Prostaglandin analogues cause more conjunctival hyperemia than timolol, but the combination with timolol reduces the risk
A systematic review «Li F, Huang W, Zhang X. Efficacy and safety of dif...»1 from 2018 examined all common monotherapies as well as combination products for their intraocular pressure lowering efficacy and conjunctival hyperemia. The study patients were to have glaucoma and the duration of the study was to be at least three months. After case selection, 54 randomized clinical trials were included in the assessment of hyperemia.
After statistical processing, a rankogram of the examined drugs was generated. The results showed that, as a group, prostaglandin analogues caused statistically significantly more conjunctival hyperemia than timolol (RR 0.23, CI 0.17-0.32 in favor of timolol). Hyperemia was also significantly higher in comparison with brimonidine and carbonic anhydrase inhibitors. However, when comparing the compounds, it was found that the combination of the prostaglandin analog with timolol reduced the risk of hyperemia (RR 0.84, CI 0.56-1.25 in favor of timolol).
A systematic review and meta-analysis «Quaranta L, Biagioli E, Riva I ym. Prostaglandin a...»2 of 2013 included glaucoma and OHT patients from a total of 18 clinical and randomized trials. The majority of the 6115 patients were Caucasian and the mean age in the study ranged from 49 to 66 years. When analyzing conjunctival hyperemia, it was found that the combination of prostaglandin analogue and timolol caused statistically significantly more hyperemia than timolol monotherapy (RR 3.04, 95% CI 3.04-4.36). However, the combination of timolol and the prostaglandin analogue had a lower risk of hyperemia than the prostaglandin analogue alone (RR 0.61, 95% CI 0.53-0.70). The risk of hyperemia of the combination was slightly lower than if the drugs were administered separately, but the result was not statistically significant (RR 0.70, 95% CI 0.43-1.14).
A meta-analysis «Aptel F, Cucherat M, Denis P. Efficacy and tolerab...»3 from 2012 examined 20 randomized clinical trials of prostaglandin analogues and combinations with timolol in a total of 4684 patients with glaucoma and OHT. Conjunctival hyperemia was statistically more common with all combination products tested relative to timolol (bimatoprost-timolol RR 3.32, 95% CI 2.07-5.32, latanoprost-timolol RR 2.25, 95% CI 1.11-4.57 and travoprost- timolol RR 7.75 95% CI 2.42-24.76). When comparing the combination of timolol and a prostaglandin analogue to the prostaglandin analogue monotherapy, the risk was lower (bimatoprost monotherapy RR 0.61, 95% CI 0.50-0.74, latanoprost RR 0.66, 95% CI 0.43-1.01 and travoprost RR 0,94, 95% CI 0.50-1.77) .