Download Guidelines for Autogeneic Serum Eye Drops

New York State Council on Human Blood and Transfusion Services
GUIDELINES FOR
AUTOGENEIC SERUM EYE DROPS
2012
New York State Council on Human Blood and Transfusion Services
New York State Department of Health
Wadsworth Center
Empire State Plaza; P.O. Box 509
Albany, New York 12201-0509
2012
New York State Council on Human Blood and Transfusion Services
Blood and Tissue Resources Program
Wadsworth Center
New York State Department of Health
Empire State Plaza; P.O. Box 509
Albany, New York 12201-0509
Phone:
Fax:
E-mail:
(518) 485-5341
(518) 485-5342
[email protected]
For additional information, this and the Council’s other blood services guidelines are available at:
www.wadsworth.org/labcert/blood_tissue
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NEW YORK STATE COUNCIL ON HUMAN BLOOD AND TRANSFUSION SERVICES
Members (2012)
Donna L. Skerrett, M.D., M.S., Chairperson
Chief Medical Officer
Mesoblast Ltd
New York, NY
David Huskie, R.N.
Petersburg, NY
Philip L. McCarthy, M.D.
Clinical Blood and
Marrow Transplant Director
Roswell Park Cancer Institute
Buffalo, NY
Joseph Chiofolo, D.O.
Medical Director, Transfusion Service
Winthrop University Hospital
Mineola, NY
Lazaro Rosales, M.D.
Director, Blood Bank
SUNY Health Science Center
Syracuse, NY
Rachel Elder, M.D.
Director of Laboratory
Crouse Hospital
Syracuse, NY
Nirav R. Shah, M.D., M.P.H.
(Ex-officio)
Commissioner
New York State Department of Health
Albany, New York
Alicia E. Gomensoro, M.D.
Director, Blood Bank
Maimonides Medical Center
Brooklyn, NY
Kathleen Grima, M.D.
Blood Bank Director
The Brooklyn Hospital Center
Downtown Campus
Brooklyn, NY
Jeanne V. Linden, M.D., M.P.H.
Executive Secretary
Director, Blood and Tissue Resources
Wadsworth Center
New York State Department of Health
Albany, New York
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NEW YORK STATE COUNCIL ON HUMAN BLOOD AND TRANSFUSION SERVICES
BLOOD SERVICES COMMITTEE
Members (2012)
Joseph Chiofolo, D.O., Chairperson *
Medical Director, Transfusion Service
Winthrop University Hospital
Mineola, NY
Patricia T. Pisciotto, M.D.
Chief Medical Officer
American Red Cross
Northeast Division Blood Services
Farmington, CT
Visalam Chandrasekaran, M.D.
Associate Professor
School of Health Professions and Nursing
Long Island University
Brookville, NY
Timothy Hilbert, M.D., Ph.D., J.D.
Medical Director, Blood Bank
NYU Langone Medical Center
New York, NY
Helen Richards, M.D.
Blood Bank Director
Harlem Hospital
New York, NY
†
Beth Shaz, M.D.
Chief Medical Officer
New York Blood Center
New York, NY
Joan Uehlinger, M.D.
Director, Blood Bank
Montefiore Medical Center
Bronx, NY
Jeanne V. Linden, M.D., M.P.H. *
Director, Blood and Tissue Resources
Wadsworth Center
New York State Department of Health
Albany, NY
†
Chairperson, Guideline Working Group
* Member, Guideline Working Group
The Council gratefully acknowledges the assistance of the following Wadsworth Center staff member in
preparation of this document:
Danuta Olkowska, M.D.
Associate Director, Blood and Tissue Resources Program
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NEW YORK STATE COUNCIL ON HUMAN BLOOD AND TRANSFUSION SERVICES
GUIDELINES FOR AUTOGENEIC SERUM EYE DROPS
Introduction
Autogeneic serum eye drops (ASEs) may be used to promote corneal re-epithelialization in
cases of severe dry eye or persistent corneal epithelial defects that are unresponsive to
conventional therapy.1 The primary source of the corneal epithelium’s nutrition is natural tears,
but lacrimation may be insufficient to promote epithelialization in severe epithelial disorders.
ASEs without preservatives are non-allergenic, and have biomechanical and biochemical
properties similar to those of natural tears. The pH and osmolarity of serum equal those of
natural tears, and serum contains growth factors, the adhesion factor fibronectin,
immunoglobulins, complement, and vitamins needed for corneal repair.
ASEs have been used to relieve symptoms of dry eye and promote healing in ocular
surface disorders associated with autoimmune conditions, neurotrophic keratides, and
after cornea transplantation or LASIK surgery.
Duration of treatment is variable. Most patients show subjective and/or objective
improvement in one to four weeks and treatment can be tapered. Some erosions may
recur, necessitating resumption of therapy. Patients with severe conditions such as
advanced ocular cicatricial pemphigoid and Stevens-Johnson syndrome may need to
use the eye drops every 15 minutes during waking hours indefinitely.
The number of reported complications is small, but complications are difficult to evaluate
because some may be attributed to the patient’s disease or other concurrently applied
therapies. Microbial contamination is the biggest concern and may lead to microbial
keratitis. Other adverse effects attributed to the use of ASEs include inflammatory
response, eczema, and scleral vasculitis in a patient with rheumatoid arthritis.
Contraindications include elevated bilirubin or protein, active viral or fungal infection, and
certain medications that may injure the cornea.
The clinician will order preparation of ASEs following documented patient informed
consent. Preparation of ASEs from autogeneic whole blood is considered a reinfusion
procedure as defined in 10 NYCRR, Subpart 58-2 (Blood Banks). Hospitals and blood centers
holding a Department permit in Blood Services – Collection or Blood Services – Transfusion
may perform reinfusion procedures under such a permit. Other sites must be approved by the
Department as a Limited Reinfusion Service (LRS). An LRS application packet can be obtained
from the Blood and Tissue Resources Program at (518) 485-5341 or
[email protected].
There must be written protocols for all procedures pertinent to ASEs. Currently there is
no single accepted method of preparation of ASEs and no FDA requirements for establishments
producing or distributing these products. Geerling and colleagues sought to develop a
standardized manufacturing process and, in 2004, following consideration of many factors,
published a detailed protocol.2
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Blood Collection
Microbial contamination is possible during ASE preparation and at point of use.
Precautions should be taken to minimize this risk, including disinfection of the
phlebotomy site using methods generally accepted for collection of blood for transfusion.
Blood should be collected into a sterile blood bag, without anticoagulant, or other
container with a sterile interior and sterile entrance port.
The person drawing the blood should initial or sign the records pertaining to the
collection and attest that the patient identification on the blood and on the pertinent
records is correct.
Testing for infectious disease markers may be required by the collecting or processing
facility.
Preparation
Blood specimens and ASEs must be stored and transported in an appropriate container,
to maintain the required temperature as determined by either the collector or processor.
Eye drop preparation should be carried out using aseptic technique. Maintenance of a
closed system may not be possible during aliquoting of the final product. Passage
through a 0.2µ filter may reduce microbes, but this cannot be relied on to assure sterility.
Dilution of serum (1:4) may be appropriate to decrease the concentration of transforming
growth factor-beta (TGF-beta), which has an inhibitory effect on the epithelialization
process. Diluents may include preservative-free balanced salt solution or saline. Some
practitioners advocate use of an antibiotic as a diluent, but this can cause allergic
reactions.
Labeling
Accurate identification must be in place throughout the process.
All containers that are used in the collection, processing, and/or final packaging must be
properly labeled. Collection and final packaging containers must be labeled with two
forms of identification, one of which must be the patient’s name. The final product label
or labeling materials must also include a description of the contents and the expiration
date, if applicable.
Packaging/Dispensing/Storage
The final product should be packaged into aliquots in sterile screw cap dropper vials.
The ASEs can be stored frozen in a home freezer, then a dropper bottle thawed and
stored at 4°C after opening. Thawing a fresh aliquot each day is preferred. Some
practitioners have advocated storage at 4°C for up to one week or even 30 days.
However, one study demonstrated increasing frequency of microbial contamination after
initially sterile bottles with droppers were stored refrigerated in a residential setting.3 If
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aliquots are to be stored refrigerated for more than one day, the safety of such an
extended shelf-life should be validated.
The shelf-life for frozen storage, based on stability of growth factors in frozen serum, has
been reported to be 3 months.
Patient education and detailed instructions for use and storage are important elements
to reduce microbial contamination at the point of use. Patients may be advised to use
antibiotic eye drops concurrently.
Records
Complete and accurate records of all steps in the process must be created and
maintained.
All pertinent records must be retained for a minimum of seven years.
Quality Management
In hospitals, the collection, processing, and dispensing of ASEs are subject to review by
the Transfusion Committee or hospital Quality Committee. ASE procedures must
comply with written protocols approved by:
o
the director of the transfusion service and the transfusion committee;
o
the director of the hospital department collecting the blood and/or dispensing
ASEs; and
o
the director of the hospital department or facility where processing is performed,
if different.
In blood centers, the collection, processing, and/or dispensing of ASEs are the
responsibility of the director. ASE procedures must comply with written protocols
approved by the director.
In other settings, the collection, processing, and/or dispensing of ASEs, including record
keeping and the reporting of errors and accidents, are the responsibility of the director of
the limited reinfusion service. ASE procedures must comply with written protocols
approved by the director of the limited reinfusion service.
All errors and accidents in collection, testing, preparation, storage or distribution of
autogeneic serum eye drops that may affect the safety or purity of the product, or health
of the recipient, must be reported to the NYS Department of Health with sufficient detail
to facilitate evaluation and investigation, within seven days of occurrence or discovery.
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REFERENCES
1. Yamada C, King KE, Ness PM. Autologous serum eye drops: Literature review and
implications for transfusion medicine specialists. Transfusion 2008;48:1245-55.
2. Geerling G, MacLennan, Hartwig D. Autologous serum eye drops for ocular surface
disorders. Br J Ophthalmol 2004;88:1467-74.
3. Sauer R, Blüthner K, Seitz B. Sterility of non-preserved autologous serum eye drops for
treatment of persistent corneal epithelial defects. Ophthalmologe 2004;101:705-9.
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OTHER PERTINENT LITERATURE
American Academy of Ophthalmology Cornea/External Disease Panel. Preferred practice
pattern®: Dry eye syndrome – limited revision. San Francisco, CA: American Academy of
Ophthalmology, 2011. Available at: www.aao.org/ppp.
Jover Botella A, Márquez Peiró JF, Márques K, et al. Effectiveness of 100% autologous serum
drops in ocular surface disorders. Farm Hosp 2011;35(1):8-13.
Lagnado R, King AJ, Donald F, Dua HS. A protocol for low contamination risk of autologous
serum drops in the management of ocular surface disorders. Br J Ophthalmol 2004;88:464-5.
Liu L, Hartwig D, Harloff S, et al. An optimised protocol for the production of autologous serum
eyedrops. Graefe’s Arch Clin Exp Ophthalmol 2005;243:706-14.
Noble BA, Loh RSK, MacLennan S, et al. Comparison of autologous serum eye drops with
conventional therapy in a randomized controlled crossover trial for ocular surface disease.
Br J Ophthalmol 2004;88:647-52.
Ogawa Y, Okamoto S, Mori T, et al. Autologous serum eye drops for the treatment of severe
dry eye in patients with chronic graft-versus-host disease. Bone Marrow Transplant
2003;31:579-83.
Partal A, Scott E. Low-cost protocol for the production of autologous serum eye drops by blood
collection and processing centres for the treatment of ocular surface diseases. Transfus Med
2011;21(4):271-7.
Reed-Kane D, Carlson RA, Kupiec TC. Applications and sterility of autologous serum eye
drops. Int J Pharm Comp 2009;13:541-3.
Research in dry eye: Report of the Research Subcommittee of the International Dry Eye
Workshop (2007). Ocul Surf 2007;5(2):179-93.
Sanz-Marco E, Lopez-Prats MJ, Garcia-Delpech S, et al. Fulminant bilateral Haemophilus
influenza keratitis in a patient with hypovitaminosis A treated with contaminated autologous
serum. Clin Ophthalmol 2011;5:71-3.
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Schulze SD, Sekundo W, Kroll P. Autologous serum for the treatment of corneal epithelial
abrasions in diabetic patients undergoing vitrectomy. Am J Ophthalmology 2006;142:207-11.
Tananuvat N, Daniell M, Sullivan LJ, et al. Controlled study of the use of autologous serum in
dry eye patients. Cornea 2001;20(8):802-6.
Tsubota K, Goto E, Fujita H, et al. Treatment of dry eye by autologous serum application in
Sjögren’s syndrome. Br J Ophthalmol 1999;83:390-5.
Tsubota K, Goto E, Shimmura S, Shimazaki J. Treatment of persistent corneal epithelial defect
by autologous serum application. Ophthalmology 1999;106:1984-9.
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