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Enhancing Glaucoma Management
A Marriage of Structural and Functional Analysis.
BY IKE K. AHMED, M.D., F.R.C.S., D.A.B.O.

Structural and functional analyses have long been utilized in glaucoma practices to diagnose and manage glaucoma. The primary difficulty in truly marrying these two assessments, however, is in understanding the benefits and role each should play in helping to manage a patient across the glaucoma continuum. Today, the primary challenges practitioners face are diagnosing the disease early and clearly monitoring progression, so the most effective and correct treatment can be applied.

Several advanced tools are available for glaucoma detection and management that assess either the structure or function of the eye. Ultimately, combining strategies ensures that physicians are obtaining the most comprehensive information about the eye and can achieve optimal outcomes for glaucoma patients. This article will address the productive use of combined strategies.

The Glaucoma Continuum

As the local loss of the nerve fibers reaches more than 25%, early visual field changes may occur. Standard Automated Perimetry (SAP) has long been a mainstay of glaucoma diagnosis and management, but optic nerve damage is known to precede visual field loss associated with glaucoma. However, early structural abnormalities in the optic nerve and in the retinal nerve fiber layer can be difficult to discern. Many "normal" patients have an unusual or anomalous optic nerve head or a suspicious visual field, so we cannot assume that a single defect points to a glaucoma diagnosis.

For instance, elevated IOP is a major risk factor, but not a diagnostic characteristic. Routine measurement of IOP as a screening test is ineffective, considering many patients have ocular hypertension and never develop glaucoma, and many glaucoma patients present with normal intraocular pressures. Interestingly, IOP happens to be the only treatable risk factor. In fact, in certain patients, lowering IOP has been shown to be effective in slowing progression through the glaucoma continuum, as demonstrated consistently in several studies, such as the Ocular Hypertension Treatment Study (OHTS), the Early Manifest Glaucoma Trial (EMGT) and the Advanced Glaucoma Intervention Study (AGIS). Lowering IOP even a small amount at an early stage can help practitioners preserve patient vision.

The integration of diagnostic methods holds the potential to improve outcomes in the glaucoma clinic. Earlier diagnosis leads to earlier treatment. In the past, physicians did not treat patients with early-stage glaucoma because there was no way to easily identify them. Now, by monitoring optic nerve damage as one of the first signs of glaucoma, physicians are creating an earlier opportunity to treat these patients.

In the end, no single test can definitively detect the presence or progression of glaucoma. Each test provides different – not necessarily better or worse – information, and combined together the information helps "bring out the defect," so practitioners can make a more accurate diagnosis and treatment recommendation. Although the choice and aggressiveness of therapy will always be a matter of individual clinical judgment, new technology makes it easier to gather the relevant patient data earlier and more accurately than previously possible.

New Tests Aid in Earlier Diagnosis

Visual field testing has been the gold standard for evaluating function and has served as the first line of defense. However, by the time defects are detected, significant and irreversible damage may have already occurred. Considering the need for more aggressive treatment in more advanced disease, it is obvious that earlier treatment is beneficial.

As a result, there has been a significant need to improve methods of evaluating the visual field. The eye is "smart" and can compensate for minor changes. It is also redundant, and diagnostic instruments must be highly sensitive and capable of recognizing small, less obvious changes.

There are serious limitations to SAP. These tests have low reproducibility, and patients – particularly the elderly who are at greater risk of glaucoma – have difficulty performing the test accurately. Because of the well-known learning curve, initial visual defects are often not repeatable on subsequent exams. By the time a reproducible visual field defect is detected, 20% to 50% of the RNFL can be damaged.

Today, newer perimetric tests are designed to recognize damage earlier by detecting visual field loss 3 to 5 years before standard perimetry and have been shown to have greater reproducibility.

Three systems are worth considering for the practice interested in fully leveraging glaucoma technology. The first is short wavelength automated perimetry (SWAP), also called blue-yellow perimetry. By focused testing of the low number of blue cones, SWAP leverages the principle that blue-yellow perimetry is more sensitive to glaucomatous loss at a much earlier point in the damage of the ganglion cells than standard perimetry.

To accelerate test time, Swedish Interactive Thresholding Algorithm (SITA) has now been combined with SWAP to enable blue-yellow testing in about one third the standard time. Bringing test times to reasonable levels increases patient compliance with the test, while still maintaining high levels of accuracy in the results. The SITA SWAP combination allows practitioners to detect glaucoma earlier, faster and more accurately than traditional methods.

Frequency doubling technology (FDT) has shown tremendous application and seems to have a less steep learning curve. FDT assesses visual field loss by targeting a subset of retinal ganglion cells in the magnocellular pathway. Patterns of flickering black and white bars trigger a reaction in these cells, creating the perception that twice the number of bars is actually present. Researchers have demonstrated this subset of retinal ganglion cells to be the earliest of the cells damaged in glaucomatous loss; combined with the low redundancy in these cells, early detection becomes possible.

Expanding on SAP's definitive role in the management of glaucoma, Humphrey Glaucoma Progression Analysis (GPA) Software (Carl Zeiss Meditec, Dublin, Calif.) helps practitioners accurately identify clinically significant progression of visual field loss in glaucoma patients. The GPA highlights any changes from selected baseline exams that are larger than typical clinical variability and provides simple plain-language indicators whenever changes show consistent and repeatable patterns of loss. The software analyzes a series of visual field exams. The analysis corrects for ocular media effects in order to help the practitioner differentiate between localized loss typical of glaucoma, and overall depression.

Complementary Information

Clinical studies, such as the OHTS1 and Baltimore Eye Survey,2 have made it clear that structural assessments are critical in the glaucoma clinic. Structural exams help facilitate an earlier diagnosis, eliminate the need for more difficult diagnostic tests and answer the question: whom do we treat and when?

According to the Baltimore Eye Survey, RNFL damage may occur up to 6 years before a patient develops detectable visual field changes,2 and according to OHTS, 50% of glaucoma patients with ocular hypertension have optic nerve changes without accompanying visual field loss.3 Taking these structural changes into account, the diagnosis and management of glaucoma must incorporate assessment of the optic nerve and RNFL into the glaucoma work-up.

In recent years, new technology has emerged to permit objective, reproducible measurements of the optic nerve structures. This structural information complements perimetric tests and helps practitioners gain a more complete picture.

Although optic nerve examination is a well-established protocol, RNFL examinations can extend our assessment capabilities. It is well known in the clinical practice that RNFL defects are very early signs of glaucoma.4 As a result, observation of the RNFL holds great promise for early diagnosis, as well as measurement of glaucoma progression. Retinal nerve analysis instruments such as the Heidelberg Retina Tomograph II (Heidelberg Engineering) and the GDx Scanning Laser Polarimeter and the Stratus OCT (both Carl Zeiss Meditec) aid in this evaluation.

A Match Made for Management

What is the benefit of marrying structure and function? Because half of the glaucoma population is unaware that they have the disease.5 It is clear that glaucoma is under-treated. Today, instead of grappling with whether structural or functional tests are the ideal approach, the practitioner must recognize that a true integration of both strategies can lead to more accurate detection, earlier diagnosis and better long-term management across the glaucoma continuum, ultimately preserving vision into the future.

Ike K. Ahmed, M.D., is a fellowship-trained glaucoma, cataract, and anterior segment surgeon practicing in Toronto, Ontario. He is an assistant professor at the University of Toronto, and a clinical assistant professor at the University of Utah.

References

1. Gordon, MO, Kass MA and the Ocular Hypertension Treatment Study (OHTS) Group: The Ocular Hypertension Treatment Study: Design and baseline description of the participants. Archives of Ophthalmology. 1999, 117:573-583.

2. Sommer, A., "Glaucoma risk factors observed in the Baltimore Eye Survey," Current Opinion in Ophthalmology. 1996;7:93-98.

3. Gordon, MO, Kass MA and the Ocular Hypertension Treatment Study (OHTS) Group: The Ocular Hypertension Treatment Study: Design and baseline description of the participants. Archives of Ophthalmology. 1999, 117:573-583.

4. Tuulonen A, Airaksinen J. "Polarimetry of the retinal nerve fiber layer," Current Opinion in Ophthalmology. 1996;7:34-38.

5. Prevent Blindness America, "Frequently Asked Questions About Glaucoma," www.preventblindness.org