Comparison of Patient Comfort After Two Anesthetic Protocols for Injections Into the Eye

• Sponsor: Miami VA Healthcare System (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT01087489
• Collaborator: University of Miami (Other), Bascom Palmer Eye Institute (Other)
• Enrollment: 53
• Location: 1
• Arms: 2
• Duration (Months): 14
• Patients Per Site Per Month: 3.8

Study Details

Study Description

Brief Summary

Patient comfort during and after eye injections will be compared after two numbing (anesthetic) protocols, an eye preparation utilizing three cotton swabs soaked in 4% lidocaine drops versus a preparation using 3.5% lidocaine hydrochloride ophthalmic gel.

Condition or Disease	Intervention/Treatment	Phase
Pain	Drug: 4% lidocaine; Drug: 3.5% ophthalmic lidocaine gel	N/A

Detailed Description

The primary goal of this investigation is to determine the relative comfort of an intravitreal injection (same day and the next day) after a preparation utilizing three cotton swabs soaked in 4% lidocaine versus a preparation using 3.5% lidocaine hydrochloride ophthalmic gel. Based on the available data, the researchers contend that a preparation based on viscous 3.5% ophthalmic lidocaine gel, which coats the surface and remains in contact with the eye longer, may provide greater anesthesia and result in greater patient comfort than the topical 4% lidocaine, which is part of the standard preparation routinely utilized in the ophthalmology department currently. Secondary outcome measure is the intraocular pressure rise after the injection, and the authors will generate prospective data to study whether softening the eye with cotton swabs prior to the injection lowers post-injection pressure spike.

Study Design

• Study Type: Interventional
• Actual Enrollment: 53 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: Clinical Comparison of Two Anesthetic Preparations for Intravitreal Injection
• Study Start Date: Apr 1, 2010
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 4% lidocaine Eyes were anesthetized with 0.5% proparacaine and then with three cotton swabs soaked in 4% liquid lidocaine applied with moderate pressure to the site of the injection inferotemporally to the limbus. Each participant was assigned to have this prep during one of the consecutive study visits if unilateral or in one eye if patient requires bilateral injections given the same day	Drug: 4% lidocaine; The eye will be topically anesthetized with 0.5% proparacaine drops and 4% lidocaine drops and a 10% povidone-iodine scrub of the lids and lashes will be performed. A sterile speculum will be placed between the lids. Five percent povidone-iodine drops will then be applied over the ocular surface followed in three rounds by additional 5% povidone iodine and a sterile cotton swab soaked in sterile 4% lidocaine applied with gentle pressure to the area designated for injection in the infero-temporal quadrant.; Other Names: lidocaine
Experimental: 3.5% ophthalmic lidocaine gel Eye was anesthetized with 0.5% proparacaine and then with 3.5% ophthalmic lidocaine gel applied to the surface of the eye. Each participant was randomly assigned to receive this preparation during one of two consecutive intravitreal injection (if unilateral disease) or in one eye if requiring bilateral injections given on the same day.	Drug: 3.5% ophthalmic lidocaine gel; The eye will be topically anesthetized with 0.5% proparacaine drops and 5% povidone iodine will be placed over the eye. Two drops of preservative-free 3.5% lidocaine hydrochloride ophthalmic gel will be placed into inferior conjunctival sac. The patient will be asked to close the eye for 7 minutes. Next, a 10% povidone-iodine scrub of the lids and lashes will be performed. A sterile speculum will be placed between the lids. Five percent povidone-iodine drops will then be applied over the ocular surface and allowed to remain in contact with the eye for at least 2 minutes. The eye will then be rinsed with antibiotic drops.; Other Names: Akten

Outcome Measures

Primary Outcome Measures

1. Discomfort Level and Patient Satisfaction With the Preparation Protocol and Intravitreal Injection [immediately after injection, 1- hour later, and next day]

   Discomfort according to the Eye Sensation Scale: 1-none, 2- mild, 3- moderate, 4- severe, 5- extremely severe Patient satisfaction scale: 1=very unsatisfied, 2=unsatisfied, 3=neutral, 4=satisfied, 5= extremely satisfied

Secondary Outcome Measures

1. Intraocular Pressure Change After Intravitreal Injection With Each Anesthetic Method, Results Reported in mmHg [immediately after injection, at 5, 10, 15 minutes]

   intraocular pressure (IOP) was measured immediately after the injection, and at 5, 10, and 15 minutes after the injection (until it was 30 mmHg or below). Prior to injection IOP and post-injection IOP were compared to find the IOP change after injection.

2. Presence and Severity of Keratopathy and the Size of Subconjunctival Hemorrhage [within 10 minutes of the injection]

   Presence of corneal staining after the injection: Quadrants of fluorescein staining: 0 1 2 3 4 Density of staining: 0- None 1- Mild 2- Moderate 3- Severe 4- corneal abrasion Size of subconjunctival hemorrhage: in clock hours

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Has required repeat Ranibizumab injections and has had at least 3 injections prior to recruitment

• Informed consent

• Age ≥ 18 years

• Clinical need for a therapeutic ranibizumab intravitreal injection regardless of the medical indication

• Able to understand and read English

Exclusion Criteria:

• Pregnancy (positive pregnancy test)

• Mental disability

• Prisoners

• Patients with fluctuating or impaired decision-making capacity

• Inability to comply with study or follow-up procedures

• Previous reaction to the same drug class

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Miami Veterans Affairs Medical Center	Miami	Florida	United States	33125

Sponsors and Collaborators

• Miami VA Healthcare System
• University of Miami
• Bascom Palmer Eye Institute

Investigators

• Principal Investigator: Ninel Gregori, MD, Miami VA Healthcare Systems

Study Documents (Full-Text)

None provided.

More Information

Publications

• Bardocci A, Lofoco G, Perdicaro S, Ciucci F, Manna L. Lidocaine 2% gel versus lidocaine 4% unpreserved drops for topical anesthesia in cataract surgery: a randomized controlled trial. Ophthalmology. 2003 Jan;110(1):144-9.
• Busbee BG, Alam A, Reichel E. Lidocaine hydrochloride gel for ocular anesthesia: results of a prospective, randomized study. Ophthalmic Surg Lasers Imaging. 2008 Sep-Oct;39(5):386-90.
• Caudle LE, Williams KA, Pesudovs K. The Eye Sensation Scale: an ophthalmic pain severity measure. Optom Vis Sci. 2007 Aug;84(8):752-62.
• Chalam KV, Murthy RK, Agarwal S, Gupta SK, Grover S. Comparative efficacy of topical tetraVisc versus lidocaine gel in cataract surgery. BMC Ophthalmol. 2009 Aug 17;9:7. doi: 10.1186/1471-2415-9-7.
• Cintra LP, Lucena LR, Da Silva JA, Costa RA, Scott IU, Jorge R. Comparative study of analgesic effectiveness using three different anesthetic techniques for intravitreal injection of bevacizumab. Ophthalmic Surg Lasers Imaging. 2009 Jan-Feb;40(1):13-8.
• Friedman SM, Margo CE. Topical gel vs subconjunctival lidocaine for intravitreous injection: a randomized clinical trial. Am J Ophthalmol. 2006 Nov;142(5):887-8.
• Kozak I, Cheng L, Freeman WR. Lidocaine gel anesthesia for intravitreal drug administration. Retina. 2005 Dec;25(8):994-8.
• Page MA, Fraunfelder FW. Safety, efficacy, and patient acceptability of lidocaine hydrochloride ophthalmic gel as a topical ocular anesthetic for use in ophthalmic procedures. Clin Ophthalmol. 2009;3:601-9. Epub 2009 Nov 2.
• Soliman MM, Macky TA, Samir MK. Comparative clinical trial of topical anesthetic agents in cataract surgery: lidocaine 2% gel, bupivacaine 0.5% drops, and benoxinate 0.4% drops. J Cataract Refract Surg. 2004 Aug;30(8):1716-20.

• Responsible Party: Ninel Gregori, Assistant Professor of Clinical Ophthalmology, Miami VA Healthcare System
• ClinicalTrials.gov Identifier: NCT01087489
• Other Study ID Numbers: 00825
• First Posted: Mar 16, 2010
• Last Update Posted: Nov 20, 2012
• Last Verified: Nov 1, 2012

• Keywords provided by Ninel Gregori, Assistant Professor of Clinical Ophthalmology, Miami VA Healthcare System: pain; discomfort; anesthetic drugs; topical drug administration; injections, intraocular; lidocaine; intraocular pressure; keratopathy
• Additional relevant MeSH terms: Lidocaine

Study Results

Participant Flow

Recruitment Details	Miami VA Medical Center retina injection clinic; patients needing frequent intravitreal injections of ranibizumab were approached and recruited between April 2010 and March 2011
Pre-assignment Detail	Patients were randomized upon recruitment and received the first anesthetic method on the day of recruitment, no wash out or transitional periods were necessary

Arm/Group Title	Bilateral	Unilateral
Arm/Group Description	Participants were given bilateral injections with 4% lidocaine prep in one eye and 3.5% lidocaine gel in the other.	Each participant was randomly assigned to receive an intravitreal injection with 4% lidocaine prep on one visit and 3.5% lidocaine gel on the next visit.
Period Title: Overall Study
STARTED	19	34
COMPLETED	19	31
NOT COMPLETED	0	3

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	Each participant was randomly assigned to receive either anesthetic preparation during one of two consecutive intravitreal injection (if unilateral disease) or in one eye if requiring bilateral injections given on the same day.
Overall Participants	53
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	9 17%
>=65 years	44 83%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	74 (12)
Sex: Female, Male (Count of Participants)
Female	3 5.7%
Male	50 94.3%
Region of Enrollment (participants) [Number]
United States	53 100%

Outcome Measures

1. Primary Outcome

Title	Discomfort Level and Patient Satisfaction With the Preparation Protocol and Intravitreal Injection
Description	Discomfort according to the Eye Sensation Scale: 1-none, 2- mild, 3- moderate, 4- severe, 5- extremely severe Patient satisfaction scale: 1=very unsatisfied, 2=unsatisfied, 3=neutral, 4=satisfied, 5= extremely satisfied
Time Frame	immediately after injection, 1- hour later, and next day

Outcome Measure Data

Analysis Population Description

all 50 patients who completed the study were included in the analysis, each patient received both anesthetic preparations prior to two consecutive (if unilateral disease) intravitreal injections on consecutive visits or in fellow eyes (if bilaterla disease) on the same day

Arm/Group Title	4% Liquid Lidocaine Method	3.5% Ophthalmic Lidocaine Gel
Arm/Group Description	Each participant was randomly assigned to receive this preparation during one of two consecutive intravitreal injection (if unilateral disease) or in one eye if requiring bilateral injections given on the same day. This method involved application of 0.5% proparacaine and then 3 cotton swabs soaked in 4% liquid lidocaine applied with moderate pressure to the site of injection.	Each participant was randomly assigned to receive this preparation during one of two consecutive intravitreal injection (if unilateral disease) or in one eye if requiring bilateral injections given on the same day. This method involved application of 0.5% proparacaine and then 3.5% ophthalmic lidocaine gel to the injection site.
Measure Participants	50	50
Discomfort during anesthetic preparation	2.1 (1.1)	2.09 (0.8)
Discomfort during needle penetration	1.7 (0.9)	2.0 (0.9)
Satisfaction with entire prep and injection	4.3 (1.0)	4.5 (0.8)
Discomfort 1 h after injection	2.4 (1.0)	2.1 (1.1)
Discomfort day after injection	1.8 (0.8)	1.6 (0.8)
Next day satisfaction with injection	4.3 (1.0)	4.3 (0.9)

2. Secondary Outcome

Title	Intraocular Pressure Change After Intravitreal Injection With Each Anesthetic Method, Results Reported in mmHg
Description	intraocular pressure (IOP) was measured immediately after the injection, and at 5, 10, and 15 minutes after the injection (until it was 30 mmHg or below). Prior to injection IOP and post-injection IOP were compared to find the IOP change after injection.
Time Frame	immediately after injection, at 5, 10, 15 minutes

Outcome Measure Data

Analysis Population Description

48 participants were included in each arm, i.e. each participant received both methods, one eye twice if unilateral or both eyes if bilateral disease were randomily assigned to alternate prep on consecutive or same visit respectively

Arm/Group Title	4% Liquid Lidocaine Method	3.5% Ophthalmic Lidocaine Gel
Arm/Group Description	Each participant was randomly assigned to receive this preparation during one of two consecutive intravitreal injection (if unilateral disease) or in one eye if requiring bilateral injections given on the same day. This method involved application of 0.5% proparacaine and then 3 cotton swabs soaked in 4% liquid lidocaine applied with moderate pressure to the site of injection.	Each participant was randomly assigned to receive this preparation during one of two consecutive intravitreal injection (if unilateral disease) or in one eye if requiring bilateral injections given on the same day. This method involved application of 0.5% proparacaine and then 3.5% ophthalmic lidocaine gel to the injection site.
Measure Participants	48	48
Measure eyes	48	48
baseline IOP before injection	15.5 (3.3)	15.9 (3.0)
IOP change after 0.05 cc injection	25.7 (9.2)	30.9 (9.9)

3. Secondary Outcome

Title	Presence and Severity of Keratopathy and the Size of Subconjunctival Hemorrhage
Description	Presence of corneal staining after the injection: Quadrants of fluorescein staining: 0 1 2 3 4 Density of staining: 0- None 1- Mild 2- Moderate 3- Severe 4- corneal abrasion Size of subconjunctival hemorrhage: in clock hours
Time Frame	within 10 minutes of the injection

Outcome Measure Data

Analysis Population Description

all eyes for which data were available were included

Arm/Group Title	4% Liquid Lidocaine Method	3.5% Ophthalmic Lidocaine Gel
Arm/Group Description	Each participant was randomly assigned to receive this preparation during one of two consecutive intravitreal injection (if unilateral disease) or in one eye if requiring bilateral injections given on the same day. This method involved application of 0.5% proparacaine and then 3 cotton swabs soaked in 4% liquid lidocaine applied with moderate pressure to the site of injection.	Each participant was randomly assigned to receive this preparation during one of two consecutive intravitreal injection (if unilateral disease) or in one eye if requiring bilateral injections given on the same day. This method involved application of 0.5% proparacaine and then 3.5% ophthalmic lidocaine gel to the injection site.
Measure Participants	49	49
Measure eyes	49	49
Corneal fluorescein staining	3.0 (1.0)	2.3 (1.3)
Density of corneal staining	1.9 (0.7)	1.3 (0.7)

Adverse Events

Arm/Group Title	4% Liquid Lidocaine Method		3.5% Ophthalmic Lidocaine Gel
Arm/Group Description	Each participant was randomly assigned to receive this preparation during one of two consecutive intravitreal injection (if unilateral disease) or in one eye if requiring bilateral injections given on the same day. This method involved application of 0.5% proparacaine and then 3 cotton swabs soaked in 4% liquid lidocaine applied with moderate pressure to the site of injection.		Each participant was randomly assigned to receive this preparation during one of two consecutive intravitreal injection (if unilateral disease) or in one eye if requiring bilateral injections given on the same day. This method involved application of 0.5% proparacaine and then 3.5% ophthalmic lidocaine gel to the injection site.
All Cause Mortality
	4% Liquid Lidocaine Method		3.5% Ophthalmic Lidocaine Gel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	4% Liquid Lidocaine Method		3.5% Ophthalmic Lidocaine Gel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/53 (1.9%)		1/53 (1.9%)
Gastrointestinal disorders
death	1/53 (1.9%)	53	1/53 (1.9%)	53
Other (Not Including Serious) Adverse Events
	4% Liquid Lidocaine Method		3.5% Ophthalmic Lidocaine Gel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/53 (0%)		0/53 (0%)

Limitations/Caveats

discomfort One hour after injection was assessed the next day via telephone and might be affected by recall bias.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.