Transient monocular vertical hemifield loss as a rare acute oxaliplatin-induced ophthalmological side effect: a case report and review of the literature

Abstract

Oxaliplatin commonly induces acute, transient peripheral neurotoxicity, most often presenting as cold-induced paresthesia. Ocular adverse events are rare and poorly understood. This case describes a rare, reproducible transient monocular visual field loss associated with oxaliplatin exposure. We report a patient treated with FOLFOX (5-FU + oxaliplatin) for metastatic rectal cancer who developed recurrent transient visual symptoms temporally associated with oxaliplatin infusion. Biological, neurological, and ophthalmological evaluations were performed. The patient experienced recurrent, transient left monocular vertical hemifield loss during oxaliplatin administration. Extensive neurological and ophthalmological investigations were unremarkable. Symptoms were fully reversible and reproducible across treatment cycles, occurring exclusively after oxaliplatin exposure. This case adds to the limited literature on oxaliplatin-associated ocular neurotoxicity and emphasizes that transient visual symptoms may represent a reversible form of acute neurotoxicity. Recognizing this entity is important to avoid premature discontinuation of an effective chemotherapy regimen.

Plain language summary

Temporary vision loss as a eye-related side effect of oxaliplatin: a case report and review of the literature

Oxaliplatin is a chemotherapy drug that has been commonly used to treat digestive cancers for around thirty years. A well-known side effect is temporary nerve irritation, usually felt as tingling in the hands or around the mouth. Eye-related side effects are very rare. We describe a patient who experienced brief episodes of vision loss affecting one eye, occurring only during oxaliplatin treatment and resolving completely afterward. Medical examinations showed no damage to the eyes or brain. Recognizing this rare but reversible side effect may help doctors avoid stopping effective treatment unnecessarily.

Introduction

Since the early 2000s, the MOSAIC ¹ and EORTC ² trials have established the FOLFOX regimen—combining 5-fluorouracil (5-FU) and oxaliplatin—as a standard treatment for locally advanced colorectal cancer. Oxaliplatin is widely used in gastrointestinal oncology, and its toxicity profile is well documented. The most common adverse effects involve the hematological, gastrointestinal (e.g., nausea, vomiting, and diarrhea), and neurological systems, as well as hypersensitivity-related reactions (e.g., infusion reactions).

Two distinct forms of oxaliplatin-induced neurotoxicity are classically described:

1. Acute, transient neurotoxicity, occurring during or shortly after infusion.

2. Cumulative chronic sensory neurotoxicity, which may persist and impair quality of life.

Acute neurotoxicity affects approximately 85%–95% of patients and typically manifests as peripheral or perioral paresthesia, often triggered or exacerbated by cold exposure. ³ Less frequently, pharyngolaryngeal dysesthesia may occur. ⁴ These symptoms are usually brief and reversible, appearing during infusion or within hours following administration. Electrophysiological abnormalities, such as repetitive muscle action potentials and neuromyotonic discharges, have been described within 24–48 h of oxaliplatin infusion. ⁵ Acute symptoms generally peak around day 3 and progressively resolve thereafter. ⁶ These phenomena are attributed to acute peripheral nerve hyperexcitability without structural injury. ⁷

When acute neurotoxicity occurs, patient education and supportive care measures are recommended, including avoidance of cold exposure during and in the days following infusion and reassurance regarding symptom reversibility. ³ In severe cases, prolonging oxaliplatin infusion to 4–6 h may reduce symptom intensity. Pharmacological interventions such as calcium and magnesium infusions, carbamazepine, or gabapentin have not demonstrated consistent benefit in preventing acute neurotoxicity.^8,9 Oncologic management should therefore be individualized, balancing toxicity against the therapeutic benefit of oxaliplatin.

In contrast, chronic neurotoxicity develops cumulatively, may be partially irreversible, and can significantly affect daily activities.^10,11

For more than two decades, rare cases of ophthalmologic toxicity associated with oxaliplatin-based chemotherapy have been reported in the literature. The most frequently reported manifestations are transient visual disturbances or vision loss,^{12 –27} which are sometimes associated with ptosis.^13,14 These manifestations may be considered acute ophthalmologic toxicity related to oxaliplatin. Only one case of permanent vision loss has been reported and was attributed to retinal vein thrombosis, which may have been related to the underlying malignancy or the treatment. In most of the reported cases, oxaliplatin was discontinued.

We report here an unusual ophthalmologic presentation of acute oxaliplatin-induced neurotoxicity, characterized by transient unilateral visual disturbances in the absence of detectable abnormalities on neurological or ophthalmological evaluation. Although rare, similar cases have been sporadically reported in the literature.^{12 –27}

This case report has been reported in accordance with the CARE reporting guidelines (Supplemental Material). ²⁸ Informed consent was obtained from the patient for publication of this case report.

Case presentation

We present the case of a 72-year-old man with a history of well-controlled hypertension—treated with irbesartan and hydrochlorothiazide, and benign prostatic hyperplasia—treated with Serenoa repens (Permixon^®). He was a former smoker with an estimated 30 pack-year history. The patient had been taking medication for benign prostatic hyperplasia for 5 years prior to starting oncology care and did not take any other natural supplements.

He underwent cataract surgery of the right eye in May 2023 and of the left eye in June 2023. The latter procedure was complicated by capsular rupture, requiring vitrectomy and implantation of a customized intraocular lens. In January 2024, he developed Irvine–Gass syndrome (postoperative cystoid macular edema), which responded to intravitreal triamcinolone (Kenacort^®). Follow-up fluorescein angiography in March 2024 showed sequelae of venous occlusion with optic disc shunt vessels and peripheral hemorrhages, without ischemic areas.

The patient had no prior oncologic history.

In the context of epigastric pain, imaging revealed suspicious hepatic nodules. Further investigations confirmed a moderately differentiated rectal adenocarcinoma of Lieberkühn type with liver metastases, without other distant disease. The multidisciplinary tumor board (MDT) recommended perioperative chemotherapy with curative intent using the FOLFOX regimen.

The first cycle was administered in December 2024 according to the standard FOLFOX protocol. On day 1, all drugs were administered intravenously as follows: oxaliplatin at 85 mg/m², leucovorin at 200 mg/m², a 5-FU bolus at 400 mg/m². This was followed by a 46-h continuous 5-FU intravenous infusion at 2400 mg/m² starting on day 1 and continuing through day 2. The patient returned home with the portable infusion pump.

Within hours after oxaliplatin infusion, the patient experienced several episodes of painless transient left monocular vertical hemifield loss, described as a black vertical veil progressing from the temporal to the nasal visual field, sparing central vision. Each episode lasted approximately 15 s. The patient did not report any associated dizziness during these episodes. Ophthalmologic examination the following day after the end of the 5-FU infusion showed normal visual acuity (10/10), normal pupillary reflexes, and no papilledema or vascular abnormalities. Optical coherence tomography angiography revealed no new findings, and both confrontation testing and automated perimetry were normal.

The patient was urgently referred to a neurovascular unit. Retrochiasmatic homonymous hemianopsia was excluded due to strictly monocular symptoms. Brain MRI showed no acute ischemic lesions, hemorrhage, or microbleeds. Doppler ultrasound of the supra-aortic trunks revealed no significant stenosis.

Transient monocular blindness (amaurosis fugax) was considered; however, the vertical distribution and rapid reversibility of symptoms were atypical for vascular pathology.

Orbital-focused MRI showed no intra- or extra-axial lesions or orbital abnormalities.

At MDT discussion, both 5-FU–induced vasospasm and oxaliplatin-induced neurotoxicity were considered.

A second cycle was administered under inpatient monitoring, following the same sequence as in the first cycle (oxaliplatin first). During the 5-FU infusion, approximately 10 episodes of transient left monocular vertical hemifield loss occurred over 9 h. Neurological and metabolic evaluations were normal (the blood sugar level was measured at 1.3 g/L and all viral investigations, including Herpes Simplex Virus testing, were negative). The 5-FU infusion was discontinued.

For the third cycle, drug sequencing was modified, administering 5-FU before oxaliplatin. The patient tolerated the 46-h 5-FU infusion without incident. During subsequent oxaliplatin infusion, he again experienced recurrent brief episodes of painless left monocular vertical hemifield loss. The fourth cycle reproduced the same pattern. Blood glucose levels were repeatedly measured and remained normal. Viral testing was not repeated, as previous results had been negative.

The patient subsequently underwent bi-segmental hepatic resection, radiofrequency ablation, and rectosigmoid resection. Pathology revealed ypT0N0 (0/25), M1, TRG3.

Adjuvant intra-arterial hepatic FOLFOX was recommended. During intra-arterial oxaliplatin administration, only three brief episodes of monocular vertical hemifield loss occurred, still painless, suggesting reduced systemic exposure. Subsequent intravenous 5-FU infusions caused no symptoms.

By this stage, the patient had received a total cumulative dose of 850 mg of oxaliplatin intravenously and 588 mg intra-arterially. For each intravenous infusion of oxaliplatin, the drug was administered over a period of 2 h. For arterial infusion, the infusion duration was 2 h and 10 min. Throughout treatment, no dose adjustments were made to oxaliplatin or any other component of the FOLFOX regimen. All chemotherapy cycles were administered every 2 weeks, in line with the standard protocol. In this case, no cycle was delayed due to ocular adverse effects.

No medicines or supportive treatments were introduced during the period in question.

Patient had an ophthalmological exam months after the end of oxaliplatin infusions, which was completely normal.

The sequence of events described is summarized in the timeline (Figure 1).

Figure 1.

Timeline.

× × ophthalmological symptoms occurrence; Cx, cycle of treatment number x; IA, intra-arterial; IV, intravenous.

Discussion

This case illustrates a rare and atypical manifestation of acute oxaliplatin-induced neurotoxicity, presenting as recurrent, transient monocular vertical hemifield loss. The suspected pathophysiological mechanism underlying the patient’s symptoms may involve transient dysfunction affecting the anterior visual pathways, potentially rendered more vulnerable by the patient’s prior ophthalmologic history, possibly through oxaliplatin-induced neuronal hyperexcitability related to voltage-gated ion channel dysfunction. This presentation is therefore consistent with a transient optic pathway dysfunction, likely reflecting an acute neurotoxic effect of oxaliplatin. Reversal of the treatment sequence from the third cycle onward, with administration of 5-FU prior to oxaliplatin and without recurrence of the visual symptoms during the entire 5-FU infusion period—previously observed only following oxaliplatin infusion—supports the hypothesis that the symptoms are attributable to oxaliplatin rather than to 5-FU.

Also, the literature reports very rare cases of ophthalmic toxicity attributed to 5-FU. Most commonly, this involves damage to the corneal epithelium, which may lead to keratitis in very rare reported cases.^29,30 For the same reason, topical 5-FU ophthalmic drops are frequently used for the primary treatment of ocular surface squamous neoplasia.^31,32 In addition, arterial vasospasm associated with 5-FU use has been reported in the literature in patients presenting with abnormal ophthalmologic findings, supporting the hypothesis of a vascular mechanism underlying certain ocular adverse events. ³³

In contrast, ocular toxicity associated with oxaliplatin appears to be an underrecognized, acute, and reversible phenomenon, likely related to transient neurotoxicity, as supported by pharmacovigilance data and case-based analyses. ³⁴

Additionally, several elements support a causal relationship with oxaliplatin: exclusive occurrence after oxaliplatin administration irrespective of route, reproducibility across cycles, dose–exposure relationship suggested by fewer events during intra-arterial administration, complete reversibility, and normal extensive neurological and ophthalmological workup.

Ocular involvement in oxaliplatin-induced neurotoxicity remains rare; however, it appears to be more frequently reported than with other platinum-based agents, with only sporadic cases described for cisplatin and exceptional reports for carboplatin, suggesting a distinct, predominantly functionally driven neurotoxicity profile. ³⁵

Table 1 summarizes the cases of ocular toxicity following oxaliplatin chemotherapy in the literature.

Table 1.

Reported cases of ocular toxicities following chemotherapy with oxaliplatin.

References	Year of publication	Age	Sex	Chemotherapy protocol	Cycle when symptoms appeared	Ocular symptoms and duration, if available	Examinations	Management	Supportive care, if mentioned	Evolution of symptoms	Diagnosis
O’Dea et al. 12	2006	45	F	FOLFOX a	C3	Visual loss affecting the peripheral to central visual field	Significant bilateral reduction in visual acuity	Oxaliplatin temporarily discontinued; 5-FU l likely continued (not explicitly detailed in the report)	NA g	Progressive improvement until complete recovery. No recurrence after new oxaliplatin exposure	Oxaliplatin adverse effect, not more detailed
O’Dea et al. 12	2006	57	M	FOLFOX a	C1	Tunnel vision	Altered visual field Overall visual acuity largely preserved	Oxaliplatin definitively discontinued; 5-FU l likely continued (not explicitly detailed in the report)	NA g	Progressive improvement	Oxaliplatin adverse effect, not more detailed
O’Dea et al. 12	2006	52	M	Oxaliplatin monotherapy	C2	Tunnel vision	Altered visual field	Oxaliplatin definitively discontinued	NA g	Progressive improvement	Oxaliplatin adverse effect, not more detailed
O’Dea et al. 12	2006	29	F	FOLFOX a	C1	Visual loss affecting the lower half of the visual field	Loss of the lower half of the visual field, visual acuity partially preserved	Oxaliplatin definitively discontinued; 5-FU l likely continued (not explicitly detailed in the report)	NA g	Progressive improvement	Oxaliplatin adverse effect, not more detailed
La Verde et al. 13	2007	58	F	FOLFOX a	C2	Transient bilateral ptosis lasting 24 h, dysarthria, paresthesia, and dyspnea	Normal MRI	Oxaliplatin definitively discontinued; 5-FU l likely continued	Antihistamine and steroid	Complete recovery of ptosis within 24 h	Acute neurotoxicity related to oxaliplatin
La Verde et al. 13	2007	72	F	Oxaliplatin monotherapy	C2	Transient bilateral ptosis appeared at day 2 and lasting 6 h	Normal MRI and EEG i	Prolonged infusion of oxaliplatin (6 h) at C3	Glutathione as preventive neuroprotector	Complete recovery. No recurrence after C3	Acute neurotoxicity related to oxaliplatin
Lau and Shibata 14	2009	76	F	EOX b	C2–C5	Transient bilateral ptosis followed by blurred vision, lasting between 15 and 30 min	Normal ophthalmological examination	Prolonged infusion of oxaliplatin (4 h then 6 h); oxaliplatin dose reduction	NA g	Complete resolution after dose reduction (100 mg/m²)	Acute neurotoxicity related to oxaliplatin
Mesquida et al. 15	2010	52	F	FOLFOX a	C3	Visual loss and color vision impairment lasting 3 weeks	Altered ophthalmological examination (loss of visual acuity, altered Ishihara color test, severe bilateral concentric scotoma with mild central defect on visual field, electrooculogram test with deeply diminished response) Fundus examination, OCT j of macula and optic nerve normal	Chemotherapy discontinued	NA g	Progressive improvement within 3 weeks after discontinuation then complete recovery	Retinal pigment epithelium and optic nerve damage (chronic sensory neurotoxicity related to oxaliplatin)
Gilbar and Sorour 16	2012	50	M	CAPOX c  + Bevacizumab	C1 -Neoadjuvant treatment	Right eye vision loss preceded by transient blurred vision after each cycle lasting 3 days post C1 and 45 days post C2	Visual acuity 6/36 (right eye); fundus examination showing optic disk edema, fundal hemorrhages, dilated tortuous veins Brain and orbital CT normal	No adjuvant treatment	None (symptoms identified remotely)	No recovery	Retinal vein thrombosis possibly related to malignancy, surgery, or treatment (5-FU or bevacizumab)
Painhas et al. 17	2014	54	F	FOLFOX a	C2	Transient visual obscurations for 4 days, headache, nausea, and occasional vomiting lasting months	Bilateral disk swelling; Goldmann visual fields: exclusion and enlarged blind spot; normal brain MRI; lumbar puncture with an elevated opening pressure of 290 mm H2O with normal compounds	Oxaliplatin definitively discontinued	Oral acetazolamide, maintained for 1 month	Progressive improvement of ocular and systemic symptoms within 3 weeks then complete recovery. Disk swelling gradually improved in the following months. Complete recovery at 1 year.	Idiopathic intracranial hypertension possibly related to oxaliplatin
Fanetti et al. 18	2018	54	F	FOLFOX a	C3	Bilateral palpebral ptosis and dyspnea without bronchospasm or laryngospasm, lasting 1 h	Not reported in the abstract	Oxaliplatin dose reduction	Chlorphenamine and hydrocortisone	Progressive improvement within 1 h then complete recovery	Neurological toxicity related to oxaliplatin
Noor et al. (19)	2019	71	M	FOLFIRINOX d	C1–C2	Transient complete right eye vision loss followed by tunnel vision lasting 2 days	Normal ophthalmological examination	Switched to gemcitabine + Nab-paclitaxel	NA g	Progressive improvement within 2 days then complete recovery	Oxaliplatin adverse effect, not more detailed
Patel et al. 20	2021	52	F	FOLFOX a	C2	Visual impairment associated with severe motor slowing, delayed and incomplete grip and dorsiflexion, speech difficulty, leg cramping and tingling, lasting 24 h	Normal biologic analyses	Prolonged infusion; oxaliplatin dose reduction	NA g	Progressive improvement within 24 h then complete recovery	Neurological toxicity related to oxaliplatin
Ah-Thiane et al. 21	2021	50	F	FOLFOX a	C1	Bilateral transient vision loss (6–10 episodes/day, lasting some minutes), over 1 week	Normal cerebral imaging and ophthalmological examination	Oxaliplatin definitively discontinued; 5-FU l continued until cycle 3	None	Complete recovery within 1 week and no further ocular event until HIPEC k oxaliplatin	Acute neurotoxicity related to oxaliplatin
Ah-Thiane et al. 21	2021	57	F	FOLFIRINOX d	C3	Recurrent transient right eye vision loss lasting seconds, over 4 days	Normal ophthalmological examination	Oxaliplatin definitively discontinued; 5-FU l continued until cycle 12	NA g	Complete recovery and no recurrence after C4	Acute neurotoxicity related to oxaliplatin
Kubo et al. 22	2021	70	M	SOX e	C1–C5	Darkening of the right visual field with transient vision loss (~1 min, ~7 episodes/day) lasting 1 week	Normal ophthalmological examination; normal orbital MRI, Doppler ultrasound, and carotid ultrasound	Oxaliplatin discontinued at cycle 6; S-1 continued	None	Complete recovery	Oxaliplatin-associated amaurosis fugax (acute neurotoxicity)
Beaumont et al. 23	2021	72	M	GEMOX f	NA g	Progressive painless bilateral vision loss described as a “black fog” during infusions lasting months	Reduced visual acuity; bilateral cataracts; bilateral optic disk edema (Frisen grade 3 right, grade 4 left); OCT j and fluorescein angiography confirming optic disk leakage; bilateral cecocentral scotomas; normal brain and spinal MRI; normal inflammatory markers	Oxaliplatin definitively discontinued; Gemcitabine continued	NA g	Partial recovery with resolution of optic disk edema; persistent blind spot enlargement	Bilateral optic disk swelling related to oxaliplatin
Tunio et al. 24	2022	52	M	CAPOX c	C1	Recurrent transient right eye vision loss (7–9 episodes, lasting between few minutes and 20 min)	Normal ophthalmological examination; normal brain and orbital MRI; normal CT angiography	Chemotherapy discontinued	None	No recurrence	Amaurosis fugax could be related to the vasospasm of retinal vessels (vasospastic): acute neurotoxicity
Tunio et al. 24	2022	26	M	FOLFIRINOX d	C3	Blurred vision for a few hours followed by transient painless right eye blindness (~10 min)	Normal neuro-ophthalmological workup	Continuation of treatment without modification	None	No recurrence after C3	Acute neurotoxicity related to oxaliplatin
Tunio et al. 24	2022	54	F	CAPOX c	C2	Blurred vision followed by right eye vision loss (~30 min)	Normal neuro-ophthalmological workup	Oxaliplatin definitively discontinued; Capecitabine continued	None	No recurrence after C2	Acute neurotoxicity related to oxaliplatin
Guido Schiappacasse 25	2023	60	M	FOLFOX a  + Bevacizumab	C1	6 episodes of transient tunnel vision in the right eye, lasting less than 30 s, over 48 h	Ishihara test mild protanopia (red color vision deficit) right eye; electrooculogram borderline abnormal right eye; remaining ophthalmologic examination normal; normal brain and orbital MRI; normal glycemia levels; negative antibody studies; negative viral panel	Switched to FOLFIRI h  + Bevacizumab	None	Normalization of ophtalmological findings within 3 months with no recurrence	Right retrobulbar optic neuritis due to oxaliplatin
Shahi et al. 26	2024	72	F	CAPOX c	NA g	Ocular irritation, foreign body sensation, and visual loss in her right eye	Reduced visual acuity; bilateral small pterygium; mild-to-moderate nuclear cataract; funduscopy showing scattered yellowish iridescent dots with diffuse retinal pigmentary changes; OCT j showing outer retinal atrophy with severe retinal thinning, ellipsoid zone disruption and irregular retinian pigment epithelium damage; abnormal fundus autofluorescence and infrared imaging; abnormal electroretinography and electrooculography	Oxaliplatin definitively discontinued; information about capecitabine unavailable	NA g	Partial recovery	Crystalline retinopathy related to oxaliplatin
Zhao et al. 27	2025	47	F	SOX e	C3	Permanent acute bilateral vision loss	Multiple iris cysts in ophtalmological exam, anterior chamber inflammation, exudative retinal detachment, and bilateral dense cataracts; elevated systemic and aqueous humor IL-6 levels; normal orbital CT and MRI	S-1 discontinued; oxaliplatin continued	Oral prednisone acetate with poor adherence; phacoemulsification surgery in both eyes	Partial restoration after surgical intervention	Oxaliplatin adverse effect, not more detailed

^aOxaliplatin + fluorouracil + leucovorin; ^bEpirubicin + oxaliplatin + capecitabine; ^cCapecitabine + oxaliplatin; ^dOxaliplatin + irinotecan + fluorouracil + leucovorin; ^eS-1 + oxaliplatin; ^fGemcitabine + oxaliplatin; ^gNot available; ^hFluorouracil + irinotecan; ⁱElectroencephalogam; ^jOptical Coherence Tomography; ^kHyperthermic intraperitoneal chemotherapy; ^l5-fluorouracil.

Reported cases include transient visual loss, visual field defects, altered color perception, or ptosis, typically without imaging abnormalities.^{12 –27} Most reports lack standardized documentation or comprehensive diagnostic evaluation, leading to premature discontinuation of oxaliplatin despite reversibility.

Our case is distinguished by detailed diagnostic workup, systematic drug sequencing, and observation of symptom modulation by administration route. Although electrophysiological testing (e.g., visual evoked potentials) during symptoms might have been informative, the brief duration of episodes likely limited diagnostic yield.

We propose a standardized diagnostic approach including comprehensive ophthalmologic examination, brain and orbital MRI, and vascular assessment to exclude alternative diagnoses. When workup is negative, and symptoms are reversible, continuation of oxaliplatin with optional dose adjustment or prolonged infusion, based on a benefit-risk assessment and oncologic treatment goals, should be considered rather than systematic discontinuation.

In the present case, the MDT decision to continue oxaliplatin at full dose intensity without infusion prolongation was based on a deliberate risk–benefit assessment. The visual episodes were brief, painless, fully reversible, free of any objective deficit, and did not worsen across cycles—below the severity thresholds that generally warrant dose reduction or infusion prolongation in painful or disabling forms of acute oxaliplatin-induced neurotoxicity. As the regimen was curative intent and oxaliplatin its principal active agent, reducing dose intensity carried an oncological cost that the observed benign toxicity did not justify. Infusion prolongation, moreover, is evidence-based for cold-triggered peripheral symptoms but has no established efficacy in this ocular manifestation. Risk was instead mitigated through inpatient monitoring and drug re-sequencing.

From a drug safety perspective, this case fulfills several criteria supporting a causal relationship between oxaliplatin and the observed visual symptoms: temporal association, reproducibility, reversibility, exclusion of alternative diagnoses, and modulation by route of administration.

Importantly, lack of awareness of this rare toxicity may lead to premature discontinuation of oxaliplatin. This report supports a cautious, conservative management strategy when a thorough diagnostic evaluation is reassuring.

Conclusion

This case highlights a rare, reversible ophthalmologic manifestation of acute oxaliplatin-induced neurotoxicity that may be underrecognized. Improved documentation and standardized diagnostic strategies are essential to avoid unnecessary treatment discontinuation and to better characterize this uncommon toxicity.