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Allogeneic Versus Autologous Serum Eye Drops

Not Applicable
Completed
Conditions
Dry Eye Syndrome
Interventions
Other: Autologous serum eye drops
Other: Allogeneic serum eye drops
Registration Number
NCT03085290
Lead Sponsor
Sanquin Research & Blood Bank Divisions
Brief Summary

Serum eye drops (SEDs) are used to treat patients with extreme dry eyes and other corneal defects. Serum is used in severe ophthalmic cases where conventional eye drops (artificial tears) have insufficient effect. The use of SEDs in dry eye patients usually has a rapid effect. Most patients claim the effect to be instantaneous, and all symptoms improve within 48 hours.

There is evidence suggesting that substances in serum may help in the healing of epithelial defects, such as epidermal growth factor, fibroblast growth factor, fibronectin, and/or vitamin A. However, the precise serum factor responsible for alleviating the patient's complaints is currently not known. Commonly, autologous SEDs are used, but they are replaced more and more by allogeneic SEDs prepared from donor serum.

Allogeneic SED are derived from healthy voluntary, non-remunerated male donors with blood group AB. The use of allogeneic SED could provide blood bank controlled quality, a safer product in larger quantities that is quickly available for each patient.

No double-blind randomized trials are known to exist to detect a difference in result between the effect of allogeneic SED or autologous SED. This pilot study is intended to obtain insight in the ability of autologous and allogeneic SEDs to improve patient dry eye sensation. Our hypothesis is that autologous SEDs (in a 1:1 dilution with saline) result in an improvement of the patient dry eye sensation, while allogeneic SEDs (in a 1:1 dilution with saline) do not.

Detailed Description

Serum eye drops (SEDs) are used to treat patients with dry eyes and other diseases, like corneal defects. SEDs are used in ophthalmic cases where conventional eye drops have insufficient effect. The use of SEDs in dry eye patients usually has a rapid effect. Most patients claim the effect to be instantaneous and all symptoms improve by 48 hours \[1\].

There is evidence suggesting that serum may enhance corneal epithelial healing \[2\]. Some biologically active substances are thought to contribute to the positive effects, like epidermal growth factor, fibroblast growth factor, fibronectin, and vitamin A.

Autologous SEDs are used internationally on a regular basis, and allogeneic SEDs are becoming increasingly popular. In the Netherlands, only autologous SEDs are in use.

Obtaining autologous SED is an organizational burden. Patient-related problems are old age, travelling, or travelling with low vision and sometimes immobility due to other diseases. Sometimes venipuncture is impossible due to poor access. Medical conditions such as inability to donate large amounts of whole blood due to previous cerebrovascular accidents or cardiovascular disease, anemia, or use of certain medication may prevent collection of blood for SEDs. Patients affected with hematological diseases, bacterial, viral or fungal infections are also unsuitable for production of autologous SEDs. In 2.3% of donors for preparing autologous SEDs, a systemic infection can be detected \[3\]. In the UK, use of autologous SED is restricted largely due to cost \[4\]. Logistically, it is a problem that it takes time as well as joint effort of several departments in the hospital to prepare the SEDs, causing considerable waiting time for the patient. Further, the use of allogeneic drops allows immediate access to SEDs in case time is limited to prevent corneal scars, ulcers, infiltrates or even transplants, epithelial defects or low vision due to epithelial surface disease.

Allogeneic SEDs are derived from healthy donors and are produced by a blood bank facility. Blood banks are experienced and equipped to produce blood products in a good manufacturing practice (GMP) environment. They can perform quality control, and are able to produce larger quantities that are quickly available. For our study, donors with blood group AB will be selected to ensure ABO compatibility. Donors are further selected to be males that never had a blood transfusion to minimize anti-HLA titers.

No prospective double blind randomized cross-over trials are known to exist to detect a difference in result between the effect of allogeneic SED or autologous SED for ocular surface disease. This pilot study is intended to obtain insight in the ability of autologous and allogeneic SEDs to improve patient dry eye sensation. Our hypothesis is that autologous SEDs (in a 1:1 dilution with saline) result in an improvement of the patient dry eye sensation, while allogeneic SEDs (in a 1:1 dilution with saline) do not.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
18
Inclusion Criteria
  • chronic dry eye syndrome
  • age 18 or higher
  • expected to benefit from SEDs
  • can donate sufficient blood to prepare autologous SEDs
  • meet the donor guidelines of Sanquin (except for age, donation frequency and hemoglobin concentration)
Exclusion Criteria
  • has corneal lesions more than punctates
  • has a history of unstable Herpes simplex virus (HSV) keratitis or is treated for HSV keratitis
  • currently already uses SEDs
  • pregnancy, lactating, or intending the become pregnant in the next 3 months
  • unable or unwilling to give informed consent
  • active (systemic) microbial infection
  • immuno-deficiency
  • poor venous access

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Group BAllogeneic serum eye dropsSubjects assigned to this arm will receive allogeneic serum eye drops first, followed by a washout period and then autologous serum eye drops.
Group AAutologous serum eye dropsSubjects assigned to this arm will receive autologous serum eye drops first, followed by a washout period and then allogeneic serum eye drops.
Group AAllogeneic serum eye dropsSubjects assigned to this arm will receive autologous serum eye drops first, followed by a washout period and then allogeneic serum eye drops.
Group BAutologous serum eye dropsSubjects assigned to this arm will receive allogeneic serum eye drops first, followed by a washout period and then autologous serum eye drops.
Primary Outcome Measures
NameTimeMethod
Ocular Surface Disease Index (OSDI)One month after starting with serum eye drops

Normalized OSDI score

Secondary Outcome Measures
NameTimeMethod
Tear production (Schirmer's test)One month after starting with serum eye drops

Millimeter

Tear break up timeOne month after starting with serum eye drops

Number of seconds before a dry spot appears in the tear film

Corneal punctatesOne month after starting with serum eye drops

Number

Trial Locations

Locations (1)

Radboudumc

🇳🇱

Nijmegen, Netherlands

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