Speculum-Free Intravitreal Injection Using Cotton-Tipped Applicator Retraction: A Randomized Trial of Pain, Procedure Time, Patient Satisfaction, and Safety (IVI-RETRACT)

Speculum-Free Intravitreal Injection Using Cotton-Tipped Applicator Retraction: A Randomized Controlled Trial Comparing Pain Perception, Procedure Duration, Patient Satisfaction, and Safety Between Eyelid Speculum and Cotton-Tipped Applicator Retraction Techniques

This randomized controlled trial compares two techniques for eyelid retraction during intravitreal injection (IVI) of anti-VEGF agents: the standard wire eyelid speculum (Group A) versus cotton-tipped applicator retraction (Group B) in patients with neovascular AMD, diabetic macular edema, or retinal vein occlusion.

The study evaluates four outcomes: (1) patient pain perception measured by a 10-cm visual analogue scale immediately after injection; (2) procedure duration from retraction device placement to removal; (3) patient satisfaction assessed by a 5-item Likert scale; and (4) safety including rates of subconjunctival hemorrhage, corneal abrasion, endophthalmitis, and intraocular pressure elevation.

A novel syringe cap technique using the Terumo 31G insulin syringe plastic cap as an injection-site marker (3.5 mm for pseudophakic eyes, 5.0 mm for phakic eyes from the limbus) is employed in both groups, replacing the traditional caliper.

Randomization is stratified by diagnosis and prior injection history using permuted block randomization (block sizes 4 and 6). The target sample size is 120 patients (60 per group) at Walailak University Hospital, Nakhon Si Thammarat, Thailand.

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetic Macular Edema; Retinal Vein Occlusion; Intravitreal Injections; Neovascular Age-Related Macular Degeneration (nAMD)
• Intervention / Treatment: Procedure: Eyelid Speculum Retraction; Procedure: Cotton-Tipped Applicator Retraction

Detailed Description

Background:

Intravitreal injection is one of the most frequently performed ophthalmic procedures worldwide. Eyelid specula are standard for keeping the eye open during injection but may cause discomfort, corneal exposure, and patient anxiety. Cotton-tipped applicator retraction is an alternative technique that may reduce pain and improve patient experience, but comparative randomized data on procedure time, satisfaction, and safety are lacking.

Study Design:

Single-center, prospective, parallel-group randomized controlled trial. Patients are randomly assigned 1:1 to speculum (Group A) or cotton-tipped applicator retraction (Group B). Stratified permuted block randomization is performed using Study Randomizer software with six strata: diagnosis (nAMD / DME / RVO) × prior injection history (injection-naïve / previously injected).

Interventions:

All patients receive standard preparation: topical tetracaine 0.5% (two instillations), 5% povidone-iodine ophthalmic drops (≥5 min contact), and 10% povidone-iodine periocular skin preparation. Anti-VEGF agents used are bevacizumab, aflibercept, or faricimab (per clinical indication), injected via Terumo 31G insulin syringe at the superotemporal quadrant. Post-injection levofloxacin 0.5% drops are instilled immediately after needle withdrawal.

Outcome Measures:

Primary: Pain VAS (0-10 cm) immediately post-procedure; procedure duration (seconds) from retraction device placement to removal. Secondary: Patient satisfaction (5-item Likert scale, total 5-25); safety outcomes (subconjunctival hemorrhage, corneal abrasion, endophthalmitis, IOP elevation) at Day 0, Day 1 (telephone), and Week 4.

Blinding:

Patients cannot be blinded to retraction method. Pain VAS is assessed by an independent assessor blinded to group assignment. Procedure timing is recorded by a circulating nurse blinded to the randomization list.

Sample Size:

Based on Chen et al. (2025), assuming pooled SD of 1.71 for pain VAS (Cohen's d = 0.57), with Bonferroni correction (α = 0.025, power 80%), 52 patients per group are required for pain and 46 for procedure duration. With 15% dropout allowance, the final target is 60 patients per group (120 total).

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jakkrit Juhong, MD; Phone Number: +66816773406; Email: jakkrit.ju@wu.ac.th

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18 years or older
2. Diagnosed with neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), or retinal vein occlusion (RVO)
3. Scheduled for intravitreal anti-VEGF injection (bevacizumab, aflibercept, or faricimab)
4. Able to provide written informed consent

Exclusion Criteria:

1. Active ocular infection or inflammation
2. Known allergy to povidone-iodine, tetracaine, or levofloxacin
3. Inability to cooperate with the injection procedure
4. Concurrent participation in another interventional clinical trial
5. Anatomical eyelid abnormality precluding use of either retraction technique

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Eyelid Speculum (Group A); Intravitreal anti-VEGF injection performed using a wire eyelid speculum for eyelid retraction. The speculum is inserted immediately before injection and removed immediately after needle withdrawal.	Procedure: Eyelid Speculum Retraction; A wire eyelid speculum is inserted to retract the eyelids prior to intravitreal anti-VEGF injection (bevacizumab, aflibercept, or faricimab) using a Terumo 31G insulin syringe at the superotemporal quadrant. The speculum is removed immediately after needle withdrawal.
Experimental: Cotton-Tipped Applicator (Group B); Speculum-free intravitreal anti-VEGF injection using two sterile cotton-tipped applicators for eyelid retraction. Applicators are placed on the upper and lower eyelid margins immediately before injection and removed immediately after needle withdrawal.	Procedure: Cotton-Tipped Applicator Retraction; Two sterile cotton-tipped applicators are used to retract the eyelids (speculum-free) prior to intravitreal anti-VEGF injection (bevacizumab, aflibercept, or faricimab) using a Terumo 31G insulin syringe at the superotemporal quadrant. Applicators are removed immediately after needle withdrawal.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Perception	Patient-reported pain score measured using a 10-cm visual analog scale (VAS) immediately after the injection procedure, assessed by an independent blinded nurse.	Immediately after intravitreal injection (Day 0)
Procedure Duration	Time in seconds from placement of retraction device (speculum or cotton-tipped applicators) to its removal after needle withdrawal, measured by a blinded circulating nurse using a stopwatch.	During intravitreal injection procedure (Day 0)
Patient Satisfaction	Total score on a 5-item Likert satisfaction questionnaire (score range 5-25; higher scores indicate greater satisfaction), administered 15-30 minutes after injection.	15-30 minutes after intravitreal injection (Day 0)
Procedure-Related Complications	Incidence of ocular complications including conjunctival hemorrhage, corneal abrasion, vitreous hemorrhage, endophthalmitis, retinal detachment, and elevated intraocular pressure, assessed at Day 0, Day 1 (phone call), and Week 4.	Day 0, Day 1, and Week 4 post-injection

Collaborators and Investigators

• Sponsor: Jakkrit Juhong
• Investigators: Principal Investigator: Jakkrit Juhong, MD, Walailak University

Publications and helpful links

General Publications

• Chen HRQ, de Andrade GC, Arimori LK, et al. Comparison of intravitreal injection techniques with and without a speculum using eyelid retraction with a cotton-tipped applicator. Int J Retina Vitreous. 2025;11:119. doi:10.1186/s40942-025-00739-5

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: March 13, 2026
• First Submitted That Met QC Criteria: March 13, 2026
• First Posted (Actual): March 18, 2026

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 13, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: randomized controlled trial; intravitreal injection; anti-VEGF; patient satisfaction; injection pain; procedure time; eyelid speculum; cotton-tipped applicator
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Eye Diseases; Embolism and Thrombosis; Retinal Diseases; Venous Thrombosis; Thrombosis; Behavior; Treatment Adherence and Compliance; Health Behavior; Retinal Vein Occlusion; Patient Satisfaction
• Other Study ID Numbers: WURCT5954

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No