Reviews/Dry Eye Disease Treatment/Diquafosol improves tear film break-up time in dry eye
Secretagogues · DED-SEC-01 · v2
Across many studies in different kinds of dry eye, patients treated with diquafosol eye drops tended to show longer tear film break-up times after treatment than before it [5][6][13]. Some controlled studies that compared diquafosol head-to-head with other drops found it did better on break-up time in specific groups, such as after cataract surgery and in diabetic patients [4][3], and one small randomised study saw break-up time lengthen with diquafosol but not with artificial tears [5]. The one trial that compared diquafosol against a dummy (placebo) drop, however, found no clear difference in break-up time [10]. Much of the remaining support comes from studies with no comparison group, which cannot rule out that the eye simply recovered or that any lubricating drop would help [11][12][13]. Against other active drops such as sodium hyaluronate, diquafosol often improved break-up time by a similar amount rather than a greater one [2][8]. Taken together the direction of the evidence favours diquafosol improving break-up time, but the strongest causal test did not confirm it.
Within-group tear film break-up time improves on diquafosol across short-BUT-type, diabetic, post-surgical, paediatric and real-world dry eye populations [6][13][7][11][17]. Several controlled trials carry a diquafosol-specific signal: break-up time lengthened with diquafosol but not artificial tears in short-BUT eyes [5], and NITBUT or TBUT was significantly superior to sodium hyaluronate after cataract surgery [4] and in diabetic dry eye (NITBUT 9.00 ± 6.56 vs 6.95 ± 4.49 s, P = 0.011) [3]. Head-to-head trials against sodium hyaluronate frequently show comparable rather than superior gains, with diquafosol and hyaluronate improving break-up time by 1.046 ± 1.797 and 0.832 ± 1.775 s respectively and no significant intergroup difference [2], and no statistically significant intergroup difference in another comparison [8]. Against rebamipide the break-up time changes were comparable [14][19]. The contested point: The evidence divides on whether the broad break-up time improvement is diquafosol-specific or a generic effect. The single placebo-controlled trial [10] (n = 286) found no significant difference in BUT versus placebo, while active-comparator trials versus sodium hyaluronate often show no greater improvement [2][8]; set against this are controlled results where diquafosol outperformed its comparator on TBUT/NITBUT [3][4][5].
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One reviewer's only job is to attack the finding. The challenges below were weighed before the grade was set.
The only placebo-controlled trial in the corpus [10] (double-masked, n=286) found 'no significant differences in BUT compared with placebo' — the most rigorous causal test of this exact outcome is negative, so the broad within-group improvements may substantially reflect placebo, vehicle lubrication, regression to the mean and natural recovery rather than a diquafosol-specific effect on break-up time.
A large share of the supporting evidence is uncontrolled single-arm before/after ([11] n=3000 real-world, [12], [13], [7]), which cannot separate the TBUT change from confounders; within-group significance is not evidence of a treatment effect.
Where it remains uncertain. The only placebo-controlled trial found no significant BUT difference versus placebo [10], and comparator trials versus hyaluronate frequently show no greater improvement [2][8].
Aleatory
Tear film break-up time is an inherently variable, short-timescale measurement, adding noise within and between the small samples in several trials ([5] n = 17 randomised arm, [14] n = 28, [19] n = 30).
Epistemic
The only placebo-controlled trial [10] found no significant BUT difference versus placebo, so a diquafosol-specific effect on break-up time is not confirmed against an inert control.
Inferential
Uncontrolled single-arm studies ([11] n = 3000, [12], [13], [7]) cannot separate the break-up time change from regression to the mean, vehicle lubrication or natural recovery.
The load-bearing papers from a corpus of 19, each classified by what it does to the claim. Every DOI is taken from the corpus the claim was graded on.
Large RCT showing TBUT improvement with DQS, comparable to hyaluronate
“diquafosol and HA improved tear film breakup time by 1.046±1.797 and 0.832±1.775 s, respectively (no significant intergroup difference).”
Panel auditInternal validity: medium · scope of inference: Dry eye patients in China and Singapore over 4 weeks.Key limitations: no placebo · within-group TBUT significance not reported · TBUT a secondary measure
Randomised evidence of greater NITBUT with DQS than hyaluronate in diabetic dry eye
“A comparison between the DQS group and HA group found in the mean NITBUT (9.00 ± 6.56 vs. 6.95 ± 4.49 s, P = 0.011)”
Panel auditInternal validity: medium · scope of inference: Patients with diabetes and dry eye disease over 8 weeks.Key limitations: no placebo · diabetic-only population · active comparator
RCT showing significantly superior TBUT with DQS versus active comparator in post-cataract dry eye
“The diquafosol group showed significantly superior TBUT (P < .001), corneal fluorescein (P = .045), and conjunctival staining (P = .001) compared to the sodium hyaluronate group throughout the study period.”
Panel auditInternal validity: medium · scope of inference: Dry eye patients after cataract surgery.Key limitations: single centre · no placebo · post-cataract population
NITBUT, among all assessed parameters, showed significant improvement by week 8 (and at week 4).
Panel auditInternal validity: low · scope of inference: Type 2 diabetic dry eye patients over 8 weeks.Key limitations: no control · preliminary · diabetic-only · sample size not given
4 of 19 papers shown. The full review lists all of them, with the panel’s arbitration →
Claims are graded at each quarterly release, and re-graded between releases only when a pivotal trial lands. Every change is a new version of the claim.
Consistent controlled and uncontrolled evidence that diquafosol improves TBUT supports a Likely verdict, held below Established by a negative placebo-controlled result on break-up time and frequent no-intergroup-difference findings versus comparators.
Release 2026-q4 re-graded every claim from its corpus under protocol v0.19. An earlier release's grade is shown for the record; it came from an earlier protocol and is not a movement.
Assumptions that carry weight but are not themselves established.
The panel records the gap that would most move the claim, and the study that would close it.
Placebo-controlled trial powered on break-up time. The single placebo comparison [10] was negative on BUT and did not treat break-up time as the primary endpoint, so the causal question on this outcome is unresolved. The panel rates this the highest-importance open gap for the claim, and names the study design that would close it: A double-masked, placebo-controlled RCT in general dry eye with tear film break-up time pre-specified as the primary endpoint and adequate power.
Open question: Does diquafosol improve tear film break-up time more than an inert placebo when break-up time is the primary endpoint? Why it is still open: The only placebo-controlled trial [10] found no significant BUT difference versus placebo and did not power on this outcome.
Priors is a sceptical first reader, not peer review, and not medical advice.
Release 2026-q4 · graded 21 Oct 2026 · protocol v0.19