Point-of-care diagnostics similar to home COVID-19 tests were able to detect microbial keratitis (MK) caused by Aspergillus fungus with good accuracy, according to a prospective study.
An Aspergillus-specific lateral-flow device already FDA-approved for pulmonary aspergillosis testing was able to detected MK with high sensitivity for both corneal scrape (0.89, 95% CI 0.74-0.95) and swab samples (0.94, 95% CI, 0.73-1.00).
Overall accuracy was 0.94 (95% CI 0.90-0.97) and 0.88 (95% CI 0.73-0.96), respectively, reported Bethany Mills, PhD, of the University of Edinburgh, Scotland, and colleagues in JAMA Ophthalmology.
The study was “a useful proof-of-concept” for rapid detection of pathogens causing the infection, which could allow a more targeted treatment approach, Mills told MedPage Today.
Microbes causing the condition are bacteria in half of cases and fungi like Aspergillus in the other half, but clinicians usually can’t distinguish without testing, Mills said. That makes microbiological diagnosis especially important, she said, but it requires highly skilled lab workers at tertiary care centers. These facilities can be hundreds of kilometers from sites in Africa and Asia, she said, and testing can take a week.
The disease is more severe and more common in tropical and subtropical regions, where it often causes blindness and eye loss, particularly in poorer nations.
The disease “is an acute ophthalmic emergency,” Mills said. “Across Asia and Africa, it is the second most common cause of single-eye vision loss following cataracts. In these regions, 60% of patients are left with moderate or worse visual outcomes, and up to 15% require surgery that’s often unsuccessful. Current treatment strategies include topical antimicrobials, antibiotics, and/or antifungals, and then surgery.”
For the study, researchers used a lateral-flow device known as AspLFD that is FDA-approved to test for pulmonary aspergillosis and costs about $12 in Western countries. “It has never been looked at in the context of keratitis,” Mills said. “To our knowledge, no lateral flow or point-of-care device has been looked at for keratitis.”
As Mills explained, “think of this as being like a COVID lateral flow test, which everyone is familiar with. Instead of swabbing your nose, your cornea is scraped or swabbed to retrieve the sample, with a numbing drop added first. The sample is then placed into a buffer and then put onto the lateral flow test.”
The researchers suggested “swabs could be used to collect corneal samples from patients with suspected MK in settings where the routine method of specimen collection by scraping is not possible, such as primary care.”
Their group tested the diagnostic on corneal swab and scrape samples taken from 198 individuals ages 15 or older with MK (63.6% male, mean age 51) from 2022-2023 at a single eye hospital in Madurai, India. Some had already been treated with antibiotics, antifungals, or both at the time of sampling.
The samples were placed into the AspLFD devices, and a laboratory microbiologist inspected them after 20 minutes.
Among corneal scrape samples, 39 were positive for Aspergillus according to the AspLFD test. A reference culture test revealed that 31 were actually positive and eight were false positives. Of the 159 negative scrape samples by the AspLFD test, the reference culture test revealed that 155 were negative and four were false negatives.
Twenty corneal swab samples were positive per the AspLFD test, of which reference culture test revealed that 16 were actually positive and four were false positives. Another 20 samples were deemed negative by the test, with one being a false negative by the reference culture test.
The researchers noted that “while not included within the formal AspLFD analysis, 5 of the 76 culture-negative, fungal smear-positive scrape samples also had positive AspLFD results, suggesting that these patients likely had a missed Aspergillus species infection.”
The study authors noted limitations. For one, the subjects often had “relatively advanced” stages of MK, making it unclear how the test would work in those with less severe cases. Researchers also had to eyeball the test results looking for the band to determine whether the results were positive or negative. Some of the bands were faint. To improve resolution, the researchers looked at photos of the devices that were taken using open-source software and a smartphone.
What’s next? While testing kits may not be readily available, “we believe that ophthalmologists may start using them now,” said study co-author Venkatesh Prajna, MD, of Aravind Eye Hospital in India, in an interview.
The study was funded by the U.K. Engineering and Physical Sciences Research Council and the U.K. Research and Innovation Future Leaders Fellowship.
The study authors reported no disclosures.
Source Reference: Gunasekaran R, et al “Rapid point-of-care identification of Aspergillus species in microbial keratitis” JAMA Ophthalmol 2023; DOI: 10.1001/jamaophthalmol.2023.4214.