August 2017

COVER FEATURE

Steroids roundup
Steroid options abound in ophthalmology


by Vanessa Caceres EyeWorld Contributing Writer


Acute allergic conjunctivitis is one condition that can be treated with topical steroids.
Source: Henry Perry, MD




Acanthamoeba keratitis in a daily wear soft contact lens patient initially treated with tobramycin/
dexamethasone drops for bilateral ocular burning and redness
Source: David Verdier, MD


Aggressive treatment with potent steroids preferred when appropriate

When it comes to steroids, more potent is usually better—depending on the extent of the patient’s inflammation, of course.
Surgeons interviewed about topical steroids used in ophthalmology concurred that their go-to steroid treatment for more severe cases is difluprednate (Durezol, Alcon, Fort Worth, Texas) because it’s the strongest choice available and can treat inflammation more quickly. That means there’s less medication to use over time and better patient compliance.
“I think it’s better to treat with the strongest steroid first and taper rather than start with a weaker steroid and then increase the dosage. I want to aggressively treat inflammation as efficiently as I can,” said Edward Holland, MD, director of cornea services, Cincinnati Eye Institute, and professor of clinical ophthalmology, University of Cincinnati.
“For surgical inflammation, uveitis, and keratitis, the sooner you can quell the inflammation with the strongest tolerable anti-inflammatory, the better the outcome will be,” said John Sheppard, MD, president, Virginia Eye Consultants, Norfolk, Virginia.
Difluprednate is Dr. Holland’s go-to choice for corneal and ocular surface transplants, routine cataract surgery patients, and for conjunctival surgery.
Because difluprednate is dosed less frequently than other steroids, patient compliance is usually less of an issue. In a Phase 3 study with uveitis patients, difluprednate used four times a day was as effective as prednisolone acetate (Pred Forte, Allergan, Dublin, Ireland) used eight times a day.1,2 This research is often cited when surgeons state their preference for difluprednate.
One example of a dosing regimen for difluprednate was shared by Christopher Starr, MD, associate professor of ophthalmology, director of the cornea fellowship, director of refractive surgery, and director of ophthalmic education, Weill Cornell Medicine, New York-Presbyterian Hospital, New York. “I typically start at four times a day for the first week for most patients,” he said. “If there is significant inflammation, edema, or a complex uveitis patient, I sometimes increase to six to eight times a day. In routine cataract cases, I’ll decrease to two times or even one time a day at the 1-week visit, assuming the inflammation is negligible and corneal edema is resolved, which it almost always is.”
He then has patients do either twice a day for 1 week and then once a day for 1 week or once a day for 1 week and then stop. For higher risk patients with complex cases, Dr. Starr will begin a 4-3-2-1 taper at the 1-week postoperative visit.

Other steroid choices

Other steroids have a role as well, depending on what you are treating and the inflammation present or expected. “We’re fortunate in ophthalmology that we have several different options in terms of corticosteroid medications varying from mild to potent,” said Henry Perry, MD, Ophthalmic Consultants of Long Island, Rockville Centre, New York.
For most ocular surface disorders and laser vision correction surgery on low myopes, Dr. Starr defaults to loteprednol (Lotemax, Bausch + Lomb, Bridgewater, New Jersey). “If there is a bacterial component to the ocular surface pathology, I’ll use a combination steroid like Zylet [loteprednol/tobramycin, Bausch + Lomb] or TobraDex ST [tobramycin/dexamethasone, Alcon],” he said.
For contact lens-related stem cell deficiency, David Verdier, MD, Verdier Eye Center, Grand Rapids, Michigan, has found occasional success with prednisolone acetate four times a day over many weeks. He’ll use that same agent for severe epidemic keratoconjunctivitis and short bursts for allergic eye disease. He finds that Thygeson’s superficial punctate keratitis responds to lower strength steroids like fluorometholone. For low- to moderate-risk corneal transplants, he prefers prednisolone acetate four times a day for postop month 1 and 2, three times a day for the third month and two times a day for the fourth month, and then once a day (he’ll use fluorometholone if the patient is a steroid responder). After a year, he’ll switch to fluorometholone and continue long term unless the patient is phakic or a steroid responder. After pterygium and conjunctival allograft surgery, Dr. Verdier prescribes prednisolone acetate four times a day for 1 month.
For cataract surgery, Dr. Verdier prescribes prednisolone acetate four times a day for 2 weeks, followed by three times a day for a week, two times a day for a week, and once a day for one more week before discontinuing. However, if the patient has diabetes, an epiretinal membrane, or uveitis, he prescribes difluprednate twice a day and nepafenac (Ilevro, Alcon) once a day for 3 weeks, difluprednate once a day and nepafenac once a day for 2 more weeks, and then stop. If there is a history or presence of cystoid macular edema (CME), Dr. Verdier prescribes difluprednate b.i.d. and nepafenac q.d. for a full 2 months, and longer if CME is ongoing.
In addition to a postoperative regimen, Dr. Perry will also prescribe steroid use preoperatively for 1 to 3 days. “One thing we’ve found is if you treat preoperatively, we have significantly less inflammatory problems, better pupillary dilation, and the pupil tends to stay larger throughout the case,” he said. He’ll taper steroids over 2 to 3 weeks except in heavily pigmented individuals and patients with diabetes; in the latter two patient groups, he’ll prescribe steroids for 6 weeks.
There’s one area where Dr. Verdier has found less use for steroids. “I think topical steroids are overutilized for the treatment of dry eye, for which they should be used sparingly and for several weeks at most. There are other better treatments available for chronic treatment of dry eyes,” he said. He also finds that vernal disease can be tough to treat even with high doses of steroids.

Steroid and cataract/ IOP connection

One concern surgeons have about steroid use is the risk for an IOP rise/glaucoma and the risk for cataract formation.
“There’s no free lunch,” Dr. Verdier said. “The better the steroid anti-inflammatory effect, the greater the risk of associated steroid-related increased IOP as well as other concerns such as cataract formation.”
Dr. Perry always keeps in mind the pecking order of steroid potency when making his treatment choice. “Durezol is the strongest we have, but it increases IOP,” he said.
Ophthalmic surgeons must consider the steroid potency and associated risk of IOP rise (or cataracts) when deciding which to use. “Some newer molecules, loteprednol being one, are more potent than people realize and yet they carry a lower risk of steroid response,” Dr. Starr said.
“Stronger steroids don’t increase the number of patients who respond to them, but they do increase the level of IOP rise in that responding group. It’s estimated that 10% of patients are IOP responders to ketone steroids,” Dr. Holland said. For patients with a need for long-term steroid use, Dr. Holland will consider tapering to a slightly less potent but safer steroid. For instance, loteprednol is a very effective steroid but has been found to only raise the pressure in 1.8% of the population.
However, there can be different ways to think about side effects like glaucoma or cataracts. Dr. Sheppard thinks that the cataract concern is lessened because cataracts are so easily treatable. In fact, he’s seen treatment backfire because patients didn’t receive enough steroids to treat inflammation due to a fear of this occasional side effect.
“The biggest problem I see in a referral corneal practice is that patients don’t get enough steroids, and the disease is allowed to remain smoldering or undercontrolled,” he said. One exception he makes is in children, where the risks from steroid therapy are higher. For this reason, he works closely with pediatric rheumatologists and parents of patients to make sure they adhere to strict medication regimens and return to all follow-up appointments.

Cost issues

With cost an ever-present concern for many patients, one guiding principle surgeons keep in mind is that a more potent steroid will be used for less time—and that often means less money spent.
Although there has been a big push for generic prescriptions over branded ones throughout medicine because of their perceived lower cost, that approach seems to backfire in some markets. “Many generics have increased significantly in
price. In many markets, branded difluprednate is cheaper than generic prednisolone,” Dr. Holland said. “We shouldn’t assume generics will be cheaper.”
Manufacturer coupons or discount cards have been another option to help keep costs reasonable, Dr. Holland said.
If patients must pay out of pocket, there are a couple of other options. Dr. Sheppard occasionally refers patients to Canadian pharmacies that can obtain cheaper medications. “In not so serious diseases, we may give the generic and pray they’ll be compliant,” he said.
In Dr. Perry’s market, the use of generic prednisolone acetate provides the best value if a patient can’t afford difluprednate.
Cost issues may be an important consideration, but Dr. Starr also likes to stick to the most efficacious steroid for a given scenario. “I think that’s what’s best for treating patients. If there is a patient call about prohibitively high cost, which is quite rare, then I’m happy to switch to the next best option,” he said.
Although Dr. Verdier prefers generics unless there is a clear advantage with a branded drug, he has also found generics can be high priced. “My office staff checks weekly to see where the best prices may be, often through mail order, and we share that information with patients,” he said.
To assist with compliance issues, Drs. Holland and Sheppard said they are looking forward to greater availability of steroid implants with sustained release delivery and injectable options.

Reference

1. Foster CS, et al. Durezol (difluprednate ophthalmic emulsion 0.05%) compared with Pred Forte 1% ophthalmic suspension in the treatment of endogenous anterior uveitis. J Ocul Pharmacol Ther. 2010;26:475–83.
2. Sheppard JD, et al. Difluprednate 0.05% versus prednisolone acetate 1% for endogenous anterior uveitis: a phase III, multicenter, randomized study. Invest Ophthalmol Vis Sci. 2014;55:2993–3002.  

Editors’ note: Dr. Holland has financial interests with Alcon and Allergan. Drs. Perry and Sheppard have financial interests with Alcon, Allergan, and Bausch + Lomb. Dr. Starr has financial interests with Alcon and Bausch + Lomb. Dr. Verdier has no financial interests related to his comments.

Contact information

Holland
: eholland@holprovision.com
Perry: hankcornea@gmail.com
Sheppard: docshep@hotmail.com
Starr: cestarr@med.cornell.edu
Verdier: daverdier@aol.com

Steroid options abound in ophthalmology Steroid options abound in ophthalmology
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