ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12625001188426p

Ethics application status

Submitted, not yet approved

Date submitted

29/09/2025

Date registered

30/10/2025

Date last updated

30/10/2025

Date data sharing statement initially provided

30/10/2025

Type of registration

Prospectively registered

Titles & IDs

Public title

Silent Thief of Sight Study

Scientific title

Silent Thief of Sight Study: Effect of polygenic risk score profiling for glaucoma screening on diagnostic rate in patients aged 64 to 69 years old

Additional trial identifiers [1]

None

Universal Trial Number (UTN)

Trial acronym

STOSS

Related trial records

Health condition

Health condition(s) studied:

Glaucoma

Condition category

Condition code

Eye

Diseases / disorders of the eye

Intervention/exposure

Study type

Interventional

Description of the intervention or exposure

Glaucoma-specific polygenic risk profiling:

PARTICIPANT INVOLVEMENT:
Recruitment will occur through medical and pharmaceutical prescription history: This recruitment pathway will be conducted with assistance from Services Australia, formerly known as the Department of Human Services.

After receiving the invitation letter from Services Australia, individuals who are interested in participating in the study can scan a QR code to reach the study website, or alternatively we will provide the direct website link, an email address and a direct telephone line for people to register in the trial.

For people who log in online via the QR code or direct website link. The process will involve the following steps:
1. An introductory page will appear with an instruction page to begin the survey.
2. The participation information sheet, eligibility checklist and general consent forms will appear, one at a time; participants will be able to save their work at any time and return later. The survey gives the option to not give consent and not participate. If this is indicated they will be directed to a refusal page where they are thanked for their interest and given contact details if they have any questions.
3. Upon completion of both the eligibility checklist and consent forms, a thank you page will appear.
4. Potentially eligible individuals will be sent an email to confirm their consent, assigned a Unique Study Identifier (UID), the next steps for their allocated study group i.e. direct clinical examination or genetic test.

Online Pre-screening Questionnaire: After completing the initial compulsory section of the consent and eligibility check, participant can choose to complete basic demographics questions and quality of life (QoL) assessment with several well validated questionnaires: Geriatric Anxiety Inventory Short Form (GAI-SF (5 items)), Geriatric Depression Scale (Short Form) (GDS-15 (15 items)), EuroQol 5 Dimensions 5 Levels (EQ-5D-5L AU index), EuroQoL Visual Analogue Scale (EQ-VAS), and Subjective Numeracy Scale (8 items) (SNS-8) establish emotional/utility baselines and decision quality before screening.
Hard copy Questionnaire: If the participant does not have internet access and would like to take part, we will mail them a hard copy of the participant information, consent forms, and the QoL questionnaires, with a prepaid envelope for them to return the forms.
For people who agree to enrol in the study and have signed the consent but do not complete the questionnaires, we will send up to three SMS/text, email, or mail reminders at 7, 14, 28 days, and telephone them directly at day 30 as a final communication.

Confirmation email: Following the completion of the online checklist and consent, the participant will receive an email inviting them to donate a saliva sample for polygenic risk score (PRS) profiling analysis. The email will ask for confirmation that the participant is ready to receive the saliva kit and to confirm contact details. Participants who completed the hard copy questionnaire, will be contacted by mail to have these details confirmed.

Saliva Sample collection: The saliva sample collection kit will be sent to the participant. SeonixBio will coordinate mailing of the saliva kits to people who have consented online, completed the survey and agreed to provide a sample. SeonixBio® is company which has a well established and robust genetic risk score calculation platform using a simple, saliva-based testing approach. We will supply SeonixBio® with details of the people to be sent a saliva kit (names, contact details and unique identification code). The saliva collection kits will be barcoded, and SeonixBio will link the barcode to the person’s unique identification code and distribute:
- An information sheet with instructions on how to provide the sample
- A hard copy version of the consent form to confirm the consent for the saliva sample
- Saliva collection kit
- Pre-paid and pre-labeled envelope

The SightScoreTM pipeline is a class III in-house in vitro diagnostic (IVD) medical devices and under the Australian regulatory framework has been accredited by NATA and accepted into the Therapeutic Goods Administration's in-house IVD notification database (DV-2024-IVI-39362-1). Seonix Bio have genetic counsellors and clinical geneticists to assist in specific questions regarding the PRS testing.

Participants will post the envelope as instructed back to SeonixBio for DNA analysis. Seonix Bio will send up to three SMS/text, email, or mail reminders at 7, 14, 28 days, and we will telephone them directly at day 30 as a final communication.

SeonixBio will email the final PRS report to all the participants in the PRS profiling group. For people with the top 5% PRS will receive a separate follow-up email or mail which invites them for an optometry examination. The process will be the same as people who are in the direct clinical screening group. For people with the bottom 95% PRS, we will randomise 600 participants to be a nested control group which will be invited to complete the same clinical examination as individuals with the top 5% PRS.

Clinical screening:
Participants allocated to clinical screening will receive an email requesting them to go to the local optometrist. The email will ask the optometrist to upload their assessment and imaging through a secure online portal link to the same participant.

Optometry examination: When the participant presents to the local optometry with their email/letter, they will receive an comprehensive eye examination including best-corrected visual acuity (BCVA), intraocular pressure (IOP), Van Herick grade, Humphrey Visual Field test (HVF 24-2), optic disc-centred photographs and Optical Coherence Tomography Retinal Nerve Fibre Layer (OCT RNFL). The optometrist is required to enter all the assessment results and upload the images with the participant’s study ID through the online portal.

Once all assessment results migrate into our database, fellowship trained ophthalmologists masked to the participant’s PRS profile, will grade clinical data, independently assign a diagnosis ranked on a scale of certainty: none, possible, probable or definite glaucoma and consensus to be reached by discussion.
For people who receive confirmation email/mail but do not complete eye examination, we will send up to three SMS/text, email, or mail reminders at 7, 14, 28 days, and telephone them directly at day 30 as a final communication.

Clinical examinations will be conducted by local optometrists. Any clinically significant incidental finding (e.g., suspected glaucoma, macular degeneration, diabetic retinopathy etc.) will be managed as part of usual care. Such findings would be explained to the participant and, with consent, communicated to their GP/ophthalmologist. The research team will receive coded data for analysis and will not participate in clinical decisions.

After completing the screening process, all the participants will receive a post screening questionnaire. For direct clinical screening and the 5% PRS groups, the follow up email will be sent 14 days after they complete the eye examination. For the remaining PRS profiling participants, the online link will be sent to the participants 14 days after they receive their PRS profiling report.

Post-genetic screening questionnaire: Psychological Consequences Questionnaire (PCQ) – screening context will be used as the endpoint for all the participants. In addition, Feelings About Genomic Testing Results (FACToR) is the main psychosocial endpoint (genomic-testing–specific) for all participants who complete PRS profiling, which will be used as a parallel endpoint. Other questionnaires are including Decision Regret Scale (DRS), repeat EQ-5D-5L, GAI-SF, GlauCAT, and the comprehension/behaviour items to capture acute impact and early actions. This mirrors the published glaucoma PRS psychosocial protocol (GRADE/INSiGHT). The online link will be sent to the participants 2 days after they receive their PRS profiling report or after they attend optometrist appointments.

In a population screening context where most participants will not have symptomatic disease, the dominant QoL signal is psychosocial (worry, uncertainty, satisfaction/regret, behavior) rather than vision-function impairment. Accordingly, instruments specific to genomic result impact (FACToR, DRS) and utility/QALY capture (EQ-5D-5L or AQoL) are most informative. Vision-specific QoL tools (e.g., National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), Glaucoma Quality of Life-15 (GQL-15)) are valuable after diagnosis or with measurable functional loss, but have limited sensitivity for asymptomatic, screened populations.

Longitudinal follow up post screening questionnaires: if participants opt in for questionnaires they will receive a combination of quantitative and qualitative questionnaires one, two and three years after they complete the trial. This survey will collect information on an individual's eye care history within the timeframes and any further development of glaucoma and treatment. It will also repeat some of QoL domains and gather information related to cost-effectiveness analysis.

Intervention code [1]

Early detection / Screening

Description of the comparator or control

Routine clinical screening.

PARTICIPANT INVOLVEMENT:
Recruitment will occur through medical and pharmaceutical prescription history: This recruitment pathway will be conducted with assistance from Services Australia, formerly known as the Department of Human Services.

After receiving the invitation letter from Services Australia, individuals who are interested in participating in the study can scan a QR code to reach the study website, or alternatively we will provide the direct website link, an email address and a direct telephone line for people to register in the trial.

For people who log in online via the QR code or direct website link. The process will involve the following steps:
1. An introductory page will appear with an instruction page to begin the survey.
2. The participation information sheet, eligibility checklist and general consent forms will appear, one at a time; participants will be able to save their work at any time and return later. The survey gives the option to not give consent and not participate. If this is indicated they will be directed to a refusal page where they are thanked for their interest and given contact details if they have any questions.
3. Upon completion of both the eligibility checklist and consent forms, a thank you page will appear.
4. Potentially eligible individuals will be sent an email to confirm their consent, assigned a Unique Study Identifier (UID), the next steps for their allocated study group i.e. direct clinical examination or genetic test.
Online Pre-screening Questionnaire: After completing the initial compulsory section of the consent and eligibility check, participant can choose to complete basic demographics questions and quality of life (QoL) assessment with several well validated questionnaires: Geriatric Anxiety Inventory Short Form (GAI-SF (5 items)), EuroQol 5 Dimensions 5 Levels (EQ-5D-5L AU index), GlauCAT, EuroQoL Visual Analogue Scale (EQ-VAS), and Subjective Numeracy Scale (8 items) (SNS-8) establish emotional/utility baselines and decision quality before screening.
Hard copy Questionnaire: If the participant does not have internet access and would like to take part, we will mail them a hard copy of the participant information, consent forms, and the QoL questionnaires, with a prepaid envelope for them to return the forms.
For people who agree to enrol in the study and have signed the consent but do not complete the questionnaires, we will send up to three SMS/text, email, or mail reminders at 7, 14, 28 days, and telephone them directly at day 30 as a final communication.

Confirmation email: Following the completion of the online consent forms, the participant will receive a correspondence email directing them to go to the local optometrist. The email will ask the optometrist to upload their assessment and imaging through a secure online portal link to the same participant.

Optometry examination: When the participant presents to the local optometry with their email/letter, they will receive an comprehensive eye examination including best-corrected visual acuity (BCVA), intraocular pressure (IOP), Van Herick grade, Humphrey Visual Field test (HVF 24-2), optic disc-centred photographs and Optical Coherence Tomography Retinal Nerve Fibre Layer (OCT RNFL). The optometrist is required to enter all the assessment results and upload the images with the participant’s study ID through the online portal.
Once all assessment results migrate into our database, fellowship trained ophthalmologists masked to the participant’s polygenic risk score (PRS) profile, will grade clinical data, independently assign a diagnosis ranked on a scale of certainty: none, possible, probable or definite glaucoma and consensus to be reached by discussion.

For people who receive confirmation email/mail but do not complete eye examination, we will send up to three SMS/text, email, or mail reminders at 7, 14, 28 days, and telephone them directly at day 30 as a final communication.

Any clinically significant incidental finding (e.g., suspected glaucoma, macular degeneration, diabetic retinopathy etc.) will be managed as part of usual care. Such findings would be explained to the participant and, with consent, communicated to their GP/ophthalmologist. The research team will receive coded data for analysis and will not participate in clinical decisions.

After completing the screening process, all the participants will receive a post screening questionnaire. For direct clinical screening and the 5% PRS groups, the follow up email will be sent 14 days after they complete the eye examination.

Post-genetic screening questionnaire: Psychological Consequences Questionnaire (PCQ) – screening context will be used as the endpoint for all the participants. Other questionnaires are including Decision Regret Scale (DRS), repeat EQ-5D-5L, GAI-SF, GDS-15, and the comprehension/behaviour items to capture acute impact and early actions. This mirrors the published glaucoma PRS psychosocial protocol (GRADE/INSiGHT).26 The online link will be sent to the participants 2 days after they receive their PRS profiling report or after they attend optometrist appointments.

In a population screening context where most participants will not have symptomatic disease, the dominant QoL signal is psychosocial (worry, uncertainty, satisfaction/regret, behaviour) rather than vision-function impairment. Accordingly, instruments specific to genomic result impact (FACToR, DRS) and utility/QALY capture (EQ-5D-5L or AQoL) are most informative. Vision-specific QoL tools (e.g., National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), GlauCAT, Glaucoma Quality of Life-15 (GQL-15)) are valuable after diagnosis or with measurable functional loss, but have limited sensitivity for asymptomatic, screened populations.

Longitudinal follow up post screening questionnaires: if participants opt in for questionnaires they will receive a combination of quantitative and qualitative questionnaires one, two and three years after they complete the trial. This survey will collect information on an individual's eye care history within the timeframes and any further development of glaucoma and treatment. It will also repeat some of QoL domains and gather information related to cost-effectiveness analysis.

Control group

Active

Outcomes

Primary outcome [1]

Number of people diagnosed with definite or probable glaucoma.

Timepoint [1]

Following completion of first clinical examination.

Secondary outcome [1]

Proportion of individuals undertaking clinical profiling, after completing the initial eligibility screening questionnaire.

Timepoint [1]

At the conclusion of study.

Secondary outcome [2]

Patient-reported outcome measures (PROMs) PROMs/Quality of life (QoL) assessment will be undertaken using several well validated questionnaires: Geriatiric Anxiety Inventory Short Form (GAI-SF (5 items)), GlauCAT, EuroQol 5 Dimensions 5 Levels (EQ-5D-5L AU index), EuroQoL Visual Analogue Scale (EQ-VAS). These measures will be assessed as a composite secondary outcome and reported a single outcome for difference in overall 'quality of life".

Timepoint [2]

Following completion of first clinical examination.

Secondary outcome [3]

Cost-effectiveness of Polygenic Risk Score (PRS)-profiling in prioritising people for clinical profiling.

Timepoint [3]

This will be assessed at the conclusion of the enrolment and collation of the baseline data, and repeated at the conclusion of the study (year 5).

Eligibility

Key inclusion criteria

Age 64 to 69 years old
Be able to read and comprehend English (upper-primary to early-secondary school (Flesch–Kincaid Grade ˜ 8-10):
Not seen by an optometrist/ophthalmologist in last 3 years
Not diagnosed with glaucoma, or have had procedures for glaucoma, or have been prescribed a glaucoma medication

Minimum age

64 Years

Maximum age

69 Years

Sex

Both males and females

Healthy volunteers

Yes

Key exclusion criteria

1) Age < 64 years or > 69 years
2) Self-reported diagnosed with glaucoma
3) Not seen an optometrist or ophthalmologist in the preceding three years (ie no MBS items: 104, 105, 111, 115, 10905, 11221, 11224, 10910, 10911, 10913, 10914, 10938, 10939, 10940, 10941), or have been treated for glaucoma (topical medication, surgery or laser (MBS items: 42782, 42744, 42746, 42752, 42504, 42705, 42794; or PBS codes for ophthalmic anti-glaucoma medications including: Betaxolol; Latanoprost; Travoprost; Bimatoprost; Brimonidine; Timolol; Brinzolamide; Dorzolamide; Pilocarpine and their combination products)

Study design

Purpose of the study

Diagnosis

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Allocation concealment will be undertaken by Services Australia at the time of participant recruitment.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Permuted block randomisation

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Not Applicable

Type of endpoint/s

Efficacy

Statistical methods / analysis

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

1/03/2026

Actual

Date of last participant enrolment

Anticipated

1/03/2027

Actual

Date of last data collection

Anticipated

1/03/2029

Actual

Sample size

Target

7000

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

National Health and Medical Research Council

Address [1]

Country [1]

Australia

Primary sponsor type

University

Name

University of Tasmania

Address

Country

Australia

Secondary sponsor category [1]

Other Collaborative groups

Name [1]

QIMR Berghofer Medical Research Institute

Address [1]

Country [1]

Australia

Ethics approval

Ethics application status

Submitted, not yet approved

Ethics committee name [1]

University of Tasmania Human Research Ethics Committee

Ethics committee address [1]

http://www.utas.edu.au/research-admin/research-integrity-and-ethics-unit-rieu

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

28/09/2025

Approval date [1]

Ethics approval number [1]

Summary

Brief summary

Glaucoma is one of the most heritable of all complex diseases, and when untreated causes irreversible blindness. Despite advances in imaging technology, approximately half of all cases in our community are undiagnosed, and many people with glaucoma continue to present at advanced stages of the disease. We have recently developed a polygenic risk score, which in retrospective cohorts robustly identifies people at risk of disease. We now aim to conduct a randomized, single-blinded, parallel-controlled trial, to investigate the utility of polygenic risk profiling as the key intervention to identify people at high-risk of developing glaucoma and requiring clinical screening. We will recruit people who are aged between 64 and 68 years old, and have not had a clinical examination by an optometrist or ophthalmologist within the preceding 3 years. Services Australia will contact approximately 132,000 people across 320 postal regions in Australia. Participants will be randomly allocated to a) direct optometry examination regardless of genetic risk (control) or b) polygenic risk score-based prioritised (top 5% of population) clinical profiling (case). As such, we will be able to determine, and directly compare the prevalence rates of definite or probable glaucoma between screening groups.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Alex Hewitt

Address

Menzies Institute for Medical Research; 17 Liverpool St, Hobart, TAS 7000

Country

Australia

Phone

+61 407359824

Fax

[email protected]

Contact person for public queries

Name

Alex Hewitt

Address

Menzies Institute for Medical Research; 17 Liverpool St, Hobart, TAS 7000

Country

Australia

Phone

+61 407359824

Fax

[email protected]

Contact person for scientific queries

Name

Alex Hewitt

Address

Menzies Institute for Medical Research; 17 Liverpool St, Hobart, TAS 7000

Country

Australia

Phone

+61 407359824

Fax

[email protected]

Data sharing statement

Will the study consider sharing individual participant data?

Yes

Will there be any conditions when requesting access to individual participant data?

Persons/groups eligible to request access:
• Researchers
Conditions for requesting access:
• Yes, conditions apply:
• Requires review on a case-by-case basis by the trial custodian, sponsor or data sharing committee
• Requires a scientifically sound proposal or protocol
• Requires approval by an ethics committee
• Requires a data sharing agreement between data requester and trial custodian or sponsor

What individual participant data might be shared?

• De-identified individual participant data:
• All outcomes data
• Published results
• Primary outcome(s)

What types of analyses could be done with individual participant data?

• Systematic reviews and meta-analyses
• Studies exploring new research questions
• Health economic analyses
• Studies testing whether findings can be repeated or confirmed
• Teaching research methods or developing new statistical techniques

When can requests for individual participant data be made (start and end dates)?

From:
At the end of the study
To:
No end date

Where can requests to access individual participant data be made, or data be obtained directly?

• Email of trial custodian, sponsor or committee: [email protected]

Are there extra considerations when requesting access to individual participant data?

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.

Trial Review

Documents added manually

Documents added automatically