September 23, 2019
5 min read
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Nontraditional agents can supplement dry eye therapy

Two clinicians sometimes reach for platelet rich plasma tears or compounded hormones as part of their treatment regimen.

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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.

Managing the severe dry eye patient continues to be a difficult task for the eye care professional. There are only a few commercially available treatments, and often they are not enough. Therefore, many dry eye experts need to dig deep into their bag of tricks for unusual options to treat these patients.

This month, Melissa Toyos, MD, FACS, and Mark S. Milner, MD, FACS, discuss some of their favorite alternative therapies for severe dry eye disease. We hope you enjoy the discussion.

Kenneth A. Beckman, MD, FACS
OSN CEDARS/ASPENS Debates Editor

Platelet rich plasma tears for dry eye

Melissa Toyos, MD, FACS
Melissa Toyos

Elite athletes whose livelihoods depend on their physical performance figured it out first — Kobe Bryant, Tiger Woods, A-Rod, Peyton Manning. All of them traveled to a little-known clinic in Dusseldorf, Germany, for the orthopedic surgery they needed and the magical Regenokine treatment developed by Peter Wehling, MD, PhD, there.

The idea is to inject a sufficient amount of the patient’s own blood after concentrating healing factors. First used in European soccer players, this mixture amplified the healing and regenerative response and seemed to cut healing time, especially in areas with sluggish blood flow and slower capacity for healing.

Of course, “blood tears” were first reported in 1975 by Ralph and colleagues to help heal the signs and symptoms of dry eye. Some patients were simply told to squeeze an extra blood drop out of their fingers onto the ocular surface after testing their blood sugar. Other doctors did, and still do, draw a few cc’s of blood and spin them down on a tabletop centrifuge.

The platelet rich plasma (PRP) machine used in the successful orthopedic trials was the impetus for a trial in our clinic looking at 60 cc of centrifuged blood spun down in a standardized way to create 3 cc to 5 cc of concentrated PRP. PRP contains a multitude of healing factors, from fibroblast growth factor to nerve growth factor to epidermal growth factor and much more. The questions are: How much of each are contained in a typical PRP formula? How do they interact? Now that Dompé’s recombinant growth factor is available for the healing of recalcitrant neurotrophic ulcers, is the concentration greater than what is found in a patient’s own PRP? How do the other growth factors interact with healing, and which ones are necessary for best results?

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Our study looked retroactively at refractory dry eye patients who received autologous serum tears made with the Genius PRP (Reinvent Biologics). Autologous blood was spun down and divided evenly into a proprietary blend of preserved over-the-counter tears. Patients refrigerated the drops constantly except for use and applied them topically two to four times daily as needed for ocular pain or irritation. The average age of the patients was 55 years, and they were predominantly female. They could continue on any topical or oral dry eye medication, light therapy or injectable steroid as long as they had been stable for 3 months.

The average baseline Ocular Surface Disease Index (OSDI) score was 62, and the average treatment length was 11 months (range, 4 months to 26 months). The final OSDI score was 49. No patients reported worsening of their disease. No treatment-emergent adverse events were reported, although potential side effects included bacterial contamination, infection, product clotting and/or immunoglobulin deposits in the cornea.

PRP tears made with PRP machines widely accepted for orthopedic use create more concentrated and possibly more efficacious serum tears to treat patients, especially those with refractory eye pain related to dry eye disease. More study is warranted to examine the effects the specific growth factors and the mixtures may have on epithelial healing and corneal nerve regeneration.

Disclosure: Toyos reports she is a consultant for Lumenis, Mallinckrodt, Mixto, Shire, Sun, Valeant and Zeiss; is a speaker for Iridex, Lumenis, Sun and Valeant; conducts research for DigiSight, Iridex, Kala, Lumenis, Mallinckrodt, Mixto, Shire, Sun, Valeant and Zeiss; and is a spouse of an employee of Lumenis.

Consider adding compounded hormones

Mark S. Milner, MD, FACS
Mark S. Milner

Dry eye, like glaucoma, is often a multi-treatment disease. With glaucoma, if you reach 50% of your target IOP lowering with one medication, that drug is considered successful, and another one is added. However, with dry eye, doctors may start with Restasis (cyclosporine ophthalmic emulsion 0.05%, Allergan) or Xiidra (lifitegrast ophthalmic solution 5%, Novartis) — and Cequa (cyclosporine A 0.09%, Sun) will soon be launched — see only 30% or 40% success, consider it a failure, stop the treatment and try something else. The treatment is actually a success; the patient just needs additional medications.

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Patients with aqueous-deficient dry eye may benefit from topical hormone drops. We know that they work to improve the lacrimal gland as well as the goblet cells. And although there is a dearth of good evidence-based studies, anecdotally, they have been shown to have some good anti-inflammatory effects.

We are using medroxyprogesterone, which has some anti-inflammatory effects, but it is also used for people with corneal melts because it may prevent collagenase activity. We are also using DHEA, which is a topical androgen, because we know that people who go through menopause have a decrease in androgens, and androgens are critical to tear production and meibomian gland secretion. And we started using a 50-50 testosterone-progesterone mix, again, due to its anti-inflammatory effects.

We prescribe these drops four times a day, and there is no systemic absorption. We have had good success using them for aqueous deficiency, and in some cases, especially the DHEA, we have had good success treating those patients who need more in addition to Restasis, Xiidra or Cequa.

It is important to note that these products are not commercially available. They are compounded, and this use is off label. They are to be used at the discretion of the physician, as there are few studies that prove their efficacy. A lot of this information is anecdotal and based on other studies that show improvement from systemic treatments.

In addition to compounded hormones, we compound metronidazole as an ophthalmic ointment as Metrogel (Galderma) is not made for the eye, and it is an amazing treatment for posterior blepharitis, used at bedtime. Also, for those who cannot tolerate oral doxycycline, we compound doxycycline drops for use twice a day.

Compounded albumin is also a great treatment for aqueous-deficient patients. Compounded vitamin A is great for goblet cell-deficient patients. It is commercially available overseas as VitA-POS (AFT Pharmaceuticals).

Disclosure: Milner reports he is a speaker and consultant for Allergan, Sun and Takeda and has a financial interest in Ocular Science.