Accepted Manuscript Title: Commentary on technical specifications and safety requirements of serum eye drops: keeping a close eye on the content in cytokines Author: Jerard Seghatchian, Aurora Espinosa, Thierry Burnouf PII: DOI: Reference:
S1473-0502(16)00026-4 http://dx.doi.org/doi: 10.1016/j.transci.2016.01.024 TRASCI 1967
To appear in:
Transfusion and Apheresis Science
Please cite this article as: Jerard Seghatchian, Aurora Espinosa, Thierry Burnouf, Commentary on technical specifications and safety requirements of serum eye drops: keeping a close eye on the content in cytokines, Transfusion and Apheresis Science (2016), http://dx.doi.org/doi: 10.1016/j.transci.2016.01.024. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Commentary on technical specifications and safety requirements of serum eye drops: Keeping a close eye on the content in cytokines Jerard Seghatchiana, Aurora Espinosa b, Thierry Burnoufc a
International Consultancy in Blood Components Quality/Safety, Audit/Inspection and DDR Strategies, London, UK b
Department of Immunology and Transfusion Medicine, St. Olav’s University Hospital, Trondheim, Norway c
Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan
Correspondence: [email protected] Keywords: Technical specification of SED; Safety requirements of SED; Cytokines content of SED
Standardisation of the requirements for the production of autologous and allogeneic serum eye drops (SEDs) is needed [1]. In addition to already agreed technical and safety specifications, additional tests should be considered for the production of allogeneic SEDs to avoid potentially the cytokine imbalance, which may contribute to a poorer clinical response.
The use of SEDs was first described by Fox et al. in 1984 [2] and the first in vivo study showing the efficacy of allogeneic SEDs was performed by C-C Chiang et al. [3]. In this study, patients who did not respond to conventional autologous SEDs were treated with allogeneic SEDs produced from the patient’s relative’s serum. One of the contraindications for autologous serum eye drops (SEDs) is their use in patients with autoimmune diseases, due to the presence of inflammatory mediators and/or traces of medications. The authors concluded that the treatment with allogeneic SEDs was a safe alternative option for therapy.
Serum contains a variety of substances such as vitamin A, fibronectin and epidermal growth factors that promote epithelial cell migration and have anti-apoptotic effects [4], thought to be responsible of the healing effects of the SEDs [5].
Page 1 of 3
Patients with autoimmune diseases may have an imbalance between pro-and antiinflammatory cytokines that may affect the outcome of the treatment. This was shown by Hwang et al. [6] in a recent study, where the authors compared the effect of autologous SEDs in patients with primary and secondary Sjögren syndrome (SS). They found that autologous serum eye drops were effective in patients with primary SS, but not in secondary SS. They concluded that the content of pro- and anti-inflammatory cytokines was different in these patients groups, with and increased level of proinflammatory cytokines in patients with secondary SS compared to primary SS.
The importance of the cytokine composition in the serum eye drops was recently shown by Stenwall PA et al. [7]. In their study, the authors measured the content of several cytokines in the serum from healthy allogeneic blood donors. They found that the cytokine composition of the serum may differ, also in healthy blood donors. The authors suggest screening the serum from the allogeneic blood donors for cytokine content to improve the clinical efficacy. As the cytokine measurement before release may be inconvenient and may require trained personnel, surrogate markers for inflammation should be performed in the blood donors.
In view of the current available data on the need for standardisation of the requirements for the production of autologous and allogeneic SEDs, recently highlighted in theme articles on this topic, TRASCI 2015), as well as, the agreement regarding technical and safety specification, some added quality criterion might be pertinent to avoid cytokine imbalance. Clinical trials comparing autologous vs. allogeneic SEDs in the same patient group are warranted.
Page 2 of 3
References: [1] Segatchian J, Espinosa A, Burnouf T. Quality, safety and sustained therapeutic efficacy of blood-derived serum eye drops to treat dry eye syndrome: R&D road map for future progress. Transfus Apher Sci. in press. [2] Fox RI, Chan R, Michelson JB, Belmont JB, Michelson PE. Beneficial effect of artificial tears made with autologous serum in patients with keratoconjunctivitis sicca. Arthritis Rheum. 1984;27:459-61. [3] Chiang CC, Chen WL, Lin JM, Tsai YY. Allogeneic serum eye drops for the treatment of persistent corneal epithelial defect. Eye (Lond). 2009;23:290-3. [4] Semeraro F, Forbice E, Braga O, Bova A, Di Salvatore A, Azzolini C. Evaluation of the efficacy of 50% autologous serum eye drops in different ocular surface pathologies. Biomed Res Int. 2014;2014:826970. [5] Geerling G, Maclennan S, Hartwig D. Autologous serum eye drops for ocular surface disorders. The British journal of ophthalmology. 2004;88:1467-74. [6] Hwang J, Chung SH, Jeon S, Kwok SK, Park SH, Kim MS. Comparison of clinical efficacies of autologous serum eye drops in patients with primary and secondary Sjogren syndrome. Cornea. 2014;33:663-7. [7] Stenwall P-A, Bergström M, Seiron P, Sellberg F, Olsson T, Knutson F, et al. Improving the anti-inflammatory effect of serum eye drops using allogeneic serum permissive for regulatory T cell induction. Acta Ophthalmologica. 2015;93:654-7.
Page 3 of 3
S1473-0502(16)00026-4 http://dx.doi.org/doi: 10.1016/j.transci.2016.01.024 TRASCI 1967
To appear in:
Transfusion and Apheresis Science
Please cite this article as: Jerard Seghatchian, Aurora Espinosa, Thierry Burnouf, Commentary on technical specifications and safety requirements of serum eye drops: keeping a close eye on the content in cytokines, Transfusion and Apheresis Science (2016), http://dx.doi.org/doi: 10.1016/j.transci.2016.01.024. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Commentary on technical specifications and safety requirements of serum eye drops: Keeping a close eye on the content in cytokines Jerard Seghatchiana, Aurora Espinosa b, Thierry Burnoufc a
International Consultancy in Blood Components Quality/Safety, Audit/Inspection and DDR Strategies, London, UK b
Department of Immunology and Transfusion Medicine, St. Olav’s University Hospital, Trondheim, Norway c
Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan
Correspondence: [email protected] Keywords: Technical specification of SED; Safety requirements of SED; Cytokines content of SED
Standardisation of the requirements for the production of autologous and allogeneic serum eye drops (SEDs) is needed [1]. In addition to already agreed technical and safety specifications, additional tests should be considered for the production of allogeneic SEDs to avoid potentially the cytokine imbalance, which may contribute to a poorer clinical response.
The use of SEDs was first described by Fox et al. in 1984 [2] and the first in vivo study showing the efficacy of allogeneic SEDs was performed by C-C Chiang et al. [3]. In this study, patients who did not respond to conventional autologous SEDs were treated with allogeneic SEDs produced from the patient’s relative’s serum. One of the contraindications for autologous serum eye drops (SEDs) is their use in patients with autoimmune diseases, due to the presence of inflammatory mediators and/or traces of medications. The authors concluded that the treatment with allogeneic SEDs was a safe alternative option for therapy.
Serum contains a variety of substances such as vitamin A, fibronectin and epidermal growth factors that promote epithelial cell migration and have anti-apoptotic effects [4], thought to be responsible of the healing effects of the SEDs [5].
Page 1 of 3
Patients with autoimmune diseases may have an imbalance between pro-and antiinflammatory cytokines that may affect the outcome of the treatment. This was shown by Hwang et al. [6] in a recent study, where the authors compared the effect of autologous SEDs in patients with primary and secondary Sjögren syndrome (SS). They found that autologous serum eye drops were effective in patients with primary SS, but not in secondary SS. They concluded that the content of pro- and anti-inflammatory cytokines was different in these patients groups, with and increased level of proinflammatory cytokines in patients with secondary SS compared to primary SS.
The importance of the cytokine composition in the serum eye drops was recently shown by Stenwall PA et al. [7]. In their study, the authors measured the content of several cytokines in the serum from healthy allogeneic blood donors. They found that the cytokine composition of the serum may differ, also in healthy blood donors. The authors suggest screening the serum from the allogeneic blood donors for cytokine content to improve the clinical efficacy. As the cytokine measurement before release may be inconvenient and may require trained personnel, surrogate markers for inflammation should be performed in the blood donors.
In view of the current available data on the need for standardisation of the requirements for the production of autologous and allogeneic SEDs, recently highlighted in theme articles on this topic, TRASCI 2015), as well as, the agreement regarding technical and safety specification, some added quality criterion might be pertinent to avoid cytokine imbalance. Clinical trials comparing autologous vs. allogeneic SEDs in the same patient group are warranted.
Page 2 of 3
References: [1] Segatchian J, Espinosa A, Burnouf T. Quality, safety and sustained therapeutic efficacy of blood-derived serum eye drops to treat dry eye syndrome: R&D road map for future progress. Transfus Apher Sci. in press. [2] Fox RI, Chan R, Michelson JB, Belmont JB, Michelson PE. Beneficial effect of artificial tears made with autologous serum in patients with keratoconjunctivitis sicca. Arthritis Rheum. 1984;27:459-61. [3] Chiang CC, Chen WL, Lin JM, Tsai YY. Allogeneic serum eye drops for the treatment of persistent corneal epithelial defect. Eye (Lond). 2009;23:290-3. [4] Semeraro F, Forbice E, Braga O, Bova A, Di Salvatore A, Azzolini C. Evaluation of the efficacy of 50% autologous serum eye drops in different ocular surface pathologies. Biomed Res Int. 2014;2014:826970. [5] Geerling G, Maclennan S, Hartwig D. Autologous serum eye drops for ocular surface disorders. The British journal of ophthalmology. 2004;88:1467-74. [6] Hwang J, Chung SH, Jeon S, Kwok SK, Park SH, Kim MS. Comparison of clinical efficacies of autologous serum eye drops in patients with primary and secondary Sjogren syndrome. Cornea. 2014;33:663-7. [7] Stenwall P-A, Bergström M, Seiron P, Sellberg F, Olsson T, Knutson F, et al. Improving the anti-inflammatory effect of serum eye drops using allogeneic serum permissive for regulatory T cell induction. Acta Ophthalmologica. 2015;93:654-7.
Page 3 of 3
