Article

Drug advances for refractive and cataract surgery

Today’s premium visual outcomes incorporate newer combination agents, molecules, and delivery systems.

By Conni Bergmann Koury

Refractive and cataract patients have an expectation of superior visual outcomes after their procedures. That is just one piece of the puzzle, however, as patients also want a superior surgical experience. Pharmaceutical options that leverage emerging delivery techniques, advanced molecules, and combination agents aim to deliver on both of these expectations with fewer drops and easier dosing regimens.

Inflammation is a common consequence of cataract extraction, and keeping it under control is crucial to preventing complications as well as ensuring overall satisfaction for patients.1 Postoperative complications caused by inflammation include cystoid macular edema, increased intraocular pressure, posterior capsular opacification, chronic uveitis, fibrin formation, and protein leakage from the breakdown of the blood-aqueous barrier.2,3 Patients also may experience mild to severe ocular pain and other discomfort, such as itchiness, burning, foreign-body sensation, and tearing.4

Despite their common use, the delivery of postoperative refractive and cataract surgery medications via topical drops can be a concern. Potential downsides of drops include poor adherence by patients and formulations’ suboptimal and inconsistent bioavailability. Numerous studies show patients have difficulty successfully administering the correct number of drops and they often miss their eye.5-8

Here are the latest drug technologies aimed to improve the surgical outcome and patient experience.

Sustained-release technology

Dextenza (dexamethasone ophthalmic insert [0.4 mg], Ocular Therapeutix) is FDA-approved to treat ocular inflammation and pain following ophthalmic surgery. The preservative-free insert replaces a drop schedule with a consistent and tapered dose of drug delivered to the ocular surface for up to 30 days.

“The potential market opportunity for postoperative ocular pain and inflammation is substantial, and there remains an important unmet need to address the issue of non-compliance given currently available treatment options,” says Antony Mattessich, Ocular Therapeutix president and CEO.

The surgeon places the intracanalicular insert through the punctum and into the canaliculus; Dextenza softens and resorbs after treatment, exiting through the nasolacrimal system. The insert is conjugated with fluorescein, making it easy to visualize in place using blue light with a yellow filter. The surgeon can remove the insert irrigating with saline or manually expressing it, if necessary, in the case of a steroid responder for example.

The Centers for Medicare and Medicaid Services (CMS) issued a permanent product-specific J-code for Dextenza and pass-through status. J-codes are widely recognized by commercial insurance and Medicare Advantage and Part B plans, allowing for a simpler and more convenient reimbursement process.

Dexycu (dexamethasone intraocular suspension 9%, EyePoint Pharmaceuticals) is a single-dose sustained-release intracameral steroid FDA-approved for the prevention and treatment of postoperative inflammation, obviating the need for postoperative steroidal drops. It is injected into the ciliary sulcus at the end of cataract surgery, where it delivers a tapered dose of dexamethasone for 30 days. Dexycu uses the company’s Verisome technology, allowing the “pearl” of steroid to bioerode gradually.

“Dexycu offers a single-dose, sustained-release treatment option conveniently administered at the end of cataract surgery, which can eliminate the complicated and burdensome steroid eyedrop regimen following surgery,” says Nancy Lurker, president and CEO of EyePoint.

CMS assigned Dexycu a specific and permanent J-code (J1095) and pass-through status. In Medicare Part B, pass-through products are paid separately, in addition to the packaged procedural payment by CMS, for cataract procedures.

Combination agents

OMIDRIA (phenylephrine and ketorolac intraocular solution 1%/0.3%, Omeros Corporation) is FDA-approved and contains a nonsteroidal inflammatory agent indicated for intraocular use. The agent is added to ophthalmic irrigating solution during cataract surgery or lens replacement, maintaining pupil size by preventing intraoperative miosis and reducing postoperative ocular pain.

In a randomized, controlled, prospective study evaluating OMIDRIA during cataract surgery in men taking tamsulosin, patients who received OMIDRIA during cataract surgery experienced significantly less miosis, pupil billowing, and incidence of iris prolapse, which are hallmark characteristics of intraoperative floppy iris syndrome (IFIS).9 Tamsulosin, an alpha-1 receptor antagonist that blocks symptoms of benign prostatic hypertrophy, adversely affects the iris during cataract surgery, putting patients at greater risk of IFIS.

Also, in multiple clinical studies, OMIDRIA without the use of steroids decreased CME rates three- to 15-fold over commonly published rates. In addition, the drug showed a nearly 80% reduction in the need for intraoperative fentanyl and a marked decrease in postoperative opioid use. Further evidence reveals that OMIDRIA results in decreased intraoperative and postoperative complications, less need for pupil-dilating devices, and a reduction in surgical times.10-12

CMS assigned a permanent J-code for OMIDRIA, J1097, simplifying billing and payment and enhancing patient access to the product.

“With the expanding body of evidence demonstrating the clinical benefits of OMIDRIA—from prevention of IFIS to reduction in both CME and opioid use—physician demand continues to grow, and the J-code makes appropriate reimbursement of OMIDRIA even more reliable,” says Gregory A. Demopulos, MD, chairman and CEO of Omeros.

Enhanced formulations

Inveltys (loteprednol etabonate ophthalmic suspension 1%, Kala Pharmaceuticals) is a corticosteroid FDA-approved in a twice-daily dosing for treatment of postoperative inflammation and pain after ocular surgery. According to the manufacturer, Inveltys employs the company’s proprietary AMPPLIFY drug-delivery technology, designed to enhance penetration through the mucus barrier and deliver increased concentration of loteprednol etabonate to the target ocular tissue.

“Inveltys offers patients and their eye-care professionals the first and only b.i.d. (twice daily) ocular corticosteroid therapy that has been shown in clinical trials to be clinically effective while maintaining a proven safety profile, which may improve compliance and prove less burdensome for patients,” says Kim Brazzell, PhD, Kala’s chief medical officer. “We believe Inveltys is an important addition to eye-care professionals’ treatment armamentarium.”

Inveltys successfully completed two Phase 3 clinical trials that showed statistical significance for its primary efficacy endpoints of complete resolution of inflammation and pain at postoperative day 8 through day 15 compared with placebo.13

Lotemax SM (loteprednol etabonate ophthalmic gel 0.38%, Bausch + Lomb) is a gel formulated with submicron technology for the treatment of postoperative inflammation and pain following ocular surgery. Compared to the previous formulation (loteprednol etabonate ophthalmic gel 0.5%), the SM, or submicron product, allows for faster drug dissolution in tears.14,15 Also, it provides two-times greater penetration to the aqueous humor compared to Lotemax gel.(16)

Lotemax SM also offers a pH close to that of human tears and the lowest BAK preservative percentage of any other loteprednol etabonate formulation (0.003%), says Yolande Barnard, vice president and general manager, U.S. Pharmaceuticals, Bausch + Lomb. “We’re pleased to offer eye-care professionals this exciting formulation option to help them address the needs of their patients undergoing ocular surgery who experience postoperative inflammation and pain.”

Compounded drugs

The use of compounded ophthalmic medications is another approach to lessening the burden of complicated postoperative drop regimens. Although not FDA-approved, these products can give patients access to medications that may otherwise be unavailable or unaffordable. The combinations save patients money compared with many branded options and offer convenient dosing options to enhance compliance.

Ocular Science’s Omni formulations are for postoperative cataract and LASIK surgery. The company notes that each formulation is “water-soluble, mild in nature and is shipped directly to the practice, surgery center or patient’s home at no cost.” The company’s lab uses the highest grade active pharmaceutical ingredients available, employs the latest technology and equipment, and strictly adheres to USP 795 and 797 compounding guidelines.

Available Omni combinations include:

  • Prednisolone sodium phosphate 1%; gatifloxacin 0.5%; bromfenac 0.075%
  • Prednisolone sodium phosphate 1%; bromfenac 0.075%
  • Prednisolone phosphate 1%; gatifloxacin 0.5%; ketorolac tromethamine 0.5%
  • Prednisolone phosphate 1%; gatifloxacin 0.5%

ImprimisRx delivers its safe, high-quality compounded formulations from a patient-specific 503A pharmacy and an 503B FDA-registered outsourcing facility — 503B facilities undergo the same FDA scrutiny as the traditional pharmaceutical companies. The formulations are proprietary, physicians can order the medications in bulk.

Injectable formulations include:

  • Dropless: Tri-Moxi (triamcinolone acetonide and moxifloxacin)
  • LessDrops: Dex-Moxi (dexamethasone + moxifloxacin), Dex-Moxi-Ketor (dexamethasone + moxifloxacin + ketorolac tromethamine)

Another combination agent for cataract surgery from ImprimisRx, MKO Melt, is a nonopioid, sublingual (IV-free) conscious sedation option. The combination consists of midazolam, ketamine, and ondansetron.

“We have a high degree of confidence in our equipment, our facilities, our certified sterile technicians, and the quality release requirements we enforce to provide these unique high-quality formulations to our customers,” says John Saharek, ImprimisRx president.

Conclusion

Complex drop regimens can present a real burden to patients. With this complexity, as well as myriad other potential factors like patient forgetfulness and their often-compromised physical dexterity—particularly in the elderly, the efficacy of postoperative agents is compromised and visual outcomes suffer. Industry has responded by introducing various approaches to simplifying postoperative drop routines for enhanced compliance and positive visual outcomes. OP

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