LYNX: Long-Term Non-Interventional Latanoprost Study

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01265719
• Collaborator: (none)
• Enrollment: 175
• Locations: 29
• Actual Duration (Months): 62
• Patients Per Site: 6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a non-interventional, prospective, longitudinal cohort study. A total of 150 pediatric subjects with glaucoma or elevated intraocular pressure, including 75 latanoprost-treated subjects and 75 non-topical prostaglandin analogue treated subjects, will be enrolled from ophthalmic hospital clinics and academic ophthalmic centers. As a non-interventional study, the study subjects' continued use of latanoprost and assessments of ocular events will be obtained through the routine medical follow-up with treating ophthalmologists or other designated members of the medical care team.

Condition or Disease	Intervention/Treatment	Phase
Glaucoma; Ocular Hypertension	Other: No intervention other than routine medical care; Other: No intervention other than routine medical care

Detailed Description

At least 40 subjects in each of the following age groups: 1-<5 years and 5-<18 years. No minimum required numbers in the <1 year age group.

Study Design

• Study Type: Observational
• Actual Enrollment: 175 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: A Prospective, Non-interventional, Longitudinal Cohort Study To Evaluate The Long-term Safety Of Latanoprost Treatment In Pediatric Populations
• Actual Study Start Date: Dec 1, 2010
• Actual Primary Completion Date: Feb 1, 2016
• Actual Study Completion Date: Feb 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Latanoprost-treatment group	Other: No intervention other than routine medical care; Subjects continuously treated with Latanoprost for at least one month Latanoprost treatment during the study period.; Other Names: Observational
Non-topical prostaglandin analogue treatment group	Other: No intervention other than routine medical care; Subjects not treated with any topical prostaglandin analogues or continuously treated with topical prostaglandin analogues for less than one month before the baseline examination, and unlikely to be treated with topical prostaglandin analogues during the study period.; Other Names: Observational

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to Last Available Observation in Best Corrected Visual Acuity (BCVA) (Snellen or Equivalent) [Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months]

   Patients familiar with the letters of the alphabet were evaluated using Snellen visual acuity. Patients who were unable or unfamiliar with the letters of the alphabet were evaluated using charts made up of numbers, pictures (eg, Schering's Children's Eye Chart or Allen Cards), E's, or Landolt's broken rings, and other methods which were equivalent to Snellen acuity eg, HOTV testing).

Secondary Outcome Measures

1. Number of Participants With Clinically Meaningful Change in Refractive Error [Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months]

   The refractive error [cycloplegic where appropriate (eg, those unable to cooperate with manifest refraction)] were determined at the baseline visit and assessed at the following visits.

2. Change From Baseline to Last Available Observation in Horizontal Corneal Diameter (by Caliper and/or Ruler) [Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months]

   The horizontal corneal diameter was measured along the horizontal meridians. Diameter was measured using either a series of transparent plates with holes of different diameters in quarter-millimeter increments or with calibrated calipers compared against a ruler. When using calipers, the corneal diameter measurement was taken from limbus to a similar point 180° away at the opposite limbus. When not examining the children with anesthesia, it was recommended to use a tape measure across the head while measuring horizontal corneal diameter by photographic method.

3. Change From Baseline to Last Available Observation in Intraocular Pressure (IOP) [Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months]

   IOP was preferably measured using 1 of 3 applanation-contact methods: Goldmann applanation tonometry, Perkins tonometry, or TonoPen® (tonometry). iCare® rebound tonometer was also allowed if it was used consistently throughout the study.

4. Cup-to-disc Ratio (for Assessment of Optic Nerve Changes/Structures) - Number of Participants With Clinically Significant Deterioration in Cup/Disc Ratios [Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months]

   The cup/disc ratio was recorded horizontally and vertically for each examination, and reported in 0.1 increments.

5. Visual Field Defects - Number of Participants With Clinically Significant Deterioration of Visual Field Defects. [Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months]

   A visual field examination was performed for those patients who can cooperate automated perimetry utilizing a threshold program. All visual fields was conducted utilizing the standard white background with a Goldmann size III white stimulus. For those patients who can not perform formal visual field testing, then field to confrontation test was used for younger, non-verbal children, central, steady and maintains fixation was used.

6. Iris Color Darkening [Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months]

   Changes from baseline in iris color were reported at each follow-up visit. Photographs were taken at the discretion of investigators as per standard of care.

7. Localized Pigmentation (Nevi or Freckles) of Conjunctiva, Iris and Choroid [Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months]

   Changes from baseline in localized pigmentation (nevi and freckles) of the conjunctiva, iris and choroid were reported at each follow-up visit. Photographs were taken at the discretion of investigators as per standard of care.

8. Eyelash Darkening/Thickening [Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months]

   Changes from baseline in eyelash darkening/thickening/lengthening were reported at each follow-up visit. Photographs were taken at the discretion of investigators as per standard of care.

9. Change From Baseline to Last Available Observation in Length of Eyelash (by Caliper and/or Ruler) [Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months]

   The longest eyelash (mm) measured by caliper or ruler was recorded at baseline and each follow-up visit.

10. Change From Baseline to Last Available Observation in Corneal Thickness (Pachymeter) [Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months]

    Central corneal thickness was measured using a calibrated pachymeter, preferably an ultrasonic pachymeter.

11. Conjunctival/Ocular Hyperemia [Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months]

    Conjunctiva hyperemia was assessed by slit-lamp examination. When slit-lamp examination is not possible due to subject cooperation, a fixation light and 20-diopter lens (for magnification) was used to assess this parameter. Conjunctival hyperemia was assessed and graded by ophthalmologist at baseline and follow-up visits from grades 0-3 and is as follows: 0 = None, Normal: few vessels of palpebral or bulbar conjunctiva easily observed = Mild, Reddening of the palpebral or bulbar conjunctiva = Moderate, Bright reddening of the palpebral or bulbar conjunctiva = Severe, Deep, bright, and diffuse reddening of the palpebral or bulbar conjunctiva

12. Number of Participants With a Change in Anterior Segment Biomicroscopy [Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months]

    Slit-lamp biomicroscopy (mounted or hand-held) without fluorescein and without dilation of the pupil was performed. When slit-lamp examination was not possible, a fixation light and 20-diopter lens (for magnification) was used. At each scheduled visit, deposition of pigment on the corneal endothelial layer or the lens capsule or any abnormalities of the lids, conjunctivae, cornea, anterior chamber, iris, or lens was examined.

13. Number of Participants With Abnormalities in Fundoscopy Posterior Segment at Baseline [Evaluated at Baseline]

    Fundoscopy was performed after dilation of the pupils (eg, 1 % tropicamide or cyclopentolate and 2 ½ % phenylephrine, or a clinically- appropriate dose according to the clinician's standard care of each particular patient). The examination included an evaluation of the vitreous body, retina (including the macula), and optic nerve head. The fundoscopy e-CRF was completed only at baseline because the investigators were required to perform slit lamp, direct or indirect ophthalmoscopy at each visit and report any AEs observed which included the vitreous, retina and optic nerve.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Day to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female <18 years of age (neonates must be at least 36 weeks gestational age).

• Diagnosis of pediatric glaucoma or elevated intraocular pressure.

• Evidence of a personally signed and dated informed consent document indicating that the subject (and/or a legally acceptable representative) has been informed of all pertinent aspects of the study. A signed and dated assent will be required where applicable according to local laws.

For treated subjects only:

• Continuously treated with latanoprost for at least 1 month within the year prior to the baseline examination.

For untreated subjects only:

• Continuously treated with latanoprost or other topical prostaglandin analogues for less than one month prior to the baseline examination (based on the best knowledge of treating ophthalmologists), and unlikely to be treated with latanoprost or other topical prostaglandin analogues during the three-year study period; OR

• No prior treatment with latanoprost or other topical prostaglandin analogues, and unlikely to be treated with latanoprost or other topical prostaglandin analogues during the three-year study period.

Exclusion Criteria:

• Unable/unwilling to comply with protocol.

• Pregnant or nursing females at baseline.

• For treated subjects only: a history of allergy or hypersensitivity to any of the ingredients contained in latanoprost (e.g., hypersensitivity to benzalkonium chloride).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Universitair Ziekenhuis Antwerpen, Dienst Oftalmologie	Edegem		Belgium	2650
2	Universitair Ziekenhuis Leuven - Campus Sint-Raphaël	Leuven		Belgium	3000
3	Clinica de Oftalmologia San Diego	Medellin	Antioquia	Colombia	050016
4	Fakultni nemocnice Brno	Brno		Czechia	613 00
5	Fakultni nemocnice v Motole	Praha 5		Czechia	150 06
6	Rigshospitalet - Glostrup	Glostrup		Denmark	2600
7	Fondation Ophtalmologique Adolphe de Rothschild	Paris	Cedex 19	France	75940
8	CHU d'Amiens -Centre Saint Victor	Amiens		France	80000
9	Hopital Claude Huriez	Lille Cedex		France	59037
10	Universitaetsklinikum Giessen und Marburg	Giessen		Germany	35392
11	Universitaetsklinikum Hamburg-Eppendorf	Hamburg		Germany	20246
12	Universitaetsklinikum Mainz	Mainz		Germany	55131
13	University General Hospital of Thessaloniki AHEPA	Thessaloniki		Greece	54636
14	Azienda Ospedaliero Univ.	Catania	CT	Italy	95123
15	Ospedale Pediatrico Bambino Gesu	Fiumicino (Roma)		Italy	00050
16	Istituto Giannina Gaslini, Divisione di Oculistica	Genova		Italy	16147
17	Unita' Operativa di Oculistica Pediatrica, Azienda Ospedaliera Ospedale Niguarda Ca'Grande	Milano		Italy	20162
18	Óptima Visión	Miraflores	Lima	Peru	L 18
19	AIBILI - Associação para a Investigação Biomédica e Inovação em Luz e Imagem	Coimbra		Portugal	3000-548
20	Detska Fakultna nemocnica s poliklinikou Bratislava	Bratislava		Slovakia	83340
21	Hospital Sant Joan de Deu	Esplugues de Llobregat	Barcelona	Spain	08950
22	Hospital Clinico San Carlos	Madrid		Spain	28040
23	Hospital Virgen Del Rocio	Sevilla		Spain	41013
24	Hospital Universitario Miguel Servet	Zaragoza		Spain	50009
25	Akademiska Sjukhuset	Uppsala		Sweden	751 85
26	Ögonkliniken, Centrallasarettet	Västerås		Sweden	721 89
27	Manchester Royal Eye Hospital	Manchester	Gt Man	United Kingdom	M13 9WH
28	Birmingham and Midland Eye Centre, Consultant Ophthalmologist	Birmingham		United Kingdom	B18 7QH
29	Richard Desmond Childrens Eye Centre	London		United Kingdom	EC1V 2PD

Sponsors and Collaborators

• Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• ClinicalTrials.gov Identifier: NCT01265719
• Other Study ID Numbers: A6111143; PFI-LAT-2009-01; LYNX
• First Posted: Dec 23, 2010
• Last Update Posted: Feb 3, 2021
• Last Verified: Feb 1, 2018

• Keywords provided by Pfizer's Upjohn has merged with Mylan to form Viatris Inc.: Prospective; non-interventional; longitudinal; cohort study
• Additional relevant MeSH terms: Ocular Hypertension

Study Results

Participant Flow

Recruitment Details	A total of 175 patients were enrolled into the study in 14 countries in Europe and South America: 102 in the latanoprost treatment group and 73 in the non-Prostaglandin (PG) treatment group.
Pre-assignment Detail	No significant events prior to group assignment are to be reported. This was a non-interventional, prospective, longitudinal cohort study. Pediatric patients with glaucoma or elevated intra ocular pressure (IOP) were enrolled into 2 groups: Latanoprost-treated patients and non-PG treated patients.

Arm/Group Title	Latanoprost Group	Non Prostaglandin Group
Arm/Group Description	Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination and treated with latanoprost during the study period. Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination only.	Patients continuously treated with latanoprost or other topical PG analogues for less than 1 month before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period. Patients not treated with latanoprost or other topical PG analogues before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period.
Period Title: Overall Study
STARTED	102	73
COMPLETED	88	60
NOT COMPLETED	14	13

Baseline Characteristics

Arm/Group Title	Latanoprost Group	Non Prostaglandin Group	Total
Arm/Group Description	Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination and treated with latanoprost during the study period. Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination only.	Patients continuously treated with latanoprost or other topical PG analogues for less than 1 month before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period. Patients not treated with latanoprost or other topical PG analogues before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period.	Total of all reporting groups
Overall Participants	102	73	175
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	8.8 (4.96)	6.4 (4.76)	7.8 (5.01)
Sex: Female, Male (Count of Participants)
Female	48 47.1%	28 38.4%	76 43.4%
Male	54 52.9%	45 61.6%	99 56.6%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Last Available Observation in Best Corrected Visual Acuity (BCVA) (Snellen or Equivalent)
Description	Patients familiar with the letters of the alphabet were evaluated using Snellen visual acuity. Patients who were unable or unfamiliar with the letters of the alphabet were evaluated using charts made up of numbers, pictures (eg, Schering's Children's Eye Chart or Allen Cards), E's, or Landolt's broken rings, and other methods which were equivalent to Snellen acuity eg, HOTV testing).
Time Frame	Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months

Outcome Measure Data

Analysis Population Description

The Full Analysis population included all enrolled subjects.

Arm/Group Title	Latanoprost Group	Non Prostaglandin Group
Arm/Group Description	Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination and treated with latanoprost during the study period. Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination only.	Patients continuously treated with latanoprost or other topical PG analogues for less than 1 month before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period. Patients not treated with latanoprost or other topical PG analogues before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period.
Measure Participants	102	73
<5 years	0.25 (0.17)	-0.07 (0.09)
5 to <18 years	0.01 (0.02)	0.04 (0.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Latanoprost Group, Non Prostaglandin Group
	Comments	<5 years
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1126
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference
	Estimated Value	0.33
	Confidence Interval	(2-Sided) 95%; -0.09 to 0.74
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.20
	Estimation Comments	Change from baseline to last available observation in BCVA was analyzed using an ANCOVA model with fixed effect for treatment group with baseline BCVA value as covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Latanoprost Group, Non Prostaglandin Group
	Comments	5 to <18 years
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4840
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference
	Estimated Value	-0.03
	Confidence Interval	(2-Sided) 95%; -0.12 to 0.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.04
	Estimation Comments	Change from baseline to last available observation in BCVA was analyzed using an ANCOVA model with fixed effect for treatment group with baseline BCVA value as covariate.

2. Secondary Outcome

Title	Number of Participants With Clinically Meaningful Change in Refractive Error
Description	The refractive error [cycloplegic where appropriate (eg, those unable to cooperate with manifest refraction)] were determined at the baseline visit and assessed at the following visits.
Time Frame	Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months

Outcome Measure Data

Analysis Population Description

The Full Analysis population included all enrolled subjects.

Arm/Group Title	Latanoprost Group	Non Prostaglandin Group
Arm/Group Description	Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination and treated with latanoprost during the study period. Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination only.	Patients continuously treated with latanoprost or other topical PG analogues for less than 1 month before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period. Patients not treated with latanoprost or other topical PG analogues before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period.
Measure Participants	102	73
Number [Participants]	8 7.8%	2 2.7%

3. Secondary Outcome

Title	Change From Baseline to Last Available Observation in Horizontal Corneal Diameter (by Caliper and/or Ruler)
Description	The horizontal corneal diameter was measured along the horizontal meridians. Diameter was measured using either a series of transparent plates with holes of different diameters in quarter-millimeter increments or with calibrated calipers compared against a ruler. When using calipers, the corneal diameter measurement was taken from limbus to a similar point 180° away at the opposite limbus. When not examining the children with anesthesia, it was recommended to use a tape measure across the head while measuring horizontal corneal diameter by photographic method.
Time Frame	Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months

Outcome Measure Data

Analysis Population Description

The Full Analysis population included all enrolled subjects.

Arm/Group Title	Latanoprost Group	Non Prostaglandin Group
Arm/Group Description	Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination and treated with latanoprost during the study period. Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination only.	Patients continuously treated with latanoprost or other topical PG analogues for less than 1 month before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period. Patients not treated with latanoprost or other topical PG analogues before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period.
Measure Participants	102	73
<5 years	0.33 (0.22)	0.37 (0.19)
5 to <18 years	0.08 (0.12)	0.05 (0.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Latanoprost Group, Non Prostaglandin Group
	Comments	<5 years
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.9020
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.63 to 0.56
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.30
	Estimation Comments	Change from baseline to last available observation in HCD was analyzed using an ANCOVA model with fixed effect for treatment group with baseline HCD value as covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Latanoprost Group, Non Prostaglandin Group
	Comments	5 to <18 years
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.8826
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; -0.37 to 0.43
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.20
	Estimation Comments	Change from baseline to last available observation in HCD was analyzed using an ANCOVA model with fixed effect for treatment group with baseline HCD value as covariate.

4. Secondary Outcome

Title	Change From Baseline to Last Available Observation in Intraocular Pressure (IOP)
Description	IOP was preferably measured using 1 of 3 applanation-contact methods: Goldmann applanation tonometry, Perkins tonometry, or TonoPen® (tonometry). iCare® rebound tonometer was also allowed if it was used consistently throughout the study.
Time Frame	Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months

Outcome Measure Data

Analysis Population Description

The Full Analysis population included all enrolled subjects.

Arm/Group Title	Latanoprost Group	Non Prostaglandin Group
Arm/Group Description	Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination and treated with latanoprost during the study period. Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination only.	Patients continuously treated with latanoprost or other topical PG analogues for less than 1 month before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period. Patients not treated with latanoprost or other topical PG analogues before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period.
Measure Participants	102	73
<5 years	-1.01 (0.94)	0.61 (0.78)
5 to <18 years, IOP <21mmHg at Baseline	1.52 (0.43)	1.62 (0.61)
5 to <18 years, IOP ≥21mmHg at Baseline	-4.26 (1.22)	2.40 (1.99)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Latanoprost Group, Non Prostaglandin Group
	Comments	<5 years
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2003
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference
	Estimated Value	-1.62
	Confidence Interval	(2-Sided) 95%; -4.13 to 0.89
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.25
	Estimation Comments	Change from baseline to last available observation in IOP was analyzed using an ANCOVA model with fixed effect for treatment group with baseline IOP value as covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Latanoprost Group, Non Prostaglandin Group
	Comments	5 to <18 years (IOP <21mmHg at Baseline)
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.8940
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference
	Estimated Value	-0.10
	Confidence Interval	(2-Sided) 95%; -1.59 to 1.39
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.75
	Estimation Comments	Change from baseline to last available observation in IOP was analyzed using an ANCOVA model with fixed effect for treatment group with baseline IOP value as covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Latanoprost Group, Non Prostaglandin Group
	Comments	5 to <18 years (IOP ≥21mmHg at Baseline)
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0184
	Comments
	Method	ANCOVA
	Comments	The results were interpreted with caution because of the very small sample size of non-PG treatment group (n=4).
Method of Estimation	Estimation Parameter	LS Mean difference
	Estimated Value	-6.66
	Confidence Interval	(2-Sided) 95%; -11.95 to -1.36
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.41
	Estimation Comments	Change from baseline to last available observation in IOP was analyzed using an ANCOVA model with fixed effect for treatment group with baseline IOP value as covariate.

5. Secondary Outcome

Title	Cup-to-disc Ratio (for Assessment of Optic Nerve Changes/Structures) - Number of Participants With Clinically Significant Deterioration in Cup/Disc Ratios
Description	The cup/disc ratio was recorded horizontally and vertically for each examination, and reported in 0.1 increments.
Time Frame	Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months

Outcome Measure Data

Analysis Population Description

The Full Analysis population included all enrolled subjects.

Arm/Group Title	Latanoprost Group	Non Prostaglandin Group
Arm/Group Description	Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination and treated with latanoprost during the study period. Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination only.	Patients continuously treated with latanoprost or other topical PG analogues for less than 1 month before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period. Patients not treated with latanoprost or other topical PG analogues before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period.
Measure Participants	102	73
Number [Participants]	1 1%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Latanoprost Group, Non Prostaglandin Group
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	>0.999
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; -13.97 to 15.90
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Visual Field Defects - Number of Participants With Clinically Significant Deterioration of Visual Field Defects.
Description	A visual field examination was performed for those patients who can cooperate automated perimetry utilizing a threshold program. All visual fields was conducted utilizing the standard white background with a Goldmann size III white stimulus. For those patients who can not perform formal visual field testing, then field to confrontation test was used for younger, non-verbal children, central, steady and maintains fixation was used.
Time Frame	Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months

Outcome Measure Data

Analysis Population Description

The Full Analysis population included all enrolled subjects.

Arm/Group Title	Latanoprost Group	Non Prostaglandin Group
Arm/Group Description	Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination and treated with latanoprost during the study period. Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination only.	Patients continuously treated with latanoprost or other topical PG analogues for less than 1 month before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period. Patients not treated with latanoprost or other topical PG analogues before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period.
Measure Participants	102	73
Number [Participants]	1 1%	1 1.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Latanoprost Group, Non Prostaglandin Group
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	>0.999
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -15.32 to 14.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Iris Color Darkening
Description	Changes from baseline in iris color were reported at each follow-up visit. Photographs were taken at the discretion of investigators as per standard of care.
Time Frame	Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months

Outcome Measure Data

Analysis Population Description

The Full Analysis population included all enrolled subjects.

Arm/Group Title	Latanoprost Group	Non Prostaglandin Group
Arm/Group Description	Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination and treated with latanoprost during the study period. Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination only.	Patients continuously treated with latanoprost or other topical PG analogues for less than 1 month before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period. Patients not treated with latanoprost or other topical PG analogues before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period.
Measure Participants	102	73
Number [Participants]	4 3.9%	2 2.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Latanoprost Group, Non Prostaglandin Group
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	>0.999
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 95%; -13.78 to 16.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Localized Pigmentation (Nevi or Freckles) of Conjunctiva, Iris and Choroid
Description	Changes from baseline in localized pigmentation (nevi and freckles) of the conjunctiva, iris and choroid were reported at each follow-up visit. Photographs were taken at the discretion of investigators as per standard of care.
Time Frame	Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months

Outcome Measure Data

Analysis Population Description

The Full Analysis population included all enrolled subjects.

Arm/Group Title	Latanoprost Group	Non Prostaglandin Group
Arm/Group Description	Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination and treated with latanoprost during the study period. Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination only.	Patients continuously treated with latanoprost or other topical PG analogues for less than 1 month before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period. Patients not treated with latanoprost or other topical PG analogues before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period.
Measure Participants	102	73
Number [Participants]	3 (0.17) 2.9%	3 (0.09) 4.1%

9. Secondary Outcome

Title	Eyelash Darkening/Thickening
Description	Changes from baseline in eyelash darkening/thickening/lengthening were reported at each follow-up visit. Photographs were taken at the discretion of investigators as per standard of care.
Time Frame	Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months

Outcome Measure Data

Analysis Population Description

The Full Analysis population included all enrolled subjects.

Arm/Group Title	Latanoprost Group	Non Prostaglandin Group
Arm/Group Description	Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination and treated with latanoprost during the study period. Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination only.	Patients continuously treated with latanoprost or other topical PG analogues for less than 1 month before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period. Patients not treated with latanoprost or other topical PG analogues before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period.
Measure Participants	102	73
Number [Participants]	3 2.9%	1 1.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Latanoprost Group, Non Prostaglandin Group
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6414
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	1.6
	Confidence Interval	(2-Sided) 95%; -13.39 to 16.48
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Change From Baseline to Last Available Observation in Length of Eyelash (by Caliper and/or Ruler)
Description	The longest eyelash (mm) measured by caliper or ruler was recorded at baseline and each follow-up visit.
Time Frame	Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months

Outcome Measure Data

Analysis Population Description

The Full Analysis population included all enrolled subjects.

Arm/Group Title	Latanoprost Group	Non Prostaglandin Group
Arm/Group Description	Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination and treated with latanoprost during the study period. Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination only.	Patients continuously treated with latanoprost or other topical PG analogues for less than 1 month before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period. Patients not treated with latanoprost or other topical PG analogues before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period.
Measure Participants	102	73
<5 years	1.14 (0.40)	0.53 (0.33)
5 to <18 years	0.44 (0.19)	0.65 (0.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Latanoprost Group, Non Prostaglandin Group
	Comments	<5 years
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2437
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference
	Estimated Value	0.61
	Confidence Interval	(2-Sided) 95%; -0.43 to 1.65
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.52
	Estimation Comments	Change from baseline to last available observation in longest lash length (LLL) was analyzed using an ANCOVA model with fixed effect for treatment group with baseline LLL value as covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Latanoprost Group, Non Prostaglandin Group
	Comments	5 to <18 years
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.5199
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference
	Estimated Value	-0.21
	Confidence Interval	(2-Sided) 95%; -0.85 to 0.43
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.32
	Estimation Comments	Change from baseline to last available observation in LLL was analyzed using an ANCOVA model with fixed effect for treatment group with baseline LLL value as covariate.

11. Secondary Outcome

Title	Change From Baseline to Last Available Observation in Corneal Thickness (Pachymeter)
Description	Central corneal thickness was measured using a calibrated pachymeter, preferably an ultrasonic pachymeter.
Time Frame	Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months

Outcome Measure Data

Analysis Population Description

The Full Analysis population included all enrolled subjects.

Arm/Group Title	Latanoprost Group	Non Prostaglandin Group
Arm/Group Description	Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination and treated with latanoprost during the study period. Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination only.	Patients continuously treated with latanoprost or other topical PG analogues for less than 1 month before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period. Patients not treated with latanoprost or other topical PG analogues before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period.
Measure Participants	102	73
<5 years	-8.67 (11.51)	-5.99 (10.27)
5 to <18 years	5.30 (2.75)	6.17 (4.01)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Latanoprost Group, Non Prostaglandin Group
	Comments	<5 years
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.8643
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference
	Estimated Value	-2.68
	Confidence Interval	(2-Sided) 95%; -34.30 to 28.94
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 15.54
	Estimation Comments	Change from baseline to last available observation in corneal thickness was analyzed using an ANCOVA model with fixed effect for treatment group with baseline corneal thickness value as covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Latanoprost Group, Non Prostaglandin Group
	Comments	5 to <18 years
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.8591
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference
	Estimated Value	-0.87
	Confidence Interval	(2-Sided) 95%; -10.54 to 8.80
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.87
	Estimation Comments	Change from baseline to last available observation in corneal thickness was analyzed using an ANCOVA model with fixed effect for treatment group with baseline corneal thickness value as covariate.

12. Secondary Outcome

Title	Conjunctival/Ocular Hyperemia
Description	Conjunctiva hyperemia was assessed by slit-lamp examination. When slit-lamp examination is not possible due to subject cooperation, a fixation light and 20-diopter lens (for magnification) was used to assess this parameter. Conjunctival hyperemia was assessed and graded by ophthalmologist at baseline and follow-up visits from grades 0-3 and is as follows: 0 = None, Normal: few vessels of palpebral or bulbar conjunctiva easily observed = Mild, Reddening of the palpebral or bulbar conjunctiva = Moderate, Bright reddening of the palpebral or bulbar conjunctiva = Severe, Deep, bright, and diffuse reddening of the palpebral or bulbar conjunctiva
Time Frame	Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months

Outcome Measure Data

Analysis Population Description

The Full Analysis population included all enrolled subjects.

Arm/Group Title	Latanoprost Group	Non Prostaglandin Group
Arm/Group Description	Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination and treated with latanoprost during the study period. Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination only.	Patients continuously treated with latanoprost or other topical PG analogues for less than 1 month before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period. Patients not treated with latanoprost or other topical PG analogues before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period.
Measure Participants	102	73
Number [Participants]	6 5.9%	1 1.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Latanoprost Group, Non Prostaglandin Group
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2413
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	4.5
	Confidence Interval	(2-Sided) 95%; -10.49 to 19.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Number of Participants With a Change in Anterior Segment Biomicroscopy
Description	Slit-lamp biomicroscopy (mounted or hand-held) without fluorescein and without dilation of the pupil was performed. When slit-lamp examination was not possible, a fixation light and 20-diopter lens (for magnification) was used. At each scheduled visit, deposition of pigment on the corneal endothelial layer or the lens capsule or any abnormalities of the lids, conjunctivae, cornea, anterior chamber, iris, or lens was examined.
Time Frame	Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months

Outcome Measure Data

Analysis Population Description

The Full Analysis population included all enrolled subjects.

Arm/Group Title	Latanoprost Group	Non Prostaglandin Group
Arm/Group Description	Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination and treated with latanoprost during the study period. Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination only.	Patients continuously treated with latanoprost or other topical PG analogues for less than 1 month before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period. Patients not treated with latanoprost or other topical PG analogues before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period.
Measure Participants	102	73
Number [Participants]	0 (0.17) 0%	0 (0.09) 0%

14. Secondary Outcome

Title	Number of Participants With Abnormalities in Fundoscopy Posterior Segment at Baseline
Description	Fundoscopy was performed after dilation of the pupils (eg, 1 % tropicamide or cyclopentolate and 2 ½ % phenylephrine, or a clinically- appropriate dose according to the clinician's standard care of each particular patient). The examination included an evaluation of the vitreous body, retina (including the macula), and optic nerve head. The fundoscopy e-CRF was completed only at baseline because the investigators were required to perform slit lamp, direct or indirect ophthalmoscopy at each visit and report any AEs observed which included the vitreous, retina and optic nerve.
Time Frame	Evaluated at Baseline

Outcome Measure Data

Analysis Population Description

The Full Analysis population included all enrolled subjects.

Arm/Group Title	Latanoprost Group	Non Prostaglandin Group
Arm/Group Description	Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination and treated with latanoprost during the study period. Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination only.	Patients continuously treated with latanoprost or other topical PG analogues for less than 1 month before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period. Patients not treated with latanoprost or other topical PG analogues before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period.
Measure Participants	102	73
Vitreous body	3 2.9%	1 1.4%
Optic nerve head	43 42.2%	29 39.7%
Retina macula choroid	12 11.8%	1 1.4%

Adverse Events

Time Frame	Adverse events were reported from the signing of the informed consent throughout the entire study period or 28 calendar days after the last administration of latanoprost within the observational period, whichever is latest.
Adverse Event Reporting Description	One patient was missed in the adverse event raw data; no collection AE start date on case report form page hence the number of participants in Non Prostaglandin group is 72.
Arm/Group Title	Latanoprost Group		Non Prostaglandin Group
Arm/Group Description	Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination and treated with latanoprost during the study period. Patients continuously treated with latanoprost for at least 1 month within 1 year before the baseline examination only.		Patients continuously treated with latanoprost or other topical PG analogues for less than 1 month before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period. Patients not treated with latanoprost or other topical PG analogues before the baseline examination, and unlikely to be treated with latanoprost or other topical PG analogues during the study period.
All Cause Mortality
	Latanoprost Group		Non Prostaglandin Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Latanoprost Group		Non Prostaglandin Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/102 (10.8%)		2/72 (2.8%)
Congenital, familial and genetic disorders
Developmental glaucoma	1/102 (1%)		0/72 (0%)
Neurofibromatosis	1/102 (1%)		0/72 (0%)
Eye disorders
Glaucoma	2/102 (2%)		0/72 (0%)
Iris incarceration	1/102 (1%)		0/72 (0%)
Posterior capsule opacification	0/102 (0%)		1/72 (1.4%)
Retinal detachment	1/102 (1%)		0/72 (0%)
Infections and infestations
Pilonidal cyst	1/102 (1%)		0/72 (0%)
Investigations
Intraocular pressure increased	3/102 (2.9%)		1/72 (1.4%)
Optic nerve cup/disc ratio increased	1/102 (1%)		0/72 (0%)
Metabolism and nutrition disorders
Hyperkalaemia	0/102 (0%)		1/72 (1.4%)
Nervous system disorders
Epilepsy	1/102 (1%)		1/72 (1.4%)
Seizure	1/102 (1%)		0/72 (0%)
Surgical and medical procedures
Eye operation	0/102 (0%)		1/72 (1.4%)
Other (Not Including Serious) Adverse Events
	Latanoprost Group		Non Prostaglandin Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/102 (19.6%)		14/72 (19.4%)
Eye disorders
Conjunctival hyperaemia	5/102 (4.9%)		1/72 (1.4%)
Eye pain	4/102 (3.9%)		0/72 (0%)
Iris hyperpigmentation	4/102 (3.9%)		2/72 (2.8%)
Infections and infestations
Nasopharyngitis	4/102 (3.9%)		4/72 (5.6%)
Investigations
Intraocular pressure increased	9/102 (8.8%)		9/72 (12.5%)

Limitations/Caveats

Inherent limitations of an observational study design (eg, lack of randomization), this was subject to the design/data-related limitations mainly Visual acuity, IOP, and visual field assessments in <5 years old age group were less reliable

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.