Related Experiment Video
Updated: Jun 23, 2025
Author Spotlight: Overcoming Anti-VEGF Resistance Through Advanced Vascular Morphology Assessment in Choroidal Neovascularization
Published on: August 11, 2023
International Classification System for Ocular Complications of Anti-VEGF Agents in Clinical Trials
Marko M Popovic1, Michael Balas1, SriniVas R Sadda2
1Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Canada.
Purpose:
Complications associated with intravitreal anti-VEGF therapies are reported inconsistently in the literature, thus limiting an accurate evaluation and comparison of safety between studies. This study aimed to develop a standardized classification system for anti-VEGF ocular complications using the Delphi consensus process.
Design:
Systematic review and Delphi consensus process.
Participants:
Twenty-five international retinal specialists participated in the Delphi consensus survey.
Methods:
A systematic literature search was conducted to identify complications of intravitreal anti-VEGF agent administration based on randomized controlled trials (RCTs) of anti-VEGF therapy. A comprehensive list of complications was derived from these studies, and this list was subjected to iterative Delphi consensus surveys involving international retinal specialists who voted on inclusion, exclusion, rephrasing, and addition of complications. Furthermore, surveys determined specifiers for the selected complications. This iterative process helped to refine the final classification system.
Main Outcome Measures:
The proportion of retinal specialists who choose to include or exclude complications associated with anti-VEGF administration.
Results:
After screening 18 229 articles, 130 complications were categorized from 145 included RCTs. Participant consensus via the Delphi method resulted in the inclusion of 91 complications (70%) after 3 rounds. After incorporating further modifications made based on participant suggestions, such as rewording certain phrases and combining similar terms, 24 redundant complications were removed, leaving a total of 67 complications (52%) in the final list. A total of 14 complications (11%) met exclusion thresholds and were eliminated by participants across both rounds. All other remaining complications not meeting inclusion or exclusion thresholds also were excluded from the final classification system after the Delphi process terminated. In addition, 47 of 75 proposed complication specifiers (63%) were included based on participant agreement.
Conclusions:
Using the Delphi consensus process, a comprehensive, standardized classification system consisting of 67 ocular complications and 47 unique specifiers was established for intravitreal anti-VEGF agents in clinical trials. The adoption of this system in future trials could improve consistency and quality of adverse event reporting, potentially facilitating more accurate risk-benefit analyses.
Financial Disclosure(S):
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Insights
A new standardized classification system for anti-vascular endothelial growth factor (anti-VEGF) ocular complications was developed using the Delphi consensus process. This system aims to improve safety reporting consistency in clinical trials for anti-VEGF therapies.
Area of Science:
- Ophthalmology
- Clinical Trials
- Medical Informatics
Background:
- Inconsistent reporting of complications from intravitreal anti-VEGF therapies hinders safety evaluations.
- Standardized classification is needed for accurate comparison of anti-VEGF safety profiles across studies.
Purpose of the Study:
- To develop a standardized classification system for ocular complications associated with intravitreal anti-VEGF agents.
- To enhance consistency and comparability of safety data in clinical trials.
Main Methods:
- Systematic literature review of randomized controlled trials (RCTs) involving anti-VEGF therapy.
- Delphi consensus process involving 25 international retinal specialists.
- Iterative surveys to refine complication definitions and specifiers.
Main Results:
- A comprehensive list of 130 complications was initially identified from 145 RCTs.
- The Delphi process resulted in a final classification of 67 ocular complications and 47 specifiers.
- Participant consensus achieved inclusion of 52% of identified complications and 63% of proposed specifiers.
Conclusions:
- A standardized classification system for intravitreal anti-VEGF ocular complications was successfully established.
- Adoption of this system can improve adverse event reporting consistency and quality in clinical trials.
- This standardization will facilitate more accurate risk-benefit analyses of anti-VEGF therapies.
Related Concept Videos
01:27Open Angle Glaucoma: Treatment
Drugs such as carbonic anhydrase inhibitors, α2- and...
01:25Glaucoma: Overview
01:28Angle Closure Glaucoma: Treatment