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Time will tell, but it is possible that we are poised to see new changes in the management of keratitis (microbial, HSV), recurrent corneal erosions, corneal abrasions, and other anterior segment conditions with amniotic membrane.
It’s easy to take for granted the enormous growth that has occurred in eye care and optometry. Interested in fitting contact lenses? The market has seen expansion from yearly and two-week soft lenses and small-diameter RGPs to daily, monthly standard, and silicone hydrogels and small, medium, and scleral RGPs.
Interested in treating ocular disease? It’s easy to forget that 35 years ago, optometrists were worried about having the opportunity to dilate eyes. Practice scope has grown to routinely include dilation and treatment of eye infections, and management and treatment of eye disease.
Time will tell, but it is possible that we are poised to see new changes in the management of keratitis (microbial, HSV), recurrent corneal erosions, corneal abrasions, and other anterior segment conditions with amniotic membrane. Recently approved for reimbursement in optometry, this specially designed biologic corneal bandage will likely make a significant improvement in the recovery from injury or disease for some patients.
What is amniotic membrane?
Simply stated, amniotic membrane is a turbocharged biologic contact lens. Practitioners have been keenly aware of the fact that an approved bandage contact lens will improve patient comfort and support healing by reducing eyelid and corneal surface interaction.
Amniotic membrane such as Prokera (BioTissue) is an active carrier of amniotic membrane cells and utilizes, as a result of harvesting, a number of chemical mediators including heavy chain hyaluronic acid, PTX 3 [HC-HA activator], collagens (types I, III, IV, V, and VI), fibronectin, laminin, proteoglycans, and growth factors.1
It is believed that the heavy chain hyaluronic acid is the key component and that it works by neutralizing neutrophil activity and downgrading the inflammation pathway. This is important because the reduction of inflammation decreases the likelihood of scarring.
What are the indications for using amniotic membrane? A number of options include neurotrophic persistent epithelial defects, dry eye, exposure keratopathy, filamentary keratitis, infectious keratitis, recurrent corneal erosion, Salzmann’s degeneration, post-DSEK bullous keratopathy, and post-PRK haze.
In situations where the epithelium is broken, amniotic membrane can be used to cover the wound and speed the recovery. In situations where there are no epithelial breaks, such as basement membrane changes or Salzmann’s, the pathology is debrided, and amniotic membrane is applied. Do the anti-inflammatory properties of amniotic membrane make a difference in healing? Let’s look at some studies.
Looking at the literature
While optometry is now being included in the utilization of the device, Prokera has been available for use since 2005. Prokera was studied on 35 eyes of 33 patients between 2008 and 2012 on patients with diagnoses ranging from non-healing corneal ulcers, neurotrophic keratitis, chemical injury, and other indications. The authors did note complete or partial success that ranged from a low of 44percent for the nine eyes with non-healing ulcers to a high of 80percent for the five eyes treated for chemical injury.2
It is interesting to note, that the mean age of the patients treated was 68, the mean follow-up was 164 days, and that the overwhelming majority of the patients (25 of 35 eyes) treated in study were male. One might surmise that the better healing in an aged population is significant, but there are not sufficient comparisons to other types of treatment. Seventeen percent of patients noted discomfort with the lens.
In late 2013, Prokera Slim with a slimmer profile was introduced to the market to optimize patient comfort.
In another series of patients, 20 eyes were treated with Prokera for a variety of conditions, including corneal neovascularization with or without stem cell failure, band keratopathy, corneal ulceration with thinning, pterygium and pseudopterygium, persistent epithelial defects, benign hereditary intraepithelial dyskeratosis, and anophthalmic orbit contraction.3
The advantage of using Prokera was faster healing and less pain. Disadvantages included expulsion of the lens and irritation. While subsequent studies by others seemed to be involved with more significant ocular complications,4 this initial study and another seemed to support the safety of Prokera.5
Stevens-Johnson (SJ) syndrome is a devastating finding and a great concern for the patient and the doctor. Briefly, the condition involves a hypersensitivity reaction of the skin and mucous membranes to certain medications or infections, resulting in cell death. In the eye, SJ causes blisters, erosions, and potentially blinding scars and is very difficult to treat. Kolomeyer and colleagues treated a 19-year-old patient who developed SJ after taking oral antibiotics. The patient had presented with bilateral corneal and conjunctival abrasions.
Three weeks after the placement of the lenses, the patient achieved reepithelialization. At three months, the patient had recovered her vision, and there was no evidence of scarring. Fourteen months post procedure, the patient had no problems with discomfort, dry eye, or scarring.6 In late 2013, Prokera Plus was introduced to treat severe indications, such as SJÃ. This new Prokera Plus has multiple layers of amniotic membrane and should provide longer biologic and healing properties on the ocular surface.
In another patient, Prokera was used to treat bilateral corneal and conjunctival abrasions associated with toxic epidermal necrolysis. The 5-year-old patient achieved significant improvement with the lenses, but in the long term, the patient developed trichiasis in both eyes and marginal keratinization and entropion in one eye.7
This was not deemed a failure by the authors of the treatment, but it does point out a significant concern about the treatment; because the lens covers only the cornea and conjunctival areas, these tissues derived the benefit of the amniotic membrane cells imbedded in the lens. The fornix, tarsus, and eyelid margins are not covered by the cells and may still be at risk for long-term damage. This would certainly explain the development of trichiasis and entropion.
Prokera has also been used in cases of severe microbial keratitis. Sheha and colleagues treated three eyes of three patients with infiltration greater than 50 percent of the corneal thickness, greater than five mm in size, and involving territory within the central three mm of the visual axis. In all three cases, epithelialization was achieved in addition to pain resolution, and visual acuity was improved in two of the three eyes.8
Prokera three ways
Prokera is available in three different designs. Prokera Slim is recommended for cases of keratitis, recurrent erosions, and mild to moderate abrasions. Prokera Slim is 100 µm thick and has a lower profile and comfort ring design to improve patient comfort. The original Prokera is recommended for neurotrophic ulcers, severe microbial keratitis, bullous keratopathy, and high-risk corneal transplantations. It also has a 100-µm thickness.
Prokera Plus is recommended for patients with severe indications, such as SJ or chemical burns. Patients wearing the device and with minimal injury might find a mild reduction in visual acuity.9 Prokera Plus is 200 µm thick because of double thick amniotic membrane. Those with more severe disease might benefit from using a tape tarsorrophy to reduce likelihood of Prokera moving or being ejected from the eye.
The average doctor is going to want to know about coding. And it’s important. The established CPT code is 65778. Reimbursement can range between $1,200 to $1,700, depending on the state. V2790 can also be submitted as a supply code for some commercial carriers for additional reimbursement of the device. The manufacturer worked to help create this code for reimbursement in 2011 for use by ophthalmologists. Bio-Tissue entered the optometry space in 2013 and is investing in gaining approval for code 65778 to be used by optometrists.
Precertification might be advised for situations in which there might be time to get things organized, including Salzmann’s debridement or recurrent erosion, but neurotrophic keratitis or severe infectious situations don’t afford the patient or the doctor much time to determine if an expensive treatment will be covered. Typically, this is not required for Medicare or commercial plans, but consulting with your carriers prior to use might be a good idea.
Using amniontic membrane
To maintain its therapeutic and healing effects, Prokera needs to be stored in a separate office refrigerator, not one with lunch or last year’s salad. Furthermore, application and removal should be performed using gloves. The device is 16.5 mm in size and needs to be applied by having the patient look down while the upper lid is retracted, and the device pushed in and slid down under the lower lid.
After application, the patient should be rechecked within a week and then at a schedule that the doctor determines. Prokera is contraindicated in fungal infections or in patients with a glaucoma drainage device.
It would not be appropriate to suggest that amniotic membrane should be used in all situations. In clinical practice, the doctor is uniquely qualified to make the determination if Prokera, biologic corneal bandage, a regular bandage contact lens, or no treatment at all is best suited for a patient’s condition.
Frankly, this is important. A doctor can use his clinical judgment to determine if, for instance, an abrasion is barely visible or peripherally located to be deemed non-threatening to the patient. Indeed, if the patient were asymptomatic, treatment with Prokera might not be appropriate.
However, if there was a substantial central abrasion, or even a recurrence of central epithelial erosion affecting the patient’s vision, then more aggressive therapy might certainly be indicated to ensure the quickest recovery with the least likelihood of scarring. After all, there might not be many other options that reduce inflammation and promote healing while giving the patient the best opportunity for a superior outcome.ODT
1. Prokera website. Available at:http://www.prokerainfo.com. Accessed 01/31/2014.
2. Suri K, Kosker M, Raber IM, et al. Sutureless amniotic membrane Prokera for ocular surface disorders: short-term results. Eye Contact Lens. 2013 Sep;39(5):341-7.
3. Pachigolla G, Prasher P, Di Pascuale MA, et al. Evaluation of the role of Prokera in the management of ocular surface and orbital disorders. Eye Contact Lens. 2009 Jul;35(4):172-5.
4. Celik T, Katircioglu YA, Singar E, et al. Clinical outcomes of amniotÃ±c membrane transplantatÃ±on in patients with corneal and conjunctival disorders. Semin Ophthalmol. 2013 Jan;28(1):41-5.
5. Yildiz EH, Nurozler AB, Ozkan Aksoy N, et al. Amniotic membrane transplantation: indications and results. Eur J Ophthalmol. 2008 Sep-Oct;18(5):685-90.
6. Kolomeyer AM, Do BK, Tu Y, et al. Placement of Prokera in the management of ocular manifestations of acute Stevens-Johnson syndrome in an outpatient. Eye Contact Lens. 2013 May;39(3):e7-11.
7. Shay E, Khadem JJ, Tseng SC. Efficacy and limitation of sutureless amniotic membrane transplantation for acute toxic epidermal necrolysis. Cornea. 2010 Mar;29(3):359-61.
8. Sheha H, Liang L, Li J, et al. Sutureless amniotic membrane transplantation for severe bacterial keratitis. Cornea. 2009 Dec;28(10):1118-23.
9. Ijiri S, Kobayashi A, Sugiyama K, et al. Evaluation of visual acuity and color vision in normal human eyes with a sutureless temporary amniotic membrane patch. Am J Ophthalmol. 2007 Dec;144(6):938-942.