Silent Thief of Sight Study

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.