OGS PRESIDENT'S MESSAGE

I would like to thank everyone for the warm response we received in regards to the introduction of the OGS Electronic Journal. Please tell your colleagues about this new endeavor. Back issues as well as the ability to sign up to receive the e-journal are available at www.optometricglaucomasociety.org. The editorial team consisting of our editor in chief, Paul Spry; our associate editors Brad Fortune, Shaban Demirel, and Algis Vingrys; and the editorial board look forward to crafting a journal that meets the needs of optometrists engaged in the management of glaucoma. Please continue to provide us with feedback and questions.

One new and important topic related to glaucoma is the issue of patient adherence with a treatment regimen. Put another way, there is a profound lack of persistency on the part of many patients in maintaining therapy. We hope to explore this topic in future issues.

Why is it that recently published studies show many patients do not continue their therapy? In a recent discussion I had with a friend, who is a nephrologist by training and actively involved in patient-doctor communication education, he remarked that no matter how simple you create the treatment regimen or how great the drug is, these factors will only improve compliance so far. His belief is that the unforgotten and much harder component to enhance adherence is doctor-patient communication. This skill (and I refer to it as a skill similar to performing other procedures) is often overlooked and underappreciated. Good communication is difficult, in part because many of us are not used to listening to our patients. Still as I thought about this, I realized that when I came away from a doctor’s visit impressed with the clinician, it was often because of his/her interpersonal skills.

When I was in optometry school, an instructor who taught the ophthalmic optics course had a saying that you could do the best refraction but if the patient could not wear the glasses, what have you really accomplished? Well, maybe the modern day version is that you can make the best diagnosis, but if the patient is not using your prescribed therapy, again what has been accomplished?

Murray Fingeret, OD
President, Optometric Glaucoma Society
murrayf@optonline.net

EDITORIAL

IOP: down but not out.

Knowledge regarding glaucoma continues to grow at an immense rate: it doesn’t seem like long ago that many texts reported elevated intraocular pressure (IOP) and open-angle glaucoma were synonymous. Of course, now we are all very well aware that elevated IOP is neither necessary nor sufficient to cause glaucoma. Like many other chronic diseases, glaucoma is best explained as a multi-causal paradigm: IOP simply complements and interacts with the susceptibility of individuals. The days of elevated IOP as an essential element of glaucoma’s diagnostic triad, alongside optic nerve appearance and loss of visual function, are therefore over. However, unless it is put into context, this apparent ‘downgrading’ of raised IOP from diagnostic to risk factor status, alongside the confounding effects of corneal thickness on tonometric validity, may give the misleading impression that IOP measurement is a less important part of routine clinical examination than it used to be.

Fortunately, there are many studies to dispel such a misconception. The highest body of evidence to support IOPs’ current status in glaucoma care comes from randomised controlled trials. Key trials are summarised in this issue’s Clinical Trial Review. Whilst each trial differs in objectives and methodology, the consensus is that reducing IOP improves glaucoma group outcomes. Although IOP is only a risk factor, at present it is also the only currently proven modifiable risk factor that we can use to help our glaucoma patients.

Paul GD Spry, PhD MCOptom, Editor-in-Chief
paul.spry@ubht.swest.nhs.uk

Your first patient is 50 years old and has ocular hypertension. His risk factors for developing glaucoma include: no diabetes, a corneal thickness of 590 microns, cup to disc ratio (C/D) of 0.7, pattern standard deviation of 2.1, and an intraocular pressure of 26 mm Hg in both eyes. Do you treat with ocular hypotensive medications? Or do you watch?

Trying to decide whether to treat the above patient is complex without a tool to simplify the estimate of risk. For example, the Ocular Hypertension Treatment Study (OHTS)(1,2) suggests that this patient has a lower risk of developing glaucoma based on age (50 years vs. the average age of the OHTS patients of 56 years), corneal thickness (590 microns vs. 572.5 within OHTS), and diabetes (history of diabetes was protective); but a higher risk based on C/D (0.7 vs. 0.39 in the OHTS study), pattern standard deviation (2.1 vs. 1.9 average in the OHTS study), and intraocular pressure (26 mm Hg vs. 24.9 mm Hg in the OHTS). Even if one divides the continuous variables of age, corneal thickness, IOP, and PSD into thirds and uses 9 different combinations for C/D (0.0-0.8), 1458 (3x3x3x3x2x9) different combinations of variables exist for ocular hypertension patients. This creates a large number of different combinations of variables for any one ocular hypertension patient. Only by using a risk calculator or a prediction model can one simplify these complex results.

Using our risk calculator(3), the above ocular hypertension patient has a risk of 21.9% of developing glaucoma over 5 years (Figure). Clinicians and patients can use this information- in conjunction with other characteristics such as life expectancy and likelihood to be compliant with medications- to decide whether to treat. Risk calculators will allow clinicians to identify and treat only those patients most likely to develop glaucoma, resulting in decreased costs to society and decreased side effects to patients.

However, clinicians should only use a risk calculator based on OHTS for those patients who meet the inclusion and exclusion criteria of OHTS. For example, clinicians should not assume that eyes with secondary causes of ocular hypertension, such as pseudoexfoliation or pigmentary dispersion syndrome, would have similar risk factors to the OHTS study population.

Recently, other investigators have created risk calculators for ocular hypertension patients using similar methods(4). Other calculators using larger sample sizes and new technologies are likely to improve the precision of the risk estimate in the future. For example, the OHTS group will be releasing a risk calculator based on the five year results of the OHTS(1,2) and European Prevention Study(5). Other calculators may improve the predictive ability by using selective functional testing such as short-wavelength automated perimetry, or objective structural testing such as confocal scanning laser ophthalmoscopy(6). In summary, eye care providers should use one of the currently available risk calculators, but other risk calculators will be available in the future.

Risk calculators provide an objective method of determining the risk of developing glaucoma from ocular hypertension. Their results are easy to understand and easy to apply. Patients, providers, and society will benefit from their use.

Devers Eye Institute/Discoveries in Sight, 1040 NW 22nd Avenue, Suite 200, Portland, OR 97210. Telephone 503-413-6453; Telefax 503-413-6937 Email: smansberger@deverseye.org.

Steven L. Mansberger, MD, MPH

1. Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol 2002;120:701-13; discussion 829-30.
2. Gordon MO, Beiser JA, Brandt JD, et al. The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol 2002;120:714-20; discussion 829-30.
3. Mansberger SL. A risk calculator to determine the probability of glaucoma. J Glaucoma 2004;13:345-7.
4. Medeiros FA, Weinreb RN, Sample PA, et al. Validation of a predictive model to estimate the risk of conversion from ocular hypertension to glaucoma. Arch Ophthalmol 2005;123:1351-60.
5. Miglior S, Zeyen T, Pfeiffer N, Cunha-Vaz J, Torri V, Adamsons I. Results of the European Glaucoma Prevention Study. Ophthalmology 2005;112:366-75.
6. Zangwill LM, Weinreb RN, Beiser JA, et al. Baseline topographic optic disc measurements are associated with the development of primary open-angle glaucoma: the Confocal Scanning Laser Ophthalmoscopy Ancillary Study to the Ocular Hypertension Treatment Study. Arch Ophthalmol 2005;123:1188-97.
7. Devers OHTN to Glaucoma Risk Calculator: Devers Eye Institute, Legacy Health System, 2003. PC, MAC, Palm, and C++ versions are available free at: www.discoveriesinsight.org.

NEW IDEAS & NEW PAPERS

OPTIC NERVE REVIEW

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Zone beta is more specific to glaucoma damage of the optic nerve. There is an association of adjacent thinning of the neuro-retinal rim tissue and decrease in RNFL with an increase in size of zone beta. Zone alpha has less specificity for glaucoma damage and is frequently seen in normal eyes. On visual field testing, zone beta will correlate to an absolute scotoma (enlarged blind spot) and zone alpha to a relative scotoma. An increase in PPA has also been shown to correlate with progressive glaucoma damage.

In summary, PPA is a less specific sign of glaucoma damage and should be considered as a secondary level of importance in glaucoma management. It is still prudent to scrutinize for PPA which may uncover subtle thinning of the neuro-retinal rim tissue. Comparison of PPA in longitudinal optic nerve photographs can assist in determining glaucoma progression.

Anthony B. Litwak, OD, FAAO
Len V. Hua

1. Jonas, JB. Clinical implications of peripapillary atrophy in glaucoma. Curr Opin Ophthalmol 2005; 16:84-88.
2. Curicio, CA, Saunders PL, Younger PW, et al. Peripapillary Chorioretinal Atrophy. Bruch's membrane changes and photoreceptor loss. Ophthalmology 2000;107:334-343.
3. Uchida H, Ugurlu S, Caprioli J. Increasing peripapillary atrophy is associated with progressive glaucoma. Ophthalmology 1998;105:1541-1545.

VISUAL FIELD REVIEW

Does the 24-2 pattern detect all early glaucoma?

Does this sound like a common debate that you have in the bar with your colleagues? It really stems from the era of kinetic perimetry (Goldmann bowl). In those days glaucoma was considered a peripheral disease which, by default, needed a peripheral field test for detection. This concept was supported by the many clinical trials in the 70’s and 80’s that found some 1-15% of patients with glaucoma have defects that lie outside of the central 30° region. Does his mean that we need peripheral tests to detect glaucoma or is the 24-2 adequate?

It is my opinion that we do not need a peripheral test and that the 24-2 may not detect all early losses.

Over the years, the need for peripheral testing has been eroded with the recognition that the capacity to find central losses is dependent on the nature and quality of the visual field test. Threshold tests are now recognised as providing the best method of defect exposure, and if we add to this the development of tests that reduce stimulus redundancy, such as FDT, then it is likely that central defects will always be present in early glaucoma making central testing the method of choice. This does not mean to imply that a peripheral test should not be used to give fuller or better definition of the affected area.

But for the purpose of detection, it is useful to review the regions affected by the disease. The seminal work from Tübingen, based on a cross sectional study of 2,000 patients with definite or suspect glaucoma, found the following patterns of field loss:
paracentral (10°-30°)
arcuate
nasal step
a temporal loss beyond the blindspot (see Figure)
threat to fixation (encroach within 10°)

Of note is the fact that a mean or average reduction in sensitivity was not part of this classification but has been recognized by later work.

The most significant recent research on this issue has been performed by the Ocular Hypertension Treatment Study (OHTS) Group and its members(1). This study is particularly informative for clinicians because it has followed a group of high-risk patients for many years and noted the development of glaucoma in a subset of people. These investigators find that field loss in early glaucoma can involve any area of visual space, with most lying in the arcuate region (59%). The fact that these people were detected with central testing implies that central field patterns can adequately expose this disease, although this prospect was not formally tested. Moreover, the interesting findings are, that:
threats to fixation can be found in 1% of cases with early glaucoma
general depressions (mean defects) are found in 8% of cases, and
that temporal wedges are observed relatively often (3.3%)
about 10-14% of initial field loss occurred in points beyond the 24-2 pattern

All of these findings indicate the need for a pattern of points that will be able to characterise losses across the field including the central 30° and temporal regions (see Figure).

Does this mean that the 24-2 does not have a place in clinical practice--of course not. In patients who have established loss within 25° it might be best to use the 24-2 because testing is faster and that pattern can just as well be used to monitor the loss. The Figure is a field from a glaucoma suspect showing many of the attributes just described, have a look at the clinical profile and figure out whether you feel it is glaucoma or not--the answer will be given at the end of this issue.

Algis Vingrys BScOptom., PhD

1. Keltner JL, Johnson CA, Cello KE, Edwards MA, Bandermann SE, Kass MA, Gordon MO and the Ocular Hypertension Treatment Study Group. Classification of visual field abnormalities in the ocular hypertension treatment study. Arch Ophthalmol. 2003 May;121(5):643-50.

IMAGE REVIEW

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

This 54 year-old African American male was diagnosed with primary open angle glaucoma. The optic disc is average in size and the ISNT rule is not obeyed in either eye. Retinal nerve fiber layer (RNFL) dropout is noted in each eye, OD between 7-9 o’clock (Figure 1) and OS at 5 o’clock (Figure 2). Peripapillary atrophy is present in each eye temporally but far more obvious in the OS. There are no signs of disc hemorrhage in either eye.

The HRT printout (Figure 3) is broken out into several parts: Cup, Rim, and RNFL. The image quality is very good for the OD and excellent for the OS. The printout shows the cup/disc ratio to be 0.78 OD and 0.79 OS and the cup/shape measure is abnormal in both eyes. The rim area and volume are also reduced significantly and the RNFL measurements are abnormal in the OS. The Moorfields Regression Analysis (MRA) is abnormal in each eye (noted by the different symbols on the rim segment). The combined RNFL profiles show the OS to be thinner. The Glaucoma Probability Score (GPS) printout (Figure 4) used a relevance vector machine analysis and is done independent on the contour line. Similar to the Moorfields Analysis, both global and sector scores are provided. In this case, the OD is seen as borderline while OS is evaluated as being outside normal limits.

The GDx images (Figure 5) are of high quality as seen by the Q scores of 9 for each eye. The optic nerve is in focus, evenly illuminated and centered. The GDx printout also has several sections: the fundus image, RNFL map, deviation map, and TSNIT curves. The large RNFL defect in the OS is clearly visible in the left fundus image. The thickness maps are color-coded with brighter images corresponding to thicker areas. From these diagrams, it is apparent that the OS thickness is significantly reduced. Viewing the deviation maps, both eyes have points flagged at a significant level and the TSNIT curves show the OD to be barely within the "normal range" while the OS reduced.

The OCT images are of an acceptable quality: signal strength of 7 OD and 8 OS. The images are centered, evenly illuminated and no clipping present. The left side of the printout shows the TSNIT curves, with the OD barely in the "normal green range" and the OS reduced (in the red area), especially inferiorly. In the middle of the page are the sector and quadrants tables, color coded based upon significance. The OD appears to be adequate in thickness (all areas are green) but several sectors and quadrants for the OS are flagged (seen by the yellow or red colors over the score), especially inferiorly. This indicates that these thickness values are rarely seen in a normal population. Several of the parameters are also flagged for the OS.

All the imaging printouts for this patient show similar results, done in slightly different manner. The OS has greater damage, larger cupping and a thinner RNFL with greater loss inferiorly.

Murray Fingeret, OD

QUARTERLY CASE

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5a

Figure 5b

To treat or not to treat ocular hypertension

This 64 year-old patient was sent by a local practitioner for evaluation. His impression was that she may be a candidate for glaucoma therapy but had unconvincing evidence on which to base a treatment recommendation. Looking at her clinical findings, the best corrected visual acuity is 20/25 in each eye due to cataract. She has been treated for hypertension for the past 10 years with a diuretic. She reports no family history of glaucoma. She is not a migraineur or diabetic.

Where does one start? We have clinical data on IOP, central corneal thickness (CCT), optic disc observations and visual fields. (see Figures 1 and 2). The Goldmann applanation reading is 24 mmHg in each eye and the CCT is 585u and 589u in the right and left eyes, respectively. The CCT values would suggest that the IOP may be lower than measured but this is only the first reading for this patient.

Looking closely at the optic discs, the first thing to strike me is the asymmetry (Figure 1) in cup-to-disc ratio (CDR) as well as optic disc size. This is a clinical observation that each of us would recognize and increase our suspicion. As the IOP is identical in each eye, I would evaluate the visual fields to see if there is any asymmetry that corresponds with that observed in the discs. The right visual field shows some asymmetry across the horizontal midline making the glaucoma hemifield test (GHT) outside normal limits. But this is due to a trial lens artifact in the right eye. This field needs to be repeated, paying careful attention to the position of the patient and trial lens. In the OHTS, nearly 90% of initial visual field defects were not confirmed on retest which indicates that repeatability cannot be overemphasized. The left visual field result shows numerous fixation losses which make it appear to be unreliable. This is due to the blind spot being incorrectly plotted. Note that the triangle marking the position where the perimeter believes the blind spot is (and where it places the targets) is just nasal to the location marked with a zero. The zero marks the actual blind spot position, and the high number of fixation losses is due to our not correctly plotting the blind spot and not indicative of poor performance. The technician performing the fields is alerted to a high number of fixation losses early in the testing process and should have paused the test and replotted the blind spot. The other reliability finding of note is the borderline number of false negative responses (10%) in the left eye, which is often seen the first time a patient takes the test. It usually disappears with experience. It has a great deal to do with the patient searching for their own criterion of when to depress the patient response button.

Let’s go back to the optic disc evaluation. We are handicapped by the two-dimensional representation here. Although the cup looks larger in the left eye there are few other features of glaucomatous optic neuropathy present. The rim tissue may appear by color to be healthier in the right eye. Applying either the ISNT rule(1) or the 5 Rs(2), there appears to be little evidence for significant damage to either the right or left optic disc. The disc margins are distinct in both eyes with no PPA. The CDR appears to be larger in the left eye but the optic disc is larger as well. The rim tissue in each eye appears to be robust and no nerve fiber layer defects are obvious. There are no nerve fiber layer hemorrhages present in either eye. These observations support an impression of physiological disc status and the absence of pathological changes.

Clinically, we can apply one of the recently reported glaucoma risk calculators to this patient. Using Mansberger’s glaucoma risk calculator(3), there is a 33.9% and 12.7% risk of developing glaucoma in the next five years for the right and left eyes, respectively, without treatment (Figure 3), although these data are dependent on reliable visual field results. This disagrees with the structural optic disc data, which suggests that the left eye might be at higher risk (larger cup). Most importantly, the right eye data is based upon a visual field PSD that is elevated due to a lens rim artifact and not indicative of the actual visual field status. If we do the calculations again using a PSD of 1.80 for the OD (normal PSD and similar to the OS), the calculated risk reduces to 10.3% without therapy and 6% with therapy. This is a HUGE change and indicative that you need to be careful if using data that may be suspect. In addition, theoretically risk should be calculated for both eyes by averaging the results. With this in mind, the risk for both eyes is 13.2% without therapy and 7.9% with therapy. This would indicate that the patient is at a borderline risk and observation would be the appropriate course for now. If data changes, we would need to evaluate again.

We can also look to digital imaging for another opinion. The GDx data show relatively normal values for NFI (23, 32) with some superior temporal thinning in the left eye (see Figure 4).

A recent publication from the ancillary study to the OHTS, which looked at a subset of patients’ HRT data, suggested several parameters that would be predictive of future glaucomatous damage: the Moorfield’s Regression Analysis (MRA) overall HRT classification has a 14% positive predictive value and the MRA temporal sector analysis has a PPV of 40% for values outside the 95% normal range(4). These data suggest that the patient is at low risk for conversion (see figures 5a and b). Note that in the GRC, the C/D values used are from HRT data.

In this case, our decision was to observe this patient as an ocular hypertensive without treatment with a six-month follow-up visit. With this volume of baseline data and the availability of risk calculators(3,5), we now have a source of information on which to base future treatment decisions. Note that the risk calculators should not be generalized to all OHT cases: they can only be applied to individual scenarios typical of those used in their design otherwise spurious and inappropriate results will be obtained. The management recommendation was proposed to and accepted by the patient. At follow up, we would look for more reliable visual field data and whether data in support of the diagnosis of glaucoma are repeatable.

Each of us faces dilemmas such as represented by this case. Careful follow up will guide us to the correct decision. The availability of risk calculators allows another data point. Treatment decisions should not be undertaken lightly, but with an abundance of corroborative information, they can be made with greater confidence.

Leo Semes, OD

1. Jonas JB, Budde WM, Panda-Jonas S. Ophthalmoscopic evaluation of the optic nerve head. Surv Ophthalmol. 1999; 43: 293-320.
2. Fingeret M, Medeiros FA, Susanna R Jr, Weinreb RN. Five rules to evaluate the optic disc and retinal nerve fiber layer for glaucoma. Optometry. 2005; 76 :661-8.
3. Mansberger SL. A risk calculator to determine the probability of glaucoma. J Glaucoma. 2004;13: 345-7. (http://www.discoveriesinsight.org)
4. Zangwill LM, Weinreb RN, Berry CC, et al. The confocal scanning laser ophthalmoscopy ancillary study to the ocular hypertension treatment study: study design and baseline factors. Am J Ophthalmol. 2004;137: 219-27.
5. Medeiros FA, Weinreb RN, Sample PA, et al. Validation of a predictive model to estimate the risk of conversion from ocular hypertension to glaucoma. Arch Ophthalmol. 2005; 123: 1351-60.

PEARLS FROM THE EXPERTS

In this issue, our pearls are responses from our experts to questions posed by readers.

Visual Field Variability
"I understand that variability increases as glaucoma defects get worse BUT I am also under the impression that in early glaucoma, scotomas may be present on one field and disappear on the next. Am I confusing variability with stability?"

Chris A. Johnson, Ph.D. answers, "First of all, you are not alone when it comes to confusion about visual field variability and stability in glaucoma. A number of investigators are initiating new test strategies designed to reduce variability from one examination to the next, developing mathematical models to better understand variability, and designing innovative statistical methods to evaluate longitudinal visual field data that is robust to variability. Progress has been made in all three of these areas, although additional work is needed. Ocular pathology (e.g., glaucoma) is one of many sources that increases variability from one test to another, but there are many other factors that increase variability as well. The multicenter trials in glaucoma are in agreement that it is currently necessary to confirm visual field changes by repeated testing in order to maintain high sensitivity and specificity. In particular, the Ocular Hypertension Treatment Study (OHTS) reported that more than 85% of initial visual field abnormalities are not confirmed on the next visual field test. A good rule of thumb is that it is best to repeat the visual field test if a change is suspected. Because poor sleep, illness and many other factors besides pathology can increase variability, it is best to repeat the testing on a separate day to minimize the influence of these factors. Also, the analysis tools that are currently available on automated perimeters should be employed to assist in clinical determination of stability, progression or improvement of the visual field status. This is currently our best solution to the problem, but we hope that additional research will provide simpler, easier and more cost-effective solutions in the future."

Ron Harwerth OD, PhD answers, "There are several sources of variability that affect the accuracy and precision of visual field measurements, some are physiological and others are subject-related factors. The variability of sensitivity that increases as glaucoma defects get worse and is generally assessed by the slope of the psychometric (frequency-of-seeing) function probably has a physiological basis. A couple of examples that support the physiological basis of variability are: 1) Henson, et al. (IOVS, 38:426-435, 1997) showed that variability increases with the depth of defect and, therefore, must be related to the amount of ganglion cell loss, and 2) Wall, et al. (IOVS, 41:417-421, 2000) demonstrated that variability is greater with the Size III stimulus than a Size V stimulus, suggesting that the loss of ganglion cells results in a reduced sampling of the test target. An increased variability associated with ganglion cell loss is present for all patients, whether or not they are experienced in visual field measurements. Another source of increased variability, subject-related factors, would be expected to affect new patients more than patients with a lot of perimetry experience and includes shifts in attention, response criterion, fixation, fatigue, etc. Subject-related variability will affect the accuracy of visual field measurements and could result in an apparent localized scotoma that is present in one exam and absent in the next, which is why most clinicians consider clusters of abnormal locations more important than single points.

Both variability and stability are reflections of the precision of subjective measurements of visual sensitivity, but as I understand the usage, clinicians use "variability" to describe normal pointwise measurement fluctuations that determine whether the sensitivity at a given location is statistically normal, within a certain confidence range. In contrast, "stability" is a clinical description of reproducibility over time and whether the fluctuations of a patient’s data are within statistical probability of being unchanged across measurements. Therefore, I think that the visual defect that disappears on subsequent measurement would be described as instability, but it is a consequence of measurement variability."

Contraindications to Treatment
"We have all been told that Prostaglandins should be used with caution in patients with active anterior uveitis. I have one patient who presented with anterior uveitis while on travatan. I discontinued the travatan and treated her but left her on it in the other eye. 3 days later she came in with iritis in the eye still on the travatan and the one off the travatan was better. I took her off it in both eyes and waited 3 weeks and tried her back on Xalatan. Within 3 days she was back with active anterior uveitis. She had no prior history of uveitis. I have since sent her for surgery and she is scheduled for Trabeculectomy next month because she has advanced glaucoma and we have run out of treatment options. My question is, in your experience , when is this most likely to happen and why. What has the experience been elsewhere and what types of uveitis are we to be concerned with when using prostaglandins? For example can we use them safely with post-op cataract patients?"

Douglas R. Anderson, M.D. answers, "The prostaglandin analogues infrequently cause a true inflammation, even if they cause vessel dilation of the conjunctiva (hyperemia) and some stinging. However, uveitis specialists do believe that they aggravate an underlying uveitis or tendency toward uveitis in some individuals (not all). In some ways it is not surprising that a prostaglandin analogue would incite inflammation, and it was a big concern when these drugs were first being developed, because physiologically some prostaglandins are local mediators of an inflammatory response. (Other prostaglandins perform other functions). The scientists developing these drugs for glaucoma studied the slight chemical differences in various prostaglandins to determine which parts of the molecule were responsible for particular responses, and the happy surprise was that they were able to find one with minimal inflammatory tendency that had a big effect on IOP. However, given genetic differences between people, some may have receptors that produce inflammation when stimulated by a prostaglandin that in most people would not produce inflammation. In the big picture, it is therefore not surprising that some people respond differently than others to a drug--for example, some are more responsive than others to the beneficial effect of lowering IOP, and some are more responsive than others to the adverse effects as well."

MEETING NEWS

The OGS annual meeting was held on December 7th, 2005 in La Jolla, California (see photo above). The meeting was filled with cutting edge material from some outstanding researchers. The majority of presentations were from the faculty of the Hamilton Glaucoma Center, UC San Diego. Some of the presentations included: 1) The use of functional magnetic resonance imaging (fMRI) and other novel imaging techniques to map out areas of the brain that no longer receive input in patients with glaucoma 2) Machine learning classifiers (sophisticated mathematical processes that can separate groups based on features that may not be obvious) that are able to detect subtle damage in the visual field of glaucoma suspects before they would be classified as abnormal using conventional visual field analysis techniques 3) A discussion of glaucoma risk calculation based on the findings of the OHTS study and incorporated into a user-friendly ‘slide rule’ 4) A study to examine nocturnal IOP curves in several hundred patients which has led to a reevaluation of when the IOP is highest 5) A presentation by our honoree, Dr Stephen Drance, about lessons learned from the Normal Tension Glaucoma Study. This presentation was peppered with insightful comments, anecdotes and a healthy ‘back and forward’ between Drs Drance and a past honoree, Dr. Douglas Anderson. A supplement of the meeting will be delivered with the March issue of Review of Optometry. A PDF version will be available in March online at www.optometricglaucomasociety.org.

The International Perimetric Society will hold its XVIIth meeting in Portland, Oregon, July 11th - 14th, 2006. Approximately 90 papers and posters will feature all aspects of automated perimetry, the development and/or evaluation of new perimetric and psychophysical tests, use of statistical methods for identifying glaucomatous abnormality and progression, and related research in glaucoma detection and monitoring. There will also be a special session on optic nerve head and nerve fiber layer imaging with emphasis on new techniques for assessing structure and detecting change. The social program includes an opening reception, a concert by New York diva Ann Hampton Callaway, an excursion to the Columbia River Gorge, and the IPS Banquet, which includes a tradition of delegates singing in national groups. More information can be obtained from the IPS. The abstract submission deadline is fast approaching.

INTERNATIONAL COLUMN

The Role of New Zealand Optometrists in Glaucoma Management

Optometrists in New Zealand have always played some role in the detection and referral of patients with glaucoma. More recently, and particularly with the recent introduction of Optometric therapeutic laws, the role of NZ Optometrists in glaucoma management is becoming better defined.

The Health Practitioners Competence Assurance Act 2003 (HPCAA) came into effect in 2004, bringing with it the right for suitably trained Optometrists to prescribe a range of topical medications, but excluding those for glaucoma. Therefore, Optometrists in NZ do not currently have the right to prescribe or change glaucoma medications. This said, Optometrists are increasingly working closely with Ophthalmology in the early detection of glaucoma and ensuring already diagnosed patients receive timely monitoring, including IOPs, visual fields and drug compliance. In some instances, patients with stable glaucoma will see their optometrist at intervals between their ophthalmology visits, with the optometrist reporting findings back to the ophthalmologist.

As already mentioned, the major change recently in the practice of Optometry in NZ has been the introduction of prescribing rights to a wide range of topical therapeutic agents.
The classes of drugs currently available to Optometrists include: a select list of antibiotics, anti-virals, anti-allergy medications and anti-inflammatories as well as combination drugs from these classes.

Prescribing Optometrists need to have undergone an accredited TPA course, the majority of whom have undergone, or are in the process of undergoing, the University of Auckland’s therapeutic course. The University of Auckland’s Optometry course (BOptom) has progressively undergone modifications over the past few years so that the present (2006) final year optometry students will be the first to graduate with full therapeutic training.

Geraint Phillips is Clinic Director, Department of Optometry and Vision Science
The University of Auckland, Auckland, New Zealand.

Geraint Phillips BSc, MCOptom, DCLP, OD, Algis Vingrys BScOptom, PhD

CLINICAL TRIAL REVIEW

Multi-center clinical trials for glaucoma and related ocular disorders have been quite limited except for the past 15-20 years. These recent investigations have provided valuable insights into some fundamental questions concerning the management of glaucoma, spanning a range of clinical concerns. This paper will provide a brief review of five clinical trials: the Advanced Glaucoma Intervention Study (AGIS), the Collaborative Initial Glaucoma Treatment Study (CIGTS), the Collaborative Normal Tension Glaucoma Study (CNTGS), the Early Manifest Glaucoma Trial (EMGT) and the Ocular Hypertension Treatment Study (OHTS).

AGIS
AGIS was a multi-center study (11 clinical centers) that began in 1988 and ended in 2001. Medically uncontrolled open-angle glaucoma patients (591 patients, 789 eyes) were randomized to a treatment sequence of (1) argon laser trabeculoplasty, trabeculectomy and trabeculectomy (ATT), or (2) trabeculectomy argon laser trabeculoplasty and trabeculectomy (TAT). The main findings include a race-treatment interaction for trabeculoplasty and trabulectomy (African Americans respond better to argon laser trabeculoplasty first, while Whites do better with trabeculectomy first after 7 years of follow-up), a decrease in visual field progression with lower intraocular pressure, an increased risk of cataract formation following trabeculectomy, and identification of risk factors for failure of the two treatments.

CIGTS
CIGTS enrolled 607 patients and followed them between 1993 and 1997 to determine whether medical therapy or surgical treatment (trabeculectomy) was more effective in managing newly diagnosed glaucoma patients at 14 clinical centers. The study revealed no difference in visual field loss between the two groups. Trabeculectomy patients had lower intraocular pressures, a greater risk of visual acuity loss and cataract development and local eye symptoms. The findings do not support any alteration of current practices for managing newly diagnosed glaucoma patients.

CNTGS
CNTGS was a multi-center (24 clinical centers) trial of normal tension glaucoma patients (20 mm or less intraocular pressure) that enrolled one eye of 230 patients. Two hypotheses were evaluated: (1) that glaucoma is intraocular pressure independent, and (2) that intraocular pressure participates in producing glaucomatous damage in normal tension glaucoma. One group was carefully observed without treatment, while the other group had medical and/or surgical treatment to produce a 30% or more reduction in intraocular pressure. The main findings were that intraocular pressure reduction was beneficial to normal tension glaucoma patients by diminishing the rate of progression, and that treatment should be individualized according to the stage of glaucoma and rate of progression.

EMGT
EMGT is a clinical trial designed to evaluate the effectiveness of reducing intraocular pressure in early, previously untreated patients with open-angle glaucoma by comparing one group undergoing trabeculoplasty and medical therapy to another group undergoing careful observation. In the treated group, progression of glaucomatous damage was significantly reduced by approximately 50%. Older age, higher intraocular pressure, exfoliation and worse Mean Deviation were found to be important risk factors for progression.

OHTS
OHTS evaluated more than 1,600 patients (25% of which are African American) at risk of developing glaucoma, but who had reliable visual fields and optic nerve heads that were within normal limits at baseline. Half of the patients were randomly assigned to treatment and half underwent careful observation. Topical medical treatment for five years (20% or more intraocular pressure reduction) significantly reduced the incidence of glaucoma by more than 50%, with slightly more than half of the glaucoma endpoints being optic disc changes and only about 10% of the endpoints being both optic disc and visual field endpoints. Risk factors for development of glaucoma included older age, larger horizontal or vertical cup-to-disc ratio, higher intraocular pressure, greater pattern standard deviation and thinner central corneal measurements.

A quick literature search can provide references to the full reports from these studies for those readers wishing to become familiarized with more detailed information. The results of these trials generally indicate that treatment significantly reduces the onset and progression of glaucomatous damage, throughout the entire spectrum of the disease process. It should also be noted that there are many other clinical trials underway or completed to evaluate the safety and efficacy of various treatment regimens, most of which are sponsored by the pharmaceutical industry. Through these combined efforts, we have gained a better understanding of the diagnosis and treatment of glaucoma and have identified a number of additional clinical research questions that need to be evaluated.

Chris A. Johnson, PhD

QUESTIONS & ANSWERS

This section contains questions from readers of the journal with answers and comments from editorial board members.

Imaging
"I would like to purchase an optic imaging instrument to help to diagnose glaucoma. Which of the instruments - OCT, GDX, HRT - has the most validity in diagnosing who has glaucoma vs. glc suspects? Do GDX and OCT give the same results, or is one significantly more valid? Can I "hang my hat" and rely on the results of any one of them?"

Murray Fingeret OD answers, "Imaging instrumentation is rapidly becoming part of the glaucoma workup, and its role is to supplement the examination findings (optic nerve, visual field), not drive the diagnosis. For example, someone with an apparent healthy optic nerve and elevated IOP, imaging may reveal subtle changes to the retinal nerve fiber layer or rim tissue. Several studies have shown that in 25-40% of conversions, the initial glaucomatous findings are in the visual field. Does this mean that the optic nerve is entirely healthy? Probably not, but more likely for different reasons (i.e. small optic nerve), the changes are difficult to detect. In regards to which instrument may be "more valid" in diagnostic capabilities, there are few head to head studies using present day instruments. Older studies are misleading because they use instruments or software no longer being made. From the few studies available, the instruments appear to perform remarkably similar in regards to their diagnostic capabilities. Still for an individual patient, the OCT may reveal loss that the GDx may underestimate or vice versa. The same may occur when comparing the HRT and the RNFL instruments. In regards to "can I hang my hat and rely on the results", no imaging instrument offers 100% sensitivity and specificity. Thus the user needs to recognize when the device may be over or under calling a situation and use the data appropriately. The imaging instruments represent a large advance in how we can evaluate the RNFL/Optic Nerve BUT they are far from perfect and it is the "astute" clinician who understands how to integrate the analysis into the clinical picture."

Optic Nerve Assessment
"It has been my experience, as an optometrist in the Indian Health Service for more than 16 years, that the ISNT rule does not apply to normal optic nerves in most cases. Usually, the inferior rim is thicker than the superior in the normal nerve, but the nasal rim is thicker than both the superior and the temporal rims. The more appropriate expression of normality with respect to rim thickness would be IS, then NT."

Douglas R. Anderson, M.D. answers, "The observation that the nasal side can seem larger than either the inferior or superior rim is correct, but it depends on whether you include the major vessels that line the cup as part of the neuro-retinal rim, I think. If you include only the tissue that is outside the vascular trunk, the remaining nasal tissue, which is after all the neural tissue, is generally thinner than the superior or inferior rim. The trick is to think of the neuro-retinal tissue proper and count the vessels as being part of the cavity. In my experience the ISNT rule does apply to just about any disc, although some disagree about the validity of the rule in large discs. And it is possible you have stumbled on a particular exception among native Americans. Perhaps you could send photographic examples for us all to see.

"Now, in rare cases with a temporal wedge field defect, there is localized loss of tissue in the nasal neuro-retinal rim as the earliest sign of glaucoma, and this is recognized when there is excavation nasal to the trunk of vessels. Of course, because anatomy of the disc in the absence of disease is highly variable, there remain times when any rule is mimicked by an anomaly, and sometimes it is impossible to say with certainty that a disc is glaucomatous or not glaucomatous on a single occasion, but it takes observation over time to see change in anatomy as a sign of glaucoma."

Clinical Examination
"I have a patient that is level 5 mentally retarded. It requires restraint to examine him in any way and would require general anesthetic to get IOPs or retinoscopy or autorefractor (I've tried the Welch Allyn hand held). He is taking Topamax. Should I be concerned? Should I have him put under to determine his status?"

Thom Zimmerman M.D., Ph.D., answers, "With a patient that is level 5 MR I would put him under general anesthetic in order to get baseline information on everything. Then, I would follow him the best that I could until I suspected a change in condition. Then I would put him back under to verify changes from the established baseline."

Douglas R. Anderson, M.D. answers, "On the mentally retarded patient, it is simply a difficult patient to examine, and therefore difficult to be certain of his state. Topomax can cause problems, but obviously doesn't in everyone. Because he is on Topomax, you might look at his iris with a flashlight inconspicuously to the side while playing with him, you may get an idea of the convexity of the iris, feeling relieved if there is none and considering an examination under anesthesia if the iris plane seems bulged forward. You might also be helped by observing his behavior while not being disturbed by your attempt to touch and examine him. Are his eyes red, does he seem to have pain and rub his eyes, can he see small things like sugar sprinkles, etc. If you have no reason to suspect an ocular problem, you may not need to go looking for one. Why even do a refraction if he sees sufficiently for whatever daily activities he has. I don't think anyone can really help you decide what to do without seeing the patient."

If you would like us to answer a clinical question, please send it to paul.spry@ubht.nhs.uk with "OGS question" as the subject. The questions can concern anything related to glaucoma, for example analysis of an optic nerve image, optic disc, a challenging case or side effect of a medication. We welcome your questions and we will try to address as many as possible in each issue.

Editor in Chief Paul Spry PhD MCOptom Associate Editors Brad Fortune, OD, PhD Shaban Demirel, BScOptom, PhD Algis Vingrys BScOptom, PhD

Editorial Board Douglas Anderson MD Paul Artes PhD MCOptom Dick Bennett OD Murray Fingeret, OD Ron Harwerth, PhD Chris Johnson, PhD Tony Litwak, OD John McSoley, OD Ron Melton, OD Bruce Onofrey, OD, RPh Leo Semes, OD Randall Thomas, OD Thom Zimmerman, MD, PhD   Art/Production Director Joe Morris Project Coordinator Janice Miller