How to Detect and Follow Glaucoma Progression
A clear picture of the various methods used to monitor this progressive disease.
Robert Murphy, Contributing Editor
Awidely cited definition of glaucoma describes it as a progressive optic neuropathy.1 Progression is so sufficiently integral to its diagnosis and management that some clinicians consider it essential to the condition's definitive criteria. A diagnosis of glaucoma requires not only spotting the condition's characteristic signs, but also determining the rate of structural and functional progression.
A patient's rate of progression — especially when it comes to optic nerve changes and visual field defects — is likewise critical to the clinical follow-up schedule and serves as a hallmark for treatment decisions. It's the progression that is to blame for the vision-threatening advanced disease. A key clinical objective, therefore, is to slow or arrest progression. Or, as a rather ghoulish cliché has it, “Our goal is that our patients die before they go blind.”
Here, we encounter a major limitation. After all these years, intraocular pressure (IOP) remains the sole glaucomatous risk through which we have any control. In light of normal tension glaucoma, we know that IOP contributes to the disease's pathogenesis to a limited degree, while many other contibutory risk factors remain beyond clinical control. Even so, IOP remains as critical as ever: Numerous studies demonstrate that reducing IOP slows glaucoma's progression.
The classic triad of elevated IOP, structural optic nerve changes and repeatable visual field defects still holds as diagnostic for glaucoma progression in many cases. Yet, the astute clinician must remain aware that glaucoma can develop in its early stages despite the absence of one or more of these hallmark signs. Clinicians are also well-advised to make optimal use of a range of diagnostic means that provide further evidence of glaucoma. It comes down to putting together the pieces of a puzzle in which variability may test the diagnostic skills of even the most seasoned diagnostician, say those interviewed for this article.
On the trail of a suspect
Among the variations in a glaucoma presentation is that some patients progress more rapidly than others, even as some who obtain adequate IOP control may find their progression halted altogether. But that isn't known at the start.
A glaucoma suspect may present with any of several findings consistent with the disease, that together do not add up to a glaucoma diagnosis.
“Nowadays, we know that you can have glaucoma with normal (intraocular) pressure,” says Jerome Sherman, O.D., distinguished teaching professor at the State University of New York College of Optometry. “We know you can have glaucoma before a visual field defect. We call that ‘preperimetric glaucoma.’ That means the visual field may be normal, but other information makes us consider very seriously the diagnosis of glaucoma.” Likewise, glaucoma can present in the presence of a normal cup.
Long-standing personal risk factors still hold. Blacks and Latinos have a greater risk for developing glaucoma than that of whites. Those with a family history of advanced glaucoma — particularly on the maternal side — likewise have an increased risk.
Left: An image of an optic nerve with drance hemorrhages. Note the resolving hemorrhage on the rim side at 2 pm and a larger one at 4 pm. Center and right: A myopic female (45 years old) with optic nerve hemorrhage and resolution at 90 days out.
Optic nerve findings
Don't be fooled by what looks like a large cup. A large physiologic cup — let's say .8 in a large disc — may well be normal, even as a .5 cup in a small disc should raise your suspicion. Asymmetric cups between the two eyes likewise are suspicious for glaucoma.
The cup-to-disc ratio is just one of several structural optic nerve-related findings that may contribute to a diagnosis.
► Ganglion cell loss. Glaucoma expert Robert Weinreb, M.D., of the University of California, San Diego (UCSD), has identified ganglion cell loss as the first optic nerve-related finding to occur in glaucoma. Elsewhere, the ganglion cell complex has been shown to be highly sensitive and specific for diagnosing glaucoma and monitoring its progression.2
Centered around the fovea, ganglion cell loss eludes detection with indirect ophthalmoscopy, but can be readily picked up by SD-OCT.
► Retinal nerve fiber layer dropout. This is a classic sign of glaucoma that can be picked up through indirect ophthalmoscopy. “You can use red-free photography, or you can simply look carefully at the nerve fiber layer itself with a handheld indirect lens,” says Christopher J. Quinn, O.D., president of Omni Eye Services in Iselin, N.J. “And you can appreciate the diffuse loss of the nerve fiber layer.”
This brings up a key point: Despite the wonders of SD-OCT, indirect ophthalmoscopy still plays a pivotal role in diagnosing glaucomatous optic nerve changes.
“In my mind, it remains the most important thing,” Dr. Quinn says. “We're all happy to have the imaging technology that we have, OCT or HRT. But those tools should simply be supplements. They can't replace the direct observation of a skilled examiner looking at that nerve and really being able to detect whether, a) there's progression or, b) whether there is glaucomatous optic atrophy.”
► Neural rim thinning. The neural rim surrounding the cup normally has an equal width in all areas. “In glaucoma, often the neural rim gets thinner, usually at either 12 o'clock or 6 o-clock,” Dr. Sherman says. “Obviously, if there is a thin rim at 12-or 6 o'clock, then you have to be concerned.”
► Drance (flame-shaped) hemorrhage. “I look for the presence or absence of an optic nerve head hemorrhage,” says Ian Benjamin Gaddie, O.D., owner of Gaddie Eye Centers in Louisville, Ky., and an adjunct assistant professor at Northeastern State University College of Optometry. “Their presence, especially in a glaucoma suspect or a patient who is being treated for glaucoma, is significant for focal ischemia of the rim.”
Don't let a single normal IOP reading fool you. Normally, a patient's IOP should not vary more than about 3.5 mmHg-to-4.0 mmHg in a day. A glaucoma patient may go from 15 mmHg-to-30 mmHg between sunup and sundown. “I've seen it, and it's very scary,” Dr. Sherman says.
A single IOP reading is therefore insufficient. Ideally, you might want to have the patient come to the office in the morning and return every two hours for a series of diurnal readings. If this is not feasible, the next best approach is to schedule follow-up visits at different times of day to obtain IOPs.
But there's one issue. “The problem is there is good evidence that the highest pressures occur when patients are not in your office,” Dr. Sherman says. “It used to be thought that pressures were higher during the day and lower at night.”
Dr. Sherman cites the work of Dr. Weinreb taking place in a sleep lab at UCSD and concerning IOP. “[Dr. Weinreb] has been able to demonstrate that a lot of patients have their highest pressures at night,” Dr. Sherman says. “So the pressures at night can actually be higher than the pressures during the day.”
A visual field defect, especially one that corresponds to a structural change of the optic nerve, is a hallmark sign of glaucoma progression. In a patient previously diagnosed with preperimetric glaucoma, the onset of a field defect may suffice for a full-blown glaucoma diagnosis.
“It's impossible to know what the rate of progression is going to be for an individual patient at the outset,” Dr. Gaddie says. “It's important during the first 18-to-24 months that you get a frequent visual field test to get an idea if this patient is going to be a quick progressor or not.”
You may wish to schedule your visual field testing regimen — and that of OCT — according to the patient's perceived rate of progression.
Two additional signals of glaucoma progression can be found by examining the cornea:
► Corneal thickness. “We know from the Ocular Hypertension Treatment Study that patients who have thin corneas were much more likely to have glaucoma in the setting of ocular hypertension,” Dr. Gaddie says. “So there's something about a thin cornea that puts a patient at extra risk.”
While the causative link remains elusive — and a matter of controversy — a thin cornea is an independent risk factor for glaucoma. “A lot of people feel that the structure of the cornea may be a proxy for what's going on at the optic nerve and the structure of the lamina cribosa,” Dr. Quinn says.
► Corneal hysteresis. This is another potential risk factor for glaucoma. Corneal hysteresis (CH) is the direct measure of corneal biomechanical properties, such as rigidity. Research shows that CH is an independent risk factor for progression, as glaucoma patients tend to have a much lower CH.3,4
Two further tests may point to glaucoma and its progression.
► Relative afferent pupillary defect. The diagnosis of any optic nerve disease is supported by the presence of an asymmetric relative afferent pupillary defect.
► Visual evoked potential (VEP). This test measures the functional response of the entire visual pathway from the anterior segment to the visual cortex. Recent research shows that early glaucoma patients have abnormal VEP. Once confined to hospitals and academic settings, VEP units are increasingly finding their way into clinics.
In addition, research increasingly suggests that the disease's core etiology lies not in the eye but in the brain, namely the lateral geniculate nucleus. “It seems with experimental animals, you can sometimes pick it up in the brain before you pick it up in the eye,” Dr. Sherman says.
Implications for treatment
The decision to initiate glaucoma treatment is specific to each patient and requires that the clinician assemble numerous disparate pieces of the diagostic puzzle, such as what has been discussed, to justify the move. After all, once a patient starts treatment, it's a lifetime decision, not to mention a costly one. Plus, all glaucoma medications have side effects.
Some clinicians offer patients the option of selective laser trabeculoplasty (SLT) as a first-line treatment. Typically, SLT is a late-stage therapeutic maneuver. The success or failure to control pressures with an initial regimen signals the need to switch or add medicines, and ultimately to consider SLT.
“…the more O.D.s who are involved in uncovering and managing the disease, the better the outcome will be for the visual welfare of the population.”
— Ian Benjamin Gaddie, O.D.
Uncontrolled IOP shows up most obviously on tonometry. Yet the key measures that impact treatment decisions are structural optic nerve changes and functional visual field deterioration. If you've maxed out the patient with two or three medications plus SLT, consider obtaining a surgical consult for a filtering procedure. Until then, optometrists can treat and monitor glaucoma patients before progression extends beyond clinical control.
Optometrists taking control
Practitioners will provide clinical eye care to the extent of their comfort level and confines of the law, whether you're talking glaucoma or any other sight-threatening eye disease.
“I wish more O.D.s would take charge of glaucoma care, and not just identify it and ship it out to an ophthalmologist,” Dr. Gaddie says. “I think there are O.D.s out there who are aggressive, properly trained and experienced and take care of glaucoma, the whole gamut. And there are people who can identify it and are uncomfortable with it and refer it out. Sometimes, they want to treat but are locked out of insurance panels or paid in a discriminate manner. But I think the trend is definitely for more optometrists getting more involved in both diagnosing and treating glaucoma. So, the more O.D.s who are involved in uncovering and managing the disease, the better the outcome will be for the visual welfare of the population.” OM
1. Medeiros FA, Weinreb RN. Medical backgrounders: glaucoma. Drugs Today (Barc.) 2002 Aug;38:563-70.
2. Zanquill LA. The evolving role of imaging in glaucoma diagnosis. Ophthalmol Update (suppl) 2012;July/Aug:6-9.
3. Clinical Applications of Ocular Response Analyzer Measurements. http://doclibrary.com/MSC167/PRM/ORA_Clinical_Applications1502.pdf (Accessed 8/12/12′)
4. Congdon NG, Broman AT, Bandeen-Roche K, et al. Central corneal thickness and corneal hysteresis associated with glaucoma damage. Am J Optholmol. 2006 May;141 (5): 868-75. Epub 2006 Mar 9.
|Robert Murphy is a freelance medical writer in Philadelphia. He has spent several years reporting on the eyecare field. You can e-mail him at rmur firstname.lastname@example.org. Or send comments to optometricmanagement@ gmail.com.|