Article Date: 12/1/2008

Using Advanced Technology to Revolutionize Glaucoma Diagnosis and Treatment

Using Advanced Technology to Revolutionize Glaucoma Diagnosis and Treatment

Learn how the latest advances in digital imaging help detect structural damage earlier and more accurately for better patient management.

By John E. Warren, OD

The definition of glaucoma and the way we diagnose it has changed dramatically over the last decade. Much of the change is a result of technological advances that have allowed us to gain a better understanding of the ocular structures affected by glaucoma. Until computer software became sophisticated enough to analyze the data collected by emerging imaging techniques, we were able to only examine and photograph the ocular anatomy. Now, we have the ability to measure structures in the posterior segment and view them in cross section, as well as see inside the structures with virtual anatomical reconstructions.

We can document, measure and analyze the structures involved in glaucoma, such as the optic nerve, retinal nerve fiber layer (RNFL) and macula. New technology allows us to detect structural damage earlier and more accurately, as well as pinpoint and document change in these structures over time. Not only can we detect and diagnose glaucoma earlier, but we can objectively measure glaucomatous change in these structures as the disease progresses.

One of the more difficult aspects of early glaucoma detection and diagnosis is deciding which patients are glaucoma suspects. Historically, there have been several different clinical findings along with a comprehensive, medical and ophthalmic history that have moved patients from the "not glaucoma suspect" to "glaucoma suspect" category. As technology improves, some of these findings have become less important and some have become more important. The findings now available to primary care clinicians didn't exist in the past.

Clues to Positive Diagnosis

Because structural damage can precede functional vision loss by months or years, one of the first clues a patient may be developing glaucoma can be a change in posterior segment structure. While functional changes, such as visual field loss, give clinicians indications of the presence of glaucoma, if this is the first clinical sign of the disease, the patient already has a moderate-to-severe case that wasn't detected and diagnosed early in the process.

Some of the classic signs that would prompt a clinician to consider further testing or perform a full glaucoma work-up may include:

As one can see from most of the signs on this list, many require very accurate and consistent evaluation and documentation of the optic nerve head and/or nerve head cupping. Unfortunately, the accuracy and consistency of traditional optic nerve head evaluation and documentation doesn't allow for accurate detection of subtle optic nerve and RNFL changes even when the same doctor performs the examination. When more than one clinician is involved in the evaluation and documentation, even more variability is introduced into the analysis.

A better way to detect those patients who may be at risk for glaucoma or who may be in the very early stages of the disease is needed.

Optic Nerve Head Evaluation

The optic nerve is the core of all structural evaluation and analysis in glaucoma. Because of this, it's long been the focus of clinical evaluation and documentation. Considerable overlap exists between normal optic nerves and those of glaucoma patients, especially early in the disease. The classic image of a glaucomatous optic nerve with the bean pot .95 × .95 optic nerve cupping won't be thought of as normal, but many patients exhibit much more subtle appearances early on in glaucoma, which may not be apparent upon typical cursory examination.

Because of this overlap, it's difficult to identify glaucoma patients who have early disease, especially if we're relying on clinician observation and the limits of typical documentation. However, because an optic nerve head evaluation is part of every comprehensive eye examination, it's an obvious finding to determine the potential for glaucoma.

The signs of glaucoma listed earlier include many optic nerve head findings. Let's take a look at some of them.

Asymmetry in optic nerve cupping between eyes. Glaucoma is indeed a disease of asymmetry, in structural changes as well as visual field loss. A significant difference in right eye and left eye optic nerve morphology can indeed be a sign of glaucomatous optic nerve damage. Just how much is significant is open to discussion, but a difference in cupping of .20 or greater between eyes, especially in the vertical cup-to-disc ratio, should be considered a risk factor for glaucoma.

Large amounts of optic nerve cupping upon initial presentation. When the horizontal or vertical cup-to-disc ratio is greater than .60 on initial presentation, glaucoma must be considered a possibility and should be ruled out with further testing. Reviewing past medical records, which include a glaucoma evaluation or work-up that's negative, may be sufficient to reduce concerns about glaucoma.

Vertical cupping is .20 or greater than horizontal cupping. If the vertical cup-to-disc ratio is .20 or greater than the horizontal cup-to-disc ratio, this should raise clinical suspicion. While some optic nerves have an oval shape, which may nullify this finding, an oval cup in a round nerve is a strong indicator of potential glaucoma.

Optic nerve head notching. For many years, optic nerve head notching has been associated with glaucoma, much like vertical elongation of the cup. Optic nerve head notching is one of the observations of the optic nerve head that's easiest to determine, even during a cursory examination of the optic nerve. Clinicians can use previous photographs to evaluate earlier presence of this finding. Without firm proof that this isn't a new finding, a full glaucoma work-up must be performed to rule out glaucoma.

Optic nerve pallor. Pallor of the optic nerve typically occurs in late glaucoma or in other optic neuropathies. The presence of optic nerve head pallor, whether monocular or binocular, must be accounted for clinically and treated as if it's not a finding that occurs in a normal healthy eye. While grading pallor is a totally subjective undertaking, it does have some value, particularly when you're comparing one optic nerve to the other in the same patient.

Superior Digital Imaging

In order to accurately quantify changes in the optic nerve, digital imaging technologies, such as the Retinal Thickness Analyzer (RTA 5, Talia Technology Ltd.), Heidelberg Retinal Tomograph II (HRT II, Heidelberg Engineering, Heidelberg, Germany), or spectral domain and time domain optical coherence tomography (OCT) devices, must be employed. These instruments not only determine the current status of the optic nerve in many quantitative measurements, they also detect if there have been changes in these measurements over time with much more sensitivity than even a well-trained observer. Each of these devices includes a specific method for determining the boundary between the optic nerve rim and the beginning of the cup. The method doesn't really matter as long as it stays consistent from one measurement or calculation to the next. Using these data will help determine early glaucomatous optic nerve changes, typically much sooner in the disease process than if the clinician relies on direct observation and documentation.

In a follow-up report from the RTA 5 (Figure 1), there are red areas on the lower image of the optic nerve. These represent areas where there has been a loss in optic nerve tissue and an increase in cupping. This subtle loss of tissue usually isn't detected by observing, whether working from a typical medical record or from a fundus photograph.

Figure 1. This RTA 5 follow-up report shows a loss in optic nerve tissue and an increase in cupping in the red areas on the lower image of the optic nerve.

RNFL Evaluation

We know the RNFL thins in glaucoma. In moderate to advanced cases of focal glaucomatous damage, clinicians can view these defects with ophthalmoscopy. In early disease, these defects aren't nearly as easy to see and are impossible to quantify. It's difficult for clinicians to produce documentation of these areas of RNFL loss or thinning. Photographs rarely provide adequate imaging of these defects to allow a clinician to determine if the defect has grown in size or depth, and hand-drawn images have obvious limitations.

Fortunately, clinicians can use several technologies that not only detect these early defects but also determine if they've progressed. The RTA 5, HRT II, GDx and OCT devices are all capable of measuring these changes and determining if they've progressed. An image of an RNFL defect (Figure 2) from the RTA 5 features a round depiction of peripapillary retinal thickness that also shows thinning in the corresponding region, confirming the area of thinning radiating from the optic nerve.

Figure 2. This image of an RNFL defect from the RTA 5 shows a round depiction of peripapillary retinal thickness that also features thinning in the corresponding region, confirming the area of thinning radiating from the optic nerve.

Neither the location of the defect further out into the macula, nor the expected location of any corresponding visual field defect can be determined from the peripapillary area of thinning. Clinicians can determine if the defect would be superior or inferior, but whether it will be temporal or nasal or pericentral can't be inferred from only peripapillary thickness data.

Macula Evaluation

Because less overlap exists between the macular thickness of normal and glaucomatous eyes, macular thickness measurements can be helpful in identifying individuals who've lost ganglion cell bodies and their accompanying radiations back to the optic nerve. In order for macular thickness data to be helpful in the detection of glaucoma suspects, the device capturing the data must have adequate data density to ensure that small areas of thinning can be detected. The RTA 5 is one of the devices with such data density. Because the device's data points are all within at least one degree of each other across the entire area of retinal thickness and optic nerve head measurement, it's very unlikely that an area of thinning would fall between data points.

The overall thickness of the macula is rarely the finding that triggers a suspicion of glaucoma. In my clinical experience, patterns of thinning and their location are much more meaningful when looking for early glaucoma or early glaucoma progression. Often, I'll see thinning in the inferior temporal and superior temporal regions of the mapped area, as well as groove-like thinning along the superior or inferior edge of the foveal cone. Superior/inferior asymmetry in the same eye, or asymmetry when compared with the fellow eye, often is an indicator of early retinal thinning due to glaucoma. There are other conditions that can cause thinning, but the location and pattern of the thinning takes on a typical appearance in glaucoma. Just as visual field defects can result from many causes, glaucomatous visual field loss also has typical patterns.

Retinal thickness maps (Figures 3 and 4) show both a normal and a glaucomatous appearance. Notice the superior/inferior asymmetry in the glaucomatous eye.

Figures 3 and 4. Retinal thickness maps from the RTA 5 show both a normal and glaucomatous eye, which has superior/inferior asymmetry. Superior/inferior asymmetry, when compared with the nonglaucomatous fellow eye, often is an indicator of early retinal thinning due to glaucoma.

Identifying Glaucoma Suspects

Because so much overlap exists between normal and glaucomatous eyes, developing a very sensitive yet specific strategy for differentiating between the two is a challenge. As we know, the optic nerve is a structure that we need to monitor for change over time when following glaucoma patients. But the considerable overlap between normal and glaucomatous eyes makes the optic nerve a less than perfect structure to rely on when detecting early structural damage.

The RNFL exhibits less overlap between normal and glaucomatous eyes and may be useful when trying to determine if a patient has early glaucoma. The RNFL, however, doesn't allow us to identify the locus of the damage, just the thinning along the radiations of the RNFL as it moves toward the optic nerve. Smaller areas of subtle loss may be masked more by the surrounding fibers.

The macula has much less overlap than the optic nerve and is an area that exhibits focal thinning (as well as overall thinning) that's much more apparent than the peripapillary RNFL does. Small and focal areas of damage show up quite dramatically on accurate retinal thickness maps and are very hard to miss. This makes the macula one of the best places to examine for signs of early focal damage from glaucoma.

In my practice, we use the RTA Vision Wellness Examination to gather structural data from patients. This provides me with an excellent set of baseline data about the patient's posterior pole (optic nerve, RNFL and macular status). The data isn't analyzed or compared to the device's normative database, so no deviation probability of the optic nerve, peripapillary RNFL or optic nerve is returned or available. I'm able to quickly determine if the patient exhibits any of the typical structural changes that we see in glaucoma (or many other pathologies). This data is available to me for future comparison and for progression analysis at subsequent visits if I perform tests again. Frequently, I'll find patients with early RNFL or macular thinning that I wouldn't have detected for years to come if I were to wait for visible RNFL defects or optic nerve head changes. One of my glaucoma patients was identified with the RTA Vision Wellness Examination in the absence of any of the typical signs of glaucoma (Figure 5.)

Figure 5. The RTA 5 revealed glaucoma in a patient who had no typical signs of the disease.

Because this is a wellness-based test, it's not reported to the patient's major medical carrier. We bill the patient separately for the testing, regardless of their insurance status or clinical findings. If the results call for further examination or evaluation, all future structural analysis is billed with either the code for scanning laser ophthalmoscopy (92135) or fundus photography (92250).

Patients have been very receptive to this testing, and they appreciate the extensive baseline and analytical data it provides. My patients are used to seeing separate charges for specific tests, such as refraction, contact lens services and so on, so this is just another line item on their invoice. Patients rarely hesitate to pay for the testing. In fact, they often tell their friends and family about the tests and the level of care they've received in my office.

Monitoring for Change

Once a patient has been diagnosed with glaucoma, or glaucoma can't be ruled out and they're being followed for change over time, the structure of the optic nerve, RNFL and macula must be followed closely to ensure that any disease progression is detected as soon as possible. In my office, a stable glaucoma patient typically is examined every 6 months. The examination consists of the following:

I'll bill for these services with a primary visit code, which could be an E&M code or one of the ophthalmic codes: 92083 for the visual field, and either 92135 (once for the right eye and once for the left eye) or 92250. Because the RTA provides a high-resolution fundus photo and scanning laser ophthalmoscopy data, clinicians can choose either procedure code to accurately report the service. Typically, I'll use 92135 and 92250 at alternate visits to minimize reimbursement issues and speed payment.

Other diagnostic tests, such as gonioscopy, refraction and pachymetry, are performed as needed but not at every visit. This exam protocol provides me with all of the information I need about my patient to ensure detection of any disease progression on a subjective and objective level. Because structural change frequently precedes a repeatable functional change or loss, I prefer to have the structural imaging information at each exam. Over the last 6 years of using structural analysis in my clinical practice, I've had many patients manifest structural progression 6 to 12 months before their visual fields showed progression. Knowing this allows me to intervene once I know there's been a structural change — whether the visual field has caught up to the structural change or not. Once visual function is lost, it can't be restored.

This begs the question: How much structural change warrants a modification in treatment? Much like visual field analysis and progression, this answer may require you to employ more art than science. We're seeking patterns of structural change or thinning. The appearance of new areas of thinning in the macula is a primary concern as this indicates a new region of damage, which will result in a new area of visual loss if the damage is allowed to become severe enough. This doesn't mean that every small area of minimal thinning results in a treatment change, but it gives me an additional area of damage to monitor. An increase in thinning or an enlarging of a previous area of thinning is also cause for concern. I rely on the progression probability on the follow-up report to tell me how likely an area is to have thinned. The darker the color blue in the area, the more likely it represents an increase in thinning compared with the patient's baseline examination, and the more concerned I become.

RNFL changes are represented on the follow-up report from the RTA very much the same way macular thickness is. I base progression and treatment changes on the same considerations as with macular thickness.

Optic nerve head changes also are a vital part of the clinical decision-making process. I analyze them in two ways with data from the RTA — and from direct observation, which is much more difficult to quantify. The first thing I look at is the optic nerve section of the follow-up report. This report graphically depicts areas of tissue loss with a red overlay. Areas of red highlight a change in either cupping or cup contour. The RTA 5 also enables me to look at the numerical indices of the optic nerve (Figure 6) as well as measures, such as rim area, cup area, cup volume and so on to determine if any changes were detected.

Figure 6. The RTA 5 enables you to look at the numerical indices of the optic nerve as well as measures, such as rim area, cup area, cup volume and so on to determine if any changes were detected.

Some of the findings have statistical norms, a deviation from what will result in a notation in the Deviation Probability column furthest to the right on the report. By comparing these numerical indices for change over time, I can quantify change in several of the structures important to glaucoma.

In addition, I'll look at the other numerical and graphical display options of the RTA 5. I can look at the optic nerve and thickness maps in three dimensions (Figures 7, 8 and 9) and the numerical data of the thickness maps. Each data point on the hybrid graphical/numerical view represents the average of 16 adjacent data points. There are times when this type of data analysis helps me make the distinction between stability and progression and whether or not to alter or escalate treatment by changing or adding a medication or considering surgical intervention.

Figures 7, 8 and 9. The RTA 5 provides other numerical and graphical display options. You can view the optic nerve and thickness maps in three dimensions and the numerical data of the thickness maps. This type of data analysis will help you make the distinction between stability and progression, which can help you decide if you should alter the patient's treatment course.

Between direct observation (which provides good qualitative information about the optic nerve), the follow-up report (which shows subtle changes in optic nerve head structure in a graphical manner) and careful observation of the numerical indices reports, I'm confident that I'll pick up any structural changes in the optic nerve at the earliest point.

If I find a significant change in visual field that suggests disease progression, I'll ask the patient to come back in a few weeks for a repeat of the visual field test. Usually, I'll obtain IOP measurements at that visit to add more IOP data points to the clinical picture. Because of the subjective nature of visual-field testing, patients have to validate any apparent field loss before I'll consider changing their course of treatment or referring them for surgical intervention.

When considering IOP changes or elevations at follow-up visits, again I need to validate the rise in IOP. Clinicians must consider patient compliance with treatment any time a change occurs. The patient simply may have missed a dose of his medication or failed to correctly instill a dose, both of which will result in a higher IOP reading. Clinicians must consider many factors regarding patient compliance. It may consist of what I call "Willful Misconduct," such as deciding not to take a medication due to expense, side effects or some other reason. Patients also may be confused about dosage frequencies, instillation instructions and so on. If a patient's IOP increased from his normal reading, and I rule out compliance, only then will I consider a chance in treatment.

Early, Accurate Detection is Key

As with any other chronic disease, early detection and appropriate treatment is the clinical goal when examining and screening patients for glaucoma. Structural analysis of the posterior segment is a critical part of meeting this goal. There's no replacement for careful clinical examination, using traditional techniques, such as ophthalmoscopy, tonometry and visual field testing. Adding structural imaging to your clinical practice will unquestionably improve the level of eye care you provide to patients.

The American healthcare system and the consumers of health care, our patients, expect their physicians to practice wellness-based medicine and provide the best care possible. Fortunately, structural imaging is accepted technology in glaucoma care, and it isn't the type of technology that adds expense to your practice without adding revenue to offset that expense.

Adding structural analysis via the Retinal Thickness Analyzer was the single best addition to my technologically advanced practice. Patients benefit. I provide care I can be proud of, and there's an additional revenue stream I didn't have before I added the RTA to my practice. OM

Dr. Warren is the owner of a group practice that includes several optometrists and an ophthalmologist in Racine, Wis. This practice setting provides a varied patient base that offers many clinical challenges on a daily basis. You can reach him at

Optometric Management, Issue: December 2008