Corneal and Conjunctival Infectious Disease Diagnostics

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Infectious keratitis is one of the leading causes of corneal blindness in both developed and developing countries.1–3 In the United States, there are at least 30,000 cases of infectious keratitis each year.4,5 There are 930,000 outpatient clinic visits and 58,000 emergency department visits for keratitis or contact lens-related disorders in the United States each year.6 The estimated cost of these visits totaled nearly $175 million and 250,000 hours of clinician time.6 The burden is even greater in the developing world. In India, there are approximately 840,000 cases of infectious keratitis each year, and 85% of all corneal blindness in China is thought to be secondary to infection.7,8 Infectious keratitis is the leading indication for keratoplasty in children and adults in the developing world.9,10
Sound clinical judgment is vital for appropriate diagnosis and management of infectious keratitis, but it is not enough. Using clinical acumen alone, cornea specialists can differentiate bacterial and fungal keratitis only two thirds of the time, and can accurately predict gram stain, genus, and species in 46%, 25%, and 10% of cases, respectively.11 Polymicrobial keratitis is even more difficult to diagnose clinically, is more challenging to treat, and is associated with poorer outcomes than bacterial or fungal keratitis alone.12 Herpes simplex virus (HSV) epithelial keratitis can often be diagnosed clinically, especially when characteristic dendrites are present, but stromal keratitis is more difficult to diagnose, as the differential is more broad. Studies have reported experienced clinicians misdiagnose herpetic keratitis in up to two thirds of cases.13 The uncertainty associated with identifying the infecting organism can lead to delay in diagnosis, poorer visual outcomes, and increased risk for surgical interventions or loss of the eye.14,15
There is a clear need for accurate diagnostic tests as a supplement to good clinical judgment in the diagnosis and management of infectious keratitis. Many tools exist, with the oldest being traditional culture plates and smears. More recently, in vivo confocal microscopy (IVCM) and polymerase chain reaction (PCR) assays have gained significant attention as methods that have better sensitivity and specificity and lead to earlier diagnosis. As commercial interest has grown, several point-of-care tests have been introduced for the rapid diagnosis of adenoviral conjunctivitis (eg, AdenoPlus; Rapid Pathogen Screening Diagnostics Inc., Sarasota, FL) and HSV (eg, Checkmate Herpes Eye; Wakamoto Pharmaceutical Co., Tokyo, Japan). More such tests are likely to follow. Lastly, as imaging resolution improves, anterior segment optical coherence tomography (AS-OCT) may play a more important role in this field. This review aims to summarize the current state of technology and future directions in the diagnosis of corneal and conjunctival infectious diseases.
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