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Editors Selection IGR 11-4
Medical Therapy: Mechanism of PGA action
Comment by Douglas Rhee on:
26649 Efficacy and mechanisms of intraocular pressure reduction with latanoprost and timolol in participants with ocular hypertension: A comparison of 1 and 6 weeks of treatment, Johnson TV; Fan S; Zhan G et al., Journal of Glaucoma, 2010; 19: 356-364
Understanding the mechanism of action of medications allows us to make better treatment decisions. With regard to prostaglandin analogues (PGA), we have an incomplete understanding of their mechanism of action which makes interpretation of some clinical observations about its IOP lowering abilities difficult; specifically: (1) some have found that the initial IOP drop may only represent a portion of the maximal effect on IOP; (2) some have observed that there is a greater effect of IOP from latanoprost after six months; and (3) some have found that tachyphylaxis can occur with topical beta-blockers.
It is possible that maximal IOP lowering with PGAs can be seen as early as one week
The inconsistency of these observations have clinical relevance with regard to when IOP should be checked to determine if the PGA has been effective, and if there will be a greater (or lesser) effect after six months. Johnson et al. (1337) have reported that the primary effects of timolol and latanoprost, decreasing aqueous humor production and increasing uveoscleral outflow, respectively, on aqueous humor dynamics is unchanged between one and six weeks after beginning treatment with either of these agents.
Is it possible that extracellular matrix continues to remodel even after six months of PGA treatment?
These data answer some of the mechanistic questions, particularly with regard to the clinical observations seen with latanoprost. These findings strongly implicate the possibility that the maximal IOP lowering with PGAs can be seen as early as one week. With PGAs, additional studies with patients at six and twelve months are needed to fully examine the issue of further IOP lowering, possibly due to further remodeling of extracellular matrix, after six months of treatment. With topical beta-blockers, additional studies at one and two years would be helpful to examine the possible mechanism of tachyphylaxis that has been noted by several groups.
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