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We read with great interest the article by Chiba and co-workers about
the possible effect on intraocular pressure (IOP) induced by non-steroidal
anti-inflammatory (NSAID) ophthalmic solution in patients affected by
primary open angle glaucoma (POAG) or ocular hypertension (OH) and treated
with latanoprost .
In 2003, Kashiwagi and Tsukahara (two co-authors of
the above-mentioned Chiba et al...
In 2003, Kashiwagi and Tsukahara (two co-authors of
the above-mentioned Chiba et al. paper) have already published a similar
study conducted on a very small number of healthy volunteers (thirteen
Japanese young adults), concluding that the co-administration of bromfenac
significantly inhibited latanoprost induced IOP reduction . In June
2005, we have published an article on the same topic, but carried out on
thirty-two POAG patients . This paper described discrepant results as
compared to those obtained by both Chiba and co-workers , and Kashiwagi
and Tsukahara . In fact, within our Caucasian glaucomatous study group,
diclofenac eyedrops significantly enhances the ocular hypotensive effect
We have tried to explain the contradictory data obtained
in 2003 by Kashiwagi and Tsukahara , in comparison with our results 
and those achieved by Sponsel et al. in 2002 , also indicating several
possible bias of the first mentioned trial. Finally, we have speculatively
discussed the reliable pathophysiological causes of this more marked,
latanoprost-induced IOP reduction in NSAID-treated POAG patients 
mainly considering that: i. therapeutic and side-effect profiles of
latanoprost is explainable by its prevalent action on FP, EP and TP
prostaglandin (PG) receptors [5-7]; ii. in human cultured ciliary muscle
(CM) cells the same NSAID level, obtained after drug topical
administration, inhibits the PGs synthesis ; iii. in experimental
models, an up-regulation of PG receptors occurs via cyclooxygenases
Rationally, we have concluded that a NSAID-related fall
in endogenous PGs synthesis could be responsible for a PG receptors over-
expression, increasing the IOP-lowering effect of topical PG analogues.
The effect of this pharmacological interaction, essentially based on the
well-known plasticity of PG receptors system [9-13], should be
realistically investigated only in patients with a definite and definitive
diagnosis of glaucoma, such as POAG patients studied by ours in 2005 .
In fact, only in glaucomatous CM cells an over-expression of PG receptors
occurs , whereas these receptors are scarcely present in the same
cells of healthy subjects  and, reliably, also in CM of OH patients.
This hypothesis has been developed starting from different points of view
respect to Chiba et al. , whose paper has also briefly commented by Alm
in an Editorial published in the same BJO issue .
In our opinion, none of the investigations existing in the current
literature are able to conclusively verify the possibility of an
interaction between NSAIDs and PG analogues. Particularly, the recent
study of Chiba et al. is characterized by an insufficient and
heterogeneous patient's recruitment (just nine POAG and four OH subjects),
resembling the crucial weak-point of Kashiwagi and Tsukahara trial, which
was previously conducted on healthy volunteers [1,2].
and co-workers have not considered these biases. On the contrary, they
have emphasized, at the top of the Discussion section, that their "study
clearly demonstrated that ophthalmic NSAID inhibits the IOP reduction by
latanoprost ophthalmic solution in glaucomatous eyes", partially or
totally ignoring: i. the results of other Authors who had utilized a more
numerous and / or homogeneous study populations [3, 4, 15]; ii. the possible
variability of PG receptors expression in different ethnic groups [16,
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