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Cryopreserved amniotic membrane can treat compromised ocular surface
For patients with conditions such as neurotrophic keratitis, CAM helps recover ocular surface health and regenerate corneal nerves.
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The cornea is the most densely innervated tissue of the body. In addition to providing sensation, corneal nerves help maintain the integrity of the cornea and promote epithelial proliferation. These nerves have been shown to be reduced in a variety of ocular and systemic conditions, which can result in a compromised ocular surface as well as reduced tear function.
Neurotrophic keratitis (NK) is a degenerative disease caused by damage to the trigeminal nerve. Any condition affecting the trigeminal nerve or its branches can cause corneal anesthesia. The most common causes of NK are herpetic infections, such as simplex or zoster. Other risk factors for NK include corneal surgery, chronic use of topical medications or contact lenses, and systemic disease such as diabetes. NK can impair corneal sensitivity, cause spontaneous breakdown of the epithelium and poor corneal healing, and result in corneal ulceration, melting and perforation.
There is a strong correlation between dry eye disease (DED) severity and the loss of corneal nerves in NK, suggesting that corneal nerve density can be used to gauge the severity of DED. In fact, some of the discrepancies between signs and symptoms in DED are likely due to neurosensory abnormalities. Corneal nerves are required to maintain a healthy ocular surface. The response to DED treatment may depend on the patient’s corneal nerve density. Ahmed and colleagues illustrated this relationship in a study that demonstrated significant improvement in corneal staining and subjective symptoms in patients with normal corneal nerve density compared with those with low nerve density.
Some studies using in vivo confocal microscopy have shown a correlation in the reduction of total number of corneal nerves and decreased corneal sensation in patients with herpes zoster and simplex and in patients who have undergone refractive surgery. Similar studies have shown a decrease in corneal nerve fiber density, increased nerve tortuosity and a significant correlation with the severity of peripheral neuropathy. These findings support the need for a therapeutic intervention that stimulates regeneration of the trigeminal nerve and its branches.
Diagnosis and treatment options
Early stages of NK can be misdiagnosed as DED, chronic eye rubbing, exposure keratopathy, topical drug toxicity or contact lens-related keratopathy. Early diagnosis of NK is necessary to prevent progressive damage, and close monitoring of these patients is critical especially because this disease is often asymptomatic. We cannot rely on patient feedback to gauge worsening of the condition due to their loss of corneal sensation. Testing corneal sensation can be measured qualitatively with a piece of twisted cotton or quantitatively with a Cochet-Bonnet esthesiometer.
The aim of NK treatment is to prevent breakdown of the epithelium and progression of the disease.
Treatment options include a high-quality omega-3 supplement, preservative-free tears, gel or ointment, autologous serum, punctal occlusion, therapeutic contact lenses, cryopreserved amniotic membrane (CAM) or neurostimulation with a device such as TrueTear (Allergan), which produces mucin, aqueous and lipid — the elements of a complete tear. In addition, Oxervate (cenegermin, Dompé farmaceutici), a recombinant form of human nerve growth factor, was recently approved by the FDA for NK.
CAM is a particularly effective therapy for patients with NK. Prokera (Bio-Tissue) is currently the only CAM available for ophthalmic indications. It provides analgesic and anti-inflammatory activity and restores the epithelium and epithelial tissue to its natural state; mounting proof suggests that CAM can help regenerate corneal nerves after a single placement. Even after a 5-day treatment with Prokera, the biologics that have been released onto the ocular surface continue to regenerate and remodel the cornea for weeks and months (Figure 1).
Source: Bio-Tissue
CAM clinical data
CAM’s corneal nerve regeneration capability is supported by a prospective, randomized, controlled clinical trial by John and colleagues that demonstrated that Prokera Slim accelerated the recovery of the corneal surface for up to 3 months (the duration of the study) in patients with moderate to severe DED. The study found that pain scores and symptoms improved significantly in patients in the CAM arm of the study, as did corneal staining and tear film stability. Perhaps most noteworthy was the statistically significant improvement in corneal nerve density and sensitivity. These findings suggest that a single CAM placement had lasting effects on corneal nerve regeneration, treating the root of neurosensory abnormalities in ocular surface disease. Specifically, Prokera’s proprietary cryopreservation method ensures that it retains the key active HC-HA/PTX3 complex, unique components that — when bonded together — regulate and promote the regenerative tissue process.
In my experience, neurotrophic patients treated with CAM often begin to feel their eyes again as nerves are regenerated; they are able to sense when they need to put drops in their eyes or better explain how their eyes feel at follow-up appointments.
- References:
- Ahmed Z, et al. Cell Death Dis. 2011;doi:10.1038/cddis.2011.54.
- Cheng AM, et al. Ocul Surf. 2016;doi:10.1016/j.jtos.2015.07.003.
- Cruzat A, et al. Semin Ophthalmol. 2010;doi:10.3109/08820538.2010.518133.
- Hamrah P, et al. Ophthalmology. 2010;doi:10.1016/j.ophtha.2010.07.010.
- Hamrah P, et al. Ophthalmology. 2013;doi:10.1016/j.ophtha.2012.07.036.
- John T, et al. J Ophthalmol. 2017;doi:10.1155/2017/6404918.
- McDonald MB, et al. Clin Ophthalmol. 2018;doi:10.2147/OPTH.S162203.
- Rosenthal P, et al. Ocul Surf. 2009;doi:10.1016/S1542-0124(12)70290-2.
- Tseng SCG. Invest Ophthalmol Vis Sci. 2016;doi:10.1167/iovs.15-17637.
- For more information
- Alice T. Epitropoulos, MD, FACS, can be reached at The Eye Center, 262 Neil Ave., Suite 410, Columbus, OH 43215; email: eyesmd33@gmail.com.
Disclosure: Epitropoulos reports she is a consultant for Alcon, Allergan, Bausch + Lomb, Bio-Tissue, BlephEx, Bruder, Kala, Omeros, PRN, Shire Pharmaceuticals, Sun Ophthalmics, TearLab, Eyevance and TearScience-Johnson & Johnson.