A comparison of country-level data from the VISIONARY study examining treatment outcomes with preservative-free tafluprost/timolol fixed-dose combination therapy

Figures & data

Table 1. Baseline demographics (total VISIONARY study population).

	Italy (n = 160)	Hungary (n = 96)	Spain (n = 92)	Russia (n = 87)	UK (n = 65)	Latvia (n = 51)	Ireland (n = 17)	Norway (n = 13)	Denmark (n = 8)	Netherlands (n = 1)	Sweden (n = 1)
Sex, n (%)
Male	73 (45.6)	40 (41.7)	45 (48.9)	24 (27.6)	28 (43.1)	15 (29.4)	8 (47.1)	6 (46.1)	2 (25.0)	0	0
Female	87 (54.4)	56 (58.3)	47 (51.1)	63 (72.4)	37 (56.9)	36 (70.6)	9 (52.9)	7 (53.9)	6 (75.0)	1 (100.0)	1 (100.0)
Age (years)
Mean (SD)	68.7 (11.5)	66.1 (11.3)	68.3 (12.1)	63.9 (11.8)	68.9 (11.0)	71.3 (11.1)	72.4 (10.6)	70.8 (10.0)	67.5 (8.9)	72.1 (N/A)	70.8 (N/A)
Range	27.3–89.0	33.1–89.7	39.7–89.8	23.7–84.3	39.7–96.1	44.8– 89.9	51.8–87.8	50.4–85.1	49.9–79.0	72.1–72.1	70.8–70.8
Diagnosis, n (%)
POAG	109 (68.1)	77 (80.2)	56 (60.9)	79 (90.8)	43 (66.2)	49 (96.1)	7 (41.2)	8 (61.5)	2 (25.0)	0	0
OHT	40 (25.0)	14 (14.6)	24 (26.1)	4 (4.6)	16 (24.6)	2 (3.9)	3 (17.6)	5 (38.5)	4 (50.0)	1 (100.0)	0
Pseudoexfoliative glaucoma	4 (2.5)	2 (2.1)	9 (9.8)	1 (1.2)	2 (3.1)	0	0	0	0	0	1 (100.0)
NTG	2 (1.2)	2 (2.1)	2 (2.2)	2 (2.3)	4 (6.2)	0	7 (41.2)	0	0	0	0
Pigmentary glaucoma	2 (1.2)	1 (1.0)	0	1 (1.2)	0	0	0	0	1 (12.5)	0	0
Other glaucoma	3 (1.9)	0	1 (1.1)	0	0	0	0	0	1 (12.5)	0	0
IOP at baseline, mmHg
Mean (SD) GAT	19.6 (3.61)	20.8 (3.40)	21.9 (3.97)	23.8 (5.37)	22.0 (4.50)	24.0 (4.65)	17.0 (2.65)	22.9 (4.27)	18.7 (2.87)	20.0 (N/A)	30.0 (N/A)
Mean (SD) iCare							18.6 (5.12)
Previous monotherapy
Beta-blocker	54 (33.7)	38 (39.6)	12 (13.0)	20 (23.0)	6 (9.2)	31 (60.8)	1 (5.9)	0	0	0	0
PGA	106 (66.3)	58 (60.4)	80 (87.0)	67 (77.0)	59 (90.8)	20 (39.2)	16 (94.1)	13 (100.0)	8 (100.0)	1 (100.0)	1 (100.0)
Reason(s) for change of therapy, n (%)^#
Insufficient IOP control	103 (64.4)	77 (80.2)	80 (87.0)	73 (83.9)	61 (93.8)	50 (98.0)	14 (82.3)	13 (100.0)	8 (100.0)	1 (100.0)	1 (100.0)
Poor local tolerance	40 (25.0)	18 (18.8)	2 (2.2)	23 (26.4)	18 (27.7)	5 (9.8)	0	0	0	0	0
Progression of glaucoma	37 (23.1)	12 (12.5)	18 (19.6)	16 (18.4)	7 (10.8)	0	3 (17.7)	4 (30.8)	0	0	0
Poor compliance	5 (3.1)	2 (2.1)	1 (1.1)	1 (1.1)	1 (1.5)	0	0	0	0	0	0
Conversion of OHT	1 (0.6)	1 (1.0)	2 (2.2)	3 (3.4)	0	0	0	1 (7.7)	0	0	0
Other reasons	0	2 (2.1)	1 (1.1)	0	2 (3.1)	0	0	0	0	0	0

#Investigators could select more than one reason/n for change of therapy. Abbreviations. GAT, Goldmann applanation tonometry; IOP, intraocular pressure; N/A, not available; NTG, normal tension glaucoma; OHT, ocular hypertension; POAG, primary open-angle glaucoma; SD, standard deviation.

Table 2. Change in mean intraocular pressure from baseline according to country (Country-level Subanalysis Population – countries recruiting ≥20 patients).

Country	Visit	N	Mean (SD) IOP, mmHg	Mean (SD) IOP reduction from baseline, mmHg	Mean IOP reduction from baseline (%)	p value*
Italy	Baseline	160	19.6 (3.61)
	Week 4	158	14.8 (2.49)	4.8 (3.39)	23.1	<.0001
	Week 12	153	14.4 (2.42)	5.1 (3.38)	24.7	<.0001
	Month 6	160	14.5 (2.55)	5.1 (3.70)	24.1	<.0001
Hungary	Baseline	96	20.8 (3.40)
	Week 4	93	16.0 (2.60)	4.8 (3.21)	21.7	<.0001
	Week 12	78	15.2 (2.29)	5.5 (3.37)	25.0	<.0001
	Month 6	96	15.8 (2.98)	5.0 (3.77)	22.6	<.0001
Spain	Baseline	92	21.9 (3.97)
	Week 4	85	16.6 (3.63)	5.5 (3.08)	24.3	<.0001
	Week 12	74	16.3 (3.07)	5.6 (3.25)	24.5	<.0001
	Month 6	92	16.7 (3.51)	5.2 (4.04)	22.3	<.0001
Russia	Baseline	87	23.8 (5.37)
	Week 4	83	16.7 (2.53)	7.3 (5.17)	28.6	<.0001
	Week 12	81	16.7 (2.69)	7.4 (5.40)	28.7	<.0001
	Month 6	87	16.7 (3.22)	7.1 (5.10)	28.1	<.0001
UK	Baseline	65	22.0 (4.50)
	Week 4	52	17.2 (3.55)	4.9 (3.75)	20.8	<.0001
	Week 12	52	16.6 (3.25)	5.4 (3.99)	22.9	<.0001
	Month 6	65	16.2 (2.94)	5.8 (3.95)	24.9	<.0001
Latvia	Baseline	51	24.0 (4.65)
	Week 4	51	18.6 (4.25)	5.4 (3.27)	21.9	<.0001
	Week 12	50	17.2 (3.37)	6.9 (3.40)	27.6	<.0001
	Month 6	51	16.2 (3.21)	7.8 (3.40)	31.8	<.0001

*Significant testing using two-sided paired t-test for change in mean IOP from baseline.

Statistical analysis was not conducted for country-level subgroups comprising <20 patients.

Abbreviations. IOP, Intraocular pressure; N/A, not available; SD, standard deviation.

Figure 1. Percentage of responders according to different intraocular pressure reduction cut-off values at Month 6, according to country (Country-level Subanalysis Population -countries recruiting ≥20 patients). Abbreviations. IOP, intraocular pressure.

Table 3. Mean (SD) intraocular pressure change according to baseline monotherapy, by country (Country-level Subanalysis Population – countries recruiting ≥20 patients).

Visit	N	Mean (SD) IOP, mm Hg	Mean (SD) reduction in IOP from baseline, mm Hg	Mean percentage of IOP reduction from baseline	p value*
Italy
PGA users
Baseline	106	19.5 (3.70)
Week 4	105	14.9 (2.37)	4.6 (3.52)	21.6	<.0001
Week 12	102	14.5 (2.32)	5.0 (3.46)	23.7	<.0001
Month 6	106	14.7 (2.30)	4.8 (3.61)	22.7	<.0001
Beta-blocker users
Baseline	54	19.8 (3.48)
Week 4	53	14.5 (2.71)	5.3 (3.07)	26.0	<.0001
Week 12	51	14.2 (2.61)	5.5 (3.25)	26.6	<.0001
Month 6	54	14.2 (2.97)	5.6 (3.88)	26.8	<.0001
Hungary
PGA users
Baseline	58	19.9 (3.35)
Week 4	55	16.0 (2.82)	3.8 (2.60)	18.4	<.0001
Week 12	48	15.4 (2.43)	4.5 (2.78)	21.4	<.0001
Month 6	58	16.2 (3.43)	3.7 (3.30)	17.6	<.0001
Beta-blocker users
Baseline	38	22.3 (3.00)
Week 4	38	16.1 (2.27)	6.2 (3.53)	26.5	<.0001
Week 12	30	15.0 (2.06)	7.2 (3.62)	30.8	<.0001
Month 6	38	15.2 (2.02)	7.1 (3.57)	30.2	<.0001
Spain
PGA users
Baseline	80	22.2 (3.78)
Week 4	73	16.7 (3.66)	5.6 (2.89)	24.9	<.0001
Week 12	65	16.3 (3.10)	5.7 (3.23)	25.0	<.0001
Month 6	80	16.7 (3.49)	5.5 (3.88)	23.5	<.0001
Beta-blocker users
Baseline	12	20.4 (4.98)
Week 4	12	15.6 (3.48)	4.8 (4.13)	21.1	N/A
Week 12	9	16.6 (3.00)	4.8 (3.42)	21.0	N/A
Month 6	12	16.9 (3.87)	3.5 (4.83)	14.6	N/A
Russia
PGA users
Baseline	67	23.4 (5.71)
Week 4	64	16.6 (2.72)	6.9 (5.52)	27.3	<.0001
Week 12	65	16.8 (2.77)	6.7 (5.67)	26.5	<.0001
Month 6	67	16.9 (3.24)	6.5 (5.06)	25.7	<.0001
Beta-blocker users
Baseline	20	25.3 (3.79)
Week 4	19	16.9 (1.76)	8.7 (3.56)	32.8	N/A
Week 12	16	16.4 (2.39)	10.1 (2.83)	37.8	N/A
Month 6	20	15.9 (3.06)	9.5 (4.61)	36.0	<.0001
UK
PGA users
Baseline	59	22.1 (4.59)
Week 4	48	17.2 (3.67)	5.0 (3.61)	21.4	<.0001
Week 12	47	16.8 (3.34)	5.4 (3.93)	22.8	<.0001
Month 6	59	16.1 (3.02)	6.0 (3.98)	25.5	<.0001
Beta-blocker users
Baseline	6	21.3 (3.72)
Week 4	4	17.0 (1.83)	3.5 (5.69)	13.9	N/A
Week 12	5	15.6 (2.30)	5.6 (5.03)	24.0	N/A
Month 6	6	17.0 (2.00)	4.3 (3.56)	18.9	N/A
Latvia
PGA users
Baseline	20	24.2 (3.62)
Week 4	20	18.2 (3.45)	6.1 (3.53)	24.5	<.0001
Week 12	20	16.7 (2.96)	7.5 (3.53)	30.3	<.0001
Month 6	20	16.3 (2.25)	7.9 (3.40)	31.8	<.0001
Beta-blocker users
Baseline	31	23.9 (5.26)
Week 4	31	18.9 (4.73)	4.9 (3.07)	20.3	<.0001
Week 12	30	17.5 (3.63)	6.4 (3.31)	25.7	<.0001
Month 6	31	16.1 (3.73)	7.8 (3.48)	31.8	<.0001

*Significant testing using two-sided test for change in mean IOP from baseline.

Statistical analysis was not conducted for country-level subgroups comprising <20 patients. Abbreviations: IOP, intraocular pressure; N/A, not available; PGA, prostaglandin analogue; SD, standard deviation.

Figure 2. Mean percentage change in IOP at Month 6 according to baseline pressure and country, at each VISIONARY study visit (Country-level Subanalysis Population – countries recruiting ≥20 patients). Abbreviations. IOP, intraocular pressure.

Table 4. Change in mean intraocular pressure from baseline according to timing of PF tafluprost/timolol FC dosing, by country (Country-level Subanalysis Population – countries recruiting ≥20 patients).

Visit	N	Mean (SD) IOP, mm Hg	Mean (SD) reduction in IOP from baseline, mmHg	Mean percentage of IOP reduction from baseline	p value*
Italy
Morning dose
Month 6	16	15.1 (3.03)	4.9 (4.58)	22.2	N/A
Evening dose
Month 6	128	14.4 (2.45)	4.9 (3.57)	23.7	<.0001
Hungary
Morning dose
Month 6	1	12.0 (N/A)	8.0 (N/A)	40.0	N/A
Evening dose
Month 6	91	16.0 (2.99)	4.7 (3.64)	21.4	<.0001
Russia
Morning dose
Month 6	15	18.4 (2.35)	4.3 (3.81)	17.8	N/A
Evening dose
Month 6	63	16.3 (3.02)	7.5 (4.38)	30.1	<.0001
Spain
Morning dose
Month 6	1	12.0 (N/A)	2.0 (N/A)	14.3	N/A
Evening dose
Month 6	89	16.8 (3.53)	5.2 (4.06)	22.3	<.0001
UK
Morning dose
Month 6	15	15.7 (3.45)	7.6 (4.76)	30.2	N/A
Evening dose
Month 6	31	16.6 (3.06)	5.2 (3.81)	22.5	<.0001
Latvia
Morning dose
Month 6	5	17.8 (1.48)	5.4 (1.14)	23.3	N/A
Evening dose
Month 6	45	16.0 (3.34)	8.2 (3.47)	32.9	<.0001

Statistical analysis was not conducted for country-level subgroups comprising <20 patients.

*Two-sided significance testing using paired t-test for change in mean IOP from baseline.

Abbreviations. IOP, Intraocular pressure; N/A, not available; SD, standard deviation.

Table 5. Change in mean intraocular pressure at Month 6 from baseline according to diagnosis, by country (Country-level Subanalysis Population – countries recruiting ≥20 patients).

Visit	N	Mean (SD) IOP, mmHg	Mean (SD) reduction in IOP from baseline, mmHg	Mean percentage of IOP reduction from baseline	p value*
Italy
OHT
Baseline	40	20.9 (3.18)
Month 6	40	14.3 (2.43)	6.5 (3.35)	30.3	<.0001
POAG
Baseline	109	19.2 (3.68)
Month 6	109	14.5 (2.36)	4.7 (3.62)	22.5	<.0001
NTG
Baseline	2	15.0 (1.41)
Month 6	2	12.5 (0.71)	2.5 (0.71)	16.5	N/A
Pseudoexfoliative glaucoma
Baseline	4	21.2 (4.11)
Month 6	4	15.2 (4.99)	6.0 (3.37)	28.5	N/A
Hungary
OHT
Baseline	14	21.6 (3.46)
Month 6	14	17.7 (2.67)	3.9 (4.60)	15.0	N/A
POAG
Baseline	77	20.7 (3.37)
Month 6	77	15.2 (2.51)	5.4 (3.45)	24.9	<.0001
NTG
Baseline	2	20.5 (2.12)
Month 6	2	14.0 (1.41)	6.5 (3.53)	31.0	N/A
Pseudoexfoliative glaucoma
Baseline	2	21.0 (7.07)
Month 6	2	23.0 (4.24)	–2.0 (2.83)#	12.5#	N/A
Russia
OHT
Baseline	4	25.2 (5.00)
Month 6	4	17.2 (2.22)	8.0 (2.94)	30.9	N/A
POAG
Baseline	79	23.8 (5.51)
Month 6	79	16.7 (3.29)	7.1 (5.25)	27.9	<.0001
NTG
Baseline	2	20.5 (0.71)
Month 6	2	15.5 (4.95)	5.0 (5.66)	23.9	N/A
Pseudoexfoliative glaucoma
Baseline	1	26.0 (N/A)
Month 6	1	15.0 (N/A)	11.0 (N/A)	42.3	N/A
Spain
OHT
Baseline	24	23.0 (3.91)
Month 6	24	16.7 (2.95)	6.3 (4.33)	25.8	<.0001
POAG
Baseline	56	21.6 (3.92)
Month 6	56	16.4 (3.42)	5.2 (3.62)	22.7	<.0001
NTG
Baseline	2	16.0 (2.82)
Month 6	2	15.5 (4.95)	0.5 (2.12)	4.4	N/A
Pseudoexfoliative glaucoma
Baseline	9	21.3 (3.24)
Month 6	9	18.7 (5.20)	2.7 (4.39)	12.6	N/A
UK
OHT
Baseline	16	25.0 (5.88)
Month 6	16	16.1 (3.30)	8.8 (4.29)	34.0	N/A
POAG
Baseline	43	21.6 (3.23)
Month 6	43	16.4 (2.80)	5.2 (3.29)	22.9	<.0001
NTG
Baseline	4	16.0 (1.63)
Month 6	4	14.7 (1.71)	1.2 (2.06)	7.3	N/A
Pseudoexfoliative glaucoma
Baseline	2	19.0 (4.24)
Month 6	2	14.0 (5.66)	5.0 (1.41)	27.8	N/A
Latvia
OHT
Baseline	2	23.5 (3.53)
Month 6	2	17.0 (2.83)	6.5 (0.71)	27.7	N/A
POAG
Baseline	49	24.0 (4.72)
Month 6	49	16.1 (3.24)	7.9 (3.46)	32.0	<.0001

#Increase in IOP versus baseline.

*Significance testing using two-sided paired t-test for mean reduction in IOP from baseline.

Statistical analysis was not conducted for country-level subgroups comprising <20 patients.

Abbreviations. IOP, intraocular pressure; N/A, not available; NTG, normal tension glaucoma; OHT, ocular hypertension; POAG, primary open-angle glaucoma; SD, standard deviation.

Table 6. Reported treatment-related adverse events according to country (Full Analysis Set).

System/organ class	Number of treatment-related AEs	Intensity
Italy
Ocular
Eyelash growth	1	Mild
Hungary
Ocular
Blepharal pigmentation	1	Mild
Eye discharge	1	Mild
Eye pain	3	Mild
Lacrimation increased	1	Mild
Ocular discomfort	1	Mild
Ocular hyperemia	1	Mild
Russia
Ocular
Dry eye	1	Mild
Respiratory
Status asthmaticus	1	Moderate
Spain
Cardiovascular
Bradycardia	1	Mild
Neurological
Dizziness	1	Mild
General
Fatigue	1	Moderate
UK
Ocular
Blepharal pigmentation	1	Mild
Conjunctival hyperemia	1	Mild
Erythema of eyelid	1	Moderate
Eye pain	12	Mild
Eye pain	1	Moderate
Eye pain	1	Severe
Eye pruritus	1	Moderate
Eyelid pain	1	Mild
Foreign body sensation in eyes	2	Mild
Ocular hyperemia	2	Moderate
Dermatological
Abnormal hair growth	1	Mild
Neurological
Dizziness	1	Mild
General
Fatigue	1	Severe
Denmark
Ocular
Iris hyperpigmentation	1	Mild
Dermatological
Skin hyperpigmentation	1	Mild

No treatment-related AEs were reported among the FAS population from Latvia, Netherlands, Norway, Ireland and Sweden.

Data availability statement

The datasets used during and/or analyzed during the current study are available from the corresponding author on reasonable request.