Skip to main content

Advertisement

SpringerLink
Log in

Corneal Transplantation in the Setting of Neurotrophic Keratopathy—Risks and Considerations

  • Corneal Transplantation (P Hamrah, Section Editor)
  • Published:
Current Ophthalmology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The aim of this study is to review diagnosis and clinical characteristics of neurotrophic keratitis and discuss both medical and surgical treatment options depending on disease severity.

Recent Findings

Management of NK depends upon identifying the severity and etiology of denervation and co-exiting ocular disorders. For active disease, the objective is to halt progression of melting, to provide structural support, and to prevent secondary infection. This can be accomplished through conjunctival flaps, amniotic membrane grafts, and tissue glue for small perforations. Surgery for visual restoration is best performed when the disease is quiescent. Full or partial thickness keratoplasty can be performed in conjunction with punctal occlusion, tarsorrhaphy, and amniotic membrane transplantation to aid in restoration of the ocular surface.

Summary

Neurotrophic keratitis can lead to chronic epithelial breakdown, poor healing, and eventual stromal lysis. The underlying etiology should be recognized and treated. Medical treatments should be initiated first, and if appropriate, escalated to surgical intervention to first restore globe integrity in active disease. In quiescent disease, if keratoplasty is needed, the ocular surface should be optimized, and inflammation should be controlled prior to surgery. Close follow-up to maintain the health of the ocular surface is vital to graft survival and success. Future research should focus on studying how graft survival is impacted by adjunctive therapy during or following surgical intervention for NK.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Nishida T, Saika S. Cornea and sclera: anatomy and physiology. In: Krachmer JH, Mannis MJ, Holland EJ, editors. Cornea fundamentals diagnosis and management, vol. 1. 3rd ed. Amsterdam: Mosby; 2011. p. 4–19.

    Google Scholar 

  2. Müller LJ, Marfurt CF, Kruse F, Tervo TMT. Corneal nerves: structure, contents and function. Exp Eye Res. 2003;76(5):521–42.

    Article  PubMed  Google Scholar 

  3. Grupcheva CN, Wong T, Riley AF, McGhee CNJ. Assessing the sub-basal nerve plexus of the living healthy human cornea by in vivo confocal microscopy. Clin Experiment Ophthalmol. 2002;30(3):187–90.

    Article  PubMed  Google Scholar 

  4. Ueda S, del Cerro M, LoCascio JA, Aquavella JV. Peptidergic and catecholaminergic fibers in the human corneal epithelium: an immunohistochemical and electron microscopic study. Acta Ophthalmol Suppl. 1989;192:80–90.

    CAS  PubMed  Google Scholar 

  5. Yamada M, Ogata M, Kawai M, Mashima Y. Decreased substance P concentrations in tears from patients with corneal hypesthesia. Am J Ophthalmol. 2000;129(5):671–2.

    Article  CAS  PubMed  Google Scholar 

  6. Sigelman S, Friedenwald JS. Mitotic and wound-healing activities of the corneal epithelium; effect of sensory denervation. AMA Arch Ophthalmol. 1954;52(1):46–57.

    Article  CAS  PubMed  Google Scholar 

  7. Gilbard JP, Rossi SR. Tear film and ocular surface changes in a rabbit model of neurotrophic keratitis. Ophthalmology. 1990;97(3):308–12.

    Article  CAS  PubMed  Google Scholar 

  8. Chang BH, Groos EB. Neurotrophic keratitis. In: Cornea fundamentals diagnosis and management, vol. 1. 3rd ed. Amsterdam: Mosby; 2011. p. 1101–8.

    Google Scholar 

  9. Bonini S, Rama P, Olzi D, Lambiase A. Neurotrophic keratitis. Eye Lond Engl. 2003;17(8):989–95. doi:10.1038/sj.eye.6700616.

    CAS  Google Scholar 

  10. Sacchetti M, Lambiase A. Diagnosis and management of neurotrophic keratitis. Clin Ophthalmol Auckl NZ. 2014;8:571–9. doi:10.2147/OPTH.S45921.

    Google Scholar 

  11. Liesegang TJ. Ocular herpes simplex infection: pathogenesis and current therapy. Mayo Clin Proc. 1988;63(11):1092–105.

    Article  CAS  PubMed  Google Scholar 

  12. Cobo LM. Corneal complications of herpes zoster ophthalmicus. Prevention and treatment Cornea. 1988;7(1):50–6.

    CAS  PubMed  Google Scholar 

  13. Lambiase A, Sacchetti M, Mastropasqua A, Bonini S. Corneal changes in neurosurgically induced neurotrophic keratitis. JAMA Ophthalmol. 2013;131(12):1547–53. doi:10.1001/jamaophthalmol.2013.5064.

    Article  PubMed  Google Scholar 

  14. Lockwood A, Hope-Ross M, Chell P. Neurotrophic keratopathy and diabetes mellitus. Eye Lond Engl. 2006;20(7):837–9. doi:10.1038/sj.eye.6702053.

    CAS  Google Scholar 

  15. Mackie I. Neuroparalytic keratitis. In: Fraunfelder F, Roy F, Meyer S, editors. Current ocular therapy. Philadelphia: WB Saunders; 1973.

    Google Scholar 

  16. Golub LM, Ramamurthy N, McNamara TF, et al. Tetracyclines inhibit tissue collagenase activity. A new mechanism in the treatment of periodontal disease. J Periodontal Res. 1984;19(6):651–5.

    Article  CAS  PubMed  Google Scholar 

  17. Ralph RA. Tetracyclines and the treatment of corneal stromal ulceration: a review. Cornea. 2000;19(3):274–7.

    Article  CAS  PubMed  Google Scholar 

  18. Katzman LR, Jeng BH. Management strategies for persistent epithelial defects of the cornea. Saudi J Ophthalmol. 2014;28(3):168–72. doi:10.1016/j.sjopt.2014.06.011.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Grey F, Carley F, Biswas S, Tromans C. Scleral contact lens management of bilateral exposure and neurotrophic keratopathy. Contact Lens Anterior Eye J Br Contact Lens Assoc. 2012;35(6):288–91. doi:10.1016/j.clae.2012.07.009.

    Article  Google Scholar 

  20. Matsumoto Y, Dogru M, Goto E, et al. Autologous serum application in the treatment of neurotrophic keratopathy. Ophthalmology. 2004;111(6):1115–20. doi:10.1016/j.ophtha.2003.10.019.

    Article  PubMed  Google Scholar 

  21. Szerenyi K, Sorken K, Garbus JJ, Lee M, McDonnell PJ. Decrease in normal human corneal sensitivity with topical diclofenac sodium. Am J Ophthalmol. 1994;118(3):312–5.

    Article  CAS  PubMed  Google Scholar 

  22. Hersh PS, Rice BA, Baer JC, et al. Topical nonsteroidal agents and corneal wound healing. Arch Ophthalmol Chic Ill 1960. 1990;108(4):577–83.

    Article  CAS  Google Scholar 

  23. Singer DD, Kennedy J, Wittpenn JR. Topical NSAIDs effect on corneal sensitivity. Cornea. 2015;34(5):541–3. doi:10.1097/ICO.0000000000000309.

    Article  PubMed  Google Scholar 

  24. Naik MN, Gangopadhyay N, Fernandes M, Murthy R, Honavar SG. Anterior chemodenervation of levator palpebrae superioris with botulinum toxin type-A (Botox) to induce temporary ptosis for corneal protection. Eye Lond Engl. 2008;22(9):1132–6. doi:10.1038/sj.eye.6702866.

    CAS  Google Scholar 

  25. Fogle JA, Kenyon KR, Foster CS. Tissue adhesive arrests stromal melting in the human cornea. Am J Ophthalmol. 1980;89(6):795–802.

    Article  CAS  PubMed  Google Scholar 

  26. Alino AM, Perry HD, Kanellopoulos AJ, Donnenfeld ED, Rahn EK. Conjunctival flaps. Ophthalmology. 1998;105(6):1120–3. doi:10.1016/S0161-6420(98)96017-1.

    Article  CAS  PubMed  Google Scholar 

  27. Lugo M, Arentsen JJ. Treatment of neurotrophic ulcers with conjunctival flaps. Am J Ophthalmol. 1987;103(5):711–2.

    Article  CAS  PubMed  Google Scholar 

  28. Rodríguez-Ares MT, Touriño R, López-Valladares MJ, Gude F. Multilayer amniotic membrane transplantation in the treatment of corneal perforations. Cornea. 2004;23(6):577–83.

    Article  PubMed  Google Scholar 

  29. Goins KM. New insights into the diagnosis and treatment of neurotrophic keratopathy. Ocul Surf. 2005;3(2):96–110. doi:10.1016/S1542-0124(12)70158-1.

    Article  PubMed  Google Scholar 

  30. Boudreau N, Werb Z, Bissell MJ. Suppression of apoptosis by basement membrane requires three-dimensional tissue organization and withdrawal from the cell cycle. Proc Natl Acad Sci U S A. 1996;93(8):3509–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Chen HJ, Pires RT, Tseng SC. Amniotic membrane transplantation for severe neurotrophic corneal ulcers. Br J Ophthalmol. 2000;84(8):826–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Said DG, Nubile M, Alomar T, et al. Histologic features of transplanted amniotic membrane: implications for corneal wound healing. Ophthalmology. 2009;116(7):1287–95. doi:10.1016/j.ophtha.2009.01.034.

    Article  PubMed  Google Scholar 

  33. Prabhasawat P, Tesavibul N, Komolsuradej W. Single and multilayer amniotic membrane transplantation for persistent corneal epithelial defect with and without stromal thinning and perforation. Br J Ophthalmol. 2001;85(12):1455–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Hick S, Demers PE, Brunette I, La C, Mabon M, Duchesne B. Amniotic membrane transplantation and fibrin glue in the management of corneal ulcers and perforations: a review of 33 cases. Cornea. 2005;24(4):369–77.

    Article  PubMed  Google Scholar 

  35. Khokhar S, Natung T, Sony P, Sharma N, Agarwal N, Vajpayee RB. Amniotic membrane transplantation in refractory neurotrophic corneal ulcers: a randomized, controlled clinical trial. Cornea. 2005;24(6):654–60.

    Article  PubMed  Google Scholar 

  36. Solomon A, Meller D, Prabhasawat P, et al. Amniotic membrane grafts for nontraumatic corneal perforations, descemetoceles, and deep ulcers. Ophthalmology. 2002;109(4):694–703.

    Article  PubMed  Google Scholar 

  37. Kruse FE, Rohrschneider K, Völcker HE. Multilayer amniotic membrane transplantation for reconstruction of deep corneal ulcers. Ophthalmology. 1999;106(8):1504–10. discussion 1511 doi:10.1016/S0161-6420(99)90444-X.

    Article  CAS  PubMed  Google Scholar 

  38. Kurbanyan K, Colby K. Cataract and refractive surgery in herpetic eye disease. Int Ophthalmol Clin. 2010;50(1):13–24. doi:10.1097/IIO.0b013e3181c5533a.

    Article  PubMed  Google Scholar 

  39. Liesegang TJ. Corneal complications from herpes zoster ophthalmicus. Ophthalmology. 1985;92(3):316–24.

    Article  CAS  PubMed  Google Scholar 

  40. Knickelbein JE, Hendricks RL, Charukamnoetkanok P. Management of herpes simplex virus stromal keratitis: an evidence-based review. Surv Ophthalmol. 2009;54(2):226–34. doi:10.1016/j.survophthal.2008.12.004.

    Article  PubMed  Google Scholar 

  41. Kennedy DP, Clement C, Arceneaux RL, Bhattacharjee PS, Huq TS, Hill JM. Ocular HSV-1: Is the cornea a reservoir for viral latency or a fast pit stop? Cornea. 2011;30(3):251–9. doi:10.1097/ICO.0b013e3181ef241d.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Kaye SB, Lynas C, Patterson A, Risk JM, McCarthy K, Hart CA. Evidence for herpes simplex viral latency in the human cornea. Br J Ophthalmol. 1991;75(4):195–200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Higaki S, Fukuda M, Shimomura Y. Virological and molecular biological evidence supporting herpes simplex virus type 1 corneal latency. Jpn J Ophthalmol. 2015;59(2):131–4. doi:10.1007/s10384-014-0369-6.

    Article  CAS  PubMed  Google Scholar 

  44. Wang J, Zhao G, Xie L, Chen M, Zhao J. Therapeutic effect of deep anterior lamellar keratoplasty for active or quiescent herpetic stromal keratitis. Graefes Arch Clin Exp Ophthalmol Albrecht Von Graefes Arch Für Klin Exp Ophthalmol. 2012;250(8):1187–94. doi:10.1007/s00417-012-1947-2.

    Article  Google Scholar 

  45. Cohen EJ, Laibson PR, Arentsen JJ. Corneal transplantation for herpes simplex keratitis. Am J Ophthalmol. 1983;95(5):645–50.

    Article  CAS  PubMed  Google Scholar 

  46. Lomholt JA, Baggesen K, Ehlers N. Recurrence and rejection rates following corneal transplantation for herpes simplex keratitis. Acta Ophthalmol Scand. 1995;73(1):29–32. doi:10.1111/j.1600-0420.1995.tb00008.x.

    Article  CAS  PubMed  Google Scholar 

  47. Cobo LM, Coster DJ, Rice NS, Jones BR. Prognosis and management of corneal transplantation for herpetic keratitis. Arch Ophthalmol Chic Ill 1960. 1980;98(10):1755–9.

    Article  CAS  Google Scholar 

  48. Sterk CC, Jager MJ, Swart-vd Berg M. Recurrent herpetic keratitis in penetrating keratoplasty. Doc Ophthalmol Adv Ophthalmol. 1995;90(1):29–33.

    Article  CAS  Google Scholar 

  49. Tanure MA, Cohen EJ, Grewal S, Rapuano CJ, Laibson PR. Penetrating keratoplasty for varicella-zoster virus keratopathy. Cornea. 2000;19(2):135–9.

    Article  CAS  PubMed  Google Scholar 

  50. Reed JW, Joyner SJ, Knauer WJ. Penetrating keratoplasty for herpes zoster keratopathy. Am J Ophthalmol. 1989;107(3):257–61.

    Article  CAS  PubMed  Google Scholar 

  51. Foster CS, Duncan J. Penetrating keratoplasty for herpes simplex keratitis. Am J Ophthalmol. 1981;92(3):336–43.

    Article  CAS  PubMed  Google Scholar 

  52. Ficker LA, Kirkness CM, Rice NS, Steele AD. The changing management and improved prognosis for corneal grafting in herpes simplex keratitis. Ophthalmology. 1989;96(11):1587–96.

    Article  CAS  PubMed  Google Scholar 

  53. Foster CS, Barney NP. Systemic acyclovir and penetrating keratoplasty for herpes simplex keratitis. Doc Ophthalmol Adv Ophthalmol. 1992;80(4):363–9.

    Article  CAS  Google Scholar 

  54. Kaye S, Choudhary A. Herpes simplex keratitis. Prog Retin Eye Res. 2006;25(4):355–80. doi:10.1016/j.preteyeres.2006.05.001.

    Article  PubMed  Google Scholar 

  55. Sarnicola V, Toro P. Deep anterior lamellar keratoplasty in herpes simplex corneal opacities. Cornea. 2010;29(1):60–4. doi:10.1097/ICO.0b013e3181a317d3.

    Article  PubMed  Google Scholar 

  56. Awan MA, Roberts F, Hegarty B, Ramaesh K. The outcome of deep anterior lamellar keratoplasty in herpes simplex virus-related corneal scarring, complications and graft survival. Br J Ophthalmol. 2010;94(10):1300–3. doi:10.1136/bjo.2009.169300.

    Article  CAS  PubMed  Google Scholar 

  57. Ghosh S, Jhanji V, Lamoureux E, Taylor HR, Vajpayee RB. Acyclovir therapy in prevention of recurrent herpetic keratitis following penetrating keratoplasty. Am J Ophthalmol. 2008;145(2):198–202. doi:10.1016/j.ajo.2007.10.005.

    Article  CAS  PubMed  Google Scholar 

  58. Ramappa M, Chaurasia S, Chakrabarti S, Kaur I. Congenital corneal anesthesia. J Am Assoc Pediatr Ophthalmol Strabismus. 2014;18(5):427–32. doi:10.1016/j.jaapos.2014.05.011.

    Article  Google Scholar 

  59. Ruben M, Colebrook E. Keratoplasty sensitivity. Br J Ophthalmol. 1979;63(4):265–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Rao GN, John T, Ishida N, Aquavella JV. Recovery of corneal sensitivity in grafts following penetrating keratoplasty. Ophthalmology. 1985;92(10):1408–11.

    Article  CAS  PubMed  Google Scholar 

  61. Mathers WD, Jester JV, Lemp MA. Return of human corneal sensitivity after penetrating keratoplasty. Arch Ophthalmol Chic Ill 1960. 1988;106(2):210–1.

    Article  CAS  Google Scholar 

  62. Lin X, Xu B, Sun Y, Zhong J, Huang W, Yuan J. Comparison of deep anterior lamellar keratoplasty and penetrating keratoplasty with respect to postoperative corneal sensitivity and tear film function. Graefes Arch Clin Exp Ophthalmol Albrecht Von Graefes Arch Für Klin Exp Ophthalmol. 2014;252(11):1779–87. doi:10.1007/s00417-014-2748-6.

    Article  Google Scholar 

  63. Inoue K, Amano S, Oshika T, Tsuru T. Risk factors for corneal graft failure and rejection in penetrating keratoplasty. Acta Ophthalmol Scand. 2001;79(3):251–5.

    Article  CAS  PubMed  Google Scholar 

  64. Chang H-YP, Luo ZK, Chodosh J, Dohlman CH, Colby KA. Primary implantation of type I Boston keratoprosthesis in nonautoimmune corneal diseases. Cornea. 2015;34(3):264–70. doi:10.1097/ICO.0000000000000357.

    Article  PubMed  Google Scholar 

  65. Pavan-Langston D, Dohlman CH. Boston keratoprosthesis treatment of herpes zoster neurotrophic keratopathy. Ophthalmology. 2008;115(2 Suppl):S21–3. doi:10.1016/j.ophtha.2007.10.013.

    Article  PubMed  Google Scholar 

  66. Ramaesh K, Stokes J, Henry E, Dutton GN, Dhillon B. Congenital corneal anesthesia. Surv Ophthalmol. 2007;52(1):50–60. doi:10.1016/j.survophthal.2006.10.004.

    Article  CAS  PubMed  Google Scholar 

  67. Dellaert MM, Casey TA, Wiffen S, et al. Influence of topical human epidermal growth factor on postkeratoplasty re-epithelialisation. Br J Ophthalmol. 1997;81(5):391–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Chen Y-M, Hu F-R, Huang J-Y, Shen EP, Tsai T-Y, Chen W-L. The effect of topical autologous serum on graft re-epithelialization after penetrating keratoplasty. Am J Ophthalmol. 2010;150(3):352–359.e2. doi:10.1016/j.ajo.2010.03.024.

    Article  PubMed  Google Scholar 

  69. Puangsricharern V, Tseng SC. Cytologic evidence of corneal diseases with limbal stem cell deficiency. Ophthalmology. 1995;102(10):1476–85.

    Article  CAS  PubMed  Google Scholar 

  70. Marsh RJ, Cooper M. Ocular surgery in ophthalmic zoster. Eye Lond Engl. 1989;3(Pt 3):313–7. doi:10.1038/eye.1989.45.

    Google Scholar 

  71. Sivasubramaniam P. Mode of action of tarsorrhaphy in neuroparalytic keratitis. Br J Ophthalmol. 1958;42(8):483–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Cosar CB, Cohen EJ, Rapuano CJ, et al. Tarsorrhaphy: clinical experience from a cornea practice. Cornea. 2001;20(8):787–91.

    Article  CAS  PubMed  Google Scholar 

  73. Seitz B, Das S, Sauer R, Mena D, Hofmann-Rummelt C. Amniotic membrane transplantation for persistent corneal epithelial defects in eyes after penetrating keratoplasty. Eye. 2009;23(4):840–8. doi:10.1038/eye.2008.140.

    Article  CAS  PubMed  Google Scholar 

  74. Seitz B, Das S, Sauer R, Hofmann-Rummelt C, Beckmann MW, Kruse FE. Simultaneous amniotic membrane patch in high-risk keratoplasty. Cornea. 2011;30(3):269–72. doi:10.1097/ICO.0b013e3181eae8ea.

    Article  PubMed  Google Scholar 

  75. Kamble N, Sharma N, Maharana PK, et al. Evaluation of the role of umbilical cord serum and autologous serum therapy in reepithelialization after keratoplasty: a randomized controlled clinical trial. Eye Contact Lens. 2016; doi:10.1097/ICL.0000000000000277.

    PubMed  Google Scholar 

  76. Rosenthal P, Cotter JM, Baum J. Treatment of persistent corneal epithelial defect with extended wear of a fluid-ventilated gas-permeable scleral contact lens. Am J Ophthalmol. 2000;130(1):33–41.

    Article  CAS  PubMed  Google Scholar 

  77. Arora R, Gupta S, Taneja M, Raina UK, Mehta DK. Disposable contact lenses in penetrating keratoplasty. CLAO J Off Publ Contact Lens Assoc Ophthalmol Inc. 2000;26(3):127–9.

    CAS  Google Scholar 

  78. Rosenthal P, Cotter J. The Boston Scleral Lens in the management of severe ocular surface disease. Ophthalmol Clin N Am. 2003;16(1):89–93.

    Article  Google Scholar 

  79. McDonald TO, Borgmann AR, Roberts MD, Fox LG. Corneal wound healing. I. Inhibition of stromal healing by three dexamethasone derivatives. Investig Ophthalmol. 1970;9(9):703–9.

    CAS  Google Scholar 

  80. Phillips K, Arffa R, Cintron C, et al. Effects of prednisolone and medroxyprogesterone on corneal wound healing, ulceration, and neovascularization. Arch Ophthalmol Chic Ill 1960. 1983;101(4):640–3.

    Article  CAS  Google Scholar 

  81. Newsome NA, Gross J. Prevention by medroxyprogesterone of perforation in the alkali-burned rabbit cornea: inhibition of collagenolytic activity. Invest Ophthalmol Vis Sci. 1977;16(1):21–31.

    CAS  PubMed  Google Scholar 

  82. Soong HK, Schwartz AE, Meyer RF, Sugar A. Penetrating keratoplasty for corneal scarring due to herpes zoster ophthalmicus. Br J Ophthalmol. 1989;73(1):19–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Ophthalmology and Visual Sciences, University of Maryland School of Medicine, 419 W. Redwood Street, Suite 470, Baltimore, MD, 21201, USA

    Jordan Ambrose Margo & Bennie Hau Jeng

Authors
  1. Jordan Ambrose Margo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bennie Hau Jeng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bennie Hau Jeng.

Ethics declarations

Conflict of Interest

Bennie Jeng and Jordan Margo declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Financial Disclosures

Neither author has any relevant financial interests with the subject matter discussed.

Additional information

This article is part of the Topical Collection on Corneal Transplantation

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Margo, J.A., Jeng, B.H. Corneal Transplantation in the Setting of Neurotrophic Keratopathy—Risks and Considerations. Curr Ophthalmol Rep 5, 14–22 (2017). https://doi.org/10.1007/s40135-017-0118-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40135-017-0118-3

Keywords

Search

Navigation