Transmission of Creutzfeldt-Jakob disease in corneal graftsBMJ 1997; 315 doi: https://doi.org/10.1136/bmj.315.7122.1553 (Published 13 December 1997) Cite this as: BMJ 1997;315:1553
Observing the exclusion criteria for donated grafts should ensure the risk is small
The public and political profile of transmissible spongiform encephalopathies has changed dramatically with the identification of a new variant of Creutzfeldt-Jakob disease1 and continued uncertainty about the size of the threat this may represent. Against this background, the Scottish Office confirmed last month that ocular tissue from a donor who was later found to have classic (sporadic) Creutzfeldt-Jakob disease had been transplanted into three patients. Press coverage of this announcement is certain to stimulate concern among potential recipients of corneal grafts and a reanalysis of measures to prevent iatrogenic disease transmission.
latrogenic transmission of Creutzfeldt-Jakob disease was first reported in 1974 in a 55 year old woman who developed symptoms 18 months after corneal transplantation from a donor who was found to have died of the disease.2 Two similar cases have since been identified,3 and the potential for transmission of spongiform encephalopathies, including Creutzfeldt-Jakob disease, via transplanted corneal tissue has been shown in animals.4 As well as being a well identified route of entry for infection, the eye is thought to harbour a relatively high titre of the infective agent in Creutzfeldt-Jakob disease.5
Although implantation of any tissue may theoretically introduce infection, all known cases of iatrogenic Creutzfeldt-Jakob disease have resulted from exposure to brain or ocular tissue.5 Prominent examples are transmission of Creutzfeldt-Jakob disease via human growth hormone derived from cadaveric pituitary pools and in association with dura mater patch grafting.6 Recombinant technology is now used to manufacture pituitary hormones for therapeutic use, and dura mater patch grafts have not been used in Britain since the early 1990s. For the cornea, sterilisation of tissue for full thickness grafts is not possible and alternatives are not available. Artificial corneas are probably several years away.7
No information on infectivity during the incubation phase of Creutzfeldt-Jakob disease is available. Therefore truly accurate advice about the risk of acquiring the disease through an ocular tissue graft is impossible. For classic Creutzfeldt-Jakob disease the risk is vanishingly small. The lifetime risk of acquiring the disease is around 1/40 000 for a potential donor in the general population. Over 3000 corneal grafts are performed a year in Britain alone, and worldwide only three cases of corneal transmission have been reported in the past 20 years.
For the new variant of Creutzfeldt-Jakob disease the current prevalence is also unknown. In the worst case scenario, derived from projections based on mathematical models relating prevalence estimates to possible incubation periods for the new disease, up to 80 000 individuals may be affected,8 giving a risk for encountering an infected donor in the British population (approximately 55 million) of around 1/700. More accurate risk estimates should be available with time. Meanwhile, it is probably reasonable to emphasise during patient counselling that this figure is based on a worst case estimate. Even assuming that these potential donors were all infective while incubating the disease, genetic susceptibility may be required to develop Creutzfeldt-Jakob disease after exposure.5
Since there is currently no method of screening for latent human spongiform encephalopathy the most practical step in risk management is probably to ensure that the exclusion criteria for potential eye donors are well disseminated. In addition to patients diagnosed with Creutzfeldt-Jakob disease and recipients of human pituitary hormones, current guidelines exclude any donors with unexplained neurological disease or central nervous system disease of unknown cause, including multiple sclerosis, motor neurone disease, and Parkinson's disease. Also excluded are patients with active viral disease, some ocular conditions, and haematological malignancies.
Most corneal donor tissue used for transplantation in Britain is stored at eye banks in Bristol and Manchester using organ culture methods. Bovine calf serum used in the organ culture medium is imported from countries free of bovine spongiform encephalopathy. Tissue can be stored for up to one month, and death from an unknown cause is not a contraindication to eye donation if a postmortem examination is pending. Clearly, however, accurate information about the cause of death must be communicated to the eye bank before transplantation.
Most corneal grafts result in a sustained visual benefit and considerable improvement in the quality of life.9 The possibility of iatrogenic disease transmission in corneal grafts remains real—but a sense of proportion is required. For Creutzfeldt-Jakob disease, including the new variant, the risk may be no greater than that of other hazards associated with the procedure, such as death from general anaesthetic, which are not normally rehearsed explicitly in preoperative discussions with patients.