This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Dorzolamide-timolol Drops With Injections to Treat AMD, RVO or DME. (NCT02571972), a na phase 2 study. The primary outcome is Mean Central Subfield Thickness (CST).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02571972 |
| Phase | Phase 2 |
| Condition | Wet Macular Degeneration, Age-related Macular Degeneration, Diabetic Macular Edema |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 14 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Wills Eye |
| Results posted | Yes |
2. Clinical Question
Population
The study summary describes non-responders with wet age-related macular degeneration. The official title and listed conditions also refer to retinal vein occlusions and diabetic macular edema. The registry record does not report the number of participants in each condition or further details of the enrolled population.
Intervention
Dorzolamide-timolol drops, a topical aqueous suppressant, were used alongside intravitreal anti-VEGF injections. The planned visit description says patients would receive the same intravitreal pharmacologic agent administered at the prior visit.
Comparator
There was no concurrent control group: the trial is listed as single-group, with allocation recorded as NA. Measurements before enrollment may provide a within-eye reference, but they are not a randomized or like-for-like control group.
Primary question
The primary outcome was mean central subfield thickness on SD-OCT. The clinical question was whether adding topical aqueous suppression was associated with a change in this anatomical measure during follow-up. The registry record does not report the primary outcome result, so the direction and size of any change cannot be assessed from the posted information.
The stated study aim concerns the anatomic and functional response to intravitreal anti-VEGF injections after topical aqueous suppression. Visual acuity was listed as a secondary outcome, alongside maximum subretinal fluid height and maximum pigment epithelial detachment height. These measures address different aspects of retinal anatomy and visual function; they should not be treated as interchangeable outcomes.
Because there was no concurrent comparison group, any change over time would describe the treated group rather than establish what would have happened without the drops. The record does not report an analysis separating the effect of dorzolamide-timolol from the effects of ongoing injections, time, or other influences.
3. Trial Design
This phase 2 study is registered as completed and uses a single-group model. Allocation is recorded as NA and masking as none. The registry lists Wills Eye as sponsor, an enrollment of 14, a start date of 2015-02-01, and a primary completion date of 2015-09-30. The listed intervention is dorzolamide-timolol.
The study summary describes evaluating topical aqueous suppression in non-responders with wet age-related macular degeneration. The official title also names retinal vein occlusions and diabetic macular edema, and those conditions appear in the condition list. The record does not give condition-specific enrollment or results, so it is not possible to determine how the enrollment was distributed across diagnoses.
At enrollment, the planned assessments included visual acuity, intraocular pressure, dilated fundoscopic examination, and SD-OCT. The visit description says participants would then receive the same intravitreal pharmacologic agent administered at the prior visit. Subsequent follow-up was planned at an interval identical to the pre-enrollment interval, but the complete visit description is not available in the registry record.
The primary outcome timeframe is described as 3 visits (8-12 weeks). Its population note says only 8 of 10 eyes completed study visit 3 and that the protocol required follow-up only through study visit 2. These statements distinguish the described visit-3 completion from the minimum protocol follow-up; they do not supply a primary outcome estimate.
A single-group longitudinal design can describe how measurements change in the observed group. Without a randomized or concurrent comparison, it cannot by itself distinguish an intervention-associated change from natural fluctuation, regression to the mean, continuing intravitreal treatment, or other time-related influences. The registry record does not report a detailed protocol, a control condition, or a statistical analysis plan.
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
| Stage | Dorzolamide-timolol |
|---|---|
| STARTED | 14 |
| COMPLETED | 10 |
| NOT COMPLETED | 4 |
Reasons for not completing this period:
| Reason | Dorzolamide-timolol |
|---|---|
| Protocol Violation | 2 |
| Withdrawal by Subject | 2 |
Analysis population for the primary outcome, as defined in the registry: Only 8 of 10 eyes completed study visit 3. The protocol only required follow-up through study visit 2.
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.
| Characteristic | Unit | Dorzolamide-timolol |
|---|---|---|
| Participants analysed | 10 | |
| Age, Continuous | years | 78.2 (65 to 91) |
| Sex: Female, Male: Female | Participants | 4 |
| Sex: Female, Male: Male | Participants | 6 |
| Region of Enrollment: United States | participants | 10 |
| Intravitreous anti-vascular endothelial growth factor (VEGF) agent: Aflibercept | Eyes | 8 |
| Intravitreous anti-vascular endothelial growth factor (VEGF) agent: Ranibizumab | Eyes | 2 |
| Prior injections with same anti-VEGF drug | Injections | 21.9 (7 to 32) |
| Pseudophakic | Eyes | 8 |
| Current treatment interval: Every 4 weeks | Eyes | 8 |
| Current treatment interval: Every 5 weeks | Eyes | 1 |
| Current treatment interval: Every 6 weeks | Eyes | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Mean Central Subfield Thickness (CST), measured over 3 visits (8-12 weeks).
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | microns |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is mean central subfield thickness (CST), measured in microns using spectral domain optical coherence tomography (SD-OCT). CST is an anatomical measure of retinal thickness at the central subfield. In a study concerning retinal disease and response to injections, a structural measure can describe changes in retinal anatomy. It complements, rather than replaces, a functional measure such as visual acuity.
The endpoint description covers CST on a visit before enrollment and visits after study enrollment. Its timeframe is listed as 3 visits (8-12 weeks). Repeated measurements can show the course of a measure over time, but the registry record does not provide the visit-specific means, a change estimate, variability, confidence interval, or statistical test. Accordingly, the endpoint definition is available, but the size and precision of the observed change are not reported in the registry record.
The endpoint is a mean, and its listed dispersion measure is the standard deviation. A mean describes the central value of the measured observations; a standard deviation describes how spread out observations are around that mean. Neither quantity is a treatment comparison on its own. In this single-group study, interpretation also depends on how measurements are linked across visits and which eyes are included in each analysis. Those analysis details are not reported in the registry record.
The population note reports that only 8 of 10 eyes completed visit 3, while the protocol required follow-up through visit 2. That completion information matters when interpreting later measurements, but it does not establish which observations were used for the primary analysis. The analysis population and handling of incomplete measurements are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a clinically relevant question: whether topical aqueous suppression is associated with an anatomical or functional response among patients receiving intravitreal anti-VEGF injections. It identifies CST as the primary outcome, and it describes a single-group study using dorzolamide-timolol. However, the posted record does not report the primary outcome analysis. No CST mean, standard deviation, change estimate, confidence interval, or p-value is reported in the registry record. As a result, the direction, magnitude, and precision of any observed change cannot be evaluated from these registry entries.
The study status is completed, but completion status is not itself evidence of an outcome or an effect. Enrollment was 14. The primary outcome population note reports that only 8 of 10 eyes completed study visit 3; it also says that protocol follow-up was required only through study visit 2. Those details indicate incomplete visit-3 observations in the described group, but do not show how missing measurements were handled or whether visit-3 results were analyzed.
The design places important limits on causal interpretation. With no concurrent control group and no masking, a change after enrollment would be a before-and-after observation in the study group. It would not isolate the effect of the drops from the ongoing injection regimen, disease course, measurement variation, or other changes over time. The visit plan states that the same intravitreal agent used at the prior visit would be administered, making the drops an addition to ongoing treatment rather than a replacement described in the record.
The registry lists four outcome measures: CST and three secondary outcomes, visual acuity, maximum subretinal fluid height, and maximum pigment epithelial detachment height. It reports zero analyses. The presence of outcome names does not show that results were analyzed or establish the relative importance of any observed changes. No outcome-specific results, analysis populations, or multiplicity approach are reported in the registry record.
Safety figures report zero serious adverse events among 14 at risk, zero other adverse events among 12 at risk, and zero deaths. These are descriptive counts as recorded, not proof that an event could not occur. The record does not provide further detail about adverse-event collection, follow-up completeness, or the definitions and observation periods used.
There is also a planning illustration described as using a fraction of the observed effect, two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. Such planning calculations are not observed power, and the single-group design does not have the two randomized arms assumed by that illustration. The underlying effect and numerical planning outputs are not reported in the registry record. Overall, the record allows the study question and some design features to be described, but it does not support a numerical conclusion about treatment response.
9. Statistical Methods Explained
The registry record describes a continuous primary outcome: mean CST in microns, with standard deviation as the dispersion measure. The primary outcome is measured repeatedly, with a pre-enrollment visit and visits after enrollment described. It is useful to separate three ideas when reading such an endpoint: the value being measured, the change or contrast of interest, and the uncertainty around that estimate. The registry record names the measure but does not report an estimate or uncertainty for it.
What does a mean describe?
In general, a mean is an average of measured values. It provides a summary of the center of a group of observations, but it does not show the entire distribution. The standard deviation describes the spread of individual observations around their mean. It is not the same as the uncertainty in the mean, and it does not by itself indicate whether a change is important. No CST means or standard deviations are reported in the registry record, so the actual distribution and average values cannot be characterized.
What would a confidence interval add?
In general, a confidence interval expresses the uncertainty around an estimated quantity under a statistical model. A narrow interval indicates greater precision than a wide interval, while an interval's location conveys which values are compatible with the analysis. A confidence interval is not reported for the primary endpoint in the registry record. Without an estimate and its interval, neither the magnitude nor precision of a possible change can be assessed.
How do repeated measurements affect analysis?
In general, repeated measurements on the same eye are related rather than independent. An analysis should account for that within-eye relationship when estimating changes over time or comparing visits. A paired analysis, for example, uses the fact that each eye contributes measurements at more than one time; other longitudinal models can handle repeated observations in different ways. These are general statistical approaches, not methods documented for this study. The registry record does not identify the model, the visit contrast, or the unit of analysis used in an outcome analysis.
The population note refers to eyes, while the enrollment figure refers to participants. These units should not be silently treated as interchangeable. The record does not explain how participants with measurements from more than one eye were handled, or whether any analysis accounted for possible correlation between eyes from the same participant. No such analytic procedure can be assumed.
Why does a comparison group matter?
In general, a concurrent control group helps distinguish changes associated with an intervention from changes that might occur over the same period for other reasons. Random allocation can help balance prognostic factors between groups, while masking can reduce some forms of assessment or conduct bias. This study is registered as single-group, allocation NA, and masking none. A pre-enrollment measurement can be a reference for change within the group, but it cannot provide the same counterfactual comparison as a concurrently followed control group. Any pre-post change would therefore have limited causal interpretation.
What do the planning assumptions mean?
The record describes a planning illustration based on the observed effect. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and detection of a stated fraction of the observed effect. In general, a sample-size calculation asks how much information a proposed study might need to detect a specified effect under chosen assumptions. It is prospective planning, not evidence that the completed study had a particular probability of detecting an effect. It should not be called observed power.
The assumptions describe two arms even though the registered trial is single-group. The illustration therefore does not describe the actual study design. The numerical sample-size outputs and the observed CST effect used as a basis for the illustration are not reported in the registry record. A planning calculation cannot fill the gap left by missing outcome results, and it does not constitute an analysis of the trial.
What is missing from the statistical record?
The registry reports zero analyses. It does not report a statistical analysis plan, a primary comparison, an adjustment strategy, a missing-data method, or an analysis population. It also does not report test statistics or p-values. In general, these details help readers understand which observations contributed to an estimate and how uncertainty was quantified. Their absence prevents a fuller assessment of the methods and reproducibility of any outcome analysis.
The study lists one primary outcome and three secondary outcomes. If multiple outcomes or time points are tested, multiplicity can increase the chance of at least one apparently notable result by chance. General approaches include pre-specifying a primary comparison, adjusting inference across a defined family of tests, or interpreting secondary findings as exploratory. The registry record does not report a multiplicity plan, so no particular approach should be attributed to the study.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary outcome, mean CST, and three secondary outcomes: visual acuity, maximum subretinal fluid height, and maximum pigment epithelial detachment height. It reports four outcome measures and zero analyses. No outcome estimates or inferential results are reported in the registry record.
When several outcomes, visits, or comparisons are examined, multiplicity is a statistical concern: the more opportunities there are to find a result that meets a chosen threshold, the more important it is to specify which comparisons are primary and how other tests will be interpreted. This is a general principle, not a description of an analysis documented for this trial. The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a plan for handling multiple visits.
The endpoint note says only 8 of 10 eyes completed study visit 3 and that protocol follow-up was required through study visit 2. This indicates that visit-3 completion was not complete among the eyes described in that note. It does not state why observations were missing, whether incomplete observations occurred at earlier visits, or how missing data were treated. No imputation method, complete-case approach, sensitivity analysis, or other missing-data method is reported in the registry record.
The analysis population is also not described. The record does not say whether analyses were intended to include all enrolled participants, only participants with specified follow-up, or another defined group. It does not explain the relationship between participant enrollment and eye-level measurements in the analysis. These omissions limit assessment of selection and missing-data bias.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Dorzolamide-timolol | 0 | 14 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Dorzolamide-timolol | 0 of 14 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Dorzolamide-timolol | 0 of 12 |
The registry reports 14 at risk for serious adverse events and 0 affected. It reports 12 at risk for other adverse events and 0 affected, with 0 deaths. These are the recorded counts for the dorzolamide-timolol group. The at-risk counts differ between the serious and other adverse-event categories, so each figure should be read with its own reported denominator rather than assumed to describe an identical observation set.
Zero recorded events means that no affected participants are listed in those categories in the registry record. It does not establish that the intervention has no risk or that no event occurred outside the recorded reporting framework. In general, safety counts depend on how events are defined, collected, and followed over time. The registry record does not provide further details about event definitions, collection procedures, observation periods, or completeness of safety follow-up.
The record lists no serious adverse-event terms. These safety counts are descriptive and do not compare the intervention with a control group, because the study is single-group. They should not be interpreted as a comparative safety estimate.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a phase 2, single-group study of dorzolamide-timolol alongside intravitreal anti-VEGF injections was completed. It identifies mean CST as the primary outcome and lists visual acuity and two fluid or detachment measures as secondary outcomes. It also reports safety counts. These details describe the study's question and some aspects of its conduct, but they do not provide the primary outcome result.
The record does not report the change in CST, its variability, a confidence interval, or a statistical test. It is therefore not possible to state whether CST increased or decreased, how large any change was, or how precisely it was estimated. The same limitation applies to the listed secondary outcomes: their names are recorded, but their results are not reported.
Even if a before-and-after change were reported, the single-group design would not establish that the drops caused it. Measurements over time can be influenced by ongoing intravitreal treatment, the course of the condition, measurement variability, and other factors. The record does not include a concurrent untreated or alternative-treatment group to help separate these influences.
The safety record lists zero serious events, zero other events, and zero deaths, with different at-risk counts for serious and other events. Those are descriptive registry figures, not evidence that risk is absent. The record does not describe the detailed safety collection procedures or follow-up needed to interpret completeness.
Accordingly, the posted information supports a description of the planned question, design, endpoint, follow-up note, and recorded safety counts. It does not support a numerical conclusion about anatomical response, functional response, causal effect, or comparative safety. Those conclusions would require outcome and analysis information not reported in the registry record.
13. Why This Trial Matters Statistically
This study is statistically interesting because it asks whether topical aqueous suppression might be associated with a change in response to ongoing intravitreal treatment, while using repeated anatomical measurements. CST offers a quantitative structural endpoint, and visual acuity adds a distinct functional outcome. Considering both types of outcome can help describe different dimensions of response, but their interpretation depends on clearly reported estimates and analysis methods.
The single-group design makes the distinction between change and treatment effect especially important. Repeated measurements can characterize what happened in the observed group, but without a concurrent comparison they cannot show how the same group would have changed without the drops. The plan to continue the same intravitreal pharmacologic agent also means that a time-related change would occur in the context of ongoing treatment.
The record also illustrates why reporting denominators and follow-up completion matters. The primary outcome note distinguishes the visit-3 completion among eyes from the protocol's required follow-up through visit 2. That context is relevant to completeness, but further information about analysis populations and missing observations would be needed to assess possible bias.
Finally, outcome definitions alone are not results. The registry names the primary and secondary measures but reports zero analyses and no outcome estimates. This makes the record useful for understanding the intended question and design, while leaving the effect and its precision unevaluable. For biostatistical interpretation, the separation of study aim, design, observed results, and causal claims is central.
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 most consequential limitation of the available record is that it does not report the primary outcome analysis. The primary measure is identified, but no CST values, change estimate, uncertainty interval, or test result is available. The same lack of reported results applies to the secondary outcomes. The completed status does not resolve this absence.
The single-group design has no concurrent comparator, and masking is recorded as none. Any observed change over visits would not by itself distinguish the drops' contribution from continued intravitreal injections, natural variation in the condition, or other time-related influences. The registry record does not report a randomized comparison or an alternative control condition.
The population description is not fully aligned in scope across the record: the study summary focuses on non-responders with wet AMD, while the official title and condition list also name RVO and DME. Condition-specific enrollment and outcomes are not reported. The record also does not explain how participant-level enrollment relates to eye-level endpoint observations.
Follow-up information is incomplete for interpretation. The endpoint note reports that only 8 of 10 eyes completed visit 3, while protocol follow-up was required only through visit 2. Reasons for incomplete visit-3 data, the analysis population, and missing-data handling are not reported in the registry record.
Other limitations include the absence of a reported statistical analysis plan, outcome estimates, and multiplicity approach. The safety counts lack detail about collection and observation procedures. The planning illustration assumes equal allocation between two arms, unlike the registered single-group design, and its numerical outputs are not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Dorzolamide-timolol Drops With Injections to Treat AMD, RVO or DME. — NCT02571972.
- Registry record last updated 2019-12-03; status last verified 2019-12.
- Results first posted 2019-12-03.
- 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.
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18. Record Summary
NCT02571972 is a completed phase 2, single-group study sponsored by Wills Eye. The registry lists enrollment of 14, no masking, and dorzolamide-timolol as the intervention. The study summary describes non-responders with wet AMD; the official title and condition list also refer to RVO and DME.
The primary outcome was mean CST in microns measured by SD-OCT, with a timeframe of 3 visits (8-12 weeks). The record notes that only 8 of 10 eyes completed visit 3 and that protocol follow-up was required through visit 2. Visual acuity, maximum subretinal fluid height, and maximum pigment epithelial detachment height were secondary outcomes.
The registry reports zero analyses and does not report outcome estimates. Safety counts are 0 serious events among 14 at risk, 0 other events among 12 at risk, and 0 deaths. The single-group design does not provide a concurrent control comparison.