Impact of Home Intraocular Pressure Telemonitoring on Intraocular Pressure Control and Glaucoma Progression

Study Overview
=================
Brief Summary
-----------------
The goal of this clinical trial is to conduct a study randomizing glaucoma patients to home intra-ocular pressure (IOP) telemonitoring combined with Smart phone-based intervention (Management Paradigm I) or Smart phone-based intervention alone (Management Paradigm II), with the objectives to compare (1) Goldmann applanation tonometry (GAT) intra-ocular pressure (IOP) measurements over the entire study period (primary outcome measure) and (2) the rates of Retinal nerve fiber layer (RNFL) thinning (secondary outcome measure) between the two Management Paradigms. We hypothesize that glaucoma patients randomized to Management Paradigm I will (1) attain lower levels of intra-ocular pressure (IOP), and (2) a slower rate of Retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GCIPL) thinning compared with those randomized to Management Paradigm II because of having a more precise assessment of intra-ocular pressure (IOP) to guide intra-ocular pressure (IOP)- lowering therapy would be feasible in Management Paradigm I. It aims to: to compare (1) Goldmann applanation tonometry (GAT) intra-ocular pressure (IOP) measurements over the entire study period (primary outcome measure) and (2) the rates of Retinal Nerve Fiber Layer (RNFL) thinning (secondary outcome measure) between the two Management Paradigms. Participants will asked to do, Management Paradigm I: will be provided with an iCare Home and instructed to measure and upload 6 intra-ocular pressure (IOP) measurements weekly (2 days a week, 1 measurement in the early morning (5 am to 9 am), 1 during the mid-day (12 pm to 4 pm) and 1 in the evening (7 pm to 11pm)) to a secure server via iCare CLINIC (the number of weekly intra-ocular pressure (IOP) measurements follows the number of weekly blood pressure measurements in the HyperLink study). The morning measurement will include two readings with the first obtained in the supine position before getting out of the bed and the second obtained in the upright position right after. Patients may take additional intra-ocular pressure (IOP) measurements in supine position if they wake up in bed from sleep, as well as other times of the day, but this is not mandatory. These additional intra-ocular pressure (IOP) measurements will not be included for treatment decisions during the study period. Management paradigm II: Patients will be treated with a topical prostaglandin analogue after baseline intra-ocular pressure (IOP) measurements.

Detailed Description
-----------------
Study design This is a 30-month prospective, multicenter, randomized clinical trial to compare the treatment outcomes between two management paradigms: (I) home IOP telemonitoring combined with smart phone-based intervention, and (II) standard care plus smart phone- based intervention, in 142 patients with newly diagnosed primary open-angle glaucoma (POAG). Both management paradigms aim to decrease the IOP by the same degree according to the disease severity. For mild to moderate glaucoma (visual field MD ≥ -12 dB), we aim to decrease the IOP by at least 20% from the baseline (methods of baseline IOP measurements are described below) targeting the IOP levels <21 mmHg; for advanced glaucoma (visual field MD <-12 dB), we aim to decease the IOP by at least 25% from the baseline targeting the IOP levels <15 millimeters of mercury (mmHg). The unit of observation for sample size estimation and randomization will be based on subject. Patients will be randomized by minimization, stratified by demographics (age, gender, and axial length) and clinical parameters (baseline IOP levels and baseline RNFL thickness of the better eye). For analysis of outcome measures, both eyes will be included if both eyes are eligible for inclusion (described below), taking account for clustering between fellow eyes. Intent-to-treat analyses will be performed. The primary outcome measure will be clinic-measured GAT measurements collected at 3-month intervals over 30 months of study follow-up. The secondary outcome measures include the rates of change of global, superotemporal and inferotemporal RNFL thicknesses, and the rates of change of global and regional GCIPL thicknesses. We expect that (1) GAT measurements over 30 months of follow-up for patients randomized to Management Paradigm I to be smaller compared with those randomized to Management Paradigm II; and that (2) the rates of RNFL/GCIPL thinning would be slower for those randomized to Management Paradigm I compared with those randomized to Management Paradigm II. Additional analyses include (i) comparisons of visual field (VF) survival probabilities (defined by the Early Manifest Glaucoma Trial (EMGT) criteria) and (ii) the number of ocular hypotensive medications between the treatment groups during the study follow-up; and (iii) investigation of risk factors associated with the rate of RNFL/GCIPL thinning including mean IOP (measured by iCare Home or GAT), long-term IOP fluctuations (IOP deviated from the mean during study follow-up), and glaucoma severity (baseline average RNFL thickness). Study safety endpoints will include: (i) visual field (VF) progression; (ii) decrease in visual acuity (VA) ≥2 lines; and (iii) IOP≥35mmHg on 2 consecutive visits. Patients will exit the study and receive additional treatment(s) if any of the study safety endpoints is reached. Patients randomized to have IOP measured by iCare Home will continue the home IOP measurements until the completion of study. All patients in Management Paradigms I and II will be followed up 3-monthly in the clinic for GAT, optical coherence tomography retinal nerve fiber layer (OCT RNFL) imaging and perimetry.

Official Title
-----------------
Impact of Home Intraocular Pressure Telemonitoring on Intraocular Pressure Control and Glaucoma Progression - A Randomized Control Trial

Conditions
-----------------
Glaucoma, Intraocular Pressure, Primary Open Angle Glaucoma

Intervention / Treatment
-----------------
* Device: Standard care and home IOP telemonitoring with smart phone-based intervention


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Newly diagnosed primary open-angle glaucoma (POAG) Best corrected visual acuity (VA) ≥20/40 for the included eye(s) Exclusion Criteria: IOP >35 millimeters of mercury (mmHg) Dry eye syndrome Central corneal thickness <500μm or >600μm Failure to complete the iCare Home certification procedure at the baseline visits Only one eye with functional vision Inability to perform reliable visual field (VF) Pathological myopia (eyes with axial length≥26mm with lacquer cracks and chorioretinal atrophy) Suboptimal quality of optical coherence tomography (OCT) images (described below in RNFL imaging) Previous intraocular surgery or corneal refractive surgery other than uncomplicated cataract extraction Diabetic retinopathy/maculopathy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

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

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

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

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: iCare Home2 tonometer
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Management Paradigm I: Standard care and home IOP telemonitoring with smart phone-based intervention<br>Eligible patients randomized to Management Paradigm I will be provided with an iCare Home and instructed to measure and upload 6 IOP measurements weekly (2 days a week, 1 measurement in the early morning (5 am to 9 am), 1 during the mid-day (12 pm to 4 pm) and 1 in the evening (7 pm to 11pm)) to a secure server via iCare. Patients will be treated with topical prostaglandin analogue after baseline IOP measurements. A text message will be sent to the patient's smart phone to (1) inform whether the treatment goal is achieved over the past 4 weeks (i.e., ≥75% of the self- measured IOP measurements are below the target IOP) and (2) remind adherence to medications. The patients will need to reply via a text message reporting how many times eyedrops are missed over the past 4 weeks. A nurse will phone the patient if a reply message is not received or the number of home IOP measurements is less than 20 over the past 4 weeks. | Device: Standard care and home IOP telemonitoring with smart phone-based intervention<br>* We expect that (1) GAT measurements over 30 months of follow-up for patients randomized to Management Paradigm I to be smaller compared with those randomized to Management Paradigm II; and that (2) the rates of RNFL/GCIPL thinning would be slower for those randomized to Management Paradigm I compared with those randomized to Management Paradigm II<br>|
| No Intervention: Management paradigm II: Standard care and smart phone-based intervention<br>Patients will be treated with a topical prostaglandin analogue after baseline IOP measurements (described below). Additional treatment will be provided in the following order: carbonic anhydrase inhibitor, brimonidine, beta blocker, and selective laser trabeculoplasty (SLT) when the target IOP is not achieved. Fixed combination will be given whenever possible to improve adherence. Similar to Management Paradigm I, smart phone-based intervention includes (1) a text message from the investigators to inform whether the target pressure is attained (with reference to the latest clinic GAT measurement) and remind medication adherence every 4 weeks and (2) a reply message from the patients regarding how many times eyedrops are missed over the past 4 weeks. | |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinic-measured Goldmann applanation tonometry measurements collected at 3-month interval over 30 months of study follow-up. | Goldmann applanation tonometry is an instrument measures intra-ocular pressure based on Imbert-Fick law. The Goldmann equation states: Po = (F/C) + Pv [Po is the IOP in millimeters of mercury (mmHg), F is the rate of aqueous formation, C is the facility of outflow, and Pv is the episcleral venous pressure]. | From baseline to 30 months, at 3-month intervals | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of changes of global, superotemporal and inferotemporal Retinal Nerve Fiber Layer (RNFL) thickness, and the rate of changes of global and regional Ganglion cell-inner plexiform layer (GCIPL) thickness. | RNFL and GCIPL thickness could be assessed by Optical coherence tomography (OCT), which analyze the temporal delay of backscattered light from tissue structures. RNFL thickness (µm) could be measured by an optic disc cube OCT scan. RNFL thickness is presented on 2 circular charts, 1 with 12 equal sized sectors, and the other with 4 equal sectors each representing 1 quadrant (superior, nasal, temporal and inferior). GCIPL thickness (µm) could be measured by a macular OCT scan. GCIPL thickness is presented on a thickness map, with 6 equal sized sectors. | From baseline to 30 months, at 3-month intervals | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Ophthalmology, Glaucoma