PENETRATING KERATOPLASTY SEMINAR new.pptx

Penetrating keratoplasty

1. PENETRATING KERATOPLASTY PRESENTER- DR. VAISHALI BANSAL MODERATOR- DR. GAURAV KOHLI

2. KERATOPLASTY Corneal transplantation (grafting) refers to the replacement of diseased host corneal tissue by healthy donor cornea .

3. CLASSIFICATION OF KERATOPLASTY

4. A. AUTOKERATOPLASTY ROTATIONAL KEDRATOPLASTY In this, patient's own cornea is trephined Cornea is rotated to transfer the pupillary area having a small corneal opacity to the periphery.

5. CONTRALATERAL KERATOPLASTY Corneas of the two eyes are exchanged with each other. Indication- W hen cornea of one eye of the patient is opaque and the other eye is blind due to posterior segment disease (e.g. optic atrophy and retinal detachment, etc.) with clear cornea.

6. B. Allografting or Allo-keratoplasty Here the patient's diseased cornea is replaced by the donor's healthy cornea . It can be of following types: Penetrating keratoplasty (Full-thickness graft) Lamellar keratoplasty (Partial-thickness graft) Anterior lamellar (ALK) Posterior lamellar (PLK) Small patch graft - for small defects Full-thickness Partial-thickness

7. PENETRATING KERATOPLASTY Penetrating keratoplasty (PK) is the procedure of corneal transplantation comprising of replacement of the full thickness host corneal tissue with a full thickness donor corneal tissue. It can be- Simple- When only corneal transplantation is done. Combined- When keratoplasty is combined with other ocular surgeries.

8. COMBINED Procedure Penetrating keratoplasty may be combined with cataract surgery, secondary intraocular lens implantation, glaucoma surgery, and retinal surgery. In cases of combined retinal surgery, often a temporary keratoprosthesis is sutured in place first to allow for the retina surgeon to visualize the posterior segment. After completion of the retinal surgery, the temporary keratoprosthesis is replaced with the permanent corneal graft. Keratoprosthesis : Boston K-Pro type I

9. CLASSIFICATION OF PENETRATING KERATOPLASTY

10. INDICATIONS OPTICAL KERATOPLASTY Pseudophakic / aphakic corneal decompensation Stromal corneal dystrophies Granular dystrophy Lattice dystrophy Macular dystrophy Pseudophakic bullous keratopathy Corneal dystrophy

11. Primary corneal endotheliopathies Fuch's endothelial dystrophy Congenital hereditary endothelial dystrophy Posterior polymorphous dystrophy Iridocorneal endothelial syndrome Corneal ectasias and thinning Keratoconus Keratoglobus Fuch's endothelial dystrophy

12. Congenital corneal opacity Peter's anomaly Sclerocornea Congenital glaucoma/ buphthalmos . Acquired corneal scars Postviral keratitis Post infectious keratitis Healed keratomalacia Post-traumatic corneal/ corneo-iridic scars Post infectious keratitis corneo-iridic scar Peter's anomaly

13. Non-infectious ulcerative keratitis Post rheumatoid corneal melt Exposure keratopathy Immune corneal melts secondary to systemic vasculitides , keratoconjunctivitis sicca Moorens's ulcer. Corneal degenerations Failed corneal grafts Moorens's ulcer Post rheumatoid corneal melt

14. TECTONIC GRAFTING T o either reconstruct the ocular surface e.g. corneal perforations, descematocele T o strengthen the cornea. E.g. I n cases with corneal melts with thinning/ ectasias Post chemical injury corneal damage . Tectonic lamellar patch graft for descemetocoele

15. THERAPEUTIC CORNEAL TRANSPLANTATION Non-healing infectious keratitis Infectious keratitis with perforation Post chemical injury with corneal melt COSMETIC GRAFTING It may be performed to improve the appearance of the eye, but is a rare indication. Severe corneal ulcer with stromal necrosis and perforation

16. Contraindications to ocular tissue donation Death from unknown cause. Certain systemic infections such as human immunodeficiency virus (HIV), viral hepatitis, syphilis, congenital rubella, tuberculosis , septicaemia and active malaria. Prior high-risk behaviour for HIV and hepatitis. Within the last 12 months: sex with someone who has engaged in high-risk behaviour , who has received blood clotting factor concentrates or has undergone tattooing, acupuncture, ear/ body piercing.

17. Infectious diseases of the central nervous system, such as systemic sclerosing panencephalitis , encephalitis , Alzheimer disease, Parkinson disease, multiple sclerosis and motor neuron disease. Receipt of a transplanted organ. Receipt of human pituitary-derived growth hormone. Brain or spinal surgery. Most haematological malignancies. Ocular disease such as inflammation and disease likely to compromise graft outcome some malignant ocular tumours (e.g. retinoblastoma) C orneal refractive surgery.

18. DONOR TISSUE/graft characteristics Donor corneas must have been harvested from cadaveric donors within 6–8 hours after death. Sometimes, they can be harvested up to 12 hours after death in countries with cold climates or if the donor is refrigerated Corneas from infants (3 years and under) are used only very occasionally, even for paediatric transplants, as they are associated with surgical, refractive and rejection problems.

19. Blood (serum or plasma) must test non-reactive to the following required infectious diseases : Human Immunodeficiency Virus Types 1 and 2: anti -HIV-1 , anti-HIV-2 Hepatitis C Virus (HCV): anti-HCV Hepatitis B Virus (HBV): HBsAg Syphilis COVID-19 The corneal-scleral segment should have been examined grossly for clarity, epithelial defects, foreign objects and contamination and scleral color. e.g., jaundice.

20. The graft tissue should have been stored in appropriate storage media depending upon the duration of storage. Slit lamp biomicroscopy should have been performed to look for corneal scars, significant arcus , edema , folds, striae , epithelial defects, guttata changes,foreign bodies and infiltrates. Adequate endothelial cell count must be evaluated using Specular microscopy. Cornea thickness should be adequate.

21. PROGNOSis after surgery Description of outcomes after corneal grafting surgery has been elaborated in four major categories by Buxton et al . Group 1: Excellent prognosis with expected success rate of > 90 percent Keratoconus Central/ paracentral corneal scars Stromal dystrophy-granular, lattice Early central Fuch's endothelial dystrophy Stromal dystrophy-granular

22. Group 2 : Very good prognosis with expected success rate of 80 to 90 percent Advanced Fuch's endothelial dystrophy Aphakic / pseudophakic corneal edema and bullous keratopathy Inactive herpetic keratitis Macular stromal dystrophy Pseudophakic bullous keratopathy Macular stromal dystrophy

23. Group 3: Fair prognosis with expected success rate of 50 to 80 percent Active microbial keratitis Active herpetic keratitis Congenital hereditary endothelial dystrophy Corneal grafts in young children Mild chemical injury Moderate keratoconjunctivitis sicca Active herpetic keratitis Moderate keratoconjunctivitis sicca

24. Group 4: Poor prognosis with expected success rate of < 50 percent Severe chemical injury Radiation injury Ocular cicatricial pemphigoid Stevens-Johnson's syndrome Neuroparalytic disease Congenital glaucoma Epithelial downgrowth Anterior segment mesodermal dysgenesis Multiple failed graft Ocular cicatricial pemphigoid

25. STEPS OF PENETRATING KERATOPLASTY GLOBE EXPOSURE- Appropriate sized lid speculum with proper positioning is imperative to minimize pressure on the lids which might produce undue increase in IOP during surgery and globe distortion.

26. SCLERAL FIXATION RING Scleral fixation ring is secured on to the globe with four interrupted 7-0 vicryl (or 5-0 dacron sutures) with partial thickness scleral bites. The size of the fixation ring is chosen such that its diameter is slightly less than the interpalpebral fissure size. Too large a ring may transmit undue pressure on to the globe

27. HOST CORNEA MARKING The donor cornea graft is to be centered on the host cornea or the pupillary axis which is usually slightly nasal. The optical axis is marked using gentian violet or marking pen . A stained 8 or 12 prong radial marker may be used to mark the corneal surface for placement of sutures for better alignment and symmetry

28. TREPHINE SIZING An epithelial mark is placed on the cornea by gentle pressure using the trephine of the desired size. Selection of host trephine size depends on various factors which include: Host cornea size Host corneal pathology Rejection risk.

29. H ost cornea diameter = 11.5 mm or less: Host trephine size = 7.5 mm or 7.75 mm H ost cornea diameter = 12.5 mm or more- Host trephine size = 8.25 mm or 8.5 mm The donor trephine size is usually 0.25 mm larger than the host trephine size as current surgical technique utilizes donor corneal tissue cut from the endothelial side. Inferior decentered penetrating keratoplasty in a case of corneo-iridic scar

30. DONOR CORNEA TREPHINATION The donor corneoscleral button is placed on the Teflon block, endothelial side up, with meticulous attention to proper centration It is cut by punching from the endothelial side using the trephine of the appropriate size. Donor corneal tissue may be submerged in storage media or coated with ocular visco -elastic such as viscoat to enable optimal endothelial protection . O ptimal cut- Perpendicular cut edges with minimal trauma to the donor endothelium.

31. HOST CORNEA TREPHINATION Done with Suction trephines Handheld trephines Suction trephine systems such as the Hessberg -Baron or Hanna trephine systems enable performing uniformly perpendicular cuts with less tilting . After obtaining adequate suction, the trephine is continuously rotated allowing its sharp edges to penetrate into the host corneal tissue up to 90 percent depth or till anterior chamber is entered .

32. The anterior chamber entry is performed using a sharp blade The host cut is then completed with beveled corneoscleral scissors. Any tag of tissue remaining is trimmed using a Vannas scissors Excision of host tissue. (A) Partial-thickness trephination; (B) incision into the anterior chamber; (C) and (D) completion of excision

33. DONOR TISSUE PLACEMENT ON RECIPIENT BED After filling the anterior chamber with visco -elastic, the prepared donor corneal button is placed on the recipient window and rotated carefully into optimal position. Care is taken to avoid contact of the endothelium with iris surface or with instruments.

34. SUTURING OF DONOR CORNEAL TISSUE Placement of cardinal sutures: Given using 10.0 monofilament nylon interrupted suture Ist cardinal suture- at the 12 O'clock position at approximately 90 percent tissue depth . Second cardinal suture- at 180° away, at the 6 O'clock position. 3 rd cardinal suture- At 3 O’clock position 4 th cardinal suture- at 9 o’clock position

35. Fixation of donor button

36. Suturing is then finished with an additional 12 radial interrupted sutures or alternatively a continuous suture technique can be employed. The knots are rotated and buried on the donor side . A subconjunctival injection of antibiotic and steroid is administered and an eye pad with a shield or bandage is applied

37. TYPES OF SUTURING CONTINUOUS INTERRUPTED TYPE (IF ANY) TORQUE ANTI TORQUE INDICATION Eyes with inflammation/vascularised cornea Difficulty to follow-up cases Vascularization in host corneal bed Multiple failed grafts Inflammatory conditions P ediatric grafts Therapeutic grafts Host bed with irregular thickness SUTURE USED 10-0 monofilament nylon suture 10.0 monofilament nylon with a 160° curved spatulated 6 mm needle ADVANTAGE Incite least inflammation Impede vascular in growth Enables adjusting suture tension in the early postoperative period in order to control astigmatism. Ease of placement and removal Early visualisation Rapid wound healing Selective suture removal of interrupted sutures for control of astigmatism or vascularization cases without compromising wound integrity DISADVANTAGE Slow healing If one breaks, entire suture becomes loose Long interval before removal Flattening Fragments can be retained while removal

38. KEY SURGICAL POINTS- A common graft size is 7.5 mm. Smaller grafts may lead to high astigmatism L arger diameters are associated with an increasing tendency to peripheral anterior synechiae formation and raised intraocular pressure (IOP). The donor button is usually about 0.25 mm larger in diameter than the host site. Preparation of donor cornea should always precede excision of host tissue, in case a problem with the former means that the surgery cannot be completed.

39. Suture depth should be approximately 90% of the corneal stroma to avoid full thickness penetration and later suture removal. It is imperative to bury all of the knots . A preferred technique is to bury them in the anterior stroma on the donor side with suture tails pointed away from the epithelium to aid in easy suture removal and reduce the number of broken sutures. Selective suture removal can begin around 4 months when there is adequate healing of the graft-host junction.

40. Postoperative Care Postoperatively, the donor epithelium is shed off, leading to an early postoperative epithelial defect which is then replaced with host epithelium and heals in the next 3–5 days . The early postoperative period is focused on decreasing inflammation and avoiding infection. Inflammation can be controlled with topical steroids drops, initially prednisolone 1% used every 2 hours, then decreasing to 4 times daily for approximately 4 months before tapering further. Topical antibiotic drops can be used 4 times daily for approximately 1 month.

41. Visual recovery could be immediate or take a few months due to initial graft oedema and astigmatism. Follow-up is weekly or fortnightly for the first 3 months and then monthly till 6 months, every 2 months for 1 year and yearly thereafter.

42. Complications INTRAOPERATIVE COMPLICATIONS Intraoperative Complications-Related to the Surgical Technique Scleral Perforation: Scleral perforation during the time of placement of bridle sutures of the recti or at the time of placement of the scleral fixation ring can occur . Prevention- Careful suture placement using partial thickness bites with rounded rather than cutting needles. Management- Eye is to patched following cryotherapy and followed up closely postoperatively.

43. Problems Related to Trephination: Due to improper sizing of trephines: U se of smaller size trephine for donor cornea- difficulty in suturing the donor tissue onto the recipient bed and securing water tight closure. Postoperative flat corneal curvature and hyperopia might result. Angle compression due to tight sutures also leads to rise in postoperative intraocular pressure Due to eccentric trephination: Due to improper centration of the trephine on the host cornea leading to increased astigmatism and risk of rejection.

44. Due to improper trephination: Damage to the donor button may occur due to partial trephine cut requiring repunching and resulting in significant endoth elial damage. Inadvertent dropping of donor tissue before or after trephination will also severely damage the donor endothelium and increase the risk of microbial contamination.

45. Irido -lenticular damage: Full thickness trephination of the host cornea, either in one region or 360° will result in damage to the iris tissue or the lens. Prevention- Achieving proper globe hypotony , inflating anterior chamber with viscoelastics prior to host bed trephination, partial thickness trephination followed by blade entry, pupillary constriction with miotics . Management- Repair of damaged iris tissue and lens extraction with intraocular lens implant is to be performed.

46. Retained Descemet's Membrane: Due to placement of the corneoscleral scissors anterior to the Descemet's membrane while completing the trephine cut. Results in inadvertent retaining of the host Descemet's membrane leading to postoperative double chamber formation and subsequent clouding and failure of the graft. Management: Retained descemet’s membrane has to be carefully identified and dissected out. Careful postoperative evaluation and early intervention to remove the membrane or YAG laser opening to maintain the health of the donor graft.

47. Endothelial damage- May also occur due to iris, lenticular or intraocular lens touch during surgery, when the anterior chamber is not optimally reformed. Increased instrumentation in the anterior chamber during surgery can also lead to endothelial decompensation . May lead to primary graft failure.

48. Intraocular Hemorrhage: Bleeding into the anterior chamber may occur in cases of visualized corneo-iridic scars, during intraocular lens explantation in cases of pseudophakic bullous keratopathy , iridodialysis or synechiolyis at the angle in cases of therapeutic keratoplasty for severe microbial keratitis.

49. Management- Mild hemorrhage can be ignored. Severe bleeding might get controlled only with rapid restoration of intraocular pressure by suturing the donor tissue into place. Use of cellulose sponges soaked in 1:1000 dilutions adrenaline might help. Vitreous Loss: Posterior capsular dehiscence with vitreous loss may complicate combined surgery involving penetrating keratoplasty and cataract extraction with lens implantation

50. Management- Decreasing positive vitreous pressure with good preoperative and intraoperative hypotony will greatly serve to reduce this complication. In the event of posterior capsular rupture, adequate anterior vitrectomy and peripheral iridectomy are mandatory before placement of the intraocular lens either in the capsular bad or in the sulcus

51. 2. Intraoperative Complications- Unrelated to the Surgical Technique Expulsive Choroidal Hemorrhage: Risk factors- Inflammed eyes, trauma, myopia, glaucoma, and advanced age Prevention- Good preoperative hypotony with ideal anaesthesia and akinesia , ocular massage, achieving adequate vitreous detergence, control of pre-existing glaucoma, systemic hypertension control.

52. Slow globe decompression during entry of the anterior chamber is strongly recommended. Management- Wound closure with the thumb or finger and immediate posterior sclerotomy via a stab incision in the conjunctiva in the inferotemporal quadrant in order to allow the blood contents to egress. Multiple sclerotomies may be necessary. In the event of unsalvageable damage, evisceration might be the only option left

53. POSTOPERATIVE COMPLICATIONS- Immediate post-op complications- Wound leak: Wound leak in the early postoperative period leads to a shallow or flat anterior chamber with low intraocular pressure. If the anterior chamber remains formed in the presence of wound leak, a pressure patch or bandage contact lens might help to tamponade the leak. Persistent epithelial defect Postoperative inflammation Persistent epithelial defect

54. Suture related infiltrates Suture induced vascularization Raised intraocular pressure Pupillary block Anterior synechiae formation Choroidal detachment/ hemorrhage Suture induced vascularization Anterior synechiae

55. Late post-op complications- Post-PK astigmatism Graft infection Graft rejection Post-PK glaucoma

56.  GRAFT REJECTION Corneal graft rejection is defined as a complex immune-mediated process resulting in decompensation of the transplanted cornea . It is characterized by one of the following- Development of epithelial and or endothelial rejection line and stromal rejection line Recent unilateral anterior chamber reaction with keratic precipitates. Increase in corneal thickness (edema) in a previously clear compact graft with visible aqueous cells.

57. The process usually starts at three weeks or more in a successful clear graft The inflammatory process is limited primarily to the graft The process starts at graft margin nearest to the most proximal blood vessel There is movement of the inflammatory reaction towards the center to involve the entire graft PATHOPHYSIOLOGY- Corneal graft rejection is primarily a cell mediated response controlled by the CD4+ T cell . Inflammation and trauma induces vessels and lymphatics growth into the cornea

58. Inflammatory stimuli attract antigen presenting cells (APC) into the central corneal stroma . The recognition of the foreign histocompatibility antigens on the cells of the corneal allografts by the host immune system leads to the initiation of the immune cascade-afferent immune response arm It results in host sensitization followed by a efferent immune response arm, which comprises of specific immune response against these antigens, producing decompensation of the graft tissue.

59. RISK FACTORS- Donor factors A ntigenic load of the donor depending upon the HLA and ABO compatibility between the donor and host. Method and duration of storage of the donor cornea and nature of donor button cutting. Influenza vaccination precipitating a bilateral graft rejection and rejection following vaccination Host factors- Vascularization of the host cornea Previously rejected graft

60. Ocular surface diseases such as severe dry eye, severe chemical burns, radiation burns, ocular pemphigoid , Stevens-Johnson syndrome and neuroparalytic disease Inflammation due to active keratitis (bacterial, viral or fungal) Young patients B ilateral graft Post immunized patients and patients with high T4/T8 ratio Atopic dermatitis Number of previous grafts History of previous anterior segment surgery Ocular pemphigoid Viral keratitis

61. Preoperative glaucoma Quadrants of anterior synechiae Quadrants of stromal vessels A primary diagnosis of chemical burn Blood group ABO incompatibility Herpetic eye disease Pilocarpine therapy Excimer laser phototherapeutic keratectomy Deep corneal stromal vessels

62. CLASSIFICATION- Corneal graft rejection can be classified as: Epithelial rejection Chronic stromal rejection Hyperacute stromal rejection Chronic focal rejection or endothelial rejection.

63. Sub epithelial infiltrates known as Krachmer spots Epithelial rejection line

64. Khodadoust Line : Endothelial rejection is characterized by a linear pattern of keratic precipitates.

65. MANAGEMENT PREVENTION Preoperative measures to minimizing antigenic difference between the host and the donor tissue. Intraoperative factors consist of adopting meticulous surgical technique including avoiding decentration of the recipient bed trephination, optimal suturing and good graft host apposition. Postoperative measures include controlling or alleviating the host immune response to the foreign donor tissue. Need for optimal postoperative care and close follow-up of keratoplasty patients for timely interventions in terms of suture management.

66. TREATMENT Early intensive treatment greatly improves the likelihood of reversing the rejection. The most aggressive regimen is generally required for endothelial rejection, followed by stromal, sub-epithelial and epithelial. Intraocular pressure monitoring is critical. Preservative-free topical steroids H ourly for 24 hours are the mainstay of therapy. The frequency is reduced gradually over several weeks. Steroid ointment can be used at bedtime as the regimen is tapered.

67. B. Topical cycloplegia e.g . Homatropine 2% or atropine 1% once or twice daily C. Cytotoxic agents- Azathioprine- It inhibits cell replication during a specific phase of the cell cycle, so it is helpful in early phase of rejection but not in late phase. Given in a dose of 1-2 mg/kg/day orally along with topical corticosteroids. Cyclosporine A ( CsA )- It is an immunomodulator and works on T cells by binding to the intracellular peptide- cyclophilin . It inhibits antigen presentation and thus lymphokine production. a) Topical Cyclosporine A (0.05 % to 2 %)- Given QID along with the topical corticosteroid drop in high-risk patients both pre and post operatively.

68. Systemic CsA - Recommended dosage is 15 mg/kg/day for two days followed by 7.5 mg/kg/day for two days and then adjusted to maintain trough blood levels of 100-200 µg/l for six months after reversal of acute rejection episode . Combined methyl prednisolone and CsA therapy : Combined intravenous pulse methylprednisolone and oral CsA in the treatment of acute corneal graft rejection is safe and effective in reversing the rejection process D. Systemic steroids Oral prednisolone 1 mg/kg/day for 1–2 weeks with subsequent tapering. If given within 8 days of onset, intravenous methylprednisolone 500 mg daily for up to 3 days may be particularly effective, suppressing rejection and reducing the risk of further episodes.

69. D. Newer immunomodulatory agents- Tacrolimus Rapamycin 15-deoxyspergualin (DSG) Mycophenolate mofetil (MMF)

70. Graft Failure Graft failure is characterized by dysfunction of endothelial cells and subsequent irreversible corneal edema . Primary graft failure occurs in the early postoperative period and can be due to issues with the donor tissue or surgical trauma. Secondary graft failure occurs in a graft which was initially clear but becomes irreversibly cloudy. The risk of secondary graft failure can be related to donor characteristics such as age, episodes of rejection, or need for subsequent surgeries. The treatment for graft failure is repeat corneal transplant.