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Highlights of the Glaucoma Research Society meeting

February 20-23, 2008, Queenstown, New Zealand

Introduction

Anders Heijl

The biannual meeting of the Glaucoma Research Society meeting was well attended, and as usual most of the time was used for discussions rather than presentations. The sessions were very productive and are summarized in bullet form below. New, modern bylaws were adopted. The board was expanded with two new positions: the chairmen of the new Programme Committee and Membership and Nominating Committee. Many new members were elected to the board. Heijl stepped down as President and Quigley was elected new President. The next meeting will be held in Kyoto, Japan. Meeting participants also enjoyed a superb social programme with a touch of Maori culture - see the enclosed photographs of a Maori Chief and Drs Baerveldt, leBlanc and Molteno learning Maori dancing.

Screening for glaucoma - what do we know and what studies do we need?

Chairpersons: M. Araie and P. Foster

• The case for population screening for glaucoma alone is controversial. A stronger case can be made for screening for visual dysfunction from all causes.
• Opportunistic glaucoma case-finding in ophthalmic and optometric practice should be actively promoted.
• No single test offers sufficiently high discriminative performance in the community setting where early coexistent ophthalmic and neurological pathology is relatively widespread.
• Combined psychophysical and imaging tests do offer good sensitivity and specificity for detection of glaucoma.

Diagnosis of glaucoma - when is early diagnosis important? What is the standard in the developed world?"

Chairpersons: L. Zangwill and T. Garway-Heath

• Zeyen summarized the epidemiological evidence supporting and disputing the idea that a glaucoma damaged nerve is more likely to progress.
• Burgoyne outlined the difficulties of studying optic nerve head susceptibility to glaucomatous damage in experimental models by emphasizing the need to control for age and deliver similar levels of IOP insult (magnitude and duration) and blood flow (optic nerve head perfusion pressure) to both groups of eyes in which one is hypothesized to be more or less susceptible than the other. To do so requires the ability to constantly monitor and eventually control both variables. These capabilities currently do not exist but are the goal of several research groups.

In a point-counterpoint debate, Budenz outlined the importance of detecting the earliest signs of structural damage to diagnose glaucoma stating that:

• Early functional damage is too late;
• Early glaucoma is easier to treat;
• It is easier to prevent blindness if glaucoma is detected early;
• And it costs less to individual and society.
• Gandolfi stressed the lack of evidence that diagnosing and treating a pre-perimetric glaucoma does make a difference in terms of long term incidence of glaucoma-related blindness. In fact, reducing the number of underdiagnosed unquestionable glaucomas seems to be a more committing and compelling public need.

In a point-counterpoint debate, the use of tests of selective visual function to identify the earliest signs of functional damage was debated.

• Both FDT and SWAP have been shown in longitudinal studies to detect early glaucoma defects sooner than standard white-on-white testing, and those defects are more reproducible on repeat testing.
• Heijl countered: using accepted methods for systematic literature reviews there is no evidence that SWAP or FDT detects glaucomatous field loss earlier than SAP. SAP offer advantages: long experience, good methods for computer-as-sisted analysis, mature technology, and large dynamic range.

Making a diagnosis

• Garway Heath summed up by showing that, in making a diagnosis, it is possible to use likelihood ratios for given test values to identify a probability for the presence of glaucoma, and in this way two or three test results (say, IOP, perimetry and imaging) can be combined to calculate the probability for glaucoma. As a research community, we need to decide on the severity of disease we feel we all should be able to identify (for instance, severity equivalent to an MD of -2dB, -3dB or -5dB) and the level of probability at which we should make the diagnosis.

Judging progression of glaucoma - Is it necessary to follow both structure and function or is one enough?

Chairpersons: B. Chauhan and A. Heijl

• Heijl and Chauhan presented contrasting viewpoints on the tools that should be used to monitor glaucoma patients once glaucoma damage was confirmed. Heijl argued that perimetry alone was sufficient while Chauhan felt that monitoring the op-tic disc was also valuable. The discussion focused on whether one measure can be used as a surrogate for the other and how frequently clinical decisions were made on the basis of changes in the visual field versus the optic disc.
• EMGT results suggest that visual field testing is much superi-or to inspection of optic disc photographs in detecting glaucoma progression in eyes that have field loss. Fields show visual function - we know the margin to visual disability and loss of QoL. Structural change, on the other hand, cannot be immediately translated to visual function/disability. Repeated perimetry can tell us rate-of-progression and thus help assess the risk for functional disability. Studies show that in clinical practice visual field testing often is not performed often enough, and disc or RNFL imaging or photography should not be performed at the expense of perimetry.
• Nicolela discussed how much change in the optic disc and visual field is enough to warrant changes in management. He stressed the differences between deciding on visual field and optic disc end points for clinical trials versus clinically significant changes on individual patients. Different criteria for optic disc and visu-al field progression were reviewed and clinical cases were presented in which other relevant patient information has to be taken into consideration before new management decisions are reached.
• Sherwood presented ideas on encouraging ophthalmologists that measuring visual field and optic disc progression is important. He discussed obstacles currently present, including issues of training and resources. For the developed societies:
  • time consuming to do accurately;
  • cost of equipment, training - doctor and staff;
  • accuracy and variability of measurements;
  • mental upset of patient if progression detected - no one likes to be the 'bearer of bad news';
  • side effects of new therapy to address progression.

  and for the less-developed societies:

  • limited resources to buy and service equipment;
  • large patient numbers;
  • low Dr/patient ratio;
  • uncertain follow-up;
  • ocular co-morbidities confounding testing;
  • level of training.

Computerized systems are helpful adjuncts but a good careful exam comparing the disc to a previous stereoscopic photograph is still the gold standard for early disease (although time consuming) and monitoring computerized fields is most helpful for moderate to advanced disease and Goldmann fields are generally best for fol-lowing for progression in very advanced glaucoma.

The GRS membership might:

1. Give leadership by setting community standards;
2. Stimulate research on how best to detect progression and defining cost-effective care for different societies;
3. Promote education to local ophthalmologists and exchanging ideas globally;
4. Raise political awareness of glaucoma needs.

Medical treatment of glaucoma - Resource management in the developed and underdeveloped world

Chairpersons: A. Tuulonen and R. Thomas

• To improve the cost efficiency of present health care expenditures for glaucoma, we should work to improve the worldwide performance of glaucoma care and allocation of resources. In addition to individual points of view (patients), we need to consider also societal points of view (populations).
• We need team work to attack the problem, with other health care professionals (including optometrists) and other societies both within glaucoma and other fields in ophthalmology (e.g., AMD and diabetic retinopathy) as well as experts within related disciplines (e.g., health economics, epidemiology).
• To start with, for proper decision making we need to produce high-quality, evidence-based data which currently is practical-ly missing. In order to define what we want to accomplish, we need to know the future need for services. In addition, we have to gain better understanding of the magnitude of glaucoma-induced visual disability and allocation of resources. For example, there are examples in various places around the world in which there is over-testing and others where there is under-testing for glaucoma. Likewise, over- and undertreatment and over-and under spending are found within and across regions.
• There is a strong worldwide incentive to improve the current knowledge and teaching of residents, general ophthalmologists and all health care professionals working within the field of glaucoma. We need to define levels of care (from minimum to the highest level of care) and to consider division and delegation of tasks between these levels among different professionals.
• We need to gather data on the impact of technology on costs and outcomes, especially visual disability rates, and define its role in glaucoma care (e.g., when delegating tasks).

Basic science research in glaucom

Chairpersons: R. Susanna and C. Burgoyne

Highlights of the basic science session included:

• Gupta summarized the current knowledge on central nervous system involvement in the optic neuropathy of glaucoma: Lateral geniculate nucleus atrophy in glaucoma patients with advanced disease can be detected in vivo by 1.5 Tesla MRI.
• Chauhan (discussed by Wax) presented an update how optic nerve head astrocytes may be involved in glaucomatous optic neuropathy. One of the mechanisms discussed was the role of endothelin and endothelin receptor mediated actions on astrocytes causing a disruption in the neuron-glia relationship leading to eventual axonal loss.
• Burgoyne (discussed by Jonas) presented a report of the performance of Spectralis high resolution 3D OCT imaging of the optic nerve head in early experimental glaucoma, which suggested that current, clinical, high-resolution spectral domain OCT imaging is capable of expanding beyond peripapillary retinal NFL thickness measurements to detect alterations in lamina cribrosa and peripapillary scleral position very early in the neuropathy.
• Alward explained the new genetic findings in a 2007-report in Science by Thorleifsson et al. in pseudoexfoliation (discussed by Mackey) that showed that sequence variations in the gene LOXL1 accounted for the increased risk of exfoliation in Iceland. This has been confirmed in populations around the world. While this is a very important finding, it is important to recognize that the vast majority of people with LOXL1 sequence variations do not develop exfoliation (85% of control individuals had this variation).

Surgical treatment of glaucoma - are we doing too much or too little?

Chairpersons: D. Minckler and F. Grehn

• New surgical procedures such as the ExPRESS shunt, canaloplasty (iScience), Trabectome (NeoMedix), and the trans-trabecuar shunt (Glaukos), all of which claim to normalize IOP with fewer complications, and also anti-VEGF therapy are innovative and clinically exciting. However, there is as yet no or only minimal published information about these procedures, none of which have been rigorously tested via prospective randomized clinical trials.