Sir,

The authors would like to thank Drs Kountouras, Zavos and Chatzopoulos for their letter regarding our paper published in Eye (2004) on the treatment of exfoliation glaucoma with latanoprost vs timolol. We appreciate their interest in this manuscript, their obvious effort to respond regarding potential side effects of prostaglandins, and their concern for ophthalmic patients.

The authors are correct in stating that glaucoma medicines ‘when instilled topically’ can be absorbed systemically through the nasal mucosa. Also, we heartily agree that ophthalmologists should be aware of potential systemic and ocular side effects from latanoprost as well as from any glaucoma medication. However, the authors’ statements that the upper respiratory infection in our study was attributable to latanoprost specifically and that prostaglandins are apt to cause ocular immune disease and cancer are difficult to support.

In general, the effects of prostaglandins in the body are dependent upon three factors:

  1. 1)

    the appropriate receptor at the target tissue

  2. 2)

    the specific class of prostaglandin

  3. 3)

    the tissue levels of the prostaglandin

Latanoprost is an F2a prostaglandin analog with a very high specificity to FP receptors. Such receptors have generally higher concentrations in the eye, smooth muscle cells, and corpus luteum. The authors’ conclusions about latanoprost, as an F2a prostaglandin analog, appear generally based on research of other prostaglandin subtypes and are not generally applicable to latanoprost. Making such a direct comparison of other prostaglandin research to specific clinical effects of an F2a prostaglandin analog is hazardous and potentially misleading.

F2a prostaglandins are not known to cause immune suppression, angiogenesis, or cancer. Further, these effects have certainly not been shown with latanoprost specifically. Latanoprost is the leading selling glaucoma medication worldwide and has 8 years of treatment experience. Case reports of series of tumours, immune problems, or angiogenesis have not been published. Further, such related side effects were not observed in well-controlled regulatory trials or in postapproval studies.

In addition, the clinical effect of a prostaglandin depends upon the available tissue levels. Two drops of latanoprost completely absorbed and dispersed into the total body water would have a peak plasma concentration of approximately 3 × 10−8 M (14 mg/l). Tissue studies show that it is very difficult to stimulate the FP receptor at this concentration. Further, the half-life of latanoprost in the plasma is probably 15 min. For this reason, latanoprost has not been shown conclusively to cause any systemic side effect.

Again, we agree with the authors in encouraging all ophthalmologists to be aware of side effects of glaucoma medicines. However, caution in the use of a glaucoma medicine must be based on rational knowledge of pharmacology and known side effects balanced with clinical efficacy and need of a medicine in the population to prevent blindness.