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Referencias

References to studies included in this review

Celebi 2014 {published data only}

Celebi AR, Ulusoy C, Mirza GE. The efficacy of autologous serum eye drops for severe dry eye syndrome: a randomized double‐blind crossover study. Graefes Archives of Clinical and Experimental Ophthalmology 2014;252(4):619‐26. CENTRAL

Kojima 2005a {published data only}

Kojima T, Ishida R, Dogru M, Goto E, Matsumoto Y, Kaido M, et al. The effect of autologous serum eyedrops in the treatment of severe dry eye disease: a prospective randomized case‐control study. American Journal Ophthalmology 2005;139(2):242‐6. CENTRAL
Kojima T, Ishida R, Goto E, Matsumoto Y, Dogru M, Tsubota K. The efficacy of autologous serum eye drops for Keratoconjunctivitis Sicca ‐ a prospective study. Investigative Ophthalmology and Visual Science 2004;45:ARVO E‐abstract 3894. CENTRAL

Noda‐Tsuruya 2006 {published data only}

Noda‐Tsuruya T, Asano‐Kato N, Toda I, Tsubota K. Autologous serum eye drops for dry eye after LASIK. Journal of Refractive Surgery 2006;22(1):61‐6. CENTRAL

Tananuvat 2001 {published data only}

Tananuvat N, Daniell M, Sullivan LJ, Yi Q, McKelvie P, McCarty DJ, et al. Controlled study of the use of autologous serum in dry eye patients. Cornea 2001;20(8):802–6. CENTRAL

Urzua 2012 {published data only}

Urzua CA, Vasquez DH, Huidobro A, Hernandez H, Alfaro J. Randomized double‐blind clinical trial of autologous serum versus artificial tears in dry eye syndrome. Current Eye Research 2012;37(8):684‐8. CENTRAL

References to studies excluded from this review

Albegger 1972 {published data only}

Albegger KW, Tilz GP. Sjogren's syndrome and its therapy. A therapeutic attempt using antilymphocyte serum [Zum Sjogren‐syndrom und seiner behandlung. Ein therapieversuch mit antilymphozytenglobulin]. Zeitschrift Fur Laryngologie, Rhinologie, Otologie Und Ihre Grenzgebiete 1972;51(7):429‐37. CENTRAL

Alvarado 2004 {published data only}

Alvarado Valero MC, Martinez Toldos JJ, Borras Blasco J, Alminana Alminana A, Perez Ramos JM. Treatment of persistent epithelial defects using autologous serum application [Tratamiento de defectos epiteliales persistentes mediante suero autologo]. Archivos De La Sociedad Espanola De Oftalmologia 2004;79(11):537‐42. CENTRAL

Anderson 2004 {published data only}

Anderson NG, Regillo C. Ocular manifestations of graft versus host disease. Current Opinion in Ophthalmology 2004;15(6):503‐7. CENTRAL

Badami 2009 {published data only}

Badami K, McKellar M. Allogeneic serum eye drops ‐ a useful alternative for those unable to be autologous donors. Transfusion. Proceedings of the AABB Annual Meeting and TXPO; 2009 Oct 24 ‐27; New Orleans (LA). 2009. CENTRAL

Bradley 2008 {published data only}

Bradley JC, Bradley RH, Mccartney DL, Mannis MJ. Serum growth factor analysis in dry eye syndrome. Clinical and Experimental Ophthalmology 2008;36(8):717‐20. CENTRAL

Brown 2005 {published data only}

Brown SM, Bradley JC. The effect of autologous serum eye drops in the treatment of severe dry eye disease: a prospective randomized case‐control study. American Journal of Ophthalmology 2005;140(3):565. CENTRAL

Chiang 2007 {published data only}

Chiang CC, Lin JM, Chen WL, Tsai YY. Allogeneic serum eye drops for the treatment of severe dry eye in patients with chronic graft‐versus‐host disease. Cornea 2007;26(7):861‐3. CENTRAL

Craig 2008 {published data only}

Craig JP. A natural solution to dry eye?. Clinical and Experimental Ophthalmology 2008;36(2):109‐10. CENTRAL

Fea 2016 {published data only}

Fea AM, Aragno V, Testa V, Machetta F, Parisi S, D'Antico S, et al. The effect of autologous platelet lysate eye drops: an in vivo confocal microscopy study. BioMed Research International 2016;2016:8406832. CENTRAL

Fuchsluger 2005 {published data only}

Fuchsluger TA, Steuhl KP, Meller D. Neurotrophic keratopathy ‐ a post‐LASIK case report. Klinische Monatsblatter fur Augenheilkunde 2005;222(11):901‐4. CENTRAL

Geerling 2002 {published data only}

Geerling G, Hartwig D. Autologous serum‐eye‐drops for ocular surface disorders. A literature review and recommendations for their application [Autologe serum‐augentropfen zur therapie der augenoberflache eine ubersicht zur wirksamkeit und empfehlungen zur anwendung]. Ophthalmologe 2002;99(12):949‐59. CENTRAL

Geerling 2004 {published data only}

Geerling G, Maclennan S, Hartwig D. Autologous serum eye drops for ocular surface disorders. British Journal of Ophthalmology 2004;88(11):1467‐74. CENTRAL

Geerling 2008 {published data only}

Geerling G, Unterlauft JD, Kasper K, Schrader S, Opitz A, Hartwig D. Autologous serum and alternative blood products for the treatment of ocular surface disorders [Eigenserum und alternative Blutprodukte zur Behandlung von Augenoberflachenerkrankungen]. Ophthalmologe 2008;105(7):623‐31. CENTRAL

Harritshoj 2011 {unpublished data only}

Harritshoj LH, Hansen MB, Julian HO. Ready‐made allogenic serum eye drops for severe dry eye disease. Vox Sanguinis. Proceedings of the 21st Regional Congress of the International Society of Blood Transfusion; 2011 Jun 18‐22; Lisbon, Portugal. 2011. CENTRAL

Hwang 2014 {published data only}

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. CENTRAL

Hyon 2007 {published data only}

Hyon JY, Lee YJ, Yun PY. Management of ocular surface inflammation in Sjogren syndrome. Cornea 2007;26(9 Suppl 1):S13‐5. CENTRAL

Jaksche 2005 {unpublished data only}

Jaksche A, Sbeity Z, Domeier E, Fimmers R, Holz F, Loeffler KU. Undiluted versus diluted autologous serum eye drops (ASED): a prospective, randomized, double‐blind study in patients with refractory dry eye‐syndrome. Investigative Ophthalmology and Visual Science 2005;46:ARVO E‐abstract 2045. CENTRAL

Koffler 2006 {published data only}

Koffler BH. Autologous serum therapy of the ocular surface with novel delivery by platelet concentrate gel. Ocular Surface 2006;4(4):188‐95. CENTRAL

Kojima 2005b {published data only}

Kojima T, Dogru M, Matsumoto Y, Goto E, Tsubota K. Tear film and ocular surface abnormalities after eyelid tattooing. Ophthalmic Plastic and Reconstructive Surgery 2005;21(1):69‐71. CENTRAL

Kojima 2008 {published data only}

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(Suppl 1):25‐30. CENTRAL

Li 2015 {published data only}

Li J, Zhang X, Zheng Q, Zhu Y, Wang H, Ma H, et al. Comparative evaluation of silicone hydrogel contact lenses and autologous serum for management of Sjogren syndrome‐associated dry eye. Cornea 2015;34(9):1072‐8. CENTRAL

Messmer 2005 {published data only}

Messmer EM. Management of keratoconjunctivitis sicca in Sjogren's syndrome. Aktuelle Rheumatologie 2005;30(1):59‐65. CENTRAL

Movahedan 2006 {published data only}

Movahedan H, Ghassemifar V. Treatment of persistent corneal epithelial defect with autologous serum. Asian Journal of Ophthalmology 2006;8(6):236‐41. CENTRAL

Mukhopadhyay 2015 {published data only}

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. British Journal of Ophthalmology 2015;99(1):108‐12. CENTRAL

NCT02752763 {published data only}

NCT02752763. Comparison of autologous serum versus preservative free artificial tear. clinicaltrials.gov/ct2/show/NCT02752763 (accessed 13 December 2016). CENTRAL

Noble 2004 {published data only}

Noble BA, Loh RS, MacLennan S, Pesudovs K, Reynolds A, Bridges LR, et al. Comparison of autologous serum eye drops with conventional therapy in a randomised controlled crossover trial for ocular surface disease. British Journal of Ophthalmology 2004;88(5):647–52. CENTRAL

Ogawa 2003 {published data only}

Ogawa Y, Okamoto S, Mori T, Yamada M, Mashima Y, Watanabe R, et al. Autologous serum eye drops for the treatment of severe dry eye in patients with chronic graft‐versus‐host disease. Bone Marrow Transplantation 2003;31(7):579‐83. CENTRAL

Poon 2001 {published data only}

Poon AC, Geerling G, Dart JK, Fraenkel GE, Daniels JT. Autologous serum eyedrops for dry eyes and epithelial defects: clinical and in vitro toxicity studies. British Journal of Ophthalmology 2001;85(10):1188‐97. CENTRAL

Watson 2010 {published data only}

Watson S L, Daniels JT, Geerling G, Dart JK. Clinical trials of therapeutic ocular surface medium for moderate to severe dry eye. Cornea 2010;29(11):1241‐6. CENTRAL

Yoon 2007 {published data only}

Yoon KC, Heo H, Im SK, You IC, Kim YH, Park YG. Comparison of autologous serum and umbilical cord serum eye drops for dry eye syndrome. American Journal of Ophthalmology 2007;144(1):86‐92. CENTRAL

AAO 2011

American Academy of Ophthalmology Cornea/External Disease Panel. Preferred Practive Pattern Guidlines. Dry Eye Syndrome ‐ Limited Revision. American Academy of Ophtalmology. www.aao.org/ppp (accessed 13 March 2012).

Akpek 2011

Akpek EK, Lindsley KB, Adyanthaya RS, Swamy R, Baer AN, McDonnel PJ. Treatment of Sjögren's Syndrome‐associated dry eye. Ophthalmology 2011;118:1242‐52.

Alfonso 1999

Afonso AA, Monroy D, Stern ME, Feuer WJ, Tseng SC, Pflugfelder SC. Correlation of tear fluorescein clearance and Schirmer test scores with ocular irritation symptoms. Ophthalmology 1999;106(4):803‐10.

Baudouin 2001

Baudouin C. The pathology of dry eye. Survey of Ophthalmology 2001;45(Suppl 2):S211‐20.

Baudouin 2010

Baoudouin C, Labbe A, Liang H, Pauly A, Brignole‐Baudouin F. Preservatives in eyedrops: the good, the bad and the ugly. Progress in Retinal and Eye Research 2010;29(4):321‐34.

Begley 2003

Begley CG, Chalmers RL, Abetz L, Venkataraman K, Mertzanis P, Caffery BA, et al. The relationship between habitual patient‐reported symptoms and clinical signs among patients with dry eye of varying severity. Investigative Ophthalmology and Visual Science 2003;44(11):4753‐61.

Behrens 2006

Behrens A, Doyle JJ, Stern L, Chuck RS, McDonnell PJ, Azar DT, et al. Dysfunctional tear syndrome: a Delphi approach to treatment recommendations. Cornea 2006;25(8):900‐7.

Blomquist 2010

Blomquist PH. Ocular complications of systemic medications. American Journal of Medical Science2011; Vol. 342, issue 1:62‐9.

Bron 2003

Bron A, Evans VE, Smith JA. Grading of corneal and conjunctival staining in the context of other dry eye tests. Cornea 2003;22(7):640‐50.

Campos 1992

Campos M, Hertzog L, Garbus JJ, McDonnell PJ. Corneal sensitivity after photorefractive keratectomy. American Journal of Ophthalmology 1992;114(1):51‐4.

Chambers 1999

Chambers CT, Giesbreacht K, Craig KD, Bennett SM, Huntsman E. A comparison of faces scales for the measurement of pediatric pain: children's and parent's ratings. Pain 1999;83(1):25‐35.

Chodosh 1994

Chodosh J, Dix RD, Howell RC, Stroop WG, Tseng SC. Staining characteristics and antiviral activities of sulforhodamine B and lissamine green. Investigative Ophthalmology and Vision Science 1994;35(3):1046‐58.

de Paiva 2008

de Paiva CS, Pflugfelder SC. Rational for anti‐inflammatory therapy in dry eye syndrome. Arquivos Brasileiros de Oftalmolgia 2008;71(Suppl 6):89‐95.

Demato 1984

Demato BE, Allan D, Murray SB, Lee WR. Senile atrophy of the human lacrimal gland: the contribution of chronic inflammatory disease. British Journal of Ophthalmology 1984;68(9):674‐80.

DEWS 2007

Anonymous. The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye Workshop. Ocular Surface 2007;5(2):75‐92.

Dogru 2011

Dogru M, Tsubota K. Pharmacotherapy of dry eye. Expert Opinion on Pharmacotherapy 2011;12(3):325‐34.

Doughty 1997

Doughty MJ, Fonn D, Richter D, Simpson T, Caffery B, Gordon K. A patient questionnaire approach to estimating the prevalence of dry eye symptoms in patients presenting to optometric practices across Canada. Optometry and Vision Science 1997;74(8):624‐31.

Ervin 2010

Ervin A‐M, Wojciechowski R, Schein O. Punctal occlusion for dry eye syndrome. Cochrane Database of Systematic Reviews 2010, Issue 9. [DOI: 10.1002/14651858.CD006775.pub2]

Foulks 2003

Foulks GN. The evolving treatment of dry eye. Ophthalmology Clinics of North America 2003;16(1):29‐35.

Fox 1984

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 and Rheumatism 1984;27(2):459‐61.

Fox 2006

Fox RI, Liu AY. Sjogren's syndrome in dermatology. Clinics in Dermatology 2006;24(5):393‐413.

Fuentes‐Paez 2011

Fuentes‐Paez G, Herreras JM, Cordero Y, Almaraz A, Gonxalez MJ, Calonge M. Lack of concordance between dry eye syndrome questionnaires and diagnostic tests [Falta de concordancia entre los cuestionarios y las pruebas diagnosticas en el sindrome de ojo seco]. Archivos de la Sociedad Espanola de Oftalmologia 2011;86(1):3‐7.

Glanville 2006

Glanville JM, Lefebvre C, Miles JN, Camosso‐Stefinovic J. How to identify randomized controlled trials in MEDLINE: ten years on. Journal of the Medical Library Association 2006;94(2):130‐6.

Gordon 1995

Gordon JF, Johnson P, Musch DC. Topical fibronectin ophthalmic solution in the treatment of persistent defects of the corneal epithelium. American Journal of Ophthalmology 1995;119(3):281‐7.

GRADEpro 2014 [Computer program]

GRADE Working Group, McMaster University. GRADEpro. Version accessed 13 December 2016. Hamilton (ON): GRADE Working Group, McMaster University, 2014.

Higgins 2003

Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ 2003;327:557‐60.

Higgins 2011a

Higgins JP, Altman DG, Sterne JAC, editor(s). Chapter 8: Assessing risk of bias in included studies. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. handbook.cochrane.org.

Higgins 2011b

Higgins JP, Deeks JJ, Altman DG, editor(s). Chapter 16: Special topics in statistics. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. handbook.cochrane.org.

Imanishi 2000

Imanishi J, Kamiyama K, Iguchi I, Kita M, Sotozone C, Kinoshita S. Growth factors: importance in wound healing and maintenance of transparency of the cornea. Progress in Retinal and Eye Research 2000;19(1):113‐29.

Joh 1986

Joh T, Itoh M, Katsumi K, Yokoyama Y, Takeuchi T, Kato T, et al. Physiological concentrations of human epidermal growth factor in biological fluids: use of a sensitive enzyme immunoassay. Clinica Chima Acta 1986;158(1):81‐90.

Kumar 2005

Kumar V, Abbas AK, Fausto N. Robbins and Cotran Pathologic Basis of Disease. 7th Edition. Philadelphia: Elsevier Saunders, 2005.

Langnado 2004

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. British Journal of Ophthalmology 2004;88(4):464‐5.

Lee 2008

Lee GA, Chen SX. Autologous serum in the management of recalcitrant dry eye syndrome. Clinical and Experimental Ophthalmology 2008;36(2):119‐22.

Lemp 1995

Lemp MA. Report of the National Eye Institute/Industry workshop on clinical trials in dry eyes. The CLAO Journal 1995;21(4):221‐32.

Lemp 2008

Lemp MA. Management of dry eye disease. American Journal of Managed Care 2008;14(Suppl 3):S88‐101.

Lemp 2011

Lemp MA, Bron AJ, Baudouin C, Benitez del Castillo JM, Geffen D, Tauber J, et al. Tear osmolarity in the diagnosis and management of dry eye disease. American Journal of Ophthalmology 2001;151(5):792‐8.

Lin 2003

Lin PY, Tsai SY, Cheng CY, Liu JH, Chou P, Hsu WM. Prevalence of dry eye among an elderly Chinese population in Taiwan: the Shihpai Eye Study. Ophthalmology 2003;110(6):1096‐101.

Liu 2005

Liu L, Hartwig D, Harloff S, Herminghaus P, Wedel T, Geerling G. An optimised protocol for the production of autologous serum eyedrops. Graefe's Archive for Clinical and Experimental Ophthalmology 2005;243(7):706‐14.

Marci 2000

Marci A, Pflugfelder S. Correlation of the Schirmer 1 and fluorescein clearance tests with the severity of corneal epithelia and eyelid disease. Archives of Ophthalmology 2000;118(12):1632‐38.

Matsumoto 2004

Matsumoto Y, Dogrou M, Goto E, Ohashi Y, Kojima T, Ishida R, et al. Autologous serum application in the treatment of neurotrophic keratopathy. Ophthalmology 2004;111(6):1115‐20.

McCarty 1998

McCarty C, Bansal AK, Liningston PM, Stanislavsky YL, Taylor HR. The epidemiology of dry eye in Melbourne, Australia. Ophthalmology 1998;105(6):1114‐9.

McCluskey 1987

McCluskey P, Wakefield D, York L. Topical fibronectin therapy in persistent corneal ulceration. Australia and New Zealand Journal of Ophthalmology 1987;15(4):257‐62.

McDonnell 1988

McDonnell PJ, Schanzlin DJ, Rao NA. Immunoglobulin deposition in the cornea after application of autologous serum. Archives of Ophthalmology 1988;106(10):1423‐5.

Meadows 2005

Meadows M. Dealing with dry eye. FDA Consumer Magazine2005; Vol. 39, issue 3.

Nelson 1988

Nelson JD, Farris RL. Sodium hyaluronate and polyvinyl alcohol artificial tear preparations. A comparison in patients with keratoconjunctivitis sicca. Archives of Ophthalmology 1988;106:484‐7.

Nelson 1992

Nelson JD, Gordon JF. Topical fibronectin in the treatment of keratoconjunctivitis sicca. Chiron Keratoconjunctivitis Sicca Study Group. American Journal of Ophthalmology 1992;114(4):441‐7.

Nichols 2004

Nichols KK, Mitchell GL, Zadnik K. The repeatability of clinical measurements of dry eye. Cornea 2004;23(3):272‐85.

Nishida 1983

Nishia T, Ohasai Y, Awata T, Manabe R. Fibronectin. A new therapy for corneal trophic ulcer. Archives of Ophthalmology 1983;101(7):1046‐8.

Nishida 1987

Nishida T, Nakamura M, Ofuji K, Reid TW, Mannis MJ, Murphy CJ. Synergistic effects of substance P with insulin‐like growth factor‐1 on epithelia migration of the cornea. Journal of Cell Physiology 1996;169(1):156‐66.

Ozcura 2007

Ozcura F, Aydin S, Helvaci MR. Ocular surface disease index for the diagnosis of dry eye syndrome. Ocular Immunology and Inflammation 2007;15(5):389‐93.

Pancholi 1998

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. Graefe's Archive for Clinical and Experimental Ophthalmology 1998;236(1):1‐8.

Partal 2011

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 disease. Transfusion Medicine2011; Vol. 21, issue 4:271‐7.

Patel 2002

Patel SJ, Lundy DC. Ocular manifestations of autoimmune disease. American Family Physician 2002;66(6):991‐8.

Patrick 2011

Patrick D, Guyatt GH, Acquardro C. Chapter 17: Patient‐reported outcomes. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. handbook.cochrane.org.

Perry 2004

Perry HD, Donnenfeld ED. Dry eye diagnosis and management in 2004. Current Opinion in Ophthalmology 2004;15(4):299‐304.

Pflugfelder 2004

Pfludgfelder SC. Antiinflammatory therapy for dry eye. American Journal of Ophthalmology 2004;137(2):337‐42.

Phan 1987

Phan TM, Foster CE, Bourochoff SA, Zagachin LM, Colvin RB. Topical fibronectin in the treatment of persistent corneal epithelial defects and trophic ulcers. American Journal of Ophthalmology 1987;104(5):494‐501.

Phasukkijwatana 2011

Phasukkijwatana N, Lertrit P, Liammongkolkul S, Prabhasawat P. Stability of epitheliotrophic factors in autologous serum eye drops from chronic Stevens‐Johnson syndrome dry eye compared to non‐autoimmune dry eye. Current Eye Research 2011;36(9):775‐81.

Pucker 2016

Pucker AD, Ng SM, Nichols JJ. Over the counter (OTC) artificial tear drops for dry eye syndrome. Cochrane Database of Systematic Reviews 2016, Issue 2. [DOI: 10.1002/14651858.CD009729.pub2]

Quinto 2008

Quinto GG, Campos M, Behrens A. Autologous serum for ocular surface disease. Arguivos Brasileiros de Oftalmologia 2008;71(Suppl 6):47‐54.

Ralph 1975

Ralph RA, Doane MG, Dohlman CH. Clinical experience with a mobile ocular perfusion pump. Archives of Ophthalmology 1975;93(10):1039‐43.

RevMan 2014 [Computer program]

Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014.

Roback 2008

Roback JD, Coombs MR, Grossman BJ, Hillyer CD. Technical Manual. 16th Edition. Bethesda, MD: American Association of Blood Banks, 2008.

Rocha 2000

Rocha EM, Pelegrino FS, de Paiva CS, Vigorito AC, de Sourza CA. GVHD dry eye treated with autologous serum tears. Bone Marrow Transplant 2000;25(10):1101‐3.

Sall 2000

Sall K, Stevenson OD, Mundorf TK, Reis BL. Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease. CsA Phase 43 Study Group. Ophthalmology 2000;107(4):631‐9.

Schaumberg 2003

Schaumberg DA, Sullivan DA, Buring JE, Dana MR. Prevalence of dry eye syndrome among US women. Ophthalmology 2003;136(2):318‐26.

Schein 1997

Schein OD, Tielsch JM, Munõz B, Bandeen‐Roche K, West S. Relation between signs and symptoms of dry eye in the elderly. A population‐based perspective. Ophthalmology 1997;104(9):1395‐401.

Stern 2004

Stern ME, Gao J, Siemasko KF, Beurerman RW, Pflugfelder SC. The role of the lacrimal functional unit in the pathophysiology of dry eye. Experimental Eye Research 2004;78(3):409‐16.

Stevenson 2000

Stevenson D, Tauber J, Reis BL. Efficacy and safety of cyclosporin A ophthalmic emulsion in the treatment of moderate‐to‐severe dry eye disease: a dose‐ranging, randomized trial. The Cyclosporin A Phase 2 Study Group. Ophthalmology 2000;107(5):967‐74.

Toda 2004

Toda I, Asano‐Kato N, Hori‐Komai Y, Tsubota K. Ocular surface treatment before last in situ keratomileusis in patients with severe dry eye. Journal of Refractive Surgery 2004;20(3):270‐5.

Toker 2010

Toker E, Asfuroglu E. Corneal and conjunctival sensitivity in patients with dry eye: the effect of topical cyclosporine therapy. Cornea 2010;29(2):133‐40.

Tomlinson 2006

Tomlinson A, Khanal S, Ramaesh K, Diaper C, McFadyen A. Tear film osmolarity: determination of a referent for dry eye diagnosis. Investigative Ophthalmology and Visual Science 2006;47(10):4309‐15.

Tomlinson 2009

Tomlinson A, McCann L, Pearce EI. Comparison of OcuSense and Clifton Nanolitre Osmometers. Investigative Ophthalmology and Vision Science 2009;50:ARVO E‐abstract 534.

Tsubota 1996

Tsubota K, Satake Y, Ohyama M, Toda I, Takano Y, Ono M, et al. Surgical reconstruction of the ocular surface in advanced ocular cicatricial pemphigoid and Stevens‐Johnson syndrome. American Journal of Ophthalmology 1996;122(1):38‐52.

Tsubota 1999

Tsubota K, Goto E, Fujita H, Ono M, Inoue H, Saito I, et al. Treatment of dry eye by autologous serum applications in Sjögren's syndrome. British Journal of Ophthalmology 1999;83(4):390‐5.

Tsubota 2000

Tsubota K, Higuchi A. Serum application for the treatment of ocular surface disorders. International Ophthalmology Clinics 2000;40(4):113‐122.

Versura 2012

Versura P, Profazio V, Buzzi M, Stancari A, Arpinati M, Malavolta N, et al. Efficacy of standardized and quality‐controlled cord blood serum eye drop therapy in the healing of severe corneal epithelial damage in dry eye. Cornea 2012;32(4):412‐8.

Viso 2012

Viso E, Rodriguez‐Ares MT, Abelenda D, Oubina B, Gude F. Prevalence of asymptomatic and symptomatic meibomian glad dysfunction in the general population of Spain. Investigative Ophthalmology and Visual Science 2012;53(6):2601‐6.

Wilson 2007

Wilson SE, Perry HD. Long‐term resolution of chronic dry eye symptoms and signs after topical cyclosporine treatment. Ophthalmology 2007;114(1):76‐9.

Yamada 1990

Yamada K, Hayasaka S, Setogawa T. Test results in patients with Sjogren's syndrome defined by the Japanese criteria. Acta Ophthalmogica 1990;68(1):80‐6.

References to other published versions of this review

Pan 2011

Pan Q, Angelina A, Marrone M, Daoud Y, Stark WJ, Heflin T, et al. Autologous serum eye drops for dry eye syndrome. Cochrane Database of Systematic Reviews 2011, Issue 9. [DOI: 10.1002/14651858.CD009327]

Pan 2013

Pan Q, Angelina A, Zambrano A, Marrone M, Stark WJ, Heflin T, et al. Autologous serum eye drops for dry eye. Cochrane Database of Systematic Reviews 2013, Issue 8. [DOI: 10.1002/14651858.CD009327.pub2]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Celebi 2014

Methods

Study design: 2‐period cross‐over, randomized controlled trial

Unit of randomization: individual

Number randomized:

Total: 20 participants

Per sequence: 10 randomized to each sequence

Unit of analysis: individual

Number analyzed:

Total: 20 participants

Per sequence: 10 per sequence

Participants

Country: Turkey

Mean age: 56 years

Gender: 18 women; 2 men

Underlying conditions: severe, refractory dry eye

Inclusion criteria:
Severe DES, defined as tear BUT < 5 seconds, Schirmer’s test score with anesthesia < 5 mm, corneal and conjunctival fluorescein staining ≥ grade 1 according to the Oxford Scale, and OSDI score > 40, refractory to conventional treatment (e.g., artificial tears, sodium hyaluronate, cyclosporine)

Exclusion criteria:
Active ocular infection or any other inflammation not associated with dry eye, eyelid or eyelash abnormality, associated glaucoma, graft‐versus‐host disease, severe anemia, uncontrolled cerebrovascular and cardiovascular disease, history of refractive surgery, current contact lens use or use of any type of topical eye drops other than dry eye medications, severe associated ocular allergy, pregnant or lactating women, inability to complete the study protocol

Interventions

Sequence 1: washout ‐ 20% AS ‐ washout ‐ artificial tears
Sequence 2: washout ‐ artificial tears ‐ washout ‐ 20% AS

AS protocol: 20% AS solution used 4 times a day for 1 month

Artificial tears protocol: artificial tears (Refresh) used 4 times a day for 1 month
Washout protocol: preservative‐free isotonic saline (0.9% sodium chloride) used 4 times a day for 2 weeks

Length of follow‐up:

Planned: 3 months

Actual: 3 months

Outcomes

Participant questionnaire: Ocular Surface Disease Index (OSDI)

Tear function:Tear BUT and Schirmer’s test
Ocular surface:fluorescein staining according to Oxford Scale score

Notes

Trial registration: not reported

Source of funding: not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"Each patient was randomized to one of the two treatment groups. Using the random number table method, a random treatment assignment code was created and every patient was given a sealed opaque envelope with their secret code"

Allocation concealment (selection bias)

Low risk

"Each patient was randomized to one of the two treatment groups. Using the random number table method, a random treatment assignment code was created and every patient was given a sealed opaque envelope with their secret code"

Masking of participants of the allocated intervention (Performance bias).

Low risk

"Only the biochemistry specialist (CU), who was not responsible for patient evaluation, knew which patient received which treatment during two different study periods"

Vials for both AS and artificial tears were "likewise wrapped with aluminum foil by a biochemistry specialist (CU) for blinding the patients. The droppers were also wrapped with aluminum foil for further blinding the patient while applying the eye drops"

Masking of study personnel of the allocated intervention (Performance bias)

Low risk

"Only the biochemistry specialist (CU), who was not responsible for patient evaluation, knew which patient received which treatment during two different study periods"

Masking of outcome assessors during follow‐up – patient reported symptoms (Detection bias)

Low risk

"Only the biochemistry specialist (CU), who was not responsible for patient evaluation, knew which patient received which treatment during two different study periods"

Masking of outcome assessors during follow‐up – clinical examination (Detection bias)

Low risk

"Only the biochemistry specialist (CU), who was not responsible for patient evaluation, knew which patient received which treatment during two different study periods"

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All participants completed the trial

Selective reporting (reporting bias)

Unclear risk

All outcomes were reported as described in the Methods section; however, although the study reported outcome data between treatment groups, investigators reported only P values, and thus we were unable to extract paired data for quantitative analysis

Other bias

Low risk

We believed the cross‐over design was appropriate given the relative stability of dry eye, eliminating the potential for a temporal treatment effect, and given that participants received their treatments in clearly random order. Use of a 2‐week washout between treatment periods ensured no carry‐over effect from one treatment period to the next.

Kojima 2005a

Methods

Study design: parallel‐group, randomized controlled trial

Unit of randomization: individual

Number randomized:

Total: 20 participants (37 eyes)

Per group: 10 participants

Unit of analysis: individuals

Number analyzed:

Total: 20 participants

Per group: 10 participants

Participants

Country: Japan

Mean age:  

AS: 62 years

Artificial tears: 65 years

Gender:

AS: 8 women; 2 men

Artificial tears: 8 women; 2 men

Underlying conditions: 8 of 10 participants in the AS group and 9 of 10 participants in artificial tears group had Sjögren's syndrome

Inclusion criteria:

All participants met diagnostic criteria of the Japanese Dry Eye Research Group:

Schirmer's 1 test < 5 mm, or tear film BUT < 5 seconds

Exclusion criteria:

History of punctal occlusion, ocular or systemic disease, or history of drug or contact lens use that would alter the ocular surface

Interventions

Intervention 1: 20% AS (saline)

Intervention 2: preservative‐free artificial tears

Length of follow‐up:

Planned: 2 weeks

Actual: 2 weeks

Outcomes

Participant questionnaire: Absence of any pain constituted a score of 0 points on visual analogue pain scales; intense, unbearable pain was considered a full pain score of 100 points

Tear function:Tear film BUT was measured 3 times, and the mean value was calculated. Tear film BUT was considered abnormal if < 5 seconds. Schirmer's test was considered abnormal if < 5 mm. 

Ocular surface: The ocular surface was examined by the double vital staining method. 2 mL of a preservative‐free combination of 1% Rose Bengal and 1% fluorescein dye was instilled in the conjunctival sac: 

“According to the study protocol, tear film BUT analysis was performed initially, followed by fluorescein and Rose Bengal vital staining of the ocular surface. The Schirmer 1 test was then performed. Tear film BUT, vital staining of the ocular surface, and visual analog pain symptom scores were compared before and after treatment”

Notes

Trial registration: not reported 

Source of funding: Japanese Ministry of Education and Science (Tokyo) and Hightech Research Center at Tokyo Dental College (Chiba, Japan) 

Study author provided additional information not included in published report

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

"After washout, all patients were randomly assigned to two groups..."

Allocation concealment (selection bias)

Unclear risk

"After washout, all patients were randomly assigned to two groups..."

Masking of participants of the allocated intervention (Performance bias).

Unclear risk

Study authors described the collection and production of autologous serum, including venipuncture, as well as storage requirements, but it was unclear whether only the autologous serum group underwent the necessary collection procedures or received the same storage instructions 

Masking of study personnel of the allocated intervention (Performance bias)

Unclear risk

No information provided in the published report revealed whether study personnel were aware of each participant's treatment assignment. Specific instructions were given to study participants regarding proper care and storage of autologous serum vials

Masking of outcome assessors during follow‐up – patient reported symptoms (Detection bias)

Unclear risk

"patients were asked to check a point on the line corresponding to their degree of pain"

Masking of outcome assessors during follow‐up – clinical examination (Detection bias)

Low risk

“The examiner who carried out the tear function and ocular surface evaluations was masked to the type of the eyedrops prescribed to the patients in this study”

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

A total of 39 eyes from 20 participants were analyzed and reported in a conference abstract; 37 eyes from 20 patients were analyzed in the full‐text publication. No explanation was provided for eyes excluded from the full‐text report

Selective reporting (reporting bias)

Unclear risk

No protocol or clinical trial registry record was found; all outcomes were reported as described in the Methods section

Other bias

Low risk

No other potential sources of bias were identified

Noda‐Tsuruya 2006

Methods

Study design: parallel‐group, randomized controlled trial

Unit of randomization: individual

Number randomized:

Total: 27 participants (54 eyes)

Per group:

AS: 12 participants (24 eyes)

Saline: 15 participants (30 eyes) 

Unit of analysis: eyes

Number analyzed:

1 month

BUT: AS 20, saline 23

Schirmer’s: AS 20, saline 19

Rose Bengal: AS 20, saline 15

Fluorescein: AS 20, saline 23

3 months

BUT: AS 18, saline 15

Schirmer’s: AS 16, saline 15

Rose Bengal: AS 16, saline 11

Fluorescein: AS 18, saline 15

6 months

BUT: AS 8, saline 10

Schirmer’s: AS 8, saline 10

Rose Bengal: AS 6, saline 10

Fluorescein: AS 8, saline 10

Participants

Country: Japan

Mean age: 30 years

Gender: 100% men

Underlying conditions: All participants had LASIK surgery 1 week before the start of the study

Concurrent dry eye treatments: One week after LASIK surgery, all participants received topical steroids, antibiotics, and hyaluronic acid eye drops 5 times per day and discontinued use at 1 week postoperatively 

Inclusion criteria: post‐LASIK, men

“All patients revealed normal findings by routine preoperative ophthalmologic examination including tear function and vital staining. None of the patients had worn contact lenses before LASIK” 

Interventions

Intervention 1: 20% AS (saline) 

Intervention 2: preservative‐free, saline‐based tears (Soft Santear, Santen)

Length of follow‐up:

Planned: 1 week post LASIK to 6 months post LASIK

Actual: 1 week post LASIK to 6 months post LASIK

Outcomes

Participant questionnaire: Dry eye symptoms were graded by participants, who used a written questionnaire according to the following criteria: 0, none; 1, mild; 2, moderate; 3, strong; and 4, very strong

Tear function:Schirmer's test with anesthesia, tear clearance rate, and tear BUT

Ocular surface staining:Fluorescein staining was graded from 0 to 3 for each of the upper, middle, and lower thirds of the cornea. Rose Bengal staining was graded from 0 to 3 for the temporal conjunctiva, cornea, and nasal conjunctiva. The grading scale was decided according to the extent of staining: 0, negative; 1, minute scattering; 2, moderately spotty; and 3, diffuse blotchy staining. Total of scores in the 3 areas was defined as fluorescein or Rose Bengal score

Notes

Trial registration: not reported

Source of funding: not reported

Contacted study author for additional information but did not receive information not included in the published report

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

"All candidates for the study were selected, and patients were randomly divided into two groups"

Allocation concealment (selection bias)

Unclear risk

"All candidates for the study were selected, and patients were randomly divided into two groups"

Masking of participants of the allocated intervention (Performance bias).

Unclear risk

Study authors described the collection and production of autologous serum, including venipuncture, as well as storage requirements, but it was unclear whether only the autologous serum group underwent the necessary collection procedures or received the same storage instructions 

Masking of study personnel of the allocated intervention (Performance bias)

Unclear risk

No information provided in the published report revealed whether study personnel were aware of each participant's treatment assignment, but specific instructions were given to study participants regarding proper care and storage of autologous serum vials

Masking of outcome assessors during follow‐up – patient reported symptoms (Detection bias)

Unclear risk

"Typical dry eye symptoms were graded by the patients using a written questionnaire according to the following criteria: 0, none; 1, mild; 2, moderate; 3, strong; and 4, very strong"

Masking of outcome assessors during follow‐up – clinical examination (Detection bias)

Unclear risk

"To evaluate tear function, Schirmer test with anesthesia, tear clearance rate, and tear break‐up time (BUT) were measured as previously described." No other description revealed whether outcome assessment was done by a masked investigator

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Study authors reported the number of eyes for each outcome at all time points across both treatment arms but did not provide reasons for missing outcome data

Selective reporting (reporting bias)

Unclear risk

No protocol or clinical trial registry record was found. Reported all outcomes at all time points for outcomes described in the Methods section, although reported information was insufficient for review authors to extract usable data for quantitative summary analysis

Other bias

Unclear risk

Unit of randomization was the participant, and results were reported per eye

Tananuvat 2001

Methods

Study design: paired‐eye, randomized controlled trial

Unit of randomization: eyes 

Number randomized:

Total: 26 eyes of 13 participants

Per group: 13 eyes of 13 participants

Unit of analysis: eyes

Number analyzed:

Total: 12 eyes of 12 participants

Per group: 12 eyes of 12 participants

Participants

Country: Australia 

Mean age: 60 years

Gender:

Men: 5

Women: 7 

Underlying conditions: 5 participants had Sjögren’s syndrome: 2 had primary Sjögren’s syndrome and 3 had secondary Sjögren’s syndrome. Non‐Sjögren’s‐type dry eyes included non‐Hodgkin’s lymphoma (n = 1), graft‐versus‐host disease (n = 1), Stevens‐Johnson syndrome (n = 1), rheumatoid arthritis (n = 1), and idiopathic (n = 3)

Concurrent dry eye treatments: artificial tears as needed 

Inclusion criteria:
"Patients with bilateral severe dry eye were enrolled in this study. All had low Schirmer test scores and positive rose bengal staining and symptoms of dry eye despite frequent lubricants or previous punctal occlusion"

Exclusion criteria:
"Patients were excluded if they had active ocular infection or inflammation not related to dry eye, had ocular surgery within 3 months, were monocular, or had other conditions that may mimic dry eye symptoms such as allergic conjunctivitis or lid or lash abnormalities"

Interventions

Intervention 1: 20% AS  

Intervention 2: unpreserved saline solution and dilute fluorescein solution

Length of follow‐up:

Planned: 2 months

Actual: 2 months

Outcomes

Participant questionnaire: Symptoms of dry eye (discomfort, foreign body sensation, dryness, and photophobia) were recorded at every visit and were graded according to severity as grade 0, no symptoms; 1, mild; 2, moderate; and 3, severe

Tear function: assessed by Schirmer’s test with anesthesia and tear BUT at baseline and 2 months after treatment

Ocular surface: examined with vital dye staining with fluorescein and Rose Bengal. Fluorescein staining was rated from 0 to 3 but only on the cornea. For Rose Bengal staining, the degree of staining was recorded separately for temporal and nasal conjunctivae and cornea on a scale of 0 to 3. Maximum score for each area was 3. Scores for each area were added together to obtain the total score for each eye. Therefore, maximum score for each eye was 9. Conjunctival impression cytology and slit‐lamp photography were performed to document the change in ocular surface 

Corrected visual acuity and slit‐lamp examinations were performed on each visit, and application of additional topical lubricants was recorded for both treatment groups

Notes

Trial registration: not reported

Source of funding: not reported

Study author provided additional information for assessing risk of bias not included in published report

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

High risk

Investigators used blocks of 2 for randomization when the right eye of participant 1 was assigned to be the study eye and the fellow eye was the control eye. For participant 2, the left eye was assigned as the study eye and the fellow eye was the control. (correspondence from study investigator)

Allocation concealment (selection bias)

High risk

Investigators used blocks of 2 for randomization when the right eye of participant 1 was assigned to be the study eye and the fellow eye was the control eye. For participant 2, the left eye was assigned as the study eye and the fellow eye was the control. (correspondence from study investigator)

Masking of participants of the allocated intervention (Performance bias).

Low risk

Participants were masked to treatment assignment (correspondence from study investigator)

Masking of study personnel of the allocated intervention (Performance bias)

High risk

The investigator who assessed outcomes was not masked to treatment assignments (correspondence from study investigator)

Masking of outcome assessors during follow‐up – patient reported symptoms (Detection bias)

High risk

The investigator who assessed outcomes was not masked to treatment assignments (correspondence from study investigator)

Masking of outcome assessors during follow‐up – clinical examination (Detection bias)

High risk

The investigator who assessed outcomes was not masked to treatment assignments (correspondence from study investigator). Although these were objective clinical tests, detection bias was possible if investigators conducting the test and interpreting the results were aware of participants' treatment assignments

Incomplete outcome data (attrition bias)
All outcomes

Low risk

"One patient with ocular cicatricial pemphigoid was excluded after enrollment because of asymmetry of the severity of dry eye between the two eyes." No other missing data were reported

Selective reporting (reporting bias)

Unclear risk

No protocol or clinical trial registry record was found. Reported all outcomes at all time points for outcomes described in the Methods section, although reported information was insufficient for review authors to extract usable data for quantitative summary analysis

Other bias

Unclear risk

Participants used lubricant artificial tears as needed during the study. This may have had an effect on results. Frequency and quantity of application of the drops for each participant were unknown

Urzua 2012

Methods

Study design: 2‐period cross‐over, randomized controlled trial

Unit of randomization: individual

Number randomized: 12 participants
Unit of analysis: individual

Number analyzed: 12 participants

Participants

Country: Chile

Mean age: 52 years

Gender: 11 women; 1 man

Underlying conditions: severe non‐Sjögren's dry eye

Inclusion criteria:

At least 18 years old with severe dry eye, as defined by OSDI score ≥ 40, tear BUT < 5 seconds, cornea‐conjunctival epithelial defects measured by fluorescein staining and evaluation using Oxford score and Schirmer's score < 5 mm/5 min; "all had used previous treatment with artificial tears with preservative"

Exclusion criteria:

Ocular surface disease other than dry eye, severe anemia, previous use of autologous serum or concomitant use of other topical ocular drug (i.e., topical steroids or cyclosporine), hypersensibility to any proposed interventions, inability to complete study protocol

Interventions

Sequence 1: 20% AS ‐ washout ‐ artificial tears
Sequence 2: artificial tears ‐ washout ‐ 20% AS

AS protocol: 20% AS solution used 4 times a day for 2 weeks

Artificial tears protocol: artificial tears (Systane) used 4 times a day for 2 weeks
Washout protocol: 0.9% sodium chloride used 4 times a day for 1 week

Length of follow‐up:

Planned: 5 weeks

Actual: 5 weeks

Outcomes

Participant questionnaire: score reduction in OSDI

Tear function:tear BUT (in seconds)
Ocular surface:corneal‐conjunctival staining according to the Oxford Scale score (6 categories)
Vision: best‐corrected visual acuity

Notes

Trial registration: NCT00779987

Source of funding: not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"Using random number tables method, a random treatment assignment code was created and every patient was given a sealed opaque envelope with the secret code"

Allocation concealment (selection bias)

Low risk

"Using random number tables method, a random treatment assignment code was created and every patient was given a sealed opaque envelope with the secret code. Then, the patient handed the envelope to the Cell Therapy Laboratory operator who delivered the treatment set"

Masking of participants of the allocated intervention (Performance bias).

Low risk

"Both groups of treatments were given a set of 14 identical, opaque flasks (containing either AS or artificial tears) with instructions of keeping them frozen at ‐20°C"

Masking of study personnel of the allocated intervention (Performance bias)

Low risk

"Both DES patient groups, clinical evaluators, and data analyst were masked to group intervention assignment through the whole completion of the protocol (double‐masked design)"

Masking of outcome assessors during follow‐up – patient reported symptoms (Detection bias)

Low risk

"Both DES patient groups, clinical evaluators, and data analyst were masked to group intervention assignment through the whole completion of the protocol (double‐masked design)"

"Clinical evaluation of each patient (OSDI, BCVA, TBUT, and OXFORD) was assessed at baseline, beginning and end of treatment by two researchers (Cristhian A. Urzua and Dario H. Vasquez) in a masked way"

Masking of outcome assessors during follow‐up – clinical examination (Detection bias)

Low risk

"Both DES patient groups, clinical evaluators, and data analyst were masked to group intervention assignment through the whole completion of the protocol (double‐masked design)"

"Clinical evaluation of each patient (OSDI, BVCA, TBUT, and OXFORD) was assessed at baseline, beginning and end of treatment by two researchers (Cristhian A. Urzua and Dario H. Vasquez) in a masked way"

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All participants completed the trial

Selective reporting (reporting bias)

Unclear risk

Reported data for all outcomes described in CT.gov record; however, although the study report described paired analyses to take advantage of the within‐participant design, outcome data were reported according to treatment group; thus we were not able to extract paired data

Other bias

Unclear risk

Differences in eligibility criteria between the CT.gov record and the published report, including non‐Sjogren's syndrome and Schirmer’s score < 5 mm/5 min

We believed the cross‐over design was appropriate given the relative stability of dry eye, eliminating the potential for a temporal treatment effect, and that participants received their treatments in a clearly random order. Use of a 1‐week washout between treatment periods ensured no carry‐over effect from one treatment period to the next.

APL: autologous platelet lysate.
AS: autologous serum eye drops.
BCVA: best‐corrected visual acuity.
DES: dry eye syndrome.
BUT: break‐up time.
LASIK: laser‐assisted in situ keratomileusis.
OSDI: ocular surface disease index.
TBUT: tear film break‐up time.

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Albegger 1972

Not a randomized controlled trial

Alvarado 2004

Non‐randomized case series

Anderson 2004

Non‐randomized case series

Badami 2009

Non‐randomized case series

Bradley 2008

Non‐randomized case series

Brown 2005

Non‐randomized case series

Chiang 2007

Non‐randomized case series

Craig 2008

Non‐randomized case series

Fea 2016

Randomized trial comparing autologous platelet lysate drops with artificial tears

Fuchsluger 2005

Non‐randomized case report

Geerling 2002

Overview about efficacy and recommendations for autologous serum for dry eye disease; not a randomized controlled trial

Geerling 2004

Non‐randomized case series

Geerling 2008

Review of autologous blood products in the treatment of dry eye; not a randomized controlled trial

Harritshoj 2011

Retrospective study investigating allogenic (donor) serum

Hwang 2014

Non‐randomized case series

Hyon 2007

Retrospective study

Jaksche 2005

Randomized trial comparing 50% autologous serum drops with 100% autologous serum drops

Koffler 2006

Non‐randomized case series

Kojima 2005b

Non‐randomized case series

Kojima 2008

Non‐randomized case series

Li 2015

Randomized trial comparing autologous serum eye drops with bandage contact lenses

Messmer 2005

Not a randomized controlled trial

Movahedan 2006

Non‐randomized case series

Mukhopadhyay 2015

Randomized trial in participants with Hansen's disease (leprosy); comparison of cord blood serum eye drops vs autologous serum eye drops vs artificial tears

NCT02752763

Randomized trial in participants using isotretinoin (vitamin A derivative); comparison of autologous serum eye drops vs artificial tears

Noble 2004

Conventional treatment arm with different pharmacological agents for each participant

Ogawa 2003

Non‐randomized case series

Poon 2001

Non‐randomized case series

Watson 2010

Non‐randomized case series

Yoon 2007

Comparison group for umbilical cord serum did not meet the criteria for our included studies

Data and analyses

Open in table viewer
Comparison 1. Autologous serum (20%) versus artificial tears

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Participant‐reported symptoms (severe dry eye) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

Analysis 1.1

Comparison 1 Autologous serum (20%) versus artificial tears, Outcome 1 Participant‐reported symptoms (severe dry eye).

Comparison 1 Autologous serum (20%) versus artificial tears, Outcome 1 Participant‐reported symptoms (severe dry eye).

1.1 Change from baseline at 2 weeks' follow‐up

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

2 Fluorescein (severe dry eye) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

Analysis 1.2

Comparison 1 Autologous serum (20%) versus artificial tears, Outcome 2 Fluorescein (severe dry eye).

Comparison 1 Autologous serum (20%) versus artificial tears, Outcome 2 Fluorescein (severe dry eye).

2.1 Change from baseline at 2 weeks' follow‐up

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

3 Rose Bengal (severe dry eye) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

Analysis 1.3

Comparison 1 Autologous serum (20%) versus artificial tears, Outcome 3 Rose Bengal (severe dry eye).

Comparison 1 Autologous serum (20%) versus artificial tears, Outcome 3 Rose Bengal (severe dry eye).

3.1 Change from baseline at 2 weeks' follow‐up

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

4 TBUT (severe dry eye) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

Analysis 1.4

Comparison 1 Autologous serum (20%) versus artificial tears, Outcome 4 TBUT (severe dry eye).

Comparison 1 Autologous serum (20%) versus artificial tears, Outcome 4 TBUT (severe dry eye).

4.1 Change from baseline at 2 weeks' follow‐up

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

5 Schirmer's 1 test (severe dry eye) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

Analysis 1.5

Comparison 1 Autologous serum (20%) versus artificial tears, Outcome 5 Schirmer's 1 test (severe dry eye).

Comparison 1 Autologous serum (20%) versus artificial tears, Outcome 5 Schirmer's 1 test (severe dry eye).

5.1 Two weeks' follow‐up

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

Open in table viewer
Comparison 2. Autologous serum (20%) versus saline solution

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Rose Bengal (post‐LASIK dry eye) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

Analysis 2.1

Comparison 2 Autologous serum (20%) versus saline solution, Outcome 1 Rose Bengal (post‐LASIK dry eye).

Comparison 2 Autologous serum (20%) versus saline solution, Outcome 1 Rose Bengal (post‐LASIK dry eye).

Results obtained by searching for studies for inclusion in the review.
Figuras y tablas -
Figure 1

Results obtained by searching for studies for inclusion in the review.

Methodological quality summary: risk of bias review authors' judgements about each risk of bias item for each included study.
Figuras y tablas -
Figure 2

Methodological quality summary: risk of bias review authors' judgements about each risk of bias item for each included study.

Comparison 1 Autologous serum (20%) versus artificial tears, Outcome 1 Participant‐reported symptoms (severe dry eye).
Figuras y tablas -
Analysis 1.1

Comparison 1 Autologous serum (20%) versus artificial tears, Outcome 1 Participant‐reported symptoms (severe dry eye).

Comparison 1 Autologous serum (20%) versus artificial tears, Outcome 2 Fluorescein (severe dry eye).
Figuras y tablas -
Analysis 1.2

Comparison 1 Autologous serum (20%) versus artificial tears, Outcome 2 Fluorescein (severe dry eye).

Comparison 1 Autologous serum (20%) versus artificial tears, Outcome 3 Rose Bengal (severe dry eye).
Figuras y tablas -
Analysis 1.3

Comparison 1 Autologous serum (20%) versus artificial tears, Outcome 3 Rose Bengal (severe dry eye).

Comparison 1 Autologous serum (20%) versus artificial tears, Outcome 4 TBUT (severe dry eye).
Figuras y tablas -
Analysis 1.4

Comparison 1 Autologous serum (20%) versus artificial tears, Outcome 4 TBUT (severe dry eye).

Comparison 1 Autologous serum (20%) versus artificial tears, Outcome 5 Schirmer's 1 test (severe dry eye).
Figuras y tablas -
Analysis 1.5

Comparison 1 Autologous serum (20%) versus artificial tears, Outcome 5 Schirmer's 1 test (severe dry eye).

Comparison 2 Autologous serum (20%) versus saline solution, Outcome 1 Rose Bengal (post‐LASIK dry eye).
Figuras y tablas -
Analysis 2.1

Comparison 2 Autologous serum (20%) versus saline solution, Outcome 1 Rose Bengal (post‐LASIK dry eye).

Summary of findings for the main comparison. Summary of findings: autologous serum compared with artificial tears

Autologous serum compared with artificial tears for dry eye

Patient or population: participants with dry eye

Settings: eye clinics

Intervention: autologous serum 20%

Comparison: artificial tears

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Artificial tears

Autologous serum

Participant‐reported symptoms

Range of scale: 0‐100, where a higher score is worse

Follow‐up: 2‐4 weeks

Mean change in symptom score in the control group was 7.2 point improvement

Mean change in symptom score in the autologous serum group was 12.0 points more improved (20.16 to 3.84 more improved)

20
(1 RCT)

⊕⊕⊝⊝
lowa,b

Trial investigators of 2 other studies reported more symptomatic improvement in the autologous serum group than in the artificial tears group; however, studies used a cross‐over design and did not provide sufficient data for comparison of treatments between groups

Tear hyperosmolarity

Follow‐up: 2‐4 weeks

Not reported

Fluorescein staining

Range of scale: 0‐9, where a higher score is worse

Follow‐up: 2‐4 weeks

Mean change in fluorescein score in the control group was 0.2 point improvement

Mean change in fluorescein score in the autologous serum group was 0.9 points more improved (1.47 to 0.33 more improved)

20
(1 RCT)

⊕⊕⊝⊝
lowa,b

Trial investigators of 2 other studies reported a non‐significant difference in Oxford Scale scores; however, studies used a cross‐over design and did not provide sufficient data for comparison of treatments between groups

Rose Bengal staining

Range of scale: 0‐9, where a higher score is worse

Follow‐up: 2‐4 weeks

Mean change in Rose Bengal score in the control group was 0.1 point improvement

Mean change in Rose Bengal score in the autologous serum group was 2.2 points more improved (2.73 to 1.67 more improved)

20
(1 RCT)

⊕⊕⊝⊝
lowa,b

Trial investigators of 2 other studies did not report data for this outcome

Tear film break‐up time

Follow‐up: 2‐4 weeks

Mean change in tear film break‐up time in the control group was 0.1 seconds

Mean change in tear film break‐up time in the autologous serum group was 2.00 seconds longer (0.99 to 3.01 longer)

20
(1 RCT)

⊕⊕⊝⊝
lowa,b

Trial investigators of 2 other studies reported the difference in TBUT between groups as 1 and 2 seconds; however, studies used a cross‐over study design and did not provide sufficient data for comparison of treatments between groups

Schirmer’s test

Score < 4 mm indicates severe dry eye

Follow‐up: 2‐4 weeks

Mean Schirmer’s test score in the control group was 3.7 mm

Mean Schirmer’s test score in the autologous serum group was
0.40 mm lower (2.91 lower to 2.11 mm higher)

20
(1 RCT)

⊕⊕⊝⊝
lowa,b

Trial investigators of 1 other study reported no difference in Schirmer’s test scores between groups; however, the study used a cross‐over design and did not provide sufficient data for comparison of treatments between groups

Adverse events

Not reported

*The basis for the assumed risk is the control group risk across studies. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)
CI: confidence interval; RR: risk ratio

GRADE Working Group grades of evidence
High‐certainty: Further research is very unlikely to change our confidence in the estimate of effect
Moderate‐certainty: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate
Low‐certainty: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate
Very low‐certainty: We are very uncertain about the estimate

aDowngraded (‐1) for imprecision (wide confidence intervals)
bDowngraded (‐1) for unclear risk of bias, such as performance and detection bias (lack of masking) and reporting bias (lack of quantitative data from relevant trials)

Figuras y tablas -
Summary of findings for the main comparison. Summary of findings: autologous serum compared with artificial tears
Summary of findings 2. Summary of findings: autologous serum compared with saline

Autologous serum compared with saline for dry eye

Patient or population: participants with dry eye

Settings: eye clinics

Intervention: autologous serum 20%

Comparison: saline

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Saline

Autologous serum

Participant‐reported symptoms

Follow‐up: 2‐4 weeks

See comment

Trial investigators of 2 studies reported no difference in symptom scores between groups; however, studies did not provide sufficient data for comparison of treatments between groups

Tear hyperosmolarity

Follow‐up: 2‐4 weeks

Not reported

Fluorescein staining

Range of scale: 0‐9, where a higher score is worse

Follow‐up: 2‐4 weeks

See comment

Trial investigators of 2 studies reported no difference in fluorescein staining scores between groups; however, studies did not provide sufficient data for comparison of treatments between groups

Rose Bengal staining

Range of scale: 0‐9, where a higher score is worse

Follow‐up: 2‐4 weeks

Mean Rose Bengal score in the control group was 0.9 points

Mean Rose Bengal score in the autologous serum group was 0.60 points lower (1.11 to 0.09 lower)

35
(1 RCT)

⊕⊝⊝⊝
very lowa

Trial investigators of 1 other study reported no difference in Rose Bengal staining scores between groups; however, the study did not provide sufficient data for comparison of treatments between groups

Tear film break‐up time

Follow‐up: 2‐4 weeks

See comments

Trial investigators of 1 study reported no difference in tear film break‐up time between groups; however, the study did not provide sufficient data for comparison of treatments between groups

Schirmer’s test

Score < 4 mm indicates severe dry eye

Follow‐up: 2‐4 weeks

See comments

Trial investigators of 1 study reported no difference in Schirmer's test scores between groups; however, the study did not provide sufficient data for comparison of treatments between groups

Adverse events

See comments

One study reported that 2 of 12 participants had signs of conjunctivitis with negative culture; in both cases, symptoms resolved later with proper treatment. It was not stated whether affected eyes were assigned to the AS group or the control group

*The basis for the assumed risk is the control group risk across studies. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)
CI: confidence interval; RR: risk ratio

GRADE Working Group grades of evidence
High‐certainty: Further research is very unlikely to change our confidence in the estimate of effect
Moderate‐certainty: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate
Low‐certainty: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate
Very low‐certainty: We are very uncertain about the estimate

aDowngraded (‐3) for high or unclear risk of selection, performance, detection, and reporting bias

Figuras y tablas -
Summary of findings 2. Summary of findings: autologous serum compared with saline
Comparison 1. Autologous serum (20%) versus artificial tears

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Participant‐reported symptoms (severe dry eye) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

1.1 Change from baseline at 2 weeks' follow‐up

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

2 Fluorescein (severe dry eye) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

2.1 Change from baseline at 2 weeks' follow‐up

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

3 Rose Bengal (severe dry eye) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

3.1 Change from baseline at 2 weeks' follow‐up

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

4 TBUT (severe dry eye) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

4.1 Change from baseline at 2 weeks' follow‐up

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

5 Schirmer's 1 test (severe dry eye) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

5.1 Two weeks' follow‐up

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

Figuras y tablas -
Comparison 1. Autologous serum (20%) versus artificial tears
Comparison 2. Autologous serum (20%) versus saline solution

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Rose Bengal (post‐LASIK dry eye) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

Figuras y tablas -
Comparison 2. Autologous serum (20%) versus saline solution