therapeutic insights
Prescribing for Glaucoma
See why it's important to match the best medication to each patient's circumstances.
Robert B. DiMartino, O.D., M.S., F.A.A.O.

When D.C., a 41-year-old Caucasian woman, entered my care, she complained of distance and near blur.

In the beginning

D.C.'s entrance acuity with current spectacle correction was 20/30 at distance and .4/1.2 M at 40 cm with each eye. Manifest refraction demonstrated a hyperopic and presbyopic shift and the corresponding distance visual acuities (VAs) improved to 20/20; near acuities were .4/.4 M each eye. Pupillary status was normal and there was no afferent defect. Extraocular motility was normal. An automated visual field screening was without defect. D.C.'s binocular status was normal.

An external slit lamp examination was within normal limits with the singular exception of a shallow anterior chamber that by Van Herrik estimation was grade 2 bilaterally. The intraocular pressure (IOP) was 16 mm Hg OU by applanation tonometry and the corneal thickness was 540 µm bilaterally. Four-mirror gonioscopic evaluation confirm-ed that the anterior chambers were shallow, but scleral spur was visible in all four quadrants.

I concluded that the anterior chamber was deep enough to permit a low-risk mydriatic evaluation of the posterior segment. Based on these findings, I asked D.C. about intermittent blurred vision that could be separated from her refractive complaint. I also asked her about halos around lights or headaches. She denied all of these symptoms.

Her crystalline lens was normal and the vitreous was clear. The optic nerve head was round and normal in size and color. The cup-to-disc ratio was 0.3/0.3 OU. The neural rim followed the ISNT description with the inferior neural rim width greater than the superior rim width and the nasal rim width greater than the temporal rim. The retinal vessels and the maculae were normal. The periphery was clear by indirect evaluation OU.

Forming a plan for follow up

I prescribed a new progressive spectacle correction, which, upon dispensing, addressed D.C.'s presenting complaint. I advised D.C. to return for yearly re-evaluation based on two factors:

1) my expectation that her refractive error was progressive

2) my concern related to the likelihood that her anterior chamber would shallow further.

I also advised her to return promptly upon the development of intermittent blur, halos around lights or unexplained headaches.

Findings at seven years

Over the next seven years, I evaluated D.C. on an annual basis. Her refractive error increased as expected and I changed her spectacle correction as indicated. During this interval, D.C. did not report any of the symptoms I'd advised her about. With the exception of refractive error, all of her findings remained unchanged -- until her most recent visit.

My slit lamp biomicroscopic evaluation of the anterior segment revealed a further narrowing of the anterior chamber. Now the VanHerrick estimation was a slit angle temporally and a grade 1- nasally OU.

Gonioscopic evaluation confirmed a bilateral shallowing of the anterior chamber. As expected, the inferior angles were the widest, with a portion of the functional trabeculum visible. The superior angles demonstrated only non-functional trabeculum.

No trabeculum was visible in temporal and nasal angles. With indentation 4-mirror gonioscopy, the anterior chamber deepened 360°. With indentation I was able to visualize scleral spur in the temporal angle. I measured her IOPs at 17 mm Hg OU.

It's time for surgery

Based on the anterior chamber findings at this recent evaluation, my impression was that D.C. had declared herself a high-risk patient for angle closure with pharmacologic mydriasis. If I reach the conclusion that mydriasis cannot be performed safely, I make the clinical judgement that the patient is also at risk for spontaneous angle closure. Because the complications of angle closure can be significant and this clinical situation is "curable" with appropriate therapy, I felt compelled to obtain a consultation for a laser peripheral iridotomy (LPI). The patient accepted my recommendation and D.C. was scheduled for evaluation with my glaucoma surgeon.

The surgeon confirmed my findings, and D.C. underwent an uncomplicated bilateral YAG LPI. She returned to me after these procedures for postoperative follow up. Her anterior chamber was now deeper than on her initial consultation with me some eight years ago. Four-mirror gonioscopic evaluation revealed scleral spur visible in all four quadrants. A patent iridotomy was present in far superior peripheral iris of each eye. The intraocular pressure remained in the mid-teens at 16 mm Hg OD and 17 mm Hg OS. I re-evaluated D.C. three months later with a similar postoperative appearance.

Based on the findings, I concluded that D.C.'s potential for intermittent or acute angle closure attack had been eliminated and her "glaucoma" cured. With the success of this procedure in hand, I concluded that her status was stable and advised her to return for annual re-evaluations.

Post surgery, one year

I had the opportunity to re-examine D.C. one year after her LPI procedure. Her distance manifest refraction had remained stable but her presbyopic refractive error had increased slightly. D.C.'s anterior segment findings remained stable with a grade 2+ deep anterior chamber by slit-lamp and by 4-mirror gonio-scopy scleral spur was visualized in all four quadrants OU. Interestingly, the intraocular pressure was now measured at 20 mm Hg OD and 21 mm Hg OS.

The posterior segment findings were unchanged from D.C.'s baseline examination. Her threshold visual field result was without defect. The apparent change in intraocular pressure alone was sufficient for me to recommend that D.C. be re-evaluated in three months.

She returned for a re-evaluation of her IOP as was recommended. Her intraocular pressure was measured to be 21 mm Hg OU. The anterior chamber remained deep by slit-lamp and gonioscopic examination. Based on a confirmed increase in intraocular pressure, I advised D.C. to return for quarterly re-evaluations.

Follow up doesn't end

Over the next 15 months, I observed a gradual but progressive increase in D.C.'s intraocular pressure. Her tonometric values were now 25 mm Hg OD and 26 mm Hg OS. Her anterior chamber remained deep and her visual fields and optic nerve head were unchanged. In spite of D.C.'s visual field, optic nerve head, and anterior chamber remaining normal, the intraocular pressure had continued to increase. Furthermore, this increase of 8 mm Hg to 9 mm Hg had occurred in less than a three-year period.

Because I hadn't detected any optic nerve damage and the threshold visual field was full, I changed D.C.'s diagnosis to a glaucoma suspect. The relatively short time interval and the magnitude of the increase in IOP were compelling factors in my recommendation that medical therapy was indicated. Because D.C. hadn't sustained any clinically evident optic nerve damage, I set her target pressure at 18 mm Hg OU, representing about a 30% reduction in IOP.

Choosing a medication

D.C.'s medical history had changed in the 10 years I had treated her. She was now taking fluoxetine (Prozac) for depression and had chronic low blood pressure. In selecting the appropriate topical agent for her glaucoma, I considered a number of factors.

Beta blockers. Beta-blocking agents, which have been useful in glaucoma therapy since the early 80s, could be sufficient to reach the target pressure. While other beta-blocking agents can be more effective in reducing IOP, I like to use betaxolol HCl 0.25% (Betoptic-S) because of its safety profile.

A majority of this cardio-selective drug's action is blocking beta-1 receptors. This reduces the risk of respiratory complications, which are a well-documented adverse reaction from all topical beta-blocking agents. Additionally, betaxolol is prepared as a suspension that increases its contact time with the eye and further minimizes its systemic side effects.

While beta-blocking agents might be successful in reducing D.C.'s IOP, they're not an appropriate choice for her. Recall that she's now taking a selective serotonin re-uptake inhibitor for depression. One of the possible side effects of beta blockers is their potential for depression or for exacerbating a depressed state. So I chose not to use a drug from the beta-blocker class of anti-glaucoma medications.

Alpha₂ agonists. Another treatment option might be a drug in the alpha₂ agonist class of drugs. These agents are effective and might achieve our target of a 30% decrease in IOP. Apraclonidine (Iopidine) was efficacious in reducing IOP. This medicine fell out of favor for chronic glau-coma therapy because of the high incidence of conjunctiva allergic reactions.

Brimonidine (Alphagan) has a much lower incidence of allergic response. Currently, the reformulation of this drug (as Alphagan-) should further reduce the incidence of allergic reaction. I chose not to use Alphagan-P because of the drug's potential systemic effect on blood pressure.

Alpha₂ agonists have been used in the treatment of systemic hypertension. Recall that this patient already suffers from chronic low blood pressure; systemic absorption of this agent might exacerbate the condition.

Prostaglandins. This is one of the newer drug classes for anti-glaucoma therapy. These drugs increase outflow by enhancing the uveal-scleral pathway and may be effective in achieving our target pressure. They're relatively safe and have few systemic side effects.

I avoid using prostaglandins in patients with a current or past history of ocular inflammation. These medicines should be used with caution in aphakes or patients with a history of cystoid macular edema. Patients who have hazel irises can experience darkening of their irides and you should warn them of this possibility. You shouldn't use these drugs for the monocular treatment of glaucoma because patients might develop heterochromia. They can also cause the eye lashes to grow and may cause the periocular skin to become pigmented.

With one exception, the drugs in this class are used once a day at bedtime so they're convenient.

Deciding upon initial drug

D.C. had no contraindications to the drugs in this class. I chose latanoprost (Xalatan) as my initial drug and started a monocular trial of latanoprost q.h.s OS because it had the highest pressure. On re-evaluation one month later, D.C. reported no side effects from the topical medicine. Her IOP was 25 mm Hg OD and 23 mm Hg OS.

This small decrease in IOP wasn't what I'd expect from latanoprost. I queried the patient about compliance and reviewed the instillation procedure with her. I asked her to continue with latanoprost q.h.s., OS and scheduled an evaluation at one month. After two months of a monocular trial, D.C.'s left eye still had a tonometric reading of 23 mm Hg. It was time to try another medication.

Although D.C. didn't get the pressure reducing effect with latanoprost that my experience with the drug lead me to expect, I thought it reasonable to try another drug in this class. My next choice was brimatoprost (Lumigan). Like latanoprost patients use it once a day at bedtime.

Moving on to brimatoprost

I switched D.C. to brimatoprost again in a left eye monocular trial and asked her to return in one month. When she came in, I measured the following pressures: 25 mm Hg OD and 17 mm Hg OS. I had achieved my target pressure in D.C.'s treated eye with brimatoprost.

I changed her treatment plan to include the non-treated eye and I re-evaluated in another month. At this next visit, D.C. returned using brimatoprost q.h.s. OU with IOP of 17 mm Hg OD and 18 mm Hg OS. Her target pressure had been achieved with one medication that D.C. tolerated without side effects.

At her three-month follow-up, D.C.'s IOP remained at or below her target. She continues to use brimatoprost one year later with adequate IOP control and without side effects.

Learning glaucoma lessons

I learned a number of important lessons from D.C.:

• The depth of a patient's anterior chamber can change over time.
• Eyes with shallow anterior chambers have less tolerance before they reach the potential for acute angle closure.

This case also reinforces the importance of gonioscopy in the evaluation of glaucoma patients. The technique is the only method of ensuring that an LPI is effective in deepening the anterior chamber. Without the findings that this procedure yielded, medical treatment might have taken a wrong direction.

D.C.'s case also reminds us that patients can have more than one kind of glaucoma or disease at the same time. Always consider all of the possibilities and be prepared to treat each of the conditions. This patient's changing medical history is a further reminder to carefully consider all the systemic factors before starting a medicine, regardless of whether it's topical or oral.

Finally, D.C.'s case points out an important guideline in medical glaucoma therapy: If an initial drug choice in a class of anti-glaucoma agents isn't effective, consider selecting another drug from the same class of medications. The second drug may be even more effective than your original choice.

Dr. DiMartino is associate professor of clinical optometry at the University of California Berkeley School of Optometry. He's also an associate at Lafayette Optometric Group.

Dr. Christensen has a partnership practice in Midwest City, Okla. He's a diplomate in the Cornea and Contact Lens Section of the American Academy of Optometry. He's also a member of National Academies of Practice.