Electric Stimulation of the Eye to Improve Vision After Trauma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Electric Stimulation of the Eye to Improve Vision After Trauma (NCT02019927), a randomized na study. The primary outcome is Evaluation of the Effectiveness and Safety of Transcorneal Electrical Stimulation to Improve Visual Acuity.

2. Clinical Question

3. Trial Design

The study was registered as a randomized, double-masked, parallel-group trial of transcorneal electrical stimulation and sham treatment. It was sponsored by Wills Eye, listed as phase NA, and has a registry status of completed. The recorded enrollment is 97. The study began in 2013-07, and primary completion is recorded as 2017-09.

The registry separates participants into condition-specific groups: non-arteritic ischemic optic neuropathy, multiple sclerosis, and ocular trauma. Each condition has an active-treatment group and a sham group. The posted primary outcome denominators are 46 and 23 for active and sham NAION groups, 9 and 5 for active and sham multiple sclerosis groups, and 10 and 4 for active and sham ocular trauma groups. These are the numbers attached to the outcome results; the record does not explain how they relate to all enrolled participants or whether any participants lacked outcome data.

The arm descriptions place the NAION treatment at least 6 months after the event, and the multiple sclerosis and ocular trauma treatments at least 3 months after visual changes or trauma. These timings describe the groups in the registry, not the full eligibility rules. Further details about recruitment, allocation procedures, masking procedures, adherence, treatment schedule, or follow-up beyond the primary assessment are not reported in the registry record.

Because the results are divided by condition, the posted means should be read within each condition rather than as a single pooled estimate across all participants. The record does not report a combined estimate or a formal comparison between active treatment and sham within each condition. Its description of randomization and masking identifies broad design features, but does not by itself supply the details needed to assess how those procedures were implemented.

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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Evaluation of the Effectiveness and Safety of Transcorneal Electrical Stimulation to Improve Visual Acuity, measured over Change from Baseline (week 1) to 1-week post initial treatment (week 8).

The primary endpoint is change in high-contrast visual acuity, expressed in logMAR. Participants read letters from a chart and receive a point for each letter correctly identified; scores are converted to the logMAR scale. The recorded timeframe is change from baseline at week 1 to one-week post initial treatment at week 8.

The direction of this scale matters for interpretation: the registry defines improvement as a decrease in logMAR of 0.2 or more. Accordingly, a negative mean change indicates that the group’s average score decreased over the stated interval. That group average does not say that every participant improved, and it does not show the distribution of individual changes.

Visual acuity is used as the primary measure because the trial question concerns visual function after ocular trauma or disease. High-contrast chart acuity captures performance on a standardized letter-reading task, while the other listed outcomes address additional aspects of eye function and participant-reported visual functioning. The posted primary results are means with 95% confidence intervals; standard deviations or other measures of participant-level variability are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change represent?

For a continuous outcome, a mean change summarizes the average difference between a participant’s follow-up value and baseline value within a group. In this trial, the outcome is visual acuity on the logMAR scale, and the registry reports one mean change for each condition and assignment. A group mean can be useful for describing the direction and typical level of change, but it does not reveal whether changes were similar for all participants or concentrated among a few. The record does not provide individual values or a measure such as a standard deviation.

The sign of the change must be interpreted using the scale’s direction. The registry states that a decrease in logMAR represents improvement and defines improvement as a decrease of 0.2 or more. Thus the negative posted means indicate decreases in the group averages. They do not show how many individuals reached the registry’s threshold. An average can also conceal differing patterns within a group, so a mean alone is not a complete description of participant outcomes.

What does a 95% confidence interval convey?

A confidence interval communicates uncertainty about an estimated group mean. In general, a narrower interval indicates greater precision for that estimate, while a wider interval indicates less precision. It is not an interval containing a stated percentage of individual participant outcomes. Nor does it directly quantify the probability that the true value lies in the particular interval once the interval has been calculated.

The posted intervals accompany each group mean. For some groups they extend across zero, while others are entirely below zero. This describes uncertainty around each group’s change, not uncertainty around the difference between the active and sham groups. A formal comparison would estimate that between-group contrast and report its uncertainty. Such a contrast is not reported in the registry record, so the group-level intervals cannot substitute for it.

Why is the between-group contrast important?

In a randomized trial, a comparative analysis ordinarily asks whether outcomes differ between participants assigned to the intervention and those assigned to the comparator. The relevant estimate is the contrast between those assignments, rather than whether either group changed from baseline on its own. Changes can occur over time for reasons not attributable to the assigned intervention; a sham group helps provide a concurrent reference. Randomization is intended, in general, to support a fair comparison of assigned groups, but the registry’s posted group means do not give the result of that comparison.

The registry lists the control as the sham NAION group and the skip note says values are missing or not estimable for a two-arm comparison of the continuous endpoint. The record lists zero analyses. It therefore does not provide a reported comparative estimate for the primary continuous outcome. No treatment effect, p-value, or adjusted result should be inferred from subtracting or otherwise comparing the group means informally.

What do the planning illustrations mean?

General sample-size planning uses assumptions about the effect a future study aims to detect, the significance level, allocation, and a statistical model. The planning assumptions associated with this record specify a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the target effect is expressed as a stated fraction of the observed effect. These are planning illustrations based on the posted effect, not the original trial’s design calculations. The sample-size justification used for this trial is not reported in the registry record.

Planning numbers are prospective illustrations of the sample size that could be needed under stated assumptions. They are not observed power, do not show the chance that this completed trial detected an effect, and do not change the interpretation of its posted estimates. The record does not report that its own design used these planning assumptions. A sample-size illustration also cannot supply a missing treatment contrast or resolve uncertainty in the posted results.

Why can variability matter?

General statistical methods distinguish the mean from the variability of individual measurements. If outcomes are highly dispersed, the mean may be less representative of an individual participant and its estimate may be less precise. For continuous outcomes, the precision of a mean depends on both the amount of information and the variability. The registry provides confidence intervals but does not provide standard deviations or an explicit variance model for these results. The posted information therefore supports interpretation of mean estimates and their intervals, but not a full reconstruction of the underlying outcome distribution.

General methods may also account for features such as repeated measurements, baseline values, or differences among clinical groups. The registry record does not describe whether the primary analysis adjusted for baseline, used repeated-measures methods, or included other covariates. No particular model should be assumed from the fact that the endpoint is a change score.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists secondary outcomes including intra-ocular pressure, visual field mean deviation, retinal nerve fiber layer thickness in the superior, nasal, inferior, temporal, and center quadrants, and the National Eye Institute’s Visual Functioning Questionnaire - 25. It reports 9 secondary outcomes posted and 10 outcome measures overall. Results or analysis details for these outcomes are not included in the registry record for this interpretation.

When a trial evaluates multiple outcomes or multiple comparisons, the chance of at least one apparently unusual result can increase. General statistical approaches may address this multiplicity through a prespecified hierarchy, adjusted significance thresholds, or other methods. Whether any such approach was used, which outcomes were considered confirmatory, and how secondary outcomes were prioritized are not reported in the registry record. The primary result should not be treated as adjusted for multiplicity without that information.

The record lists zero analyses and does not supply a formal comparative analysis for the continuous primary endpoint. It does not report the analysis population, handling of missing outcome data, reasons for missingness, imputation methods, or sensitivity analyses. It is therefore unclear from the registry record whether the posted outcome denominators represent all randomized participants with available data, a specified analysis set, or another population.

Randomized assignment and the population used in analysis are related but distinct issues. General intention-to-treat analysis retains participants according to assignment, while other analysis populations can impose additional requirements. The registry record does not identify which approach was used. Without this information, readers cannot determine how missing outcomes or departures from assigned treatment were handled, or assess the robustness of the group estimates to those choices.

11. 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 reports serious adverse events for each condition-specific active and sham group. No serious adverse events were recorded in any listed group, and deaths were recorded as zero in every group. The numbers at risk for serious adverse events were 45 for active NAION, 23 for sham NAION, 9 for active multiple sclerosis, 5 for sham multiple sclerosis, 9 for active ocular trauma, and 4 for sham ocular trauma. These denominators should be read as the record lists them; they are not identical to every primary outcome denominator.

The registry also records other adverse events: 15 participants among 45 at risk in active NAION, none among 23 at risk in sham NAION, 3 among 9 at risk in active multiple sclerosis, none among 5 at risk in sham multiple sclerosis, 5 among 9 at risk in active ocular trauma, and none among 4 at risk in sham ocular trauma. The record does not provide event terms in the registry record for this interpretation, and the list of top serious event terms is empty.

These counts describe what the registry reports; they do not establish that events were caused by the device or that no unrecorded events occurred. Safety follow-up duration, event definitions beyond the serious/other categories, and detailed event-level descriptions are not reported in the registry record. The absence of recorded serious events in these group counts should not be read as a complete safety assessment.

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

The posted data describe average changes in high-contrast visual acuity among condition-specific groups assigned to transcorneal electrical stimulation or sham. The mean changes are negative in each group, which is the direction the registry defines as improvement on the logMAR scale. The precision differs by group, with confidence intervals that are wider in the smaller multiple sclerosis and ocular trauma groups.

These results do not provide a formal estimate of the difference between active stimulation and sham. A within-group change is not equivalent to a randomized treatment effect: it includes change over time among that group, while a treatment effect requires a comparison with the concurrent control. Since no such estimate or test is reported in the registry record, the data do not establish whether the assigned groups differed on the primary endpoint.

The group means also do not give the number or proportion of participants who achieved the registry’s stated improvement threshold of a decrease in logMAR of 0.2 or more. Nor do they show how individual participants’ outcomes varied. The confidence intervals characterize uncertainty around group means, not the spread of individual responses.

Finally, the findings are specific to the condition groups and the assessment interval recorded for this trial. The registry does not provide enough information to assess missing-data handling, the analysis population, multiplicity procedures, or the details of the statistical model. The posted results should therefore be interpreted as descriptive evidence about group mean changes at the stated assessment, with important uncertainty about the comparative effect and the analysis process.

13. Why This Trial Matters Statistically

This trial is statistically notable for bringing together three clinical groups with different underlying conditions and presenting results separately for each. That layout preserves condition-specific information, but it also means that the group estimates are based on different and sometimes small outcome denominators. The estimates should not be assumed to represent one common effect across the clinical groups.

The registry includes a randomized, double-masked design and a sham comparator, features intended in general to support a controlled comparison. Yet the posted primary results are group mean changes rather than treatment-versus-sham contrasts. This distinction is central to reading randomized trials: evidence that a group changed from baseline is not the same as evidence that its change differs from the comparator group.

Precision is another important statistical issue. Confidence intervals accompany the means, allowing readers to see uncertainty in each estimate. The smaller condition-specific groups have broad intervals, so their mean changes are less precisely estimated. The registry’s results do not include the between-group intervals that would directly describe uncertainty in comparative effects.

The record also illustrates why reporting analysis methods matters. It does not specify the handling of missing data, the analysis population, or multiplicity procedures, and it lists zero analyses. Those omissions make it difficult to evaluate the inferential framework behind the posted values. The result is a useful descriptive record of measured changes, but not a complete account of the statistical evidence needed to answer the comparative question.

14. 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 limitation is that the registry reports group means and confidence intervals but no formal active-versus-sham estimate for the primary endpoint. The skip note identifies values as missing or not estimable for a two-arm continuous-endpoint comparison, and the record lists zero analyses. Consequently, the posted summaries do not directly quantify the comparative effect or its precision.

Outcome counts vary substantially among the condition-specific groups. The smallest groups have broad confidence intervals, limiting precision. The record does not explain why the primary outcome denominators differ from the enrollment figure, or why the safety denominators differ from some primary outcome denominators. Participant flow, exclusions, and missing outcomes are not reported in the registry record.

Important analysis details are also absent: the statistical model, whether baseline adjustment was used, the analysis population, missing-data handling, and any sensitivity analyses are not reported in the registry record. The handling of multiple outcomes is likewise not reported. These details matter when interpreting estimates and judging how robust they are to analysis choices.

Further limitations include the lack of standard deviations or individual outcome distributions, the lack of reported proportions meeting the defined improvement threshold, and limited safety detail beyond group counts. Information about adverse-event terms, follow-up duration for safety, and implementation of masking is not reported in the registry record. These gaps restrict interpretation of both effectiveness estimates and safety counts.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Electric Stimulation of the Eye to Improve Vision After Trauma — NCT02019927.
• Registry record last updated 2020-01-18; status last verified 2020-01.
• Results first posted 2020-01-18.
• 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.

18. Record Summary

The registry describes a completed, randomized, double-masked, parallel-group study sponsored by Wills Eye, with enrollment of 97. It evaluated transcorneal electrical stimulation against sham in separate groups with NAION, multiple sclerosis, or ocular trauma. The primary endpoint was mean change in high-contrast logMAR visual acuity from baseline at week 1 to one-week post initial treatment at week 8.

All posted group means were negative, but the record does not report a formal treatment-versus-sham estimate for the primary continuous outcome. It lists secondary outcomes and safety counts, including no recorded serious adverse events or deaths in the listed groups. Details of the statistical plan, missing-data methods, analysis population, and multiplicity handling are not reported in the registry record.