New steroid options allow surgeons to better tailor postoperative treatment
With four new steroid options on the market to treat pain and inflammation after ocular surgery, ophthalmologists can now better tailor their postoperative regimens for their individual patients.
The FDA approved Dexycu (dexamethasone intraocular suspension 9%, EyePoint Pharmaceuticals) in February 2018 as a single injection to treat postoperative inflammation. In August 2018, the FDA approved Inveltys (loteprednol etabonate ophthalmic suspension 1%, Kala Pharmaceuticals) as a twice-daily ocular steroid for the treatment of inflammation and pain after ocular surgery. Dextenza (dexamethasone ophthalmic insert 0.4 mg, Ocular Therapeutix) was approved in November 2018 as an intracanalicular insert to treat postoperative ocular pain, with the added indication of treating ocular inflammation being approved in June. Lotemax SM (loteprednol etabonate ophthalmic gel 0.38%, Bausch + Lomb) was approved in February for the treatment of postoperative inflammation and pain after ocular surgery.
These corticosteroid drug delivery platforms represent a significant advancement in ophthalmic drug development, OSN Cataract Surgery Board Member Alice T. Epitropoulos, MD, FACS, said.
“I am very excited about the new corticosteroid drug delivery platforms that have been approved, whether it’s the new mucus-penetrating product Inveltys, the submicron drug delivery drops with Bausch + Lomb’s Lotemax SM, the intracanalicular dexamethasone insert from Ocular Therapeutix or the intracameral drug delivery corticosteroid from EyePoint Pharmaceuticals. It’s great to have these options so we can tailor our therapy and our protocol to the patient,” she said.
The formulations and drug delivery platforms represent a “major step forward” in the ophthalmic field and offer ophthalmologists the potential to dramatically change how patient care is approached, she said.
More options are better
The more branded steroid options there are, the better it is for ophthalmic surgeons, OSN Refractive Surgery Board Member Mitchell A. Jackson, MD, said.
Branded steroids have less toxicity and more available data and clinical evidence to support their use than their generic counterparts, he said.
“I stay away from generic steroid drops as they do not have FDA studies that branded versions do supporting clinical efficacy and safety. Generic options are not always cheaper, either. With a Lotemax SM coupon and/or co-pay card, for example, it’s cheaper than any generic,” he said.
These newly approved options could also help address issues of poor patient compliance and cost, OSN Cataract Surgery Board Member Zaina Al-Mohtaseb, MD, said.
Al-Mohtaseb said her practice at Baylor College of Medicine typically uses either topical Durezol (difluprednate ophthalmic emulsion 0.05%, Novartis) or Lotemax (loteprednol etabonate ophthalmic suspension 0.5%, Bausch + Lomb) in addition to a once-daily NSAID for 4 weeks postoperatively after uncomplicated cataract surgery to control pain and inflammation. While her practice has yet to use all four new products, the group is excited that there are more options.
“Innovation of drug delivery, whether it is in improving penetration in the eye with Inveltys and Lotemax SM or placement externally with Dextenza or intraocularly with Dexycu, will most likely improve patient compliance and reduce ocular toxicity. I don’t think it makes the market crowded. In fact, it offers many choices for physicians so they can better base treatment on patient needs,” she said.
Deciding which product will work depends on its efficacy, safety, price and accessibility and the patient’s compliance. Ophthalmic surgeons may opt to give a premium IOL patient a different steroid from a patient with ocular surface disease or an underlying inflammatory disease, she said.
Each steroid has unique features
Ophthalmic surgeons cannot predict a patient’s exact healing response. Postoperative inflammation is determined by surgical trauma and exposures of lens proteins, medications used to quell inflammation and the patient’s own healing response, Healio.com/OSN Section Editor Uday Devgan, MD, said.
“We want to be minimally invasive and surgically efficient to induce as little trauma as possible. Then we want to tailor the medication to the specific patient,” he said.
Each of the newly approved steroids can offer something different. One of the biggest advantages of Inveltys is its mucus-penetrating nanoparticle technology, which enhances penetration without compromising efficacy and therefore twice-daily dosing, Al-Mohtaseb said.
In two phase 3 clinical trials, Inveltys showed statistical significance for complete resolution of inflammation and pain at postoperative day 8 through 15 compared with placebo, according to a press release from Kala Pharmaceuticals.
The mucus-penetrating particle technology uses selectively sized particles to penetrate the mucus barrier, which is a significant barrier to drugs. This helps deliver increased concentrations of the drug to the target ocular tissues, Epitropoulos said.
Inveltys and Lotemax SM are variations of loteprednol, an ester steroid, which tends to have a different profile from other ketone-based steroids such as prednisolone or dexamethasone. Ester steroids have less propensity for increased IOP and may be a better long-term steroid, Devgan said.
“I have used both medications, and I find them effective, though not as potent as stronger fluorinated steroids like difluprednate. For patients with a known history of steroid-responsive glaucoma, using loteprednol etabonate medications may be the best choice,” he said.
Lotemax SM, which is dosed three times a day, contains the lowest concentration of loteprednol corticosteroid available for the treatment of postoperative inflammation and pain for ocular surgery, Epitropoulos said. The Lotemax molecule has been in existence for the past 21 years, so ophthalmic surgeons know it has a proven history of safety and efficacy, she said.
“It’s 80% smaller than the Lotemax Gel (loteprednol etabonate ophthalmic gel 0.5%, Bausch + Lomb), and the benefit of having a smaller particle is that it increases the total surface area exposed to tears, driving rapid drug dissolution and more efficient penetration of ocular tissue. SM is also gentle to the ocular surface because it contains two proprietary moisturizers, a pH close to that of human tears and the lowest concentration of BAK (0.003%),” Epitropoulos said.
Lotemax SM and Inveltys are both efficacious and can often be used interchangeably, OSN Cataract Surgery Board Member Audrey R. Talley Rostov, MD, said.
If concerns exist regarding the ocular surface, Lotemax SM, with its lower benzalkonium chloride concentration, may be a more appropriate choice, she said, whereas if a patient has uveitis or underwent a previous corneal transplant, Inveltys, with its smaller particle size and greater cornea and anterior chamber penetrating capabilities, may be a better option.
“Both are great new formulations of tried and true loteprednol, with a good safety and efficacy profile and much less tendency for increasing IOP,” Talley Rostov said.
Cost can affect accessibility
No matter how efficient or safe a steroid is, cost will always be a factor in an ophthalmic surgeon’s decision to use one drug over another, Epitropoulos said.
Both Kala Pharmaceuticals and Bausch + Lomb offer coupons to commercial and Medicare patients to offset the cost of the steroids, Epitropoulos said. Kala provides a $35 commercial coupon and a $55 Medicare coupon for Inveltys. Bausch + Lomb has a $25 commercial coupon and a $60 Medicare coupon for Lotemax SM.
“It’s a welcome change. In the past, Medicare recipients haven’t been able to take advantage of these coupons. The companies have made it a priority to make sure that these new topical drops and delivery systems are accessible for patients,” Epitropoulos said.
Dextenza received a unique C-code, C9048, which was slated to become effective on July 1, and transitional pass-through payment status from CMS. The C-code facilitates the reimbursement of Dextenza until a J-code is approved and becomes effective. According to Ocular Therapeutix, CMS has included Dextenza on a list of products preliminarily recommended for a new dedicated J-code, which could go into effect on Jan. 1, 2020, if approved.
Dexycu has a permanent reimbursement J-code that went into effect on Jan. 1.
“It is very important to consider the cost, especially if you own your own ambulatory surgical center. Insurance coverage and designation as a ‘pass-through’ for Dextenza may be a potential advantage here, depending on the insurance. In addition, both Lotemax SM and Inveltys have competitive coupons and programs to reduce the cost of their drugs to the patients,” Talley Rostov said.
Dexycu and Dextenza are both depot versions of dexamethasone, Devgan said, so each is useful for patients who have difficulty with drop compliance or self-administration.
Eye drop compliance has always been a concern for ophthalmic surgeons, Devgan said. In a 2014 study published in Journal of Cataract and Refractive Surgery, researchers evaluated 54 eye drop-naive postoperative cataract patients and their success in administering postoperative eye drops.
In the cohort, 42% believed they never missed their eye when instilling drops and 58.3% believed they never touched their eye with the bottle tip. However, 92.6% of patients showed an improper administration technique, with 31.5% missing their eyes, 64% instilling an incorrect number of drops, 57.4% contaminating the bottle tip and 78% failing to wash hands before drop instillation.
Both Dexycu and Dextenza take patient compliance out of the equation, Epitropoulos said.
“The approval of both represents a significant advancement in our field. The options offer a single administration of a sustained-release corticosteroid immediately after surgery. They improve compliance, reduce the burden of using drops postoperatively and reduce corneal toxicity,” she said.
Dextenza provides a full course of tapered delivery of postoperative steroids for 30 days after insertion. The sustained-release drug allows for around the clock delivery and removes the concern of patient noncompliance, Epitropoulos said.
One Dextenza insert is equivalent to 70 topically applied drops. The insert reabsorbs on its own but can also be removed by irrigation or expression through the puncta, Epitropoulos said.
There is a learning curve associated with the insert, but it is a short one. Most ophthalmic surgeons have previously placed plugs, and this is not much different. However, the surgeon cannot get the insert wet before it is inserted into the eye. If it begins to hydrate before insertion, it is recommended to discard the insert and use a new one, she said.
Jackson said he uses the insert for his premium IOL patients because it helps improve the health of the ocular surface.
“I like this for my premium IOL patients because their cataracts usually aren’t as dense, and you don’t need as much anti-inflammatory coverage postoperatively. It really does help the ocular surface,” he said.
Dexycu uses a novel drug delivery technology to dispense a biodegradable extended-release formulation of dexamethasone into the posterior chamber of the eye, Epitropoulos said.
The ideal location for the depot is behind the iris; it is a liquid technology, so it tends to want to stick to the cannula. There is also a learning curve with the injection, but it is short, she said.
“Both Dextenza and Dexycu are quick to insert, about 15 seconds. With either of these delivery systems, you leave the operating room knowing that this patient has a steroid onboard,” she said.
Jackson said that he has not observed any breakthrough inflammation with Dexycu, but the depot can rarely migrate from under the iris and touch the cornea, which can result in slight corneal edema, but this resolves once the insert dissolves.
Both Dexycu and Dextenza are appropriate for patients who may not be able to physically place drops or who need therapy tailored to their limitations. Placing a depot form of steroid would be ideal for an elderly patient with Alzheimer’s disease and limited family support, according to Devgan.
Great step in a new direction
These corticosteroids with innovative drug delivery technologies will become increasingly popular with ophthalmic surgeons. They fulfill an unmet need for patients and address the challenges associated with topical medications, such as poor compliance, corneal toxicity, discomfort and cost, Epitropoulos said.
“Given the breadth of options already available or in development, drug delivery will inevitably change greatly over the next several years. The approval of these options is a great step in the next direction,” she said. – by Robert Linnehan
- An JA, et al. J Cataract Refract Surg. 2014;doi:10.1016/j.jcrs.2014.02.037.
- Dextenza receives C-code, pass-through payment status. www.healio.com/ophthalmology/ophthalmic-business/news/online/%7B5db64cfd-c76b-495a-9653-8234bcdedf8f%7D/dextenza-receives-c-code-pass-through-payment-status. Published May 29, 2019. Accessed June 5, 2019.
- Dexycu receives permanent J-code. www.healio.com/ophthalmology/ophthalmic-business/news/online/%7Ba3bdae5d-a952-400e-ba00-1f8c9b88b32c%7D/dexycu-receives-permanent-j-code. Published Nov. 12, 2018. Accessed June 4, 2019.
- FDA approves Dextenza for treatment of ocular inflammation. www.healio.com/ophthalmology/ophthalmic-business/news/online/%7Bdf51e46d-526f-45d3-a7ef-62b1016b08a2%7D/fda-approves-dextenza-for-treatment-of-ocular-inflammation. Published June 21, 2019. Accessed June 21, 2019.
- FDA approves Dextenza for treatment of postoperative ocular pain. www.healio.com/ophthalmology/cataract-surgery/news/online/%7B378b3c36-bd30-4d4d-aede-46c483d7656d%7D/fda-approves-dextenza-for-treatment-of-postoperative-ocular-pain. Published Dec. 3, 2018. Accessed June 5, 2019.
- FDA approves Dexycu to treat cataract surgery inflammation. www.healio.com/ophthalmology/cataract-surgery/news/online/%7Bda87ce59-acb9-4aba-ad73-9c23e7d7fd83%7D/fda-approves-dexycu-to-treat-cataract-surgery-inflammation. Published Feb. 12, 2018. Accessed June 5, 2019.
- FDA approves Inveltys for treatment of inflammation, pain after ocular surgery. www.healio.com/ophthalmology/cataract-surgery/news/online/%7Bef827c6d-648b-4a9f-8a93-7fab69b73622%7D/fda-approves-inveltys-for-treatment-of-inflammation-pain-after-ocular-surgery. Published Aug. 23, 2018. Accessed June 4, 2019.
- FDA approves Lotemax SM for postoperative pain, inflammation. www.healio.com/ophthalmology/cataract-surgery/news/online/%7ba90155da-d366-4b35-ae97-2958962f9fb4%7d/fda-approves-lotemax-sm-for-postoperative-pain-inflammation. Published Feb. 25, 2019. Accessed June 4, 2019.
- NDA for Inveltys to treat postoperative inflammation, pain accepted. www.healio.com/ophthalmology/cataract-surgery/news/online/%7b55f94770-38e0-4786-a56d-fefac2bb56e0%7d/nda-for-inveltys-to-treat-postoperative-inflammation-pain-accepted. Published Jan. 8, 2018. Accessed June 5, 2019.
- Supplemental NDA accepted for Dextenza inflammation indication. www.healio.com/ophthalmology/cataract-surgery/news/online/%7B1f30729f-dc6b-4a54-9bc4-3499c3177ed2%7D/supplemental-nda-accepted-for-dextenza-inflammation-indication. Published April 2, 2019. Accessed June 10, 2019.
- For more information:
- Zaina Al-Mohtaseb, MD, can be reached at Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030; email: email@example.com.
- Uday Devgan, MD, can be reached at Devgan Eye Surgery, 11600 Wilshire Blvd. #200, Los Angeles, CA 90025; email: firstname.lastname@example.org.
- Alice T. Epitropoulos, MD, FACS, can be reached at Ophthalmic Surgeons & Consultants of Ohio at The Eye Center, 262 Neil Ave., Suite 410, Columbus, OH 43215; email: email@example.com.
- Mitchell A. Jackson, MD, can be reached at Jacksoneye, 300 N. Milwaukee Ave., Suite L, Lake Villa, IL 60046; email: firstname.lastname@example.org.
- Audrey R. Talley Rostov, MD, can be reached at Northwest Eye Surgeons, 10330 Meridian Ave. N., Suite 370, Seattle, WA 98133; email: email@example.com.
Disclosures: Al-Mohtaseb reports she is a consultant for Alcon, Bausch + Lomb, Kala Pharmaceuticals and Ocular Therapeutix. Devgan reports he is a consultant and speaker for Novartis and a former consultant and speaker for Bausch + Lomb. Epitropoulos reports she was a primary investigator in the FDA trials for Lotemax SM, Inveltys and Dextenza, and is a consultant for Ocular Therapeutix, EyePoint Pharmaceuticals, Kala Pharmaceuticals and Bausch + Lomb. Jackson reports he is a consultant for Bausch + Lomb, Kala Pharmaceuticals, Ocular Therapeutix and EyePoint Pharmaceuticals and was involved in FDA trials for Inveltys. Talley Rostov reports she is a consultant for Bausch + Lomb and Kala Pharmaceuticals.
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