Abstract
In this study, we made a comparative efficacy and safety assessment of two different fixed combinations of drugs, viz., tafluprost/timolol (TAF/TIM) and latanoprost/carteolol (LAT/CAR), by determining their effects on intraocular pressure (IOP) in ocular normotensive monkeys and examining their toxic effects on ocular surface using human corneal epithelial cells. TAF/TIM was found to be more effective in lowering IOP for a longer duration compared to LAT/CAR. We found that the difference in the intensity of IOP-lowering effect was because of the differences in the strength of timolol compared with that of carteolol as a beta-adrenergic antagonist and strength of tafluprost compared with that of latanoprost as a prostaglandin analogue. In addition, TAF/TIM showed much less cytotoxic effects compared to LAT/CAR on the human corneal epithelial cells. Our findings showed that TAF/TIM is better than LAT/CAR with regard to the IOP-lowering effect in monkeys and toxicity on ocular surface.
Highlights
Glaucoma is a neurodegenerative disease of the eyes characterised by selective retinal ganglion cell loss, followed by progressive defects in visual field, resulting in the principal cause of irreversible blindness worldwide[1,2,3,4]
latanoprost/carteolol Fixed combination (FC) (LAT/CAR estimated formulation (CAR)) was recently approved in Japan, and in 2000, latanoprost/timolol FC (LAT/TIM formulation (TIM)) was the first approved prostaglandin analogues (PGAs)/beta-FC in Sweden
We previously reported that TAF/TIM had a greater intraocular pressure (IOP)-lowering effect and lower cytotoxicity compared to LAT/TIM27
Summary
Glaucoma is a neurodegenerative disease of the eyes characterised by selective retinal ganglion cell loss, followed by progressive defects in visual field, resulting in the principal cause of irreversible blindness worldwide[1,2,3,4]. Several FCs of commonly employed drugs that lower IOP have been developed in the 2000 s for the purpose of maximising medication compliance in patients[21]. These include combinations of PGA with beta-adrenergic antagonist and beta-adrenergic antagonist with carbonic anhydrase inhibitor or alpha-2-adrenergic agonist. Among the FCs that are recently developed, the combinations of PGA with beta-adrenergic antagonist (PGA/beta-FC) have attracted considerable attention as they combine two separate mechanisms of action Both PGA and beta-adrenergic antagonist are frequently employed for glaucoma treatment; a significant reduction in IOP is expected[22]. We made a comparative assessment of the IOP-lowering effect and toxicity on ocular surface of TAF/TIM versus LAT/CAR, to clarify their efficacy and safety
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