Effectiveness of Intense Pulsed Light for Improving Dry Eye Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effectiveness of Intense Pulsed Light for Improving Dry Eye Syndrome (NCT03396913), a randomized na study. The primary outcome is Change of Baseline Tear Breakup Time (TBUT).

2. Clinical Question

The registry record describes a randomized comparison of intense pulsed light (IPL) followed by meibomian gland expression (MGX) against sham IPL followed by MGX. The question was whether the groups differed in change in tear breakup time (TBUT) in the study eye from baseline to follow-up at 10 weeks. TBUT is measured in seconds, and higher values are defined in the record as better.

3. Trial Design

This was a randomized, parallel-group trial with single masking, according to the registry record. It lists enrollment of 88 and a completed status. The record identifies Lumenis Be Ltd. as the sponsor. The listed study start was 2018-01-10, and primary completion was 2019-08-15.

The experimental arm received IPL followed by MGX. The sham comparator arm received sham IPL followed by MGX, so MGX was part of both assigned regimens. The record describes four treatment sessions for each study arm. It also describes an intended study duration of 10 weeks for each subject. The identity of the people who were masked, the method used to maintain masking, and whether masking was assessed are not reported in the registry record.

The primary endpoint was change in study-eye TBUT from baseline to follow-up at 10 weeks. The posted arm summaries include 43 participants in Sham+MGX and 39 in IPL+MGX for this outcome. These outcome counts do not match the enrollment figure, and the reasons for the difference are not reported in the registry record. The record also lists adverse-event groups with different numbers at risk than the primary outcome groups; it does not explain how those safety groups relate to the outcome populations.

Two secondary outcomes are posted: change from baseline in the Ocular Surface Disease Index (OSDI) and change from baseline in Eye Dryness Score (EDS), both at 10 weeks. Although the registry lists 13 outcome measures, only these two secondary outcomes have results presented in the posted results. Details of the recruitment setting, eligibility criteria, participant characteristics, and the trial's original design assumptions are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Change of Baseline Tear Breakup Time (TBUT), measured over 10 weeks.

TBUT is the time measured in seconds until the tear film breaks up after a blink. The registry defines the primary outcome as change in TBUT in the study eye from baseline to the 10-week follow-up, and states that higher values mean a better outcome. The outcome is continuous: each participant's measurement can take a range of values rather than representing a category or event.

Change from baseline expresses follow-up values relative to each participant's starting measurement. The group summaries therefore describe mean change, not the mean TBUT level at follow-up alone. A positive mean change indicates an increase relative to baseline under the measure's stated direction. The comparison of interest is the difference between the average changes in the randomized groups.

TBUT is used as a sign of tear-film stability. In this trial, it is the primary endpoint, so it is the main outcome specified in the results record for comparing the treatment regimens. The registry does not report why this endpoint was selected over other signs or symptoms, how TBUT was measured in detail, or how the study eye was selected. Those design and measurement details are not reported in the registry record.

7. Results Posted in the Registry

• IPL+MGX: mean 1.99 versus 0.75 on control; difference 1.24 (95% CI 0.27 to 2.21), standardized effect d = 0.55; z-test p = 0.012.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change From Baseline Ocular Surface Disease Index (OSDI)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • IPL+MGX: mean -29.89 versus -25.90 on control; difference -3.99 (95% CI -14.22 to 6.24), standardized effect d = -0.17; z-test p = 0.445.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between IPL+MGX and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline Eye Dryness Score (EDS)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • IPL+MGX: mean -32.96 versus -25.90 on control; difference -7.06 (95% CI -17.56 to 3.44), standardized effect d = -0.29; z-test p = 0.188.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between IPL+MGX and the control. The interval gives the range of effects that remain compatible with the data.

The two posted secondary outcomes concern symptoms: change in OSDI and change in EDS at 10 weeks. The arm means move in the same general direction as symptom improvement for both groups, with the IPL+MGX group showing a more negative mean change in each measure. Their reported mean differences and intervals are in the posted results, but the intervals include zero and the unadjusted p-values do not provide strong evidence against a no-difference model for either comparison.

This pattern is not identical to the primary TBUT result. The primary outcome's reported interval lies above zero, while the secondary-outcome intervals include zero. Differences between signs and symptom scores are possible because they measure different aspects of dry eye and have different scales and variability. The registry does not report a planned hierarchy or a rationale for how these outcomes should be combined, so the secondary results should not be treated as a confirmation or contradiction of the primary result on their own.

These secondary comparisons carry less weight because the record lists 13 outcome measures and does not report a multiplicity adjustment or a prespecified strategy for interpreting multiple outcomes. When many outcomes or analyses are considered, some results may appear noteworthy by chance. Without the statistical plan and the complete set of results, it is difficult to judge how selectively the posted results represent the analyses conducted.

The registry reports no separate analyses for the secondary outcomes. The posted summaries are therefore best read as descriptive comparisons with unadjusted uncertainty, rather than as definitive tests that settle whether the regimens differ on symptoms. They add context to the primary sign-based endpoint but do not establish a single overall conclusion across all outcomes.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change From Baseline Ocular Surface Disease Index (OSDI)
• Change From Baseline Eye Dryness Score (EDS)

9. Statistical Interpretation

10. Statistical Methods Explained

The main comparison is a difference between group means for change in a continuous outcome. The endpoint is change in TBUT, measured in seconds, and the registry reports a mean change for each group. The comparison is stated as IPL+MGX versus Sham+MGX, with the Sham+MGX group serving as the control.

What does a mean difference describe?

A mean difference subtracts one group's average from the other group's average, using the comparison's stated direction. Here, the posted value of 1.24 seconds is the mean difference for IPL+MGX versus Sham+MGX. Since higher TBUT is defined as better, a positive difference represents greater mean change in the IPL+MGX group. The estimate is in seconds, making its scale directly interpretable against the TBUT measure.

A group mean summarizes the center of the observed measurements. It does not describe every participant's response, and it can conceal variation within each group. Two groups may have different averages while individual measurements overlap substantially. The registry provides summaries rather than participant-level observations, so the shape of the outcome distributions and the degree of overlap cannot be assessed directly.

What is a standard error?

The posted arm summaries report standard errors. In general, a standard error describes the precision of an estimated quantity, such as a group mean: smaller standard errors indicate less sampling uncertainty around that estimate, all else equal. It is not the same as the standard deviation, which describes variability among individual observations. The record reports standard errors of 0.34 and 0.36 for the two primary-outcome group means, as well as a pooled standard deviation of 2.238 for the comparison.

The distinction matters because a standard error is used to describe uncertainty in a mean, while a standard deviation describes the spread of measurements. The standard errors should not be read as ranges containing most individual participants. The registry does not provide the raw observations or a distributional plot from which further distribution features could be checked.

How should the confidence interval be understood?

A confidence interval is an uncertainty range around an estimate, constructed by a statistical procedure. In general, a narrower interval indicates greater precision, while a wider interval leaves more possible values compatible with the data and method. For the primary mean difference, the reported interval lies entirely above zero. This indicates that the interval's compatible values are positive under the reported calculation. It does not mean that every plausible value is equally likely, and it does not establish clinical importance.

The registry does not state the confidence level or give details of the calculation method for the posted interval. The interval should therefore be read as the reported uncertainty range, without attributing unreported analysis choices to it. The comparison's p-value is explicitly unadjusted, and no adjustment for testing multiple outcomes is reported.

What does the p-value add?

The unadjusted p-value for the primary comparison is 0.012. In general, a p-value evaluates how unusual the observed data, or data more extreme, would be under a specified null model and assumptions. It is not an effect-size measure and does not quantify the probability that the result arose by chance. It also does not state whether an effect is clinically meaningful. The magnitude and precision of the estimate should be considered alongside the p-value.

Because the record does not report a multiplicity adjustment, this p-value is not adjusted for the number of outcomes or other analyses. The registry lists 13 outcome measures, and two secondary outcomes have posted results. The full set of analyses performed and the plan for selecting or interpreting them are not reported in the registry record.

Why can over-dispersion matter in general?

For count outcomes, over-dispersion means the observed variation exceeds what a simple count model assumes. If it is ignored, standard errors can be too small and intervals can be too narrow. This is a general statistical issue; it is not the relevant model description for the primary endpoint here, which is continuous. The registry reports a mean-based comparison for TBUT and does not report a count model for this endpoint.

More generally, statistical conclusions depend on the analysis model and its assumptions. The registry record does not report the full model specification, diagnostic checks, or adjustment variables for the primary comparison. The posted summaries therefore support interpretation of the reported mean difference and uncertainty, but not reconstruction of every analytical choice.

11. Confidence Intervals and Precision

The primary estimate is a mean difference of 1.24 seconds, and the reported interval runs from a positive lower bound to a positive upper bound. Its position entirely above zero indicates that the range of values covered by this interval is positive. The interval still spans a range of possible effect magnitudes; the point estimate should not be treated as an exact or certain value.

Precision concerns the width of the uncertainty interval, not whether an estimate is important. A narrow interval would constrain the range more tightly, while a wider interval would leave more uncertainty about the size of the difference. The registry's reported interval supplies information beyond the point estimate and unadjusted p-value, but the confidence level and calculation details are not reported in the registry record.

The outcome group means are accompanied by standard errors of 0.34 seconds and 0.36 seconds. These quantify uncertainty in the estimated means, not participant-to-participant variability. The registry also reports a pooled standard deviation of 2.238 for the comparison. Keeping these quantities distinct helps avoid interpreting the standard errors as the range of individual responses.

Precision is affected by the amount and variability of outcome information, among other factors. The primary outcome summaries list 43 participants in Sham+MGX and 39 in IPL+MGX. The registry does not report why those counts differ from the enrollment figure, whether observations were missing, or how missing values were handled. Those omissions limit assessment of how the analysis population and missingness may have affected the interval. No claim about precision beyond the posted summary can be made without those details.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm for this continuous outcome; they are not total event counts. The registry's sample-size illustration uses a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It considers effects equal to the stated fraction of the observed effect. The trial's original sample-size assumptions and design justification are not reported in the registry record.

The 80% power column gives the estimated participants per arm for a future study to have an 80% chance of detecting the specified effect under the listed assumptions, if that effect and the assumptions were correct. The 90% power column gives the corresponding planning figure for a 90% chance. These are design probabilities under assumed conditions, not guarantees about a future result.

The rows that plan for 100% of the observed effect use the observed estimate as the target effect. Rows planning for 75% or 50% of the observed effect use smaller target effects. Smaller effects are harder to distinguish from random variation, so they require more participants under the same assumptions. The listed figures are planning illustrations based on the observed effect, not the original trial's sample-size plan. They are not observed power.

The sample-size curve should be interpreted in the same planning context: it relates the target effect to the number of participants needed under the stated assumptions. It does not show the number of participants actually analyzed, nor does it establish the effect that a future trial will observe. The registry record does not report whether the original trial used these assumptions.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 1.240; pooled standard deviation σ = 2.238.
2. n = 2 × (1.96 + 0.842)² × 2.238² / 1.240² = 51.2, rounded up to 52 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 1.24                      # observed difference in means
sigma <- 2.23841685125894                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(3396913)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 52 (80% power), 69 (90% power)
 75% of observed effect: n per arm = 91 (80% power), 122 (90% power)
 50% of observed effect: n per arm = 205 (80% power), 274 (90% power)
power.t.test: 52.1 
Simulated power at n = 52 per arm: 0.801 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists 13 outcome measures, including the primary TBUT endpoint and two secondary outcomes with posted results: OSDI and EDS. The record does not report how many outcomes were specified in the original protocol, whether outcome definitions or time points changed, or whether a hierarchy determined which result would be considered primary for inference.

Multiplicity arises when several outcomes, time points, groups, or analyses are tested. In general, the more comparisons made, the greater the chance that at least one unadjusted result may appear statistically unusual even when no corresponding effect exists. Approaches such as prespecifying a primary endpoint or adjusting for multiple tests can address particular multiplicity concerns, but the registry does not report whether any such approach was used. The primary p-value is identified as unadjusted, and no adjustment is stated for the secondary comparisons.

The registry record reports zero listed analyses for the primary outcome and no reported analyses for the secondary outcomes, while still presenting group summaries and comparisons. This means the record does not supply a detailed analysis plan or a complete account of analytical decisions. It does not establish that no analyses were performed in the study; it establishes only that these details are not reported in the registry record.

Missing-data methods and analysis populations are also not reported. The record does not say whether the comparisons followed an intention-to-treat approach, used another population definition, imputed missing measurements, or analyzed available cases. Nor does it explain the difference between the overall enrollment figure and the primary-outcome group counts. Without these details, the potential effect of missing observations or exclusions cannot be evaluated from the registry summaries.

The record also does not describe baseline adjustment, model diagnostics, handling of protocol deviations, or sensitivity analyses. These omissions do not invalidate the posted estimates, but they limit the ability to assess robustness and reproduce the analysis from the registry entry alone.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists serious adverse events for groups with 43 participants at risk in Sham+MGX and 45 at risk in IPL+MGX. No serious adverse events were reported in either group. Deaths are listed as zero in both groups. These are the posted counts; the record does not provide event descriptions for serious events because none are listed.

For other, non-serious adverse events, the record reports 9 affected participants among 43 at risk in Sham+MGX and 4 among 45 at risk in IPL+MGX. These counts describe the registry's event reporting during the recorded period. The record does not provide the types, severity, timing, or attribution of these events, nor does it explain how safety follow-up was conducted.

The safety group sizes differ from the outcome group sizes, and the registry does not explain the difference. The counts alone should not be read as a complete comparison of risk or as proof that an event was caused by either regimen. They summarize the adverse-event information posted in the registry record.

16. What the Result Does, and Does Not, Mean

The posted primary result shows a higher mean change in TBUT in the IPL+MGX group than in the Sham+MGX group at 10 weeks. The estimated difference is reported in seconds, and the uncertainty interval lies above zero. The unadjusted p-value is 0.012. Taken together, these summaries describe evidence of a between-group difference in the recorded primary outcome under the analysis represented in the registry.

That result does not establish that the difference is clinically important. The registry does not provide a threshold for a meaningful TBUT change or explain how the observed difference relates to participants' day-to-day experience. TBUT is a sign, while OSDI and EDS are symptom measures; their results do not show the same degree of separation between groups. The posted data therefore do not reduce the trial to a single, comprehensive measure of dry eye outcomes.

The result also does not isolate the contribution of IPL from MGX, because both randomized groups received MGX and differed in active versus sham light. It compares the assigned regimens as described, not IPL alone against no procedure. Further, the record does not report enough detail about masking, missing data, analysis populations, or the statistical plan to fully assess potential bias and robustness.

The trial's posted outcomes address follow-up at 10 weeks. They do not establish whether differences persist beyond that time or whether the same results would occur in other populations or settings. The registry record does not report longer-term outcomes, participant characteristics, or the full eligibility criteria.

These results are a statistical description of the recorded trial comparison, not medical advice. They neither guarantee individual outcomes nor by themselves establish an overall clinical judgment about the regimens.

17. Why This Trial Matters Statistically

This trial illustrates why an endpoint's measurement scale and direction matter. TBUT is measured in seconds, and the registry explicitly states that higher values mean better outcome. That makes the sign of the reported mean difference interpretable without converting it into a different scale. Keeping the comparison in its original units also preserves the practical meaning of the endpoint.

It also shows why point estimates, intervals, and p-values answer different questions. The mean difference describes the estimated contrast, the interval conveys uncertainty around it, and the unadjusted p-value evaluates compatibility with a no-difference model under assumptions. None of these alone describes clinical importance, and the registry does not report a threshold for meaningful change.

The different pattern across the primary and secondary outcomes is another important statistical lesson. TBUT is a sign measure, while OSDI and EDS are symptom measures. Their posted summaries do not give interchangeable evidence about one underlying quantity. Reading each endpoint in its own terms avoids treating unlike measures as though they were duplicates.

Finally, the record highlights the value of complete reporting. The listed enrollment, outcome group counts, and safety group sizes do not align, and explanations for these differences are not reported. The registry also does not report its original sample-size assumptions, multiplicity strategy, missing-data handling, or full analysis plan. Those details are important for understanding how precisely and robustly a result can be interpreted, even when a headline estimate and p-value are available.

18. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry entry leaves several trial-specific questions unanswered. It does not report eligibility criteria beyond the condition and description of dry eye due to meibomian gland dysfunction, or describe participant characteristics. The results therefore cannot be contextualized by age, disease severity, prior treatment, or other features that might affect generalizability.

The study-eye selection rule, measurement procedures for TBUT, and details of outcome assessment are not reported. The record identifies the trial as single-masked but does not say who was masked or how the sham procedure maintained masking. These omissions limit assessment of measurement consistency and the potential for knowledge of treatment assignment to influence outcomes.

The primary outcome group counts are 43 and 39, whereas enrollment is listed as 88. The safety groups list 43 and 45 at risk. The reasons for these different figures are not reported in the registry record. Missing-data amounts, reasons for missingness, analysis populations, and methods for handling missing values are also not reported.

The registry does not report a protocol-level statistical analysis plan, multiplicity control, baseline adjustment, or sensitivity analyses. It lists 13 outcome measures but posts results for only two secondary outcomes. The record therefore does not permit a full assessment of selective outcome reporting or the consistency of conclusions across all measures.

Finally, the posted efficacy outcomes cover the 10-week timeframe. Longer follow-up and details on the durability of any observed differences are not reported in the registry record. These limitations concern what can be evaluated from the registry entry and do not, by themselves, determine the validity of the trial.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Effectiveness of Intense Pulsed Light for Improving Dry Eye Syndrome — NCT03396913.
• Registry record last updated 2020-12-09; status last verified 2020-09.
• Results first posted 2020-12-09.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

22. Record Summary

NCT03396913 is a completed, randomized, parallel-group, single-masked trial sponsored by Lumenis Be Ltd. It lists enrollment of 88 and studies intense pulsed light followed by meibomian gland expression against sham light followed by the same procedure for dry eye syndrome due to meibomian gland dysfunction.

The primary outcome was change in study-eye TBUT at 10 weeks. Mean change was 0.75 seconds in Sham+MGX and 1.99 seconds in IPL+MGX, with a posted mean difference of 1.24 seconds and an unadjusted p-value of 0.012. The reported interval for that difference lies above zero.

OSDI and EDS are the two secondary outcomes with posted results. The registry does not report the original sample-size rationale, detailed statistical plan, multiplicity approach, missing-data methods, or reasons for differing outcome and safety group counts.