Dear Editor

We read with interest the paper by Lim et al.[1] The authors interestingly showed the importance of tonometer head wiping in reducing corneal epithelial cell count and the significance of damaged prism surfaces in trapping debris. They hypothesised the possible risk of vCJD transmission from cornea epithelial cells present on the tonometer surface. The question is really one of what constitutes the infectious dose of vCJD, for this mode of transmission, and this is currently unknown.

There has been one definite, one probable and two possible cases of CJD through corneal transplantation but one can hardly compare the prion load in a full thickness corneal graft compared to a mean epithelial cell counts of 9 /10 (after wiping or wipe/Milton). Two of the four cases of transmission had had multiple graft procedures.

The evidence from animal studies on CJD infected corneal transmission is also variable. Herzberg transplanted CJD infected corneas onto two Capuchin monkeys, both remained disease free for up to four years.[2] Manuelidis et al. showed the transmission of CJD, if infected corneas were placed directly into the anterior chamber of uninfected guinea pigs [3] but did not show transmission of CJD after penetrating keratoplasty. Tateishi injected emulsified CJD-infected cornea into the brains of six mice and only one developed characteristic changes after 2.8 years.[4]

Certainly the studies suggest an intraocular / intracerebral delivery must be needed for transmission and even then inocula that produced disease after intracerebral inoculation only irregularly transmit disease after peripheral (intraocular) inoculation.[5] Even then host genetic factors (homozygosity at codon 129) will also determine ones risk of susceptibility.[6] There is also convincing evidence that the agent strain and host genotype will determine whether ocular involvement even occurs in experimental rodent models of scrapie.[7]

More recently western blot analysis on eyes of patients that had been infected with sporadic CJD and v CJD [8] confirmed earlier results also in human eyes that could only detect levels of PrPSc in the retina and not in cornea or sclera. The risk of transmission from tonometry from the scientific evidence would suggest this to be more theoretical than practical and this may be reduced further, as the authors suggest, by adequate wiping or regular replacement of tonometer prisms. The question of risk can only be truly resolved by transmission studies using primary human diseased eye tissue.

References

(1) Lim R, Dhillon B, Kurian KM et al. Retention of corneal epithelial cells following Goldmann tonometry: implications for CJD risk. Br J Ophthalmol 2003;87:583-6.

(2) Herzberg L. Creutzfeldt-Jakob disease and corneal grafts. Med J Aust 1979;1:248.

(3) Manuelidis EE, Angelo JN, Gorgacz EJ et al. Experimental Creutzfeldt-Jakob disease transmitted via the eye with infected cornea. N Engl J Med 1977;296(23):1334-1336.

(4) Tateishi J. Transmission of Creutzfeldt-Jakob disease from human blood and urine into mice. Lancet 1985;2:1074.

(5) Brown P, Gibbs DJ, Rodgera-Johnson P et al. Human spongiform encephalopathy: the National Institutes of Health series of 300 cases of experimental transmitted disease. Ann Neurol 1994;35:513-29.

(6) Mehta JS, Franks WA. The sclera, the prion, and the ophthalmologist. Br J Ophthalmol 2002;86:587-592.

(7) Foster JD, Fraser H, Bruce ME. Retinopathy in mice with experimental scrapie. Neuropathol Appl Neurobiol1986;12:185-96.

(8) Head MW, Northcott V, Rennison K et al. Prion Protein Accumulation in Eyes of Patients with Sporadic and variant CJD. IOVS 2003;44(1):342-6.