General indications

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  Optical keratoplasty is performed to improve vision. Important indications include keratoconus, scarring, corneal dystrophies ( Fig. 7.1A ), pseudophakic bullous keratopathy and corneal degenerations.

  
  

  
  

  
  

  

  
  

  
  

  (A) Optical penetrating keratoplasty for macular corneal dystrophy; (B) tectonic lamellar patch graft for descemetocoele; (C) penetrating keratoplasty for pseudomonas keratitis – a dense cataract and posterior synechiae are visible

  
  

  (Courtesy of S Tuft – fig. B)

  
  

  
  

  

  
  

  
  

  

  
  
  
  
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  Tectonic grafting may be carried out to restore or preserve corneal integrity in eyes with severe structural changes such as thinning with descemetocoele (US spelling – descemetocele; Fig. 7.1B ).

  
  
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  Therapeutic corneal transplantation facilitates removal of infected corneal tissue in eyes unresponsive to antimicrobial therapy ( Fig. 7.1C ).

  
  
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  Cosmetic grafting may be performed to improve the appearance of the eye, but is a rare indication.

Donor tissue

Donor tissue should be removed within 12–24 hours of death. There is an attempt to age-match donors and recipients; 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. Most corneas are stored in coordinating ‘eye banks’ prior to transplantation, where pre-release evaluation includes medical history review and donor blood screening to exclude contraindications, and microscopic examination of the cornea including endothelial cell count determination. Corneas are preserved in hypothermic storage (up to 7–10 days) or organ culture medium (4 weeks) until needed; culture allows extended testing for infective contamination. Contraindications to ocular tissue donation are set out below, though there is international variation and the list is not exhaustive:

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  Death from unknown cause.

  
  
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  Certain systemic infections such as human immunodeficiency virus (HIV), viral hepatitis, syphilis, congenital rubella, tuberculosis, septicaemia and active malaria.

  
  
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  Prior high-risk behaviour for HIV and hepatitis such as sex with someone HIV-positive, men who have sex with men, intravenous drug abuse and prostitution.

  
  
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  Within the last 12 months: sex with someone who has engaged in high-risk behaviour, or who lives in parts of Africa, or who has received blood clotting factor concentrates; tattooing, acupuncture or ear/body piercing; imprisonment.

  
  
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  Infectious and possibly infectious diseases of the central nervous system, such as Creutzfeldt–Jakob disease, systemic sclerosing panencephalitis, progressive multifocal leukoencephalopathy, encephalitis, Alzheimer disease and other dementias, Parkinson disease, multiple sclerosis and motor neurone disease.

  
  
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  Receipt of a transplanted organ.

  
  
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  Receipt of human pituitary-derived growth hormone.

  
  
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  Brain or spinal surgery before 1992.

  
  
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  Most haematological malignancies.

  
  
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  Ocular disease such as inflammation and disease likely to compromise graft outcome, some malignant ocular tumours (e.g. retinoblastoma) and corneal refractive surgery.

Recipient prognostic factors

The following host factors may adversely affect the prognosis of a corneal graft and if possible should be optimized prior to surgery. In general, the most favourable cases are keratoconus, localized scars and dystrophies.

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  Severe stromal vascularization ( Fig. 7.2 ), absence of corneal sensation, extreme thinning at the proposed host–graft junction and active corneal inflammation.

  
  

  
  

  
  

  

  
  

  
  

  Retroillumination of heavily vascularized cornea resulting from recurrent herpes simplex keratitis

  
  

  (Courtesy of C Barry)

  
  
  
  
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  Abnormalities of the eyelids, such as blepharitis, ectropion, entropion and trichiasis; these should be addressed before surgery.

  
  
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  Recurrent or progressive forms of conjunctival inflammation, such as atopic conjunctivitis and ocular cicatricial pemphigoid.

  
  
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  Tear film dysfunction.

  
  
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  Anterior synechiae.

  
  
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  Uncontrolled glaucoma.

  
  
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  Uveitis.

Postoperative management

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  Topical steroids (e.g. prednisolone acetate 1%, dexamethasone phosphate 0.1%) are used to decrease the risk of immunological graft rejection. Initial administration is typically every 2 hours with gradual tapering depending on the likelihood of rejection and clinical progress. Long-term instillation at low intensity, such as once daily for a year or more, is usual.

  
  
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  Other immunosuppressants such as oral azathioprine and topical and systemic ciclosporin are usually reserved for high-risk patients.

  
  
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  Cycloplegia (e.g. homatropine 2% twice daily) is typically used for 1–2 weeks.

  
  
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  Oral aciclovir may be used in the context of pre-existing herpes simplex keratitis to minimize the risk of recurrence.

  
  
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  Monitoring of IOP . Applanation tonometry is relatively unreliable so measurement is commonly performed during the early postoperative period with a non-applanation method.

  
  
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  Removal of sutures is performed when the graft–host junction has healed. This is often after 12–18 months, although in elderly patients it may take much longer. Removal of broken or loose individual sutures is performed as soon as identified, to avoid promoting rejection.

Postoperative complications

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  Early complications include persistent epithelial defects, loose or protruding sutures (risk of infection – Fig. 7.5A , marked sterile reaction, papillary hypertrophy), wound leak (sometimes with flat anterior chamber or iris prolapse), uveitis, elevation of intraocular pressure, traumatic graft rupture ( Fig. 7.5B ), cystoid macular oedema, microbial keratitis ( Fig. 7.5C ), endophthalmitis ( Fig. 7.5D ) and rejection (see below). A rare complication is a fixed dilated pupil (Urrets–Zavalia syndrome).

  
  

  
  

  
  

  

  
  

  
  

  Early postoperative complications. (A) Loose continuous suture with probable infection and rejection; (B) traumatic graft rupture and extrusion of intraocular lens implant; (C) microbial keratitis; (D) endophthalmitis

  
  

  (Courtesy of C Barry – fig. A; R Bates – fig. B; S Tuft – fig. D)

  
  

  
  

  

  
  

  
  

  

  
  

  
  

  

  
  
  
  
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  Late complications include astigmatism, recurrence of underlying disease, late wound dehiscence, retrocorneal membrane formation, glaucoma, rejection (see below) and failure without rejection.

Corneal graft rejection

Immunological rejection of any layer of the cornea can occur. Rejection of separate layers (endothelial, stromal and epithelial) can occur in isolation, but typically a combination is present. Simple graft failure can occur in the absence of rejection, although rejection is a common contributory factor.

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  Pathogenesis. The corneal graft is immunologically privileged, with an absence of blood vessels and lymphatics and the presence of relatively few antigen-presenting cells; inflammation and neovascularization contribute to loss of this privilege. Important predisposing factors for rejection include eccentric or larger grafts (over 8 mm in diameter), infection (particularly herpetic), glaucoma and previous keratoplasty. If the host becomes sensitized to histocompatibility antigens present in the donor cornea, rejection may result. Human leukocyte antigen (HLA) matching has a small beneficial effect on graft survival.

  
  
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  Symptoms. Blurred vision, redness, photophobia and pain are typical, but many cases are asymptomatic until rejection is established. The timing of onset is very variable, occurring from days to years after keratoplasty.

  
  
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  Signs vary depending on the type of graft.

  
  
  
  
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    Ciliary injection associated with anterior uveitis is an early manifestation ( Fig. 7.6A ).

    
    

    
    

    
    

    

    
    

    
    

    Allograft rejection. (A) Ciliary injection; (B) elevated epithelial line in epithelial rejection; (C) Krachmer spots; (D) endothelial rejection with Khodadoust line

    
    

    (Courtesy of S Tuft – figs A, B and C)

    
    

    
    

    

    
    

    
    

    

    
    

    
    

    

    
    
    
    
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    Epithelial rejection may be accompanied by an elevated line of abnormal epithelium ( Fig. 7.6B ) in a quiet or mildly inflamed eye, occurring at an average of 3 months; increased treatment may not be required.

    
    
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    Subepithelial rejection is characterized by subepithelial infiltrates, reminiscent of adenoviral infection (Krachmer spots – Fig. 7.6C ) on the donor cornea, with deeper oedema and infiltrative opacification.

    
    
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    Stromal rejection features deeper haze. It can be chronic or hyperacute, the latter in association with endothelial rejection.

    
    
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    Endothelial rejection is characterized by a linear pattern of keratic precipitates (Khodadoust line – Fig. 7.6D ) associated with an area of inflammation at the graft margin.

    
    
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    Stromal oedema is indicative of endothelial failure.

  
  
  
  
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  Management. Early intensive treatment greatly improves the likelihood of reversing the rejection. The most aggressive regimen is generally required for endothelial rejection, followed in order of severity by stromal, subepithelial and epithelial. Intraocular pressure monitoring is critical.

  
  
  
  
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    Preservative-free topical steroids hourly 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. High-risk patients can be maintained on the highest tolerated topical dose (e.g. prednisolone acetate 1% four times daily) for an extended period.

    
    
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    Topical cycloplegia (e.g. homatropine 2% or atropine 1% once or twice daily).

    
    
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    Topical ciclosporin 0.05% to 2% may be of benefit, but the onset of action is delayed.

    
    
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    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.

    
    
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    Subconjunctival steroid injection (e.g. 0.5 ml of 4 mg/ml dexamethasone) is sometimes used.

    
    
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    Other systemic immunosuppressants such as ciclosporin, tacrolimus or azathioprine.

  
  
  
  
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  Differential diagnosis includes graft failure (no inflammation), infective keratitis including fungal and herpetic, uveitis, sterile suture reaction, raised IOP and epithelial ingrowth.