Page 58 - DUOKOPT BIBLIOBOOK

DUOKOPT - bibliography book - CONFIDENTIAL - document for exclusive use by personnel of Laboratoires Théa – DO NOT DISTRIBUTE
®

Ophthalmology Volume 105, Number 10, October 1998

Table 6. Emergent or Worsening Ocular Symptoms Occurring dorzolamide, additional IOP lowering of at least 3 mmHg
in 1% of Patients in Any Treatment Group: No. (%) was gained at both peak and trough for patients receiving
the combination. This additional reduction in IOP could be
Combination Dorzolamide Timolol clinically valuable for many patients. The fixed combination
(N 114) (N 109) (N 112) solutions of timolol 0.5% and pilocarpine, 2% and 4%, also
Patients evaluated 114 (100) 109 (100) 111 (99) have been compared to monotherapy with the individual
Patients with any ocular components. These studies defined adequate IOP control as
9
symptoms* 70 (61) 63 (58) 34 (31)
Blurred vision† 23 (20) 19 (17) 10 (9) an IOP less than or equal to 21 mmHg and found that the
Burning eye* 30 (26) 31 (28) 10 (9) combination was superior to either of its components since
Dryness of eye 2 (2) 7 (6) 8 (7) a significantly greater proportion of patients receiving the
Eye pain 4 (4) 0 (0) 2 (2) combination had an IOP less than or equal to 21 mmHg than
Eyelid pain or discomfort 1 (1) 2 (2) 1 (1)
Foreign body sensation 4 (4) 2 (2) 4 (4) did patients receiving either of its components. Interest-
Itching, eye 8 (7) 9 (8) 4 (4) ingly, if the same definition of adequate IOP were applied to
Photophobia 1 (1) 1 (1) 2 (2) this study, the mean IOP achieved with the dorzolamide–
Redness, eye 2 (2) 2 (2) 1 (1) timolol combination meets this definition at all timepoints
Stickiness, eye 4 (4) 1 (1) 0 (0)
Stinging eye‡ 25 (22) 19 (17) 9 (8) during the study. However, dorzolamide does not meet it at
Tearing eye‡ 11 (10) 6 (6) 1 (1) any study timepoint, and timolol does not meet this defini-
Vision cloudy 6 (5) 6 (6) 4 (4) tion for three of the four trough timepoints (week 2, months
2 and 3).
* Combination versus timolol, P 0.001. A previous study of the combination showed the value of
† Combination versus timolol, P 0.023. the combination in patients inadequately controlled on timo-
‡ Combination versus timolol, P 0.005. lol alone (Strohmaier et al. Invest Ophthalmol Vis Sci
1996;37:S1102), whereas this study extends those findings
by showing that the combination is also superior to its
components in patients not receiving or discontinued from
ences between the combination and dorzolamide groups in the previous ocular hypotensive therapy. The additive effect of
proportion of patients reporting any ocular symptom; however, dorzolamide and timolol is perhaps not surprising since
significantly more patients reported ocular symptoms in the com- each component of the combination drug affects inflow by
bination group than in the timolol group (61% vs. 31%, P a different mechanism. Dorzolamide decreases aqueous hu-
0.001). Specifically, when compared to the timolol group, the
combination group had a significantly greater incidence of blurred mor secretion by inhibiting carbonic anhydrase isoen-
vision, burning eye, stinging eye, and tearing eye. Of the 71 reports zyme-II in the ciliary process of the eye; this presumably
of burning eye in this study, 66 (93%) were graded mild by slows the formation of bicarbonate ions with subsequent
investigators, 3 (4%) were graded moderate, and only 2 (3%) were reduction in sodium and fluid transport into the posterior
graded severe. Of the 53 reports of stinging eye, 42 (79%) were chamber of the eye. 10 Although the precise mechanism of
mild, 11 (21%) were moderate, and none were severe. the ocular hypotensive action of timolol is not established
There were no statistically significant differences among the clearly, it appears to be mediated via decreased production
groups with regard to any specific laboratory adverse experience or of cyclic adenosine monophosphate. This decreases active
the incidence of adverse events noted on physical examination.
Additionally, there were no statistically significant differences ion transport, which has been linked to decreased aqueous
between the treatment groups when they were compared for emer- humor production. 11,12
gent or worsening ocular signs, visual acuity, visual field results, The safety profile of the combination was also evaluated
optic nerve cup-to-disc ratio, blood pressure and pulse rate, or closely in this study and was compared to that of its com-
laboratory measures. ponents administered as monotherapy. Overall, incidence
rates of specific adverse experiences were similar for all
three treatment groups with the exception of burning and
Discussion stinging, which occurred more frequently in the combina-
tion and dorzolamide groups than in the timolol group. The
The primary objective of this study was to compare the adverse events attributed to the combination are essentially
IOP-lowering effect of the dorzolamide–timolol combina- the sum of those of the components, with no adverse effects
tion to that of each of its components administered in their observed that were unique to the combination. The mild
usual monotherapy dose regimens in untreated patients. nature of the symptoms and the low number of discontinu-
This was accomplished by evaluating the combination at ations for burning and stinging indicate that these symptoms
morning trough (hour 0, the primary timepoint of interest) are not a significant limitation to the use of the combination
and at morning peak (hour 2). The results showed that the product.
combination had a superior IOP-lowering effect relative to In summary, the dorzolamide–timolol combination,
either of its individual components at the primary timepoint when dosed twice a day, has been shown to be a highly
and at all other timepoints measured during the study. For effective and generally well-tolerated therapy for the treat-
patients receiving the combination, IOP was lowered, on ment of elevated IOP. As such, it represents a valuable
average, an additional 1.5 to 3 mmHg compared to patients alternative to concomitant therapy in patients in whom
receiving timolol alone. Compared to patients receiving aggressive lowering of IOP is indicated.

1950

58