Long-Term Non-Interventional Latanoprost Study

Study Overview
=================
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.

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.

Official Title
-----------------
A Prospective, Non-interventional, Longitudinal Cohort Study To Evaluate The Long-term Safety Of Latanoprost Treatment In Pediatric Populations

Conditions
-----------------
Glaucoma, Ocular Hypertension

Intervention / Treatment
-----------------
* Other: No intervention other than routine medical care
* Other: No intervention other than routine medical care


Participation Criteria
=================
Eligibility Criteria
-----------------
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).

Ages Eligible for Study
-----------------
Minimum Age: 1 Day
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Latanoprost-treatment group<br> | Other: No intervention other than routine medical care<br>* Subjects continuously treated with Latanoprost for at least one month Latanoprost treatment during the study period.<br>* Other names: Observational;|
| Non-topical prostaglandin analogue treatment group<br> | Other: No intervention other than routine medical care<br>* 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.<br>* Other names: Observational;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Last Available Observation in Best Corrected Visual Acuity (BCVA) (Snellen or Equivalent) | 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). | Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinically Meaningful Change in Refractive Error | 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. | Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months | 
| Change From Baseline to Last Available Observation in Horizontal Corneal Diameter (by Caliper and/or Ruler) | 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. | Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months | 
| Change From Baseline to Last Available Observation in Intraocular Pressure (IOP) | 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. | Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months | 
| Cup-to-disc Ratio (for Assessment of Optic Nerve Changes/Structures) - Number of Participants With Clinically Significant Deterioration in Cup/Disc Ratios | The cup/disc ratio was recorded horizontally and vertically for each examination, and reported in 0.1 increments. | Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months | 
| Visual Field Defects - Number of Participants With Clinically Significant Deterioration of Visual Field Defects. | 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. | Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months | 
| Iris Color Darkening | 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. | Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months | 
| Localized Pigmentation (Nevi or Freckles) of Conjunctiva, Iris and Choroid | 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. | Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months | 
| Eyelash Darkening/Thickening | 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. | Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months | 
| Change From Baseline to Last Available Observation in Length of Eyelash (by Caliper and/or Ruler) | The longest eyelash (mm) measured by caliper or ruler was recorded at baseline and each follow-up visit. | Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months | 
| Change From Baseline to Last Available Observation in Corneal Thickness (Pachymeter) | Central corneal thickness was measured using a calibrated pachymeter, preferably an ultrasonic pachymeter. | Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months | 
| Conjunctival/Ocular Hyperemia | 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 | Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months | 
| Number of Participants With a Change in Anterior Segment Biomicroscopy | 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. | Evaluated at Baseline, 6 months, 12 months, 24 months and 36 months | 
| Number of Participants With Abnormalities in Fundoscopy Posterior Segment 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. | Evaluated at Baseline | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Prospective, non-interventional, longitudinal, cohort study