Rare Eye Complication Emerges After Combined Cisplatin and Capecitabine Chemotherapy

A 50-year-old woman undergoing treatment for anal canal cancer developed sudden, painless blurred vision in both eyes just sixteen days after finishing her final cycle of chemotherapy, and clinicians in Beijing traced the striking changes in her optic nerves back to the two drugs she had been taking. The case, published in Frontiers in Ophthalmology, describes bilateral optic disc edema with papillophlebitis-like features following combined cisplatin and capecitabine therapy, an ocular adverse event so uncommon that only a handful of comparable reports exist in the medical literature. What makes the case particularly notable is the outcome: with no steroids and no immunosuppressive treatment of any kind, the swelling resolved completely and her vision returned to normal within two months.

The patient had been treated for squamous cell carcinoma of the anal canal, staged as cT4N1M0, with a regimen that combined pelvic radiotherapy and chemotherapy. She received twenty-eight fractions of dose-painted intensity-modulated radiotherapy, delivering 60 Gy in 25 fractions to involved pelvic lymph nodes, 56 Gy in 28 fractions to the primary anal canal tumor, and 45 Gy in 25 fractions to the elective nodal basin. Alongside the radiation, she completed four 28-day cycles of chemotherapy, each comprising cisplatin at 75 mg/m² and oral capecitabine at 1,000 mg in the morning and 1,500 mg in the evening. The first two cycles ran concurrently with radiotherapy and the final two as consolidation, bringing her cumulative cisplatin exposure to 300 mg/m². Her medical history was otherwise unremarkable, with no hypertension, diabetes, thromboembolic disease, autoimmune conditions, prior eye problems, or hereditary optic neuropathy.

Sixteen days after the last chemotherapy cycle, she noticed blurred vision in both eyes. Crucially, the symptoms were painless: no discomfort on eye movement, no headache, no nausea, and no vomiting, a pattern that would later help clinicians rule out several dangerous alternatives. At the referring hospital, her best-corrected visual acuity measured 0.6 in the right eye and 0.4 in the left, and examination revealed bilateral optic disc edema with hyperemia. Brain magnetic resonance imaging was recommended, but no specific ophthalmic treatment was started, and the visual symptoms persisted, prompting referral to the Air Force Medical Center of PLA in Beijing.

On arrival, her visual acuity was 0.6 in both eyes with no improvement on refraction, intraocular pressure was normal, and there was no relative afferent pupillary defect, a sign that the optic nerves were conducting signals symmetrically. Slit-lamp examination showed no inflammatory exudation or aqueous flare in either the anterior or posterior segments. But fundus photography told a dramatic story: both optic discs were diffusely swollen and hyperemic, ringed by radial flame-shaped hemorrhages, with the retinal veins dilated and tortuous. Visual field testing revealed an inferonasal defect in the right eye and a nasal defect in the left. Although formal color vision testing was not performed, bedside red-green comparison showed no subjective difference between the eyes.

Optical coherence tomography confirmed diffuse thickening of the peripapillary retinal nerve fiber layer in both eyes, consistent with genuine optic disc edema rather than pseudopapilledema. Fundus fluorescein angiography added a critical piece of evidence: marked late-phase hyperfluorescence and leakage from both optic discs, with areas of blocked fluorescence corresponding to the hemorrhages, but no segmental delay or defect in retinal vascular filling. That absence of filling defects was important, because it argued against non-arteritic anterior ischemic optic neuropathy, one of the leading alternative diagnoses in a patient of this age.

To hunt for secondary causes of the swelling, the team launched a comprehensive systemic work-up. Laboratory investigations revealed macrocytic hyperchromic anemia, lymphopenia, and elevated total cholesterol, LDL cholesterol, and gamma-glutamyl transferase. Serum CA125 was mildly elevated, and anti-SOX1 antibodies were weakly positive, but infectious and autoimmune evaluations and the remaining tumor markers were unremarkable. Contrast-enhanced brain MRI showed multiple lacunar infarcts in the bilateral frontoparietal subcortical white matter and corona radiata, plus a pituitary lesion suggestive of a Rathke cleft cyst, but no intracranial or orbital metastasis, compressive lesion, or mass effect. Oncology consultation and follow-up CT found no tumor recurrence or distant metastasis. Two neurological examinations revealed no focal signs, and the intracranial imaging findings were judged unrelated to the optic disc edema. Lumbar puncture was recommended to assess intracranial pressure directly, but the patient declined. Atorvastatin was started for the hyperlipidemia.

Based on the full clinical picture, the team considered optic neuritis, NAION, compressive or infiltrative lesions, and paraneoplastic syndrome unlikely. Although intracranial hypertension could not be definitively excluded without the lumbar puncture, the overall findings pointed toward a possible association between the bilateral optic disc edema and the cisplatin-plus-capecitabine regimen. The patient received neither glucocorticoids nor immunosuppressants. During hospitalization, her visual acuity improved to 0.8 in both eyes with marked resolution of the disc edema and hyperemia. At the two-month follow-up, best-corrected visual acuity had reached 1.2 bilaterally, fundus photography showed near-complete resolution of the hemorrhages and swelling, visual field defects had improved, and OCT demonstrated reduced peripapillary nerve fiber layer thickness compared with earlier scans. Visual function remained well preserved without any anti-inflammatory therapy.

The discussion in the report places this case in the context of decades of scattered evidence on platinum-associated ocular toxicity. Cisplatin has been linked to optic neuropathy, retinal damage, and optic disc edema, and a disproportionality analysis of the US Food and Drug Administration Adverse Event Reporting System identified 69 ocular safety signals related to platinum agents, including optic disc hyperemia with oxaliplatin and cortical blindness with cisplatin. Bilateral optic neuropathy with central scotomas was reported as far back as 1997 following high-dose cisplatin and carboplatin, with gradual visual recovery over a year. Capecitabine, an oral prodrug of 5-fluorouracil, has been associated primarily with ocular surface irritation, corneal abnormalities, and transient visual symptoms, though severe corneal toxicity and a case of severe visual loss temporally associated with the drug have also been described. Bilateral optic disc edema has been reported after FOLFOX therapy, which combines 5-fluorouracil, leucovorin, and oxaliplatin, and optic neuritis has rarely been linked to 5-fluorouracil itself.

Two mechanisms may plausibly explain the combination of findings. Cisplatin-related ocular toxicity has been attributed to ion-channel dysfunction, endothelial injury, and increased vascular permeability, with cumulative exposure potentially raising the risk of damage. Capecitabine-derived 5-fluorouracil has been reported to promote vascular smooth muscle contraction through protein kinase C activation and endothelin-1 upregulation, potentially causing vasospasm and impaired optic disc perfusion. The authors propose that such vasospasm, acting together with cisplatin-related endothelial injury and increased vascular permeability, may have produced the bilateral hemorrhagic optic disc edema. Recent cohort data also suggest dose-related structural effects: in 36 pediatric oncology patients, higher cumulative cisplatin exposure was associated with reduced central foveal retinal thickness and thinning of the nasal-superior retinal nerve fiber layer.

The spontaneous resolution carries its own diagnostic weight. The favorable outcome suggests a potentially reversible chemotherapy-associated vascular or endothelial injury rather than severe irreversible ischemic damage to the optic nerve. Prior reports show heterogeneous outcomes for platinum-associated optic disc edema: carboplatin-associated bilateral papilledema has resolved within weeks to months after drug discontinuation, oxaliplatin-related ocular neurotoxicity has been reversible after treatment cessation, yet other cases of carboplatin- and oxaliplatin-associated optic disc edema left persistent visual impairment and residual field defects despite prompt withdrawal and corticosteroid treatment. Differences in cumulative exposure, injury severity and duration, the extent of optic nerve involvement, and the timing of drug withdrawal likely explain the variation. The authors also note that the absence of vascular risk factors such as hypertension and diabetes may have favored recovery in this patient.

The report comes with candid limitations. Intracranial hypertension could not be definitively excluded because the lumbar puncture was declined. Color vision was assessed only by subjective bedside comparison. And as a single case without rechallenge, drug-level measurements, or a clear dose-response relationship, causality could not be established, nor could the responsible agent be identified among the two drugs. The authors are careful about what the case does and does not justify: it does not support routine baseline OCT or fundus imaging for all platinum-treated patients, nor automatic cessation of essential therapy. Instead, they recommend that patients receiving potentially ocular-toxic chemotherapy be advised to report new visual symptoms promptly, that baseline and follow-up imaging be considered for selected high-risk patients or regimens, and that OCT, with OCT angiography when available, may be considered during follow-up, particularly for patients receiving higher cumulative doses. Decisions to withhold, modify, or resume chemotherapy should balance the ocular findings, oncologic benefit, alternative treatments, and patient preferences, ideally through multidisciplinary assessment.

Subject of Research: Chemotherapy-associated bilateral optic disc edema with papillophlebitis-like features following cisplatin and capecitabine treatment

Article Title: Case Report: Bilateral optic disc edema with papillophlebitis-like features following combined cisplatin and capecitabine chemotherapy

Article References: Cao, S., Wang, L., Chen, W., & Liu, Y. (2026). Case Report: Bilateral optic disc edema with papillophlebitis-like features following combined cisplatin and capecitabine chemotherapy. Frontiers in Ophthalmology, 6, Article 1961914. https://doi.org/10.3389/fopht.2026.1961914

Image Credits: AI Generated

DOI: 10.3389/fopht.2026.1961914

Keywords: cisplatin, capecitabine, optic disc edema, papillophlebitis, chemotherapy ocular toxicity, optical coherence tomography, fluorescein angiography, anal canal cancer, 5-fluorouracil, vasospasm, endothelial injury, case report