Preservative-free versus preserved latanoprost eye drops in patients with open-angle glaucoma or ocular hypertension

Figures & data

Figure 1. Study design.

Figure 2. Patient disposition.

Table 1. Demographic and other baseline characteristics.

Baseline characteristic^a	All patients (N = 30)
Age (mean ± SD) (years)	50.7 ± 12.8
Gender
Male	21 (70.0)
Female	9 (30.0)
Visual field
Normal	4 (13.3)
Abnormal	26 (86.7)
Funduscopy – pathologic cup to disk ratio ≥0.4	22 (73.3)
Pachymetry (μm ± SD) (worse eye)	540 ± 28.0
Slit lamp examinations (worse eye)
Conjunctival hyperemia	0 (0.0)
Corneal staining punctuations
None	29 (96.7)
<10%	1 (3.3)
Folliculo-papillary conjunctivitis	0 (0.0)
Palpebral abnormality	2 (6.7)
Anterior chamber flare	0 (0.0)
Other
Moderate left exotropia	1 (3.3)
Moderate endothelial pigment	1 (3.3)
Ocular symptoms
Eye dryness	3 (10.0)
Irritation/stinging/burning	2 (6.7)
Itching	7 (23.3)
Disturbing	7 (23.3)
Tearing	5 (16.6)
Present but not disturbing	4 (13.3)
Disturbing	1 (3.3)
Foreign body sensation	3 (10.0)
Present but not disturbing	3 (10.0)
Photophobia	5 (16.6)
Present but not disturbing	4 (13.3)
Disturbing	1 (3.3)
Heart rate (beats per minute)	77.1 ± 9.3

^a With the exception of age (years), pachymetry (μm), and heart rate (bpm), data presented as number (%) of subjects.

Abbreviation. SD, standard deviation.

Table 2. Mean ± SD IOP in the worse eye at baseline and following treatment in each group (PP set).

Time of day	Mean ± SD IOP (mmHg)
	Baseline	After 6 weeks (42 days) of treatment (N = 26)
		Preserved latanoprost	Preservative-free latanoprost	Difference^a	95%CI
08:00	22.8 ± 2.9	16.2 ± 2.9	16.6 ± 2.2	0.5 ± 2.5	−0.56	1.49
12:00	23.6 ± 3.6	16.4 ± 2.9	16.5 ± 2.6	0.1 ± 2.8	−1.06	1.18
16:00	22.6 ± 3.7	16.4 ± 3.0	15.9 ± 3.0	−0.4 ± 2.6	−1.49	0.64
20:00	21.9 ± 4.4	16.6 ± 3.2	16.3 ± 3.3	−0.3 ± 3.7	−1.74	1.24
Diurnal	22.7 ± 3.0	16.4 ± 2.6	16.3 ± 2.4	−0.0 ± 2.1	−0.89	0.81

^a Preservative-free minus preserved latanoprost.

Abbreviations. SD, standard deviation; IOP, intraocular pressure; CI, confidence interval.

Table 3. Ocular symptoms that occurred upon instillation and that occurred but not upon instillation (safety set).

Symptom	Preserved latanoprost (N = 30)	Preservative-free latanoprost (N = 30)
Upon instillation:
Burning/stinging
Overall	5	3
Frequent/very frequent	2	0
Rarely/infrequent	3	3
Pruritus
Overall	4	4
Frequent/very frequent	1	2
Rarely/infrequent	3	2
Sticky eye
Overall	1	6
Frequent/very frequent	0	4
Rarely/infrequent	1	2
Blurred vision
Overall	1	2
Frequent/very frequent	0	2
Rarely/infrequent	1	0
Foreign body
Overall	0	1
Frequent/very frequent	0	0
Rarely/infrequent	0	1
Eye dryness
Overall	0	1
Frequent/very frequent	0	1
Rarely/infrequent	0	0
Not upon instillation:
Burning/stinging/irritation
Overall	2	3
Present but not disturbing	2	3
Itching
Overall	9	8
Present but not disturbing	9	7
Disturbing	0	1
Tearing
Overall	3	2
Present but not disturbing	3	2
Foreign body
Overall	3	4
Present but not disturbing	3	4
Photophobia
Overall	2	2
Present but not disturbing	2	2

Data presented as number of patients with symptom.

Table 4. Slit lamp examination for the worse eye (safety set).

	Preserved latanoprost (N = 30)	Preservative-free latanoprost (N = 30)
Conjunctival hyperemia	7	5
Conjunctival vessels moderately dilated	4	5
Conjunctival and episcleral vessels dilated	3	0
Corneal staining punctuations	3	2
Some stained punctuations <10%	2	1
Diffused stained punctuations ≤50%   of corneal area	1	1
Folliculo-papillary conjunctivitis	0	2
Palpebral abnormality	1	2
Anterior chamber flare	0	0

Data presented as number of patients with finding.

Figure 3. Individual plasma concentration data of latanoprost (Day 42 and Day 84).

Table 5. Summary of AUC_0–30, C_max, and t_max (PK set).

Parameter	BLQ^a (pg/mL)		Preserved latanoprost (N = 29)	Preservative-free latanoprost (N = 29)	Preserved/preservative-free (N = 29)
AUC0–30	0	Arithmetic mean	1063.5	726.0	NC
(mins*pg/mL)		Geometric mean	515.5	316.9	0.615
		95% CI	708.57; 1418.45	469.60; 982.30	0.348; 1.085
		SD	933.11	673.94	NC
	20	Arithmetic mean	1379.0	1086.3*	NC
		Geometric mean	1203.0	992.4*	0.825
		95% CI	1080.80; 1677.26	892.74; 1279.85	0.697; 0.796
		SD	784.03	508.84	NC
	39	Arithmetic mean	1678.8	1428.6*	NC
		Geometric mean	1583.3	1393.7*	0.880
		95% CI	1429.41; 1928.13	1287.98; 1569.26	0.792; 0.978
		SD	655.56	369.74	NC
Cmax	0	Arithmetic mean	70.8	47.9*	NC
(pg/mL)		Geometric mean	61.5	46.0*	0.748
		95% CI	51.97; 89.68	34.94; 60.78	0.621; 0.901
		SD	49.57	33.97	NC
	20	Arithmetic mean	74.3	52.7*	NC
		Geometric mean	61.5	46.0*	0.748
		95% CI	57.22; 91.33	42.26; 63.11	0.621; 0.901
		SD	44.84	27.41	NC
	39	Arithmetic mean	77.5	57.3*	NC
		Geometric mean	69.0	54.0*	0.783
		95% CI	61.89; 93.21	48.69; 65.86	0.679; 0.903
		SD	41.18	22.57	NC
tmax		Arithmetic mean	7.3	10.7	NC
(mins)		95% CI	6.22; 8.37	9.26; 12.10	NC

^a AUC_0–30 and C_max calculated using BLQs of 0, LOQ/2, and LOQ.

* p < 0.05 compared to preserved latanoprost.

Abbreviations. NC, not calculated; AUC, area under the curve; PK, pharmacokinetics; BLQ, below the limit of quantitation; CI, confidence interval; SD, standard deviation; LOQ, limit of quantification.