CASE 1: LOW-TENSION GLAUCOMA

A 40-year-old woman received a diagnosis of glaucoma and was referred for further evaluation. She has a history of low blood pressure and migraine headaches. She has multiple disc hemorrhages. Her highest IOP was 19 mm Hg, and central corneal thickness is average. Figure 1 shows scans of both eyes taken with optical coherence tomography (OCT). The thickness profile of the right eye shows a definite reduction inferiorly. The quality of the scan of the left eye is not quite as good, but it clearly shows thinning of the nerve fiber layer. The cup is large compared to the surrounding rim, and little rim tissue remains. In the right eye, the border of the retinal pigment epithelium (RPE) does not reach the edge of the optic nerve's scleral canal. The OCT uses the RPE edge as the limit of the optic nerve. In the right eye, the OCT sets the optic nerve border more peripherally than as seen on clinical examination, and the cupping that was seen clinically is less evident.

Visual fields (Figure 2) correlate closely to the OCT findings. There is a dense superior arcuate defect with nasal step in the right eye, whereas in the left eye, there is a dense superior and inferior arcuate defect similar to a central island. How would you manage this patient with apparent open-angle glaucoma?

In young patients with myopic discs and less pronounced visual field losses, suspicious optic nerves, even with visual field loss, could be physiologic in nature, and clinicians might opt to observe. In this case, however, with the more advanced visual field changes, this patient should be treated.

Because this patient may have advanced disease and her highest pressure was 19 mm Hg, fairly aggressive treatment is appropriate. In the Collaborative Normal Tension Glaucoma Study (CNTGS), the goal of treatment was a 30% reduction in IOP.1 For this patient, a pressure of 13 mm Hg would be a reasonable goal. In the CNTGS, reducing pressures by 30% reduced the progression rate from 35% to 12%. Even with that aggressive pressure reduction, however, 12% of the treated patients in that study progressed. Furthermore, only about half of the patients were able to achieve those pressure goals with only medications or laser treatment. By committing to an aggressive pressure goal, you may be committing to a more aggressive form of treatment.

Various first-line treatment options are available. Topical ß-blockers have been shown to be effective pressure- reducing agents for most patients, and once-a-day dosing is usually sufficient. Some clinicians may avoid a topical ß-blocker as a first choice in patients with lowtension glaucoma because of hemodynamic considerations. 2 Specifically, there are concerns that a reduced heart rate or, possibly, reduced blood pressure may lead to reduced perfusion of the optic nerve in patients with abnormal autoregulation of blood flow, which may be associated with low-tension glaucoma and migraines. The literature is complex and varied, but there may be reductions in some of the hemodynamic parameters in the retrobulbar and intrabulbar circulation.

Another option for this patient is a topical prostaglandin analogue. Prostaglandin analogues offer once-daily dosing, have a safe systemic profile, and often achieve good reductions in IOP.

A twice-daily α-agonist, such as brimonidine, is also an option for this patient. In the Low-Pressure Glaucoma Treatment Study (LoGTS), patients with low-tension glaucoma were randomized to either timolol or brimonidine and observed for 4 years.3 Both groups had similar reductions in IOP. Interestingly, after 4 years, visual field progression was statistically less frequent in the brimonidinetreated patients (9%) than in the timolol-treated patients (31%). These findings were seen with three different field grading algorithms. The research does not directly answer the question of why brimonidine proved more effective than timolol in preserving visual field. Possible explanations include a neuroprotective effect of brimonidine or a deleterious effect of timolol on the optic nerve directly or via hemodynamic effects.

Many studies show that laser trabeculoplasty, even in low-tension glaucoma, can achieve pressure reduction. Its safety and efficacy have been shown to be equal to that of topical medications,4,5, and it takes compliance out of the equation. Laser trabeculoplasty is effective initially in about 80% of patients, however, and the effect persists for only 2 to 4 years.6 Selective laser trabeculoplasty reduces mean IOP and IOP variation in normal-tension glaucoma patients. Although it can be a helpful adjunct, it often does not replace topical therapy.

As we think about our goal pressure of 13 mm Hg, we must acknowledge it may take more than one of these treatments to achieve that goal for this patient.

CASE 2: ADVANCED GLAUCOMA

A 70-year-old man has open-angle glaucoma. His initial IOPs were 20 mm Hg in the right eye and 42 mm Hg in the left eye. He recalls having a severe impact to his left eye from a tennis ball at age 40. His pressures have been well controlled with various medications (9 mm Hg to 17 mm Hg). His central corneal thickness is markedly reduced in both eyes (< 500 μm). He has had trabeculectomies in both eyes and a tube shunt in the left eye. Figure 3 shows advanced cupping of both optic nerves, and Figure 4 shows advanced field loss, with a central island in the right eye and a small central island in the left eye. The patient feels his vision has been worsening in recent years despite the pressure control. What should be done for this patient?

In certain patients, it may be advisable to measure pressures in the office throughout the day, as this may reveal pressure spikes that put the patient at a greater risk of progression. Serologies would not be unreasonable in this case. Although the patient clearly has open-angle glaucoma, he could also have an autoimmune-related or infectious retinopathy or optic neuropathy.

With progressive glaucoma, in the absence of explanations for visual field progression, some practice guidelines suggest magnetic resonance imaging to look for tumors or other compressive lesions. This patient has had all of these tests, which were normal.

This patient has a history of hypertension, requiring multiple medications. We instructed him to monitor his blood pressure at home and found, with his current medication regimen, his blood pressure was fluctuating from very high in the morning to extremely low overnight. We consulted with the patient's cardiologist, who adjusted the medication regimen. The patient's overall blood pressure stabilized to a level that was safe for his heart and, at the same time, would maintain a more even perfusion to his optic nerve. We have evidence from the Los Angeles Latino Eye Study (LALES)7 and others that uncontrolled or very low blood pressure may lead to greater risk of progressive optic neuropathy in glaucoma. Additionally, studies have shown that patients taking multiple blood pressure medications may be at greater risk for optic nerve cupping.8

CASE 3: COMPLEMENTARY THERAPIES FOR PRIMARY OPEN-ANGLE GLAUCOMA

A 71-year-old man with open-angle glaucoma has a history of myopia and combined cataract and glaucoma surgery. His central corneal thicknesses are 538 and 531 μm. His pressures had been 15 mm Hg or lower for years, but he had visual field progression in recent years and started taking dorzolamide and timolol. His pressures ranged from 8 mm Hg to 12 mm Hg with this regimen. On examination at this visit, his optic nerves are tilted with peripapillary atrophy, consistent with his history of myopia before cataract surgery. Glaucomatous optic neuropathy in the form of cupping is evident. As shown by the disc drawings (Figure 5), the clinician believed the glaucomatous cupping, not the tilt, was problematic. The patient said his vision was deteriorating almost on a weekly basis, making it more difficult to participate in activities he enjoys. At the top of the series of visual fields for the right eye (Figure 6), a central island is visible. Although there is a great deal of variation field to field, the last field in the series has almost the same mean deviation as the first field in the series. Visual fields for the left eye (Figure 7) show a dense paracentral scotoma with nasal extension consistent with glaucoma. In patients with myopia, we often see these paracentral scotomas earlier in the course of glaucoma. Although there may be an increased paracentral scotoma inferiorly early in this series of fields, significant progressive changes to match the patient's complaints are not obvious. On the 10-2 field from the left eye (Figure 8), we can see a dense defect approaching fixation that was also fairly stable on follow-up. When considering stability in such a scenario, we should remember that points registering “0” on the field are not necessarily blind to all stimuli but are beyond what the machine can test. Thus, real changes may not be evident. On the other hand, most clinicians are reluctant to consider aggressive interventions without objective evidence.

This patient has read just about everything there is to read about glaucoma, including information on alternative therapies that do not rely on pressure reduction. He asks what else can be done for him.

Many patients have heard that bilberry was used by pilots during World War II to improve night vision and ocular health. There is little evidence, however, that bilberry changes the course of glaucoma or improves visual function in patients who have glaucoma.

Eyebright is another popular supplement purported to aid vision. Perhaps it is helpful, but there are no controlled, randomized studies showing improvement in glaucoma.

Ginkgo biloba has been used to improve neuronal function in various diseases. In one study, 27 subjects with normal-tension glaucoma and established field loss had baseline visual field testing on gingko biloba and placebo in a masked, randomized, crossover study.9 Half the subjects took placebo and half ginkgo for 4 weeks and then underwent field testing. After washout, each group took the other treatment for 4 weeks and underwent field testing again. In this study, the patients' visual fields were better while they were taking ginkgo than placebo, with a more than 20% reduction in mean deviation. This was a limited study, and there have been no repeat or long-term studies. This study provides at least some reasonably scientific evidence, however, that ginkgo may be helpful for selected patients. At the same time, ginkgo can thin the blood, so it may not be a safe choice for patients with clotting disorders or patients taking blood thinners or high-dose vitamin E.

In a prospective, multicenter trial, patients with lowtension glaucoma were randomized to placebo or memantine. Although findings from this study have not been published, the company that funded the study reported the primary endpoint of better preservation of vision was not met with memantine. So, although it is used in other neurodegenerative diseases, we have no evidence to date that memantine is neuroprotective in glaucoma.

In the LoGTS, brimonidine was shown to be potentially neuroprotective in low-tension glaucoma. This patient is not currently taking brimonidine, so we could discuss those findings with him and consider adding that agent to his regimen or possibly substituting it for dorzolamide or timolol.

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  2. Hayreh SS, Podhajsky P, Zimmerman MB. ß-blocker eyedrops and nocturnal arterial hypotension. Am J Ophthalmol. 1999;128:301-309.
  3. Krupin T, Liebmann JM, Greenfield DS, et al.; Low-Pressure Glaucoma Study Group. A randomized trial of brimonidine versus timolol in preserving visual function: results from the Low-Pressure Glaucoma Treatment Study. Am J Ophthalmol. 2011;151:671-681.
  4. Barkana Y, Belkin M. Selective laser Trabeculoplasty. Surv Ophthalmol. 2007;52:634-654.
  5. Katz LJ, Steinmann WC, Kabir A, Molineaux J, Wizov SS, Marcellino G. Selective laser trabeculoplasty versus medical therapy as initial treatment of glaucoma: a prospective, randomized trial. J Glaucoma. 2011 May 3. [Epub ahead of print].
  6. El Mallah MK, Walsh MM, Stinnett SS, Asrani SG. Selective laser trabeculoplasty reduces mean IOP and IOP variation in normal tension glaucoma patients. Clin Ophthalmol. 2010;4:889-893.
  7. Varma R, Ying-Lai M, Francis BA, et al; Los Angeles Latino Eye Study Group. Prevalence of open-angle glaucoma and ocular hypertension in Latinos: the Los Angeles Latino Eye Study. Ophthalmology. 2004;111:1439-1448.
  8. Topouzis F, Coleman AL, Harris A, et al. Association of blood pressure status with the optic disk structure in non-glaucoma subjects: the Thessaloniki eye study. Am J Ophthalmol. 2006;142:60-67.
  9. Quaranta L, Bettelli S, Iva MG, et al. Effect of ginkgo biloba extract on preexisting visual field damage in normal tension glaucoma. Ophthalmology. 2003;110:359-362.