ODs pursue latest treatments for conjunctivitis, shingles

“I don’t think we really know the prevalence of bacterial vs. viral conjunctivitis,” Spencer D. Johnson, OD, FAAO,told Primary Care Optometry News in an interview.

“What has been reported in the literature is that it varies by patient population and region, and the conclusion we are coming to is that unless you have some way of objectively testing for pathogens, you don’t know what you’re dealing with in most cases,” said Johnson, associate professor and researcher at the Oklahoma College of Optometry in Tahlequah, Okla.

A thorough case history in patients with suspected conjunctivitis is necessary, as there may be overlap in clinical signs between allergic, bacterial or viral conjunctivitis, Caroline Beesley Pate, OD, FAAO,associate professor at the University of Alabama Birmingham School of Optometry, told PCON.

Both clinicians utilize the AdenoPlus (Quidel) point-of-care testing to help identify viral cases.

The in-office procedure takes about 10 minutes to get a result and will help indicate whether or not the redness is due to adenovirus, Pate said.

In order to perform the test in office, she recommends obtaining a Clinical Laboratory Improvement Amendment (CLIA) certificate of waiver through CMS, “which allows your office to operate as a laboratory to help diagnose and determine a management strategy.”

Johnson said that he and his colleagues also use polymerase chain reaction (PCR) in their research to help determine if the results they are getting with the AdenoPlus are accurate.

With PCR, “A sample is obtained and then sent to a lab for analysis, which can take several days to get results,” he said. “It is considered the gold standard to definitively diagnose adenoviral conjunctivitis.”

When bacterial conjunctivitis is not improving

In cases where patients have been prescribed an antibiotic – usually by a primary care physician or urgent care center – but are not getting better, Pate encourages finishing the course of antibiotics and avoiding ending it abruptly to prevent antibiotic resistance.

“However, if a drug was obviously causing medicamentosa, I would discontinue it and switch the patient to a more palliative treatment like cold compresses and preservative-free tears,” she said.

Except in cases where there is suspicion of a resistant bug, Johnson said he may add a steroid to hasten resolution of symptoms.

Pate said: “Many times, the red eye is due to inflammation or a viral etiology, so trying to narrow down what the actual problem is through point-of-care testing can help you determine the proper course of action for treatment.”

She recommends Polytrim Ophthalmic (trimethoprim/polymyxin B ophthalmic, Allergan) for mild and non-vision threatening cases of bacterial conjunctivitis, which she sees mostly in children.

“It’s an old tried and true treatment,” she said. “It has good coverage.”

Johnson added that the drug is more accessible cost-wise.

He recommends patients stay home from school or work until the eye is no longer red or irritated, and any discharge has ceased.

“In the case of bacterial conjunctivitis, after 24 to 48 hours of aggressive antibiotic dosing, I would feel confident that the patient is no longer contagious,” Johnson added. “Adding a steroid and a doctor’s note may help a day care provider feel more confident as well.”

If the conjunctivitis is viral, especially epidemic keratoconjunctivitis (EKC), the patient may be contagious for several days and should limit public contact accordingly, he noted.

Treatments in development

Johnson is a principal investigator in the Reducing Adenoviral Patient Infected Days (RAPID) clinical study, which is exploring the efficacy of 5% Betadine (povidone-iodine, Alcon) in a one-time dosage to reduce adenoviral load over time. The RAPID study concluded recruitment in June, and study results will be out in the fall, he said.

Shire is currently testing a lower concentration of Betadine, in a combination drop with dexamethasone at 4 times per day. Johnson’s RAPID study is administering solely 5% Betadine at one administration, in-office.

Okogen Inc. announced in March that it received funding to support the development of OKG-0301, an ophthalmic formulation of ranpirnase, for treatment of viral conjunctivitis. Ranpirnase is a potent ribonuclease with established broad-spectrum antiviral properties. The company plans to enroll more than 200 patients in a phase 2, multicenter, double-masked clinical trial.

Treatment challenges

A clinical roadblock in viral cases is a lack of a good, FDA-approved treatment, Pate said.

Johnson typically tells patients with viral conjunctivitis that the condition resembles a cold and must run its course.

“A lot of treatments are off-label,” Pate said. “For patients who want to get back to work or school sooner rather than later, Betadine has shown good promise in eradicating the virus off the ocular surface.”

Antibiotic-steroid combinations are not appropriate here, she added, as there is no bacterial component.

“In that situation, I may employ a topical steroid if the viral infection has caused infiltrates in the cornea that are reducing a patient’s vision or if the patient is uncomfortable, but certainly an antibiotic in that patient is not necessary,” Pate said. She added that she would select a straight topical steroid option, such as Lotemax gel (loteprednol etabonate ophthalmic gel 0.5%, Bausch + Lomb), for which her office can provide coupons to patients.

Conceptually, she is looking forward to being able to use the combination Betadine/dexamethasone drop from Shire. “I think it’s got great promise,” she said. “Right now, our toolbox is really limited, so this will be the first new option we’ve had in a long time.”

In patients with red eyes with discharge due to a viral etiology, the viral pathogens can live on contacted surfaces for weeks, Pate said.

“It is important to reinforce hygiene at home so they do not re-infect themselves or others,” she said.

If patients are concerned about time lost from work or school due to adenoviral infection, she recommends off-label Betadine treatment.

“Every patient is different, so I don’t have a set time that I keep people at home,” she added. “They certainly should stay at home until their eye is no longer red and there is no more discharge.”

Johnson said if he is confident that the diagnosis is EKC, the worst manifestation of viral conjunctivitis, he will administer Betadine.

In regard to the AdenoPlus test, Johnson noted that the few published studies that have evaluated its sensitivity have shown mixed results. He said he hopes that the RAPID study will be able to shed more light on its clinical usefulness.

Herpes zoster virus

Ocular herpes zoster makes primary care physicians nervous because it can affect the front or back of the eye with episcleritis, glaucoma, uveitis, scleritis, keratitis, iris atrophy, retinitis, choroiditis, optic neuritis or cranial nerve palsy, private practitioner and lecturer Greg Caldwell, OD, FAAO, said in an interview.

“They want the patient to have a comprehensive eye exam with dilation and have a report back so they can treat the patient properly, as they know vision loss can occur,” he said. “I think that’s why optometrists see a lot more zoster, because the PCP knows there could be potentially sight-threatening ocular involvement.”

If you are certain a patient has shingles, place them on Valtrex (valacyclovir, GSK) at 1 G, three times a day for 1 week, Joseph P. Shovlin, OD, FAAO, private practitioner, American Academy of Optometry president and PCON Editorial Board Member, said in an interview.

“The problem with orals is that zoster virus doesn’t respond quite the same way that simplex does, thereby requiring a higher dose of oral antivirals,” Shovlin said. “Patients who are atopic or those with reduced immunity shed the virus like they have acute chicken pox.”

In shingles with periorbital involvement but no conjunctival/corneal involvement, Johnson’s go-to treatment is acyclovir 800 mg, five times a day for 10 days.

“With conjunctival involvement it gets more complicated,” he said. “If it’s just the conjunctiva, use erythromycin ointment, and if it looks like corneal involvement and just the surface of the cornea, then prescribe preservative-free artificial tears every few hours and ointment at night. If it involves the stroma, we prescribe a steroid four times a day, with a very slow taper, usually at least 4 weeks, but sometimes as long as several months.”

How aggressively he treats it depends on how deep it is into the cornea, he said.

Acyclovir is the only oral medication that is approved for the treatment of ocular herpes simplex and zoster, Caldwell said. While Famvir (famciclovir, Novartis) and Valtrex are approved for genital herpes, “there is plenty of evidence-based medicine that shows that because Valtrex is more efficient as a prodrug, it is definitely able to be used for ocular conditions,” Caldwell said. “You can use it off-label as long as there is a standard of care.”

Zoster vaccine

The CDC recommends Shingrix (zoster vaccine recombinant, adjuvanted, GSK) for anyone older than 50 years. It requires two injections generally 8 weeks apart, according to Shovlin.

“Make sure there’s adequate vaccine for the second round before they get the first shot,” he added.

“Shingrix was just approved at our facility a few weeks ago,” Johnson said, “and based on the CDC’s guidelines, I am certainly going to encourage my patients who are 50 years and older to get it.”

Even if patients have previously had Zostavax (zoster vaccine live, Merck), Shingrix is recommended.

Optometrists can take a more active role in counseling patients by understanding that there are two types of vaccines available, Caldwell said.

Shingrix is adjuvant therapy, has high efficiency and is potent, he said.

“Patients will come in and have already been vaccinated with Zostavax and now want Shingrix,” Caldwell said. “It’s confusing, but they can be vaccinated again with Shingrix; these are two different mechanisms of action.”

While Zostavax is the true, live, but attenuated (or weakened) virus being injected into the body, Shingrix is an antigen mimicking the virus, Caldwell explained. The adjuvant therapy enhances the outcome with Shingrix.

From ages 50 to 59 years, the efficacy of Shingrix is 96%; when you get to 70 to 79 years it drops to 91%, Caldwell said.

“This means that 91% to 97% of patients who get Shingrix are not getting shingles,” he said. “That’s the combination of the antigen and the adjuvant therapy.”

“Optometrists can play an active role in recommending the vaccine,” Shovlin said. “Hopefully we will be more successful in getting patients vaccinated. The burden of zoster is just incredible from a cost standpoint and in causing depression and postherpetic neuralgia. Everyone over the age of 50 should be vaccinated.”

The chicken pox factor

Caldwell said that many people misclassify chicken pox virus and shingles based on age.

“When you get the virus for the first time, it is disseminated throughout your whole body, or ‘chicken pox,’” he said.

Herpes types 1, 2 and 3 (zoster) are neuronal, Caldwell continued.

“Once you have chicken pox, it’s in your body and hangs out in your neurons. That’s why when we get it a second time it comes out in a very specific ganglion type of pattern and it’s very localized, because it’s coming out through the neurons,” he said.

If the immune system is not strong enough, and an older person gets it for the first time, it can be disseminated throughout the whole body, according to Caldwell. An older patient with shingles can end up in the hospital on an antiviral IV.

For patients looking for alternative medicine, the amino acid lysine, or L-lysine, may offer relief, he said. The body does not manufacture it naturally, but evidence has linked it to a decrease in outbreaks in patients who get cold sores or zoster outbreaks.

Because some clinicians may be concerned about using a Goldmann tonometer in these patients, Pate noted that the CDC recommends soaking the tip in either hydrogen peroxide, which her institution does, or a 1:10 diluted bleach followed by a thorough saline rinse, to ensure efficacy against all pathogens.

Caldwell noted that simplex zoster is easily killed with 70% isopropyl alcohol, “but if you want to play it safe in your office, follow the CDC recommendations.” – by Abigail Sutton

• References:
• Migneco M. Reducing adenoviral patient infected days (RAPID): Study design and baseline characteristics. https://www.aaopt.org/detail/knowledge-base-article/reducing-adenoviral-patient-infected-days-rapid-study-design-and-baseline-characteristics. 2015. Accessed June 27, 2018.
• Sutton A, Okogen receives funding to advance ranpirnase for viral conjunctivitis. www.Healio.com/PCON. Posted March 26, 2018.

• For more information:
• Greg Caldwell, OD, FAAO, is in private practice in Duncansville and Johnstown, Pa., and serves on many American Optometric Association committees and boards. He can be reached at: grubod@gmail.com.
• Spencer D. Johnson, OD, FAAO, is associate professor and researcher at the Northeastern State University Oklahoma College of Optometry in Tahlequah, Okla. He can be reached at: johns137@nsuok.edu.
• Caroline Beesley Pate, OD, FAAO, is associate professor at the University of Alabama Birmingham School of Optometry. She can be reached at: cbeesley@uab.edu.
• Joseph P. Shovlin, OD, FAAO, is president of the American Academy of Optometry and has practiced at Northeastern Eye Institute, in and around Scranton, Pa., since 1985.

Disclosures: Caldwell has lectured for Aerie, Allergan, BioTissue, Optovue and Shire. Pate reported that she formerly served on an advisory board for Shire. Shovlin is on the global advisory panel for Allergan, Johnson & Johnson Vision and Shire. Spencer reported no relevant financial disclosures.