PAIR Study-PAP And IOP Relationship: Study 2 (PAIR2)

Positive Airway Pressure and Intraocular Relationship: Study 2- The Impact of CPAP on Nocturnal IOP.

Some people with Primary Open-angle Glaucoma (POAG) also suffer from Obstructive Sleep Apnoea (OSA), a common sleep disorder which is known to affect heart and blood vessels, and may contribute to glaucoma progression. Obstructive Sleep Apnoea is treated with Continuous Positive Airway Pressure (CPAP); however using this type of breathing support may raise intraocular pressure (IOP). The evidence for this is limited and the potential mechanisms involved are poorly understood.

In this study we will determine whether CPAP applied at night changes IOP and ocular perfusion pressure (OPP). We will also assess its possible impact on ocular microvasculature. Two groups of patients will be included: those with POAG and OSA, and those with OSA without glaucoma. They will attend for two overnight assessments: the first before starting CPAP and the second 4-6 weeks into the treatment. Repeated measurements of IOP at night will be performed and participants will continue self-measuring IOP at home in the day. An Ocular Coherence Tomography Angiography (OCT Angiography) of the optic disc and the surrounding retina will be performed at baseline and after a few weeks of CPAP treatment.

Study Overview

• Status: Completed
• Conditions: Primary Open-angle Glaucoma; Obstructive Sleep Apnoea
• Intervention / Treatment: Device: Continuous Positive Airway Pressure

Detailed Description

People with OAG and concomitant OSA associated with the relevant symptoms, particularly daytime sleepiness, currently receive standard treatment with CPAP. However, the impact of CPAP on their glaucoma is unknown. There are concerns that CPAP increases IOP, currently the only modifiable factor in glaucoma, though the evidence for this is limited.

Understanding the influence of CPAP on IOP is important as it may inform the management of people with OSA and concomitant glaucoma. If CPAP is shown to raise IOP or alter OPP to levels that pose clinical risk it will be necessary to assess available alternative treatment options for OSA. If, however, CPAP does not alter these parameters, there would be a rationale for assessing long-term effects of CPAP, most probably in the form of a randomised interventional trial, informed by the findings of this research.

This is a prospective controlled study which will examine the impact of CPAP on nocturnal IOP and OPP in people with OSA with and without POAG. In addition, we will assess ocular microvasculature before and a few weeks into CPAP treatment.

Objectives:

Primary: to determine if IOP increases at night following treatment with CPAP in people with OSA with and without POAG.

Main Secondary:(i) to investigate whether diurnal IOP raises after CPAP treatment; (ii) to investigate whether CPAP alters peri-papillary and macular microcirculation measured with OCT Angiography.

Participants: People with newly diagnosed OSA who require treatment with CPAP will be invited. We will recruit participants with POAG and people without glaucoma (control subjects). All participant will undergo a detailed ocular assessment including: visual acuity, IOP measurement, OCT and visual field test.

Sample Size: 30 participants: 15 per group.

Study Visits:

Visit 0: Baseline ocular examination to confirm or exclude glaucoma will be undertaken during this visit unless a participant already had this examination within the last 6 months.

Visit 1: Participants will attend the sleep centre (Respiratory Support and Sleep Centre-RSSC, Papworth Hospital) where they will be admitted to a separate ward. Consented participants will undergo the following:

Baseline assessment: A brief medical history, spirometry and anthropomorphic measurements.

Repeated measurements: IOP will be measured in each eye using a rebound tonometer (Icare Pro, Finland Oy). Blood pressure and ocular perfusion pressure will be checked simultaneously.

Participants will be advised to sleep at their habitual hours. Sleep onset and duration will be recorded. All the above measurements will be repeated every 2 hours starting from 10pm and finishing at 8am. In the morning OCT Angiographic will be performed.

Participants will then self-measure IOP at home using a rebound tonometer (Icare Home, Finland Oy). The measurements will be performed in the daytime every 2 hours before they start CPAP and 4-6 weeks into the treatment.

Visit 2: Participants will return for the second overnight assessment 4-6weeks after initiation of CPAP treatment.

CPAP usage data will be downloaded. All the measurements following the same procedure as for Visit 1 will be repeated this time with participants using CPAP. OCT Angiographic will be performed immediately after removing CPAP in the morning.

• Study Type: Observational
• Enrollment (Actual): 28

Contacts and Locations

Study Locations

• United Kingdom
  • Cambridge, United Kingdom
    • Papworth Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

There are two recruitment sources:

i. Eligible participants who have completed the POSAG trial (NCT02713152) and were diagnosed with OSA for which CPAP treatment was recommended.

ii. Patients who attend Sleep Disturbance Clinic (SDC) at Papworth.

We aim to recruit 15 participants with OSA and POAG (Glaucoma group) and 15 participants with OSA and no Glaucoma (Control group). Patients with OSA and POAG will be recruited first and control participants matched for OSA severity subsequently. Matching will be performed according to 3 OSA categories: mild (AHI:5-15), moderate (AHI:15-30), severe (AHI>30)).

Description

Inclusion Criteria:

• Newly diagnosed, untreated OSA with indications for CPAP
• Age >40 years
• Able to give informed consent and attend for the study visits.

Exclusion Criteria:

• Known or suspected pregnancy
• Any contraindications to rebound tonometry, including: corneal scarring, microphtalmos, buphthalmos, nystagmus, keratoconus, abnormal central corneal thickness, corneal ectasia, , active corneal infection, , and corneal dystrophies
• Eye diseases known to affect IOP, including: treated wet age related macular degeneration (ARMD), central retinal vein occlusion (CRVO), branch retinal vein occlusion (BRVO), uveitis and diabetic retinopathy.
• Indications to start CPAP treatment urgently unless the study visits can be organised in a way there is no delay in treatment initiation.
• Irregular sleep pattern
• Insomnia
• Acute infectious diseases
• Inability to undergo screening ophthalmic examination

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
POAG group; Patients diagnosed with POAG and OSA who require treatment with CPAP	Device: Continuous Positive Airway Pressure; Continuous Positive Airway Pressure
Control group; Patients with OSA and without POAG who require treatment with CPAP	Device: Continuous Positive Airway Pressure; Continuous Positive Airway Pressure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraocular pressure (IOP)	Difference between baseline IOP at night and nocturnal IOP on CPAP	On completion of study visit 2: 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diurnal IOP change	A difference in diurnal IOP self-measured at home at baseline and during CPAP treatment.	On completion of study visit 2: 6 weeks
Differences in change in IOP between the study group	Differences in IOP change (ΔIOP; IOPCPAP -IOPbaseline) between the groups	On completion of study visit 2: 6 weeks
Relationship between change in IOP on CPAP with OSA severity	Correlation between IOP change (ΔIOP) and AHI (Apnoea-Hypopnoea Index)	On completion of study visit 2: 6 weeks
Relationship between change in IOP on CPAP with POAG severity	Correlation between IOP change (ΔIOP) and VFI (Visual Field Index)	On completion of study visit 2: 6 weeks
Ocular Perfusion Pressure (OPP)	Difference between baseline OPP at night and nocturnal OPP on CPAP in each group	On completion of study visit 2: 6 weeks
Optic disc vessel density	Optic disc vessel density at baseline and after 4-6 weeks of CPAP treatment	On completion of study visit 2: 6 weeks
Peripapillary vessel density	Peripapillary vessel density at baseline and after 4-6 weeks of CPAP treatment	On completion of study visit 2: 6 weeks

Collaborators and Investigators

• Sponsor: Papworth Hospital NHS Foundation Trust
• Collaborators: Hinchingbrooke Healthcare NHS Trust
• Investigators: Principal Investigator: Dariusz Wozniak, MBBS, MRCP, Papworth Hospital NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2017
• Primary Completion (Actual): February 10, 2018
• Study Completion (Actual): February 10, 2018

Study Registration Dates

• First Submitted: May 4, 2017
• First Submitted That Met QC Criteria: May 4, 2017
• First Posted (Actual): May 9, 2017

Study Record Updates

• Last Update Posted (Actual): June 6, 2018
• Last Update Submitted That Met QC Criteria: June 5, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Intraocular pressure; CPAP; IOP
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Eye Diseases; Ocular Hypertension; Sleep Apnea Syndromes; Glaucoma; Sleep Apnea, Obstructive; Glaucoma, Open-Angle
• Other Study ID Numbers: P02145

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No