glaucoma suspects

Sussing out Suspects

Glaucoma experts discuss how to identify a glaucoma suspect, when they feel disease conversion occurs and their management styles.

Robert J. Murphy, Contributing Editor

Although, the Ocular Hypertension Treatment Study reveals that only 15% of glaucoma suspects convert to full-blown disease, recent studies indicate that upwards of 50% of glaucoma patients go undiagnosed, says Leo P. Semes, O.D., a professor at the University of Alabama at Birmingham College of Optometry, in Birmingham, Ala. This latter statistic may have more to do with socioeconomic status and lack of access to health care than anything else, but it nevertheless underscores the case for heightened vigilance in identifying glaucoma suspects. Yet, because glaucoma is a mischievously multifactor disease and two of its cardinal findings are prone to fluctuations, the glaucoma suspect diagnosis is far from cut and dry.

As a result, we tracked down some of optometry's glaucoma experts and asked them: “How do you identify these patients, and since this scenario may mark the beginning of a long-term clinical battle, what do you do next?” Their answers follow.

Identifying suspects

To identify glaucoma suspects, you must determine whether the patient has risk factors for the disease and weigh those risk factors with your clinical findings, say those interviewed. In other words, the glaucoma suspect diagnosis is relative to each patient.

The risk factors:

► Age. The incidence of glaucoma increases with age, say those interviewed. In fact, those older than age 60 are at high risk of developing glaucoma, and 8% of those older than age 70 have high levels of intraocular pressure (IOP), according to the Glaucoma Research Foundation (GRF). That said, don't discount younger patients, as everyone from babies on is at risk for the disease, with roughly 2% of the age 40-to-50 population having high levels of IOP, the GRF says.

► Diabetes. Comorbid diabetes has been controversial, as some large population-based studies have established a link, while others have not. This inconsistency is the result of selection-, recall- and/or survival bias or misclassification due to the low incidence of the two diseases.¹ That said, other studies have revealed that diabetes affects both vascular tissues and compromises neuronal and glial functions and metabolism in the retina — all of which ultimately causes apoptic death of retinal neurons, including retinal ganglion cells. The impaired metabolism of neurons and glia by diabetes may render retinal ganglion cells susceptible to additional stresses related to openangle glaucoma (OAG), such as elevated IOP. Given this information, you may want to include diabetes as a risk factor for the disease, those interviewed say.

► Ethnicity. Ethnicity remains a consistent risk factor, whereby Blacks, Latinos and most recently, Asian Americans have a high prevalence of glaucoma, say those interviewed. In fact, glaucoma is six-to-eight times more common in Black Americans than in whites, according to the GRF. The reason: A recent study reveals that blacks have higher ocular oxidative metabolism than whites, and increased oxygen, or oxygen metabolites, may increase oxidative stress, cell damage, IOP and the risk of developing glaucoma.²

With regard to Latinos, the Los Angeles Latino Eye Study revealed that almost 5% of the subjects, primarily of Mexican descent, had OAG, while the prevalence of ocular hypertension was 3.5%. The reason: The study's principle investigator surmises that the optic nerves of Latinos may be more susceptible to IOP changes or that vascular factors may pay a role in this population's risk vs. those of European ancestry.

The prevalence of glaucoma in Asian Americans was similar to that of Latinos and higher than that of non-Hispanic whites, according to a recent study.³ Further, narrow angle glaucoma and normal tension glaucoma were considerably higher among Asian Americans (3.01% and 0.73%, respectively) relative to other races. And, after adjustment for potential confounding factors, Asian Americans had a 51% increased hazard of OAG. The lead researcher of this study surmises the inner angle anatomy of patients of Chinese or Vietnamese ancestry may play a role in these numbers.

► Ocular trauma. Blunt injuries that “bruise” the eye or injuries that actually penetrate the eye can damage the eye's drainage system, causing secondary OAG, says the GRF. Secondary OAG can occur immediately post-injury or years after the incident. Sports-related injuries from boxing and baseball, in particular, have been implicated as a cause for this type of glaucoma. As a result, be sure to include a question regarding ocular trauma on your patient history form, say those interviewed.

► Familial history. Be sure to include a question on your patient history form regarding family history of glaucoma, along with specific follow-up questions regarding the course of the family member's disease, says Kathy Yang-Williams, O.D., of Seattle. The reason: The answers may help paint a picture of what both you and the patient can expect with regard to the disease, she says.

You should ask: “At what age did they [the family member] develop glaucoma, did they suffer from any vision loss or blindness related to glaucoma, and how, specifically, were they treated — with medicine, surgery?” explains Dr. Yang-Williams.

► Vascular perfusion pressure-reducing activities. As recent studies have revealed that patients can have a normal IOP, though increased visual field (VF) defects in-office, it's essential you do your best to prevent the latter by asking the patient what type of activities he participates in and how often (days/times of day), says Dr. Yang-Williams. This way, you can assess whether any of these activities may be compromising the optic nerve's vascular perfusion pressure to lead to temporary IOP spikes profound enough to create greater risk for optic nerve damage, she says.

“Patients who spend a lot of time in yoga inversions, for example, may be at risk for elevated IOP that could cause optic nerve damage,” Dr. Yang-Williams says. “As a result, if the patient said she participated in a lot of yoga, I would make the patient aware of the potential contributions that this activity might make to disease progression and suggest that the individual work with their teacher to modify the pose.”

Andrew S. Gurwood, O.D., a professor at the Pennsylvania College of Optometry at Salus University, in Elkins Park, Pa., adds that you may want to take the patient questioning a step further by asking whether he or she does any activity during the day that places his head at an unnatural angle.

“A male patient recently presented with 60% cupping, OU, glaucomatous arcuate visual field defects, OU in the setting of a normal IOP OU,” he explains. “So, I asked him whether he did any activity that placed his head at an unnatural angle, and he explained that his reclining chair was broken, allowing him to lay with his head lower than his feet.”

Dr. Gurwood adds that upon questioning, the man explained that he would fall asleep in the chair and as the chair sagged back, his head lied below the rest of his body.

In this case, compromised vascular perfusion pressure at the optic nerve led to a normal tension glaucoma process producing the resultant nerve damage and VF defects, Dr. Gurwood says. This was confirmed through consultation with a glaucomologist. He adds that sleep apnea, vasospastic pathology, such as migraine headache, and excessive blood pressure treatment, which can lower perfusion to the optic nerve and its supporting tissues, particularly at night, increase glaucomatous risk.

Sleep apnea has been shown responsible for a change in the nychthemeral rhythm of IOP, and one study revealed that the positive correlation between IOP and the apnea-hypopnea index suggests that increased IOP values may reflect the severity of sleep apnea.^4,5 The good news: Continuous positive airway pressure (CPAP), devices have been found to normalize the abnormal rhythms linked with the condition.⁴ Therefore, if the patient reports the symptoms of sleep apnea (e.g. daytime lethargy, snoring, etc.), though has not yet been diagnosed, you can refer him for a sleep study, to see whether he has the condition and can get a CPAP to hopefully prevent further VF loss.

With regard to blood pressure medication, one study showed that a nocturnal blood pressure fall of more than 10% in patients with well-controlled arterial hypertension was associated with a greater VF defect and greater degeneration of the optic nerve fibers.⁶

Finally, one study revealed that migraine headaches are a significant risk factor for the progression of VF abnormalities, as these headaches are associated with temporary alterations in blood flow and peripheral vasospasm.⁷

► Steroid use. Steroid use is a notorious culprit for elevated IOP. Mostly, this occurs with topical steroids, and less so with oral medications, says James L. Fanelli, O.D., of Wilmington, N.C.

“In a majority of cases, the IOP spike is temporary, as it usually dissipates once the steroid is ultimately discontinued. In addition, the dosing and duration of use is usually such that it does not affect the health of the optic nerve,” he says. “If, however, the patient must use a steroid for an extended a period of time, consider prescribing IOP-lowering medications while the patient is using the steroid to prevent possible optic nerve damage.”

The clinical findings:

► Optic neuropathy. The appearance of vertically elongated cupping, Drance hemorrhages, splinter-like hemorrhages adjacent to the optic nerve, the characteristics of the neuroretinal rim — inferior, superior, nasal temporal (ISNT) rule, notching and saucerization — focal constriction of the blood vessels at the disc margin and evidence of nerve fiber layer dropout and retinal ganglion cell complex thinning are all individual red flags for the glaucoma suspect diagnosis, say those interviewed. All can be observed via a dilated fundus exam, with stereoscopic photos, or via the latest in automated digital scanning devices, such as ocular coherence tomography, retinal tomography or nerve fiber layer analysis, which provide photos and numerical data.

“Histologically the optic nerve is at its weakest inferotemporally and superotemporally,” says Randall K. Thomas, O.D., M.P.H., of Concord, N.C. “If you have a compromise to the temporal optic nerve tissues, that will often give way to a visual defect in the nasal visual field.” This is what's called a nasal step, he says.

Dr. Semes adds that early retinal cell complex thinning may be the first sign of glaucomatous damage.

“‘Crying axons’ (under pathologic stress) can be saved with appropriate treatment. However, infarcted axons, you never get back,” Dr. Gurwood adds. “You never have someone with glaucoma exhibiting a reversal of cupping or a significant regeneration of the nerve fiber layer.”

► VF defects. VF defects along the nasal area that correspond with tissue damage to the optic nerve's inferotemporal and superotemporal aspects is the classic sign that deems a patient a glaucoma suspect, says Dr. Thomas. Confrontational VF analysis, Amsler grid, static perimetry (computerized visual field analyzers), kinetic perimetry (Goldmann perimeter) and frequency doubling analysis remain the aids in the diagnosis of VF defects.

Obtaining repeat VF testing on glaucoma suspects and those who have been diagnosed as converted to glaucoma is crucial to understanding visual function and rate-of-change, as the outcomes of the tests fluctuate, sometimes drastically, from one session to another, says Dr. Gurwood.

“These fluctuations can occur as a result of variable user observational skills, the patient's mood, level of alertness, familiarity with the process and ability to work the clicker,” he says.

► Elevated IOP. Whereas 20 years ago many clinicians adhered to a numbers game and even defined glaucoma as IOP elevation, today's glaucoma experts are less inclined to provide specific “safe” numbers. The reason: Mounting evidence exists that glaucoma can develop in the face of IOPs of 12mmHg, while a patient who has consistent IOPs of 20mmHg can deliver repeatable pristine VF test results. In addition, recent studies have revealed that IOP fluctuates and, therefore, requires repeat measurements at different times of day.

Some optometrists, however, are willing to stick their neck out regarding IOP numbers.

“In my opinion, any pressure over 28mmHg is just not doing the patient any good over the long-run,” says Dr. Gurwood. “An IOP consistently measured over 32mmHg is rarely nonpathologic. Even in the circumstance where at the time of discovery, the nerve appears healthy with structure and function preserved, it would be unusual for the system to avoid eventual decompensation.”

Charles H. Aldridge Jr., O.D., of Burnsville, N.C., says he bases his approach on the findings of the Advanced Glaucoma Intervention Study and the Collaborative Normal-Tension Glaucoma Study.

“If you have a patient with an elevated pressure greater than 21mmHg, I want to reduce it to below 18mmHg,” he says. “But, if I'm dealing with a normal-tension glaucoma patient, where IOP is below 20mmHg, I want to take the IOP down at least 30%.”

Although IOP doesn't command the respect it once did, clinicians do recognize it as a risk factor that must be considered when determining a patient's glaucoma suspect status. In addition, it remains the only risk factor eyecare practitioners can control through therapeutic recourse (e.g. IOP-lowering drops and laser procedures) in an attempt to halt glaucoma progression.

► Abnormally thin central corneal thickness. Multiple studies have shown that an abnormally thin central cornea (i.e. below 540nm), as measured via pachymetry, is associated with a high risk of glaucoma. Yet, researchers have yet to determine the link. So, until someone can elucidate a causative mechanism, chalk this up as another risk factor to plug into your decisionmaking regarding the glaucoma suspect diagnosis.

Now what?

If by now your clinical puzzle — history, demographics, optic nerve assessment, VF testing, IOP, central corneal thickness — looks blatantly characteristic of glaucoma, you may justifiably elect to immediately initiate treatment with IOP-lowering drops. If, however, the various pieces of the puzzle don't reveal a dangerous picture, you have time to monitor the situation, say those interviewed.

“The best glaucomologists in the world hardly ever pull the trigger [i.e. initiate treatment] based upon one examination. In most instances, open-angle glaucoma is not a fast-moving disease,” Dr. Gurwood says. “And because most open-angle cases employ a slow-moving process over a lifetime, it often takes five-to-10 years from the point at which IOP becomes excessive for documentable damage to ensue. In most circumstances, you have time to acquire data and determine whether the findings are both repeatable and correlable to the nerve's appearance and structure.”

Dr. Fanelli agrees that monitoring is the best course of action for a glaucoma suspect. And to ensure he stays on top of these patients, he says he has them return for periodic followup visits, with the time between visits based on the following glaucoma suspect classifications: low-, moderate-, and high-risk (depending on the severity of the earlier findings).

“Low-risk patients return yearly, moderate-risk every six months, and high-risk every four months,” he says. “All three patient types undergo the same testing.”

Dr. Yang-Williams says she offers high-risk glaucoma suspects treatment as an option vs. monitoring.

“Some patients are highly anxious and select treatment rather than run the risk of functional damage, especially if there are strong indicators that treatment will become necessary in the future,” she explains. “Some patients are more cavalier and will resist any suggestion toward treatment, especially since there are no symptoms in the early stages.”

Conversion and treatment

So, when does a glaucoma suspect become a glaucoma patient? Those interviewed say significant progression in either the most important functional test, VF, or the key structural test, optic nerve evaluation, places these patients in the full-fledged glaucoma patient category.

Dr. Thomas says he places special emphasis on VF changes.

“In my experience, 10% to 15% of glaucoma suspects ultimately go on to develop frank disease,” he says. “And so you say, ‘Golly, how do you define frank disease?’ I would say, evidence of a repeatable — of a repeatable — visual field defect. That's sort of the Holy Grail of the glaucoma diagnosis.”

Progressive optic nerve changes, as indicated by stereoscopic fundus photos or serial digital nerve fiber layer analysis, are reliable indicators of progression, in that Unlike IOP and VFs, these measures are highly accurate, say those interviewed.

Still, if the patient's IOP climbs through time, especially in concordance with other key glaucomatous findings, this too may be a legitimate sign of conversion, say those interviewed.

Topical prostaglandin analogues and beta-blockers remain the go-to IOP-lowering drugs, say those interviewed.

“Combination medications can be used as starter agents in cases of newly discovered advanced disease, however, typically they are not used as firstline agents when monotherapy has not been attempted,” says Dr. Gurwood. “ They are valuable as adjuncts, permitting convenience.”

Second- or third-line options are alpha-agonists or carbonic anhydrase inhibitors. If the patient has achieved maximum IOP reduction with drops yet is still progressing, refer him for selective laser trabeculoplasty (SLT) or argon laser trabeculoplasty (ALT), as either procedure may lower IOP to 8mmHg-to-10mmHg, say those interviewed.

“Multiple publications, have demonstrated that SLT is equally effective as ALT.^8,9 Given its less caustic nature, its repeatability and low profile of side effects, SLT is rapidly becoming the procedure of choice amongst surgeons,” Dr. Gurwood says.

Arguably, no other condition will test your clinical skills more demandingly than identifying and managing glaucoma suspects. However, the aforementioned information and advice should lessen the burden the silent thief of sight places on your decision-making. OM

1. Nakamura M, Kanamori A, Negi A. Diabetes mellitus as a risk factor for glaucomatous optic neuropathy. Ophthalmologica. 2005 Jan-Feb;219(1):1-10.
2. Siegfried CJ, Shui YB, Holekamp NM, et al. Racial differences in ocular oxidative metabolism: implications for ocular disease. Arch Ophthalmol. 2011 Jul;129(7):849-54.
3. Stein JD, Kim DS, Niziol LM, et al. Differences in Rates of Glaucoma among Asian Americans and Other Racial Groups, and among Various Asian Ethnic Groups. Ophthalmology. 2011 Jun;118(6):1031-7.
4. L. Melki, M. Haller, J.L. Pépin, et al. Sleep Apnea and Intraocular Pressure: Effects of Continuous Positive Airway Pressure Treatment. Invest Ophthalmol Vis Sci 2005;46: E-Abstract 4834.
5. Karakucuk S, Goktas S, Aksu M, et al. Ocular blood flow in patients with obstructive sleep apnea syndrome (OSAS). Graefes Arch Clin Exp Ophthalmol. 2008 Jan;246(1):129-34.
6. Krasinska B, Karolczak-Kulesza M, Krasinski Z, et al. A marked fall in nocturnal blood pressure is associated with the stage of primary open-angle glaucoma in patients with arterial hypertension. Blood Press. 2011 Jun;20(3): 171-81.
7. Tsai JC. Influencing ocular blood flow in glaucoma patients: the cardiovascular system and healthy lifestyle choices. Can J Ophthalmol. 2008 Jun;43(3): 347-50.
8. Kóthy P, Tóth M, Holló G. Influence of selective laser trabeculoplasty on 24-hour diurnal intraocular pressure fluctuation in primary open-angle glaucoma: a pilot study. Ophthalmic Surg Lasers Imaging. 2010 May-Jun;41(3):342-7.
9. Russo V, Barone A, Cosma A, et al. Selective laser trabeculoplasty versus argon laser trabeculoplasty in patients with uncontrolled open-angle glaucoma. Eur J Ophthalmol. 2009 May-Jun; 19(3):429-34.