Optic Nerve Head Structural Response to IOP Elevation in Patients With Keratoconus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Optic Nerve Head Structural Response to IOP Elevation in Patients With Keratoconus (NCT03560609), a non-randomized na study. The primary outcome is Number of Patients With Tissue Deformation in ONH Region.

2. Clinical Question

The scientific motivation in the record is that IOP is a major risk factor for glaucoma and that the lamina cribrosa may be a site of primary damage in glaucoma pathogenesis. The study sought to examine how tissue at the optic nerve head and lamina cribrosa responds when IOP is modulated, using keratoconus as a population of interest because the record describes abnormal collagen properties in people with the condition. These statements explain the study rationale; they are not findings from this trial.

The record identifies the primary question but does not report a completed assessment of tissue deformation. It therefore cannot establish whether the proposed response occurred, how large any response was, or whether the response differed between the planned groups.

3. Trial Design

The registry describes a non-randomized, parallel study with no masking. Its phase is listed as not applicable. The named arms were “Subjects With Keratoconus” and “Subjects with Glaucoma,” but the arm descriptions are blank. Enrollment was 3. The record states that all 3 enrolled participants were in the keratoconus arm, with 0 enrolled in the glaucoma arm.

The study was terminated. The registry explains that termination followed the Principal Investigator’s departure from the sponsoring institution. The listed study start is 2018-11-15, and the primary completion date is 2023-02-10. The record does not report a protocol amendment, a revised recruitment plan, or a reason beyond the investigator’s departure.

The listed devices were an ophthalmodynamometer, Goldmann applanation tonometer, Pentacam, ORA, and OCT. The primary outcome description says tissue deformation would be determined from OCT images. Although the title and summary describe IOP elevation or modulation, details of the intervention procedure, measurement schedule, and device-specific roles are not reported in the registry record.

Non-randomized assignment means that the registry does not describe random allocation to the arms. In general, randomized allocation can help balance known and unknown participant characteristics between groups; without it, differences between groups may reflect characteristics other than the study condition. In this record, that concern is compounded by the absence of participants in the glaucoma arm and the absence of primary outcome assessments. There is consequently no completed between-arm comparison to interpret.

The enrollment figure is not a count of participants with observed primary-outcome data: the registry explicitly reports 0 assessed for that outcome. The record does not report why no participant was assessed, whether any measurements were attempted, or whether outcome data were collected but not included. Those details 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.

Before assignment: This study was terminated due to the departure of the Principal Investigator from the Sponsoring institution. 3 participants were enrolled in the study; none of these participants were assessed for outcome measures. No participants (n=0) were enrolled into the "Subjects with Glaucoma" arm.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: This study was terminated due to the departure of the Principal Investigator from the Sponsoring institution. N=3 participants were enrolled in the study in the "Subjects with Keratoconus" arm, N=0 participants were enrolled in the "Subjects with Glaucoma". N=0 participants were assessed for outcome measures prior to study closure.

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.

Population: This study was terminated due to the departure of the Principal Investigator from the Sponsoring institution. No participants (n=0) were enrolled into the "Subjects with Glaucoma" arm.

6. Primary Endpoint

The registry lists the primary outcome as Number of Patients With Tissue Deformation in ONH Region, measured over 1 Day.

The primary endpoint is titled “Number of Patients With Tissue Deformation in ONH Region.” The registry says that tissue deformation would be determined from OCT images and gives a timeframe of 1 Day. ONH refers to the optic nerve head, the tissue region named in the study title and outcome description.

An endpoint of this kind would count participants meeting a definition of tissue deformation, rather than report the magnitude of deformation as a continuous measurement. A count can be useful when the research question concerns how many participants show a specified finding. However, interpreting such a count depends on a clear definition of deformation, the method used to judge OCT images, and the population assessed. The registry record does not report a threshold or decision rule for classifying deformation, whether image assessment was blinded, or how disagreements in image interpretation would be handled.

The stated scientific rationale concerns the lamina cribrosa’s biomechanical response to IOP modulation. An OCT-based structural observation could be relevant to that question if its measurement and timing were specified and the resulting observations were available. The record does not report the detailed acquisition protocol, the exact relationship between the 1 Day timeframe and IOP modulation, or a separate quantitative measure of response magnitude.

Most importantly, the registry reports that 0 participants were assessed for the primary outcome. Thus, it gives the planned endpoint but no observed endpoint count, no OCT-derived deformation result, and no estimate of the frequency of deformation. The endpoint description should not be mistaken for an observed finding.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record gives a study design and a planned endpoint, but it does not report a statistical analysis plan for the primary outcome. It lists 0 analyses. The following concepts explain what would generally be relevant to this kind of research; they are not descriptions of analyses completed in this trial.

What does a count endpoint represent?

The primary endpoint is a count of patients with tissue deformation in the optic nerve head region, determined from OCT images. A count endpoint first requires an operational definition: the rule that separates a finding classified as deformation from one not classified that way. It also requires clarity about which participants were assessed and how missing or uninterpretable images are handled. The registry does not report these rules.

For a count to be interpreted as a frequency, its denominator must be clear. The enrolled population and the population assessed can differ, so reporting both is important. This record gives enrollment by arm and states that 0 participants were assessed for the primary outcome. It does not report an observed count of participants with deformation or an assessed denominator containing outcome observations. Consequently, no endpoint frequency can be interpreted from the posted results.

What would a group comparison require?

The study names keratoconus and glaucoma arms, and its title and summary indicate interest in biomechanical response to IOP modulation. A comparative analysis would ordinarily need a defined contrast, such as a difference in the proportion meeting an outcome definition or a difference in a measured structural response. The suitable method depends on the outcome scale, the measurement procedure, the design, and the amount of data.

In general, non-randomized groups may differ for reasons that are not part of the treatment or condition under study. Randomization can reduce this concern by making allocation independent of participant characteristics on average; it does not guarantee balance in every study. This registry lists non-randomized allocation and reports 0 participants in the glaucoma arm. It therefore has no populated comparator group for the stated clinical question, and no adjustment method or covariate set is reported.

What role does uncertainty play?

Statistical estimates are usually accompanied by uncertainty measures, such as confidence intervals. In general, a confidence interval indicates a range of effect values compatible with the observed data under the chosen method and assumptions. Wider intervals generally indicate less precision. For a sparse count endpoint, uncertainty can be substantial, and standard methods may be inappropriate if their assumptions are not met. But this record reports no outcome estimate or interval, so there is no precision measure to interpret.

A p-value, in general, assesses how compatible data are with a specified null hypothesis under a statistical model. It does not measure clinical importance, prove a hypothesis, or describe the probability that the null hypothesis is true. No p-value or hypothesis test for the primary endpoint is reported in the registry record. The record also does not describe a statistical model, adjustment procedure, or test selection.

Why do analysis assumptions matter?

For a binary classification such as whether deformation is present, an analysis may use methods for proportions or binary outcomes. The choice depends on how many observations are available, whether the observations are independent, and whether there are repeated measurements or clustering. If repeated measurements are collected from the same participant, those measurements are not generally independent. The registry record does not report whether the primary endpoint involved repeated readings, how images were sampled, or whether multiple observations per participant were planned.

Over-dispersion is a general concern when count variation exceeds what a selected statistical model expects. It can lead to uncertainty estimates that are too small if the model does not account for the extra variation. This is a general issue for count analyses, not a finding in this study. The record does not report a count model, a dispersion assessment, or any completed analysis from which over-dispersion could be evaluated.

How should planning illustrations be understood?

Sample-size calculations are planning tools. In general, they rely on assumptions about the effect to detect, variability, significance level, allocation, and analysis method. They are not observed results and are not a measure of the evidence obtained in a completed study. The registry’s planning description characterizes its calculations as illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It also states that the relevant effect is a stated fraction of the observed effect.

Those assumptions are distinct from the trial’s own design justification. The registry record does not report a sample-size justification for the trial. It also reports 0 primary outcome assessments and no primary effect estimate, so the posted results do not provide an observed primary effect to interpret. Any planning illustration should therefore not be read as evidence of study precision, as an observed power calculation, or as a result of the trial’s analysis. The record does not report interim analyses or a prespecified stopping rule.

In this study, the most important methodological limitation is not the choice among statistical tests; it is the absence of reported primary outcome observations. With no assessed participants, an analysis method cannot recover the missing endpoint information. Statistical methods can describe uncertainty in collected data, but they cannot turn an unmeasured endpoint into an observed result.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures and 0 analyses. It identifies the primary outcome as the number of patients with tissue deformation in the optic nerve head region, determined from OCT images, with a timeframe of 1 Day. The posted record does not give results for the primary outcome or describe analyses of the other outcome measures.

Multiplicity arises when several outcomes, timepoints, subgroups, or statistical tests are considered. In general, making many inferential comparisons can increase the chance of at least one apparently notable finding by chance. Prespecified outcome hierarchies or adjustment procedures can help address this, but the suitable approach depends on the analysis plan. The registry record does not report a multiplicity strategy, a hierarchy among outcomes beyond naming the primary outcome, or which outcomes were intended for inferential testing. With 0 analyses listed, no multiplicity-adjusted or unadjusted findings are available to interpret.

Missing outcome information is especially consequential. The registry explicitly states that 0 participants were assessed for the primary outcome. It does not report whether assessments were not attempted, whether images were unavailable or unusable, or whether outcome data were collected but not entered in the registry. It also does not report a missing-data method, imputation procedure, or sensitivity analysis. No missingness mechanism can be inferred from the record.

The record does not define analysis populations, such as an enrolled, eligible, or outcome-assessed population for statistical analysis. It reports enrollment by arm and separately reports the absence of primary outcome assessments. It does not report exclusions, protocol deviations, or an intention-to-treat analysis. These details are not reported in the registry record, so readers cannot determine how participants would have been included in a planned analysis or how missing observations would have been handled.

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.

The safety record lists serious adverse event counts by arm. In the keratoconus group, 3 participants were at risk and 0 serious adverse events were reported. In the glaucoma group, 0 participants were at risk and 0 serious adverse events were reported. The registry also lists 0 other adverse events among 3 participants at risk in the keratoconus group and 0 among 0 participants at risk in the glaucoma group. Deaths are listed as 0 in both groups.

These are the safety figures recorded in the registry, not evidence about the primary OCT outcome. In general, an event count is interpreted in the context of the number of participants at risk, the duration and completeness of safety monitoring, and the way events were defined and collected. The registry record does not provide additional details about safety surveillance, event definitions, or the timing of collection.

A zero count in a group with 0 participants at risk does not provide information about event occurrence among exposed participants in that group. Likewise, 0 reported events in the keratoconus group should not be taken as proof that an event could not occur; it describes only what the record reports for the participants at risk. The registry does not list serious adverse event terms.

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

The record establishes that a study was planned to examine optic nerve head structural response to IOP elevation or modulation among people with keratoconus, with a glaucoma group named as a comparator. The primary endpoint was the number of patients with tissue deformation in the optic nerve head region, assessed from OCT images at a timeframe of 1 Day. These are descriptions of the question and intended measurement, not evidence that deformation was observed.

The record reports 3 participants enrolled in the keratoconus arm and 0 in the glaucoma arm. It also reports that 0 participants were assessed for the primary outcome. The study was terminated following the Principal Investigator’s departure from the sponsoring institution. Thus, the posted results do not provide an estimate of tissue deformation, a comparison between the named groups, or an assessment of the hypothesis concerning lamina cribrosa response.

This does not show that the proposed response is absent. It also does not show that the response is present, abnormal, or different between groups. Those conclusions require outcome observations and an analysis appropriate to the design. The registry record does not report either for the primary endpoint.

The safety counts are separate from the structural endpoint. The record reports 0 serious adverse events among 3 participants at risk in the keratoconus group and 0 among 0 at risk in the glaucoma group. Such counts describe reported safety events within the stated risk groups; they do not answer the study’s biomechanical question or establish the absence of risk beyond the observed record.

The most defensible reading is therefore limited: this is a terminated, non-randomized study record with enrollment in the keratoconus arm, no enrollment in the glaucoma arm, and no primary outcome assessments. Its scientific rationale and hypothesis may motivate further research, but the posted results cannot be used to estimate a structural effect or support a comparative conclusion.

13. Why This Trial Matters Statistically

This study matters statistically because it illustrates the distinction between a research question, a planned endpoint, and an observed result. The record presents a biologically motivated question about the lamina cribrosa’s response to IOP modulation, and it names an OCT-based primary outcome. But a stated question and measurement plan do not constitute outcome evidence. The registry reports 0 participants assessed for that endpoint.

Recruitment alone is not sufficient for an analysis. The record reports 3 enrolled participants with keratoconus, but without assessed outcome data it cannot provide a count of participants with tissue deformation or quantify a structural response. The glaucoma arm also has 0 enrolled participants, so it cannot function as a populated comparator in the posted results. This distinction helps prevent readers from treating the enrollment figure as if it were an analysis denominator.

The non-randomized design is also important. In general, comparison groups formed without random allocation can differ in ways related to the outcome. Statistical adjustment can sometimes address measured differences, but it cannot guarantee removal of unmeasured confounding. Here, there is no enrolled glaucoma group and no outcome analysis, so the issue is not merely how to adjust a comparison; the comparison itself is unavailable.

The record also demonstrates why transparent reporting of endpoint definitions, assessment procedures, missing data, and analysis plans matters. Without a deformation threshold, image assessment details, or missing-data explanation, a reader cannot determine how the planned outcome would have been classified or how absent assessments would have been handled. Those details are not reported in the registry record.

Finally, the record keeps safety reporting distinct from efficacy or mechanistic evidence. The posted event counts describe safety reporting, while the primary structural endpoint remains unassessed. Clear separation of these evidence types is essential when interpreting an incomplete trial record.

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 primary limitation is that the registry reports 0 participants assessed for the primary outcome. No observed OCT-based tissue deformation count, effect estimate, uncertainty interval, or inferential analysis is reported. The study therefore does not answer its primary structural question in the posted results.

The planned glaucoma comparator group has 0 enrolled participants, while the study is described as non-randomized. This leaves no populated comparison group and prevents interpretation of a between-group result. The record does not report participant characteristics, eligibility criteria, or reasons for non-enrollment in that arm, so the comparability and intended composition of the groups cannot be evaluated.

The endpoint description is brief. Although it identifies OCT images and a timeframe of 1 Day, the registry record does not report the deformation definition, image acquisition and reading procedures, measurement reliability, or how the measurement was linked in time to IOP modulation. The listed devices do not by themselves establish how each was used or what measurements were obtained.

The record does not report a trial-specific sample-size justification, a statistical analysis plan, analysis populations, missing-data procedures, or a multiplicity strategy. It lists 8 outcome measures but 0 analyses. The reason no participants were assessed for the primary outcome, and whether any measurements were attempted, are not reported in the registry record.

Termination is attributed to the Principal Investigator’s departure from the sponsoring institution. This explains the stated reason for termination but does not establish how far study procedures had progressed or whether additional data existed outside the posted results. The registry’s safety counts also have limited interpretability because detailed monitoring and event definitions are not reported. These limitations constrain what can be concluded from this record; they are not evidence for or against the biological hypothesis.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Optic Nerve Head Structural Response to IOP Elevation in Patients With Keratoconus — NCT03560609.
• Registry record last updated 2025-01-29; status last verified 2025-01.
• Results first posted 2025-01-29.
• 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 record concerns NCT03560609, “Optic Nerve Head Structural Response to IOP Elevation in Patients With Keratoconus,” sponsored by NYU Langone Health. It lists a non-randomized, non-masked, parallel design and a phase of not applicable. The study began on 2018-11-15, has a primary completion date of 2023-02-10, and is listed as terminated following the Principal Investigator’s departure from the sponsoring institution.

Enrollment was 3 in the keratoconus arm and 0 in the glaucoma arm. The primary endpoint was the number of patients with tissue deformation in the optic nerve head region, assessed from OCT images at 1 Day. The registry reports that 0 participants were assessed for this outcome and lists 0 analyses.

Safety reporting lists 0 serious adverse events in the keratoconus group among 3 at risk and 0 in the glaucoma group among 0 at risk. The posted record does not contain primary outcome results or a group comparison, so it does not establish whether the hypothesized biomechanical response occurred.