REACHING CONSENSUS:
LESSONS FROM THE
EUROPEAN GLAUCOMA SOCIETY "TERMINOLOGY AND GUIDELINES" PROJECT

Professor Carlo E. Traverso

Clinica Oculistica
Di.N.O.G. University of Genova, Italy

The European Glaucoma Society “Terminology and Guidelines” prioject is an attempt to rationalize treatment for this disease. The first edition of the EGS guidelines was published in 1998.

In general, the guidelines are intended to support the general ophthalmologist in managing glaucoma patients. They’re also designed to offer diagnostic and treatment protocols but leave to the physician the variations for care individualized to the patient and socioeconomic milieu.

The second edition, released in 2003, builds on the work of the previous one. Glaucoma guidelines also existed from the American Academy of Ophthalmology (in the form of preferred practice patterns) and the Royal College of Ophthalmology. These guidelines were based on expert panels amplified by other contributions but with limited lists of references.

Following there is a brief overview of the European Glaucoma Society project, the results, and the evidence that now affirms various ideas introduced during its development.

The first steps

The first step in developing our guidelines was to identify the terminology and disease definitions. The scope of terminology, classifications, and definitions, however, varies based on whether you’re using them for a prospective clinical trial, health planning, coding for third-party payers, review of existing clinical data, or classifying patients to obtain an individualized treatment. The level of detail and differentiation might not be the same for all those settings.

To reach consensus, the classification and disease definitions must be acceptable to most ophthalmologists on both theoretical and practical grounds. Ophthalmologists don’t like arbitrary terms, but without some arbitrary terms, one would never get through this type of effort.

The next steps were to provide management options and suggest the evaluation of the outcome. Where no scientific evidence is present, expert opinion can be a substitute. In 1997 not many randomized controlled trials in glaucoma could justify IOP-lowering treatment.

Furthermore, guidelines had to be acceptable both in content and format. Large tomes are not popular for rapid access and consultation, even though they could be accurate. Guidelines must be flexible, but still clearly guide the practitioner. They must have understandable evidence and a science-based background. They must have verifiable, reputable, peer-recognized sources and financial support is needed to produce them. They must be dated, gather feedback on the impact, and finally they should be periodically reviewed.

Distribution to the practitioners

The draft was produced by the European Glaucoma Society’s Education and Research Committee. The Executive Committee worked on the final edition; many experts contributed anonymous reviews, comments, and suggestions. The whole process was sponsored by educational grants from pharmaceutical firms.

The resulting booklet, “1998 Terminology and Guidelines for Glaucoma by European Glaucoma Society,” has been printed in seven languages with over 35,000 copies distributed. On the Web, the work is downloadable for a nominal fee from www.eugs.org.

Distributed through and outside Europe, the guidelines have also been used in proceedings by the FDA. They’ve also been employed in trials to defend ophthalmologists in Europe.

Points of interest

The guidelines offer this mission statement: Preservation of visual function adequate to the individual needs with minimal or no side effects, for the expected lifetime of the patient, without any disruption of his/her normal activities at a sustainable cost.

The EGS guidelines stressed visual field staging and rate of decay; evidence now supports their importance.They emphasized disc photos and suggested that sophisticated imaging systems were still under development.

On IOP measurements and cornea, the guidelines featured one full page on IOP measurement alterations from cornea thickness and curvature. They suggested gonioscopy as a routine procedure in any adult examination; this was likely the first time such a strong position on gonioscopy was taken.

On the IOP lowering efficacy, it was stated that when you start a patient on monotherapy, if you reach his/her target IOP, the same drug is to be continued and the endpoints verified. If you don’t reach the target but the IOP lowering effect is still relevant, a second drug can be added.

If this second drug doesn’t reach the target, a switch to a different compound rather than adding one is suggested. If your first drug doesn’t have any substantial effect on IOP, the monotherapy should be changed.

Target IOP

The target IOP definition was: the mean IOP obtained with treatment that prevents further glaucomatous damage. Although this definition sounds reasonable, it is arbitrary.

You can calculate target IOP from initial pressure, life expectancy, and stage of disease. If the initial pressure is high, life expectancy short, and the stage of disease is early, consider a higher target IOP. If findings are the opposite, consider a lower target.

In clinical practice, unfortunately, many times the findings go in different directions, complicating decisions. The guidelines advocated individualizing treatment.

The guidelines provided a diagram for target IOP. This featured a cut-off arbitrary level of 21 mm Hg – that is, no patient with unquestionable glaucomatous disease should have a IOP level over 21 mm Hg. (See Target IOP)

The guidelines proposed, then arbitrarily, that patients with a confirmed defect should have at least a 20% decrease from baseline, but always stay below 21 mm Hg. Patients with moderate disease should have at least at least a 30% decrease, and patients with advanced disease at least a 40% decrease.

Some evidence

Today, evidence suggests that some of those arbitrary statements might be valid. Among others, the Hattenaver study (Hattenaver, Johnson et al.; Ophthalmology, 1998) found that the risk of legal blindness 20 years after diagnosis with glaucoma is staggering: 54% in one eye, 22% in both eyes (with other non-glaucoma causes not excluded). The most important risk factor for blindness was severity of glaucoma damage at diagnosis. In the same study, in the sample of patients that had filtration surgery, the probability of legal blindness within 5 years was 22% and at 15 years was 60%. The major risk factor was advanced field loss with scotomas in both hemimeridians.

Recently, results from the Early Manifest Glaucoma Trial (EMGT) were released. They show that lowering the IOP had a protective effect independently from age, exfoliation, baseline IOP, type of glaucoma, and stage. Each 1 mm of IOP lowering accounted for a 10% difference in progression rate.

For the first time, the EMGT proved through a randomized trial with an untreated control group that reducing IOP slows disease progression. The treatment had positive effects on all groups of patients.

Disease progression rates, however, varied widely between individuals, which supports individualizing treatment and follow-up. Clinicians should probably follow patients more closely with visual function tests during the first few years after patients are diagnosed than is commonly done. The EMGT results don’t imply that all glaucoma patients should receive maximum treatment. Some patients don’t show any disease progression even after several years without treatment. Patients at lower risk for serious progression could be reasonably left untreated and followed closely as long as they remained unchanged. Also, with the definitive proof that treatment has positive effects, clinicians should reconsider population screening for patients with undetected glaucoma. The Advanced Glaucoma Intervention Study (AGIS) concluded that lower IOP was associated with reduced progression of visual field defects, supporting evidence of a protective role for low IOP against visual field deterioration. But no stratification for stage of disease was performed, so more aggressive treatment to all wasn’t justified. What’s more, patients who received surgery had a high rate of increased risk of cataract.

Finally, the Collaborative Normal-Tension Glaucoma Study Group found that significantly lowering IOP improved the course of visual field progression of patients with glaucomatous optic nerve damage and field loss with normal IOP (normal-tension glaucoma) but only after adjusting for cataract. Of surgically treated patients, 50% developed cataract during the follow-up as opposed to 25% of those medically treated. Note that the EMGT also showed an increase in nuclear opacities, which is significant when compared to the untreated eyes for patients treated only with medications. With these study results in mind, the statement “Individualize the target IOP according to stage and risk factors” is now evidence-based.

Observations in the last few years in clinical trials justify the then-arbitrary statements in the guidelines regarding the need for visual field staging and assessing the rate of decay. No evidence has yet surfaced to make sophisticated imaging techniques clinically more relevant than disc photos.

IOP measurements and cornea made it to the main stage after the Ocular Hypertension Treatment Study. In the first edition, the EGS guidelines offered one full-page diagram on the IOP measurement effects of various corneal conditions. No recent publication supports or doesn’t support gonioscopy, but it is likely to be the most under-performed diagnostic technique for glaucoma patients.

Consider individualized target IOP as well as the true IOP lowering efficacy of each drug given to the patient, with the final goal of maintaining or improving the patient’s quality of life. Finally, independent prospective randomized trials confirm that the side effects of filtration surgery may affect aversely vision and quality of life. The second edition of the EGS Terminology and Guidelines for Glaucoma is now released. Only time will assess if it will impact usefully the practical management of patients.