Efficacy of IPL Treatment of Dry Eye and Ocular Rosacea: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy of IPL Treatment of Dry Eye and Ocular Rosacea (NCT03194698), a randomized na study. The primary outcome is Change in Ocular Surface Disease Index (OSDI) Symptom Survey Score.

2. Clinical Question

The study focused on symptoms reported by participants rather than on a single clinical sign. OSDI asks about dry eye symptoms and their effects on vision-related function over the past week. Its score combines responses about ocular symptoms, vision-related function, and environmental triggers. The registry also reports two secondary outcomes concerning the percentage of blocked meibomian pores in the lower lids.

This comparison addresses the added treatment component: both groups received MGX, while one also received IPL. It does not compare either treatment plan with no intervention or with another treatment. The study was described as a pilot, and the registry record does not report a target population beyond the listed conditions or additional eligibility details.

3. Trial Design

This was a randomized, parallel-group pilot study sponsored by Mayo Clinic. The registry lists an enrollment of 20 and describes two groups: MGX plus IPL and MGX alone. Each group included 10 participants in the posted primary outcome results. The study was completed; its phase is listed as not applicable.

The treatment groups received the same stated number of visits and MGX treatments: 4 visits and 4 MGX treatments. The combined-treatment group also received 4 IPL treatments. The trial therefore compared MGX with the same procedure accompanied by IPL, rather than comparing two unrelated treatment approaches.

The registry lists masking as none. This means the record does not indicate that participants or study personnel were masked to the assigned treatment. The method used to generate the random allocation sequence, allocation concealment, and any procedures to reduce the influence of unmasked treatment knowledge are not reported in the registry record.

The primary outcome was change in OSDI symptom survey score, with the outcome timeframe described as baseline and 3 months. The two secondary outcomes concerned changes in the percentage of blocked meibomian pores in the right and left lower lids. The registry lists 3 outcome measures and 3 reported analyses.

The original sample-size justification, planned statistical analysis details beyond the analysis listed with the results, analysis populations, handling of missing observations, and any interim analyses are not reported in the registry record. The planning illustrations associated with the observed results are not evidence about the assumptions used to design the original trial.

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

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 in Ocular Surface Disease Index (OSDI) Symptom Survey Score, measured over baseline, 3 months.

The primary endpoint was change in the Ocular Surface Disease Index (OSDI) symptom survey score from baseline to 3 months. OSDI is a 12-item questionnaire that asks about dry eye symptoms and their effects on vision-related function during the past week. Its three subscales cover ocular symptoms, vision-related function, and environmental triggers. Participants rate responses on a scale from 0, “none of the time,” to 4, “all of the time.”

The final score ranges from 0 to 100. The registry describes scores from 0 to 12 as normal, 13 to 22 as mild dry eye disease, 23 to 32 as moderate dry eye disease, and scores greater than 33 as severe dry eye disease. The outcome is reported as a percentage of change in OSDI score, with a mean and standard deviation for each group.

A symptom questionnaire is used to capture participants’ reported experience, including effects on everyday visual function that may not be represented by a gland measure alone. It is distinct from the secondary outcomes, which assess the percentage of blocked meibomian pores in the lower lids. The registry record describes the questionnaire and the assessment timeframe, but does not report additional details about how the endpoint was selected or how missing questionnaire responses were handled.

7. Results Posted in the Registry

• Meibomian Gland Expression (MGX): mean -2.00 versus -25.90 on control; difference 23.90 (95% CI 7.26 to 40.54), standardized effect d = 1.26; z-test p = 0.005.

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 in Meibomian Glands Open - Right Lower Lid

• 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 deviations.
• Result:
  • Meibomian Gland Expression (MGX): mean 5.00 versus 6.90 on control; difference -1.90 (95% CI -11.54 to 7.74), standardized effect d = -0.17; z-test p = 0.699.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Meibomian Gland Expression (MGX) and the control. The interval gives the range of effects that remain compatible with the data.

Change in Meibomian Glands Open - Left Lower Lid

• 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 deviations.
• Result:
  • Meibomian Gland Expression (MGX): mean 10.00 versus 14.40 on control; difference -4.40 (95% CI -17.66 to 8.86), standardized effect d = -0.29; z-test p = 0.516.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Meibomian Gland Expression (MGX) and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes concern blocked meibomian pores in the right and left lower lids. Across these measures, the reported and recalculated comparisons do not show the same degree of separation between groups as the primary OSDI comparison. The re-calculated intervals for both secondary mean differences include zero, and the sponsor-reported rank-test results do not indicate a clear group separation. These findings are best read as an overall pattern of limited evidence for differences on the posted gland measures, rather than as a repetition of the symptom result.

That pattern does not establish that symptom changes and gland findings are unrelated. OSDI measures reported symptoms and vision-related effects, whereas the secondary endpoints measure the percentage of blocked pores in particular lower lids. Different measures can capture different aspects of a condition, and the registry record does not report analyses of how changes in these outcomes relate within individual participants.

The secondary outcomes carry less weight than the primary endpoint because they are designated secondary and there are several reported outcome analyses. In general, repeated testing across outcomes increases the chance of finding an unusual result by chance. The registry record does not report a multiplicity adjustment or a detailed outcome hierarchy beyond identifying the primary measure and the secondary measures. The secondary results should therefore be treated as exploratory context rather than as independent confirmation of the primary result.

The study’s small enrollment also limits the ability to distinguish modest group differences from random variation in these secondary measures. Their results do not settle whether the interventions differ on other gland measures, symptoms, or timeframes not reported in the registry.

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

• Change in Meibomian Glands Open - Right Lower Lid
• Change in Meibomian Glands Open - Left Lower Lid

9. Statistical Interpretation

10. Statistical Methods Explained

The registry reports a randomized, parallel-group comparison, with no masking listed. The primary outcome is continuous: it is a numerical percentage change in OSDI score. The posted group summaries give a mean and standard deviation for each group, and a simple unadjusted recalculation uses those summaries to estimate a difference in group means and an interval for that difference.

What does a mean difference describe?

A mean is the arithmetic average of observed values in a group. A difference in means expresses the distance between two group averages on the outcome’s scale. Here, the calculated contrast is 23.9 for the percentage change in OSDI score, comparing the MGX-plus-IPL group with the MGX-alone group. The signs and direction depend on which group is subtracted from which; the reported contrast is oriented to the combined-treatment group relative to the MGX-alone group.

A mean difference can be informative about the average contrast, but it does not show how every participant’s result compared. The standard deviation describes how dispersed observations are around a group mean. It is not a confidence interval and does not represent the range of individual outcomes. In this study, the posted standard deviations are 20.0 and 17.9 for the primary outcome.

What does the reported rank test do?

The registry identifies the sponsor-reported method as the Wilcoxon (Mann-Whitney) test. This is a rank-based method for comparing two independent groups. Rather than relying directly on a difference between arithmetic means, it orders the observations and assesses how values in one group tend to rank relative to values in the other. It can be useful when a rank-based comparison is chosen for the outcome, but its interpretation is not identical to a test of the difference in means.

The registry reports p = 0.031 for this primary analysis. A p-value describes how compatible the observed data are with a specified no-difference model under the assumptions of the test. It is not the probability that the null model is true, nor does it give the size or practical importance of a treatment contrast. The registry record does not report further details of the test implementation, such as how ties were handled.

Why is there also a recalculated result?

The recalculated comparison uses the posted means, standard deviations, and group sizes to estimate a mean difference and an unadjusted p-value. It gives a mean difference of 23.9, an interval from 7.264 to 40.54, and p = 0.005. This calculation is a summary-statistic re-analysis, not the rank-based test reported by the sponsor. Because the approaches use different information and answer their comparisons in different ways, their p-values need not match. The registry record does not explain the difference. The reported Wilcoxon result remains the trial’s listed analysis, while the recalculation provides a separate view based on the posted summaries.

“Unadjusted” means the calculation is not adjusted for other outcomes or covariates. The registry does not report a covariate-adjusted primary analysis. It also does not report whether the primary analysis followed an intention-to-treat population, a per-protocol population, or another defined set of participants.

What can an interval tell a reader?

An interval estimates a range of values compatible with a statistical procedure and the observed data. In general, wider intervals indicate less precision and narrower intervals indicate greater precision, all else being equal. The recalculated interval runs from 7.264 to 40.54. Its confidence level is not reported in the registry record, so no confidence percentage should be attached to it. The interval is derived from the recalculated mean comparison; the registry does not list an interval for the Wilcoxon result.

What do the secondary analyses add?

The two secondary outcomes measure the percentage of blocked meibomian pores in the right and left lower lids. The registry also reports Wilcoxon (Mann-Whitney) analyses for these outcomes. These measures address gland findings rather than the symptom questionnaire, and they are not substitutes for the primary endpoint. The registry does not report whether the secondary analyses were prespecified in a detailed statistical analysis plan or whether any multiplicity adjustment was applied.

In general, testing several outcomes creates more opportunities for a result to appear unusual by chance. Adjustments or a clearly defined outcome hierarchy can help interpret a collection of tests, but the relevant plans and procedures are not reported in the registry record. The secondary p-values should therefore be considered alongside their role as secondary outcomes, rather than as independent definitive evidence.

Finally, statistical methods describe comparisons in the observed sample; they do not by themselves establish why group results differ or how well the estimates will generalize. The small pilot enrollment, absence of masking, and unreported information about missing data and analysis populations limit what can be inferred beyond the posted comparisons.

11. Confidence Intervals and Precision

The recalculated primary mean difference is 23.9, with an interval from 7.264 to 40.54. The interval gives a range of estimates compatible with the summary-statistic calculation, but the registry record does not report its confidence level. It is therefore not appropriate to describe it as a particular confidence interval level. The reported Wilcoxon analysis has no interval listed in the registry record.

In general, an interval is useful because it conveys uncertainty about an estimated contrast rather than presenting a single number alone. A narrow interval suggests more precision than a broad interval, while a broad interval leaves more uncertainty about the magnitude of the contrast. The interval spans a substantial range of possible mean differences. Its limits are both above zero, but that does not remove uncertainty about the exact size of the mean contrast.

The precision should also be read in the context of the group sizes: 10 participants in each group in the posted primary results. The standard deviations, 20.0 and 17.9, describe the spread of observed OSDI changes within the groups. With a small study, group averages and estimated contrasts can be sensitive to the particular participants enrolled. The interval does not describe the range of individual participant responses, and it does not imply that every participant had a result close to the group mean.

The sponsor-reported rank-test p-value, 0.031, does not come with a reported interval. The interval and p-value from the recalculation are based on a different summary-statistic comparison and should not be merged into a single analysis. The record does not give enough information to quantify uncertainty for the rank-based result beyond its reported p-value.

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 sample-size planning figures are participants per arm, not total participants or total events. They are illustrations based on the observed effect, not the trial’s original design justification. The registry record does not report the original sample-size assumptions.

The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set as a stated fraction of the observed effect. The displayed planning figures use the primary-outcome contrast: planning for 100% of the observed effect gives 10 participants per arm for 80% power and 14 participants per arm for 90% power; planning for 75% of the observed effect gives 18 participants per arm for 80% power and 24 participants per arm for 90% power; planning for 50% of the observed effect gives 40 participants per arm for 80% power and 54 participants per arm for 90% power.

In plain terms, the 80% power column gives the number of participants per group that the planning calculation estimates would be needed to detect the specified effect with 80% power under those assumptions. The 90% power column gives the corresponding estimate for 90% power. Higher planned power requires more participants for a fixed effect, and smaller effects require more participants to detect than larger effects. The plotted planning relationship conveys this same general trade-off.

These are planning illustrations, not observed power. They do not show the probability that the completed trial detected an effect, and they should not be read as the original enrollment target or as evidence that the trial was designed using 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 = 23.900; pooled standard deviation σ = 18.979.
2. n = 2 × (1.96 + 0.842)² × 18.979² / 23.900² = 9.9, rounded up to 10 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 <- 23.9                      # observed difference in means
sigma <- 18.9790674164986                     # 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(3194698)
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 = 10 (80% power), 14 (90% power)
 75% of observed effect: n per arm = 18 (80% power), 24 (90% power)
 50% of observed effect: n per arm = 40 (80% power), 54 (90% power)
power.t.test: 10.9 
Simulated power at n = 10 per arm: 0.758 (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. Analyses Reported by the Sponsor

The registry-reported primary analysis uses a Wilcoxon (Mann-Whitney) test and gives p = 0.031. The separate recalculation uses the posted group means, standard deviations, and sample sizes to estimate a mean difference of 23.9, an interval from 7.264 to 40.54, and an unadjusted p-value of 0.005.

These results are not identical because they come from different analytic approaches: the registry-reported test is rank-based, while the recalculation is based on a mean comparison from summary statistics. The registry record does not explain the difference, and it does not give an interval for the sponsor-reported test. The recalculation should therefore be read as a complementary, unadjusted summary-based analysis, not as a correction to or replacement for the reported test.

The registry record does not indicate a discrepancy between the posted group summaries and the listed sponsor analysis. Nonetheless, the reported Wilcoxon result is the trial’s documented analysis, while the recalculation supplies a different statistical summary. Neither p-value alone describes the magnitude or practical importance of the observed group contrast.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and two secondary outcomes, with 3 analyses reported. Testing multiple outcomes can increase the chance that at least one result appears statistically unusual even when there is no underlying difference. Statistical plans sometimes address this through a prespecified outcome hierarchy or an adjustment to account for multiple tests. Whether either approach was used is not reported in the registry record.

The primary OSDI comparison is identified separately from the two secondary lower-lid pore measures. That distinction supports giving the primary outcome greater interpretive weight, while treating the secondary comparisons as less conclusive. The record does not report whether the secondary analyses were considered confirmatory or exploratory, nor does it describe any adjustment to their p-values.

Missing-data procedures are not reported in the registry record. The posted primary outcome summaries list 10 participants in each group, but the record does not explain whether all randomized participants contributed data at the stated assessment, how incomplete questionnaires or missed visits were handled, or whether any imputation was used. The analysis population is also not reported: it is not clear from the registry whether the results include all randomized participants or a defined subset.

The record does not report a detailed statistical analysis plan, covariate adjustment, interim analyses, or procedures for handling protocol deviations. These absences do not demonstrate that such procedures were not used; they mean the registry entry does not provide enough information to evaluate them. As a result, interpretation is centered on the posted group summaries and reported tests, with limited information about the analysis decisions behind them.

16. 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.

The registry reports 10 participants at risk for serious adverse events in each group. It records 0 affected participants in the MGX-plus-IPL group and 0 in the MGX-alone group. The reported number of deaths was 0 in each group. The registry also records 10 participants at risk for other adverse events in each group and 0 affected participants in either group.

These figures describe events recorded in this study; they do not establish that adverse events cannot occur. The groups were small, and the registry record does not provide further details about event collection, definitions, follow-up completeness, or the duration of safety monitoring. No serious adverse event terms are listed. The figures should therefore be read as the posted counts for this trial, not as a comprehensive estimate of safety in broader populations or over other time periods.

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

The posted primary results show a greater average decrease in OSDI score in the group receiving MGX plus IPL than in the group receiving MGX alone over the baseline-to-3-month assessment. The registry-reported rank-based comparison gives p = 0.031. A separate unadjusted recalculation from the posted summaries estimates a mean difference of 23.9, with an interval from 7.264 to 40.54. These findings describe the observed results and the precision of one summary-based comparison in this pilot study.

They do not establish that every participant experienced a similar change. Group means can conceal substantial variation, and the primary outcome standard deviations indicate spread in the observed scores. The study enrolled 20 participants, with 10 in each group, so the findings are based on a small sample. The interval also leaves uncertainty about the magnitude of the mean contrast, and its confidence level is not reported in the registry record.

The result does not establish what would happen in a larger or different group of participants, how long any observed differences might persist, or how the two treatment plans compare with interventions not studied. The recorded endpoint was assessed at baseline and 3 months; longer-term results are not reported in the registry record.

The result also does not show that the groups differed in every relevant clinical measure. The secondary measures concern lower-lid pore blockage, not the same symptom construct as OSDI, and their overall pattern is less separated. Nor do the posted results explain a biological mechanism for any observed difference.

Finally, the absence of reported adverse events in these groups is a record of the posted counts, not proof that no risk exists. The study’s size and the safety-reporting details available in the registry limit the conclusions that can be drawn from those counts.

18. Why This Trial Matters Statistically

This study illustrates a common statistical challenge in small clinical trials: the estimated group contrast can appear notable while its size remains uncertain. The primary result includes both group averages and their variation, and the recalculated interval makes clear that a single point estimate is not the whole story. Readers can distinguish the observed direction of the group means from the uncertainty around the magnitude of the mean difference.

It also shows why the analysis method matters. The registry reports a rank-based test, while the accompanying recalculation compares means using posted summary statistics. These approaches yield different p-values and do not answer precisely the same statistical question. Keeping the sponsor-reported analysis distinct from an unadjusted recalculation helps prevent the two results from being conflated.

The pilot format and small enrollment are important to interpretation. Estimates from a small study can be imprecise, and planning calculations based on the observed effect can be optimistic when that effect is unusually large. The planning illustrations are useful for understanding how required group size changes with the effect being targeted, but they are not a record of the trial’s original design assumptions or of its observed power.

The secondary endpoints add another statistical lesson: distinct outcomes can tell different parts of a clinical story, and multiple comparisons require caution. A symptom measure and a gland measure are not interchangeable. Clear identification of primary and secondary outcomes, along with reporting of multiplicity and missing-data procedures, would help readers assess the strength and scope of the evidence. Those procedural details are not reported in the registry record.

19. 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 main trial-specific limitation is the small enrollment: 20 participants overall, with 10 in each group in the posted outcome summaries. Such a small comparison provides limited precision and may be sensitive to individual observations. The broad interval for the recalculated primary mean difference reflects uncertainty about its magnitude.

The registry lists no masking. Awareness of treatment assignment can influence participant-reported outcomes such as OSDI, as well as their assessment or collection. The record does not report steps taken to limit this possibility. It also does not report the method of random sequence generation or allocation concealment, so those aspects of the randomization process cannot be assessed from the registry entry.

The primary endpoint timeframe is baseline and 3 months. The registry does not report longer follow-up for this outcome, so persistence beyond the measured period cannot be assessed. Both groups received MGX, meaning the comparison addresses the addition of IPL to MGX; it does not isolate either treatment against no treatment or a different comparator.

Other important details are not reported in the registry record, including participant demographics, detailed eligibility criteria, the original sample-size justification, the analysis population, handling of missing observations, and whether analyses were adjusted for multiple outcomes. The secondary outcomes are limited to lower-lid meibomian pore measures, and they do not provide a comprehensive account of all possible clinical effects.

Finally, safety counts show no affected participants in the posted groups, but the registry does not give detailed event-collection or monitoring procedures. The limited sample and reporting details mean those counts should not be interpreted as establishing the absence of risk.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Efficacy of IPL Treatment of Dry Eye and Ocular Rosacea — NCT03194698.
• Registry record last updated 2020-01-03; status last verified 2019-12.
• Results first posted 2020-01-03.
• 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.

23. Record Summary

NCT03194698 is a completed randomized, parallel-group pilot study sponsored by Mayo Clinic, with enrollment of 20. It compared 4 visits of MGX plus 4 IPL treatments with 4 visits of MGX alone. Masking is listed as none.

The primary outcome was change in OSDI symptom score from baseline to 3 months. The reported Wilcoxon (Mann-Whitney) comparison gave p = 0.031. The posted group summaries support an unadjusted recalculated mean difference of 23.9, with an interval from 7.264 to 40.54; that recalculation is separate from the registry-reported test.

Two secondary outcomes measured lower-lid meibomian pore blockage. The registry reports no affected participants for serious or other adverse events in either group and 0 deaths in each group. Details about missing data, analysis populations, multiplicity procedures, and the original sample-size justification are not reported in the registry record.