Clinical trials continue to shape nearly every aspect of modern eye care, influencing approvals from the US Food and Drug Administration (FDA), standards of care, insurance coverage, and clinical practice guidelines, said Mohammad Rafieetary, OD, FAAO, FORS, ABO, and Roya Attar, OD, MBA, DHA, FAAO, FORS, in their “Clinical Trials in Eye Care: From Protocol to Practice” presentation at Optometry’s Meeting 2026 in Phoenix. Further, they said, eyecare providers are increasingly getting more involved in clinical trials at each stage.

The first randomized controlled trial in ophthalmology in the United States occurred during the 1950s when ophthalmologist Arnall Patz studied oxygen levels and retinopathy of prematurity, Drs. Rafieetary and Attar explained, though the first placebo-controlled trial was conducted in 1863 for rheumatism. Fast-forward to the 1980s when the Early Treatment Diabetic Retinopathy Study established rigorous trial methods and changed the standard of care for diabetic retinopathy. The timeline increased in momentum in the 2000s with major trials such as MARINA/ANCHOR, CATT, OAKS/DERBY, and increased again with gene therapies, device trials for sustained drug delivery, and now for AI screening, which Drs. Rafieetary and Attar said improves screening accuracy, access, and efficiency in ocular disease detection.

Optometrists are getting involved as primary or subinvestigators, as well as in screening, referral, recruitment, imaging, data collection, and comanagement, they explained. Therefore, they said, it’s important for optometrists to understand how clinical trials function and what to expect if they get involved.

Clinical trials can be categorized into 5 primary groups, they explained:

1. treatment trials,

2. prevention trials,

3. screening trials,

4. diagnostic trials, and

5. quality-of-life or supportive-care trials.

This research is conducted in 4 phases:

• Phase 1: safety,

• Phase 2: early efficacy,

• Phase 3: large validation, and

• Phase 4: postmarket surveillance.

And there are multiple roles:

Sponsors—including pharmaceutical companies, device manufacturers, academic institutions, and research organizations—initiate, fund, and oversee trials. Their responsibilities include protocol development, site selection, regulatory submissions, and data analysis.

Contract research organizations (CROs) are often hired by sponsors to manage operational elements such as monitoring, data collection, logistics, and regulatory support.

Clinical research associates (CRAs) monitor study sites to ensure compliance with protocol requirements, Good Clinical Practice standards, informed consent procedures, and safety reporting.

Institutional Review Boards (IRBs) are independent ethics committees that are responsible for protecting patient rights, safety, and welfare throughout a study.

Within research sites, key personnel include:

• Principal investigators (PIs) who maintain responsibility for protocol compliance, regulatory adherence, patient safety, and overall study integrity.

• Subinvestigators (Sub-Is) conduct examinations, procedures, assessments, injections, and patient follow-up.

• Clinical research coordinators are the “operational backbone” of a research site. They are responsible for scheduling, regulatory paperwork, sponsor communication, consent documentation, and workflow management.

• Photographers/imagers are responsible for obtaining standardized imaging—including OCT, OCT-A, fundus photography, fundus autofluorescence, angiography, and ERG data—according to protocol specifications.

• Masked examiners are intentionally blinded to treatment assignments to minimize bias during visual acuity and outcome assessments.

Daily research operations involve protocol-driven scheduling, imaging certification, source documentation, reading centers, drug accountability, and monitoring visits.

Patients are often motivated to participate in trials because of access to innovative therapies, hope for themselves or future generations, altruism, financial support for transportation or insurance-related costs, and closer monitoring and care, Drs. Rafieetary and Attar said. However, they added, time burdens, anxiety, and misconceptions can all be barriers to patients’ participation. Common misconceptions about clinical trials are that patients are treated like “guinea pigs,” clinical trials are reserved only for end-stage disease, placebo groups receive no care, and research patients are monitored less closely.

To obtain informed consent from participants in an ethical study, researchers must discuss risks, potential benefits, and available alternatives. Patients must also know that their participation is voluntary and that they can withdraw at any time. Drs. Rafieetary and Attar also discussed the foundational ethical principles that guide clinical research, including the World Medical Association’s Declaration of Helsinki, IRB oversight, data monitoring committees, and protections for vulnerable populations.

Trials are designed with inclusion and exclusion criteria, visit schedules, endpoints, safety reporting, laboratory testing, and imaging and diagnostic requirements. Specific endpoints in optometric and ophthalmic research are functional (best-corrected visual acuity, low-luminance visual acuity, and reading speed), anatomical (central subfield thickness, geographic atrophy growth, and fluid reduction), and patient-reported (quality of life, mobility, and symptom reporting).

In addition to barriers to patient participation that can affect recruitment and retention, protocol deviations, missed visits, staff turnover, sponsor changes, and study discontinuation are other potential challenges that studies may encounter.

Evolving technology is expected to influence future ophthalmic trials, Drs. Rafieetary and Attar said. Recent advances in remote monitoring with home OCT and wearable technologies is one factor, they said, as are AI-assisted screening, decentralized trials, and gene therapy. Decentralized trials and remote monitoring could alter how patients participate in trials and how data are collected outside traditional clinic settings, they said.

Continuing staff shortages and increased patient demand in health care mean that optometrists are increasingly involved in not only early disease detection but also other trial roles, depending on state regulations, sponsor requirements, site infrastructure, training, certification, and distinctions between PI and Sub-I roles.

ODs who are interested in building research programs should focus on dedicating space in their practice for equipment and patient volume, training staff, creating standard operating procedures, and seeking regulatory support as well as relationships with trial sponsors. ODs can also tailor their careers for research: In addition to taking on investigator roles and coordination, they can specialize in trial imaging, medical affairs, industry consulting, and CRO positions, Drs. Rafieetary and Attar explained. OM