Corneal Allograft Rejection

5,272 views
5,103 views

Published on

Published in: Health & Medicine, Technology
0 Comments
9 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
5,272
On SlideShare
0
From Embeds
0
Number of Embeds
6
Actions
Shares
0
Downloads
414
Comments
0
Likes
9
Embeds 0
No embeds

No notes for slide

Corneal Allograft Rejection

  1. 1. CORNEAL ALLOGRAFT REJECTION BY SURASARIT KHAWLAOR
  2. 2. OUTLINES  STRUCTURE OF CORNEA, ENDOTHELIAL FUNCTION AND IMMUNE PRIVILEGE  CORNEAL ALLOGRAFT REJECTION  Keratoplasty  Risk factor & Types of rejection  clinical features  Immune mechanism of corneal allograft rejection  PREVENTION & TREATMENT OF CORNEAL ALLOGRAFT REJECTION
  3. 3. STRUCTURE OF CORNEA  Consist of 3 major layers  Anterior surface : 6-8 cell-deep epithelial layer  Main thickness (stroma) : collagen fiber supported by scattered keratocytes  Posterior surface : endothelial monolayer (maintenance of corneal transparency) & supported by Descemet’s membrane Hongmei Fu.Transplantation Reviews 2008;105-115
  4. 4. STRUCTURE OF CORNEA Hongmei Fu.Transplantation Reviews 2008;105-115
  5. 5. ENDOTHELIAL FUNCTION  Endothelial cells  nonreplicative in humans  pump water from stroma to anterior chamber  If loss of sig. number  decompensation of pump function  stromal swelling  loss of transparency & vision Hongmei Fu.Transplantation Reviews 2008;105-115
  6. 6. IMMUNE PRIVILEGE OF CORNEA  Cornea is immune privileged tissue  Absence of lymphatic & blood vessels in corneal graft bed  Expression of Fas ligand on corneal cells  Low-level expression of MHC class I and II molecules on corneal cells  Paucity of indigenous professional antigen- presenting mФ, Langerhans cells Hongmei Fu.Transplantation Reviews 2008;105-115
  7. 7. IMMUNE PRIVILEGE OF CORNEA  Cornea is immune privileged tissue(cont.)  Phenomenon of anterior chamber-associated immune deviation (ACAID) down regulation of systemic DTH from alloantigens in anterior chamber  Presence of immunomodulatory cytokines in aqueous humor in anterior chamber such as Α-melanocyte-stimulating hormone Transforming growth factor Hongmei Fu.Transplantation Reviews 2008;105-115
  8. 8. IMMUNE PRIVILEGE OF CORNEA rejection rate at the final observation (8 weeks) in the FasL- group (89%) was significantly higher than in the FasL+ control group (47%)
  9. 9. IMMUNE PRIVILEGE OF CORNEA Jerry Y. Niederkorn. Ocular Immunology & Inflammation 2010; 18(3); 162–171
  10. 10. IMMUNE PRIVILEGE OF CORNEA  Anterior chamber–associated immune deviation (ACAID)  form of eye-derived tolerance which TH1 & TH2- mediated immunity is suppressed  characterized by a selective deficiency in delayed type hypersensitivity (DTH) and Ig isotypes that fix complement Koh-Hei Sonoda . J. Exp. Med 1999 ; 190 (9): 1215–1225
  11. 11. ACAID camero-splenic axis J.Wayne Streilein. NATURE REVIEWS IMMUNOLOGY 2003 :879-880
  12. 12. IMMUNE PRIVILEGE OF CORNEA  Anterior chamber–associated immune deviation (ACAID)  CD4+ Treg known as “afferent Treg” suppress initial activation & differentiation of naïve T cell into TH1 effector cells : secondary lymphoid organs  CD8+ Treg known as “efferent Treg” inhibit expression of TH1-mediated immunity, such as DTH : periphery(eye) J.Wayne Streilein. NATURE REVIEWS IMMUNOLOGY 2003 :879-880
  13. 13. IMMUNE PRIVILEGE OF CORNEA Wilbanks, G. A 1992 Taylor, A. W. 1992 Taylor, A. W. 1994 Taylor, A. W. 1998 Sheibani, N. 2000 Apte, R. S. 1998 Kennedy, M. C. 1995 Sohn, J. H., 2000 Sugita, S. et al. 2000 J.Wayne Streilein. NATURE REVIEWS IMMUNOLOGY 2003 :879-880
  14. 14. IMMUNE PRIVILEGE OF CORNEA Junko Hori. Cornea 2009; 28(9): S58-S64
  15. 15. IMMUNE PRIVILEGE OF CORNEA  Conclusion  Immune privilege consists of 3 majors mechanism 1) Anatomical, molecular barriers in eye 2) Eye-derived immunological tolerance known as “ACAID” 3) Immune suppressive intraocular microenvironment
  16. 16. OUTLINES  STRUCTURE OF CORNEA, ENDOTHELIAL FUNCTION AND IMMUNE PRIVILEGE  CORNEAL ALLOGRAFT REJECTION  Keratoplasty  Risk factor & Types of rejection  clinical features  Immune mechanism of corneal allograft rejection  PREVENTION & TREATMENT OF CORNEAL ALLOGRAFT REJECTION
  17. 17. CORNEAL ALLOGRAFT REJECTION  Keratoplasty  plastic surgery of the cornea  lamellar keratoplasty a partial thickness graft of the cornea only epithelium and superficial stroma is removed replaced by donor tissue from penetrating or full-thickness grafting
  18. 18. CORNEAL ALLOGRAFT REJECTION  Keratoplasty (cont.)  optic keratoplasty  transplantation of corneal material to replace scar tissue that interferes with vision  penetrating keratoplasty  a full thickness of the cornea is removed and replaced with donor tissue, 1st performed in 1906  tectonic keratoplasty transplantation of corneal material to replace tissue that has been lost
  19. 19. CORNEAL ALLOGRAFT REJECTION  Common indications to perform keratoplasty  therapeutic(e.g. keratoconus, corneal ulcer)  cosmetic (e.g. removing an unsightly opacity)
  20. 20. CORNEAL ALLOGRAFT REJECTION RISK FACTORS Tham and Abbott. International Ophthalmology Clinic 2002;42(1):105-113
  21. 21. CORNEAL ALLOGRAFT REJECTION TYPES OF REJECTION A. Epithelial rejection  host epithelium grows inward from remaining host cornea & limbus to cover the graft B. Subepithelial rejection  subepithelial infiltrates with leukocytes  Both types are  steroid responsive  generally self-limited  tends not to cause visual disturbance  asymptomatic or only of minimal irritation
  22. 22. CORNEAL ALLOGRAFT REJECTION TYPES OF REJECTION C. Endothelial rejection  Classic rejection presents with endothelial rejection line (Khodadoust line : consist of mononuclear white cells) usually begins at vasculaized portion of peripheral graft-host junction & progress across endothelial surface  Damaged endothelium is unable to dehydrate corneal graft  cloudy & edematous stroma
  23. 23. CORNEAL ALLOGRAFT REJECTION CLINICAL FEATURES Tham and Abbott. International Ophthalmology Clinic 2002;42(1):105-113
  24. 24. CORNEAL ALLOGRAFT REJECTION Jerry Y. Niederkorn. Current Eye Research 2007; 32: 1005-1016
  25. 25. CORNEAL ALLOGRAFT REJECTION Tham and Abbott. International Ophthalmology Clinic 2002;42(1):105-113
  26. 26. CORNEAL ALLOGRAFT REJECTION IMMUNE MECHANISM  Inflamed cornea contribute to erosion of privilege  With inflammation  Bone marrow-derived cells are recruited into cornea through limbal circulation  Those cells capable of processing & presenting antigens  when inflammation is resolved  persist for months or years  The greater number of bone marrow-derived cells in host cornea at time of surgery the higher the rejection rate  Chronic inflammation induces generation of blood vessels & lymphatics in normally avascular cornea DJ Coster et al. Eye 2009; 23: 1894-1897
  27. 27. CORNEAL ALLOGRAFT REJECTION IMMUNE MECHANISM  With inflammation (cont.)  Induces vessels to leak, facilitating ingress of cells & proteins into cornea  Macrophage produce VEGF-C which induce growth of lymphatics  Pro-inflammatory cytokines gain access to cornea & anterior chamber  encourage rejection DJ Coster et al. Eye 2009; 23: 1894-1897
  28. 28. CORNEAL ALLOGRAFT REJECTION IMMUNE MECHANISM  Antigen processing can occur at cornea, ocular environs and draining lymph nodes  Recipient T cells recognition of donor MHC alloantigens plays central role in rejection by 2 mechanisms  Direct pathway : donor APCs are recognized directly by recipient T cells (important role in acute graft rejection)  Indirect pathway : recipient APCs process antigen then present it to recipient T cells (associated with chronic graft rejection)  Direct pathway weakens with time (donor APCs migrate out of graft) but indirect be permanently active cause of recipient APCs traffic through the graft DJ Coster et al. Eye 2009; 23: 1894-1897 Hongmei Fu et al. Transplantation Review 2008; 22: 105-115
  29. 29. CORNEAL ALLOGRAFT REJECTION IMMUNE MECHANISM conclusion Jerry Y. Niederkorn. Current Eye Research 2007; 32: 1005-1016
  30. 30. CORNEAL ALLOGRAFT REJECTION IMMUNE MECHANISM Jerry Y. Niederkorn. Current Eye Research 2007; 32: 1005-1016
  31. 31. CORNEAL ALLOGRAFT REJECTION IMMUNE MECHANISM Jerry Y. Niederkorn. Current Eye Research 2007; 32: 1005-1016
  32. 32. CORNEAL ALLOGRAFT REJECTION IMMUNE MECHANISM T.H. Flynn et al. American Journal of Transplantation 2008; 8: 1537-1543
  33. 33. CORNEAL ALLOGRAFT REJECTION IMMUNE MECHANISM T.H. Flynn et al. American Journal of Transplantation 2008; 8: 1537-1543
  34. 34. CORNEAL ALLOGRAFT REJECTION IMMUNE MECHANISM peripheral During Blood rejection rejection Aq. Humor peripheral control T.H. Flynn et al. American Journal of Transplantation 2008; 8: 1537-1543
  35. 35. CORNEAL ALLOGRAFT REJECTION IMMUNE MECHANISM cytometric bead array of inflammatory cytokines & chemokines T.H. Flynn et al. American Journal of Transplantation 2008; 8: 1537-1543
  36. 36. CORNEAL ALLOGRAFT REJECTION IMMUNE MECHANISM  Conclusion  Few absolute principles T cell-dependent Heavily depent upon CD4+ T cells Dependent upon intact repertoire of resident APC (macrophage, monocyte) T.H. Flynn et al. American Journal of Transplantation 2008; 8: 1537-1543
  37. 37. OUTLINES  STRUCTURE OF CORNEA, ENDOTHELIAL FUNCTION AND IMMUNE PRIVILEGE  CORNEAL ALLOGRAFT REJECTION  Keratoplasty  Risk factor & clinical features  Immune mechanism of corneal allograft rejection  PREVENTION & TREATMENT OF CORNEAL ALLOGRAFT REJECTION
  38. 38. PREVENTION OF CORNEAL ALLOGRAFT REJECTION  Incidence of corneal graft rejection from 2.3%-68% in different studies, at least one episode of rejection may occur 30% of graft  Polack(1973) report an incidence of homograft rejection in good prognosis cases to be 9–12%, whereas in retrospective study over 12 years Smiddy et al.(1986) state incidence to be approximately 16%  Overall  12% of low-risk  40% of high-risk  Rejection most common occurs 4-18 Mo following transplantation (may seen any time after surgery) 53.3% occurr during the 1st year after transplantation Alireza Baradaran-Rafii et al. Iranian Journal of Ophthalmic Research 2007; 2(1) : 7-14 Sangwan VS et al. Clin Experiment Ophthalmol 2005; 33(6):623-627
  39. 39. PREVENTION OF CORNEAL ALLOGRAFT REJECTION Dj Coster and KA Williams. Eye 2003; 17: 996-1002
  40. 40. PREVENTION OF CORNEAL ALLOGRAFT REJECTION  Low risk  Topical corticosteroids (prednisolone) still universally used for routine postoperative management during 1st 6 Mo, after 6 Mo generally prescribed less frequently  25% switch to loteprednol, 20% to fluorometholone in phakic patients (due to their lesser effect on intraocular pressure )  In Pseudophakic/Aphakic eyes topical corticosteroids (prednisolone) used as phakic patients but % usage of this preparation increased greater than the latter J. Bradley Randleman and R. Doyle Stulting. Cornea 2006; 25(3): 286-290
  41. 41. PREVENTION OF CORNEAL ALLOGRAFT REJECTION J. Bradley Randleman and R. Doyle Stulting. Cornea 2006; 25(3): 286-290
  42. 42. PREVENTION OF CORNEAL ALLOGRAFT REJECTION  Intermediate-high risk  Topical corticosteroids (prednisolone) still universally used for routine postoperative management during 1st 6 Mo, and remained high % usage after that  Topical cyclosporine is used about 48%, evidences are controversial  Sytemic steroids (oral)  In USA used lesser than before , compared in 1989 and 2004  In UK used greater than in USA J. Bradley Randleman and R. Doyle Stulting. Cornea 2006; 25(3): 286-290
  43. 43. PREVENTION OF CORNEAL ALLOGRAFT REJECTION J. Bradley Randleman and R. Doyle Stulting. Cornea 2006; 25(3): 286-290
  44. 44. PREVENTION OF CORNEAL ALLOGRAFT REJECTION J. Bradley Randleman and R. Doyle Stulting. Cornea 2006; 25(3): 286-290
  45. 45. PREVENTION OF CORNEAL ALLOGRAFT REJECTION Price MO and Price FW Jr. Ophthalmology 2006; 113(10): 1785-1790
  46. 46. PREVENTION OF CORNEAL ALLOGRAFT REJECTION regimen B had sig. more rejection than regimen A regimen C did not reduce incidence of rejection Price MO and Price FW Jr. Ophthalmology 2006; 113(10): 1785-1790
  47. 47. PREVENTION OF CORNEAL ALLOGRAFT REJECTION Alexander Poon FRANZCO et al. Clinical and Experimental Ophthalmology 2008; 36: 415-421
  48. 48. PREVENTION OF CORNEAL ALLOGRAFT REJECTION Alexander Poon FRANZCO et al. Clinical and Experimental Ophthalmology 2008; 36: 415-421
  49. 49. PREVENTION OF CORNEAL ALLOGRAFT REJECTION J. Bradley Randleman and R. Doyle Stulting. Cornea 2006; 25(3): 286-290
  50. 50. TREATMENT OF CORNEAL ALLOGRAFT REJECTION  Hill and colleagues (1991) demonstrated in prospective study that  IV methylprednisolone 500 mg single dose was more effective and better tolerated than daily oral prednisolone 60-80 mg when combined with topical steroids in graft rejection  Survival rate of graft 92% versus 55% when pts. were treated within 8 days of onset of symptoms (no difference in outcome in who presented later than day 8) Vivien M.-B. Tham and Richard L. Abbott. International Ophthalmology Clinics 2002; 42(1): 105-113
  51. 51. TREATMENT OF CORNEAL ALLOGRAFT REJECTION
  52. 52. TREATMENT OF CORNEAL ALLOGRAFT REJECTION J. Bradley Randleman and R. Doyle Stulting. Cornea 2006; 25(3): 286-290
  53. 53. TREATMENT OF CORNEAL ALLOGRAFT REJECTION T Hudde et al. British Journal of Ophthalmology 1999; 83: 1348-1352
  54. 54. TREATMENT OF CORNEAL ALLOGRAFT REJECTION T Hudde et al. British Journal of Ophthalmology 1999; 83: 1348-1352
  55. 55. TREATMENT OF CORNEAL ALLOGRAFT REJECTION  In case of mild rejection  Topical prednisolone acetate 1% hourly and dexamethasone ointment at night was sufficient to reverse the rejection  In severe case of rejection  Topical prednisolone acetate 1% hourly, one dose of pulsed IV methylprednisolone 500 mg and oral prednisolone 1 mg/kg/day for 5 days were recommended The collaborative corneal transplantation studies Arch Ophthalmol 1992;110:1392–1403 Vivien M.-B. Tham and Richard L. Abbott. International Ophthalmology Clinics 2002; 42(1): 105-113
  56. 56. TREATMENT OF CORNEAL ALLOGRAFT REJECTION  In severe case of rejection(cont.)  In 1989 Hill found that graft survival improved if systemic cyclosporine was used in addition to systemic & topical steroids (89%) compared to use of topical steroids alone (10%) Maximum effect was obtained if cyclosporine was used for 12 Mo (93% survival rate) compared with 6 Mo (69% survival rate) Vivien M.-B. Tham and Richard L. Abbott. International Ophthalmology Clinics 2002; 42(1): 105-113
  57. 57. TREATMENT OF CORNEAL ALLOGRAFT REJECTION  In severe case of rejection(cont.)  In1999 Alexander Reis et al. reported a prospectively randomised clinical trial about mycophenolate mofetil versus cyclosporn A Due to wide range of S/E of cyclosporin A (diabetogenicity, arterial hypertension, HLP, nephrotoxicity) which could be found about 10% and to need lab. monitoring of drug levels between 120-150 ng/ml  very costly Alexander Reis et al. British Journal of Ophthalmology 1999; 83: 1268-1271
  58. 58. TREATMENT OF CORNEAL ALLOGRAFT REJECTION MMF is just as effective as CSA in preventing acute rejection following high risk corneal transplantation Alexander Reis et al. British Journal of Ophthalmology 1999; 83: 1268-1271
  59. 59. TREATMENT OF CORNEAL ALLOGRAFT REJECTION  Recent study from Joseph A and colleagues found that systemic tacrolimus daily dose 2.5 mg is safe and effective in reducing rejection & prolonging graft survival in pts. With high-risk keratoplasty compared with pts who did not use. A Joseph et al. British Journal of Ophthalmology 2007; 91: 51-55
  60. 60. Mechanism of immunosuppressive
  61. 61. THANK YOU FOR YOUR ATTENTION

×