Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000961640
Ethics application status
Approved
Date submitted
16/08/2023
Date registered
5/09/2023
Date last updated
7/04/2024
Date data sharing statement initially provided
5/09/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Individualised Visual field progression observations in glaucoma
Scientific title
Individualised Perimetry progression observations in glaucoma using the Australian Reduced Range Extended Spatial Test
Secondary ID [1] 310406 0
None
Universal Trial Number (UTN)
Trial acronym
IPPOG
Linked study record

Health condition
Health condition(s) or problem(s) studied:
glaucoma 331158 0
Condition category
Condition code
Eye 327931 327931 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a single centre, interventional, longitudinal study comparing several methods of evaluating the status of the visual field in people with glaucoma. Visual field assessments of peripheral vision will be compared to several forms of ophthalmic imaging. Current clinical visual field testing procedures for glaucoma use the same regularly spaced test grid for all people. The intervention to be tested is a visual field testing grid that is customised for the specific individual being tested (for example, to avoid retesting locations in visual space that are known to be blind, and to instead test areas along the border of these regions). This study will compare whether customised testing grids are better able to observe progressing damage to the visual field than the current approach of using the same test grid for all (known as the 24-2 testing grid). The study will also relate measured visual field status and progression rates to structural biomarkers of glaucoma measured with ophthalmic imaging. Specifically, the study will measure visual fields using a 24-2 test pattern and using the Australian Reduced Range Extended Spatial Test (ARREST) (Turpin, Morgan et al. 2018, Muthusamy, Turpin et al. 2020), which customises the stimulus placement. Each of these tests take approximately 5-8 minutes to complete per eye and will be conducted on the Compass perimeter hardware (CentreVue, SpA, Italy). The Compass perimeter is a commercially available visual field testing machine. Participants look into the machine, and press a button every time they see a small white light appear anywhere in their visual field. In addition to the visual field tests, the study will collect: a) structural Optical Coherence Tomography (OCT) image of the optic nerve, retinal nerve fibre layer, and macular regions using the Spectralis OCT (Heidelberg Engineering, GmBH, Germany) : b) OCT angiography measures of the optic nerve and macular regions to non-invasively estimate blood flow (using the Spectralis OCT; c) retinal photography using the Compass Perimeter; d) two additional measures of visual function: 1) macular ON-OFF pathway function (measured using a customised test on an iPad; and 2) an estimate of individual psychometric function slope for Size III perimetric targets in normal regions of visual field (measured using custom software on the Compass Perimeter hardware). All imaging methods (OCT, OCT Angiography and retinal photograph) are well accepted clinical assessments that each take no more than 2 minute to collect (including set-up time, imaging acquisition is a few seconds). Participants sit in a darkened room and view a fixation target while the images are acquired. The ON-OFF pathway test involves looking a a chequered pattern on an iPad and pressing a button on the tablet to indicate whether 1, 2 or 3 dark or light targets are seen embedded in the chequered pattern. This test takes approximately 5 minutes. In total, the study visit will take approximately 90 minutes.
The study will observe the natural history of glaucomatous progression using these different methodologies. Measurements will be taken (visual fields using the standard and customised test patterns, and ophthalmic imaging) every 4 months for 3 years. ON-OFF pathway function and psychometric function slope will only be measured at the first and last visit. Tests will be conducted by AHPRA registered optometrists or trained ophthalmic technicians.
Intervention code [1] 326804 0
Diagnosis / Prognosis
Comparator / control treatment
The standard test grid will be the 24-2 test pattern (a regular grid of 6 degree spacing that assesses the central 24 degrees of the visual field).
Control group
Active

Outcomes
Primary outcome [1] 335790 0
The number of eyes classified as having visual field progression as determined by the Australian Reduced Range Extended Spatial Test, compared to the number of eyes classified as having visual field progression for the 24-2 test pattern
Timepoint [1] 335790 0
Cumulative total at 3 years post first study visit, if classified as having progressed using Permutation of Pointwise Linear Regression at any visit.
Primary outcome [2] 335791 0
The number of eyes classified as having visual field progression as determined by the Australian Reduced Range Extended Spatial Test, compared to the number of eyes classified as having visual field progression for the 24-2 test pattern
Timepoint [2] 335791 0
Cumulative total at 2 years post first study visit, if classified as having progressed using Permutation of Pointwise Linear Regression at any visit.
Secondary outcome [1] 425632 0
Visual field volume determined by the Australian Reduced Range Extended Spatial Test compared to the visual field volume determined by the 24-2 test pattern.
Timepoint [1] 425632 0
3 years post first study visit
Secondary outcome [2] 425633 0
Change in retinal nerve fiber thickness as estimated by linear regression on the 4 monthly collected data obtained from the Spectralis OCT Glaucoma Module Premium Edition software.
Timepoint [2] 425633 0
2 years post first study visit using data collected at all available previous 4 monthly visits
Secondary outcome [3] 425634 0
Change in retinal nerve fiber thickness as estimated by linear regression on the 4 monthly collected data obtained from the Spectralis OCT Glaucoma Module Premium Edition software.
Timepoint [3] 425634 0
3 years post first study visit using data collected at all available previous 4 monthly visits
Secondary outcome [4] 425635 0
Change in composite Macular Ganglion Cell and Inner Plexiform Layer thickness as estimated by linear regression on the 4 monthly collected data obtained from the Spectralis OCT Glaucoma Module Premium Edition software.
Timepoint [4] 425635 0
3 years post first study visit using data collected at all available previous 4 monthly visits
Secondary outcome [5] 425636 0
Change in composite Macular Ganglion Cell and Inner Plexiform Layer thickness as estimated by linear regression on the 4 monthly collected data obtained from the Spectralis OCT Glaucoma Module Premium Edition software.
Timepoint [5] 425636 0
2 years post first study visit using data collected at all available previous 4 monthly visits
Secondary outcome [6] 425637 0
Change in vessel density (macula) as measured by the Spectralis OCT, and analysed using the Erlangen AngioTool; estimated by linear regression on the 4 monthly collected data.
Timepoint [6] 425637 0
2 years post first study visit using data collected at all available previous 4 monthly visits
Secondary outcome [7] 425638 0
Change in vessel density (macula) as measured by the Spectralis OCT, and analysed using the Erlangen AngioTool, estimated by linear regression on the 4 monthly collected data.
Timepoint [7] 425638 0
3 years post first study visit using data collected at all available previous 4 monthly visits
Secondary outcome [8] 425639 0
Change in vessel density (optic nerve head) as measured by the Spectralis OCT, and analysed using the Erlangen AngioTool, estimated by linear regression on the 4 monthly collected data.
Timepoint [8] 425639 0
2 years post first study visit using data collected at all available previous 4 monthly visits
Secondary outcome [9] 425640 0
Change in vessel density (optic nerve head) as measured by the Spectralis OCT, and analysed using the Erlangen AngioTool, estimated by linear regression on the 4 monthly collected data.
Timepoint [9] 425640 0
3 years post first study visit using data collected at all available previous 4 monthly visits
Secondary outcome [10] 425641 0
Visual field volume determined by the Australian Reduced Range Extended Spatial Test compared to the visual field volume determined by the 24-2 test pattern.
Timepoint [10] 425641 0
2 years post first study visit

Eligibility
Key inclusion criteria
• established diagnosis of primary open-angle or pseudoexfoliative glaucoma or pigment dispersion open angle glaucoma (OAG), (as defined by the treating ophthalmologist in accordance with internationally accepted clinical criteria).
• prior history of repeatable evidence of visual field defects on the 24-2 test pattern consistent with the diagnosis of glaucomatous optic neuropathy, with at least 2 locations in the visual field with visual field sensitivity < 17dB in at least ONE eye (locations do not need to be contiguous).
• aged between 18 – 80 years.
• participants whom in the opinion of the investigator are considered likely to attend for 3 visits per annum for the next 3 years , in addition to an additional baseline study visit
• one of more clinical features that increase the likelihood of visual field progression including: visual field progression over the last 2 years, disc haemorrhages, age greater than 60 years, intra-ocular pressure (IOP) above target pressure, family history of glaucoma-related vision loss, thin central cornea (<510um).
• best corrected visual acuity better than 6/12 at enrolment.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Patients with significant ocular comorbidities (other than glaucoma)
• Patients that have had previous glaucoma surgery and have IOP less than 12 mm Hg
• Patients with advanced glaucoma with MD greater than -20 dB
• Patients with visually significant cataracts in which surgery is planned or anticipated within the next 6 months.
• Patients with primary angle closure glaucoma or narrow angles in which laser iridotomy is planned or anticipated within the next 3 months.
• Patients with a history of LASIK surgery
• Patients with myopia greater than -6.0 diopters.
• Patients with hyperopia greater than +6.0 diopters.
• People with poorly controlled diabetes, type I diabetes, diabetic retinopathy, or other significant systemic condition that is likely to influence visual function over the course of the study.
• Any other medical condition which would prohibit them from making all study visits within the 36 months
• In the investigator's opinion, any patient that cannot satisfactorily complete all of the structural and functional testing included in the protocol
• Patients unable to perform reliable VF testing (reliable testing defined as: false positive rate of 20% or less) at the time of study entry

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
All participants will perform a customised visual field testing procedure (ARREST) where the visual field algorithm automatically chooses the stimulus testing grid based on the nature of the individual's visual field loss. The test grid will vary between people but all other features of the test are identical.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size is determined for the primary outcome measure which is a comparison between the 24-2 and ARREST visual field test patterns in the proportion of eyes that are classified as having progressed after 3 years (end of trial) according to the PoPLR method (O'Leary, Chauhan et al. 2012) with a specificity of 95%.
The following assumptions were made for determination of sample size.
1) One eye of each participant is used for the primary outcome measure
2) Power of 80%
3) Alpha equal to 0.05%
Assumptions regarding the number of participants likely to progress used the following empirical data:
162 eyes followed over 5 years at the same study site in a previous longitudinal study. These patients are a similar demographic and will likely receive similar treatment decisions. Using PoPLR, at 95% specificity, 88/162 (54.3%) eyes progressed. At 99% specificity, 60/162 (37%) eyes progressed. Sample size estimate was determined for McNemar’s test on proportions for paired data, assuming two-sided hypothesis testing. (Connor 1987) . A required sample of 113 is required: assuming a 20% withdrawal/non-completion rate leads to a desired sample of 141 participants.
Secondary analyses will use generalized linear mixed modelling analysis incorporating random factors such as participant ID and eye to assess the effect of key explanatory imaging variables on the rate of visual field progression

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
2/10/2023
Actual
2/10/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
141
Accrual to date
63
Final
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 314611 0
University
Name [1] 314611 0
University of Western Australia
Country [1] 314611 0
Australia
Funding source category [2] 314612 0
Charities/Societies/Foundations
Name [2] 314612 0
Lions Eye Institute Ltd.
Country [2] 314612 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Lions Eye Institute, Ltd
Address
Lions Eye Institute
12 Verdun St
Nedlands, 6009
Western Australia
Country
Australia
Secondary sponsor category [1] 316573 0
None
Name [1] 316573 0
Address [1] 316573 0
Country [1] 316573 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313639 0
University of Western Australia Human Research Ethics Committee
Ethics committee address [1] 313639 0
Ethics committee country [1] 313639 0
Australia
Date submitted for ethics approval [1] 313639 0
Approval date [1] 313639 0
27/07/2023
Ethics approval number [1] 313639 0
2023/ET000445

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 128834 0
Prof Allison McKendrick
Address 128834 0
Lions Eye Institute and University of Western Australia12 Verdun StNedlands6008Western Australia
Country 128834 0
Australia
Phone 128834 0
+61 08 64887409
Fax 128834 0
Email 128834 0
[email protected]
Contact person for public queries
Name 128835 0
Allison McKendrick
Address 128835 0
Lions Eye Institute and University of Western Australia12 Verdun StNedlands6008Western Australia
Country 128835 0
Australia
Phone 128835 0
+61 08 64887409
Fax 128835 0
Email 128835 0
[email protected]
Contact person for scientific queries
Name 128836 0
Allison McKendrick
Address 128836 0
Lions Eye Institute and University of Western Australia12 Verdun StNedlands6008Western Australia
Country 128836 0
Australia
Phone 128836 0
+61 08 64887409
Fax 128836 0
Email 128836 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
To support an open-science agenda, deidentified datasets of the visual field data and clinical imaging summary metrics will be made available alongside relevant scientific publications.
When will data be available (start and end dates)?
Immediately following (synchronous with) publication with no end date.
Available to whom?
Anyone who wishes to access
Available for what types of analyses?
Any purpose
How or where can data be obtained?
A link to online data of relevance to each publication will be provided with each publication. Depending on the specific journal, this might be provided as "supplementary material" within the journal archive. If this is not available, data will be hosted on a secure institutional server.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.