8th Congress of the EuropeanGlaucoma Society

Berlin, Germany, 1st – 6th June 2008

Industries SponsoredSymposia

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SANTEN SPONSORED SYMPOSIUM IN SEARCH OF IMPROVEDGLAUCOMA THERAPY

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UNMET NEEDS IN THE TREATMENT OF GLAUCOMARELATED TO ADHERENCE, TOLERABILITY ANDCONCOMITANT DRY EYEJ. Thygesen, Department of Ophthalmology, Rigshospitalet University ofCopenhagen, Denmark

Background: Adherence to long-term topical treatment ofglaucoma can be less than optimal, which may decrease theefficacy of the treatment. This presentation summarises theunmet needs in the current topical treatment of glaucoma re-lated to adherence, tolerability and concomitant dry eye anddiscusses the expectations for future therapies.Results: Glaucoma is a life long conditions and its manage-ment is multifactorial. However, adherence to topical glauco-ma treatment can be less than optimal. Forgetfulness andtopical side effects have been identified as important reasonsfor non-adherence. Topical side effects decrease the quality oflife of the patient, which impacts on compliance.Dry eye and glaucoma are often concomitant diseases.Therefore, it is advisable to consider the management ofboth diseases together for the optimal care for these pa-tients. The benefits of preservative free medications are wellacknowledged for the treatment of dry eye. Preservativefree preparations may also have benefits for the long termtreatment of glaucoma patients, especially those withdry/sensitive eyes.Conclusions: Adherence remains a key issue in the manage-ment of glaucoma. Glaucoma and dry eye as concomitant dis-eases present specific challenges for the optimal care of thepatient.

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OCULAR SURFACE AND GLAUCOMAC. Baudouin Department of Ophthalmology III, Quinze-Vingts NationalOphthalmology Hospital, Paris, France

Background: The use of antiglaucoma medications is oftenassociated with ocular adverse reactions. These undesirableeffects may lead to treatment discontinuation and reducedquality of life in patients with glaucoma. The presentationsummarizes the current data regarding the impact of glauco-ma treatment on the ocular surface.Results: Antiglaucoma medications often contain benzalkoni-um chloride (BAK) as preservative. Animal studies and in vit-ro and in vivo experiments have demonstrated various dosedependant adverse effects of BAK. Clinical studies have alsoshown an increased incidence of adverse events with BAK andhave demonstrated that withdrawal of the preservative re-duces these effects.Conclusions: Collectively, these data suggest that preserva-tive-free antiglaucoma treatments have clinically relevantbenefits for patients.

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UPDATE ON PROSTAGLANDINS USED FOR GLAUCOMATREATMENTJ. StjernschantzDepartment of Neuroscience, Uppsala University, Uppsala,Sweden

Background: Prostaglandins (PGs) are widely used as intraoc-ular pressure (IOP) reducing agents for glaucoma treatment.The purpose of this presentation is to give a brief overview ofthe PGs on the market, or in late development stage for glau-coma treatment. Results: Three PGF2α analogues are widely available in variousparts of the world, namely latanoprost (Xalatan®), travoprost(Travatan®) and bimatoprost (Lumigan®). A fourth analogue,tafluprost, is expected to receive regulatory approval in Europesoon. PGF2α analogues are highly potent and selective FPprostanoid receptor agonists. The highest potency appears to beexerted by tafluprost, an interesting new bi-fluorinated PGF2α

analogue. All the above PGs appear to reduce IOP at least partlyby enhancing the uveoscleral outflow of aqueous humour. Theanalogues are administered once daily, and exert similar IOP re-ducing capacity in open-angle glaucoma. The main side-effectsof the PGs comprise conjunctival hyperemia, an irreversible orlonglasting hyperpigmentation of the iris in predisposed pa-tients, and a reversible effect on the eyelashes/eyelids. Conclusions: The PGs overall are effective and reasonablywell tolerated glaucoma drugs with few systemic side-effects.Their use in aphakic or pseudophakic compromised eyes re-mains somewhat controversial.

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OVERVIEW OF THE PROFILE OF TAFLUPROSTL. PillunatUniversity Eye Hospital, Dresden, Germany

Background: Tafluprost (Taflotan®) is a new potent PGF2_analogue for the treatment of glaucoma. Tafluprost is expect-ed to be the first prostaglandin available as a preservativefree form. This presentation summarizes the pre-clinical andclinical profile of tafluprost.Results: Tafluprost has a favourable pharmacological profilewith a high binding affinity for the human FP receptor. It low-ers IOP by increasing the uveoscleral outflow. Tafluprost hadpotent IOP lowering effect in normotensive and ocular hyper-tensive monkeys, unsurpassed by latanoprost. In healthy vol-unteers tafluprost was generally well tolerated and safe andeffective in IOP lowering. Based on dose finding studies 15micrograms/ml was chosen as the final concentration. Thisconcentration had a comparable IOP lowering effect to la-tanoprost in P-II studies. Effective IOP lowering was con-firmed in pivotal clinical studies. All adverse effects reportedwere well known for the prostaglandin class. The most fre-quently reported adverse event was hyperaemia. It was re-ported in 13% of patients. A preservative free form oftafluprost showed equal efficacy and pharmacokinetics to thepreserved form. Preservative free tafluprost has low or nopro-apoptotic, pronecrotic or pro-oxidative effects in vitrocompared to preservative-containing prostaglandin formula-tions latanoprost, travoprost and bimatoprost.Conclusions: Tafluprost (Taflotan®) is a new effective IOP re-ducing agent that is generally safe and well tolerated.Tafluprost is the first prostaglandin eye drop without preser-vative. This is expected to present a clinical advantage espe-cially for glaucoma patients with dry/sensitive eyes.

MSDSPONSORED SYMPOSIUM COMPREHENSIVE CARE FOR THEGLAUCOMA PATIENT

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CHAIRMAN’S WELCOME & INTRODUCTION:COMPREHENSIVE GLAUCOMA MANAGEMENTR.A HitchingsMoorfields Eye Hospital, London, United Kingdom

Dear Friends and Colleagues, It gives me great pleasure to welcome you this afternoon tothis symposium. The overall title of the symposium is‘Comprehensive care for the glaucoma patient’ and it hasbeen sponsored by Merck. Ophthalmologists by their calling and personality tend to havea very focused view on their patients. The cynic would saythat such focus means that they rarely get to look outside theeye when discussing a particular patient’s problem with them.Clearly this is a fault and it behoves us clinicians to rememberthat behind every ophthalmological problem there is a patientwith anxieties, cares, worries as well as a varying number ofco-morbidities that could influence any management planthat we should wish to take. As many of the chronic ophthal-mological problems, and glaucoma is one such, tend to occurin the elderly then the chances of such extra ocular co-mor-bidity rises considerably. This symposium is designed to ad-dress these issues. Firstly we need to look at the major riskfactor for glaucoma, pressure and Dr Konstas will be address-ing the subject of ‘out of office’ intraocular pressure. ThenClive Migdal will look at issues that lie beyond intraocularpressure and what may affect our assessment for any one in-dividual. Josef Flammer will address the issue of ischemia inthe glaucoma patient, stressing again the merits of ‘bloodflow’ and its alterations. This symposium concludes with a question and answer ses-sion giving the opportunity for you in the audience to discusswith the speakers particular concepts and concerns. I hope that this symposium succeeds in ensuring that whenwe treat diseases of the eye we treat the patient as a whole.

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THE IMPORTANCE OF THE OUT-OF-OFFICE IOPA.G.P. KonstasGlaucoma Unit, 1st University Dept of Ophthalmology, AHEPAHospital, Thessaloniki, Greece

Glaucoma is a 24-hour disease and worse 24-hour character-istics are a significant risk factor for progression. Currentglaucoma practice involves single IOP readings at each visitowing to time, convenience and cost considerations. A singleIOP measurement however, does not reflect the dynamicequilibrium of IOP during the 24-hour cycle nor reflects thequality or 24-hour IOP control obtained with therapy. A 24-hour IOP evaluation can provide a more complete picture ofthe real efficacy of all glaucoma treatment options. Resultsfrom a recent, prospective, crossover, comparative 24-hourstudy evaluating glaucoma patients insufficiently controlledon latanoprost monotherapy, suggest that both the dorzo-lamide/timolol fixed combination (DTFC) dosed twice dailyand the latanoprost/timolol fixed combination (LTFC) given inthe evening obtain significantly better 24-hour IOP controlthan latanoprost monotherapy. No statistical differences

were found between DTFC (19.9 ± 3.2 mmHg) and LTFC(19.5 ± 3.1 mmHg) in a pairwise comparison (p >0.39). Theaddition of DTFC to latanoprost provided the lowest mean24-hour IOP (16.5 ± 2.8 mmHg) versus latanoprostmonotherapy (p < 0.0001) and the lowest IOP at each indi-vidual time point (p < 0.0032). This study showed that DT-FC, LTFC and the addition of DTFC to latanoprost significantlydecrease 24-hour IOP compared to latanoprost alone, butthe latter therapy regime obtains the greatest 24-hour IOPreduction.

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WHAT LIES BEYOND IOP?C. MigdalWestern Eye Hospital, London, United Kingdom

Progress has been considerable over the past decades in ourunderstanding of the pathogenesis and natural history ofglaucoma. We now know more about the relationship be-tween IOP and visual field loss, as well as the risks for pro-gression in glaucoma. We know that IOP is the most impor-tant risk factor in this disease, and that raised IOP causesdamage. But some patients still have damage at low IOPs. Glaucoma is not just a disease of IOP. Our further under-standing of factors associated with neuronal cell death (bothprimary and secondary causes) encourage the developmentof future therapies, other than IOP-lowering, which may slowor prevent death of RGC axons and maintain function. Riskfactors contributing to RGC death, and factors promoting RGCsurvival will be discussed.We now have a large and effective range of therapies. Weneed to use them appropriately. However, certain high-riskpatients or non-responders to IOP-lowering therapy may needsomething more. There may well be a place for developingnew therapies aimed at directly preventing RGC damage andpreserving function, independent of IOP lowering.

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ISCHEMIA IN THE GLAUCOMA PATIENT J. FlammerOutpatient Neurology Clinic, University Hospital Basel, Basel,Switzerland

Glaucoma is phenomenologically defined as a disease withcharacteristic loss of retinal ganglian cells and their axonscombined with a tissue remodelling of the optic nerve headand the innermost layer of the retina. This leads clinically to avisible cupping of the disc and to a measurable thinning ofthe nerve fiber layer of the retina. The patients experience aprogressive visual field damage together with a decrease incontrast and color sensitivity.A number of major risk factors are meanwhile well known.Some can be influenced such as IOP increase, blood pressuredrops or a vascular dysregulation. Others can not be influ-enced such as genetic predisposition, refraction, race, genderand age.The exact mechanisms by which these risk factors lead to thedamage is not yet known. We know that some ganglian cellsdie by apoptosis, but we do not know exactly the individualsteps that initiate the apoptosis. We know that the glial cellsare involved in the tissue remodelling and probably also inthe neural cell damage. Astrocytes are activated both by me-chanical as well as by ischemisc stress.Based on the known facts, we can assume today that is-chemia/reperfusion plays a major role in these pathomech-anisms. Glaucoma patients have on the average a reducedocular perfusion. Whereas the baseline blood flow in some

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glaucoma patients is still normal, an insufficient response to achallenge such an increase of IOP or a decrease of bloodpressure can already be observed. Most of the patients withprogressive glaucomatous damage despite an only moderate-ly elevated or even normal IOP have altered autoregulation ofocular perfusion. Interestingly, signs of reperfusion damagecould even be found in the circulating lymphocytes. Gene ex-pression analysis of lymphocytes gives further insight into the

pathomechanisms of individual patients and indicates whethera damage is present or not.The future basic reserach will establish the pathomechanismon a molecular level and the clinical research will establishfurther the connection of the risk factors with the damage.An ideal glaucoma treatment leads to a reduced and sta-bilised IOP and to an increased OBF with a better autoregula-tion.

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PFIZERSPONSORED SYMPOSIUM EFFECTIVE DIAGNOSIS:CHALLENGES AND SOLUTIONSACROSS THE CLINICAL SPECTRUM

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REALISING THE VALUE OF EFFECTIVE DIAGNOSISN. PfeifferExperimental Ophthalmology, Dept. of Ophthalmology,University of Mainz

Glaucoma is a significant public health problem. It is estimat-ed that glaucoma affects more than 67 million people world-wide; a projection of these data to Europe estimates that9.25 million patients are affected by glaucoma1. The preva-lence is expected to increase in developed countries as theelderly population grows2. Glaucoma is the second leadingcause of blindness in developed countries, resulting in morethan 6.8 million cases of bilateral blindness3. Glaucoma canresult in significant morbidity and impaired functioning, aswell as posing a significant economic burden2. Data suggest that more than 50% of cases remain undiagnosed4.However, early, accurate diagnosis and appropriate treatment hasmany benefits, not least for affected patients. If glaucoma is de-tected early, the disease progression that can result in irre-versible vision loss can be delayed with suitable treatment3. Morecomprehensive screening programmes might also be of value;recent data have suggested that even routine tonometry can leadto a reduction in the proportion of patients becoming blind, aswell as being more cost-effective in the long-term5. An increase in the rate of glaucoma diagnosis might also beeconomically advantageous. Recent data have shown that di-rect treatment costs and resource utilisation for glaucomamanagement increase as disease severity worsens1,2. Thissuggests that earlier diagnosis, coupled with appropriatemanagement to prevent disease progression, could be eco-nomically beneficial and lead to cost savings and a decreasedburden on healthcare systems1,2.

References

1. Traverso CE, Walt JG, Kelly SP, Hommer AH, Bron AM, Denis P,Nordmann JP, Renard JP, Bayer A, Grehn F, Pfeiffer N, Cedrone C,Gandolfi S, Orzalesi N, Nucci C, Rossetti L, Azuara-Blanco A,Bagnis A, Hitchings R, Salmon JF, Bricola G, Buchholz PM, KotakSV, Katz LM, Siegartel LR, Doyle JJ. Direct costs of glaucoma andseverity of the disease: a multinational long term study of re-source utilisation in Europe. Br J Ophthalmol. 2005;89:1245-1249.

2. Lee PP, Kelly SP, Mills RP, Traverso CE, Walt JG, Doyle JJ, KatzLM, Siegartel LR. Glaucoma in the United States and europe:predicting costs and surgical rates based upon stage of disease.J Glaucoma. 2007;16:471-478.

3. Weinreb RN, Khaw PT. Primary open-angle glaucoma. Lancet.2004;363:1711-1720.

4. Quigley HA. Number of people with glaucoma worldwide. BritishJournal of Ophthalmology. 1996;80:389-393.

5. Peeters A, Schouten JS, Webers CA, Prins MH, Hendrikse F,Severens JL. Cost-effectiveness of early detection and treat-ment of ocular hypertension and primary open-angle glaucomaby the ophthalmologist. Eye. 2008;22:354-362.

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GLAUCOMA DIAGNOSIS: THE HIDDEN CHALLENGER.N. WeinrebUCSD Hamilton Glaucoma Center, La Jolla, CA, USA

Glaucoma can present to the practitioner at various stages

along a continuum from undetectable disease to asympto-matic disease and functional impairment. The continuum ischaracterised by accelerated retinal ganglion cell death, sub-sequent axonal loss and optic nerve damage, and visual fieldloss1. Detection of glaucoma at an early stage of the continu-um would allow for an appropriate management plan to beimplemented, which might slow disease progression and pre-vent functional loss2. Accurate diagnosis and staging of the patient along the glau-coma continuum is difficult. Use of individual diagnostic testsin isolation might not be adequate to accurately diagnose andstage glaucoma. Initial changes in the retinal nerve fibre layerand optic disc are often asymptomatic and undetectable withstandard techniques1. Therefore, the use of a combination ofstructural and functional tests could have advantages com-pared with any single diagnostic test. Use of newer diagnostic technologies could provide a meansof complementing clinical diagnosis to enhance glaucoma di-agnosis and staging. This session will use case studies todemonstrate the ways in which a multifaceted approach canhelp to ensure an accurate diagnosis and appropriate stagingof the patient on the disease continuum.

References

1. Weinreb RN, Friedman DS, Fechtner RD et al. Risk assessmentin the management of patients with ocular hypertension. Am JOphthalmol. 2004; 138:458-467.

2. Weinreb RN, Khaw PT. Primary open-angle glaucoma. Lancet.2004; 363: 1711-1720.

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OVERCOMING BARRIERS TO EFFECTIVE DIAGNOSIS INTHE CLINICH. LemijRotterdam Eye Hospital, Rotterdam, The Netherlands

Recent research has highlighted the difficulties in glaucomadiagnosis. Clinical assessment of the optic nerve head is therecommended standard1,2; however, structural abnormalitiescan be difficult to detect, requiring careful observation of theoptic disc and retinal nerve fibre layer (RNFL)3. Results from the Thessalonki Eye Study (TES) indicate thatthe presence of known risk factors for glaucoma, includingpseudoexfoliation, is associated with a decreased rate of un-diagnosed glaucoma. This suggests that the identification ofrisk factors for glaucoma leads to a more thorough examina-tion of the optic disc by the ophthalmologist, increasing thechance of an accurate diagnosis4. Interim findings from the European Optic DiscAssessment Trial (EODAT) indicate that the accuracy ofEuropean ophthalmologists in classifying stereoscopic op-tic disc photographs varies between individual ophthal-mologists and between countries. The EODAT alsodemonstrated that automated analysis of measurementswith scanning laser polarimetry with variable cornealcompensation (SLP-VCC) and confocal scanning ophthal-moscopy (CSLO) had, on average, a higher accuracy inclassifying optic disc photographs compared with ophthal-mologists5. This suggests that imaging technologies couldsupplement clinical diagnosis and help to overcome someof the challenges faced by ophthalmologists when assess-ing an “at risk” patient. Ophthalmologists should be familiar with glaucomatouschanges in components of the optic disc, such as optic discsize, neuroretinal rim shape and RNFL loss, to enable an ac-curate diagnosis3,6. More comprehensive examination guide-lines coupled with use of the available technologies mightaugment diagnosis in the clinic3,4.

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References

1. Mardin CY, Junemann AG. The diagnostic value of optic nerveimaging in early glaucoma. Curr Opin Ophthalmol.2001;12:100-104.

2. European Glaucoma Society. Terminology and Guidelines forGlaucoma. 2nd edition. Savona, Italy: DOGMA Srl; 2003.

3. Susanna R, Jr., Vessani RM. New findings in the evaluation ofthe optic disc in glaucoma diagnosis. Curr Opin Ophthalmol.2007;18:122-128.

4. Topouzis F, Coleman AL, Harris A, et al. Factors associated withundiagnosed open-angle glaucoma: the Thessaloniki Eye Study.Am J Ophthalmol. 2008;145:327-335.

5. Reus NJ, Lemij HG, European Optic Disc Assessment Trial (EO-DAT) group. Assessment of stereoscopic optic disc photographsin glaucoma by European ophthalmologists. Invest OphthalmolVis Sci. 2007;48:Abstract 1970.

6. Moreno-Montanes J, Anton A, Garcia N, et al. GlaucomaProbability Score vs Moorfields Classification in Normal, OcularHypertensive, and Glaucomatous Eyes. Am J Ophthalmol.2008;145:360-368.

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ENABLING ACCURATE DIAGNOSIS WITH IMAGINGTECHNOLOGYD. Garway-HeathMoorfields Eye Hospital, London, United Kingdom

Several imaging technologies have become available duringthe past decade to augment clinical diagnosis of glaucoma1.These include confocal scanning laser ophthalmoscopy (e.g.Heidelberg Retina Tomograph [HRT]), scanning laser po-larimetry (e.g. GDx), and optical coherence tomography(OCT). These devices all allow objective, quantitative meas-urement of nerve structure2. New technologies have alsobeen developed for perimetric testing, including frequency-doubling technology (FDT). Imaging technologies provide additional structural information,which can complement clinical assessment and perimetric test-ing in the diagnosis and staging of glaucoma.2 Measurementreproducibility is an issue for both functional tests, such asstandard automated perimetry (SAP)3, and imaging devices2,and could mask true change (progression). The identification oftrue change might require follow-up with both perimetry andimaging, if all progressing patients are to be identified. Each diagnostic technology has specific advantages and dis-advantages, and the appropriateness of a technology andanalysis strategy for each individual patient will vary2. Theclinical use of these technologies is likely to expand in the fu-ture1 and this will offer opportunities for ophthalmologists tooptimise diagnostic procedures.

References

1. European Glaucoma Society. Terminology and Guidelines forGlaucoma. 2nd. Savona, Italy: DOGMA Srl; 2003.

2. Greenfield DS. Optic nerve and retinal nerve fiber layer analyz-ers in glaucoma. Curr Opin Ophthalmol. 2002;13:68-76.

3. Artes PH, Hutchison DM, Nicolela MT, LeBlanc RP, Chauhan BC.Threshold and variability properties of matrix frequency-dou-bling technology and standard automated perimetry in glauco-ma. Invest Ophthalmol Vis Sci. 2005;46:2451-2457.

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PREVENTING PROGRESSION: EARLY DIAGNOSIS FORAPPROPRIATE MANAGEMENTC. MigdalWestern Eye Hospital, London

Glaucoma is a progressive disease and when a patient is di-agnosed, irreparable damage has already occurred. An early,accurate diagnosis could delay further damage and functionalloss1.The Early Manifest Glaucoma Trial (EMGT) showed overallprogression in approximately two thirds of patients when thefollow-up period ended (median, 8 years). Progression riskwas halved following intraocular pressure (IOP)-loweringtreatment2. Accurate diagnosis and documentation are veryimportant and glaucoma management should depend onthese factors, rather than relying on IOP only. Although treatment can delay progression, both early andadvanced glaucoma might progress even when treated.The Advanced Glaucoma Intervention Study (AGIS) ob-served progression in 30% of treated patients during thefollow-up period (median, 10.8 years)3. Patients with moreadvanced glaucoma might be at risk of more pronouncedfunctional loss occurring earlier. Early, accurate diagnosisis therefore necessary to provide the information an oph-thalmologist needs to make the best-informed manage-ment decisions1.

References

1. Weinreb RN, Khaw PT. Primary open-angle glaucoma. Lancet2004; 363:1711-1720.

2. Leske MC, Heijl A, Hyman L, Bengtsson B, Dong L, Yang Z.Predictors of long-term progression in the early manifest glau-coma trial. Ophthalmology 2007;114: 1965-1972.

3. The Advanced Glaucoma Intervention Study (AGIS): 12.Baseline risk factors for sustained loss of visual field and visualacuity in patients with advanced glaucoma. Am J Ophthalmol.2002;134: 499-512.

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