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Blood-derived products have application in ocular surface disease therapy

UPMC Eye Center is using eye platelet-rich plasma to treat conditions such as severe dry eye, Sjögren's syndrome and graft-versus-host disease.

The ocular surface is severely affected in diseases such as Sjögren’s syndrome, persistent epithelial defect, recurrent corneal erosion, neurotrophic keratopathy, post-LASIK dry eye syndrome, graft-versus-host disease and ocular cicatricial pemphigoid. The treatment of ocular surface disorders is difficult, and conventional therapy is often not enough to solve the problem. Scientists and clinicians have been searching for a long time for a substance that would be similar to tears in composition and may stimulate the healing process of the tissues affected in ocular surface disorders.

Blood-derived products

Blood-derived products have demonstrated their capacity to enhance healing and stimulate the regeneration of different tissues, and this enhancing effect is attributed to the growth factors and bioactive proteins that are synthesized and present in blood. Different blood-derived formulations, such as autologous serum, plasma enriched with platelets and preparations rich in growth factors, have been used to promote wound healing in multiple tissues. The serum is the clear liquid part of full blood after cellular components and clotting proteins have been removed.

Since Fox and colleagues first used autologous serum eye drops in the treatment of keratoconjunctivitis sicca, it has been the preferred blood-derived topical preparation in the treatment of ocular surface diseases such as persistent epithelial defects, neurotrophic ulcers, superior limbic keratoconjunctivitis, and other types of dry eye symptoms such as graft-versus-host disease or after LASIK. Autologous serum has also been used as an adjunctive treatment in ocular surface reconstruction with different results. Unlike artificial tears, serum eye drops have pH, osmolarity and biomechanical properties that resemble natural tears, and they are non-preserved. When used topically, they supply essential nutrients to the ocular surface, such as growth factors, vitamins, and bacteriostatic products such as IgG, lysozyme and complement. Plasma, unlike serum, contains clotting proteins of full blood, such as fibrin.

Ladan Espandar

Although the acellular component of blood contains growth factors, it is well known that platelets are great reservoirs of growth factors that enhance proliferation and wound healing. The alpha-granules in platelets contain more than 30 bioactive proteins such as epidermal growth factor, platelet-derived growth factor, vascular endothelial growth factor, insulin-like growth factor 1 and transforming growth factor beta, as well as cytokines and proteins, which promote tissue repair and influence the reactivity of vascular and other blood cells in angiogenesis and inflammation. Growth factors released from activated platelets initiate and modulate wound healing in both soft and hard tissues. The plasma also contains concentrated quantities of some important cell adhesion molecules, which promote epithelial migration, such as fibrin, fibronectin and vitronectin.

Platelet-rich plasma

Platelet-rich plasma (PRP), which has a high concentration of growth factors, can improve the cornea wound-healing process by inducing corneal cell migration, proliferation and differentiation. PRP has been used clinically for more than a decade as a complement to tissue regeneration procedures in specialties such as oral and maxillofacial surgery, reconstructive surgery, orthopedics, cardiovascular surgery and plastic surgery. A meticulous review of the literature showed that blood-derived products such as plasma enriched with platelets and growth factors has not been as widely used in ophthalmology as it has been in other disciplines that deal with wound healing.

Eye platelet-rich plasma (E-PRP) is an autologous preparation of plasma rich in platelets and has been used in treatment of dormant ulcers, which are epithelial defects of the cornea that fail to heal despite at least 2 weeks of conventional treatment, severe dry eye syndrome and post-LASIK dry eye syndrome. The production of autologous PRP with the use of new technology such as the Magellan (Arteriocyte) is much simpler. It requires a minimum volume of autologous blood and simplified equipment, contributes to obtain a higher concentration of growth factors, and does not require bovine thrombin. By using a 100% autologous blood technique, autologous PRP is free from the risk of disease transmission.

UPMC Eye Center is one of the first centers in the country to use Magellan technology to produce customized PRP product for each patient from his or her own blood. PRP is being used in our center to treat severe dry eye, Sjögren’s syndrome, graft-versus-host disease and any other severe ocular surface diseases. In severe cases, E-PRP has been started for 2 months with serum drops and then used for maintenance therapy. We will soon start a phase 1 clinical trial to evaluate the safety and efficacy of E-PRP in ocular graft-versus-host disease.

Visit UPMCPhysicianResources.com/Ocular to learn more about neurotrophic keratopathy. You can also submit clinical questions or read the most recent questions asked of the UPMC Eye Center’s ophthalmology experts.

Disclosure: Espandar reports no relevant financial disclosures.

The ocular surface is severely affected in diseases such as Sjögren’s syndrome, persistent epithelial defect, recurrent corneal erosion, neurotrophic keratopathy, post-LASIK dry eye syndrome, graft-versus-host disease and ocular cicatricial pemphigoid. The treatment of ocular surface disorders is difficult, and conventional therapy is often not enough to solve the problem. Scientists and clinicians have been searching for a long time for a substance that would be similar to tears in composition and may stimulate the healing process of the tissues affected in ocular surface disorders.

Blood-derived products

Blood-derived products have demonstrated their capacity to enhance healing and stimulate the regeneration of different tissues, and this enhancing effect is attributed to the growth factors and bioactive proteins that are synthesized and present in blood. Different blood-derived formulations, such as autologous serum, plasma enriched with platelets and preparations rich in growth factors, have been used to promote wound healing in multiple tissues. The serum is the clear liquid part of full blood after cellular components and clotting proteins have been removed.

Since Fox and colleagues first used autologous serum eye drops in the treatment of keratoconjunctivitis sicca, it has been the preferred blood-derived topical preparation in the treatment of ocular surface diseases such as persistent epithelial defects, neurotrophic ulcers, superior limbic keratoconjunctivitis, and other types of dry eye symptoms such as graft-versus-host disease or after LASIK. Autologous serum has also been used as an adjunctive treatment in ocular surface reconstruction with different results. Unlike artificial tears, serum eye drops have pH, osmolarity and biomechanical properties that resemble natural tears, and they are non-preserved. When used topically, they supply essential nutrients to the ocular surface, such as growth factors, vitamins, and bacteriostatic products such as IgG, lysozyme and complement. Plasma, unlike serum, contains clotting proteins of full blood, such as fibrin.

Ladan Espandar

Although the acellular component of blood contains growth factors, it is well known that platelets are great reservoirs of growth factors that enhance proliferation and wound healing. The alpha-granules in platelets contain more than 30 bioactive proteins such as epidermal growth factor, platelet-derived growth factor, vascular endothelial growth factor, insulin-like growth factor 1 and transforming growth factor beta, as well as cytokines and proteins, which promote tissue repair and influence the reactivity of vascular and other blood cells in angiogenesis and inflammation. Growth factors released from activated platelets initiate and modulate wound healing in both soft and hard tissues. The plasma also contains concentrated quantities of some important cell adhesion molecules, which promote epithelial migration, such as fibrin, fibronectin and vitronectin.

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Platelet-rich plasma

Platelet-rich plasma (PRP), which has a high concentration of growth factors, can improve the cornea wound-healing process by inducing corneal cell migration, proliferation and differentiation. PRP has been used clinically for more than a decade as a complement to tissue regeneration procedures in specialties such as oral and maxillofacial surgery, reconstructive surgery, orthopedics, cardiovascular surgery and plastic surgery. A meticulous review of the literature showed that blood-derived products such as plasma enriched with platelets and growth factors has not been as widely used in ophthalmology as it has been in other disciplines that deal with wound healing.

Eye platelet-rich plasma (E-PRP) is an autologous preparation of plasma rich in platelets and has been used in treatment of dormant ulcers, which are epithelial defects of the cornea that fail to heal despite at least 2 weeks of conventional treatment, severe dry eye syndrome and post-LASIK dry eye syndrome. The production of autologous PRP with the use of new technology such as the Magellan (Arteriocyte) is much simpler. It requires a minimum volume of autologous blood and simplified equipment, contributes to obtain a higher concentration of growth factors, and does not require bovine thrombin. By using a 100% autologous blood technique, autologous PRP is free from the risk of disease transmission.

UPMC Eye Center is one of the first centers in the country to use Magellan technology to produce customized PRP product for each patient from his or her own blood. PRP is being used in our center to treat severe dry eye, Sjögren’s syndrome, graft-versus-host disease and any other severe ocular surface diseases. In severe cases, E-PRP has been started for 2 months with serum drops and then used for maintenance therapy. We will soon start a phase 1 clinical trial to evaluate the safety and efficacy of E-PRP in ocular graft-versus-host disease.

Visit UPMCPhysicianResources.com/Ocular to learn more about neurotrophic keratopathy. You can also submit clinical questions or read the most recent questions asked of the UPMC Eye Center’s ophthalmology experts.

Disclosure: Espandar reports no relevant financial disclosures.