What Causes Conjunctivitis? A Panoply of Pathogens, Study Shows

Pathogens associated with acute infectious conjunctivitis varied among regions, a cross-sectional study showed.

Among 52 patients from four sites in the U.S. and one in Israel, RNA deep sequencing found human adenovirus species D in a quarter of patients, with a wide range of pathogens, including human coronavirus 229E, SARS-CoV-2, and herpes simplex virus type 1, also identified, reported Thuy Doan, MD, PhD, of the University of California San Francisco, and colleagues.

Of these patients, 62% presented with purulent discharge, often thought to be a sign of bacterial infection, but only 8% of patients were confirmed to have bacterial conjunctivitis. A majority (54%) were infected with viruses, which do not respond to antibiotics, the authors noted in JAMA Ophthalmology.

"This study demonstrates it is harder to predict pathogens by clinical presentation than we may have thought," said co-author Gerami D. Seitzman, MD, also of the University of California San Francisco. "The local profile of pathogens is different depending on geography. In some places it will be viral, but in other places it will be pathogens the doctor had not thought of."

As Seitzman told MedPage Today, "pink eye remains a public health issue. For example, Pakistan recently shut down over 50,000 schools with over 300,000 documented conjunctivitis cases. The etiology is presently unknown."

This study challenges traditional beliefs about conjunctivitis, he noted. "Classically, we are taught that the majority of conjunctivitis cases are viral, although the causative pathogens are rarely confirmed. Additionally, we are taught -- and we teach -- that if a patient is tearing, their etiology is more likely viral. And if they have purulent discharge, it is more likely to be bacterial."

But it turns out that pathogenic causes vary widely from place to place, he added.

Study co-author Edmund Tsui, MD, of the UCLA Stein Eye Institute in Los Angeles, told MedPage Today that the RNA testing used in the study isn't ready for prime time.

"Insurance does not cover it yet, as it is not a clinic-based test for ocular infectious diseases," he explained. "Over time, this technology will become less expensive and more readily available. It is ideal for surveillance because it is 'unbiased.' This means sequencing will let you know about any pathogen in the sample. In the case of culture or PCR [polymerase chain reaction], the doctor has to 'guess' which media or which primers to test for."

Anat Galor, MD, MSPH, an ophthalmologist at the University of Miami, who was not involved in this study, praised the research in an interview with MedPage Today, noting that the findings highlight the need for better testing in conjunctivitis.

"Our clinical diagnosis is OK, but not great. Anyone who thought they were right 100% of the time should read this," she said. "Fortunately, most conjunctivitis is self-limiting. But diagnostic testing will make it easier to correctly treat the disease and figure out who should be sent home to avoid infecting others."

As for better testing, Galor agreed that RNA deep sequencing tests aren't yet practical in the clinic, but she added that there's plenty of interest in developing better tests.

Moving forward, Tsui emphasized that "pink eye may be one of the first signs of an epidemic or pandemic." (Seitzman noted that COVID-19 was first detected by an ophthalmologist. The Chinese eye doctor, who is credited with spreading the word about the disease, died of COVID-19 after facing government censure.)

"Public surveillance is important, and paying attention to infectious eye diseases is important," Tsui added.

For this cross-sectional study, Doan and colleagues took samples from the eyes and noses of 52 patients with acute infectious conjunctivitis in Hawaii, California, and Israel from March 2021 to March 2023. Mean age was 48, and 60% were women. Patients with allergic or toxic conjunctivitis were excluded.

Using RNA deep sequencing to examine the samples, the team found human adenovirus species D in 13 patients from California, and two cases of human adenovirus species B in Israel. There were two cases of Epstein-Barr virus, three cases of herpes simplex virus type 1, two cases of varicella-zoster virus, one case of human metapneumovirus, one case of SARS-CoV-2, three cases of human coronavirus 229E, one case of molluscum contagiosum, four cases of bacteria, and two cases of fungi. No pathogens were found in 18 cases.

The researchers noted limitations to their study, including its small size, the small number of participating locations, and the lack of "traditional microbial detection via polymerase chain reaction or culture, although any type of diagnostic testing is rarely performed in the ambulatory setting for presumed acute infectious conjunctivitis."

They also said that information about cost was not collected, so there's no way to know if this kind of testing is cost-effective.

Randy Dotinga is a freelance medical and science journalist based in San Diego.

Disclosures

The study was funded by the National Eye Institute and an unrestricted grant from Research to Prevent Blindness to the Department of Ophthalmology at the University of California San Francisco.

Doan reported no conflicts of interest. Seitzman reported receiving consulting fees from Dompé. Tsui reported receiving consulting fees from EyePoint Pharmaceuticals, Kowa, and Cylite, and grant support from Pfizer. Another co-author reported receiving grants from the National Institutes of Health.

Galor reported no disclosures.

Primary Source

JAMA Ophthalmology

Source Reference: Tsui E, et al "Pathogen surveillance for acute infectious conjunctivitis" JAMA Ophthalmol 2023; DOI: 10.1001/jamaophthalmol.2023.4785.

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