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Corneal transplant rejection following influenza vaccination
  1. M S Wertheim1,
  2. M Keel2,
  3. S D Cook3,
  4. D M Tole3
  1. 1Bristol Eye Hospital, Lower Maudlin Street, Bristol BS1 2LX, UK
  2. 2Pembroke Road Surgery, 111 Pembroke Road, Bristol BS8 3EU, UK
  3. 3Bristol Eye Hospital, Lower Maudlin Street, Bristol BS1 2LX, UK
  1. Correspondence to: Mr Michael S Wertheim Bristol Eye Hospital, Lower Maudlin Street, Bristol BS1 2LX, UK; drwertie{at}

Statistics from

Corneal transplant is the most commonly performed transplant surgery in the United Kingdom. From 1995 to 2005, over 23 000 corneal transplants have been performed in the United Kingdom alone, with 2378 performed from 2004 to 2005.1 This equates to a rate of 40.3 per million population per year in the United Kingdom.1 The reported rates of corneal transplant rejection vary from 8% to 37%.2 We report on three cases (two patients) of corneal transplant rejection following influenza vaccination. General practitioners, ophthalmologists, and their relevant patients should be aware of this small but potentially sight threatening complication. Appropriate patients should be informed and warned of the symptoms of corneal transplant rejection before consenting to having the influenza vaccination. If diagnosed early, corneal transplant rejection is potentially reversible, albeit with endothelial cell loss.

A 67 year old woman presented to the eye department with a 5 day history of a red, uncomfortable left eye associated with blurring of her vision. She had undergone an uncomplicated corneal transplant 8 months before this consultation. Ocular examination revealed classic signs of corneal transplant rejection in the epithelium (Krachmer spots), stroma (oedema and swelling) and endothelium (keratic precipitates) (fig 1). On further questioning it was revealed that she was given the influenza vaccination (Sanofi-Pasteur MSD, UK) 2 weeks before the onset of her symptoms. This patient was started on hourly drops of prednisolone acetate 1% to treat her acute corneal transplant rejection episode. She made a good recovery and the transplant settled satisfactorily. The prednisolone acetate 1% was tapered to one drop per day. Four months after the influenza vaccination the patient is symptom free and the corneal transplant remains clear and devoid of signs of active rejection.

Figure 1

 Slit lamp photograph showing subepithelial infiltrates (small arrows) and a keratic precipitate (large arrow) on the endothelium. These are both classic signs of corneal graft rejection.

Another 67 year old woman presented to the eye casualty department with a 3 week history of a red, painful right eye associated with blurring of her vision. She had undergone an uncomplicated, routine corneal transplant 7 months before this assessment. The patient had signs of corneal transplant endothelial rejection, including inflammation in the anterior chamber, keratic precipitates, and a swollen, oedematous cornea. She had had an influenza vaccination (Sanofi-Pasteur MSD, UK) 3 weeks before developing these symptoms. She was successfully treated with a tapering dose of prednisolone acetate 1% and the rejection resolved.

The same patient presented to the eye department 1 year later with a 1 week history of a painful, red right eye with blurred vision. Slit lamp examination revealed another acute episode of corneal transplant endothelial rejection with a swollen, oedematous cornea and keratic precipitates. This patient had undergone her yearly influenza vaccination 4 weeks before developing the symptoms of rejection. After intensive steroid drop therapy the patient’s symptoms resolved and the cornea cleared, and the rejection episode was successfully treated.


The exact immunological mechanism of corneal graft rejection is not fully understood. Numerous animal and experimental models have been created to further understand the mechanism. The cornea is a site of immune privilege. Immune privilege is due, in part, to the fact that the cornea is devoid of blood and lymph vessels in the host bed and the lack of MHC class II antigen presenting cells in the donor cornea3 and therefore systemic immunosuppression is not prescribed routinely in patients undergoing routine, low risk corneal transplantation. Therefore, unlike other solid organ transplant recipients, corneal transplant patients do not require immunosuppression and therefore can mount a normal host response to antigen. There are no reported cases of transplant rejection in liver, lung, and kidney recipients following the influenza vaccination.4 There are however conflicting reports on whether the influenza vaccination may or may not cause low level rejection in heart transplant patients.4 The Department of Health recommends that all immunosuppressed patients be vaccinated against influenza; this includes patients on systemic immunosuppression.5

In 1996, Solomon et al reported a case of bilateral corneal transplant rejection following influenza vaccination6 (table 1). Steineman et al reported on five patients with corneal transplant rejection associated temporally with hepatitis B, tetanus booster, and influenza vaccinations7 (table 1). To our knowledge there are no further reports of corneal transplant rejection associated with the influenza vaccination.

Table 1

 Comparison of the literature of corneal transplant rejection following influenza vaccination

General practitioners and ophthalmologists should be aware of this small but potentially sight threatening complication following flu vaccination. We do not advocate that the influenza vaccination not be administered to these patients, but patients should be told of the possible link between the influenza vaccination and corneal transplant rejection. If patients have symptoms of corneal transplant rejection, including blurred vision, injected eye and discomfort, they should contact their general practitioner or ophthalmologist immediately. Rejection can take place up to 2 months after influenza vaccination and is potentially reversible. However each rejection episode leads to the inexorable loss of endothelial cells and potentially irreversible graft failure. Owing to the increased publicity of potential influenza pandemics and the increased uptake of vaccination, we think that it is important that this causal relation, between influenza vaccination and corneal transplant rejection, be recognised and publicised.


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