COREGULATION OF IOP AND VASCULAR RISK FACTORS IN GLAUCOMA MANAGEMENT
By Elliot M. Kirstein, O.D., F.A.A.O.
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Optometrists have long considered high intraocular pressure (IOP) as the primary culprit in glaucomatous visual field loss, but recent investigations suggest that comprehensive glaucoma management should involve consideration of a wider range of known risk factors. Classically, management decisions have hinged upon IOP measurements, threshold visual field analyses, ophthalmoscopic optic nerve head evaluations, gonioscopy, and family history. Currently, clinicians may have access to additional data such as digital optic nerve head analysis, pachymetry and ocular blood flow analysis, which can enrich and support the quality of information used to develop treatment plans.
This course will focus on the role of ocular hemodynamics in the pathogenesis and management of glaucoma. It will present arguments that support of ocular ischemia as a factor in glaucoma etiology. It will also describe methods for clinically evaluating ocular blood flow, and present a rational for the clinical application of blood flow data in the early diagnosis of glaucoma.
Optometrists are occasionally faced with a patient who has clear and irrefutable clinical evidence of existing glaucoma. A diagnosis of glaucoma is not difficult when extreme IOP is combined with extensive cupping and corresponding threshold visual field loss. However, more often we have to make a diagnosis in a situation that is not nearly so black and white, especially when we strive to treat early in the progression of glaucoma in the hope of minimizing field loss.
As a model, it is useful to compare the complex, multi-factorial origin of glaucoma to coronary artery disease. The risk factors in both conditions are subtle, beginning with heredity and early lifestyle. Like coronary artery disease, issues such as diet and aerobic fitness may be pivotal variables. Another, perhaps anecdotal, similarity is that, until recently medical therapy for both pathologies was prescribed only near the end stages of the diseases and was dramatically interventional.
A new paradigm in the management of coronary artery disease and glaucoma involves assessing a wide range of risk factors along with earlier diagnosis and treatment designed to prevent needless disease progression.
As optometric physicians, we tend to care for the younger and healthier 65% of Americans. We are charged with making accurate and early diagnoses as well as providing effective therapies that attenuate glaucomatous progression. Fortuitously, new inroads in diagnosis and preventative therapies appear to help reduce morbidity in heart disease and glaucoma. The newly coined term "pre-parametric glaucoma," or "glaucoma before threshold visual field loss," is testimony to our recent commitment to managing glaucoma more aggressively and at an earlier stage. At the very least, use of the term affirms that glaucoma does exist before we can document field loss.
As we expand our understanding of the disease and analyze the many risk factors that contribute to glaucoma, we can diagnose the condition in its early stages. This leads to a shift in our management paradigm that has been supported by findings from studies such as The Advanced Glaucoma Intervention Study (AGIS) and The Ocular Hypertensive Treatment Study (OHTS) and the Normal Tension Glaucoma Study (NTGS). (21)
In the late 1800's, an eminent British ophthalmic surgeon, Priestly Smith, described glaucoma as:
"The excavation of the disc in glaucoma is not a purely mechanical result of exalted pressure; it is, in part at least, an atrophic condition which, though primarily due to pressure, includes vascular changes and impaired nutrition of the substance of the optic discwhich may possibly progress even though all excessive pressure be removed." (26)
Given the technology of his time, it is amazing that Dr. Priestly made such a stunning and profound observation. One can only speculate on why for the bulk of the twentieth century glaucoma was exclusively managed as a disease of elevated intraocular pressure with little regard for other risk factors such as ocular blood flow. Nonetheless, since the 1960's, researchers have provided a convincing rational for glaucoma as a multi-factorial disease in which IOP and ocular blood flow work in some combination to impact survival of the optic nerve. (1,11)
In fact, high IOP and low pulsatile ocular blood flow (POBF) may well be co-existing risk factors in glaucoma. Together, they behave as fraternal twins and can impose lethal stress on retinal neurons in the vicinity of the disc. When IOP is high and POBF is low, the eye is at greatest risk. Conversely, when IOP is low and POBF is normal, the risk of glaucomatous axonal damage is low. Beyond the wealth of scientific evidence that has accumulated on this topic, it seems intuitively clear that excessive IOP combined with ischemia will threaten optic nerve vitality.
Anatomy of the Optic Nerve Blood Supply and Watershed Zones
The main blood supply to the optic disc is from the ophthalmic and carotid arteries to the short posterior ciliary arteries (PCAs), which supply the choroid and the circle of Zinn-Haller. The circle of Zinn-Haller is a doughnut-shaped vascular plexus that encircles the papilla and is part of the choroidal vascular bed. It is the portion of the choroid that nourishes most of the orbital portion of the optic nerve.
On their way to the globe, the PCAs give
off small branches extending through the dura matter and forming
and anastomosing plexus with the pia matter. This pial plexus
is also supplied by branches from the central retinal artery at
its entrance to the optic nerve.
Near the posterior wall of the globe, the PCAs divide into about
10 to 20 small branches. Direct branches travel to the lamina,
the choroid or the circle of Zinn-Haller. Solan Singh Hayreh suggested
that the peripapillary vascular supply is not evenly distributed
around the optic disc and can vary significantly between individuals.
(9-14) Hayreh also reported that the medial and temporal quadrants
are more often well perfused, while the superior and inferior
quadrants have less arterial influx. These areas with less perfusion
may often behave as watershed indicator zones; optic nerve axons
are more susceptible to ischemic insult in the hypo-perfused areas
at the inferior and superior disc margins.
Additionally, when IOP increases, resistance against the systemic blood pressure also increases and this compromises perfusion to the peripapillary watershed zone. When IOP decreases, blood flow to the choroidal bed is less problematic. Technologies such as Doppler flowimetry and pulsatile ocular blood flow analysis now enable us to observe and quantify these effects.(10,16,19,20)
Figure 1. Blood pathway from the heart to the short posterior ciliary arteries.
Figure 2. Short Posterior ciliary arteries running parallel to the optic nerve and entering the globe.
Figure 3. Hypo-perfused (watershed zone) area around the disc. (25) Image courtesy of S. Karger AG, Basel, Switzerland.
Pulsatile Ocular Blood Flow (POBF) and POBF Analysis
New technologies offer us more information about the ocular blood supply. One such device is the Ocular Blood Flow Analyzer (BFA), Paradigm Medical Industries). This pneumotonometer records and analyzes the dynamics of the mire pulsation that we observe during Goldmann applanation.(12)
Figure 4. Paradigm-Dicon pulsatile ocular blood flow analyzer
Maurice Langham originally developed the BFA in the late 1970s. Since then, several technical updates have increased the accuracy and repeatability of its measurements, and have made the instrument easier to operate.
Here's how the BFA works:
During the systemic pulse, the globe expands and contracts as the erectile choroidal vasculature fills and empties. IOP also rises and falls during the pulse cycle. In an average individual, approximately 900 microlitres (about one teaspoon) of blood passes through the eye per minute. The BFA tracks changes in IOP at a frequency of 200 Hz, then it transforms these data into a volume profile for the eye.
The device differentiates the volume profile to produce a rate of change against time.(13) The blood flow analyzer essentially measures the entire orbital pulse. Clinically, the pulsatile component of this value is reasonably well correlated to the quality of the blood supplied to the orbital portion of the nerve as measured in microlitres per second (ul/sec).
Studies have demonstrated a bell curve distribution of pulsatile ocular blood flow values in the normal population with typical values ranging from 12 to 22 ul/sec. Patients with values below 12 ul/sec either already have glaucomatous field loss or are at risk of impending loss. Individuals with blood flow values greater than 12 ul/sec are less likely to sustain field loss resulting from hypo-perfusion.(1)
The BFA reports IOP, pulse amplitude in mm Hg, and pulsatile ocular blood flow in ul/sec. The instrument produces a detailed report, which provides the time, date, and a graphic representation of the patient's test results.
The BFA test is performed in a manner similar to Goldmann applanation tonometry. However, unlike in Goldmann tonometry, the instrument will not display a test result unless the data received meets certain quality criteria. IOP values are considered to be more accurate than Goldmann values because the BFA probe is smaller in diameter than that of the Goldmann and thus is less influenced by variations in corneal thickness.(12)
Figure 5. Distribution of pulsatile ocular blood flow in normal males and females
Figure 6. Distribution of POBF for normal and glaucomatous populations.
Figure 7. Typical variation in IOP over time. Pulse amplitudes of 3 mm Hg are common.
Figure 8. Pneumotonometer applanation tip on the cornea
Acute Perfusion Pressure Effect
When glaucoma treatment reduces IOP, a corresponding effect on ocular blood flow occurs. Measuring and understanding the relationship between IOP and blood flow is a key factor in glaucoma management.
The acute perfusion pressure effect (APPE) is the first and most dramatic change in pulsatile ocular blood flow that results from significant changes in IOP (greater than 4 mm Hg). A significant IOP reduction is usually followed by a similarly significant increase in the POBF. An equally dramatic drop in POBF, representing diminished ocular perfusion, usually follows a significant rise in IOP. Less significant variations in IOP (1 to 3 mm Hg) are not often associated with a measurable change in POBF because of the stabilizing effect of the autoregulatory response.(10)
Factors that effect APPE are the relative quality of the patient's autoregulation mechanism, variations in individual microvascular architecture, vascular health, and ocular/systemic drug use.(9, 14-17)
Autoregulation
Autoregulation is the mechanism that modulates intraluminal pressure of the capillary bed systemic blood pressure and IOP vary. The purpose of autoregulation is to accommodate the metabolic requirements of ocular neural tissues despite wide swings in the systemic blood pressure or IOP, e.g., diurnal variation.
During sleep, when systemic blood pressure is typically at its lowest, the autoregulatory mechanism causes decreased microvascular resistance, thus facilitating choroidal perfusion. The same is true with small changes in IOP; autoregulation will, within limits, adjust blood flow when IOP changes by small amounts (1 to 3 mm Hg). Endothelin 1 and nitric oxide, derived from the microvascular endothelium, may cause the contraction and relaxation of the vessels that supply the choroidal bed.(11)
Existing knowledge suggests that autoregulation is a local myogenic process that takes precedence over autonomic influences and spontaneous metabolic tissue demands. Researchers believe that autoregulation can be defective and have limitations, which vary widely between individuals. They further speculate that these defects and limitations are somehow responsible for some types of glaucomatous field loss.
A decrease in the limits of autoregulation has been demonstrated in some glaucomatous individuals. This means that a change in IOP in a healthy individual might have less effect on POBF as compared to the same IOP change in a patient with advanced glaucoma.
A rational explanation for the positive therapeutic results achieved by IOP reduction is that positive APPE helps to mitigate the effects of inadequate microvascular blood supply in glaucomatous eyes. It also reduces the direct insult of high IOP on the axonal bed.(3-8, 10, 18-20) When medical therapy yields a significant drop in IOP, we also enhance pulsatile ocular blood flow. The implication is that clinicians should strive for a robust pressure reduction even with early glaucoma thereby augmenting blood flow via overriding the limits of autoregulation.
Normal Tension Glaucoma (NTG)
There is mounting epidemiological evidence that NTG is far more common than was previously recognized. Recent surveys from different populations reveal that 35 to 60% of newly diagnosed open angle glaucoma patients have NTG.(32) A general consensus seems to have formed that NTG has a vascular origin. Although a vascular etiology for NTG has long been suspected, recent investigations have helped to reinforce that notion.
Hitchings et al. at Moorfields Eye Hospital measured POBF values in 777 normal eyes and compared them to 236 eyes with NTG.(1) Their investigation clearly demonstrated that NTG eyes tended to have reduced POBF as compared to normal eyes. In a second study, Hitchings demonstrated reduced POBF in asymmetric NTG; lower POBF values were found in eyes with more advanced disease.(24) This research implies that the clinical profile of NTG is one in which the patient has average IOP combined with reduced POBF.
Clinicians commonly have difficulty with the evaluation of patients who have suspicious nerves, normal fields and average IOP. Is the cupping physiological, or is there early disease? In practice, ocular blood flow analysis can be used to help answer this question. The finding of average to high POBF, along with the aforementioned parameters, points to a conservative treatment approach and withholding pressure-lowering medications or procedures. The same parameters, combined with statistically low POBF strongly suggest a diagnosis of early NTG and the initiation of IOP lowering therapy.(40)
Optic Nerve Disc Hemorrhage (ONDH) and Peripapillary Atrophy (PPA)
Optic nerve disc hemorrhage is now considered to be not only a clinical feature but also a risk factor for the progression of optic disc damage in NTG. Regardless of the basic mechanism, ONDH most likely reflects impaired integrity of the vascular wall and therefore may be considered a major vascular factor in NTG. Likewise, PPA seems to be another risk factor for optic nerve damage in NTG.(34,36)
"Zone beta" is the newly coined term used for the zone of obliterated choroidal vessels, which often surround the disc in glaucomatous eyes.(1,4,8,11)
ONDH, secondary to excessive liberation of vaso-active substances (possibly endothelin-1), is associated with migraine, decreased systemic blood pressure, silent myocardial infarction, and reduced POBF.(27,31,33) These relationships, combined with the statistical correlation between ONDH, PPA, and NTG help validate our intuition about the vascular etiology of NTG.
For several years the cause of OBDH has been in question, but it is now reasonable to consider that some type of malfunction (or over action) of endothelin-1 and autoregulation cause a hemorrhagic breach in the optic nerve vessel walls.
Flame hemorrhages anywhere in the retinal nerve fiber layer (NFL) are most often the result of an ischemic event or process. Until proven otherwise, we should assume that NFL hemorrhage on the disc margin is of the same origin.
Figure 9 Reduced POBF with Drance hemorrhage.
Fig. 10 Drance hemorrhage.
Figure 11 Zone beta, hypo-vascular peripapillary choroid.
Myopia
Although myopia is a known risk factor for glaucoma, the mechanism of that risk remains in question.
What is different about the highly myopic eye that makes it more prone to glaucoma? Is the glaucoma associated with myopia somehow different from other glaucomas?
What we can agree upon is that myopic eyes are larger and, from an ophthalmoscopic view, appear to be stretched irregularly beyond their appropriate limits. Myopic eyes can be thought of as having a sort of "substandard" ocular architecture. In high myopia, the peripapillary retina is often stretched, creating an avascular zone, which is easily observed during ophthalmoscopy. One might imagine that this causes the vitality of the adjacent optic nerve and overlying nerve fiber layer could be challenged by inadequate blood supply.
As an additional question, what happens to a highly myopic eye as the body ages and other risk factors become relevant? The onset of processes like arterial sclerosis, diabetes or reduced cardiac output might take the fragile myopic eye over the edge, causing vision threatening ischemic nerve fiber loss.
The relative POBF decrease in highly myopic eyes is easily observed with pulsatile ocular blood flow analysis. A large, myopic eye can be considered to be more difficult to irrigate with blood than a smaller emetropic or hypermetropic eye.
To investigate this possibility, ocular pulse amplitude and pulsatile ocular blood flow values were studied in 80 eyes from 80 subjects with refractive errors between +3.00 and -28.00 diopters using the Ocular Blood Flow System. Significant positive correlations were found between PA and axial length, and between PA and refractive error. Longer and more myopic eyes tended to have higher PA values. Significant negative correlations were found between POBF and axial length, and between POBF and refractive error. Longer and more myopic eyes tended to have lower POBF values.(35)
Migraine
Studies show that 47% of NTG patients suffer from migraine (27) and that patients with this disease have a significantly increased incidence of vasospasm, and significantly reduced finger blood flow (28) with prolonged stasis following cold water provocation.(29)
Magnetic resonance imaging studies showed that NTG patients also have shown an increased incidence of ischemic tissue alteration in the brain.(30) The relationship of migraine with glaucoma is well established and clearly points to the conclusion that hypo-perfusion of the optic nerve represents a significant risk for glaucoma.
Nocturnal Hypotension
Recently, greater attention has been given to the role of systemic blood pressure in the pathogenesis of NTG. Studies using 24-hour blood pressure monitors have demonstrated an increased frequency of nocturnal hypotension for NTG patients. For example, Kaiser et al. demonstrated a 15 to 20 mm Hg blood pressure difference between normal and NTG subjects at 3:30 am.(37,38) This implies that reduced nocturnal systemic blood pressure is likely to be involved in glaucomatous damage.
Another consideration may be the use of systemic medications such as antidepressants or beta-blockers, which have the potential to depress blood pressure to unacceptably low levels. Patients on blood pressure lowering medications, and some patients with normal tension glaucoma, may exhibit an excessive fall in systolic and diastolic blood pressure while asleep. This could reduce ocular perfusion pressure unless IOP also falls. For this reason, glaucoma patients should be questioned about any systemic hypotensive medications that they are taking.
Figure 12. Mean systolic blood pressures
Ophthalmic Medication and Surgical Treatments: Choices for Therapy
With the understanding that we can alter and often improve pulsatile ocular blood flow by significantly reducing IOP, how should we design treatment plans? Obviously, our goals must be to reduce IOP, improve POBF, and protect the optic nerve, but how do we design therapies that make sense for our patients? This begs the questions: Which medications are best for ocular blood flow? And, which elicit the greatest POBF augmentation with concomitant reduction in IOP?
It would be advantageous to know which medications would enhance axonal blood supply beyond the APPE, perhaps by adjusting inadequate autoregulation.
Anecdotal evidence (and some research) suggests using caution when prescribing beta-blockers to reduce systemic blood pressure, particularly at bedtime. It is possible that the blood pressure-lowering effects of non-selective beta-blockers, along with the body's proclivity toward reduced systemic blood pressure during sleep, might further compound ischemic axonal insult to the nerve.(14, 41-43)
For years European doctors have endorsed using cardio-selective beta-blockers for their normotensive glaucoma patients. Other researchers suggest that topical carbonic anhydrase inhibitors augment perfusion to the axonal bed by inhibiting the vasoconstrictive action of endothelin-1. Recent investigations suggest that unoprostone and the widely accepted prostaglandins may have a beneficial effect on the availability of rich oxygenated blood to the orbital portion of the retinal nerve fiber layer.(22)
An acute rise in POBF resulting from pressure-lowering surgeries such as ALT or filtration can easily be demonstrated. Additionally, many clinicians are now considering the effects of systemic medications on ocular blood flow in the absence of influence on IOP. It is also reasonable to consider how individual aerobic fitness, smoking, arteriosclerosis and migraine may influence the course of glaucoma by altering blood flow, blood pressure, and possibly even IOP.(23, 41-43)
Lacking clear evidence that any single medicine or treatment is best for enhancing blood flow, the most appropriate clinical approach remains the drug or procedure that most effectively reduces IOP to target pressure. Fortunately, because of the acute perfusion pressure effect, an acceptable IOP response is generally accompanied by some degree of blood flow augmentation and nerve preservation.
The Role of Co-Regulation
Given our ability to evaluate POBF and observe how therapies affect an individual's ocular blood flow and IOP, we can begin to co-regulate these variables. Most likely, having knowledge of our patients' POBF values (along with the more traditional management cornerstones such as IOP, NFL analysis, threshold fields, gonioscopy, and history) will sharpen our management skills, especially with regard to when to initiate or modify therapy.
Multicenter studies, including the Ocular Hypertension Treatment Study, suggest that early diagnosis and aggressive therapy can help prevent field loss.(21) And, comprehensive assessment of risk factors can help us to make therapeutic decisions while glaucoma still exists in its pre-perimetric phase.
Still, understanding and evaluating the vascular component in the pathogenesis of glaucoma is often complicated. Variables such as cardiovascular health and lifestyle often contribute to and complicate an individual's prognosis. We are often confronted with a set of borderline findings showing suspect IOPs, inconclusive fields, suspicious optic nerves, and vague family history.
Given this scenario, finding that our patient has robust POBF can allow us to feel more comfortable with following the patient without medical or surgical intervention. Conversely, a finding of statistically poor blood flow should cause us to become more aggressive in our management. Every additional piece of clinical data that helps us to break the tie in our decision-making process is of great value.
Case Study
The following case report illustrates the use of pulsatile ocular blood flow analysis in making clinical treatment decisions.
J. R. is a 32-year-ols Puerto Rican male who presented for a routine eye examination at Harper's Point Eye Associates on 5/2/2001. J. R. was employed as a computer software engineer and had no complaints about his vision. He reported having no problems with his general health or ocular health, with the exception of astigmatism. His last routine medical examination was one year ago. He reported allergy to penicillin with no other known allergies. His family ocular history was positive for glaucoma, including both grandparents, parents, and an older brother who started taking eye drops for glaucoma at age 40. J. R. reported that his deceased paternal grandfather had late onset diabetes and systemic hypertension.
Ocular Examination:
Manifest refraction at distance of OD +.75 2.00 x 100 and OS =.50 2.25 x 87 yielded 20/20 and 20/20- for the right and left eyes respectively, with J1 for each eye. Extraocular movements were smooth and extensive to six positions of gaze. Pupils were equal, round, reactive to light and accommodative stimulus, with no afferent defect in either eye. Blood pressure was 115/75 with pulse of 65 beats per minute (bpm).
Biomicroscopic examination revealed clear adenxa, lids, conjunctiva and cornea in each eye. Anterior chambers were clear, with no cells or flare. Irides were brown with uniform pigment distribution. Goldmann applanation tensions at 10:00 am taken before pupil dilation were 21 and 20 mm Hg respectively. Pachymetric measurements for apical corneal thickness were average at OD= 545 microns and OS= 541 microns. Three-mirror gonioscopic view revealed grade 3 open angles 360 degrees with flat irides and 1+ dust like pigment in each eye. The ciliary body was visible 360 degrees in each eye. The corneal endothelium was clear of pigment deposition and there was no iris trans-illumination in either eye.
Dilated funduscopic examination with the Volk 78 and BIO using Fluress, 1% tropicamide, and 2.5% phenylepherine, revealed clear disc margins, vein/artery = 3/2, cup/disc = .65v/. 6h, thin yet healthy and symmetrical nerve margins, brisk foveal reflex and normal periphery in the right eye. Examination of the left eye revealed clear and thin disc margins, vein/artery 3/2, and cup/disc - .70v/. 70h, healthy and symmetrical disc margins, brisk foveal reflex and normal periphery.
Threshold visual fields, measured with the Octopus 123 tendency oriented perimetry (TOP) algorithm showed a slight Bjerrum shaped depression in the superior field of each eye. The mean deviation was OD = 1.5 and OS = 1.2 decibels. The loss variance was OD = 3.9 and OS = 4.3 decibels. Although the reliability of the right field test was excellent, the left eye result showed a false positive response, which diminished reliability.
Heidelberg HRT-2 tomographic initial results showed enlarged, yet symmetric, cupping in each eye with no areas of nerve fiber loss at the disc margin of either eye, as compared the HRT-Moorfields normative database. Pulsatile ocular blood flow analysis (POBF) showed 7.5 and 6.6 microlitres/second values in the right and left eyes respectively, which often indicates hypo-perfusion of the axonal beds. Values were in the lower 5th percentile as compared to established norms.
Figure 13. HRT-2 image of suspicious optic nerve
Assessment:
Bilateral mixed astigmatism
Possible early normal tension glaucoma
Plan:
After a thorough review of initial findings and a thorough discussion with J. R. to discuss the nature, onset, and management of normal tension glaucoma and astigmatism, J. R. was asked to schedule for follow-up and repeat glaucoma testing within one week at a late-day appointment. An updated spectacle prescription was written, for J. R., with the recommendation to have it filled on an elective basis.
Follow-up #1
J. R. returned for follow-up on 5/7/2001. He reported no changes in health or visual status. Habit visual acuities were 20/20 in each eye. Goldman applanation tensions were 21mm Hg OD and 19 mm Hg OS at 6:30 pm. Dilated Biomicroscopic and funduscopic examinations were unchanged from his previous visit.
After extensive discussion with J. R. with regard to his ocular findings and family history, and a review of the potential side effects of betaxolol, we agreed to initiate a monocular therapy trial of betaxolol 0.25% one drop B.I.D O.D. He was trained on drop instillation with punctual occlusion and scheduled to return for follow-up in three weeks.
Follow-up #2
J. R. returned for follow-up examination on 5/18/01 reporting no difficulties in using the eye drops and no changes in vision and health. He explained that because of his travel schedule he pushed the appointment up a few days. Visual acuities were unchanged. Applanation tensions were OD = 17mm and OS = 22mm at 10:15 am. POBF values were increased to OD = 9.4 microlitres/sec and OS = 8.7 microlitres/sec.
Given the 20% initial reduction in IOP for the right eye (which appeared to meet our goal), J. R. was instructed to use the betaxolol in each eye B.I.D. and to return for follow-up in 2-3 months.
Follow-up #3
J. R. returned for 3-month follow-up evaluation on 7/17/2001. He reported that he had used the medicine as instructed and that his health and vision were excellent. Corrected acuities were OD = 20/20- and OS = 20/20. Goldmann applanation tensions were 16 mm Hg OU at 9:30 am. Biomicroscopic anterior segment exam and funduscopic exam (without dilation) with the Volk 90 diopter lens was unchanged. Systemic pulse rate was 63 beats per minute.
J. R. was instructed to stay on the same medicine and return for repeat HRT-2 and intraocular pressure testing in three months.
Follow-up #4
At the 10/10/2001 follow-up, J. R. reported no changes in his vision or health. Corrected acuities were OD = 20/20- and OS = 20/20-. Intraocular pressures were OD = 16 mm Hg and OS = 17 mm Hg. Systemic pulse rate = 65 bpm. Heidelberg optic nerve analysis showed possible nerve fiber layer loss in the 11:00 position of the right optic nerve. The left nerve appeared unchanged. No visible changes were apparent with Volk 78D funduscopic view. J. R. was scheduled for follow-up with threshold testing in 3 months.
Follow-up #5
J. R. returned for follow-up on 3/4/2002. He reported no changes in his health or vision. He reported that he had been faithful in using his medicine as directed. Corrected acuities remained unchanged. Goldmann tensions were 18mm Hg OD and 16mm OS. Dilated (1% tropicamide x 1 OU) funduscopic examination was unchanged in each eye.
HRT2 analyses showed loss of optic nerve rim tissue temporally and inferiorly in the right eye and no significant change in the left. Threshold visual fields showed an increase in para-central depression in each eye and showed better reliability for each eye. The mean deviation was OD = 3.6 and OS = 3.4 decibels. The loss variance was OD = 4.6 and OS = 3.5 decibels. Pulsatile ocular blood flow analysis revealed 5 microlitres/sec pulsatile flow in the right eye and 7 in the left.
After a thorough discussion of our clinical observations with J. R., he was instructed to discontinue the betaxolol in the right eye and commence one gtt. qhs latanoprost in that eye. He was told to continue the betaxolol, b.i.d., in the left eye. Additionally, we discussed the potential side effects of latanoprost. Repeat IOP and blood flow analysis was scheduled for 4 weeks.
Summary
Until recently, implementing medicinal therapy for glaucoma without frank and repeatable threshold field loss was discouraged. However, new varieties of clinical data, such as laser nerve fiber analysis and pulsatile ocular blood flow analysis, now allow us to understand more about an individual's risk for glaucomatous nerve fiber loss and to consider therapy at an earlier point in disease progression.
At his initial evaluation, J. R. had no single risk factor that was diagnostic of normal tension glaucoma, yet all factors were at least borderline, and collectively they pointed to that diagnosis. His fields were marginal for both eyes and somewhat unreliable for the left eye. His strong family history, suspicious nerves, and dramatically low ocular perfusion values, along with his youth added up to a convincing argument for treatment.
J. R.'s youth was a serious consideration as compared to a 90 year-old patient who would be unlikely to require the use of his optic nerves for another seventy years. Because glaucomatous axonal death seems to accelerate over the course of the disease, and given our new armamentarium of glaucoma medications which are more acceptable to patients, current protocols encourage earlier intervention.
Our decision to initiate therapy for J. R. with betaxolol was based on the borderline nature of his case and the positive literature with regard to betaxolol's ability to increase ocular perfusion in normal tension glaucoma patients. In addition, betaxolol has an excellent safety record for those individuals with no known risk factors for its side effects.
Initially, we set a target for an IOP reduction of 20%. On his most recent visit, J. R. showed a diminished response to the betaxolol, with elevated IOPs and reduced pulsatile ocular blood flow, which points to disease progression and or the extinction phenomenon. Even though his progression in the past year might be considered subtle, more aggressive therapy was initiated with the goals of a one third reduction in IOP, a more substantial increase in ocular perfusion, and stabilization of threshold fields and optic nerve imaging values.
Today, it seems logical that IOP reduction and POBF enhancement are fundamental tools for retarding glaucomatous field loss. Although glaucoma is a progressive and incurable disorder, we can use our best and most reasonable clinical tools including threshold visual fields, optic nerve head imaging, pachymetry, and pulsatile ocular blood flow analysis to achieve earlier and more accurate diagnoses, and provide the most appropriate interventions, when indicated.
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Contact the Author:
Elliot M. Kirstein, O.D., F.A.A.O.
11304 Montgomery Road
Cincinnati, Ohio 45249-2313
drkirstein@drkirstein.com
Dr. Kirstein is the director of an optometric group practice in Cincinnati, Ohio, specializing in glaucoma and primary eye care. He has lectured for Interzeag (Haag-Streit), and, for the past five years, he has worked as a consultant and lecturer for Ocular Blood Flow Labs of the U.K. and Paradigm Dicon Medical Industries.
A previous version of this work appeared in Review of Optometry 2002; 139:07.
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