Use of Intravitreal Aflibercept Injection for Neovascular Glaucoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Use of Intravitreal Aflibercept Injection for Neovascular Glaucoma (NCT01711879), a randomized na study. The primary outcome is Incidence of Adverse Events.

2. Clinical Question

The study concerns patients with neovascular glaucoma (NVG), a condition named in the registry record. Its stated clinical question is whether intravitreal aflibercept, used alone on a repeated schedule, is associated with a different course of neovascularization, comfort, visual field, and safety than aflibercept followed by panretinal photocoagulation. The investigators’ summary describes a hypothesis that neovascularization of the iris and angle could resolve more quickly with aflibercept alone, with potential differences in pain relief, intraocular pressure, and visual-field preservation. These are stated aims and hypotheses, not findings established by the posted results.

The registry also lists outcomes concerning resolution of neovascularization, intraocular pressure, visual acuity, visual-field comparison, and visual-acuity changes. These outcomes indicate the broader questions the trial set out to assess, but the posted primary endpoint is safety-focused. The registry record does not establish that every listed outcome was analyzed or reported. In particular, it does not provide a posted inferential comparison of the two groups for the primary endpoint, and the available information cannot establish whether either regimen is better on clinical outcomes.

3. Trial Design

This is a randomized, parallel-group study with no masking reported. The record describes the trial as completed, with enrollment of 7 participants. The start is listed as 2013-01 and primary completion as 2015-10. The phase is recorded as NA, and the sponsor is the University of Colorado, Denver.

The two groups differ in their aflibercept and laser schedules. The Aflibercept group received 2mg (0.05ml) intravitreal aflibercept at baseline, with two additional injections at 4 weeks and 8 weeks, then injections every 8 weeks for a total of 52 weeks. The Aflibercept With Laser group received one 2mg (0.05ml) baseline injection followed by standard-of-care laser, with observation for a total of 52 weeks. The registry summary characterizes the comparison as aflibercept injections versus standard-of-care panretinal photocoagulation, while the arm descriptions specify that the laser group also received a baseline injection.

Random allocation is intended to assign participants to groups by chance. In a sufficiently large study, this can help balance measured and unmeasured participant characteristics on average, but randomization does not ensure balance in a very small sample. With 7 participants overall, the group counts are small: the posted safety data list 3 participants at risk in Aflibercept With Laser and 4 in Aflibercept. Any imbalance in participant characteristics could therefore affect how the outcomes appear.

The registry describes the study as a 52 week study, while the primary endpoint timeframe is recorded as 2 year. The record does not explain this difference. It also does not report details such as the randomization procedure, allocation concealment, eligibility criteria, masking of outcome assessors, or the planned analysis methods. Those design details cannot be inferred from the parallel, randomized, and unmasked labels alone.

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 Incidence of Adverse Events, measured over 2 year.

The primary endpoint is the incidence of adverse events, measured as a count of participants. In plain terms, this endpoint is intended to count participants who experienced an adverse event during the stated observation period. It is a safety outcome: it describes whether adverse events were experienced, rather than measuring improvement in glaucoma or vision. The registry lists its timeframe as 2 year.

The posted primary counts are 3.0 participants for Aflibercept With Laser and 4.0 participants for Aflibercept. The registry record lists 3 participants at risk in the first group and 4 in the second group in its adverse-event data. Because the endpoint is reported as participant counts, the counts alone do not describe the number, type, timing, or severity of all events each person may have experienced. A participant count also differs from an event count if one participant experiences more than one event.

A participant-based safety endpoint is useful for describing how many people experienced an event, but its interpretation depends on clear definitions of an adverse event, the observation period, and how events were collected and attributed. Those operational details are not reported in the registry record. The 2 year endpoint timeframe also does not match the 52 weeks described for the assigned regimens, and the record does not explain the timing. The counts therefore should be read as posted, with that follow-up detail unresolved. They are descriptive results, not evidence by themselves that one regimen caused more or fewer events.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The trial has a binary safety endpoint expressed as a count of participants with an event. A binary outcome classifies each participant into one of two categories for a defined outcome, such as event or no event. A participant count is a summary of how many people fall into the event category. It is not the same as counting every event, because one person may experience multiple events. The posted primary counts are 3.0 and 4.0 participants in the two groups.

To interpret a count as an incidence or risk, readers need both the event count and the number of participants observed, along with a clear time window and event definition. The adverse-event record lists 3 and 4 participants at risk in the groups. The primary endpoint timeframe is 2 year, while the treatment descriptions specify regimens lasting 52 weeks. The registry does not explain how follow-up for the endpoint relates to the treatment period, whether observation was uniform, or how missing follow-up was handled.

A comparison of binary outcomes can be expressed using several kinds of estimates. A risk difference describes the absolute difference between group risks; a risk ratio compares those risks multiplicatively; and an odds ratio compares the odds of the outcome. These are general statistical concepts, not results reported for this trial. Each requires a clearly defined denominator and an analysis approach. The registry record does not report such an effect estimate for the primary endpoint, nor a confidence interval or p-value. No comparison should be reconstructed from the counts as if it were the sponsor’s analysis.

A confidence interval is a range of estimates produced by a statistical procedure that conveys uncertainty under its assumptions. A narrow interval generally indicates greater precision than a wide one. In a study this small, estimates from one or two participants may be unstable, and a suitable interval could be wide. But no interval is reported, and its bounds should not be guessed or calculated from the posted summaries. A p-value, if reported, would address compatibility of data with a specified null model; it would not measure clinical importance or prove that a treatment caused an outcome. No primary-endpoint p-value is reported in the registry record.

Randomization is a design method for allocating participants to groups by chance. It can support causal interpretation when the trial is conducted and analyzed according to a sound plan, but it does not remove uncertainty. In a small trial, random assignment can still leave groups different in characteristics that affect outcomes. The registry record gives the randomized design label but does not report the sequence-generation method, concealment procedure, stratification factors, or an analysis plan. The extent to which the randomization process protected against selection bias therefore cannot be assessed from the record.

The study is unmasked, meaning masking is recorded as none. In general, lack of masking can affect expectations, reporting, follow-up decisions, and assessment, especially for outcomes requiring judgment. A count of adverse-event participants may still depend on how events are solicited, classified, and attributed. The registry does not report procedures for event adjudication or whether outcome assessors were masked, so the potential role of those processes cannot be characterized further.

The record includes a sample-size planning illustration based on the observed effect, with two-sided significance level 0.05, equal allocation between groups, and a normal approximation. It defines the effect to detect as a stated fraction of the observed effect. The record also specifies that non-time-to-event planning values are participants per arm, whereas time-to-event values are total events. No usable planning value is available for this binary comparison because values are missing or not estimable for a two-arm comparison. These illustrations, when available, are planning calculations, not observed power and not proof that the trial was adequately sized. The trial’s own sample-size justification is not reported in the registry record.

Observed power is not a substitute for an uncertainty interval. In general, power is a design-stage probability tied to an assumed effect, sample size, and analysis, while post-study data are better interpreted through estimates and their uncertainty. The planning illustration’s assumptions do not reveal the original trial rationale, and no sample-size justification, interim-analysis plan, or detailed statistical analysis plan is reported in the registry record.

Over-dispersion is a general concern when observed variation exceeds what a statistical model assumes. It matters for some count outcomes, where event counts may vary more than a simple model allows. The primary endpoint is a count of participants with an event, not a reported total count of repeated events, and the registry does not provide enough detail to assess over-dispersion or a model for repeated events. No modeling approach is reported, so it would be inappropriate to attribute a particular method to the investigators.

The registry lists 15 outcome measures and 13 posted secondary outcomes. A count of posted secondary outcomes does not reveal which analyses were prespecified, which results were omitted, or how outcomes were selected for reporting. The analysis population is also not described in enough detail to determine whether the primary analysis included all randomized participants, only participants with observed outcomes, or another group. These omissions limit appraisal of the statistical methods and the completeness of the evidence.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Aflibercept With Laser", "Aflibercept")
n      <- c(3, 4)
events <- c(3, 4)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Aflibercept With Laser  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4
ARM  Aflibercept  4  4  100.0  39.8  100.0  51.0  100.0  47.8  99.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures and reports 13 secondary outcomes as posted. It does not explain how many outcomes were prespecified as primary or secondary in the protocol, whether some were exploratory, or how the family of comparisons was defined. When a study assesses multiple outcomes, the chance of at least one apparently unusual result can increase if each is tested separately. General approaches include prespecifying a hierarchy, adjusting significance thresholds, or treating analyses as exploratory. The registry record does not report a multiplicity strategy, so it is not possible to determine whether any adjustment was planned or applied.

The primary endpoint is adverse events, while listed secondary outcomes include neovascularization, intraocular pressure, visual acuity, and visual field. The posted information does not provide sufficient outcome-level estimates and uncertainty measures to evaluate the secondary findings as a coherent set. The record does not report a prespecified analysis hierarchy or distinguish confirmatory from exploratory analyses.

Missing-data methods are also not reported in the registry record. It does not state how many participants completed follow-up, whether any outcome measurements were unavailable, how deaths or withdrawals were handled for each endpoint, or whether any imputation or sensitivity analysis was used. Without those details, the completeness of the observed outcome data cannot be assessed.

The analysis population is not specified. The record does not say whether analyses followed an intention-to-treat principle, included only participants who received the assigned regimen, or used another population definition. Randomization supports comparison when participants are analyzed in a manner that preserves the allocation, but the registry information does not establish which approach was used. No claim about adherence, protocol deviations, missingness, or population-specific analysis should be inferred from the posted counts.

12. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: death (33.3%).

The serious adverse-event record lists 1 participant affected among 3 at risk in Aflibercept With Laser, and 0 among 4 at risk in Aflibercept. These figures describe participants with serious adverse events, not necessarily the total number of serious events. A participant may experience more than one event, and the record does not provide enough detail to infer event counts from participant counts.

The record lists other adverse events for 3 participants among 3 at risk in Aflibercept With Laser and 4 among 4 at risk in Aflibercept. It also lists Death as a serious-event term at 33.3%, and the group data record 1 death in Aflibercept With Laser and 0 in Aflibercept. The record does not explain the cause, timing, or relationship to treatment of the death. It does not establish whether the serious-event term and the group-level death count represent the same underlying report, so that connection should not be assumed.

These safety counts are descriptive and based on very small groups. They cannot establish that one regimen is safer or more hazardous. The record does not report event narratives, severity grading beyond the serious-event classification, attribution, exposure-adjusted rates, or a formal comparative analysis. The endpoint timeframe is listed as 2 year, whereas the assigned regimen descriptions cover 52 weeks; the registry does not explain the follow-up relationship. Interpret the counts as registry entries, not as a complete account of individual clinical circumstances.

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

The posted results establish that the registry records adverse-event participant counts of 3.0 for Aflibercept With Laser and 4.0 for Aflibercept. The serious adverse-event entries record 1 participant in the first group and 0 in the second, while the record also lists a death in the first group. These are observations from a trial with 7 participants, not precise estimates of what would happen in a broader population.

The results do not establish a causal effect of either schedule on adverse events. Randomization is a useful design feature, but the very small enrollment leaves substantial uncertainty, and the record does not provide a formal effect estimate or confidence interval for the primary endpoint. The counts also do not show the timing, duration, or possible recurrence of events. They cannot determine whether a reported event was related to aflibercept, laser, the underlying condition, or another cause.

The trial’s stated hypothesis concerns resolution of iris and angle neovascularization, comfort, pain relief, intraocular pressure, and visual-field preservation. The primary endpoint counts do not answer those efficacy questions. The registry lists secondary outcomes related to these topics, but the information available does not supply the complete statistical results needed to judge their magnitude, precision, or consistency.

Nor do the posted data establish that the two regimens are equivalent. A lack of a reported statistical comparison is not evidence of no difference. Conversely, a numerical difference in counts would not alone establish a meaningful or treatment-caused difference. The registry record does not report a protocol-based sample-size justification, detailed analysis plan, or uncertainty estimates that could support stronger conclusions.

The defensible interpretation is therefore narrow: the registry contains descriptive safety counts from a small randomized, unmasked study of two aflibercept-based schedules, and it leaves major questions about follow-up, event characterization, and comparative analysis unresolved. The results may be useful as a record of what was observed in this study, but they do not settle the clinical questions posed in the study summary.

14. Why This Trial Matters Statistically

This trial is statistically notable because a randomized design is paired with enrollment of only 7 participants. Randomization is valuable for reducing systematic allocation bias, but it does not guarantee that the groups start out comparable when the sample is very small. In this setting, each participant’s outcome can substantially influence the displayed counts, and estimates of differences would be highly uncertain.

The study also illustrates why endpoint form matters. The primary endpoint is a count of participants with adverse events, while the registry separately records serious and other adverse events. These summaries answer different descriptive questions and should not be conflated with the number of events, severity, causal attribution, or an exposure-adjusted rate. Clear definitions and follow-up information are essential to interpret any safety measure.

Another statistical issue is the gap between a stated study period and the primary endpoint timeframe. The regimen descriptions specify 52 weeks, while the primary endpoint is recorded with a 2 year timeframe. Without an explanation of follow-up, the observation window cannot be reconciled with the intervention schedule. Such clarity matters because event counts depend on how long and how consistently participants are observed.

The registry also highlights the distinction between a research hypothesis and evidence that tests it. The study summary names clinical outcomes of interest, but the available primary result is a safety count and no formal comparison is reported. Outcome lists alone do not show which analyses were completed or how uncertain the estimates are. The record therefore supports a careful description of design and recorded counts, while leaving the efficacy and comparative-safety questions unresolved.

15. 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 small enrollment is the main limitation specific to interpreting this trial: 7 participants were enrolled, with the safety record listing 3 at risk in Aflibercept With Laser and 4 in Aflibercept. These numbers give little information about uncommon outcomes and make group summaries sensitive to individual observations. No confidence intervals or formal primary comparison are reported, so precision cannot be quantified from the registry record.

The record is unmasked and does not report whether outcome assessors were masked. Adverse-event ascertainment can depend on participant reporting and clinical judgment, and the registry does not describe event collection, adjudication, attribution, or severity procedures. This limits interpretation of both the participant counts and serious-event classifications.

Follow-up is not fully clear from the record. Treatment schedules are described for 52 weeks, but the primary endpoint timeframe is 2 year. The record does not explain when adverse events were assessed or whether follow-up was complete for all participants. Missing-data handling, withdrawals, adherence, and analysis-population definitions are also not reported.

Finally, the available registry information does not include a detailed analysis plan, sample-size justification, multiplicity strategy, or inferential results for the primary endpoint. Although the registry lists secondary outcomes and reports 13 secondary outcomes as posted, it does not provide sufficient information to assess each clinical outcome’s estimate and uncertainty. These limitations mean the record is best read as a sparse description of a small study, not as a definitive comparison of the regimens.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Use of Intravitreal Aflibercept Injection for Neovascular Glaucoma — NCT01711879.
• Registry record last updated 2022-03-18; status last verified 2022-02.
• Results first posted 2021-01-05.
• 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.

19. Record Summary

The registry record describes a completed randomized, parallel, unmasked study sponsored by the University of Colorado, Denver, with enrollment of 7 participants. The study start is listed as 2013-01 and primary completion as 2015-10. It compares repeated intravitreal aflibercept through 52 weeks with a regimen of one baseline aflibercept injection followed by standard-of-care laser and observation through 52 weeks.

The primary endpoint is incidence of adverse events, measured as participants, with a recorded timeframe of 2 year. Posted primary counts are 3.0 for Aflibercept With Laser and 4.0 for Aflibercept. The safety record lists 1 serious adverse-event participant and 1 death in the laser group, and 0 serious adverse-event participants and 0 deaths in the aflibercept group. The record does not report a formal comparative estimate, confidence interval, or p-value for the primary endpoint.

The registry lists outcomes concerning neovascularization, intraocular pressure, visual acuity, and visual field. The available record does not provide enough detail to assess their comparative effects or the study’s analysis procedures. The small enrollment, unclear relation between the stated follow-up periods, and missing analysis details limit interpretation.