Dry eye is the common denominator of every ocular surface disease. Thus, managing dry eye effectively is the first critical step in treating complex ocular surface diseases. A stable tear film is essential for a healthy ocular surface.

Compositional factors (mucins, lipids, and aqueous fluids) and hydrodynamic factors (eyelid blinking and closure) work together to maintain a stable tear film when the eye is open.¹ In this process of neuroanatomic integration, the first branch of the trigeminal nerve generates the sensory input, triggering the tearing and blinking reflexes.

While many factors contribute to a stable tear film, neuroanatomical integration makes them work together. That is why Bio-Tissue has placed such a high value on studying nerve function.

We also recognize the value of anti-inflammatory action. Conventional dry eye therapies, such as steroids, nonsteroidal anti-inflammatory drugs, cyclosporine ophthalmic emulsion, and others, target one specific cell type and one particular biological action, which may lead to dose-dependent adverse effects. We believe we have a better alternative, a novel solution.

UNIQUE EXTRACELLULAR MATRIX

In 2001, the FDA approved the use of cryopreserved amniotic membrane transplantation in ophthalmology to promote wound healing via proven anti-inflammation, anti-scarring, and anti-angiogenesis properties. In subsequent studies from 2002 to 2014, we sought to identify the active components in that tissue.

This 12-year effort enabled us to identify HC-HA/PTX3.² This unique extracellular matrix suppresses inflammation, and, unlike the other small molecules (e.g., cyclosporine), it targets three cell types. More importantly, HC-HA/PTX3 triggers only the activator cells and not the resting cells. The selectivity of down-regulating the activator cells is important, as it will not cause an immune-compromised or deficient state. We also found that HC-HA/PTX3 can directly control scarring independently.

These two actions are important, because if you cannot control inflammation, you cannot control scarring. The scarring indicates the lack of regeneration, and the scar tissue on the cornea impairs vision.

HC-HA/PTX3 has a third important action. It affects stem cells and promotes regenerative healing, which translates to many biological benefits.

CORNEAL NERVE REGENERATION

For the first time, there is clinical evidence that PROKERA® might regenerate the corneal nerve. Why is this important? When dry eye progresses from mild to severe, corneal nerve density decreases, triggering a vicious cycle leading to further worsening of dry eye. By regenerating the corneal nerve, we can deliver a lasting effect, unlike the conventional topical therapies that tend to be short-lived. This is important when the disease progresses to a severe state, because PROKERA would restore the nerve function and help accelerate healing. Accelerated healing with PROKERA is regenerative healing with minimal or no scarring.

A recent single-site, randomized clinical trial demonstrated that one application of PROKERA for 3 to 5 days resulted in remission of symptoms for 3 or more months.³ The same finding of lasting effect has been replicated in a retrospective review of 10 sites by McDonald and colleagues.⁴

SUMMARY

We believe we have provided a novel solution for a complex ocular surface disease by recognizing dry eye as the common denominator in the beginning stage (Figure 1). PROKERA in all of its forms — PROKERA Slim, PROKERA Clear, and PROKERA Plus — has changed how we treat not only dry eye, but the entire neurotrophic disease spectrum. We believe this therapy results in better outcomes, fewer visits, and lower costs. ●

REFERENCES

1. Tseng SC, et al. Am J Ophthalmol. 1997;124:825-835.
2. Tseng SC. Invest Ophthalmol Vis Sci. 2016;57:ORSFh1-8
3. John T, et al. J Ophthalmol. 2017;2017:644918.
4. McDonald M, et al.; DREAM Study Group. Clin Ophthalmol. 2018.