A person with early stage glaucoma feels nothing. No pain, no blur, no warning. The optic nerve is losing fibres in the background of an otherwise ordinary day. By the time vision loss becomes noticeable, it is permanent. Worldwide, more than nine in ten people living with glaucoma do not know they have it [1]. Nearly half of the estimated 4.22 million people with the condition in the United States are unaware of their diagnosis [2].

This is the quiet problem sitting inside ophthalmology clinical trials and it rarely gets discussed outside the industry. Protocols are built on strong science: clear endpoints, defined populations or a solid rationale for intervention. What they are not always built for is a participant who does not feel sick and has no daily reminder of why the trial matters.

The disengagement paradox

Clinical trials lose participants at a striking rate, and published retention analyses suggest ophthalmology sits inside the same pattern with a specific twist: retention appears closely linked to how much a condition disrupts a patient’s daily life [3]. Vision-threatening, symptomatic disease tends to keep people engaged. Slow-moving, asymptomatic disease often does not, even when the long-term stakes such as permanent vision loss, are just as serious.

Taken together, these figures point to a possible structural mismatch. The patients who may benefit most from a trial’s outcome, those with early, treatable, asymptomatic disease, can also be the ones with the least daily motivation to stay in it. A participant who does not notice their condition worsening has no internal signal telling them the visits are worth the disruption. Industry retention research suggests that patients in a placebo arm who see no improvement may conclude the trial is not working for them and disengage [3].

When the protocol outweighs the disease

Ophthalmology protocols tend to ask more of participants than many other therapeutic areas: repeated imaging, functional testing and long-term follow-up, often on a tighter cadence than routine eye care [4]. For a person who feels well, the trial itself can become the most tangible impact of their condition.

Distance appears to compound this. One retention model reported that reducing patients’ average one-way travel from 67 miles to 13 miles was associated with improved study completion [4]. Across trials generally, travel friction, rigid scheduling and complex assessment windows are cited among the leading reported drivers of dropout [5]. None of this is a surprise; what is harder to see in advance is how quickly a protocol that looks reasonable on paper can become a burden that outweighs a patient’s perceived benefit.

What operational realism looks like at TFS

In ophthalmology trials, success depends on more than strong science. It depends on whether a protocol is practical for sites to run and sustainable for patients to complete. One question we encourage sponsors to ask early is: “Can sites execute this protocol consistently, and will patients remain engaged throughout the study?”

Retention rarely fails all at once. It erodes through the exact pressures the data above points to: frequent visits, lengthy assessments, travel requirements, or competing personal commitments. Over time, these factors can impact engagement, retention, and ultimately study outcomes.

At TFS, we believe the best protocols are designed with that reality in mind from the start, looking beyond the schedule of assessments to understand what participation will feel like for patients and site teams. By maintaining close partnerships with sites, we can identify emerging challenges early and work with sponsors to address them before they affect retention, compliance, or data quality.

That is what operational realism means in practice: building feasibility, patient experience and site feedback into trial design from day one, helping sponsors create studies that work in both theory and practice.