OGS PRESIDENT'S MESSAGE

It is with great pride and humility that I write my first President’s message. Pride in the achievements of the Optometric Glaucoma Society. Humility in the size 20 boots I have been asked to fill as the OGS’s second President. There will never be another founding President of the OGS, and there will certainly never be another Murray Fingeret. Murray’s vision, energy, integrity and guidance has taken an idea, first discussed over dinner in Philadelphia during the AAO meeting of 2001, into a society that has turned its mission "to promote excellence in the care of patients with glaucoma through professional education and scientific investigation" into an overwhelming success. The OGS is a full member of the World Glaucoma Associations, enjoys an exceptional annual meeting with a widely circulated Proceedings series, holds a Residents training program, educates the educators, sponsors and promotes research, organizes symposia for the AAO, is well on the way to sponsoring its first Ezell Fellowship and produces this unprecedented E-journal, which enjoys a circulation of over 4500. As a Society we are grateful, as a profession we should be proud of these considerable achievements.

As the OGS comes of age other founding officers are stepping down and should be publicly thanked for their tireless contributions. In particular Mike Patella, the outgoing Secretary, Tom Lewis, our new Treasurer and former Vice President, John McSoley our Meeting Chair and Peter Lalle our first Treasurer. These were the pioneers.

Appropriate though it may be to reflect from where we came, I am excited about where we will be going in 2008. The annual meeting is expanding into a second day, we will be defining and developing glaucoma curricula with the educators, planning for the 3rd World Glaucoma Congress taking place in Boston in 2009, and helping optometry promote World Glaucoma Day.

The first World Glaucoma Day is on March 6th, 2008. I encourage you to get involved. This is an ideal opportunity for optometry to promote its important role in the care of patients with glaucoma. The World Glaucoma Associations are promoting the initiative "No More than 20 by 2020" with the goal of reducing the 50% undiagnosed rate of glaucoma to 20% by the year 2020 with the help of awareness and screening campaigns (see http://www.worldglaucoma.org/). The OGS supports this initiative and will be providing materials for the promotion of patient awareness.

Finally I would like to thank the exemplary editorial team of the E-Journal and its sponsor, Pfizer Ophthalmics. Associate Editors Brad Fortune, Shaban Demirel and Algis Vingrys, under the dedicated leadership of Editor-in-Chief Paul Spry have, over the last 8 issues, produced an informative, stylish, authoritative and popular journal for the promotion of all things glaucoma. For those of you new to the format, you can find a link to previous journals through the OGS website (http://www.optometricglaucomasociety.org/).

To all of you I wish a peaceful and productive 2008, and don’t forget World Glaucoma Day on March 6th.

John Flanagan PhD, MCOptom, FAAO
President, Optometric Glaucoma Society
jgflanag@quark.uwaterloo.ca

Reviewing the Evidence-Base

Clinicians of every background are familiar with the term, "Evidence-based medicine." The concept is a simple one: a body of information should exist to underpin care provided to patients. In the context of glaucoma management in 2008, specific aspects of clinical practice can be justified in this manner with individual, supportive building blocks of evidence reported from high quality investigations providing a consensus on which practice can be based. The obvious example of such evidence-based practice in glaucoma care is therapeutic IOP lowering. This is now supported by a wealth of evidence building blocks, specifically reports from numerous high-power randomised controlled trials (RCTs) that all differed slightly in their specific objectives, but came to common agreement that IOP lowering improves visual prognosis. It is easy to define such a specific evidence-based intervention once a consensus of such evidence is available, but much more difficult earlier in the research process, when uncertainties exist. So how exactly do we know when an adequate evidence-base exists? Unfortunately there is no straightforward answer to this important question. Establishing an evidence-base is therefore a long process, and uncertainty exists as to how many ‘building blocks’ of supportive information are required to reach consensus, or the minimum acceptable quality level for each piece of evidence.

This issue of the E-Journal features two review articles of new evidence building blocks on matters where the evidence-base is incomplete but growing rapidly, thereby having a high potential to inform future evidence-based glaucoma practice. In a review of the role of perfusion-pressure in glaucoma, epidemiologist Dr Leske describes the latest evidence on the importance of perfusion-pressure for glaucoma onset and progression. These findings come from both incidence studies and longitudinal RCTs that, by design, extract information on relationships between exposure variables and outcomes that are hard to identify with any degree of statistical power from cruder or cross-sectional study designs. In the visual field review, Dr Swanson reviews evidence that questions a widely stated view that a substantial proportion of nerve fibres or ganglion cells have to be lost before a visual field defect occurs. This has implications not only for how best to examine visual function, and to detect early glaucoma but more fundamentally for our understanding of the disease. Although these two articles are on quite different subjects, they conclude in exactly the same manner, by calling for further information. This tells us the certainty in establishing an evidence-base: that it can never be too large.

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

A possible link exists between ocular perfusion pressure and open-angle glaucoma (OAG), as discussed in various summary reviews (1-5). The aims of this report are to: a) provide a brief overview on the hypothesized relationship; b) present new data on ocular perfusion pressure, blood pressure and OAG; and c) outline some potential implications.

Ocular Perfusion Pressure and OAG – a Possible Link?
As a general definition, ocular perfusion pressure is expressed as the difference between the blood pressure (BP) and the intraocular pressure (IOP). Therefore, depending on the blood pressure measurement used for the calculation, it is necessary to specify whether one refers to systolic, diastolic or mean perfusion pressure.

An adequate perfusion is key to maintaining normal tissue function. A low ocular perfusion pressure at the optic disc may be deleterious by causing ischemia and decreased blood flow, thus leading to glaucoma damage. Vascular dysregulation has been proposed as an important mechanism in this process (1-5), as it may cause unstable perfusion pressure with wide fluctuations, e.g., with nocturnal dips. The abnormalities in ocular perfusion pressure and vascular status may be potential ‘risk factors’ for developing new incident glaucoma in susceptible, previously normal individuals. In addition, they may be ‘progression factors’ for worsening the disease in patients with pre-existing glaucoma.

Risk factor data.
Various population-based epidemiologic studies have reported associations between low ocular perfusion pressure & OAG. These include cross-sectional or prevalence studies in populations of varying ancestries, with consistent findings among European-derived, African-derived and Hispanic populations (6-12). For example, the Baltimore Eye Study, Proyecto VER, and the Egna-Markt Study, among others, found significant associations between OAG prevalence and low diastolic perfusion pressure, e.g., under 50 mmHg. However, to determine risk factors, stronger evidence originates from longitudinal studies, which follow individuals over a specific time period and are thus able to determine factors related to the development or incidence of the disease. The first such data were provided by the Barbados Eye Studies, which determined the frequency and risk factors for all major eye diseases, including OAG(12). The data were based on a large population-based cohort mainly of African descent (n=4,631 at baseline), with high participation. After four years, individuals with low ocular perfusion pressure at baseline had a 3-fold increased risk of newly developing OAG, as compared to those with higher perfusion pressures (13).

Recently, the new 9-year data from the Barbados Eye Studies have confirmed these findings. In the latest follow-up, the 9-year risk of developing glaucoma was significantly increased among persons with low ocular perfusion pressure at baseline, whether one considered systolic, diastolic or mean perfusion pressures. For example, in persons with low mean perfusion pressure, the Relative Risk (RR) for developing OAG was 2.6, an increase of about two and a half times (14).

Progression data.
Studies of glaucoma patients have also yielded evidence that implicates lower perfusion pressure and ocular blood flow as relevant to the clinical course of established OAG (15,16). The most recent data stem from the Early Manifest Glaucoma Trial, a randomized clinical trial that evaluated the role of immediate treatment, as compared to no initial treatment, on glaucoma progression. In the long-term follow-up of the trial (up to 11 years), progression was increased in patients with low systolic perfusion pressure at baseline (17). In these patients, the Hazard Ratio (HR) was significantly increased to 1.42, suggesting almost a 1.5-times increased hazard of progression.

Blood Pressure and OAG - Inconsistent Findings
A positive association between blood pressure (BP) and IOP has been established clearly in many studies (6,18-22). Moreover, of the known variables related to IOP, most studies find that BP is the strongest factor explaining the variation in IOP. In contrast, there is mixed evidence for a link between BP and OAG (6-12, 22-29). The epidemiologic prevalence studies report mainly weak associations with either high BP or low BP, or they report non-statistically significant relationships (6-12, 22, 23, 25). As such, based on cross-sectional data, BP is not an established factor associated with OAG. Evidence from incidence studies also do not support a clear-cut relationship (13, 14). In the latest 9-year incidence data from the Barbados Studies, the association with BP was weak and in the protective direction, with a RR of 0.91 per 10 mmHg of systolic BP (14). Similarly, in persons with systemic hypertension at baseline, the RR was 0.8 and non-statistically significant, overall and in all age groups (14).

When considering the role of BP as a progression factor for established OAG, the recent article from the Early Manifest Glaucoma Trial found similar results. Patients with higher systolic BP at baseline had lower hazards for progression, with HRs of 0.44 to 0.69 (p= 0.04-0.10) in the various analyses (17). In patients with systemic hypertension, the HR was 0.8 and non-significant.

Potential Implications
As outlined in this overview, the associations of glaucoma and low perfusion pressure are consistent, strong, and biologically plausible. However, these findings could be influenced by low BP, high IOP, treatment to lower BP or IOP, or some combination of these variables. As such, the results must be interpreted carefully and consider all these issues. Since BP and IOP are influenced by many factors and have marked variation across populations, it is also possible that perfusion pressure relationships vary accordingly.

Given these caveats, what can we conclude from the evidence to date?

Although BP is known to be positively associated with IOP, a clear link between BP and OAG has not been established. In contrast, ocular perfusion pressure reflects the vascular status at the optic disc and seems a more relevant factor than BP alone, as it includes both BP and IOP.

OAG is a multifactorial disease, which is influenced by the interaction of genetic and non-genetic factors. It is very likely that perfusion pressure and vascular factors are part of this interaction and thus play a role on the development of OAG, its progression, or both. While the data are suggestive, the importance and magnitude of this role remains to be determined.

What are the Possible Clinical Implications?
A relationship of perfusion pressure to OAG incidence or progression may have implications for patient management. However, a careful measurement of BP is not always performed in all patients presenting for eye care.

Should one consider ocular perfusion pressure in clinical practice? If so, should we avoid an excessive lowering of BP in ocular hypertensive patients and OAG patients? This is a concern, as patients with high IOP often have systemic hypertension.

Although the definitive answer to these questions must await the results of new research, there is mounting evidence for a role of vascular factors in glaucoma and the potential importance of perfusion pressure.

M. Cristina Leske, MD, MPH, DSc (hon)
Distinguished Professor; Distinguished Service Professor; Preventive Medicine and Ophthalmology, Department of Preventive Medicine, Stony Brook School of Medicine, Stony Brook, NY 11794-8036

References
1. Grieshaber MC, Flammer J. Blood flow in glaucoma. Curr Opin Ophthalmol 2005;16:79-83
2. Harris A, Rechtman E, Siesky B, et al. The role of optic nerve blood flow in the pathogenesis of glaucoma. Ophthalmol Clin North Am 2005;18:345-53, v.
3. Flammer J, Orgul S, Costa VP, et al. The impact of ocular blood flow in glaucoma. Prog Retin Eye Res 2002;21:359-93.
4. Gherghel D, Hosking SL, Orgul S. Autonomic nervous system, circadian rhythms, and primary open-angle glaucoma. Surv Ophthalmol 2004;49:491-508.
5. Chung HS, Harris A, Evans DW et al. Vascular aspects in the pathophysiology of glaucomatous optic neuropathy. Surv Ophthalmol. 1999 Jun;43 Suppl 1:S43-50.
6. Leske MC, Podgor MJ. Intraocular pressure, cardiovascular risk variables, and visual field defects. Am J Epidemiol 1983;118:280-7.
7. Tielsch JM, Katz J, Sommer A, et al. Hypertension, perfusion pressure, and primary open-angle glaucoma: a population-based assessment. Arch Ophthalmol 1995;113:216-21.
8. Leske MC, Warheit-Roberts L, Wu SY. Open-angle glaucoma and ocular hypertension: the Long Island Glaucoma Case-Control Study. Ophthalmic Epidemiol 1996;3:85-96.
9. Bonomi L, Marchini G, Marraffa M, et al. Vascular risk factors for primary open angle glaucoma: the Egna-Neumarkt Study. Ophthalmology 2000;107:1287-93.
10. Quigley HA, West SK, Rodriguez J, et al. The prevalence of glaucoma in a population-based study of Hispanic subjects: Proyecto VER. Arch Ophthalmol 2001;119:1819-26.
11. Hulsman CA, Vingerling JR, Hofman A et al. Blood Pressure, Arterial Stiffness, and Open-angle Glaucoma: The Rotterdam Study. Arch Ophthalmol. 2007 Jun;125(6):805-12.
12. Leske MC, Connell AM, Wu SY, et al. Risk factors for open-angle glaucoma: the Barbados Eye Study. Arch Ophthalmol 1995;113:918-24.
13. Leske MC, Wu SY, Nemesure B et al. Incident open-angle glaucoma and blood pressure. Arch Ophthalmol 2002;120:954-9.
14. Leske, MC, Wu SY, Hennis A et al. Risk Factors for Incident Open-Angle Glaucoma. Ophthalmology 2007. In press.
15. Zeitz O, Galambos P, Wagenfeld L et al. Glaucoma progression is associated with decreased blood flow velocities in the short posterior ciliary artery. Br. J. Ophthalmol., Oct 2006; 90: 1245 - 1248.
16. Fuchsjager-Mayrl G, Wally B, Georgopoulos M et al. Ocular blood flow and systemic blood pressure in patients with primary open-angle glaucoma and ocular hypertension. Invest Ophthalmol Vis Sci. 2004 Mar;45(3):834-9.
17. Leske, MC, Heijl A, Hyman, L et al. Predictors of long-term progression in the Early Manifest Glaucoma Trial. Ophthalmology 2007. In press
18. Bengtsson B. Some factors affecting the distribution of intraocular pressure in a population. Acta Ophthalmol (Copenh) 1972;50:33-46.
19. Klein BEK, Klein R. Intraocular pressure and cardiovascular risk factors. Arch Ophthalmology 1981;99:837-9.
20. Wu S-Y, Leske MC and the Barbados Eye Studies Group. Associations with Intraocular Pressure in the Barbados Eye Study. Arch Ophthalmol 1997;115:1572-1576.
21.Bulpitt CJ, Hodes C, Everitt MG. Intraocular pressure and systemic blood pressure in the elderly. Brit J Ophthalmol 1975;59:717-20.
22.Dielemans I, Vingerling JR, Algra D, et al. Primary open-angle glaucoma, intraocular pressure, and systemic blood pressure in the general elderly population. Ophthalmology 1995;102:54-60.
23. Mitchell P, Lee AJ, Rochtchina E et al. Open-angle glaucoma and systemic hypertension: the Blue Mountains Eye Study. J Glaucoma 2004;13:319-26.
24.Pache M, Flammer J. A sick eye in a sick body? Systemic findings in patients with primary open-angle glaucoma. Surv Ophthalmol 2006;51:179-212.
25. Topouzis F, Coleman AL, Harris A, et al. Association of blood pressure status with the optic disk structure in non-glaucoma subjects: the Thessaloniki Eye Study. Am J Ophthalmol 2006;142:60-7.
26. Jonas JB. Association of blood pressure status with the optic disk structure. Am J Ophthalmol 2006;142:144-5.
27. Grunwald JE, Piltz J, Hariprasad SM, et al. Optic nerve blood flow in glaucoma: effect of systemic hypertension. Am J Ophthalmol 1999;127:516-22.
28. Orzalesi N, Rossetti L, Omboni S et al. Vascular risk factors in glaucoma: the results of a national survey. Graefes Arch Clin Exp Ophthalmol. 2007 Jun;245(6):795-802.
29. Punjabi OS, Stamper RL, Bostrom AG et al. Does treated systemic hypertension affect progression of optic nerve damage in glaucoma suspects? Curr Eye Res. 2007 Feb;32(2):153-60.

DECONSTRUCTING THE DOCTRINE OF "FUNCTIONAL RESERVE"

It has been widely believed about glaucoma that extensive ganglion cell loss has to occur before perimetric defects can be found, and that patients in the early stages of glaucoma have "pre-perimetric glaucoma" in which ganglion cell loss progresses silently. This belief is a logical extension of the doctrine of "excess neural capacity", also referred to as neural "redundancy" or "functional reserve". This doctrine asserts that most adults have more ganglion cells than needed to see perimetric stimuli, so extensive ganglion cell loss must occur before perimetric loss begins. This doctrine implies that vast numbers of people with progressing glaucoma are being left untreated because they do not yet have visual field defects. This doctrine is adopted in the 2006 American Academy of Ophthalmology's Preferred Practice Pattern, which lists the three stages of glaucoma as mild, moderate & severe, where any form of visual field defect means that the glaucoma has progressed past "mild".

The past two decades have seen development of new tests intended to identify the presumably large numbers of people with undetected pre-perimetric glaucoma: new perimetric tests to reduce redundancy, and imaging tests to detect early ganglion cell loss. Recent studies have shown that the new tests are no better than conventional perimetry at identifying glaucomatous damage and progression. When different tests are evaluated at equal levels of specificity, they tend to have similar sensitivities yet be in substantial disagreement as to which patients they identify(1-4). That is, approximately equal numbers of patients are identified by each of the tests, yet many patients are only identified by one of the tests.

In recent years, the doctrine of functional reserve has been deconstructed, as described in an excellent review by Hood & Kardon(5). Five years ago, in New York and London, two laboratories independently concluded that perimetric sensitivity is linearly related to ganglion cell number, and that the doctrine of functional reserve is based on a statistical artefact produced by using a decibel (dB) scale for perimetric measures versus a linear scale (e.g., RNFL thickness, rim area) for imaging measures. A few years after the linear model was proposed, its predictions were confirmed in clinical studies (6-12) and were also supported by quantitative modelling(12-14).

From a vision science perspective, seeing a perimetric stimulus is a matter of detecting a signal in noise, where noise at the cortical level is added to the incoming signal embedded in noise from the retino-thalamic input. The signal is embedded in the spike trains of many ganglion cells, so any loss in ganglion cell number should reduce signal relative to noise. This means that even minor losses in ganglion cell number should be accompanied by a decline in perimetric sensitivity. Indeed, the rate of decline in ganglion cell number with normal aging is consistent with the decline in visual sensitivity(15).

Assertions that perimetry is not affected by early stages of ganglion cell loss have not addressed vision science issues of detecting a signal in noise, but instead have cited histological studies for support. As Hood & Kardon demonstrate, the actual data in the histological studies provide no support for the doctrine of a functional reserve. The largest histological study of human eyes with glaucoma was that of Kerrigan-Baumrind et al.(16), who expressed ganglion counts for each retinal location as percent of mean normal for that location. When they grouped test locations by probability score for perimetric defect, the locations with p < 5% on perimetry had ganglion cell counts averaging 97% of mean normal. In other words, many of the locations with perimetric sensitivity below the normal range must have had ganglion cell counts above the mean normal value. Even for locations with more severe perimetric damage (p < 0.5%), the average value for ganglion cell number was 71% of mean normal, well within normal limits based on the means and SDs given in their Figure 1. Overall, most locations had ganglion cell numbers in the normal range yet still had statistically significant perimetric defects. Considering global indices, we can see from their Figure 3 that linear regression predicted that MD would be -6 dB when ganglion cell number is at 100% of mean normal; this is a highly significant perimetric defect with no ganglion cell defect. In sum, human histological data provide no support for the doctrine of a functional reserve.

Similar results have been obtained by Harwerth and colleagues(17-20), in monkeys with experimental glaucoma. They summarized the relations between perimetric sensitivity and ganglion cell loss in an empirical model that has been shown to apply to human data as well. Like the linear model, the empirical model shows a continuous decline in perimetric sensitivity with ganglion cell number and does not support the functional reserve doctrine. The empirical model shows an even more rapid decline in perimetric sensitivity than the linear model, in the opposite direction than the functional reserve doctrine.

Histological counts of ganglion cell bodies assess the final stage of ganglion cell damage, the loss of nucleus and cell body. A ganglion cell will probably stop functioning before the cell body disappears, at least once the axon is lost. Before a cell stops functioning, it may have reduced responsiveness as dendrites shrink and synaptic contacts are reduced (21).

Hood & Kardon use the linear model to provide a powerful new framework for comparing imaging and functional measures of glaucomatous damage in terms of the amount of ganglion cell loss. They address the problems of the large normal ranges for both ganglion cell number and perimetry, and of substantial non-neural components to RNFL thickness as measured in blind eyes. Their framework provides a rational way to compare structural and functional measures, and should be particularly useful for longitudinal studies.

William H. Swanson, PhD
Indiana University School of Optometry

References
1. Artes, P.H. and B.C. Chauhan, Longitudinal changes in the visual field and optic disc in glaucoma. Prog Retin Eye Res, 2005. 24(3): p. 333-54.
2. Strouthidis, N.G., et al., Optic disc and visual field progression in ocular hypertensive subjects: detection rates, specificity, and agreement. Invest Ophthalmol Vis Sci, 2006. 47(7): p. 2904-10.
3. Deleon-Ortega, J.E., et al., Discrimination between glaucomatous and nonglaucomatous eyes using quantitative imaging devices and subjective optic nerve head assessment. Invest Ophthalmol Vis Sci, 2006. 47(8): p. 3374-80.
4. Sample, P.A., et al., Identifying glaucomatous vision loss with visual-function-specific perimetry in the diagnostic innovations in glaucoma study. Invest Ophthalmol Vis Sci, 2006. 47(8): p. 3381-9.
5. Hood, D.C. and R.H. Kardon, A framework for comparing structural and functional measures of glaucomatous damage. Prog Retin Eye Res, 2007.
6. Hood, D.C., Relating retinal nerve fiber thickness to behavioral sensitivity in patients with glaucoma: application of a linear model. J Opt Soc Am A Opt Image Sci Vis, 2007. 24(5): p. 1426-30.
7. Hood, D.C., et al., Retinal Nerve Fiber Structure versus Visual Field Function in Patients with Ischemic Optic Neuropathy A Test of a Linear Model. Ophthalmology, 2007.
8. Hood, D.C., et al., Structure versus function in glaucoma: an application of a linear model. Invest Ophthalmol Vis Sci, 2007. 48(8): p. 3662-8.
9. Kanadani, F.N., et al., Structural and functional assessment of the macular region in patients with glaucoma. Br J Ophthalmol, 2006. 90(11): p. 1393-7.
10. Schlottmann, P.G., et al., Relationship between visual field sensitivity and retinal nerve fiber layer thickness as measured by scanning laser polarimetry. Invest Ophthalmol Vis Sci, 2004. 45(6): p. 1823-9.
11. Pan, F., W.H. Swanson, and M.W. Dul, Evaluation of a two-stage neural model of glaucomatous defect: an approach to reduce test-retest variability. Optom Vis Sci, 2006. 83(7): p. 499-511.
12. Sun, H., M.W. Dul, and W.H. Swanson, Linearity can account for the similarity among conventional, frequency-doubling, and gabor-based perimetric tests in the glaucomatous macula. Optom Vis Sci, 2006. 83(7): p. 455-65.
13. Swanson, W.H., J. Felius, and F. Pan, Perimetric defects and ganglion cell damage: interpreting linear relations using a two-stage neural model. Invest Ophthalmol Vis Sci, 2004. 45(2): p. 466-72.
14. Pan, F. and W.H. Swanson, A cortical pooling model of spatial summation for perimetric stimuli. J Vis, 2006. 6(11): p. 1159-71.
15. Pearson, P.M., et al., Ganglion cell loss and age-related visual loss: a cortical pooling analysis. Optom Vis Sci, 2006. 83(7): p. 444-54.
16. Kerrigan-Baumrind, L.A., et al., Number of ganglion cells in glaucoma eyes compared with threshold visual field tests in the same persons. Invest Ophthalmol Vis Sci, 2000. 41(3): p. 741-8.
17. Harwerth, R.S., et al., Visual field defects and neural losses from experimental glaucoma. Prog Retin Eye Res, 2002. 21(1): p. 91-125.
18. Harwerth, R.S., E.L. Smith, 3rd, and M. Chandler, Progressive visual field defects from experimental glaucoma: measurements with white and colored stimuli. Optom Vis Sci, 1999. 76(8): p. 558-70.
19. Harwerth, R.S. and H.A. Quigley, Visual field defects and retinal ganglion cell losses in patients with glaucoma. Arch Ophthalmol, 2006. 124(6): p. 853-9.
20. Harwerth, R.S. and J.L. Wheat, Modeling the effects of aging on retinal ganglion cell density and nerve fiber layer thickness. Graefes Arch Clin Exp Ophthalmol, 2007.
21. Weber A.J., Harman C.D. Structure-function relations of parasol cells in the normal and glaucomatous primate retina. Invest Ophthalmol Vis Sci, 2005. 46(9): p. 3197-207.

Gonioscopy.org
Wallace L.M. Alward, the Frederick C. Blodi Chair in Ophthalmology and Director, Glaucoma Service at University of Iowa Carver College of Medicine has launched a new video atlas of gonioscopy. This site is dedicated to teaching gonioscopy through the use of videography. It covers the basic examination techniques and more advanced techniques, such as indentation and the corneal wedge. There are video examples of most glaucoma-related diseases. The site uses streaming video and is free to view.

Prostaglandins in Cosmetics
A November 16th press release from the U.S. Food and Drug Administration (FDA) reported that they had seized a large quantity of an unapproved and misbranded cosmetic product called, “Age Intervention Eyelash” because of the risk to vision in some users. This product, containing bimatoprost was promoted to increase eyelash growth and was sold and distributed by Jan Marini Skin Research.

The FDA recommended that anyone who may still have this product should discontinue use and discard any remaining. Consumers were recommended to consult their health care provided if they have experienced any adverse events that they suspect to be related to the product’s use. Click here to read the full FDA press release.

NEW IDEAS AND PAPERS

Do reductions in the cup disc ratio occur with medical therapy?

In a recent issue of the E-Journal (Volume 2, Number 3, June, 2007) a case was presented demonstrating changes in the appearance of the optic disc that were opposite to what we usually seek to detect in our glaucoma patients and suspects. That is, there appeared to be an increase in the neuroretinal rim area relative to the total disc area and a decrease in the area of the cup relative to the total disc area. Evidently, there was no accompanying decrease of intraocular pressure (IOP) between the two time points when the photos were obtained, which might otherwise have helped to explain the changes in optic disc architecture.

In light of that provocative case presentation, it seems rather timely that Meredith and colleagues have published a paper in the September 2007 issue of the Journal of Glaucoma, entitled "The acute morphologic changes that occur at the optic nerve head induced by medical reduction of intraocular pressure." (1) The authors acknowledge previous publications documenting changes in optic disc appearance, which had either been observed over longer intervals, as a result of surgery, or from acute IOP changes induced by scleral suction cup, which they argue, may itself have altered optic disc or globe architecture. Thus, Meredith et al. were interested to determine whether acute reduction of IOP by medical means (systemic acetazolamide in combination with topical apraclonidine) would result in acute morphologic changes of the optic disc. To measure optic disc changes sensitively and objectively, the authors chose confocal scanning laser tomography (CSLT) and thus used a Heidelberg Retinal Tomograph (HRT-1) to obtain images of the optic disc at baseline and 1 hour after the medical IOP-lowering had been initiated.

The results revealed several statistically significant changes including a decrease in the cup volume below surface, cup volume below reference, mean cup depth, cup:disc area ratio, and an increase in the rim area. The most robust of these effects were the decrease of cup volume below surface and the decrease of mean cup depth (with 86% and 76% of the 38 eyes studied showing the effect, respectively, and statistical significance remaining high after correction for inclusion of both eyes of each subject). Because there was no significant change in the mean height of the contour line (i.e. of the peripapillary retinal nerve fiber layer), the authors interpreted their results as representing an acute anterior deformation of the lamina cribrosa. Whether the changes that were determined to be statistically significant were also of physiological significance is unknown. Towards this, it would have been helpful if the authors had provided the absolute values from which they computed changes, because these provide a perspective on the relative magnitude of the changes. The same change in some measure, say median cup volume below reference, could represent a small fraction for a large cup and/or disc or a large fraction of a small cup and/or disc.

It should be noted, however, that although their results are consistent with this most parsimonious explanation, they do not provide direct evidence of this conclusion. CSLT provides information about surface topography, changes below the surface can only be inferred, or estimated using computational models. As the authors did note, models have suggested that deformations of the optic nerve head surface do not necessarily correlate with deformations of the underlying lamina. Direct measurements of both surface and lamina cribrosa deformation are needed to determine how each surface deforms. This could come from imaging technologies capable of imaging deep structural elements within the optic nerve head, optimally including the surface of the lamina cribrosa and Bruch’s membrane opening. Moreover, changes in those structures will also need to be distinguished from changes in the prelaminar tissues. Preliminary studies suggest that spectral-domain optical coherence tomography (sd-OCT) will provide such capabilities.

Brad Fortune OD, PhD and Ian A. Sigal PhD
Devers Eye Institute, Portland, Oregon, USA

Reference
1. Meredith SP, Swift L, Eke T, Broadway DC. The acute morphologic changes that occur at the optic nerve head induced by medical reduction of intraocular pressure. J Glaucoma. 2007;16:556-61.

Should a discussion of increased risk for falls be part of managing some of your glaucoma patients?

In a recent paper, Freeman et al. (1) describe a large, prospective longitudinal study of falls in older adults and investigate the impact of several visual and non-visual risk factors.

Approximately 2300 elder subjects (age 74.1 +/- 5.2 years) maintained monthly calendars of their falls, defined as “unintentionally coming to rest on the ground or at some other level.” They also undertook a multifaceted clinical examination, including visual acuity, contrast sensitivity, stereo acuity and screening visual fields that tested 81 locations out to 60 degrees. The screening exam used would classify a location as abnormal if the 24dB stimulus on the Humphrey Field Analyzer was not detected. Bear in mind that not seeing a 24dB stimulus actually represents a different amount of damage depending on eccentricity and age. Visual fields were measured monocularly but a binocular visual field was estimated via a composite of the two monocular fields.

In multivariate regression models that accounted for many other covariates (age, race, sex, depressive symptoms, grip strength, Parkinson’s disease, arthritis, stroke, use of sedatives, and poor balance) the odds ratio associated with having 10 abnormal locations anywhere within the binocular visual field was 1.10. This means that for each additional 10 binocularly abnormal visual field locations there is an additional 10% risk of falling. When divided into central (inside 20 degrees) and peripheral visual field defects, only peripheral defects by themselves were significantly associated with increased risk of falling. There was a 7% increased risk of falling for every 4 additional binocularly abnormal locations in the peripheral field.

Ideally, the visual field exam would have been a threshold test rather than a single level screening. Single level screening exams do not account for the physiological decline of sensitivity with eccentricity and therefore de-emphasize the degree of central defects relative to peripheral ones. Therefore, in this publication, failure to detect a 24dB stimulus was counted the same regardless of whether it occurred in a part of the field where the normal threshold was 32dB (an 8dB defect) or 26dB (a 2dB defect). Substantial damage within the central field, which might have caused patients to be more likely to fall, would not have necessarily been captured on a single level screening test. However, the linkage between having a visual field defect and being at increased risk for falls would remain.

Although not specifically about glaucoma, the results of this study are particularly pertinent to readers of this e-Journal. Practitioners treating glaucoma are arguably the most likely to see elderly patients with bilateral (especially peripheral) visual field loss. Falls have grave consequences in the elderly, including high rates of hospitalization, nursing home admission and death. It may be that many of your glaucoma patients do not even know they are at increased risk of falls. As a practitioner treating glaucoma, you may have some of the most useful information available for giving advice in this regard.

Shaban Demirel BScOptom, PhD.

Reference
1) Freeman EE, Munoz B, Rubin G, West SK. Visual field loss increases the risk of falls in older adults: the Salisbury eye evaluation. Invest Ophthalmol Vis Sci. 2007;48:4445-50.

 

QUARTERLY CASE

An asymptomatic 85 year old female presented for examination. Questioning revealed that she was in good general health. There was a strong family history of open-angle glaucoma with her son, mother and maternal aunt affected. She was bilaterally pseudophakic, with cataract extractions having been performed 1999 OD and 2002 OS. The cataract extraction OD had been complicated, with conversion from planned phacoemulsification to extracapsular cataract extraction (ECCE) using an enlarged scleral incision due to inability to complete capsulorhexis.

Figure 1.

Figure 2.

Best corrected visual acuities were OD 20/25 and OS 20/20. Anterior segment examination OD revealed a diffuse swelling of the conjunctiva above the limbus (Figure 1) with generalized conjunctival chemosis. The anterior chamber was clear and the iris had a normal appearance, with no visible iridectomy. Because of the unusual conjunctival appearance, gonioscopy was performed that demonstrated a wide open angle with physiological appearance throughout the inferior ~270°. The superior angle was severely disrupted, with no trabecular features visualised (Figure 2). The area normally occupied by the angle structures was pearlescent white and recessed. Anterior segment examination and gonioscopy OS was normal. Posterior chamber intraocular implant lenses were present bilaterally. Goldmann tonometry (9.30am) was OD 10 and OS 20 mmHg with central corneal thickness (CCT) OD 494 and OS 508µm.

Figure 3a.

Figure 3b.

Dilated stereo disc assessment showed the optic nerve heads to be of average size. The cup-to-disc ratio (CDR) was 0.55 in the right eye, with the ISNT ruled obeyed. Excepting beta peripapillary atrophy (PPA), no other features of glaucomatous optic neuropathy (GON) were present (Figure 3a) although the inferotemporal neuroretinal rim (NRR) was possibly eroded. In the left eye, the disc was excavated with a CDR of 0.75 and thinnest area of NRR inferotemporally with adjacent beta PPA. All other aspects of fundus examination were normal (Figure 3b).

Figure 4a.

Figure 4b.

Visual fields are shown in Figure 4 and 4b. 24-2 SITA-Fast fields were performed because this was the patient’s first threshold examination, with future tests planned to be SITA-Standard. Results from both eyes are reliable with gaze tracking from the right eye demonstrating excellent fixation throughout the test, except 3 short-duration eye movements. The OD test returned a borderline glaucoma hemifield test (GHT). The pattern deviation (PD) probability plot demonstrated a cluster of test locations with reduced sensitivity superonasally consistent with a nerve fibre bundle type defect, although 3 of the 6 depressed locations were edge locations. Both Mean Deviation (MD) and Pattern Standard Deviation (PSD) were flagged as at the lower end of the normal range. In the left eye, GHT was outside normal limits and the PD plots showed large clusters of test locations with reduced sensitivity in both superior and inferior arcuate regions, with the superior hemifield being more affected. Both MD and PSD were in the lowest 1% of the normal range.

On the basis of the glaucomatous disc features and corresponding visual field appearance in the left eye, this patient was given a diagnosis of chronic open angle glaucoma, with the right eye status being suspicious, although not definitely glaucomatous. The OD anterior segment appearance was consistent with drainage surgery, with a bleb of raised conjunctiva although the patient had not received any drainage procedure in the past. The bleb over the site of the extended scleral incision from complicated cataract extraction combined with the likely gonioscopic visualisation of the thinned sclera strongly suggests that the old wound was either unstable or associated with scleral thinning probably occurring as a result of the complicated surgery whereby the planned phacoemulsification procedure had to be changed to ECCE.

Further investigation of the wound was not considered necessary due to the absence of signs and symptoms over the period since surgery. This anterior segment appearance, combined with the considerable IOP asymmetry, strongly suggested that the patient had inadvertently received a drainage procedure that had lowered IOP and protected her from glaucoma development. Also of clinical relevance are the thin CCTs bilaterally, whereby the IOP values measured are likely to be underestimations. The patient was commenced on travoprost once daily OS only and arrangements were made for her review in two months to check drug effectiveness and compliance. The left target IOP was the mid teens. Although the right ONH did not exhibit definite GON, it was suspicious due to the presence of greatest PPA adjacent to the area of thinnest NRR inferotemporally. Also, the right visual field test was borderline and therefore repeat field testing will also be performed at the next attendance to determine repeatability, in which case treatment may be commenced bilaterally.

Paul GD Spry PhD BSc MCOptom DipGlauc

OPTIC NERVE REVIEW

Blood Vessels, Blood Supply and Glaucoma

The relationship between glaucoma and optic nerve blood flow is complex. The primary vascular supply to the laminar and immediately prelaminar portions of the anterior optic nerve are via a capillary network derived from the short posterior ciliary arteries, while the most anterior layer (i.e. the pre-laminar retinal nerve fiber layer) of the anterior optic nerve is served by capillaries originating from the central retinal artery (1,2). Loss of ganglion cell axons appears to be accompanied by a proportional dropout of capillary beds in the optic nerve head (3), although the order of these events remains unknown. This proportion of capillaries in the optic nerve head (~1% of total tissue) maintains an orange-red appearance to the remaining neural-retinal rim tissue of the optic nerve. Pallor of the remaining intact neural-retinal rim tissue is not characteristic of glaucoma and a diagnosis of optic nerve infarction, inflammation or compression should be pursued when pallor appears in excess of cupping (i.e. when the rim tissue appears pale, see figure 1a and 1b).

Figure 1a. Glaucomatous optic neuropathy, note remaining neural-retinal rim tissue maintains an orange-red color.

Figure 1b. Non-glaucomatous optic atrophy, note remaining neural-retinal rim tissue has a pale appearance. This patient had anterior ischemic optic neuropathy.

The central retinal artery (CRA) is a minor blood supply to the anterior optic nerve in the region of the laminar cribrosa, the primary site of injury in glaucoma (though, as mentioned above, the CRA does supply the most anterior surface layer of the optic nerve head, as well as the retrolaminar regions of the intraorbital optic nerve). However changes in the appearance of the optic disc blood vessels may be helpful in identifying glaucoma damage. It is paramount to judge (I prefer using a 78 diopter lens at the slit lamp) the contour of the neural-retinal rim tissue with the deflections of the blood vessels as they transverse the neural-retinal rim tissue to the base of the cup. Judging the color difference (rather than contour) between the orange-red rim tissue and the pallor of the optic cup may result in under estimation of cupping. Scrutinizing the contour of the blood vessels will result in a more accurate assessment of the amount of neural-retinal rim tissue.

Figure 2a. Baseline photograph of the optic nerve in a glaucoma suspect patient.

Figure 2b. Same patient two years later showing glaucomatous change. Note change in the deflection of the optic disc vessel at 5 o’clock corresponding to a loss of neural-retinal rim tissue in this area.

Figure 3. Baring of a circumlinear disc vessel superiorly. This sign occurs from loss of rim tissue that previously supported the disc vessel.

Figure 4. Bayoneting of the disc vessel. Note sharp edge of the two disc vessels at 12 o’clock in a patient with bean potting of the optic nerve from end-stage glaucoma.

Acquisition of stereo optic nerve photographs on any new glaucoma or glaucoma suspect patient as a baseline is extremely valuable for future review. The clinical appearance at successive attendances can be compared with this baseline to identify any change in landmarks. Serial photos can be compared to identify changes in the optic nerve and nerve fiber layer. A documented change in the deflection of disc vessels may provide objective evidence of loss of neural-retinal rim tissue (see figure 2a and 2b). In many glaucoma textbooks, authors have described a variety of disc vessel changes, such as "baring of a circumlinear vessel" (see figure 3) or an "over hanging disc vessel" as evidence of glaucoma damage. Although useful when observed, these vessel signs are relatively uncommon and they may not be specific for glaucoma damage. In end-stage glaucoma, there can be lateral excavation of the optic nerve causing a bean potting shape of the optic cup. Retinal blood vessels may take on a "bayoneting appearance" (figure 4) as they disappear beneath the lip of scleral tissue and then reappear on the surface of the optic cup. This sign also has limited usefulness for the diagnosis of glaucoma because of other obvious characteristic nerve head signs consistent with glaucomatous optic neuropathy. However, observations of change over time in this sign can be clinically useful for identification of progressive disc damage.

Tony Litwak, OD, FAAO

References
1. Cioffi GA, Granstam E, Alm A. Ocular Circulation. In: Kaufman PL, Alm A, eds. Adler's Physiology of the Eye: Clinical Application. St. Louis: Mosby; 2003: 747-784.
2. Hayreh SS. Evaluation of optic nerve head circulation: review of the methods used. J Glaucoma. 1997;6:319-330.
3. Quigley HA, Hohman RM, Addicks EM, Green WR. Blood vessels of the glaucomatous optic disc in experimental primate and human eyes. Invest Ophthalmol Vis Sci. 1984;25:918-931.

PEARLS FROM THE EXPERTS

Some patients with MS and NTG have confirmed cupping, repeatable VF defects, and marked diffuse NFL loss by OCT. Does a connection exist between MS and NTG? Can MS produce pseudocupping, although it seems unlikely that it would cause NFL loss on OCT since neurons are not the primary target of the disease.

Claude Burgoyne MD answered:

The question of what kind of "cupping" occurs in a variety of optic neuropathies has been of interest to many and is currently a central focus of our laboratory's research. In the November 2007 issue of IOVS, our group published a paper that proposes to break all forms of clinical cupping into "prelaminar" and "laminar" components. The article suggests that there is a central confusion regarding the vocabulary of cupping, and this has led to a very confusing literature on this subject. Here are the first 3 paragraphs from that article. They introduce the concepts that I think are central to your question.

"Cupping" is a clinical term which is used to describe enlargement of the optic nerve head (ONH) cup in all forms of optic neuropathy. However, "cupping" is also used as a synonym for the pathophysiology of glaucomatous damage to the ONH neural and connective tissues. Because the clinical and pathophysiologic contexts for "cupping" are seldom clarified there is a large and often confusing literature regarding the presence, importance and meaning of "cupping" in a variety of optic neuropathies, including those of glaucoma, compressive orbital masses, ischemia, inflammation, and hereditary disorders.

We propose that in all optic neuropathies, regardless of the location and etiology of the primary insult to the visual system, the clinical phenomenon of "cupping", (herein referred to as clinical cupping) has two principal pathophysiologic components--"prelaminar thinning" and "laminar deformation". We define "prelaminar thinning" to be that portion of cup enlargement that results from thinning of the prelaminar tissues due to physical compression and/or loss of retinal ganglion cell (RGC) axons. We define "laminar deformation" to be that portion of cup enlargement that results from lamina cribrosa, scleral flange and peripapillary scleral connective tissue damage followed by permanent, intraocular pressure (IOP)-induced deformation.

We further propose that the following clinical and pathophysiologic concepts regarding prelaminar thinning and laminar deformation are true:
1) prelaminar thinning results in a clinically shallow form of cupping (being limited to the prelaminar tissues) that occurs in all forms of RGC axon loss and is therefore non-specific;
2) laminar deformation results in a clinically deeper form of cupping that occurs only in those optic neuropathies in which the ONH connective tissues have been damaged and have become susceptible to permanent, IOP-induced deformation (whether the IOP is normal or elevated.)

In this paper we proposed a strategy for 3D quantification of the "prelaminar" and "laminar" components of cupping within 3D histomorphometric reconstructions of the peripapillary sclera and ONH. We believe our strategy is important because we hope the next generation of 3D OCT reconstructions will provide the first opportunity to quantify these same two components of cupping clinically. This development will provide a quantitative vocabulary for clinical cupping that does not now currently exist. Our paper also suggests it will offer exciting new opportunities for early change detection in all OHT patients.

The optic neuropathy of MS involves damage to the RGC axon myelin within the orbital optic nerve which presumably leads to axonal degeneration and RGC loss. So, we should not at all be surprised to see a pre-laminar form of cupping in this setting (lamina nicely stretched across the scleral portion of the neural canal--not posteriorly deformed) with loss of the prelaminar neural tissues that manifests as central enlargement of the cup. We should also not be surprised to see peripapillary retinal NFL loss in this setting. However, I think it is most common for the ONH axons to be replaced by scar tissue, so it is most commonly the case that the nerve chiefly looks pale, without profound change in the ONH surface architecture.

In distinguishing the above clinical setting from a "glaucomatous" process, if the ONH is merely pale and the VF loss is diffuse--it is comfortable to say the optic neuropathy neither appears nor behaves in a way that is "glaucomatous".

If the disc looks "cupped" and the pattern of VF loss is compatible with glaucoma, then the problem is more difficult. To distinguish between glaucomatous "cupping" and that due to other optic neuropathies the following questions should be answered:

1) Is the field loss truly glaucomatous? I happen to believe that IOP-related damage to the ONH can lead to more than the classic forms of glaucomatous field loss, but for the purposes of this exercise, lets ask for it to be classically arcuate or perifoveal in nature.

2) Do these patients have a "laminar" or "deep" or "glaucomatous" form of cupping? By this I mean is the lamina bowed back, out of the plane of the sclera? Are there focal pits or notches in the lamina? Is there true excavation of the rim tissue (and vessels) beneath the clinically visible optic disc margin?

3) Has either the clinical cupping or visual field change progressed under your care? Or, do you have very good evidence of progression from others?

To finally answer your question--can MS cause NTG?

1) Because MS causes an optic neuropathy, we should expect it to cause clinical cupping (or not) and peripapillary NFL dropout and visual field loss.

2) If we ask if it can cause an optic neuropathy that looks and behaves in a glaucomatous fashion - my answer is that it would not surprise me if this were true, but for me this requires two things--a "laminar" component of cupping and a "glaucomatous" pattern of field loss. It is more likely if the "laminar" deformation could be shown to have progressed.

3) If you truly have a laminar component of cupping that is caused by MS then here is what must happen for the lamina to permanently bow back and deform. Some aspect of the insult must weaken the previously normal lamina, making it susceptible to damage and failure at "normal" levels of IOP. So here is where many people will get uncomfortable--if the lamina is truly posteriorly deformed, the only way this can have occurred is that the current level of IOP exceeds the strength of the (weakened) lamina, and it begins to fail (yield - deform - remodel - stabilize or pull apart).

The point of number 3 is that once you have evidence that the lamina has actively deformed, IOP must be contributing to the neuropathy. The lamina does not move backward, and the tissues do not pull apart on their own, and in all of our work to date, there is no retrolaminar scar tissue pulling it backward (though it is possible that is part of the mechanism in MS--but I really doubt this). Thus, the patient has NTG, it’s just that in these patients, you have a primary non-IOP-related insult that has made the ONH susceptible to normal levels of IOP. Once this has happened, then we should expect to see the "orbital" pattern of ONH loss of MS overlaid with the "ONH" pattern of field loss that is classic for glaucoma.

We could ask the question for how MS might primarily weaken the lamina? Basically my guess would be that the initial orbital MS insults occur close enough to the lamina that it is secondarily damaged by associated inflammation. I have no idea whether this can be true or if the lamina can be weakened as a secondary response to MS induced axon loss further back in the orbit.

We will always have a hard time discovering the role of IOP in a variety of optic neuropathies that appear to occur at "normal" levels of IOP including aging. IOP telemetry will help us once available in that it will identify patients who exceed normal ranges of telemetrically characterized IOP. But until proven otherwise the clinical characterization of active ONH connective tissue deformation assures that IOP is involved in the neuropathy (either primarily or secondarily).

Claude Burgoyne, MD is Senior Scientist and Van Buskirk Chair in Ophthalmic Research; Research Director, Optic Nerve Head Research Laboratory at Devers Eye Institute, Portland, OR

Reference
1. Yang H, Downs JC, Bellezza A, Thompson H, Burgoyne CF.3-D histomorphometry of the normal and early glaucomatous monkey optic nerve head: prelaminar neural tissues and cupping. Invest Ophthalmol Vis Sci. 2007 Nov;48(11):5068-84.

CLINICAL QUESTIONS AND ANSWERS

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.

Question:If you had an 80 year old patient with recently diagnosed atrial fibrillation and arrhythmia of the heart would you leave this patient on a topical beta-blocker or would you discontinue that drug and switch to a different class, like a prostaglandin?

Douglas Anderson, MD, answers: It is a decision that should be made by the cardiologist managing the atrial fibrillation. He would be in the best position to know whether beta-blockers might be potentially helpful or harmful for the patient. It could be either way, depending on the details of the fibrillation and any atrio-ventricular heart block that might be present. One clue would be that if the cardiologist prescribed systemic beta blocker to help control the problem, then it would not be necessary to stop topical beta blocker.

Bruce Onofrey, OD, RPh, answers: In general it is not a good idea to add a topical beta blocker to a patient already using a systemic beta blocker. There is less efficacy in IOP lowering effect and side-effects can be more severe and occur more quickly.

It is true that the treatment of certain cardiac arrhythmias, including atrial fibrillation, does potentially include the use of a beta blocker. However, the proper management must include a careful titration (adjusted) oral dose of the beta-blocker. The additional use of a topical beta-blocker provides a rapidly absorbed, intermittent amount of drug that can easily affect the proper dose of an administered oral agent in an unpredictable manner. This can result in episodes of bradycardia and reduced cardiac output. This can result in unpredictable hypotensive events, ischemia and potential end organ damage (ischemic). The internist/cardiologist should be free to administer a predictable, stable dose of medication. Furthermore, the treatment may also include the use of digoxin and/or a calcium channel blocker. Both drugs increase the risk of bradycardia, particularly in combination with a beta-blocker. The use of a topical beta blocker in this situation can dramatically exacerbate the side-effects of these agents.

 

 

POLL RESULTS FROM PREVIOUS ISSUE

Clinical trials and wisdom of experience have supported the development and use of treatment goals. Target intraocular pressure is the level of intraocular pressure where the progression of glaucomatous damage is believed to be arrested or sufficiently slowed to be clinically insignificant relative to the patient’s life expectancy. This target level may need to be revised during the course of follow-up. Several factors are considered in the selection of the target IOP. These include but are not limited to the level of intraocular pressure, extent of damage, rapidity of onset of damage if known, as well as other risk factors. While not an exact science, it is our educated best estimate of the level of intraocular that is most likely to result in preservation of vision and quality of life.

The results of our most recent poll have been tabulated. Ninety per cent of respondents selected a target IOP for their glaucoma patients although not all record this routinely. Fifty per cent of respondents reported always selecting a target intraocular pressure and recording this in the patient’s chart.

When evaluating the ocular hypertensive patient a majority of respondents make an assessment of risk. Eighteen percent reported basing their decision on intraocular pressure and central corneal thickness. Twenty-eight percent use a risk calculator to assess risk and as an aid in treatment decisions whereas 54% reported making their own assessment of risk on which they base their therapeutic decisions. Interestingly, no one based their decision to treat on intraocular pressure alone.

Thanks to all who participated. Please take the time to respond to our future polls.

John McSoley, OD

MEETING NEWS

Annual OGS Meeting Focuses on the Future

Having had the good luck to begin its existence at a time of explosive growth in the understanding of glaucoma, the Optometric Glaucoma Society (OGS) is now setting its sights on the future. How the last decade of fertile research in diagnosis, therapy and patient management will drive standards of care in the coming years was the primary theme of yesterday’s annual OGS meeting. The 100 or so attendees and members of the six-year-old organization also heard up-to-the-minute reports on vascular aspects of glaucoma and aqueous outflow issues.

Blood flow took up the first morning session. After opening remarks by President Murray Fingeret, OD, FAAO, and Program Chairman John Flanagan, PhD, MCOptom, FAAO, the audience heard from Ezell Fellowship scholar and this year’s OGS travel award recipient, Subha Venkataraman, BSOptom, FAAO, of the University of Waterloo College of Optometry, who reviewed what is known about blood flow to the lamina cribrosa and its implications in glaucoma development.

Dr. Venkataraman then presented a study that assessed retinal arteriolar and capillary vascular reactivity response to hypercapnia in patients with untreated POAG and others with progressive POAG. The study found vascular reactivity response of retinal arterioles and capillaries to hypercapnia reduced in both patients with progressive and untreated POAG when compared with controls. Additionally, treatment with Trusopt (dorzolamide, Merck) improved vascular reactivity in patients with untreated POAG.

Attendees then heard from Douglas R. Anderson, MD, professor of ophthalmology and Douglas Anderson Chair in Ophthalmology at the Bascom Palmer Eye Institute, University of Miami School of Medicine. A leading thinker in the study of how disruptions in autoregulation may relate to glaucoma, Dr. Anderson explained the mechanisms of capillary blood flow regulation in the lamina cribrosa. Researchers believe inadequate blood flow could put the optic nerve at risk. Even when overall systemic conditions are healthy, characteristics of the tiny capillaries in the optic nerve may cause damage, said Dr. Anderson, explaining how pericytes--the contractile mural cells in capillaries--could play a role in determining risk for disease.

Problems with blood flow remain the prime suspect in normal-tension glaucoma’s (NTG) mysterious etiology, but other puzzles surround NTG as well, which was the topic of a talk by David S. Greenfield, MD, of the Bascom Palmer Eye Institute. Evidence suggests that occult intracranial mass lesions may simulate NTG. Also, some believe thin corneas artificially lower IOP readings, confusing the clinician as to whether NTG is present. Certain studies suggest a relationship between NTG and asymmetric visual fields and IOP, yet other findings contradict this, Dr. Greenfield noted.

The second morning session dealt with assessing structure and function. Indiana University Professor of Optometry William H. Swanson, PhD, FAAO, presented research on novel ways to relate functional deficits in visual field tests to underlying cellular pathophysiology.

Michael J. Sinai, PhD, senior director of clinical affairs at Optovue, Inc., followed with a talk on the future of structure assessment. Rapid technological advances continue to occur in the three established imaging devices: confocal scanning laser ophthalmology (HRT), scanning laser polarimetry (GDx), and optical coherence tomography (OCT). After summarizing these advances, Dr. Sinai entertained the possibility of an all-in-one imaging device that could assess the anterior chamber, blood flow, and structure and function all at once.

As people age, uveoscleral outflow of aqueous humor slows, according to a presentation by Paul L. Kaufman, MD, chairman of the Ophthalmology Department at the University of Wisconsin. This may be a contributing factor to glaucoma, and thus, as life expectancy rises, glaucoma incidence could rise with it. Dr. Kaufman speculated that replacing lost trabecular meshwork cells with stem cells may be possible in the future.

In the next speech, Thomas F. Freddo, OD, PhD, FAAO, director of the School of Optometry at the University of Waterloo, unveiled data indicating that elevated IOP leads to progressive herniations of the inner wall of Schlemm’s canal and the juxtacanalicular tissue (JCT). This fact may explain elevated outflow resistance in POAG, he said.

After lunch, Dr. Greenfield delivered the Presidential Lecture, in which he spoke of recent advances in the three mainstay imaging technologies: HRT--the use of discriminant functions and/or regression analyses to differentiate normal optic discs from borderline abnormal ones; GDx--a modification of variable corneal compensation designed to reduce a newly discovered artifact caused by patterns of peripapillary birefringence; and OCT--hard evidence that OCT can detect RNFL changes.

Next, Richard Parrish, MD, and Dr. Kaufman, of the University of Wisconsin, gave back-to-back presentations on the topic of medical therapy, entitled, "Where Have We Been? Where Are We Going?" The doctors provided a comprehensive overview of the various mechanisms by which ganglion cell death may be circumvented, including increasing trabecular and uveoscleral outflow, neuroprotection, and gene therapy. They also previewed possible future advances, such as continuous monitoring of IOP using micro- and nano-sensors and watching ganglion cells die in vivo.

The final speaker, Steven J. Gedde, MD, of the Bascom Palmer Eye Institute, addressed surgical options. He discussed the trend toward lower doses of mitomycin C in trabeculectomies and the growing popularity of selective laser trabeculoplasty (SLT), which demonstrates similar efficacy to argon laser trabeculoplasty (ALT) but theoretically could offer enhanced repeatability. He also reviewed the decade-long decline in trabeculectomy surgeries in favor of new and improved drainage implant options.

Frank Celia
Mr. Celia is a freelance medical writer based in the Philadelphia area who frequently writes about eye care.

The 2007 and 2008 OGS Board of Directors.

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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 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

 

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