Beyond IOP in glaucoma treatment

By Fred Gebhart

Intraocular pressure (IOP) is only the starting point for glaucoma treatment. Successful treatment begins with establishing an IOP goal, but there are multiple considerations that affect treatment choices.

“We currently have an array of medications that we can use to try to treat our glaucoma patients,” said Robert Stamper, MD, professor of ophthalmology and director emeritus  of the glaucoma service at the University of California, San Francisco. “It is pretty clear from the 24-hour proficiency in lowering IOP, both in amount and duration, that prostaglandins are our treatment of choice. But there are reasons to avoid them.”

Robert Stamper, MD, explored the considerations that go into drug selection for glaucoma. Dr. Stamper pointed out that it is easy to forget that the patient with glaucoma likely has other medical problems and is taking other medications. (Photo by Stevan Nordstrom)

Dr. Stamper explored the considerations that go into drug selection during a session on “Glaucoma Medications: Beyond IOP.” None of the factors that should influence drug selection are new, he said, but it is easy to forget that the patient with glaucoma likely has other medical problems and is taking other medications.

“You want to maximize treatment safety by using as few medications as possible, matching medications to your patient’s needs and being cognoscente of what other medications your patient may be taking,” he said.” Keep the treatment regimen as simple as possible and watch for quality-of-life issues. In glaucoma, as in any condition, make sure the benefits of therapy outweigh the risks. We have many good choices and well over 90% of patients will benefit from drug treatment.”

Treatment should begin with the lowest possible dose of the least toxic agent or argents, Dr. Stamper continued. Dosing should not be increased based on an automatic schedule, but on the patient’s actual condition. If glaucoma is not progressing, there is probably no positive reason to escalate dosing or switch to a more toxic agent.

Proactive communications

The key to successful treatment is communication. Patients are probably not aware that there are contraindications to prostaglandins. The clinician must be proactive in screening for factors, such as pregnancy, recent ocular surgery, active uveitis, recent herpes activity, and other events that require a change or a halt to prostaglandin use.

Cosmetic appearance has emerged as a significant issue, especially for patients who are using prostaglandins in only one eye. Unilateral dosing typically brings unilateral changes, such as hyperemia, thickened eyelashes, and darkening of the skin beneath the eye. It is easier to ignore, or at least to accept, these cosmetic changes if they affect both eyes, but a dramatic change to just one eye is more difficult for patients.

There is also increasing evidence that long-term prostaglandin use may be associated with orbital fat loss. Significant fat loss can affect both the cosmetic appearance of the face and visual functioning.

Preservatives are a real issue in ophthalmic medications. The most common ophthalmic preservative, benzalkonium chloride (BAK), can exacerbate ocular surface disease.

“In patients with ocular surface disease, you want to make a conscious effort to reduce BAK load, especially in patients who are taking multiple medications,” Dr. Stamper advised. “One can consider agents, such as Travatan Z or Zioptan, that use a preservative other than BAK or none at all in these patients. It may also be worthwhile to remember that generic medications can be compounded without any preservative by a compounding pharmacy.”

Other issues

Beta adrenergic antagonists present other complications. These agents are less effective when taken at night, compared to daytime dosing. They can reduce blood pressure, exacerbate the symptoms of Alzheimer’s disease, and are a risk factor for falls in the elderly, as well as induce psychological and sexual problems.

What may be less often recognized is that beta adrenergic antagonists can have an additive effect with systemic beta blockers and lower blood pressure to inappropriate levels. If beta adrenergic blocking agents must be used, dosage should be minimized. Once-daily morning dosing can provide a similar therapeutic effect as a twice-daily regimen that includes nighttime dosing. There is also a relatively high rate of tachyphylaxis with these agents, Dr. Stamper noted. In many cases, stopping the drug altogether has no effect whatsoever on IOP.

Brimonidine is an important fallback agent, he continued. It is clearly effective at lowering IOP and may offer some degree of neuroprotection. Dr. Stamper said it can be helpful for patients whose glaucoma continues to progress despite showing good IOPs. Brimonidine is also available with a non-BAK preservative, which can make it a good choice for patients with ocular surface problems.

On the negative side, brimonidine has high rates of hyperemia and allergic reactions. Dry mouth and somnolence are common problems, especially with the higher doses, and there have been questions of safety in young children.

“People don’t often associate eye drops with problems like dry mouth and sleepiness, but these are two of the more significant side effects of this agent,” Dr. Stamper said. “Just moving from 0.2% to 0.15% gives a much lower incidence of side effects. That reduction is probably even more notable with the 0.1% formulation.”