Perspective

Early use of cryopreserved amniotic membrane can prevent further corneal damage

Dry eye disease impacts — and is impacted by — a number of social and environmental challenges that we face today.

First, the disease is pervasive and growing, as is our associated dependence on smart phones and screen time. Second, dry eye disease (DED) symptoms are tied to a multitude of uncontrollable environmental conditions such as air conditioning and air travel. Third, researchers estimate that approximately $3.8 billion is spent annually on DED treatments, and those expenditures are likely to increase as climate change escalates, according to the NEI. These factors are among the many reasons why providing safe and effective treatment options for patients with DED symptoms is a growing imperative in my practice.

Douglas K. Devries

As such, amniotic membrane (AM) tissue with its corneal epithelialization, inflammation reduction, fibrosis prevention and antimicrobial properties, has become a key component of my ocular surface disease treatment strategy. Cryopreserved amniotic membrane (CAM), in particular, is my go-to choice for patients who have recalcitrant DED.

Types of amniotic membrane

Two types of AM are available for ophthalmic use: cryopreserved and dehydrated. Cryopreserved AM (Prokera, BioTissue) is kept frozen and brought to room temperature before application. Dehydrated AM, such as AmbioDisk (IOP Ophthalmics/Katena) and BioDOptix (Integra LifeSciences) is stored at room temperature but must be rehydrated for clinical use.

Cryopreserved AM retains heavy chain-hyaluronic acid and pentraxin 3 (HC-HA/PTX3), which is the specific biologic matrix that has been identified as responsible for AM’s anti-inflammatory and regenerative healing properties. Research also suggests that HC-HA/PTX3 helps reduce scar formation that can lead to impaired vision (Cheng et al.). AM tissue that is dehydrated does not retain this critical biologic compound (Cooke et al.).

Patient with moderate to severe dry eye disease (Dry Eye Workshop level 3) exhibiting dense central and inferior corneal superficial punctate keratitis.
Source: Bio-Tissue

Prokera cryopreserved AM is FDA-cleared for therapeutic properties, such as its anti-inflammatory, protective and wound healing effects. FDA labeling indicates that dehydrated AM’s utility is limited to wound coverage. I find CAM to be more user friendly and more useful – given its wound healing properties; however, dehydrated AM maintains a loyal following of users who have confidence in its ocular surface rehabilitation capabilities.

Clinical data, experience

In my practice, as well as in clinical trials, cryopreserved amniotic membrane (CAM) produces excellent results. For instance, in a small 20-patient prospective trial where patients were randomized for CAM or conventional therapy, patients in the CAM group had a significant decrease in their pain score, Standardized Patient Evaluation of Eye Dryness score and DED symptoms from baseline to 1 month and 3 months, whereas those markers remained relatively unchanged in the conventional therapy control group (John et al.).

In a larger, retrospective study of approximately 100 patients who had moderate to severe DED and were not responding to maximum conventional therapies, 88% demonstrated an improved corneal staining score along with a notable reduction in the severity of their symptoms (McDonald et al.). Just 10% required repeat CAM placement to complete healing, and those were patients who had exposure keratitis or epithelial defects. Apart from mild discomfort after CAM placement, there were no adverse events.

CAM in practice

In addition to dry eye, CAM may be used treat chemical burns of the ocular surface, corneal epithelial defects such as those associated with bullous or band keratopathy, epithelial basement membrane dystrophy, recurrent corneal erosions, keratitis, corneal ulcers and persistent epithelial defects, among other things.

The corneal surface was completely re-epithelialized in 5 days after Prokera placement. The severity of DED was reduced to DEWS level 1, and the cornea was stable for more than 3 months.

I also find that self-retained CAM is ideal for patients who are contact lens intolerant, as it can facilitate corneal healing when I initiate prescription eye drops.

Patient response

Patients in search of relief from intractable DED symptoms typically have a positive response to my recommendation of CAM. When I tell a patient that the next step we are going to take is to apply a cryopreserved amniotic membrane to activate the healing process in their eye, I have never gotten any pushback. In fact, patients are typically eager to get on with the process.

When the cryopreserved AM centers well, and the PMMA ring does not touch the limbus, you can expect the patient to be comfortable. If it touches the limbal area, the patient may experience irritation upon blinking, so in those cases I use a tape tarsorrhaphy to minimize movement during the blink. I apply tape over the superior lid at the lash line and extend it to the crease in the superior fornix to decrease the translation of the ring upon blinking and minimize discomfort.

I have not personally experienced adverse events with CAM. I have, however, had a few instances where placement of dehydrated AM resulted in complications. On three separate occasions, a diffuse inflammation developed between the flap and the cornea when I placed dehydrated AM in patients who were experiencing severe DED symptoms 8 to 15 years after LASIK. These patients have experienced an allergic reaction to something used in the dehydration process, resulting in a pro-inflammatory response.

Emerging research suggests that in addition to stimulating active healing, CAM initiates corneal nerve regeneration (John et al.). Unfortunately, all too often, eye care providers reserve CAM as a last resort, when earlier use could have introduced important healing properties and prevented further corneal surface deterioration. This knowledge can go a long way toward preemptively mitigating ocular surface disease in its earliest stages.

Disclosure: Devries reports he is a consultant for Alcon, Allergan, Avellino, Bausch + Lomb, BioTissue, BVI, Eyes 4 Lives, Johnson & Johnson Vision, Kala Pharmaceutical, Lumenis, OcuSoft, Ophthalmic Resources, RPS, RySurg, ScienceBased Health, Sun Pharmaceutical, Takeda, Tear Care and TearLab.

Dry eye disease impacts — and is impacted by — a number of social and environmental challenges that we face today.

First, the disease is pervasive and growing, as is our associated dependence on smart phones and screen time. Second, dry eye disease (DED) symptoms are tied to a multitude of uncontrollable environmental conditions such as air conditioning and air travel. Third, researchers estimate that approximately $3.8 billion is spent annually on DED treatments, and those expenditures are likely to increase as climate change escalates, according to the NEI. These factors are among the many reasons why providing safe and effective treatment options for patients with DED symptoms is a growing imperative in my practice.

Douglas K. Devries

As such, amniotic membrane (AM) tissue with its corneal epithelialization, inflammation reduction, fibrosis prevention and antimicrobial properties, has become a key component of my ocular surface disease treatment strategy. Cryopreserved amniotic membrane (CAM), in particular, is my go-to choice for patients who have recalcitrant DED.

Types of amniotic membrane

Two types of AM are available for ophthalmic use: cryopreserved and dehydrated. Cryopreserved AM (Prokera, BioTissue) is kept frozen and brought to room temperature before application. Dehydrated AM, such as AmbioDisk (IOP Ophthalmics/Katena) and BioDOptix (Integra LifeSciences) is stored at room temperature but must be rehydrated for clinical use.

Cryopreserved AM retains heavy chain-hyaluronic acid and pentraxin 3 (HC-HA/PTX3), which is the specific biologic matrix that has been identified as responsible for AM’s anti-inflammatory and regenerative healing properties. Research also suggests that HC-HA/PTX3 helps reduce scar formation that can lead to impaired vision (Cheng et al.). AM tissue that is dehydrated does not retain this critical biologic compound (Cooke et al.).

Patient with moderate to severe dry eye disease (Dry Eye Workshop level 3) exhibiting dense central and inferior corneal superficial punctate keratitis.
Source: Bio-Tissue

Prokera cryopreserved AM is FDA-cleared for therapeutic properties, such as its anti-inflammatory, protective and wound healing effects. FDA labeling indicates that dehydrated AM’s utility is limited to wound coverage. I find CAM to be more user friendly and more useful – given its wound healing properties; however, dehydrated AM maintains a loyal following of users who have confidence in its ocular surface rehabilitation capabilities.

Clinical data, experience

In my practice, as well as in clinical trials, cryopreserved amniotic membrane (CAM) produces excellent results. For instance, in a small 20-patient prospective trial where patients were randomized for CAM or conventional therapy, patients in the CAM group had a significant decrease in their pain score, Standardized Patient Evaluation of Eye Dryness score and DED symptoms from baseline to 1 month and 3 months, whereas those markers remained relatively unchanged in the conventional therapy control group (John et al.).

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In a larger, retrospective study of approximately 100 patients who had moderate to severe DED and were not responding to maximum conventional therapies, 88% demonstrated an improved corneal staining score along with a notable reduction in the severity of their symptoms (McDonald et al.). Just 10% required repeat CAM placement to complete healing, and those were patients who had exposure keratitis or epithelial defects. Apart from mild discomfort after CAM placement, there were no adverse events.

CAM in practice

In addition to dry eye, CAM may be used treat chemical burns of the ocular surface, corneal epithelial defects such as those associated with bullous or band keratopathy, epithelial basement membrane dystrophy, recurrent corneal erosions, keratitis, corneal ulcers and persistent epithelial defects, among other things.

The corneal surface was completely re-epithelialized in 5 days after Prokera placement. The severity of DED was reduced to DEWS level 1, and the cornea was stable for more than 3 months.

I also find that self-retained CAM is ideal for patients who are contact lens intolerant, as it can facilitate corneal healing when I initiate prescription eye drops.

Patient response

Patients in search of relief from intractable DED symptoms typically have a positive response to my recommendation of CAM. When I tell a patient that the next step we are going to take is to apply a cryopreserved amniotic membrane to activate the healing process in their eye, I have never gotten any pushback. In fact, patients are typically eager to get on with the process.

When the cryopreserved AM centers well, and the PMMA ring does not touch the limbus, you can expect the patient to be comfortable. If it touches the limbal area, the patient may experience irritation upon blinking, so in those cases I use a tape tarsorrhaphy to minimize movement during the blink. I apply tape over the superior lid at the lash line and extend it to the crease in the superior fornix to decrease the translation of the ring upon blinking and minimize discomfort.

PAGE BREAK

I have not personally experienced adverse events with CAM. I have, however, had a few instances where placement of dehydrated AM resulted in complications. On three separate occasions, a diffuse inflammation developed between the flap and the cornea when I placed dehydrated AM in patients who were experiencing severe DED symptoms 8 to 15 years after LASIK. These patients have experienced an allergic reaction to something used in the dehydration process, resulting in a pro-inflammatory response.

Emerging research suggests that in addition to stimulating active healing, CAM initiates corneal nerve regeneration (John et al.). Unfortunately, all too often, eye care providers reserve CAM as a last resort, when earlier use could have introduced important healing properties and prevented further corneal surface deterioration. This knowledge can go a long way toward preemptively mitigating ocular surface disease in its earliest stages.

Disclosure: Devries reports he is a consultant for Alcon, Allergan, Avellino, Bausch + Lomb, BioTissue, BVI, Eyes 4 Lives, Johnson & Johnson Vision, Kala Pharmaceutical, Lumenis, OcuSoft, Ophthalmic Resources, RPS, RySurg, ScienceBased Health, Sun Pharmaceutical, Takeda, Tear Care and TearLab.

    Perspective
    Jeffrey Varanelli

    Jeffrey Varanelli

    The global amniotic membrane market was valued at $2.26 billion in 2017, with an expectation to reach $5.81 billion by 2025, according to Grand View Research Inc. It appears obvious that the use of amniotic membranes and their healing capabilities will continue to be viable treatment options for our patients. 

    From personal experience, I have used both cryopreserved and dehydrated amniotic membranes to successfully treat a myriad of ocular surface diseases. Human dehydrated amnion/chorion membrane laminates have been shown to promote healing of many ocular surface conditions that we routinely encounter in practice. These include recurrent corneal erosions, chemical injuries and keratitis, among others. The ability to retain the biologically active growth factors during the processing of amniotic tissues is a critically important step. It is the presence of these growth factors and other cytokines that have been shown to reduce inflammation, pain and scarring while promoting accelerated wound healing.

    The use of dehydrated amniotic membranes represents an effective treatment that can be easily applied in office. If not already, they should be an integral part of our treatment paradigm for the management of our patients with ocular surface changes.


    References:

    Koob TJ, et al. J Biomed Mater Res B Appl Biomater. 2014:doi:10.1002/jbm.b.33265.

    Dua HS, et al. Surv Ophthalmol. 2004;49(1):51–77.

    • Jeffrey Varanelli, OD
    • Director, optometric services, Simone Eye Center
      Warren and Macomb Township, Mich.

    Disclosures: Varanelli reports he has received honoraria or support from Allergan, BioDOptix, Bio-Tissue, Johnson & Johnson Vision Care, Katena, Seed Biotech and Shire.