In-office testing, off-label therapy may be best approach for EKC
With no FDA-approved treatment, clinicians are otherwise limited to supportive and palliative measures.
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Welcome to another edition of CEDARS/ASPENS Debates. CEDARS/ASPENS is a joint society of cornea, cataract and refractive surgery specialists, here to discuss some of the latest hot topics in ophthalmology.
Acute viral conjunctivitis is often disabling and difficult to treat. Few therapies have been shown to be particularly effective. These patients are often quite miserable and have difficulty tolerating the period of time needed for the infection to run its natural course. In addition, those in contact with the patient are at high risk to catch the virus themselves.
This month, Alice T. Epitropoulos, MD, FACS, and Priyanka Sood, MD, discuss the use of povidone-iodine for the treatment of acute viral conjunctivitis. We hope you enjoy the discussion.
Kenneth A. Beckman, MD, FACS
OSN CEDARS/ASPENS Debates Editor
Povidone-iodine safe, inexpensive
Differentiation between bacterial, viral and noninfectious epidemic keratoconjunctivitis (EKC) is typically made clinically, but it is often difficult because they manifest similar symptoms.
Cell culture in combination with immunofluorescence has been the gold standard for identifying adenovirus in conjunctival specimens. However, isolating the virus requires technical skill and expertise and is time-consuming. Real-time polymerase chain reaction (PCR) has been used more recently as an alternative to cell culture and is often considered the criterion standard to detect adenovirus; however, it does not allow for rapid decisions to be made regarding patient management.
The QuickVue adenoviral conjunctivitis test (Quidel) was developed as a single-use point-of-care test for the rapid diagnosis of adenoviral conjunctivitis. It is an antigen-based immunoassay that utilizes direct sampling microfiltration technology.
The appearance of both a blue line in the control zone and a red line in the result zone suggests a positive result, indicating the presence of adenovirus antigens in the tear fluid. Negative results do not exclude adenovirus infection nor are they intended to rule out other infections of the conjunctiva; the results of AdenoPlus should not be used as the single basis for treatment or other management decisions.
Viral conjunctivitis is self-limiting, usually lasting 7 to 10 days in mild cases and up to 3 weeks in advanced cases. Patients who have a more severe case with photophobia, inflammation or subepithelial infiltrates, or those whose vision is affected, may benefit from topical corticosteroids. Before initiating a topical steroid, it is important to rule out the possibility of herpes simplex virus keratitis because corticosteroids can exacerbate it.
A study at Bascom Palmer Eye Institute including close to 2,000 patients showed that 5% of clinically diagnosed cases of HSV were truly adenovirus and 4.8% of clinically diagnosed cases of adenovirus were actually HSV. This may be a reason to consider obtaining a culture if there is uncertainty in the diagnosis.
There are currently no FDA-approved medications to treat adenoviral conjunctivitis, with options limited to supportive therapies and palliative measures. Standard care as recommended by the American Academy of Ophthalmology and American Optometric Association is instillation of artificial tears to relieve symptoms and possibly reduce the virus load.
The following options are currently being used to treat viral eye diseases involving the anterior segment of the eye: topical ganciclovir 0.15% or trifluridine (or oral antivirals) for epithelial herpes simplex and oral antivirals for shingles and/or chicken pox.
Promising results have been noted in the treatment of adenoviral conjunctivitis with the use of povidone-iodine, which is currently being used by some clinicians off label.
Betadine 5% (povidone-iodine, Alcon) is a broad-spectrum antiseptic ophthalmic solution that has been used for years to prophylactically reduce bacterial flora in preparation of eye surgery. Studies have confirmed high microbial kill rates when using a 5% sterile ophthalmic preparation. It has been shown to be effective against Fusarium, Candida, Mycobacterium tuberculosis and viruses, but the literature regarding its efficacy against Acanthamoeba is conflicting.
The idea of using a Betadine rinse in patients with suspected adenoviral conjunctivitis is to reduce the viral load in the eye.
While protocols vary, a topical anesthetic should always be instilled initially because povidone-iodine causes stinging. I then follow this with a topical NSAID and then several drops of 5% povidone-iodine in both eyes. The earlier this treatment is initiated, the more likely patients will respond.
I believe there is significant value to this therapy and hope to see more research and publications on this treatment option; plausibly by shortening the viral residence time on the ocular surface, it is conceivable that the occurrence of serious sequelae including persistent subepithelial infiltrates, pseudomembrane formation, iridocyclitis and nummular keratitis could be reduced. In addition to the more rapid clinical resolution, the Betadine treatment may shorten the infectious period.
If the patient has been acutely symptomatic for more than 5 or 6 days, I usually do not treat with Betadine because EKC is self-limiting and usually resolves within 7 to 10 days.
Betadine 5% is safe, inexpensive, widely available and immune to the development of bacterial/viral resistance. This treatment has the potential to significantly affect the clinical management of “pink eye” worldwide and may become the preferred therapy for treating this contagious and potentially vision-threatening condition. Future studies are needed to further evaluate the safety and efficacy of this treatment.
- References:
- Chronister DR, et al. J Ocul Pharmacol Ther. 2010;doi:10.1089/jop.2010.0018.
- Gordon JS. Adenoviral and other nonherpetic viral diseases. In: Smolin G, Thoft RA, eds. The Cornea. 3rd ed. Boston:Little, Brown & Co, 1994:215-227.
- Marangon FB, et al. Arq Bras Oftalmol. 2007;doi:10.1590/s0004-27492007000200002.
- Miura-Ochiai R, et al. J Clin Microbiol. 2007;doi:10.1128/JCM.01603-0645:958-67.
- Pelletier JS, et al. J Cataract Refract Surg. 2011;doi:10.1016/j.jcrs.2010.11.028.
- Saitoh-Inagawa W, et al. J Clin Micro. 1996;34:2113-2116.
- For more information:
- Alice T. Epitropoulos, MD, FACS, can be reached at Ophthalmic Surgeons & Consultants of Ohio at The Eye Center, 262 Neil Ave., Suite 410, Columbus, OH 43215; email: eyesmd33@gmail.com.
Disclosure: Epitropoulos reports she was involved in the multicenter clinical trial on infectious conjunctivitis sponsored by Shire Pharmaceuticals.
Betadine used at initial evaluation
A diagnosis of adenovirus keratoconjunctivitis is most commonly achieved by history and physical examination under a slit lamp. AdenoPlus can be used, especially when the diagnosis is unclear. Initial studies involving AdenoPlus suggested high sensitivity and specificity, and subsequent studies achieved similar specificity but were not able to repeat the high sensitivity results.
Treatment remains supportive in many cases, as the infection is often self-limited with minimal long-term sequelae. Cold artificial tears and cold compresses can be soothing, but it is most important to emphasize hand hygiene to prevent spread. In my practice, a drop of 5% Betadine is used at the time of the initial evaluation to decrease the viral burden and try to decrease the period during which the patient is contagious. Steroids are mainly used when patients have developed pseudomembranes, and I prefer using an ointment for comfort and to decrease symblepharon formation. Otherwise, steroids have been shown to increase the duration of disease and, thus, are not recommended.
When subepithelial infiltrates develop after punctate epithelial keratitis, my threshold to start topical steroids or cyclosporine is low. If left untreated, corneal scarring can develop, and if these lesions are in the visual axis, they can be visually significant. Tapering steroids in these patients can be challenging, and thus, cyclosporine is potentially a better option for long-term treatment.
Editor’s note: This article was updated to correct the brand name of the QuickVue adenoviral conjunctivitis test.
- References:
- Holtz KK, et al. Mayo Clin Proc. 2017;doi:10.1016/j.mayocpiqo.2017.06.001.
- Kam KY, et al. Br J Ophthalmol. 2015;doi:10.1136/bjophthalmol-2014-306508.
- Sambursky R, et al. JAMA Ophthalmol. 2013;doi:10.1001/2013.jamaophthalmol.513.
- For more information:
- Priyanka Sood, MD, can be reached at Emory Eye Center, 1365 Clifton Road, Atlanta, GA 30324; email: psood2@emory.edu.
Disclosure: Sood reports no relevant financial disclosures.