Optimize Outcomes

Referral, testing, treatment and follow-up care—each step is crucial to provide patients with the best possible care.

Treat glaucoma early and aggressively—it's a familiar refrain. Eyecare practitioners routinely screen patients for the disease, identify glaucoma suspects and attempt to make early diagnoses. Doing this effectively can require repeat visits and tests, which help form the most accurate picture of the patient's status. Once physicians diagnose glaucoma, they have to choose from a range of treatment options, but most practices follow the familiar pattern of least-to-most disruptive to the eye and the patient's quality of life.

Diagnosis

When performing a comprehensive ophthalmological evaluation, stereoscopic evaluation of the optic disc is critical in the early detection of glaucoma.

Routine glaucoma screening typically entails IOP measurement, examination of the optic nerve, central corneal thickness measurement, slit lamp examination and gonioscopy. If the patient is at high risk for developing the disease or if the practitioner notes something suspicious, the patient receives further testing and possibly a referral.

In Pittsburgh, some of those referrals see Robert J. Noecker, MD, MBA, director of the glaucoma service and vice chairman at the University of Pittsburgh Medical Center Eye Center. “The goal the first time we see patients is twofold: 1) Get information about whether the patient is average or an outlier compared to the general population, and 2) Set up baseline measurements for the future,” he explains. “Glaucoma is a marathon, not a sprint, so we're always thinking 5 to 10 years into the future.”

Dr. Noecker's basic workup for referred glaucoma suspects includes visual acuity, IOP, corneal thickness, visual field testing and imaging with the confocal scanning laser ophthalmoscope and high-definition optical coherence tomography (HD-OCT). He performs fundus imaging at an early return exam, where he also obtains additional visual fields and IOP tests to develop an accurate baseline.

“Visual field testing can be the most sensitive indicator of glaucoma, but software analysis gives us a great deal of qualitative data about imaging the retinal nerve fiber layer (RNFL),” explains Dr. Noecker. “So we evaluate IOP and corneal thickness to start. Our devices have evolved to give us normative database comparisons so that we know, for example, if a patient is suspicious, or an outlier, on visual fields or SD-OCT. Information about RNFL thinning, high IOP and other risk factors help us judge what's best for the patient.”

Whether Dr. Noecker makes a diagnosis of glaucoma or not, the patient relationship doesn't end there.

“Patients get referred for a reason, such as a suspicious nerve or family history,” he points out. “Our analysis of the test results determines what we do in the future. If we diagnose glaucoma, then treatment and follow-up are the path we take. But if the patient doesn't have glaucoma, we still follow up with visual field testing and nerve fiber layer images in 6 months, a year, or 2 years—depending on the risk—to make sure he hasn't developed the disease.”

Prostaglandins First

Angelo P. Tanna, MD, Vice Chairman of Ophthalmology and director of the Glaucoma Service at Northwestern University Feinberg School of Medicine, Chicago says, “Among patients with open-angle glaucoma, the only proven means of reducing the risk of progression is to lower the IOP. Also, among patients with ocular hypertension who are at high risk of progression to glaucoma, IOP-lowering therapy should be considered.”

“We have a mandate to lower eye pressure first, and then as patients move into the normal pressure range, we may consider other things such as blood flow and neuro-protection,” says Dr. Noecker. “In most cases, we start patients on a prostaglandin analogue (PGA) because, on average, it's best at lowering eye pressure. It's also safe systemically and easy to take once a day.”

Dr. Tanna points out that although beta-blockers are an option, prostaglandins offer a major advantage. “Beta-blockers lower diurnal IOP very well. PGAs lower IOP during an entire 24-hour period, whereas beta-blockers have no nocturnal IOP-lowering efficacy.”

In addition to IOP-lowering ability, ocular surface considerations are factors in choosing which prostaglandin to prescribe. Because patients with glaucoma are typically older, they're likely to have some dry eye symptoms. Over-the-counter and prescription drugs may exacerbate the problem, as do any other challenges to the eyes, such as surgery or injections for age-related macular degeneration. Even younger glaucoma patients may be using allergy drops, artificial tears or topical cyclosporine.

Long-term use of drops preserved with benzalkonium chloride (BAK) can increase dry eye discomfort. Some prostaglandins use a gentler preservative, which helps keep the ocular surface clear and calm over time.

E. Randy Craven, MD, principal of Specialty Eye Care in Denver, Colo., and associate clinical professor of ophthalmology at Rocky Vista University in Parker, Colo., weighs BAK and several other factors when choosing a prostaglandin.

“I consider each patient's tolerance for redness, and if red eyes would drive them crazy, then I use latanaprost or bimatoprost 0.01% because they cause less redness than other options,” he explains. “Patients' insurance guidelines are important, since they may dictate which medication is covered. The factor that ideally should be first is efficacy of the drug, and it is possible to achieve that efficacy with a BAK-free prostaglandin if patients are sensitive to the preservative.”

Options and Additions

Despite their advantages, prostaglandins are not for all patients. “They should be avoided in patients who have an iris that is susceptible to color change and who are unwilling to accept that risk. Increased lower eyelid skin pigmentation and conjunctival hyperemia may also limit their use in some patients. Laser trabeculoplasty or beta-blockers may be reasonable alternatives,” Dr. Tanna says.

Dr. Tanna uses PGAs with caution in patients who are aphakic or pseudophakic or if there is an open posterior capsule that puts the eye at risk for the development of cystoid macular edema. The same applies for patients with a history of uveitis because, although they've been shown to be mostly safe and effective in such cases, there is a risk of exacerbation of uveitis. Additionally, there may be an increased risk of reactivation of herpetic keratitis, particularly if patients aren't receiving prophylactic anti-viral therapy.

Medications such as beta-blockers also can be added to prostaglandin therapy. “If we wanted an 8-mm reduction and the patient got 5 mm, we may add a beta-blocker, an alpha agonist, a topical carbonic anhydrase inhibitor (CAI), or a combination drug,” Dr. Noecker says. “We also can switch within the prostaglandin class. But if a patient doesn't tolerate the prostaglandin or the medication isn't effective, we need to go with something else.”

Follow Up

Once patients begin therapy, practitioners generally wait 4 to 6 weeks (depending on the disease severity) to have the patient return to evaluate how well the medication is working. If the pressure is in the target range, then the next visit may be in 4 to 6 months.

“Pressure can drop precipitously to start, and it takes about a month to find a steady state that tells us if the medication is working. Since it takes about a month for the medication to leave the system, that month-long follow-up wait is the same whether we're adding or removing a medication,” Dr. Noecker says.

That visit is short, Dr. Noecker says, because he just needs to check the patient's tolerance of the medication, determine if the patient is experiencing side effects, and see if the medication is lowering the IOP as intended.

“With a prostaglandin, I'm checking for eye redness, as well as for darkening of the skin, which sometimes occurs when a patient uses too much medication and it runs onto the skin. For beta-blockers, I want to see if there are any breathing problems, general fatigue, a slow heart rate or reduced blood pressure. Alpha agonists can make thin people lightheaded or drowsy, and CAIs can cause stinging and irritation,” he explains.

Need for Surgery

Ophthalmologists have several surgical options, but when should you consider surgery? “It depends on the patient profile,” says Dr. Noecker. “We start with medication because the side effects generally are reversible and low risk, but sometimes if treatment fails or there are compliance problems, we consider surgery. Non-incisional surgery—laser trabeculoplasty—is often a first choice.”

Dr. Tanna also favors medical or laser therapy (laser trabeculoplasty) prior to incisional surgery. “Trabeculectomy is the most commonly utilized surgery in eyes that haven't had previous surgical procedures that cause conjunctival scarring. However, in eyes with such scarring or in eyes with active inflammation, evidence generally supports the use of an aqueous drainage device surgery instead of trabeculectomy.” Regarding the use of endoscopic cyclophotocoagulation combined with cataract surgery, Dr. Tanna cautions, “The theoretical short- and long-term risks aren't justified in a patient who is medically controlled.”

Although these reasons to consider surgery are shared by Nathan Radcliffe, MD, he finds that in practice, failure with prostaglandins is a red flag. He explains, “The prostaglandin analogue class of medications is so effective that a patient who breaks through on this therapy should probably be considered for surgery.”

New Surgical Options

According to Dr. Radcliffe, an assistant professor of ophthalmology and director of the glaucoma service at Weill Cornell Medical College and New York-Presbyterian Hospital in New York, the three primary options for incisional surgery are standard trabeculectomy, trabeculectomy with the Express Glaucoma Filtration Device (Alcon) or a glaucoma drainage device such as the Baerveldt tube shunt. Dr. Noecker adds canaloplasty (not a full thickness incision) and ab interno shunts such as the CyPass glaucoma shunt (Transcend Medical) options. In the future, devices from Glaukos and others may provide new treatment alternatives.

“Trabeculectomy has been our first choice, and we've generally reserved the Baerveldt tube shunt as a later option because options may be more limited after a Baerveldt device fails,” he explains.

“But I was impressed recently by a report by Good and Kahook¹ that demonstrated patients with the Express drainage device implantation required fewer postoperative visits and recovered faster than patients who had standard trabeculectomy. For some patients, this shunt is probably preferable to standard trabeculectomy.” (See “Surgical Interventions” of this issue.)

Dr. Tanna agrees. “Canaloplasty may be ideal for someone who needs pressure control in the mid-teens, since it can achieve this without necessarily requiring formation of a bleb, which carries a risk of future infection, leaks and hypotony,” he says. “But canaloplasty and some of the new trabeculecular bypass procedures typically don't get patients to the low teens, which is sometimes required for stable control of their glaucoma.”

Dr. Tanna also points out that cataract extraction alone, on average, has an IOP-lowering effect. “This is an important factor to keep in mind when interpreting the results of studies that purport to demonstrate the efficacy of an IOP-lowering treatment that is combined with cataract surgery. In eyes with open angle glaucoma, cataract surgery should not be used with the primary goal of lowering IOP,” he says.

Management After Surgery

Once the patient has recovered from surgery, eyecare practitioners continue to manage glaucoma patients the same way, regularly evaluating the IOP and monitoring for progression in the visual field and RNFL. But first, patients need a whole new battery of tests.

“After you've done an incisional surgery and impacted the IOP, you need to reset your baselines,” explains Dr. Radcliffe. “Obtain a visual field and choose new tests to act as your baseline to determine how the patient is progressing after intervention.”

Reference

1. Good TJ, Kahook MY. Assessment of bleb morphologic features and postoperative outcomes after Ex-PRESS drainage device implantation versus trabeculectomy. Am J Ophthalmol. 2011;151:507-513.

Keys to Diagnosis and Monitoring

Technology brings sensitivity and qualitative data to tests of structure and function.

Glaucoma is a chronic disease, one that eyecare practitioners and their patients manage together for many years. Today's highly sensitive testing technologies have the potential to help diagnose glaucoma early, as well as the sensitivity to detect the most minor changes in visual fields or retinal nerve fiber layer (RNFL). As technology improves, it gradually enhances the doctor's ability to make a diagnosis and prognosis, and helps guide key decisions about therapy.

Multiple-test Baselines

It's impossible to predict future disease progression at an initial referral appointment, points out Nathan Radcliffe, MD. When Dr. Radcliffe first sees a glaucoma suspect, he asks himself what information he can collect that day to give him an advantage down the line.

“Traditionally, we sought to diagnose glaucoma by comparing patients to normative databases, but a more accurate way is to use today's software to compare patients to themselves over time,” Dr. Radcliffe says. “It's an ideal strategy because many patients aren't within the normal range and have not had normal anatomy since birth. Defining glaucoma as change over time is more specific than defining it as different from normal.”

Based on this definition, effective diagnosis and progression analysis require repeat visits.

“An adequate baseline assessment really consists of high-quality optic disc photography, two good, reliable perimetric evaluations and several OCT optic nerve measurements,” says Dr. Radcliffe. “That's important because results can fluctuate, especially given the learning curve with visual field testing. I want a second field within a few months of the first, then the Visual Field Index (VFI, Carl Zeiss Meditec) software lets me merge those two fields for a baseline.”

Dr. Radcliffe may not always obtain a second visual field or OCT scan right away, but he typically has suspects return a few months later to repeat baseline testing. They understand the necessity.

“I explain that we need to make an initial investment in getting quality information, and they understand that one look on one day is not enough. We need solid, reliable baseline data to confidently detect a change down the road.”

Setting a Target IOP

“We use the disease stage, the baseline IOP, overall health and anticipated longevity to formulate a target pressure,” says Angelo P. Tanna, MD. “Of course, determining an accurate assessment of baseline and follow-up IOP means checking IOP on different days and at different times of the day.”

“Generally, I'm looking for an IOP reduction of 30% from baseline, and if we're not achieving it, we may need to change therapies,” explains Robert J. Noecker, MD, MBA. “I also want to know if the patient has experienced vision changes, and of course we follow up the whole range of testing to look for changes.”

Dr. Noecker says that because it's very difficult to detect change over a period of less than 6 months, he has most of his glaucoma patients visit twice per year if they appear to be stable.

E. Randy Craven, MD, says he takes an individualized approach to determining the frequency of patient visits. “It's based on the level of disease and how well it's controlled. I see well-controlled patients with no damaged structure for monitoring once per year. If visual field testing makes me concerned about progression, I see the patient every 3 or 4 months, but I might see a patient with significant elevated pressure who is at risk for damage every month.”

Tracking Visual Fields

Glaucoma progression can be detected in a number of different ways based on changes to structure and function. Visual field testing is very sensitive and often detects changes in vision that the patient does not perceive. As an indicator of glaucoma progression, it has both stand-alone power and the right characteristics to help correlate structure and function.

“It's not easy to see structural changes, and we commonly see them before we see visual field damage. I have seen either structure or function damage precede the other. Visual fields are still our primary way to detect progression,” Dr. Craven says.

Dr. Tanna obtains visual fields for most mild to moderate glaucoma patients annually, while Dr. Radcliffe tries to obtain them from one to three times per year, depending on the patient's progression risk and disease severity.

Dr. Craven points out the benefits of getting visual fields from multiple devices. “I think it's helpful to switch between visual field technologies because a patient's ability to perform a test varies from perimeter to perimeter,” he says. “It can be surprising to see how much better a patient does when you switch perimeters.”

No matter how frequently you test or which test you use, key software features put it all in perspective.

• Visual Field Index (VFI): This measure of visual field loss ranges from 0 to 100%, where 100% is a perfectly normal field. Software analyzes pattern deviation and total deviation, determines which points in the test are abnormal, and weights abnormal points based on location (central weighted more heavily than peripheral) and arrives at a score that tells the clinician the patient's percentage of age-matched visual field remaining.

“The VFI gives you an idea grossly of how much of the field has been lost, as well as what pattern loss has occurred,” says Dr. Craven. “It is an age-adjusted index of the overall sensitivity. The VFI can be plotted and checked against prior VFIs to get an idea of stability or progression. We know that if a patient has a VFI in the 80s or 90s, then the brightness of the field is pretty good. A score in the 70s or 80s means there's some loss, and the 60s indicate moderate loss. We can look at how much loss is average or normal based on age.”

• Guided Progression Analysis (GPA): The GPA printout for the Cirrus HD-OCT (Carl Zeiss Meditec) and the Humphrey Field Analyzer (HFA II-i, Carl Zeiss Meditec) includes a linear regression plot, which is expressed in terms of the patient's age. For example, if the patient is 53 years old and has been undergoing visual field testing since age 48, GPA will plot her VFI on the HFA for 10 years: age 48 to age 58. Linear regression analysis determines how much age-adjusted visual function that patient is losing per year and shows the doctor how much additional decline could occur if current trends continue.

“If GPA shows likely progression, but the VFI slope is very shallow, then the patient has gotten a little worse over a long time. She might not have symptomatic vision loss at this pace for 20 years—a problem for a 50-year-old patient, but less of a problem for an 85-year-old patient,” Dr. Tanna says. “The goal is to maintain visual function for a lifetime, so slow progression for the 85-year-old patient may not justify the risks of advancing therapy. On the other hand, a rapid and alarming 10% progression per year in the VFI would require major intervention, even in an 85-year-old if she were fairly healthy.”

Detecting Structural Change

RNFL examination using HD-OCT offers a more highly detailed image than practitioners had in the past, allowing doctors to look carefully at contours and thicknesses. Rather than comparing images side by side, doctors can see baseline images with perfectly registered serial images superimposed. This makes detecting small changes in the RNFL easier, and the software quantifies changes such as RNFL loss at high resolution.

Dr. Radcliffe uses the Cirrus HD-OCT, which has GPA software that helps him see what's happening now and what may happen in the future.

“GPA looks at the RNFL thickness map over time. The baseline is made up of two images taken on different days to account for inherent variation, and then GPA incorporates as many follow up tests as you provide. The report displays the baseline thickness circle scan values, superimposed by follow-up values,” Dr. Radcliffe explains. “The map presents deviation from baseline, as well as RNFL thickness plotted against age, similarly to the visual field GPA. We can see whether the overall thickness is stable. We also can see if the patient is changing in a very specific location, which we can then check against visual field changes.”

Dr. Tanna also uses OCT to correlate structural and functional changes in patients with glaucoma.

“If I see visual field progression on just one test, it might take a while to repeat the test and verify that the progression is real, as opposed to a bad test or random fluctuation. But if a structural test such as OCT also demonstrates structural changes that correlate with the functional change, then I have sufficient evidence to confirm progression with greater confidence and speed than I would with visual field testing alone,” he says. “If I confirm visual field progression in the absence of evidence of structural change, then I may lower the target pressure and advance therapy on that basis alone. If the reverse happens (structural change on the basis of imaging data) without visual field progression, that doesn't trigger a change in therapy. I usually watch those patients more closely, but I generally don't change therapy as long as they're at or below the target pressure.”

Vision and Tenacity

Tracking glaucoma progression is often a decades-long process. Follow-up intervals and testing practices vary from practitioner to practitioner, but the basic principles are the same. Start with solid baselines established at multiple visits, schedule follow-up visits based on risk and severity, and use the visual field and imaging technologies to get a highly sensitive picture of the trend.

“When visual field and OCT change together, it gives us a lot of confidence, but that isn't always the case,” Dr. Noecker says. “By tightening up surveillance, we can detect marginal cases and minor changes, make effective decisions about therapy, and make our decisions earlier instead of waiting for major loss of vision or RNFL. We've really expanded our knowledge to encompass the quality, rather than just the quantity of structure and function.”