Rapid Tests Diagnose Dry Eye, Adenovirus Conjunctivitis

Daniel M. Keller, PhD

January 15, 2013

Two articles published in the January issue of JAMA Ophthalmology (formerly Archives of Ophthalmology) describe 2 sensitive and specific point-of-care tests that can help clinicians quickly and easily reach a diagnosis in conditions that previously have been a conundrum: adenoviral conjunctivitis and dry eyes (now more formally called dysfunctional tear syndrome).

Both tests use direct sampling microfiltration and are based on lateral flow technology, similar to a home pregnancy test. The tests produce visual results, with a blue control line and, if positive, a red test line.

The first article, evaluates the adenovirus test (AdenoPlus, Rapid Pathogen Screening Inc), which detects the most common cause of viral conjunctivitis. Adenovirus-associated conjunctivitis may lead to significant ocular morbidity and is associated with substantial healthcare costs.

Researchers led by Robert Sambursky, MD, a cornea specialist at the Manatee Sarasota Eye Clinic and Laser Center in Sarasota, Florida, compared this recently US Food and Drug Administration–cleared second-generation test with traditional gold standard tests.

"Ophthalmologists and optometrists that have access to a slit lamp biomicroscope and who should be the experts are somewhere between 25% to 60% accurate at making a differentiation between a viral and bacterial disease...and that impacts treatment," Dr. Sambursky told Medscape Medical News.

For the multicenter trial, the researchers recruited 128 patients (76 females, 52 males) with a clinical diagnosis of acute viral conjunctivitis in a prospective, sequential manner within 7 days of developing a red eye. Patients ranged in age from 5 to 90 years, with a mean duration of symptoms among patients from each center of between 2.8 and 3.7 days.

Tear samples were collected with the test device as well as for testing by viral cell culture with confirmatory immunofluorescence assay (CC-IFA) and for polymerase chain reaction (PCR). If either CC-IFA or PCR were positive, the patient was considered definitively positive for adenoviral conjunctivitis. If both were negative, the patient was considered negative for adenoviral infection. The AdenoPlus test, which requires only 10 minutes to develop after sample collection, was read by an independent healthcare professional masked to the clinical examination results.

High Sensitivity and Specificity

Of the 128 patients, 36 were positive by either CC-IFA or PCR. Cell culture has been the traditional definitive test for adenovirus infection. "Compared to [that] gold standard, AdenoPlus has a 90% sensitivity and a 96% specificity," Dr. Sambursky said. "When you actually compare it to PCR, that specificity goes up to about 98% and still maintains a good sensitivity in the mid-80s." Compared with CC-IFA, the test had a positive predictive value of 88% and a negative predictive value of 97%. Compared with PCR, the positive predictive value was 94% and the negative predictive value was 95%.

"[T]he rapidity is a major advantage" of the new test, Dr. Sambursky said. Making a diagnosis early allows withholding inappropriate antibiotics from patients with viral disease instead of treating them empirically, thereby reducing the potential for developing antibiotic resistance, complications, and toxicities. "[N]ot treating is as important as treating effectively," he noted.

Stephanie Marioneaux, MD, a cornea specialist in private practice in Chesapeake, Virginia, and an expert spokesperson from the American Academy of Ophthalmology, commended the trial for comparing AdenoPlus with the gold standard tests, which "are so burdensome, and they are not readily available to your average clinician," she told Medscape Medical News. "[W]hereas this now makes the test much more widely accessible." She noted that the researchers used appropriate patient eligibility criteria, a wide age range of patients, and masked examiners.

Dr. Marioneaux said the test "will add a lot to the clinician's ability to rapidly diagnose something that is extremely contagious and is often very difficult to diagnose." Getting infected patients out of the office quickly is an advantage, she said, because the virus is highly contagious and can persist on surfaces for weeks.

"The Great Masquerade"

In the second study, also led by Dr. Sambursky, researchers evaluated a rapid test (InflammaDry, Rapid Pathogen Screening Inc) to detect matrix metalloproteinase 9 (MMP9), a biomarker of inflammation expressed in dry eyes. He said it is important to detect the condition for patient comfort, for preventing ocular morbidity, and for other management decisions.

To test InflammaDry, researchers enrolled 143 patients aged 18 years or older with clinical signs and symptoms of dry eyes and 63 healthy control individuals. All were assessed and determined to have dry eyes or to be healthy using the Ocular Surface Disease Index, the Schirmer tear test, tear breakup time, and keratoconjunctival staining. The 10-minute test detects MMP9 levels greater than 40 ng/mL. Previous studies have shown that the severity of dry eye correlates well with the level of MMP9 in the tears.

The results of this prospective, sequential, masked, multicenter study showed the test has a sensitivity of 85% and specificity of 94% (P < .001 for both), with a positive predictive value of 97% and a negative predictive value of 73%.

Dr. Sambursky commented that this new rapid test may replace more cumbersome tests such as the Schirmer tear test and the tear breakup time. Furthermore, "it's hard to get accurate results" with those tests, he noted.

Dr. Marioneaux commented that the test should help clinicians target treatments better. "I sort of refer to [dry eye] as the great masquerade syndrome because it has so many different symptoms that the patient never connects with the dry eye — the unstable vision; the blurring vision; the burning of the eye; the sandy, gritty feeling; the sensitivity to light; the stabbing pain," Dr. Marioneaux explained. "Some people overreact, and some people underreact. So at least you'll have a more definitive and more consistent way of testing it."

The studies were sponsored by Rapid Pathogen Screening Inc. Dr. Sambursky is an executive officer and director of Rapid Pathogen Screening Inc. The other authors and Dr. Marioneaux have disclosed no relevant financial relationships.

JAMA Ophthalmol. 2013;131:17-21, 24-28. Adenovirus abstract, Dry eye abstract

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