Early Detection Betters the Odds

Early glaucoma diagnosis can get you a jump on treatment, but it takes more to deliver optimal care.

BY DIANE DONOFRIO ANGELUCCI, CONTRIBUTING EDITOR

A number of clinical trials indicate that early diagnosis is essential in arresting glaucoma and reducing the need for more intensive therapy. In this article, glaucoma experts share their opinions about early glaucoma detection and discuss how to fine-tune diagnosis, assess progression and use this information to optimize outcomes.

Value of Early Detection

"The bottom line is, the worse the glaucoma is when it's detected, the more likely it is that the disease will progress," says Joel S. Schuman, M.D., F.A.C.S., Eye and Ear Foundation professor and chairman of ophthalmology, University of Pittsburgh School of Medicine. "And the rationale for early detection is to be able to treat less intensively over the course of the disease in order to prevent disease progression, so that less intensive therapy is required when the disease is discovered earlier in its course."¹

"In the Ocular Hypertension Treatment Study [OHTS], the treated patients had half the risk of developing early glaucoma," says Jonathan S. Myers, M.D., associate attending surgeon, Glaucoma Service, Wills Eye Institute, Philadelphia. "In the Early Manifest Glaucoma Treatment [EMGT] study, with even mild treatment patients were shown to be less likely to go on to develop significant glaucoma."

Nevertheless, others question whether the benefits of early detection are clear-cut. "We have some large health-care systems — the Canadian system and even Medicare — wondering about the cost-effectiveness of screening for early glaucoma because of lack of consensus of methods, high false-positive rates even in high-risk populations and lack of follow-up after screening," says Adam C. Reynolds, M.D., Intermountain Eye Centers, Boise, Idaho. Two theories suggest why early diagnosis is important, he says: One is that severe disease is harder to control, and the second is that, with longer life spans, disease can present a serious problem later in life if it is not detected earlier and treated more aggressively earlier.

Figure 1. Cupping of 0.6 c/d in a glaucoma patient. Optic nerve evaluation is more compelling than IOP evaluation alone in initial detection of glaucoma.

However, he says, some research has questioned whether in the long run early detection is cost-effective because the disease in general is very slow to progress, most patients do not suffer severe vision loss and ophthalmologists do not currently have effective ways to sort out who needs more aggressive treatment when identifying a patient with early disease.

Dr. Myers, on the other hand, maintains the importance of detection of those with actual glaucoma, citing multiple studies, including one by Hattenhauer et al. at the Mayo Clinic, reporting that over a 20-year period, the risk of bilateral legal blindness from glaucoma was 27% in one eye and 9% in both eyes.² "For every patient who becomes blind from glaucoma, there are many more patients who may not be legally blind but whose daily living is affected by their disease," Dr. Myers says. "So, once true disease is established, early treatment in those at long-term risk may be crucial. We don't know yet what the long-term implications are of allowing progression before initiating therapy. Of course, the intensity of the treatment must be tailored to the patient's level of risk."

"OHTS showed that early treatment prevents or delays the onset of glaucoma, the EMGT showed that lowering pressure in newly diagnosed glaucoma patients slowed visual field loss, and almost every long-term study is showing a measurable benefit to treatment," says Robert D. Fechtner, M.D., professor of ophthalmology, New Jersey Medical School-UMDNJ, Newark, N.J. "There can't be any remaining question that, on average, treatment is helpful. We now need to focus down on the individual, to find those who will most benefit and pick the best treatments for them."

Ike Ahmed, M.D., University of Toronto, says early recognition of progression rate is probably more important than early detection. If ophthalmologists can determine a patient's progression rate, that can provide a clue as to how aggressively the patient should be treated, he says.

"If we detect someone early who will have very slowly progressive glaucoma, they might see very well for their entire lifetime with minimal or no intervention," Dr. Fechtner says. "On the other hand, if we detect someone early and we document what I would call ‘fast glaucoma,’ this is someone who may need very aggressive early intervention."

Pinpointing Disease

Despite the variety of technologies available, early diagnosis can be a challenge. "Detecting and verifying early glaucoma is probably one of the hardest things glaucoma specialists do," Dr. Reynolds says.

"A high pressure has been emphasized for so long that oftentimes clinicians will utilize pressure as their screening tool," says Douglas Rhee, M.D., assistant professor, Harvard Medical School, Massachusetts Eye & Ear Infirmary, Boston. "And what the screening tool should really be is the optic nerve exam (Figure 1). We know from the Baltimore Eye Study and numerous other studies that low-tension glaucoma or glaucoma that occurs with pressures less than 21 can account for up to 30% to even 40% of glaucoma in American populations. … and you could potentially miss that if you're only thinking about the pressure."³

Early diagnosis begins with a complete history and ophthalmic examination, including gonioscopy to examine the angle structures, Dr. Rhee says. If glaucoma is suspected, he recommends obtaining central corneal thickness, achromatic automated visual field test and optic nerve imaging with photos to monitor the patient over time. The Heidelberg Retinal Tomograph (Heidelberg Engineering, Vista, Calif.), optical coherence tomography (OCT), such as with the Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, Calif.) (Figure 2), and the GDx nerve fiber analyzer (Carl Zeiss Meditec) also may detect glaucoma before change is observed on the visual field, he says. In addition, the Retinal Thickness Analyzer (RTA, Marco, Jacksonville) may work for this application. Frequency-doubling perimetry and SITA-SWAP (Carl Zeiss Meditec) have been shown to be able to detect visual field changes before automated achromatic field testing, Dr. Rhee says. "I utilize both the SWAP and the anatomic imaging in early suspected cases to try to see if they have detectable damage that isn't seen on the automated achromatic, white on white."

Figure 2. Retinal nerve fiber layer (RNFL) imaging with the Cirrus HD-OCT (Carl Zeiss Meditec). Right eye shows glaucomatous RNFL loss, but the left eye is within normal limits.

"I think both structural and functional tests are needed to diagnose glaucoma early," says Linda M. Zangwill, Ph.D., professor, Department of Ophthalmology, Hamilton Glaucoma Center, University of California, San Diego. "OHTS and the European Glaucoma Prevention Study both had structural and functional endpoints in their studies and they both found that you need both — that in some people the first sign of glaucoma was a visual field defect and in others the first sign of glaucoma was a structural defect, and in those studies it was based on stereo photography."

Dr. Schuman agrees that both structural and functional evidence is important. "We do get false positives with imaging technologies, whether it's the HRT, GDx or OCT — any of them can give you a false positive," Dr. Schuman says. "You can have artifact that affects the results of those tests, giving you a false positive, so you are really better off if you're able to put all of the pieces together, and by that I mean visual field, assessment of the optic nerve clinically and also by imaging."

Despite available technology, clinicians still should emphasize the clinical exam, Dr. Reynolds says, because ophthalmologists can see changes that current technology cannot. "We don't give ourselves credit sometimes for the effectiveness of doing careful clinical exams of optic nerves, considering the entire medical context of a given patient, then putting that together with what's going on with our diagnostic tools, especially in terms of progression. We really need to be looking at the nerves of these suspect patients carefully every time they come in and not just rely on the technology," he says.

Screening may play a role in early detection, Dr. Myers explains, but tests may pick up more false positives than true positives in unselected populations. "The most effective way to pick up early glaucoma in the screening sense often is for a clinician to say to the glaucoma patient that any first-degree relative of his needs to be seen on a yearly basis because he is at increased risk," he says.

How Early Detection Affects Management

Early detection and monitoring help ophthalmologists refine their treatment, Dr. Ahmed says. "How aggressive do we need to be? Do we need to lower pressure to a lower target? So this is where it gives us the confidence in making those decisions. In the past, when we didn't know if someone had glaucoma or we didn't know how fast it was progressing, we were very much relying on more indirect decision-making processes."

"When I evaluate patients, I try to in some way assess their risk of having a visual disability during their lifetime," Dr. Fechtner says. "I'm not going to speak to early detection — if I see a patient who is progressing in a measurable way over the first few years I know them, it's fast glaucoma and it suggests that either the treatment is not sufficient or that this is a patient who may not do well in the long run."

Glaucoma type also influences management. "Both acute and chronic angle-closure glaucoma can be much more episodic and dramatic in its progression," Dr. Myers says. "People with exfoliation syndrome — another type of open-angle glaucoma, which is not at all uncommon in people of northern European ancestry — typically have a much more abrupt onset and often much quicker progression."

"With periodic regular monitoring of the glaucoma patient, you can initiate therapy as soon as progression is detected," Dr. Schuman says. When patients have stable glaucoma, he usually examines and tests them every 6 months. "If change occurs and I can confirm it, then I will advance therapy," he says. "I think that's a critical point. When we first see a patient and make a diagnosis, we set a target intraocular pressure based on population data from the literature based on the degree of that person's glaucoma damage. But after that point we need to adjust that target pressure based on that individual patient's course."

Monitoring Patients

A variety of techniques are available to measure progression, including clinical examination with documentation; visual fields (that may include progression software); and imaging technology (that may include progression software). "There are many different tools available," Dr. Zangwill says. "It is important that both structural and functional examinations are completed."

The current standard in assessing progression is optic nerve examination and visual fields, Dr. Rhee says. However, once a defect is seen on achromatic automated testing in early through moderate glaucoma, visual field testing is most often the method by which progression is first detected, as was seen with the EMGT and Advanced Glaucoma Intervention Study. "I believe that further research is needed to demonstrate that the newer technologies are able to detect progression earlier," he says.

"Once you know that a patient has glaucoma, it's critical to assess whether or not they're getting worse, and that's very hard to do with a visual inspection of the optic nerve," Dr. Schuman says. "It's possible, but it's difficult, and so for that we use visual field testing and we also use imaging." After imaging, he says, "You can then look also at functional testing like visual fields to determine whether you have a structure-function match. I do like to put together structure and function whenever I can, although the two may not progress simultaneously, so you may see progression on one and not on the other," Dr. Schuman says. "And that sort of drives you back to the patient. You have to consider the whole picture, and unfortunately you can't just take any one of these parameters in a vacuum."

Dr. Reynolds says ophthalmology is still scratching the surface in assessing progression, especially in using new technologies. "There have been numerous updates of machinery and software, and this makes things difficult because you've got to look at progression trends over 5 to 10 years," he says. "We just don't have the data yet, and this is a particularly important area to have good data, to prove the utility of these newer technologies to identify progression in early disease before visual fields become abnormal."

Improving Outcomes

"I think that early detection is good," Dr. Ahmed says. "We need to look at it in the context of the patient — in terms of age and other clinical issues — and I would say that early detection does not mean early or more aggressive treatment necessarily. What's probably more important than early detection is early recognition or early documentation of the rate of progression. I can't emphasize that enough. We need to be able to determine how fast someone is getting worse because those are the patients that really need our help, not the ones who may have glaucoma at an earlier stage."

In addition to assessments, family history is an important key in early detection. "One can very efficiently and easily increase the detection of early glaucoma in people who might not otherwise have been picked up by recognizing this: that if a patient on history tells you that he has a family member with glaucoma, that his nerves should be looked at more closely," says Dr. Myers. Further, he urges physicians to encourage patients who have glaucoma to bring their family members in for examination. OM

References

1. Grant WM, Burke JF Jr. Why do some people go blind from glaucoma? Ophthalmol. 1982;89:991-998.

2. Hattenhauer MG, Johnson DH, Ing HH, Herman DC, Hodge DO, Yawn BP, Butterfield LC, Gray DT. The probability of blindness from open-angle glaucoma. Ophthalmol. 1998;105:2099-2104.

3. Tielsch JM, Katz J, Singh K, Quigley HA, Gottsch JD, Javitt J, Sommer A. A population-based evaluation of glaucoma screening: The Baltimore Eye Survey. Am J Epidemiol 1991;134:1102-1110.

Editor's Note: Drs. Ahmed and Fechtner are consultants for Carl Zeiss Meditec. As an OCT inventor, Dr. Schuman receives royalties from Massachusetts Eye and Ear Infirmary for intellectual property licensed by Massachusetts Institute of Technology to Carl Zeiss Meditec; he received research support from Carl Zeiss Meditec, Optovue and Heidelberg; and he receives research funding from the National Institutes of Health. Dr. Zangwill's department receives equipment donations from Carl Zeiss Meditec, Heidelberg, Nidek and Optovue. Drs. Myers, Rhee and Reynolds have no financial interests related to this article.