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 eventually lead to transplant failure. The incidence of graft rejection depends on the presence of risk characteristics, e.g. corneal neovascularization. In ‘high-risk’ corneal transplant recipients up to 70% fail within 10 years despite local or systemic immunosuppressive therapy

Corneal transplant rejection may be reversible or irreversible and can affect both full thickness and lamellar transplants, although rejection is 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)

Symptoms of corneal transplant rejection

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

Signs of corneal transplant rejection

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 deep anterior lamellar transplantation (DALK)

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

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 him or her to attend the local hospital eye department or hospital A&E the same day, explaining that you will leave a message so that he or she is 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 immunosuppressant 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.

Armitage WJ, Goodchild C, Griffin MD, Gunn DJ, Hjortdal J, Lohan P, Murphy CC, Pleyer U, Ritter T, Tole DM, Vabres B. High-risk Corneal Transplantation: Recent Developments and Future Possibilities. Transplantation. 2019;103(12):2468-2478

Bachmann B, Taylor R, Cursiefen C: Corneal Neovascularization as a Risk Factor for Graft Failure and Rejection after Keratoplasty. Ophthalmology 2010;117(7):1300-5

Borderie V et al: Graft rejection and graft failure after Anterior Lamellar versus Penetrating Keratoplasty. Am J Ophthalmol 2011;151(6):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

Stulting RD, Lass JH, Terry MA, Benetz BA, Cohen NJ, Ayala AR, et al; Cornea Preservation Time Study Group. Factors Associated With Graft Rejection in the Cornea Preservation Time Study. Am J Ophthalmol. 2018;196:197-207

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 the functioning of this tissue keeps the cornea clear, a rejection of this layer must be treated quickly and thoroughly if the sight of the eye is to be saved.

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

Corneal transplant rejection
Version 12
Date of search 19.06.20
Date of revision 18.12.20
Date of publication 06.08.21
Date for review 18.06.22
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