August 2017

COVER FEATURE

Steroids roundup
The who, what, where, when, why, and how of steroids and cataract surgery


by Liz Hillman EyeWorld Staff Writer


Dropless cataract surgery reduces or eliminates the post-cataract surgery drop routine.
Source: John Gastaldo/Imprimis Pharmaceuticals

Physicians discuss their corticosteroid regimens for routine and non-routine cataract surgery, drug delivery options, and more

In its updated Cataract in the Adult Eye Preferred Practice Pattern guidelines, the American Academy of Ophthalmology (AAO) Cataract and Anterior Segment Panel wrote that physicians’ usage pattern and mode of delivery of antibiotic, steroid, and nonsteroidal anti-inflammatory drugs (NSAIDs) varies.1
When should corticosteroids be used—before, during, or after cataract surgery, or in some combination thereof? How should a steroid regimen differ for a routine cataract patient compared to a non-routine case, such as a patient with diabetic eye disease or iridocyclitis? Does branded vs. generic matter? What role do NSAIDs play? What about delivery options other than topical drops—injection, punctal plugs, or slow-release implants?
“There are no controlled investigations that establish optimal regimens for the use of topical agents. Therefore, it is the decision of the operating surgeon to use any or all of these products singly or in combination,” the panel stated in the guidelines.
The physicians that EyeWorld interviewed had some similarities but also some differences on this front, providing a range of thought on cataract surgery and steroid use.

Who, what, and when?

The 2016 ASCRS Clinical Survey, which included more than 1,500 unique respondents from the U.S. and around the world, found the vast majority of physicians use corticosteroids in some capacity before, during, or after cataract surgery.
For standard cataract cases, slightly more than 30% of U.S. respondents to the survey said they prescribe topical steroids at least 3 days preop; 72% said they prescribe them for at least 3 days postop. On that front, most (65%) recommend steroid drops for 4 weeks postop for the majority of cataract patients. About two-thirds of respondents reported that their primary goal with the steroid is to reduce anterior chamber inflammation; about 69% said they use NSAIDs for cystoid macular edema (CME) prophylaxis. The majority of respondents think that using both a corticosteroid and NSAID is important for inflammation and pain control postop.
The survey also identified generic prednisolone acetate 1% as the most commonly preferred topical steroid for routine cataract surgery among U.S. ophthalmologists, followed by difluprednate 0.05%. The preferred NSAID among respondents, overall, was nepafenac. When it came to branded vs. non-branded medications, about 51% of respondents to the survey said their ocular prescriptions were branded.
John Hovanesian, MD, Harvard Eye Associates, San Clemente, California, said he begins steroids and nonsteroidals 3 days preop, continuing the steroid four times a day for 3 weeks postop, cutting it down to three times a day during the fourth week. Nonsteroidals are administered once a day for 4 weeks postop.
He said he prefers branded prednisolone acetate but is willing to allow generic substitutes if that is the patient’s preference. The reason? He said branded prednisolone acetate is a suspension, which he thinks is more consistent when it comes to dosing.
T. Hunter Newsom, MD, Newsom Eye, Tampa, Florida, starts his steroid/NSAID/antibiotic regimen postoperatively, advising each be administered topically three times a day, assuming these drugs are generics. Generics are “typically what we use and what most patients end up wanting and using.”
If the patient has a history of dry or irritable eye, Dr. Newsom said he will drop the NSAID or recommend branded Prolensa (bromfenac ophthalmic solution 0.07%, Bausch + Lomb, Bridgewater, New Jersey) or Ilevro (nepafenac ophthalmic suspension 0.3%, Novartis, Basel, Switzerland), which he said brings NSAID drops to just once a day. He noted that you have to be careful about insurance coverage and cost with these medications.
While prednisolone is Dr. Newsom’s steroid of choice in most cases, if the patient has iridocyclitis (uveitis), he will switch to Durezol (difluprednate ophthalmic emulsion 0.05%, Novartis) three to six times a day and the strongest NSAID once a day, depending on the patient’s condition. Dr. Newsom noted that Prolensa or Ilevro as the NSAID at one drop per day might be easier on patients using Durezol at this higher frequency.
The AAO guidelines recommend additional or oral corticosteroids for uveitis cataract patients, even if patients are on anti-inflammatory medication already. “The medical regimen should be individualized based on the severity and sequelae of past episodes of uveitis and the ease with which inflammation has been previously controlled,” the panel wrote.
Patients with diabetic retinopathy having cataract surgery face a higher risk for CME.2 The AAO guidelines state that CME, associated with post-surgical inflammation, can be prevented with anti-inflammatories, and NSAIDs alone or with topical corticosteroids can decrease risk of postop CME.
Dr. Hovanesian said he’ll use a steroid and NSAID in diabetic patients to reduce CME risk and will continue it for 2–3 months after surgery. Dr. Newsom said retina specialists in his practice watch these patients closely, keeping them on steroids and NSAIDs for a prolonged period of time.
“If you’re a diabetic and you have cataract surgery, we know cataract surgery is going to make diabetic retinopathy worse,” Dr. Newsom said. “We have a lot of diabetics in our practice, so we’re extremely aggressive at making sure we minimize any type of macular edema.”
The only time Dr. Newsom said he would consider dropping the steroid and using an NSAID alone would be if patients said they have an allergy and are adamant about not using steroids. In glaucoma patients, who might be at risk for an IOP spike with steroids, Dr. Newsom said he will still provide a steroid for a short period of time (a week or so).
“A lot of times in cataract surgery now, if they do have a steroid response, those are glaucoma patients that we’re performing glaucoma or IOP-lowering procedures on as well, like an [endocyclophotocoagulation] or a stent,” he said, noting that he finds having a steroid on board in these cases is still appropriate.

Where and how?

While Drs. Hovanesian and Newsom discussed their practices for topical drugs and cataract surgery, John Berdahl, MD, Vance Thompson Vision, Sioux Falls, South Dakota, uses a “dropless” formulation of dexamethasone/moxifloxacin/ketorolac (Dex-Moxi-Ketor, Imprimis Pharmaceuticals, San Diego) injected pars plana into the vitreous.
“I like the intracameral antibiotic and the fact that there’s an NSAID present in the injection, but from a steroid perspective, it’s clear, so patients don’t experience floaters like they do with triamcinolone injections,” Dr. Berdahl said.
While the dexamethasone wears off faster because it’s a solution, not a suspension, he said this isn’t a concern because despite the injection, he still prescribes a once-a-day NSAID or a once-a-day NSAID/prednisolone/moxifloxacin combination drop.
Dr. Berdahl said that his practice made the switch to intravitreal injections of these drugs based on literature showing lower infection rates with intracameral antibiotics and due to a better patient experience.
“From the patient experience standpoint, the worst part of cataract surgery is the postop drops, and oftentimes it is the most expensive out-of-pocket part of cataract surgery for the patient,” Dr. Berdahl said. “The confluence of those factors—good science supporting intracameral antibiotics, a better patient experience, and more favorable patient economics and system-wide economics—caused us to move in that direction.”
Dr. Berdahl said in diabetic patients the only change to his regimen would be to use a topical NSAID for 3 months. He also said he is not concerned about injecting steroids in glaucoma patients unless they have a known steroid response.
Dr. Newsom said his practice used to perform dropless cataract surgery, but ultimately abandoned it (except in certain circumstances) due to issues with higher rates of CME and rebound iritis, which had a significant impact due to the practice’s surgical volume. He said rebound iritis in dropless patients was also more severe than that seen in patients who were prescribed drops.
Dr. Newsom said, however, there are certain conditions in which he will inject antibiotics and steroids, such as in patients with uveitis and patients who have trouble instilling drops.
“On a random basis, this is a great option, but for us to use this 100 times this week, our practice can’t deal with 10 rebounds this week, 10 next week, 10 the week after. … That was too much of a burden for us,” he said.
Dr. Hovanesian said he tries to avoid routine use of compounded medications.
“Compounded medications are not FDA approved. They’re combinations of drugs that may individually be approved in different formulations by different manufacturers, but we’re mixing them in ways that the FDA has never investigated or approved and, in doing so, we’re assuming a risk on behalf of the patient and on behalf of the surgeon, which we don’t have if we use an FDA-approved product,” he said, also noting the higher likelihood of rebound inflammation.

What’s next?

The ideal situation for an anti-inflammatory drug would be one that has a high dose initially that slowly tapers and discontinues on its own, Dr. Hovanesian said. The dose would be low enough to avoid pressure spikes, and it wouldn’t require any compliance from the patient’s standpoint, he continued. This is what the punctal plug depot delivery method Dextenza (dexamethasone, Ocular Therapeutix, Bedford, Massachusetts) aims to accomplish, he said.
In clinical trials, Dextenza resulted in no significant inflammation, it had no complications, and pressure spikes were similar to that of the placebo, Dr. Hovanesian said. With FDA approval expected later this year, Dr. Hovanesian thinks patients could someday receive an injected antibiotic and this punctal plug steroid depot, eliminating the need for drops.
Intravitreal, slow-release steroid implants are mostly designed for treatment of conditions like macular edema and uveitis. A rod-shaped biodegradable implant inserted into the anterior chamber to reduce inflammation post-cataract surgery, Surodex (dexamethasone, Allergan, Dublin, Ireland), was in development several years ago and approved for use in some countries outside the U.S. A study published in 2004 compared the dexamethasone implant to dexamethasone eye drops, finding that both were effective at controlling intraocular inflammation after cataract surgery.3 Ozurdex (Allergan), a dexamethasone implant for macula edema following branch retinal vein occlusion or central retinal vein occlusion, in one study was implanted in the capsular bag after phacoemulsification and IOL implantation and resulted in effective inflammation control with no significant side effects.4
“One of the things that’s fascinating is how quickly our postoperative medication regimens are evolving,” Dr. Berdahl said. “Just a few years ago we used nothing inside the eye and all topical drops. Now we use a hybrid of most of the medication at the time of surgery and a little bit of topical adjunctive therapy once a day. As we move forward with other drug delivery mechanisms, I think the paradigm is going to continue to evolve. If we can have a depot that allows the right medication to get to the right place at the right time and favorable economics for the patient, the payer, and doctors, we have the ability to affect all 3.5 million cataracts that are removed every year. I think surgeons will make decisions based on the available safety and efficacy data, the economics, and patient convenience.”

References

1. Olson RJ, et al. Cataract in the Adult Eye Preferred Practice Pattern. Ophthalmology. 2017;124:1–119.
2. Henderson BA, et al. Clinical pseudophakic cystoid macular edema. Risk factors for development and duration after treatment. J Cataract Refract Surg. 2007;33:1550–8.
3. Wadood AC, et al. Safety and efficacy of a dexamethasone anterior segment drug delivery system in patients after phacoemulsification. J Cataract Refract Surg. 2004;30:761–8.
4. Vianna LM, et al. Intracapsular dexamethasone implant in patients undergoing phacoemulsification and intraocular lens implantation. Arg Bras Oftalmol. 2013;74:226–8.

Editors’ note: Dr. Hovanesian has financial interests with Ocular Therapeutix, Bausch + Lomb, Alcon (Fort Worth, Texas), and Sun Pharmaceuticals (Mumbai, India). Dr. Berdahl has financial interests with Alcon, Allergan, Bausch + Lomb, Imprimis Pharmaceuticals, Ocular Therapeutix, and Envisia Therapeutics (Durham, North Carolina). Dr. Newsom has no financial interests related to his comments.

Contact information

Berdahl
: johnberdahl@gmail.com
Hovanesian: DrHovanesian@harvardeye.com
Newsom: hunter@newsomeye.net

The who, what, where, when, why, and how of steroids and cataract surgery The who, what, where, when, why, and how of steroids and cataract surgery
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