Article Date: 5/1/2002

Effects of Refractive Surgery on Early Glaucoma Detection
Your equipment may function differently; here's what you need to know.

With an estimated 3 million patients expected to undergo laser-assisted in situ keratomileusis (LASIK) surgery in 2002, there's a good chance that you'll see refractive surgery patients, including some who may be diagnosed with glaucoma, in your practice sometime soon.

Glaucoma treatment options are moot if the diagnosis isn't made in an accurate and timely manner. Fortunately, new diagnostic equipment such as the GDx (Laser Diagnostic Technologies) supplies more information about the retinal nerve fiber layer (RNFL). And equipment such as the Heidelberg Retinal Tomograph (HRT), from Heidelberg Engineering, details the optic nerve head (ONH).

Aside from evaluating the ONH, early detection of glaucoma also includes measuring intraocular pressure (IOP), taking a thorough history and visual field analysis. It's important to realize that refractive surgery can cause corneal alterations that affect glaucoma testing equipment.

It's your responsibility to adjust your diagnostic skills after the cornea has been altered by refractive surgery. Let's look at some of the hallmark diagnostic tests used in glaucoma diagnosis and consider the effects that LASIK could have on them.

Checking things out

Here are glaucoma tests and the effects they have that you should know about:

Nerve fiber analysis. LASIK flattens the central corneal curvature when performed for myopia but steepens it when performed for hyperopia. This change in curvature has a direct effect on the accuracy of equipment that assumes a corneal curvature.

The GDx uses a confocal scanning laser and an ophthalmoscope with an integrated polarimeter to evaluate the thickness of the RNFL. By using the birefringent properties of the retinal ganglion cells' axons, the GDx can determine the thickness of the nerve fiber layer. Good correlation between structural damage to the RNFL and visual field loss has been reported.

However, when a patient undergoes LASIK, the change in corneal curvature alters the polarization properties, thus affecting the internal compensator that allows the measurement to be independent of the crystalline lens and cornea inherent polarization. The total mean RNFL and superior, inferior, temporal and nasal mean RNFL thickness is less after LASIK. The thinner RNFL reading indicates missing nerve tissue that appears to be glaucomatous. Therefore, you must consider the potential for "false positives" when using GDx for the post-LASIK patient.

This summer, Laser Diagnostic Technologies will release a custom compensator for the GDx that aims to address post-surgical retardation. Other nerve fiber analyzers, such as Heidelberg Engineering's HRT II, Talia Technology's Retinal Thickness Analyzer, and Humphrey Instrument's Optical Coherence Tomography don't rely on polarimetry and are therefore not influenced by post-surgical changes in the cornea.

Visual field analysis. For decades, this test has been the mainstay for monitoring glaucoma progression and for identifying an anomalous ONH. Yet it depends on the ability of small luminance changes in the central and peripheral retina to stimulate the retinal ganglion cells. Complicated LASIK or photorefractive keratectomy (PRK) patients may have corneal scarring or corneal changes that reduce the transmission of this light stimulus, accounting for "false positives" and, to a lesser extent, "false negatives." The erratic responses make this important test unpredictable and useless.

Even more important, a LASIK patient's contrast sensitivity function (CSF) changes. The ONH consists of 1.2 million axons, 1 million of which originate from the parvocellular laminae region (p-cells) and the remainder from the magno- cellular region (m-cells) of the lateral geniculate body. The p-cells are responsible for long wavelengths and acuity, and they give a more tonic response.

The 200,000 larger bodied m-cells detect the shorter wavelengths and contrast sensitivity function, and they give a more phasic response and are sensitive to motion. Researchers have shown that because of their abundance and neural redundancy, p-cells can withstand more than 50% axon death before detection by black-and-white field analyzers.

Other studies of glaucomatous pathologic characteristics have demonstrated that the retinal ganglion cells with larger cell bodies (m-cells) are preferentially damaged earlier in glaucoma. The less abundant m-cells are detected by blue-yellow analyzers and therefore make the short-wavelength automated perimetry (SWAP) method useful for detecting glaucoma.

Unlike the p-cells, the m-cells carry no neural redundancy. Glaucoma can be detected if only 10% to 15% of these cells die. Though SWAP isn't considered a screening tool (it's too slow, tiring to the patient, and influenced by cataracts) frequency doubling of low spatial frequency and high temporal frequency, which specifically detects m-cell function, has been proven to be a quick and reliable test.

Humphrey's Frequency Doubling Technique (FDT) can screen patients using contrast sensitivity defects. These defects are secondary to m-cell loss, which occurs early in glaucomatous optic neuropathies. Yet LASIK gives the cornea a more oblate shape and thus decreases the CSF.

This change may produce a misdiagnosis of glaucoma by the mapping specificity of these new field analyzers. Again, you're left with a powerful tool that may not render reliable post-surgical results. Without a way of measuring the baseline CSF loss secondary to LASIK, the FDT might not detect early changes in the optic nerve. You'll need to perform a contrast sensitivity test to determine if the FDT is reliable in this patient or rely on other modes of diagnosis.

Cup/disc evaluation. Much like visual field analysis, the C/D ratio is a critical piece of the glaucoma diagnostic jigsaw puzzle. Dense corneal haze, more common in patients who've undergone PRK, can have a devastating impact on the visibility of the ONH. Newer scanning excimer lasers, pretreatments and laser-assisted stromal epithelial keratomileusis (LASEK) have dramatically reduced the appearance of this post-surgical complication. However, in our population of patients who still have 3 to 4+ haze, we need to rely on other diagnostic tools (such as IOP peripheral visual field testing) and family history to diagnose glaucoma.

Irregular or decentered astigmatism also may distort the appearance of the ONH, elong-
ating the C/D ratio and thereby creating the potential for misdiagnosis of C/D symmetry.

IOP measurement. The cornea is the first point of contact for tonometers to measure the IOP. Moreover, the gold standard in IOP measurement continues to be the Goldmann applanation tonometer (GAT), which depends on specific standards for the cornea.

The GAT's use of the Imbert-Fick principle and a 3.06-mm diameter applanation cancels out the surface tension of the tear film and corneal rigidity, but only if the cornea measures 520 (and if the rigidity is constant and equal in all corneas. Although the average preoperative cornea does measure 520, the average postoperative thickness is usually less). This thinner cornea nullifies the accuracy of the GAT in postoperative keratorefractive patients.

Getting an accurate measurement

We know that thinner, flatter corneas measured with GAT will produce a false low IOP reading. A fudge factor has been suggested to account for the changes in the IOP after LASIK. It might apply in cases where no signs of glaucoma are obvious. But what should you do when you're following someone you know or suspect has glaucoma? Can you rely on a rule of thumb to give the most accurate measurement?

A recent report from the Advanced Glaucoma Intervention Study 7 (AGIS) may inadvertently have answered the question of how important a few mm Hg of mercury are when following a glaucoma patient. IOP targets for our glaucoma patients may be even more relevant. The AGIS report evaluated IOP and extent of visual field progression in chronic open-angle glaucoma patients who had exhausted all medical options, randomizing them to different surgical options. They then separated the patients into four groups depending on the amount of time the IOP was less than 18 mm Hg during the 8-year follow up.

The report found that the group with an average IOP of 12.3 mm Hg over 8 years had stable visual fields, and the other groups all had a greater amount of visual field decay beginning 3 to 4 years after therapy.

These results demonstrate that the lower the IOP, the better our chance of maintaining our patients' visual fields. They also imply that we can't simply guess what a LASIK patient's IOP is, and that we need better methods to measure it postoperatively. Simple instruments like Bausch & Lomb's Proview, which uses a spring-activated pin that produces a phosphene, may replace GAT in this population. However, when 1 mm Hg or 2 mm Hg is important for our glaucoma patients, this device may not be specific enough.

The hand-held Tono-Pen XL (Medtronic Solan) tonometer may provide the needed specificity. Unlike GAT, the Tono-Pen XL uses MacKay-Marg tonometry with a micro strain gauge transducer that generates changes in the voltage relative to changes in pressure.

This tonometer only uses a 1.5-mm diameter head as compared to the 3.03 mm diameter of the GAT. This smaller applanation diameter allows the Tono-Pen to be less affected by corneal surface and curvature changes and therefore more accurate than the GAT.

The Tono-Pen XL takes four measurements in seconds and averages the pressures for a final measure-
ment with a standard deviation. Even more beneficial, you can use it outside the central cornea and away from the effects of keratorefractive surgery.

In our practice, we measure all patients postoperatively with a Tono-Pen XL in the peripheral cornea. We've concluded that this is the most correlative to pre-operative central IOP.

Further research has shown that the best place to measure on the cornea with the Tono-Pen XL is the nasal side of the cornea.


Glaucoma Genetic Test


InSite Vision has launched OcuGene, a test that screens for a genetic marker and mutations in the region of the TIGR gene and can help you identify patients at risk of developing primary open-angle glaucoma. The test is noninvasive, using two swabs from the inside of a patient's cheek. Patients who test positive have up to a 100% probability of developing glaucoma.

Be careful

Though in the future surgical procedures might not focus on the cornea (phakic intraocular lenses, for example), for now LASIK is the best and safest procedure we have.

We must check LASIK patients for glaucoma with those diagnostic tools that will provide the most accurate and useful information. Diagnostic equipment is meant to help us diagnose, not to muddy the waters. We can't rely on just one test to diagnose or monitor the progression of glaucoma.

Research into glaucoma treatment is progressing rapidly. Although post-LASIK glaucoma patients may represent only a small (but growing) fraction of our practices, we can't overlook them. Make sure you continue to identify those patients who will benefit from new treatment options. Take the time to educate yourself, your staff and your patients about the challenges in glaucoma diagnosis that may follow even successful LASIK procedures.

Safeguard yourself by using techniques that will generate the most accurate, reproducible results.

Dr. Bloomenstein is refractive clinic medical director at Barnet Dulaney Perkins Eye Center in Phoenix, Ariz. He's also adjunct assistant professor at the New England College of Optometry (Boston) and Southern California College of Optometry (Fullerton, Calif.). He lectures nationally and has published literature on topics related to the anterior segment and surgery.


Optometric Management, Issue: May 2002