Exfoliation Syndrome and Exfoliative Glaucoma 207representative for the true 24-hour IOP lowering efficacy of these medications
in XFG since 2 of the 3 time points coincided with the post-instillation peak
efficacy period of the dorzolamide/timolol fixed combination, thus
overestimation of IOP lowering effect of the fixed combination was possible.
In a 24-hour, investigator-masked, crossover trial made on XFG patients,
latanoprost 0.005% and travoprost 0.004% lowered the mean untreated 24-
hour IOP (25.1 mmHg) by 7.3 mmHg (30.8%) and 7.8 mmHg (31.1%),
respectively [55]. The efficacy difference between the two treatments was
statistically significant mostly due to the IOP difference at the 6 p.m. time
point (17.9 mmHg on latanoprost vs16.7 mmHg on travoprost, p<0.01).
In a 3-month, prospective, multicenter, investigator-masked, crossover
trial comprising 129 XFG patients, the efficacy of latanoprost 0.005% and
bimatoprost 0.03% was compared [56]. The mean untreated diurnal IOP was
26.9 mmHg. Bimatoprost provided statistically and clinically significantly
lower mean diurnal and individual time point IOP than latanoprost. The mean
diurnal IOP values were 18.6 mmHg for latanoprost and 17.6 mmHg for
bimatoprost. Only 34 patients (26.4%) on latanoprost versus 55 patients
(42.6%) on bimatoprost achieved mean diurnal IOP<17 mmHg. This
difference is clinically relevant because a mean diurnal IOP<17 mmHg has
been shown to lower the risk of progression in XFG [25].
A 2-month, crossover, prospective, investigator-masked study conducted
on treatment-naive XFG patients assessed the efficacy of latanoprost 0.005%
dosed in the evening and dorzolamide/timolol fixed combination dosed twice
daily [57]. The mean untreated IOP (measured at 10 a.m.) was 31.2 mmHg,
which decreased by 40.2% to 18.9 mmHg with latanoprost and by 42.8% to
18.1 mmHg with the fixed combination (P=0.21). The results indicate that the
2 - hour post-instillation peak efficacy of the dorzolamide/timolol fixed
combination and the 14-hour post-instillation efficacy of latanoprost
monotherapy are comparable in XFG.
The efficacy of fixed combinations of a prostaglandin analogue
(latanoprost 0.005%, travoprost 0.004%, bimatoprost 0.03% or tafluprost
0.0015%) and timolol 0.5% has also been investigated in XFG [58-61]. In
general, the use of fixed combinations offers a number of advantages:
convenient once daily dosing, decreased ocular tissue exposure to
preservatives, reduced systemic absorption of timolol compared to twice daily
administration, and increased efficacy compared to that of the individual
constituents [52,62,63]. The investigators of a 3-month, 24-hour crossover
study found that in XFG patients the evening dosed travoprost/timolol fixed
combination reduced the mean 24-hour IOP from 28.5 mmHg (untreated