OGS PRESIDENT'S MESSAGE

One of the most exciting aspects of being "a professional" is the ever-changing world within which we are expected to operate. This can be the world of science, full of hope and awe such as the promise of stem cell therapy, or simply the humbling experience of a happy patient saying a heart felt thank you. Our rewards can be great. Then there are times so profoundly disturbing that you can be left to question the sanity of the world around you. Recent developments in my adopted home of Canada fall firmly into this latter category. In an extraordinary turn of events the provincial government of beautiful British Columbia responded to a legal decision against an internet company providing contact lenses and glasses, by effectively deregulating all aspects of refraction, eye examination and the dispensing of corrective lenses, including contact lenses. This reckless abandonment of the citizens of British Columbia came into effect on May 1st, and was trumpeted as being evidence driven policy. As might be expected the changes were also introduced without consultation with any of the eye care professions and with only a few weeks of warning.

Much has been written in Canada about the situation, including national media coverage, and legal challenges are likely, especially given Health Canada's policies on contact lenses as a medical device. The claim of "evidence", or lack there of, has been robustly challenged. So why do I bring this situation to your attention? As a glaucoma society our patients and specialty area of interest are particularly at threat. With a disease like glaucoma, which relies upon skilled, opportunistic diagnosis, the deregulation of eye examinations and dispensing has serious ramifications. It has been estimated that even in the most sophisticated health care systems 50% of glaucoma remains undiagnosed and untreated. What hope for early intervention without routine eye examinations, at least following the onset of presbyopia? Without going into detailed epidemiology of the disease, the bottom line is our need for vigilance. If such a travesty of political judgment can happen in a place like British Columbia and in a country like Canada, with its well established system of supposed universal health care, I promise you it can happen anywhere.

On a more pleasant note I would like to take this opportunity to celebrate the retirement of one of our members. Pam Sample recently announced her retirement as Professor of Ophthalmology at the Shiley Eye Center, University of California, San Diego and Director of Clinical Vision Research at the Hamilton Glaucoma Center. Many of you will know Pam from her previous contributions to the OGS and AAO meetings, and her prolific publications. Pam has enjoyed a distinguished research career, particularly in the area of clinical psychophysics and glaucoma. Pam, you will be greatly missed. We wish you well.

John Flanagan, PhD, MCOptom, FAAO
President, Optometric Glaucoma Society
[email protected]

More Evidence on Risk of Glaucoma in Ocular Hypertension is NICE.

Welcome to the spring issue of the Optometric Glaucoma Society Electronic Journal. This issue covers a variety of topics including columns discussing the effects of learning and variability on clinical visual field testing and the implications of the Canadian Glaucoma Study.

In our New Ideas and New Papers section, Dr. Shaban Demirel has reviewed the most recent publication from the Ocular Hypertension Treatment Study (OHTS). As a further paper from a widely cited randomised controlled trial, this will undoubtedly be of interest to those involved in glaucoma care, whatever their background. This study provides further valuable supportive evidence for the importance of determining risk of conversion from ocular hypertension (OH) to primary open angle glaucoma (POAG).

Aside from its obvious clinical relevance, I found this to be particularly interesting because treatment of OH according to risk (stratified by age, IOP level and central corneal thickness) was recently recommended in England and Wales as part of the clinical management guideline for chronic open angle glaucoma and ocular hypertension published one year ago by the United Kingdom's National Institute of Health and Clinical Excellence (NICE). If you have missed this, it was described in the last issue of this E-Journal.

For those of us practicing in England and Wales where the guideline is currently undergoing a 3-5 year implementation period, the time since publication has seen controversy and reaction. This has centred on recommended changes in both clinical management of glaucoma suspects and ocular hypertensives and also care delivery for these patient groups, for which a consistent, common strategy in England and Wales was previously lacking until publication of NICE's evidence-based recommendations.

Whilst approaches to care delivery may vary around the world, increasing evidence from OHTS is timely because it underscores the value of risk stratification amongst patients with OH and will inform, or in the case of the NICE guideline reinforce, care provision strategies for individuals at risk of visual loss due to glaucoma.

Paul GD Spry, PhD, BSc, MCOptom DipGlauc
Editor-in-Chief
[email protected]

Practice and learning effects have been well-documented for a number of different skills, as documentation in the Psychology literature can clearly confirm (1). Perhaps the most notable report of practice and learning effects is evident from studies of hand-rolling cigars in Cuba (2). Even after many years of performing the task of hand-rolling cigars, it was found that these individuals could perform this task more efficiently and continue to reduce the time required to complete this undertaking.

There are many investigations that have now reported that performance on visual field examinations will improve with repeated tests (3-6). I have cited just a few of these studies, but there are many more that are available in the literature, both for standard perimetry (automated or manual) and for specialized forms of visual field testing. More than thirty years ago, I was interested in practice and feedback on performance for visual psychophysical measures of motion detection and visual acuity in the peripheral visual field (7,8). These studies indicated that large improvements in performance (more than a factor of 2 in many instances) could be achieved in 4 to 7 test sessions, with the amount of improvement increasing with eccentricity such that the number of sessions needed to achieve maximal performance was higher for greater eccentricities. However, these studies were conducted on young, skilled psychophysical observers under laboratory conditions employing a large number of stimulus trials. This is considerably different to the typical diagnostic test procedures, such as perimetry, that are performed in the eye clinic on elderly patients with limited or no prior psychophysical experience. There are a variety of factors that may influence clinical visual sensitivity measures, and this discussion will provide a brief overview of practice and learning effects on perimetry and visual field testing using clinical test instruments.

Standard automated perimetry (SAP) determines the visual increment threshold (detection sensitivity) by determining the minimum amount of light from a small target that needs to be added to a uniform background in order to make it just distinguishable from the background. Many investigators have found that the learning or practice effect is greatest between the first and second visual field examinations, and that learning and practice improvements become negligible after three or more perimetric tests (3-6). Usually, these studies are performed within a relatively short time period, which is different from the typical test sequence that is routinely performed in the clinic. In this view, a recent publication has reported that practice and learning effects can be identified for up to six years when visual field testing is being performed on an annual basis (9). This was not only true for standard automated perimetry, but also for Short Wavelength Automated Perimetry (SWAP). The magnitude of these improvements becomes smaller with increasing numbers of examinations, but this does complicate follow-up of patients over time and determination of the status of vision function as stable, declining or improving.

In addition to SAP, there are many other types of visual field tests such as Short Wavelength Automated Perimetry (SWAP (9-11)), Frequency Doubling Technology (FDT) and Matrix perimetry (12-15), motion perimetry (17) and Rarebit perimetry (16), that have been evaluated for practice and learning effects. As a general rule, most of these procedures will demonstrate a practice or learning effect that has its largest change associated with the first 2 or 3 examinations. However, similar to SAP results, annual examinations with SWAP also demonstrate improvements over six years, and the magnitude of these improvements may be larger than for SAP (9).

Figure 1. Change in overall visual field sensitivity for Size III standard automated perimetry (top left), Size V standard automated perimetry (top right), Motion perimetry (bottom left) and Matrix FDT perimetry (bottom right) over 5 visits obtained once per week for five weeks.

Some investigators have questioned whether experience gained while performing one type of perimetric test will improve performance on a different visual field test procedure (transfer of training, practice and experience). The psychology and psychophysics literature indicates that the greater the similarity between two tasks, the larger the amount of transfer of skills from one task to another. This also appears to be the case for visual field testing, as indicated in Figure 1. In this study, we evaluated 90 glaucoma patients who performed four different visual field tests (standard automated perimetry Size III SITA Standard, standard automated perimetry Size V Full Threshold, Motion Perimetry (17) and Humphrey Matrix perimetry) once a week for five successive weeks. The order of testing was counterbalanced across subjects and test sessions to minimize fatigue effects. Figure 1 presents the change in average visual field sensitivity (in dB) from the initial test session as a function of visit number. The results for each of the tests was set to zero for the visual field obtained on the first visit, and the change from the first visit is presented for subsequent visits along with the standard deviation of values. All four tests showed some degree of improvement over the five visits, but the results for Size III and Size V were not statistically significantly different from the initial visit (i.e. no significant learning effect). On the other hand, motion and Matrix perimetry results showed statistically significant improvements in sensitivity over the five visits. The standard deviation of these measures was approximately 0.5 to 1 dB for all tests. We attribute these results to the fact that the glaucoma patients had prior experience with visual field testing using Size III targets before this study, and the Size III and Size V tests were highly similar to each other, whereas motion and Matrix perimetry were quite different in their stimulus presentation test strategy and familiarity to the patients. These results are consistent with the prior findings from psychology and psychophysics.

In glaucoma and other disorders where progressive loss can be slow, these effects can be a challenge because deterioration due to disease can be occurring at the same time that improvements are being realized through practice. What can be done to overcome this clinical dilemma? One solution is to perform multiple visual field tests at initial visits to minimize practice effects, although this is not always possible in a busy clinic. Alternatively, providing the patient with an explanation of the test, an opportunity to perform a demonstration pre-test examination, and giving them clear instructions can help. Ideally, it would be desirable to have a statistical analysis procedure that is able to separate declines due to disease progression from improvements due to practice. This has not yet been realized, but it represents a wonderful opportunity for new investigators to make some meaningful and significant contributions for the future. For those who wish to embark on this task, I offer my sincere enthusiasm and encouragement!

Chris A. Johnson, PhD

References
1. Polat U. Making perceptual learning practical to improve visual functions. Vision Research, 2009, 49: 2566-2573.
2. Crossman ERFW. A theory of acquisition of speed-skill. Ergonomics, 1958, 2: 153-166.
3. Werner EB, Krupin T, Asdelson AS, Feitl ME. Effect of patioent experience on the results of automated perimetry in glaucoma suspect patients. Ophthalmology, 1990, 97: 44-48.
4. Marra G, Flammer J. The learning and fatigue effect in automated perimetry. Graefes Arch Clin Exp Ophthalmology, 1991, 229: 501-504.
5. Wild JM, Searle AET, Dengler-Harles M, O’Neill EC. Long-term follow-up of baseline learning and fatigue effects in the automated perimetry of glaucoma and ocular hypertensive patients. Acta Ophthalmologica, 1991, 69: 210-216.
6. Heijl A, Bengtsson B. The effect of perimetric experience in patients with glaucoma. Arch Ophthalmol, 1996, 114: 19-22.
7. Johnson CA, Leibowitz HW. Practice, refractive error and feedback as factors influencing peripheral motion thresholds. Percept Psychophys, 1974, 15: 276-280.
8. Johnson CA, Leibowitz HW. Practice effects for visual resolution in the periphery. Percept Psychophys, 1979, 25: 439-442.
9. Gardiner SK, Demirel S, Johnson CA. Is there evidence for continued learning over multiple years in perimetry? Opt. Vis Science, 2008, 85: 1043-1048.
10. Wild JM, Kim LS, Pacey IE, Cunliffe IA. Evidence for a learning effect in short-wavelength automated perimetry. Ophthalmology, 2006, 113: 206-215.
11. Rosetti L, Fogagnolo P, Miglior S, Centrofanti M, Vetrugno M, Orzalesi N. Learning effect of short-wavelength automated perimetry in patients with ocular hypertension. J. Glaucoma, 2006, 15: 399-404.
12. Joson PJ, Kamantigue ME, Chen PP. Learning effects among perimetric novices in frequency doubling technology perimetry. Ophthalmology, 2002, 109: 757-760.
13. Matsuo H, Tomita G, Suzuki Y, Mraie M. Learning effect and measurement variability in frequency doubling technology perimetry in chronic open angle glaucoma. J Glaucoma, 2002, 11: 467-473.
14. Contestabile MT, Perdicchi A, Amodeo S, Recupero V, Recupero SM. The influence of learning effect on frequency doubling technology perimetry (Matrix). J Glaucoma, 2007, 16: 297-301.
15. Hong S, Na K, Kim CY, Seong GJ. Learning effect of Humphrey Matrix perimetry. Can J Ophthalmology. 2007, 42: 707-711.
16. Salvatet ML, Zeppieri M, Parisi L, Brusini P. Rarebit perimetry in normal subjects: test-retest variability, learning effect, normative range, influence of optical defocus and cataract extraction. Invest Ophthalmol Vis Sci. 2007, 48: 5320-5331.
17. Wall M, Jennisch CS, Munden PM. Motion perimetry identifies nerve fiber bundlelike defects in ocular hypertension. Arch Ophthalmol. 1997, 115:26-33.

NEW IDEAS AND NEW PAPERS

How to Identify Patients with Progressive Glaucoma

In a study recently published in Ophthalmology (1) by Chauhan, Nicolela and Artes, the investigators sought to test the hypothesis that glaucoma patients exhibiting optic disc changes during an initial period of longitudinal follow-up would be more likely to exhibit visual field changes during a subsequent follow-up period than those patients whose optic discs were stable. Optic disc changes were quantified using Confocal Scanning Laser Tomography (CSLT), specifically using the Topographical Change Analysis (TCA) of the Heidelberg Retina Tomograph (HRT), which is known to perform as well or better than expert evaluations of optic disc photographs in terms of reliability and diagnostic accuracy. There were three levels of optic disc surface topographic change defined: liberal, moderate and conservative criteria having known false alarm rates of 19%, 6% and 3%, respectively, in a group of normal subjects followed the same way over 5 years (thus, using the conservative TCA criterion of a significant cluster covering ≥2% of the disc area and having a depth change of ≥100 µm, only 3% of normal eyes would be expected to exhibit disc change in 5 years). In this study, 22% of the glaucoma patients met this conservative criterion of disc change in just over 5 years of follow-up. Visual field change was defined using the criteria from the Early Manifest Glaucoma Trial (EMGT), which required significant change from baseline in ≥3 visual field locations in 3 consecutive visual field exams. The authors found that patients exhibiting optic disc change (by HRT TCA) during the initial follow-up period were more likely to develop visual field loss during the subsequent follow-up period than those patients without significant optic disc changes and that their mean time to visual field progression was shorter. Glaucoma patients with optic disc changes during the initial follow-up period also exhibited steeper negative slopes (more rapid decline) in the visual field mean deviation (MD, in dB per year) during the subsequent follow-up than patients without optic disc surface topography changes. What was clear in their data is that the group of glaucoma patients with significant optic disc surface changes during the initial follow-up period include a number of cases in which rapidly progressive visual field changes occurred during the subsequent follow-up, in some cases reaching -1 dB per year (which would correspond to progressing from normal to blindness in ~30 years) despite treatment. The group of patients without optic disc changes during initial follow-up did not include cases of such rapid visual field loss during the subsequent follow-up period. Thus, longitudinal observation of optic disc surface height by HRT TCA has both positive and negative predictive value for future visual field changes in glaucoma patients.

A very interesting "control analysis" was also included in the same paper. In this secondary analysis, the investigators evaluated the predictive value of visual field changes detected by longitudinal follow-up during the same initial period for subsequent development of visual field changes. They used three similarly varying criteria (i.e. a more liberal criterion of ≥1 locations with significant change on the pattern deviation plot; a moderate criterion of ≥2 locations; and a more conservative criterion of ≥3 locations changing significantly on the pattern deviation plot during the initial follow-up period). Although fewer eyes exhibited visual field change during the initial follow-up as compared with optic disc changes for each criterion, there was an even greater ability to predict visual field loss occurring (or not) during the subsequent follow-up period. Both positive and negative predictive values were higher for initial visual field follow-up than for initial optic disc follow-up in terms of visual field loss occurring during the subsequent follow-up period. Glaucoma patients with progressive visual field loss during the initial follow-up period had shorter intervals to developing subsequent visual field progression and had the most rapid rates of decline in their MD during the subsequent follow-up period as compared with those eyes that did not exhibit visual field changes during the initial follow-up period.

Thus, in summary, the paper by Chauhan, Nicolela and Artes provides evidence to support one aspect of clinical wisdom and to underscore an important clinical concept: those glaucoma patients showing either optic disc changes or visual field changes over time are more likely to exhibit subsequent progressive visual field loss, even when treated, than patients with stable optic discs and visual fields. This means that optic disc and visual field status must be evaluated and documented regularly, concentrating on detection of change. Patients with the most significant change either by optic disc, visual field changes or both must be followed extremely carefully as they are most likely to continue changing and at the most rapid rate.

Brad Fortune, OD, PhD

Reference
1. Chauhan BC, Nicolela MT, Artes PH. Incidence and rates of visual field progression after longitudinally measured optic disc change in glaucoma. Ophthalmology. 2009 Nov;116(11):2110-2118. PMID: 19500850

Insights on the Natural History of Glaucoma

A recent paper by Heijl and colleagues (1) used data from the Early Manifest Glaucoma Trial (EMGT) to provide prospective information on the natural history of three common glaucoma types: high-tension glaucoma (HTG, IOP≥21mmHg), normal-tension glaucoma (NTG, IOP<21mmHg), and pseudoexfoliative glaucoma (PEXG).

The EMGT's study design included patients with newly diagnosed and previously untreated glaucoma who had mild to moderate optic nerve damage. Patients were recruited via population screenings in Malmö and Helsingborg, Sweden and ages ranged from 50 to 80 years. Subjects were randomized to treated and non-treated groups and followed every 3 months. Unless glaucomatous 'progression' occurred, treatment status did not change. Progression was defined as significant visual field deterioration determined through computerized analysis, or increased disk cupping detected through masked grading of disc photographs. The most recent report from the EMGT included data from 118 patients (94% of the 126 patients in the untreated control group) who were followed for at least 6 years without treatment or, if progression was noted within 6 years treatment may have been instituted. Progression of visual field was quantified in one of three different ways; progression versus non-progression, time to progression, and rate of progression.

After 6 years of close monitoring without treatment, 80 of 118 (68%) patients progressed according to the definition established for the study. Progression occurred in 56% of NTG patients, 74% of HTG patients, and 93% of PEXG patients. The median time to progression was 42.8 months for the entire group, but differed considerably between the three sub groups. The PEXG group had the most rapid median time to progression at 19.5 months, followed by the HTG group at 44.8 months, and the NTG group with 61.1 months. To determine the rate of progression, investigators used the mean deviation (MD) index from the Humphrey Full Threshold 30-2 field. The rate of progression was expressed as the slope of a simple linear regression analysis of MD values over time. The mean rate of progression measured -0.36dB/yr for NTG, -1.31dB/yr for HTG, and -3.13 dB/yr for PEXG. These results are clinically important as a 1dB/yr rate of decline will lead to significant visual disability or blindness if extrapolated out to 25-30 years. However, they also found considerable variation among patients in all groups, with many patients demonstrating a slow progression rate and a considerable minority progressing quickly. The fast progressing subjects skewed the mean progression rates to more negative values. Even so, these data clearly demonstrate that previously untreated glaucoma patients progress without treatment and that PEXG progresses faster than HTG and NTG. The significant variability in progression rates between subjects serves as a reminder to carefully consider each glaucoma patient as an individual; each with the potential to progress quickly.

Clinicians recognize PEXG as a more volatile form of glaucoma and this study confirms that impression. Despite a relatively low number of PEXG subjects (n=15) the differences in progression rates between groups were highly significant. Interestingly, and somewhat unexpectedly, the mean baseline IOP values for the PEXG and HTG groups were similar. This stands in contrast to the common belief that PEXG is more dangerous due to higher IOP and suggests that either pseudoexfoliation may be a risk factor independent of IOP, or alternatively that IOP behavior in PEXG may be more volatile but that this variation is not captured during clinical IOP measurements. Additionally, glaucoma was found to progress much more quickly as a function of age for NTG and HTG groups. That is, visual field progression rates for patients younger that 68 years, when compared with those 68 years and older were similarly high for the group with PEXG, while in the NTG and HTG patient groups the patients aged 68 years and above had notably more rapid progression rates than younger study participants. Although one might surmise that this is due to cumulative disc damage, this finding deserves additional corroborative investigation. It is worth noting that about 50% of untreated NTG did not progress within the 6 year study duration.

The EMGT is the only prospective glaucoma treatment study to include an untreated control group consisting of the most common open angle glaucoma types. It has many strengths such as a prospective design, use of perimetrically experienced subjects, frequent visual field testing, excellent subject retention, and data that appear comparable to other studies on the natural history of glaucoma. Study limitations are few, but include the largely Caucasian patient profile. It is well known that glaucoma affects other races to a greater degree and perhaps in a different way. Due to ethical considerations, it is unlikely that future studies will yield information on the natural history of glaucoma. As clinicians, we have the occasional and often unfortunate glance into the natural history of glaucoma through our patient exposures. The EMGT provides clinicians with valuable information that will help us better serve our patients and raises interesting questions that will hopefully inspire those in the research community.

Carl H. Jacobsen, OD, FAAO

Reference
1. Heijl, A, Bengtsson B, Hyman, L, Leske, MC. Natural history of open-angle glaucoma. Ophthalmology. 2009 Nov;116(11):2271-2276. PMID: 19854514

Delaying Treatment of Ocular Hypertensives Does Not Necessarily Close the Door on a Successful Treatment Outcome.

In March or this year, the most recent information from the Ocular Hypertension Treatment Study (OHTS) was published (1). The main aim of this publication from the OHTS group was to determine if there was a detrimental effect of a delay in reducing the IOP of ocular hypertensive (OH) patients. At the end of phase 1 of the study (completed May 31, 2002), all patients originally randomized to the observation arm of the study were offered topical ocular hypotensive therapy. By comparing outcomes for the originally treated group, who had been treated for the entire duration of the study, with the originally observed group (untreated for the first 7.5 years) it was possible to determine if there was a penalty associated with delayed treatment.

The first OHTS main outcome paper (2) showed that there was a greater chance of converting from OH to primary open angle glaucoma (POAG) among the patients randomized to observation. It is not surprising then that the originally observed patients had a higher 'disease burden' and a significantly higher proportion of patients with POAG in both eyes and with both functional and structural endpoints at the end of approximately 13 years of follow-up. However, once treated, the originally observed group tended to develop POAG at the same rate as the originally treated group. There was no evidence, for the group as a whole, that their disease had become harder to treat or more aggressive.

If subjects were broken down according to their baseline 5-year risk of conversion to POAG, it seemed that there might be some detrimental effect of delaying treatment for those that were at higher baseline risk. At first glance it appeared that race played an important role in determining whether a patient would go on to develop POAG. However, with further scrutiny it became apparent that African Americans had higher levels of baseline risk than the other races due to reasons that weren't race per se. Once the confounding effect of increased baseline risk was controlled (through CCT and vertical C/D ratio), there was no evidence of additional risk associated with being self identified as African American. The authors therefore suggest that African American OHs be managed according to their risk, rather than according to their race.

It should be noted that the study only addressed the proportion of subjects meeting one particular criterion, that adopted by the OHTS investigators, for the diagnosis of POAG. It does not tell us if the originally observed subjects are bound to suffer a greater level of disability or blindness than those treated from the outset. The patients would need to be followed from 5 to 20 years longer to address that question.

When patients with the lowest baseline risk were examined separately it was apparent that there was practically no difference in the proportion of patients that developed POAG between the originally treated and observed groups. These subjects tended to do quite well whether initially treated or observed. Might this finding suggest that patients without elevated risk have a small chance of conversion to glaucoma that may be unrelated to their moderately elevated IOP? It may also suggest that treating those with low baseline risk might not be wise as there is little benefit but there is the additional cost, inconvenience and the side effects of ocular hypotensive medications.

Several of the findings of the OHTS 2 study point to one thing; it is absolutely necessary to calculate the risk of conversion to POAG for all OHT patients in your care. Tools for performing this are readily available to all clinicians and their use should be strongly encouraged*.

Some comfort can also be taken from this study. Comfort in the knowledge that only 1 in 5 of the originally observed group developed POAG after approximately 13 years of follow-up, even when they were untreated for the first 7.5 years. In addition, the median duration between enrolment in the OHTS (VF and ONH within normal limits, IOP ranges etc) and conversion to POAG was about 6 years. So, if you lose some of your OHT patients to follow up, for example if they fail to attend for routine appointments (they decide to take a 5-year holiday from coming to see you) then, on average, chances are reasonable that they will still not have developed POAG by the time you next see them. Furthermore, this is for an unselected group, the proportions and intervals are probably better for those OHs with low baseline risk levels, but of course may be worse for others with a higher risk profile, underscoring the importance of regular review for those at risk.

Shaban Demirel, BScOptom, PhD.

*The OHTS risk calculator can be used or downloaded from http://ohts.wustl.edu/risk/calculator.html

References
1. Kass MA, Gordon MO, Gao F, et al. Delaying treatment of ocular hypertension: The ocular hypertension treatment study. Arch Ophthalmol. 2010;128(3):276-87. http://www.ncbi.nlm.nih.gov/pubmed/20212196
2. 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. Archives of Ophthalmology 2002;120:701-13; discussion 829-30. http://www.ncbi.nlm.nih.gov/pubmed/12049574?dopt=Citation

VISUAL FIELD REVIEW

To Treat or Not to Treat—the Million Dollar Question.

Visual field testing is subject to many corrupting influences as detailed in this issue by Dr. Chris Johnson who describes one of these factors; i.e. that learning can improve visual field thresholds. But even in the presence of reliable data, the finding of field loss in a glaucoma patient presents a difficult challenge and gathering field data on which clinical decisions can be made may require several retests.

This case demonstrates the diagnostic dilemma faced daily in clinical practice. Here we show a sequence of visual fields gathered from a 66 year old male who is being treated for primary open angle glaucoma in his RE but is untreated in his LE because of its borderline status. He has been receiving follow-up care, including routine visual field testing, for the past 3 years. The LE shows no clinically detectable disc changes, as evident in the HRT scan which suggests a normal Retinal Nerve Fibre layer but a thin neural rim profile at the temporal disc margin. This case clearly demonstrates the clinical challenge of interpreting visual field results as it shows variability, changing from mildly suspicious nasal loss (2/2007), to a rim artefact with suspicious nasal loss (2/2008), to a nasal step (6/2008), to a normal outcome with poor reliability, especially poor fixation (9/2008) and finally a reliable and normal result (3/2010).

So what would you do in this case? Interpreting these fields presents a diagnostic challenge that requires many factors to be weighed before treatment is commenced. Where the visual field is concerned, repeatability of a defect is essential in establishing a glaucoma diagnosis and some guidance is available from the results of clinical trials.

A series of visual field results (Courtesy Dr. Spry) for the LE of a 66 year old male who has glaucoma in his fellow eye. The results show a mildly suspicious outcome in the nasal area (2/2007), to a rim artefact with suspect nasal loss (2/2008), to a nasal step (6/2008), to a normal outcome with low reliability (9/2008) and finally a reliable but normal outcome (3/2010). The HRT scan taken at the time of the last field test is also shown.

The Ocular Hypertensive Treatment Study (OHTS) reported that 85.9% of all patients who initially produced an abnormal field result failed to confirm this abnormality when retested (1) as in our case (6/2008 to 9/2008). In a follow-up study, the OHTS group reported that it is difficult to distinguish between true visual field loss and long-term variability even with retesting (2). They noted that confirmation of an abnormal visual field result at the next test (within 8 weeks of the initial abnormality) yielded a limited sensitivity for abnormality (only 34% continue to remain abnormal at future tests) compared with observing three consecutive abnormal results (initial abnormality and 2 confirmation) where 88% remain abnormal.

The findings of the large scale clinical trials and those from the patient discussed in this piece set visual field abnormality in perspective. All visual field abnormalities need to be confirmed at least once and clinicians should refrain from making treatment changes in the absence of other signs supporting the diagnosis, such as: a high risk profile, optic nerve head or nerve fibre layer abnormalities, haemorrhages or progressive optic nerve head or nerve fibre layer changes. In these cases, or in the presence of equivocal signs/profile, the OHTS group recommend waiting for successive visual field abnormalities before suggesting the initiation of treatment to the patient.

Algis Vingrys, BScOptom, PhD

References
1.Keltner JL, Johnson CA, et al. Confirmation of visual field abnormalities in the Ocular Hypertension Treatment Study: Ocular Hypertension Treatment Study Group. Arch Ophthalmol. 2000;118:1187-94.
2.Keltner JL, Johnson CA, et al. Normal Visual Field Test Results Following Glaucomatous Visual Field End Points in the Ocular Hypertension Treatment Study. Arch Ophthalmol. 2005;123:1201-06.

 

CLINICAL TRIAL REVIEW

Risk Factors for Progression—Evidence from the Canadian Glaucoma Study.
Many patients with glaucoma continue to progress despite reduction of their IOP, and it is clear that there are factors other than IOP that influence the risk of progression. The Canadian Glaucoma Study (CGS) was designed specifically to shed light on these factors. In this article, we comment on some of the important findings that have recently emerged from this study.

The CGS was a prospective longitudinal multicentre study. At five sites in Halifax, Toronto, Montreal and Vancouver, 258 patients with glaucoma and early to moderate visual field damage (median MD at baseline, -4.0 dB) were followed over an average of 5.3 years. Visual fields were examined every 4 months, and progression was based on a strict criterion of confirmed change from baseline. The overall progression rate after 5 years of follow-up was 31%.

Four variables were found to be independently associated with progression. Patients with abnormal anticardiolipin antibody (ACA) levels were almost 4 times more likely to show progression. Women were nearly twice as likely to progress compared to men. For each 1 mmHg increase in mean IOP over the follow-up period, the risk of progression increased by 20%. Finally, older patients were more likely to progress, with a 4% increased risk of progression associated with each year of advancing age.

Negative findings were as noteworthy as positive ones. One of the primary hypotheses of the CGS had been that vasospastic patients benefit more from IOP reduction than their peers, but no convincing evidence emerged in support of this hypothesis. Further, diabetes, systemic hypertension, heart disease, migraine, and pseudoexfoliation were not shown to be significantly associated with an increased risk of progression in the CGS.

What is reassuring, and what is surprising about these findings? First of all, the CGS underscores the importance of IOP. The large bearing of IOP on the risk of progression had previously been reported in all major glaucoma-related trials, but this had not been an objective of the CGS. On the contrary, the CGS enforced a tight control of pressure levels—75% of participants had a mean IOP between 15 and 18 mmHg during follow-up—to increase its ability to detect the influence of other risk factors. Despite the narrow range of IOPs, the strong relationship between IOP and progression in the CGS serves as a powerful reminder that IOP reduction is of primary importance when it comes to minimising risk of progression.

A higher progression risk in women had previously been reported in the Collaborative Normal Tension Glaucoma Treatment Study (CNGTS), but was not shown in the Early Manifest Glaucoma Trial (EMGT). Conversely, an increased risk of progression with age had been reported in the EMGT, but not the CNGTS. Sometimes, the apparently conflicting evidence from clinical studies can be confusing, and it is not always clear how they should best be applied to individual patients in clinical practice. Results from studies such as these always reflect the make-up of the patients who participate in them, but may not be generalisable to all other populations. This is why evidence-based medicine does not lend itself to a rule-book approach, but requires clinicians to consider the individual and how closely their risk profile matches that of patients enrolled in clinical studies.

Studies such as the CGS have an important role in creating new knowledge about factors that predispose patients to lose vision to glaucoma. At the same time, positive findings unrelated to the original hypotheses can be coincidental and difficult to interpret. For example, the finding that patients with elevated ACA levels progress more rapidly than others needs corroboration from further studies.

Finally, absence of evidence is not evidence of absence. The lack of statistical significance for an association between progression and peripheral vasospasm, for example, does not mean that this hypothesis has been rejected once and for all, that vasospasm has been ruled out as an important factor and no longer needs to be considered. However, the findings of the CGS strongly suggest that vasospasm, or at least the finger blood flow measures that were used to quantify it, are probably less important for the long-term prognosis of glaucoma patients than reduction of IOP.

Paul Artes, PhD

Reference
Chauhan BC, Mikelberg FS, Balaszi AG, LeBlanc RP, Lesk MR, Trope GE, Canadian Glaucoma Study Group. Canadian Glaucoma Study: 2. Risk Factors for the Progression of Open-Angle Glaucoma. Arch Ophthalmol. 2008, 126(8): 1030-6.

 

 

QUARTERLY CASE

A Case of Pigment Dispersion Syndrome?

A 48 year-old white male presented to the clinic in late 2002. He had previously been treated for glaucoma by a local optometrist. The patient had a presumptive diagnosis of pigment dispersion syndrome (PDS) and secondary ocular hypertension (OHT). Treatment consisted of brimonidine 0.2% (Alphagan) twice daily, and this had been taken for the past three to four years. On the day of examination, the patient stated that he had run out of his drops about three weeks ago.

There was no relevant medical history, with no medications being taken except topical glaucoma medications. The patient did not smoke and only drank alcohol occasionally. He reported using a daily multi-vitamin. His most recent physical examination was within the past six months. The family history was significant for glaucoma (mother, treated with topical medications).

Figure 1. Fundus photographs taken in March 2009. Optic discs do not appear glaucomacomatous. Note the flat choroidal naevus nasal to the disc OD.

With myopic and astigmatic refractive correction, best-corrected visual acuity (BCVA) was 20/20 (6/6) in each eye. Blood pressure was recorded as 118/78. Ocular anterior segment examination was unremarkable with the exception of a light pigment dusting on the endothelium of each cornea. The pigment arrangement was central and resembled a Krukenburg’s spindle pattern. Importantly, there was no sign of iris transillumination. Intraocular pressure (IOP) by Goldmann applanation tonometry was 23 mmHg and 25 mmHg in the right and left eyes, respectively (9:35 AM). Gonioscopy showed a wide-open angle, with trabecular meshwork visible, with mild concavity in the periphery of the iris and only minimal pigment inferiorly on the trabecular meshwork. Dilated fundus examination was unremarkable, without any evidence of glaucomatous optic neuropathy (GON). Visual fields that were within normal limits when tested with the Humphrey Field Analyzer (HFA) 24-2 SITA Fast. Digital photos of the right and left optic nerves were requested from the treating optometrist. The patient was asked to restart the brimonidine.

The patient resumed care with their original optometrist, but then returned to the clinic nearly seven years later in 2009 (aged 54 years old). The medical and family histories were unchanged. At this visit, visual acuity and refractive correction for distance had not changed and Frequency- Doubling Technology (FDT) perimetry was within normal limits. Untreated IOP was 22/24 mmHg at 4:09 PM. Again, there were no signs of GON on optic disc examination and a healthy retinal nerve fiber layer was evident by binocular indirect ophthalmoscopy (see Figure 1). The patient was prescribed 0.15% brimonidine twice daily (Alphagan-P, Allergan) and asked to return in 3 months for an IOP check, gonioscopy, visual field testing and pachymetry.

Figure 2. Reliable visual fields within normal limits OU, May 2008.

At this 3-month follow-up visit, the patient reported adherence with their topical brimonidine. Ophthalmic findings were as follows; BCVA: 20/20 (OD & OS); IOP: 25/26 mmHg 8:45 AM; Pachymetry: 577, 611 µm. Anterior segment findings were unchanged. GDx results showed a small ONH OD, average sized ONH OS; NFI = 21, 24 (OD, OS). Intraocular pressure was considered to be insufficiently controlled and so it was suggested that the patient continue the brimonidine 0.15% and add travoprost 0.004% (Travatan-Z) once daily. Results of standard automated visual field testing on this date were reliable and within normal limits (see Figure 2).

The IOP behavior over the period of observation from 2002 with a hiatus until 2008 are summarized in Table 1. It can be seen that IOP was substantially elevated at time points when the patient was not using their topical medication, with a maximum recorded IOP of 29 mmHg OU. OCT data at this time revealed that RNFL thickness was within the normal range (average 93/87 µm OD, OS) and there was a normal "double hump" pattern associated with the contour of each eye.

Figure 3. A non-specific sensitivity reduction OD present in August 2009 remains unconfirmed.

Throughout observations to date, the patient's optic nerve heads remain unchanged from their initial physiological appearance. At no point was even a single optic-disc hemorrhage noted. The visual fields were normal over nearly 7 years of follow-up (though a non-specific abnormality on the most recent exam of the left eye remains to be confirmed (see Figure 3). The appearance of a sporadic central depression in the left visual field was not repeatable. Presence of pigment on the corneal endothelium and potentially an excess in the trabecular meshwork along with raised IOP are all consistent with a diagnosis of ocular hypertension secondary to PDS, but the absence of GON or glaucomatous visual field defects therefore indicates this is not pigmentary glaucoma. The 5 year risk of developing glaucoma in at least one eye was 6.5% according to the OHTS risk calculator.

Discussion

Pigment deposition on the corneal endothelium may result from a variety of causes. These include trauma (including surgical), inflammation, iris cysts, pseudoexfoliation syndrome (PXF) and pigment dispersion syndrome (PDS). The latter is of interest in the context of glaucoma because it increases risk of IOP elevation. PDS, of course, can lead to pigmentary glaucoma (PDG) (1)

In PDS, the source of the pigment is melanin granules from iris pigment epithelial cells. The mechanism of pigment release is a posteriorly bowed peripheral iris allowing contact with the zonules which rub against the posterior iris surface during iris movement resulting in pigment liberation. The necessary anatomical configuration is more commonly seen in myopic eyes. The reason for IOP elevation is likely to be a combination of mechanical obstruction and resulting trabeculocyte change in the trabecular meshwork, where a large proportion of liberated pigment usually settles. In addition to trabecular pigmentation, other signs associated with PDS include mid-peripheral spoke-like iris transillumination defects corresponding to loci of pigment release, corneal endothelial pigmentation (Kruckenberg's spindle), pigmentation on the anterior iris surface and, occasionally, in the posterior chamber between the posterior capsule and areas of zonular adherence ("Scheie's line"). Pigment granules can sometimes be seen in the anterior chamber following exercise or pharmacologic pupillary dilation.

Table 1.

Date OD OS On Topical Medication 12/2002 23 22 Yes 2/2008 22 24 No 5/8/08 25 26 Yes 5/29/08 18 18 Yes 9/4/08 17 15 Yes 12/15/08 20 22 Yes 1/26/09 18 18 Yes 4/24/09 18 18 Yes 7/23/09 21 26 Yes 8/25/09 21 21 Yes 9/29/09 24 24 Yes 10/20/09 24 24 Yes 11/24/09 29 29 Yes 12/8/09 29 28 No 1/5/10 28 25 Yes

In this case, the patient exhibited no iris transillumination, mild posterior bowing of the peripheral iris and some characteristic pigment deposition on the corneal endothelium and in the anterior chamber angle. Because the patient had no history of intraocular inflammation, surgery or blunt trauma the diagnosis of PDS was made, with ocular hypertension (OHT) being a differential diagnosis. PDS occurs most commonly in younger myopic male patients and therefore this patient is atypical being 48 years old. However, because PDS signs can decrease after the period of greatest pigment release, this diagnosis is still probable, given that the patient's age is older than expected at presentation, and that other causes of pigment related IOP elevation have been excluded, in particular PXF.

Not all cases of PDS result in OHT and epidemiologic information on PDS and its association with OHT and pigmentary glaucoma is surprisingly scant. A report from a screening study estimated that 2.45% of individuals have PDS (2), whilst other studies have indicated that up to 50% of individuals with PDS convert to glaucoma (3). It may be reasonable to consider this risk similarly to that of conversion amongst patients with 'primary' OHT. As such, prognostic factors for conversion from ocular hypertension to glaucoma have been discerned from the OHTS including age, IOP, C/D ratio, PSD, CCT (4). This case is instructive precisely because it illustrates that differentiation between 'primary' OHT and OHT secondary to PDS is not so clear-cut and thus representative of many patient encounters in which the presenting signs are not 'text book'.

At the present time, the management plan for this patient consists of monitoring the IOP without treatment for optic disc and visual field changes. This would be modified if the depressions in the left eye are repeatable or thinning of the RNFL is documented, either of which would suggest conversion to pigmentary glaucoma.

Leo Semes, OD, FAAO

References
1. Ritch R (1998). Pigment dispersion syndrome. Am J Ophthalmol 1998; 126: 442-6.
2. Ritch R, Steinberger d, Liebmann JM (1993). Prevalence of pgment dispersion syndrome in a population undergoing population screening. Am J Ophthalmol; 115; 707-710.
3. Scheie HG, Fleischhauer HW (1958). Idiopathic atrophy of the epithelial layers of the iris and ciliary body. Arch Ophthalmol; 59: 216-228.
4. Gordon MO, Beiser JA, Brandt JD, et al. (2002) The ocular hypertension treatment study. Baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol 2002; 120:714-720.

 

 

CLINICAL QUESTIONS AND ANSWERS

If you would like us to answer a clinical question, please send it to [email protected] 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!

 

 

POLL RESULTS FROM PREVIOUS ISSUE

Question one revealed only 37% of respondents routinely check blood pressure in their glaucoma patients. Interestingly, while question 2 suggests an equal number of respondents do not regularly consider blood pressure in their glaucoma patients, the balance (62%) consider the role of blood pressure in some or all of their patients with glaucoma. Twenty six percent consider blood pressure in all their glaucoma patients while smaller percentages only consider this in cases of normal tension glaucoma (14%) or in those patients with evidence of progression despite presumably controlled intraocular pressure (11%).

Nearly half of respondents consider systemic medications and their potential impact on pathophysiology in all their glaucoma patients.

The complex association of systemic conditions and the eye including blood pressure, blood flow and perfusion pressure continues to be explored. Improved understanding and practical application of this will drive future practice patterns. Clinicians can look forward to more information on the horizon.

John McSoley, OD

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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 G. Richard Bennett, MS, 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   Art/Production Director Joe Morris

 

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