Temporary Central Vision Blindness After Oseltamivir Administration in a 15-Year-Old Pediatric Male Positive for Influenza A

Abstract

Objective: A 15-year-old pediatric male patient was influenza A positive and started on oseltamivir at an outpatient clinic. Method: The next morning the patient presented to the emergency department (ED) with a chief complaint of visual disturbances including decreased central vision. Prior to presenting to the ED the patient was evaluated by his optometrist and his eye exam tested 20/400 bilaterally. His previous year’s eye exam was normal, 20/25 bilaterally. Results: In the ED, the patient had an MRI which showed a normal appearing optic nerve, chiasm, and optic tracts. The oseltamivir therapy was discontinued, and the patient followed up with an ophthalmologist outpatient. Conclusion: At a 10-week follow-up visit the patient had 90% recovery of his vision.

Introduction

According to the Centers for Disease Control and Prevention (CDC), the 2017 to 2018 influenza season was classified as a high severity season and a high level of outpatient clinic and emergency department (ED) visits for influenza-like illness (ILI) symptoms. ¹ Since the 2003 to 2004 influenza season, the CDC has used a methodology to classify seasonal severity. ¹ The 2017 to 2018 influenza season was the first season which was classified as a high severity season for all age groups. ¹ It is known within the pediatric patient population, optic neuritis can appear after a systemic infection, including from a viral infection, or after vaccinations for measles, rubella, hepatitis B, and influenza.^2-4

Case Presentation

A 15-year-old pediatric male with a past medical history of seasonal allergies and asthma was seen at an urgent care with ILI symptoms, which had been present for 1 day. The patient’s sister had been diagnosed with influenza A, a few days earlier. The patient’s vaccines were up to date, except the patient had not received his annual influenza vaccine. The patient didn’t smoke, use alcohol, or illicit drugs. At the urgent care clinic, the patient tested positive for influenza A and was subsequently started on oseltamivir 75 mg by mouth twice daily for 5 days. The patient took his first dose of oseltamivir the same evening about 8:00 pm. The following morning the patient woke up with bilateral visual disturbances in the form of decreased central vision. The patient did take his second dose of oseltamivir with breakfast before being evaluated by an optometrist later in the morning. The patient’s optometrist referred the patient to the ED. The patient’s optometrist spoke with the ED provider and reported the patient’s vision a year ago was 20/25 bilaterally and today found to be 20/400 bilaterally. The optometrist rated this as binocular disease and was concerned with a central nervous system pathology. The patient’s optometrist reported the macula was in good condition, positive reflex, and there was no optic nerve damage or edema. The optometrist did report a mild peripheral vision loss on his exam. The patient’s optometrist had dilated the patient’s eyes and reported no other abnormalities, no abrasions, and normal pressures.

In the ED, on exam the patient had peripheral vision and could distinguish the number of fingers in all 4 quadrants. However, the patient reported only seeing “shapes” in his central vision and couldn’t distinguish the number of fingers. The patient’s MRI was normal with normal appearance of the optic nerve, chiasm, and optic tracts. There was an incidental finding of a right parotid 1.3 cm lesion—likely benign mixed tumor or a Warthin tumor. The ophthalmologist on call recommended nepafenac eye drops for inflammation and follow-up with an ophthalmologist the following week, as the patient was seen on the weekend. The patient was instructed to discontinue taking the oseltamivir. The patient had taken 2 doses of oseltamivir prior to the medication being discontinued.

As depicted in Figure 1, 4 days after the patient tested positive for influenza A and started oseltamivir, the patient followed-up with an ophthalmologist and was diagnosed with acute macular neuroretinopathy. The ophthalmologist believed the vision disturbances were due to the patient’s viral illness and would spontaneously resolve in 8 to 10 weeks. At the 10-week follow-up office visit the patient had a 90% recovery of his vision. Some blind spots remained in both eyes with more in the right eye than the left. The patient also reported electronic screens were the worst for his visual acuity and schoolwork printed on pink paper was the easiest for him to read. The ophthalmologist expected the patient will have a full recovery of vision within the next 4 months.

Figure 1.

Symptom onset and acute phase of vision disturbances.

Discussion

With the sudden onset of central vision loss affecting the patient’s eyes bilaterally, it was clear to the ED staff the patient’s afflictions were related to CNS pathology, though he was afebrile, without nuchal rigidity, and had normal mentation. When posed with the question, “Is the oseltamivir causing these visual changes?” the ED physician, nurse, and physician’s assistant turned to pharmacy to initiate the query to identify what visual changes oseltamivir can cause.

The influenza virus has been known to cause acute optic neuritis resulting in temporary blindness which mostly resolves within 10 weeks, but bilaterally visual changes are not as frequent.^2,5 Bilateral optic neuritis has been associated with intranasal live influenza vaccine and the intramuscular inactivated influenza vaccine.^2,6 Case reports discussing acute optic neuritis after influenza vaccination reported symptoms appearing 9 to 14 days after vaccine administration.^2,3,6 However, oseltamivir is also known to cause visual disturbances, such as blurred vision, angle-closure glaucoma, transient myopia, and diplopia.^7-11 The visual disturbances can appear within 5 hours to days of initiating oseltamivir therapy.^8-10 As the patient fell asleep after the first dose and awoke with symptoms, this could match previous case reports for oseltamivir causing vision disturbances. Oseltamivir is well known for causing neuroexcitation leading to psychiatric symptoms, such as visual hallucinations, mood swings, suicidal ideation, and insomnia.^12-15 These symptoms typically appear within a few days of starting oseltamivir therapy. While the time frame for psychiatric symptoms matched the patient case’s time frame from initiating oseltamivir therapy, the patient presented in this case had no psychiatric symptoms and was appropriately concerned about his acute changes in vision. The information uncovered by pharmacy during a literature search indicated no known instances of oseltamivir causing acute macular neuroretinopathy or central blindness. Utilizing the Narajo adverse reaction scoring method, the oseltamivir is possibly causing the adverse drug reaction of decreased central vision. The score of 2 was from the adverse event appearing after the suspected drug was given, improved when the drug was discontinued, and the influenza virus could have caused the reaction. ¹⁶

Initially, it was decided in the ED to stop the oseltamivir for 2 reasons. First, if the damage was caused by a virus, the damage was already done. It was thought a neuraminidase inhibitor would likely offer minimal benefit to the recovery from acute macular neuroretinopathy. One case study was found which demonstrated early treatment of influenza with oseltamivir did not affect the ophthalmic outcome from the induced acute macular neuroretinopathy. ¹⁷ Second if the visual disturbances were caused by oseltamivir, stopping the oseltamivir would prevent further damage and allow the body a chance to heal. Once neuronal damage occurs, the nerve can regenerate at 1 mm/day regardless of the mechanism of injury except if the nerve is cut, in which case the damage can be permanent. ¹⁸ Stopping the oseltamivir would be of greater benefit to the patient than the reduced time with ILI symptoms offered by oseltamivir therapy.^2,3

Conclusion

Ultimately, it cannot be definitively determined if the oseltamivir caused or contributed to the temporary central vision loss by causing acute macular neuroretinopathy in this patient, or if it was the influenza A virus itself. However, oseltamivir cannot been entirely ruled out. ¹¹ It is the authors’ hope by compiling those visual changes in this report, it will provide other healthcare providers a prompt and concise answer in any ambulatory or hospital setting to the likelihood and which visual disturbances are caused by oseltamivir.^7-10 Regardless of whether the virus, medication, or combination caused the damage, cessation of oseltamivir reduced a potential risk which offered minimal benefit to the patient.