# Immediate aflibercept with vision of 20/25 or better · Two-year vision loss — Evidence Check

Verdict 2960 · Evidence Check

Stored-material review date: Not recorded  
Original evidence cut-off: 2026-08-26  
Review-criteria version: 1.0  
Public page/material preparation date: 2026-10-12

Clinical papers were not read directly; existing review summaries were checked. No new clinical-literature search was performed. Unverified does not mean that research is absent or that there is no effect.

## Assessment scope

- Population: Protocol V concerns eyes with diabetic macular edema and vision of 20/25 or better. Distinguish the randomized 702 participants/702 eyes at 91 US and Canadian sites (226/240/236) from two-year observed denominators (205/212/208). Do not transfer populations/denominators to separate treatment trials for eyes already seeing 20/50 or worse. Detailed eligibility, baseline vision/edema, other eyes and observation/missing data are unverified.
- Ingredient, formulation and route: Initial immediate aflibercept injection strategy. Drug/dose, injection intervals/counts, actual exposure/adherence and additional treatment remain unverified in detail. No generalized effect for all anti-VEGF/preemptive treatment or new injection/treatment-choice/dosing guidance is created.
- Dose: Preserve the original immediate/laser/observation strategies and actual rescue-injection starts: observation 34%, laser 25%, with about two thirds of observation eyes receiving no injection. Original worsening of at least 10 letters once or 5–9 letters twice consecutively is preserved only as trial procedure. No new participant/injection/percentage calculations, dose conversions or implementation guidance are created.
- Comparator: Initial laser or observation with rescue aflibercept under the original worsening criteria. Do not turn observation into abandonment of care or a permanently injection-free control. Actual visits/additional treatment, concurrent care, strategy deviations and exposure are unverified. Original quotations on allocation, assessor masking and ITT/imputation are historical, rather than current procedural review.
- Measured outcome: Proportion of eyes losing at least five letters from baseline at two years (104 weeks). Preserve immediate injection 33/205 (16%), laser 36/212 (17%), observation 39/208 (19%), and immediate versus observation RR 0.83 (95% CI 0.55–1.27), original risk difference −3 percentage points (−11 to 4), P=.79. Preserve the original Korean/English statements about three comparisons/“the same” as historical wording, rather than new equivalence, exactly zero effect or exclusion of all meaningful benefit. A separate clinical minimum-effect threshold and actual models/imputation/multiplicity are unverified.
- Duration: Distinguish the primary two-year/104-week time point, original rescue treatment/annual examinations and actual individual visits/exposure. Other visits, assessment windows/discontinuation and long-term outcomes are unverified. Protocol W’s two/four-year mention concerns another trial/question.
- Questions outside this scope: Mixing populations, drugs, comparisons, later strategies, denominators or outcomes from preemptive treatment at 20/25 or better with treatment of already impaired vision at 20/50 or worse; Turning original observation/rescue into an abandoned-care/no-treatment control, or original worsening criteria into personal treatment/injection-start guidance; Treating randomized 226/240/236, observed 205/212/208, people/eyes and ITT/imputation as the same complete-case denominators, or calculating new missing/event totals, percentages or intervals; Turning original RR 0.83, risk difference −3 percentage points/P=.79 and “same three strategies” wording into a newly established exactly zero effect, equivalence or exclusion of all important benefit; Calculating new injection-start participant counts, injection counts or percentages from observation 34%, laser 25% and about two thirds; Creating invented direct bibliographies, reports, effects, intervals or independent-replication certification from narrative mentions of VISTA/VIVID or Protocol T/W; Adding the same Protocol V people/eyes, three arms/sites, time points/outcomes, bibliography/registration or sibling sheets as new independent trials or participants; Transferring Protocol V funding/product support, company/Network roles, B0/registration or harms to separate trials in impaired vision; Turning ATC/pressure findings, small event counts or possible visit-related detection bias into safety certification, established harm or new treatment methods; Inheriting parent scores/axes, historical cross-checks or original narratives as subclaim scores, current review or external reading; Creating new calculations, invented values, effects/intervals, grades, independence certification or injection/treatment-choice/dosing instructions

## Checklist items

### N01 · Selected question and subclaim grade D

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: Preserve grade D and its note for the claim that immediate injection reduces two-year vision loss in eyes seeing 20/25 or better. Parent D with 30 points and axes are parent context.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials are unread and content review is incomplete. The subclaim has no score, status or axes; do not fill them with parent values. No new grade or effect verdict is created. Content review remains incomplete.
- Reason for missing information: The subclaim has no score, status or axes; do not fill them with parent values. No new grade or effect verdict is created.
- Required materials and conditions: Selected existing question, grade/note, parent context and presence of score/status/axes
- Materials to obtain first: Data distinguishing the selected row from the original parent verdict
- Further research: Connect the original question to additional materials in proposed update research; no new investigation, calculation or trial is performed now.
- Conditions for verification: Selected existing question, grade/note, parent context and presence of score/status/axes: relevant original material and analysis scope must be provided with unverified matters distinguished. This conversion links preserved wording; existing content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing Selected original question, grade/note and parent context; presence of score, status and axes to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M03 §3.1, §3.2.1–3.2.4 question-clarification principles; detailed separation rules are custom design; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom design; M04 §4.5, §4.6.3; limits on current material conversion reflect the review scope and custom design
- Related sources: S01

### N02 · Diabetic macular edema with vision of 20/25 or better

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: The selected question concerns a preemptive strategy for eyes with diabetic macular edema and vision of 20/25 or better. Do not convert it into treatment evidence for eyes already seeing 20/50 or worse.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials are unread and content review is incomplete. Detailed eligibility, baseline vision distribution, edema and baseline characteristics, other-eye treatment and arm-specific data are unverified. Content review remains incomplete.
- Reason for missing information: Detailed eligibility, baseline vision distribution, edema and baseline characteristics, other-eye treatment and arm-specific data are unverified.
- Required materials and conditions: Baseline vision, disease/recruitment criteria and actual population
- Materials to obtain first: Recruitment/eligibility, vision/edema and arm-specific baseline data
- Further research: Proposed follow-up research on applicability by vision and population criteria; no new investigation, calculation or trial is performed here.
- Conditions for verification: Original source materials and the relevant analysis scope for Baseline vision, disease/recruitment criteria and actual population must be available, and unresolved issues must be distinguishable. Here preserved wording is connected; content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing Baseline vision, disease/recruitment criteria and actual population to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M03 §3.2.1; Detailed population criteria are designed by CHAMGAP; M03 §3.2.1–3.2.4; Dose, duration and effect-modification details are designed by CHAMGAP; M03 §3.2.2–3.2.3; Reverse labels and test adaptations are designed by CHAMGAP
- Related sources: S01

### N03 · Immediate aflibercept strategy

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: Preserve the Protocol V strategy comparison of immediate aflibercept against initial laser or observation. Do not extend it to all anti-VEGF drugs or all early treatment.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials are unread and content review is incomplete. Dose, administration intervals, product/batch, actual injections/adherence and additional treatment remain unverified in detail. No new injection or treatment regimen is provided. Content review remains incomplete.
- Reason for missing information: Dose, administration intervals, product/batch, actual injections/adherence and additional treatment remain unverified in detail. No new injection or treatment regimen is provided.
- Required materials and conditions: Drug, strategy and actual exposure in the initial intervention
- Materials to obtain first: Original strategy, drug/exposure and actual implementation/additional-treatment data
- Further research: Proposed follow-up research on the relationship between initial strategy and actual exposure; no new investigation, calculation or trial is performed here.
- Conditions for verification: Original source materials and the relevant analysis scope for Drug, strategy and actual exposure in the initial intervention must be available, and unresolved issues must be distinguishable. Here preserved wording is connected; content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing Drug, strategy and actual exposure in the initial intervention to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labels and checking adaptations are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M03 §3.2.1–3.2.4; dose, duration and effect-modification details are internally designed
- Related sources: S01

### N04 · Observation with rescue treatment when needed

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: Observation was a rescue strategy that started aflibercept according to the original prespecified worsening criteria, rather than abandonment of care. Do not describe it as a no-treatment or injection-prohibited control.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials are unread and content review is incomplete. Actual visits/vision, strategy deviations, later injections/adherence/discontinuation and concurrent exposure are unverified. Content review remains incomplete.
- Reason for missing information: Actual visits/vision, strategy deviations, later injections/adherence/discontinuation and concurrent exposure are unverified.
- Required materials and conditions: Actual comparator strategy, later treatment and exposure
- Materials to obtain first: Original observation/rescue plan and actual implementation/exposure data
- Further research: Proposed follow-up research on the relationship between the comparator strategy and later treatment; no new investigation, calculation or trial is performed here.
- Conditions for verification: Original source materials and the relevant analysis scope for Actual comparator strategy, later treatment and exposure must be available, and unresolved issues must be distinguishable. Here preserved wording is connected; content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing Actual comparator strategy, later treatment and exposure to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are Chamgap’s own design; M03 §3.2.3 and M08 §8.2.2–8.2.3; Chamgap application; M08 §8.2.2 and M15 §15.3.1; Chamgap application
- Related sources: S01

### N05 · Initial laser strategy and three arms

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: Preserve the three-arm allocation: 226 participants/eyes to immediate aflibercept, 240 to laser and 236 to observation. The laser arm also used rescue treatment under the original worsening criteria.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials are unread and content review is incomplete. Laser conditions/repetition, additional treatment and other care by arm, and original models for each direct comparison are unverified. No new implementation method is created. Content review remains incomplete.
- Reason for missing information: Laser conditions/repetition, additional treatment and other care by arm, and original models for each direct comparison are unverified. No new implementation method is created.
- Required materials and conditions: Population, later treatment and arm correspondence for the three initial strategies
- Materials to obtain first: Initial/later strategies in the three arms and comparison-specific data
- Further research: Proposed follow-up research on actual exposure and outcomes by initial strategy; no new investigation, calculation or trial is performed here.
- Conditions for verification: Original source materials and the relevant analysis scope for Population, later treatment and arm correspondence for the three initial strategies must be available, and unresolved issues must be distinguishable. Here preserved wording is connected; content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing Population, later treatment and arm correspondence for the three initial strategies to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M03 §3.2.2–3.2.3; Reverse labels and test adaptations are designed by CHAMGAP; M03 §3.2.4, M15 §15.3.1–15.3.3; Question-specific outcome adaptations are designed by CHAMGAP; M03 §3.2.3, M08 §8.2.2–8.2.3; CHAMGAP adaptation; M08 Table 8.2.a, M04 §4.6.3; CHAMGAP adaptation
- Related sources: S01

### N06 · Original worsening criteria for rescue treatment

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: Preserve the original trial procedure: laser/observation started rescue treatment after a one-time loss of at least 10 letters or a 5-to-9-letter loss at two consecutive visits. This sheet creates no personal injection-start or dosing guidance.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials are unread and content review is incomplete. Examination/visit windows, actual decisions/implementation, exceptions/deviations and event-specific exposure are unverified. Content review remains incomplete.
- Reason for missing information: Examination/visit windows, actual decisions/implementation, exceptions/deviations and event-specific exposure are unverified.
- Required materials and conditions: Planned worsening, confirmation/visits and actual implementation
- Materials to obtain first: Original worsening criteria, visits/examinations and actual decisions/deviation records
- Further research: Proposed follow-up research on the relationship between later-treatment rules and observed outcomes; no new investigation, calculation or trial is performed here.
- Conditions for verification: Original source materials and the relevant analysis scope for Planned worsening, confirmation/visits and actual implementation must be available, and unresolved issues must be distinguishable. Here preserved wording is connected; content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing Planned worsening, confirmation/visits and actual implementation to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M03 §3.2.3, M08 §8.2.2–8.2.3; CHAMGAP adaptation; M08 Table 8.2.a, M03 §3.2.4; CHAMGAP adaptation; M08 §8.2.2, M15 §15.3.1; CHAMGAP adaptation; M03 §3.2.4, M15 §15.3.1–15.3.3; Question-specific outcome adaptations are designed by CHAMGAP
- Related sources: S01

### N07 · 34% with observation and 25% with laser

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: Preserve the original account that only 34% of observation eyes and 25% of laser eyes started injections, while about two thirds of the observation arm received no injection. No new participant, injection or percentage calculations are made.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials are unread and content review is incomplete. Exact starting denominators, timing, repeated injections/actual exposure, reasons/discontinuation and correspondence with incomplete follow-up are unverified. Content review remains incomplete.
- Reason for missing information: Exact starting denominators, timing, repeated injections/actual exposure, reasons/discontinuation and correspondence with incomplete follow-up are unverified.
- Required materials and conditions: Units, timing and denominators for starting actual rescue injections
- Materials to obtain first: Rescue-treatment starts, actual injections and observed denominator data
- Further research: Proposed follow-up research on actual exposure, burden and outcomes by strategy; no new investigation, calculation or trial is performed here.
- Conditions for verification: Original source materials and the relevant analysis scope for Units, timing and denominators for starting actual rescue injections must be available, and unresolved issues must be distinguishable. Here preserved wording is connected; content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing Units, timing and denominators for starting actual rescue injections to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M03 §3.2.3, M08 §8.2.2–8.2.3; CHAMGAP adaptation; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; Design-specific adaptations are designed by CHAMGAP; M08 §8.2.2, M15 §15.3.1; CHAMGAP adaptation; Distinction between studies and reports in M04 §4.6.1–4.6.2; Cohort/outcome connections are CHAMGAP adaptations
- Related sources: S01

### N08 · 91 sites and 702 participants/702 eyes

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: Preserve 702 participants/702 eyes at 91 US and Canadian sites and the randomized 226/240/236 allocation. Do not add people, eyes, arms or sites as new trials or participants.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials are unread and content review is incomplete. Baseline data by site/arm, nonstudy eyes, observation/analysis correspondence and individual data are unverified. Content review remains incomplete.
- Reason for missing information: Baseline data by site/arm, nonstudy eyes, observation/analysis correspondence and individual data are unverified.
- Required materials and conditions: People/eyes, sites and randomized denominators by arm
- Materials to obtain first: Flow data for people/study eyes, sites and arms
- Further research: Proposed follow-up research on population/measurement units and site heterogeneity; no new investigation, calculation or trial is performed here.
- Conditions for verification: Original source materials and the relevant analysis scope for People/eyes, sites and randomized denominators by arm must be available, and unresolved issues must be distinguishable. Here preserved wording is connected; content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing People/eyes, sites and randomized denominators by arm to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; Design-specific adaptations are designed by CHAMGAP; Distinction between studies and reports in M04 §4.6.1–4.6.2; Cohort/outcome connections are CHAMGAP adaptations; M03 §3.2.1; Detailed population criteria are designed by CHAMGAP; M08 §8.2.2, M15 §15.3.1; CHAMGAP adaptation
- Related sources: S01

### N09 · Web allocation, blocks and stratification

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: Preserve the original quotation on computer allocation through the website, permuted blocks of 3/6 and stratification by site and recent/planned CI-DME treatment in the nonstudy eye. Historical B0 wording is not inherited as current review.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials are unread and content review is incomplete. Actual allocation access/concealment, changes/deviations and stratification-specific data have not been read. Content review remains incomplete.
- Reason for missing information: Actual allocation access/concealment, changes/deviations and stratification-specific data have not been read.
- Required materials and conditions: Original sequence generation/concealment, stratification and actual procedure
- Materials to obtain first: Original allocation/access, stratification and change/deviation records
- Further research: Proposed follow-up research on the relationship between allocation procedure and actual groups; no new investigation, calculation or trial is performed here.
- Conditions for verification: Original source materials and the relevant analysis scope for Original sequence generation/concealment, stratification and actual procedure must be available, and unresolved issues must be distinguishable. Here preserved wording is connected; content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing Original sequence generation/concealment, stratification and actual procedure to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M08 §8.1–8.2.3; CHAMGAP adaptation; Material collection/selection principles in M04 §4.5–4.6; Separating access from reading and defining hyperlink behavior are designed by CHAMGAP; M03 §3.2.1; Detailed population criteria are designed by CHAMGAP
- Related sources: S01

### N10 · Masking at annual vision examinations

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: Preserve the original quotation that examination technicians were masked to allocation at annual visits, while investigators and participants were not masked.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials are unread and content review is incomplete. Actual measurement standards, maintenance/unmasking of assessors and procedures at other visits or for rescue decisions are unverified. Do not extend masking to every visit. Content review remains incomplete.
- Reason for missing information: Actual measurement standards, maintenance/unmasking of assessors and procedures at other visits or for rescue decisions are unverified. Do not extend masking to every visit.
- Required materials and conditions: Role-specific measurement and masking for assessors, participants and investigators
- Materials to obtain first: Examination, masking and decision records by role and visit
- Further research: Proposed follow-up research on measurement/decision procedures and bias; no new investigation, calculation or trial is performed here.
- Conditions for verification: Original source materials and the relevant analysis scope for Role-specific measurement and masking for assessors, participants and investigators must be available, and unresolved issues must be distinguishable. Here preserved wording is connected; content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing Role-specific measurement and masking for assessors, participants and investigators to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M08 Table 8.2.a, M03 §3.2.4; CHAMGAP adaptation; Material collection/selection principles in M04 §4.5–4.6; Separating access from reading and defining hyperlink behavior are designed by CHAMGAP
- Related sources: S01

### N11 · Two years, 104 weeks and the five-letter event

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: Preserve the original quotation defining the primary outcome as the proportion of eyes losing at least five letters from baseline at the two-year (104-week) visit. Distinguish it from rescue worsening criteria, mean vision and anatomical outcomes.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials are unread and content review is incomplete. Measurement scale/error, assessment windows, confirmation/repetition, baseline/final values and other time points remain unverified in detail. Content review remains incomplete.
- Reason for missing information: Measurement scale/error, assessment windows, confirmation/repetition, baseline/final values and other time points remain unverified in detail.
- Required materials and conditions: Prespecified primary time point, vision-loss definition and unit
- Materials to obtain first: Original outcome/vision examinations, visits/decisions and repeated-measure handling
- Further research: Proposed follow-up research distinguishing event definitions/time points from other measures; no new investigation, calculation or trial is performed here.
- Conditions for verification: Original source materials and the relevant analysis scope for Prespecified primary time point, vision-loss definition and unit must be available, and unresolved issues must be distinguishable. Here preserved wording is connected; content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing Prespecified primary time point, vision-loss definition and unit to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom design; M08 Table 8.2.a, M03 §3.2.4; custom application; M08 Table 8.2.a, M04 §4.6.3; custom application; M03 §3.2.4; custom extension boundary
- Related sources: S01

### N12 · Two-year events and denominators by arm

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: Preserve immediate injection 33/205 (16%), laser 36/212 (17%) and observation 39/208 (19%). These differ from randomized 226/240/236 denominators; no new percentages or missing-data totals are calculated.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials are unread and content review is incomplete. Reasons for unobserved outcomes by arm, actual assessment/imputation correspondence, complete-case/analysis populations and individual events are unverified. Content review remains incomplete.
- Reason for missing information: Reasons for unobserved outcomes by arm, actual assessment/imputation correspondence, complete-case/analysis populations and individual events are unverified.
- Required materials and conditions: Original arm-specific events/observed denominators and analysis correspondence
- Materials to obtain first: Randomization-to-observation/analysis flow, arm-specific events and missing data
- Further research: Proposed follow-up research on the relationship between observed and original analysis denominators; no new investigation, calculation or trial is performed here.
- Conditions for verification: Original source materials and the relevant analysis scope for Original arm-specific events/observed denominators and analysis correspondence must be available, and unresolved issues must be distinguishable. Here preserved wording is connected; content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing Original arm-specific events/observed denominators and analysis correspondence to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is custom design; M08 §8.2.2, M15 §15.3.1; custom application; M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is a custom application
- Related sources: S01

### N13 · Immediate injection versus observation: RR, CI and P

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: Preserve RR 0.83 (95% CI 0.55–1.27), P=.79 for immediate injection versus observation. Do not turn this into a new effect for another comparator, an exactly zero effect or equivalence certification.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials are unread and content review is incomplete. Clustering/stratification, adjustment/multiplicity, original model/exact output and comparison-specific plans have not been read. Content review remains incomplete.
- Reason for missing information: Clustering/stratification, adjustment/multiplicity, original model/exact output and comparison-specific plans have not been read.
- Required materials and conditions: Original estimate, precision, test and model for the selected comparison
- Materials to obtain first: Original analysis, selected comparison/test and exact output
- Further research: Proposed follow-up research on precision under the same estimate/comparison definition; no new investigation, calculation or trial is performed here.
- Conditions for verification: Original source materials and the relevant analysis scope for Original estimate, precision, test and model for the selected comparison must be available, and unresolved issues must be distinguishable. Here preserved wording is connected; content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing Original estimate, precision, test and model for the selected comparison to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M15 §§15.3.1–15.3.3; Chamgap adaptation; M08 §8.2.2 and M15 §15.3.1; Chamgap adaptation; M08 Table 8.2.a, M15 §15.3 and M19 §§19.1.2–19.2.4; design-specific adaptation is Chamgap-designed; M08 Table 8.2.a and M04 §4.6.3; Chamgap adaptation
- Related sources: S01

### N14 · Original risk difference of −3 percentage points and interval

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: The risk difference of −3 percentage points (−11 to 4) is the original immediate-versus-observation result. Do not mix it with the RR interval or calculate a new risk difference, NNT, effect or interval.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials are unread and content review is incomplete. The original model, exact units/precision, imputation/adjustment and original output have not been read. Content review remains incomplete.
- Reason for missing information: The original model, exact units/precision, imputation/adjustment and original output have not been read.
- Required materials and conditions: Risk-difference units, comparison, interval and distinction from other estimates
- Materials to obtain first: Original risk-difference estimation method and output
- Further research: Proposed follow-up research on uncertainty and meaning by estimate; no new investigation, calculation or trial is performed here.
- Conditions for verification: Original source materials and the relevant analysis scope for Risk-difference units, comparison, interval and distinction from other estimates must be available, and unresolved issues must be distinguishable. Here preserved wording is connected; content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing Risk-difference units, comparison, interval and distinction from other estimates to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M15 §15.3.1–15.3.3; CHAMGAP adaptation; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; Design-specific adaptations are designed by CHAMGAP; M08 §8.2.2, M15 §15.3.1; CHAMGAP adaptation
- Related sources: S01

### N15 · Nonsignificance, meaningful benefit and “the same”

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: Preserve the original wording that the three strategies were the same/null and that there was no separate clinical minimum-effect threshold. Do not declare that the interval excluded all meaningful benefit or established formal equivalence.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials are unread and content review is incomplete. Prespecified important differences, an equivalence specification, original analysis/sensitivity and clinical-interpretation materials are unverified. Content review remains incomplete.
- Reason for missing information: Prespecified important differences, an equivalence specification, original analysis/sensitivity and clinical-interpretation materials are unverified.
- Required materials and conditions: Prespecified important differences, precision and the original “same” wording
- Materials to obtain first: Prespecified plans, important differences and precision/interpretation materials
- Further research: Proposed follow-up research distinguishing nonsignificance from important differences and uncertainty; no new investigation, calculation or trial is performed here.
- Conditions for verification: Original source materials and the relevant analysis scope for Prespecified important differences, precision and the original “same” wording must be available, and unresolved issues must be distinguishable. Here preserved wording is connected; content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing Prespecified important differences, precision and the original “same” wording to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M15 §15.3.1–15.3.3; CHAMGAP adaptation; M08 Table 8.2.a, M04 §4.6.3; CHAMGAP adaptation; M04 §4.6.3, M15 §15.3.1–15.3.3; Status distinctions are designed by CHAMGAP
- Related sources: S01

### N16 · ITT plan and multiple imputation

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: Preserve the original quotations on the ITT plan including all randomized eyes in their original assigned arms and multiple imputation for eyes missing the two-year visit. Do not describe observed denominators and imputed analysis as the same complete-case population.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials are unread and content review is incomplete. The imputation model, missing-data assumptions, unobserved/complete outcomes by arm, sensitivity and actual original analysis have not been read. Content review remains incomplete.
- Reason for missing information: The imputation model, missing-data assumptions, unobserved/complete outcomes by arm, sensitivity and actual original analysis have not been read.
- Required materials and conditions: Randomized eyes/original allocation, missing data and estimation model
- Materials to obtain first: Original ITT/imputation plan, arm-specific flow and sensitivity data
- Further research: Proposed follow-up research on missing-data assumptions and assigned-strategy effects; no new investigation, calculation or trial is performed here.
- Conditions for verification: Original source materials and the relevant analysis scope for Randomized eyes/original allocation, missing data and estimation model must be available, and unresolved issues must be distinguishable. Here preserved wording is connected; content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing Randomized eyes/original allocation, missing data and estimation model to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M08 §8.2.2, M15 §15.3.1; CHAMGAP adaptation; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; Design-specific adaptations are designed by CHAMGAP; Material collection/selection principles in M04 §4.5–4.6; Separating access from reading and defining hyperlink behavior are designed by CHAMGAP
- Related sources: S01

### N17 · Registration, prespecified outcome and multiplicity

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: Preserve the historical statement that NCT01909791 matched the prespecified primary objective. Original Korean/English wording about P=.79 and the three comparisons remains in the complete preserved source.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials are unread and content review is incomplete. Original registration history, plans/changes, comparison-specific testing and multiplicity/SAP have not been read. The shared-P wording is not promoted to new verification or calculation. Content review remains incomplete.
- Reason for missing information: Original registration history, plans/changes, comparison-specific testing and multiplicity/SAP have not been read. The shared-P wording is not promoted to new verification or calculation.
- Required materials and conditions: Registration, protocol/SAP and specifications for three comparisons and time points
- Materials to obtain first: Registration history, protocol/SAP and original output by comparison
- Further research: Proposed follow-up research connecting prespecified specifications to outcome reporting; no new investigation, calculation or trial is performed here.
- Conditions for verification: Original source materials and the relevant analysis scope for Registration, protocol/SAP and specifications for three comparisons and time points must be available, and unresolved issues must be distinguishable. Here preserved wording is connected; content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing Registration, protocol/SAP and specifications for three comparisons and time points to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M08 Table 8.2.a, M04 §4.6.3; custom application; M04 §4.5–4.6 material-collection/selection principles; separation of access/reading and hyperlink conventions are custom design; M04 §4.5, §4.6.3; limits on current material conversion reflect the review scope and custom design
- Related sources: S01

### N18 · Concurrent care and the nonstudy eye

Verification status: Unverified  
Reading scope: Summary read; external material unread

- Current findings: Preserve the original account of stratification by recent or planned CI-DME treatment in the nonstudy eye.
- Why unverified: Information currently required is unverified in the stored summary. Blood glucose/blood pressure, other eye treatment/products, injections/visits, nonstudy-eye exposure and actual adherence/crossover are unverified. No new management or treatment guidance is created. Content review remains incomplete.
- Reason for missing information: Blood glucose/blood pressure, other eye treatment/products, injections/visits, nonstudy-eye exposure and actual adherence/crossover are unverified. No new management or treatment guidance is created.
- Required materials and conditions: Distinguish original stratification from other exposure/care
- Materials to obtain first: Concurrent care, exposure/adherence by arm and nonstudy-eye data
- Further research: Proposed follow-up research on concurrent exposure and attribution of strategy outcomes; no new investigation, calculation or trial is performed here.
- Conditions for verification: Original source materials and the relevant analysis scope for Distinguish original stratification from other exposure/care must be available, and unresolved issues must be distinguishable. Here preserved wording is connected; content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing Distinguish original stratification from other exposure/care to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M03 §3.2.3, M08 §8.2.2–8.2.3; custom application; M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are custom design; M03 §3.2.1–3.2.4; dose/duration/effect-modification details are custom design
- Related sources: S01

### N19 · Public NEI and NIDDK funding

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: Preserve the original account of NEI/NIDDK support.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials are unread and content review is incomplete. Contracts, institution/author roles, detailed support/contributions and original disclosures have not been read. Public funding alone does not certify every aspect of independence. Content review remains incomplete.
- Reason for missing information: Contracts, institution/author roles, detailed support/contributions and original disclosures have not been read. Public funding alone does not certify every aspect of independence.
- Required materials and conditions: Funding and roles in research, analysis and publication
- Materials to obtain first: Original funding contracts, roles/contributions and disclosures
- Further research: Proposed follow-up research distinguishing support roles from reporting relationships; no new investigation, calculation or trial is performed here.
- Conditions for verification: Original source materials and the relevant analysis scope for Funding and roles in research, analysis and publication must be available, and unresolved issues must be distinguishable. Here preserved wording is connected; content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing Funding and roles in research, analysis and publication to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: Chamgap independence/attribution conditions. The referenced official method sections do not certify every detail of these items; Data collection/selection principles in M04 §4.5–4.6; Access/reading separation and hyperlink rules are Chamgap design
- Related sources: S01

### N20 · Regeneron drug donation and site costs

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: Preserve Regeneron’s donation of study drug and payment of part of clinical-site costs. Do not turn this into verification of all cost, analysis or writing support.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials are unread and content review is incomplete. Site-specific payments, contracts and details of other analysis/writing/publication-cost support have not been read. Content review remains incomplete.
- Reason for missing information: Site-specific payments, contracts and details of other analysis/writing/publication-cost support have not been read.
- Required materials and conditions: Separate free product/site payments from other support
- Materials to obtain first: Product/site-cost support, separate support contracts and disclosures
- Further research: Proposed follow-up research on individual support and reporting relationships; no new investigation, calculation or trial is performed here.
- Conditions for verification: Original source materials and the relevant analysis scope for Separate free product/site payments from other support must be available, and unresolved issues must be distinguishable. Here preserved wording is connected; content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing Separate free product/site payments from other support to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: Chamgap independence/attribution conditions. The referenced official method sections do not certify every detail of these items; Data collection/selection principles in M04 §4.5–4.6; Access/reading separation and hyperlink rules are Chamgap design
- Related sources: S01

### N21 · Company comments and Network control

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: The original account says the company commented on the protocol/manuscript but did not participate in conduct, collection/management, analysis/interpretation or the submission decision, while the Network retained data/editorial control.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials are unread and content review is incomplete. Original disclosures and actual roles/access, incorporation of comments/writing and author contributions have not been read. The declaration is not converted into current independence certification. Content review remains incomplete.
- Reason for missing information: Original disclosures and actual roles/access, incorporation of comments/writing and author contributions have not been read. The declaration is not converted into current independence certification.
- Required materials and conditions: Protocol/manuscript comments and roles controlling conduct, analysis and submission
- Materials to obtain first: Roles/authority, contributions/writing, comments and disclosures
- Further research: Proposed follow-up research on declarations and actual role relationships; no new investigation, calculation or trial is performed here.
- Conditions for verification: Original source materials and the relevant analysis scope for Protocol/manuscript comments and roles controlling conduct, analysis and submission must be available, and unresolved issues must be distinguishable. Here preserved wording is connected; content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing Protocol/manuscript comments and roles controlling conduct, analysis and submission to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: Chamgap independence/attribution conditions. The referenced official method sections do not certify every detail of these items; Data collection/selection principles in M04 §4.5–4.6; Access/reading separation and hyperlink rules are Chamgap design
- Related sources: S01

### N22 · Employee authors and COI gaps

Verification status: Unverified  
Reading scope: Summary read; external material unread

- Current findings: Connect the original account of company and Network roles.
- Why unverified: Information currently required is unverified in the stored summary. Employee authors, individual employment/contributions, COI, equity/other relationships and publication disclosures have not been read. Do not use the company-role statement to fill each relationship as absent. Content review remains incomplete.
- Reason for missing information: Employee authors, individual employment/contributions, COI, equity/other relationships and publication disclosures have not been read. Do not use the company-role statement to fill each relationship as absent.
- Required materials and conditions: Author-specific affiliations/contributions, employment, equity and other relationships
- Materials to obtain first: Original author contributions, affiliations/employment and COI disclosures
- Further research: Proposed follow-up research distinguishing author relationships from support roles; no new investigation, calculation or trial is performed here.
- Conditions for verification: Original source materials and the relevant analysis scope for Author-specific affiliations/contributions, employment, equity and other relationships must be available, and unresolved issues must be distinguishable. Here preserved wording is connected; content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing Author-specific affiliations/contributions, employment, equity and other relationships to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: Chamgap independence/attribution conditions. The referenced official method sections do not certify every detail of these items; Data collection/selection principles in M04 §4.5–4.6; Access/reading separation and hyperlink rules are Chamgap design
- Related sources: S01

### N23 · ATC vascular events in people

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: Preserve the original ATC-defined vascular-event counts: immediate injection 15 people (7%), laser 13 (5%) and observation 8 (3%), and the account that small event counts did not establish treatment harm.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials are unread and content review is incomplete. Original ATC definition, arm-specific harm-observation denominators/duration, repetition/relatedness adjudication and precision are unverified. No new harm percentages, RR or causality are created. Content review remains incomplete.
- Reason for missing information: Original ATC definition, arm-specific harm-observation denominators/duration, repetition/relatedness adjudication and precision are unverified. No new harm percentages, RR or causality are created.
- Required materials and conditions: Harm definitions, arm-specific events/denominators and observation scope
- Materials to obtain first: Harm definitions, populations/denominators and event/adjudication materials
- Further research: Proposed follow-up research on arm-specific harm observation and uncertainty; no new investigation, calculation or trial is performed here.
- Conditions for verification: Original source materials and the relevant analysis scope for Harm definitions, arm-specific events/denominators and observation scope must be available, and unresolved issues must be distinguishable. Here preserved wording is connected; content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing Harm definitions, arm-specific events/denominators and observation scope to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Supplement gaps in safety materials for the selected subclaim. Do not judge safety from visual efficacy or parent safety wording, or generate harm incidence or new use instructions.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M19 §19.1.2–19.2.4; Detailed distinctions are designed by CHAMGAP; M19 §19.1.2–19.2.4; CHAMGAP adaptation; CHAMGAP’s interpretation boundary, informed by M19 principles; no official causality tool was run; M19 §19.1.2–19.2.4; CHAMGAP adaptation
- Related sources: S01

### N24 · Intraocular pressure and visit-related detection bias

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: Preserve the original account that pressure elevation was more common with immediate injection, with possible detection bias from different visit frequency.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials are unread and content review is incomplete. Definitions/thresholds, actual events/denominators, measurements/visits, model/interval and subsequent follow-up are unverified. Do not turn this into safety certification, established harm or new treatment guidance. Content review remains incomplete.
- Reason for missing information: Definitions/thresholds, actual events/denominators, measurements/visits, model/interval and subsequent follow-up are unverified. Do not turn this into safety certification, established harm or new treatment guidance.
- Required materials and conditions: Pressure-outcome definitions/populations and visit/measurement differences
- Materials to obtain first: Intraocular pressure, examinations/visits and harm observation/denominators
- Further research: Proposed follow-up research on monitoring frequency and harm detection; no new investigation, calculation or trial is performed here.
- Conditions for verification: Original source materials and the relevant analysis scope for Pressure-outcome definitions/populations and visit/measurement differences must be available, and unresolved issues must be distinguishable. Here preserved wording is connected; content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing Pressure-outcome definitions/populations and visit/measurement differences to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Supplement gaps in safety materials for the selected subclaim. Do not judge safety from visual efficacy or parent safety wording, or generate harm incidence or new use instructions.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M19 §19.1.2–19.2.4; Detailed distinctions are designed by CHAMGAP; M19 §19.2.2–19.2.4, M03 §3.2.3; CHAMGAP adaptation; M19 §19.1.2–19.2.4; CHAMGAP adaptation; M19 §19.1.2–19.2.4, M04 §4.6.3; CHAMGAP adaptation; M19 §19.1.2–19.2.4; CHAMGAP adaptation; M19 §19.1.2–19.2.4; CHAMGAP adaptation
- Related sources: S01

### N25 · Already impaired vision and separate trials

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: References to benefits in eyes seeing 20/50 or worse in VISTA/VIVID and Protocol T concern other populations/questions. Do not count them as independent replication of preemptive treatment for vision of 20/25 or better.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials are unread and content review is incomplete. Direct bibliographies, formulations/comparators, denominators, outcomes and intervals for those separate trials are not individually linked in the preserved source and remain unverified. Content review remains incomplete.
- Reason for missing information: Direct bibliographies, formulations/comparators, denominators, outcomes and intervals for those separate trials are not individually linked in the preserved source and remain unverified.
- Required materials and conditions: Relationship between other vision populations/treatment trials and the selected strategy
- Materials to obtain first: Population, intervention/comparison and outcome materials for each separate trial
- Further research: Proposed follow-up research distinguishing baseline vision and treatment-strategy differences; no new investigation, calculation or trial is performed here.
- Conditions for verification: Original source materials and the relevant analysis scope for Relationship between other vision populations/treatment trials and the selected strategy must be available, and unresolved issues must be distinguishable. Here preserved wording is connected; content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing Relationship between other vision populations/treatment trials and the selected strategy to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M04 §4.6.3, M15 §15.3.1–15.3.3; Status distinctions are designed by CHAMGAP; M03 §3.2.1; Detailed population criteria are designed by CHAMGAP; M03 §3.2.2–3.2.3; Reverse labels and test adaptations are designed by CHAMGAP; M03 §3.2.1–3.2.4; Dose, duration and effect-modification details are designed by CHAMGAP; Distinction between studies and reports in M04 §4.6.1–4.6.2; Cohort/outcome connections are CHAMGAP adaptations
- Related sources: S01

### N26 · Protocol W: anatomy and vision

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: Preserve only the original mention that preventive aflibercept in Protocol W reduced anatomical complications without visual benefit at two/four years. Do not create a new direct report with the same population/outcome as Protocol V.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials are unread and content review is incomplete. Original report bibliography, population, arms/denominators, anatomical definitions, vision estimates/intervals and trial relationships are unverified. Content review remains incomplete.
- Reason for missing information: Original report bibliography, population, arms/denominators, anatomical definitions, vision estimates/intervals and trial relationships are unverified.
- Required materials and conditions: Populations, anatomical/visual outcomes and timing in another trial
- Materials to obtain first: Original Protocol W report/population, outcomes and time-specific data
- Further research: Proposed follow-up research on anatomical outcomes and vision/trial relationships; no new investigation, calculation or trial is performed here.
- Conditions for verification: Original source materials and the relevant analysis scope for Populations, anatomical/visual outcomes and timing in another trial must be available, and unresolved issues must be distinguishable. Here preserved wording is connected; content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing Populations, anatomical/visual outcomes and timing in another trial to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M04 §4.6.3, M15 §15.3.1–15.3.3; Status distinctions are designed by CHAMGAP; M03 §3.2.4; CHAMGAP’s boundary for extensions; M03 §3.2.4, M15 §15.3.1–15.3.3; Question-specific outcome adaptations are designed by CHAMGAP; Distinction between studies and reports in M04 §4.6.1–4.6.2; Cohort/outcome connections are CHAMGAP adaptations
- Related sources: S01

### N27 · The same people/eyes, trial and reports

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: Do not add the sole Baker 2019 Protocol V bibliography, 702 participants/702 eyes, three arms, injection/observation time points, vision/harm outcomes or sibling sheets as new independent trials or participants. Original R1/I1 are historical axes.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials are unread and content review is incomplete. Full-text comparison of unique populations/report correspondence, later materials and independent replication under the same conditions is unverified. Content review remains incomplete.
- Reason for missing information: Full-text comparison of unique populations/report correspondence, later materials and independent replication under the same conditions is unverified.
- Required materials and conditions: Distinguish trials, reports, study eyes, arms, outcomes and independent replication
- Materials to obtain first: Report/registration, eyes/people and outcome relationships, with separate replication data
- Further research: Proposed follow-up research distinguishing reused materials from separate evidence; no new investigation, calculation or trial is performed here.
- Conditions for verification: Original source materials and the relevant analysis scope for Distinguish trials, reports, study eyes, arms, outcomes and independent replication must be available, and unresolved issues must be distinguishable. Here preserved wording is connected; content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing Distinguish trials, reports, study eyes, arms, outcomes and independent replication to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is a custom application; M04 §4.6.1–4.6.2, M15 §15.3.1; custom application; M04 §4.5, §4.6.3; limits on current material conversion reflect the review scope and custom design
- Related sources: S01

### N28 · Other vision levels, durations and generalization

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: This sheet compares an immediate initial strategy with observation/rescue for eyes seeing 20/25 or better. Do not extend it to all diabetic macular edema, anti-VEGF, long-term vision/blindness or treatment guidance to choose observation.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials are unread and content review is incomplete. Other vision levels/diseases, drugs/strategies and long-term outcomes/harms are unverified. Content review remains incomplete.
- Reason for missing information: Other vision levels/diseases, drugs/strategies and long-term outcomes/harms are unverified.
- Required materials and conditions: Populations, durations and clinical outcomes outside the selected vision/strategy
- Materials to obtain first: Additional materials by vision/population, strategy and long-term outcome
- Further research: Proposed follow-up research distinguishing the selected question from other conditions; no new investigation, calculation or trial is performed here.
- Conditions for verification: Original source materials and the relevant analysis scope for Populations, durations and clinical outcomes outside the selected vision/strategy must be available, and unresolved issues must be distinguishable. Here preserved wording is connected; content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing Populations, durations and clinical outcomes outside the selected vision/strategy to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M03 §3.2.1–3.2.4; Dose, duration and effect-modification details are designed by CHAMGAP; M03 §3.2.4; CHAMGAP’s boundary for extensions; M03 §3.2.1; Detailed population criteria are designed by CHAMGAP; M03 §3.2.2–3.2.3; Reverse labels and test adaptations are designed by CHAMGAP
- Related sources: S01

### N29 · Original axes, Korean/English wording, dates and corrections

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: Preserve subclaim D/note, parent D with 30 points/Caution, B/P/R1/I1/E0/B0/C0, three false flags, empty override reasons, complete Korean/English wording, 2026-08-26 and empty correction/deliberation records in the complete source.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials are unread and content review is incomplete. Historical B0 quotations, registration/cross-checks and “same” wording do not constitute current review, full-text access or newly satisfied conditions. Missing subclaim score/status/axes and parent facet information are not filled in. Content review remains incomplete.
- Reason for missing information: Historical B0 quotations, registration/cross-checks and “same” wording do not constitute current review, full-text access or newly satisfied conditions. Missing subclaim score/status/axes and parent facet information are not filled in.
- Required materials and conditions: Distinguish subclaim/parent verdicts, original values, dates/corrections and history
- Materials to obtain first: Original verdict, corrected/changed text and user feedback
- Further research: Propose update research on source-material changes and production versions; no new investigation, calculation or trial is performed now.
- Conditions for verification: Original source materials and the relevant analysis scope for Distinguish subclaim/parent verdicts, original values, dates/corrections and history must be available, and unresolved issues must be distinguishable. Here preserved wording is connected; content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing Distinguish subclaim/parent verdicts, original values, dates/corrections and history to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M04 §4.5, §4.6.3; limits of this material conversion follow the review scope and internal design; M03 §3.1, §3.2.1–3.2.4 question-clarification principles; detailed separation rules are internally designed
- Related sources: S01

### N30 · Summary read; external material unread

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: Read the preserved JSON summary for preparation and connect the PMID 31037289 bibliography/URL. External papers, registration, protocol/SAP, support and COI remain unread and access was not attempted.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials are unread and content review is incomplete. Bibliographies/URLs, original quotations and registration IDs alone do not upgrade acquisition, reading or review status; no link/click check is performed. Content review remains incomplete.
- Reason for missing information: Bibliographies/URLs, original quotations and registration IDs alone do not upgrade acquisition, reading or review status; no link/click check is performed.
- Required materials and conditions: Actual reading, identity/URLs and additional-material gaps for each material
- Materials to obtain first: Original paper, registration/plans, disclosures and user feedback
- Further research: Propose scoped update research based on materials actually acquired; no new investigation, calculation or trial is performed now.
- Conditions for verification: Original source materials and the relevant analysis scope for Actual reading, identity/URLs and additional-material gaps for each material must be available, and unresolved issues must be distinguishable. Here preserved wording is connected; content review remains incomplete.
- Why this condition is needed: Preparation item distinguishing Actual reading, identity/URLs and additional-material gaps for each material to connect materials needed for the selected question with the materials currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M04 §4.5–4.6 material collection/selection principles; acquisition/reading separation and hyperlink specifications are internally designed; M04 §4.5, §4.6.3; limits of this material conversion follow the review scope and internal design
- Related sources: S01

## Evidence and sources

### S01

Baker CW et al. 2019 DRCR Protocol V

[PubMed](https://pubmed.ncbi.nlm.nih.gov/31037289/)

Materials actually read: Summary read; external material unread  
Findings recorded in the summary: 16%, 17% and 19%; immediate injection versus observation RR 0.83 (95% CI 0.55–1.27), risk difference −3 percentage points (−11 to 4), P=0.79. Preserve original “same”/null and all-P statements as historical commentary; no new equivalence, exactly zero effect or exclusion of important benefit is certified.  
Record level: Outcome wording in the stored summary  
Independent replication: S01 Baker 2019/NCT01909791 Protocol V compares initial immediate aflibercept, laser and observation strategies for eyes with diabetic macular edema and vision of 20/25 or better. Distinguish 702 participants/702 eyes randomized at 91 sites (226/240/236) from two-year observed denominators (205/212/208). Preserve loss of at least five letters: 33/205 (16%), 36/212 (17%), 39/208 (19%), immediate versus observation RR 0.83 (0.55–1.27), original risk difference −3 percentage points (−11 to 4), P=.79. Controls include rescue aflibercept under prespecified worsening criteria; preserve observation 34%/laser 25% injection starts and about two thirds receiving no injection. Narrative mentions of benefits in already impaired vision at 20/50 or worse in VISTA/VIVID or Protocol T, and of Protocol W, concern other questions/trials without direct bibliographies/results here. Do not transfer the good-vision Protocol V effect/denominators to impaired-vision treatment. Do not add the same people/eyes, arms/sites, time points/injections, vision/harms, reports/registration or sibling sheets as new independent trials or participants. Report/material-slot counts are not totals of unique clinical trials, participants or independent replications; no new summation or independence certification is performed.

| Material | Public availability | Access status | Actually read | Notes |
|---|---|---|---|---|
| Stored summary | Stored file | Stored summary | Summary read | Only stored-summary and bibliographic content was used for production. External material verification/review is not complete. |
| External paper | Public availability unverified; only bibliography links preserved | Unread; access not attempted | Not read | No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status. |
| Registration material | Public availability unverified; only bibliography links preserved | Unread; access not attempted | Not read | No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status. |
| Protocol | Public availability unverified; only bibliography links preserved | Unread; access not attempted | Not read | No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status. |
| Statistical analysis plan | Public availability unverified; only bibliography links preserved | Unread; access not attempted | Not read | No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status. |
| Funding, product-support and COI material | Public availability unverified; only bibliography links preserved | Unread; access not attempted | Not read | No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status. |

## Review criteria and methods

These are Chamgap's own application conditions, informed by the relevant sections of official methodological guidance. They do not constitute official assessment-tool certification or a new efficacy score.

- M03 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03) · §3.1, §3.2.1–3.2.3, MECIR C5/C7/C13 · Clearly record the question, eligibility conditions and reasons for changes, and distinguish variations in interventions. · Preserved method HTML copies; no current method-content re-review or official tool execution
- M04 [Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04) · §4.5, §4.6.1–4.6.3, MECIR C42 · Distinguish studies from reports and link them; do not omit a study solely because results are unreported. · Preserved method HTML copies; no current method-content re-review or official tool execution
- M08 [Cochrane Handbook 6.5 (2024), chapter updated 2019-10](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08) · §8.1–8.2.3, Table 8.2.a · Define the outcome and effect of interest, then examine randomization, deviations, missing data, measurement and selective reporting. · Preserved method HTML copies; no current method-content re-review or official tool execution
- M15 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15) · §15.2.4, §15.3.1–15.3.3 · Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision. · Preserved method HTML copies; no current method-content re-review or official tool execution
- M19 [Cochrane Handbook 6.5 (2024), chapter updated 2019-10](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19) · §19.1.2, §19.2.1–19.2.4 · Harm questions may require different designs, populations and follow-up from efficacy questions. Case reports do not establish incidence rates. · Preserved method HTML copies; no current method-content re-review or official tool execution

## What the statuses mean

- Met: Status for necessary evidence confirmed after existing content review. No completion is declared in the current presentation.
- Partly verified: Some information in the stored summary is linked into the table. External comparison/content review is not complete.
- Unverified: The article leaves this unverified, or required material is absent from the current stored summary. This is distinct from zero, absence or safety.
- Review incomplete: Existing content review remains incomplete.
- Not reported: Not reported within the stored material actually read; not extended to the entire primary paper.
- Inaccessible: Means an actual access failure. Access not attempted here is not assigned this state.
- Not applicable: Not used as a substitute for an evidence gap.
- Conflicting data: Requires an observed disagreement under the same comparison criteria; not automatically judged in this production.
- Insufficient evidence for the conditions: Marks a gap in additional material required by the selected conditions; not a new efficacy grade.

## Change history

2026-10-12 · Public page/materials 1.0. The public page and data were prepared from the existing 30 items. No new clinical search, verification-status change or scoring was performed.