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Washout and Rescue Protocols in April 2026 IOP-Lowering Studies · Glaucoma, Vision & Longevity: Supplements & Science

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  SPEAKER_00: Clinical trials of new glaucoma, intraocular pressure lowering medications often pause patients' existing eye drops to establish a clear, untreated baseline pressure.
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  SPEAKER_00: This is known as a washout period.
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  SPEAKER_00: By measuring eye pressure after stopping prior treatment, researchers can accurately judge how much the new drug lowers pressure.
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  SPEAKER_00: However, taking patients off therapy raises safety concerns, pressure can rebound and can cause some people to fail screening.
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  SPEAKER_00: Trials therefore include strict rescue rules to restart treatment if pressure gets too high and careful monitoring.
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  SPEAKER_00: Understanding these washout and rescue protocols helps explain why trial results may differ from everyday practice.
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  SPEAKER_00: Washout durations and sequences by medication class.
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  SPEAKER_00: Trials use different washout lengths for different drug classes based on how long medications linger in the eye.
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  SPEAKER_00: In general, prostaglandin analogues, PGAs, e.g.
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  SPEAKER_00: latanoprost, travoprost, bimatoprost, washout periods are often around four to eight weeks.
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  SPEAKER_00: A systematic review found that patients typically return to baseline pressure about four to five weeks after stopping latanoprost.
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  SPEAKER_00: However, PGA effects can variably persist.
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  SPEAKER_00: One study found some patients still had slightly lowered pressure eight weeks after stopping latanoprost.
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  SPEAKER_00: Travoprost and bimatoprost also generally need several weeks.
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  SPEAKER_00: Most studies use four weeks, although evidence is limited.
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  SPEAKER_00: Patients on PGAs may undergo multiple checks up to six to eight weeks after stopping.
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  SPEAKER_00: Beta blockers, e.g.
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  SPEAKER_00: timolol, these are typically washed out by stopping the drop for four weeks.
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  SPEAKER_00: Research showed that a two-week break is usually too short.
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  SPEAKER_00: After stopping timolol, pressure often edges back toward a higher baseline by three to four weeks.
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  SPEAKER_00: Alpha-2 agonists, bromonidine, these often require about four to five weeks off.
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  SPEAKER_00: In one trial, 15 patients washed out bromonidine over five weeks to reach baseline.
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  SPEAKER_00: Carbonic anhydrase inhibitors, CAIs, dorzolamide, brinzolamide.
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  SPEAKER_00: Although less well studied, trials commonly use around two to four weeks off as their effects diminish more quickly than PGAs.
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  SPEAKER_00: Meiotics, e.g., pylocarpene, these have a very short duration of effect, usually a break of one to two weeks suffices.
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  SPEAKER_00: Meiotics are rarely used long term today.
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  SPEAKER_00: In trials where patients are on more than one medication, the protocols may pause all drops at once or sometimes stagger them.
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  SPEAKER_00: Typically, all prior medications are stopped together and sufficient time is allowed for the slowest drug to clear.
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  SPEAKER_00: The washout lengths above are chosen so that most patients return to their true untreated IOP.
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  SPEAKER_00: As noted by Stewart et al.
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  SPEAKER_00: too short a washout might make a new drug look less effective, while an unnecessarily long washout only prolongs high-risk pressure.
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  SPEAKER_00: Stewart and colleagues found, for example, that stopping bromonidine needed about five weeks to return to baseline, whereas stopping latinoprost sometimes took up to eight weeks.
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  SPEAKER_00: They also showed that travoprost effects were not fully gone after two weeks.
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  SPEAKER_00: Because evidence is limited, many trials simply follow industry standards.
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  SPEAKER_00: Often four to six week washouts for PGAs and four weeks for older drugs, based on these and other data.
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  SPEAKER_00: Rescue criteria and safety monitoring.
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  SPEAKER_00: During washout, patient safety is paramount.
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  SPEAKER_00: Trials define rescue criteria to determine when therapy must be restarted.
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  SPEAKER_00: Rescues prevent sustained dangerously high IOP.
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  SPEAKER_00: A common rule is: if pressure rises back to the patient's original baseline or exceeds a preset threshold, the prior medication is reinstated immediately.
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  SPEAKER_00: For example, a study on stopping PGAs asked patients to resume drops if their pressure returned to pre-study levels at any point.
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  SPEAKER_00: Other trials set specific cutoff IOP values, often around 30 to 32 mm HERGRAUS.
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  SPEAKER_00: If after washout a patient's pressure exceeds this safety limit, they are withdrawn or given immediate treatment instead of continuing the trial.
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  SPEAKER_00: In fact, some protocols require that after washout the enrolled patients must have an IOP in a given range, for example, to bullets 22, 2, and 32 mm Hergrams.
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  SPEAKER_00: Anyone above 32 millimeter Hergs would be excluded.
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  SPEAKER_00: This protects patients from dangerously high pressure.
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  SPEAKER_00: Safety monitoring during washout is intensive.
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  SPEAKER_00: Participants typically see the doctor several times, sometimes daily or weekly, to check IOP and eye health.
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  SPEAKER_00: For instance, the Mont Blanc trial measured pressure at three times of day, 8 a.m., 10 a.m.
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  SPEAKER_00: on two consecutive visits after washout, ensuring no harmful spikes were missed.
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  SPEAKER_00: Patients are instructed to report symptoms, like eye pain or vision changes, immediately.
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  SPEAKER_00: Some protocols even provide emergency contact info if patients develop worrisome signs.
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  SPEAKER_00: Additionally, visual fields or optic nerve exams may be monitored at baseline and later visits, ensuring long-term safety, though this is more an ongoing safety check than washout specific.
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  SPEAKER_00: The key is that trials must balance learning about the new drug against any harm from taking away therapy.
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  SPEAKER_00: Frequent IOP checks and strict thresholds minimize risk.
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  SPEAKER_00: Permitted concomitant medications.
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  SPEAKER_00: Aside from the study drug, most trials permit only non-IOP lowering medications.
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  SPEAKER_00: Commonly allowed extras include ocular lubricants, artificial tears, allergy drops, if needed, or treatments for unrelated eye issues since these do not affect pressure.
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  SPEAKER_00: Systemic medications for other health problems are generally allowed unless they are known to influence IOP.
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  SPEAKER_00: By contrast, no other glaucoma drops or systemic pressure-lowering drugs are allowed during the trial.
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  SPEAKER_00: This ensures that any pressure changes reflect the study medication alone.
• 5:49
  SPEAKER_00: Each protocol spells out allowed versus forbidden medications.
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  SPEAKER_00: For example, most protocols forbid ocular steroids, which raise IOP and any additional IOP lowering drugs.
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  SPEAKER_00: In practice, patients usually can keep using dry eye drops, controlled medications for other conditions, or those needed for general health, but not any extra glaucoma medications.
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  SPEAKER_00: Screening failure rates and patient safety impact.
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  SPEAKER_00: Stringent washout requirements significantly affect who can join a trial.
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  SPEAKER_00: Many trials perform washout before final screening.
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  SPEAKER_00: Patients stop their drops for the required period, then doctors check their IOP.
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  SPEAKER_00: If the pressure is too high or too low or does not meet the protocol criteria, the patient fails screening and cannot enroll.
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  SPEAKER_00: For example, one trial required post-washout IOP between 22 and 32 millimeter HORGREGs.
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  SPEAKER_00: Patients falling outside that range were excluded.
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  SPEAKER_00: Johnson and Jample's analysis of large trials found that patients on multiple medications often had very large IOP rises after washout.
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  SPEAKER_00: Such patients are more likely to hit the cutoff and fail enrollment.
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  SPEAKER_00: In practical terms, lengthy washouts and tight pressure limits can cause high screen failure rates.
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  SPEAKER_00: Some patients simply cannot tolerate being off drops long enough, their pressure goes too high.
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  SPEAKER_00: Others might not have glaucoma that's severe enough, pressure too low off meds, and are excluded on the low end.
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  SPEAKER_00: These criteria protect patient safety but can make trials less reflective of all glaucoma patients.
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  SPEAKER_00: Those most at risk from washout, e.g., on 3-4 medications, may be underrepresented because they either fail screening or require early rescue.
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  SPEAKER_00: Crucially, strict washouts reduce risk in the trial itself.
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  SPEAKER_00: By excluding anyone whose pressure spikes dangerously high, trials avoid subjecting volunteers to prolonged uncontrolled glaucoma.
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  SPEAKER_00: This keeps participants safer, but it also means trial results come from a somewhat select group able to meet the washout criteria.
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  SPEAKER_00: Real-world applicability of efficacy estimates.
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  SPEAKER_00: Washout protocols can make trial results optimistic compared to real-world use.
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  SPEAKER_00: In trials, baseline IOP is measured after stopping all prior medications, so it is artificially higher than a patient's everyday treated pressure.
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  SPEAKER_00: A new drug's effect, e.g., an 8 to 10 mm drop, is therefore calculated from this high baseline.
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  SPEAKER_00: In practice, patients often add a new drug on top of existing therapy without washout.
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  SPEAKER_00: Their starting pressure will be lower and the incremental drop from the new drug will be smaller.
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  SPEAKER_00: For example, Johnson and Jampel found that patients on one or two glaucoma drops typically saw IOP rise by 6 to 7 mmherg after washout.
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  SPEAKER_00: If a new drug then lowered pressure by 8 mmHz from that raw untreated baseline, a patient already on one drop might only get a net 2-3 mmhergrams additional drop when the drug is added, since their treated baseline was 6 to 7 mm higher than the trial baseline.
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  SPEAKER_00: Indeed, some trials now measure both scenarios.
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  SPEAKER_00: In the Claris QLS-111 phase 2 studies, one trial, Osprey, enrolled patients after full washout and found each patient's IOP fell about 3.7 mmhergram on QLS 111 alone.
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  SPEAKER_00: Another trial, Apteryx, added QLS111 on top of Latanoprost and found an extra 3.2-3.6 mm grams drop above what Latanoprost alone provided.
• 9:19
  SPEAKER_00: These additive results, roughly 3-4 mmhergrams, are smaller than the full drop numbers one might quote if starting from an untreated baseline.
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  SPEAKER_00: Thus, efficacy estimates from washout trials tend to overstate actual IOP reduction in patients already on medication.
• 9:35
  SPEAKER_00: Doctors and patients should be aware that a 10 mmHAG drop in a trial context might translate to a more modest improvement in practice.
• 9:44
  SPEAKER_00: It's important for clinicians to look at how trials define baseline and whether data from add-on studies are available.
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  SPEAKER_00: Conclusion: Washout and rescue rules are essential parts of glaucoma drug trials, designed to ensure accurate baseline measurements and patient safety.
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  SPEAKER_00: Different drug classes require different washout lengths, often four to six weeks for prostaglandins, about four weeks for timelol, etc., to clear residual effects.
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  SPEAKER_00: Trials carefully monitor IOP during this period and rescue patients if pressures rise too high.
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  SPEAKER_00: These procedures do increase screening failures.
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  SPEAKER_00: Patients with extreme IOP spikes are excluded, but keep subjects safe.
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  SPEAKER_00: Finally, because trial baselines are inflated by washout, the pressure drops seen in studies may exceed what a patient would experience on add-on therapy.
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  SPEAKER_00: In other words, real-world IOP control may appear less dramatic than trial numbers suggest.
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  SPEAKER_00: Patients and clinicians should bear this in mind when considering new glaucoma treatments.
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  SPEAKER_00: All links to sources are available in the text version of this article.
• 10:50
  SPEAKER_00: You can find the full article at visualfieldtest.com.
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  SPEAKER_00: Thanks for listening.
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  SPEAKER_00: To check your visual field, click the link at the bottom of this article or visit visualfieldtest.com.