Abstract

Background

Many patients with malignancies benefit from advances in chemotherapeutic treatments; however, in parallel chemotherapeutic agents present a wide spectrum of toxic effects. Visual impairment occurred as an infrequent form of chemotherapeutic toxicity, and chemotherapy reportedly induces irreversible or reversible visual loss in recent years. As reported in one study, a male patient suffered from acute unilateral blindness after 5 cycles of cisplatin/gemcitabine (cisplatin 80 mg/m², gemcitabine 1250 mg/m²) for lung cancer [1]. Visual complications related to chemotherapy might come to light when vision loss occurred after receiving chemotherapy and it is imperative to consult at ophthalmology department.

Case presentation

A 48-year-old woman developed tinnitus and enlarged cervical lymph nodes. Nasopharyngoscopy examination and biopsy confirmed nasopharyngeal squamous cell carcinoma; thus, she received anti-tumor therapy of a combination of docetaxel, cisplatin and fluorouracil (TPF: docetaxel used on the first day at 75mg/m², cisplatin used on the first and second day at 75mg/m² and fluorouracil used from the first day to fifth day at 500mg/m²) which was repeated every four weeks. The patient complained of visual loss in the right eye two weeks after the first cycle of chemotherapy, and she received the second cycle of chemotherapy as planned.

One week later, she made the first visit to an ophthalmologist because of progressive vision loss and visual acuity was tested (VOD: visio oculus dexter, for the right eye; VOS: visio oculus sinistra, for the left eye). She had worse visual acuity of 0.4 in the right eye (VOD0.4) than before (VOD1.0) and the presence of relative afferent pupillary defect (RAPD) was measured in the right eye. She had a history of high myopia and amblyopia in her left eye evidenced by the low visual acuity (VOSCF/25cm, meaning that she could only count fingers at the distance of 25 cm ahead). The current vision impairment in her right eye therefore seriously affected her quality of life. Ophthalmoscope examination and fundus photograph showed optic disc edema, fuzzy boundary and linear hemorrhages in the right eye (Fig. 1a). Typical fundus changes of high myopia were observed in the left eye, such as atrophic arc around optic disc, fuchs spot and tigroid fundus (Fig. 1b). The cerebral magnetic resonance imaging (MRI) provided evidence of no tumor involvement in orbits and central visual pathways (Fig. 1c and 1d). The long optic axis of the left eye is a typical feature of high myopia eyeball (Fig. 1d). The patient received neurotrophic drug treatment, including mecobalamine and citicoline. Three weeks later, the visual acuity in the right eye decreased to 0.3 and the signs of optic disc mentioned above also existed.

About one week after the third cycle of chemotherapy, she made the third visit to the ophthalmologist. The VOD was determined to be 0.3. The optic disc edema subsided, the upper part of the optic disc became gray and residual retinal hemorrhage was located on the inferior rim. Macular pucker, depigmented macules and hard exudate were observed in the macular area (Fig. 2a). The optic disc optical coherence tomography (OCT) of the right eye showed that the thickness from inner limiting membrane to retinal pigment epithelium (ILM-RPE) at the superior side and nasal side was thinner than that in normal eyes (Fig. 2b). Visual field (VF) examination of the right eye indicated severe visual field defects (Fig. 2c). Fundus fluorescein angiography (FFA) as the most important assistant examination revealed capillary underdevelopment at the nasal and superior temporal area of the optic disc in the early phase and capillary fluorescein leakage in the late phase (Fig. 2d-2f). Thus, a diagnosis of NAION was made in the right eye, and gradually reduced high-dose oral prednisone along with neuroprotective drugs were used for treatment. Meanwhile, retrobulbar injection of compound betamethasone (1 ml) was given to the right eye, combined with eye drops of ocular hypotensive agents.

One month after finishing three cycles of induction chemotherapy, concomitant intravenous antitumor therapy with radiotherapy was started. Due to the suspicious ocular toxicities of cisplatin, a targeted agent Nimotuzumab was recommended for alternative treatment. The patient made the fourth visit to the ophthalmologist and VOD of the right eye was determined to be 0.4. The optic disc edema subsided with clear boundary, but the color of optic disc was still gray (Fig. 3a). OCT showed the secondary macular epiretinal membrane (Fig. 3b). The VF improved obviously compared with the image three weeks ago, which meant the function of the optic nerve was partially repaired (Fig. 3c). The ERG results of the right eye showed that the amplitudes of a-type wave and b-type, and P1-type wave were almost normal, suggesting the normal function of the retina (Fig. 3d). The incubation period of P100-type wave in P-VEP test was lengthened, suggesting that the function of optic nerve was partially impaired (Fig. 3e).

On finishing radiotherapy, the patient had not been treated with chemotherapy for 3 months and she made her follow-up visit at the ophthalmic clinic. The VOD improved to be 0.5. The color of optic disc was not so gray as before while the macular epiretinal membrane still existed (Fig. 4a and 4b). The amplitude and incubation period of P2-type wave from the right eye were almost normal in F-VEP-1HZ test, which meant the function of the optic nerve was mostly repaired (Fig. 4c). About 7.5 months after chemotherapy, the visual acuity remained at VOD 0.5. The VF of the right eye improved dramatically (Fig. 4d). The results of ophthalmologic examinations during her follow-up period are presented in Table 1.

Discussion and Conclusions

Neck mass constitutes the most common presenting symptom of patients with nasopharyngeal carcinoma (NPC) [ 2]. Impaired vision as the initial presentation due to optic nerve involvement was rarely reported. Neoadjuvant chemotherapy was currently reported to reduce local-regional recurrences and distant metastases [ 3]. Fluorouracil and cisplatin are commonly used, and the major toxicities include myelo-suppression and vomiting. Ocular toxicities have not been widely recognized and are difficult to be detected. NPC has a favorable prognosis and, thanks to the advance in anti-cancer therapies the patients live a longer life. Vision represents an important part of life quality. Here we reported the case aimed at raising attention to chemotherapy-induced ocular toxicity in the treatment of NPC.

Due to sharp decrease of visual acuity, the patient consulted to ophthalmology clinic for etiological diagnosis and potential therapy. Glaucoma, cataracts, macular degeneration and other eye diseases were excluded and the right optic disk edema was observed by funduscopic examination, and a diagnosis of NAION was made with etiology unknown. NAION is the most common cause of acute visual loss in people aged over 50, resulting from non-inflammatory small vessel ischemic damage to the anterior portion of the optic nerve. The cause and pathogenesis of this disorder remains unclear [ 4, 5]. Neuroprotective drugs or agents acting on the disc edema are often included in the treatment of NAION, however, currently no therapy has been yet proved to be effective [ 6]. Given the temporal relationship between chemotherapy and vision loss of the patient, we considered that the onset of NAION might be attributed to the intravenous chemotherapy. Because of a combination of drugs, it is difficult to identify the specific agent accounting for the followed vision loss. Since the toxic effect on retinal or optic nerve might result in irreversible vision loss, early detection of ocular toxicity and cessation of anti-cancer therapy are required. However, sometimes it is a trade-off for clinicians and patients between the risk of permanent visual damage and the effectiveness of anti-cancer therapy.

Vision loss related to cisplatin, docetaxel and fluorine has been reported in several studies. Cisplatin-associated retinal toxicity was dose-dependent or unique to high doses, including blurred vision, color vision defects, and electroretinographic (ERG) changes. A patient received five cycles of cisplatin/gemcitabine treatment for lung cancer. Unfortunately, the patient was admitted to the emergency room complaining of acute blindness in his left eye. Fundus examination were normal in both eyes, and the MRI of the left optic nerve and orbit did not reveal any relevant findings. A diagnosis of left retrobulbar optic neuritis was made [1]. A 55-year-old man planned to receive a 4-day continuous infusion of cisplatin at a dose of 25 mg/m² daily as part of a chemotherapeutic salvage regimen for non-Hodgkin lymphoma. Inadvertently, the actual cisplatin dose was 100 mg/m² daily for 4 days. Immediately after treatment, except anorexia, nausea and tinnitus, he developed bilateral decreased vision. The ERG showed diminished a-wave and missed b-wave [ 7]. A clinical study of 52 patients determined the prevalence rates of 5-FU-associated ocular abnormalities [ 8]. The results showed that the most common presentation was tearing (26.9%), followed by blurred vision (11.5%). After receiving 12 courses of intravenous 5-FU for metastatic breast cancer, a 72-year-old woman complained of a sudden visual loss and after the discontinuation of anti-cancer agent her vision improved. A deficiency of dihydropyrimidine dehydrogenase (DPD) was detected and it was considered that 5-FU was responsible for the visual loss, associated with DPD deficiency [ 9]. A female received monthly intravenous infusion of docetaxel for metastastic breast cancer, and 2 months later she complained of blurred vision in both eyes. Then docetaxel was replaced by Xeloda and her vision improved [ 10].

Chemotherapy-induced NAION should be considered when patients receiving cancer chemotherapy suddenly developed vision loss. Most ophthalmic complications are readily reversible if recognized early. Dosage reduction or agent cessation could rescue patients from vision loss. However, if optic nerve or retinal was involved, patients might develop irreversible vision loss. Induction chemotherapy plays an important role in the therapy of local advanced nasopharyngeal carcinoma, and presented here was one case of severe visual impairment induced by chemotherapy. It is warranted that cancer patients benefiting from chemotherapy simultaneously suffer from the risk of vision loss.

Although it has been reported that intravenous chemotherapy of cisplatin and docetaxel caused retinal toxicity, this is the first case in which intravenous administration of chemotherapy (TPF) for NPC induced NAION, enough causing irreversible vision loss. This reported case suggests that ophthalmic complications should be considered when patients receiving chemotherapy suddenly develop visual impairment. As soon as symptoms are recognized, the patient should be scheduled for a follow-up examination in ophthalmology clinic. Oncologists and ophthalmologists should work together for subsequent treatment.

List of Abbreviations

VF-visual field; VEP-visual evoked potential; ERG-electroretinogram; FP-fundus photograph; FFA-fundus fluorescein angiography; OCT-optical coherence tomography; NAION-nonarteritic anterior ischemic optic neuropathy; NPC-nasopharyngeal carcinoma; ILM-inner limiting membrane; RAPD-relative afferent pupillary defect; MRI-magnetic resonance imaging; VOD-visio oculus dexter, for the right eye; VOS-visio oculus sinistra.

Declarations

Ethics approval and consent to participate

The report of patient data was approved by the Institutional Animal Care and Use Committee and Ethics Committee.

Consent for publication

Written consent was obtained from the patient for the publication of the patient's details.

Availability of data and material

The data supporting the conclusions of this article are included within the article.

Competing interests

The authors have no conflicts of interest to disclose.

Fundings

This research did not receive any funding.

Authors' contributions

M.L. conceived the idea, participated in information gathering, literature search and data analysis. X.Y. participated in information gathering, literature search, data analysis and drafting the final manuscript. Y.F. performed the ophthalmologic examination and composed this manuscript. D.L participated in drafting the final manuscript and editing the figures. All authors read and approved the final manuscript.

Acknowledgements

We thank the patient for consenting and for assenting to the publication of this article.

References

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Table 1

Table 1. The results of ophthalmologic examinations in the right eye during the follow-up period.

Note: On October 31st, 2017 the patient received the first cycle of chemotherapy. On November 30th, 2017, she received the second cycle of chemotherapy. On December 29th, 2017, she received the third cycle of chemotherapy. From January 26th, 2018 to March 22th, 2018, she received radiotherapy combined with targeted therapy. VEP: visual evoked potential; ERG: electroretinogram; OCT: optical coherence tomography.