1. Corneal Transplantation 1 PHRM-520,L.S.No-5.1

2. Review of Corneal Anatomy 1. Epithelium 2. Bowman’s layer 3. Stroma 4. Descemets 5. Endothelial layer 2

3. Endothelial layer Born with approx 4200 cells/mm 2 Born with approx 4200 cells/mm 2 Cells have a pump mechanism for removing fluid from the cornea Cells have a pump mechanism for removing fluid from the cornea No ability to replicate No ability to replicate Cell death throughout life Cell death throughout life Cells are easily injured Cells are easily injured Normal adult count 2800 c/mm 2 Normal adult count 2800 c/mm 2 Gross corneal edema with vision Gross corneal edema with vision change if <800 cells/mm 2 change if <800 cells/mm 2 3

4. Indications for Corneal Transplantation Lack of corneal clarity (scar) Lack of corneal clarity (scar) Corneal curvature abnormalities (ectasia) Corneal curvature abnormalities (ectasia) Corneal edema Corneal edema Lack of corneal integrity Lack of corneal integrity 4

5. Why Corneal Grafting? Corneal Opacity Corneal Opacity Corneal Clouding Corneal Clouding Corneal Ectasias Corneal Ectasias Corneal Edema Corneal Edema Fuchs Endothelial Dystrophy Fuchs Endothelial Dystrophy 5

6. Corneal Opacity Corneal scarring from firework accident 6

7. Corneal Clouding Granular stromal dystrophyFungal keratitis 7

8. Corneal Clouding 8

9. Corneal Ectasias Keratoconus- progressive corneal thinning and steepening. Presents in late teens and causes astigmatism that may not be correctable with glasses or rigid contact lenses Keratoconus- progressive corneal thinning and steepening. Presents in late teens and causes astigmatism that may not be correctable with glasses or rigid contact lenses Pellucid marginal degeneration Pellucid marginal degeneration 9

10. Corneal Edema Pseudophakic bullous keratopathy (PBK) – swelling related to endothelial dysfunction. Common problem with early lens implants. Pseudophakic bullous keratopathy (PBK) – swelling related to endothelial dysfunction. Common problem with early lens implants. 10

11. Fuchs Endothelial Dystrophy Inherited condition- AD w/ variable penetrance. Endothelial cells die at a faster rate due to corneal guttata. Poor vision due to edema, or to glare caused by the guttata. Inherited condition- AD w/ variable penetrance. Endothelial cells die at a faster rate due to corneal guttata. Poor vision due to edema, or to glare caused by the guttata. 11

12. Fuchs 12

13. Loss of corneal Integrity Corneal perforation or melt (infectious or rheumatologic) Corneal perforation or melt (infectious or rheumatologic) Infectious melt due to wire injury One month post-op PK 13

14. History 1906 – Dr. Eduard Konrad Zirm in Moravia performed the first successful penetrating keratoplasty (PK) on a farmer in Prague who sustained bilateral alkali burns after cleaning his chicken coop with lime. Bilateral 5 mm grafts from a single donor (11 yo boy who required enucleation) 1906 – Dr. Eduard Konrad Zirm in Moravia performed the first successful penetrating keratoplasty (PK) on a farmer in Prague who sustained bilateral alkali burns after cleaning his chicken coop with lime. Bilateral 5 mm grafts from a single donor (11 yo boy who required enucleation) 14

15. History Essential Principles (still in use) Essential Principles (still in use) 1. Donor must be human 2. Aseptic technique 3. No antiseptic agents should go on cornea 4. Protect graft w/ saline moistened gauze 15

16. Limitations good understanding of corneal physiology or immunology good understanding of corneal physiology or immunology fine sutures or operating microscope fine sutures or operating microscope pharmacologic ability to treat or prevent rejection pharmacologic ability to treat or prevent rejection 16

17. History Elschnig (Prague) 1920 report first clinical series of corneal transplants Elschnig (Prague) 1920 report first clinical series of corneal transplants Reported another series of 174- confirmed partial PK better then total. 22% success rate (graft clarity) Reported another series of 174- confirmed partial PK better then total. 22% success rate (graft clarity) Filatov (Odessa) reported 800 grafts from 1922-1945, started to use cadaver corneas Filatov (Odessa) reported 800 grafts from 1922-1945, started to use cadaver corneas 17

18. History Ramon Castroviejo (New York) 1930’s designed a square graft “watermelon plug” to have better wound coaptation. Improved suturing and instrumentation. Ramon Castroviejo (New York) 1930’s designed a square graft “watermelon plug” to have better wound coaptation. Improved suturing and instrumentation. 18

19. von Hippel clockwork trephine (trephine: a surgical instrument for cutting out circular sections) 19

20. History 1945 R. Townley Paton started the first Eye Bank in NYC. Early tissue was acquired from prisoners executed at Sing-Sing prison 1945 R. Townley Paton started the first Eye Bank in NYC. Early tissue was acquired from prisoners executed at Sing-Sing prison A. Edward Maumenee at Wilmer Eye Hospital advanced the field with his work in corneal physiology and immunology. A. Edward Maumenee at Wilmer Eye Hospital advanced the field with his work in corneal physiology and immunology. Coincided w/ the advent of topical corticosteroids which had a profound effect on modern corneal transplantation Coincided w/ the advent of topical corticosteroids which had a profound effect on modern corneal transplantation Surgical success was followed by optical success Surgical success was followed by optical success 20

21. 1950 to present Operating microscope Operating microscope New trephines and laser trephination New trephines and laser trephination New suture needles New suture needles Viscoelastics Viscoelastics Steroids and other immunomodulators Steroids and other immunomodulators Better antibiotics Better antibiotics Eye Bank Association of America (1961) Eye Bank Association of America (1961) Improved storage medium for donor corneas Improved storage medium for donor corneas 21

22. Eye Bank Association of America contraindications for donor corneas Death of unknown cause Death of unknown cause Unknown central nervous system disease Unknown central nervous system disease Infections including HIV or hepatitis Infections including HIV or hepatitis Active ocular inflammation Active ocular inflammation Leukemia or lymphoma Leukemia or lymphoma Cancer in the eye Cancer in the eye Congenital corneal dystrophies or ectasias (e.g. keratoconus) Congenital corneal dystrophies or ectasias (e.g. keratoconus) Prior refractive surgery (e.g. LASIK) Prior refractive surgery (e.g. LASIK) 22

23. Storage Media Optisol GS allows for storage up to 10 days. Allows surgery to be scheduled electively Optisol GS allows for storage up to 10 days. Allows surgery to be scheduled electively D to P (death to preservation) preferably less than 12 hours D to P (death to preservation) preferably less than 12 hours 23

24. Types of Corneal Transplants Penetrating keratoplasty (PK) Penetrating keratoplasty (PK) Lamellar keratoplasty (LK) Lamellar keratoplasty (LK) Anterior lamellar keratoplasty (ALK) Anterior lamellar keratoplasty (ALK) Deep anterior lamellar keratoplasty (DALK) Deep anterior lamellar keratoplasty (DALK) Posterior lamellar keratoplasty (PLK) Posterior lamellar keratoplasty (PLK) Endothelial keratoplasty (EK) Endothelial keratoplasty (EK) Deep lamellar endothelial keratoplasty (DLEK) Deep lamellar endothelial keratoplasty (DLEK) Descemet’s stripping endothelial keratoplasty (DSEK) Descemet’s stripping endothelial keratoplasty (DSEK) 24

25. PK Surgery: Full Thickness Surgery Recipient tissue removed Donor tissue sutured into recipient Smooth Surface with only endothelial disease Full thickness block of tissue removed just to get to the endothelium Central trephine cut made made Sutures create an irregular surface with astigmatism and blurring 25

26. PK instruments  Trephine with suction for host cornea Donor cornea punch  26

27. Penetrating keratoplasty for keratoconus 27

28. Penetrating keratoplasty 28

29. Indications for corneal transplant Indication1970s (%)1980s (%)1990(%) PBK1.7 18.9 21.1 ABK9.2 8.4 4.0 Fuchs6.4 10.6 13.4 Keratoconus16.5 16.0 13.4 Regrafts26.2 18.9 11.8 Scars4.2 7.3 0.4 Ulcers2.7 3.0 4.6 Corneal dystrophy4.7 2.5 2.8 Chemical Burn3.2 0.6 0.4 Trauma3.7 2.1 2.0 Interstitial keratitis5.8 2.2 0.3 Congenital0.4 0.6 1.3 Virus12.1 5.5 1.4 Other3.0 3.3 23.1 29

30. Problems with PK: Unpredictable astigmatism and corneal power Unpredictable astigmatism and corneal power Infection Infection Ulceration Ulceration Vascularization Vascularization Rejection Rejection Poor Wound Healing: Risk of Rupture Poor Wound Healing: Risk of Rupture 30

31. Severe Complications of Penetrating Keratoplasty: Suture Problems and Wound Healing Problems Endophthalmitis: From retained suture fragment Expulsive Hemorrhage: From mild blunt trauma five years after PK 31

32. Deep Lamellar Endothelial Keratoplasty First described by Dr. Gerrit Melles- 1998 First described by Dr. Gerrit Melles- 1998 First done in the US by Mark Terry, M.D. First done in the US by Mark Terry, M.D. Terry has done> 250 between 2000-05 Terry has done> 250 between 2000-05 Terry has trained> 100 cornea specialists to perform DLEK, and formed EKG (Endothelial Keratoplasty Group) Terry has trained> 100 cornea specialists to perform DLEK, and formed EKG (Endothelial Keratoplasty Group) Initially all procedures done under IRB Initially all procedures done under IRB 32

33. DLEK Surgery: Split Thickness Surgery to replace only the diseased tissue Recipient tissue removed Donor tissue placed into recipient Scleral incision, deep corneal pocket, and endothelium trephined with Terry Trephine Just endothelium on posterior stromal disc removed from pocket Endothelium replaced with no sutures, supported by air bubble in anterior chamber. Surface remains smooth with no astigmatism 33

34. EK Large air bubble is left in the eye at the end of surgery to help support the graft while adhering. Patient is to be supine the rest of the day and night Large air bubble is left in the eye at the end of surgery to help support the graft while adhering. Patient is to be supine the rest of the day and night If the bubble is too big, pupillary block glaucoma can occur If the bubble is too big, pupillary block glaucoma can occur 34

35. Advantages of EK over PK Faster visual recovery Faster visual recovery Less postoperative astigmatism (confirmed by corneal topography) Less postoperative astigmatism (confirmed by corneal topography) Stronger globe integrity due to lack of full- thickness corneal incision Stronger globe integrity due to lack of full- thickness corneal incision No suture related infections No suture related infections 35

36. Disadvantages of DLEK More time consuming and difficult procedure due to lamellar dissection More time consuming and difficult procedure due to lamellar dissection Graft dislocation- 5-20% on post-op day 1 Graft dislocation- 5-20% on post-op day 1 Not as many patients get to 20/20 as with PK; may be interface problem Not as many patients get to 20/20 as with PK; may be interface problem 36

37. DSEK- Descemets Stripping Endothelial Keratoplasty 2005 Price, Gorovoy- eliminated the recipient dissection by just removing descemets membrane and the endothelium 2005 Price, Gorovoy- eliminated the recipient dissection by just removing descemets membrane and the endothelium Surgeon still had to perform the lamellar dissection on the donor. If it went badly, the tissue was wasted. Surgeon still had to perform the lamellar dissection on the donor. If it went badly, the tissue was wasted. 37

38. DSAEK Replaced donor dissection with a cut made by an automated lamellar keratome (used for LASIK refractive surgery) Replaced donor dissection with a cut made by an automated lamellar keratome (used for LASIK refractive surgery) Cut can be made by the surgeon or at the eye bank Cut can be made by the surgeon or at the eye bank 38

39. DSAEK at UVA We undertook an IRB approved prospective study to look at the DSAEK procedure as described by Terry (Ophthalmology 2008; 115:1179-1186) We undertook an IRB approved prospective study to look at the DSAEK procedure as described by Terry (Ophthalmology 2008; 115:1179-1186) Dr. Paul Phillips (previous resident at UVA and Terry fellow 2007-2008) performed initial procedures and taught LAO Dr. Paul Phillips (previous resident at UVA and Terry fellow 2007-2008) performed initial procedures and taught LAO Strictly followed the procedure Strictly followed the procedure First case performed 9/16/09 First case performed 9/16/09 All tissue was pre-cut at Portland Eye Bank All tissue was pre-cut at Portland Eye Bank 39

40. DSAEK: Complications Dislocation Primary Graft Failure Price (n=200) (n=200)8%2% Mearza (n=11) (n=11)83%9% Koenig (n=34) (n=34)27%9% Terry (n=200) (n=200)1.5%0% 40

41. Cases – J.S 62 yo F w/ Fuchs 62 yo F w/ Fuchs LAO did PK OD 8/03 – did “well” LAO did PK OD 8/03 – did “well” 20/40 -3.25+4.75x025 (unable to tolerate RGP) 20/40 -3.25+4.75x025 (unable to tolerate RGP) 9/16/09 TCC Phaco/IOL and 8.0mm DSAEK – PP 9/16/09 TCC Phaco/IOL and 8.0mm DSAEK – PP 20/25 Va unaided at 1 month post-op 20/25 Va unaided at 1 month post-op VERY HAPPY patient VERY HAPPY patient 41

42. P.R. 58 yo F w/ Fuchs 58 yo F w/ Fuchs LAO did PK OS 5/05 – did “well” LAO did PK OS 5/05 – did “well” 20/30 +4.50+1.25x055 20/30 +4.50+1.25x055 5/19/09 TCC Phaco/IOL and 8.0mm DSAEK – LAO 5/19/09 TCC Phaco/IOL and 8.0mm DSAEK – LAO 20/20-1 unaided 1 month post-op 20/20-1 unaided 1 month post-op VERY HAPPY patient VERY HAPPY patient 42

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46. Summary Corneal transplantation has evolved dramatically over the past century. Corneal transplantation has evolved dramatically over the past century. The most recent advances have allowed the procedure to become less invasive and more optically successful for the recipient, but more challenging for the surgeon. The most recent advances have allowed the procedure to become less invasive and more optically successful for the recipient, but more challenging for the surgeon. 46

47. Thank You 47