. He had metastatic prostate cancer and was being treated with intravenous docetaxel. The McGovern School of Medicine (MA), The University of Texas Health Science Center, Houston, Texas; Department of Ophthalmology (SAA, OAD, NL, AGL), Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas; Department of Ophthalmology (SAA), The University of Jordan, Amman, Jordan; Department of Ophthalmology (SAA, AGL), University of Texas Medical Branch, Galveston, Texas; Department of Ophthalmology (AGL), Cullen Eye Institute, Baylor College of Medicine, Houston, Texas; Departments of Ophthalmology, Neurology, and Neurosurgery (AGL), Weill Cornell Medicine, New York, New York; Department of Ophthalmology (AGL), University of Texas MD Anderson Cancer Center, Houston, Texas; Texas A&M College of Medicine (AGL), Bryan, Texas; and Department of Ophthalmology (AGL), The University of Iowa Hospitals and Clinics, Iowa City, Iowa. The authors report no conflicts of interest. Address correspondence to Andrew G. Lee, MD, Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, 6560 Fannin Street, Suite 450, Houston, TX 77030; E-mail: aglee@ houstonmethodist.org doi: 10.1097/WNO.0000000000002059 © 2023 by North American Neuro-Ophthalmology Society Ameri et al: J Neuro-Ophthalmol 2024; 44: e595-e596 patient presented to the emergency department the morning after his third infusion of docetaxel with progressive painless vision loss of his right eye. He had no headache, jaw claudication, or symptoms of giant cell arteritis (GCA). Ophthalmic examination showed a visual acuity of 20/ 200 in the right eye and 20/40 in the left eye. There was a relative afferent pupillary defect in the right eye. Ophthalmoscopy showed optic disc edema with peripapillary hemorrhage and superior sector retinal edema suggestive of a CRAO with concomitant anterior ischemic optic neuropathy. Automated perimetry (automated visual field 24-2) showed diffuse generalized depression superiorly and inferiorly with a small area of central cilioretinal artery sparing in the right eye and was normal in the left eye (Fig. 1). Optical coherence tomography showed thickening and edema of the inner retina and sparing of the outer retina of the right eye consistent with CRAO. The remainder of the ocular examination was normal. Fluorescein angiography showed diffuse vascular perfusion defect with cilioretinal artery sparing in the right eye (Fig. 2) and macular edema with optic disc leakage in the right eye. An erythrocyte sedimentation rate was 41 mm/h and C-reactive protein was 6.5 mg/dL. MRI of the brain with and without contrast MRA of head and neck was normal. Complete blood count with differential, electrocardiogram, and echocardiogram were unremarkable. A temporal artery ultrasound was negative for GCA but no temporal artery biopsy was performed. The docetaxel was discontinued. The visual acuity improved to 20/40 in the right eye, and he was started on aspirin-81. Previous notable studies of taxane-induced ocular side effects includes one by Esmaeli et al2 of 58 patients that showed 64% of patients experienced epiphora and one by Chan et al that reported an incidence of 88% independent of nasolacrimal duct obstruction on lacrimal drainage evaluation. A Mayo Clinic study by Fortes et al3 showed that 1.1% of 1,918 patients on taxanes had ophthalmic adverse effects but only 2 required discontinuations of drug. Overall, the most commonly reported docetaxel-related ocular side effects were canalicular obstruction, meibomian gland disease and blepharitis, chalazion, and eyelid edema. However, less commonly reported side effects included anisocoria, cranial nerve 6 palsy, and CRAO. Of these patients, one had paclitaxel-related cystoid macular edema and one had docetaxel-related canalicular obstruction. e595 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. Automated visual field of the right eye showing diffuse generalized depression superiorly and inferiorly with a small area of central sparing inferiorly consistent with cilioretinal artery sparing seen ophthalmoscopically. FIG. 2. Fundus photograph and fluorescein angiography of the right eye (A) shows retinal nonperfusion and hypofluorescence in the superior and inferior arcades. B. Mid-phase of the angiogram with delayed filling of the retinal arteries, more pronounced on the inferior arcades along with optic disc hyperfluorescence consistent with leakage. C. Delayed filling of the retinal arcades with more pronounced leakage around the optic disc. The one prior report of CRAO after paclitaxel was similar to our patient. In our case, concomitant optic disc edema and macular edema in the setting of a CRAO with cilioretinal artery sparing after the third dose of docetaxel suggests a possible taxane-related adverse effect rather than a typical CRAO related to the hypercoagulable state of malignancy alone. A full stroke evaluation for alternative thrombotic, vasculitic (e.g., GCA), or embolic etiologies for CRAO was negative. Although typical CRAO does not include macular or disc edema, more proximal ophthalmic level ischemia and ocular ischemic syndrome can produce these ophthalmoscopic findings. Interestingly, our patient also improved after dechallenge from the docetaxel, with final visual acuity improving from 20/200 to 20/40 in the right eye and an improved perimetric defect in the right eye. e596 Clinicians should be aware of both the hypercoagulable state of malignancy and the possibility of treatmentinduced ocular adverse effects (including CRAO). Further work is necessary to determine if taxane chemotherapy is causal or coincidental for CRAO or other ocular ischemic events. REFERENCES 1. Khadka S, Byanju R, Poon S. Chemotherapy-induced central retinal artery occlusion in gestational trophoblastic neoplasia: case report. Int Med Case Rep J. 2020;13:431–435. 2. Esmaeli B, Hidaji L, Adinin RB, et al. Blockage of the lacrimal drainage apparatus as a side effect of docetaxel therapy. Cancer. 2003;98:504–507. 3. Fortes BH, Liou H, Dalvin LA. Ophthalmic adverse effects of taxanes: the Mayo Clinic experience. Eur J Ophthalmol. 2022;32:602–611. Ameri et al: J Neuro-Ophthalmol 2024; 44: e595-e596 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.