Anterior segment clinical trials: Key considerations for successful study delivery

Ophthalmology clinical trials are sometimes discussed as though they form one broad consistent category. Operationally, however, front-of-the-eye and back-of-the-eye studies can require very different approaches to site selection, recruitment and patient management.

Front-of-the-eye, or anterior segment research includes indications such as dry eye disease, glaucoma, ocular surface disease, corneal disorders and cataracts. Although these studies may involve less specialized infrastructure than many retinal trials, delivering them well still requires careful planning around sites, recruitment, assessment consistency and participant experience.

Match sites to the protocol, not just the indication

Anterior segment studies can draw from a comparatively broad investigator pool that includes general ophthalmologists, optometrists, cornea specialists, glaucoma specialists and high-volume community practices. This availability creates real opportunities for sponsors, but a larger pool does not mean every site is suited to every protocol.

Feasibility should look beyond patient counts and examine whether a site's workflow can accommodate the study's specific demands. For dry eye trials, tear breakup time remains a widely used but inherently subjective endpoint, since it relies on an investigator detecting a break in the tear film by eye while simultaneously timing it with a stopwatch, a combination of factors that introduces real variability. At the scale of a multi-site trial, with dozens of investigators and hundreds of patients, this kind of variability becomes not just a quality issue but a financial one, since poorly standardized assessments lead to noisier data, larger required sample sizes and a smaller likelihood of detecting a true treatment difference.¹

Ophthalmology clinical trial site selection should weigh training capacity and a willingness to standardize procedures as heavily as patient volume.

Build recruitment around the realities of the patient population

Front-of-the-eye studies typically benefit from larger eligible populations than rare or treatment-naive retinal conditions. Enrollment channels can include site database searches, community outreach, digital campaigns and optometrist referrals.

Even so, recruitment planning should reflect what is actually happening across the clinical trial landscape. In a 2024 global survey of more than 850 clinical research sites, 38% identified the complexity of clinical trials as their top challenge, ahead of recruitment and retention at 36%, and a related industry analysis found that 70% of site staff reported trials had become much more difficult to manage over the previous five years.²  Sponsors who assume that a large front-of-the-eye population will translate automatically into fast enrollment may be underestimating the practical burden that screening, pre-screening and record review place on site coordinators who are already stretched.

A useful question during protocol design is whether eligibility criteria and visit requirements are truly necessary for scientific integrity, or whether some can be simplified without weakening the data.

Plan for endpoint consistency across sites

Common anterior segment endpoints include intraocular pressure, corneal staining, hyperemia grading, tear production and validated symptom questionnaires. The FDA draft guidance for dry eye drug development illustrates how detailed these expectations can be, outlining recommendations for eligibility criteria, trial design and efficacy endpoints, including standardized clinical evaluations and safety considerations specific to the disease.³

Because several of these measures depend on investigator judgment rather than automated capture, protocol design and site training should address how each assessment is conducted, timed and documented. Clear reference standards, calibrated equipment and structured rater training sessions can help reduce the kind of inter-site and inter-rater variability that erodes statistical power over the course of a trial.

Keep the patient experience in view

Anterior segment studies generally place less burden on participants than imaging or injection intensive retinal programs, but visit frequency, treatment administration and washout periods can still affect adherence. Clear, accessible patient materials and visit schedules built around real-world routines can help maintain engagement through to study completion.

Look beyond perceived simplicity

Front-of-the-eye studies may offer a larger site pool and more conventional recruitment paths, but these advantages only translate into results when converted into consistent execution. Early attention to site fit, realistic recruitment expectations and endpoint standardization can help sponsors avoid the data variability and enrollment delays that continue to affect ophthalmology trials industry wide.

Learn more about how Fortrea can support your anterior segment study

References

1. Pucker AD, Yalamanchili R. Modernizing endpoints in ophthalmic clinical trials. The Ophthalmologist. Published August 4, 2025. Accessed October 21, 2026. https://www.theophthalmologist.com/issues/2025/articles/august/modernizing-endpoints-in-ophthalmic-clinical-trials/
2. WCG. 2024 Clinical Research Site Challenges Report. Published 2024. Accessed October 21, 2026. https://www.wcgclinical.com/wp-content/uploads/2024/10/WCG_2024_Clinical_Research_Site_Challenges_Report.pdf
3. U.S. Food and Drug Administration. Dry Eye: Developing Drugs for Treatment, Guidance for Industry (Draft). Published December 2020. Accessed October 21, 2026. https://www.fda.gov/media/144594/download