Quadrant-Specific Pain in Intravitreal Injection: A Systematic Review and Meta-analysis.
Publisher DOI
PubMed ID
41820757
Abstract
Introduction
Patient-reported pain during intravitreal injection (IVI) may vary by injection quadrant and influence adherence to repeated treatments. Hence, this study aimed to quantify whether patient-reported pain differs by IVI quadrant and identify the least-painful approach.
Methods
We searched 13 literature databases on 15 October 2025 for clinical studies reporting patient-reported IVI pain stratified by injection quadrant (superotemporal [ST], superonasal [SN], inferotemporal [IT], inferonasal [IN]). Random-effects meta-analyses synthesized mean differences (MD) in 0-10 visual analogue scale (VAS) pain across all six pairwise quadrant contrasts. All eligible studies were included for a qualitative review and a meta-analysis. The review was prospectively registered (PROSPERO CRD420251164189).
Results
Seven studies comprising 2048 IVI were included (ST 611, SN 469, IT 556, IN 412). Most injections involved anti-VEGF agents. All injections were performed under topical anesthesia (100%; drops or gel), with no subconjunctival anesthesia reported (0%), and pain was recorded immediately post-procedure using VAS-derived scales. Across all six pairwise contrasts, pooled mean differences between quadrants were small (typically < 1 VAS unit on a 0-10 scale), and all 95% confidence intervals crossed zero. Across quadrant comparisons, pooled pain differences were small and inconsistent; none of the pairwise pooled estimates demonstrated a statistically consistent difference, and between-study heterogeneity was substantial to considerable (I2 generally > 80%).
Conclusions
Current evidence does not demonstrate a clearly less painful quadrant for intravitreal injections. Estimates varied across studies and heterogeneity was substantial, limiting confidence in any single average quadrant effect. Efforts to minimize IVI-related pain should prioritize optimized anesthesia protocols, communication, and injection technique, while future studies should standardize pain measurement and quadrant allocation to clarify whether subtle quadrant effects exist.
Trial Registration
PROSPERO registration: CRD420251164189.
Patient-reported pain during intravitreal injection (IVI) may vary by injection quadrant and influence adherence to repeated treatments. Hence, this study aimed to quantify whether patient-reported pain differs by IVI quadrant and identify the least-painful approach.
Methods
We searched 13 literature databases on 15 October 2025 for clinical studies reporting patient-reported IVI pain stratified by injection quadrant (superotemporal [ST], superonasal [SN], inferotemporal [IT], inferonasal [IN]). Random-effects meta-analyses synthesized mean differences (MD) in 0-10 visual analogue scale (VAS) pain across all six pairwise quadrant contrasts. All eligible studies were included for a qualitative review and a meta-analysis. The review was prospectively registered (PROSPERO CRD420251164189).
Results
Seven studies comprising 2048 IVI were included (ST 611, SN 469, IT 556, IN 412). Most injections involved anti-VEGF agents. All injections were performed under topical anesthesia (100%; drops or gel), with no subconjunctival anesthesia reported (0%), and pain was recorded immediately post-procedure using VAS-derived scales. Across all six pairwise contrasts, pooled mean differences between quadrants were small (typically < 1 VAS unit on a 0-10 scale), and all 95% confidence intervals crossed zero. Across quadrant comparisons, pooled pain differences were small and inconsistent; none of the pairwise pooled estimates demonstrated a statistically consistent difference, and between-study heterogeneity was substantial to considerable (I2 generally > 80%).
Conclusions
Current evidence does not demonstrate a clearly less painful quadrant for intravitreal injections. Estimates varied across studies and heterogeneity was substantial, limiting confidence in any single average quadrant effect. Efforts to minimize IVI-related pain should prioritize optimized anesthesia protocols, communication, and injection technique, while future studies should standardize pain measurement and quadrant allocation to clarify whether subtle quadrant effects exist.
Trial Registration
PROSPERO registration: CRD420251164189.
Date Issued
2026
Publication Type
Article
Subject(s)
Subjects
Intravitreal injection
•
Meta-analysis
•
Pain
•
Quadrants
•
Systematic review
•
Visual analogue scale
Language(s)
en
Author(s)
Sabaner, Mehmet Cem | |
Gunes, Irem | |
Divarci, Abdullah | |
van Dijk, Elon H C | |
Cehofski, Lasse Jørgensen | |
Subhi, Yousif |
Journal
Ophthalmology and Therapy
Publisher
Springer
ISSN
2193-8245
2193-8245
Access(Rights)
open.access