Clinical trial NCT05875090: Glaucoma Portugal Screening Trial
Official title: Screening Trial for Glaucomatous Optic Discs in Portugal
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Glaucoma
Keywords: Screening
Lead sponsor: Centro Hospitalar Universitário Lisboa Norte
Sponsor class: OTHER
Collaborators: name: Unidade Local de Saúde do Alto Minho
name: ACES Lisboa Norte
name: Equipa Regional dos Programas de Rastreio da Região de Saúde de Lisboa e Vale do Tejo
name: ACES Alto Minho
First posted: 2023-05-25
Enrollment: 6000
Sex: ALL
Minimum age (years): 55
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two models of population-based glaucoma screening will be tested. Lisbon center will conduct screening using an Artificial-Intelligence software based on optic disc centered retinographies. The Minho center will conduct screening based on OCT-based findings on the retinal nerve fibre layer thickness (RNFL)
Primary purpose: SCREENING

Brief summary: Two primary care-based screening systems will be used to identify subjects with referrable glaucoma to hospital care.

Subjects between 55 to 65 years old living in two primary care areas (urban area in Lisbon ; countryside setting in Minho) will be invited to a one-time assessment of optic disc and intraocular pressure (IOP).

Criteria for referral will differ between centers, with one arm (Lisbon) using an artificial intelligence (AI) reading software of the optic disc picture, the other (Minho) will base their referral based on optical coherence tomography (OCT) retinal nerve fibre layer abnormality.

A masked reading center will be established to set the ground truth for diagnosis.

This pilot screening trial will explore the level of agreement between both systems as well as their cost effectiveness and identify diagnostic composite scores that could maximize the screening process. Secondary analyses will include the identification of population characteristics that increase effectivity of screening process as well as determining the population less likely to adhere to screening programmes.

Detailed description: Glaucoma diagnosis is currently based on opportunistic case finding, which makes the case for up to 50% of patients remaining undiagnosed. Diagnostic technology has been deemed efficient in diagnosing, but cost and (hospital) location acts as a barrier for effective screening for this asymptomatic disease with a low population-based prevalence

Portuguese National Strategy for Visual Health, published in 2018 asks for a pilot study aimed at a one-time intervention at the primary care setting at the age of 60 years to do both an optic disc analysis and an intraocular pressure (IOP) measurement as a screening system for glaucoma

Two Portuguese centers have applied for this pilot. An urban-based center (Lisbon) and a countryside center (Minho) will conduct an invitation-based screening for those registered in their global primary care area. Age range was increased to 55 to 65 to capture a spectrum of data, enabling to later refine the target population.

Screening Intervention will be the same in both centers. Both will assess reasons for undergoing or rejecting screening and demographic and ophthalmological-related parameters, including glaucoma family history and a known personal glaucoma diagnosis. IOP will be non-invasively checked by rebound tonometry and optic disc retinographies will be performed on both centers. The Minho arm will additionally perform an optical coherence tomography (OCT) on all subjects.

Decision to refer will be made on one (or both) two findings:

1. IOP of 24mmHg or higher
2. referrable glaucoma

The Lisbon arm will use an Artificial intelligence (AI) system to rank the retinography findings into a binary referrable vs non-referrable system, based on a pre-defined threshold (0.73).

The Minho arm will base their referral on the existence of optical coherence tomography (OCT) retinal nerve fibre layer abnormality (defined as one sector thickness being outside normal limits)

Subjects flagged as referrable will be sent to the hospital Glaucoma Clinic, where functional and structural examinations will be performed and a standard of care clinical decision will be made by the glaucoma expert.

A reading center, with two masked experts, will be established to determine an unbiased ground truth for the comparison analysis. Reading center will conduct analysis on 3 tier level:

First round will include masked fundus pictures of all recruited subjects from both centers (both positive and negative referrals).

Second Round will include all subjects from Minho arm, who will have both fundus picture and OCT data.

Third round will include data analysis from all positive referrals from both arms, which includes all clinical data from the CRF plus all hospital exams (excluding clinical impression).

Outcomes of the reading center will be twofold:

1. "Glaucoma diagnosis label"

1. "normal"
2. "glaucoma suspect"
3. "definite glaucoma" (which implies a glaucomatous visual field) 2) Score (0-100) of likeliness of definitive glaucoma Disagreements on any category will be solved by a third masked referee (in the case of the scoring system, a difference larger than 10% would be considered a disagreement)

Eligibility criteria: Inclusion Criteria:

* subjects age between 55 to 65 years old registered in the primary care area of either ACES Lisbon Norte (Lisbon arm) or in the area of ACES Alto Minho (Minho arm)
* willingness to sign an informed consent for the screening process

Exclusion Criteria:

- none

Poor quality in screening image will be included in the intention to treat analysis, but excluded from the diagnostic comparator outcome.

Patients with a known glaucoma diagnosis will not be excluded from the screening

Primary outcomes:
measure: Diagnostic agreement between referring decision and reading center decision
timeFrame: Duration of the study (8 months)
Secondary outcomes:
measure: Comparison between level of agreement (with ground truth) from both screening models
timeFrame: Duration of the study (8 months)
measure: Level of performance of agreement by number of diagnostic testing
timeFrame: Duration of the study (8 months)
measure: Cost effective analysis of both screening models
timeFrame: Duration of the study (8 months)
measure: Subjects parameters associated with positive screening
timeFrame: Duration of the study (8 months)
measure: Parameters associated with accepting screening system by the patients
timeFrame: Duration of the study (8 months)
measure: Level of agreement (in %) between AI-risk score and human-based assessment of disease severity
timeFrame: Duration of the study (8 months)
Other outcomes:
Locations:
city: Lisbon
country: Portugal
facility: Equipa Regional dos Programas de Rastreio da Região de Saúde de Lisboa e Vale do Tejo
city: Lisbon
country: Portugal
facility: Centro Hospitalar Lisbon Norte
city: Viana Do Castelo
country: Portugal
facility: Unidade Local Saude Alto Minho
Study officials:
affiliation: Centro Hospitalar Universitário Lisboa Norte
name: Luis Abegão Pinto, MD, PhD
role: STUDY_CHAIR
affiliation: Unidade Local Saude Alto Minho
name: Sérgio Azevedo, MD
role: STUDY_CHAIR
References:
citation: US Preventive Services Task Force; Mangione CM, Barry MJ, Nicholson WK, Cabana M, Chelmow D, Coker TR, Davis EM, Donahue KE, Epling JW Jr, Jaen CR, Krist AH, Kubik M, Li L, Ogedegbe G, Pbert L, Ruiz JM, Simon MA, Stevermer J, Wong JB. Screening for Primary Open-Angle Glaucoma: US Preventive Services Task Force Recommendation Statement. JAMA. 2022 May 24;327(20):1992-1997. doi: 10.1001/jama.2022.7013.
citation: Hemelings R, Elen B, Barbosa-Breda J, Lemmens S, Meire M, Pourjavan S, Vandewalle E, Van de Veire S, Blaschko MB, De Boever P, Stalmans I. Accurate prediction of glaucoma from colour fundus images with a convolutional neural network that relies on active and transfer learning. Acta Ophthalmol. 2020 Feb;98(1):e94-e100. doi: 10.1111/aos.14193. Epub 2019 Jul 25.
citation: Sousa DC, Leal I, Nascimento N, Marques-Neves C, Tuulonen A, Abegao Pinto L. Use of Ocular Hypotensive Medications in Portugal: PEM Study: A Cross-sectional Nationwide Analysis. J Glaucoma. 2017 Jun;26(6):571-576. doi: 10.1097/IJG.0000000000000668.