Non and then long agone, beta blockers were a clinician's primary medical weapon against chronic high intraocular force per unit area. Today, many other options are available; prostaglandins, in particular, have go most clinicians' get-go line of defence when treating glaucoma—at to the lowest degree in the United states of america.

Nonetheless, beta blockers are however in wide use. With that in mind, we asked iii ophthalmologists with extensive noesis of beta blockers to provide an update on how and why beta blockers are beingness used today—and how clinicians could make fifty-fifty amend use of them.

Prostaglandins vs. Beta Blockers

"Beta blockers are good drugs that have gotten a bad rap," says Toni Realini, MD, associate professor in the department of ophthalmology at the Due west Virginia University Eye Establish. "When they were all nosotros had, nosotros loved them. Today, with the advent of prostaglandins and other drug classes, beta blockers are less popular. Nevertheless, they're still completely advisable for many patients every bit first-line therapy."

Dr. Realini notes that prostaglandins accept come to the fore in recent years because they offer a rare constellation of advantages. "Prostaglandins are unique in medicine in that they are the most powerful drug in the arsenal, and also the safest," he says. "That rarely happens in medicine. To get the most ability, yous almost invariably take to go to an unfavorable safety profile. But prostaglandins have essentially no systemic side effects that occur with any significant frequency.

"Nevertheless, some patients volition respond better to a beta blocker," he continues. "In almost comparative studies the difference between beta blockers and prostaglandins is pocket-size to moderate,i-three and in at least i report the effects were equivalent." 4

Robert D. Fechtner, Dr., FACS, director of the glaucoma sectionalization at the University of Medicine and Dentistry of New Jersey, observes that the popularity of item treatments every bit first-line therapy depends on whether you lot're considering the United States or the world as a whole. "In the U.South. where patients ordinarily have piece of cake access to medications, prostaglandins have largely taken over as initial offset-line therapy," he says. "Nosotros select them because they're once-daily and they have a very favorable adverse-effect contour; they're very well-tolerated systemically. Also, as a form they probably lower pressure a little better than beta blockers. But when patients don't have access to prostaglandins, beta blockers are the logical alternative."

Ehsan Sadri, Physician, banana clinical professor of ophthalmology at University of California, Irvine, agrees. "We often must care for patients who are already on two or three eye drops and however getting worse," he says. "In that situation you take to consider taking the patient to surgery. Yet, if the patient hasn't already tried beta blockers and his history shows no contraindication, I would trying switching to a beta blocker and then calculation other medications equally required, before resorting to surgery. Studies say that prostaglandins lower pressure better, but I've had patients who responded better to beta blockers."

"Beta blockers have positives and negatives," he adds. "If yous've got a young patient with calorie-free irides who doesn't want long eyelashes, a beta blocker is an first-class option, especially if you lot apply it one drop per twenty-four hour period. Likewise, cost is a huge factor. Many patients on a lipid analog enquire me when they tin can go back to a beta blocker once more. And I've known pharmacists to encourage patients to use a less expensive beta blocker when the patient has a prescription for a prostaglandin analog. Nosotros ought to provide the patient with something he can be economically compliant with as well every bit clinically compliant."

The Side Effects Factor

Dr. Sadri notes that possible systemic side effects are ordinarily seen equally the main "negative" of beta blockers. "This class of medications has to be used in select patients," he says. "Some clinicians overlook this and use them on everybody—they don't call up about the cardiovascular bug. Other doctors are leery of beta blocking patients if at that place's any hint of a cardiac effect.

"The most important thing to remember is that you accept to become a proficient history," he continues. "The number one rule is: Know your patient. Beta blockers are contraindicated in anyone with a previous myocardial infarction, a history of arrhythmia or bradycardia, pulmonary issues such equally chronic obstructive pulmonary affliction, or emphysema. On the other paw, if the patient is already on beta blockers systemically, which many of our patients are, adding a topical heart drop is non going to throw him into sinus bradycardia; systemic levels of oral beta blockers are much higher than topically administered beta blockers."

"It's the safety issue that has propelled prostaglandins to the front line," agrees Dr. Realini. "Beta blocker heart drops accept a minimal systemic effect in salubrious people, but you can discover information technology in the claret stream—some of it does make it. I've heard ane clinician say, 'I similar to use a prostaglandin considering I don't have to bother to take a careful medical history.' I wouldn't want to exist that doctor's patient, but I understand why he said that. With a beta blocker there are a number of of import comorbidities that y'all have to rule out beforehand. With prostaglandins, you don't have to inquire all of those questions."

However, Dr. Fechtner notes that in that location are situations in which he would besides hesitate to choose prostaglandins as beginning-line therapy because of possible side furnishings. "I'thousand cautious about using the prostaglandins when a patient has uveitis, cystoid macular edema or herpes simplex keratitis," he says. "While there's no proven causal link between them, the question of an association has been raised. So in those patients I might choose a beta blocker every bit first-line therapy."

"Nosotros've shied away from the beta blockers a petty considering of their potential for systemic side furnishings," he adds. "But with 30 years of experience nosotros should exist very comfortable with this class of drugs."

Dr. Sadri also points out that some minor side effects favor beta blockers. "In my experience, the most of import gene affecting compliance is that the majority of medicines now used to care for glaucoma comprise benzalkonium chloride or other preservatives which tin can cause chronic hyperemia," he says. "Every twenty-four hour period I see patients who don't like having chronic scarlet eyes; they want to switch to something else. Too, chronic hyperemia is bad for the eye; it can cause leakage of fluid and chronic edema that can as well pb to other deleterious effects such equally scarring, making future glaucoma surgeries more hard.

"Relative to other medications, beta blockers tend to crusade less hyperemia," he continues. "I see 60 patients a day, and I can tell the difference when patients use beta blockers; their optics aren't as red. This difference ultimately translates into patients beingness more compliant virtually taking their medications."

Beta Blockers: Less is More?

Dr. Fechtner points out that twice-a-day use of beta blockers, while commonplace, isn't the only pick. "Many ophthalmologists recognize that 0.5% timolol is approved for once-daily usage," he points out. "Prostaglandins came out with the convenience of in one case-daily dosing in a marketplace in which we were almost uniformly using beta blockers twice a twenty-four hour period. That was our habit. Only if you become back to the FDA-approved label for Timoptic and read it carefully, it says, 'If the intraocular pressure is maintained at satisfactory levels [with twice-daily dosing], the dosage schedule may exist changed to i driblet in one case a day in the affected eye(s).' That dosing also has a very favorable side-effect profile.

"In fact, this may be the appropriate fashion to use it: one time daily in the morning," he continues. "There's reason to believe that 0.five% twice a day is way too much beta blocker. When the original dose response research on beta blockers was being done, people didn't know that information technology takes several weeks to get the total beta-blocker effect. Today, nevertheless, we take data suggesting that the night effect of timolol is minimal. If we were going to practise it all over again, we'd probably try lower doses, less frequent dosing and having patients stay on it longer before determining the lowest dose that'southward constructive."

He notes that the toll differential between prostaglandins and once-a-twenty-four hour period beta blockers can also make a difference to patients. "Our clinic has many patients with no insurance," he says. "They have to pay for their own medicines, and they have very express resources. One time-daily beta blockers can be very toll-effective."

"In medicine, we're taught to 'start low and go slow' when we're prescribing a new medication," notes Dr. Realini. "In the example of beta blockers, there are lots of ways to minimize exposure while still reaping the benefits of the drug. For instance, I think a very large subset of the glaucoma population tin be just as well controlled on once-daily beta blockers equally on twice-daily, whether the drug is used every bit monotherapy or adjunctive therapy. In addition, there are various preparations that are thicker than solutions, designed to stick to the heart longer and get more drug absorbed before they're washed away by tears and blinking. And many patients would be just as well controlled on timolol 0.25% as on timolol 0.5%, yet that formulation is very infrequently used."

Ane electric current production that is approved for in one case-daily utilise is Istalol (Ista Pharmaceuticals). "Ista did their homework," says Dr. Fechtner. "They did their clinical trials right and showed that you tin offset patients on beta blockers one time a 24-hour interval. The fact that this data exists is a good reason to view Istalol for initial once-a-day apply." However, Dr. Fechtner notes that Istalol isn't the first beta blocker to exist approved for in one case-daily use. "Timoptic XE was approved for once-daily use. Betagan is recommended for utilise one time or twice daily. And timolol maleate solution, once a patient is stable, is also indicated for once-daily apply."

Dr. Sadri says he especially likes Istalol because of the once-a-day approval. "Some other major advantage is that it causes less blur in my patients," he says. "That's a big departure between the regular or generic formulations and Istalol. Information technology tends to be a trivial more expensive, merely given what it provides, it'southward a very skilful medication to use in lieu of topical prostaglandin analogues. That's peculiarly true with a young person who doesn't desire the side furnishings of a prostaglandin."

Getting Combinations Approved

As every ophthalmologist knows, combination drug centre drops have several pregnant advantages over using multiple carve up drops when patients need a 2nd medication to lower intraocular pressure level. Today, beta blockers seem to exist an inevitable role of this concept. "Every stock-still-combination drug that's in development includes a beta blocker," notes Dr. Fechtner. "Elsewhere in the world, timolol has been combined with bimatoprost, travoprost, latanoprost, pilocarpine, dorzolamide, and recently brimonidine. Of the drugs in my toolbox, the only one I haven't seen combined with timolol is brinzolamide."

Despite this, none of the fixed combination prostaglandin/beta blockers have been approved in the United States. "One reason for this," says Dr. Fechtner, "is that in the clinical trials the prostaglandin monotherapy was very effective, and the combination drug was not tremendously more effective than the prostaglandin alone at the report endpoints." Yet, he notes that this may non reflect some practical realities. "In some individuals, adding a beta blocker to a prostaglandin can be very effective," he says. He as well notes that real-globe utilize may differ from use in clinical trials. "For example, our experience with the timolol/dorzolamide combination (Cosopt)—which is the merely approved fixed combination in the United states—suggests that in real life it tin can piece of work better than information technology did in controlled clinical trials.

"Besides, key factors may exist very unlike when you put the ii drops in the aforementioned bottle, particularly when you're giving the drops at night, when beta blockers work least well," he continues, noting that this was washed in many of the combination trials. "Nosotros typically dose prostaglandins at dark, but if we apply beta blockers equally monotherapy, we dose them in the morning. If they're both in the same canteen, I'm not certain when you should dose them to go the best efficacy profile."

"At that place'southward fairly compelling evidence that prostaglandins can be dosed with essentially equal efficacy in the morning or at nighttime,"5,half dozen comments Dr. Realini. "There are small-scale differences, but overall the diurnal blood pressure profile seems to be fairly comparable either way. So I think that morning dosing of a beta blocker/prostaglandin combination product would be perfectly reasonable."

Dr. Realini notes that the Food and Drug Administration's reluctance to corroborate a combination of beta blocker and prostaglandin may be having more than negative effects than positive. "Right now, the majority of patients who need an adjunct to a prostaglandin are prescribed a beta blocker," he points out. "So the FDA'southward statement that the combination doesn't appear efficacious enough to justify the hazard of topical beta blockers becomes somewhat spurious. They're not really protecting patients from that combination; that combination is already available in 2 separate bottles and in wide use. These components are not experimental; they're already FDA-approved.

"On the other manus," he continues, "if the FDA approved these combinations, it would facilitate compliance, minimize exposure to vehicle components such as preservatives that can be toxic to the eye in chronic therapy, and reduce the number of co-pays for people who accept a prescription drug do good. So the lack of approving isn't protecting patients from the two drugs; it's only depriving patients of the benefits of combination therapy."

Despite prostaglandins currently existence favored every bit first-line therapy in the The states, beta blockers clearly will remain role of the clinicians' armamentarium for the foreseeable future. "Nosotros're non giving up on them," notes Dr. Fechtner.

"We utilise beta blockers because they're good drugs," adds Dr. Realini. "Yous just take to carefully select the patients you utilise them in."

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