December 2018

CORNEA

Pharmaceutical focus
Biologics in the dry eye mix


by Maxine Lipner EyeWorld Senior Contributing Writer

“I think that anything that we could do to help patients garner
insurance coverage or better access to these medications would be a step in the right direction.”
—Preeya Gupta, MD

What these therapies can offer patients

Many dry eye patients respond well to traditional therapies such as Restasis (cyclosporine, Allergan, Dublin, Ireland) and Xiidra (lifitegrast, Shire, Lexington, Massachusetts). However, some may require use of biological products such as serum tears, amniotic fluid, or plasma rich in growth factors to quell their dry eyes, according to Bennie Jeng, MD, professor and chair, Department of Ophthalmology and Visual Sciences, University of Maryland School of Medicine, Baltimore.
Dr. Jeng thinks biologics should be kept in mind for dry eye, but pointed out that patients with more severe cases usually come to these after a plethora of traditional treatments have been tried. One important step can be to first confirm that the patient has been diagnosed correctly. “Just because they have staining doesn’t mean that they have dry eyes,” Dr. Jeng said, adding that if there is any sort of eye lid component, this must be addressed. If it does prove to be a dry eye issue, since usually these more severe patients have already been given treatments such as Restasis or Xiidra or a steroid to cut inflammation, the next step if they are still symptomatic could be the use of serum, a scleral lens or amniotic membrane, Dr. Jeng noted.

Considering biologics

Preeya Gupta, MD, associate professor of ophthalmology, Duke University Eye Center, Durham, North Carolina, thinks that many moderate to severe dry eye patients can benefit from serum tears, amniotic fluid, or albumin. However, she initiates FDA-approved commercially available treatments for which there is insurance first, making them more financially and logistically feasible. “For patients, ease of access and the financial aspects of treating dry eye cannot be overlooked because as we escalate our therapy, the cost of the treatment becomes higher,” Dr. Gupta said.
For those who may have failed traditional therapy, Dr. Gupta’s first “go-to” class of biologics is Genesis (Ocular Science, Manhattan Beach, California), amniotic cytokine extract, made from amniotic membrane, which contains growth factors, active cytokines, and anti- inflammatory molecules. “When you look at how or why these are working well, a lot of repair and regeneration of the surface relies on things like different growth factors, making it a friendlier environment for the limbal stem cells as well as improving the body’s ability to repair itself,” she said. Another reason Dr. Gupta likes the drop is because it’s made at a compounding pharmacy that ships the vials directly to the patient who can freeze them until needed.
The other biologic that Dr. Gupta likes to use for some of these dry eye patients is autologous serum tears. However, the process of making the serum tears is a little cumbersome for the patients, she pointed out. “It requires a blood draw every 6 weeks or so,” she said, adding that some blood banks are able to manage batches so that the patient can go less frequently. Still, it requires the patient to give blood, which is then spun down, made into serum and mixed with balanced salt solution to make the drop, which the patient must then keep frozen or refrigerated.
Because of such involved logistics, she opts for the amniotic extract first. “It’s a little easier for the patient,” she said. “In terms of efficacy, I’ve been pleasantly surprised with the amniotic eye drops.” Dr. Gupta has found that in her practice these have similar efficacy to the serum tears. But if someone does not respond to the amniotic eyes drops, she may move to the serum tears.
Dr. Jeng also considers biologic agents for cases involving persistent epithelial defects. First, however, he tries other possibilities such as bandage contact lenses, lubrication, and preservative-free tears before asking patients if they would prefer use of serum, amniotic membrane, a scleral lens, or tarsorrhaphy. Dr. Jeng uses either serum tears or amniotic membrane as his biologic go-to. He finds when such patients choose serum tears, the nutrients in these can help with epithelial proliferation.
As for amniotic membrane, there are two ways to use this for persistent epithelial defects, he pointed out. “You take the patient into the OR and sew the membrane on, or you can put in a self-retaining amniotic membrane, Prokera [Bio-Tissue, Miami, Florida], in the office,” he said, adding that in this case, the membrane is attached to a 15-mm PMMA ring and placed on the eye like a large contact lens.
The newer models of the self-retaining amniotic membrane are purportedly more comfortable than the old ones, with which his patients sometimes complained of discomfort, Dr. Jeng noted. There are also other forms of the membrane available now, including dehydrated versions. “Now I give patients a choice. I say, ‘If we’re going to do it, the easiest thing is to put this in, in the office, or the other option would be to get your blood drawn for autologous serum,’” he said.
Obtaining biologics for any patients can be more complicated than traditional medications. For the serum tears, which must be created in a certified laboratory, practitioners may have to take different steps to acquire these. “I’ve been at two institutions where the (onsite) blood bank would draw the blood and send it to a compounding pharmacy to finish the processing,” Dr. Jeng said. However, at the center where he currently practices, they use a compounding establishment that has contracted with various local phlebotomy sites for the blood drawing instead. This is sent on to the pharmacy, where they dilute the serum to the concentration specified by the doctor.
Dr. Gupta pointed out that there are other more seldom-used biologic products in the mix, including albumin and platelet-rich plasma. While there was use of albumin around 2003, with some efficacy reported, it never became popular, she noted. “I think part of it is that it’s not easy to produce, so you have to find a good compounding pharmacy that’s able to process it into an eye drop, and there hasn’t been an easy way to get it,” Dr. Gupta said, adding that the same is true for platelet-rich plasma. While with proper equipment clinicians can potentially spin the blood down themselves in the office, this may open a sterilization and safety Pandora’s box, she said.

Eyeing the evidence

Evidence at this point on the efficacy of biologic products for dry eye tends to be anecdotal, Dr. Jeng pointed out. While there aren’t currently any randomized controlled trials, there are case series available. A Cochrane review1 showed that there was no definitive evidence to suggest that these agents are better than traditional treatments for dry eye. “But they’re used differently,” Dr. Jeng said. “Generally, this is used for people who have failed many other things, so if you talk to cornea specialists, they will say that it does work in the right patients.”
Dr. Gupta took part in a retrospective chart review2 involving 21 patients who took amniotic cytokine drops twice daily for 30 days to attempt to quell their dry eye disease. Investigators found that patients’ dryness scores after 4 weeks dropped down to 41.4 from 68, and mean corneal staining was down to 3.2 from 7.2, Dr. Gupta reported.
Overall, with success such as this and compounding becoming more available, Dr. Gupta expects to see other biologics come out of this category. “I think that anything that we could do to help patients garner insurance coverage or better access to these medications would be a step in the right direction,” she said.

References

1. Pan Q, et al. Autologous serum eye drops for dry eye. Cochrane Database Syst Rev. 2017;2:CD009327.
2. Gupta PK. Clinical outcomes of amniotic cytokine extract in the treatment of dry eye disease. Presented at the 2017 American Academy of Ophthalmology Annual Meeting.

Editors’ note: Dr. Gupta has financial interests with Ocular Science. Dr. Jeng has financial interests with TissueTech (Miami, Florida).

Contact information

Gupta
: preeya.gupta@duke.edu
Jeng: BJeng@som.umaryland.edu

Biologics in the dry eye mix Biologics in the dry eye mix
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