Case Reports Detail Vision Loss Linked to Recalled Artificial Tears

Two case reports published in JAMA Ophthalmology on Wednesday offered more details into the outbreak of vision-threatening eye infections linked to artificial tears, which according to the CDC now encompasses 68 cases across 16 states, including three deaths.

In the first, Ahmed Omar, MD, of University Hospitals Eye Institute and Case Western Reserve University School of Medicine in Cleveland, Ohio, and colleagues described the case of an older woman who presented with vision loss of the left eye for a week following use of the over-the-counter drops for dry eye syndrome.

Cultures from her left eye grew multi-drug resistant (MDR) P. aeruginosa, which was susceptible only to cefiderocol. Comparable P. aeruginosa was identified in cultures of the patient's EzriCare artificial tear drops as well.

On physical exam, the 72-year-old woman retained visual acuity of light perception, and the exam was otherwise notable for "a hypopyon filling the anterior chamber with an epithelial defect involving most of the cornea," while the right eye was unremarkable (she had bilateral dry eye syndrome).

The patient was treated with intravenous cefiderocol, along with topical antibiotics (imipenem/cilastatin; polymyxin B/trimethoprim), noted Omar and colleagues, but "her course was complicated by a serous choroidal detachment detected by B-scan ultrasonography."

At 2-month follow up, left-sided vision only remained for light perception.

In the second case, Marissa Shoji, MD, and colleagues from the Bascom Palmer Eye Institute and the University of Miami Miller School of Medicine, offered details on a severe case of MDR P. aeruginosa keratitis in a 72-year-old man who presented with a day of pain and partial sight loss in his right eye after use of EzriCare artificial tears.

Of all the medications prescribed by ophthalmologists, artificial tears are generally considered the "most benign," according to Christina Prescott, MD, PhD, and Kathryn Colby, MD, PhD, of New York University Langone Health in New York City, writing in an accompanying commentary.

The current outbreak of MDR P. aeruginosa "associated with the use of carboxymethylcellulose sodium (EzriCare) multidose preservative-free artificial tears may be a wake-up call for the field," the editorialists wrote, and "is a harsh reminder that all eye drops, including artificial tears, are medications with potential adverse effects, most commonly ocular but potentially systemic."

Prescott and Colby pointed out that multiple patients in the current outbreak have had positive cultures from non-ocular sites, including sputum swabs or bronchial washes, as well as from rectal swabs, urine, and blood, the editorialists noted.

This particular strain of P. aeruginosa, previously unseen in the U.S., is similar to one implicated in an endophthalmitis outbreak in India thought to be due to contaminated trypan blue dye, they wrote.

At this time, said Prescott and Colby, "it is unclear why many of the infections in the current outbreak are associated with products produced by EzriCare. It may be related to a design flaw in the packaging or a contaminant in the production facility."

Unlike with ophthalmic medications and devices, "manufactures of artificial tears are not required to perform clinical trials to market their products if they follow the guidelines in the FDA ophthalmic drug products for over-the-counter human use monograph, which may mean there is less oversight of their quality," the editorialists said. "The current situation is a tangible reminder that any type of eye drop can have untoward effects. We all need to be vigilant observing and reporting unexpected events."

Vision Loss in a 72-Year-Old Man

In the case detailed by Shoji's group, the patient had a medical history of coronary artery disease, diabetes, and chronic obstructive pulmonary disease. His ocular history was unremarkable. He reported using contact lenses, but told clinicians he always removed them before going to bed, and did not overuse them.

An eye exam revealed that "his best-corrected visual acuity was hand motion in the right eye and 20/20 in the left," the case authors noted. Intraocular pressures were 29 mm Hg in the right eye and 14 mm Hg in the left. Clinicians noted diffuse conjunctival hyperemia and a large central corneal infiltrate measuring 6 mm × 5 mm with an overlying epithelial defect accompanied by a 2 mm hypopyon. Ultrasound findings were normal without membranes or vitritis.

Corneal ulcers, which can cause permanent sight loss, tend to be associated with use of contact lenses, eye injury, and persistent disease affecting the ocular surface, noted Shoji and coauthors.

Given concerns for an MDR infection due to the patient's use of EzriCare drops and the recent CDC warning, clinicians initiated treatment "with topical fortified vancomycin, fortified tobramycin, and trimethoprim-polymyxin drops every hour while awake."

Cultures of the patient's cornea and his EzriCare artificial tear drops were taken, and both were positive for P. aeruginosa with high resistance to fluoroquinolones, aminoglycosides, and cephalosporins. Moderate carbapenem resistance was seen with the corneal culture, while higher resistance was observed in the EzriCare culture.

"Based on bacterial sensitivities, the patient continued trimethoprim-polymyxin every hour and switched to imipenem-cilastatin every 2 hours, as this antibiotic class had the lowest resistance of those tested," wrote Shoji and coauthors. "To date, he is undergoing treatment with close monitoring, as he had persistent infection and vision loss at his last follow-up."

Importantly, reported cases of MDR P. aeruginosa have been on the rise, the case authors said, and have created "treatment challenges and worse outcomes compared to drug-sensitive infections."

People who use lubricant ointment, bandage contact lenses, or have a compromised ocular surface are at an increased risk for infection with MDR P. aeruginosa, according to Shoji's group. Severe infections can also occur due to contaminated products. In addition to trypan blue, they noted that "contaminated steroid and glaucoma drops and contact lens solutions have been associated with infectious keratitis."

In the current outbreak, over 10 different brands of artificial tears have been implicated, according to the CDC. The infections have resulted in serious outcomes, including permanent blindness, hospitalization, and systemic infection causing death.

Shoji and coauthors noted that of seven patients at their Bascom Palmer Eye Institute diagnosed with keratitis due to MDR P. aeruginosa, their case reported here is the only one specifically linked to the EzriCare drops.