As a lower-viscosity topical anesthetic, IHEEZO™ poses no barrier to antisepsis

By Haroon Ilyas, MD

When new products are approved that have the potential to improve ocular surgery, ophthalmologists tend to be interested, yet cautious.

Through years of experience in the operating room (OR), most of us develop preferences for specific ophthalmic formulations, so we understandably want evidence of safety and efficacy before we try something new.

That demand for data motivated me to conduct a study of IHEEZO™ (chloroprocaine hydrochloride ophthalmic gel 3%), the first topical ocular anesthetic approved by the U.S. Food and Drug Administration in 14 years.¹ My goal was to learn more about how the new treatment interacts with some of the drugs used before cataract, glaucoma, and retinal surgeries and prior to other routine procedures, such as retinal injections.

I was intrigued by IHEEZO not only because a phase III randomized trial confirmed its safety and effectiveness as an anesthetic monotherapy during routine eye surgery, but also because it promised additional benefits. Due to its rapid hydrolysis by pseudocholinesterase, the active ingredient in IHEEZO has the safest toxicological profile among local anesthetics.² In addition, the new gel is preservative-free, while older solutions such as tetracaine are sometimes preserved with benzalkonium chloride (BAK), which stings upon administration and has been shown to damage conjunctival, corneal epithelial, and corneal endothelial cells.^3,4

While I was eager to make IHEEZO a part of my OR routine, I first wanted to confirm that it wouldn’t interfere with the effectiveness of povidone-iodine, our field’s gold standard for preventing the surgery-related endophthalmitis that occurs in 1% to 3% of cases. Although I hadn’t witnessed the problem in my own practice, I was aware of research showing that high-viscosity anesthetics such as lidocaine gel, traditionally administered before povidone-iodine to maximize comfort, could act as a barrier to antisepsis.^5-9

Would IHEEZO, with its semi-viscous consistency, cause the same problem?

In our study published in Clinical Ophthalmology on March 14, 2024,¹⁰ my co-author and I were pleased to find that it did not. Despite being more viscous than its study comparator, tetracaine, IHEEZO performed at least as well alongside povidone-iodine, with patients in each group demonstrating similar mean reductions in colony-forming units after administration of the bactericidal solution.

This finding should reassure ophthalmologists about the safety of IHEEZO as part of a presurgical drug regimen, encouraging surgeons across our field to embrace a more comprehensive toolbox of anesthetic options.

A Compelling Study

Investigating IHEEZO in concert with povidone-iodine was a compelling experiment, as the viscosity of the new anesthetic sits somewhere between thick lidocaine jelly and thinner tetracaine, which, unlike lidocaine, has no history of interfering with antisepsis. While lidocaine ophthalmic gel 3.5% has a viscosity of 4000 to 9000 centipoise (cP) and lidocaine jelly has a viscosity of 12,000 to 14,000 cP,^11-15 tetracaine 0.5% has a viscosity of 10 to 60 cP,¹⁶ similar to that of human tears.¹⁷ Meanwhile, the viscosity of IHEEZO hovers between 1200 and 2000 cP,¹⁰ straddling the line between liquid and gel.

Due to its composition, we hypothesized that IHEEZO would not interfere with the effectiveness of povidone-iodine. For our single-site, prospective, randomized, patient-masked study, we chose tetracaine 0.5% as a comparator because of its liquid consistency and near-universal use in ocular surgery prep.

We investigated between June and October 2023, logging evaluable results from 82 adults. Our primary endpoint was the mean percentage change from baseline in colony-forming units after the application of anesthetic and povidone-iodine. We timed administration of the drugs to mimic a real-world scenario, waiting a few minutes between doses of anesthetic and povidone-iodine.

The eyes of each patient were randomized into separate cohorts, with IHEEZO administered in 1 eye and tetracaine in the other. Treatment always started with the right eye, and investigators completed the full cycle of drug administration and culturing before moving on to the left eye. We began each cycle by swabbing the lids, lashes, and palpebral conjunctiva at baseline for aerobic cultures, which were found to encompass primarily Staphylococcus aureus. Immediately afterward, we administered 2 drops of anesthetic, and after a 2-minute break, we treated with povidone-iodine. After another 3 minutes, we completed the treatment cycle by adding an additional drop of anesthetic before conducting a final swab for bacteria.

We found that the mean reduction in colony-forming units from baseline was 79.3% in the IHEEZO group (a drop from 41.9 to 8.7) and 72.1% in the tetracaine group (a drop from 38.9 to 10.8). This trended toward a greater reduction in colony-forming units with IHEEZO than with tetracaine, although that difference was not statistically significant.

IHEEZO was confirmed to be non-inferior to tetracaine, and that was supported by the proportion of patients who had no colonies after the application of povidone-iodine, which was the same in both groups: 32 individuals (43.2%).

We considered these results especially meaningful because the tetracaine used in the study was preserved with BAK, which has proven antimicrobial activity.¹⁸ As a result, we might have expected tetracaine to be more successful in reducing colony-forming units. Instead, we found a greater mean reduction of colonies with IHEEZO.

Integrating IHEEZO Into Surgical Practice

Based on our findings, we believe IHEEZO is well-suited for use as part of a routine presurgical regimen. But how does it fare in a real-world OR, where surgeons use an even broader array of drugs?

In my practice, I’ve found that the new anesthetic integrates extremely well with my anti-infection routine, which involves 2 days’ worth of antibiotic drops prior to surgery followed by 3 rounds of the drops in the pre-operative area—in addition to presurgical povidone-iodine. I’m proud that it’s been 5 or 6 years since any of my patients has developed endophthalmitis, and I’m determined to keep that record strong by using anesthetics that are proven to interact well with anti-infection measures.

Along with IHEEZO, my presurgical regimen includes the sublingual MKO Melt, which gently sedates my patients with midazolam 3 mg, ketamine HCI 25 mg, and ondansetron 2 mg. Together, these 2 products are so effective that I don’t need to administer opioids during routine surgeries. That’s an advantage not only because of the addictive nature of opioids but also because patients can respond to them unpredictably, with the potential for sudden waking and body movement. As we’ve all seen in the OR, patients may feel groggy after treatment with narcotics, meaning they will have to wait longer in the recovery room before being allowed to go home.

As a preservative-free product that comes in sterile, single-use packaging, I also appreciate that IHEEZO may be less toxic than anesthetic eyedrops containing BAK, which can cause inflammation or keratitis.

Finally, because IHEEZO has an assigned J code,¹⁹ its use can represent a net positive for ophthalmology practices. While surgery centers usually include anesthesia costs in the flat fee they bill for ocular procedures, the J code allows them to invoice for IHEEZO separately, as an additional reimbursement, when patients have insurance coverage for the medication.

Expanding the Anesthetic Toolbox

I’m pleased to have contributed to our field’s body of knowledge about topical anesthetic options with a simple yet elegant exploration of IHEEZO.

With these data now available to support the suitability of IHEEZO for use alongside povidone-iodine—along with previous findings confirming the product’s safety and efficacy — I believe that ophthalmologists will become increasingly confident about introducing this new anesthetic into their ORs.

That’s an important milestone, as IHEEZO is the first new topical ocular anesthetic to have been approved by the FDA in over a decade and the first to have gained that approval based on a well-controlled, randomized, multi-site study that tested it against an active comparator during a surgical intervention.¹⁰ With this option now on the table, ophthalmic surgeons have gained a key new avenue for providing the safe, comfortable, and pleasant surgical experiences their patients deserve.

Haroon Ilyas, MD, is a board-certified ophthalmologist with Brandon Eye Associates in Florida who offers the latest treatments and surgical procedures, including astigmatism management and femtosecond laser-assisted cataract surgery.

Disclosures: Dr. Ilyas received funding from Harrow to support his recent study titled “The Effects of Low Viscosity Preservative-Free Chloroprocaine Ophthalmic Gel 3% versus BAK-Containing Tetracaine 0.5% on the Bactericidal Action of Povidone-Iodine.”

References

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