Preservative-free Topical Anesthetics for Post-PRK Pain

Preservative-free Topical Anesthetics for the Management of Postoperative Pain Following Photorefractive Keratectomy

The goal of this interventional comparative study is to assess the efficacy and safety of a novel regimen of preservative-free unit-dose topical anesthetics for controlling early postoperative pain following single-step transepithelial PRK surgery.

The main research questions to answer are:

• Question 1: Are topical anesthetics effective in reducing post-PRK pain?
• Question 2: Are short-term topical anesthetics toxic to the cornea?
• Question 3: How to prevent abuse of topical anesthetics by patients at home?

Participants were planned to undergo a bilateral single-step transepithelial PRK surgery to correct their refractive errors and received a standard post-PRK treatment regimen for both eyes. Additionally, one eye was offered a preservative-free topical anesthetic as an experimental group and the other eye was offered a preservative-free artificial tear as a control group.

Study Overview

• Status: Completed
• Conditions: Myopia
• Intervention / Treatment: Drug: Preservative-free Benoxinate hydrochloride 0.4% (Benoxidia unit-dose vials [UD], Orchidia pharmaceutical Ind., Egypt); Drug: Preservative-free Sodium hyaluronate 0.2% (Polyfresh unit-dose vials [UD], Orchidia pharmaceutical Ind., Egypt).

Detailed Description

Photorefractive keratectomy (PRK) is a well-established surface ablation procedure for correction of refractive errors which involves the removal of corneal epithelium in a large diameter usually more than 6 mm followed by stromal ablation.

Early postoperative pain within the first few days after surgery is one of the commonest complications reported after PRK. The classic postoperative treatment includes the prescription of topical antibiotics and frequent preservative-free lubricants to accelerate epithelial healing.

The current treatment regimens also includes topical steroids, topical non-steroidal anti-inflammatory drugs (NSAID) and oral NSAID to reduce inflammation and post-PRK pain.

Earlier studies suggested that topical anesthetics in diluted concentrations and fractional doses didn't delay corneal epithelial regeneration after PRK but their use didn't gain popularity because of problems with topical formulation, stability and preservation.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Assiut, Egypt, 71516
    • TIBA Eye Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Patients who are candidate for PRK surgery with

1. Myopia up to - 6 diopters or myopic astigmatism up to - 4 diopters.
2. Corneal thinnest pachymetry of 500 µm
3. Residual stromal bed more than 350 µm after epithelial ablation.

Exclusion Criteria:

Patients with

1. Corneal scars or dry eye disease,
2. Past ocular surgery,
3. History of contact lens wear,
4. Systemic diseases such as diabetes mellitus and autoimmune diseases,
5. History of oral analgesics abuse.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Preservative-free topical anesthetics group; Patients in this group had the standard post-PRK treatment regimen in addition to the prescription of preservative-free topical anesthetics for pain control following single-step transepithelial PRK surgery in one eye.	Drug: Preservative-free Benoxinate hydrochloride 0.4% (Benoxidia unit-dose vials [UD], Orchidia pharmaceutical Ind., Egypt); For each patient, one eye was treated with preservative-free Benoxinate hydrochloride 0.4%. The prescribed regimen comprises of the instillation of one drop immediately, 2, 4, 6 and 8 hours after the end of surgery. Every patient was given 5 UD vials only of preservative-free Benoxinate hydrochloride 0.4% at each follow up visit for the next postoperative day usage administered 5 times daily (every 3 hours while awake) for the first 3 postoperative days giving clear instructions to immediately discard the vial after single use.
Placebo Comparator: Preservative-free artificial tears group; Patients in this group had the standard post-PRK treatment regimen in addition to the prescription of preservative-free artificial tears as a placebo following single-step transepithelial PRK surgery in the other eye.	Drug: Preservative-free Sodium hyaluronate 0.2% (Polyfresh unit-dose vials [UD], Orchidia pharmaceutical Ind., Egypt).; The other eye was treated with preservative-free Sodium hyaluronate 0.2%. The prescribed regimen comprises of the instillation of one drop immediately, 2, 4, 6 and 8 hours after the end of surgery. Every patient was given 5 UD vials only of preservative-free Sodium hyaluronate 0.2% at each follow up visit for the next postoperative day usage administered 5 times daily (every 3 hours while awake) for the first 3 postoperative days giving clear instructions to immediately discard the vial after single use.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative pain score on the verbal rating scale (VRS)	The doctor asks the patient to choose the word that best describes his/her pain and then gives it a score from zero to 4 (Zero for no pain, 1 for mild pain, 2 for moderate pain, 3 for severe pain and 4 for unbearable pain).	1 week
Postoperative pain score on the visual analogue scale (VAS)	The patient is asked to rate his/her pain by choosing a number on a scale from zero to 10 considering zero as no pain and 10 as worst possible pain.	1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Corneal epithelial healing duration	Time for the corneal epithelium to heal reported in days after PRK surgery	1 week
Endothelial cell density (ECD)	Specular microscopy was used to assess endothelial cell count before and after PRK surgery	from preoperative to 1 month postoperative.

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Principal Investigator: Mahmoud Abdel-Radi, MD, Assiut University

Publications and helpful links

General Publications

• Steigleman WA, Rose-Nussbaumer J, Al-Mohtaseb Z, Santhiago MR, Lin CC, Pantanelli SM, Kim SJ, Schallhorn JM. Management of Pain after Photorefractive Keratectomy: A Report by the American Academy of Ophthalmology. Ophthalmology. 2023 Jan;130(1):87-98. doi: 10.1016/j.ophtha.2022.07.028. Epub 2022 Oct 4.

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2023
• Primary Completion (Actual): April 15, 2023
• Study Completion (Actual): April 15, 2023

Study Registration Dates

• First Submitted: January 30, 2023
• First Submitted That Met QC Criteria: February 8, 2023
• First Posted (Actual): February 17, 2023

Study Record Updates

• Last Update Posted (Actual): May 24, 2023
• Last Update Submitted That Met QC Criteria: May 23, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Single-step PRK; Post-PRK pain; Preservative-free topical anesthetics
• Additional Relevant MeSH Terms: Eye Diseases; Refractive Errors; Myopia; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Immunologic Factors; Protective Agents; Adjuvants, Immunologic; Anesthetics, Local; Viscosupplements; Hyaluronic Acid; Benoxinate
• Other Study ID Numbers: PFTAPRK

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