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Comparison of fixed topical combination glaucoma drugs in patients with open-angle glaucomsa or ocular hypertension
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Bakhritdinova Fazilat Arifovna, Tashkent medical academy, Minister of Health of Republic of Uzbekistan
E-mail: bakhritdinova@mail.ru Karimov Ulugbek Rasulovich, Syrdarya regional ophthalmologic hospital, Uzbekistan E-mail: dr_karimov@mail.ru Mirrakhimova Saida Sh., Tashkent medical academy, Minister of Health of Republic of Uzbekistan
Akshey Khera,
Ophthalmic clinic “Vedanta medical”, Tashkent E-mail: dr_khera@hotmail.com
Comparison of fixed topical combination glaucoma drugs in patients with open-angle glaucomsa or ocular hypertension
Abstract: The purpose of study was to compare the intraocular pressure lowering efficacy, safety and cost-efficiency of fixed combinations travoprost 0.004 %/timolol 0.5 % (tim + tarv), brimonidine 0.2 %/timolo0.5 % (tim + brim), brinzol-amide 1 %/timolol 0.5 % (tim + brinz) and pilocarpin 2 %/timolol 0.5 % (tim + pil) in patients with ocular hypertension or open-angle glaucoma. In this prospective, randomized clinical trial included 80 qualifying patients (4 groups) during six month. It was found that the fixed combination travoprost 0.004 %/timolol with 0.5 % is more effective, stabile and safe combination and recommend for long-term therapy of POAG and ocular hypertension. Combination of brimonidine + 0.2 %/timolol 0.5 % and timol + brinsolamid are recommend for fast and effective reduction IOP, short term cost effective therapy of POAG. Combination of pilocarpin 2 % and timolol 0.5 % usually is not recommend for therapy of POAG, but can be use as costly treatment for short time.
Keywords: open angle glaucoma, therapy, fixed combination glaucoma drops.
Bakcgroud
According to the literature to compensate for the intraocular pressure are often (25 to 70 %) is used two or more antihypertensive drug [1; 2; 3]. Today, our market represented a significant arsenal of the fixed combination of antihypertensive drugs, and it is necessary to compare the effectiveness of drugs to determine their characteristics and hypotensive activity. However, the authors of contradictory results [3; 4; 5; 6; 7; 8]. Perhaps this is due to the fact that studies have been conducted in different ethnic groups or different stages of glaucoma, with enough informative methods of research.
According to the requirements of evidence-based medicine, the most reliable are objective imaging technique of the optic nerve — the data of optical coherence tomography (O CT) of the optic nerve (optic disc), and color duplex scanning (CDS) orbit vessels. OCT will identify and quantify the dynamic aspect of the reduction of peripapillary nerve fiber layer (NFL), which is the best indicator of glaucomatous lesions, compared with the computer perimeter [9; 10; 11; 12]. However, the practical application of color duplex scanning orbital vessels, will allow to quantify the condition of blood circulation of the
orbital vessels supplying the optic nerve [13; 14; 15; 16; 17]. According to the literature the most important and reliable parameter of orbital vascular blood flow rate is “resistance index» (Pourcelot's ratio IR) arteria ophthalmica (AO) and posterior short ciliary arteries (PSCA) [18; 19; 20; 21; 22]. resistance index in the AO and PSCA can serve as predictor of progressive deterioration of visual functions in POAG; The authors offer the best of its values: 0.72 and
0.65 for the AO to PSCA [23; 24; 25; 26; 27]. In addition to the above-mentioned indicators are also important indicators of safety, efficiency and ease of use of drugs.
Purpose — to evaluate the features of the hypotensive effect of the fixed combination of timolol 0.5 % + travoprost 0.004 % (tim + trav), timolol 0.5 % brimonidine + 0.2 % (tim + brim), timolol 0.5 % + 1 % brinzolamide (tim + brinz), timolol 0.5 % pilocarpine + 2 % (tim + pil) and their impact on clinical and functional parameters of eye in patients with POAG.
Materials and methods
The survey of 80 patients (158 eyes) with POAG II — III stage. Parameters patient groups are shown in Table 1. The four groups of patients have been formed; The first group (40 eyes) buried
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combination timolol + travoprost (Duotrav, the Alcon, Belgium), the second group (40 eyes) — timolol + brimonidine (Brimoptik, Liquor, Armenia), the third group (40 eyes) — timolol + brinzo-lamide (Azarga, the Alcon, Belgium), the fourth group (38 eyes) were buried timolol + pilocarpine (Fotil, Santen, Finland). The median age was 65 years, patients with predominated dark and light brown iris in 96.6 % cases. Patients with advanced glaucoma
was — 56.2 % (86 eyes), the advanced stage of — 43.8 % (72 eyes). The level of IOP patients were distributed as follows: 15 with normal (9.4 %) eyes with moderately elevated 101 (64 %) eyes with high intraocular pressure — 42 (26.6 %) eyes. From studies have excluded patients with severe mental and somatic diseases. Study design masked, prospective, randomized. All patients were examined in terms of 1, 3 and 6 months of treatment.
Table 1. - Patient Information
О rS II b£ 2g (n = 20) 3g (n = 20) О rS II b£ ■"t
Mean age 62.5 ± 7 62.4 ± 6 65.2 ± 8 64.3 ± 7
Sex: M 11 (55 %) 10(50 %) 12 (60 %) 11 (55 %)
F 9 (45 %) 10(50 %) 8 (40 %) 9 (45 %)
Central corneal thickness 522.4 ± 28.2 528.5 ± 32.4 536.8 ± 18.4 524.4 ± 36.3
Iris color:
Dark 11 (55 %) 10(50 %) 11 (55 %) 10 (50 %)
Light brown 7 (35 %) 9 (45 %) 8 (40 %) 7 (35 %)
Bright 2 (10 %) 1 (5 %) 1 (5 %) 3 (15 %)
Glaucoma stage:
II: 11 10 11 12
III: 9 10 9 8
All patients underwent standard ophthalmic examinations: biomicroscopy, ophthalmoscopy, tonometry, perimetry, gonios-copy, diurnal IOP fluctuation test. Acute drug test for use of the drug has been put before treatment to patients. Color duplex scanning Doppler mapping of the orbital arteries was performed on the unit Aloka SSD 1700 ( Japan) probe 7.5 MHz .; were examined by ophthalmic artery (AO) and posterior short ciliary artery (PSCA) according to a standard protocol [11]. To evaluate the optic disc parameters and the average thickness of the peripapillary nerve fibers (NFL) patients were tested for optical coherence tomography Stratus OCT 3000 (Carl Zeiss, Germany). To evaluate the safety
and comfort conducted questioning among patients. Price-efficacy was calculated in terms of; cost one percent of the average IOP reduction for 3 months in US dollars [28]. Statistical data processing has been done with the program Statistics 8.
Results
In general, patients tolerated the prescribed treatment, a significant decrease in intraocular pressure have been reported in all groups. A significant reduction in IOP was observed already after 2 hours, the maximum reduction at 4 hours after instillation. Under travoprost + timolol, unlike other groups IOP level kept at a low level even after 12 hours after the instillation (Fig. 1).
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Comparison of fixed topical combination glaucoma drugs in patients with open-angle glaucomsa or ocular hypertension
During therapy with a combination of travoprost + timolol observed reduction in IOP from baseline by an average of 33.01 % at the end of the first, and reliable stabilization of the IOP by the end of the 6th month (Po = 0.001). A month later, in patients treated with a combination of timolol + brimonidine, hypotensive activity was high and amounted to 38.1 %; After 3 months — 30.24 %
and decreased to 21.81 % (Po = 0.01) from the original — half a year, roughly the same trend in the third group of patients. In the fourth group showed a marked decrease in IOP to the beginning of the third month of treatment, and then IOP was rising again and by the end of 6 months of treatment reached values close to baseline (Fig. 2).
Fig. 2. Mean IOP in dynamics (* — Po = 0.0005 (Tim + Taf, Tim + Brinz); ** — Po = 0.001 (Tim + Brim, Tim + Pil))
Parameters of diurnal IOP after 1, 3 and 6 months of treat- In the other groups oscillation IOP remained within physiologic
ment showed a relatively low level of fluctuations in IOP in group during the first three months, but rose (fig. 3) further level of di-
timolol + travoprost (Po = 0.001) for the time of observation. urnal fluctuations.
Fig. 3. Diurnal IOP (* — Po = 0.002 (all groups compared to baseline))
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In the analysis of the resistance index (RI) AO/PSCA in all group timolol + brimonidine resistance performance remained low
groups, except the fourth (timolol + pilocarpine), observed a signifi- even at relatively high rates IOP to 3 and 6 months of treatment.
cant decrease in the third month, more indicators remained stable Our findings are consistent with the opinion of the authors, show a
and at the end of 6 months (tab. 2). It should be noted that in the significant vasoconstrictor properties of brimonidine [29; 30; 31].
Table 2. - Comparative data orbital hemodynamics. Resistance Index (M ± m) of the ophthalmic artery and short posterior ciliary arteries
Before 3 months 6 months Po
Tim + Trav AO 0.79 ± 0.05 0.72 ± 0.02 0.71 ± 0.02 Po =0.01
PSCA 0.78 ± 0.03 0.62 ± 0.02 0.62 ± 0.03 Po =0.01
Tim + Brim AO 0.80 ± 0.05 0.69 ± 0.02 0.70 ± 0.02 Po =0.002
PSCA 0.78 ± 0.04 0.60 ± 0.04 0.61 ± 0.03 Po =0.002
Tim + Brinz AO 0.79 ± 0.06 0.69 ± 0.03 0.70 ± 0.02 Po =0.001
PSCA 0.79 ± 0.03 0.61 ± 0.02 0.60 ± 0.03 Po =0.001
Tim + Pil AO 0.80 ± 0.04 0.73 ± 0.03 0.75 ± 0.03 Po =0.05
PSCA 0.78 ± 0.03 0.70 ± 0.02 0.73 ± 0.02 Po =0.05
In the analysis of structural parameters for OCT retinal most important parameter is the average thickness in the peripapillary nerve fiber retina. Patients in all groups after 6 months showed a significant thickening NFL except group timolol + pilocarpine, wherein the thickness NFL indicators did not change significantly, compared with those of before treatment (tab. 3).
When analyzing the superior performance using the formulations according to the patients (90 %), most comfortably recognized timolol + travoprost combination and timolol + brimoptik, using timolol + brinzolamide combinations
and timolol + pilocarpine this conclusion 85 and 75 % of patients, respectively (Figure 4).
Table 3. - Thickness NFL (M ± m)
Before 3 months 6 months
Tim + Trav 68.13 ± 6.62 81.26 ± 5.39 79.47 ± 4.28 *
Tim + Brim 69.78 ± 4.51 83.94 ± 6.59 79.11 ± 4.96 *
Tim + Brinz 68.42 ± 6.35 80.87 ± 4.56 77.38 ± 3.81 *
Tim + Pil 70.72 ± 3.61 81.93 ± 2.88 74.90 ± 3.61 **
Note: * — Po = 0.02; ** — Po = 0.05.
Analysis of the cost and effectiveness of treatment showed that the most inexpensive was a combination of timolol + pilocarpine, a little more expensive than the combination of timolol + brimonidine, but the combination of travoprost + timolol and timolol + brinzolamide treated patients 2.5 times more expensive.
Discussions and conclusions
Within 6 months of therapy, a combination of travoprost + timolol observed stable IOP compensation, the drug has a high, stable hypotensive and neuroprotective activity and IOP decreases gradually. A small amount of local side effects and which reach through
a minimum time of application, the drug can be used safely and continuously. The combination of travoprost + timolol appropriate to prescribe long-term therapy for primary open angle glaucoma and ocular hypertension.
A combination of timolol+brimonidine significantly reduce IOP effectively in comparison with the combination of timolol + travoprost in the first 2 months of treatment. It has good neuroprotective activity, confirmed a significant reduction in the coefficient of resistance of the AO, PSCA, but also a considerable thickening of the peripapillary nerve fiber layer. With prolonged use, at 6 months
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Comparison of fixed topical combination glaucoma drugs in patients with open-angle glaucomsa or ocular hypertension
hypotensive effect is reduced, but the neuroprotective activity is stabilizing. Some local adverse effects identified in the course of treatment, can be expressed in the form of eye redness, burning, foreign body sensation, and sleepiness. The combination of timolol+brimonidine is advisable to apply for the purpose ofrapid and strong decrease in IOP for short-term treatment of POAG and ocular hypertension. After reaching normal levels of IOP it is recommended to transfer the patient to a more stable combination of travoprost + timolol.
The combination of timolol + brinzolamide is effective in reducing intraocular pressure (up to 39 % from baseline), significantly
improves the retrobulbar hemodynamics and restores NFL thickness in patients with POAG. Since the prolonged use of anti-hypertensive effect is weakened, it is recommended to eventually replace other more stable drug combination drug.
When using a combination of timolol + pilocarpine IOP level is reduced to 34 % from baseline, but we should not forget about the local adverse reactions that occur due to the high concentration of pilocarpine. Although this combination is not recommended for long-term use in POAG, it allowed the use of this combination for short-term treatment of POAG.
Fig. 5. Indicator cost/efficiency. The $ USD per 1 % reduction in IOP within 3 months
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Karimov Shavkat Ibrohimovich, Academician, Rector of the Tashkent Medical Academy, Professor in the department of faculty and hospital surgery of the Tashkent Medical Academy, Republic of Uzbekistan Khakimov Murod Shavkatovich, Professor, Chief of the department of faculty and hospital surgery of the Tashkent Medical Academy, Republic of Uzbekistan
Ashurov Sheroz Ermatovich, Assistant of the department of faculty and hospital surgery of the Tashkent Medical Academy, Republic of Uzbekistan E-mail: sheroz100682@mail.ru
Prognosing of perforation of chronic gastroduodenal ulcers
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