Blood-Based Treatments for Severe Dry Eye Disease: The Need of a Consensus
Abstract
:1. Introduction
2. The Rationale for Use of Blood-Derived Eye Drops
3. Literature Review
3.1. Search Strategy
3.2. Study Selection
3.3. Eligibility Criteria
3.4. Data Extraction
3.5. Quality Assessment
4. Autologous Serum Eye Drops
4.1. Pending Issues
4.1.1. Dilution
4.1.2. Storage
4.1.3. Safety
4.2. Clinical Results
5. Allogeneic Adult Peripheral Blood Serum Eye Drops
Clinical Results
6. Allogeneic Umbilical Cord Blood Serum Eye Drops
Clinical Results
7. Platelet Derived Eye Drops
7.1. Preparations
7.2. Clinical Results
8. Data Analysis and Criticism
9. Conclusions
Author Contributions
Conflicts of Interest
References
- Craig, J.P.; Nichols, K.K.; Akpek, E.K.; Caffery, B.; Dua, H.S.; Joo, C.K.; Liu, Z.; Nelson, J.D.; Nichols, J.J.; Tsubota, K.; et al. TFOS DEWS II definition and classification report. Ocul. Surf. 2017, 15, 276–283. [Google Scholar] [CrossRef] [PubMed]
- Stapleton, F.; Alves, M.; Bunya, V.Y.; Jalbert, I.; Lekhanont, K.; Malet, F.; Na, K.S.; Schaumberg, D.; Uchino, M.; Vehof, J.; et al. TFOS DEWS II epidemiology report. Ocul. Surf. 2017, 15, 334–365. [Google Scholar] [CrossRef] [PubMed]
- Craig, J.P.; Nelson, J.D.; Azar, D.T.; Belmonte, C.; Bron, A.J.; Chauhan, S.K.; de Paiva, C.S.; Gomes, J.A.P.; Hammitt, K.M.; Jones, L.; et al. TFOS DEWS II report executive summary. Ocul. Surf. 2017, 15, 802–812. [Google Scholar] [CrossRef] [PubMed]
- Benítez-Del-Castillo, J.; Labetoulle, M.; Baudouin, C.; Rolando, M.; Akova, Y.A.; Aragona, P.; Geerling, G.; Merayo-Lloves, J.; Messmer, E.M.; Boboridis, K. Visual acuity and quality of life in dry eye disease: Proceedings of the OCEAN group meeting. Ocul. Surf. 2017, 15, 169–178. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jones, L.; Downie, L.E.; Korb, D.; Benitez-Del-Castillo, J.M.; Dana, R.; Deng, S.X.; Dong, P.N.; Geerling, G.; Hida, R.Y.; Liu, Y.; et al. TFOS DEWS II management and therapy report. Ocul. Surf. 2017, 15, 575–628. [Google Scholar] [CrossRef] [PubMed]
- Ralph, R.A.; Doane, M.G.; Dohlman, C.H. Clinical experience with a mobile ocular perfusion pump. Arch. Ophthalmol. 1975, 93, 1039–1043. [Google Scholar] [CrossRef] [PubMed]
- Fox, R.I.; Chan, R.; Michelson, J.B.; Belmont, J.B.; Michelson, P.E. Beneficial effect of artificial tears made with autologous serum in patients with keratoconjunctivitis sicca. Arthritis Rheum. 1984, 27, 459–461. [Google Scholar] [CrossRef] [PubMed]
- Soni, N.G.; Jeng, B.H. Blood-derived topical therapy for ocular surface diseases. Br. J. Ophthalmol. 2016, 100, 22–27. [Google Scholar] [CrossRef]
- Giannaccare, G.; Versura, P.; Buzzi, M.; Primavera, L.; Pellegrini, M.; Campos, E.C. Blood derived eye drops for the treatment of cornea and ocular surface diseases. Transfus. Apher. Sci. 2017, 56, 595–604. [Google Scholar] [CrossRef]
- Kojima, T.; Higuchi, A.; Goto, E.; Matsumoto, Y.; Dogru, M.; Tsubota, K. Autologous serum eye drops for the treatment of dry eye diseases. Cornea 2008, 27, S25–S30. [Google Scholar] [CrossRef]
- Tsubota, K.; Goto, E.; Shimmura, S.; Shimazaki, J. Treatment of persistent corneal epithelial defect by autologous serum application. Ophthalmology 1999, 106, 1984–1989. [Google Scholar] [CrossRef]
- Freire, V.; Andollo, N.; Etxebarria, J.; Durán, J.A.; Morales, M.-C. In vitro effects of three blood derivatives on human corneal epithelial cells. Invest. Ophthalmol. Vis. Sci. 2012, 53, 5571–5578. [Google Scholar] [CrossRef] [PubMed]
- Liu, L.; Hartwig, D.; Harloff, S.; Herminghaus, P.; Wedel, T.; Kasper, K.; Geerling, G. Corneal epitheliotrophic capacity of three different blood-derived preparations. Invest. Ophthalmol. Vis. Sci. 2006, 47, 2438–2444. [Google Scholar] [CrossRef] [PubMed]
- Huang, C.-J.; Sun, Y.-C.; Christopher, K.; Pai, A.S.-I.; Lu, C.-J.; Hu, F.-R.; Lin, S.-Y.; Chen, W.-L. Comparison of corneal epitheliotrophic capacities among human platelet lysates and other blood derivatives. PLoS ONE 2017, 12, e0171008. [Google Scholar] [CrossRef] [PubMed]
- Gipson, I.K. The ocular surface: The challenge to enable and protect vision: The Friedenwald lecture. Invest. Ophthalmol. Vis. Sci. 2007, 48, 4391–4398. [Google Scholar] [CrossRef] [PubMed]
- Funderburgh, J.L.; Funderburgh, M.L.; Du, Y. Stem cells in the limbal stroma. Ocul. Surf. 2016, 14, 113–120. [Google Scholar] [CrossRef] [PubMed]
- Geerling, G.; Maclennan, S.; Hartwig, D. Autologous serum eye drops for ocular surface disorders. Br. J. Ophthalmol. 2004, 88, 1467–1474. [Google Scholar] [CrossRef] [Green Version]
- Higuchi, A. Autologous serum and serum components. Invest. Ophthalmol. Vis. Sci. 2018, 59, DES121–DES129. [Google Scholar] [CrossRef]
- Drew, V.J.; Tseng, C.-L.; Seghatchian, J.; Burnouf, T. Reflections on dry eye syndrome treatment: Therapeutic role of blood products. Front. Med. 2018, 5, 33. [Google Scholar] [CrossRef]
- Klenkler, B.; Sheardown, H.; Jones, L. Growth factors in the tear film: Role in tissue maintenance, wound healing, and ocular pathology. Ocul. Surf. 2007, 5, 228–239. [Google Scholar] [CrossRef]
- Mandić, J.J.; Kozmar, A.; Kusačić-Kuna, S.; Jazbec, A.; Mandić, K.; Mrazovac, D.; Vukojević, N. The levels of 12 cytokines and growth factors in tears: Hyperthyreosis vs euthyreosis. Graefes Arch. Clin. Exp. Ophthalmol. 2018, 256, 845–852. [Google Scholar] [CrossRef] [PubMed]
- Nurden, A.T. The biology of the platelet with special reference to inflammation, wound healing and immunity. Front. Biosci. 2018, 23, 726–751. [Google Scholar] [CrossRef]
- Imanishi, J.; Kamiyama, K.; Iguchi, I.; Kita, M.; Sotozono, C.; Kinoshita, S. Growth factors: Importance in wound healing and maintenance of transparency of the cornea. Prog. Retin. Eye Res. 2000, 19, 113–129. [Google Scholar] [CrossRef]
- Trosan, P.; Svobodova, E.; Chudickova, M.; Krulova, M.; Zajicova, A.; Holan, V. The key role of insulin-like growth factor I in limbal stem cell differentiation and the corneal wound-healing process. Stem Cells Dev. 2012, 21, 3341–3350. [Google Scholar] [CrossRef] [PubMed]
- Ljubimov, A.V.; Saghizadeh, M. Progress in corneal wound healing. Prog. Retin. Eye Res. 2015, 49, 17–45. [Google Scholar] [CrossRef] [PubMed]
- Liu, C.-Y.; Kao, W.W.-Y. Corneal epithelial wound healing. Prog. Mol. Biol. Transl. Sci. 2015, 134, 61–71. [Google Scholar] [PubMed]
- Hongo, M.; Itoi, M.; Yamaguchi, N.; Imanishi, J. Distribution of epidermal growth factor (EGF) receptors in rabbit corneal epithelial cells, keratocytes and endothelial cells, and the changes induced by transforming growth factor-β1. Exp. Eye Res. 1992, 54, 9–16. [Google Scholar] [CrossRef]
- Aprili, G.; Gandini, G.; Guaschino, R.; Mazzucco, L.; Salvaneschi, L.; Vaglio, S. SIMTI recommendations on blood components for non-transfusional use. Blood Transfus. 2013, 11, 611–622. [Google Scholar]
- About Preferred Practice Patterns (PPPs)—American Academy of Ophthalmology. Available online: https://www.aao.org/about-preferred-practice-patterns (accessed on 2 August 2019).
- Marks, D.C.; van der Meer, P.F. Biomedical Excellence for Safer Transfusion (BEST) collaborative serum eye drops: A survey of international production methods. Vox Sang. 2017, 112, 310–317. [Google Scholar] [CrossRef]
- Liu, L.; Hartwig, D.; Harloff, S.; Herminghaus, P.; Wedel, T.; Geerling, G. An optimised protocol for the production of autologous serum eyedrops. Graefes Arch. Clin. Exp. Ophthalmol. 2005, 243, 706–714. [Google Scholar] [CrossRef]
- Pancholi, S.; Tullo, A.; Khaliq, A.; Foreman, D.; Boulton, M. The effects of growth factors and conditioned media on the proliferation of human corneal epithelial cells and keratocytes. Graefes Arch. Clin. Exp. Ophthalmol. 1998, 236, 1–8. [Google Scholar] [CrossRef]
- Torricelli, A.A.M.; Santhanam, A.; Wu, J.; Singh, V.; Wilson, S.E. The corneal fibrosis response to epithelial-stromal injury. Exp. Eye Res. 2016, 142, 110–118. [Google Scholar] [CrossRef] [PubMed]
- Pan, Q.; Angelina, A.; Marrone, M.; Stark, W.J.; Akpek, E.K. Autologous serum eye drops for dry eye. Cochrane Database Syst. Rev. 2017, 2, CD009327. [Google Scholar] [CrossRef] [PubMed]
- Jeng, B.H.; Dupps, W.J. Autologous serum 50% eyedrops in the treatment of persistent corneal epithelial defects. Cornea 2009, 28, 1104–1108. [Google Scholar] [CrossRef] [PubMed]
- Lekhanont, K.; Jongkhajornpong, P.; Anothaisintawee, T.; Chuckpaiwong, V. Undiluted serum eye drops for the treatment of persistent corneal epitheilal defects. Sci. Rep. 2016, 6, 38143. [Google Scholar] [CrossRef] [PubMed]
- Cho, Y.K.; Huang, W.; Kim, G.Y.; Lim, B.S. Comparison of autologous serum eye drops with different diluents. Curr. Eye Res. 2013, 38, 9–17. [Google Scholar] [CrossRef]
- Hussain, M.; Shtein, R.M.; Sugar, A.; Soong, H.K.; Woodward, M.A.; DeLoss, K.; Mian, S.I. Long-term use of autologous serum 50% eye drops for the treatment of dry eye disease. Cornea 2014, 33, 1245–1251. [Google Scholar] [CrossRef]
- López-García, J.S.; García-Lozano, I.; Rivas, L.; Ramírez, N.; Raposo, R.; Méndez, M.T. Autologous serum eye drops diluted with sodium hyaluronate: Clinical and experimental comparative study. Acta Ophthalmol. 2014, 92, e22–e29. [Google Scholar] [CrossRef]
- Bradley, J.C.; Simoni, J.; Bradley, R.H.; McCartney, D.L.; Brown, S.M. Time-and temperature-dependent stability of growth factor peptides in human autologous serum eye drops. Cornea 2009, 28, 200–205. [Google Scholar] [CrossRef]
- Tsubota, K.; Goto, E.; Fujita, H.; Ono, M.; Inoue, H.; Saito, I.; Shimmura, S. Treatment of dry eye by autologous serum application in Sjögren’s syndrome. Br. J. Ophthalmol. 1999, 83, 390–395. [Google Scholar] [CrossRef]
- Fischer, K.R.; Opitz, A.; Böeck, M.; Geerling, G. Stability of serum eye drops after storage of 6 months. Cornea 2012, 31, 1313–1318. [Google Scholar] [CrossRef] [PubMed]
- WHO. Expert Committee on Specifications for Pharmaceutical Preparations; World Health Organization: Geneva, Switzerland, 2011; pp. 1–428. [Google Scholar]
- Marchand, M.; Harissi-Dagher, M.; Germain, M.; Thompson, P.; Robert, M.-C. Serum drops for ocular surface disease: National survey of Canadian cornea specialists. Can. J. Ophthalmol. 2018, 53, 266–271. [Google Scholar] [CrossRef] [PubMed]
- Tahmaz, V.; Gehlsen, U.; Sauerbier, L.; Holtick, U.; Engel, L.; Radojska, S.; Petrescu-Jipa, V.-M.; Scheid, C.; Hallek, M.; Gathof, B.; et al. Treatment of severe chronic ocular graft-versus-host disease using 100% autologous serum eye drops from a sealed manufacturing system: A retrospective cohort study. Br. J. Ophthalmol. 2017, 101, 322–326. [Google Scholar] [CrossRef] [PubMed]
- Versura, P.; Profazio, V.; Buzzi, M.; Stancari, A.; Arpinati, M.; Malavolta, N.; Campos, E.C. Efficacy of standardized and quality-controlled cord blood serum eye drop therapy in the healing of severe corneal epithelial damage in dry eye. Cornea 2013, 32, 412–418. [Google Scholar] [CrossRef] [PubMed]
- Marks, D.C.; Fisher, J.; Mondy, P.; Segatchian, J.; Dennington, P.M. Serum eye drop preparation in Australia: Current manufacturing practice. Transfus. Apher. Sci. 2015, 53, 92–94. [Google Scholar] [CrossRef] [PubMed]
- Spaniol, K.; Koerschgen, L.; Sander, O.; Koegler, G.; Geerling, G. Comparison of application systems for autologous serum eye drops. Curr. Eye Res. 2014, 39, 571–579. [Google Scholar] [CrossRef] [PubMed]
- Tananuvat, N.; Daniell, M.; Sullivan, L.J.; Yi, Q.; McKelvie, P.; McCarty, D.J.; Taylor, H.R. Controlled study of the use of autologous serum in dry eye patients. Cornea 2001, 20, 802–806. [Google Scholar] [CrossRef] [PubMed]
- Noble, B.A.; Loh, R.S.K.; MacLennan, S.; Pesudovs, K.; Reynolds, A.; Bridges, L.R.; Burr, J.; Stewart, O.; Quereshi, S. Comparison of autologous serum eye drops with conventional therapy in a randomised controlled crossover trial for ocular surface disease. Br. J. Ophthalmol. 2004, 88, 647–652. [Google Scholar] [CrossRef] [PubMed]
- Kojima, T.; Ishida, R.; Dogru, M.; Goto, E.; Matsumoto, Y.; Kaido, M.; Tsubota, K. The effect of autologous serum eyedrops in the treatment of severe dry eye disease: A prospective randomized case-control study. Am. J. Ophthalmol. 2005, 139, 242–246. [Google Scholar] [CrossRef]
- Urzua, C.A.; Vasquez, D.H.; Huidobro, A.; Hernandez, H.; Alfaro, J. Randomized double-blind clinical trial of autologous serum versus artificial tears in dry eye syndrome. Curr. Eye Res. 2012, 37, 684–688. [Google Scholar] [CrossRef]
- Celebi, A.R.C.; Ulusoy, C.; Mirza, G.E. The efficacy of autologous serum eye drops for severe dry eye syndrome: A randomized double-blind crossover study. Graefes Arch. Clin. Exp. Ophthalmol. 2014, 252, 619–626. [Google Scholar] [CrossRef] [PubMed]
- Yılmaz, U.; Küçük, E.; Koç, Ç.; Gökler, E. Comparison of autologous serum versus preservative free artificial tear in patients with dry eyes due to systemic isotretinoin therapy. Curr. Eye Res. 2017, 42, 827–831. [Google Scholar] [CrossRef] [PubMed]
- Ogawa, Y.; Okamoto, S.; Mori, T.; Yamada, M.; Mashima, Y.; Watanabe, R.; Kuwana, M.; Tsubota, K.; Ikeda, Y.; Oguchi, Y. Autologous serum eye drops for the treatment of severe dry eye in patients with chronic graft-versus-host disease. Bone Marrow Transpl. 2003, 31, 579–583. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hwang, J.; Chung, S.-H.; Jeon, S.; Kwok, S.-K.; Park, S.-H.; Kim, M.-S. Comparison of clinical efficacies of autologous serum eye drops in patients with primary and secondary Sjögren syndrome. Cornea 2014, 33, 663–667. [Google Scholar] [CrossRef] [PubMed]
- Semeraro, F.; Forbice, E.; Nascimbeni, G.; Taglietti, M.; Romano, V.; Guerra, G.; Costagliola, C. Effect of autologous serum eye drops in patients with Sjögren syndrome-related dry eye: Clinical and in vivo confocal microscopy evaluation of the ocular surface. In Vivo 2016, 30, 931–938. [Google Scholar] [CrossRef] [PubMed]
- Jirsova, K.; Brejchova, K.; Krabcova, I.; Filipec, M.; Al Fakih, A.; Palos, M.; Vesela, V. The application of autologous serum eye drops in severe dry eye patients; subjective and objective parameters before and after treatment. Curr. Eye Res. 2014, 39, 21–30. [Google Scholar] [CrossRef] [PubMed]
- Matsumoto, Y.; Dogru, M.; Goto, E.; Ohashi, Y.; Kojima, T.; Ishida, R.; Tsubota, K. Autologous serum application in the treatment of neurotrophic keratopathy. Ophthalmology 2004, 111, 1115–1120. [Google Scholar] [CrossRef] [PubMed]
- Noda-Tsuruya, T.; Asano-Kato, N.; Toda, I.; Tsubota, K. Autologous serum eye drops for dry eye after LASIK. J. Refract. Surg. 2006, 22, 61–66. [Google Scholar] [CrossRef] [PubMed]
- Schulze, S.D.; Sekundo, W.; Kroll, P. Autologous serum for the treatment of corneal epithelial abrasions in diabetic patients undergoing vitrectomy. Am. J. Ophthalmol. 2006, 142, 207–211. [Google Scholar] [CrossRef] [PubMed]
- Ziakas, N.G.; Boboridis, K.G.; Terzidou, C.; Naoumidi, T.L.; Mikropoulos, D.; Georgiadou, E.N.; Georgiadis, N.S. Long-term follow up of autologous serum treatment for recurrent corneal erosions. Clin. Exp. Ophthalmol. 2010, 38, 683–687. [Google Scholar] [CrossRef]
- Lekhanont, K.; Jongkhajornpong, P.; Choubtum, L.; Chuckpaiwong, V. Topical 100% serum eye drops for treating corneal epithelial defect after ocular surgery. Biomed. Res. Int. 2013, 2013, 521315. [Google Scholar] [CrossRef] [PubMed]
- Sul, S.; Korkmaz, S.; Alacamli, G.; Ozyol, P.; Ozyol, E. Application of autologous serum eye drops after pterygium surgery: A prospective study. Graefes Arch. Clin. Exp. Ophthalmol. 2018, 256, 1939–1943. [Google Scholar] [CrossRef] [PubMed]
- Chen, Y.-M.; Hu, F.-R.; Huang, J.-Y.; Shen, E.P.; Tsai, T.-Y.; Chen, W.-L. The effect of topical autologous serum on graft re-epithelialization after penetrating keratoplasty. Am. J. Ophthalmol. 2010, 150, 352–359.e2. [Google Scholar] [CrossRef] [PubMed]
- López-García, J.S.; Rivas, L.; García-Lozano, I.; Murube, J. Autologous serum eyedrops in the treatment of aniridic keratopathy. Ophthalmology 2008, 115, 262–267. [Google Scholar] [CrossRef] [PubMed]
- Espinosa, A.; Hjorth-Hansen, H.; Aasly, K.; Teigum, I.; Sivertsen, G.; Seghatchian, J. Implementation of a standardised method for the production of allogeneic serum eye drops from regular blood donors in a Norwegian University Hospital: Some methodological aspects and clinical considerations. Transfus. Apher. Sci. 2015, 53, 88–91. [Google Scholar] [CrossRef] [PubMed]
- Badami, K.G.; McKellar, M. Allogeneic serum eye drops: Time these became the norm? Br. J. Ophthalmol. 2012, 96, 1151–1152. [Google Scholar] [CrossRef]
- Chiang, C.-C.; Chen, W.-L.; Lin, J.-M.; Tsai, Y.-Y. Allogeneic serum eye drops for the treatment of persistent corneal epithelial defect. Eye 2009, 23, 290–293. [Google Scholar] [CrossRef]
- Chiang, C.-C.; Lin, J.-M.; Chen, W.-L.; Tsai, Y.-Y. Allogeneic serum eye drops for the treatment of severe dry eye in patients with chronic graft-versus-host disease. Cornea 2007, 26, 861–863. [Google Scholar] [CrossRef]
- Harritshøj, L.H.; Nielsen, C.; Ullum, H.; Hansen, M.B.; Julian, H.O. Ready-made allogeneic ABO-specific serum eye drops: Production from regular male blood donors, clinical routine, safety and efficacy. Acta Ophthalmol. 2014, 92, 783–786. [Google Scholar] [CrossRef]
- Na, K.-S.; Kim, M.S. Allogeneic serum eye drops for the treatment of dry eye patients with chronic graft-versus-host disease. J. Ocul. Pharmacol. Ther. 2012, 28, 479–483. [Google Scholar] [CrossRef]
- Anitua, E.; de la Fuente, M.; Merayo-Lloves, J.; Muruzabal, F.; Orive, G. Allogeneic blood-based therapies: Hype or hope? Eye 2017, 31, 509–510. [Google Scholar] [CrossRef] [PubMed]
- Hung, Y.; Elder, M.J.; Rawstron, J.A.; Badami, K.G. A retrospective crossover study of autologous and allogeneic serum eye drops for the management of ocular surface disease. Transfus. Med. 2019, 29, 69–71. [Google Scholar] [CrossRef]
- Van der Meer, P.F.; Seghatchian, J.; de Korte, D. Autologous and allogeneic serum eye drops. The Dutch perspective. Transfus. Apher. Sci. 2015, 53, 99–100. [Google Scholar] [CrossRef] [PubMed]
- Stenwall, P.-A.; Bergström, M.; Seiron, P.; Sellberg, F.; Olsson, T.; Knutson, F.; Berglund, D. Improving the anti-inflammatory effect of serum eye drops using allogeneic serum permissive for regulatory T cell induction. Acta Ophthalmol. 2015, 93, 654–657. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kang, N.H.; Lee, S.; Jun, R.M. Comparison of epitheliotrophic factors in autologous serum eyedrops from sera of chronic renal failure patients vs. normal controls. Graefes Arch. Clin. Exp. Ophthalmol. 2015, 253, 1705–1712. [Google Scholar] [CrossRef] [PubMed]
- Harloff, S.; Hartwig, D.; Kasper, K.; Wedel, T.; Müller, M.; Geerling, G. Epitheliotrophic capacity of serum eye drops from healthy donors versus serum from immunosuppressed patients with rheumatoid arthritis. Klin. Monbl. Augenheilkd. 2008, 225, 200–206. [Google Scholar] [CrossRef]
- WHO. Expert Committee on Biological Standardization; World Health Organization: Geneva, Switzerland, 2007; pp. 1–340. [Google Scholar]
- Scharman, C.D.; Burger, D.; Shatzel, J.J.; Kim, E.; DeLoughery, T.G. Treatment of individuals who cannot receive blood products for religious or other reasons. Am. J. Hematol. 2017, 92, 1370–1381. [Google Scholar] [CrossRef] [Green Version]
- Giannaccare, G.; Pellegrini, M.; Bernabei, F.; Moscardelli, F.; Buzzi, M.; Versura, P.; Campos, E.C. In vivo confocal microscopy automated morphometric analysis of corneal subbasal nerve plexus in patients with dry eye treated with different sources of homologous serum eye drops. Cornea 2019. [Google Scholar] [CrossRef]
- Yoon, K.-C.; Im, S.-K.; Park, Y.-G.; Jung, Y.-D.; Yang, S.-Y.; Choi, J. Application of umbilical cord serum eyedrops for the treatment of dry eye syndrome. Cornea 2006, 25, 268–272. [Google Scholar] [CrossRef]
- Versura, P.; Buzzi, M.; Giannaccare, G.; Terzi, A.; Fresina, M.; Velati, C.; Campos, E.C. Targeting growth factor supply in keratopathy treatment: Comparison between maternal peripheral blood and cord blood as sources for the preparation of topical eye drops. Blood Transfus. 2016, 14, 145–151. [Google Scholar]
- Buzzi, M.; Versura, P.; Grigolo, B.; Cavallo, C.; Terzi, A.; Pellegrini, M.; Giannaccare, G.; Randi, V.; Campos, E.C. Comparison of growth factor and interleukin content of adult peripheral blood and cord blood serum eye drops for cornea and ocular surface diseases. Transfus. Apher. Sci. 2018, 57, 549–555. [Google Scholar] [CrossRef] [PubMed]
- Versura, P.; Buzzi, M.; Giannaccare, G.; Grillini, M.; Terzi, A.; Pagliaro, P.; Campos, E.C. Cord blood serum-based eye drops; the impact of donor haematological and obstetric factors on the variability of epidermal growth factor levels. Blood Transfus. 2014, 12 (Suppl. S1), 44–50. [Google Scholar]
- Giannaccare, G.; Buzzi, M.; Fresina, M.; Velati, C.; Versura, P. Efficacy of 2-month treatment with cord blood serum eye drops in ocular surface disease: An in vivo confocal microscopy study. Cornea 2017, 36, 915–921. [Google Scholar] [CrossRef] [PubMed]
- Erdem, E.; Yagmur, M.; Harbiyeli, I.; Taylan-Sekeroglu, H.; Ersoz, R. Umbilical cord blood serum therapy for the management of persistent corneal epithelial defects. Int. J. Ophthalmol. 2014, 7, 807–810. [Google Scholar] [Green Version]
- Vajpayee, R.B.; Mukerji, N.; Tandon, R.; Sharma, N.; Pandey, R.M.; Biswas, N.R.; Malhotra, N.; Melki, S.A. Evaluation of umbilical cord serum therapy for persistent corneal epithelial defects. Br. J. Ophthalmol. 2003, 87, 1312–1316. [Google Scholar] [CrossRef] [Green Version]
- Yoon, K.-C.; Heo, H.; Jeong, I.-Y.; Park, Y.-G. Therapeutic effect of umbilical cord serum eyedrops for persistent corneal epithelial defect. Korean J. Ophthalmol. 2005, 19, 174–178. [Google Scholar] [CrossRef]
- Yoon, K.-C.; Heo, H.; Im, S.-K.; You, I.-C.; Kim, Y.-H.; Park, Y.-G. Comparison of autologous serum and umbilical cord serum eye drops for dry eye syndrome. Am. J. Ophthalmol. 2007, 144, 86–92. [Google Scholar] [CrossRef]
- Sharma, N.; Goel, M.; Velpandian, T.; Titiyal, J.S.; Tandon, R.; Vajpayee, R.B. Evaluation of umbilical cord serum therapy in acute ocular chemical burns. Invest. Ophthalmol. Vis. Sci. 2011, 52, 1087–1092. [Google Scholar] [CrossRef]
- Sharma, N.; Singh, D.; Maharana, P.K.; Kriplani, A.; Velpandian, T.; Pandey, R.M.; Vajpayee, R.B. Comparison of amniotic membrane transplantation and umbilical cord serum in acute ocular chemical burns: A randomized controlled trial. Am. J. Ophthalmol. 2016, 168, 157–163. [Google Scholar] [CrossRef]
- Yoon, K.C.; Jeong, I.Y.; Im, S.K.; Park, Y.G.; Kim, H.J.; Choi, J. Therapeutic effect of umbilical cord serum eyedrops for the treatment of dry eye associated with graft-versus-host disease. Bone Marrow Transpl. 2007, 39, 231–235. [Google Scholar] [CrossRef] [Green Version]
- Yoon, K.-C.; Choi, W.; You, I.-C.; Choi, J. Application of umbilical cord serum eyedrops for recurrent corneal erosions. Cornea 2011, 30, 744–748. [Google Scholar] [CrossRef]
- Kamble, N.; Sharma, N.; Maharana, P.K.; Bandivadekar, P.; Nagpal, R.; Agarwal, T.; Velpandian, T.; Mittal, S.; Vajpayee, R.B. Evaluation of the role of umbilical cord serum and autologous serum therapy in reepithelialization after keratoplasty: A randomized controlled clinical trial. Eye Contact Lens 2017, 43, 324–329. [Google Scholar] [CrossRef] [PubMed]
- Yoon, K.-C.; Oh, H.-J.; Park, J.-W.; Choi, J. Application of umbilical cord serum eyedrops after laser epithelial keratomileusis. Acta Ophthalmol. 2013, 91, e22–e28. [Google Scholar] [CrossRef] [PubMed]
- Mukhopadhyay, S.; Sen, S.; Datta, H. Comparative role of 20% cord blood serum and 20% autologous serum in dry eye associated with Hansen’s disease: A tear proteomic study. Br. J. Ophthalmol. 2015, 99, 108–112. [Google Scholar] [CrossRef] [PubMed]
- Yoon, K.-C.; You, I.-C.; Im, S.-K.; Jeong, T.-S.; Park, Y.-G.; Choi, J. Application of umbilical cord serum eyedrops for the treatment of neurotrophic keratitis. Ophthalmology 2007, 114, 1637–1642. [Google Scholar] [CrossRef] [PubMed]
- Versura, P.; Giannaccare, G.; Pellegrini, M.; Sebastiani, S.; Campos, E.C. Neurotrophic keratitis: Current challenges and future prospects. Eye Brain 2018, 10, 37–45. [Google Scholar] [CrossRef] [PubMed]
- Lubkowska, A.; Dolegowska, B.; Banfi, G. Growth factor content in PRP and their applicability in medicine. J. Biol. Regul. Homeost. Agents 2012, 26, 3S–22S. [Google Scholar] [PubMed]
- Alio, J.L.; Arnalich-Montiel, F.; Rodriguez, A.E. The role of “eye platelet rich plasma” (E-PRP) for wound healing in ophthalmology. Curr. Pharm. Biotechnol. 2012, 13, 1257–1265. [Google Scholar] [CrossRef]
- Sanchez-Avila, R.M.; Merayo-Lloves, J.; Riestra, A.C.; Anitua, E.; Muruzabal, F.; Orive, G.; Fernández-Vega, L. The effect of immunologically safe plasma rich in growth factor eye drops in patients with Sjögren syndrome. J. Ocul. Pharm. 2017, 33, 391–399. [Google Scholar] [CrossRef] [PubMed]
- Pezzotta, S.; Del Fante, C.; Scudeller, L.; Rossi, G.C.; Perotti, C.; Bianchi, P.E.; Antoniazzi, E. Long-term safety and efficacy of autologous platelet lysate drops for treatment of ocular GvHD. Bone Marrow Transpl. 2017, 52, 101–106. [Google Scholar] [CrossRef] [PubMed]
- Zallio, F.; Mazzucco, L.; Monaco, F.; Astori, M.R.; Passera, R.; Drago, G.; Tamiazzo, S.; Rapetti, M.; Dolcino, D.; Guaschino, R.; et al. A single-center pilot prospective study of topical application of platelet-derived eye drops for patients with ocular chronic graft-versus-host disease. Biol. Blood Marrow Transpl. 2016, 22, 1664–1670. [Google Scholar] [CrossRef] [PubMed]
- Alio, J.L.; Colecha, J.R.; Pastor, S.; Rodriguez, A.; Artola, A. Symptomatic dry eye treatment with autologous platelet-rich plasma. Ophthalmic Res. 2007, 39, 124–129. [Google Scholar] [CrossRef] [PubMed]
- Alio, J.L.; Pastor, S.; Ruiz-Colecha, J.; Rodriguez, A.; Artola, A. Treatment of ocular surface syndrome after LASIK with autologous platelet-rich plasma. J. Refract. Surg. 2007, 23, 617–619. [Google Scholar] [CrossRef] [PubMed]
- Alio, J.L.; Abad, M.; Artola, A.; Rodriguez-Prats, J.L.; Pastor, S.; Ruiz-Colecha, J. Use of autologous platelet-rich plasma in the treatment of dormant corneal ulcers. Ophthalmology 2007, 114, 1286–1293.e1. [Google Scholar] [CrossRef] [PubMed]
- López-Plandolit, S.; Morales, M.-C.; Freire, V.; Etxebarría, J.; Durán, J.A. Plasma rich in growth factors as a therapeutic agent for persistent corneal epithelial defects. Cornea 2010, 29, 843–848. [Google Scholar] [CrossRef] [PubMed]
- Pezzotta, S.; Del Fante, C.; Scudeller, L.; Cervio, M.; Antoniazzi, E.R.; Perotti, C. Autologous platelet lysate for treatment of refractory ocular GVHD. Bone Marrow Transpl. 2012, 47, 1558–1563. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, K.M.; Shin, Y.-T.; Kim, H.K. Effect of autologous platelet-rich plasma on persistent corneal epithelial defect after infectious keratitis. Jpn. J. Ophthalmol. 2012, 56, 544–550. [Google Scholar] [CrossRef]
- Panda, A.; Jain, M.; Vanathi, M.; Velpandian, T.; Khokhar, S.; Dada, T. Topical autologous platelet-rich plasma eyedrops for acute corneal chemical injury. Cornea 2012, 31, 989–993. [Google Scholar] [CrossRef]
- Fea, A.M.; Aragno, V.; Testa, V.; Machetta, F.; Parisi, S.; D’Antico, S.; Spinetta, R.; Fusaro, E.; Grignolo, F.M. The effect of autologous platelet lysate eye drops: An in vivo confocal microscopy study. Biomed. Res. Int. 2016, 2016, 8406832. [Google Scholar] [CrossRef]
- Lee, J.H.; Kim, M.J.; Ha, S.W.; Kim, H.K. Autologous platelet-rich plasma eye drops in the treatment of recurrent corneal erosions. Korean J. Ophthalmol. 2016, 30, 101–107. [Google Scholar] [CrossRef]
- Merayo-Lloves, J.; Sanchez-Avila, R.M.; Riestra, A.C.; Anitua, E.; Begoña, L.; Orive, G.; Fernandez-Vega, L. Safety and efficacy of autologous plasma rich in growth factors eye drops for the treatment of evaporative dry eye. Ophthalmic Res. 2016, 56, 68–73. [Google Scholar] [CrossRef] [PubMed]
- Sanchez-Avila, R.M.; Merayo-Lloves, J.; Riestra, A.C.; Fernandez-Vega Cueto, L.; Anitua, E.; Begoña, L.; Muruzabal, F.; Orive, G. Treatment of patients with neurotrophic keratitis stages 2 and 3 with plasma rich in growth factors (PRGF-Endoret) eye-drops. Int. Ophthalmol. 2018, 38, 1193–1204. [Google Scholar] [CrossRef] [PubMed]
- Sanchez-Avila, R.M.; Merayo-Lloves, J.; Fernandez, M.L.; Rodriguez-Gutierrez, L.A.; Jurado, N.; Muruzabal, F.; Orive, G.; Anitua, E. Plasma rich in growth factors for the treatment of dry eye after LASIK surgery. Ophthalmic Res. 2018, 60, 80–86. [Google Scholar] [CrossRef]
- Sanchez-Avila, R.M.; Merayo-Lloves, J.; Muruzabal, F.; Orive, G.; Anitua, E. Plasma rich in growth factors for the treatment of dry eye from patients with graft versus host diseases. Eur. J. Ophthalmol. 2018, 1120672118818943. [Google Scholar] [CrossRef] [PubMed]
- Wróbel-Dudzińska, D.; Alio, J.; Rodriguez, A.; Suchodoła-Ratajewicz, E.; Kosior-Jarecka, E.; Rymgayłło-Jankowska, B.; Ćwiklińska-Haszcz, A.; Żarnowski, T. Clinical efficacy of platelet-rich plasma in the treatment of neurotrophic corneal ulcer. J. Ophthalmol. 2018, 2018, 3538764. [Google Scholar] [CrossRef] [PubMed]
- García-Conca, V.; Abad-Collado, M.; Hueso-Abancens, J.R.; Mengual-Verdú, E.; Piñero, D.P.; Aguirre-Balsalobre, F.; Molina, J.C. Efficacy and safety of treatment of hyposecretory dry eye with platelet-rich plasma. Acta Ophthalmol. 2019, 97, e170–e178. [Google Scholar]
- Alio, J.L.; Rodriguez, A.E.; Martinez, L.M.; Rio, A.L. Autologous fibrin membrane combined with solid platelet-rich plasma in the management of perforated corneal ulcers: A pilot study. JAMA Ophthalmol. 2013, 131, 745–751. [Google Scholar] [CrossRef]
- Avila, M.Y.; Igua, A.M.; Mora, A.M. Randomised, prospective clinical trial of platelet-rich plasma injection in the management of severe dry eye. Br. J. Ophthalmol. 2019, 103, 648–653. [Google Scholar] [CrossRef]
- Rauz, S.; Koay, S.-Y.; Foot, B.; Kaye, S.B.; Figueiredo, F.; Burdon, M.A.; Dancey, E.; Chandrasekar, A.; Lomas, R. The royal college of ophthalmologists guidelines on serum eye drops for the treatment of severe ocular surface disease: Full report. Eye 2017. [Google Scholar] [CrossRef]
- Rauz, S.; Koay, S.-Y.; Foot, B.; Kaye, S.B.; Figueiredo, F.; Burdon, M.A.; Dancey, E.; Chandrasekar, A.; Lomas, R. The royal college of ophthalmologists guidelines on serum eye drops for the treatment of severe ocular surface disease: Executive summary. Eye 2018, 32, 44–48. [Google Scholar] [CrossRef]
- Akeda, K.; Yamada, J.; Linn, E.T.; Sudo, A.; Masuda, K. Platelet-rich plasma in the management of chronic low back pain: A critical review. J. Pain Res. 2019, 12, 753–767. [Google Scholar] [CrossRef] [PubMed]
Study First Name, Year | Evidence Level | Design | Condition | Inclusion Criteria | Patients (n) | Controls (n) | Control arm | Solvent | Dilution | Posology | Duration of Treatment | Main Outcomes | Results |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Tananuvat 2001 [49] | 2 | RCT | DED | Refractory to treatment (tear substitute, punctum plug) | 12 | Fellow eye | Saline solution | ISS | 20% | 6×/d | 2 Ms | Subjective symptoms, FS, RBS, and CIC | No significant improvement of symptoms and signs between the two groups |
Ogawa 2003 [55] | 2 | P, I | DED (GVHD) | Refractory to treatment (tear substitute) | 14 | / | / | ISS | 20% | 10×/d | 4–41 Ms | Subjective symptoms, FS, RBS, TBUT, and Schirmer test | Improvement of symptoms, TBUT, RBS, and FS |
Matsumoto 2004 [59] | 3 | Retrospective, non-comparative case series | NK | Refractory to treatment (therapeutic contact lenses, tear substitute, and sodium hyaluronate) | 11 | / | / | ISS | 20% | 5–10×/d | Up to 36 Ms | Changes in corneal disease state, corneal sensitivity, and BCVA | 100% healing; 64% increase of corneal sensitivity |
Noble 2004 [50] | 1 | RCT, Cross over | DED | Epitheliopathy with corneal/conjunctival RBS, ST < 5 mm/5 min and punctal occlusion | 8 + 8 | 8 + 8 | Conventional treatment | ISS | 50% | As previous therapy | 3 Ms + 3 Ms | Subjective symptoms, TBUT, ST, FS, clearance test, and CIC | Improvement of symptoms and CIC after Allo-SED |
Kojima 2005 [51] | 1 | RCT | DED | DED symptoms, positive FS or RBS, ST < 5 mm/5 min or TBUT < 5 s | 10 | 10 | Preservative-free tear substitute | ISS | 20% | 6×/d | 2 wks | Subjective symptoms, FS, RBS, TBUT, and ST | Improvement of symptoms, TBUT, RBS, and FS in Allo-SED group |
Noda-Tsuruya 2006 [60] | 1 | RCT | Post-LASIK | Patients who received LASIK | 12 | 15 | Tear substitute | ISS | 20% | 5×/d | 1 week–6 M | Subjective symptoms, FS, RBS, TBUT, and ST | Improvement of TBUT, FS, and RBS. No change in symptoms |
Schulze 2006 [61] | 2 | RCT | Corneal Epithelial Abrasions in Diabetic Patients | Diabetic patients undergoing pars plana vitrectomy who received corneal abrasion for better intraoperative visualization | 13 | 10 | NaHy | ISS | 50% | Every hour | Until epithelial healing | Size of abrasion | Faster closure of corneal epithelial wounds |
López-Garcia 2008 [66] | 2 | P, I | LSCD | Aniridic keratopathy | 13 | / | / | Isotonic saline solution | 20% | 8×/d | 2 Ms | CIC, TBUT, ST, and tear meniscus level | Improvement of symptoms epithelialization, and ST |
Ziakas 2010 [62] | 2 | P, I | Recurrent Corneal Erosion | Refractory to treatment and history of at least three relapses | 33 | / | / | ISS | 20% | 6×/d for 3 Ms, then 3×/d for 3 Ms | 6 Ms | Subjective symptomsand recurrence | 85% healing with no recurrences over the whole follow-up period |
Chen 2010 [65] | 1 | P, I | Post PK | Patients who received PK | 82 | 83 | Tear substitute | Tear substitute | 20% | 8×/d | 3 d–2 wks | Corneal epithelial healing | Improvement of healing time |
Urzua 2012 [52] | 1 | RCT, Cross over | DED (NSS) | DED symptoms score more than 40 (OSDI questionnaire), TBUT < 5 s, positive FS or ST < 5 mm/5 min | 6 + 6 | 6 + 6 | Tear substitute | ISS | 20% | 4×/d | 2 wks + 2 wks | Subjective symptoms | Improvement of OSDI after Allo-SED |
Lekhanont 2013 [63] | 2 | P, I | PED after ocular surgery | Refractory to treatment | 181 | / | / | Tear substitute | 100% | Every 2 h | Until full healing | Rate of full healing corneal epithelial defect | 93% healing within 4 d |
Cho 2013 [37] | 2 | P, I | DED (SS and NSS) PED | DED: Symptoms, TBUT ≤ 5 s, ST ≤ 5 mm/5 min, positive corneal FS PED: Refractory to treatment (tear substitute, patching, and therapeutic contact lenses) | 22 | Group 2: 35 Group 3: 28 | / | ISS; NaHy; Ceftazidime | 100% vs. 50% | 6×/d | 3 Ms | Subjective symptoms, TBUT, ST, FS, and rate of complete healing of PED | In SS and PED, Allo-SED 100% was the most effective in decreasing symptoms and FS and in accelerating healing. In NSS, Allo-SED 100% and 50% were similar in reducing symptoms and FS |
Celebi 2014 [53] | 1 | RCT, Cross-over trial | DED | Refractory to treatment | 10 + 10 | 10 + 10 | Preservative-free tear substitute | ISS | 20% | 4×/d | 1 M + 1 M | Subjective sympthoms | Significant improvement of OSDI and TBUT after Allo-SED. No change of corneal damage and ST |
Hussain 2014 [38] | 2 | Retrospective, cohort study | DED | Refractory to treatments (lubrication, topical corticosteroids, cyclosporine 0.05%, and/or punctal occlusion) | 63 | / | / | ISS | 50% | 4×/d | 3 Ms–48 Ms | Subjective symptoms, FS, TBUT, and ST | Significant improvement of TBUT, FS, and symptoms |
Lopez-Garcia 2014 [39] | 1 | RCT | DED (SS) | Diagnosis of SS | 13 + 13 | / | / | ISS | 20% | 3×/d | 2 Ms | TBUT, ST, FS, RBS, and CIC | Improvement of symptoms, epithelialization, BUT, and ST in both groups |
Hwang 2014 [56] | 2 | P, I, cross-sectional | DED (SS) | ST < 5 mm/5 min, corneal Staining above 2 (Oxford Scale) | 34 | / | / | NaHy | 50% | 8×/d | 4 wks | Subjective symptoms, FS, and TBUT | Patients with primary SS had improvements in ocular symptoms, FS, and TBUT. Patients with secondary SS had no improvement. |
Jirsova 2014 [58] | 2 | P, I | DED | ST I < 5 mm/5 min, TBUT < 5 s | 17 | / | / | ISS | 20% | Open, up to 12×/d | 3 Ms | Subjective symptoms, FS, CIC, and ST | Significant improvement of ST and symptoms |
Semeraro 2016 [57] | 2 | P, I, case-control | DED (SS) | DED symptoms, ST < 5 mm/min or TBUT < 10 s | 12 | 12 | Tear substitute | ISS | 50% | 5×/d | 12 Ms | Tear production, tear stability, and FS | Significant improvement of symptoms |
Yilmatz 2017 [54] | 1 | RCT, cross-over trial | DED (due to isotretinoin) | DED symptoms, TBUT < 10 s, ST < 10 mm/min | 24 | 24 | Preservative-free tear substitute | ISS | 20% | Not specified | 1 M + 1 M | Subjective symptoms, ST, and TBUT | Significant improvement of symptoms and TBUT in Allo-SED group |
Sul 2018 [64] | 1 | P, I, case-control | Post Pterygium excision | Patients who received Pterygium Excision | 25 | 25 | Tear substitute | CMC | 50% | 8×/d | 3–8 d | Subjective symptoms and corneal epithelial healing | Improvement of healing time and symptoms |
Study First Name, Year | Evidence Level | Design | Condition | Inclusion Criteria | Patients (n) | Controls (n) | Control Arm | Solvent | Dilution | Posology | Duration of Treatment | Main Outcomes | Results |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Chiang 2009 [69] | 2 | P,I | PED | PED since >2 wks refractory to treatment (tear substitute and soft contact lenses) | 36 | / | / | / | 100% | Every hour | Variable | Healing | Complete healing in 42% within 2 weeks |
Na and Kim 2012 [72] | 2 | P,I | DED (GVHD) | Refractory to treatment | 16 | / | / | CMC and ofloxacin | 20% | 6–8×/d | 4 wks | Subjective symptom, TBUT, ST, FS, tear osmolarity, corneal staining, and CIC | Improvement in OSDI, FS, IC, and tear osmolarity |
Harritshøj 2014 [71] | 3 | Retrospective cohort | DED, PED | Refractory to treatment | DED 20 PED 14 | / | / | ISS | 20% | 6×/d | 2–4 wks | Subjective symptoms and healing | Improvement of symptoms and FS in DED group at 4 wks. No Improvement in PED group |
Study First Name, Year | Evidence Level | Design | Condition | Inclusion Criteria | Patients (n) | Controls (n) | Control Arm | Solvent Composition | Dilution | Posology | Duration of Treatment | Main Outcomes | Results |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Vajpayee 2003 [88] | 1 | RCT | PED | Refractory to treatments (tear substitute, patching, and contact lens) | 31 | 29 | Auto-SED | ISS | 20% | 6×/d | 3 wks | BCVA, FS, TBUT, ST, and PED size | Improvement of re-epithelization rate in UCBS group |
Yoon 2005 [89] | 3 | P, I | PED | PED refractory to treatments; persisted for at least 2 weeks | 14 | / | / | ISS | 20% | 6×/d | 2 wks–1 M | PED area | 43% healing within 2 weeks; 43% healing within 4 weeks |
Yoon 2006 [82] | 2 | P, I | DED | Refractory to treatments. DED symptoms > 3 months, TBUT < 5 s, ST < 5 mm/min, positive FS or RBS | 31 | / | / | ISS | 20% | 6–10×/d | 2 Ms | Subjective symptoms, TBUT, ST, corneal sensitivity, and FS | Improvement of symptoms, TBUT, and FS |
Yoon 2007 [90] | 2 | P, I | DED | Refractory to treatments. DED symptoms > 3 months, TBUT < 5 s, ST < 5 mm/min, positive FS or RBS | 27 | 21 | Auto-SED | ISS | 20% | 6–10×/d | 2 Ms | Symptom scoring, corneal sensitivity, TBUT, ST, tear clearance rate, FS, and CIC | Symptoms, TBUT, FS, and CIC findings improved in both groups. Symptoms and FS were lower in the CBS group |
Yoon 2007 [93] | 2 | P, I | DED (GVHD) | Refractory to treatments, TBUT < 5, ST < 5 mm/min, positive FS | 12 | / | / | ISS | 20% | 6–10×/d | 6 Ms | Subjective symptoms, TBUT, ST, corneal sensitivity test, FS, and tear clearance rate | Significant improvement in symptoms, corneal sensitivity, TBUT, and FS |
Yoon 2007 [98] | 2 | P, non-comparative case series | NK | Refractory to treatment (tear substitute and contact lens) | 28 | / | / | ISS | 20% | 6×/d | 2–4 wks | Epithelial healing time, BCVA, and corneal sensitivity | 100% corneal healing after 4 weeks |
Sharma 2011 [91] | 1 | RCT | Acute Chemical Burn | Acute chemical burns of grades III, IV, and V (Dua’s classification) | Group 1: 12 | Group 2: 11 Group 3: 10 | Group 2: Auto-SED Group 3: Medical Treatment | ISS | 20% | 10×/d | 3 Ms | Time to epithelialization, subjective symptoms, PED area, extent of limbal ischemia, corneal clarity, and symblepharon formation | Significant reduction of time to epithelialization after CBS therapy compared to AS and medical treatment |
Yoon 2011 [94] | 2 | P, I, case-control | RCE | History of RCE | 18 | 17 | Tear substitute | ISS | 20% | 4–6×/d | 1 year | Number of recurrences | Reduction of recurrences in UCBS group |
Versura 2013 [46] | 2 | P, I | PED (GVHD and SS) | DED symptoms, positive FS or RBS, ST < 5 mm/5 min or TBUT < 5 s | 30 | / | / | Phosphate buffered saline | 20% | 8×/d | 1 M | PED area, subjective symptom (OSDI), ST I, TBUT, tear osmolarity, corneal esthesiometry, and CIC | Significant reduction of epithelial damage |
Yoon 2013 [96] | 2 | P, I, case-control | Epithelial defect post-LASEK | Patients underwent LASEK | 32 | 28 | Tear substitute | ISS | 20% | 4–6×/d | 3 Ms | Epithelial healing time, BCVA, Haze score (0–4), ST, and TBUT | Improvement of corneal haze and tear film parameters |
Erdem 2014 [87] | 2 | P, I | PED | Refractory to treatment (tear substitute and patching contact lens) | 14 | / | / | ISS | 20% | 10×/d then 5x/d | 3 wks | PED area | 75% healing within 12 ds |
Mukhopadhyay 2015 [97] | 1 | RCT | DED (Hansen’s disease) | ST < 5 mm/5 min | 48 | Group B: 52 Group C: 44 | Group B: Auto-SED 20% Group C: Tear substitute | ISS | 20% | 6–10×/d | 6 wks | Subjective symptom, ST I, TBUT, and CIC | Better improvement of clinical parameters in CBS group |
Sharma 2016 [92] | 1 | RCT | Acute Chemical Burn | Acute chemical burns of grades III, IV, and V (Dua’s classification) | Group 3: 15 | Group 1: 15 Group 2: 15 | Group 1: Medical treatment Group 2: AMT, Medical treatment | / | 20% | 10×/d | Open | Subjective symptoms, TBUT, and ST | UCS and AMT are equally efficacious |
Giannaccare 2017 [86] | 2 | P, I | DED | DED symptoms, positive FS or RBS, ST < 5 mm/5 min or TBUT < 5 s | 20 | / | / | ISS | 20% | 8×/d | 4 Ms | Subjective symptom (OSDI), ST I, TBUT, FS, and corneal sensitivity | Significant improvement of all clinical parameters |
Kamble 2017 [95] | 1 | RCT | Epithelial defect post-keratoplasty | Epithelial defect post PK and DALK | Group 1: 35 | Group 2: 35 Group 3: 35 | Group 2: Auto-SED 20% Group 3: Tear substitute | BSS | 20% | 6×/d | Until healing | Rate of re-epithelialization | Rate of re-epithelialization comparable between CBS and Auto-SED groups |
Study, First Name, Year, [ref] | Evidence Level | Product | Design | Disease | Inclusion Criteria | Patients (n) | Controls (n) | Control Arm | Solvent | Dilution | Posology | Duration of Treatment | Main Outcomes | Results |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Kim 2012 [109] | 2 | PRP | Retrospective | PED | Refractory to treatment (Tear substitute) | 28 | 17 | Allo-SED | ISS | 20% | 4×/d | Until healing | Epithelial healing time and rate | Higher healing rate in PRP group |
Alio 2007 [104] | 2 | PRP | P, I | DED | FS > 50%, clinical signs of inflammation | 18 | / | / | ISS | / | 4–6×/d | 1 M | Subjective symptoms, BCVA, tear meniscus height, TBUT, FS, and CIC | Improvement of symptoms (89%), BCVA (28%), tear meniscus height (56%), TBUT (50%), and FS (72%) |
Alio 2007 [106] | 2 | PRP vs. AMT | P, I | Corneal ulcers | Refractory to treatment | 38 | / | / | ISS | / | 6×/d | 6 Ms | Ulcer size, inflammation, healing, BCVA, and subjective symptoms | Improvement of signs and symptoms |
Alio 2007 [105] | 3 | PRP | P, I | DED post-LASIK | Patients who received LASIK | 13 | / | / | ISS | / | 6×/d | 1 M | Subjective symptoms, BCVA, FS, and TBUT | Improvement of symptoms (85%); BCVA from 1 to 2 lines (54%); disappearance of FS (69%); increase of TBUT > 2 s (46%) |
Lee 2016 [112] | 2 | PRP | Retrospective | RCE | Patients treated with conventional therapy | 47 | 20 | Tear substitute | ISS | 20% | Every 2 h for 2 Ms, 4×/d for 4 Ms | 6 M | Recurrence rate | Reduced recurrence rate in PRP group |
Panda 2012 [110] | 1 | PRP | RCT | Chemical injury | / | 20 | 10 | Tear substitute | ISS | / | 10×/d | 3 Ms | Corneal transparency and BCVA | Significant improvement of corneal transparency and BCVA in PRP group |
García-Conca 2018 [118] | 1 | PRP | RCT | Hyposecretory DED | ST < 5.5 mm, OSDI ≥ 13, Oxford scale score ≥ 1 | 83 | 39 | NaHy, Tear substitute | ISS | / | 6×/d | 30 ds | ST, tear osmolarity, FS, TBUT, conjunctival hyperaemia, OSDI, and CIC | Improvement of signs in PRP group |
Avila 2018 [120] | 1 | PRP injected | RCT | DED (SS) | Patients who did not receive medications like ciclosporin or topical steroids or lacrimal plugs and lacrimal occlusion | 30 | 15 | Tear substitute | ISS | / | 1 mL PRP | FS and TBUT | Improvement of lacrimal production and TBUT; reduction FS in PRP group | |
Wróbel-Dudzińska 2018 [117] | 2 | PRP | P, I | NK | Refractory to treatment | 25 | / | / | / | / | 5×/d | 3 Ms | BCVA, healing of corneal surface, subjective symptoms, and corneal thickness | Improvement of BCVA; PED full healing (80%); lack of discomfort and photophobia (96%); no progression of corneal damage |
Pezzotta 2017 [102] | 2 | PL | P | DED (GVHD) | Refractory to treatment (tear substitute for at least 3 Ms) | 23 | / | / | / | / | 4×/d | 6 Ms | Symptoms, TBUT, and FS | Improvement of symptoms (74%), TBUT (86.9%), and FS (69.6%) |
Fea 2016 [111] | 2 | PL | P, case-control | DED (SS) | Severe DED, OSDI ≥ 23, Oxford scale score ≥ 1; refractory to treatment for more than 2 Ms (tear substitute, steroids, cyclosporine A, or allo-SED) | 30 | 10 | Tear substitute | ISS | 50% | 4×/d | 3 Ms | OSDI, ST, FS, BCVA, and TBUT | Improvement of OSDI, FS, and TBUT in PL group |
Zallio 2016 [103] | 2 | PL | P, I | DED (GVHD) | Recent diagnosis of GVHD | 26 | / | / | BSS | 30% | 6×/d | 1 year | / | Improvement in symptoms (91%); remission of corneal damage, (86%) and improved National Institutes of Health scores (73%) |
Lopez-Plandolit 2010 [107] | 2 | PRGF | P, I | PED | Refractory to medical and surgical treatments | 18 | / | / | ISS | / | Every 2 h for 3 d, then variable | Until healing | Epithelial healing rate and time | 85% healing within a mean of 11 weeks |
Sanchez-Avila 2017 [101] | 2 | PRGF | Retrospective | DED (SS) | SS | 26 | / | / | ISS | / | 4×/d | 6 wks (= 1 cycle) | OSDI, VAS, and BCVA | Improvement of OSDI score, BCVA, VAS frequency, and VAS severity |
Sanchez-Avila 2018 [114] | 2 | PRGF | Retrospective | NK stage 2 and 3 | ST < 5 mm, TBUT < 5 s, severity of subjective symptoms in the level of severity of dry eye | 31 | / | / | ISS | / | 4×/d | 6 wks (1 cycle) | Ulcer closure at 4 weeks, OSDI, VAS, and BCVA | Resolution of corneal defect/ulcer (97.4%) in 11.4 weeks; reduction of OSDI (60.9%), VAS frequency (59.9%), and VAS severity (57%); improvement of BCVA (52.8%) |
Sanchez-Avila 2018 [115] | 2 | PRGF | retrospective, comparative, and descriptive | DED post-LASIK | Patients who received LASIK | 79 | 39 | Tear substitute | ISS | / | 4×/d | 6 wks (1 cycle) | VAS, OSDI, BCVA, TBUT, ST, and IOP | Improvement in OSDI (38.12%), VAS (41.89%), severity (42.47%), and ST (88.98%) in PRGF group |
Sanche-Avila 2018 [116] | 2 | PRGF | Retrospective | DED (GVHD) | Refractory to treatments for 3 Ms (tear substitute, topical/oral antibiotics, corticoids and antivirals, contact lens, punctal occlusion, Allo-SED, cyclosporine, and AMT) | 12 | / | / | ISS | / | 4×/d | 6 wks (1 cycle) | Resolution of corneal ulcers | Improvement in the area (75.7%) and density (73.3%) corneal staining, BCVA (74.7%), OSDI (75.4%), visual analog score frequency (81.4%), and VAS severity (81.9%), and an increase of 3.8 s in TBUT and 6 mm in ST |
Merayo-Lloves 2016 [113] | 2 | PRGF | Retrospective | Evaporative DED | Refractory to treatment (tear substitute, topical or/and systemic corticosteroids, AS, or cyclosporine) | 83 | / | / | ISS | / | 4×/d | 6 wks | OSDI, BCVA, VAS, and ST | Reductions in the OSDI (38.2%), BCVA (27.4%), and VAS for frequency (32%) and severity (34%) and improvement in ST (177.5%) |
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Bernabei, F.; Roda, M.; Buzzi, M.; Pellegrini, M.; Giannaccare, G.; Versura, P. Blood-Based Treatments for Severe Dry Eye Disease: The Need of a Consensus. J. Clin. Med. 2019, 8, 1478. https://doi.org/10.3390/jcm8091478
Bernabei F, Roda M, Buzzi M, Pellegrini M, Giannaccare G, Versura P. Blood-Based Treatments for Severe Dry Eye Disease: The Need of a Consensus. Journal of Clinical Medicine. 2019; 8(9):1478. https://doi.org/10.3390/jcm8091478
Chicago/Turabian StyleBernabei, Federico, Matilde Roda, Marina Buzzi, Marco Pellegrini, Giuseppe Giannaccare, and Piera Versura. 2019. "Blood-Based Treatments for Severe Dry Eye Disease: The Need of a Consensus" Journal of Clinical Medicine 8, no. 9: 1478. https://doi.org/10.3390/jcm8091478