Die Wirkung von autologen Serumaugentropfen bei therapieresistenten Erosiones und Ulcera der Kornea bei eigenem im Vergleich zu transplantiertem Gewebe

Zusammenfassung

Hintergrund Ziel dieser Arbeit war es, die Wirkung von 100% autologen Serumaugentropfen bei therapieresistenten Erosiones und Ulcera corneae auf der eigenen Hornhaut vs. transplantierter Hornhaut zu vergleichen.

Patienten und Methoden In einer retrospektiven Studie über 7 Jahre wurden 263 Behandlungen mit autologen Serumaugentropfen bei therapieresistenten Epitheldefekten untersucht, die zwischen 2007 und 2014 auftraten. Unterschieden wurde, ob der Epitheldefekt (Erosio [88%] vs. Ulcus corneae [12%]) sich auf dem Hornhauttransplantat (48,1%) oder auf der eigenen Hornhaut (51,9%) befand. Zielgröße war der komplette Epithelschluss innerhalb von 28 Tagen Therapie. Die Rezidivrate im Verlauf wurde ebenfalls untersucht.

Ergebnisse Bei 88,2% der behandelten Defekte kam es innerhalb von 28 Behandlungstagen zu einem kompletten Epithelschluss. Bei 5,1% der erfolgreich geschlossenen Defekte kam es nach Abschluss der 1-monatigen Therapie zu einem Rezidiv. Es zeigte sich kein signifikanter Unterschied zwischen der Erfolgsrate von transplantiertem Hornhautgewebe (88,6%) oder eigenem Hornhautgewebe (87,8%; p = 0,137). Die Rezidivrate lag bei transplantierter Hornhaut bei 6,4%, bei der eigenen Hornhaut bei 1,7%. Bei Ulcera (74,2%) zeigte sich eine signifikant reduzierte Erfolgsrate im Vergleich zu den Erosiones (90,3%; p < 0,001). 4,4% der Erosiones und 4,3% der Ulcera rezidivierten im Verlauf.

Schlussfolgerungen Die autologen Serumaugentropfen stellen eine gute, nicht invasive und sichere Therapiealternative bei therapieresistenten Epitheldefekten dar, ohne signifikanten Unterschied der Wirkung bei Epitheldefekten auf der eigenen Hornhaut und transplantierter Hornhaut. Die Erfolgsrate, aber nicht die Rezidivrate ist bei Hornhautulcera signifikant geringer als bei Erosiones corneae.

Abstract

Purpose The aim of this study is to compare the healing of corneal epithelial defects or ulcers on the corneal graft in comparison with the patientʼs own cornea after treatment with 100%, undiluted autologous serum eye drops.

Methods In a retrospective study over 7 years, we analysed 263 treatments with autologous serum eye drops of persistent corneal epithelial defects (erosions [88%] vs. ulcers [12%]). We compared the epithelial healing tendency of patients with defects on their own cornea (51.9%) vs. patients who had previously undergone penetrating keratoplasty (48.1%). Complete epithelial healing during the 28 days of treatment was considered as therapeutic success. In addition, the recurrence rate of the epithelial defects after finishing the therapy was analysed.

Results 88.2% of the epithelial defects healed during 28 days of therapy. The recurrence rate during follow-up was 5.1%. There was no significant difference with respect to success rate between corneal defects on the patientʼs own cornea (87.8%) and on the graft (88.6%; p = 0.137). There was a significantly lower success rate for corneal ulcers (74.2%) than for erosions (90.3%; p < 0.001). The recurrence rate of erosions was 4.4%, vs. 4.3% in ulcers during follow-up.

Conclusion The results of our study suggest that autologous serum eye drops are a non-invasive and safe alternative treatment for persistent corneal epithelial defects – with no significant difference in patients with a defect on their own cornea vs. defects on the corneal graft. The success rate, but not the recurrence rate, is significantly worse in ulcers than in erosions.

Schlüsselwörter

Kornea - autologe Serumaugentropfen - therapieresistente Epitheldefekte - Erosio - Ulcus - Keratoplastik

Key words

cornea - autologous serum eye drops - therapy resistant epithelial defects - erosion - ulcus - keratoplasty

Publication History

Received: 27 September 2022

Accepted: 04 May 2023

Accepted Manuscript online:
10 May 2023

Article published online:
12 July 2023

• Literatur

• 1 Fox RI, Chan R, Michelson JB. et al. Beneficial effect of artificial tears made with autologous serum in patients with keratoconjunctivitis sicca. Arthritis Rheum 1984; 27: 459-461
• 2 Higuchi A. Autologous Serum and Serum Components. Invest Ophthalmol Vis Sci 2018; 59: DES121-DES129 DOI: 10.1167/iovs.17-23760.
• 3 Drew VJ, Tseng CL, Seghatchian J. et al. Reflections on Dry Eye Syndrome Treatment: Therapeutic Role of Blood Products. Front Med 2018; 5: 33 DOI: 10.3389/fmed.2018.00033.
• 4 Shimmura S, Ueno R, Matsumoto Y. et al. Albumin as a tear supplement in the treatment of severe dry eye. Br J Ophthalmol 2003; 87: 1279-1283 DOI: 10.1136/bjo.87.10.1279.
• 5 Giannaccare G, Versura P, Buzzi M. et al. Blood derived eye drops for the treatment of cornea and ocular surface diseases. Transfus Apher Sci 2017; 56: 595-604 DOI: 10.1016/j.transci.2017.07.023.
• 6 Alio JL, Rodriguez AE, WróbelDudzińska D. Eye platelet-rich plasma in the treatment of ocular surface disorders. Curr Opin Ophthalmol 2015; 26: 325-332 DOI: 10.1097/ICU.0000000000000169.
• 7 Stachon T, Wu M-F, Bischoff M. et al. [Amniotic Membrane Suspension and Autologous Serum – Are they Important for Wound Healing?]. Klin Monbl Augenheilkd 2017; 234: 1015-1018 DOI: 10.1055/s-0042-122338.
• 8 Liu L, Hartwig D, Harloff S. et al. An optimised protocol for the production of autologous serum eyedrops. Graefes Arch Clin Exp Ophthalmol 2005; 243: 706-714 DOI: 10.1007/s00417-004-1106-5.
• 9 Liu L, Hartwig D, Harloff S. et al. Corneal epitheliotrophic capacity of three different blood-derived preparations. Invest Ophthalmol Vis Sci 2006; 47: 2438-2444 DOI: 10.1167/iovs.05-0876.
• 10 Wu M-F, Stachon T, Seitz B. et al. Effect of human autologous serum and fetal bovine serum on human corneal epithelial cell viability, migration and proliferation in vitro. Int J Ophthalmol 2017; 10: 908-913 DOI: 10.18240/ijo.2017.06.12.
• 11 Tsubota K, Goto E, Shimmura S. et al. Treatment of persistent corneal epithelial defect by autologous serum application. Ophthalmology 1999; 106: 1984-1989 DOI: 10.1016/S0161-6420(99)90412-8.
• 12 Poon AC, Geerling G, Dart JK. et al. Autologous serum eyedrops for dry eyes and epithelial defects: clinical and in vitro toxicity studies. Br J Ophthalmol 2001; 85: 1188-1197 DOI: 10.1136/bjo.85.10.1188.
• 13 Ferreira de Souza R, Kruse FE, Seitz B. [Autologous serum for otherwise therapy resistant corneal epithelial defects – Prospective report on the first 70 eyes]. Klin Monbl Augenheilkd 2001; 218: 720-726 DOI: 10.1055/s-2001-18663.
• 14 Akyol-Salman I. Effects of autologous serum eye drops on corneal wound healing after superficial keratectomy in rabbits. Cornea 2006; 25: 1178-1181 DOI: 10.1097/01.ico.0000208817.40237.8c.
• 15 Geerling G, Daniels JT, Dart JK. et al. Toxicity of natural tear substitutes in a fully defined culture model of human corneal epithelial cells. Invest Ophthalmol Vis Sci 2001; 42: 948-956
• 16 Sauer R, Blüthner K, Seitz B. [Sterility of non-preserved autologous serum drops for treatment of persistent corneal epithelial defects]. Ophthalmologe 2004; 101: 705-709 DOI: 10.1007/s00347-003-0962-4.
• 17 Seitz B, Grüterich M, Cursiefen C. et al. [Conservative and surgical treatment of neurotrophic keratopathy]. Ophthalmologe 2005; 102: 15-26 DOI: 10.1007/s00347-004-1161-7.
• 18 Foerster CG, Langenbucher A, Cursiefen C. et al. Delayed epithelial healing after keratoplasty for lattice corneal dystrophy. Cornea 2007; 26: 1182-1183 DOI: 10.1097/ICO.0b013e318151f8cc.
• 19 Das S, Langenbucher A, Seitz B. Delayed healing of corneal epithelium after phototherapeutic keratectomy for lattice dystrophy. Cornea 2005; 24: 283-287 DOI: 10.1097/01.ico.0000138853.26332.55.
• 20 Geerling G, Grus F, Seitz B. et al. [Legal regulations to produce serum eye drops: when is it necessary, and how can it be obtained?]. Ophthalmologe 2008; 105: 632-638 DOI: 10.1007/s00347-008-1751-x.
• 21 Tsubota K, Goto E, Fujita H. et al. Treatment of dry eye by autologous serum application in Sjögrenʼs syndrome. Br J Ophthalmol 1999; 83: 390-395 DOI: 10.1136/bjo.83.4.390.
• 22 Ogawa Y, Okamoto S, Mori T. et al. Autologous serum eye drops for the treatment of severe dry eye in patients with chronic graft-versus-host disease. Bone Marrow Transplant 2003; 31: 579-583 DOI: 10.1038/sj.bmt.1703862.
• 23 Takamura E, Shinozaki K, Hata H. et al. Efficacy of autologous serum treatment in patients with severe dry eye. Adv Exp Med Biol 2002; 506: 1247-1250 DOI: 10.1007/978-1-4615-0717-8_179.
• 24 Jeng BH, Dupps WJ. Autologous serum 50 % eyedrops in the treatment of persistent corneal epithelial defects. Cornea 2009; 28: 1104-1108 DOI: 10.1097/ICO.0b013e3181a2a7f6.
• 25 Noble BA, Loh RSK, MacLennan S. et al. 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 DOI: 10.1136/bjo.2003.026211.
• 26 Semeraro F, Forbice E, Braga O. et al. Evaluation of the efficacy of 50 % autologous serum eye drops in different ocular surface pathologies. Biomed Res Int 2014; 2014: 826970 DOI: 10.1155/2014/826970.
• 27 Hussain M, Shtein RM, Sugar A. et al. Long-term use of autologous serum 50 % eye drops for the treatment of dry eye disease. Cornea 2014; 33: 1245-1251 DOI: 10.1097/ICO.0000000000000271.
• 28 Stachs O, Zhivov A, Kraak R. et al. Structural-functional correlations of corneal innervation after LASIK and penetrating keratoplasty. J Refract Surg 2010; 26: 159-167 DOI: 10.3928/1081597X-20100224-01.
• 29 Darwish T, Brahma A, Efron N. et al. Subbasal nerve regeneration after penetrating keratoplasty. Cornea 2007; 26: 935-940 DOI: 10.1097/ICO.0b013e3180de493f.
• 30 Patel SV, Erie JC, McLaren JW. et al. Keratocyte and subbasal nerve density after penetrating keratoplasty. Trans Am Ophthalmol Soc 2007; 105: 180-189
• 31 Niederer RL, Perumal D, Sherwin T. et al. Corneal innervation and cellular changes after corneal transplantation: an in vivo confocal microscopy study. Invest Ophthalmol Vis Sci 2007; 48: 621-626 DOI: 10.1167/iovs.06-0538.
• 32 Seitz B. [Amniotic membrane transplantation. An indispensable therapy option for persistent corneal epithelial defects]. Ophthalmologe 2007; 104: 1075-1079 DOI: 10.1007/s00347-007-1661-3.
• 33 Marchand M, Harissi-Dagher M, Germain M. et al. Serum drops for ocular surface disease: national survey of Canadian cornea specialists. Can J Ophthalmol 2018; 53: 266-271 DOI: 10.1016/j.jcjo.2017.09.007.
• 34 Dietrich T, Weisbach V, Seitz B. et al. [Manufacture of autologous serum eye drops for out-patient therapy: cooperation between ophthalmic clinic and transfusion medicine department]. Ophthalmologe 2008; 105: 1036-1038 1040–1042 DOI: 10.1007/s00347-008-1692-4.
• 35 Espinosa A, Hjorth-Hansen H, Aasly K. et al. 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 DOI: 10.1016/j.transci.2015.05.014.
• 36 Hung Y, Elder MJ, Rawstron JA. et al. A retrospective crossover study of autologous and allogeneic serum eye drops for the management of ocular surface disease. Transfus Med 2019; 29: 69-71 DOI: 10.1111/tme.12572.
• 37 Yoon KC. Use of umbilical cord serum in ophthalmology. Chonnam Med J 2014; 50: 82-85 DOI: 10.4068/cmj.2014.50.3.82.
• 38 Yoon KC, You IC, Im SK. et al. Application of umbilical cord serum eyedrops for the treatment of neurotrophic keratitis. Ophthalmology 2007; 114: 1637-1642 DOI: 10.1016/j.ophtha.2006.12.014.
• 39 Yoon KC, Choi W, You IC. et al. Application of umbilical cord serum eyedrops for recurrent corneal erosions. Cornea 2011; 30: 744-748 DOI: 10.1097/ICO.0b013e31820d850f.
• 40 Yoon KC, Heo H, Jeong IY. et al. Therapeutic effect of umbilical cord serum eyedrops for persistent corneal epithelial defect. Korean J Ophthalmol 2005; 19: 174-178 DOI: 10.3341/kjo.2005.19.3.174.
• 41 Yoon KC, Im SK, Park YG. et al. Application of umbilical cord serum eyedrops for the treatment of dry eye syndrome. Cornea 2006; 25: 268-272 DOI: 10.1097/01.ico.0000183484.85636.b6.
• 42 Yoon KC, Heo H, Im SK. et al. Comparison of autologous serum and umbilical cord serum eye drops for dry eye syndrome. Am J Ophthalmol 2007; 144: 86-92 DOI: 10.1016/j.ajo.2007.03.016.
• 43 Higuchi A, Ueno R, Shimmura S. et al. Albumin rescues ocular epithelial cells from cell death in dry eye. Curr Eye Res 2007; 32: 83-88 DOI: 10.1080/02713680601147690.
• 44 Seitz B, Grüterich M, Cursiefen C. et al. [Conservative and surgical treatment of neurotrophic keratopathy]. Ophthalmologe 2005; 102: 15-26 DOI: 10.1007/s00347-004-1161-7.