Effect of dorzolamide/timolol combination on the visual field in glaucoma

Figures & data

Table 1 Clinical profile of the subjects

Characteristics	Total	NTG	POAG	P-value
				NTG versus POAG
Number of subjects	14	10	4	–
Age, years	66.1±7.3	66.7±7.3	64.8±7.9	NS (0.7233)*
Male/female	9/5	7/3	2/2	NS (0.4545)†
Right/left	7/7	6/4	1/3	NS (0.2797)†
Refraction, diopters	−3.5±2.8	−2.7±3.0	−5.5±1.5	NS (0.0619)*
Baseline intraocular pressure, mmHg	14.1±2.6	13.5±2.2	15.5±3.3	NS (0.3811)*
Prior glaucoma medication
BB	2	2		–
CAI	2	2		–
PGA+BB	7	4	3	–
PGA/BB fixed combination	1	1		–
PGA+BB+CAI	2	1	1	–

Notes:

* Two-tailed unpaired t-test

† Fisher’s exact test.

Abbreviations: NTG, normal tension glaucoma; POAG, primary open-angle glaucoma; BB, beta-blocker; CAI, carbonic anhydrase inhibitor; PGA, prostaglandin analog; NS, not significant.

Table 2 Changes of the intraocular pressure and intraocular pressure reduction rate (percentage ± standard deviation) after switching to dorzolamide/timolol fixed combination

	Total (N=14)	P-value, at baseline versus post IOP (total)^*	No increase (N=3)	Increase (N=11)	P-value, no increase versus increase^†	NTG (N=10)	POAG (N=4)	P-value, NTG versus POAG^†
IOP, mmHg
Baseline	14.1±2.6	–	13.0±1.6	14.4±2.9	0.3969	13.5±2.2	15.5±3.3	0.3811
3 months	12.6±2.2	0.0160	12.7±2.1	12.5±2.4	0.9454	11.6±1.4	15.0±2.5	0.0906
6 months	12.2±2.2	0.0035	12.7±0.9	12.1±2.5	0.5954	11.5±1.4	14.0±3.1	0.2567
12 months	12.9±2.4	0.1362	12.3±2.1	13.0±2.5	0.7120	11.6±1.5	16.0±1.2	0.0020
18 months	12.4±3.0	0.0390	12.7±2.5	12.4±3.3	0.8903	11.1±1.2	15.8±3.9	0.1292
24 months	11.6±1.8	0.0006	12.0±0.0	11.5±2.1	0.5014	11.1±1.5	13.0±1.9	0.1800
30 months	12.1±2.0	0.0032	11.7±2.1	12.2±2.1	0.7692	11.5±1.7	13.5±2.3	0.2351
36 months	12.4±2.9	0.0261	11.7±1.2	12.5±3.3	0.5401	11.5±1.6	14.5±4.4	0.3242
Mean for 36 months	12.3±2.0	0.0038	12.2±1.4	12.3±2.3	0.9467	11.4±0.8	14.5±2.7	0.1342
IOP reduction rate, %
3 months	9.6±11.8	–	2.3±12.7	11.6±11.3	0.4154	12.7±11.2	1.9±11.1	0.2009
6 months	12.2±12.2	–	1.1±13.4	15.2±10.6	0.2702	13.3±13.2	9.3±10.5	0.6100
12 months	6.8±16.8	–	4.6±14.8	7.4±18.0	0.8233	11.9±16.7	−5.8±12.1	0.0884
18 months	10.7±17.3	–	2.0±18.3	13.0±17.0	0.4942	15.6±16.9	−1.7±14.0	0.1277
24 months	16.0±11.7	–	6.2±11.9	18.7±10.7	0.2727	16.4±13.8	15.1±5.8	0.8175
30 months	13.0±12.7	–	10.8±5.2	13.6±14.6	0.6544	13.3±15.2	12.2±5.2	0.8535
36 months	11.4±14.4	–	9.7±8.2	11.8±16.3	0.7952	12.8±16.2	7.7±10.3	0.5373
Mean for 36 months	11.7±10.6	–	5.7±9.4	13.3±10.9	0.3828	13.9±11.6	6.1±6.5	0.1842

Notes: Two-tailed ^*paired or ^†unpaired Student’s t-test. Data are shown as the mean ± standard deviation.

Abbreviations: IOP, intraocular pressure; NTG, normal tension glaucoma; POAG, primary open-angle glaucoma.

Figure 1 Mean deviation (MD) before and after switching to dorzolamide/timolol (1%/0.5%) fixed combination.

Notes: The MD before baseline (Pre), at baseline and 12, 24, and 36 months after switching in all patients.

Figure 2 Annual change of mean deviation (MD slope) during the 1 year before switching to dorzolamide/timolol (1%/0.5%) fixed combination (Pre), from baseline to 12 months after switching (12 months), 12–24 months after switching (12–24 months), and 24–36 months after switching (36 months) in all patients.

Figure 3 Pattern standard deviation (PSD) and foveal sensitivity before and after switching to dorzolamide/timolol (1%/0.5%) fixed combination. Mean values after switching to dorzolamide/timolol (1%/0.5%) fixed combination were compared with baseline values (P<0.05; *paired one-tailed Student’s t-test).

Abbreviation: NS, not significant.

Figure 4 Scatter plot with regression line for the relation between the mean deviation (MD) slope (dB/year) during 1 year before switching to dorzolamide/timolol (1%/0.5%) fixed combination (Pre-MD slope) and the mean MD slope for 3 years after switching (Post-MD slope).

Table 3 Correlations among the MD and MD slope before and after switching to DTFC

	Pre-MD		Baseline MD		Pre-MD slope		Post-MD slope
	R	P-value	R	P-value	R	P-value	R	P-value
Pre-MD	–	–
Baseline MD	0.99	<0.0001	–	–
Pre-MD slope	0.43	0.1277	0.53	0.0503	–	–
Post-MD slope	−0.16	0.5781	−0.27	0.3510	−0.63	0.0150	–	–

Note: Correlation coefficients were calculated by Pearson’s product moment formula.

Abbreviations: MD, mean deviation; DTFC, dorzolamide/timolol (1%/0.5%) fixed combination; Pre-MD, mean MD value for 1 (dB) year before switching to DTFC; Baseline MD, MD value (dB) immediately before switching to DTFC; Pre-MD slope, MD slope (dB/year) before switching; Post-MD slope, MD slope for 3 years (dB/year) after switching; R, Pearson’s correlation coefficient.

Figure 5 Scatter plots and regression lines for the association between the mean deviation (MD) slope for 3 years after switching (Post-MD slope) and the intraocular pressure (IOP) reduction rate at 3 years after switching to dorzolamide/timolol (1%/0.5%) fixed combination (A) and the mean IOP reduction rate for 3 years after switching to dorzolamide/timolol (1%/0.5%) fixed combination (B).

Table 4 Correlations between the MD slope for 3 years after switching and various factors, as well as multivariate odds ratios for the MD slope for 3 years (n=14)

Variable	Correlation coefficient		Multivariate analysis
	R	P-value	Odds ratio	95% confidence interval	P-value
Age, years	0.32	0.2647	1.02	−0.1 to 0.1	0.6358
Sex, male	0.06	0.8404	0.64	−1.9 to 0.8	0.4813
Right/left, left eye	−0.11	0.7015	0.53	−2.2 to 0.7	0.3505
Refraction, diopters	0.14	0.6412	1.04	−0.2 to 0.3	0.7290
POAG/NTG (POAG)	0.09	0.7553	1.68	−1.2 to 2.0	0.4827
No-increase/increase group (increase)	−0.21	0.4743	0.44	−2.6 to 0.7	0.3011
IOP, mmHg
Baseline	0.10	0.7388	1.00	−0.3 to 0.3	0.9920
3 months	0.27	0.3525	3.4	−5.0 to 4.3	0.4854
12 months	−0.21	0.4673	1.0	−10.7 to 5.3	0.9891
24 months	0.35	0.2211	0.3	−12.1 to 4.1	0.6624
36 months	−0.15	0.5975	0.9	−0.9 to 0.4	0.7687
IOP reduction, %
3 months	−0.10	0.7265	1.1	−0.7 to 0.6	0.5941
12 months	0.38	0.1772	1.0	−1.5 to 0.8	0.9731
24 months	−0.14	0.6452	0.9	−1.5 to 0.5	0.6943
36 months	0.67	0.0091	1.0	−0.2 to 0.1	0.7239
MD, dB
12 months	−0.17	0.5709	0.9	−3.2 to 1.5	0.9198
24 months	−0.03	0.9277	0.9	−2.6 to 1.2	0.8936
36 months	0.03	0.9256	1.2	−1.5 to 1.0	0.7071

Notes: Correlations between the mean MD slope for 3 years after switching to DTFC and various factors were calculated by using the two-tailed Pearson’s product moment formula. Independent determinants of the MD slope for 3 years after switching to DTFC were investigated by multiple logistic regression analysis. No-increase/increase group indicates no change/increase in the number of glaucoma medications after switching to DTFC.

Abbreviations: MD, mean deviation; R, Pearson’s correlation coefficient; POAG, primary open-angle glaucoma; NTG, normal tension glaucoma; IOP, intraocular pressure; DTFC, dorzolamide/timolol (1%/0.5%) fixed combination.

Table 5 Comparison of IOP- and MD-related parameters between patients with and without progression of visual field loss

Parameter	Progression of visual field loss		P-value
	−	+
Subjects, N	9	5	–
Age (years)	67.7±7.3	63.4±7.1	0.3578*
Male/female	6/3	3/2	0.6224†
Right/left	5/4	2/3	0.5000†
Refraction, diopters	−3.4±2.6	−3.8±3.2	0.8483*
IOP, mmHg
Mean before baseline	13.7±2.4	13.0±1.8	0.6035*
Baseline	14.6±3.2	13.2±1.2	0.3053*
3 months	12.9±2.8	12.0±0.9	0.4265*
12 months	12.2±2.6	14.0±1.7	0.1776*
24 months	11.9±2.0	11.2±1.3	0.4947*
36 months	12.3±3.6	12.4±1.5	0.9649*
IOP reduction, %
3 months	10.0±14.7	8.9±5.1	0.8417*
12 months	13.9±17.8	−5.8±5.7	0.0160*
24 months	16.8±12.2	14.6±11.8	0.7637*
36 months	14.5±15.7	5.6±11.6	0.2925*
Mean for 36 months	13.2±12.5	8.9±6.9	0.4554*
MD values, dB
Mean for 1 year before switching	−5.5±4.9	−6.8±4.2	0.6401*
Baseline	−5.7±5.3	−6.2±4.2	0.8552*
12 months	−4.8±4.8	−6.9±4.4	0.4673*
24 months	−4.9±4.9	−7.6±4.7	0.3902*
36 months	−4.8±5.0	−7.0±5.0	0.5092*
MD slope (dB/per year)
From 12 months before switching to baseline	−0.3±0.7	0.0±0.8	0.4405*
From baseline to 12 months	0.8±1.2	−0.7±0.9	0.0274*
From 12 to 24 months	−0.1±0.9	−0.6±1.3	0.4705*
From 24 to 36 months	0.1±0.7	0.6±1.0	0.3873*
Mean from baseline to 36 months	0.2±0.3	−0.5±0.7	0.1075*

Notes:

* Two-tailed unpaired t-test

† Fisher’s exact test.

Abbreviations: IOP, intraocular pressure; MD, mean deviation.

Table 6 Correlations between progression of visual field loss after switching to DTFC and various factors, as well as multivariate odds ratios for visual field progression (n=14)

Variable	Correlation coefficient		Multivariate analysis
	R	P-value	Odds ratio	95% confidence interval	P-value
IOP	−0.24	0.4095	0.2	−5.9 to 0.5	0.2417
Baseline	−0.24	0.4095	0.2	−5.9 to 0.5	0.2417
3 months	−0.18	0.5301	329.4	−7.8 to 12.6	0.2078
12 months	0.35	0.2222	0.1	−8.6 to 1.2	0.3124
24 months	−0.18	0.5386	0.9	−3.3 to 1.5	0.9123
36 months	0.01	0.9715	0.2	−5.5 to 0.2	0.1918
IOP reduction, %
3 months	−0.05	0.8746	2.3	−1.0 to 1.7	0.1927
12 months	−0.54	0.0455	0.7	−1.3 to 0.1	0.2701
24 months	−0.09	0.7597	1.0	−0.4 to 0.2	0.8465
36 months	−0.28	0.3241	0.8	−0.7 to 0.0	0.2065
MD at baseline	−0.05	0.8620	1.0	−0.2 to 0.1	0.9946
MD slope before switching*	0.23	0.4203	1.1	−1.3 to 0.8	0.7105

Notes: Correlations between the progression of visual field loss after switching to DTFC and various factors were calculated by using the two-tailed Pearson’s product moment formula. Independent determinants of the progression of visual field loss after switching to DTFC were investigated by multiple logistic regression analysis.

* MD slope from 12 months before switching to baseline.

Abbreviations: DTFC, dorzolamide/timolol (1%/0.5%) fixed combination; R, Pearson’s correlation coefficient; IOP, intraocular pressure; MD, mean deviation.