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Diagnosing and Testing for Herpetic Keratitis
Howard Larkin reports from the 39th ESCRS Congress in Amsterdam
Herpetic keratitis is a significant ocular issue around the world, with a lifetime risk of about 1% for any individual, and about 120,000 episodes annually in the US and 90,000 more in each of the UK, Italy, and France. Adding to the concern, herpetic keratitis is often visually disabling, with visual acuity dropping below 20/200 in about 10% of cases after 20 years.
Yet like other types of infectious keratitis, diagnosis can be complicated, Marc Labetoulle MD, PhD told delegates, noting traditional methods of identifying infectious keratitis miss about half of the diagnoses.
“Biomarkers are needed to improve the reliability of diagnosis of all types of infectious agents.” Other tools such as molecular and genetic tests may also help, he added.
SLIT-LAMP FIRST Currently, herpetic keratitis is mostly diagnosed at the slit-lamp. But this can be difficult due to the diversity of its presentation, Professor Labetoulle said. It can be epithelial, appearing as superficial punctate keratitis, dendritic, geographic, limbal, or as an archipelago. It can be endothelial, appearing as disciform, diffuse, or linear; or stromal, with or without ulceration. The end-stage form is neurotrophic, which appears in three stages.
He noted it is critical to distinguish between certain types of herpetic keratitis at the outset.
One of the main questions is, “Are steroids contraindicated?” Cases that are epithelial and replicative, stromal and necrotizing, or neurotrophic should not be treated with steroids, at least until the antiviral drugs have not improved the situation, he emphasised.
He also differentiated between true dendritic keratitis that is fractal in shape with early fogging (which can be treated with antivirals), pseudodendritic (which has raised edges), and no diffusion of fluorescein (which calls for withdrawal of medications with preservatives, topical antivirals, antibiotics, and steroids). Pseudodendritic cases are better treated with lots of saline and eyedrops. Further, necrotising stromal keratitis is characterised by white and opaque lesions versus opalescent and translucent for non-necrotising.
THEN TESTING Since these variations require different treatments, a correct diagnosis is critical, Prof Labetoulle said. So, after the slit-lamp evaluation comes testing.
Serum and tear levels of herpes simplex virus (HSV) antibodies are not reliable, he noted. Nor are virus cultures, immunofluorescence, immunochemistry, or hybridisation.
PCR testing is much more efficient than these conventional tests, which Prof Labetoulle does not recommend because they waste resources. Tests of corneal scraping are much more reliable than tear samples in severe cases, but tear sampling is painless and easy to perform. However, quantitative PCR correlates to the expected rate of HSV replication on the ocular surface. Combining PCR with antibodies in tears significantly raises the sensitivity and specificity over the individual tests, raising the positive predictive value to up to 98%, he said. Pitfalls of PCR testing include inhibition of the polymerase chain reaction by eyedrops, including fluorescein, lissamine green, and Bengal rose stains.
Sampling should be considered in cases with unusual presentation and when drug resistance is suspected (this is, however, very infrequent), which can help identify treatments that may be successful. Prof Labetoulle sees the future of diagnosis as a lab on a chip, detecting multiple biomarkers from a single tear.
“A good sampling is an early sampling,” he said. He also anticipates continuing collaboration with microbiologists to investigate cases.
Marc Labetoulle MD, PhD is professor and chair, Ophthalmology Department, Université Paris-Saclay, Paris, France. marc.labetoulle@aphp.fr
