Corneal Transplant Rejection

The CMGs are guidelines on the diagnosis and management of a range of common and rare, but important, eye conditions that present with varying frequency in primary and first contact care. *GRADE recommendations always relate to the recommendation immediately above*

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Corneal Transplant Rejection







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Corneal transplant rejection is the most common cause of transplant failure in the post-operative period. 30% of transplanted corneas experience at least one episode of immune rejection, and a proportion of these lead to eventual transplant failure. The incidence of graft rejection depends on the presence of risk characteristics, e.g. corneal neovascularization

Corneal transplant rejection may be reversible or irreversible and can affect both full thickness and lamellar transplants, although rejection may be less common following lamellar procedures

Predisposing factors

  • host corneal stromal vascularisation
    – for example, risk doubled if all four quadrants involved
  • young recipient
  • donor/recipient gender mismatch
    – male donor to female recipient
  • large diameter or eccentric transplant
  • loose or exposed sutures
  • recent decrease in steroid therapy
  • previous rejection
  • previous transplant in the same eye
  • iris adhesion to transplant/host interface
  • time since operation: most rejections occur with one year of surgery, but can occur at any time
  • Herpes simplex, bacterial or other infection
  • inflammatory disease (e.g. anterior uveitis)
  • glaucoma
  • subsequent intra-ocular surgery (e.g. cataract surgery, vitrectomy)
  • tear deficiency
  • trauma (chemical, mechanical)


  • photophobia
  • redness (may be perilimbal)
  • epiphora
  • blurred vision
  • discomfort or pain


Following full-thickness corneal transplantation (Penatrating Keratoplasty, PK), rejection may involve any cellular layer of the cornea (epithelium, stroma or endothelium). Of these, endothelial rejection is potentially the most serious as it threatens the viability of the transplant. Endothelial rejection is also of concern following posterior lamellar transplantation (Descemet’s Stripping Automated Endothelial Keratoplasty, DSAEK, and Descemet’s Membrane Endothelial Keratoplasty, DMEK), although it does not occur following anterior lamellar transplantation (ALK)

Some or all of the following signs may be present:

  • sub-epithelial opacities similar in appearance to adenovirus keratitis (Krachmer spots)
  • anterior ciliary injection (perilimbal hyperaemia)
  • transplant oedema (may be regional)
  • rejection line
    • endothelial (Khodadoust line) or epithelial
  • keratic Precipitates (KP) on transplant endothelium
  • anterior chamber flare and cells
  • raised IOP

Differential diagnosis

  • transplant decompensation, also known as ‘graft failure’ (no inflammation)
  • infective keratitis
  • anterior uveitis

Management by optometrist

Practitioners should recognise their limitations and where necessary seek further advice or refer the patient elsewhere

GRADE* Level of evidence and strength of recommendation always relates to the statement(s) immediately above

Non pharmacological




Management category

A1: emergency (same day) referral; no intervention. Emphasise to the patient the urgency of the condition and instruct them to attend the local hospital eye department or hospital A & E the same day, explaining that you will leave a message so that they are expected. Telephone the department to explain what you have done, preferably leaving your message with a doctor or other health care professional.

Possible management by ophthalmologist

  • possible admission to hospital
  • intensive topical steroid therapy
  • possible addition of systemic steroid
  • possible immunosupressant therapy e.g. ciclosporin, tacrolimus
  • topical antivirals where there is a history of Herpes simplex infection

Evidence base

Abudou M, Wu T, Evans JR, Chen X. Immunosuppressants for the prophylaxis of corneal graft rejection after penetrating keratoplasty. Cochrane Database Syst Rev. 2015;8:CD007603

Akanda ZZ, Naeem A, Russell E, Belrose J, Si FF, Hodge WG. Graft rejection rate and graft failure rate of penetrating keratoplasty (PKP) vs lamellar procedures: a systematic review. PLoS One. 2015;10(3):e0119934.

Bachmann B, Taylor R, Cursiefen C: Corneal Neovascularization as a Risk Factor for Graft Failure and Rejection after Keratoplasty. Ophthalmology 2010;117:1300-5

Borderie V et al: Graft rejection and graft failure after Anterior Lamellar versus Penetrating Keratoplasty. Am J Ophthalmol 2011;151:1024-9

Di Zazzo A, Kheirkhah A, Abud TB, Goyal S, Dana R. Management of high-risk corneal transplantation. Surv Ophthalmol. 2017;62(6):816-827

Guilbert E, Bullet J, Sandali O, Basli E, Laroche L, Borderie VM. Long- term rejection incidence and reversibility after penetrating and lamellar keratoplasty. Am J Ophthalmol. 2013;155(3):560-9

Hopkinson CL, Romano V, Kaye RA et al (OTAG Study 20). The Influence of Donor and Recipient Gender Incompatibility on Corneal Transplant Rejection and Failure. Am J Transplant. 2017;17(1):210-7

Plain language summary 

After a patient has had a corneal transplant, in which tissue from a donor eye is placed or sewn into the eye, the body’s immune system can recognise the tissue as foreign and may start a reaction against it. This reaction, known as corneal transplant rejection, can usually be controlled if it is discovered early enough.

A patient with a corneal transplant rejection may experience discomfort or pain in the eye, redness, blurred vision and watering.

The seriousness of such a rejection depends on the type of transplant that was carried out. If it was a full-thickness transplant, rejection is likely to involve the deepest layer of the donor cornea, known as the endothelial layer. As a functioning endothelium is essential for the cornea to remain transparent, a rejection of this layer must be treated quickly and thoroughly.

The optometrist who diagnoses a corneal transplant rejection will refer the patient to the ophthalmologist as an emergency. This will allow treatment with the appropriate steroid and other drugs to begin as soon as possible.

Corneal transplant rejection
Version 11
Date of search 12.04.18
Date of revision 31.05.18
Date of publication 16.10.18
Date for review 11.04.20
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